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Abstract The application of nanoscale scaffolds has become a promising strategy in vaccine design, with protein-based nanoparticles offering desirable avenues for the biocompatible and efficient delivery of antigens. Here, we presented a novel endogenous capsid-forming protein, activated-regulated cytoskeleton-associated protein (ARC), which could be engineered through the plug-and-play strategy (SpyCatcher3/SpyTag3) for multivalent display of antigens. Combined with the self-assembly capacity and flexible modularity of ARC, ARC-based vaccines elicited robust immune responses against Mpox or SARS-CoV-2, comparable to those induced by ferritin-based vaccines. Additionally, ARC-based nanoparticles functioned as immunostimulants, efficiently stimulating dendritic cells and facilitating germinal center responses. Even without adjuvants, ARC-based vaccines generated protective immune responses in a lethal challenge model. Hence, this study showed the feasibility of ARC as a novel protein-based nanocarrier for multivalent surface display of pathogenic antigens and demonstrated the potential of exploiting recombinant mammalian retrovirus-like protein as a delivery vehicle for bioactive molecules. Graphic Abstract

Abstract The ORF9b protein, derived from the nucleocapsid’s open-reading frame in both SARS-CoV and SARS-CoV-2, serves as an accessory protein crucial for viral immune evasion by inhibiting the innate immune response. Despite its significance, the precise regulatory mechanisms underlying its function remain elusive. In the present study, we unveil that the ORF9b protein of SARS-CoV-2, including emerging mutant strains like Delta and Omicron, can undergo ubiquitination at the K67 site and subsequent degradation via the proteasome pathway, despite certain mutations present among these strains. Moreover, our investigation further uncovers the pivotal role of the translocase of the outer mitochondrial membrane 70 (TOM70) as a substrate receptor, bridging ORF9b with heat shock protein 90 alpha (HSP90α) and Cullin 5 (CUL5) to form a complex. Within this complex, CUL5 triggers the ubiquitination and degradation of ORF9b, acting as a host antiviral factor, while HSP90α functions to stabilize it. Notably, treatment with HSP90 inhibitors such as GA or 17-AAG accelerates the degradation of ORF9b, leading to a pronounced inhibition of SARS-CoV-2 replication. Single-cell sequencing data revealed an up-regulation of HSP90α in lung epithelial cells from COVID-19 patients, suggesting a potential mechanism by which SARS-CoV-2 may exploit HSP90α to evade the host immunity. Our study identifies the CUL5-TOM70-HSP90α complex as a critical regulator of ORF9b protein stability, shedding light on the intricate host–virus immune response dynamics and offering promising avenues for drug development against SARS-CoV-2 in clinical settings.

Abstract Background Indigenous Chinese cattle have abundant genetic diversity and a long history of artificial selection, giving local breeds advantages in adaptability, forage tolerance and resistance. The detection of selective sweeps and comparative genome analysis of selected breeds and ancestral populations provide a basis for understanding differences among breeds and for the identification and utilization of candidate genes. We investigated genetic diversity, population structure, and signatures of selection using genome-wide sequencing data for a new breed of Qinchuan cattle (QNC, n = 21), ancestral Qinchuan cattle (QCC, n = 20), and Zaosheng cattle (ZSC, n = 19). Results A population structure analysis showed that the ancestry components of QNC and ZSC were similar. In addition, the QNC and ZSC groups showed higher proportions of European taurine ancestry than that of QCC, and this may explain the larger body size of QNC, approaching that of European cattle under long-term domestication and selection. A neighbor-joining tree revealed that QCC individuals were closely related, whereas QNC formed a distinct group. To search for signatures of selection in the QNC genome, we evaluated nucleotide diversity (θπ), the fixation index (F ST) and Tajima’s D. Overlapping selective sweeps were enriched for one KEGG pathway, the apelin signaling pathway, and included five candidate genes (MEF2A, SMAD2, CAMK4, RPS6, and PIK3CG). We performed a comprehensive review of genomic variants in QNC, QCC, and ZSC using whole-genome sequencing data. QCC was rich in novel genetic diversity, while diversity in QNC and ZSC cattle was reduced due to strong artificial selection, with divergence from the original cattle. Conclusions We identified candidate genes associated with production traits. These results support the success of selective breeding and can guide further breeding and resource conservation of Qinchuan cattle.

Salvia miltiorrhiza Bunge extracts, known for their diverse biological activities, often have remarkable efficacy in treating pulmonary diseases overlooked due to their specific cardiovascular actions. With the recent outbreak of COVID-19, research into pulmonary-related diseases has garnered significant attention. Salvia miltiorrhiza Bunge extracts can be broadly categorized into lipophilic and hydrophilic components; however, a comprehensive summary of their mechanisms in treating pulmonary diseases is lacking. Therefore, this review aims to systematically summarize the therapeutic mechanisms of 10 major Salvia miltiorrhiza Bunge extracts in treating pulmonary fibrosis, lung cancer, acute lung injury, and chronic obstructive pulmonary disease, with the goal of identifying promising options for efficacious therapies.

Abstract Genetic and epigenetic alterations occur in many physiological and pathological processes. The existing knowledge regarding the association of PIWI‐interacting RNAs (piRNAs) and their genetic variants on risk and progression of prostate cancer (PCa) is limited. In this study, three genome‐wide association study datasets are combined, including 85,707 PCa cases and 166,247 controls, to uncover genetic variants in piRNAs. Functional investigations involved manipulating piRNA expression in cellular and mouse models to study its oncogenetic role in PCa. A specific genetic variant, rs17201241 is identified, associated with increased expression of PROPER (piRNA overexpressed in prostate cancer) in tumors and are located within the gene, conferring an increased risk and malignant progression of PCa. Mechanistically, PROPER coupled with YTHDF2 to recognize N6‐methyladenosine (m6A) and facilitated RNA‐binding protein interactions between EIF2S3 at 5′‐untranslated region (UTR) and YTHDF2/YBX3 at 3′‐UTR to promote DUSP1 circularization. This m6A‐dependent mRNA‐looping pattern enhanced DUSP1 degradation and inhibited DUSP1 translation, ultimately reducing DUSP1 expression and promoting PCa metastasis via the p38 mitogen‐activated protein kinase (MAPK) signaling pathway. Inhibition of PROPER expression using antagoPROPER effectively suppressed xenograft growth, suggesting its potential as a therapeutic target. Thus, targeting piRNA PROPER‐mediated genetic and epigenetic fine control is a promising strategy for the concurrent prevention and treatment of PCa.

ABSTRACT Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is crucial for protecting vulnerable individuals, yet individuals with type 2 diabetes mellitus (T2DM) often exhibit impaired vaccine responses. Emerging evidence suggests that the composition of the host microbiota, crucial in immune regulation and development, influences vaccine efficacy. This study aimed to characterize the relationships between the SARS-CoV-2 inactivated vaccine and the host microbiota (specifically, gut and lung microbiota) of C57BL/6 mice with T2DM. Employing 16S rRNA metagenomic sequencing and ultra-high-performance liquid chromatography-mass spectrometry, we observed lower alpha diversity and distinct beta diversity in fecal microbiota before vaccination and in gut microbiota 28 days post-vaccination between T2DM mice and healthy mice. Compared with healthy mice, T2DM mice showed a higher Firmicutes/Bacteroidetes ratio 28 days post-vaccination. Significant alterations in gut microbiota composition were detected following vaccination, while lung microbiota remained unchanged. T2DM was associated with a diminished initial IgG antibody response against the spike protein, which subsequently normalized after 28 days. Notably, the initial IgG response positively correlated with fecal microbiota alpha diversity pre-vaccination. Furthermore, after 28 days, increased relative abundance of gut probiotics (Bifidobacterium and Lactobacillus) and higher levels of the gut bacterial tryptophan metabolite, indole acrylic acid, were positively associated with IgG levels. These findings suggest a potential link between vaccine efficacy and gut microbiota composition. Nonetheless, further research is warranted to elucidate the precise mechanisms underlying the impact of the gut microbiome on vaccine response. Overall, this study enhances our understanding of the intricate relationships among host microbiota, SARS-CoV-2 vaccination, and T2DM, with potential implications for improving vaccine efficacy.IMPORTANCEOver 7 million deaths attributed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by 6 May 2024 underscore the urgent need for effective vaccination strategies. However, individuals with type 2 diabetes mellitus (T2DM) have been identified as particularly vulnerable and display compromised immune responses to vaccines. Concurrently, increasing evidence suggests that the composition and diversity of gut microbiota, crucial regulators of immune function, may influence the efficacy of vaccines. Against this backdrop, our study explores the complex interplay among SARS-CoV-2 inactivated vaccination, T2DM, and host microbiota. We discover that T2DM compromises the initial immune response to the SARS-CoV-2 inactivated vaccine, and this response is positively correlated with specific features of the gut microbiota, such as alpha diversity. We also demonstrate that the vaccination itself induces alterations in the composition and structure of the gut microbiota. These findings illuminate potential links between the gut microbiota and vaccine efficacy in individuals with T2DM, offering valuable insights that could enhance vaccine responses in this high-risk population.

Objective: The cause of syncope is generally determined based on clinical manifestations. There has been little discussion about the value of electrocardiograms for diagnosing neurally mediated syncope. The aim of this study was to test the predictive value of the isolated very low QRS voltage in tilt-table testing for suspected neurally mediated syncope in a Chinese population. Methods: This retrospective study enrolled patients with suspected neurally mediated syncope. Tilt-table testing was a part of the diagnostic examination. Each patient underwent echocardiography and electrocardiogram. isolated very low QRS voltage referred to a voltage of ⩽0.3 mV for the QRS complex in an isolated frontal lead or ⩽0.7 mV for the QRS complex in an isolated precordial lead. Results: In total, 157 patients were included in the tilt-table testing positive group, and 242 patients were included in the tilt-table testing negative group. Compared with the testing negative group, the testing positive group had more patients with isolated very low QRS voltage in the frontal leads ( p

SARS-CoV-2 spike protein (SARS-2-S) induced cell-cell fusion in uninfected cells may occur in long COVID-19 syndrome, as circulating SARS-2-S or extracellular vesicles containing SARS-2-S (S-EVs) were found to be prevalent in post-acute sequelae of COVID-19 (PASC) for up to 12 months after diagnosis. Although isolated recombinant SARS-2-S protein has been shown to increase the SASP in senescent ACE2-expressing cells, the direct linkage of SARS-2-S syncytia with senescence in the absence of virus infection and the degree to which SARS-2-S syncytia affect pathology in the setting of cardiac dysfunction are unknown. Here, we found that the senescent outcome of SARS-2-S induced syncytia exacerbated heart failure progression. We first demonstrated that syncytium formation in cells expressing SARS-2-S delivered by DNA plasmid or LNP-mRNA exhibits a senescence-like phenotype. Extracellular vesicles containing SARS-2-S (S-EVs) also confer a potent ability to form senescent syncytia without de novo synthesis of SARS-2-S. However, it is important to note that currently approved COVID-19 mRNA vaccines do not induce syncytium formation or cellular senescence. Mechanistically, SARS-2-S syncytia provoke the formation of functional MAVS aggregates, which regulate the senescence fate of SARS-2-S syncytia by TNFα. We further demonstrate that senescent SARS-2-S syncytia exhibit shrinked morphology, leading to the activation of WNK1 and impaired cardiac metabolism. In pre-existing heart failure mice, the WNK1 inhibitor WNK463, anti-syncytial drug niclosamide, and senolytic dasatinib protect the heart from exacerbated heart failure triggered by SARS-2-S. Our findings thus suggest a potential mechanism for COVID-19-mediated cardiac pathology and recommend the application of WNK1 inhibitor for therapy especially in individuals with post-acute sequelae of COVID-19.

Summary: Background: The ubiquitin regulatory X (UBX) domain-containing proteins (UBXNs) are putative adaptors for ubiquitin ligases and valosin-containing protein; however, their in vivo physiological functions remain poorly characterised. We recently showed that UBXN3B is essential for activating innate immunity to DNA viruses and controlling DNA/RNA virus infection. Herein, we investigate its role in adaptive immunity. Methods: We evaluated the antibody responses to multiple viruses and pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza in tamoxifen-inducible global and constitutive B cell-specific Ubxn3b knockout mice; quantified various immune populations, B lineage progenitors/precursors, B cell receptor (BCR) signalling and apoptosis by flow cytometry, immunoblotting and immunofluorescence microscopy. We also performed bone marrow transfer, single-cell and bulk RNA sequencing. Findings: Both global and B cell-specific Ubxn3b knockout mice present a marked reduction in small precursor B-II (>60%), immature (>70%) and mature B (>95%) cell numbers. Transfer of wildtype bone marrow to irradiated global Ubxn3b knockouts restores normal B lymphopoiesis, while reverse transplantation does not. The mature B population shrinks rapidly with apoptosis and higher pro and activated caspase-3 protein levels were observed following induction of Ubxn3b knockout. Mechanistically, Ubxn3b deficiency leads to impaired pre-BCR signalling and cell cycle arrest. Ubxn3b knockout mice are highly vulnerable to respiratory viruses, with increased viral loads and prolonged immunopathology in the lung, and reduced production of virus-specific IgM/IgG. Interpretation: UBXN3B is essential for B lymphopoiesis by maintaining constitutive pre-BCR signalling and cell survival in a cell-intrinsic manner. Funding: United States National Institutes of Health grants, R01AI132526 and R21AI155820.

Abstract Background Early-onset prostate cancer (EOPC, ≤ 55 years) has a unique clinical entity harboring high genetic risk, but the majority of EOPC patients still substantial opportunity to be early-detected thus suffering an unfavorable prognosis. A refined understanding of age-based polygenic risk score (PRS) for prostate cancer (PCa) would be essential for personalized risk stratification. Methods We included 167,517 male participants [4882 cases including 205 EOPC and 4677 late-onset PCa (LOPC)] from UK Biobank. A General-, an EOPC- and an LOPC-PRS were derived from age-specific genome-wide association studies. Weighted Cox proportional hazard models were applied to estimate the risk of PCa associated with PRSs. The discriminatory capability of PRSs were validated using time-dependent receiver operating characteristic (ROC) curves with additional 4238 males from PLCO and TCGA. Phenome-wide association studies underlying Mendelian Randomization were conducted to discover EOPC linking phenotypes. Results The 269-PRS calculated via well-established risk variants was more strongly associated with risk of EOPC [hazard ratio (HR) = 2.35, 95% confidence interval (CI) 1.99–2.78] than LOPC (HR = 1.95, 95% CI 1.89–2.01; I 2 = 79%). EOPC-PRS was dramatically related to EOPC risk (HR = 4.70, 95% CI 3.98–5.54) but not to LOPC (HR = 0.98, 95% CI 0.96–1.01), while LOPC-PRS had similar risk estimates for EOPC and LOPC (I 2 = 0%). Particularly, EOPC-PRS performed optimal discriminatory capability for EOPC (area under the ROC = 0.613). Among the phenomic factors to PCa deposited in the platform of ProAP (Pro state cancer A ge-based P heWAS; https://mulongdu.shinyapps.io/proap ), EOPC was preferentially associated with PCa family history while LOPC was prone to environmental and lifestyles exposures. Conclusions This study comprehensively profiled the distinct genetic and phenotypic architecture of EOPC. The EOPC-PRS may optimize risk estimate of PCa in young males, particularly those without family history, thus providing guidance for precision population stratification.

Abstract Background Autoimmune responses have been suggested to involvement in patients with Behcet’s syndrome (BS). There has been growing attention towards the roles of cutaneous lymphocyte antigen (CLA)+ regular T cells (Tregs) in autoimmune diseases. The role of CLA+ Tregs in BS is still uncertain. This study aims to clarify the impact of CLA+ Tregs on BS. Methods We collected peripheral blood from a total of 107 patients with BS and 114 healthy controls (HCs). The number of CLA+ Tregs, natural killer (NK) cells, B cells, and several subtypes of CD4+ T cells were detected using flow cytometry and compared between patients and HCs. Results The absolute number and proportion of CLA+ Tregs among CD4+ T lymphocytes and CD4+ Tregs were lower in patients with BS than in HCs. CLA+ Tregs were positively related with NK cells (r = 0.500, P

The increasing global prevalence of mosquito-borne viruses has emerged as a significant threat to human health and life. Identifying receptors for these viruses is crucial for improving our knowledge of viral pathogenesis and developing effective antiviral strategies. The widespread application of CRISPR-Cas9 screening have led to the discovery of many mosquito-borne virus receptors. The revealed structures of virus-receptor complexes also provide important information for understanding their interaction mechanisms. This review provides a comprehensive summary of both conventional and novel approaches for identifying new viral receptors and the putative entry factors of the most prevalent mosquito-borne viruses within the Flaviviridae, Togaviridae, and Bunyavirales. At the same time, we emphasize the common receptors utilized by these viruses for entry into both vertebrate hosts and mosquito vectors. We discuss promising avenues for developing anti-mosquito-borne viral strategies that target these receptors. Notably, targeting universal receptors of specific mosquito-borne viruses in both vertebrates and mosquitoes offers dual benefits for disease prevention. Additionally, the widespread use of AI-based machine learning and protein structure prediction will accelerate the identification of new viral receptors and provide new avenues for antiviral drug discovery.

AbstractObjective Accumulating evidence suggests that differentially expressed circular RNAs (circRNAs) play critical roles in immune cells of systemic lupus erythematosus (SLE) patients. Hsa_circ_0000479 has been studied in the field of cancer and infection, whereas seldom studied in autoimmune diseases. The aim of this study was to investigate the role and clinical value of neutrophil hsa_circ_0000479 in SLE.Methods The expression levels of hsa_circ_0000479 in both healthy individuals and SLE patients’ neutrophils were detected by qPCR and compared with those in peripheral blood mononuclear cells (PBMCs) . In addition, the correlation of hsa_circ_0000479 levels in neutrophils with the clinical and immunological features of SLE patients was also analysed.Results The expression levels of hsa_circ_0000479 in the patients with SLE were significantly higher in neutrophils than that of PBMCs, and also significantly higher than that in healthy controls (HCs). Moreover, the expression levels of hsa_circ_0000479 in neutrophils were negatively associated with absolute neutrophil count and complement 3 (C3), whereas positively correlated with anti-dsDNA and anti-nucleosome antibodies in SLE. In addition, SLE patients with higher levels of hsa_circ_0000479 demonstrated more several clinical manifestations, including Raynaud’s phenomenon, alopecia and leucopenia.Conclusions Hsa_circ_0000479 is up-regulated in neutrophils of SLE patients, and is also associated with several important laboratory indicators and clinical manifestations, suggesting that hsa_circ_0000479 in neutrophils was one of probable factors involved in the pathogenesis of SLE with potential clinical value.

The Maoping superlarge germanium-rich lead–zinc deposit is a typical nonmagmatic hydrothermal deposit that is structurally controlled in the Sichuan–Yunnan–Guizhou lead–zinc polymetallic metallogenic area. The orebodies are distributed in several formations. This paper is based on large-scale alteration mapping combined with porosity and permeability measurements. We delineated the mineralization–alteration zones of different ore-bearing formations, explored the geological significance of porosity and permeability, and proposed prospecting directions. The research results indicate that during the mineralization period, the ore-forming metal fluids migrated from the deep part of the SSW region to the shallow part of the NNE region along the ore-guiding structure (Maoping Fault). Through the ore distribution structure, depressurization boiling occurred in the open space of the NE-trending interlayered sinistral compressive–torsional faults in several ore-bearing formations, resulting in fluid precipitation and the formation of different brecciated hot-melt dolomite lead–zinc mineralization zones. From the orebody to the wallrock, the C2w Formation and D3zg Formation are divided into four different mineralization–alteration zones. Tectonic activity affects the properties, migration, and precipitation of fluids, thereby controlling the alteration characteristics generated during fluid migration and thus changing the porosity and permeability. The porosity and permeability of strata on the NW flank of the anticline are greater than those of strata on the SE flank. On the NW flank, the greater the degree of mineralization–alteration is, the greater the porosity and permeability are, and the porosity of the orebody is lower than that during dolomitization. Finally, we believe that the NW flank of the anticline is an important area for prospecting. The pyrite + striped altered dolomite zone (Zones II–III) in the C2w limestone and the pyrite + strong dolomite zone (Zones II–III) in the D3zg dolomite are important prospecting indicators.

Abstract The Retinoic acid-Inducible Gene I (RIG-I) like receptors (RLRs) are the major viral RNA sensors essential for the initiation of antiviral immune responses. RLRs are subjected to stringent transcriptional and posttranslational regulations, of which ubiquitination is one of the most important. However, the role of ubiquitination in RLR transcription is unknown. Here, we screen 375 definite ubiquitin ligase knockout cell lines and identify Ubiquitin Protein Ligase E3 Component N-Recognin 5 (UBR5) as a positive regulator of RLR transcription. UBR5 deficiency reduces antiviral immune responses to RNA viruses, while increases viral replication in primary cells and mice. Ubr5 knockout mice are more susceptible to lethal RNA virus infection than wild type littermates. Mechanistically, UBR5 mediates the Lysine 63-linked ubiquitination of Tripartite Motif Protein 28 (TRIM28), an epigenetic repressor of RLRs. This modification prevents intramolecular SUMOylation of TRIM28, thus disengages the TRIM28-imposed brake on RLR transcription. In sum, UBR5 enables rapid upregulation of RLR expression to boost antiviral immune responses by ubiquitinating and de-SUMOylating TRIM28.

Abstract Objective To develop a Chinese Diabetes Mellitus Ontology (CDMO) and explore methods for constructing high-quality Chinese biomedical ontologies. Materials and methods We used various data sources, including Chinese clinical practice guidelines, expert consensus, literature, and hospital information system database schema, to build the CDMO. We combined top-down and bottom-up strategies and integrated text mining and cross-lingual ontology mapping. The ontology was validated by clinical experts and ontology development tools, and its application was validated through clinical decision support and Chinese natural language medical question answering. Results The current CDMO consists of 3,752 classes, 182 fine-grained object properties with hierarchical relationships, 108 annotation properties, and over 12,000 mappings to other well-known medical ontologies in English. Based on the CDMO and clinical practice guidelines, we developed 200 rules for diabetes diagnosis, treatment, diet, and medication recommendations using the Semantic Web Rule Language. By injecting ontology knowledge, CDMO enhances the performance of the T5 model on a real-world Chinese medical question answering dataset related to diabetes. Conclusion CDMO has fine-grained semantic relationships and extensive annotation information, providing a foundation for medical artificial intelligence applications in Chinese contexts, including the construction of medical knowledge graphs, clinical decision support systems, and automated medical question answering. Furthermore, the development process incorporated natural language processing and cross-lingual ontology mapping to improve the quality of the ontology and improved development efficiency. This workflow offers a methodological reference for the efficient development of other high-quality Chinese as well as non-English medical ontologies.

Abstract The respiratory system, especially the lung, is the key site of pathological injury induced by SARS-CoV-2 infection. Given the low feasibility of targeted delivery of antibodies into the lungs by intravenous administration and the short half-life period of antibodies in the lungs by intranasal or aerosolized immunization, mRNA encoding broadly neutralizing antibodies with lung-targeting capability can perfectly provide high-titer antibodies in lungs to prevent the SARS-CoV-2 infection. Here, we firstly identify a human monoclonal antibody, 8-9D, with broad neutralizing potency against SARS-CoV-2 variants. The neutralization mechanism of this antibody is explained by the structural characteristics of 8-9D Fabs in complex with the Omicron BA.5 spike. In addition, we evaluate the efficacy of 8-9D using a safe and robust mRNA delivery platform and compare the performance of 8-9D when its mRNA is and is not selectively delivered to the lungs. The lung-selective delivery of the 8-9D mRNA enables the expression of neutralizing antibodies in the lungs which blocks the invasion of the virus, thus effectively protecting female K18-hACE2 transgenic mice from challenge with the Beta or Omicron BA.1 variant. Our work underscores the potential application of lung-selective mRNA antibodies in the prevention and treatment of infections caused by circulating SARS-CoV-2 variants.

Against the backdrop of global warming and increased rainfall, the hazards and potential risks of landslides are increasing. The rapid generation of a landslide inventory is of great significance for landslide disaster prevention and reduction. Deep learning has been widely applied in landslide identification due to its advantages in terms of its deeper model structure, high efficiency, and high accuracy. This article first provides an overview of deep learning technology and its basic principles, as well as the current status of landslide remote sensing databases. Then, classic landslide deep learning recognition models such as AlexNet, ResNet, YOLO, Mask R-CNN, U-Net, Transformer, EfficientNet, DeeplabV3+ and PSPNet were introduced, and the advantages and limitations of each model were extensively analyzed. Finally, the current constraints of deep learning in landslide identification were summarized, and the development direction of deep learning in landslide identification was analyzed. The purpose of this article is to promote the in-depth development of landslide identification research in order to provide academic references for the prevention and mitigation of landslide disasters and post-disaster rescue work. The research results indicate that deep learning methods have the characteristics of high efficiency and accuracy in automatic landslide recognition, and more attention should be paid to the development of emerging deep learning models in landslide recognition in the future.

Abstract Background Alginate oligosaccharide (AOS) holds great potential as a novel feed supplement in farm animals. However, the effects of AOS on chicken health and the underlying mechanisms are not fully understood. This study aimed to optimize the enzymatic preparation of AOS by using bacterial alginate lyases expressed in yeast, investigate the effects of the prepared AOS on the growth performance and gut health of broiler chickens, and reveal the underlying mechanisms. Results Five alginate lyases from bacteria were cloned into Pichia pastoris GS115 and the alginate lyase PDE9 was expressed at relatively high yield, activity and stability in P. pastoris. Animal trials were carried out using 320 1-day-old male Arbor Acres broilers (four groups; 8 replicates/group × 10 chicks/replicate) receiving either a basal diet or the same diet supplemented with 100, 200 and 400 mg/kg PDE9-prepared AOS for 42 d. The results showed that dietary supplementation of 200 mg/kg AOS displayed the highest activity in promoting the birds’ ADG and ADFI (P

Abstract Background Intramuscular fat (IMF) is closely related to the tenderness, marbling, juiciness, and flavor of meat. We used a combined transcriptome and metabolome analysis to investigate the molecular mechanisms underlying phenotypic variation among Qinchuan cattle. Results The IMF content was relatively high in the meat of Qinchuan cattle bulls and differed among muscle locations, namely the high rib (15.86%), ribeye (14%), striploin (10.44%), and tenderloin (8.67%). CCDC80 and the HOX gene cluster may regulate intramuscular adipose tissue deposition. Moreover, erucic acid (EA) was found to be the main metabolite in Qinchuan beef cattle, with a high concentration in IMF. The deposition of IMF could be regulated by the metabolic pathway for unsaturated fatty acids involving EA and the ACOX3, HACD2, and SCD5 genes. In addition, differentially expressed genes and metabolites were enriched in three major KEGG pathways: purine metabolism, pyrimidine metabolism, and the metabolism of glycine, serine, and threonine. Conclusions We identified a significant metabolite, EA, with variation in IMF. Its closely related genes, ACOX3, HACD2, and SCD5, co-regulate the metabolism of unsaturated fatty acids, ultimately affecting the accumulation of intramuscular adipose tissue in Qinchuan cattle. Consequently, Qinchuan cattle are an elite cultivar for high-quality beef production and have great potential for breeding.

Abstract As the largest organ of the body, the skin acts as a barrier to prevent diseases and harbors a variety of beneficial bacteria. Furthermore, the skin bacterial microbiota plays a vital role in health and disease. Disruption of the barrier or an imbalance between symbionts and pathogens can lead to skin disorders or even systemic diseases. In this review, we first provide an overview of research on skin bacterial microbiota and human health, including the composition of skin bacteria in a healthy state, as well as skin bacterial microbiota educating the immune system and preventing the invasion of pathogens. We then discuss the diseases that result from skin microbial dysbiosis, including atopic dermatitis, common acne, chronic wounds, psoriasis, viral transmission, cutaneous lupus, cutaneous lymphoma, and hidradenitis suppurativa. Finally, we highlight the progress that utilizes skin microorganisms for disease therapeutics, such as bacteriotherapy and skin microbiome transplantation. A deeper knowledge of the interaction between human health and disease and the homeostasis of the skin bacterial microbiota will lead to new insights and strategies for exploiting skin bacteria as a novel therapeutic target.

Abstract Herd immunity achieved through mass vaccination is an effective approach to prevent contagious diseases. Nonetheless, emerging SARS-CoV-2 variants with frequent mutations largely evaded humoral immunity induced by Spike-based COVID-19 vaccines. Herein, we develop a lipid nanoparticle (LNP)-formulated mRNA-based T-cell-inducing antigen, which targeted three SARS-CoV-2 proteome regions that enriched human HLA-I epitopes (HLA-EPs). Immunization of HLA-EPs induces potent cellular responses to prevent SARS-CoV-2 infection in humanized HLA-A*02:01/DR1 and HLA-A*11:01/DR1 transgenic mice. Of note, the sequences of HLA-EPs are highly conserved among SARS-CoV-2 variants of concern. In humanized HLA-transgenic mice and female rhesus macaques, dual immunization with the LNP-formulated mRNAs encoding HLA-EPs and the receptor-binding domain of the SARS-CoV-2 B.1.351 variant (RBDbeta) is more efficacious in preventing infection of SARS-CoV-2 Beta and Omicron BA.1 variants than single immunization of LNP-RBD beta . This study demonstrates the necessity to strengthen the vaccine effectiveness by comprehensively stimulating both humoral and cellular responses, thereby offering insight for optimizing the design of COVID-19 vaccines.

Osteoarthritis (OA) is a common joint disease that is characterized by inflammation and cartilage degradation. Death-associated protein kinase 1 (DAPK1) is a multi-domain serine/threonine kinase and has been reported to be involved in the progression of OA. However, its role and mechanism in OA remain unclear. Here, we found the expression of DAPK1 in OA cartilage tissues was higher than that in normal cartilage tissues. The expression of DAPK1 in chondrocytes was up-regulated by IL-1β. Knockdown of DAPK1 promoted cell viability and anti-apoptotic protein expression, while it inhibited the apoptosis rate and pro-apoptotic protein expressions in IL-1β-induced chondrocytes. In addition, DAPK1 inhibition reduced the levels of inflammatory cytokines and expressions of matrix metalloproteinases (MMPs), and increased the expressions of collagen II and aggrecan. The data of mechanistic investigation indicated that the expression of pigment epithelium-derived factor (PEDF) was positively regulated by DAPK1. Overexpression of PEDF attenuated the effects of DAPK1 knockdown on IL-1β-induced cell viability, apoptosis, inflammation, and cartilage degradation. Furthermore, PEDF overexpression restored the activity of the NF-κB pathway and NLRP3 inflammasome after DAPK1 knockdown. Collectively, down-regulation of DAPK1 inhibited IL-1β-induced inflammation and cartilage degradation via the PEDF-mediated NF-κB and NLRP3 inflammasome pathways.

AbstractIntroduction Low-dose interleukin-2 (IL-2) regulates the homeostasis of CD4+ T cells by modulating the proportions of effector and regulatory T cells, thus reducing disease activity in patients with systemic lupus erythematosus (SLE). However, to date, no research has been carried out on the efficacy of low-dose IL-2 for treating autoimmune thyroid disease (AITD). The aim of this study was to observe the effects of IL-2 on AITD patients with concurrent SLE, and explore potential mechanism of action.Methods A retrospective analysis was conducted on 29 SLE patients with concurrent AITD. Among them, 11 patients were in IL-2 therapy group and 18 patients without IL-2 treatment were considered as control group. Two groups had similar disease activities and were treated with comparable regular strategy. Free triiodothyronine (FT3), free thyroxine (FT4), thyroxine(T4), triiodothyronine(T3), thyroid stimulating hormone (TSH), thyroglobulin antibody (TG-Ab), thyroid peroxidase antibody (TPO-Ab) levels and immune cell subgroups were measured.Results After receiving low-dose IL-2 therapy, the TG-Ab and TPO-Ab levels decreased drastically (TG-Ab p = 0.008, TPO-Ab p = 0.007), and the majority of the AITD patients became seronegative, while there was no discernible change in control group. In IL-2 group, percentage of CD4+ T cells showed a significant increase after treatment (p = 0.029), with an upward trend in the ratio of regulatory T (Treg) cells to follicular helper T (Tfh) cells (Treg/Tfh). The percentage as well as absolute count of B cells demonstrated a decreasing trend.Conclusion Low-dose IL-2 may downregulate the levels of TG-Ab and TPO-Ab by modulating the immune balance of Treg/Tfh and B-cells, providing new avenue for clinical treatment of AITD.

ABSTRACTAgricultural waste represents a potential source of raw materials as natural dyes. The peel from pomegranate (Punica granatum) is a waste product, it is used in the textiles industry as dye. The objective of the study is to improve dyeing properties of pomegranate peel dyed silk fabric. We analyzed the pigment composition of pomegranate peel extract through ultraviolet-visible and Fourier-transform infrared (FTIR) spectroscopy; evaluated natural mordants and metallic mordants on fabrics dyed with pomegranate peel extracts by testing the K/S value, color characteristics, and color fastness; examined the morphology of dyed fabrics before and after color fixing treatment by scanning electron microscopy. The major pigment component in pomegranate peel is ellagic acid. An orthogonal array experiment revealed that the optimum dyeing conditions were pH 9, 60°C 60 min for silk fibers. Under the natural mordant, the K/S value of dyed fabric could acquire maximum (8.70). Moreover, the K/S value and color fastness of dyed fabrics could be further enhanced to 11.74 and level 5 by color-fixing treatment of natural gum rosin. Overall, the dyed silk samples with pomegranate peel represented good dyeing properties with natural mordant and natural color-fixing agent of gum rosin.

Abstract A full understanding of the inactivated COVID-19 vaccine-mediated antibody responses to SARS-CoV-2 circulating variants will inform vaccine effectiveness and vaccination development strategies. Here, we offer insights into the inactivated vaccine-induced antibody responses after prime-boost vaccination at both the polyclonal and monoclonal levels. We characterized the VDJ sequence of 118 monoclonal antibodies (mAbs) and found that 20 neutralizing mAbs showed varied potency and breadth against a range of variants including XBB.1.5, BQ.1.1, and BN.1. Bispecific antibodies (bsAbs) based on nonoverlapping mAbs exhibited enhanced neutralizing potency and breadth against the most antibody-evasive strains, such as XBB.1.5, BQ.1.1, and BN.1. The passive transfer of mAbs or their bsAb effectively protected female hACE2 transgenic mice from challenge with an infectious Delta or Omicron BA.2 variant. The neutralization mechanisms of these antibodies were determined by structural characterization. Overall, a broad spectrum of potent and distinct neutralizing antibodies can be induced in individuals immunized with the SARS-CoV-2 inactivated vaccine BBIBP-CorV, suggesting the application potential of inactivated vaccines and these antibodies for preventing infection by SARS-CoV-2 circulating variants.

Noncoding RNAs (ncRNAs) constitute a class of RNA molecules that lack protein-coding capacity. ncRNAs frequently modulate gene expression through specific interactions with target proteins or messenger RNAs, thereby playing integral roles in a wide array of cellular processes. The Flavivirus genus comprises several significant members, such as dengue virus (DENV), Zika virus (ZIKV), and yellow fever virus (YFV), which have caused global outbreaks, resulting in high morbidity and mortality in human populations. The life cycle of arthropod-borne flaviviruses encompasses their transmission between hematophagous insect vectors and mammalian hosts. During this process, a complex three-way interplay occurs among the pathogen, vector, and host, with ncRNAs exerting a critical regulatory influence. ncRNAs not only constitute a crucial regulatory mechanism that has emerged from the coevolution of viruses and their hosts but also hold potential as antiviral targets for controlling flavivirus epidemics. This review introduces the biogenesis of flavivirus-derived ncRNAs and summarizes the regulatory roles of ncRNAs in viral replication, vector-mediated viral transmission, antiviral innate immunity, and viral pathogenicity. A profound comprehension of the interplay between ncRNAs and flaviviruses will help formulate efficacious prophylactic and therapeutic strategies against flavivirus-related diseases.

AimTo evaluate the safety and efficacy of the His-Purkinje system pacing (HPCSP) in the treatment of individuals with atrial fibrillation (AF) complicated by heart failure (HF).MethodsThe PubMed, Cochrane Library, Web of Science, and Embase databases were searched through September 1, 2022. The literature was initially screened based on the inclusion and exclusion criteria. The baseline characteristics of the subjects, implantation success rate, New York Heart Association (NYHA) classification, left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDd), QRS duration, pacing threshold, and impedance were extracted and summarized; statistical analysis was performed using RevMan 5.3 software.ResultsIn all, 22 articles were included, involving 1,445 patients. Compared to biventricular pacing (BiVP), HPCSP resulted in improved cardiac function, including increased ejection fraction (MD = 5.69, 95% CI: 0.78–10.60, P = 0.02) and decreased LVEDd (MD = −3.50, 95% CI: −7.05–0.05, P = 0.05). It was also correlated with shorter QRS duration (MD = −38.30, 95% CI: −60.71–−15.88, P

ObjectivesCardiac resynchronization therapy (CRT) is a well-established method that improves the clinical symptoms and long-term prognosis of specific heart failure (HF) patients by restoring systolic synchronicity and enhancing myocardial function. However, the high rate of intraoperative and postoperative left ventricular (LV) lead dislocation limits its application to a great extent. The aim of this study was to demonstrate the long-term safety and effectiveness of a new approach named the loop technique for patients who experience repeated intraoperative transvenous LV lead dislocations during CRT.MethodsThe current study was a single-centre, prospective, nonrandomized controlled trial. Forty-four HF patients who underwent CRT were included. All patients were followed to death or 3 years.ResultsAmong 44 HF patients, 36 underwent the traditional operation, and 8 underwent the loop technique due to repeated intraoperative LV lead dislocations. Intergroup comparison revealed no significant differences between the two groups with respect to most preoperative indices, intraoperative pacing and sensing parameters. At the end of the 3-year follow-up, 4 (11.1%) patients in the traditional operation group and 2 (25.0%) patients in the loop technique group had died. There was no significant difference in the mortality rate (P = 0.30). No complications related to this new technique were observed, such as intracoronary thrombosis, infection or dislocation. Intergroup comparison showed no significant difference in the New York Heart Association (NYHA) class, echocardiography indices, N-terminal pro brain natriuretic peptide (NT-proBNP) level or pacemaker programming parameters.ConclusionsThe loop technique is a safe and effective alternative method for patients who experience repeated intraoperative transvenous LV lead dislocations during CRT.

To improve the control accuracy and stability of the harmonic drive system under the influence of nonlinear friction and external disturbances, we have developed an adaptive neural backstepping control approach with friction compensation. During the design process, we employ a nonlinear observer based on a novel modified LuGre model with friction compensation. This observer effectively reduces the influence of nonlinear friction on the harmonic drive system, even under dynamic changes in the environment. Additionally, we utilize a Chebyshev neural network to approximate unknown disturbances applied to the harmonic drive system. To prevent violations of output constraints, we introduce a tangent barrier Lyapunov function. Furthermore, to address the challenges of “explosion of complexity” and poor precision associated with first-order filters in backstepping, we integrate the inverse hyperbolic sine function tracking differentiator into this controller. Finally, we employ the Lyapunov criterion to prove that all errors in the closed-loop system are uniformly bounded. Simulation results confirm the feasibility of the proposed control scheme and demonstrate better closed-loop behavior compared to that obtained using a radial basis function dynamic surface controller.

Abstract To investigate if a magnetic resonance imaging (MRI)-based model reduced postoperative biochemical failure (BF) incidence in patients with prostate cancer (PCa). From June 2018 to January 2020, we retrospectively analyzed 967 patients who underwent prostate bi-parametric MRI and radical prostatectomy (RP). After inclusion criteria were applied, 446 patients were randomized into research (n = 335) and validation cohorts (n = 111) at a 3:1 ratio. In addition to clinical variables, MRI models also included MRI parameters. The area under the curve (AUC) of receiver operating characteristic and decision curves were analyzed. The risk of postoperative BF, defined as persistently high or re-elevated prostate serum antigen (PSA) levels in patients with PCa with no clinical recurrence. In the research (age 69 [63–74] years) and validation cohorts (age 69 [64–74] years), the postoperative BF incidence was 22.39% and 27.02%, respectively. In the research cohort, the AUC of baseline and MRI models was 0.780 and 0.857, respectively, with a significant difference (P

Context Isoorientin has many biological activities, including antioxidant, anti-inflammatory, antitumor. However, the effect of isoorientin on postmenopausal osteoporosis remains unclear.Objective To evaluate the effect of isoorientin on postmenopausal osteoporosis.Materials and methods Sprague-Dawley rats were divided into five groups (n = 5): sham, model, 17-β-oestradiol (E2, 10 μg/kg/day), low-dose isoorientin (L-Iso, 50 mg/kg), and high-dose isoorientin (H-Iso, 100 mg/kg). The rats were ovariectomized, treated by gavage daily for 12 weeks, and serum and femur samples were collected. Bone mineral density, bone metabolism, and oxidative stress were assessed. H&E staining, immunohistochemistry, and western blotting were employed.Results Isoorientin improved the bone mineral density of the lumbar vertebrae (2.01 ± 0.05 g/cm3 in H-Iso group vs. 1.74 ± 0.07 g/cm3 in model group) and femur (1.46 ± 0.06 g/cm3 vs. 1.19 ± 0.03 g/cm3), increased the trabecular bone number (1.97 ± 0.03 vs. 1.18 ± 0.13) and thickness (0.27 ± 0.02 vs. 0.16 ± 0.03 mm). Isoorientin decreased the separation degree of trabecular bone, ameliorated bone histomorphology changes, and significantly improved the mechanical properties. Isoorientin diminished MDA (by 60%) and increased SOD (by 49.2%), and GSH-Px (by 159%) activity. Furthermore, osteoprotegerin (OPG), nuclear factor erythroid 2-like 2 (Nrf2), haem oxygenase (HO-1), NAD(P)H quinone dehydrogenase 1(NQO1), and oestrogen receptor 1(ESR1) protein expression increased, while receptor activator of nuclear factor-κB ligand (RANKL) protein expression decreased after treatment.Conclusions Isoorientin ameliorates osteoporosis via upregulating OPG and Nrf2/ARE signalling, suggesting isoorientin maybe a potential therapeutic drug for PMOP.

Adipogenesis involves complex interactions between transcription and metabolic signalling. Exploration of the developmental characteristics of intramuscular adipocyte will provide targets for enhancing beef cattle marbling without increasing obesity. Few reports have compared bovine perirenal and intramuscular adipocyte transcriptomes using the combined analysis of transcriptomes and lipid metabolism to explore differences in adipogenic characteristics. We identified perirenal preadipocytes (PRA) and intramuscular preadipocytes (IMA) in Qinchuan cattle. We found that IMA were highly prolific in the early stages of adipogenesis, while PRA shows a stronger adipogenic ability in the terminal differentiation. Bovine perirenal and intramuscular adipocytes were detected through the combined analysis of the transcriptome and metabolome. More triglyceride was found to be upregulated in perirenal adipocytes; however, more types and amounts of unsaturated fatty acids were detected in intramuscular adipocytes, including eicosapentaenoic acid (20:5 n-3; EPA) and docosahexaenoic acid (22:6 n-3; DHA). Furthermore, differentially expressed genes in perirenal and intramuscular adipocytes were positively correlated with the eicosanoid, phosphatidylcholine (PC), phosphatidyl ethanolamine (PE), and sphingomyelin contents. Associated differential metabolic pathways included the glycerolipid and glycerophospholipid metabolisms. Our research findings provide a basis for the screening of key metabolic pathways or genes and metabolites involved in intramuscular fat production in cattle.

Abstract Objective To compare the breakage risk of lengthened sacroiliac screws and ordinary sacroiliac screws to treat unilateral vertical sacral fractures and provide a reference for clinical application. Methods A finite element model of Tile C pelvic ring injury (unilateral type Denis II fracture of the sacrum) was produced. The sacral fractures were fixed with a lengthened sacroiliac screw and ordinary sacroiliac screw in 6 types of models. The maximal von Mises stresses and stress distributions of the two kinds of screws when standing on both feet were measured and compared. Results The maximal von Mises stress of the lengthened screw was less than that of the ordinary screw. Compared with ordinary screw, the stress distribution in the lengthened screw was more homogeneous. Conclusions The breakage risk of screws fixed in double segments is lower than that of screws fixed in single segments, the breakage risk of lengthened screws is lower than that of ordinary screws, and the breakage risk of screws fixed in S2 segments is lower than that of screws fixed in S1 segments.

Abstract Dengue virus (DENV) is one of the most important arboviral pathogens in the tropics and subtropics, and nearly one‐third of the world's population is at risk of infection. The transmission of DENV involves a sylvatic cycle between nonhuman primates (NHP) and Aedes genus mosquitoes, and an endemic cycle between human hosts and predominantly Aedes aegypti. DENV belongs to the genus Flavivirus of the family Flaviviridae and consists of four antigenically distinct serotypes (DENV‐1‐4). Phylogenetic analyses of DENV have revealed its origin, epidemiology, and the drivers that determine its molecular evolution in nature. This review discusses how phylogenetic research has improved our understanding of DENV evolution and how it affects viral ecology and improved our ability to analyze and predict future DENV emergence.

THz imaging and spectroscopy always request even more efficient components. Here the authors, thanks to a modified photoconductive switch that includes a graphene layer, demonstrate a high-speed photoconductive switch without sacrificing the generated power.

BackgroundFor metastatic prostate cancer (mPCa), radical prostatectomy (RP) and radiation therapy (RT) may improve overall survival (OS) and cancer-specific survival (CSS). Compared with RT, RP shows significant advantages in improving patient outcomes. External beam radiation therapy (EBRT) even slightly elevates CSM with no statistical difference in OS compared with no local treatment (NLT).ObjectiveTo evaluate OS and CSS after local treatment (LT) (including RP and RT) versus NLT in mPCa.Design, setting, and participantsWithin the Surveillance, Epidemiology and End Results (SEER) database (2000-2018), 20098 patients with metastatic prostate cancer were selected in this study, of which 19433 patients had no local treatment, 377 patients with radical prostate treatment, and 288 patients with RT.Outcome measurements and statistical analysisMultivariable competing risks regression analysis after propensity score matching (PSM) was used to calculate CSM. Multivariable Cox regression analysis was used to identify the risk factors. Kaplan-Meier methods were used to calculate OS.Results and limitationsA total of 20098 patients were included: NLT (n = 19433), RP (n=377) and RT (n=288). In a competing risk regression analysis after PSM (ratio 1:1), RP resulted in a significantly lower CSM (hazard ratio [HR] 0.36, 95% confidence interval [CI] 0.29-0.45) than NLT, while RT showed a slightly lower CSM (HR 0.77, 95% CI 0.63-0.95). In a competing risk regression analysis after PSM (ratio 1:1), RP led to a lower CSM (HR 0.56, 95% CI 0.41-0.76) versus RT. As for all-cause mortality (ACM), RP (HR 0.37, 95% CI 0.31-0.45) and RT (HR 0.66, 95% CI 0.56-0.79). also showed a downward trend. In terms of OS, RP and RT significantly improved the survival probability compared with NLT, with the effect of RP being more pronounced. Obviously, older age, Gleason scores ≥8, AJCC T3-T4 stage, AJCC N1, AJCC M1b-M1c were all associated with higher CSM (P

Weakly supervised object detection (WSOD) in remote sensing images (RSIs) has good practical value because it only requires the image-level annotations. The existing methods usually have two problems. The first problem is that many methods mine the pseudo ground truth (PGT) instances solely depending on the class confidence score (CCS), however, the reliability of CCS is not enough because of the inter-class similarity and intra-class diversity in RSIs, consequently, the reliability of corresponding PGT instances is limited, in addition, the most discriminative part with high CCS rather than the whole object is easily selected as the PGT instance. The second problem is that the object localization solely relies on the candidate proposals generated by the selective search or edge boxes algorithm, however, the localization accuracy of the candidate proposals is not enough because of the cluttered background in RSIs. To address the first problem, a semantic segmentation guided pseudo label mining (SGPLM) module is proposed, which uses a novel metric named class-specific object confidence score (COCS) to mine high-quality PGT instances. The COCS is made up of the CCS and class-specific object overlap score (COOS) which is calculated through the weakly supervised semantic segmentation. The mined PGT instances are more robust and incline to cover the whole object by combining the COOS. To handle the second problem, an instance re-detection (IR) module is proposed for improving the localization accuracy of the WSOD model, in which an enhanced PGT instance generation strategy is designed to obtain the enhanced PGT instances on the basis of the candidate proposals, and the enhanced PGT instances are used to train the instance re-classification and re-localization branches which are jointly utilized to infer the final results. The ablation studies validate the effectiveness of the SGPLM and IR modules. The comprehensive comparisons with other advanced methods show that the performance of the proposed method is state-of-the-art on two RSI datasets.

Based on mixed lubrication analysis, considering the influence of rough interface contact stiffness, contact damping, and interface friction on the gear transmission system, the relationship between interface contact and the overall performance of the gear transmission system has been established. First, the surface topography is characterized using statistical parameters of rough surfaces, and the contact stiffness and damping for tooth surfaces with different roughnesses are calculated. Subsequently, a six degree of freedom gear tribo-dynamics coupling model is developed. Finally, the established tribo-dynamics model is employed to investigate the relationship between surface roughness and the overall performance of the gear transmission system. This study provides a more intimate connection between the contact interface and the general behavior of the gear transmission system, enabling a better representation of real-world engineering problems. The research findings reveal that contact stiffness and damping decrease with increasing surface roughness. Higher roughness leads to greater gear vibration amplitude. Moreover, elevated surface roughness results in intensified meshing force and more significant energy loss. Surprisingly, when the roughness is appropriate, gears with rough surfaces lose less energy than those with smooth surfaces.

A genome-wide association study (GWAS) is an effective tool for identifying the dominant genes of complex economic traits in livestock by statistical analysis of genotype data and measured phenotype data. In this study, we rigorously measured 14 body conformation traits in 254 Qinchuan cattle, comprising body weight (BW), body height (BOH), back height (BAH), buttock height (BUH), chest depth (CD), chest width (CW), hip cross height (HCH), body length (BL), hip width (HW), rump length (RL), pin bone width (PBW), chest girth (CG), abdomen circumference (AG), and calf circumference (CC). After quality control, 281,889 SNPs were generated for GWAS with different traits. A total of 250 suggestive SNPs (p < 3.54 × 10−6) were screened and 37 candidate genes were annotated. Furthermore, we performed a linkage disequilibrium analysis of SNP loci and considered published studies, identifying the eight genes (ADAMTS17, ALDH1A3, CHSY1, MAGEL2, MEF2A, SYNM, CNTNAP5, and CTNNA3) most likely to be involved in growth traits. This study provides new insights into the regulatory mechanisms of bovine body size development, which can be very useful in the development of management and breeding strategies.

Background Despite increasing public concerns about the widespread health effects of climate change, the impacts of ambient temperature on atopic dermatitis (AD) remain poorly understood. Objectives We aimed to explore the effect of ambient temperature on AD and to estimate the burdens of AD attributed to extreme temperature. Methods Data on outpatients with AD and climate conditions in Chengdu, China were collected. A distributed lag nonlinear model (DLNM) was adopted to explore the association between daily mean temperature and AD outpatient visits. Subgroup analysis was used to identify vulnerable populations. Attributable burden was estimated by the epidemiological attributable method. Results We analyzed 10,747 outpatient visits from AD patients at West China Hospital in Chengdu between January 1, 2015, and December 31, 2020. Both low (25.3 °C) were associated with increased AD outpatient visits, with the increase being more pronounced at low temperature, as evidenced by a 160% increase in visits when the temperature dropped below zero from the minimum mortality temperature (22.8 °C). Children and males were the most susceptible populations. Approximately 25.4% of AD outpatient visits were associated with temperatures, causing an excessive 137161.5 US dollars of health care expenditures during this 6-year period. Conclusions Both high and low temperatures, particularly low temperatures, were significantly associated with an increased risk of AD, with children and males showing the strongest associations. Extreme environmental temperature has been identified as one of the major factors promoting the development of AD. However, individual patient-level exposures still needed to be investigated in future studies to confirm the causality between temperature and AD.

Summary: The volatile collection step is important for insect behavior assays and in-depth component analysis. Here, we describe how to collect volatiles from animals, humans, and skin microbiota. Furthermore, we detail steps to improve behavioral devices adapted to the different collection techniques. This protocol provides a high-throughput and widely applicable approach to study the attracting or repelling effect of volatiles on mosquitoes. The volatile collection step is easily adaptable and time efficient.For complete details on the use and execution of this protocol, please refer to Zhang et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Abstract The accuracy of sixteen commonly used internal reference genes was assessed in skeletal muscle-derived satellite cells of Qinchuan cattle at different stages of proliferation and induction of differentiation to determine the most suitable ones. Quantitative real-time PCR and three commonly used algorithmic programs, GeNorm, NormFinder and BestKeeper, were used to evaluate the stability of expression of the candidate internal reference genes (GAPDH, ACTB, PPIA, LRP10, HPRT1, YWHAZ, B2M, TBP, EIF3K , RPS9, UXT, 18S rRNA, RPLP0, MARVELD, EMD and RPS15A) in skeletal muscle-derived satellite cells at 0, 12, 24, 36 and 48 h of growth and after differentiation for 0, 2, 4, 6 and 8 days. The expression of two satellite cell marker genes, CCNA2 and MYF5, was used for validation analysis. The results of the software analyses showed that GAPDH and RPS15A were the most stable reference gene combinations during in vitro proliferation of bovine skeletal muscle-derived satellite cells, RPS15A and RPS9 were the most stable reference gene combinations during in vitro induction of differentiation of the cells, and PPIA was the least stable reference gene during proliferation and differentiation and was not recommended. This study lays the foundation for the selection of reference genes for qRT-PCR during the proliferation and induction of differentiation of bovine skeletal muscle-derived satellite cells.

Dengue is one of the most prevalent and influential mosquito-borne viral infections in the world. According to 1 modeling estimate, the World Health Organization indicated that the annual cases of dengue virus (DENV) infection are as high as 390 million, placing more than half of the global population at risk. Despite its overwhelming prevalence, there is still no effective control method for containing this rapidly spreading disease. The only vaccine currently licensed for use is Dengvaxia, a tetravalent chimeric vaccine developed by Sanofi Pasteur in 2019. However, this vaccine fails to elicit a balanced immune response against all 4 serotypes of DENV and causes severe side effects in seronegative vaccine recipients. Vaccines naturally stimulate cellular and humoral immune responses, which are crucial for vaccine immunogenicity and clinical protection. This article focuses on these 2 immune responses triggered by DENV and their relationship with the efficacy of various vaccine candidates. This information will help us understand the vaccine immune response and relevant clinical protective efficacy further, providing insights into the development of new vaccines. Finally, we summarize feasible approaches for future vaccine development.

Background: Despite rapid advances in the treatment of prostate cancer (PCa), the optimal treatment for elderly patients with PCa remains unclear due to a lack of high-quality evidence. This study aimed to evaluate whether surgical procedures are beneficial for PCa patients aged 75 years and older and compare the effects of focal ablation and prostatectomy. Methods: Male patients aged 75 years and older who were diagnosed with Tis-T2/N0/M0 PCa between 2000 and 2017 were retrospectively identified from the Surveillance, Epidemiology, and End Results program database. Cox regression models were used to test for statistical differences between the overall survival (OS) and disease-specific survival (DSS). Results: A total of 114,506 patients aged 75 years and older with PCa were included in this study, among which 60,131 died during the study period. The most prevalent surgical procedure for these patients was focal ablation. The local excision rate increased with advancing age, while the prostatectomy rate decreased sharply with age. The proportion of the elderly patients who underwent a focal ablation also increased with the age at diagnosis. The survival rate of patients aged 75 years and older who underwent a focal ablation was significantly worse than that for those who did not undergo any surgical procedures (OS: HR, 1.32, P

Considering the large number of individuals who have already been infected and may have reinfection, the post-infection effects of COVID-19 are of great importance for clinical practice and predicting disease trends. However, our understanding of the potential long-term effects, particularly on immunity, after recovering from COVID-19 remains limited. The aim of this study was to investigate the abnormal immunological factors that contribute to the prolonged immunological effects of COVID-19. Two groups of patients were enrolled in the study, including 11 individuals with various autoimmune diseases (AIDs) and 16 patients diagnosed with systemic lupus erythematosus (SLE). Detailed clinical symptoms were closely monitored, and peripheral mononuclear cells were analyzed using flow cytometry. The clinical status was evaluated using the SLE Disease Activity Index (SLEDAI) and the Clinical Global Impressions (CGI) index. The proportions of follicular T helper cells (Tfh) exhibited significant increases in both cohorts (AID: p = 0.03; SLE: p = 0.0008). Conversely, the percentages of Foxp3+ and CD4+ regulatory T cells (Treg) were reduced in patients following COVID-19 infection (AID: p = 0.009, 0.05, resp.; SLE: p = 0.02, 0.0009, resp.). The percentages of Th2 and Th17 cells were significantly increased in SLE patients (p < 0.05). Exacerbated conditions were observed in SLE patients two months after infection (SLEDAI, p < 0.05). Our findings show that COVID-19 infection increases Tfh cells and decreases Treg cells in patients of AIDs, worsening pathogenetic immune status in post-recovery populations.

Objectives To explore the performance of targeted biopsy (TB) in combination with systematic biopsy (SB) in the detection of prostate cancer (PCa) in biopsy naïve patients. Methods From May 2018 to January 2020, 230 biopsy-naïve men with suspicious bi-parametric MRI [bpMRI; Prostate Imaging Reporting and Data System (PI-RADS) score ≥3] were enrolled. All patients had prostate-specific antigen (PSA) levels of 20 ng/ml or less. For each patient, transrectal ultrasound-guided prostate biopsy was performed. The primary endpoint was the detection rate of CSPC [clinically-significant PCa, International Society of Urological Pathology grade group (ISUP GG) 2 or higher tumors]. The secondary endpoints were the detection rates of CIPC (clinically insignificant PCa, ISUP GG 1 tumors). Results CSPC was detected in 90 patients. Twelve (13.33%) of them were detected by TB only and 18 (20.00%) by SB only. Detection of CSPC by SB and TB did not differ significantly (p = .36). In 4.35% of 230 patients, CSPC would have been missed if we performed SB only, and in 6.09% of patients if we performed TB only. Moreover, combination of TB and SB did not increase the detection of CIPC. Conclusions No significant difference was found in the detection of CSPC between TB and SB; however, both techniques revealed substantial added value and combination of TB and SB could further improve this detection rate without increasing the detection of CIPC.

Mental stress has been recognized as an essential risk factor for hypertension. Therefore, experts specializing in cardiology, psychiatry, and Traditional Chinese Medicine organized by the Psycho-Cardiology Group of College of Cardiovascular Physicians of Chinese Medical Doctor Association and Hypertension Group of Chinese Society of Cardiology proposed the expert consensus on the diagnosis and treatment of adult mental stress-induced hypertension in March 2021, which includes the epidemiology, etiology, diagnosis, and treatment of the mental stress-induced hypertension. This consensus will hopefully facilitate the clinical practice of this disorder. In addition, the COVID-19 pandemic has become one of the primary global sources of psychosocial stressors since the beginning of 2020, and the revision of this expert consensus in 2022 has increased the relevant content. This consensus consists of Part A and Part B. Part A includes (I) Background and epidemiological characteristics, (II) Pathogenesis, and (III) Diagnosis and Part B includes (IV) Treatment recommendations and (V) Prospects. This part presents the content of Part A.