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Friction spot joining (FSpJ) has been proven to be a highly competitive process for fabricating hybrid joints composed of metal and carbon fibre-reinforced thermoplastic. However, previous research has rarely focused on optimizing joint performance by controlling thermal conduction through modifying tool structures. This study systematically explores the effect of the recessed tool shoulder geometry on mechanical strength of 6061-T6 Al alloy and carbon fibre-reinforced polyamide-6 (CF/PA6) pinless-FSpJ joint. An experimentally validated three-dimensional (3D) finite element model was built to investigate the heat generation and thermal conduction. Results show that the recessed tools with different external diameters achieve higher average interface strength in lap joints compared to flat shoulder tools. Under fixed plunge depth conditions, increasing the depth of the recessed area results in a lower rate of temperature rise and a more uniform temperature distribution during heating stage. As a result, the duration of resin decomposition in the molten state is further reduced, but the time in a single molten state is extended. This benefits the wetting process of molten resin on the silanized Al surface and subsequent chemical reaction with the silane film, while alleviating decomposition defects to a certain extent. The reduction in residual tension stress at the center of Al upper surface indirectly indicates the improving effect of increased recessed tool depth on the stress state of the joint.

Abstract Objectives This study evaluated the impact of self-management interventions based on the COM-B model on peri-implant conditions in older adults with periodontitis. Materials and methods The patients were randomly divided into two groups: Group 1 (control group) received only an oral health education (OHE) pamphlet. Group 2 (test group) performed a self-management intervention based on the COM-B model. Each patient was examined for the most inflammatory implant. The measurement parameters included self-efficacy, self-management ability, and clinical indicators such as probing depth (PD), bleeding on probing (BOP), modified gingival index (mGI), modified plaque index (mPI), and peri-implant mucositis severity score (PMSS). The data was collected at baseline, 4, 8, and 12 weeks. Results 42 patients underwent testing for 3 months. After 12 weeks, the improvement of self-efficacy, self-management ability, and the reduction of BOP, mPI, and PMSS in the test group was significantly higher than in the control group. Conclusion The study suggests that self-management interventions based on the COM-B model can enhance the self-management ability of older adults with periodontitis and reduce peri-implant inflammation. This method is more effective than distributing OHE pamphlets. Trial registration The randomized controlled clinical trial was registered on Chinese Clinical Trial Registry (No. ChiCTR2400082660, Date: 03/04/2024).

The discrete Hopfield neural network 3-satisfiability (DHNN-3SAT) model represents an innovative application of deep learning techniques to the Boolean SAT problem. Existing research indicated that the DHNN-3SAT model demonstrated significant advantages in handling 3SAT problem instances of varying scales and complexities. Compared to traditional heuristic algorithms, this model converged to local minima more rapidly and exhibited enhanced exploration capabilities within the global search space. However, the model faced several challenges and limitations. As constraints in SAT problems dynamically increased, decreased, or changed, and as problem scales expanded, the model's computational complexity and storage requirements may increase dramatically, leading to reduced performance in handling large-scale SAT problems. To address these challenges, this paper first introduced a method for designing network synaptic weights based on fundamental logical clauses. This method effectively utilized the synaptic weight information from the original SAT problem within the DHNN network, thereby significantly reducing redundant computations. Concrete examples illustrated the design process of network synaptic weights when constraints were added, removed, or updated, offering new approaches for managing the evolving constraints in SAT problems. Subsequently, the paper presented a DHNN-3SAT model optimized by genetic algorithms combined with K-modes clustering. This model employed genetic algorithm-optimized K-modes clustering to effectively cluster the initial space, significantly reducing the search space. This approach minimized the likelihood of redundant searches and reduced the risk of getting trapped in local minima, thus improving search efficiency. Experimental tests on benchmark datasets showed that the proposed model outperformed traditional DHNN-3SAT models, DHNN-3SAT models combined with genetic algorithms, and DHNN-3SAT models combined with imperialist competitive algorithms across four evaluation metrics. This study not only broadened the application of DHNN in solving 3SAT problems but also provided valuable insights and guidance for future research.

Over the past six years, the Sino-US trade war has not only reshaped the relationship between the world's two largest economies but also profoundly influenced the global economic and trade patterns. This paper reviews the background, process, and implications of the Sino-US trade war, examining its impact on China, the United States, and the broader global trade landscape across various socioeconomic dimensions. We begin by reviewing the development of Sino-US trade relations in the past 20 years. Next we detail the background and evolution of the trade war. We then discuss the economic consequences of the conflict, including the effect of tariff increases on product prices, employment, investment, consumption, and welfare. Finally, we explore the reshaping of supply chains in the aftermath of the trade conflict, and the interaction between trade policies and industrial policies within the context of the Sino-US trade war.Existing literature indicates that the Sino-US trade war has resulted in significant welfare losses for both countries, with surprisingly little impact on employment. The tariffs have not achieved the intended outcome set by policymakers. Specifically, the additional tariffs imposed by the United States on China have neither effectively addressed trade imbalances nor brought manufacturing jobs back onshore. Our paper offers a new perspective on the complexity of the current international trade conflict.

Abstract Sustained injury from factors such as hypoxia, infection, or physical damage may provoke improper tissue repair and the anomalous deposition of connective tissue that causes fibrosis. This phenomenon may take place in any organ, ultimately leading to their dysfunction and eventual failure. Tissue fibrosis has also been found to be central in both the process of carcinogenesis and cancer progression. Thus, its prompt diagnosis and regular monitoring is necessary for implementing effective disease-modifying interventions aiming to reduce mortality and improve overall quality of life. While significant research has been conducted on these subjects, a comprehensive understanding of how their relationship manifests through modern imaging techniques remains to be established. This work intends to provide a comprehensive overview of imaging technologies relevant to the detection of fibrosis affecting thoracic organs as well as to explore potential future advancements in this field.

Abstract Fibrosis is a pathological process involving the abnormal deposition of connective tissue, resulting from improper tissue repair in response to sustained injury caused by hypoxia, infection, or physical damage. It can impact any organ, leading to their dysfunction and eventual failure. Additionally, tissue fibrosis plays an important role in carcinogenesis and the progression of cancer. Early and accurate diagnosis of organ fibrosis, coupled with regular surveillance, is essential for timely disease-modifying interventions, ultimately reducing mortality and enhancing quality of life. While extensive research has already been carried out on the topics of aberrant wound healing and fibrogenesis, we lack a thorough understanding of how their relationship reveals itself through modern imaging techniques. This paper focuses on fibrosis of the genito-urinary system, detailing relevant imaging technologies used for its detection and exploring future directions.

Abstract Fibrosis is the aberrant process of connective tissue deposition from abnormal tissue repair in response to sustained tissue injury caused by hypoxia, infection, or physical damage. It can affect almost all organs in the body causing dysfunction and ultimate organ failure. Tissue fibrosis also plays a vital role in carcinogenesis and cancer progression. The early and accurate diagnosis of organ fibrosis along with adequate surveillance are helpful to implement early disease-modifying interventions, important to reduce mortality and improve quality of life. While extensive research has already been carried out on the topic, a thorough understanding of how this relationship reveals itself using modern imaging techniques has yet to be established. This work outlines the ways in which fibrosis shows up in abdominal organs and has listed the most relevant imaging technologies employed for its detection. New imaging technologies and developments are discussed along with their promising applications in the early detection of organ fibrosis.

Although sows do not directly enter the market, they play an important role in piglet breeding on farms. They consume large amounts of feed, resulting in a significant environmental burden. Pig farms can increase their income and reduce environmental pollution by increasing the litter size (LS) of swine. PCR-RFLP/SSCP and GWAS are common methods to evaluate single-nucleotide polymorphisms (SNPs) in candidate genes. We conducted a systematic meta-analysis of the effect of SNPs on pig LS. We collected and analysed data published over the past 30 years using traditional and network meta-analyses. Trial sequential analysis (TSA) was used to analyse population data. Gene set enrichment analysis and protein–protein interaction network analysis were used to analyse the GWAS dataset. The results showed that the candidate genes were positively correlated with LS, and defects in PCR-RFLP/SSCP affected the reliability of candidate gene results. However, the genotypes with high and low LSs did not have a significant advantage. Current breeding and management practices for sows should consider increasing the LS while reducing lactation length and minimizing the sows’ non-pregnancy period as much as possible.

Abstract Adipose tissue development begins in the fetal period, and continues to expand after birth. Dysregulation of adipose tissue during weaning may predispose individuals to lifelong metabolic disorders. However, the developmental remodeling of adipose tissue during weaning remains largely unexplored. Here we comprehensively compare the changes in mouse subcutaneous white adipose tissue from 7 days after birth to 7 days after weaning using single-cell RNA sequencing along with other molecular and histologic assays. We characterize the developmental trajectory of preadipocytes and indicate the commitment of preadipocytes with beige potential during weaning. Meanwhile, we find immune cells unique to weaning period, whose expression of extracellular matrix proteins implies potential regulation on preadipocyte. Finally, the strongest cell-cell interaction during weaning determined by the TGFβ ligand-receptor pairs is between preadipocytes and endotheliocytes. Our results provide a detailed and unbiased cellular landscape and offer insights into the potential regulation of adipose tissue remodeling during weaning.

Abstract Objectives To evaluate the usefulness of porta hepatis lymph nodes (PHLNs) on ultrasonography (US) scans in diagnosing biliary atresia (BA) and predicting the outcomes after Kasai portoenterostomy (KPE) surgery. Methods A total of 668 patients from one hospital were enrolled in the study (542 non-BA and 126 BA). The independent and combined diagnostic efficacy of PHLNs, triangular cord (TC) thickness, and gallbladder morphology were assessed by drawing the receiver operating characteristic (ROC) curves and counting the area under the ROC curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). The US features, histopathological findings of PHLNs, and serum total bilirubin (TBIL) levels 3 months post-KPE were correlated. Results The AUC, sensitivity, specificity, PPV, and NPV of PHLNs with hyperechogenicity and a maximum length larger than 8.4 mm were 0.898, 81.8%, 97.8%, 89.6%, and 95.8%, respectively. The combination of PHLNs, TC thickness, and gallbladder morphology achieved the best overall diagnostic efficacy among all indicators with an AUC of 0.927 and a sensitivity of 99.2%. The germinal center number and bile particle number of PHLNs were positively correlated with pathological size and US echogenicity intensity of PHLNs, respectively (r = 0.591, 0.377, p = 0.001, 0.004). The pathological size of PHLNs in BA patients was negatively correlated with jaundice clearance status 3 months after KPE surgery (r = −0.385, p = 0.047). Conclusion PHLNs with hyperechogenicity and a maximum length > 8.4 mm are useful US indicators for BA diagnosis. Additionally, the enlargement of PHLNs might play a role in predicting outcomes of KPE surgery. Critical relevance statement The article proposed for the first time that PHLNs with hyperechogenicity and a maximum length > 8.4 mm are a useful US indicator for diagnosing BA. Key Points PHLNs may be helpful in diagnosing BA and predicting outcomes after surgery. Enlarged hyperechoic PHLNs are a useful diagnostic indicator for BA, and play a role in predicting surgical outcomes. These findings can assist clinicians in more accurately diagnosing BA, enabling more timely treatments. Graphical Abstract

Abstract Management of patients with acute chest pain poses a significant challenge in identifying those requiring urgent coronary reperfusion. Electrocardiogram (ECG) constitutes the cornerstone in making prompt clinical decisions by identifying ST‐segment elevation, commonly associated with ST‐segment elevation myocardial infarction. It is important to note that ST‐segment elevation can also be a manifestation of various cardiac and non‐cardiac conditions, from acute myocarditis, early repolarization syndrome, acute pericarditis, and left bundle branch block to unknown origins. The similarity of ECG changes among these conditions complicates clinical differential diagnosis, necessitating a detailed medical history and thorough examinations. Here, we presented a case of a 52‐year‐old female with chest pain and unidentified convex ST‐segment elevation. Considering the negative emergent coronary angiography results, normal echocardiography, and long‐lasting ST‐segment elevation for the following 1 year, the final diagnosis was non‐myocardial infarction, probably related to a prior cerebral haemorrhage.

This experimental work presents a comparative study on the mechanical behaviour of novel infusible methylmethacrylate matrix (Elium®) composites reinforced with different types of high-performance fibres. A vacuum-assisted resin infusion process was employed to fabricate the laminates using carbon, basalt, Kevlar®, and high molecular weight polyethene (UHMWPE) fibres. Flexural and interlaminar shear properties of the composites were evaluated. Test results revealed that carbon fibre composites had superior flexural strength, stiffness and interlaminar shear stress as compared to the other composites tested. Further, composites containing Kevlar and UHMWPE fibres demonstrated significantly higher flexural strains to failure. Post-testing, specimens were examined using scanning electron microscopy (SEM). Microscopy revealed possible interfacial interaction differences based on the reinforcement fibre type, which was further confirmed by an analytical approach for analysing the flexural behaviour of various types of composites. The sequence of damage progression in specimens was also analysed.

This paper reports a rare case of extralobar pulmonary sequestration in the posterior mediastinum of a neonate with arterial supply from the pulmonary artery. A 3-day-old male neonate was diagnosed with type II congenital pulmonary airway malformation after prenatal color Doppler ultrasonography showed a lesion with blood supply from the pulmonary artery in the left lung. Post-birth chest computed tomography(CT) showed that the lesion was located in the posterior mediastinum with low density change, mild stripe enhancement after contrast, and no obvious blood supply vessels. A neurogenic tumor was considered for the preoperative diagnosis. The mass was removed by video-assisted thoracoscopic surgery. During the surgery, the mass was observed to be a dark red solid lump with a feeding vessel originating from the pulmonary artery. The postoperative histopathological diagnosis was extralobar pulmonary sequestration. Combined with the preoperative imaging results, it was considered that the nourishing vessels might have intermittent torsion. The patient recovered well after surgery, and no recurrence was observed after 6 months of follow-up. Therefore, the possibility of extralobar pulmonary sequestration cannot be ruled out for posterior mediastinal masses that are not supplied by the descending aorta or without identified feeding vessels.

Angioleiomyoma (ALM) is a rare benign perivascular (pericytic) tumor primarily composed of well-differentiated smooth muscle and vascular components. Its clinical and radiological features lack specificity, making diagnosis challenging and prone to misdiagnosis. This report summarizes the clinical data of a patient treated at our hospital who was preoperatively misdiagnosed with rectal cancer but was subsequently found to have perirectal ALM. Additionally, a review of the relevant literature is provided.

Purpose Timely and accurate monitoring of soil salinity content (SSC) is essential for precise irrigation management of large-scale farmland. Uncrewed aerial vehicle (UAV) low-altitude remote sensing with high spatial and temporal resolution provides a scientific and effective technical means for SSC monitoring. Many existing soil salinity inversion models have only been tested by a single variable selection method or machine learning algorithm, and the influence of variable selection method combined with machine learning algorithm on the accuracy of soil salinity inversion remain further studied. Methods Firstly, based on UAV multispectral remote sensing data, by extracting the spectral reflectance of each sampling point to construct 30 spectral indexes, and using the pearson correlation coefficient (PCC), gray relational analysis (GRA), variable projection importance (VIP), and support vector machine-recursive feature elimination (SVM-RFE) to screen spectral index and realize the selection of sensitive variables. Subsequently, screened and unscreened variables as model input independent variables, constructed 20 soil salinity inversion models based on the support vector machine regression (SVM), back propagation neural network (BPNN), extreme learning machine (ELM), and random forest (RF) machine learning algorithms, the aim is to explore the feasibility of different variable selection methods combined with machine learning algorithms in SSC inversion of crop-covered farmland. To evaluate the performance of the soil salinity inversion model, the determination coefficient (R2), root mean square error (RMSE) and performance deviation ratio (RPD) were used to evaluate the model performance, and determined the best variable selection method and soil salinity inversion model by taking alfalfa covered farmland in arid oasis irrigation areas of China as the research object. Results The variable selection combined with machine learning algorithm can significantly improve the accuracy of remote sensing inversion of soil salinity. The performance of the models has been improved markedly using the four variable selection methods, and the applicability varied among the four methods, the GRA variable selection method is suitable for SVM, BPNN, and ELM modeling, while the PCC method is suitable for RF modeling. The GRA-SVM is the best soil salinity inversion model in alfalfa cover farmland, with Rv2 of 0.8888, RMSEv of 0.1780, and RPD of 1.8115 based on the model verification dataset, and the spatial distribution map of soil salinity can truly reflect the degree of soil salinization in the study area. Conclusion Based on our findings, the variable selection combined with machine learning algorithm is an effective method to improve the accuracy of soil salinity remote sensing inversion, which provides a new approach for timely and accurate acquisition of crops covered farmland soil salinity information.

Abstract Background T-cell exhaustion (TEX), a condition characterized by impaired T-cell function, has been implicated in numerous pathological conditions, but its role in acute myocardial Infarction (AMI) remains largely unexplored. This research aims to identify and characterize all TEX-related genes for AMI diagnosis. Methods By integrating gene expression profiles, differential expression analysis, gene set enrichment analysis, protein-protein interaction networks, and machine learning algorithms, we were able to decipher the molecular mechanisms underlying TEX and its significant association with AMI. In addition, we investigated the diagnostic validity of the leading TEX-related genes and their interactions with immune cell profiles. Different types of candidate small molecule compounds were ultimately matched with TEX-featured genes in the “DrugBank” database to serve as potential therapeutic medications for future TEX-AMI basic research. Results We screened 1725 differentially expressed genes (DEGs) from 80 AMI samples and 71 control samples, identifying 39 differential TEX-related transcripts in total. Functional enrichment analysis identified potential biological functions and signaling pathways associated with the aforementioned genes. We constructed a TEX signature containing five hub genes with favorable prognostic performance using machine learning algorithms. In addition, the prognostic performance of the nomogram of these five hub genes was adequate (AUC between 0.815 and 0.995). Several dysregulated immune cells were also observed. Finally, six small molecule compounds which could be the future therapeutic for TEX in AMI were discovered. Conclusion Five TEX diagnostic feature genes, CD48, CD247, FCER1G, TNFAIP3, and FCGRA, were screened in AMI. Combining these genes may aid in the early diagnosis and risk prediction of AMI, as well as the evaluation of immune cell infiltration and the discovery of new therapeutics.

Cold stress significantly affects gene expression in adipocytes; studying this phenomenon can help reveal the pathogeneses of conditions such as obesity and insulin resistance. Adipocyte triglyceride lipase (ATGL); cell death-inducing deoxyribonucleic acid (DNA) fragmentation factor subunit alpha (DFFA)-like effector (CIDEA); and uncoupling protein genes UCP1, UCP2, and UCP3 are the most studied genes in pig adipose tissues under cold stress. However, contradictory results have been observed in gene expression changes to UCP3 and UCP2 when adipose tissues under cold stress were examined. Therefore, we conducted a meta-analysis of 32 publications in total on the effect of cold stress on the expression of ATGL, CIDEA, UCP2, and UCP3. Our results showed that cold stress affected the expression of swine adipocyte genes; specifically, it was positively correlated with the expression of UCP3 in swine adipocytes. Conversely, expression of ATGL was negatively affected under cold stress conditions. In addition, the loss of functional UCP1 in pigs likely triggered a compensatory increase in UCP3 activity. We also simulated the docking results of UCP2 and UCP3. Our results showed that UCP2 could strongly bind to adenosine triphosphate (ATP), meaning that UCP3 played a more significant role in pig adipocytes.

Abstract Poaceae members shared a whole-genome duplication called rho. However, little is known about the evolutionary pattern of the rho-derived duplicates among Poaceae lineages and implications in adaptive evolution. Here we present phylogenomic/phylotranscriptomic analyses of 363 grasses covering all 12 subfamilies and report nine previously unknown whole-genome duplications. Furthermore, duplications from a single whole-genome duplication were mapped to multiple nodes on the species phylogeny; a whole-genome duplication was likely shared by woody bamboos with possible gene flow from herbaceous bamboos; and recent paralogues of a tetraploid Oryza are implicated in tolerance of seawater submergence. Moreover, rho duplicates showing differential retention among subfamilies include those with functions in environmental adaptations or morphogenesis, including ACOT for aquatic environments (Oryzoideae), CK2β for cold responses (Pooideae), SPIRAL1 for rapid cell elongation (Bambusoideae), and PAI1 for drought/cold responses (Panicoideae). This study presents a Poaceae whole-genome duplication profile with evidence for multiple evolutionary mechanisms that contribute to gene retention and losses.

Abstract Background Environmental stresses negatively impact reproductive development and yield. Drought stress, in particular, has been examined during Arabidopsis reproductive development at morphological and transcriptomic levels. However, drought-responsive transcriptomic changes at different points in reproductive development remain unclear. Additionally, an investigation of the entire transcriptome at various stages during flower development is of great interest. Results Here, we treat Arabidopsis plants with well-watered and moderately and severely limiting water amounts when the first flowers reach maturity and generate RNA-seq datasets for early, middle, and late phases during flower development at 5, 6, and 7 days following treatment. Under different drought conditions, flowers in different developmental phases display differential sets of drought-responsive genes (DTGs), including those that are enriched in different GO functional categories, such as transcriptional regulation and response to stresses (early phase), lipid storage (middle phase), and pollen and seed development and metabolic processes (late phase). Some gene families have different members induced at different floral phases, suggesting that similar biochemical functions are carried out by distinct members. Developmentally-regulated genes (DVGs) with differential expression among the three floral phases belong to GO terms that are similar between water conditions, such as development and reproduction, metabolism and transport, and signaling and stress response. However, for different water conditions, such similar GO terms correspond to either distinct gene families or different members of a gene family, suggesting that drought affects the expression of distinct families or family members during reproductive development. A further comparison among transcriptomes of tissues collected on different days after treatment identifies differential gene expression, suggesting age-related genes (ARGs) might reflect the changes in the overall plant physiology in addition to drought response and development. Conclusion Together, our study provides new insights into global transcriptome reprogramming and candidate genes for drought response, flower development, aging and coordination among these complex biological processes.

Summary: Erythropoietin-producing hepatoma (Eph) receptors, comprising the largest family of receptor tyrosine kinases (RTKs), exert profound influence on diverse biological processes and pathological conditions such as cancer. Interacting with their corresponding ligands, erythropoietin-producing hepatoma receptor interacting proteins (Ephrins), Eph receptors regulate crucial events like embryonic development, tissue boundary formation, and tumor cell survival. In addition to their well-established roles in embryonic development and cancers, emerging evidence highlights the pivotal contribution of the Ephrin/Eph family to cardiovascular physiology and pathology. Studies have elucidated their involvement in cardiovascular development, atherosclerosis, postnatal angiogenesis, and, more recently, cardiac fibrosis and calcification, suggesting a promising avenue for therapeutic interventions in cardiovascular diseases. There remains a need for a comprehensive synthesis of their collective impact in the cardiovascular context. By exploring the intricate interactions between Eph receptors, ephrins, and cardiovascular system, this review aims to provide a holistic understanding of their roles and therapeutic potential in cardiovascular health and diseases.

Summary: Heat shock transcription factors (HSFs) play a crucial role in heat stress tolerance in vegetative tissues. However, their involvement in reproductive tissues and their post-translational modifications are not well understood. In this study, we identify the E3 ligase XB3 ORTHOLOG 1 IN ARABIDOPSIS THALIANA (XBAT31) as a key player in the ubiquitination and degradation of HSFB2a/B2b. Our results show that the xbat31 mutant exhibits a higher percentage of unfertile siliques and decreased expression of HSPs in flowers under heat stress conditions compared to the wild type. Conversely, the hsfb2a hsfb2b double mutant displays improved reproductive thermotolerance. We find that XBAT31 interacts with HSFB2a/B2b and mediates their ubiquitination. Furthermore, HSFB2a/B2b ubiquitination is reduced in the xbat31-1 mutant, resulting in higher accumulation of HSFB2a/B2b in flowers under heat stress conditions. Overexpression of HSFB2a or HSFB2b leads to an increase in unfertile siliques under heat stress conditions. Thus, our results dissect the important role of the XBAT31-HSFB2a/B2b module in conferring reproductive thermotolerance in plants.

Abstract Physiological regulation of transgene expression is a major challenge in gene therapy. Onasemnogene abeparvovec (Zolgensma®) is an approved adeno-associated virus (AAV) vector gene therapy for infants with spinal muscular atrophy (SMA), however, adverse events have been observed in both animals and patients following treatment. The construct contains a native human survival motor neuron 1 (hSMN1) transgene driven by a strong, cytomegalovirus enhancer/chicken β-actin (CMVen/CB) promoter providing high, ubiquitous tissue expression of SMN. We developed a second-generation AAV9 gene therapy expressing a codon-optimized hSMN1 transgene driven by a promoter derived from the native hSMN1 gene. This vector restored SMN expression close to physiological levels in the central nervous system and major systemic organs of a severe SMA mouse model. In a head-to-head comparison between the second-generation vector and a benchmark vector, identical in design to onasemnogene abeparvovec, the 2nd-generation vector showed better safety and improved efficacy in SMA mouse model.

Abstract Background Previous studies have shown an association between gut microbiota and cardiovascular diseases (CVDs). However, the underlying causal relationship remains unclear. This study aims to elucidate the causal relationship between gut microbiota and CVDs and to explore the pathogenic role of gut microbiota in CVDs. Methods In this two-sample Mendelian randomization study, we used genetic instruments from publicly available genome-wide association studies, including single-nucleotide polymorphisms (SNPs) associated with gut microbiota (n = 14,306) and CVDs (n = 2,207,591). We employed multiple statistical analysis methods, including inverse variance weighting, MR Egger, weighted median, MR pleiotropic residuals and outliers, and the leave-one-out method, to estimate the causal relationship between gut microbiota and CVDs. Additionally, we conducted multiple analyses to assess horizontal pleiotropy and heterogeneity. Results GWAS summary data were available from a pooled sample of 2,221,897 adult and adolescent participants. Our findings indicated that specific gut microbiota had either protective or detrimental effects on CVDs. Notably, Howardella (OR = 0.955, 95% CI: 0.913–0.999, P = .05), Intestinibacter (OR = 0.908, 95% CI:0.831–0.993, P = .03), Lachnospiraceae (NK4A136 group) (OR = 0.904, 95% CI:0.841–0.973, P = .007), Turicibacter (OR = 0.904, 95% CI: 0.838–0.976, P = .01), Holdemania (OR, 0.898; 95% CI: 0.810–0.995, P = .04) and Odoribacter (OR, 0.835; 95% CI: 0.710–0.993, P = .04) exhibited a protective causal effect on atrial fibrillation, while other microbiota had adverse causal effects. Similar effects were observed with respect to coronary artery disease, myocardial infarction, ischemic stroke, and hypertension. Furthermore, reversed Mendelian randomization analyses revealed that atrial fibrillation and ischemic stroke had causal effects on certain gut microbiotas. Conclusion Our study underscored the importance of gut microbiota in the context of CVDs and lent support to the hypothesis that increasing the abundance of probiotics or decreasing the abundance of harmful bacterial populations may offer protection against specific CVDs. Nevertheless, further research is essential to translate these findings into clinical practice.

Researchers have increasingly turned their attention to the interval-valued intuitionistic fuzzy-based group decision-making (GDM) method due to the vagueness and uncertainty that characterize decision-making problems in today’s complex social environments. In the GDM process, determining the weights of experts and measuring the proximity of two decision matrices are two important aspects. In recent years, researchers have enriched and improved the study of GDM methods by using projection measures. However, existing normalized projection measures still have flaws and lack specific regret matrices for GDM methods where the evaluation information is interval-valued intuitionistic fuzzy. To address these problems, this study first develops a new normalized vector projection measure formula that can be used to directly measure the proximity of two interval-valued intuitionistic fuzzy matrices. The study then provides an objective method for determining the weights of experts based on the evaluation matrix of the experts, using the weighted geometric mean operator and the normalized projection measure formula developed in this study. Finally, the study extends the ViseKriterijumska Optimizacija I Kompromisno Resenje (VIKOR) method using the normalized projection measure formula it developed, constructing a new GDM method integrating group utility, regret, and satisfaction measures for the problem of evaluating the evaluation information as interval-valued intuitionistic fuzzy numbers. This study improves the classical VIKOR method by adding the measure of the group satisfaction matrix and giving specific group regret and satisfaction matrices. It investigated the feasibility and validity of the method in this study through three applied practical cases. Experimental comparative analysis with methods in the existing literature, it confirms that the GDM method it constructed is feasible and shows that the method can continuously promote group consensus and obtaining stable ranking results.

Abstract Introduction ‘Let’s Talk About Children’ is a brief family focused intervention developed to improve mental health outcomes of children of parents with mental illness (COPMI). This study aims to assess the efficacy of LTC in improving mental health of children of parents with schizophrenia or bipolar disorder in China. Methods The planned study is a multicentre parallel group randomized wait-list controlled trial. A total of 400 eligible families with children aged 8 to 18 years will be recruited, 200 each for families with parental schizophrenia or bipolar disorder. The intervention group will receive Let’s Talk About Children delivered by a trained therapist, while the control group will receive treatment as usual. The primary outcomes are child mental health measured by the strengths and difficulties questionnaire and parent–child communication measured using the parent-adolescent communication scale. Parental mental health and family functioning are secondary outcomes. This study also plans to explore mediating factors for the effect of Let’s Talk About Children on child mental health, as well as conduct a cost-effectiveness analysis on using Let’s Talk About Children in China. Conclusion The present study will provide evidence for the efficacy of Let’s Talk About Children in families with parental schizophrenia and bipolar disorder in China. In addition, it will evaluate potential mechanisms of action and cost-effectiveness of Let’s Talk About Children, providing a basis for future implementation. Trial registration ChiCTR2300073904.

Accurate measuring magnetic induction intensity is important for some scientific research. In the paper, the conventional nuclear magnetic resonance (NMR) experiment under static magnetic field has been extended to longitudinal time-varying magnetic field (TVMF), and the time domain transient solution of the Bloch equations for spin nuclei exhibits the so-called non-steady state nuclear magnetic resonance (NSS-NMR) phenomenon. Based on the above effect and the precise gyromagnetic ratio of spin nucleus, a new magnetic field measurement method and corresponding experimental apparatus have been developed in longitudinal TVMF environment. The orthogonal dual-coil probe, radio frequency (RF) exciting and receiving hardware, key signal processing algorithms, host computer controlling and analysis software are deeply studied. In order to improve the signal-to-noise ratio of the NSS-NMR signal, the RF signal envelope shaping and the low-frequency pre-emphasis probe matching techniques are designed and verified by the invented circuit-field-nuclear multi-domain joint simulation subassembly (CFN-MDJS) which is integrated in the host computer software. Furthermore, the multi-tone RF excitation signal substituting the bandpass continuous spectrum signal for NSS-NMR experiment is also verified by the CFN-MDJS. The experimental results under longitudinal 50Hz TVMF environment has demonstrated the authentic existence of the NSS-NMR effect and simultaneously verified the effectiveness of the experimental scheme and signal processing algorithms proposed in the paper.

Abstract Purpose Colorectal cancer (CRC) screening has been implemented in Tianjin, China since 2012. The objective was to estimate the neoplasia detection rate in a high-risk population by age and sex and to investigate the potential factors associated with colorectal neoplasia. Patients and methods This study is based on data of the Tianjin CRC screening program from 2012 to 2020. Residents with a positive high-risk factors questionnaire (HRFQ) or a positive faecal immunochemical test (FIT) were identified as high-risk participants and were subsequently recommended for a free colonoscopy. Results A total of 4,117,897 eligible participants aged 40–74 years completed both a HRFQ and FIT, and 217,164 (5.3%) of them were identified as high-risk participants. Positive rates of preliminary screening increased with age and were higher in females than in males. For 57,971 participants undertaking colonoscopy, the detection rates of nonadvanced adenoma, advanced adenoma and CRC were 37.8%, 5.7% and 1.6%, respectively. Detection rates of advanced neoplasia increased from the age of 50 and were higher in males. For nonadvanced neoplasia, a strong increase was observed in males from the age of 40 and in females from the age of 50. Male sex had a greater impact on individuals aged 40–49 than on older individuals. Several factors including current smoking, drinking, and higher body mass index (BMI) were significantly associated with the presence of neoplasia, whereas, these associations were mainly restricted to individuals aged above 50 but not those aged 40–49 years. Conclusions These findings support that age-specific risk stratification and sex-specific initiating ages for CRC screening should be recommended to improve the accuracy and effectiveness of current screening strategy.

Objective: Several studies have demonstrated the possible association between gut microbiota and periodontitis. The mechanism by which gut microbiota contribute to periodontitis remains unknown. Methods: A 2-sample Mendelian randomisation (MR) study was conducted using publicly available Genome-Wide Association Studies (GWAS) data of European ancestry. The relationships between gut microbiota and tooth loss and periodontitis were assessed using summary-level data. Moreover, inverse variance weighted (IVW), MR-Egger, weighted median, and simple Mendelian were used. The results were further validated using sensitivity analyses. Results: A total of 211 gut microbiota were studied, including 9 phyla, 16 classes, 20 orders, 35 families, and 131 genera. The IVW method identified 16 bacterial genera related to the risk of periodontitis and tooth loss. Lactobacillaceae was associated with an increased risk of periodontitis (odds ratio [OR], 1.40, 95% confidence interval [CI], 1.03–1.91, P

Drought stress, as one of the most common environmental factors, seriously affects seed- ling establishment as well as plant growth and productivity. The growth of Toona ciliata is constrained by soil moisture deficit, and drought stress can reduce its productivity and limit its suitable growing environment. To explore the molecular mechanism of Toona ciliata responding to drought stress, leaves of two-year-old Toona ciliata seedlings were used as experimental materials for transcriptome sequencing and physiological index measurements. Under drought stress, the contents of Chl, MDA, POD, SP, SS, and RWC all change differently. We performed transcriptome sequencing, obtaining 4830 differential genes. The enrichment analysis indicates that the primary effects on the leaves of Toona ciliata under drought stress are related to photosynthesis and responses to plant hormone signal transduction. Transcription factor families associated with drought resistance include the NAC, WRKY, bZIP, bHLH, AP2-EREBP, C3H, GRAS, and FRAI transcription factor families. A weighted gene co-expression network analysis (WGCNA) analysis successfully identified 10 hub genes in response to drought stress in Toona ciliata leaves. Real-time quantitative PCR (RT-qPCR) validated the reliability of the transcriptomic data, and the analysis of its results showed a close correlation with the data obtained from RNA-seq. This study clarifies the transcriptional response of Toona ciliata to drought stress, contributing to the revelation of the molecular mechanisms of drought adaptation.

The nucleolus is the most prominent liquid droplet-like membrane-less organelle in mammalian cells. Unlike the nucleolus in terminally differentiated somatic cells, those in totipotent cells, such as murine zygotes or two-cell embryos, have a unique nucleolar structure known as nucleolus precursor bodies (NPBs). Previously, it was widely accepted that NPBs in zygotes are simply passive repositories of materials that will be gradually used to construct a fully functional nucleolus after zygotic genome activation (ZGA). However, recent research studies have challenged this simplistic view and demonstrated that functions of the NPBs go beyond ribosome biogenesis. In this review, we provide a snapshot of the functions of NPBs in zygotes and early two-cell embryos in mice. We propose that these membrane-less organelles function as a regulatory hub for chromatin organization. On the one hand, NPBs provide the structural platform for centric and pericentric chromatin remodelling. On the other hand, the dynamic changes in nucleolar structure control the release of the pioneer factors (i.e. double homeobox (Dux)). It appears that during transition from totipotency to pluripotency, decline of totipotency and initiation of fully functional nucleolus formation are not independent events but are interconnected. Consequently, it is reasonable to hypothesize that dissecting more unknown functions of NPBs may shed more light on the enigmas of early embryonic development and may ultimately provide novel approaches to improve reprogramming efficiency.

University sports culture is an important component of the national cultural system. It is the crystallization of material and spiritual civilization in university sports, as well as the precipitation of sports culture and sports philosophy. However, in the new era, university sports culture presents problems, such as valuing intelligence over physical fitness, lacking in sports culture concepts, and separating spirit and material. In university education, more attention is often paid to academic and intellectual development, while sports and physical exercise are lightly regarded. In fact, university sports culture often focuses only on physical education and sports events, while ignoring the development of other aspects, resulting in an imbalance in the whole sports culture system. The insufficient investment of the school in sports facilities and equipment leads to a lack of necessary material support for students to engage in physical exercise. At the same time, the students’ understanding and pursuit of sports often remain on the surface, lacking in the pursuit of the spirit of the deep-seated. In review of university sports culture, dialectical materialism can be used to analyze the connection among the social background, development trend and mutual influence of sports culture. The perspective of social constructivism can also be used to explore the social construction process of sports culture, all participants’ roles and interactions, and the significance and influence of sports culture in society. Therefore, in order to better solve the problems existing in university sports culture, promote the rapid development of university sports culture in the new era, enhance the confidence of campus sports culture and build a strong sports culture, this article used dialectical materialism method to analyze the current situation of university sports. It explained the relationship between philosophy and sports culture from a philosophical perspective, as well as the current problems in sports culture. Finally, it used the method of social constructivism to explain it from different perspectives. Finally, through the social constructivism method, it examined the university sports culture in the new era and, dialectically, analyzed the forms, functions, reconstruction paths and future thinking of university sports culture. Research has found that the sports culture of universities, in the new era, plays an important role in cultural, educational, and political aspects. The reconstruction and future development of university sports culture, in the new era, need to combine Eastern and Western cultures, inherit excellent traditional culture and achieve innovative development of sports culture.

We determined RNA spectrum of the human RSK4 (hRSK4) gene (also called RPS6KA6) and identified 29 novel mRNA variants derived from alternative splicing, which, plus the NCBI-documented ones and the five we reported previously, totaled 50 hRSK4 RNAs that, by our bioinformatics analyses, encode 35 hRSK4 protein isoforms of 35–762 amino acids. Many of the mRNAs are bicistronic or tricistronic for hRSK4. The NCBI-normalized NM_014496.5 and the protein it encodes are designated herein as the Wt-1 mRNA and protein, respectively, whereas the NM_001330512.1 and the long protein it encodes are designated as the Wt-2 mRNA and protein, respectively. Many of the mRNA variants responded differently to different situations of stress, including serum starvation, a febrile temperature, treatment with ethanol or ethanol-extracted clove buds (an herbal medicine), whereas the same stressed situation often caused quite different alterations among different mRNA variants in different cell lines. Mosifloxacin, an antibiotics and also a functional inhibitor of hRSK4, could inhibit the expression of certain hRSK4 mRNA variants. The hRSK4 gene likely uses alternative splicing as a handy tool to adapt to different stressed situations, and the mRNA and protein multiplicities may partly explain the incongruous literature on its expression and comports.

Abstract Background Marfan syndrome (MFS) is a rare genetic disorder caused by mutations in the Fibrillin‐1 gene (FBN1) with significant clinical features in the skeletal, cardiopulmonary, and ocular systems. To gain deeper insights into the contribution of epigenetics in the variability of phenotypes observed in MFS, we undertook the first analysis of integrating DNA methylation and gene expression profiles in whole blood from MFS and healthy controls (HCs). Methods The Illumina 850K (EPIC) DNA methylation array was used to detect DNA methylation changes on peripheral blood samples of seven patients with MFS and five HCs. Associations between methylation levels and clinical features of MFS were analyzed. Subsequently, we conducted an integrated analysis of the outcomes of the transcriptome data to analyze the correlation between differentially methylated positions (DMPs) and differentially expressed genes (DEGs) and explore the potential role of methylation‐regulated DEGs (MeDEGs) in MFS scoliosis. The weighted gene co‐expression network analysis was used to find gene modules with the highest correlation coefficient with target MeDEGs to annotate their functions in MFS. Results Our study identified 1253 DMPs annotated to 236 genes that were primarily associated with scoliosis, cardiomyopathy, and vital capacity. These conditions are typically associated with reduced lifespan in untreated MFS. We calculated correlations between DMPs and clinical features, such as cobb angle to evaluate scoliosis and FEV1% to assess pulmonary function. Notably, cg20223687 (PTPRN2) exhibited a positive correlation with cobb angle of scoliosis, potentially playing a role in ERKs inactivation. Conclusions Taken together, our systems‐level approach sheds light on the contribution of epigenetics to MFS and offers a plausible explanation for the complex phenotypes that are linked to reduced lifespan in untreated MFS patients.

ObjectiveThis study aimed to assess the diagnostic value of prenatal echocardiography for identifying transposition of the great arteries (TGA) during pregnancy and evaluating the associated outcomes.MethodsWe conducted a retrospective analysis of 121 prenatally diagnosed patients with TGA at our hospital between January 2012 and September 2022. This analysis included prenatal ultrasound, prenatal screening, clinical management and follow-up procedures.ResultsAmong the 103 fetuses considered in the study, 90 (87.4%) were diagnosed with complete transposition of the great arteries (D-TGA), while 13 (12.6%) exhibited corrected transposition of the great arteries (CC-TGA). Diagnoses were distributed across the trimester, with 8 D-TGA and 2 CC-TGA patients identified in the first trimester, 68 D-TGA patients and 9 CC-TGA patients in the second trimester, and 14 D-TGA and 2 CC-TGA patients referred for diagnosis in the third trimester. Induction of labour was pursued for 76 D-TGA patients (84.4%) and 11 CC-TGA patients (84.6%), and 14 D-TGA patients (15.6%) and 2 CC-TGA patients (15.4%) continued pregnancy until delivery. Among the D-TGA patients, 9 fetuses (10.0%) underwent surgery, two of which were inadvertent fatality, while the remaining seven experienced positive outcomes. Additionally, seven TGA patients received palliative care, leading to four fatalities among D-TGA patients (5.2%), whereas 1 D-TGA patients and 2 CC-TGA patients survived.ConclusionThis study underscores the feasibility of achieving an accurate prenatal diagnosis of TGA during early pregnancy. The utility of prenatal ultrasound in the development of personalized perinatal plans and the application of multidisciplinary treatment during delivery are conducive.

Osteogenesis imperfecta (OI) is a genetic disorder characterized by bone fragility, low bone mass, fractures, and extraskeletal manifestations. Since OI is commonly caused by single-nucleotide mutation(s) in the COL1A1 or COL1A2 genes encoding type I collagens, we developed a genome-editing strategy to correct a Col1a2 mutation in an OIM mouse model resembling a severe dominant form of human type III OI. Using a recombinant adeno-associated virus (rAAV), we delivered CRISPR-Cas9 to bone-forming osteoblast-lineage cells in the skeleton. Homology-directed repair (HDR)–mediated gene editing efficiency in these cells was improved when CRISPR-Cas9 was coupled with a donor AAV vector containing a promoterless partial mouse Col1a2 complementary DNA sequence. This approach effectively reversed the dysregulation of osteogenic differentiation by a Col1a2 mutation in vitro. Furthermore, systemic administration of dual rAAVs in OIM mice lowered bone matrix turnover rates by reducing osteoblast and osteoclast development while improving the cellular network of mechano-sensing osteocytes embedded in the bone matrix. This strategy significantly improved bone architecture/mass/mineralization, skeletal deformities, grip strength, and spontaneous fractures. Our study is the first demonstration that HDR-mediated gene editing via AAV-mediated delivery effectively corrects a collagen mutation in OI osteoblasts and reverses skeletal phenotypes in OIM mice.

Abstract Objective The muscle quality index (MQI) is a measurement of muscle quality that is directly related to overall health. There has been little study on the relationship between the muscle quality index and periodontitis in American people beyond 30 years. Therefore, this study aimed to explore the link between periodontitis and Muscle quality index (MQI) in older Americans. Methods Three thousand two hundred fifty-eight individuals (aged 30 to 59) who participated in the National Health and Nutrition Examination Survey (NHANES) 2011–2014 were considered eligible for the cross-sectional investigation. A hand dynamometer was used to determine the handgrip strength (HGS). Dual-energy X-ray absorptiometry was employed to calculate ASM (DXA). MQIArm was calculated by dividing the dominant hand’s HGS by the dominant arm’s ASM (in kg/kg). MQIApp was calculated by dividing the dominant hand’s HGS by the ASM (in kg/kg). MQItotal was calculated by dividing the sum of the dominant and non-dominant hands by the ASM (in kg/kg). To investigate the link between muscle quality index and periodontal disease, the weighted multivariable logistic regression models were used. Using generalized additive models, it was determined if a nonlinear connection existed. Then, we developed a two-piece linear regression model and calculated the inflection point using a recursive approach. A mediation study was performed to determine how much of the impact of MQItotal on periodontitis was mediated by potential variables. Results Three thousand two hundred fifty-eight participants from the United States were enrolled. The OR (95% CI) for the relationship between MQItotal and periodontitis in the regression model with fully adjusted variables was 0.69 (0.53–0.91), for the connection between MQIArm and periodontitis was 0.90 (0.84–0.97), and for the association between MQIApp and periodontitis was 0.49 (0.30–0.80). MQItotal and periodontitis were shown to have a J-shaped relationship with a change point of 3.64. Before the change point, the OR (95% CI) was 0.69 (0.58, 0.82). In the analysis of drinking and married status, the interaction was statistically significant. Analysis of mediation showed that alcohol use was responsible for 0.4% (0.10 to 1.2) of the effect of MQItotal on periodontitis. Conclusion In American adults aged over 30, the Muscle Quality Index (MQI) exhibited an independent negative correlation with moderate to severe periodontitis, demonstrating a J-shaped relationship. Furthermore, alcohol consumption may act as a mediator in the association between MQI and periodontitis.

Abstract Introduction A pan-genotypic and effective treatment regimen for patients with chronic hepatitis C virus (HCV) infection remains an unmet medical need in China. Alfosbuvir is a novel potent HCV NS5B polymerase inhibitor in development for the treatment of chronic HCV infection. We conducted a phase 3 study to evaluate the efficacy and safety of alfosbuvir in combination with daclatasvir in Chinese patients with HCV infection. Methods All patients received 600 mg alfosbuvir tablets plus 60 mg daclatasvir tablets once daily for 12 weeks. The primary endpoint was sustained virological response 12 weeks after the end of treatment (SVR12). A follow-up visit was done at week 4 and 12, and those who achieved SVR12 were followed up at post-treatment week 24. Results Of the 326 patients who received at least one dose of the study drug, 320 (98.2% [95% confidence interval (CI): 96.5%–99.5%]) achieved sustained virological response at post-treatment week 12 (SVR12), which was superior to the historical SVR12 rate of 88% (p

The features of the unconformity, fault and tectonic inversion in the eastern Doseo Basin, Chad, were analyzed, and the genetic mechanisms and basin evolution were discussed using seismic and drilling data. The following results are obtained. First, four stratigraphic unconformities, i.e. basement (Tg), Mangara Group (T10), lower Upper Cretaceous (T5) and Cretaceous (T4), four faulting stages, i.e. Barremian extensional faults, Aptian–Coniacian strike-slip faults, Campanian strike-slip faults, and Eocene strike-slip faults, and two tectonic inversions, i.e. Santonian and end of Cretaceous, were developed in the Doseo Basin. Second, the Doseo Basin was an early failed intracontinental passive rift basin transformed by the strike-slip movement and tectonic inversion. The initial rifting between the African and South American plates induced the nearly N-S stretching of the Doseo Basin, giving rise to the formation of the embryonic Doseo rift basin. The nearly E-W strike-slip movement of Borogop (F1) in the western section of the Central African Shear Zone resulted in the gradual cease of the near north-south rifting and long-term strike-slip transformation, forming a dextral transtension fault system with inherited activity but gradually weakened in intensity (interrupted by two tectonic inversions). This fault system was composed of the main shear (F1), R-type shear (F2-F3) and P-type shear (F4-F5) faults, with the strike-slip associated faults as branches. The strike-slip movements of F1 in Cretaceous and Eocene were controlled by the dextral shear opening of the equatorial south Atlantic and rapid expanding of the Indian Ocean, respectively. The combined function of the strike-slip movement of F1 and the convergence between Africa and Eurasia made the Doseo Basin underwent the Santonian dextral transpressional inversion characterized by intensive folding deformation leading to the echelon NE-SW and NNE-SSW nose-shaped uplifts and unconformity (T5) on high parts of the uplifts. The convergence between Africa and Eurasia caused the intensive tectonic inversion of Doseo Basin at the end of Cretaceous manifesting as intensive uplift, denudation and folding deformation, forming the regional unconformity (T4) and superposing a nearly E-W structural configuration on the Santonian structures. Third, the Doseo Basin experienced four evolutional stages with the features of short rifting and long depression, i.e. Barremian rifting, Aptian rifting–depression transition, Albian–Late Cretaceous depression, and Cenozoic extinction, under the control of the tectonic movements between Africa and its peripheral plates.

Abstract Background Recent studies have shown that deficient mismatch repair (dMMR) rectal cancer may be related to treatment resistance, resulting in a worse prognosis than proficient MMR (pMMR) rectal cancer. The purpose of this study was to explore whether surgery plus other treatments (radiotherapy and chemotherapy) can bring more benefits to these patients than surgery alone. Methods A retrospective study of 168 patients with rectal adenocarcinoma who underwent total mesorectal excision was conducted using immunohistochemical methods to determine MMR status and a propensity score matching model to minimize potential confounding factors between subgroups of patients with different treatment regimens. Kaplan–Meier analysis, log-rank tests, and Cox regression models were used to assess overall survival (OS) and disease-free survival (DFS) in patient subgroups. Results Only 6.9% (n = 168) of patients in the total cohort had dMMR rectal adenocarcinoma, and the most common cause of dMMR was a PMS2 deletion (103, 61.3%). The median DFS of the surgery alone group was 45.7 months (IQR, 40.9 to 77.8), and the median DFS of the surgery plus other treatment group was 43.9 months (IQR, 14.2 to 80.1). The surgery alone group was superior to the surgery plus other treatment group (HR, 0.16; 95% CI, 0.07 to 0.38; p = 0.005). There was no significant difference in OS (45.8 (IQR, 41.0 to 79.8) vs. 45.9 (IQR, 38.5 to 80.3)) between the two groups (HR, 0.57; 95% CI, 0.23 to 1.40; p = 0.263). Conclusions For patients with locally advanced dMMR rectal adenocarcinoma, compared with surgery alone, surgery plus other treatment options (radiotherapy and chemotherapy) do not grant long-term survival benefits but rather shorten DFS.

Abstract Multidrug resistance renders treatment failure in a large proportion of head and neck squamous cell carcinoma (HNSCC) patients that require multimodal therapy involving chemotherapy in conjunction with surgery and/or radiotherapy. Molecular events conferring chemoresistance remain unclear. Through transcriptome datamining, 28 genes were subjected to pharmacological and siRNA rescue functional assays on 12 strains of chemoresistant cell lines each against cisplatin, 5-fluorouracil (5FU), paclitaxel (PTX) and docetaxel (DTX). Ten multidrug chemoresistance genes (TOP2A, DNMT1, INHBA, CXCL8, NEK2, FOXO6, VIM, FOXM1B, NR3C1 and BIRC5) were identified. Of these, four genes (TOP2A, DNMT1, INHBA and NEK2) were upregulated in an HNSCC patient cohort (n = 221). Silencing NEK2 abrogated chemoresistance in all drug-resistant cell strains. INHBA and TOP2A were found to confer chemoresistance in majority of the drug-resistant cell strains whereas DNMT1 showed heterogeneous results. Pan-cancer Kaplan-Meier survival analysis on 21 human cancer types revealed significant prognostic values for INHBA and NEK2 in at least 16 cancer types. Drug library screens identified two compounds (Sirodesmin A and Carfilzomib) targeting both INHBA and NEK2 and re-sensitised cisplatin-resistant cells. We have provided the first evidence for NEK2 and INHBA in conferring chemoresistance in HNSCC cells and siRNA gene silencing of either gene abrogated multidrug chemoresistance. The two existing compounds could be repurposed to counteract cisplatin chemoresistance in HNSCC. This finding may lead to novel personalised biomarker-linked therapeutics that can prevent and/or abrogate chemoresistance in HNSCC and other tumour types with elevated NEK2 and INHBA expression. Further investigation is necessary to delineate their signalling mechanisms in tumour chemoresistance.

Mechanical force is the basis of cardiovascular development, homeostasis, and diseases. The perception and response of mechanical force by the cardiovascular system are crucial. However, the molecular mechanisms mediating mechanotransduction in the cardiovascular system are not yet understood. PIEZO1, a novel transmembrane mechanosensitive cation channel known for its regulation of touch sensation, has been found to be widely expressed in the mammalian cardiovascular system. In this review, we elucidate the role and mechanism of PIEZO1 as a mechanical sensor in cardiovascular development, homeostasis, and disease processes, including embryo survival, angiogenesis, cardiac development repair, vascular inflammation, lymphangiogenesis, blood pressure regulation, cardiac hypertrophy, cardiac fibrosis, ventricular remodeling, and heart failure. We further summarize chemical molecules targeting PIEZO1 for potential translational applications. Finally, we address the controversies surrounding emergent concepts and challenges in future applications.

To tackle the problem of difficult signal detection and carrier frequency synchronization faced by wireless communication among stations of the multistatic passive detection system in interference environments, an adaptive signal detection and carrier frequency offset (CFO) estimation method based on a virtual array is proposed in this paper. This is a data-aided method that utilizes a training sequence composed of three segments of sub-training sequences with different symbols. This method first uses spatial spectrum estimation to obtain the coarse frequency estimations of interference signals and CFO from virtual array signals constructed from the first two sub-training sequences. Then, beamforming is conducted accordingly on the virtual array signals constructed from the third sub-training sequence to suppress the in-band interferences and protrude the expected signal. Finally, improved performance of signal detection and CFO estimation is obtained with the beamformed signals. Simulation experiments show that a missed detection probability as low as 1 × 10−4, with a false detection probability of 1 × 10−3, can be obtained under a signal-to-interference ratio (SIR) of −10 dB and Eb/N0 of 1 dB. Moreover, the proposed method can also simultaneously achieve a CFO estimation error that is lower than 3%, with the condition of Eb/N0 being as low as −5 dB under different SIRs. Simulation results validate the proposed method and demonstrate the promising application prospects of the proposed method in networked passive detection scenarios.

Zygotic genome activation (ZGA) is a pivotal event in mammalian embryogenesis, marking the transition from maternal to zygotic control of development. During the ZGA process that is characterized by the intricate cascade of gene expression, who tipped the first domino in a meticulously arranged sequence is a subject of paramount interest. Recently, Dux, Obox and Nr5a2 were identified as pioneer transcription factors that reside at the top of transcriptional hierarchy. Through co-option of retrotransposon elements as hubs for transcriptional activation, these pioneer transcription factors rewire the gene regulatory network, thus initiating ZGA. In this review, we provide a snapshot of the mechanisms underlying the functions of these pioneer transcription factors. We propose that ZGA is the starting point where the embryo’s own genome begins to influence development trajectory, therefore in-depth dissecting the functions of pioneer transcription factors during ZGA will form a cornerstone of our understanding for early embryonic development, which will pave the way for advancing our grasp of mammalian developmental biology and optimizing in vitro production (IVP) techniques.

It is crucial to identify the structures of active sites to understand how catalysts function and to use that understanding to develop better catalytic materials. ZSM-5 zeolites with dominant Al(IV)-2 sites have been developed in this work. 1H-27Al 2D HMQC and 2D 1H TQ(DQ)-SQ NMR experiments have been performed to investigate the structural properties of this acidic site. The Al(IV)-2 sites have Brønsted and Lewis acid characteristics. The catalytic performance of Al(IV)-2 sites has been tested by n-dodecane cracking reactions. The catalytic results show that the Brønsted acidic strength of the Al(IV)-2 sites is comparable to that of the Al(IV)-1 sites, but the Al(IV)-2 sites’ Lewis acid characteristics provide extra catalytic activity. We have gained valuable insights into the characteristics of Al(IV)-2 acid sites within these materials.

How to enhance the desired signal with low signal-to-noise ratio (SNR) is a difficult problem in the estimation process of the direction-of-arrival (DOA) of the target scattering wave signal. In this paper, the feasibility of spatial spectrum estimation in the Range-Doppler (RD) domain is analyzed in principle, and the SNR gain expression of weak scattering wave signal is derived when constructing multi-snapshots virtual array data. On this basis, the mutual eigenvector singular value decomposition (MESVD) method based on RD domain mode excitation is proposed, which can robustly and effectively estimate the direction of the coherent weak signals. Simulation experiments verify that the RD domain spectral estimation method has the ability to simultaneously obtain the direction of multiple weak target scattering waves, and the direction-finding accuracy can reach the Cramer–Rao bound (CRB) of conventional spectral estimation method. The results of Monte Carlo experiments show that the root-mean-square-error (RMSE) of azimuth estimation of RD domain spatial spectrum estimation method is 5.76° lower than that of a conventional multiple signal classification (MUSIC) method. In addition, the practicability of the proposed method is demonstrated by comparing the DOA estimation results of a set of real data with Automatic Dependent Surveillance-Broadcast (ADS-B) data.

Abstract Meiotic recombination requires the specific RecA homolog DMC1 recombinase to stabilize strand exchange intermediates in most eukaryotes. Normal DMC1 levels are crucial for its function, yet the regulatory mechanisms of DMC1 stability are unknown in any organism. Here, we show that the degradation of Arabidopsis DMC1 by the 26S proteasome depends on F-box proteins RMF1/2-mediated ubiquitination. Furthermore, RMF1/2 interact with the Skp1 ortholog ASK1 to form the ubiquitin ligase complex SCFRMF1/2. Genetic analyses demonstrate that RMF1/2, ASK1 and DMC1 act in the same pathway downstream of SPO11-1 dependent meiotic DNA double strand break formation and that the proper removal of DMC1 is crucial for meiotic crossover formation. Moreover, six DMC1 lysine residues were identified as important for its ubiquitination but not its interaction with RMF1/2. Our results reveal mechanistic insights into how the stability of a key meiotic recombinase that is broadly conserved in eukaryotes is regulated.

Abstract Mouth ulcers have been associated with numerous loci in genome wide association studies (GWAS). Nonetheless, it remains unclear what mechanisms are involved in the pathogenesis of mouth ulcers at these loci, as well as what the most effective ulcer drugs are. Thus, we aimed to screen hub genes responsible for mouth ulcer pathogenesis. We conducted an imputed/in-silico proteome-wide association study to discover candidate genes that impact the development of mouth ulcers and affect the expression and concentration of associated proteins in the bloodstream. The integrative analysis revealed that 35 genes play a significant role in the development of mouth ulcers, both in terms of their protein and transcriptional levels. Following this analysis, the researchers identified 6 key genes, namely BTN3A3, IL12B, BPI, FAM213A, PLXNB2, and IL22RA2, which were related to the onset of mouth ulcers. By combining with multidimensional data, six genes were found to correlate with mouth ulcer pathogenesis, which can be useful for further biological and therapeutic research.

Abstract Gametophyte development in angiosperms occurs within diploid sporophytic structures and requires coordinated development; e.g., development of the male gametophyte pollen depends on the surrounding sporophytic tissue, the tapetum. The mechanisms underlying this interaction remain poorly characterized. The peptide CLAVATA3/EMBRYO SURROUNDING REGION-RELATED 19 (CLE19) plays a “braking” role in preventing the harmful overexpression of tapetum transcriptional regulators to ensure normal pollen development in Arabidopsis. However, the CLE19 receptor is unknown. Here, we show that CLE19 interacts directly with the PXY-LIKE1 (PXL1) ectodomain and induces PXL1 phosphorylation. PXL1 is also required for the function of CLE19 in maintaining the tapetal transcriptional regulation of pollen exine genes. Additionally, CLE19 induces the interactions of PXL1 with SOMATIC EMBRYOGENESIS RECEPTOR-LIKE KINASE (SERK) coreceptors required for pollen development. We propose that PXL1 and SERKs act as receptor and coreceptor, respectively, of the extracellular CLE19 signal, thereby regulating tapetum gene expression and pollen development.