Multiparameter spectral CT-based radiomics in predicting the expression of programmed death ligand 1 in non-small-cell lung cancer.

AIM: To explore the value of radiomics for predicting the expression of programmed death ligand 1 (PD-L1) in non-small-cell lung cancer (NSCLC) based on multiparameter spectral computed tomography (CT) images. MATERIALS AND METHODS: A total of 220 patients with NSCLC were enrolled retrospectively and divided into the training (n=176) and testing (n=44) cohorts. The radiomics features were extracted from the conventional CT images, mono-energy 40 keV images, iodine density (ID) maps, Z-effective maps, and electron density maps. The logistic regression (LR) and support vector machine (SVM) algorithms were employed to build models based on radiomics signatures. The prediction abilities were qualified by the area under the curve (AUC) obtained from the receiver operating characteristic (ROC) curve. Internal validation was performed on the independent testing dataset. RESULTS: The combined model for PD-L1 ≥1%, which consisted of the radiomics score (rad-score; p<0.0001), white blood cell (WBC; p=0.027) counts, and air bronchogram (p=0.003), reached the highest performance with the AUCs of 0.873 and 0.917 in the training and testing dataset, respectively, which was better than the radiomics model with the AUCs of 0.842 and 0.886. The combined model for PD-L1 ≥50%, which consisted of rad-score (p<0.0001) and WBC counts (p=0.027), achieved the highest performance in the training and testing dataset with AUCs of 0.932 and 0.903, respectively, which was better than the radiomics model with AUCs of 0.920 and 0.892, respectively. CONCLUSION: The radiomics model based on the multiparameter images of spectral CT can predict the expression level of PD-L1 in NSCLC. The combined model can obtain higher prediction efficiency and serves as a promising method for immunotherapy selection.

Effect of SIRT1 gene single-nucleotide polymorphisms on susceptibility to type 1 diabetes in a Han Chinese population.

AIMS: SIRT1 deficiency has been associated with diabetes, and a variant of the SIRT1 gene has been found to be involved in human autoimmune diabetes; however, it is unclear whether this genetic variation exists in Han Chinese with type 1 diabetes (T1D) and whether it contributes to development of T1D. Therefore, we aimed to explore the association of the SIRT1 gene single-nucleotide polymorphisms (SNPs) rs10997866 and rs3818292 in a Han Chinese population with T1D. METHODS: This study recruited 2653 unrelated Han Chinese individuals, of whom 1289 had T1D and 1364 were healthy controls. Allelic and genotypic distributions of SIRT1 polymorphisms (rs10997866 and rs3818292) were determined by MassARRAY. Basic characteristics, genotype and allele frequencies of selected SNPs were compared between the T1D patients and healthy controls. Further genotype-phenotype association analysis of the SNPs was performed on the T1D patients divided into three groups according to genotype. Statistical analyses included the chi-square test, Mann‒Whitney U test, Kruskal‒Wallis H test and logistic regression. RESULTS: The allelic (G vs. A) and genotypic (GA vs. AA) distributions of SIRT1 rs10997866 were significantly different in T1D patients and healthy controls (P = 0.039, P = 0.027), and rs10997866 was associated with T1D susceptibility under dominant, overdominant and additive models (P = 0.026, P = 0.030 and P = 0.027, respectively). Moreover, genotype-phenotype association analysis showed the GG genotype of rs10997866 and the GG genotype of rs3818292 to be associated with higher titers of IA-2A (P = 0.013 and P = 0.038, respectively). CONCLUSION: SIRT1 rs10997866 is significantly associated with T1D susceptibility, with the minor allele G conferring a higher risk of T1D. Moreover, SIRT1 gene rs10997866 and rs3818292 correlate with the titer of IA-2A in Han Chinese individuals with T1D.

[Analysis of related factors influencing the detection rate of mosaic embryo and the pregnancy outcomes with mosaic embryo transfers].

Objective: To explore the related factors influencing the detection rate of mosaic embryo and the pregnancy outcomes of mosaic embryo transfer in preimplantation genetic testing for aneuploidy (PGT-A) based on next generation sequencing (NGS) technology. Methods: A retrospective study was performed to analyze the clinical data of patients in 745 PGT-A cycles from January 2019 to May 2023 at Chongqing Health Center for Women and Children, including 2 850 blastocysts. The biopsy cells were tested using NGS technology, and the embryos were divided into three groups based on the test results, namely euploid embryos, aneuploid embryos and mosaic embryos. The influence of population characteristics and laboratory-related parameters on the detection rate of mosaic embryo were analyzed, and the pregnancy outcomes of 98 mosaic embryo transfer cycles and 486 euploid embryo transfer cycles were compared during the same period, including clinical pregnancy rate and live birth rate. Results: Among the embryos tested (n=2 850), the number and proportion of euploid embryos, aneuploid embryos and mosaic embryos were 1 489 (52.2%, 1 489/2 850), 917 (32.2%, 917/2 850) and 444 (15.6%, 444/2 850), respectively. Among mosaic embryos, 245 (55.2%, 245/444) were segmental mosaic embryos, 118 (26.6%, 118/444) were whole-chromosome mosaic embryos, and 81 (18.2%, 81/444) were complex mosaic embryos. NGS technology was performed in 4 genetic testing institutions and the detection rate of mosaic embryo fluctuated from 13.5% to 27.0%. The distributions of female age, level of anti-Müllerian hormone, PGT-A indications, ovulation-inducing treatments, gonadotropin (Gn) dosage, Gn days, inner cell mass grade, trophectoderm cell grade, genetic testing institutions and developmental stage of blastocyst were significantly different among the three groups (all P<0.05). Multi-factor analysis showed that the trophectoderm cell grade and genetic testing institutions were significantly related to the detection rate of mosaic embryo; compared with the trophectoderm cell graded as A, the detection rate of mosaic embryo was significantly increased in the trophectoderm cell graded as B-(OR=1.59, 95%CI: 1.04-2.44, P=0.033); compared with genetic testing institution a, the detection rate of mosaic embryo was significantly higher (OR=2.89, 95%CI: 2.10-3.98, P<0.001) in the testing institution c. The clinical pregnancy rate and live birth rate with mosaic embryos transfer were significantly lower than those of euploid embryos transfer (clinical pregnancy rate: 51.0% vs 65.2%, P=0.008; live birth rate: 39.4% vs 53.2%, P=0.017). After adjustment for age, PGT-A indications, trophectoderm cell grade and days of embryo culture in vitro, the clinical pregnancy rate and live birth rate with mosaic embryos transfer were significantly lower than those of euploid embryos transfer (clinical pregnancy rate: OR=0.52, 95%CI: 0.32-0.83, P=0.007; live birth rate: OR=0.50, 95%CI: 0.31-0.83, P=0.007). Conclusions: The trophectoderm cell grade and genetic testing institutions are related to the detection rate of mosaic embryo. Compared with euploid embryos transfer, the clinical pregnancy rate and live birth rate with mosaic embryos transfer are significantly reduced. For infertile couple without euploid embryos, transplantable mosaic embryos could be recommended according to the mosaic ratio and mosaic type in genetic counseling to obtain the optimal pregnancy outcome.

Morphology and Dendrite-Specific Synaptic Properties of Midbrain Neurons Shape Multimodal Integration.

Multimodal integration facilitates object recognition and response to sensory cues. This depends on spatiotemporal coincidence of sensory information, recruitment of NMDA-type glutamate receptors and inhibitory feedback. Shepherd's crook neurons (SCNs) in the avian optic tectum (TeO) are an ideal model for studying cellular mechanism of multimodal integration. They receive different sensory modalities through spatially segregated dendrites, are important for stimulus selection and have an axon-carrying dendrite (AcD). We performed whole-cell patch-clamp experiments in chicken midbrain slices of both sexes. We emulated visual and auditory input in vitro by stimulating presynaptic afferents electrically. Simultaneous stimulation enhanced responses inversely depending on stimulation amplitude demonstrating the principle of inverse effectiveness. Contribution of NMDA-type glutamate receptors prolonged postsynaptic events for visual inputs only, causing a strong modality-specific difference in synaptic efficacy. We designed a multicompartment model to study the effect of morphological and physiological parameters on multimodal integration by varying the distance between soma and axonal origin and the amount of NMDA receptor (NMDAR) contribution. These parameters changed the preference of the model for one input channel and adjusted the range of input rates at which multimodal enhancement occurred on naturalistic stimulation. Thus, the unique morphology and synaptic features of SCNs shape the integration of input at different dendrites and generates an enhanced multimodal response.SIGNIFICANCE STATEMENT Multimodal integration improves perception and responses to objects. The underlying cellular mechanism depends on a balance between excitation and inhibition, and NMDA-type glutamate receptors that are involved in the multiplicative nature of enhancement following the principle of inverse effectiveness. Based on a detailed analysis of an identified multimodal cell type in the vertebrate midbrain, we studied the influence of cellular morphology and unimodal synaptic properties on multimodal integration. We can show that the combination of cellular morphology and modality-specific synaptic properties including NMDA receptor (NMDAR) contribution is optimal for nonlinear, multimodal enhancement and determines the dynamic response range of the integrating neuron. Our findings mechanistically explain how synaptic properties and cellular morphology of a midbrain neuron contribute to multimodal enhancement.

Genetic influences of the effect of circulating inflammatory cytokines on osteoarthritis in humans.

OBJECTIVE: The causal relationship between inflammatory cytokines and Osteoarthritis (OA) has not been well investigated. This study investigated the causal role of inflammatory cytokines in the risk of OA and total joint arthroplasty using the Mendelian randomization (MR) method. METHOD: Single nucleotide polymorphisms (SNPs) robustly associated with inflammatory cytokines were used as instrumental variables. The inverse-variance weighted (IVW) method with false discovery rate (FDR) adjusted P-value (q-value) for multiple comparisons were used as the main MR method to estimate causal effects based on the summary-level data for OA (knee and hip OA, respectively) and total joint arthroplasty (TJA). Sensitivity analyses validated the robustness of the results and ensured the absence of heterogeneity and horizontal pleiotropy. RESULTS: After FDR adjustment, macrophage colony-stimulating factor (MCSF) and vascular endothelial growth factor (VEGF) were identified as causally associated with knee OA (MCSF, odds ratio [OR]: 1.16, 95% confidence interval [CI]: 1.09-1.23, q = 5.05 × 10-5; VEGF, OR: 1.09, 95% CI: 1.04-1.15, q = 0.011). We also observed that genetically predicted MCSF and VEGF were positively associated with the risk of TJA, and MCP3 was negatively associated with for the risk of TJA, although the effects seem fairly modest. Sensitivity analysis further excluded the influence of heterogeneity and horizontal pleiotropy. CONCLUSIONS: Inflammatory cytokines, namely MCSF and VEGF, were causally associated with knee OA, which could enhance our understanding of inflammation in OA pathology.

Correlation study between apparent diffusion coefficients and the prognostic factors in breast cancer.

AIM: To analyse the correlation between apparent diffusion coefficients (ADC) derived from intratumoural and peritumoural regions with prognostic factors and immune-inflammatory markers in breast cancer (BC). MATERIALS AND METHODS: In this retrospective study, 89 patients (age range, 28-66 years; median, 45 years) with a diagnosis of invasive BC who underwent routine blood tests and multiparametric magnetic resonance imaging (MRI) were enrolled. The study cohort was stratified according to tumour maximum cross-section ≥20 mm, lymph node metastasis (LNM), time-signal intensity curve (TIC) type, and receptor status. Minimum, maximum, mean, and heterogeneity values of tumour ADC (ADCtmin, ADCtmax, ADCtmean, and ADCheter), maximum values of peritumoural ADC (ADCpmax), and the ratio of peritumoural-tumour ADC (ADCratio) were obtained on the ADC maps. Linear regression analyses were performed to investigate the correlation between immune-inflammatory markers, prognostic factors and ADC values. RESULTS: HER-2 was positively associated with ADCtmax, ADCtmean, and ADCpmax values (ß = 0.306, p=0.004; ß = 0.283, p=0.007; ß = 0.262, p=0.007, respectively), while platelet-to-lymphocyte ratio (PLR) was positively associated with ADCpmax and ADCratio values (ß = 0.227, p=0.020; ß = 0.231, p=0.020, respectively). Among ADC parameters, ADCpmax showed the highest predictive values for evaluating the presence of LNM (AUC, 0.751; sensitivity, 70.4%; specificity, 77.1%). CONCLUSION: The ADCpmax value could provide additional assistance in predicting prognostic factors of BC.

Application of B-flow imaging and its enhanced mode in perforator mapping.

AIM: To explore the value of B-flow (B-mode blood flow) imaging and its enhanced mode in perforator mapping. MATERIALS AND METHODS: Before surgery, B-flow imaging, enhanced B-flow imaging, colour Doppler flow imaging (CDFI), and contrast-enhanced ultrasound (CEUS) were used to detect the skin-perforating vessels and small vessels in the fat layer of the donor site. Taking the intra-operative results as the reference standard, the diagnostic consistency and efficiency of the four modes were compared. Statistical analysis was performed using the Friedman M-test, Cochran's Q-test, and the Z-test. RESULTS: Thirty flaps were excised, with 34 skin-perforating vessels and 25 non-skin-perforating vessels, as confirmed during surgery. In order of the number of skin-perforating vessels detected, the results showed that enhanced B-flow imaging detected more vessels than B-flow imaging and CDFI (all p<0.05), CEUS detected more vessels than B-flow imaging and CDFI (all p<0.05), B-flow imaging detected more vessels than CDFI (p<0.05). All four modes had remarkable and satisfactory diagnostic consistency and effectiveness, but B-flow imaging was the best (sensitivity 100%, specificity 92%, Youden index 0.92). In order of the number of small vessels in the fat layer detected, the results showed that enhanced B-flow imaging detected more vessels than CEUS, B-flow imaging, and CDFI (all p<0.05). CEUS detected more vessels than B-flow imaging and CDFI (all p<0.05). CONCLUSION: B-flow imaging is an alternative method for perforator mapping. Enhanced B-flow imaging can reveal the microcirculation of flaps.

Redisposition of acremonium-like fungi in Hypocreales.

Acremonium is acknowledged as a highly ubiquitous genus including saprobic, parasitic, or endophytic fungi that inhabit a variety of environments. Species of this genus are extensively exploited in industrial, commercial, pharmaceutical, and biocontrol applications, and proved to be a rich source of novel and bioactive secondary metabolites. Acremonium has been recognised as a taxonomically difficult group of ascomycetes, due to the reduced and high plasticity of morphological characters, wide ecological distribution and substrate range. Recent advances in molecular phylogenies, revealed that Acremonium is highly polyphyletic and members of Acremonium s. lat. belong to at least three distinct orders of Sordariomycetes, of which numerous orders, families and genera with acremonium-like morphs remain undefined. To infer the phylogenetic relationships and establish a natural classification for acremonium-like taxa, systematic analyses were conducted based on a large number of cultures with a global distribution and varied substrates. A total of 633 cultures with acremonium-like morphology, including 261 ex-type cultures from 89 countries and a variety of substrates including soil, plants, fungi, humans, insects, air, and water were examined. An overview phylogenetic tree based on three loci (ITS, LSU, rpb2) was generated to delimit the orders and families. Separate trees based on a combined analysis of four loci (ITS, LSU, rpb2, tef-1α) were used to delimit species at generic and family levels. Combined with the morphological features, host associations and ecological analyses, acremonium-like species evaluated in the present study are currently assigned to 63 genera, and 14 families in Cephalothecales, Glomerellales and Hypocreales, mainly in the families Bionectriaceae, Plectosphaerellaceae and Sarocladiaceae and five new hypocrealean families, namely Chrysonectriaceae, Neoacremoniaceae, Nothoacremoniaceae, Pseudoniessliaceae and Valsonectriaceae. Among them, 17 new genera and 63 new combinations are proposed, with descriptions of 65 new species. Furthermore, one epitype and one neotype are designated to stabilise the taxonomy and use of older names. Results of this study demonstrated that most species of Acremonium s. lat. grouped in genera of Bionectriaceae, including the type A. alternatum. A phylogenetic backbone tree is provided for Bionectriaceae, in which 183 species are recognised and 39 well-supported genera are resolved, including 10 new genera. Additionally, rpb2 and tef-1α are proposed as potential DNA barcodes for the identification of taxa in Bionectriaceae. Taxonomic novelties: New families: Chrysonectriaceae L.W. Hou, L. Cai & Crous, Neoacremoniaceae L.W. Hou, L. Cai & Crous, Nothoacremoniaceae L.W. Hou, L. Cai & Crous, Pseudoniessliaceae L.W. Hou, L. Cai & Crous, Valsonectriaceae L.W. Hou, L. Cai & Crous. New genera: Bionectriaceae: Alloacremonium L.W. Hou, L. Cai & Crous, Gossypinidium L.W. Hou, L. Cai & Crous, Monohydropisphaera L.W. Hou, L. Cai & Crous, Musananaesporium L.W. Hou, L. Cai & Crous, Paragliomastix L.W. Hou, L. Cai & Crous, Proliferophialis L.W. Hou, L. Cai & Crous, Proxiovicillium L.W. Hou, L. Cai & Crous, Ramosiphorum L.W. Hou, L. Cai & Crous, Verruciconidia L.W. Hou, L. Cai & Crous, Waltergamsia L.W. Hou, L. Cai & Crous; Clavicipitaceae: Subuliphorum L.W. Hou, L. Cai & Crous; Neoacremoniaceae: Neoacremonium L.W. Hou, L. Cai & Crous; Nothoacremoniaceae: Nothoacremonium L.W. Hou, L. Cai & Crous; Plectosphaerellaceae: Allomusicillium L.W. Hou, L. Cai & Crous, Parafuscohypha L.W. Hou, L. Cai & Crous; Pseudoniessliaceae: Pseudoniesslia L.W. Hou, L. Cai & Crous; Sarocladiaceae: Polyphialocladium L.W. Hou, L. Cai & Crous. New species: Bionectriaceae: Alloacremonium ferrugineum L.W. Hou, L. Cai & Crous, Al. humicola L.W. Hou, L. Cai & Crous, Acremonium aerium L.W. Hou, L. Cai & Crous, A. brunneisporum L.W. Hou, L. Cai & Crous, A. chlamydosporium L.W. Hou, L. Cai & Crous, A. ellipsoideum L.W. Hou, Rämä, L. Cai & Crous, A. gamsianum L.W. Hou, L. Cai & Crous, A. longiphialidicum L.W. Hou, L. Cai & Crous, A. multiramosum L.W. Hou, Rämä, L. Cai & Crous, A. mycoparasiticum L.W. Hou, L. Cai & Crous, A. stroudii K. Fletcher, F.C. Küpper & P. van West, A. subulatum L.W. Hou, L. Cai & Crous, A. synnematoferum L.W. Hou, Rämä, L. Cai & Crous, Bulbithecium ammophilae L.W. Hou, L. Cai & Crous, B. ellipsoideum L.W. Hou, L. Cai & Crous, B. truncatum L.W. Hou, L. Cai & Crous, Emericellopsis brunneiguttula L.W. Hou, L. Cai & Crous, Gliomastix musae L.W. Hou, L. Cai & Crous, Gossypinidium sporodochiale L.W. Hou, L. Cai & Crous, Hapsidospora stercoraria L.W. Hou, L. Cai & Crous, H. variabilis L.W. Hou, L. Cai & Crous, Mycocitrus odorus L.W. Hou, L. Cai & Crous, Nectriopsis ellipsoidea L.W. Hou, L. Cai & Crous, Paracylindrocarpon aurantiacum L.W. Hou, L. Cai & Crous, Pn. foliicola Lechat & J. Fourn., Paragliomastix rosea L.W. Hou, L. Cai & Crous, Proliferophialis apiculata L.W. Hou, L. Cai & Crous, Protocreopsis finnmarkica L.W. Hou, L. Cai, Rämä & Crous, Proxiovicillium lepidopterorum L.W. Hou, L. Cai & Crous, Ramosiphorum echinoporiae L.W. Hou, L. Cai & Crous, R. polyporicola L.W. Hou, L. Cai & Crous, R. thailandicum L.W. Hou, L. Cai & Crous, Verruciconidia erythroxyli L.W. Hou, L. Cai & Crous, Ve. infuscata L.W. Hou, L. Cai & Crous, Ve. quercina L.W. Hou, L. Cai & Crous, Ve. siccicapita L.W. Hou, L. Cai & Crous, Ve. unguis L.W. Hou, L. Cai & Crous, Waltergamsia alkalina L.W. Hou, L. Cai & Crous, W. catenata L.W. Hou, L. Cai & Crous, W. moroccensis L.W. Hou, L. Cai & Crous, W. obpyriformis L.W. Hou, L. Cai & Crous; Chrysonectriaceae: Chrysonectria crystallifera L.W. Hou, L. Cai & Crous; Nectriaceae: Xenoacremonium allantoideum L.W. Hou, L. Cai & Crous; Neoacremoniaceae: Neoacremonium distortum L.W. Hou, L. Cai & Crous, N. flavum L.W. Hou, L. Cai & Crous; Nothoacremoniaceae: Nothoacremonium subcylindricum L.W. Hou, L. Cai & Crous, No. vesiculophorum L.W. Hou, L. Cai & Crous; Myrotheciomycetaceae: Trichothecium hongkongense L.W. Hou, L. Cai & Crous; Plectosphaerellaceae: Brunneomyces polyphialidus L.W. Hou, L. Cai & Crous, Parafuscohypha proliferata L.W. Hou, L. Cai & Crous; Sarocladiaceae: Chlamydocillium acaciae L.W. Hou, L. Cai & Crous, C. antarcticum L.W. Hou, L. Cai & Crous, C. guttulatum L.W. Hou, L. Cai & Crous, C. lolii L.W. Hou, L. Cai & Crous, C. soli L.W. Hou, L. Cai & Crous, C. terrestre L.W. Hou, L. Cai & Crous, Parasarocladium chondroidum L.W. Hou, L. Cai & Crous,Polyphialocladium fusisporum L.W. Hou, L. Cai & Crous, Sarocladium agarici L.W. Hou, L. Cai & Crous, S. citri L.W. Hou, L. Cai & Crous, S. ferrugineum L.W. Hou, L. Cai & Crous, S. fuscum L.W. Hou, L. Cai & Crous,S. theobromae L.W. Hou, L. Cai & Crous; Valsonectriaceae: Valsonectria crystalligena L.W. Hou, L. Cai & Crous, V. hilaris L.W. Hou, L. Cai & Crous. New combinations: Bionectriaceae: Acremonium purpurascens (Sukapure & Thirum.) L.W. Hou, L. Cai & Crous, Bulbithecium arxii (Malloch) L.W. Hou, L. Cai & Crous, Bu. borodinense (Tad. Ito et al.) L.W. Hou, L. Cai & Crous, Bu. pinkertoniae (W. Gams) L.W. Hou, L. Cai & Crous, Bu. spinosum (Negroni) L.W. Hou, L. Cai & Crous, Emericellopsis exuviara (Sigler et al.) L.W. Hou, L. Cai & Crous, E. fimetaria (Pers.) L.W. Hou, L. Cai & Crous, E. fuci (Summerb. et al.) L.W. Hou, L. Cai & Crous, E. moniliformis (A. Giraldo et al.) L.W. Hou, L. Cai & Crous, E. salmonea (W. Gams & Lodha) L.W. Hou, L. Cai & Crous, E. tubakii (Gams) L.W. Hou, L. Cai & Crous, Fusariella arenula (Berk. & Broome) L.W. Hou, L. Cai & Crous, Hapsidospora chrysogena (Thirum. & Sukapure) L.W. Hou, L. Cai & Crous, H. flava (W. Gams) L.W. Hou, L. Cai & Crous, H. globosa (Malloch & Cain) L.W. Hou, L. Cai & Crous, H. inversa (Malloch & Cain) L.W. Hou, L. Cai & Crous, Hydropisphaera aurantiaca (C.A. Jørg.) L.W. Hou, L. Cai & Crous, Lasionectria atrorubra (Lechat & J. Fourn.) L.W. Hou, L. Cai & Crous, L. bisepta (W. Gams) L.W. Hou, L. Cai & Crous, L. castaneicola (Lechat & Gardiennet) L.W. Hou, L. Cai & Crous, L. cerealis (P. Karst.) L.W. Hou, L. Cai & Crous, L. olida (W. Gams) L.W. Hou, L. Cai & Crous, Lasionectriopsis dentifera (Samuels) L.W. Hou, L. Cai & Crous, Lasionectriella arenuloides (Samuels) L.W. Hou, L. Cai & Crous, La. marigotensis (Lechat & J. Fourn.) L.W. Hou, L. Cai & Crous, Monohydropisphaera fusigera (Berk. & Broome) L.W. Hou, L. Cai & Crous, Musananaesporium tectonae (R.F. Castañeda) L.W. Hou, L. Cai & Crous, Mycocitrus zonatus (Sawada) L.W. Hou, L. Cai & Crous, Nectriopsis microspora (Jaap) L.W. Hou, L. Cai & Crous, Ovicillium asperulatum (A. Giraldo et al.) L.W. Hou, L. Cai & Crous, O. variecolor (A. Giraldo et al.) L.W. Hou, L. Cai & Crous, Paracylindrocarpon multiloculatum (Samuels) L.W. Hou, L. Cai & Crous, Pn. multiseptatum (Samuels)L.W. Hou, L. Cai & Crous, Paragliomastix chiangraiensis (J.F. Li et al.) L.W. Hou, L. Cai & Crous, Px. luzulae (Fuckel) L.W. Hou, L. Cai & Crous, Px. znieffensis (Lechat & J. Fourn.) L.W. Hou, L. Cai & Crous, Protocreopsis rutila (W. Gams) L.W. Hou, L. Cai & Crous, Proxiovicillium blochii (Matr.)L.W. Hou, L. Cai & Crous, Stanjemonium dichromosporum (Gams & Sivasith.) L.W. Hou, L. Cai & Crous, Verruciconidia persicina (Nicot) L.W. Hou, L. Cai & Crous, Ve. verruculosa (W. Gams & Veenb.-Rijks) L.W. Hou, L. Cai & Crous, Waltergamsia citrina (A. Giraldo et al.) L.W. Hou, L. Cai &Crous, W. dimorphospora (A. Giraldo et al.) L.W. Hou, L. Cai & Crous, W. epimycota (Samuels) L.W. Hou, L. Cai & Crous, W. fusidioides (Nicot) L.W. Hou, L. Cai & Crous, W. hennebertii (W. Gams) L.W. Hou, L. Cai & Crous, W. parva (A. Giraldo et al.) L.W. Hou, L. Cai & Crous, W. pilosa (A. Giraldo et al.) L.W. Hou, L. Cai & Crous, W. zeylanica (Petch) L.W. Hou, L. Cai & Crous; Cephalothecaceae: Phialemonium thermophilum (W. Gams & J. Lacey) L.W. Hou, L. Cai & Crous; Clavicipitaceae: Subuliphorum camptosporum (W. Gams) L.W. Hou, L. Cai & Crous; Coniochaetaceae: Coniochaeta psammospora (W. Gams) L.W. Hou, L. Cai & Crous; Nothoacremoniaceae: Nothoacremonium exiguum (W. Gams) L.W. Hou, L. Cai & Crous; Neoacremoniaceae: Neoacremonium minutisporum (Sukapure & Thirum.) L.W. Hou, L. Cai & Crous; Ne. taiwanense (K.L. Pang et al.) L.W. Hou, L. Cai & Crous; Ne. vitellinum (W. Gams) L.W. Hou, L. Cai & Crous; Plectosphaerellaceae: Allomusicillium domschii (W. Gams) L.W. Hou, L. Cai & Crous, Brunneomyces pseudozeylanicus (W. Gams) L.W. Hou, L. Cai & Crous; Pseudoniessliaceae: Pseudoniesslia minutispora (W. Gams et al.) L.W. Hou, L. Cai & Crous; Sarocladiaceae: Chlamydocillium curvulum (W. Gams) L.W. Hou, L. Cai & Crous, Parasarocladium funiculosum (Sukapure & Thirum.) L.W. Hou, L. Cai & Crous; Valsonectriaceae: Valsonectria inflata (C.H. Dickinson) L.W. Hou, L. Cai & Crous, V. roseola (G. Sm.) L.W. Hou, L. Cai & Crous. Epitype (basionym): Sphaeria violacea J.C. Schmidt ex Fr. Neotype (basionym): Mastigocladium blochii Matr. Citation: Hou LW, Giraldo A, Groenewald JZ, Rämä T, Summerbell RC, Zang P, Cai L, Crous PW (2023). Redisposition of acremonium-like fungi in Hypocreales. Studies in Mycology 105: 23-203. doi: 10.3114/sim.2023.105.02.

Sustainable management of water-agriculture-ecology nexus system under multiple uncertainties.

The shrinkage and ecological degradation of the Aral Sea resulting from the uncontrolled use of water resources and the unregulated expansion of agriculture activities call for sustainable management of water-agriculture-ecology (WAE) nexus from a basin perspective. However, managers face thorny challenges brought by multiple uncertainties in the management and planning processes. In this study, an interval stochastic fuzzy programming (ISF) method is developed for tackling multiple uncertainties presented as probability distributions, flexible variables and interval parameters. Then, an ISF-WAE model is formulated for Aral Sea Basin, which considers 108 planning scenarios that reflect different food-security and ecology-restoration requirements, as well as risk-response attitudes of decision maker over a long-term planning horizon (2021-2050). Results reveal that for Aral Sea Basin: (i) managers should set strict acreage benchmarks for cereal crops, in which wheat would account for a range of [29.1, 31.2] % of the total agricultural area; (ii) for promoting ecological restoration, the proportion of agricultural water allocation should decrease by a range of [12.7, 16.1] % during the planning horizon; (iii) due to low water requirement and high ecological value of grassland, it is recommended to expand grassland area to improve the sustainability of the Aral Sea Basin in the case of limited water resources.

Effect of L-4-Thiazolylalanine (Protinol™) on skin barrier strength and skin protection.

OBJECTIVES: Skin barrier properties are critical for maintaining epidermal water content, protecting from environmental factors and providing the first line of defense against pathogens. In this study, we investigated the non-proteinogenic amino acid L-4-Thiazolylalanine (L4) as a potential active ingredient in skin protection and barrier strength. METHODS: L4 on wound healing, anti-inflammatory and anti-oxidant properties were evaluated using monolayers and 3D skin equivalents. The transepithelial electrical resistance (TEER) value was used in vitro as a strong indicator of barrier strength and integrity. Clinical L4 efficacy was assessed for the evaluation of the skin barrier integrity and soothing benefits. RESULTS: In vitro treatments of L4 show beneficial effects in wound closure mechanism, and we demonstrate that L4 anti-oxidant benefits with markedly increased HSP70 and decreased reactive oxygen species production induced by UVs exposure. Barrier strength and integrity were significantly improved by L4, confirmed clinically by an increase in 12R-lipoxygenase enzymatic activity in the stratum corneum. In addition, soothing benefits of L4 have been shown clinically with the decrease in redness after methyl nicotinate application on the inner arm and the significant reduction of the erythema and the skin desquamation on the scalp. CONCLUSION: L4 delivered multiple skin benefits by strengthening the skin barrier, accelerating the skin repair process as well as soothing the skin and the scalp with anti-inflammaging effects. The observed efficacy validates L4 as a desirable skincare ingredient for topical treatment.

OBJECTIFS: La barrière cutanée est primordiale pour le maintien d'un épiderme hydraté, sa protection contre les facteurs environnementaux et pour conférer une première ligne de défense contre les pathogènes. Dans cette étude, nous nous intéressons à un aminoacide non-proteinogénique, L-4-Thiazolylalanine (L4) comme potentiel actif cosmétique et évaluons ses effets sur la protection de la peau et le renforcement de la barrière cutanée. MÉTHODES: Les propriétés cicatrisantes, anti-inflammatoires et antioxydantes de L4 ont été déterminées par culture cellulaire et sur modèles de peau 3D. La mesure de la résistance électrique transépithéliale a été utilisée in vitro comme indicateur de la résistance de la barrière de la peau. Des études cliniques ont été réalisées pour évaluer L4 sur ses capacités apaisantes et son impact sur l'intégrité de la barrière cutanée. RÉSULTATS: In vitro, nous déterminons qu'un traitement L4 a des effets bénéfiques dans le processus de cicatrisation mais aussi des propriétés antioxydantes, induisant une augmentation de HSP70 ainsi qu'une diminution de la production d'espèces réactives a l'oxygène induite par rayons UV. Un renforcement de la barrière cutanée et une amélioration de son intégrité sont observés après un traitement L4 et confirme cliniquement par une augmentation de l'activité enzymatique de la 12R-lipoxygenase dans le stratum corneum. De plus, les effets protecteurs de L4 ont été confirmes cliniquement avec une rougeur cutanée diminuée après application de nicotinate de methyle sur l'avant-bras interne ainsi qu'une réduction significative d'érythème et de desquamation cutanée du cuir chevelu. CONCLUSION: L4 offre de multiples bénéfices pour la peau en renforçant la barrière cutanée, accélérant le processus de cicatrisation et offrant des actions anti-inflammatoires apaisantes pour la peau et le cuir chevelu. Cela fait de L4 un ingrédient cosmétique intéressant pour une application topic.

[Effects of novel bioactive glasses on promoting remineralization of artificial dentin caries].

OBJECTIVE: To investigate the effects of novel bioactive glasses (BG) including PSC with high phosphorus component and FBG with fluorine-doped element on promoting remineralization of artificial dentin caries. METHODS: (1) BGs were used in this study as follows: PSC (10.8%P2O5-54.2%SiO2-35.0%CaO, mol.%) were synthesized using phytic acid as the phosphorus precursor through sol-gel method. FBG (6.1%P2O5-37.0%SiO2-53.9%CaO-3.0%CaF2, mol.%) and 45S5(6.0%P2O5-45.0%SiO2-24.5%CaO-24.5%Na2O, mol.%) were synthesized by traditional melt method. (2) The above BGs were soaked in simulated body fluid (SBF) for 24 hours. Then X-ray diffraction (XRD) was used to analyze the formation of hydroxyapatite (HA) crystals. (3) Prepared 1 mm thick dentin slices were soaked in 17% ethylene diamine tetraacetic acid (EDTA) for 1 week to demineralize the dentin. Then the dentin slices treated by BG were soaked in SBF for 1 week. Field emission scanning electron micro-scopy (FE-SEM) was used to observe the surface morphology of the dentin slices. (4) Four cavities were prepared to 1 mm depth in each 2 mm thick dentin slice, then were treated with lactic acid for 2 weeks to form the artificial dentin caries. Wax, mineral trioxide aggregate (MTA), PSC and FBG were used to fill four cavities as blank control group, MTA group, PSC group and FBG group respectively. Then the spe-cimens were soaked in SBF for 4 weeks. The changes of depth and density of demineralized dentin were analyzed using Micro-CT before filling and after 2 and 4 weeks filling. RESULTS: (1) PSC and FBG promoted mineral formation on the surfaces of the demineralized dentin. And the speed was faster and crystallinity was higher in PSC group than the FBG and 45S5 groups. (2) The increased mineral density of artificial dentin caries in PSC group were (185.98 ± 55.66) mg/cm3 and (213.64 ± 36.01) mg/cm3 2 and 4 weeks after filling respectively, which were significantly higher than the control group [(20.38 ± 7.55) mg/cm3, P=0.006; (36.46 ± 10.79) mg/cm3, P=0.001]. At meanwhile, PSC group was also higher than MTA group [(57.29 ± 10.09) mg/cm3; (111.02 ± 22.06) mg/cm3], and it had statistical difference (P=0.015; P=0.006). The depth of remineralized dentin in PSC group were (40.0 ± 16.9) µm and (54.5 ± 17.8) µm 2 and 4 weeks respectively, which were also statistically different from the control group (P =0.010;P=0.001). There were no statistical differences between the control group and MTA group. The above effects of FBG group were between PSC and MTA. CONCLUSION: PSC has advantages in the speed, quality and depth of mineral deposition in the demineralized layer of artificial dentin caries. It would be expected to be an ideal material to promote the remineralization of dentin caries.

[Efficacy of off-pump minimally invasive via a single left intercostal space incision compared with median sternotomy multi-vesselcoronary artery bypass grafting].

Objective: To compare the efficacy of off-pump minimally invasive cardiac surgery (MICS) via a single left intercostal space incision with median sternotomy multi-vesselcoronary artery bypass grafting (CABG). Methods: Patients who were diagnosed with multi-artery coronary artery disease (CAD) in the Ward 10 of the Department of Cardiac Surgery, Beijing Anzhen Hospital Affiliated to Capital Medical University and underwent CABG from July 2019 to January 2022 were retrospectively collected. All the patients were divided into MICS group and conventional CABG group according to the surgical methods. The perioperative outcomes were compared between thetwo groups, including intraoperative blood loss, postoperative 24 h thoracic drainage volume, ventilation duration, length of stay (LOS) in intensive care unit (ICU) and total LOS in hospital. Intraoperative blood flow of graft vesselswas measured by transit-time flow measurement (TTFM) after vascular anastomosis, and mean flow (MF) and pulsatile index (PI) were compared between the two groups. Results: A total of 444 patients were in the final analysis, with 351 males and 93 females, and the mean age of (62.0±8.9) years. There were 179 patients in MICS group and 265 cases in conventional CABG group, respectively. There were no statistically significant differences in the preoperative profiles between the two groups (all P>0.05) except that younger age [(60.7±9.3) years vs (62.8±8.5) years, P=0.017] and lower proportion of female [10.1% (18/179) vs 28.3% (75/265), P<0.001] were detected in MICS group. Likewise, there was no significant difference in the number of graft vessels between MICS group (3.18±0.74) and conventional CABG group (3.28±0.86) (P=0.234). Compared with those in conventional CABG group, patients in MICS group showed longer operation duration [ (5.10±1.09) h vs (4.33±0.86) h], fewer intraoperative blood loss [500 (200, 700) ml vs 700 (600, 900) ml], fewer postoperative 24 h thoracic drainage volume [300 (200, 400) ml vs 400 (250, 500) ml], shorter postoperative ventilation duration [15.0 (12.0, 17.0) h vs 16.5 (12.5, 19.0) h, P<0.001], LOS in ICU [18.0 (15.0, 20.0) h vs 20.0 (16.0, 23.0) h, P<0.001] and total LOS in hospital [(12.6±2.7) d vs (14.5±3.9) d, P<0.001]. MI and PI of graft vessels were similar between the two groups (both P>0.05). Moreover, there were no significant differences in major perioperative complications (i.e., repeat thoracotomy, incision infection, stroke) and mortality between the two groups (all P>0.05). Conclusion: MICS is an alternative treatment for patients with multi-vessel CAD with better perioperative outcomes compared with conventional CABG.

The influence of CYP2R1 polymorphisms and gene-obesity interaction with hypertension risk in a Chinese rural population.

BACKGROUND AND AIMS: Several studies have reported that variants in CYP2R1 have been linked with an increased risk of hypertension. However, the interaction between CYP2R1 variants and environmental factors on the susceptibility of hypertension remained unclear. Therefore, this study evaluated the influence of CYP2R1 polymorphisms on hypertension susceptibility, and explored the interaction effect of CYP2R1 variations and obesity on the disease. METHODS AND RESULTS: We included 766 incident hypertension cases matched with non-hypertension controls in a 1:1 ratio by sex, age (within 3 years). Two loci in CYP2R1 gene (rs10766197 and rs12794714) were genotyped by TaqMan probe assays. The concentration of 25-hydroxyvitamin-D was determined by human enzyme-linked immunosorbent assay (ELISA) kits. The associations of CYP2R1 polymorphisms and risks of vitamin D deficiency (VDD) were analyzed by logistic regression. Multifactor dimensionality reduction (MDR) was used to analyze the gene-environment interaction. Multiple logistic regression was used to examine the effect of CYP2R1 gene variations, and the interaction between CYP2R1 variation and obesity on hypertension susceptibility. The results showed that rs10766197 (GG vs. AA) and rs12794714 (GG vs. AA) polymorphisms were both associated with an increased risk of VDD (OR = 1.49, 95% confidence interval (CI) = 1.08-2.05 and OR = 1.63, 95% CI = 1.19-2.25, respectively), after adjustment for potential risk factors. We also found that rs12794714 polymorphism was significantly associated with elevated risk of hypertension under the dominant model (OR = 1.26, 95% CI = 1.01-1.56). In addition, the interactions between rs12794714 with both general obesity (OR = 3.93, 95% CI = 2.72-5.68) and central obesity (OR = 3.22, 95% CI = 2.29-4.52) have significant effects on hypertension susceptibility. CONCLUSIONS: The study provided further evidence that CYP2R1 variation was associated with a higher risk of hypertension in Chinese rural population. The interaction between CYP2R1 rs12794714 and obesity may increase the risk of hypertension.

A multimodality intervention to improve musculoskeletal health, function, metabolism, and well-being in spinal cord injury: study protocol for the FIT-SCI randomized controlled trial.

BACKGROUND: A spinal cord injury (SCI) is a devastating, life-changing event that has profoundly deleterious effects on an individual's health and well-being. Dysregulation of neuromuscular, cardiometabolic, and endocrine organ systems following an SCI contribute to excess morbidity, mortality and a poor quality of life. As no effective treatments currently exist for SCI, the development of novel strategies to improve the functional and health status of individuals living with SCI are much needed. To address this knowledge gap, the current study will determine whether a Home-Based Multimodality Functional Recovery and Metabolic Health Enhancement Program that consists of functional electrical stimulation of the lower extremity during leg cycling (FES-LC) plus arm ergometry (AE) administered using behavioral motivational strategies, and testosterone therapy, is more efficacious than FES-LC plus AE and placebo in improving aerobic capacity, musculoskeletal health, function, metabolism, and wellbeing in SCI. METHODS: This single-site, randomized, placebo-controlled, parallel group trial will enroll 88 community-dwelling men and women, 19 to 70 years of age, with cervical and thoracic level of SCI, ASIA Impairment Scale grade: A, B, C, or D, 6 months or later after an SCI. Participants randomized to the multimodality intervention will undergo 16 weeks of home-based FES-LC and AE training plus testosterone undecanoate. Testosterone undecanoate injections will be administered by study staff in clinic or by a visiting nurse in the participant's home. The control group will receive 16 weeks of home-based FES-LC and AE exercise plus placebo injections. The primary outcome of this trial is peak aerobic capacity, measured during an incremental exercise testing protocol. Secondary outcomes include whole body and regional lean and adipose tissue mass; muscle strength and power; insulin sensitivity, lipids, and inflammatory markers; SCI functional index and wellbeing (mood, anxiety, pain, life satisfaction and depressive symptoms); and safety. DISCUSSION: We anticipate that a multimodality intervention that simultaneously addresses multiple physiological impairments in SCI will result in increased aerobic capacity and greater improvements in other musculoskeletal, metabolic, functional and patient-reported outcomes compared to the control intervention. The findings of this study will have important implications for improving the care of people living with an SCI. TRIAL REGISTRATION: ClinicalTrials.gov :  ( NCT03576001 ). Prospectively registered: July 3, 2018.

[Identification of rare variants in exons of NLRC4 gene in patients with type 1 diabetes and their impact on gene function].

Objective: To identify rare variants in exon and exon-intron boundary of containing NLR family CARD domain protein 4 (NLRC4) in type 1 diabetes (T1DM) patients, and to explore their effects on gene function. Methods: A total of 508 T1DM patients and 527 healthy controls in the Department of Metabolic Endocrinology, Second Xiangya Hospital of Central South University from August 2017 to September 2020 were selected. The case group included 264 males and 244 females, and the age [M (Q1, Q3)] was [27 (11, 43)] years. The control group included 290 males and 237 females, and their ageï¼»M（Q1，Q3）］was [47 (36, 60)] years old. Identification of rare variants in exons of NLRC4 gene in T1DM patients and healthy controls was performed and verified by next-generation sequencing and sanger sequencing. The NLRC4 gene wild-type and mutant plasmids were constructed and transfected into 293T cells. Western blot (WB) was used to detect the expression of NLRC4 protein and cleavage products of pro-cysteinyl aspartate specific proteinase(procaspase-1). Cycloheximide (CHX) was added to 293T cells transfected with wild-type or mutant NLRC4 plasmid to detect the degradation of NLRC4 protein. The localization of NLRC4 protein was detected by immunofluorescence, and the concentration of IL-1ß in the cell supernatant was detected by enzyme-linked immunosorbent assay (ELISA). Results: The sequencing results showed that 4 patients and 2 healthy controls had a heterozygous variant c.208C>T in exon 3 of the NLRC4 gene. Two patient had a heterozygous variant c.1564T>C in exon 4, and 1 patients had c.1219G>C in exon 4. These three variants might be pathogenic variants in T1DM. In 293T cells transfected with NLRC4 wild-type and c.208C>T、c.1564T>Cc.1219G>C mutant plasmids, the expression level, degradation rate, localization of NLRC4 protein and the content of cleavage products of procaspase-1 did not change significantly. However, the concentration of IL-1ß secreted by 293T cells transfected with c.1219G>C and c.208C>T plasmid [M(Q1, Q3)] was 15.25 (12.98, 17.52) and 15.44 (13.81, 17.07) ng/L, respectively, which was lower than 18.70 (16.59, 20.81) ng/L of 293T cells transfected wild-type plasmid (P=0.020, 0.010). Conclusions: NLRC4 gene rare variants c.208C>T, c.1564T>C and c.1219G>C may not change the protein expression, degradation and localization, but c.208C>T and c.1219G>C may inhibit the secretion of IL-1ß. This result suggests that NLRC4 rare variants may have an impact on gene function.

[Characteristics and changes of sensitization patterns of major allergens in children from 2010 to 2020 in a hospital of pediatric in Beijing].

Objective: To analyze the sensitization characteristics and change of major allergens in children from 2010 to 2020 in Beijing, so as to provide basis for diagnosis, treatment and prevention of allergic diseases in children. Methods: A retrospective study was conducted to analyze the children who were suspected of allergic diseases and tested for serum immunoglobulin E (total IgE and specific IgE) in the children's Hospital Affiliated to the Capital Institute of Pediatrics from January 2010 to December 2020. A total of 45 746 children aged 0-17 years in Beijing were enrolled with a median (interquartile range) of 3.8 (2.5, 5.3) years. There were 28 918 boys (63.2%) and 16 828 girls (36.8%) and 14 984 cases (32.8%) in the infant group (<3 years old), 22 049 cases (48.2%) in the preschool group (3-6 years old), and 8 713 cases (19.0%) in the school-age group (6 years old and above). Immunocap allergen detection system (fluorescence enzyme-linked immunosorbent assay) was used to detect and the characteristics and change trend of allergens during 11 years were statistically analyzed by Chi square test. Results: The top three positive rates of single food allergens sIgE were egg white 42.6% (2 788/6 577 tests), milk 38.4% (2 606/6 782 tests) and wheat 31.8% (1 417/4 449 tests), and the sequence of single inhaled allergens were Ragweed 42.6% (440/1 034 tests), Artemisia 38.4% (1 045/3 191 tests) and Alternaria alternata 31.3% (3 358/10 725 tests). The positive detection rates of egg white 47.0%(1 904/4 048 tests), milk 41.9%(1 769/4 226 tests) and wheat 33.9%(973/2 870 tests) in the infant group were the highest, and there have statistically significant(χ2=91.495, 73.907, 16.966, P<0.05). The positive rates of fx1 (22.5%, 121/537 tests), peanut (24.9%, 111/446 tests), soybean (20.0%, 74/370 tests) and shrimp (7.48%, 44/588 tests) were the highest in the school-age group(χ²=14.436, 10.751, 11.569, 13.703, P<0.05). The most common inhaled allergens were Alternaria alternata (14.8%, 422/2 859 tests) in the infant group, Ambrosia (34.5%, 143/415 tests) and Alternaria alternata (33.5%, 1 762/5 254 tests) in the preschool group, while in the school-age group were Ambrosia (56.4%, 282/500 tests) and Artemisia (48.2%, 573/1 189 tests). The positive rates of egg white, milk, wheat, sesame seed and peanut varied from 2010 to 2020, showing a trend of falling first and then rising(χ²=10.293,χ²=12.066,χ²=7.402,χ²=32.458,χ2=31.747,P<0.05).The positive detection rates of soybean showed a significant downward trend (21.4%, 173/809 tests in 2010, 15.4%, 70/455 tests in 2020, χ²=6.751,P=0.009), while that of shrimp and crab were at a stable low level(χ²=0.263, 1.346;P>0.05). From 2010 to 2020, mold (26.7%, 1 066/3 998 tests in 2010, 40.2% 1 705/4 243 tests in 2020), grass pollen (19.8%, 259/1 308 tests in 2010, 39.3%, 1 472/3 746 tests in 2020), tree pollen(17%, 180/1 058 tests in 2010, 29.8%, 916/3 075 tests in 2020) and animal dander (18.5%, 111/601 tests in 2010, 26.6%, 672/2 522 tests in 2020) were all showed significant upward trend (χ²=168.600, 163.601, 65.931 and 17.271 respectively, P<0.001) but dust mites (30.7%, 1 270/4 132 tests in 2010, 26.7%, 1 126/4 221 tests in 2020) showed a significant downward trend(χ²=16.822,P<0.001).In 2010, the most common inhaled allergen was dust mite 30.7% (1 270/4 132 tests), followed by mold 26.7% (1 066/3 998 tests), while they were mold 40.2% (1 705/1 243 tests), and grass pollen 39.3% (1 472/3 746 texts) respectively in 2020. Conclusion: In the past 11 years, the main food allergens in children were still egg white and milk, wheat, but the mold and pollen gradually replaced dust mite as the most common inhaled allergen.

[Detection of drug resistance genes of mycobacterium tuberculosis by rolling circle amplification technique with multicolor fluorescent probes].

The aim of this study was to construct a simple, rapid and ultra-sensitive optical biosensing technique based on rolling circle amplification (RCA), and to apply it to multiple detection of drug-resistant genes of mycobacterium tuberculosis. The common mutation sites of isoniazid, rifampicin and streptomycin resistance genes are katG315 (AGC➝ACC), rpoB531 (CAC➝TAC) and rpsL43 (AAG➝AGG). For these three gene sites, from February 2020 to May 2021, in the Department of Laboratory Medicine of the First Affiliated Hospital of Army Military Medical University, the padlock probe (PLP), primers and capture probes were designed. And a solid-phase RCA constant temperature amplification reaction system based on magnetic beads was constructed and the experimental parameters were optimized. The RCA products were accurately captured by the multicolor fluorescent probes (Cy3/Cy5/ROX), and the single-tube multiple detection of three mutation genes was realized. The sensitivity, specificity and linear range of this method were further verified. The results showed that the response range of katG315 in the same reaction system ranged from 1.0 pmol/L to 0.1 nmol/L. The response range of rpoB531 and rpsL43 ranged from 1.0 pmol/L to 50.0 pmol/L and 1.0 pmol/L to 20.0 pmol/L, and the method had good specificity and sensitivity, and could accurately identify single base mutations in mixed targets, with the minimum detection limit as low as 1.0 pmol/L. The recoveries of simulated serum samples were 95.0%-105.2%. In conclusion, the constant temperature amplification multiple detection method constructed in this study can quickly realize the single-tube multiple detection of three drug resistance mutation sites. This technology is low-cost, simple and rapid, and does not rely on large equipment, providing a new analysis method for pathogen drug resistance gene detection.

[Early histological changes detected by confocal microscopy in patients with advanced keratoconus receiving collagen cross-linking therapy].

Objective: To investigate the early histological changes by confocal microscopy of patients with advanced keratoconus receiving collagen cross-linking therapy. Methods: In this prospective case series study, confocal microscopy was used to observe 23 patients (32 eyes) who were diagnosed with advanced keratoconus and treated with collagen cross-linking at the Department of Ophthalmology, Chinese PLA General Hospital from September 2017 to March 2019, aged (26±10) year. All patients were examined before and at 1 week, 1 month and 3 months after the therapy. The tissue structure changes, the density of nerve fibers, stromal cells and endothelial cells, and the depth of the corneal stroma were recorded and compared. The overall differences at different times were compared by repeated measurement analysis of variance or Friedman test, and the pairwise comparison was corrected by LSD-t test or Bonferroni test. Results: One week after collagen cross-linking, the epithelial cells were in the repair stage, showing an increased nucleolar size and an enhanced reflection, and the activated cells could be detected under the epithelium. The superficial corneal stroma was swollen and spongiform, while the deep corneal stroma was patchy or cord-like, scattered and with a strong reflection. One month after the therapy, epithelial cells recovered, subepithelial nerves began to grow, the superficial corneal stroma still showed a spongy structure, and the reflection was further enhanced. The activation of the deep corneal stroma exhibited as thicker plaques or cord-like structure. Three months after the therapy, the continuous elongation of single nerve fibers could be detected occasionally. There was statistically significant difference in the density of nerve fibers before and early after the therapy (F=233.30, P<0.001). Compared with the preoperative value [(14.60±2.57) mm/mm2], the density of subepithelial nerve fibers decreased significantly in the early postoperative period, which was (0.51±0.31), (3.65±2.21) and (8.50± 4.02) mm/mm2, respectively, at 1 week, 1 month and 3 months, and there were significant differences between different time points (all P<0.05). There was also statistically significant differences in the density of anterior stromal cells before and early after the therapy (χ2=92.48, P<0.001). Compared with the preoperative value [347.00(345.00,395.75) cells/mm2] the density of anterior stromal cells decreased significantly in the early postoperative period, which was 2.00(1.00,5.75), 2.50(1.00,5.75) and 79.00(64.25,94.00) cells/mm2, respectively, at 1 week, 1 month and 3 months, and there were significant differences between different time points (all P<0.05). Within 3 months after the therapy, the depth of the corneal stroma observed by confocal microscopy ranged from 245 to 536 µm, with an average of (400.56±86.12) µm. Histologically, the depth of the corneal stroma ranged from 245 to 536 µm [average, (402.13±89.20) µm], from 251 to 527 µm [average, (399.88±85.92) µm] and from 259 to 530 µm [average, (399.69±85.94) µm] at 1 week, 1 month and 3 months, respectively, with no significant difference (F=0.797, P=0.455). There was no significant difference in the density of posterior stromal cells [(260.6±33.2) cells/mm2 preoperatively, (264.4±44.5) cells/mm2 at 1 week, (263.9±37.6) cells/mm2 at 1 month and (266.3±40.2) cells/mm2 at 3 months] and endothelial cells [(2 707±152.6) cells/mm2 preoperatively, (2 704±148.5) cells/mm2 at 1 week, (2 705±152.6) cells/mm2 at 1 month and (2 704±150.1) cells/mm2 at 3 months] between different time points (F=1.380, 1.011; P=0.259, 0.351). Conclusions: Confocal microscopy is able to clearly document the early morphological characteristics after collagen cross-linking in the treatment of keratoconus, including the epithelial and subepithelial nerve injury repair, the spongiform superficial corneal stroma, the patchy or cord-like deep corneal stroma, and the relatively stable stromal depth change.

Assessment of the efficacy of intra-articular platelet rich plasma treatment in an ACLT experimental model by dynamic contrast enhancement MRI of knee subchondral bone marrow and MRI T2∗ measurement of articular cartilage.

OBJECTIVE: The vascularization of subchondral bone plays a significant role in the progression of knee osteoarthritis (OA). Treatment with platelet-rich plasma (PRP) has positive effects on cartilage lesions. However, PRP's efficacy for subchondral bone marrow lesions and the relationship of these lesions to cartilage are still undiscovered. Therefore, our aims were first to longitudinally investigate the change in subchondral flow by dynamic contrast enhanced MRI and degeneration of cartilage by MRI T2∗ in an anterior cruciate transection rodent (ACLT) model, and second to examine changes in parameters after intra-articular PRP injection. DESIGN: A 32-week investigation in 18 rats allocated to sham-control, ACLT with normal saline injection (ACLT + NS), and ACLT with PRP injection groups ended with histological evaluation. Another rat was used as a donor of allogenic PRP. RESULTS: Compared to the sham-control group, the ACLT + NS group had higher subchondral blood volume A (0.051, 95% confidence interval: 0.009, 0.092) and lower venous washout kel (-0.030: -0.055, -0.005) from week 4; lower permeability kep from week 18 (-0.954: -1.339, -0.569); higher cartilage T2∗ values (1.803: 1.504, 2.102) reflecting collagen loss beginning at week 10. For the PRP treatment group, subchondral bone marrow A and cartilage T2∗ decreased from week 10. Histological results confirmed and were correlated with the MRI findings. CONCLUSION: Subchondral hyper-perfusion plays a vital role in the pathogenesis of OA and was associated with cartilage degeneration. The efficacy of PRP can be observed from reduced perfusion and MRI T2∗ values.

Measurement of the Cosmic Ray Helium Energy Spectrum from 70 GeV to 80 TeV with the DAMPE Space Mission.

The measurement of the energy spectrum of cosmic ray helium nuclei from 70 GeV to 80 TeV using 4.5 years of data recorded by the Dark Matter Particle Explorer (DAMPE) is reported in this work. A hardening of the spectrum is observed at an energy of about 1.3 TeV, similar to previous observations. In addition, a spectral softening at about 34 TeV is revealed for the first time with large statistics and well controlled systematic uncertainties, with an overall significance of 4.3σ. The DAMPE spectral measurements of both cosmic protons and helium nuclei suggest a particle charge dependent softening energy, although with current uncertainties a dependence on the number of nucleons cannot be ruled out.