Ancient Mitogenomes Reveal the Maternal Genetic History of East Asian Dogs.

Recent studies have suggested that dogs were domesticated during the Last Glacial Maximum (LGM) in Siberia, which contrasts with previous proposed domestication centers (e.g. Europe, the Middle East, and East Asia). Ancient DNA provides a powerful resource for the study of mammalian evolution and has been widely used to understand the genetic history of domestic animals. To understand the maternal genetic history of East Asian dogs, we have made a complete mitogenome dataset of 120 East Asian canids from 38 archaeological sites, including 102 newly sequenced from 12.9 to 1 ka BP (1,000 years before present). The majority (112/119, 94.12%) belonged to haplogroup A, and half of these (55/112, 49.11%) belonged to sub-haplogroup A1b. Most existing mitochondrial haplogroups were present in ancient East Asian dogs. However, mitochondrial lineages in ancient northern dogs (northeastern Eurasia and northern East Asia) were deeper and older than those in southern East Asian dogs. Results suggests that East Asian dogs originated from northeastern Eurasian populations after the LGM, dispersing in two possible directions after domestication. Western Eurasian (Europe and the Middle East) dog maternal ancestries genetically influenced East Asian dogs from approximately 4 ka BP, dramatically increasing after 3 ka BP, and afterwards largely replaced most primary maternal lineages in northern East Asia. Additionally, at least three major mitogenome sub-haplogroups of haplogroup A (A1a, A1b, and A3) reveal at least two major dispersal waves onto the Qinghai-Tibet Plateau in ancient times, indicating eastern (A1b and A3) and western (A1a) Eurasian origins.

Pulmonary infection in patients with severe fever with thrombocytopenia syndrome: A multicentre observational study.

Co-infection in patients with severe fever with thrombocytopenia syndrome (SFTS) has been reported, posing a serious threat to survival and treatment. We aimed to systematically investigate the SFTS associated pulmonary infection, particularly invasive pulmonary fungal infection (IPFI). During April 2019 to October 2021, we conducted a multicentre observational study on adult hospitalized patients confirmed with SFTS from three tertiary hospital in central China. Demographic, clinical and laboratory data of patients were collected and re-assessed. A total of 443 patients (51.7% were male sex) were included for analysis with median age of 65-year-old. Among them, 190 (42.9%) patients met the criteria for pulmonary infection. Pulmonary infection was associated with shorter survival time (p < 0.0001 by log-rank test), and adjusted hazard ratio was 1.729 [95% confidence interval, 1.076-2.780] (p = 0.024). Age (odds ratio (OR) 1.040 [1.019-1.062], p < 0.001), time from onset to admission (OR 1.163 [1.070-1.264], p < 0.001), having severe status (OR 3.166 [2.020-4.962], p < 0.001) and symptoms of skin change (OR 2.361 [1.049-5.316], p < 0.001) at admission and receiving intravenous immunoglobin (OR 2.185 [1.337-3.569], p = 0.002) were independent risk factors for the occurrence of pulmonary infection. A total of 70 (15.8%) patients were defined as IPFI. Multivariate analysis showed that time from onset to admission (OR 1.117 [1.016-1.229], p = 0.022), severe status (OR 5.737 [3.054-10.779], p < 0.001), having smoking history (OR 3.178 [1.251-8.070], p = 0.015) and autoimmunity disease (OR 7.855 [1.632-37.796], p = 0.010), receiving intravenous immunoglobin (OR 3.270 [1.424-7.508], p = 0.005) were independent risk factors for the occurrence of IPFI. In SFTS patients with pulmonary infection, white blood count <2.09 × 109 per L (OR 11.064 [3.708-33.012], p < 0.001) and CD3+ CD4+ T cell count <104.0 per µL (OR 10.429 [3.395-32.038], p < 0.001) could independently predict IPFI. This study showed the high prevalence and poor outcomes of pulmonary infection and IPFI in patients with SFTS. These findings highlighted the need for active surveillance of fungal pathogens and early antifungal treatment in patients with SFTS.

Infection pattern and immunological characteristics of Epstein-Barr virus latent infection in cervical squamous cell carcinoma.

Previous studies reported the association between Epstein-Barr virus (EBV) and cervical squamous cell carcinoma (CSCC), but its infection pattern and clinical significance unclear. This study aimed to comprehensively investigate the infection pattern, clinicopathology, outcomes, and immunology of this entity in central China. We evaluated a total of 104 untreated CSCC tumor tissue specimens using in situ hybridization for EBV-encoded small RNAs (EBERs), and by employing flowcytometry fluorescence hybridization for human papillomavirus (HPV) genotyping. The expression of EBV latency proteins and immune biomarkers was evaluated and quantified by immunohistochemistry. EBERs transcripts were detected in 21 (20.2%) cases overall (in malignant epithelial cells of 13 cases and in lymphocytes of 8 cases). EBV belonged to latency type I infection in CSCC. The high-risk (HR)-HPV was detected in all of EBV-positive CSCC, and the difference of detection rate of HR-HPV was significant when compared with EBV-negative CSCC (p = 0.001). The specific clinicopathology with increased frequency of advanced clinical stages, tumor-positive lymph nodes, neural invasion, and increased infiltration depth (all p value < 0.05) were observed in cases with EBV. However, EBV infection was found to have no impact on prognosis of patients with CSCC. Increased densities of forkhead box P3 (FoxP3)+-tumor infiltrating lymphocytes (TILs) (p = 0.005) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)+-TILs (p = 0.017) and higher expression of programmed cell death-1 (PD-1) (p = 0.002) and programmed cell death-1 ligand 1 (PD-L1) (p = 0.040) were associated with EBV latent infection in CSCC, and these immunological changes were more likely to be associated with the infection in lymphocytes rather than tumor cells. Moreover, in patients with HPV-positive CSCC, similar significant differences were still found. In conclusions, EBV-positive CSCC may have specific infection pattern and clinicopathology and can exhibit an immunosuppressive microenvironment dominated by Treg cells aggregation and immune checkpoint activation.

Immunization with Pneumocystis carinii A121-85 antigen activates immune function against P. carinii.

BACKGROUND: Pneumocystis pneumonia (PcP), which is caused by Pneumocystis carinii, is a life-threatening infection that affects immunocompromised individuals. Unfortunately, chemoprophylaxis and dapsone are only effective for half of the patients with PcP, indicating that additional preventive methods are needed. We predicated the pneumocystis surface protein A12 sequence 1-85 by DNAStar software and BepiPred, and identified it as a potential vaccine candidate by bioresearch. METHODS: We used recombinant A121-85 as antigen to immunized mice and detected serum titer of IgG, expression of inflammatory factors by EILSA, qRT-PCR and flow cytometry. RESULTS: Our results showed that immunization with recombinant A121-85 increased the serum titer of IgG, promoted the secretion of T lymphocytes, increased the expression of inflammatory factors, and elevated lung inflammatory injury in mice. CONCLUSIONS: Our findings suggest that A121-85 is a potential vaccine target for preventing Pneumocystis carinii. The evaluation of A121-85-elicited antibodies in the prevention of PcP in humans deserves further investigation.

Lopinavir/ritonavir and interferon combination therapy may help shorten the duration of viral shedding in patients with COVID-19: A retrospective study in two designated hospitals in Anhui, China.

Prolonged viral shedding may pose a threat to the control of coronavirus disease-2019 (COVID-19), and data on the duration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) shedding are still limited, with the associated factors being unknown. All adult patients with laboratory-confirmed COVID-19 were included in this retrospective cross-sectional study in two designated hospitals during 21 January 2020 to 16 March 2020 in Anhui, China. In all patients, data on the duration of SARS-CoV-2 RNA shedding were analyzed by reviewing all RNA detection results during hospitalization. In addition, demographic, clinical, treatment, laboratory, and outcome data were also collected from electronic medical records. Factors associated with prolonged viral shedding were analyzed with the Cox proportional hazards model. Among 181 patients, the mean age was 44.3 ± 13.2 years, and 55.2% were male. The median duration of viral shedding from illness onset was 18.0 days (interquartile range [IQR], 15.0-24.0). Prolonged viral shedding was associated with longer hospital stays (P < .001) and higher medical costs (P < .001). The severity of COVID-19 had nothing to do with prolonged shedding. Moreover, the median time from onset to antiviral treatment initiation was 5.0 days (IQR, 3.0-7.0). Delayed antiviral treatment (hazard ratio [HR], 0.976; 95% confidence interval [CI], 0.962-0.990]) and lopinavir/ritonavir + interferon-α (IFN-α) combination therapy as the initial antiviral treatment (HR 1.649; 95% CI, 1.162-2.339) were independent factors associated with prolonged SARS-CoV-2 RNA shedding. SARS-CoV-2 showed prolonged viral shedding, causing increased hospital stays and medical costs. Early initiation of lopinavir/ritonavir + IFN-α combination therapy may help shorten the duration of SARS-CoV-2 shedding.

Diagnostic accuracy of contrast-enhanced ultrasound for detecting bland thrombus from inferior vena cava tumor thrombus in patients with renal cell carcinoma.

PURPOSE: To evaluate the role of contrast-enhanced ultrasound (CEUS) in differentiating bland thrombus from tumor thrombus of the inferior vena cava (IVC) in patients with renal cell carcinoma (RCC). MATERIALS AND METHODS: We retrospectively investigated 30 consecutive patients who underwent robot-assisted radical nephrectomy with IVC thrombectomy and had pathologically confirmed RCC. All patients underwent US and CEUS examination. Two offline readers observed and recorded thrombus imaging information and enhancement patterns. Sensitivity, specificity, accuracy, positive predictive value and negative predictive value for bland thrombus were assessed. RESULTS: Of the 30 patients, no adverse events occurred during administration of the contrast agent. Early enhancement of the mass within the IVC lumen on CEUS was na indicator of tumor thrombus. Bland thrombus showed no intraluminal flow on CEUS. There were eight (26.7%) patients with bland thrombus, including three level II, two level III, and three level IV. There were three cases with cephalic bland thrombus and five cases with caudal bland thrombus. Three caudal bland thrombi extended to the iliac vein and underwent surgical IVC interruption. Based on no intraluminal flow, for bland thrombus, CEUS had 87.5% sensitivity, 100% specificity, 96.7% accuracy, 100% positive predictive value and 95.6% negative predictive value. CONCLUSION: Our study demonstrates the potential of CEUS in the differentiation of bland and tumor thrombus of the IVC in patients with RCC. Since CEUS is an effective, inexpensive, and non-invasive method, it could be a reliable tool in the evaluation of IVC thrombus in patients with RCC.

Characterize carbapenem-resistant Klebsiella pneumoniae isolates for nosocomial pneumonia and their Gram-negative bacteria neighbors in the respiratory tract.

This study was conducted to perform an epidemiological survey of carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates for nosocomial pneumonia (NP) and visit their Gram-negative bacteria neighbors (GNNs) from the respiratory tracts. Pulsed-field gel electrophoresis and multi locus sequence typing were performed to evaluate the clonal relationships of these isolates. Statistical methods were then used to understand their possible relationship between CRKP and their GNNs. Among the 63 CRKP isolates, 84.1% produced a KPC-2 carbapenemase gene, followed by blaNDM-1 and blaIMP-38 like. 13 different STs and 29 clones were identified. Less heterogeneous clone backgrounds were observed in 53 KPC-2 K. pneumoniae isolates, and 6 STs have been found to contain KPC-2, of which the predominant ST11 harbored 47 KPC-2-producing K. pneumoniae isolates. Particularly, the two infrequent isolates co-possessing blaKPC-2 and blaIMP-38 like shared a different clonal relationship. 87 GNNs isolates of CRKP were established, the analysis present that different strains showed significant or no difference with CRKP upon antibiotics susceptibility. Conclusion, ST11 harboring KPC-2-producing K. pneumoniae isolates were dominant for NP, and both clonal spread and horizontal transfer contributed to the dissemination of CRKP. However, additional studies are needed to explore the biological relationship with their GNNs.

The Diagnostic Value of Procalcitonin Versus Other Biomarkers in Prediction of Bloodstream Infection.

BACKGROUND: We compared the diagnostic utility of procalcitonin (PCT), C-reactive protein (CRP), and hematological markers, including white blood cell count (WBC), neutrophils (NEU), percentage of neutrophils (NEU%), lymphocytes (LYM), neutrophil-lymphocyte count ratio (NLCR), and platelet count (PLT) for predicting bloodstream infection (BSI), which was confirmed by blood culture (BC). METHODS: A retrospective analysis was conducted for 1807 inpatients. The level of PCT, CRP, blood cells, and blood culture results were compared between the positive blood culture group and negative blood culture group; each indicator was analyzed in the performance of bacterial BSI diagnosis by drawing ROC curves. RESULTS: Blood cultures were positive in 230 patients; hence, the prevalence of bacteremia was 12.7%. There were significant differences in the median value for each marker between positive group BCs and negative group BCs (p < 0.05). The areas under the receiver operating characteristic curves (ROC-AUCs) of PCT, CRP, WBC, NEU, NUE%, LYM, NLCR, and PLT for discriminating positive BCs from negative BCs were 0.811, 0.654, 0.612, 0.634, 0.684, 0.595, 0.682, and 0.633 respectively. PCT concentrations of gram-negative (14.94 ng/mL, IQR 2.93  48.76) were significantly higher than gram-positive (4.74 ng/mL, IQR 1.22  17.5) and fungal (1.47 ng/mL, IQR 0.66  35.34). CONCLUSIONS: PCT proved to be the most reliable predictor of BSI, second were NEU% and NLCR. A higher PCT level was found in patients with a gram-negative BSI compared to gram-positive BSI and fungal BSI.

Overexpression of MexAB-OprM efflux pump in carbapenem-resistant Pseudomonas aeruginosa.

Efflux pump systems are one of the most important mechanisms conferring multidrug resistance in Pseudomonas aeruginosa. MexAB-OprM efflux pump is one of the largest multi-drug resistant efflux pumps with high-level expression, which is controlled by regulatory genes mexR, nalC, and nalD. This study investigated the role of efflux pump MexAB-OprM in 75 strains of carbapenem-resistant P. aeruginosa and evaluated the influence of point mutation of the regulatory genes. The minimum inhibitory concentrations of imipenem and meropenem, with or without MC207110, an efflux pump inhibitor, were determined by agar dilution method to select the positive strains for an overexpressed active efflux pump. Carba NP test and EDTA-disk synergy test were used for the detection of carbapenemase and metallo-ß-lactamases, respectively. The gene mexA, responsible for the fusion protein structure, and the reference gene rpoD of the MexAB-OprM pump were amplified by real-time PCR. The quantity of relative mRNA expression was determined simultaneously. By PCR method, the efflux regulatory genes mexR, nalC, and nalD and outer membrane protein OprD2 were amplified for the strains showing overexpression of MexAB-OprM and subsequently analyzed by BLAST. Among the 75 P. aeruginosa strains, the prevalence of efflux pump-positive phenotype was 17.3 % (13/75). Carba NP test and EDTA-disk synergy test were all negative in the 13 strains. PCR assay results showed that ten strains overexpressed the MexAB-OprM efflux pump and were all positive for the regulatory genes mexR, nalC, and nalD. Sequence analysis indicated that of the ten isolates, nine had a mutation (Gly â†’ Glu) at 71st amino acid position in NalC, and eight also had a mutation (Ser â†’ Arg) at 209th position in NalC. Only one strain had a mutation (Thr â†’ Ile) at the 158th amino acid position in NalD, whereas eight isolates had mutations in MexR. In conclusion, overexpression of efflux pump MexAB-OprM plays an important role in carbapenem-resistant P. aeruginosa. The mutations of regulatory genes may be a main factor contributing to overexpression of MexAB-OprM.

Accuracy of matrix-assisted laser desorption ionization-time of flight mass spectrometry for identification of clinical pathogenic fungi: a meta-analysis.

Fungal infections in the clinic have become increasingly serious. In many cases, the identification of clinically relevant fungi remains time-consuming and may also be unreliable. Matrix-assisted laser desorption ionization-time of flight mass spectroscopy (MALDI-TOF MS) is a newly developed diagnostic tool that is increasingly being employed to rapidly and accurately identify clinical pathogenic microorganisms. The present meta-analysis aimed to systematically evaluate the accuracy of MALDI-TOF MS for the identification of clinical pathogenic fungi. After a rigorous selection process, 33 articles, involving 38 trials and a total of 9,977 fungal isolates, were included in the meta-analysis. The random-effects pooled identification accuracy of MALDI-TOF MS increased from 0.955 (95% confidence interval [CI], 0.939 to 0.969) at the species level to 0.977 (95% CI, 0.955 to 0.993) at the genus level (P < 0.001; χ(2) = 15.452). Subgroup analyses were performed at the species level for several categories, including strain, source of strain, system, system database, and modified outcomes, to calculate the accuracy and to investigate heterogeneity. These analyses revealed significant differences between the overall meta-analysis and some of the subanalyses. In parallel, significant differences in heterogeneity among different systems and among different methods for calculating the identification ratios were found by multivariate metaregression, but none of the factors, except for the moderator of outcome, was significantly associated with heterogeneity by univariate metaregression. In summary, the MALDI-TOF MS method is highly accurate for the identification of clinically pathogenic fungi; future studies should analyze the comprehensive capability of this technology for clinical diagnostic microbiology.

A finite-time path following scheme of unmanned surface vessels with an optimization strategy.

The path-following problem of unmanned surface vessels (USVs) is solved in this paper, considering unknown interference, energy-saving strategy, input constraints, and input rate of change constraints. Firstly, the USV model considering lumped interference is given, while an interference observer based on finite-time theory is used for interference estimation where the convergence time is specified. Then, to accelerate the USV convergence to a given path, a novel improved adaptive finite-time line-of-sight (IAFTLOS) scheme is developed. The proposed IAFTLOS scheme makes the cross-path error with finite-time convergence. At the same time, an adaptive time-varying looking distance law is designed to improve the convergence performance further. Next, nonlinear model predictive control is introduced to deal with rates of change and input constraints. In addition, an energy-saving strategy is incorporated into the design of the controller. Finally, stable control of the whole cascade system is achieved, and comparative simulation cases verify the feasibility and robustness of the entire system.

Enhancing precision of defect 3D reconstruction in metal ultrasonic testing through point cloud completion.

During the ultrasound multi-layer focused scanning inspection process, the sequential images characterizing the defect morphology suffer from inter-layer contour information loss, which causes a reduction in the accuracy of defect 3D reconstruction, subsequently leading to errors in the characterization of the defect size and morphology. In order to address the above issues, a new method based on the Attention-based Residual Completion Network (ARC) is proposed for ultrasonic point cloud completion to characterize metal defects. Firstly, the ARC network extracts global contour morphological features and local edge detail features from the ultrasonic point cloud through consecutive residual convolutions. Subsequently, the two sets of features are concatenated and finally fed into a decoder based on self-attention, realizing the reconstruction of lost contour information and enhancing the 3D reconstruction accuracy of defects. In the experiment, an ultrasonic microscope was used to inspect actual steel plates. The internal defects were then completed using the ARC network, and the completion results were compared with the metallographic images of the defects. The experiment results indicated that, after completion, the characterization accuracy of defect morphology and sizes is enhanced by an average of 10.31 %. The ARC network provides a novel method for high-precision 3D characterization of internal defects in metal materials.

KEAP1 overexpression is correlated with poor prognosis and immune infiltration in liver hepatocellular carcinoma.

Purpose: Liver hepatocellular carcinoma (LIHC) is the most common type of liver cancer, but there is a lack of effective indicators for its early diagnosis and prognosis, so we explored the role of KEAP1 in LIHC patients in this study. Methods: The Cancer Genome Atlas (TCGA) dataset was used to investigate the relationship between KEAP1 expression and clinicopathological features and prognosis of LIHC patients. KEAP1 expression related pathways were enriched by Gene Ontology (GO) and gene set enrichment analysis (GSEA). Besides, KEAP1 expression-related immune infiltration was performed by single-sample GSEA (ssGSEA), and function of immune cells was detected by flow cytometry. Results: It was found that KEAP1 expression was significantly increased and correlated with overall survival of LIHC patients. A total of 231 differentially expressed genes (DEGs) between LIHC patients with high- and low-KEAP1 expression were found, which associated with various biological pathways. Besides, KEAP1 expression was positively correlated with the infiltration level of T helper cells and Th2 cells but negatively correlated with DCs and cytotoxic cells. Functional analysis revealed that the expression of IL 4 in Th2 cells and CD107a, GrA and GrB in cytotoxic cells was significantly greater in LIHC patients than in HCs. In addition, KEAP1 expression was closely correlated with liver function in LIHC patients. Conclusion: Highly expressed KEAP1 was closely related to the diagnosis, prognosis, immune cell infiltration, and liver function of LIHC, which might promote the progression of LIHC through regulating cell development, signal transduction, and abnormal immune response. The current study partially revealed the role of KEAP1 in LIHC and provided a potential biomarker for the diagnosis, prognosis and treatment of LIHC.

Abrasive Wear Properties of Wear-Resistant Coating on Bucket Teeth Assessed Using a Dry Sand Rubber Wheel Tester.

Ni60-WC coatings with different WC contents on the bucket tooth substrates were pre- pared using laser cladding technology. Their abrasive wear properties were assessed using the dry sand rubber wheel test system. The substrate and the hard-facing layer were tested for comparison. The results showed that the hardness of the Ni60-WC coatings increased with the increase in WC content. The wear resistance of the bucket tooth substrate was greatly improved by hard-facing and laser cladding Ni60-WC coatings. The wear rate of the hard-facing layer was reduced to 1/6 of that of the tooth substrate. The wear rate of the laser cladding coatings with 20-40 wt.% WC was similar to that of the hard-facing layer. It is worth mentioning that the wear rate of the coatings with 60-80 wt.% WC was only 1/4 of that of the hard-facing layer. Micro-cutting with surface plastic deformation was the main wear mechanism of the substrate to form narrow and deep furrows. The wear mechanism of the hard-facing layer was mainly plastic deformation with a wide groove, and the surface cracks promoted the removal of the material. The removal of the binder phase caused by micro-cutting was the main wear mechanism of the laser cladding Ni60-WC coatings. However, the hard phase of WC hinders micro-cutting and plastic deformation, which improves the wear resistance of the coating.

Experimental studies on the characteristics of chisel picks in coal cutting for bucket wheel excavators.

Chisel pick is a basic and important rock cutting tool, and the performance of chisel pick directly affects rock mining. In this paper, a rock cutting device was developed for chisel picks cutting experiments. The influence of the depth of cutting, width of chisel pick, rake angle, back clearance angle and tip fillet radius on the cutting performance such as cutting force, normal force, and specific energy has been comprehensively studied. In addition to the general conclusions, the experimental results show that the back clearance angle has an influence range on the cutting, and the ratio of the normal force to the cutting force decreases with the increase of the rake angle; the tip fillet radius greatly improve the mean cutting force and specific energy. The experimental results will provide data support for the design of chisel picks on rock excavation machinery and a more reasonable chisel pick cutting rock mechanics model.

Resting-state fMRI network efficiency as a mediator in the relationship between the glymphatic system and cognitive function in obstructive sleep apnea hypopnea syndrome: Insights from a DTI-ALPS investigation.

INTRODUCTION: Obstructive sleep apnea hypopnea syndrome (OSAHS) is associated with cognitive impairment and physiological complications, necessitating further understanding of its mechanisms. This study investigates the relationship between glymphatic system function, brain network efficiency, and cognitive impairment in OSAHS patients using diffusion tensor image analysis along the perivascular space (DTI-ALPS) and resting-state fMRI. MATERIALS AND METHODS: This study included 31 OSAHS patients and 34 age- and gender-matched healthy controls (HC). All participants underwent GE 3.0T magnetic resonance imaging (MRI) with diffusion tensor image (DTI) and resting-state fMRI scans. The DTI-ALPS index and brain functional networks were assessed. Differences between groups and correlations with clinical characteristics were analyzed. Additionally, the mediating role of brain network efficiency was explored. Finally, receiver operating characteristics (ROC) analysis assessed diagnostic performance. RESULTS: OSAHS patients had significantly lower ALPS-index (1.268 vs. 1.431, p < 0.0001) and moderate negative correlation with Apnea Hypopnea Index (AHI) (r = -0.389, p = 0.031), as well as moderate positive correlation with Montreal Cognitive Assessment (MoCA) (r = 0.525, p = 0.002). Moreover, global efficiency (Eg) of the brain network was positively correlated with the ALPS-index and MoCA scores in OSAHS patients (r = 0.405, p = 0.024; r = 0.56, p = 0.001, respectively). Furthermore, mediation analysis showed that global efficiency partially mediated the impact of glymphatic system dysfunction on cognitive impairment in OSAHS patients (indirect effect = 4.58, mediation effect = 26.9 %). The AUROC for identifying OSAHS and HC was 0.80 (95 % CI 0.69 to 0.91) using an ALPS-index cut-off of 1.35. CONCLUSIONS: OSAHS patients exhibit decreased ALPS-index, indicating impaired glymphatic system function. Dysfunction of the glymphatic system can affect cognitive function in OSAHS by disrupting brain functional network, suggesting a potential underlying pathological mechanism. Additionally, preliminary findings suggest that the ALPS-index may offer promise as a potential indicator for OSAHS.

Novel and recurrent hemizygous variants in BCORL1 cause oligoasthenoteratozoospermia by interfering transcription.

BACKGROUND: Oligoasthenoteratozoospermia (OAT) is a common cause of male infertility, of which the causes remain largely unknown. Recently, BCORL1 was identified as a contributor to male infertility from non-obstructive azoospermia (NOA) to OAT. OBJECTIVES: To identify novel and hotspot variants in BCORL1 from infertile men with OAT and reveal their outcomes of assisted reproductive treatments (ARTs). MATERIALS AND METHODS: Forty-six infertile men characterized by OAT were recruited from 2017 to 2022. Variants in OAT patients were identified by whole-exome sequencing (WES) and verified by Sanger sequencing. Papanicolaou staining was used for sperm morphology analysis. Pathogenicity of BCORL1 variants were analyzed by bioinformatics analysis, and further confirmed in vitro by using recombinant plasmids and cells. Meanwhile, ARTs were performed on these patients to investigate the appropriate clinical treatment strategy. RESULTS: We identified a novel hemizygous missense variant (NM_021946: c.G4171A; p.G1391R) and a recurrent variant (NM_021946: c.T2615G; p.V872G) in BCORL1 from four OAT patients. Notably, routine semen assessment and Papanicolaou staining revealed a special OAT phenotype of patients with BCORL1 variants, whose rare mature sperm characterized by acephalic and abnormal acrosome. Pathogenicity analysis showed the interaction between BCORL1 with histone deacetylases (HDACs) were disrupted after variance, accompanied with epigenetic alterations and finally the orderly transcriptions of spermatogenetic genes were interfering. Besides, clinical record presented the poor outcomes of ARTs in these patients with BCORL1 variants. DISCUSSION AND CONCLUSIONS: Our findings further expand the variant spectrum of BCORL1 related to OAT, and provide new evidences that BCORL1 acts as an important transcriptional regulator, participating in epigenetic regulation and directing the expression of key genes throughout spermatogenesis. The outcomes of ARTs will facilitate the genetic counseling and clinical treatment of infertile men with BCORL1 variants in the future.

The ecological response of Carex lasiocarpa community in the Riparian Wetlands to the environmental gradient of water depth in Sanjiang Plain, Northeast China.

The response of Carex lasiocarpa in riparian wetlands in Sanjiang Plain to the environmental gradient of water depth was analyzed by using the Gaussian Model based on the biomass and average height data, and the ecological water-depth amplitude of Carex lasiocarpa was derived. The results indicated that the optimum ecological water-depth amplitude of Carex lasiocarpa based on biomass was [13.45 cm, 29.78 cm], while the optimum ecological water-depth amplitude of Carex lasiocarpa based on average height was [2.31 cm, 40.11 cm]. The intersection of the ecological water-depth amplitudes based on biomass and height confirmed that the optimum ecological water-depth amplitude of Carex lasiocarpa was [13.45 cm, 29.78 cm] and the optimist growing water-depth of Carex lasiocarpa was 21.4 cm. The TWINSPAN, a polythetic and divisive classification tool, was used to classify the wetland ecological series into 6 associations. Result of TWINSPAN matrix classification reflected an obvious environmental gradient in these associations: water-depth gradient. The relation of biodiversity of Carex lasiocarpa community and water depth was determined by calculating the diversity index of each association.

Predictors of Occurrence and 30-Day Mortality for Co-Infection of Carbapenem-Resistant Klebsiella pneumoniae and Carbapenem-Resistant Acinetobacter baumannii.

Background: The phenomenon of co-infection with multiple carbapenem-resistant bacteria is growing, which pose a great challenge for infection control and treatment. This study aimed to analyze predictors of occurrence and 30-day mortality for carbapenem-resistant Klebsiella pneumoniae and carbapenem-resistant Acinetobacter baumannii co-infection. Methods: From June 2018 to June 2021, clinical data of 103 patients co-infected with carbapenem-resistant Acinetobacter baumannii (CRAB) and carbapenem-resistant Klebsiella pneumoniae (CRKP) were collected from a tertiary teaching hospital in Anhui Province, China. The clinical characteristics and predictors of mortality were analyzed. Meanwhile, the bacterial isolates were characterized for drug susceptibility, multi-locus sequence typing, and drug resistance genes. Results: The multivariate analysis revealed that fiberoptic bronchoscopy (p = 0.005, OR=2.72), repeat transfusions (p = 0.008, OR= 2.23) and exposure to tigecycline (p = 0.002, OR = 6.58) were independent risk factors for CRKP and CRAB co-infection. Neutrophil ≥11.9*109 (p = 0.035, adjusted HR = 3.12) and C-reactive protein ≥ 149 mg/L (p = 0.009, adjusted HR = 4.41) were found associated with 30-day mortality. Combined neutrophil with C-reactive protein could predict 30-day mortality, of which AUC value was 0.791 (95%CI: 0.661-0.921). KPC (46/51, 90.2%) was the most common carbapenemase in CRKP. 33 isolates of CRKP belong to ST11 (33/51, 64.7%), and three new ST types ST5882, ST5883, ST5885 were detected. Conclusions: Invasive operations and antibiotics exposure can lead to CRKP and CRAB co-infection. Combined neutrophil with C-reactive protein could predict 30-day mortality.

Evaluating the Clinical Performance of a Dual-Target Stool DNA Test for Colorectal Cancer Detection.

The dual-target stool DNA test, iColocomf, has potential utility for colorectal cancer (CRC) detection, but its clinical accuracy has not been validated on larger groups. We therefore evaluated the performance of iColocomf in a multicenter clinical trial. In this double-blinded case-control study, 1164 participants from three independent hospitals, including 320 CRC patients, 148 adenomas, 396 interfering diseases, and 300 healthy controls were enrolled. The primary indicators of sensitivity, specificity, and accuracy were estimated. Stool samples of participants were collected and tested by the assay. The test results were then verified by Sanger sequencing and retesting of resected participants. The sensitivity and specificity for CRC detection were 95.31% and 96.67%, respectively, with an accuracy of 90.29%. When combining the interfering diseases, the specificity was 88.39%. No statistically significant variations of positive detection rates were observed for the test in different patients' clinical features. For advanced adenomas (n = 38) and nonadvanced adenomas (n = 110), the sensitivities were 63.16% and 33.64%, respectively. The average accuracy was 99.62% for the methylation status of 375 samples verified by Sanger sequencing, and 94.12% for 34 participants who received the test after surgical resection. The iColocomf test showed robust performance for the early detection of colorectal cancer and potential monitoring ability in clinical practice.