Terahertz manipulation of nonlinear optical response in topological material PtBi2.

The substantial nonlinear optical response observed in numerous topological materials renders them well-suited for optic and photonic applications, underscoring the critical need to devise effective strategies for manipulating their nonlinearity to enhance their versatility across different applications. In this Letter, we focus on the second-harmonic generation (SHG) response of the topological material PtBi2 under intense terahertz (THz) pulses and unveil the transient nonlinearity manipulated by a THz electric field. Our findings demonstrate that upon excitation of an intense THz pulse, there emerges a substantial enhancement in the SHG signal of PtBi2, which is predominantly attributed to the linear term involving the THz field, i.e., χ(2)χ(3)ETHz. We also clearly observe the transient change in the nonlinear coefficients, which could arise from the excitation of the bands with linear dispersion via the intense THz pulse. These findings bear significant implications for achieving ultrafast modulation of nonlinearity in topological materials, thereby opening avenues for advanced applications in this field.

[Analyses of the risk factors for the progression of primary antiphospholipid syndrome to systemic lupus erythematosus].

Objectives: Analyze the clinical characteristics of patients with primary antiphospholipid syndrome (PAPS) progressing to systemic lupus erythematosus (SLE).Explore the risk factors for the progression from PAPS to SLE. Methods: The clinical data of 262 patients with PAPS enrolled in Peking Union Medical College Hospital from February 2005 to September 2021 were evaluated. Assessments included demographic data, clinical manifestations, laboratory tests (serum levels of complement, anti-nuclear antibodies, anti-double-stranded DNA antibodies), treatment, and outcomes. Kaplan-Meier analysis was used to calculate the prevalence of SLE in patients with PAPS. Univariate Cox regression analysis was employed to identify the risk factors for PAPS progressing to SLE. Results: Among 262 patients with PAPS, 249 had PAPS (PAPS group) and 13 progressed to SLE (5.0%) (PAPS-SLE group). Univariate Cox regression analysis indicated that cardiac valve disease (HR=6.360), positive anti-double-stranded DNA antibodies (HR=7.203), low level of complement C3 (HR=25.715), and low level of complement C4 (HR=10.466) were risk factors for the progression of PAPS to SLE, whereas arterial thrombotic events (HR=0.109) were protective factors (P<0.05 for all). Kaplan-Meier analysis showed that the prevalence of SLE in patients suffering from PAPS with a disease course>10 years was 9%-15%. Hydroxychloroquine treatment had no effect on the occurrence of SLE in patients with PAPS (HR=0.753, 95%CI 0.231-2.450, P=0.638). Patients with≥2 risk factors had a significantly higher prevalence of SLE compared with those with no or one risk factor (13-year cumulative prevalence of SLE 48.7% vs. 0 vs. 6.2%, P<0.001 for both). Conclusions: PAPS may progress to SLE in some patients. Early onset, cardiac-valve disease, positive anti-dsDNA antibody, and low levels of complement are risk factors for the progression of PAPS to SLE (especially in patients with≥2 risk factors). Whether application of hydroxychloroquine can delay this transition has yet to be demonstrated.

[Application of optical coherence tomography in the evaluation of cervical lesions: a multicenter study].

Objective: To explore the value of optical coherence tomography (OCT) imaging system in evaluating cervical lesions in vivo. Methods: A total of 1 214 patients with cervical lesions were collected from January 2020 to December 2021 in the Third Affiliated Hospital of Zhengzhou University, Maternal and Chlid Heaith Hospital of Gushi County, Xinyang City, Henan Province, and Maternal and Chlid Heaith Hospital of Sui County, Shangqiu City, Henan Province. The age of the patients was (38.9±10.5) years (range: 16-77 years). All patients underwent in vivo cervical OCT examination and cervical biopsy pathology examination, and summarized the OCT image features of in vivo cervical lesions. Using the pathological diagnosis as the "gold standard", the accuracy, specificity, sensitivity, positive predictive value (PPV) and negative predictive value (NPV) of OCT image interpretation results were evaluated, as well as the consistency of OCT image diagnosis and pathological diagnosis. At the same time, the in vivo cervical OCT imaging system, as a newly developed screening tool, was compared with the traditional combined screening of human papillomavirus (HPV) and Thinprep cytologic test (TCT), to assess the screening effect. Results: By comparing the OCT images of the cervix in vivo with the corresponding HE images, the OCT image characteristics of the normal cervix and various types of cervical lesions in vivo were summarized. The accuracy, sensitivity, specificity, PPV and NPV of OCT image in the diagnosis of high-grade squamous intraepithelial lesion (HSIL) and above (HSIL+) were 93.4%, 88.5%, 95.0%, 85.0% and 96.2%, respectively. The accuracy, sensitivity, specificity, PPV and NPV of OCT for low-grade squamous intraepithelial lesion (LSIL) were 84.7%, 61.7%, 96.3%, 89.3% and 83.2%, respectively. The consistency between OCT image diagnosis and pathological diagnosis was strong (Kappa value was 0.701).The accuracy, sensitivity and specificity of OCT screening, HPV and TCT combined screening were 83.7% vs 64.9% (χ²=128.82, P<0.001), 77.8% vs 64.5% (χ²=39.01, P<0.001), 91.8% vs 65.4% (χ²=98.12, P<0.001), respectively. The differences were statistically significant. Conclusions: OCT imaging system has high sensitivity and specificity in the evaluation of cervical lesions in vivo, and has the characteristics of non-invasive, real-time and high efficiency. OCT examination is expected to become an effective method for the diagnosis of cervical lesions and cervical cancer screening.

[Quantitative HER2 mRNA assay in breast cancer with HER2 immunohistochemistry 0].

Objective: To investigate HER2 mRNA expression in breast cancer with HER2 immunohistochemistry (IHC) 0 and to analyze the feasibility of distinguishing between the tumor with HER2 µltra-low expression and the one without expression of HER2 (no staining by IHC) by HER2 mRNA level preliminarily. Methods: HER2 mRNA was analyzed by reverse transcription digital PCR in 41 cases of formalin-fixed paraffin-embedded surgical tissue samples of invasive breast cancer obtained between January 2020 and March 2023 at Peking Union Medical College Hospital. The cohort included 21 HER2 IHC 1+ and 20 IHC 0 (12 ultra-low and 8 non-expression of HER2). HER2 mRNA expression level was quantitatively evaluated by the FAM (HER2)/VIC (reference gene) ratio. Results: The expression of HER2 mRNA for the cases with 1+, ultra-low, and non-expression of HER2 by IHC was 0.30 to 1.78 (average 0.90, median 0.82), 0.55 to 1.51 (average 0.93, median 0.90) and 0.22 to 0.78 (average 0.41, median 0.36), respectively. For the mean and median HER2 mRNA levels, there was no significant difference between HER2 IHC 1+ and HER2 ultra-low expression diseases (P=0.757). A remarkable difference in HER2 gene expression was found between the tumors with 1+ and non-expression of HER2 by IHC (P=0.002). And, HER2 ultra-low cases contained statistically higher levels of HER2 mRNA compared with non-expression of HER2 subgroup by IHC (P=0.001). Conclusions: Based on HER2 mRNA, HER2 non-expression and HER2 weak expression (including HER2 IHC 1+ and ultra-low) belong to two different types of the tumor and the disease with HER2 IHC 1+ and HER2 ultra-low expression may be the same. It is necessary to further test the performance of HER2 mRNA detection for stratifying the HER2 weak expression subgroup and to determine the threshold.

[Clinicopathological features of breast cancer with HER2 low expression: a real-world retrospective study].

Objective: To investigate the clinical and pathological characteristics of breast cancer with HER2 low expression. Methods: The data from 3 422 patients with invasive breast cancer which archived in Peking Union Medical College Hospital between April 2019 and July 2022 were retrospectively reviewed. Among them, 136 patients were treated with neoadjuvant chemotherapy. The tumor size, histological type, tumor differentiation, lymph node metastasis, Ki-67 index, the status of estrogen receptor, progesterone receptor and HER2 as well as pathological complete response (pCR) rate were collected. Results: The HER2 status of 3 286 patients without neoadjuvant therapy, 616 (616/3 286, 18.7%) score 0, 1 047 (1 047/3 286, 31.9%) score 1+, 1 099 (1 099/3 286,33.4%) score 2+ and 524 (524/3 286,15.9%) score 3+ by immunohistochemistry (IHC). Among the 1 070 IHC 2+ cases, 161 were classified as HER2 positive by reflex fluorescence in situ hybridization (FISH) assay. In our cohort, 1 956 cases of HER2-low (IHC 1+ and IHC 2+/FISH-) breast cancer were identified. Compared to the HER2 IHC 0 group, HER2-low tumors more frequently occurred in patients with hormone receptor (HR) positive (P<0.001), Ki-67 index below 35% (P<0.001), well or moderate differentiation (P<0.001) and over the age of 50 (P=0.008). However, there were no significant differences in histological type, tumor size, and lymph node metastasis between HER2-low and HER2 IHC 0 group. For patients who had neoadjuvant therapy, the pCR rate in the patients with HER2-low was lower than those with HER2 IHC 0 (13.3%, 23.9%), but there was no significant difference. Although HER2-low breast cancers showed a slightly lower pCR rate than HER2 IHC 0 tumors, no remarkable difference was observed between tumors with HER2-low and HER2 IHC 0 regardless of hormone receptor status. Conclusions: The clinicopathological features of HER2-low breast cancers are different from those with HER2 IHC 0. It is necessary to accurately distinguish HER2-low breast cancer from HER2 IHC 0 and to reveal whether HER2-low tumor is a distinct biological entity.

[An analysis on clinical characteristics and prognosis-related risk factors in patients with drug-induced liver injury].

Objective: To explore the drugs and clinical characteristics causing drug-induced liver injury (DILI) in recent years, as well as identify drug-induced liver failure, and chronic DILI risk factors, in order to better manage them timely. Methods: A retrospective investigation and analysis was conducted on 224 cases diagnosed with DILI and followed up for at least six months between January 2018 and December 2020. Univariate and multivariate logistic regression analyses were used to identify risk factors for drug-induced liver failure and chronic DILI. Results: Traditional Chinese medicine (accounting for 62.5%), herbal medicine (accounting for 84.3% of traditional Chinese medicine), and some Chinese patent medicines were the main causes of DILI found in this study. Severe and chronic DILI was associated with cholestatic type. Preexisting gallbladder disease, initial total bilirubin, initial prothrombin time, and initial antinuclear antibody titer were independent risk factors for DILI. Prolonged time interval between alkaline phosphatase (ALP) and alanine aminotransferase (ALT) falling from the peak to half of the peak (T(0.5ALP) and T(0.5ALT)) was an independent risk factor for chronic DILI [area under the receiver operating characteristic curve (AUC) = 0.787, 95%CI: 0.697~0.878, P < 0.001], with cutoff values of 12.5d and 9.5d, respectively. Conclusion: Traditional Chinese medicine is the main contributing cause of DILI. The occurrence risk of severe DILI is related to preexisting gallbladder disease, initial total bilirubin, prothrombin time, and antinuclear antibodies. T(0.5ALP) and T(0.5ALT) can be used as indicators to predict chronic DILI.

Association of rs35006907 Polymorphism with Risk of Dilated Cardiomyopathy in Han Chinese Population.

Background: Several investigations have demonstrated the association of MTSS1 with left ventricular (LV) structure and function. A recently published study has even revealed that rs35006907 was associated with both MTSS1 expression and the risk of dilated cardiomyopathy (DCM). Objective: Our study intended to investigate the relationship between rs35006907 and the risk of DCM in the Han Chinese population. Methods: A total of 529 DCM and 600 healthy controls were recruited. We conducted genotyping for rs35006907 in all participants. Gene association studies were performed to assess the association between rs35006907 and the risk of DCM. A series of functional assays including western blot, realtime PCR and firefly luciferase reporter gene assays were conducted to illuminate the underlying mechanism. Results: We found that rs35006907-A allele was significantly associated with reduced risk of DCM in additive (p= 0.004; OR=0.78; 95% CI=0.66-0.93) and recessive models (p= 0.0005; OR=0.56; 95%CI=0.41-0.78) when compared with the rs35006907-C allele. There were significant differences in the left ventricular end-diastolic diameter (LVEDD) and left ventricular ejection fraction (LVEF) between rs35006907-CC/AC and AA genotypes. Furthermore, the variant rs35006907-A allele presented lower reporter gene activity, reduced mRNA and protein expression levels when compared with the C allele. Conclusions: Our findings demonstrated that rs35006907-C allele increased the risk of DCM in Han Chinese population. Besides, rs35006907-C displayed higher reporter gene activity and increased MTSS1 expression in human samples.

RE-EVALUATION OF SYMPOVENTURIACEAE.

Abstract Sympoventuriaceae (Venturiales, Dothideomycetes) comprises genera including saprophytes, endophytes, plant pathogens, as well as important animal or human opportunistic pathogens with diverse ecologies and wide geographical distributions. Although the taxonomy of Sympoventuriaceae has been well studied, generic boundaries within the family remain poorly resolved due to the lack of type materials and molecular data. To address this issue and establish a more stable and reliable classification system in Sympoventuriaceae, we performed multi-locus phylogenetic analyses using sequence data of seven genes (SSU, ITS, LSU, act1, tub2, tef1 and rpb2) with increased taxon sampling and morphological analysis. The molecular data combined with detailed morphological studies of 143 taxa resolved 22 genera within the family, including one new genus, eight new species, five new combinations and one new name. Finally, we further investigated the evolutionary history of Sympoventuriaceae by reconstructing patterns of lifestyle diversification, indicating the ancestral state to be saprophytic, with transitions to endophytic, animal or human opportunistic and plant pathogens. Citation: Wei TP, Zhang H, Zeng XY, et al. 2022. Re-evaluation of Sympoventuriaceae. Persoonia 48: 219-260. https://doi.org/10.3767/persoonia.2022.48.07.. Effectively published online: 17 June 2022 [Received: 2 February 2022; Accepted: 27 April 2022].

Structural insights into peptidoglycan glycosidase EtgA binding to the inner rod protein EscI of the type III secretion system via a designed EscI-EtgA fusion protein.

Bacteria express lytic enzymes such as glycosidases, which have potentially self-destructive peptidoglycan (PG)-degrading activity and, therefore, require careful regulation in bacteria. The PG glycosidase EtgA is regulated by localization to the assembling type III secretion system (T3SS), generating a hole in the PG layer for the T3SS to reach the outer membrane. The EtgA localization was found to be mediated via EtgA interacting with the T3SS inner rod protein EscI. To gain structural insights into the EtgA recognition of EscI, we determined the 2.01 Å resolution structure of an EscI (51-87)-linker-EtgA fusion protein designed based on AlphaFold2 predictions. The structure revealed EscI residues 72-87 forming an α-helix interacting with the backside of EtgA, distant from the active site. EscI residues 56-71 also were found to interact with EtgA, with these residues stretching across the EtgA surface. The ability of the EscI to interact with EtgA was also probed using an EscI peptide. The EscI peptide comprising residues 66-87, slightly larger than the observed EscI α-helix, was shown to bind to EtgA using microscale thermophoresis and thermal shift differential scanning fluorimetry. The EscI peptide also had a two-fold activity-enhancing effect on EtgA, whereas the EscI-EtgA fusion protein enhanced activity over four-fold compared to EtgA. Our studies suggest that EtgA regulation by EscI could be trifold involving protein localization, protein activation, and protein stabilization components. Analysis of the sequence conservation of the EscI EtgA interface residues suggested a possible conservation of such regulation for related proteins from different bacteria.

Preparation and characterisation of novel casein-gum Arabic composite microcapsules for targeted in vivo delivery of Lactiplantibacillus plantarum A3.

The health benefits of probiotics in the body are predicated on their ability to remain viable in harsh gastrointestinal conditions and complex pathological microenvironments. Casein and gum Arabic (GA), with dual emulsifying and stabilising effects in colloidal systems. Therefore, the objective of this research was to develop a novel microcapsule to encapsulate Lactiplantibacillus plantarum A3 using casein and GA as wall materials to improve the survival of the bacteria during gastrointestinal digestion, storage and lyophilization. The casein and GA composite microcapsules were prepared and characterised by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and scanning electron microscopy (SEM). It was found that the microcapsules had stable morphology, uniform size and spherical shape. The results revealed that the encapsulation of microcapsules significantly improved the survival of L. plantarum A3 in gastrointestinal fluid environment (5.52 × 109 cfu/ml) and lyophilization treatment (6.25 × 109 cfu/ml). Furthermore, the microencapsulated L. plantarum A3 exhibited an improved ability to regulate intestinal microbiota by effectively increasing the relative abundance of Bacteroidetes, Proteobacteria and Actinobacteria and decreasing the relative abundance of Firmicutes in vivo. The findings of the study will help to design a lactic acid bacteria encapsulation system based on the gastrointestinal environment and provide a basis for the development of probiotic functional products.

[Fabrication and evaluation of composite hydroxyapatite coating on ordered micro-/nanotextured titanium surface].

Objective: To develope a titanium specimen with good osteogenic activity through fabrication of a composite hydroxyapatite coating on ordered micro-/nanotextured titanium surface. Methods: An ordered micro-/nanotextured structure was prepared on the surface of titanium (the control), and then hydroxyapatite was deposited on the as-prepared ordered micro-/nanotextured structure by alternative loop immersion method. The ordered micro-/nanotextured structures before and after hydroxyapatite deposition were denoted as HA and MN, respectively. Surface morphology was observed using a scanning electron microscope. Bone marrow mesenchymal stem cells (BMMSC) were seeded on the surface of three different materials. Cell morphology was observed with a scanning electron microscope. Cell adhesion and cell proliferation were evaluated using 4', 6-diamidino-2-phenylindole staining and cell counting kit-8 assay, respectively. Extracellular matrix mineralization and the expression levels of osteogenesis-related genes were evaluated by alizarin red staining and real-time quantitative PCR, respectively. Each group has three samples in every experiment. Results: After alternative loop immersing, the MN's original microholes (20 µm in diameter) were retained, and the uniform petal-like hydroxyapatite was deposited on the MN's original titania nanotubes (70 nm in diameter). Compared with the control, BMMSC on MN and HA elongated further and intersected along the micron structure with noticeable pseudopodia and pseudoplates, and the trend was more pronounced especially on HA. The number of early adherent cells on HA was remarkably larger than that on the control and MN at each time point (P<0.05). On day 1, the A value of cell proliferation on HA was significantly higher than that on the control and MN (P<0.05). The A value of cell proliferation on HA was significantly lower than that on the control and MN on day 3 (P<0.05). On day 7, the A value of cell proliferation on HA was significantly lower than that on MN (P<0.05), but there was no statistically significant difference in the A value of cell proliferation between HA and the control on day 7 (P>0.05). The Avalue of extracellular matrix mineralization on HA (0.607±0.011) was significantly higher than that on the control and MN (0.268±0.025 and 0.522±0.022, respectively) (t=-0.25, P<0.001; t=-0.34, P<0.001). The expression levels of bone related genes on HA were significantly higher than those on the control and MN (P<0.05). Conclusions: HA could promote the BMMSC adhesion and osteogenic differentiation, support BMMSC proliferation, and demonstrate good osteogenic activity.

[Feasibility study on the use of peripheral blood differentially expressed genes for objective classification of chronic subjective tinnitus: a case study on high-frequency tinnitus].

Objective: To explore the feasibility of constructing an objective tinnitus subtype model based on peripheral blood differentially expressed genes (DEGs) using a combination of Weighted Gene Co-expression Network Analysis (WGCNA) and Random Forest algorithm (RF). Methods: From October 2019 to June 2020, peripheral blood DEGs were obtained from 37 patients (from the Third Affiliated Hospital of Sun Yat-sen University)with chronic subjective high-frequency tinnitus (21 unbothersome type, 16 bothersome type) and 20 healthy volunteers through high-throughput sequencing. WGCNA was used to construct gene modules with different expression patterns and analyze their relationships with tinnitus characteristics. Subsequently, RF was employed to build subtype models, which were evaluated by the area under the receiver operating characteristic curve (AUC), accuracy, and F1-score. Results: A total of 12 351 intergroup DEGs were divided into 9 gene modules. Among them, MEblue, MEgreen, and MEbrown showed significant negative correlations with the healthy volunteer group, while MEpink showed a significant positive correlation with the tinnitus distress group. The "Tinnitus vs. Normal" and "Compensatory vs. Decompensatory" subtype models, based on MEblue and MEpink respectively, both had AUCs greater than 0.80, accuracies above 90%, and F1-scores above 0.90, indicating good performance. Conclusions: Peripheral blood DEGs are potential biological indicators for objective classification of subjective tinnitus. The combined application of WGCNA and the Random Forest algorithm should be a viable approach to constructing an objective tinnitus subtype model. However, further exploration and refinement are needed to validate the model's generalizability, cross-dataset performance, and algorithm optimization.

Relationship between PI3K/mTOR/RhoA pathway-regulated cytoskeletal rearrangements and phagocytic capacity of macrophages

The objective of this study was to investigate the relationship between PI3K/mTOR/RhoA signaling regulated cytoskeletal rearrangements and phagocytic capacity of macrophages. RAW264.7 macrophages were divided into four groups; blank control, negative control, PI3K-RNAi, and mTOR-RNAi. The cytoskeletal changes in the macrophages were observed. Furthermore, the phagocytic capacity of macrophages against Escherichia coli is reported as mean fluorescence intensity (MFI) and percent phagocytosis. Transfection yielded 82.1 and 81.5% gene-silencing efficiencies against PI3K and mTOR, respectively. The PI3K-RNAi group had lower mRNA and protein expression levels of PI3K, mTOR, and RhoA than the blank and negative control groups (Р<0.01). The mTOR-RNAi group had lower mRNA and protein levels of mTOR and RhoA than the blank and the negative control groups (Р<0.01). Macrophages in the PI3K-RNAi group exhibited stiff and inflexible morphology with short, disorganized filopodia and reduced number of stress fibers. Macrophages in the mTOR-RNAi group displayed pronounced cellular deformations with long, dense filopodia and an increased number of stress fibers. The PI3K-RNAi group exhibited lower MFI and percent phagocytosis than blank and negative control groups, whereas the mTOR-RNAi group displayed higher MFI and percent phagocytosis than the blank and negative controls (Р<0.01). Before and after transfection, the mRNA and protein levels of PI3K were both positively correlated with mTOR and RhoA (Р<0.05), but the mRNA and protein levels of mTOR were negatively correlated with those of RhoA (Р<0.05). Changes in the phagocytic capacity of macrophages were associated with cytoskeletal rearrangements and were regulated by the PI3K/mTOR/RhoA signaling pathway.