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Catastrophe theory was used to establish a safety assessment model to reduce the reliance on subjective judgments in evaluation of timber-framed heritage buildings. This study was conducted in three phases. Initially, a comprehensive evaluation index system was established from the perspective of foundation. It consisted of eight aspects and 25 safety evaluation indicators using superstructure load-bearing elements, maintenance structures, and their interconnections in timber-framed heritage buildings. The 25 safety evaluation indicators included foundation, base, stone piers, columns, beams, lintels (beams, pads, and other bending components), bracket sets, arches, maintenance walls, beam-brace connections, and roof structures. The bottom-level indicators in the index system were dimensionless. The second phase employed typical catastrophe models (cusp, swallowtail, and butterfly) for normalization, resulting in calculated catastrophe scales and evaluation levels. The case study of the Buddha Hall of Zhihua Temple, Beijing, was applied in the final phase. It was found that the catastrophe scales method solved the subjectivity issues in determining weights. Additionally, the calculations were found to be concise and reliable, providing accurate results. The model can be used as a theoretical reference for the future safety assessment of timber-framed heritage buildings.

In order to efficiently obtain solutions for large-scale multi-objective optimization problems in reality, to achieve a balance among convergence, diversity, and uniformity has gradually become one of the important goals in multi-objective optimization. This paper proposes a multi-objective discrete combinatorial optimization algorithm combining problem-decomposition and adaptive large neighborhood search (MOALNS) for complex multi-objective discrete combinatorial optimization problems. The algorithm introduces large neighborhood search strategies and adaptive adjustment mechanisms for the optimization process of each sub-problem based on problem decomposition, forming a new set of convergence-guiding criteria to break through optimization barriers and achieve a balance between global and local search in the process of searching the multi-dimensional solution space for each sub-problem. In addition, this paper proposes that configuring independent operator integration libraries for each sub-problem can effectively adjust the optimization direction of each sub-problem, solving the problem of solution direction deviation caused by different objective weights, and thus achieving a more efficient and stable multi-objective optimization process. Numerical experiments demonstrate that the proposed new multi-objective discrete combinatorial optimization algorithm exhibits good performance in terms of convergence, diversity, uniformity, and extensibility in multiple sets of standard benchmark test cases and case studies, and holds advantages compared with other classical multi-objective optimization algorithms.

Abstract Age-related microangiopathy, also known as small vessel disease (SVD), causes damage to the brain, retina, liver, and kidney. Based on the DNA damage theory of aging, we reasoned that genomic instability may underlie an SVD caused by dominant C-terminal variants in TREX1, the most abundant 3′−5′ DNA exonuclease in mammals. C-terminal TREX1 variants cause an adult-onset SVD known as retinal vasculopathy with cerebral leukoencephalopathy (RVCL or RVCL-S). In RVCL, an aberrant, C-terminally truncated TREX1 mislocalizes to the nucleus due to deletion of its ER-anchoring domain. Since RVCL pathology mimics that of radiation injury, we reasoned that nuclear TREX1 would cause DNA damage. Here, we show that RVCL-associated TREX1 variants trigger DNA damage in humans, mice, and Drosophila, and that cells expressing RVCL mutant TREX1 are more vulnerable to DNA damage induced by chemotherapy and cytokines that up-regulate TREX1, leading to depletion of TREX1-high cells in RVCL mice. RVCL-associated TREX1 mutants inhibit homology-directed repair (HDR), causing DNA deletions and vulnerablility to PARP inhibitors. In women with RVCL, we observe early-onset breast cancer, similar to patients with BRCA1/2 variants. Our results provide a mechanistic basis linking aberrant TREX1 activity to the DNA damage theory of aging, premature senescence, and microvascular disease.

Abstract Introduction Over the past decade, numerous studies have described the types of pathogens and their antibiotic resistance patterns in patients with burn injuries in China; however, the findings have generally been inconsistent. We conducted a literature search and meta-analysis to summarize the infection spectra and antimicrobial resistance patterns in patients with burn injuries. Methods We searched the PubMed, Embase, Web of Science, China National Knowledge Infrastructure, China Biomedical Literature, Wanfang, and Weipu databases for relevant articles published between January 2010 and December 2023. The DerSimonian–Laird random-effects model was used to estimate the proportions and 95% confidence intervals (CIs) of pathogens among Chinese patients with burn injuries. Meta-regression analyses were performed to explore differences in the proportions of pathogens among different subgroups and their resistance patterns. This study was registered with PROSPERO (CRD42024514386). Results The database searches yielded 2017 records; after removing duplicates and conducting initial screening, 219 articles underwent full-text screening. Ultimately, 60 studies comprising a total of 62,819 isolated strains reported the proportions of pathogens in patients with burn injuries and were included in this meta-analysis. Meta-analyses were conducted on 18 types of pathogens. The most common pathogens causing infections in Chinese patients with burn injuries were Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, and Staphylococcus epidermidis. Similar results were observed in the subgroup analysis focusing on wound infections. Since 2015, there has been a significant decrease in the proportion of Pseudomonas aeruginosa (R 2 = 4.89%) and a significant increase in the proportion of Klebsiella pneumoniae (R 2 = 9.60%). In terms of antibiotic resistance, there has been a significant decrease in the resistance of Staphylococcus aureus to multiple antibiotics and an increasing trend in the resistance of Klebsiella pneumoniae. Conclusions We systematically summarized the epidemiological characteristics and antibiotic resistance patterns of pathogens among individuals suffering from burns in China, thus providing guidance for controlling wound infections and promoting optimal empirical antimicrobial therapy. The observed high levels of antibiotic resistance underscore the need for ongoing monitoring of antibiotic usage trends.

The necrotrophic fungus, Sclerotinia sclerotiorum, employs an array of cell wall-degrading enzymes (CWDEs), including cellulase, to dismantle host cell walls. However, the molecular mechanisms through which S. sclerotiorum degrades cellulose remain elusive. Here, we unveil a novel secretory cellobiohydrolase, SsdchA, characterized by a signal peptide and a Glyco_hydro_7 (GH7) domain. SsdchA exhibits a robust expression of during early infection stages. Interestingly, colony morphology and growth rates remain unaffected across the wild-type, SsdchA deletion strains and SsdchA overexpression strains on potato dextrose agar (PDA) medium. Nevertheless, the pathogenicity and cellobiohydrolase activity decreased in the SsdchA deletion strains, but enhanced in the SsdchA overexpression strains. Moreover, the heterologous expression of SsdchA in Arabidopsis thaliana leads to reduced cellulose content and heightened susceptibility to S. sclerotiorum. Collectively, our data underscore the pivotal role of the novel cellobiohydrolase SsdchA in the pathogenicity of S. sclerotiorum.

Abstract Sclerotinia sclerotiorum is a widespread fungal pathogen responsible for significant crop losses across the globe. The challenge of breeding resistant varieties is exacerbated by the fungus's sophisticated pathogenic mechanisms. A pivotal factor in the host-pathogen interaction is the regulation of reactive oxygen species (ROS) within both the fungi and the host plants. However, there is currently no efficient strategy to leverage this interaction mechanism for developing disease-resistant crop varieties. Here, we introduce an engineered ROS scavenging system designated as syn-ROS for impairing ROS neutralization in S. sclerotiorum while concurrently fortifying it in the host. The syn-ROS system comprises gene silencing constructs targeting the S. sclerotiorum Cu/Zn superoxide dismutase (SsSOD) and its copper chaperone (SsCCS), alongside overexpression constructs for the Arabidopsis thaliana AtSOD1 and AtCCS. Transgenic plants carrying the syn-ROS system demonstrated a marked enhancement in resistance to S. sclerotiorum. Upon infection, the expression of SsSOD and SsCCS was reduced, while the expression of AtSOD1 and AtCCS was enhanced in syn-ROS transgenic plants. Moreover, the infected syn-ROS plants showed decreased Cu/Zn SOD enzyme activity and elevated ROS concentrations within the fungal cells. In contrast, the cells of A. thaliana manifested increased Cu/Zn SOD enzyme activity and lowered ROS levels. Collectively, these findings suggest a novel and promising approach for contriving plants with robust resistance by synthetically manipulating ROS scavenging activities in the interaction between the host and S. sclerotiorum.

Abstract Background Glioblastoma multiforme (GBM) is the most aggressive form of brain cancer, and chemoresistance poses a significant challenge to the survival and prognosis of GBM. Although numerous regulatory mechanisms that contribute to chemoresistance have been identified, many questions remain unanswered. This study aims to identify the mechanism of temozolomide (TMZ) resistance in GBM. Methods Bioinformatics and antibody-based protein detection were used to examine the expression of E2F7 in gliomas and its correlation with prognosis. Additionally, IC50, cell viability, colony formation, apoptosis, doxorubicin (Dox) uptake, and intracranial transplantation were used to confirm the role of E2F7 in TMZ resistance, using our established TMZ-resistance (TMZ-R) model. Western blot and ChIP experiments provided confirmation of p53-driven regulation of E2F7. Results Elevated levels of E2F7 were detected in GBM tissue and were correlated with a poor prognosis for patients. E2F7 was found to be upregulated in TMZ-R tumors, and its high levels were linked to increased chemotherapy resistance by limiting drug uptake and decreasing DNA damage. The expression of E2F7 was also found to be regulated by the activation of p53. Conclusions The high expression of E2F7, regulated by activated p53, confers chemoresistance to GBM cells by inhibiting drug uptake and DNA damage. These findings highlight the significant connection between sustained p53 activation and GBM chemoresistance, offering the potential for new strategies to overcome this resistance.

ObjectiveA longitudinal study was conducted to investigate whether rapid eye movement sleep behavior disorder affect depression in patients with Parkinson's disease through activities of daily living.MethodsA total of 387 Parkinson's disease patients' six-year follow-up data (one follow-up per year) were obtained from the Parkinson's Progression Markers Initiative. To allow causal effects to manifest, this study increased the lag period and divided the data from the six follow-ups into two groups: wave 1 (wave refers to time points), wave 3, and wave 5 as one group, and wave 2, wave 4, and wave6 as the other group. The time interval between two time points in each group was two years. To comprehensively and deeply analyze the dynamic relationships between variables, accurately infer causal relationships, control for individual differences, and detect the stability of these relationships, this study constructed the fixed effects cross-lagged panel model (CLPM), the random effects CLPM (RE-CLPM) model, and the Equating CLPM and Equating RE-CLPM models with applied restriction conditions. Additionally, a reverse path was added to verify the reverse prediction effect. The most suitable data analysis model was selected to explore the relationships between the study variables. Furthermore, the longitudinal mediating effect of daily living activities between rapid eye movement sleep behavior disorder and depression was investigated.ResultsIn the models, Equating cross-lagged panel model was the best. The lag effect was positive and significant. In wave 1, 3, 5, activities of daily living mediated 11.82% on the path from rapid eye movement sleep behavior disorder to depression; in wave 2, 4, 6, it mediated 13.13%. Therefore, attention should be paid to the treatment of activities of daily living.ConclusionLongitudinal changes in activities of daily living have indirect effects on the relationship between rapid eye movement sleep behavior disorder and depression, which highlights the importance of changes in activities of daily living ability in Parkinson's disease patients with rapid eye movement sleep behavior disorder.

Age and gender have been recognized as two pivotal covariates affecting the composition of the gut microbiota. However, their mediated variations in microbiota seem to be inconsistent across different countries and races. In this study, 613 individuals, whom we referred to as the “healthy” population, were selected from 1,018 volunteers through rigorous selection using 16S rRNA sequencing. Three enterotypes were identified, namely, Escherichia–Shigella, mixture (Bacteroides and Faecalibacterium), and Prevotella. Moreover, 11 covariates that explain the differences in microbiota were determined, with age being the predominant factor. Furthermore, age-related differences in alpha diversity, beta diversity, and core genera were observed in our cohort. Remarkably, after adjusting for 10 covariates other than age, abundant genera that differed between age groups were demonstrated. In contrast, minimal differences in alpha diversity, beta diversity, and differentially abundant genera were observed between male and female individuals. Furthermore, we also demonstrated the age trajectories of several well-known beneficial genera, lipopolysaccharide (LPS)-producing genera, and short-chain fatty acids (SCFAs)-producing genera. Overall, our study further elucidated the effects mediated by age and gender on microbiota differences, which are of significant importance for a comprehensive understanding of the gut microbiome spectrum in healthy individuals.

Free-play-induced nonlinear dynamic behavior has been one of the most important topics of aeroelastic research in recent decades. In this paper, the describing function (DF) method is developed to investigate the complex dynamic response of a popular all-movable horizontal tail with free-play. Piecewise expressions for the time history and phase portrait of limit cycle oscillation (LCO) are derived by the developed DF method, which is conducive to understand the mechanism of free-play-induced LCO. Another advantage of the developed DF method is the ability to predict the high-order harmonics, which cannot be realized by the classic DF method. A three-dimensional (3D) all-movable horizontal tail model with torsional free-play was designed and manufactured to implement wind tunnel tests via various initial parameters. A good agreement was found between the numerical and experimental results, which can demonstrate the effectiveness of the proposed method. The influence of the initial parameters of the all-movable horizontal tail on the LCO characteristics is analyzed by both numerical calculations and wind tunnel tests. The method and results in this paper can provide a significant reference for the design of all-movable horizontal tail versus the free-play-induced LCO.

Abstract Objectives To establish a predictive model for sepsis after percutaneous nephrolithotomy (PCNL) using machine learning to identify high-risk patients and enable early diagnosis and intervention by urologists. Methods A retrospective study including 694 patients who underwent PCNL was performed. A predictive model for sepsis using machine learning was constructed based on 22 preoperative and intraoperative parameters. Results Sepsis occurred in 45 of 694 patients, including 16 males (35.6%) and 29 females (64.4%). Data were randomly segregated into an 80% training set and a 20% validation set via 100-fold Monte Carlo cross-validation. The variables included in this study were highly independent. The model achieved good predictive power for postoperative sepsis (AUC = 0.89, 87.8% sensitivity, 86.9% specificity, and 87.4% accuracy). The top 10 variables that contributed to the model prediction were preoperative midstream urine bacterial culture, sex, days of preoperative antibiotic use, urinary nitrite, preoperative blood white blood cell (WBC), renal pyogenesis, staghorn stones, history of ipsilateral urologic surgery, cumulative stone diameters, and renal anatomic malformation. Conclusion Our predictive model is suitable for sepsis estimation after PCNL and could effectively reduce the incidence of sepsis through early intervention.

ObjectiveBrassinolide is an important endogenous plant hormone. In this work, an electrochemical immunosensor for in situ detection of brassinolide was constructed using screen-printed electrode (SPE).MethodsAu nanoparticles (AuNPs) were firstly electrodeposited on the surface of SPE electrode by electrochemical workstation, and then CuCl2 nanowires (CuCl2 NWs) were added to the electrode, which can not only increase the conductivity of the electrode, but also Cu2+ can be used as a REDOX probe for the sensor. Finally, Mxene and polydopamine nanocomposite (Mxene@PDA) were selected as the modification materials for SPE electrodes because Mxene has the advantages of large surface area and good electrical conductivity, which can further amplify Cu2+ signals. However, Mxene is easily oxidized and unstable in air. Polydopamine (PDA) contains a large number of catechol and amino groups, which are coated on the surface of Mxene after self-polymerization by dopamine, cutting off the path of oxygen penetration, making Mxene difficult to be oxidized. Mxene@PDA can also be used as a coupling agent to fix more antibodies on the electrode surface, improving the overall biocompatibility, and improve the overall biocompatibility.Results and DiscussionsThe sensor has a wide linear detection range: 0.1 pg/mL to 1 mg/mL, and the detection limit was 0.015 pg/ml (S/N=3). In addition, the content of endogenous brassinolide in wheat was detected by SPE electrodes in vitro and the recovery rate was 98.13% to 104.74%.While verifying the accuracy of the sensor, it also demonstrated its superior stability and sensitivity. Besides, the sensor also showed excellent application potential in the in situ detection of brassinosteroids from wheat leaves. Compared with other brassinolide detection methods, the immunosensor developed in this study has better analytical performance.ConclusionsAn electrochemical immunosensor for in situ detection of brassinolide was developed for the first time, providing a good electrochemical platform for in situ determination of brassinolide in plant leaves, which has great application potential in precision agriculture.

Ovarian cancer is one of the three most common types of gynecological cancer globally, with high-grade serous ovarian cancer being the most common and aggressive histological type. Guided treatment of high-grade serous ovarian cancer typically involves platinum-based combination chemotherapy, necessitating the assessment of whether the patient is platinum resistant. This study proposes a deep learning-based method to determine whether a patient is platinum resistant using multimodal positron emission tomography/computed tomography images. In total, 289 patients with high-grade serous ovarian cancer were included in this study. An end-to-end Squeeze-Excitation–Spatial Pyramid Pooling–Dense Convolutional Network model was built by adding a Squeeze-Excitation Block and Spatial Pyramid Pooling Layer to a Dense Convolutional Network. Multimodal data from positron emission tomography/computed tomography images of regions of interest were used to predict platinum resistance in patients. Through five-fold cross-validation, the Squeeze-Excitation–Spatial Pyramid Pooling–Dense Convolutional Network achieved a high accuracy rate and area under the curve of 92.6% and 0.93, respectively, for predicting platinum resistance in patients. The importance of incorporating the Squeeze-Excitation Block and Spatial Pyramid Pooling Layer into the deep learning model and considering multimodal data was substantiated by performing ablation studies and experiments with single-modality data. The classification results indicate that our proposed deep learning framework performs better in predicting platinum resistance in patients, which can help gynecologists make more appropriate treatment decisions.

Abstract Background Prostate cancer (PCa) is one of the most common cancers in men worldwide, and its timely diagnosis and treatment are becoming increasingly important. MRI is in increasing use to diagnose cancer and to distinguish between non-clinically significant and clinically significant PCa, leading to more precise diagnosis and treatment. The purpose of this study is to present a radiomics-based method for determining the Gleason score (GS) for PCa using tumour heterogeneity on multiparametric MRI (mp-MRI). Methods Twenty-six patients with biopsy-proven PCa were included in this study. The quantitative T2 values, apparent diffusion coefficient (ADC) and signal enhancement rates (α) were calculated using multi-echo T2 images, diffusion-weighted imaging (DWI) and dynamic contrast-enhanced MRI (DCE-MRI), for the annotated region of interests (ROI). After texture feature analysis, ROI range expansion and feature filtering was performed. Then obtained data were put into support vector machine (SVM), K-Nearest Neighbor (KNN) and other classifiers for binary classification. Results The highest classification accuracy was 73.96% for distinguishing between clinically significant (Gleason 3 + 4 and above) and non-significant cancers (Gleason 3 + 3) and 83.72% for distinguishing between Gleason 3 + 4 from Gleason 4 + 3 and above, which was achieved using initial ROIs drawn by the radiologists. The accuracy improved when using expanded ROIs to 80.67% using SVM and 88.42% using Bayesian classification for distinguishing between clinically significant and non-significant cancers and Gleason 3 + 4 from Gleason 4 + 3 and above, respectively. Conclusions Our results indicate the research significance and value of this study for determining the GS for prostate cancer using the expansion of the ROI region.

Dendritic cells (DCs) are involved in the initiation and maintenance of immune responses against malignant cells by recognizing conserved pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) through pattern recognition receptors (PRRs). According to recent studies, tumor cell-derived DNA molecules act as DAMPs and are recognized by DNA sensors in DCs. Once identified by sensors in DCs, these DNA molecules trigger multiple signaling cascades to promote various cytokines secretion, including type I IFN, and then to induce DCs mediated antitumor immunity. As one of the potential attractive strategies for cancer therapy, various agonists targeting DNA sensors are extensively explored including the combination with other cancer immunotherapies or the direct usage as major components of cancer vaccines. Moreover, this review highlights different mechanisms through which tumor-derived DNA initiates DCs activation and the mechanisms through which the tumor microenvironment regulates DNA sensing of DCs to promote tumor immune escape. The contributions of chemotherapy, radiotherapy, and checkpoint inhibitors in tumor therapy to the DNA sensing of DCs are also discussed. Finally, recent clinical progress in tumor therapy utilizing agonist-targeted DNA sensors is summarized. Indeed, understanding more about DNA sensing in DCs will help to understand more about tumor immunotherapy and improve the efficacy of DC-targeted treatment in cancer.

Summary: Quorum sensing (QS) is a cell-to-cell communication mechanism mediated by small diffusible signaling molecules. Previous studies showed that RpfR controls Burkholderia cenocepacia virulence as a cis-2-dodecenoic acid (BDSF) QS signal receptor. Here, we report that the fatty acyl-CoA ligase DsfR (BCAM2136), which efficiently catalyzes in vitro synthesis of lauryl-CoA and oleoyl-CoA from lauric acid and oleic acid, respectively, acts as a global transcriptional regulator to control B. cenocepacia virulence by sensing BDSF. We show that BDSF binds to DsfR with high affinity and enhances the binding of DsfR to the promoter DNA regions of target genes. Furthermore, we demonstrate that the homolog of DsfR in B. lata, RS02960, binds to the target gene promoter, and perception of BDSF enhances the binding activity of RS02960. Together, these results provide insights into the evolved unusual functions of DsfR that control bacterial virulence as a response regulator of QS signal.

Concussions are a serious public health problem, with significant healthcare costs and risks. One of the most serious complications of concussions is an increased risk of subsequent musculoskeletal injuries (MSKI). However, there is currently no reliable way to identify which individuals are at highest risk for post-concussion MSKIs. This study proposes a novel data analysis strategy for developing a clinically feasible risk score for post-concussion MSKIs in student-athletes. The data set consists of one-time tests (eg, mental health questionnaires), relevant information on demographics, health history (including details regarding the concussion such as day of the year and time lost) and athletic participation (current sport and contact level) that were collected at a single time point as well as multiple time points (baseline and follow-up time points after the concussion) of the clinical assessments (ie, cognitive, postural stability, reaction time and vestibular and ocular motor testing). The follow-up time point measurements were treated as individual variables and as differences from the baseline. Our approach used a weight-of-evidence (WoE) transformation to handle missing data and variable heterogeneity and machine learning methods for variable selection and model fitting. We applied a training-testing sample splitting scheme and performed variable preprocessing with the WoE transformation. Then, machine learning methods were applied to predict the MSKI indicator prediction, thereby constructing a composite risk score for the training-testing sample. This methodology demonstrates the potential of using machine learning methods to improve the accuracy and interpretability of risk scores for MSKI.

Abstract Nitrate pollution in surface water has become a significant environmental concern. Sulfur autotrophic denitrification (SAD) technology is gaining attention for its cost-effectiveness and efficiency in nitrate removal. This study aimed to investigate the structure and function of sulfur autotrophic denitrification microbial communities in systems using sodium thiosulfate (Group A) and elemental sulfur (Group B) as the sole electron donors. Metagenomic amplicon sequencing and physicochemical analysis were performed to examine the microbial communities. The results revealed that on day 13, the nitrate nitrogen removal rate in Group A was significantly higher (89.2%) compared to Group B (74.4%). The dominant genus in both Groups was Thiobacillus, with average abundances of 34.15% and 16.34% in Groups A and B, respectively. β-diversity analysis based on species level showed significant differences in bacterial community structure between the two Groups (P

The performance requirements of modern fighters meet multiple targets such as high speed, high mobility, stealth, lightweight and so on. The aircraft with a tailless flying wing configuration has the advantages of high aerodynamic efficiency, good mobility, low detectability, and flying integration. Such configuration adopts a structural design with wing and body fusion, multi-control surface and all-moving wing tip. The innovative structure of the wing tip highlights its aeroelasticity problem, in which the coupling effect between the structure of wing tip and the control surface makes the flutter behavior particularly prominent. This paper adopted the linear flutter method and the mode tracking method to study the flutter problem of all-moving wing tip. According to the study, the flutter coupling has three types for the aircraft with a tailless flying wing configuration: coupling between the first symmetrical bending of wing and the symmetric rotation of all-moving wing tip (symmetrical couple), coupling between the first anti-symmetrical bending of wing and the anti-symmetric rotation of all-moving wing tip (antisymmetric couple) and the fuselage mode in flutter. It is found that the flutter speed of the antisymmetric coupling type is lower than that of the symmetric coupling type. From the flutter result, the coupling flutter speed of the fuselage and wing is higher than that of the former two, and the coupling speed of the fuselage and the all-moving wing tip is lower than that of the former two. The main structural factors affecting the symmetric coupled flutter are wing bending stiffness and rotational stiffness of the all-moving tip, while the main structural factors affecting the antisymmetric coupled flutter are wing bending stiffness, fuselage rotational inertia and rotational stiffness of the all-moving tip. The all-moving wing tip structure is the internal factor that makes the tailless flying wing prone to flutter.

Abstract Previous studies have demonstrated that bis-(3',5')-cyclic diguanosine monophosphate (bis-3',5'-c-di-GMP) is a ubiquitous second messenger employed by bacteria. Here, we report that 2',3'-cyclic guanosine monophosphate (2',3'-cGMP) controls the important biological functions, quorum sensing (QS) signaling systems and virulence in Ralstonia solanacearum through the transcriptional regulator RSp0980. This signal specifically binds to RSp0980 with high affinity and thus abolishes the interaction between RSp0980 and the promoters of target genes. In-frame deletion of RSp0334, which contains an evolved GGDEF domain with a LLARLGGDQF motif required to catalyze 2',3'-cGMP to (2',5')(3',5')-cyclic diguanosine monophosphate (2',3'-c-di-GMP), altered the abovementioned important phenotypes through increasing the intracellular 2',3'-cGMP levels. Furthermore, we found that 2',3'-cGMP, its receptor and the evolved GGDEF domain with a LLARLGGDEF motif also exist in the human pathogen Salmonella typhimurium. Together, our work provides insights into the unusual function of the GGDEF domain of RSp0334 and the special regulatory mechanism of 2',3'-cGMP signal in bacteria.

Abstract Amidst progressive advancements in tissue engineering, there has been a significant enhancement in the efficacy of anti-inflammatory hydrogel dressings, addressing a myriad of clinical challenges on wound healing. A frequent complication during the initial stages of deep second-degree burn wound healing is the onset of an inflammatory storm, typically occurring without effective intervention. This event disrupts normal biological healing sequences, leading to undesirable regression. In response, we have customized a tunable, multidimensional anti-inflammatory hydrogel platform based on sulfated alginates (Algs), loaded with Prussian blue (PB) nanozymes. This platform competently eliminates surplus reactive oxygen species (ROS) present in the wound bed. Algs, functioning as a mimic of sulfated glycosaminoglycans (including heparin, heparan sulfate, and chondroitin sulfate) in the extracellular matrices (ECM), demonstrate a high affinity towards inflammatory chemokines such as interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1). This affinity effectively impedes the infiltration of inflammatory cells into the wound. Concurrently, Algs markedly modulate the macrophage phenotype transition from M1 to M2. Ultimately, our potent anti-inflammatory hydrogels, which strategically target inflammatory chemokines, M1 macrophages, and ROS, successfully attenuate dysregulated hyperinflammation in wound sites. Precise immunomodulation administered to deep second-degree burn wounds in mice has demonstrated promotion of neovascular maturation, granulation tissue formation, collagen deposition, and wound closure. Our biomimetic hydrogels, therefore, represent a significant expansion in the repertoire of anti-inflammatory strategies available for clinical practice.

Abstract Objectives This study aims to establish nomograms to accurately predict the overall survival (OS) and progression-free survival (PFS) in patients with non-small cell lung cancer (NSCLC) who received chemotherapy alone as the first-line treatment. Materials and methods In a training cohort of 121 NSCLC patients, radiomic features were extracted, selected from intra- and peri-tumoral regions, and used to build signatures (S1 and S2) using a Cox regression model. Deep learning features were obtained from three convolutional neural networks and utilized to build signatures (S3, S4, and S5) that were stratified into over- and under-expression subgroups for survival risk using X-tile. After univariate and multivariate Cox regression analyses, a nomogram incorporating the tumor, node, and metastasis (TNM) stages, radiomic signature, and deep learning signature was established to predict OS and PFS, respectively. The performance was validated using an independent cohort (61 patients). Results TNM stages, S2 and S3 were identified as the significant prognosis factors for both OS and PFS; S2 (OS: (HR (95%), 2.26 (1.40–3.67); PFS: (HR (95%), 2.23 (1.36–3.65)) demonstrated the best ability in discriminating patients with over- and under-expression. For the OS nomogram, the C-index (95% CI) was 0.74 (0.70–0.79) and 0.72 (0.67–0.78) in the training and validation cohorts, respectively; for the PFS nomogram, the C-index (95% CI) was 0.71 (0.68–0.81) and 0.72 (0.66–0.79). The calibration curves for the 3- and 5-year OS and PFS were in acceptable agreement between the predicted and observed survival. The established nomogram presented a higher overall net benefit than the TNM stage for predicting both OS and PFS. Conclusion By integrating the TNM stage, CT radiomic signature, and deep learning signatures, the established nomograms can predict the individual prognosis of NSCLC patients who received chemotherapy. The integrated nomogram has the potential to improve the individualized treatment and precise management of NSCLC patients.

Abstract Background Diabetes can lead to extensive damage to the enteric nervous system (ENS), causing gastrointestinal motility disorders. However, there is currently a lack of effective treatments for diabetes-induced ENS damage. Enteric neural precursor cells (ENPCs) closely regulate the structural and functional integrity of the ENS. L-Fucose, is a dietary sugar that has been showed to effectively ameliorate central nervous system injuries, but its potential for ameliorating ENS damage and the involvement of ENPCs in this process remains uncertain. Methods Genetically engineered mice were generated for lineage tracing of ENPCs in vivo. Using diabetic mice in vivo and high glucose-treated primary ENPCs in vitro, the effects of L-Fucose on the injured ENS and ENPCs was evaluated by assessing gastrointestinal motility, ENS structure, and the differentiation of ENPCs. The key signaling pathways in regulating neurogenesis and neural precursor cells properties, transforming growth factor-β (TGF-β) and its downstream signaling pathways were further examined to clarify the potential mechanism of L-Fucose on the injured ENS and ENPCs. Results L-Fucose improved gastrointestinal motility in diabetic mice, including increased defecation frequency (p

Background: Kawasaki disease (KD) is a vasculitis associated with vascular injury and autoimmune response. Inflammatory factors stimulate neutrophils to produce web-like structures called neutrophil extracellular traps (NETs). Citrullinated histone 3 (H3Cit) is one of the main protein components of neutrophil extracellular traps involved in the process of NETosis. The levels of NETs and H3Cit in the KD are not known.Objective: To determine the changes in the levels of NETs and H3Cit in KD.Methods: Children with KD were recruited and divided into the acute KD and the sub-acute KD group according to the disease phase and whether intravenous immunoglobulin (IVIG) was used or not. Peripheral venous blood was taken before and after the IVIG administration and sent for the examination of NETs by flow cytometry. The level of H3Cit was measured by enzyme-linked immunosorbent assay (ELISA).Results: The counts of NETs in the acute KD group significantly increased compared with the healthy controls (p

The common bean (Phaseolus vulgaris L.) is an economically important food crop grown worldwide; however, its production is affected by various environmental stresses, including cold, heat, and drought stress. The plant U-box (PUB) protein family participates in various biological processes and stress responses, but the gene function and expression patterns of its members in the common bean remain unclear. Here, we systematically identified 63 U-box genes, including 8 tandem genes and 55 non-tandem genes, in the common bean. These PvPUB genes were unevenly distributed across 11 chromosomes, with chromosome 2 holding the most members of the PUB family, containing 10 PUB genes. The analysis of the phylogenetic tree classified the 63 PUB genes into three groups. Moreover, transcriptome analysis based on cold-tolerant and cold-sensitive varieties identified 4 differentially expressed PvPUB genes, suggesting their roles in cold tolerance. Taken together, this study serves as a valuable resource for exploring the functional aspects of the common bean U-box gene family and offers crucial theoretical support for the development of new cold-tolerant common bean varieties.

Visual SLAM technology is one of the important technologies for mobile robots. Existing feature-based visual SLAM techniques suffer from tracking and loop closure performance degradation in complex environments. We propose the DFD-SLAM system to ensure outstanding accuracy and robustness across diverse environments. Initially, building on the ORB-SLAM3 system, we replace the original feature extraction component with the HFNet network and introduce a frame rotation estimation method. This method determines the rotation angles between consecutive frames to select superior local descriptors. Furthermore, we utilize CNN-extracted global descriptors to replace the bag-of-words approach. Subsequently, we develop a precise removal strategy, combining semantic information from YOLOv8 to accurately eliminate dynamic feature points. In the TUM-VI dataset, DFD-SLAM shows an improvement over ORB-SLAM3 of 29.24% in the corridor sequences, 40.07% in the magistrale sequences, 28.75% in the room sequences, and 35.26% in the slides sequences. In the TUM-RGBD dataset, DFD-SLAM demonstrates a 91.57% improvement over ORB-SLAM3 in highly dynamic scenarios. This demonstrates the effectiveness of our approach.

Anti-IgLON5 disease is a recently discovered autoimmune encephalopathy with sleep disorder as a hallmark in the majority of reported cases. Additional neurological manifestations include bulbar dysfunction, gait problems, movement disorders, oculomotor abnormalities, and hyperexcitability of the nervous system. At present, an increasing number of publications have dealt with the course and possible treatment options for anti-IgLON5 disease, and its clinical spectrum has expanded wider and more heterogeneous. Here, we report a case of a 66-year-old female with cognitive impairment accompanied by slow reaction, impaired memory, and decreased orientation. A positive cerebral MRI change and serum and cerebrospinal fluid (CSF) antibodies against IgLON5 were found during the diagnostic course. Subsequently the patient received immunotherapy and was generally in good health with no new symptoms during follow-up. Early testing for IgLON5 antibodies should be considered in patients with atypical neurological symptoms such as cognitive impairment, slow reaction, or decreased orientation. In clinical practice, immunotherapy should be considered in all cases of anti-IgLON5 encephalopathies.

Frank’s sign (FS) refers to a diagonal skin fold between the tragus and the outer edge of the earlobe. FS has been identified as an independent variable in coronary artery disease (CAD). Young patients with FS and previous myocardial infarction are still rarely reported in clinical studies. We report the case of a 49-year-old male smoker and diabetic, with a history of myocardial infarction, who presented to the emergency department due to 2 h typical cardiac chest pain. His urgent electrocardiography (ECG) showed ST elevation, and cardiac biomarkers were elevated after admission. A diagonal earlobe crease (DELC) was observed in physical tests. The preliminary diagnosis considered acute coronary syndrome (ACS). Subsequently, acute coronary artery angiography demonstrated a slit-like contrast defect in the proximal right coronary artery (RCA), with stenosis and occlusion in the distal segment. The percutaneous coronary intervention (PCI) was performed immediately. The patient’s chest pain symptoms were relieved significantly after intervention. Our case indicates that FS should be highly regarded as a routine cardiovascular clinical examination, which can be effortlessly applied and be easily interpreted for screening to suspect the presence of ischemic heart disease. This may set strategies for primary screening in a younger population and prompt early diagnosis and treatment.

To observe the clinical effect of Shenhong Tongluo Recipe on carotid atherosclerosis. Method: 72 patients were randomly divided into a control group (36 cases) and an experimental group (36 cases). The control group received atorvastatin calcium, while the experimental group received the Shenhong Tongluo formula. The treatment program consisted of 24 weeks. Observe the thickness of the intima media and plaque area of the carotid artery; Hs CRP, MLR (mononuclear C/lymphoid C), NLR (neutrophil C/lymphoid C); Clinical efficacy of traditional Chinese medicine and TCM syndrome score; Measurement of blood lipid levels (TG, TC, HDL, LDL); Homocysteine and uric acid; Changes in safety indicators. The total effective rate of the experimental group was higher than that of the control group (P

Fut2-mediated α1,2-fucosylation is important for gut homeostasis, including the intestinal stem cell (ISC). The stemness of ISC declines with age, and aging-associated ISC dysfunction is closely related to many age-related intestinal diseases. We previously found intestinal epithelial dysfunction in some aged Fut2 knockout mice. However, how Fut2-mediated α1,2-fucosylation affects ISC aging is still unknown. On this basis, the herein study aims to investigate the role of Fut2-mediated α1,2-fucosylation in ISC aging. Aging models in ISC-specific Fut2 knockout mice were established. ISCs were isolated for proteomics and N-glycoproteomics analysis. ISC functions and mitochondrial functions were examined in mice and organoids. Ulex europaeus agglutinin I chromatography and site-directed mutagenesis were used to validate the key target fucosylated proteins of Fut2. As a result, Fut2 knockout impaired ISC stemness and promoted aging marker expression in aged mice. Proteomics analysis indicated mitochondrial dysfunction in Fut2 knockout ISC. More injured mitochondria, elevated levels of reactive oxygen species, and decreased levels of adenosine 5′-triphosphate (ATP) in Fut2 knockout ISC were found. Moreover, respiratory chain complex impairment and mitophagy dysfunction in Fut2 knockout ISC were further noted. Finally, Fut2 was demonstrated to regulate mitochondrial functions mainly by regulating the α1,2-fucosylation of N-acyl sphingosine amidohydrolase 2 (Asah2) and Niemann–Pick type C intracellular cholesterol transporter 1 (Npc1). In conclusion, this study demonstrated the substantial role of Fut2 in regulating ISC functions during aging by affecting mitochondrial function. These findings provide novel insights into the molecular mechanisms of ISC aging and therapeutic strategies for age-related intestinal diseases.

Abstract Narrowband photodetectors conventionally rely on optical structure design or bandpass filters to achieve the narrowband regime. Recently, a strategy for filterless narrowband photoresponse based on the charge collection narrowing (CCN) mechanism was reported. However, the CCN strategy requires an electrically and optically “thick” photoactive layer, which poses challenges in controlling the narrowband photoresponse. Here we propose a novel strategy for constructing narrowband photodetectors by leveraging the inherent ion migration in perovskites, which we term “band modulation narrowing” (BMN). By manipulating the ion migration with external stimuli such as illumination, temperature, and bias voltage, we can regulate in situ the energy‐band structure of perovskite photodetectors (PPDs) and hence their spectral response. Combining the Fermi energy levels obtained by the Kelvin probe force microscopy, the internal potential profiles from solar cell capacitance simulator simulation, and the anion accumulation revealed by the transient ion‐drift technique, we discover two critical mechanisms behind our BMN strategy: the extension of an optically active but electronically dead region proximal to the top electrode and the down‐bending energy bands near the electron transport layer. Our findings offer a case for harnessing the often‐annoying ion migration for developing advanced narrowband PPDs.

BackgroundLarge sample of pregnant women vaccinated with COVID-19 vaccine has not been carried out in China. The objective of this study was to evaluate the safety and effectiveness of COVID-19 inactivated vaccine in pregnant women infected with the SARS-CoV-2 Omicron variant.MethodsA total of 1,024 pregnant women and 120 newborns were enrolled in this study. 707 pregnant women received one to three doses of the inactivated COVID-19 vaccine, and 317 unvaccinated patients served as the control group. A comparison was made between their clinical and laboratory data at different stages of pregnancy.ResultsThe incidence rate of patients infected with Omicron variant in the first, the second, and the third trimesters of pregnancy was 27.5%, 27.0%, and 45.5% in patients during, respectively. The corresponding length of hospital stay was 8.7 ± 3.3 days, 9.5 ± 3.3 days, and 11 ± 4.3 days, respectively. The hospitalization time of pregnant women who received 3 doses of vaccine was (8.8 ± 3.3) days, which was significantly shorter than that of non-vaccinated women (11.0 ± 3.9) days. (P

ABSTRACTIntestinal stem cells (ISCs) are critical for the development and rapid turnover of intestinal epithelium. The regulatory effects of gut microbiota and their metabolites on ISCs stemness remain elusive. Fucose has been demonstrated to mediate host–microbe interactions in the intestine. However, the association between fucose, gut bacteria, and ISCs stemness remains unclear. To investigate the effects of fucose on ISCs-mediated intestinal epithelial cells (IECs) development, we administered fucose to 4-week-old mice for 4 weeks. ISCs stemness, IECs proliferation, and differentiation were examined. Variations in gut microbes and metabolism were detected using 16S rDNA sequencing and metabolomic analysis. Fucose was added to the bacterial culture medium to further study its effects on metabolism. Crypts were isolated from the mouse ileum for organoids culture in vitro to evaluate the effects of metabolites and the underlying mechanism. The results showed that fucose accelerated ISCs proliferation and secretory lineage differentiation in mice, whereas antibiotics eliminated these effects. The composition and functions of gut bacteria were altered by fucose treatment, while significant increases in Akkermansia and propanoate metabolism were noted. Propionic acid and propionate have been shown to promote organoid development. Fucose fermentation increases the production of propionic acid in Akkermansia muciniphila and enhances its ability to increase the stemness of ISCs. Moreover, ileal contents from fucose-treated mice promoted organoid development in a Gpr41/Gpr43-dependent manner. Fucose administration activates the Wnt signaling pathway in ISCs, and Wnt inhibitors suppress the effects of fucose. We conclude that fucose accelerates ISC-mediated intestinal epithelial development by promoting Akkermansia-related propanoate metabolism. These findings provide new insights into the promotion of gut homeostasis and the application potential of fucose as a prebiotic.

Abstract Yellow-seed trait is a desirable breeding characteristic of rapeseed (Brassica napus) that could greatly improve seed oil yield and quality. However, the underlying mechanisms controlling this phenotype in B. napus plants are difficult to discern because of their complexity. Here, we assemble high-quality genomes of yellow-seeded (GH06) and black-seeded (ZY821). Combining in-depth fine mapping of a quantitative trait locus (QTL) for seed color with other omics data reveal BnA09MYB47a, encoding an R2R3-MYB-type transcription factor, as the causal gene of a major QTL controlling the yellow-seed trait. Functional studies show that sequence variation of BnA09MYB47a underlies the functional divergence between the yellow- and black-seeded B. napus. The black-seed allele BnA09MYB47aZY821, but not the yellow-seed allele BnA09MYB47aGH06, promotes flavonoid biosynthesis by directly activating the expression of BnTT18. Our discovery suggests a possible approach to breeding B. napus for improved commercial value and facilitates flavonoid biosynthesis studies in Brassica crops.

In this study, the mechanical behavior, with dislocation “punched zone” (strengthened microzone by particles) emphasis on the damage mechanisms of (ZrB2+B4C)/6016Al hierarchical composites was studied by both experiments and finite element analysis. The experimental results show that the introduction of nanoparticles is an effective strategy to strengthen work hardening ability, as well as the tensile mechanical property of the hierarchical composites. Establishing the microstructure-based three-dimensional (3D) finite element model considered the reinforcement distribution and the dislocation “punched zone” of the matrix, which was identified by the nano-indentation test. The model was employed to reveal the deformation behavior and damage mechanism of the (ZrB2+B4C)/6016Al hierarchical composites by analyzing the stress and strain distributions. The elastoplastic response behavior simulation was conducted by changing the content of both reinforcements to accurately predict the composites' mechanical properties. This work proposes the strategy of introducing nano reinforcements to the unreinforced zone in traditional particle reinforced metal matrix composites (PRMMCs) to improve the microzone coordinated deformation as well as provides a reference for studying and optimizing the mechanical property of hierarchical composites via microstructure-based modeling.

Abstract Suppressing persistent multidrug-resistant (MDR) bacterial infections and excessive inflammation is the key for treating chronic wounds. Therefore, developing a microenvironment-responsive material with good biodegradability, drug-loading, anti-infection, and anti-inflammatory properties is desired to boost the chronic wounds healing process; however, using ordinary assembly remains a defect. Herein, we propose a pH/enzyme dual-responsive polymyxin B (PMB) spatiotemporal-release hydrogel (GelMA/OSSA/PMB), namely, the amount of OSSA and PMB released from GelMA/OSSA/PMB was closely related the wound pH and the enzyme concentration changing. The GelMA/OSSA/PMB showed better biosafety than equivalent free PMB, owing to the controlled release of PMB, which helped kill planktonic bacteria and inhibit biofilm activity in vitro. In addition, the GelMA/OSSA/PMB exhibited excellent antibacterial and anti-inflammatory properties. A MDR Pseudomonas aeruginosa caused infection was effectively resolved by the GelMA/OSSA/PMB hydrogel in vivo, thereby significantly boosting wound closure during the inflammatory phase. Furthermore, GelMA/OSSA/PMB accelerated the sequential phases of wound repair.

Seed weight is a component of seed yield in rapeseed (Brassica napus L.). Although quantitative trait loci (QTL) for seed weight have been reported in rapeseed, only a few causal quantitative trait genes (QTGs) have been identified, resulting in a limitation in understanding of seed weight regulation. We constructed a gene coexpression network at the early seed developmental stage using transcripts of 20,408 genes in QTL intervals and 1017 rapeseed homologs of known genes from other species. Among the 10 modules in this gene coexpression network, modules 1 and 2 were core modules and contained genes involved in source–flow–sink processes such as synthesis and transportation of fatty acid and protein, and photosynthesis. A hub gene SERINE CARBOXYPEPTIDASE-LIKE 19 (SCPL19) was identified by candidate gene association analysis in rapeseed and functionally investigated using Arabidopsis T-DNA mutant and overexpression lines. Our study demonstrates the power of gene coexpression analysis to prioritize candidate genes from large candidate QTG sets and enhances the understanding of molecular mechanism for seed weight at the early developmental stage in rapeseed.

Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) play key roles in regulating testosterone secretion and spermatogenesis in male mammals, respectively, and they maintain the fertility of male animals by binding to their corresponding receptors. We designed and prepared a recombinant LH receptor (LHR) subunit vaccine and a recombinant FSH receptor (FSHR) subunit vaccine and used male Sprague Dawley (SD) rats as a model to examine their effects on testicular development, spermatogenesis, and testosterone secretion in prepubertal and pubertal mammals. Both vaccines (LHR-DTT and FSHR-DTT) significantly decreased the serum testosterone level in prepubertal rats (p < 0.05) but had no effect on the testosterone secretion in pubertal rats; both vaccines decreased the number of cell layers in the seminiferous tubules and reduced spermatogenesis in prepubertal and pubertal rats. Subunit vaccine FSHR-DTT decreased the sperm density in the epididymis in both prepubertal and pubertal rats (p < 0.01) and lowered testicular index and sperm motility in pubertal rats (p < 0.05), whereas LHR-DTT only reduced the sperm density in the epididymis in pubertal rats (p < 0.05). These results indicate that the FSHR subunit vaccine may be a promising approach for immunocastration, but it still needs improvements in effectiveness.

Bone metastasis has been reported in up to 70% of patients with advanced breast cancer. A total of 55.76% of skeletal metastases in women were derived from breast cancer. However, patients with bone metastasis from an occult primary breast cancer are a rare subset of patients. Here, we present the case of a 38-year-old woman who had sternum pain for 4 months. A whole-body PET-CT scan revealed that the FDG uptake of both the sternum and internal mammary node was significantly increased. The final diagnosis of occult breast cancer was established by immunohistochemical (IHC) staining, which is of great significance for identifying the origin of a metastatic tumor despite no visualized lesions of mammary glands.

The effective detection and monitoring of mining tailings’ leachates (MTLs) plays a pivotal role in environmental protection and remediation efforts. Electrical resistivity tomography (ERT) is a non-invasive technique widely employed for mapping subsurface contaminant plumes. However, the efficacy of ERT depends on selecting the optimal electrode array for each specific case. This study addresses this challenge by conducting a comprehensive review of published case studies utilizing ERT to characterize mining tailings. Through numerical simulations, we compare the imaging capabilities of commonly used electrode configurations, six ERT arrays, aiming to identify the optimal array for MTLs’ detection and monitoring. In addition, field surveys employing ERT were conducted at the El Mochito mine tailings site to detect zones saturated with leachates within the tailing storage facilities (TSFs). The findings indicate that the “Wenner-Schlumberger” array exhibits superior data resolution for MTL detection. However, the choice of the optimal electrode array is contingent on factors such as survey location, geological considerations, research objectives, data processing time and cost, and logistical constraints. This study serves as a practical guide for selecting the most effective electrode array in the context of pollutant penetration from mining tailings, employing the ERT technique. Furthermore, it contributes valuable insights into characterizing zones saturated with mining tailing leachates within the TSFs, providing a solid foundation for informed environmental management and remediation strategies.

Abstract Background The role of induction chemotherapy (IC) in oropharyngeal squamous cell carcinoma (OPSCC) remains controversial. Its interpretation can be confounded by heterogeneity in chemosensitivity and human papillomavirus (HPV) status. This study aimed to investigate the prognostic impact of IC response in HPV‐positive and ‐negative OPSCC. Methods Patients with OPSCC who underwent IC and concurrent chemoradiotherapy (CCRT) were retrospectively analyzed. Radiologic response to IC by ≥50% was defined as IC‐sensitive (IC‐s), while lesser response was deemed as IC‐resistant (IC‐r). Progression‐free survival (PFS) and overall survival (OS) were compared between subgroups. Results A total of 51 HPV‐positive and 57 HPV‐negative patients were included. IC‐s patients accounted for 55.6%, 62.7%, and 49.1% in the entire cohort, HPV‐positive, and HPV‐negative subgroup, respectively. Compared with IC‐r subgroup, IC‐s was associated with better clinical outcomes either in the entire cohort (3y‐PFS 91.7%vs.43.7%, P

Abstract Background Dermatomyositis (DM) is an acquired autoimmune disease that can cause damage to various organs, including the heart muscle. However, the mechanisms underlying myocardial injury in DM are not yet fully understood. Methods In this study, we utilized publicly available datasets from the Gene Expression Omnibus (GEO) database to identify hub-genes that are enriched in the immune system process in DM and myocarditis. Weighted gene co-expression network analysis (WGCNA), differentially expressed genes (DEGs) analysis, protein–protein interaction (PPI), and gene ontology (GO) analysis were employed to identify these hub-genes. We then used the CIBERSORT method to analyze immune cell infiltration in skeletal muscle specimens of DM and myocardium specimens of myocarditis respectively. Correlation analysis was performed to investigate the relationship between key genes and infiltrating immune cells. Finally, we predicted regulatory miRNAs of hub-genes through miRNet and validated their expression in online datasets and clinical samples. Results Using integrated bioinformatics analysis, we identified 10 and 5 hub-genes that were enriched in the immune system process in the database of DM and myocarditis respectively. The subsequent intersections between hub-genes were IFIT3, OAS3, ISG15, and RSAD2. We found M2 macrophages increased in DM and myocarditis compared to the healthy control, associating with the expression of IFIT3, OAS3, ISG15, and RSAD2 in DM and myocarditis positively. Gene function enrichment analysis (GSEA) showed that IFIT3, OAS3, ISG15, and RSAD2 were mainly enriched in type I interferon (IFN) signaling pathway, cellular response to type I interferon, and response to type I interferon. Finally, we verified that the expression of miR-146a-5p was significantly higher in the DM with myocardial injury than those without myocardial injury (p = 0.0009). Conclusion Our findings suggest that IFIT3, OAS3, ISG15, and RSAD2 may play crucial roles in the underlying mechanism of myocardial injury in DM. Serum miR-146a-5p could be a potential biomarker for myocardial injury in DM.

Background: The prognosis of chemotherapy is important in clinical decision-making for non-small cell lung cancer (NSCLC) patients. Objectives: To develop a model for predicting treatment response to chemotherapy in NSCLC patients from pre-chemotherapy CT images. Materials and Methods: This retrospective multicenter study enrolled 485 patients with NSCLC who received chemotherapy alone as a first-line treatment. Two integrated models were developed using radiomic and deep-learning-based features. First, we partitioned pre-chemotherapy CT images into spheres and shells with different radii around the tumor (0–3, 3–6, 6–9, 9–12, 12–15 mm) containing intratumoral and peritumoral regions. Second, we extracted radiomic and deep-learning-based features from each partition. Third, using radiomic features, five sphere–shell models, one feature fusion model, and one image fusion model were developed. Finally, the model with the best performance was validated in two cohorts. Results: Among the five partitions, the model of 9–12 mm achieved the highest area under the curve (AUC) of 0.87 (95% confidence interval: 0.77–0.94). The AUC was 0.94 (0.85–0.98) for the feature fusion model and 0.91 (0.82–0.97) for the image fusion model. For the model integrating radiomic and deep-learning-based features, the AUC was 0.96 (0.88–0.99) for the feature fusion method and 0.94 (0.85–0.98) for the image fusion method. The best-performing model had an AUC of 0.91 (0.81–0.97) and 0.89 (0.79–0.93) in two validation sets, respectively. Conclusions: This integrated model can predict the response to chemotherapy in NSCLC patients and assist physicians in clinical decision-making.

Abstract Background Our previous study showed that fucosyltransferase 2 (Fut2) deficiency is closely related to colitis. Colitis increases the risk for the development of colorectal cancer (CRC). This study aimed to investigate the effect and underlying mechanism of action of Fut2 in CRC. Methods Intestinal epithelium-specific Fut2 knockout (Fut2 △IEC) mice were used in this study. CRC was induced using azoxymethane (AOM) and dextran sulfate sodium (DSS). Immunofluorescence was used to examine the fucosylation levels. Proteomics and N-glycoproteomics analyses, Ulex Europaeus Agglutinin I (UEA-I) affinity chromatography, immunoprecipitation, and rescue assay were used to investigate the mechanism of Fut2 in CRC. Results The expression of Fut2 and α-1,2-fucosylation was lower in colorectal tumor tissues than in the adjacent normal tissues of AOM/DSS-induced CRC mice. More colorectal tumors were detected in Fut2 △IEC mice than in control mice, and significant downregulation of melanoma cell adhesion molecule (MCAM) fucosylation was detected in the colorectal tumor tissues of Fut2 △IEC mice. Overexpression of Fut2 inhibited cell proliferation, invasion and tumor metastasis in vivo and in vitro in SW480 and HCT116 cells. Moreover, fucosylation of MCAM may be a mediator of Fut2 in CRC. Peracetylated 2-F-Fuc, a fucosyltransferase inhibitor, repressed fucosylation modification of MCAM and reversed the inhibitory effects of Fut2 overexpression on SW480 cell proliferation, migration, and invasion. Our results indicate that Fut2 deficiency in the intestinal epithelium promotes CRC by downregulating the fucosylation of MCAM. Conclusions The regulation of fucosylation may be an potential therapy for CRC, especially in patients with Fut2 gene defects.

Seed number per silique (SNPS) is one of seed yield components in rapeseed, but its genetic mechanism remains elusive. Here a double haploid (DH) population derived from a hybrid between female 6Q006 with 35–40 SNPS and male 6W26 with 10–15 SNPS was investigated for SNPS in the year 2017, 2018, 2019 and 2021, and genotyped with Brassica 60K Illumina Infinium SNP array. An overlapping major QTL (qSNPS.C09) explaining 51.50% of phenotypic variance on average was narrowed to a 0.90 Mb region from 44.87 Mb to 45.77 Mb on chromosome C09 by BSA-seq. Subsequently, two DEGs in this interval were detected between extreme individuals in DH and F2 populations by transcriptome sequencing at 7 and 14 days after pollination siliques. Of which, BnaC09g45400D encoded an adenine phosphoribosyltransferase 5 (APT5) has a 48-bp InDel variation in the promoter of two parents. Candidate gene association analysis showed that this InDel variation was associated with SNPS in a nature population of rapeseed, where 54 accessions carrying the same haplotype as parent 6Q006 had higher SNPS than 103 accessions carrying the same haplotype as parent 6W26. Collectively, the findings are helpful for rapeseed molecular breeding of SNPS, and provide new insight into the genetic and molecular mechanism of SNPS in rapeseed.

The quantification of cell numbers in microscopy images plays a vital role in biomedical research and medical diagnosis. Presently, deep regression networks are widely employed to generate cell density maps, and the number of cells is obtained by integrating the density maps. However, automating cell counting remains challenging due to the variability in cell morphology, the diversity of cell types, and the interference of image backgrounds. This paper aims to address the central question: ‘Can we design a robust and efficient deep learning model that can effectively count cells in microscopy images, regardless of these challenges?’ To tackle this issue, we propose a novel multi-scale convolutional attention UNet (MSCA-UNet) based on density regression. Compared with other advanced density regression methods, our method introduces two key innovations. Firstly, we employ an MSCA block with multi-scale interaction ability as an encoder component, which, when combined with spatial attention, enhances the extraction of cell details and spatial information. Secondly, the design of the asymmetric UNet allows the encoder to extract more global information and better understand the image. In the meantime, using smaller convolutional kernels and strides in the decoder helps to restore image details and edge information, resulting in improved network performance. Our method outperformed other advanced methods on three publicly available benchmark cell datasets, including the synthetic bacterial (VGG) dataset, the modified bone marrow (MBM) dataset, and the human subcutaneous adipose tissue (ADI) dataset.

Abstract Background Rifaximin has been increasingly applied in irritable bowel syndrome (IBS) treatment. Whether there were differences in the effects of rifaximin on microbiota from different intestinal segments, especially the small intestine where rifaximin predominantly acted, has not been confirmed. Methods In this study, we used Trichinella spiralis infection to induce post infectious irritable bowel syndrome (PI-IBS) and measured visceral sensitivity of mice by means of abdominal withdrawal reflex (AWR) tests to colorectal distention (CRD). We compared the effects of rifaximin on the composition of ileal, colonic mucosal and fecal microbiota in PI-IBS mice. Results Rifaximin significantly reduced AWR scores and increased pain threshold in PI-IBS mice, and this effect was associated with the change in the relative abundance of ileal mucosal microbiota. Rifaximin could obviously decrease ileum mucosal microbiota alpha diversity assessed by Shannon microbial diversity index. Meanwhile, the analysis of beta diversity and relative abundance of microbiota at phylum, family and genus levels showed that rifaximin could improve the microbiota structure of ileal mucosa. However, for colonic mucosal and fecal microbiota, this effect of rifaximin was not obvious. Rifaximin could reshape the correlation of genera between different intestinal segments. Conclusion Rifaximin improved visceral hypersensitivity in PI-IBS mice. Rifaximin mainly affected ileal mucosal microbiota, and its improvement effect on IBS might be closely related to the improvement of ileal microbiota structure.

Abstract. Background:. Cholangiocarcinoma (CCA) is a malignant biliary tract tumor with an extremely poor prognosis. There is an urgent demand to explore novel therapeutic strategies. L-fucose has been confirmed to participate in anti-inflammation and antitumor activities. However, the effect of L-fucose on the progression of CCA has not been well investigated. This study aimed to determine whether L-fucose induced the inhibition of CCA and its possible mechanism. Methods:. The anti-growth activity was determined using Cell Counting Kit-8 assay, colony formation assays, Annexin V-fluorescein isothiocyanate/propidium iodide (FITC/PI) assay, and cell cycle analysis. The anti-metastasis activity was determined by wound healing, transwell, and invasion assays. The anti-angiogenesis activity was determined by tube formation and transwell assays. MicroRNAs that may be involved in the L-fucose-induced CCA inhibition was analyzed using bioinformatics methods. The preclinical therapeutic efficacy was mainly estimated by ultrasound in xenograft nude mouse models. Differences were analyzed via Student's t test or one-way analysis of variance. Results:. L-Fucose induced apoptosis and G0/G1 cell cycle arrest, inhibited cell epithelial-mesenchymal transition of CCA cells, and additionally inhibited tube formation of human umbilical vein endothelial cells (HUVECs) in a dose-dependent manner, leading to a decrease in cell proliferation, metastasis, and angiogenesis. Mechanistically, L-fucose induced microRNA-200b (miR-200b) upregulation, and mitogen-activated protein kinase 7 (MAPK7) downregulation was found to be targeted by miR-200b, with decreased cell proliferation and metastasis. Additionally, phosphorylated signal transducer and activator of transcription 3 was found to be downregulated after L-fucose treatment. Finally, in vivo experiments in CCA xenograft models also confirmed the antitumor properties of L-fucose. Conclusion:. L-Fucose inhibited the progression of CCA via the miR-200b/MAPK7 and signal transducer and activator of transcription 3 signaling pathways.

A field trial in Changsha, China, involving the release of a triple Wolbachia-infected strain of the mosquito, Aedes albopictus, demonstrates the feasibility of using an incompatible insect technique to suppress disease vector mosquito populations in urban subtropic environments.