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The single-nucleotide polymorphisms of genes related to DNA damage repair and inflammasomes and mutated gene expression in coal workers' pneumoconiosis (CWP) were analysed to identify the risk factors of CWP and potential biomarkers for early warning and diagnosis. Further, mutated gene pathways were analysed based on proteome and metabolome. Han Chinese male subjects were randomly selected and divided into 4 or 5 groups according to the process of CWP. MassARRAY was used to sequence single-nucleotide polymorphism genotypes. Mutated gene expression in plasma was tested using enzyme-linked immunosorbent assay (ELISA). Odds ratios (ORs) and receiver operating characteristic curves (ROC) were calculated. The serum different proteins and metabolites were identified by Ultra Performance Liquid Chromatography Quadrupole time of flight/Mass Spectrum (UPLC-Q-TOF/MS) and analysed using bioinformation software. As CWP progressed, the CC and CA genotypes of ERCC1 rs3212986 decreased and increased significantly, respectively. AA (OR = 3.016) and CA (OR = 2.130) genotypes were identified as risk factors for stage II. ERCC1 significantly decreased in processing of CWP. The cutoff value of ERCC1 was 5.265 pg/ml, with a sensitivity of 90.0% and specificity of 86.7%. ERCC1 had an indirect interaction with activator protein-1 and insulin and its pathways were mainly made with molecules related to lipid metabolism and actin dynamics. ERCC1 is a candidate biomarker for detection and precise intervention in CWP. If it reaches the threshold, workers will change other jobs in time and will not develop and diagnose as pneumoconiosis and will help the employers spend less money. Meanwhile, the signal molecules of ERCC1 pathway could be as a candidate target for drug discovery. [ABSTRACT FROM AUTHOR]

Objective: This study aims to examine the validity of the MFS by analyzing the electronic medical records on fall risk in obstetrics and gynecology wards and determine the optimal cut-off score of the Morse Fall Scale. Design: A retrospective survey. Methods: The research was conducted in an Obstetrics and Gynecology Hospital and a general hospital. The sample included 136 fall inpatients and 120 no-fall inpatients recruited from January 1st, 2020, to July 10th, 2022. The Morse Fall Scale was analyzed using the gold standard of patients who fell while hospitalized, assessing the area under the Receiver Operating Characteristic curve, sensitivity, specificity, accuracy, positive predictive value, negative predictive value, and Kappa. Results: At cut-off scores of 40, 45,50, and 55, the area under the Receiver Operating Characteristic curve was 0.772, 0.761, 0.749, and 0.763, respectively. The Youden index was 0.543, 0.521, 0.498, and 0.525, while Kappa values were 0.540, 0.518, 0.490, and 0.515. Sensitivity was 0.735, 0.713, 0.640, and 0.625; specificity was 0.808, 0.808, 0.858, and 0.900. The positive predictive values were 0.813, 0.808, 0.837, and 0.876, and the negative predictive values were 0.729, 0.713, 0.678, and 0.679. Accuracy were 0.770, 0.758, 0.742, and 0.754. Conclusions: The Morse Fall Scale demonstrates good predictive performance for assessing fall risk in gynecology and obstetrics wards. The optimal cut-off score is 40. [ABSTRACT FROM AUTHOR]

In order to study the tensile properties of rock-concrete composite disc specimens with different roughness, the surface of the gray-white sand specimen was artificially grooved, and six different roughness were configured. The test results show that the roughness size and roughness mode jointly control the tensile strength of the rock-concrete interface. With the increase of roughness, the tensile strength of the sample changes from the initial decrease to the increase and then decrease, and the tensile strength reaches the highest when the roughness is f3. The variation trend of pre-peak energy accumulation and post-peak energy accumulation of the sample is opposite, and the dissipation energy is closely related to the crack propagation strain. The roughness and crack closure strain, crack peak strain, crack propagation strain and crack closure stress show a sinusoidal periodic variation. The crack propagation strain is closely related to the change of dissipation energy. The change trend of crack closure stress is basically consistent with the change trend of tensile strength. Therefore, in the actual project, grasping the period of roughness variation and selecting the construction position can make the rock-concrete interface stable and get twice the result with half the effort. [ABSTRACT FROM AUTHOR]

A modified QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) -LC-MS/MS method was developed for the determination of hexachlorophene in fruits and vegetables. Samples were extracted by acetonitrile and then salted with an acetate buffer system. Extractants neutral alumina (Al-N), strong cation exchange silica gel bonded adsorbent (SCX) and graphitized carbon black (GCB) were used for sample purification. The method demonstrates excellent accuracy and reproducibility. Under optimized conditions, the correlation coefficients of hexachlorophene were higher than 0.995 in the range of 0.5–20 ng/mL. The limit of quantification (LOQ) was 2.0 μg/kg. The average recoveries, assessed at three spiked levels (2.0, 4.0, and 20.0μg/kg) across various matrices including cabbage, celery, tomato, eggplant, potato, radish, cowpea, chives, apple, peach, grape, citrus, bitter melon, banana and hami melon ranged from 72.0 to 100.5% with relative standard deviations from 3.2 to 9.8% (n = 6). [ABSTRACT FROM AUTHOR]

Developing T1-weighted magnetic resonance imaging (MRI) contrast agents with enhanced biocompatibility and targeting capabilities is crucial owing to concerns over current agents' potential toxicity and suboptimal performance. Drawing inspiration from "biomimetic camouflage," we isolated cell membranes (CMs) from human glioblastoma (T98G) cell lines via the extrusion method to facilitate homotypic glioma targeting. At an 8:1 mass ratio of ferric chloride hexahydrate to gallic acid (GA), the resulting iron (Fe)–GA nanoparticles (NPs) proved effective as a T1-weighted MRI contrast agent. T98G CM–coated Fe–GA NPs demonstrated improved homotypic glioma targeting, validated through Prussian blue staining and in vitro MRI. This biomimetic camouflage strategy holds promise for the development of targeted theranostic agents in a safe and effective manner. [ABSTRACT FROM AUTHOR]

The TBX1 gene plays a critical role in the development of 22q11.2 deletion syndrome (22q11.2DS), a complex genetic disorder associated with various phenotypic manifestations. In this study, we performed in-silico analysis to identify potentially deleterious non-synonymous single nucleotide polymorphisms (nsSNPs) within the TBX1 gene and evaluate their functional and structural impact on 22q11.2DS. A comprehensive analysis pipeline involving multiple computational tools was employed to predict the pathogenicity of nsSNPs. This study assessed protein stability and explored potential alterations in protein-protein interactions. The results revealed the rs751339103(C>A), rs780800634(G>A), rs1936727304(T>C), rs1223320618(G>A), rs1248532217(T>C), rs1294927055 (C>T), rs1331240435 (A>G, rs1601289406 (A>C), rs1936726164 (G>A), and rs911796187(G>A) with a high-risk potential for affecting protein function and stability. These nsSNPs were further analyzed for their impact on post-translational modifications and structural characteristics, indicating their potential disruption of molecular pathways associated with TBX1 and its interacting partners. These findings provide a foundation for further experimental studies and elucidation of potential therapeutic targets and personalized treatment approaches for individuals affected by 22q11.2DS. [ABSTRACT FROM AUTHOR]

Reactivation from latency plays a significant role in maintaining persistent lifelong Epstein-Barr virus (EBV) infection. Mechanisms governing successful activation and progression of the EBV lytic phase are not fully understood. EBV expresses multiple viral microRNAs (miRNAs) and manipulates several cellular miRNAs to support viral infection. To gain insight into the host miRNAs regulating transitions from EBV latency into the lytic stage, we conducted a CRISPR/Cas9-based screen in EBV+ Burkitt lymphoma (BL) cells using anti-Ig antibodies to crosslink the B cell receptor (BCR) and induce reactivation. Using a gRNA library against >1500 annotated human miRNAs, we identified miR-142 as a key regulator of EBV reactivation. Genetic ablation of miR-142 enhanced levels of immediate early and early lytic gene products in infected BL cells. Ago2-PAR-CLIP experiments with reactivated cells revealed miR-142 targets related to Erk/MAPK signaling, including components directly downstream of the B cell receptor (BCR). Consistent with these findings, disruption of miR-142 enhanced SOS1 levels and Mek phosphorylation in response to surface Ig cross-linking. Effects could be rescued by inhibitors of Mek (cobimetinib) or Raf (dabrafenib). Taken together, these results show that miR-142 functionally regulates SOS1/Ras/Raf/Mek/Erk signaling initiated through the BCR and consequently, restricts EBV entry into the lytic cycle. Author summary: Epstein-Barr virus (EBV) is a common herpesvirus that infects most individuals worldwide and can persist in the body for life. Long-term viral persistence is established in part through latently infected memory B cells and periodic reactivation events which maintain viral reservoirs. To investigate functional roles for host non-coding RNAs in EBV latency and reactivation—specifically microRNAs—we conducted a genome-wide CRISPR screen in EBV-positive Burkitt's lymphoma (BL) cells. By screening >1500 human miRNAs, we identified miR-142 as a potent regulator of the lytic cycle. When miR-142 was disrupted, latently infected BL cells responded rapidly to external reactivation triggers and exhibited significantly elevated levels of lytic viral proteins. Through mechanistic studies, we found that miR-142 regulates cell signaling pathways such as the Ras/Raf/Mek/Erk pathway and can target SOS1 encoding a Ras guanine nucleotide exchange factor. Heightened EBV reactivation in miR-142 mutant cells could be reversed using chemical inhibitors to Raf, Mek, or Sos1. These findings provide novel insight into the role of miR-142 in the EBV life cycle and further unveil potential for inhibiting Sos1 as a means to suppress EBV reactivation. [ABSTRACT FROM AUTHOR]

Background: The causal relationship between sex hormone-binding globulin (SHBG) and infertility has remained unclear. Thus, we used Mendelian randomization (MR) to investigate this relationship. Methods: Risk factors for SHBG were extracted from European individuals within the UK Biobank using single-nucleotide polymorphism (SNP) data. Summary-level data for infertility outcomes were obtained from the FinnGen dataset. The causal relationship between SHBG and infertility was examined using inverse variance weighted, weighted model, weighted median, and MR-Egger regression analyses. Additionally, Cochran's Q test and Egger intercept tests were used to confirm the heterogeneity and pleiotropy of identified instrumental variables (IVs). Results: Our findings revealed a significant negative association between sex hormone-binding globulin (SHBG) levels and infertility, particularly with anovulation, a specific form of female infertility. However, SHBG did not exert a causal impact on male infertility or on female infertility of tubal origin. Conclusions: SHBG expression offers protection against the development of certain types of female infertility, suggesting it is a potential therapeutic target for infertility. [ABSTRACT FROM AUTHOR]

Background: Severe acute lung failure (ALF) often necessitates veno-venous extracorporeal membrane oxygenation (VV-ECMO), where identifying predictors of weaning success and mortality remains crucial yet challenging. The study aims to identify predictors of weaning success and mortality in adults undergoing VV-ECMO for severe ALF, a gap in current clinical knowledge. Methods and analysis: PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials will be searched for cohort studies examining the predictive factors of successful weaning and mortality in adult patients on VV-ECMO due to severe ALF. Risk of bias assessment will be conducted using the Newcastle-Ottawa scale for each included study. The primary outcomes will be successful weaning from VV-ECMO and all-cause mortality. Between-study heterogeneity will be evaluated using the I2 statistic. Sensitivity, subgroup, and meta-regression analyses will be performed to ascertain potential sources of heterogeneity and assess the robustness of our results. We will use the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) tool to recommend the level of evidence. Discussion: This study seeks to provide clinically significant insights into predictors for weaning and mortality during VV-ECMO treatment for ALF, aiming to support clinical decisions and potentially influence health policy, thereby improving patient outcomes. Ethics and dissemination: Given the absence of direct engagement with human subjects or access to personal medical records, ethical approval for this study is deemed unnecessary. The study findings will be shared at a scientific conference either at the global or national level. Alternatively, the results will be presented for publication in a rigorously peer-reviewed journal regarding critical care medicine. [ABSTRACT FROM AUTHOR]

Background: Existing research has demonstrated links between airborne particulate matter and ulcerative colitis (UC) onset. Through Mendelian randomization, this study aims to further delineate the causal association between specific types of airborne particulates and UC. Methods: A two-sample Mendelian randomization analysis was undertaken to investigate the causality between airborne particulate matter and UC. Genetic datasets for both airborne particulates and UC were derived from accessible genome-wide association studies (GWAS). We employed a range of MR techniques, such as inverse variance weighted (IVW), weighted median, MR-Egger, and Wald Ratio, to validate the causality. In addition, sensitivity assessments were executed to ensure result reliability. Results: The data indicate a probable positive correlation between PM2.5 exposure and UC risk (OR: 3.6; 95% CI: [1.2–11.3]; P = 0.026). The statistical strength for causal determination via the IVW approach stood at 0.87, with a Type I error rate set at 0.025. Assessments using Cochran's Q test, MR-Egger intercept, MR-PRESSO, and leave-one-out sensitivity analyses did not identify notable heterogeneity, pleiotropy, or biases in the overall relationship between PM2.5 and UC. Furthermore, the MR-Steiger assessment indicated that PM2.5 exposure level determinants predominantly affect UC vulnerability. Conclusion: The findings underscore the potential involvement of PM2.5 in UC pathogenesis. [ABSTRACT FROM AUTHOR]

Objective: The relationship between the levels of the first 24-h PaCO2 and the prognosis of sepsis-associated encephalopathy (SAE) remains unclear, and the first 24-h optimal target for PaCO2 is currently inconclusive. This study was performed to investigate the correlation between PaCO2 and all-cause mortality for SAE patients, establish a reference range of the initial 24-hour PaCO2 for clinicians in critical care, and explain the possible pathophysiological mechanisms of abnormal PaCO2 levels as a higher mortality risk factor for SAE. Methods: The baseline information and clinical data of patients were extracted from the fourth edition Medical Information Mart for Intensive Care database (MIMIC-IV 2.0). Multivariate logistic regressions were performed to assess the relationship between PaCO2 and all-cause mortality of SAE. Additionally, restricted cubic splines, Kaplan-Meier Survival analyses, propensity score matching (PSM) analyses, and subgroup analyses were conducted. Results: A total of 5471 patients were included in our cohort. In the original and matched cohort, multivariate logistic regression analysis showed that normocapnia and mild hypercapnia may be associated with a more favorable prognosis of SAE patients, and survival analysis supported the findings. In addition, a U-shaped association emerged when examining the initial 24-hour PaCO2 levels in relation to 30-day, 60-day, and 90-day mortality using restricted cubic splines, with an average cut-off value of 36.3mmHg (P for nonlinearity<0.05). Below the cut-off value, higher PaCO2 was associated with lower all-cause mortality, while above the cut-off value, higher PaCO2 was associated with higher all-cause mortality. Subsequent subgroup analyses revealed similar results for the subcohort of GCS≤8 compared to the original cohort. Additionally, when examining the subcohort of GCS>8, a L-shaped relationship between PaCO2 and the three clinical endpoints emerged, in contrast to the previously observed U-shaped pattern. The findings from the subcohort of GCS>8 suggested that patients experiencing hypocapnia had a more unfavorable prognosis, which aligns with the results obtained from corresponding multivariate logistic regression analyses. Conclusion: The retrospective study revealed the association between the first 24-h PaCO2 and all-cause mortality risk (30-day, 60-day, and 90-day) for patients with SAE in ICU. The range (35mmHg-50mmHg) of PaCO2 may be the optimal target for patients with SAE in clinical practice. [ABSTRACT FROM AUTHOR]

Microglia-mediated neuroinflammation is involved in various neurological diseases, including ischemic stroke, but the endogenous mechanisms preventing unstrained inflammation is still unclear. The anti-inflammatory role of transcription factor nuclear receptor subfamily 4 group A member 1 (NR4A1) in macrophages and microglia has previously been identified. However, the endogenous mechanisms that how NR4A1 restricts unstrained inflammation remain elusive. Here, we observed that NR4A1 is up-regulated in the cytoplasm of activated microglia and localizes to processing bodies (P-bodies). In addition, we found that cytoplasmic NR4A1 functions as an RNA-binding protein (RBP) that directly binds and destabilizes Tnf mRNA in an N6-methyladenosine (m6A)-dependent manner. Remarkably, conditional microglial deletion of Nr4a1 elevates Tnf expression and worsens outcomes in a mouse model of ischemic stroke, in which case NR4A1 expression is significantly induced in the cytoplasm of microglia. Thus, our study illustrates a novel mechanism that NR4A1 posttranscriptionally regulates Tnf expression in microglia and determines stroke outcomes. Microglia-mediated neuroinflammation is involved in neurological diseases such as ischemic stroke, but the mechanisms that prevent unstrained inflammation are unclear. This study reveals that the canonical transcription factor NR4A1 has a novel role in microglia as an RNA-binding protein that localizes to processing bodies to destabilize pro-inflammatory transcript and alleviate ischemic brain injury. [ABSTRACT FROM AUTHOR]

Plate-based proteomic sample preparation offers a solution to the large sample throughput demands in the biotechnology field where hundreds or thousands of engineered microbes are constructed for testing is routine. Meanwhile, sample preparation methods that work efficiently on broader microbial groups are desirable for new applications of proteomics in other fields, such as microbial communities. Here, we detail a step-by-step protocol that consists of cell lysis in an alkaline chemical buffer (NaOH/SDS) followed by protein precipitation with high-ionic strength acetone in 96-well format. The protocol works for a broad range of microbes (e.g., Gram-negative bacteria, Gram-positive bacteria, non-filamentous fungi) and the resulting proteins are ready for tryptic digestion for bottom-up quantitative proteomic analysis without the need for desalting column cleanup. The yield of protein using this protocol increases linearly with respect to the amount of starting biomass from 0.5–2.0 OD*mL of cells. By using a bench-top automated liquid dispenser, a cost-effective and environmentally-friendly option to eliminating pipette tips and reducing reagent waste, the protocol takes approximately 30 minutes to extract protein from 96 samples. Tests on mock mixtures showed expected results that the biomass composition structure is in close agreement with the experimental design. Lastly, we applied the protocol for the composition analysis of a synthetic community of environmental isolates grown on two different media. This protocol has been developed to facilitate rapid, low-variance sample preparation of hundreds of samples and allow flexibility for future protocol development. [ABSTRACT FROM AUTHOR]

Smart services are expected to solve the dilemma of development and emission reduction, but there is still no conclusive evidence on whether and how they work. This article aims to explore the relationship between smart services and sustainable green transformation and the effect mechanism. To achieve this goal, a text mining analysis is performed to assess 970 Chinese listed manufacturing enterprises' smart services development; a regression analysis is then conducted. The results show that smart services have a significant positive impact on the quality and quantity of green innovation, especially for heavily polluting enterprises. The substitution of technology and labor for capital, as well as the upgrading of human resource quality, are effective mechanisms. Smart services can assist as a management strategic tool to balance environmental protection and development, but such an effect fails to work in areas not covered by new infrastructure and is weaker for private enterprises. [ABSTRACT FROM AUTHOR]

Long-term memory formation requires de novo RNA and protein synthesis. By using the differential display-polymerase chain reaction strategy, we have presently identified the Nedd4 family interacting protein 1 (Ndfip1) cDNA fragment that is differentially expressed between the slow learners and the fast learners from the water maze learning task in rats. Further, the fast learners show decreased Ndfip1 mRNA and protein expression levels than the slow learners. Spatial training similarly decreases the Ndfip1 mRNA and protein expression levels. Conversely, the Ndfip1 conditional heterozygous (cHet) mice show enhanced spatial memory performance compared to the Ndfip1flox/WT control mice. Result from co-immunoprecipitation experiment indicates that spatial training decreases the association between Ndfip1 and the E3 ubiquitin ligase Nedd4 (Nedd4-1), and we have shown that both Beclin 1 and PTEN are endogenous ubiquitination targets of Nedd4 in the hippocampus. Further, spatial training decreases endogenous Beclin 1 and PTEN ubiquitination, and increases Beclin 1 and PTEN expression in the hippocampus. On the other hand, the Becn1 conditional knockout (cKO) mice and the Pten cKO mice both show impaired spatial learning and memory performance. Moreover, the expression level of Beclin 1 and PTEN is higher in the Ndfip1 cHet mice compared with the Ndfip1flox/WT control mice. Here, we have identified Ndfip1 as a candidate novel negative regulation for spatial memory formation and this is associated with increased ubiquitination of Beclin 1 and PTEN in the hippocampus. [ABSTRACT FROM AUTHOR]

The human AAA+ ATPase CLPB (SKD3) is a protein disaggregase in the mitochondrial intermembrane space (IMS) and functions to promote the solubilization of various mitochondrial proteins. Loss-of-function CLPB mutations are associated with a few human diseases with neutropenia and neurological disorders. Unlike canonical AAA+ proteins, CLPB contains a unique ankyrin repeat domain (ANK) at its N-terminus. How CLPB functions as a disaggregase and the role of its ANK domain are currently unclear. Herein, we report a comprehensive structural characterization of human CLPB in both the apo- and substrate-bound states. CLPB assembles into homo-tetradecamers in apo-state and is remodeled into homo-dodecamers upon substrate binding. Conserved pore-loops (PLs) on the ATPase domains form a spiral staircase to grip and translocate the substrate in a step-size of 2 amino acid residues. The ANK domain is not only responsible for maintaining the higher-order assembly but also essential for the disaggregase activity. Interactome analysis suggests that the ANK domain may directly interact with a variety of mitochondrial substrates. These results reveal unique properties of CLPB as a general disaggregase in mitochondria and highlight its potential as a target for the treatment of various mitochondria-related diseases. The human AAA+ ATPase CLPB (SKD3) is a protein disaggregase in the mitochondrial intermembrane space that promotes the solubilization of various mitochondrial proteins. This structural and functional study of CLPB provides insights into its assembly and mechanism of action. [ABSTRACT FROM AUTHOR]

ADP-ribosylation factor-like protein (ARL) family members (ARLs) may regulate the malignant phenotypes of cancer cells. However, relevant studies on ARLs in breast cancer (BC) are limited. In this research, the expression profiles, genetic variations, and prognostic values of ARLs in BC have been systematically analyzed for the first time using various databases. We find that ARLs are significantly dysregulated in BC according to the TCGA database, which may result from DNA methylation and copy number alteration. Prognostic analysis suggests that ARL11 is the most significant prognostic indicator for BC, and higher ARL11 predicts worse clinical outcomes for BC patients. Further functional enrichment analysis demonstrates that ARL11 enhances the immunosuppression in BC, and dysregulation of ARL11 is significantly associated with immune infiltration in various types of cancer. Our results demonstrate the potential of ARL11 as an immune therapeutic target for BC. [ABSTRACT FROM AUTHOR]

To estimate the incidence of foodborne gastroenteritis caused by nontyphoidal Salmonella enterica, Shigella, and Vibrio parahaemolyticus in China, population surveys and sentinel hospital surveillance were implemented in six provinces from July 2010 to July 2011, and a multiplier calculation model for the burden of disease was constructed. The multiplier for salmonellosis and V. parahaemolyticus gastroenteritis was estimated at 4,137 [95% confidence interval (CI) 2,320–5,663], and for shigellosis at 4,356 (95% CI 2,443–5,963). Annual incidence per 100,000 population was estimated as 245 (95% CI 138–336), 67 (95% CI 38–92), and 806 (95% CI 452–1,103) for foodborne salmonellosis, shigellosis, and V. parahaemolyticus gastroenteritis, respectively, indicating that foodborne infection caused by these three pathogens constitutes an important burden to the Chinese healthcare system. Continuous implementation of active surveillance of foodborne diseases, combined with multiplier models to estimate disease burden, makes it possible for us to better understand food safety status in China. [ABSTRACT FROM AUTHOR]

Many plant secondary substances are feeding deterrents for insects and play a key role in the selection of host plants. The taste sensilla of phytophagous insects contain gustatory receptor neurons sensitive to deterrents but the molecular basis of deterrent chemoreception remains unknown. We investigated the function of Gr180, the most highly expressed bitter gustatory receptor in the maxillary galea of Helicoverpa armigera larvae. Functional analyses using the Xenopus oocyte expression system and two-electrode voltage clamp revealed that the oocytes expressing Gr180 responded to coumarin. Tip recording results showed that the medial sensilla styloconica of the maxilla of fifth instar larvae exhibited electrophysiological responses to coumarin. Two-choice feeding bioassays confirmed that coumarin inhibited larval feeding. A homozygous mutant strain of H. armigera with truncated Gr180 proteins (Gr180−/−) was established using the CRISPR-Cas9 system. The responses of the medial sensilla styloconica in Gr180−/− to coumarin were almost abolished, and the responses to sinigrin and strychnine, were also significantly decreased. Knockout of Gr180 alleviated the feeding deterrent effects of coumarin, sinigrin, and strychnine. Thus, we conclude that Gr180 is a receptor responding to coumarin,and also participates in sensing sinigrin and strychnine. These results enhance our understanding of the gustatory coding mechanisms of phytophagous insects to deterrents. Author summary: Phytophagous insects avoid eating most plants because of the presence of distasteful secondary compounds, which introduces the question of how these compounds are perceived by insects. The cotton bollworm is a very serious crop pest in the Old World, and its caterpillars mainly feed on the reproductive organs of many host plants. Here, we study the function of a gustatory receptor, Gr180, highly expressed in the taste organ of Helicoverpa armigera caterpillars. The oocytes of frogs expressing Gr180 selectively responded to coumarin, a bitter compound widely exist in plants. When this gene was knocked out, the response of the deterrent cells in the medial styloconic sensilla to coumarin disappeared, and the responses to other two deterrents sinigrin and strychnine were also attenuated. However, the inhibitory effect of coumarin on the sucrose cells in the lateral styloconic sensilla was not affected. At the same time, the aversive feeding responses to these compounds were reduced in the knockout caterpillars. These findings are important for revealing the mechanisms of host selection in herbivorous insects and the use of feeding deterrents for pest control. [ABSTRACT FROM AUTHOR]

Peste des petits ruminants virus (PPRV) is an important pathogen that seriously influences the productivity of small ruminants worldwide. PPRV is lymphotropic in nature and SLAM was identified as the primary receptor for PPRV and other Morbilliviruses. Many viruses have been demonstrated to engage extracellular vesicles (EVs) to facilitate their replication and pathogenesis. Here, we provide evidence that PPRV infection significantly induced the secretion levels of EVs from goat PBMC, and that PPRV-H protein carried in EVs can enhance SLAM receptor expression in the recipient cells via suppressing miR-218, a negative miRNA directly targeting SLAM gene. Importantly, EVs-mediated increased SLAM expression enhances PPRV infectivity as well as the expression of various cytokines related to SLAM signaling pathway in the recipient cells. Moreover, our data reveal that PPRV associate EVs rapidly entry into the recipient cells mainly through macropinocytosis pathway and cooperated with caveolin- and clathrin-mediated endocytosis. Taken together, our findings identify a new strategy by PPRV to enhance virus infection and escape innate immunity by engaging EVs pathway. Author summary: Peste des petitsruminants virus (PPRV) infection induces a transient but severe immunosuppression in the host, which threatens both small livestock and endangered susceptible wildlife populations in many countries. Despite extensive research, the mechanism underlying pathogenesis of PPRV infection remains elusive. Our data provide the first direct evidence that the EVs derived from PPRV-infected cells are involved in PPRV replication. In this study, the EVs derived from PPRV-infected goat PBMCs can enhance SLAM expression in the recipient cells, and more importantly, EVs-mediated increased SLAM expression enhances PPRV replication as well as the expression of various cytokines related to SLAM signaling pathway in the recipient cells. Taken together, our research has provided new insight into understanding the effect of EVs on PPRV replication and pathogenesis, and revealed a potential therapeutic target for antiviral intervention. [ABSTRACT FROM AUTHOR]

Collateral circulation in the circle of Willis (CoW), closely associated with disease mechanisms and treatment outcomes, can be effectively investigated using one-dimensional–zero-dimensional hemodynamic simulations. As the entire cardiovascular system is considered in the simulation, it captures the systemic effects of local arterial changes, thus reproducing collateral circulation that reflects biological phenomena. The simulation facilitates rapid assessment of clinically relevant hemodynamic quantities under patient-specific conditions by incorporating clinical data. During patient-specific simulations, the impact of clinical data uncertainty on the simulated quantities should be quantified to obtain reliable results. However, as uncertainty quantification (UQ) is time-consuming and computationally expensive, its implementation in time-sensitive clinical applications is considered impractical. Therefore, we constructed a surrogate model based on machine learning using simulation data. The model accurately predicts the flow rate and pressure in the CoW in a few milliseconds. This reduced computation time enables the UQ execution with 100 000 predictions in a few minutes on a single CPU core and in less than a minute on a GPU. We performed UQ to predict the risk of cerebral hyperperfusion (CH), a life-threatening condition that can occur after carotid artery stenosis surgery if collateral circulation fails to function appropriately. We predicted the statistics of the postoperative flow rate increase in the CoW, which is a measure of CH, considering the uncertainties of arterial diameters, stenosis parameters, and flow rates measured using the patients' clinical data. A sensitivity analysis was performed to clarify the impact of each uncertain parameter on the flow rate increase. Results indicated that CH occurred when two conditions were satisfied simultaneously: severe stenosis and when arteries of small diameter serve as the collateral pathway to the cerebral artery on the stenosis side. These findings elucidate the biological aspects of cerebral circulation in terms of the relationship between collateral flow and CH. Author summary: Cerebral arteries generate a ring-like network that provides alternative routes for blood supply in the case of carotid artery stenosis. This collateral circulation is closely associated with the potential risk of stroke and treatment outcomes in patients with stenosis. In this study, we propose a method to elucidate the cerebral circulation of individual patients using a blood flow simulation that incorporates the patient's clinical data. A key feature of our approach is its capability to obtain the probability of the different outputs using simulation, considering the uncertainty of patient conditions. Although this capability is essential for obtaining reliable results, the process is time-consuming and requires numerous computer resources. We solved this problem by combining the blood flow simulation with machine learning to perform predictions 43 000 times faster than conventional simulations. We applied the proposed method to predict cerebral circulation following surgery in three patients with stenosis and verified that the method can assess the surgical risk almost in real-time, even on a desktop computer. Additionally, extensive prediction results (100 000 cases for each patient) obtained using this method clarify the relationship between collateral circulation and life-threatening surgical outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Coronavirus Disease 2019 (COVID-19) has made a serious public health threat worldwide. Recent evidence has indicated that COVID-19 patients in convalescence frequently experience insomnia, which reduces their quality of life and causes unknown risks. The positive effect of cognitive behavior on insomnia has been well addressed in previous studies. Given the high infectivity and epidemicity of COVID-19, Internet-delivered intervention may be safer than face-to-face treatment. However, whether Internet-delivered cognitive behavioral therapy can effectively improve the insomnia of COVID-19 patients in convalescence has not been completely determined yet. Therefore, we conducted a meta-analysis and systematic review to evaluate the effects of Internet-delivered cognitive behavioral therapy on insomnia in COVID-19 patients in convalescence, with the aim to confer some guidance for its clinical application. Methods and analysis: This systematic review and meta-analysis has been registered in the International Prospective Register of Systematic Reviews (PROSPERO). Two researchers will retrieve the relevant literature on Internet-delivered cognitive behavioral therapy for insomnia in convalescent patients with COVID-19 in PubMed, Web of Science, Embase, MEDLINE, Cochrane Library, Clinical Trials gov, Chinese Biomedical Literature Database (CBM), and Chinese National Knowledge Infrastructure (CNKI) from inception to 11th of December. In addition, we will review the relevant trials and references of the included literature and manually searched the grey literature. The two researchers will independently extracted data and information and evaluated the quality of the included literature. The Review Manager software (version 5.3) and Stata software (version 14.0) will be used for data analysis. The mean difference or the standardized mean difference of 95% CI will be used to calculate continuous variables to synthesize the data. In addition, I2 and Cochrane will be used for heterogeneity assessment. Trial registration: PROSPERO registration number CRD42021271278. [ABSTRACT FROM AUTHOR]

Much of the work in alpha NFT has focused on evaluating changes in alpha amplitude. However, the generation mechanism of training-induced alpha activity has not yet been clarified. The present study aimed to identify sources of training-induced alpha activity through four temporal/spectral analytic techniques, i.e., the max peak average (MPA), positive average (PA), negative average (NA) and event-related spectral perturbation average (ERSPA) methods. Thirty-five healthy participants were recruited into an alpha group receiving feedback of 8–12-Hz amplitudes, and twenty-eight healthy participants were recruited into a control group receiving feedback of random 4-Hz amplitudes from the range of 7 to 20 Hz. Twelve sessions were performed within 4 weeks (3 sessions per week). The control group had no change in the amplitude spectrum. In contrast, twenty-nine participants in the alpha group showed significant alpha amplitude increases exclusively and were identified as "responders". A whole-head EEG was recorded for the "responders" after NFT. The epochs of training-induced alpha activity from whole-head EEG were averaged by four different methods for equivalent current dipole source analysis. High agreement and Cohen's kappa coefficients on dipole source localization between each method were observed, showing that the dipole clusters of training-induced alpha activity were consistently located in the precuneus, posterior cingulate cortex (PCC) and middle temporal gyrus. The residual variance (goodness of fit) for dipole estimation of the MPA was significantly smaller than that of the others. Our findings indicate that the precuneus, PCC and middle temporal gyrus play important roles in enhancing training-induced alpha activity. The four averaging methods (especially the MPA method) were suitable for investigating sources of brainwaves. Additionally, three dipoles can be used for dipole source analysis of training-induced alpha activity in future research, especially the training sites are around the central regions. [ABSTRACT FROM AUTHOR]

Manual proteomic sample preparation methods limit sample throughput and often lead to poor data quality when thousands of samples must be analyzed. Automated liquid handler systems are increasingly used to overcome these issues for many of the sample preparation steps. Here, we detail a step-by-step protocol to prepare samples for bottom-up proteomic analysis for Gram-negative bacterial and fungal cells. The full modular protocol consists of three optimized protocols to: (A) lyse Gram-negative bacteria and fungal cells; (B) quantify the amount of protein extracted; and (C) normalize the amount of protein and set up tryptic digestion. These protocols have been developed to facilitate rapid, low variance sample preparation of hundreds of samples, be easily implemented on widely-available Beckman-Coulter Biomek automated liquid handlers, and allow flexibility for future protocol development. By using this workflow 50 micrograms of protein from 96 samples can be prepared for tryptic digestion in under an hour. We validate these protocols by analyzing 47 Pseudomonas putida and Rhodosporidium toruloides samples and show that this modular workflow provides robust, reproducible proteomic samples for high-throughput applications. The expected results from these protocols are 94 peptide samples from Gram-negative bacterial and fungal cells prepared for bottom-up quantitative proteomic analysis without the need for desalting column cleanup and with protein relative quantity variance (CV%) below 15%. [ABSTRACT FROM AUTHOR]

At the end of 2019 Wuhan witnessed an outbreak of "atypical pneumonia" that later developed into a global pandemic. Metagenomic sequencing rapidly revealed the causative agent of this outbreak to be a novel coronavirus denoted SARS-CoV-2. To provide a snapshot of the pathogens in pneumonia-associated respiratory samples from Wuhan prior to the emergence of SARS-CoV-2, we collected bronchoalveolar lavage fluid samples from 408 patients presenting with pneumonia and acute respiratory infections at the Central Hospital of Wuhan between 2016 and 2017. Unbiased total RNA sequencing was performed to reveal their "total infectome", including viruses, bacteria and fungi. We identified 35 pathogen species, comprising 13 RNA viruses, 3 DNA viruses, 16 bacteria and 3 fungi, often at high abundance and including multiple co-infections (13.5%). SARS-CoV-2 was not present. These data depict a stable core infectome comprising common respiratory pathogens such as rhinoviruses and influenza viruses, an atypical respiratory virus (EV-D68), and a single case of a sporadic zoonotic pathogen–Chlamydia psittaci. Samples from patients experiencing respiratory disease on average had higher pathogen abundance than healthy controls. Phylogenetic analyses of individual pathogens revealed multiple origins and global transmission histories, highlighting the connectedness of the Wuhan population. This study provides a comprehensive overview of the pathogens associated with acute respiratory infections and pneumonia, which were more diverse and complex than obtained using targeted PCR or qPCR approaches. These data also suggest that SARS-CoV-2 or closely related viruses were absent from Wuhan in 2016–2017. Author summary: Acute respiratory infections and pneumonia are a significant public health concern on a global scale. This was brought sharply into focus by the emergence of COVID-19 at the end of 2019 in Wuhan, China. Far less is known, however, about the total "infectomes" associated with respiratory infection and pneumonia: that is, all the viruses, bacteria and fungi that might be associated with these important human diseases. Herein, we describe total infectomes in bronchoalveolar lavage fluid samples taken from 408 patients presenting with pneumonia and acute respiratory infection in a single hospital in Wuhan between 2016 and 2017. From these samples we identified 35 pathogen species, comprising 13 RNA viruses, 3 DNA viruses, 16 bacteria and 3 fungi, often at high abundance and including multiple co-infections. We found no evidence for SARS-CoV-2. These data reveal a stable core infectome comprising common respiratory pathogens as well as their history of global transmission. [ABSTRACT FROM AUTHOR]

Background: Pregnancy-related low back pain (PLBP) affects the daily living activities of pregnant women, even leading to fetal agitation and threatened abortion. Kinesio taping (KT) can improve the circulation of blood and provide elastic supports, which is a reliable method to treat low back pain. At present, although many studies have been published on the effects of KT on PLBP, the results are inconsistent, and some studies even report that KT does not affect PLBP. there is still a lack of high-level clinical evidence for the treatment of PLBP with KT. Therefore, this study proposes a protocol for a systematic review and meta-analysis of published Randomized Controlled Trials (RCTs) to evaluate the efficacy and safety of KT for PLBP. Methods: This protocol is guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols. We will search the following database sources of the RCTs: PubMed, the Cochrane Library, EMBASE, Web of Science, Chinese Biomedical Literature Database (CBM), Chinese National Knowledge Infrastructure Database (CNKI), Chinese Science, and the Wanfang Database. From the establishment of the database to April 2021. The retrieval word adopts the combination of theme words and free words. Take "Kinesiotape, Tape Athletic, Orthotic Tape, Athletic Tape, Pregnancy, Pregnancies, Gestation, low back pain" as a term for retrieval. Two independent investigators will conduct an electronic literature search, study selection, data extraction, and quality assessment to summarize and evaluate the efficacy of KT in the treatment of PLBP. Retrospective trials are not included, and the risk of bias will be assessed using the Cochrane bias risk tool. All data analysis will be conducted using Revman5.3 software. Results: Quality outcomes in systematic review studies depend on inclusion and search criteria to obtain high-quality data, as well as how the data are processed and interpreted. Among the results, this study will objectively and comprehensively evaluate the efficacy and safety of the randomized controlled trial of KT in the treatment of PLBP, and make a detailed analysis of the effect of KT in the treatment of PLBP. The results will be analyzed by the Visual Analogue Scale of Pain and the Roland Morris Dysfunction Questionnaire. If applicable, a subgroup analysis will also be performed, which will be grouped according to the duration of pregnancy, grade of pain, etc. Finally, the results are submitted to a peer-reviewed journal for publication. Conclusion: Based on the results, this study will analyze and summarize the effect of KT on improving PLBP. It includes whether KT can improve the pain and lumbar function of PLBP, or it has adverse effects and reactions on pregnant women, then analysis and interpretation of other related issues. It is expected that the results of this study will provide a reference to the method and time of taping for clinical staff, as well as high-quality evidence to resolve the effect of KT on low back pain and provide corresponding guidance for pregnant women with low back pain. It aims to improve the status of low back pain in pregnant women and improve their physical health. Protocol registration number: PROSPERO CRD42021250373; https://clinicaltrials.gov/. [ABSTRACT FROM AUTHOR]

The hepatitis B virus (HBV) core protein (HBc) functions in multiple steps of the viral life cycle. Heteroaryldihydropyrimidine compounds (HAPs) such as Bay41-4109 are capsid protein allosteric modulators that accelerate HBc degradation and inhibit the virion secretion of HBV, specifically by misleading HBc assembly into aberrant non-capsid polymers. However, the subsequent cellular fates of these HAP-induced aberrant non-capsid polymers are not well understood. Here, we discovered that that the chaperone-binding E3 ubiquitin ligase protein STUB1 is required for the removal of Bay41-4109-induced aberrant non-capsid polymers from HepAD38 cells. Specifically, STUB1 recruits BAG3 to transport Bay41-4109-induced aberrant non-capsid polymers to the perinuclear region of cells, thereby initiating p62-mediated macroautophagy and lysosomal degradation. We also demonstrate that elevating the STUB1 level enhances the inhibitory effect of Bay41-4109 on the production of HBeAg and HBV virions in HepAD38 cells, in HBV-infected HepG2-NTCP cells, and in HBV transgenic mice. STUB1 overexpression also facilitates the inhibition of Bay41-4109 on the cccDNA formation in de novo infection of HBV. Understanding these molecular details paves the way for applying HAPs as a potentially curative regimen (or a component of a combination treatment) for eradicating HBV from hepatocytes of chronic infection patients. Author summary: Hepatitis B virus (HBV) infects more than 250 million people worldwide chronically. It is a major pathogen causing liver cirrhosis and hepatocellular carcinoma now. The HBV capsid protein (HBc) plays multiple roles in the viral life cycle, and many antivirals targeting HBc such as Heteroaryldihydropyrimidine compounds (HAPs) are under clinical trial recently. This study aimed to investigate how a HAP compound Bay41-4109 induces the degradation of HBc protein. Bay41-4109 induces aberrant non-capsid polymers, which form in complex with the chaperone-binding E3 ubiquitin ligase protein STUB1 and co-chaperone BAG3 and are transported to the perinuclear compartment. Subsequently, Bay41-4109-induced aberrant non-capsid polymers are removed by p62-mediated macroautophagy and lysosomal degradation. STUB1 overexpression accelerates Bay41-4109-induced degradation of HBc protein, and thus enhances the effect of Bay41-4109 on inhibiting secretion of HBeAg and HBV virions. When Bay41-4109 are enforced during HBV infection, de novo cccDNA formation were also negatively regulated by STUB1 overexpression. Altogether, this study provides novel mechanistic insights into developing more potent and safe HAP-based antiviral treatment. [ABSTRACT FROM AUTHOR]

Background: The nursing education system has evolved with an increased emphasis on student-centred education, such as implementing flipped classroom pedagogy. Given the promising positive educational outcomes, the trend of using flipped classroom pedagogy has become increasingly popular in undergraduate nursing education. However, little is known about how these flipped classroom methods impact on nursing educational practices in limited-resource settings situated in South Asia. Objective: To assess the feasibility of implementing flipped classroom pedagogy in undergraduate nursing education from the nursing students' perspective. Methods: This mixed-methods study employed a quantitative survey and six focus group discussions conducted in three state universities in Sri Lanka. The Nursing Students' Readiness for Flipped Classroom (NSR-FC) questionnaire was used to collect quantitative data. The semi-structured focus group discussions were conducted by using 18 reflective and open-ended questions. Descriptive statistics and multivariate analysis of variance methods were employed when analysing quantitative data. An inductive thematic analysis approach was used to summarize the focus group discussions. Results: The questionnaire survey revealed that nursing students reported high levels of personal, technical, and pedagogical readiness across all three universities, while environmental readiness was perceived as low. The inductive thematic analysis identified three themes, namely: enablers, challenges, and benefits. Specifically, nursing students valued the student-centred approach. They were ready to utilize their own devices to overcome limited technological provision; however, a short training session about how to engage in the flipped classroom was desirable. Also, their exposure to basic educational technology was perceived as adequate and they were aware of the positive outcomes of flipped classroom pedagogy. Conclusion: Nursing students were ready to enrol in a flipped classroom programme. The provision of technological resources in the education environment was identified as a great challenge for flipped classroom implementation. Overall, the findings indicate there are promising feasibilities for the flipped classroom implementation. [ABSTRACT FROM AUTHOR]

This document is a retraction notice for an article titled "TGF-β1 Regulation of Estrogen Production in Mature Rat Leydig Cells." The authors of the article have requested to retract it due to unresolved issues with one of the figures and the unavailability of data. The authors stand by the findings of the article but are unable to be accountable for the reported work. They apologize for the issues with the published article. [Extracted from the article]

Objective: The relationship between the levels of the first 24-h PaCO2 and the prognosis of sepsis-associated encephalopathy (SAE) remains unclear, and the first 24-h optimal target for PaCO2 is currently inconclusive. This study was performed to investigate the correlation between PaCO2 and all-cause mortality for SAE patients, establish a reference range of the initial 24-hour PaCO2 for clinicians in critical care, and explain the possible pathophysiological mechanisms of abnormal PaCO2 levels as a higher mortality risk factor for SAE., Methods: The baseline information and clinical data of patients were extracted from the fourth edition Medical Information Mart for Intensive Care database (MIMIC-IV 2.0). Multivariate logistic regressions were performed to assess the relationship between PaCO2 and all-cause mortality of SAE. Additionally, restricted cubic splines, Kaplan-Meier Survival analyses, propensity score matching (PSM) analyses, and subgroup analyses were conducted., Results: A total of 5471 patients were included in our cohort. In the original and matched cohort, multivariate logistic regression analysis showed that normocapnia and mild hypercapnia may be associated with a more favorable prognosis of SAE patients, and survival analysis supported the findings. In addition, a U-shaped association emerged when examining the initial 24-hour PaCO2 levels in relation to 30-day, 60-day, and 90-day mortality using restricted cubic splines, with an average cut-off value of 36.3mmHg (P for nonlinearity<0.05). Below the cut-off value, higher PaCO2 was associated with lower all-cause mortality, while above the cut-off value, higher PaCO2 was associated with higher all-cause mortality. Subsequent subgroup analyses revealed similar results for the subcohort of GCS≤8 compared to the original cohort. Additionally, when examining the subcohort of GCS>8, a L-shaped relationship between PaCO2 and the three clinical endpoints emerged, in contrast to the previously observed U-shaped pattern. The findings from the subcohort of GCS>8 suggested that patients experiencing hypocapnia had a more unfavorable prognosis, which aligns with the results obtained from corresponding multivariate logistic regression analyses., Conclusion: The retrospective study revealed the association between the first 24-h PaCO2 and all-cause mortality risk (30-day, 60-day, and 90-day) for patients with SAE in ICU. The range (35mmHg-50mmHg) of PaCO2 may be the optimal target for patients with SAE in clinical practice., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Luo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)