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Abstract Background Reduced endometrium thickness and receptivity are two important reasons for recurrent implantation failure (RIF). In order to elucidate differences between these two types of endometrial defects in terms of molecular signatures, cellular interactions, and structural changes, we systematically investigated the single-cell transcriptomic atlas across three distinct groups: RIF patients with thin endometrium (≤ 6 mm, TE-RIF), RIF patients with normal endometrium thickness (≥ 8 mm, NE-RIF), and fertile individuals (Control). Methods The late proliferative and mid-secretory phases of the endometrium were collected from three individuals in the TE-RIF group, two in the NE-RIF group, and three in the control group. The study employed a combination of advanced techniques. Single-cell RNA sequencing (scRNA-seq) was utilized to capture comprehensive transcriptomic profiles at the single-cell level, providing insights into gene expression patterns within specific cell types. Scanning and transmission electron microscopy were employed to visualize ultrastructural details of the endometrial tissue, while hematoxylin and eosin staining facilitated the examination of tissue morphology and cellular composition. Immunohistochemistry techniques were also applied to detect and localize specific protein markers relevant to endometrial receptivity and function. Results Through comparative analysis of differentially expressed genes among these groups and KEGG pathway analysis, the TE-RIF group exhibited notable dysregulations in the TNF and MAPK signaling pathways, which are pivotal in stromal cell growth and endometrial receptivity. Conversely, in the NE-RIF group, disturbances in energy metabolism emerged as a primary contributor to reduced endometrial receptivity. Additionally, using CellPhoneDB for intercellular communication analysis revealed aberrant interactions between epithelial and stromal cells, impacting endometrial receptivity specifically in the TE-RIF group. Conclusion Overall, our findings provide valuable insights into the heterogeneous molecular pathways and cellular interactions associated with RIF in different endometrial conditions. These insights may pave the way for targeted therapeutic interventions aimed at improving endometrial receptivity and enhancing reproductive outcomes in patients undergoing ART. Further research is warranted to validate these findings and translate them into clinical applications for personalized fertility treatments. Trial registration Not applicable.

Tendon injury is a common disorder of the musculoskeletal system, with a higher possibility of occurrence in elderly individuals and athletes. After a tendon injury, the tendon suffers from inadequate and slow healing, resulting in the formation of fibrotic scar tissue, ending up with inferior functional properties. Therapeutic strategies involving the application of growth factors have been advocated to promote tendon healing. Growth and differentiation-5 (GDF-5) represents one such factor that has shown promising effect on tendon healing in animal models and in vitro cultures. Although promising, these studies are limited as the molecular mechanisms by which GDF-5 exerts its effect remain incompletely understood. Starting from broadly introducing essential elements of current understanding about GDF-5, the present review aims to define the effect of GDF-5 and its possible mechanisms of action in tendon healing. Nevertheless, we still need more in vivo studies to explore dosage, application time and delivery strategy of GDF-5, so as to pave the way for future clinical translation.

Abstract Background Shaoyao Decoction (SYD) is a widely recognized herbal formula utilized in traditional Chinese medicine for the treatment of diarrhea. Although it has demonstrated significant effectiveness in clinical practice for treating ulcerative colitis, the precise mechanisms by which it operates remain largely elusive. Methods The active ingredients of SYD were obtained by ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS), which were used to explore the potential pharmacological mechanism based on TCMSP (Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform) and PANTHER (Protein Analysis Through Evolutionary Relationships) classification system. In a mouse model of dextran sulfate sodium (DSS)-induced colitis, mRNA sequencing, 16S rDNA sequencing and targeted metabolomics techniques were used to elucidate the mechanisms of SYD, and immunohistochemistry, immunofluorescence, enzyme linked immunosorbent assay, real time quantitative polymerase chain reaction and western blot were used to test the key targets. In addition, QGP-1 and H9 cells were performed to validate the discoveries from the animal experiments. Results In the mouse model of DSS-induced colitis, SYD effectively alleviated symptoms such as bloody stool, tissue damage, inflammation, intestinal flora dysbiosis and abnormal gene expression. Analyses of both differential expressed genes in colonic tissue and predicted 16S rDNA genes, as well as the analyses of targeted genes from TCMSP based on the active ingredients in UPLC-MS/MS of SYD, uncovered the enrichment of pathways involved in the biosynthesis and degredation of 5-hydroxytryptamine (5-HT). Interestingly, SYD suppressed the relative abundance of key genes in 5-HT synthesis, Tph1(Tryptophan hydroxylase 1) and Ddc (Dopa decarboxylase), in faeces from DSS-induced mice, leading to a reduction in the concentration of fecal 5-HT. Moreover, SYD augmented the production of butyric acid. Subsequently, increasing butyric acid influenced the metabolism of 5-HT in the organism through G protein-coupled receptor 43 by impeding its synthesis, facilitating its transport and degredation. These findings were additionally corroborated in a model utilizing enterochromaffin cell (QGP-1 cells). Furthermore, reduced levels of 5-HT hindered the activation of T lymphocytes (H9 cells) via the PKC (Protein kinase C) and NF-κB (Nuclear factor kappa-B) signaling pathways, by means of HTR1A (5-HT receptor 1A) and HTR3 (5-HT receptor 3). Additionally, diminished secretion of 5-HT resulted in reduced secretion of associated cytokines, thereby alleviating inflammation in the colon. Conclusion Through modulation of T lymphocyte activation mediated by 5-HT metabolism in the local colon via the intestinal flora and its metabolite, SYD effectively mitigated colonic inflammation in DSS-induced mice.

ObjectivesTo develop and validate a deep learning (DL) based automatic segmentation and classification system to classify benign and malignant BI-RADS 4 lesions imaged with ABVS.MethodsFrom May to December 2020, patients with BI-RADS 4 lesions from Centre 1 and Centre 2 were retrospectively enrolled and divided into a training set (Centre 1) and an independent test set (Centre 2). All included patients underwent an ABVS examination within one week before the biopsy. A two-stage DL framework consisting of an automatic segmentation module and an automatic classification module was developed. The preprocessed ABVS images were input into the segmentation module for BI-RADS 4 lesion segmentation. The classification model was constructed to extract features and output the probability of malignancy. The diagnostic performances among different ABVS views (axial, sagittal, coronal, and multi-view) and DL architectures (Inception-v3, ResNet 50, and MobileNet) were compared.ResultsA total of 251 BI-RADS 4 lesions from 216 patients were included (178 in the training set and 73 in the independent test set). The average Dice coefficient, precision, and recall of the segmentation module in the test set were 0.817 ± 0.142, 0.903 ± 0.183, and 0.886 ± 0.187, respectively. The DL model based on multiview ABVS images and Inception-v3 achieved the best performance, with an AUC, sensitivity, specificity, PPV, and NPV of 0.949 (95% CI: 0.945-0.953), 82.14%, 95.56%, 92.00%, and 89.58%, respectively, in the test set.ConclusionsThe developed multiview DL model enables automatic segmentation and classification of BI-RADS 4 lesions in ABVS images.

ObjectiveThis study aims to investigate the pathogenesis of hyperglycemia and its associated vasculopathy using multiomics analyses in diabetes and impaired glucose tolerance, and validate the mechanism using the cell experiments.MethodsIn this study, we conducted a comprehensive analysis of the metagenomic sequencing data of diabetes to explore the key genera related to its occurrence. Subsequently, participants diagnosed with impaired glucose tolerance (IGT), and healthy subjects, were recruited for fecal and blood sample collection. The dysbiosis of the gut microbiota (GM) and its associated metabolites were analyzed using 16S rDNA sequencing and liquid chromatograph mass spectrometry, respectively. The regulation of gene and protein expression was evaluated through mRNA sequencing and data-independent acquisition technology, respectively. The specific mechanism by which GM dysbiosis affects hyperglycemia and its related vasculopathy was investigated using real-time qPCR, Western blotting, and enzyme-linked immunosorbent assay techniques in HepG2 cells and neutrophils.ResultsBased on the published data, the key alterable genera in the GM associated with diabetes were identified as Blautia, Lactobacillus, Bacteroides, Prevotella, Faecalibacterium, Bifidobacterium, Ruminococcus, Clostridium, and Lachnoclostridium. The related metabolic pathways were identified as cholate degradation and L-histidine biosynthesis. Noteworthy, Blautia and Faecalibacterium displayed similar alterations in patients with IGT compared to those observed in patients with diabetes, and the GM metabolites, tauroursodeoxycholic acid (TUDCA) and carnosine (CARN, a downstream metabolite of histidine and alanine) were both found to be decreased, which in turn regulated the expression of proteins in plasma and mRNAs in neutrophils. Subsequent experiments focused on insulin-like growth factor-binding protein 3 and interleukin-6 due to their impact on blood glucose regulation and associated vascular inflammation. Both proteins were found to be suppressed by TUDCA and CARN in HepG2 cells and neutrophils.ConclusionDysbiosis of the GM occurred throughout the entire progression from IGT to diabetes, characterized by an increase in Blautia and a decrease in Faecalibacterium, leading to reduced levels of TUDCA and CARN, which alleviated their inhibition on the expression of insulin-like growth factor-binding protein 3 and interleukin-6, contributing to the development of hyperglycemia and associated vasculopathy.

Both acute and chronic tendon injuries are the most frequently occurring musculoskeletal diseases in human and veterinary medicine, with a limited repertoire of successful and evidenced-based therapeutic strategies. Inflammation has been suggested as a key driver for the formation of scar and adhesion tissue following tendon acute injury, as well as pathological alternations of degenerative tendinopathy. However, prior efforts to completely block this inflammatory process have yet to be largely successful. Recent investigations have indicated that a more precise targeted approach for modulating inflammation is critical to improve outcomes. The nuclear factor-kappaB (NF-κB) is a typical proinflammatory signal transduction pathway identified as a key factor leading to tendon disorders. Therefore, a comprehensive understanding of the mechanism or regulation of NF-κB in tendon disorders will aid in developing targeted therapeutic strategies for human and veterinary tendon disorders. In this review, we discuss what is currently known about molecular components and structures of basal NF-κB proteins and two activation pathways: the canonical activation pathway and the non-canonical activation pathway. Furthermore, we summarize the underlying mechanisms of the NF-κB signaling pathway in fibrosis and adhesion after acute tendon injury, as well as pathological changes of degenerative tendinopathy in all species and highlight the effect of targeting this signaling pathway in tendon disorders. However, to gain a comprehensive understanding of its mechanisms underlying tendon disorders, further investigations are required. In the future, extensive scientific examinations are warranted to full characterize the NF-κB, the exact mechanisms of action, and translate findings into clinical human and veterinary practice.

Abstract Background Gastric cancer (GC) is one of the most common malignancies, affected by several genetic loci in the clinical phenotype. This study aimed to determine the association between PTGER4 and PRKAA1 gene polymorphisms and the risk of GC. Methods A total of 509 GC patients and 507 age and sex-matched healthy controls were recruited to explore the association between PTGER4 and PRKAA1 genetic polymorphisms and GC susceptibility. Logistic regression analysis was used to study the correlation between these SNPs and GC, with odd ratio (OR) and 95% confidence interval (CI) as indicators. Multifactor dimensionality reduction was utilized to analyze the genetic relationships among SNPs. was conducted to predict gene expression, the impact of SNPs on gene expression, and the signaling pathways involved in PTGER4 and PRKAA1. Results Overall, rs10036575 in PTGER4 (OR = 0.82, p = 0.029), rs10074991 (OR = 0.82, p = 0.024) and rs13361707 (OR = 0.82, p = 0.030) in PRKAA1 were associated with susceptibility to GC. Stratification analysis revealed that the effects of these SNPs in PTGER4 and PRKAA1 on GC susceptibility were dependent on smoking and were associated with a reduced risk of adenocarcinoma (p

Abstract Life science studies involving clustered regularly interspaced short palindromic repeat (CRISPR) editing generally apply the best-performing guide RNA (gRNA) for a gene of interest. Computational models are combined with massive experimental quantification on synthetic gRNA-target libraries to accurately predict gRNA activity and mutational patterns. However, the measurements are inconsistent between studies due to differences in the designs of the gRNA-target pair constructs, and there has not yet been an integrated investigation that concurrently focuses on multiple facets of gRNA capacity. In this study, we analyzed the DNA double-strand break (DSB)-induced repair outcomes and measured SpCas9/gRNA activities at both matched and mismatched locations using 926,476 gRNAs covering 19,111 protein-coding genes and 20,268 non-coding genes. We developed machine learning models to forecast the on-target cleavage efficiency (AIdit_ON), off-target cleavage specificity (AIdit_OFF), and mutational profiles (AIdit_DSB) of SpCas9/gRNA from a uniformly collected and processed dataset by deep sampling and massively quantifying gRNA capabilities in K562 cells. Each of these models exhibited superlative performance in predicting SpCas9/gRNA activities on independent datasets when benchmarked with previous models. A previous unknown parameter was also empirically determined regarding the “sweet spot” in the size of datasets used to establish an effective model to predict gRNA capabilities at a manageable experimental scale. In addition, we observed cell type-specific mutational profiles and were able to link nucleotidylexotransferase as the key factor driving these outcomes. These massive datasets and deep learning algorithms have been implemented into the user-friendly web service http://crispr-aidit.com to evaluate and rank gRNAs for life science studies.

BackgroundStenotrophomonas maltophilia is a multidrug-resistant (MDR) opportunistic pathogen with high resistance to most clinically used antimicrobials. The dissemination of MDR S. maltophilia and difficult treatment of its infection in clinical settings are global issues.MethodsTo provide more genetic information on S. maltophilia and find a better treatment strategy, we isolated five S. maltophilia, SMYN41–SMYN45, from a Chinese community that were subjected to antibiotic susceptibility testing, biofilm formation assay, and whole-genome sequencing. Whole-genome sequences were compared with other thirty-seven S. maltophilia sequences.ResultsThe five S. maltophilia strains had similar antibiotic resistance profiles and were resistant to β-lactams, aminoglycosides, and macrolides. They showed similar antimicrobial resistance (AMR) genes, including various efflux pumps, β-lactamase resistance genes (blaL1/2), aminoglycoside resistance genes [aac(6’), aph(3’/6)], and macrolide-resistant gene (MacB). Genome sequencing analysis revealed that SMYN41-SMYN45 belonged to sequence type 925 (ST925), ST926, ST926, ST31, and ST928, respectively, and three new STs were identified (ST925, ST926, and ST928).ConclusionThis study provides genetic information by comparing genome sequences of several S. maltophilia isolates from a community of various origins, with the aim of optimizing empirical antibiotic medication and contributing to worldwide efforts to tackle antibiotic resistance.

It is still a challenge to accurately identify off-target endonuclease edits. Here the authors report PEAC-seq using a Prime Editor to insert a tag to the editing sites and enrich the tagged regions with site-specific primers for sequencing: they show that PEAC-seq could identify DNA translocations.

Precise and reliable gene delivery remains technically challenging. Here, the authors show that rationally designed frameshifting splicing can be used to express genes only in targeted cell types, with the potential to enhance the specificity AAV gene delivery.

Objective: This study aimed to explore the structural and functional characteristics of the fecal-associated microbiome (FAM) between the phlegm-dampness constitution (PDC) and balanced constitution (BC), and to screen the related specific operational taxonomic unit (OTU) biomarkers. Methods: This was a cross-sectional study. After strictly identifying the constitution of subjects, their clinical index was recorded and counted. Fecal samples were collected for 16S rDNA sequencing. Alpha diversity, beta diversity, and the relative abundance of dominant bacterial taxa were used to describe the FAM structure, and the Wilcoxon rank-sum test, MetagenomeSeq, and linear discriminant analysis effect size (LEfSe) were used to screen specific bacterial taxa. Specific OTUs were screened to construct receiver operating characteristic (ROC) curves. Results: Thirty-two subjects were enrolled, including 22 subjects with BC and 10 subjects with PDC. There were significant differences in cold preference, levels of aspartate transaminase, β2-microglobulin, and creatine kinase MB, and alpha diversity indices (Shannon and Shannoneven) between the two groups. In principal coordinate analysis by abund-jaccard distance measure and partial least squares discriminant analysis, bacterial communities clustered separately between the two groups. Furthermore, based on MetagenomeSeq, LEfSe, and the Wilcoxon rank-sum test, a total of 43, 18, and 130 OTUs were differentially distributed between BC group and PDC group, respectively, and OTU200, OTU133, and OTU353 were screened when P≤ .01. The area under the ROC curve constructed from the 3 selected OTUs was 0.93. Conclusion: The FAM structure and related functional characteristics of the PDC group differed from those of the BC group. In particular, OTU200, OTU133, and OTU353 can be used as unique markers of PDC to assist clinical diagnosis.

Abstract Background Insect olfactory proteins can transmit chemical signals in the environment that serve as the basis for foraging, mate searching, predator avoidance and oviposition selection. Semanotus bifasciatus is an important destructive borer pest, but its olfactory mechanism is not clear. We identified the chemosensory genes of S. bifasciatus in China, then we conducted a phylogenetic analysis of the olfactory genes of S. bifasciatus and other species. And the expression profiles of odorant binding proteins (OBPs) genes in different tissues and different genders of S. bifasciatus were determined by quantitative real-time PCR for the first time. Results A total of 32 OBPs, 8 chemosensory proteins (CSPs), 71 odorant receptors (ORs), 34 gustatory receptors (GRs), 18 ionotropic receptors (IRs), and 3 sensory neuron membrane proteins (SNMPs) were identified. In the tissue expression analysis of OBP genes, 7 OBPs were higher expressed in antennae, among them, SbifOBP2, SbifOBP3, SbifOBP6, SbifOBP7 and SbifOBP20 were female-biased expression, while SbifOBP1 was male-biased expression and SbifOBP22 was no-biased expression in antennae. In addition, the expressed levels of SbifOBP4, SbifOBP12, SbifOBP15, SbifOBP27 and SbifOBP29 were very poor in the antennae, and SbifOBP4 and SbifOBP29 was abundant in the head or legs, and both of them were male-biased expression. While SbifOBP15 was highly expressed only at the end of the abdomen with its expression level in females three times than males. Other OBPs were expressed not only in antennae but also in various tissues. Conclusion We identified 166 olfactory genes from S. bifasciatus, and classified these genes into groups and predicted their functions by phylogenetic analysis. The majority of OBPs were antenna-biased expressed, which are involved in odor recognition, sex pheromone detection, and/or host plant volatile detection. However, also some OBPs were detected biased expression in the head, legs or end of the abdomen, indicating that they may function in the different physiological processes in S. bifasciatus.

Abstract Neutrophil migration into the site of infection is necessary for antibacterial innate defense, whereas impaired neutrophil migration may result in excessive inflammation and even sepsis. The neutrophil migration directed by extracellular signals such as chemokines has been extensively studied, yet the intrinsic mechanism for determining neutrophil ability to migrate needs further investigation. N 6 -methyladenosine (m6A) RNA modification is important in immunity and inflammation, and our preliminary data indicate downregulation of RNA m6A demethylase alkB homolog 5 (ALKBH5) in neutrophils during bacterial infection. Whether m6A modification and ALKBH5 might intrinsically modulate neutrophil innate response remain unknown. Here we report that ALKBH5 is required for antibacterial innate defense by enhancing intrinsic ability of neutrophil migration. We found that deficiency of ALKBH5 increased mortality of mice with polymicrobial sepsis induced by cecal ligation and puncture (CLP), and Alkbh5-deficient CLP mice exhibited higher bacterial burden and massive proinflammatory cytokine production in the peritoneal cavity and blood because of less neutrophil migration. Alkbh5-deficient neutrophils had lower CXCR2 expression, thus exhibiting impaired migration toward chemokine CXCL2. Mechanistically, ALKBH5-mediated m6A demethylation empowered neutrophils with high migration capability through altering the RNA decay, consequently regulating protein expression of its targets, neutrophil migration-related molecules, including increased expression of neutrophil migration-promoting CXCR2 and NLRP12, but decreased expression of neutrophil migration-suppressive PTGER4, TNC, and WNK1. Our findings reveal a previously unknown role of ALKBH5 in imprinting migration-promoting transcriptome signatures in neutrophils and intrinsically promoting neutrophil migration for antibacterial defense, highlighting the potential application of targeting neutrophil m6A modification in controlling bacterial infections.

Abstract. The vestibular system involves high-level sensory and cognitive processes, such as spatial perception, balance control, visual stability, and emotional control. Vestibular dysfunction can induce vertigo, blurred vision, postural imbalance, walking instability, and spatial discomfort, which causes serious damage to health. It has long been known that after peripheral vestibular lesion, vestibular dysfunction may spontaneously recover. This is known as vestibular compensation. However, at least 20% to 30% of patients with vestibular disorders cannot yield vestibular compensation and remain with vestibular dysfunction for the rest of their lives. The exploration of the biological characteristics and regulatory factors of the loss and reestablishment of vestibular function will establish a new understanding of the mechanism of vestibular compensation and provide new tools and strategies for promoting vestibular rehabilitation. We aim to comprehensively review the mechanism of vestibular compensation and discuss future directions in this field.

Symptoms of vertigo are frequently reported and are usually accompanied by eye-movements called nystagmus. In this article, we designed a three-dimensional nystagmus recognition model and a benign paroxysmal positional vertigo automatic diagnosis system based on deep neural network architectures (Chinese Clinical Trials Registry ChiCTR-IOR-17010506). An object detection model was constructed to track the movement of the pupil centre. Convolutional neural network-based models were trained to detect nystagmus patterns in three dimensions. Our nystagmus detection models obtained high areas under the curve; 0.982 in horizontal tests, 0.893 in vertical tests, and 0.957 in torsional tests. Moreover, our automatic benign paroxysmal positional vertigo diagnosis system achieved a sensitivity of 0.8848, specificity of 0.8841, accuracy of 0.8845, and an F1 score of 0.8914. Compared with previous studies, our system provides a clinical reference, facilitates nystagmus detection and diagnosis, and it can be applied in real-world medical practices.

ObjectiveCisplatin is a broad-spectrum anti-tumour drug commonly used in clinical practice. However, its ototoxicity greatly limits its clinical application, and no effective method is available to prevent this effect. Endoplasmic reticulum stress (ERS) is reportedly involved in cisplatin ototoxicity, but the exact mechanism remains unclear. Therefore, this study aimed to investigate the role of eukaryotic translation initiation factor 2α (eIF2α) signalling and its dephosphorylation inhibitor salubrinal in cisplatin ototoxicity.MethodsWe evaluated whether salubrinal could protect against cisplatin-induced damage in House Ear Institute-Organ of Corti 1 (HEI-OC1) cells and mouse cochlear explants. By knocking down eIF2α, we elucidated the vital role of eIF2α in cisplatin-induced damage in HEI-OC1 cells. Whole-mount immunofluorescent staining and confocal microscopy of mouse cochlear explants and HEI-OC1 cells were performed to analyse cisplatin-induced damage in cochlear hair cells and the auditory cell line.ResultsData suggested salubrinal attenuated cisplatin-induced hair cell injury by inhibiting apoptosis. In addition, salubrinal significantly reduced ERS levels in hair cells via eIF2α signalling, while eIF2α knockdown inhibited the protective effect of salubrinal.SignificanceSalubrinal and eIF2α signalling play a role in protecting against cisplatin-induced ototoxicity, and pharmacological inhibition of eIF2α-mediated ERS is a potential treatment for cisplatin-induced damage in the cochlea and HEI-OC1 cells.

As a quarantine pest of conifer, Sirex noctilio has caused widespread harm around the world. It is expected that the molecular mechanism of protein–ligand binding can be elucidated to carry out the pest control. Through studies of SnocOBP12–ligand hydrophobic binding and dynamics and responsible amino acid residues identification, we got some promising results. SnocOBP12 had a general and excellent affinity for host plant volatiles, and may be a key protein for S. noctilio to find host plants. Among the many odor molecules that are bound to SnocOBP12, (−)-α-cedrene and (E)-β-farnesene from host plants and (−)-globuol from the symbiotic fungi of Sirex noctilio stood out and formed highly stable complexes with SnocOBP12. By the molecular mechanics Poisson–Boltzmann surface area (MM-PBSA) method, the calculated free binding energy of the three complexes was −30.572 ± 0.101 kcal/mol, −28.349 ± 0.119 kcal/mol and −25.244 ± 0.152 kcal/mol, respectively. It was found that the van der Waals energy contributed to the stability of the complexes. Some key amino acid residues were also found: LEU74 and TYR109 were very important for SnocOBP12 to stably bind (−)-α-cedrene, while for (E)-β-farnesene, ILE6, MET10, and LEU74 were very important for the stable binding system. We discovered three potential ligands and analyzed the interaction pattern of the protein with them, this paper provides a favorable molecular basis for optimizing the attractant formulation. Investigation of the binding characteristics in the olfactory system at the molecular level is helpful to understand the behavior of S. noctilio and develop new methods for more effective and environmentally friendly pest control.

With the development of imaging and space-borne satellite technology, a growing number of multipolarized SAR imageries have been implemented for object detection. However, most of the existing public SAR ship datasets are grayscale images under single polarization mode. To make full use of the polarization characteristics of multipolarized SAR, a dual-polarimetric SAR dataset specifically used for ship detection is presented in this paper (DSSDD). For construction, 50 dual-polarimetric Sentinel-1 SAR images were cropped into 1236 image slices with the size of 256 × 256 pixels. The variances and covariance of both VV and VH polarization were fused into R,G,B channels of the pseudo-color image. Each ship was labeled with both a rotatable bounding box (RBox) and a horizontal bounding box (BBox). Apart from 8-bit pseudo-color images, DSSDD also provides 16-bit complex data for readers. Two prevalent object detectors R3Det and Yolo-v4 were implemented on DSSDD to establish the baselines of the detectors with the RBox and BBox respectively. Furthermore, we proposed a weakly supervised ship detection method based on anomaly detection via advanced memory-augmented autoencoder (MemAE), which can significantly remove false alarms generated by the two-parameter CFAR algorithm applied upon our dual-polarimetric dataset. The proposed advanced MemAE method has the advantages of a lower annotation workload, high efficiency, good performance even compared with supervised methods, making it a promising direction for ship detection in dual-polarimetric SAR images. The dataset is available on github.

The onset of apoptosis is characterized by a cascade of caspase activation, where initiator caspases are activated by a multimeric adaptor complex known as the apoptosome. In Drosophila melanogaster, the initiator caspase Dronc undergoes autocatalytic activation in the presence of the Dark apoptosome. Despite rigorous investigations, the activation mechanism for Dronc remains elusive. Here, we report the cryo-EM structures of an auto-inhibited Dark monomer and a single-layered, multimeric Dark/Dronc complex. Our biochemical analysis suggests that the auto-inhibited Dark oligomerizes upon binding to Dronc, which is sufficient for the activation of both Dark and Dronc. In contrast, the previously observed double-ring Dark apoptosome may represent a non-functional or "off-pathway" conformation. These findings expand our understanding on the molecular mechanism of apoptosis in Drosophila. [ABSTRACT FROM AUTHOR]

Viral proteases play key roles in viral replication, and they also facilitate immune escape by proteolyzing diverse target proteins. Deep profiling of viral protease substrates in host cells is beneficial for understanding viral pathogenesis and for antiviral drug discovery. Here, we utilized substrate phage display coupled with protein network analysis to identify human proteome substrates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral proteases, including papainlike protease (PLpro) and 3C-like protease (3CLpro). We first performed peptide substrates selection of PLpro and 3CLpro, and we then used the top 24 preferred substrate sequences to identify a total of 290 putative protein substrates. Protein network analysis revealed that the top clusters of PLpro and 3CLpro substrate proteins contain ubiquitin-related proteins and cadherin-related proteins, respectively. We verified that cadherin-6 and cadherin-12 are novel substrates of 3CLpro, and CD177 is a novel substrate of PLpro using in vitro cleavage assays. We thus demonstrated that substrate phage display coupled with protein network analysis is a simple and high throughput method to identify human proteome substrates of SARS-CoV-2 viral proteases for further understanding of virus-host interactions. [ABSTRACT FROM AUTHOR]

Promoting charge separation is still the main challenge in the rational design of photocatalysts for visible light photocatalytic reduction of CO2. Based on the unique advantages of the Eu3+ single atom and the Type-II heterojunction in the field of photocatalytic reduction, a Eu3+ single atom doped CdS/InVO4 Type-II heterojunction was successfully constructed through the combination of hydrothermal and in situ synthesis. The prepared CdS/InVO4:Eu3+ single atom composite material has excellent photocatalytic CO2 reduction activity under visible light. The XPS test results show that the In 3d, O 1s, V 2p, and Eu 3d peaks of 10-CdS/IVO:Eu3+ move slightly towards a low energy direction, while, the positions of Cd 3d and S 2p peaks are both shifted to the direction of high binding energies, which indicated that the electrons can be transferred from CdS to IVO with the help of Eu3+. The CO yield of CdS/InVO4:Eu3+ was 11.02 μmol g−1 h−1, which was almost 2.4 times that of pure InVO4 and 1.9 times that of pure CdS, and the yield of CH4 of CdS/InVO4:Eu3+ reached 8.24 μmol g−1 h−1, which was 5.3 times and 10.6 times that of InVO4 and CdS, respectively. Both the theoretical and experimental results show that the single atom Eu3+ can not only modify InVO4 and activate CO2 molecules, but can also promote charge separation between the interface and improve the photocatalytic performance. It is expected that the research results of this paper can provide a novel idea for the rational design of rare earth monatomic catalysts. [ABSTRACT FROM AUTHOR]

The legs of insects play an important role in their daily behaviour, especially reproduction. Entomologists have performed much research on the role of the leg in different behaviours of beetles, an important group in the insect family, but relatively little has been done to study the ultrastructure and transcriptome of their legs. Hence, we systematically studied the ultrastructure and gene expression of the leg of G. cantor, a polygynous beetle, and compared its male and female diversity. In this study, we found the fore-leg, mid-leg and hind-leg of the female were significantly longer than those of the male. From the perspective of intuitive structural differences, we also compared the ultrastructures of the adhesion structure (tarsal) of males and females. The tarsal functional structure of the adult leg mainly includes sensilla and an adhesion structure. The sensilla on the tarsal joint mainly include sensilla chaetica (SCh II, SCh III) and sensilla trichodea (ST II). The adhesion structure includes disc-shaped bristles (di), lanceolate bristles (la), serrated bristles (se), spatula-shaped bristles (spl) and mushroom-shaped bristles (mus). Although there was no significant difference in sensillum distribution or type between males and females, there were significant differences in the distribution and species of adhesion structures between the fore-leg, mid-leg, and hind-leg of the same sex and between males and females. Therefore, different adhesion structures play different roles in various behaviours of beetles. On the other hand, the transcriptome results of male and female legs were screened for a subset of olfaction- and mechanics-related genes. We discovered that the male leg showed upregulation of 1 odorant binding protein (OBP), 2 Olfactory receptors (ORs) and 2 Chemosensory proteins (CSPs). Meanwhile, the female leg showed upregulation of 3 OBPs, 1 OR, 1 Gustatory receptor (GR) and 3 Mechanosensitive proteins (MSPs). An in-depth examination of the ultrastructure and molecular composition of the legs can elucidate its function in the reproductive behavior of G. cantor. Moremore, this investigation will serve as a cornerstone for subsequent research into the underlying behavioral mechanisms.

Based on the latest drilling cores, thin sections, and 3D seismic data, types, features, and evolution processes of Cambrian–Ordovician carbonate platforms in the Gucheng and Xiaotang areas are studied, and favorable exploration zones in this area are also discussed. There are two types of carbonate platforms developed in the Cambrian–Ordovician in the Gucheng–Xiaotang area, namely, carbonate ramp and rimmed platforms, and the evolution process of the platform in the Gucheng area is different from that in Xiaotang area. In the Early Cambrian, the study area was a homoclinal carbonate ramp. During the Middle to Late Cambrian, it evolved into a rimmed platform, with 5 phases of mound shoals developed. In the southern area, mound shoals were in progradational arrangement and the third and fourth stages of mound shoals suffering exposure and further developed abundant karst vugs. In the northern area, the mound shoals appeared in a superposition of aggradation–weak progradation, the third, fourth, and fifth stages of mound shoals suffered exposure and dissolution, and the platform slope developed gravity flow deposits. In the Early to Middle Ordovician, the southern area gradually evolved into a distally steepened carbonate ramp, where retrogradational dolomitic shoal developed; while the northern part experienced an evolution process from a weakly rimmed platform to a distally steepened carbonate ramp, and developed two or three stages of retrogradational mound shoals. The high-frequency oscillation of sea level and local exposure and dissolution were beneficial to the formation of mound or shoal reservoirs in platform margin and ramp, and the configuration of these reservoirs with low energy slope–basin facies source rocks could form good oil-gas enrichment zones. The dolomitic shoal in the Ordovician platform ramp is the practical exploration field for increasing reserve and production in the Gucheng area. The mound shoal at the Cambrian rimmed platform margin is the key exploration object in the Xiaotang area. In addition, the Cambrian slope gravity flow deposits can be taken as the favorable exploration fields in the study area.

Based on the latest drilling core, thin section, 3D seismic, well logging data as well as exploration results, the sequence stratigraphy and sedimentary microfacies of the Middle—Lower Ordovician carbonates in Gucheng area, and their controlling effects on the development of reservoir were examined by the theories and methods of fine carbonate sedimentology. The results show that the Middle—Lower Ordovician in Gucheng area is a set of typical carbonate ramp deposits, which can be divided into 10 microfacies in 4 subfacies as follows: back ramp, inner shallow ramp, outer shallow ramp, and deep ramp. The back ramp subfacies consists of muddy-dolomitic flat and dolomitic lagoon microfacies; it is dominated by lamellar micrite dolomite tight in lithology. The inner shallow ramp subfacies includes dolomitic shoal and dolomitic flat in shoal top and dolomitic flat between shoals microfacies; it is mainly composed of crystal dolomite with metasomatic residual structure, as well as abundant karst vugs and intercrystalline pores. The crystal dolomite has an average porosity of 4.36%. The outer ramp subfacies includes medium—high and low energy grain shoal and inter-shoal microfacies; it is dominated by sandy limestone, oolitic limestone, and micrite limestone with few pores. The deep ramp subfacies is dominated by low-energy argillaceous deposits, with local presences of storm shoal microfacies. The Lower—Middle Ordovician has six third-order sequences from bottom to top, among which sequence (SQ3) represents the third member of Yingying Formation. The main reservoir has three fourth-order high-frequency sequences. Apparently, the favorable reservoir in the study area is jointly controlled by sedimentary microfacies and high frequency sequence in the carbonate ramp. The former controls the primary pore structure, and the latter controls the intensities of karstification exposure and dolomitization in the penecontemporaneous period. The dolomitic shoals and top dolomitic flats of different stages, superimposed and connected into favorable reservoirs of considerable scale like “platform margin”, are favorable exploration facies in the carbonate ramp.

Although monosodium glutamate (MSG) is a widely used food additive, its safety and systemic side effects have not been fully clarified. The intestinal flora is closely associated with human health; however, it remains unclear whether MSG consumption can affect health by acting on the intestinal flora. In this study, serum biomarkers, intestinal structure, intestinal immunity, and intestinal flora were examined to investigate the effects of different doses of sodium glutamate on the body, intestinal function, and intestinal flora of mice. The results showed that 30 mg/kg MSG had no significant effect on serum C-reactive protein, trimethylamine N-oxide, angiotensin II, intestinal interleukin (IL)-1β, IL-6, tumor necrosis factor-α, secretory IgA and fecal albumin in mice, but also promoted intestinal development and regulated the intestinal flora. Moreover, 1500 mg/kg MSG increased the risk of cardiovascular disease and damaged the intestinal structure and flora. In this study, MSG was also found to be healthier than salt at the equivalent sodium concentration. Collectively, these findings suggested that low doses of MSG were safe for mice and may have some health benefits as a probiotic by promoting intestinal development and regulating the intestinal flora.

Background: Due to the highly variable prognosis of low-grade gliomas (LGGs), it is important to find robust biomarkers for predicting clinical outcomes. Aging cancer-associated fibroblasts (CAFs) within the senescent stroma of a tumor microenvironment (TME) have been recently reported to play a key role in tumor development. However, there are few studies focusing on this topic in gliomas.Methods and Results: Based on the transcriptome data from TCGA and CGGA databases, we identified aging CAF-related genes (ACAFRGs) in LGGs by the weighted gene co-expression network analysis (WGCNA) method, followed by which LGG samples were classified into two aging CAF-related gene clusters with distinct prognosis and characteristics of the TME. Machine learning algorithms were used to screen out eight featured ACAFRGs to characterize two aging CAF-related gene clusters, and a nomogram model was constructed to predict the probability of gene cluster A for each LGG sample. Then, a powerful aging CAF scoring system was developed to predict the prognosis and response to immune checkpoint blockage therapy. Finally, the ACAFRGs were verified in two glioma-related external datasets. The performance of the aging CAF score in predicting the immunotherapy response was further validated in two independent cohorts. We also confirmed the expression of ACAFRGs at the protein level in glioma tissues through the Human Protein Atlas website and Western blotting analysis.Conclusion: We developed a robust aging CAF scoring system to predict the prognosis and immunotherapy response in LGGs. Our findings may provide new targets for therapeutics and contribute to the exploration focusing on aging CAFs.

Multiple Sclerosis (MS) is a highly disabling neurological disease characterized by inflammation, neuronal damage, and demyelination. Vision impairment is one of the major clinical features of MS. Previous studies from our lab have shown that MDL 72527, a pharmacological inhibitor of spermine oxidase (SMOX), is protective against neurodegeneration and inflammation in the models of diabetic retinopathy and excitotoxicity. In the present study, utilizing the experimental autoimmune encephalomyelitis (EAE) model of MS, we determined the impact of SMOX blockade on retinal neurodegeneration and optic nerve inflammation. The increased expression of SMOX observed in EAE retinas was associated with a significant loss of retinal ganglion cells, degeneration of synaptic contacts, and reduced visual acuity. MDL 72527-treated mice exhibited markedly reduced motor deficits, improved neuronal survival, the preservation of synapses, and improved visual acuity compared to the vehicle-treated group. The EAE-induced increase in macrophage/microglia was markedly reduced by SMOX inhibition. Upregulated acrolein conjugates in the EAE retina were decreased through MDL 72527 treatment. Mechanistically, the EAE-induced ERK-STAT3 signaling was blunted by SMOX inhibition. In conclusion, our studies demonstrate the potential benefits of targeting SMOX to treat MS-mediated neuroinflammation and vision loss.

The extensive application of building information modeling (BIM) technology has brought opportunities and challenges to safety risk management in the field of prefabricated building construction. It is of great significance to provide timely information and knowledge for safety risk decisions in prefabricated building construction, and to display this information visually. In response, based on the ontology theory and using the Revit software, in this study we aimed to establish a monitoring system for the construction of prefabricated buildings, which was verified through a practical case. The results revealed that, first, ontology technology can be applied in the Revit software through plug-in integration, and knowledge regarding construction safety risk management in prefabricated building construction can be shared, reused, and accumulated using this system. Second, problems with the design and construction models of prefabricated buildings that do not meet the specification requirements can be detected by the monitoring system in the Revit software. Third, automatic risk identification and response methods using ontology theory and BIM technologies can effectively promote construction safety risk management performance in relation to prefabricated buildings. These findings examine the application of ontology to the field of prefabricated construction safety risk management for the first time, enrich the research on ontology technology, and contribute to safety risk management in the construction of prefabricated buildings.

Background Studies have confirmed that executive function in overweight and obese children is closely related to obesity and may have a bidirectional association. Aerobic exercise, as an effective intervention, can effectively promote their brain development and cognitive function, especially executive function, but the quantitative relationship of the improvement effect still needs to be further explored. Objective To systematically evaluate the intervention effect of aerobic exercise on executive function-related indexes in overweight and obese children. Methods Randomized controlled trials of aerobic exercise interventions for executive function in overweight and obese children were searched in CNKI, Wanfang Data, CBM, Cochrane Library, PubMed, Embase, and Web of Science databases, and the timeframe for searching was from the establishment of each database to July 2023. The quality of the included literature was assessed according to the Cochrane Risk of Bias Assessment Tool, and Meta-analysis of outcome indicators was performed using RevMan 5.3 and Stata 15.0 software. Results Nine randomized controlled trials, including 940 overweight and obese children, were finally included. The results of Meta-analysis showed that a single session of aerobic exercise intervention was effective in improving the executive function of overweight and obese children (WMD=-6.98, 95%CI=-11.89 to -2.07, P=0.005). Subgroup analyses showed no significant differences in the improvement of any of the executive function subcomponents in overweight and obese children with a single intervention duration of less than 30 minutes of aerobic exercise (WMD=-0.84, 95%CI=-9.37 to 7.68, P=0.85) ; aerobic exercise with a single intervention duration longer than 30 minutes improved inhibitory function in overweight and obese children (WMD=-10.50, 95%CI=-19.15 to -1.85, P=0.02). When a long-term exercise intervention was carried out (the intervention period was 8 weeks), in contrast to the control group, the aerobic exercise improved interference control in overweight and obese children (WMD=-0.16, 95%CI=-0.18 to -0.14, P

Background Mild cognitive impairment (MCI) is highly prevalent in hypertensive patients, but the current studies on MCI in hypertension mostly focus on the elderly group, while scarcely involve young and middle-aged patients. Objective To investigate the prevalence and associated factors of MCI in young and middle-aged hospitalized patients with hypertension. Methods A convenience sample of 213 young and middle-aged hypertensive inpatients were recruited from a tertiary grade A hospital in Harbin from May to December 2021. The General Demographic Questionnaire, Montreal Cognitive Assessment (MoCA) , and the Type-D Scale-14 (DS14) were used for understanding patients' demographics, cognitive impairment status, and D-type personality prevalence, respectively. Multiple Logistic regression was used to analyze associated factors of MCI. Results The prevalence of MCI was 37.56% (80/213) . Multiple Logistic regression analysis showed that age〔OR=1.073, 95%CI (1.033, 1.115) 〕, education level〔junior college education level: OR=0.278, 95%CI (0.084, 0.920) , smoking history〔OR=2.494, 95%CI (1.146, 5.426) 〕, stage of hypertension〔stage 2: OR=3.442, 95%CI (1.252, 9.468) ; stage 3: OR=3.934, 95%CI (1.518, 10.193) 〕, D-type personality〔OR=2.160, 95%CI (1.015, 4.598) , TG〔OR=1.596, 95%CI (1.125, 2.265) 〕, and HDL-C〔OR=0.185, 95%CI (0.049, 0.707) 〕were influential factors of MCI in hypertension (P