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Abstract The prevalence of allergic diseases such as Allergic Rhinitis and Asthma is steadily increasing globally, with pollen allergy being one of the most significant sensitizing factors. However, the cross-reactivity of different pollen allergies remains unclear, posing challenges in the diagnosis and treatment of individuals with multiple sensitivities. In this study, the Component Resolved Diagnosis technique was performed to simultaneously measure the specific IgE concentrations of 52 patients against Art v and its components (Art v 1), Phl p and its components (Phl p 1, Phl p 4, Phl p 5, Phl p 6, Phl p 7, Phl p 12), Bet v and its components (Bet v 1, Bet v 2), Amb a and its component (Amb a 1), and Amb p. Additionally, sIgE inhibition tests were conducted by Art v, Phl p, and Bet v extracts. Among Art v-positive patients, 64.6% showed positivity for Art v 1. In Phl p-positive patients, Phl p 12 had the highest positivity rate (75.0%). Among Bet v-positive patients, 75.6% exhibited positivity for Bet v 2, whereas for Amb a and Amb p-positive patients, 23.7% and 29.0% respectively showed positivity for Amb a 1. The sIgE inhibition assays results revealed that Art v extract had inhibition rates greater than 73.2% against Phl p and its component Phl p 12, as well as Bet v and its component Bet v 2. Simultaneously, Phl p extract showed inhibition rates of 80.70–89.87% against Phl p 12, Bet v and Bet v 2. Bet v extract showed inhibition rates ranging from 21.9 to 59.8% against Phl p and Bet v 2, with a better inhibition rate (76.80%) against Phl p 12. In conclusion, Art v 1 is identified as the principal component of Art v. The profilin proteins of Phl p and Bet v (Phl p 12 and Bet v 2), are implicated as potential cross-reactive elements contributing to polysensitization in patients with respiratory allergies in the Northwest region of China. This cross-reactivity leads to a shared sensitization mechanism among pollen allergens such as Art v, Phl p, and Bet v.

Abstract Fruit ripening is accompanied by the development of fruit quality traits; however, this process also increases the fruit’s susceptibility to various environmental stresses, including pathogen attacks and other stress factors. Therefore, modulating the fruit ripening process and defense responses is crucial for maintaining fruit quality and extending shelf life. Membrane proteins play intricate roles in mediating signal transduction, ion transport, and many other important biological processes, thus attracting extensive research interest. This review mainly focuses on the functions of membrane proteins in regulating fruit ripening and defense responses against biotic and abiotic factors, addresses their potential as targets for improving fruit quality and resistance to environmental challenges, and further highlights some open questions to be addressed.

Abstract Small cell lung cancer (SCLC) is a highly malignant and poor-prognosis cancer, with most cases diagnosed at the extensive stage (ES). Amidst a landscape marked by limited progress in treatment modalities for ES-SCLC over the past few decades, the integration of immune checkpoint inhibitors (ICIs) with platinum-based chemotherapy has provided a milestone approach for improving prognosis, emerging as the new standard for initial therapy in ES-SCLC. However, only a minority of SCLC patients can benefit from ICIs, which frequently come with varying degrees of immune-related adverse events (irAEs). Therefore, it is crucial to investigate predictive biomarkers to screen potential beneficiaries of ICIs, mitigate the risk of side effects, and improve treatment precision. This review summarized potential biomarkers for predicting ICI response in ES-SCLC, with a primary focus on markers sourced from tumor tissue or peripheral blood samples. The former mainly included PD-L1 expression, tumor mutational burden (TMB), along with cellular or molecular components related to the tumor microenvironment (TME) and antigen presentation machinery (APM), molecular subtypes of SCLC, and inflammatory gene expression profiles. Circulating biomarkers predominantly comprised circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), cytokines, plasma autoantibodies, inflammation-related parameters, and blood TMB. We synthesized and analyzed the research progress of these potential markers. Notably, investigations into PD-L1 expression and TMB have been the most extensive, exhibiting preliminary predictive efficacy in salvage immunotherapy; however, consistent conclusions have yet to be reached across studies. Additionally, novel predictive markers developed based on TME composition, APM, transcriptomic and genomic features provide promising tools for precision immunotherapy. Circulating biomarkers offer the advantages of convenience, non-invasiveness, and a comprehensive reflection of tumor molecular characteristics. They may serve as alternative options for predicting immunotherapy efficacy in SCLC. However, there is a scarcity of studies, and the significant heterogeneity in research findings warrants attention.

Abstract Background Numerous reports indicate that both obesity and type 2 diabetes mellitus (T2DM) are factors associated with cognitive impairment (CI). The objective was to assess the relationship between abdominal obesity as measured by waist-to-hip ratio adjusted for body mass index (WHRadjBMI) and CI in middle-aged and elderly patients with T2DM. Methods A cross-sectional study was conducted, in which a total of 1154 patients with T2DM aged ≥ 40 years were included. WHRadjBMI was calculated based on anthropometric measurements and CI was assessed utilizing the Montreal Cognitive Assessment (MoCA). Participants were divided into CI group (n = 509) and normal cognition group (n = 645). Correlation analysis and binary logistic regression were used to explore the relationship between obesity-related indicators including WHRadjBMI, BMI as well as waist circumference (WC) and CI. Meanwhile, the predictive power of these indicators for CI was estimated by receiver operating characteristic (ROC) curves. Results WHRadjBMI was positively correlated with MoCA scores, independent of sex. The Area Under the Curve (AUC) for WHRadjBMI, BMI and WC were 0.639, 0.521 and 0.533 respectively, and WHRadjBMI had the highest predictive power for CI. Whether or not covariates were adjusted, one-SD increase in WHRadjBMI was significantly related to an increased risk of CI with an adjusted OR of 1.451 (95% CI: 1.261–1.671). After multivariate adjustment, the risk of CI increased with rising WHRadjBMI quartiles (Q4 vs. Q1 OR: 2.980, 95%CI: 2.032–4.371, P for trend

Abstract Background Magnetic resonance spectroscopy (MRS) studies have indicated that the imbalance between gamma-aminobutyric acid (GABA) and glutamate/glutamine (Glx) levels was the potential cause of migraine development. However, the changes in the GABA and Glx levels in patients with New daily persistent headache (NDPH) remain unclear. This study aimed to investigate the changes in GABA and Glx levels in the periaqueductal gray (PAG) and dentate nucleus (DN) in patients with NDPH using the MEGA-PRESS sequence. Methods Twenty-one NDPH patients and 22 age- and sex-matched healthy controls (HCs) were included and underwent a 3.0T MRI examination, using the MEGA-PRESS sequence to analyze GABA and Glx levels of PAG and DN. The correlations between these neurotransmitter levels and clinical characteristics were also analyzed. Results There were no significant differences in the GABA+/Water, GABA+/Cr, Glx/Water, and Glx/Cr levels in both PAG and DN between the two groups (all p > 0.05). Moderate-severe NDPH patients had lower levels of Glx/Water (p = 0.034) and Glx/Cr (p = 0.012) in DN than minimal-mild NDPH patients. In patients with NDPH, higher Glx/Water levels in the PAG (r=-0.471, p = 0.031, n = 21) and DN (r=-0.501, p = 0.021, n = 21) and higher Glx/Cr levels in DN (r=-0.483, p = 0.026, n = 21) were found to be correlated with lower Visual Analogue Scale scores. Additionally, a positive correlation was observed between the GABA+/Cr levels in the DN and the Generalized Anxiety Disorder-7 scores (r = 0.519, p = 0.039, n = 16). Conclusions The results of this study indicated that the GABA and Glx levels in the PAG and DN may not be the primary contributor to the development of NDPH. The correlations between certain clinical scales and the neurotransmitter levels may be derived from the NDPH related symptoms.

Introduction: Penicillium expansum is a harmful plant fungal pathogen that causes blue mold disease and produces mycotoxin patulin, leading to huge economic losses and food safety hazard. Set1 associated complex Set1/COMPASS deposits the methylation at lysine 4 of histone H3, which is associated with gene expression in diverse biological processes of fungi. However, the function and underlying mechanisms of Set1/COMPASS are poorly defined in P. expansum. Objectives: The study aimed to identify Set1/COMPASS and investigate its regulation mechanisms on growth, pathogenicity, and patulin biosynthesis of P. expansum. Methods: Analyses of phylogenetic relationship, conserved structural domain, and gene deletion were used to identify components of Set1/COMPASS. Phenotype analysis and stress tolerance test of gene deletion mutants were conducted to analyze the function of these components. Yeast two-hybrid, Co-Immunoprecipitation (Co-IP), and point mutation were performed to verify the protein interaction. Western blot was conducted for detection of H3K4 methylation levels. Results: P. expansum owns six components of Set1/COMPASS besides PeSet1. Absence of each component resulted in reduction of H3K4 methylation levels and impaired growth, pathogenicity, and patulin biosynthesis, as well as altered stress responses of P. expansum. One component PeBre2p was found to interact with the conserved global regulator PeVelB (VelvetLike protein B) at Asp294 of PeBre2p. This interaction affected fungal growth and utilization of fructose, lactose, glycine, and proline in P. expansum. Conclusion: This study revealed the important roles of Set1/COMPASS in P. expansum and clarified for the first time the combined regulation of PeBre2p and PeVelB in fungal growth and nutrition utilization. These results will provide potential targets for the control of blue mold disease.

Abstract Breast cancer remains a significant global health challenge, and its mechanisms of progression and metastasis are still not fully understood. In this study, analysis of TCGA and GEO datasets revealed a significant increase in CCT2 expression in breast cancer tissues, which was associated with poor prognosis in breast cancer patients. Functional analysis revealed that CCT2 promoted breast cancer growth and metastasis through activation of the JAK2/STAT3 signaling pathway. Additionally, the E3 ubiquitin ligase Trim21 facilitated CCT2 ubiquitination and degradation, significantly reversing the protumor effects of CCT2. Most interestingly, we discovered that exosomal CCT2 derived from breast cancer cells suppressed the activation and proinflammatory cytokine secretion of CD4+ T cell. Mechanistically, exosomal CCT2 constrained Ca2+-NFAT1 signaling, thereby reducing CD40L expression on CD4+ T cell. These findings highlight CCT2 upregulation as a potential driver of breast cancer progression and immune evasion. Our study provides new insights into the molecular mechanisms underlying breast cancer progression, suggesting that CCT2 is a promising therapeutic target and prognostic predictor for breast cancer.

Abstract Objectives Exploring the value of adding correlation analysis (radiomic features (RFs) of pelvic metastatic lymph nodes and primary lesions) to screen RFs of primary lesions in the feature selection process of establishing prediction model. Methods A total of 394 prostate cancer (PCa) patients (263 in the training group, 74 in the internal validation group and 57 in the external validation group) from two tertiary hospitals were included in the study. The cases with pelvic lymph node metastasis (PLNM) positive in the training group were diagnosed by biopsy or MRI with a short-axis diameter ≥ 1.5 cm, PLNM-negative cases in the training group and all cases in validation group were underwent both radical prostatectomy (RP) and extended pelvic lymph node dissection (ePLND). The RFs of PLNM-negative lesion and PLNM-positive tissues including primary lesions and their metastatic lymph nodes (MLNs) in the training group were extracted from T2WI and apparent diffusion coefficient (ADC) map to build the following two models by fivefold cross-validation: the lesion model, established according to the primary lesion RFs selected by t tests and absolute shrinkage and selection operator (LASSO); the lesion-correlation model, established according to the primary lesion RFs selected by Pearson correlation analysis (RFs of primary lesions and their MLNs, correlation coefficient > 0.9), t test and LASSO. Finally, we compared the performance of these two models in predicting PLNM. Results The AUC and the DeLong test of AUC in the lesion model and lesion-correlation model were as follows: training groups (0.8053, 0.8466, p = 0.0002), internal validation group (0.7321, 0.8268, p = 0.0429), and external validation group (0.6445, 0.7874, p = 0.0431), respectively. Conclusion The lesion-correlation model established by features of primary tumors correlated with MLNs has more advantages than the lesion model in predicting PLNM.

An existing technique for quickly obtaining the spatial distribution data of soil organic matter (SOM) involves combining an unmanned aerial vehicle (UAV) platform and imaging spectroscopy technology; this technique is suitable for precision agricultural management and real-time monitoring. In this study, the average spectral data were first extracted via circular regions of interest (ROIs) of different radii and modelled using the measured SOM to determine the optimal extraction range for the spectral data. Partial least-squares regression (PLSR) and support vector machine (SVM) models were constructed based on the raw spectra, standard normal transform spectra, multiple scattering-corrected spectra, and first-order differential spectra. The difference index, ratio index, and normalized index were calculated and analysed for their correlation with SOM content, and the spectral indices were screened to establish the SOM prediction model. Finally, the accuracy of the model was evaluated, and we selected the optimal model to map the spatial distribution of SOM. The results of our study show that 1) the radius of the ROI significantly affects the model’s accuracy; 2) the accuracy of the nonlinear SVM model is much higher than that of the linear PLSR model; 3) the prediction model based on spectral indices is better than full-band model. This study can serve as a model for the application of UAV imaging spectroscopy technology to field-scale SOM estimations and rapid monitoring, as well as provide technical support for precision agriculture and climate change studies.

Wild soybean (Glycine soja), a relative of cultivated soybean, shows high adaptability to adverse environmental conditions. We identified and characterized a wild soybean transcription factor gene, GsWRKY40, that promotes plant salt stress. GsWRKY40 was highly expressed in wild soybean roots and was up-regulated by salt treatment. GsWRKY40 was localized in nucleus and demonstrated DNA-binding activities but without transcriptional activation. Mutation and overexpression of GsWRKY40 altered salt tolerance of Arabidopsis plants. To understand the molecular mechanism of GsWRKY40 in regulating plant salt resistance, we screened a cDNA library and identified a GsWRKY40 interacting protein GsbHLH92 by using yeast two-hybrid approach. The physical interaction of GsWRKY40 and GsbHLH92 was confirmed by co-immunoprecipitation (co-IP), GST pull-down, and bimolecular fluorescence complementation (BiFC) techniques. Intriguingly, co-overexpression of GsWRKY40 and GsbHLH92 resulted in higher salt tolerance and lower ROS levels than overexpression of GsWRKY40 or GsbHLH92 in composite soybean plants, suggesting that GsWRKY40 and GsbHLH92 may synergistically regulate plant salt resistance through inhibiting ROS production. qRT-PCR data indicated that the expression level of GmSPOD1 gene encoding peroxidase was cooperatively regulated by GsWRKY40 and GsbHLH92, which was confirmed by using a dual luciferase report system and yeast one-hybrid experiment. Our study reveals a pathway that GsWRKY40 and GsbHLH92 collaboratively up-regulate plant salt resistance through impeding GmSPOD1 expression and reducing ROS levels, providing a novel perspective on the regulatory mechanisms underlying plant tolerance to abiotic stresses.

Abstract In recent years, many governments and companies have gradually launched robotaxi projects to help make transportation systems smarter, improve travel efficiency, and reduce travel costs. Robotaxi is a new mode of travel that replaces human driving with machines, freeing up social labour and enriching people’s travel choices. This study employs the Extended Unified Theory of Acceptance and Use of Technology (UTAUT2) to understand the influencing factors of users’ adoption and usage of robotaxis in China to facilitate the broader integration of robotaxis into urban transportation systems. This study surveyed the preferences of 2048 respondents and analysed the data through structural equation modelling. The results indicate that performance expectancy, hedonic motivation, and price value are the factors influencing users’ behavioural intentions, while effort expectancy and social influence affect use behaviour. In contrast, habit is an important factor that affect both behavioural intention and actual use behaviour. Based on the findings, we have proposed practical strategies to improve robotaxi services and updated the UTAUT2 model in the context of robotaxi. We suggest that robotaxi operators can promote user acceptance and use by reducing the difficulty of use, improving the cost performance and the ride experience, and making appropriate publicity and guidance.

Abstract Owing to its versatile roles in almost all aspects of plants, FERONIA (FER), a receptor-like kinase of the Catharanthus roseus receptor-like kinase 1-like (CrRLK1L) subfamily, has received extensive research interests during the past decades. Accumulating evidence has been emerged that FER homologs in horticultural crops also play crucial roles in reproductive biology and responses to environmental stimuli (abiotic and biotic stress factors). Here, we provide a review for the latest advances in the studies on FER homologs in modulating stress responses in horticultural crops, and further analyze the underlying mechanisms maintained by FER. Moreover, we also envisage the missing links in current work and provide a perspective for future studies on this star protein.

Polycystic ovary syndrome (PCOS) is a prevalent endocrine and metabolic disorder affecting women of reproductive age. The syndrome is characterized by androgen excess, ovarian dysfunction, insulin resistance (IR) and obesity, with an elevated risk of developing long-term complications, including cardiovascular disease and type 2 diabetes mellitus (T2D). The gut microbiota plays a role in the pathogenesis of PCOS by influencing the host's endocrine, metabolic and inflammatory state, as well as the gut-brain axis. Gut microbiota-derived extracellular vesicles (GMEVs) are lipid bilayer nanoparticles secreted by the gut microbiota and contain a variety of components, including proteins, lipids and nucleic acids. They serve as signaling molecules, facilitating bacterial-bacterial and bacterial-host communications. Bacterial extracellular vesicles (BEVs) affect host cells through the delivery of bioactive substances and physical interaction through membrane components, thereby participating in the regulation of metabolic, immune, and other cellular processes. Furthermore, BEVs, which are distinguished by low toxicity, high biocompatibility and stability, and the capacity to cross biological barriers, present a promising avenue for the development of novel drug delivery systems. The isolation and characterization of BEVs also facilitate the investigation of disease-specific biomarkers. Consequently, BEVs have immense potential for a range of medical research applications, including disease diagnosis and treatment. This article discusses the potential therapeutic effects and mechanisms of GMEVs in the treatment of PCOS.

Nanotechnology has emerged as a promising innovative avenue for therapeutic intervention in cancer research. However, achieving satisfactory accumulation of nanoparticles in the tumor and fabricating optimized nanoparticles remain challenging. In this work, we developed a novel polymeric micelle system to actively target integrin receptors, which are usually overexpressed in breast cancer. We first synthesized a targeted peptide-modified cyclic (Arg-Gly-Asp-D-Phe-Cys) (c(RGDfc))-polyethylene glycol-acitretin amphipathic conjugate (RPA) and prepared doxorubicin (DOX)-loaded RPADm (RPA@DOX) micelles with a high drug loading content of more than 11 %. Compared with unmodified DOX-containing micelles, RPADm demonstrated increased cytotoxicity and cellular uptake by MCF-7 cells. Importantly, competitive binding experiments confirmed that the observed enhancement effect was attributed to the modification of c(RGDfc) on the surface of the micelles. Furthermore, due to its active tumor-targeting ability, compared with the other DOX-based formulations, the RPADm exhibited the highest tumor distribution and strongest therapeutic efficacy in MCF-7 tumor-bearing nude mice. Additionally, the safety evaluation experiments revealed that the DOX-loaded micelles had no obvious systemic toxicity. These results suggest that the developed micelles modified with c(RGDfc) are promising candidates for tumor-active targeting therapies.

Abstract Ferroptosis is a novel form of cell death caused by the accumulation of lipid peroxides in an iron‐dependent manner. However, the precise mechanism underlying the exploitation of ferroptosis by influenza A viruses (IAV) remains unclear. The results demonstrate that IAV promotes its own replication through ferritinophagy by sensitizing cells to ferroptosis, with hemagglutinin identified as a key trigger in this process. Hemagglutinin interacts with autophagic receptors nuclear receptor coactivator 4 (NCOA4) and tax1‐binding protein 1 (TAX1BP1), facilitating the formation of ferritin‐NCOA4 condensates and inducing ferritinophagy. Further investigation shows that hemagglutinin‐induced ferritinophagy causes cellular lipid peroxidation, inhibits aggregation of mitochondrial antiviral signaling protein (MAVS), and suppresses the type I interferon response, thereby contributing to viral replication. Collectively, a novel mechanism by which IAV hemagglutinin induces ferritinophagy resulting in cellular lipid peroxidation, consequently impairing MAVS‐mediated antiviral immunity, is revealed.

Abstract ImageGP is an extensively utilized, open‐access platform for online data visualization and analysis. Over the past 7 years, it has catered to more than 700,000 usages globally, garnering substantial user feedback. The updated version, ImageGP 2 (available at https://www.bic.ac.cn/BIC), introduces a redesigned interface leveraging cutting‐edge web technologies to enhance functionality and user interaction. Key enhancements include the following: (i) Addition of modules for data format transformation, facilitating operations such as matrix merging, subsetting, and transformation between long and wide formats. (ii) Streamlined workflows with features like preparameter selection data validation and grouping of parameters with similar attributes. (iii) Expanded repertoire of visualization functions and analysis tools, including Weighted Gene Co‐Expression Network Analysis, differential gene expression analysis, and FASTA sequence processing. (iv) Personalized user space for uploading large data sets, tracking analysis history, and sharing reproducible analysis data, scripts, and results. (v) Enhanced user support through a simplified error debugging feature accessible with a single click. (vi) Introduction of an R package, ImageGP, enabling local data visualization and analysis. These updates position ImageGP 2 as a versatile tool serving both wet‐lab and dry‐lab researchers with expanded capabilities.

Patients with supraclavicular lymph node (SLN) metastasis from esophageal cancer encounter significant variations in treatment approaches due to differences in pathological subtypes and the lack of a unified regional staging system between East Asian and Western countries. The Tiger study aims to develop an internationally recognized staging system and to delineate the extent of regional lymph node dissection. In the context of esophageal squamous cell carcinoma (SCC) with SLN metastasis, the treatment paradigms from East Asia offer valuable insights. The Japan Esophageal Society (JES) 12th edition staging system guides a tailored comprehensive treatment strategy, emphasizing either radiotherapy and chemotherapy or surgical intervention. In contrast, esophageal adenocarcinoma (AC) predominates in Western countries, where the 8th edition of the American Joint Committee on Cancer (AJCC) staging system classifies SLN metastasis as a distant metastasis, advocating for systemic therapy as the primary treatment modality. Nonetheless, compelling evidence suggests that a multidisciplinary treatment approach, incorporating either radiotherapy and chemotherapy or surgery as the initial treatment, can yield superior outcomes for these patients compared to chemotherapy alone.

Abstract Triple‐negative breast cancer (TNBC) is the most malignant subtype of breast cancer. TP53, which has a mutation rate of ≈70%–80% in TNBC patients, plays oncogenic roles when mutated. However, whether circRNAs can exert their effects on TNBC through regulating mutant TP53 has not been well evaluated. In this study, circCFL1, which is highly expressed in TNBC cells and tissues and has prognostic potential is identified. Functionally, circCFL1 promoted the proliferation, metastasis and stemness of TNBC cells. Mechanistically, circCFL1 acted as a scaffold to enhance the interaction between HDAC1 and c‐Myc, further promoting the stability of c‐Myc via deacetylation‐mediated inhibition of K48‐linked ubiquitylation. Stably expressed c‐Myc further enhanced the expression of mutp53 in TNBC cells with TP53 mutations by directly binding to the promoter of TP53, which promoted the stemness of TNBC cells via activation of the p‐AKT/WIP/YAP/TAZ pathway. Moreover, circCFL1 can facilitate the immune escape of TNBC cells by promoting the expression of PD‐L1 and suppressing the antitumor immunity of CD8+ T cells. In conclusion, the results revealed that circCFL1 plays an oncogenic role by promoting the HDAC1/c‐Myc/mutp53 axis, which can serve as a potential diagnostic biomarker and therapeutic target for TNBC patients with TP53 mutations.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/policies/article-withdrawal).This article has been retracted at the request of the authors. The manuscript was submitted before a final round of revision by the authors. As a result, not all authors had the opportunity to review the final manuscript and approve it, and there are a series of errors that should have been rectified prior to publication. These are: • Some figures do not contain the reference to the original source (permissions was obtained to reproduce the figures but this has not been properly represented). • Some sentences in the Introduction were taken verbatim from other sources while no reference was included to the original source. • The authors need to further supplement some data and discussion to improve the paper.The authors apologise for this error.

This article has been retracted: Please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/locate/withdrawalpolicy).This article has been retracted at the request of the authors. The manuscript was submitted before a final round of revision by the authors. As a result, not all authors had the opportunity to review the final manuscript and approve it, and there are a series of errors that should have been rectified prior to publication. These are:• Some figures do not contain the reference to the original source (permissions was obtained to reproduce the figures but this has not been properly represented).• Some sentences in the Introduction were taken verbatim from other sources while no reference was included to the original source.• The authors need to further supplement some data and discussion to improve the paper.The authors apologise for this error.

Abstract Background LncRNA colorectal neoplasia differentially expressed (CRNDE) was found to be an important regulator in many cancers. This project focuses on the function of CRNDE on macrophage metabolic reprogramming and Hepatocellular carcinoma (HCC). Method qRT-PCR and Immunofluorescence were used to analyze Arg-1, IL-10, CD163, CCL-18, CD206, and CRNDE expression in HCC tissues and macrophages. Western Blotting was used to analyze ERK and p-ERK expression. Edu assay, transwell assay and xenograft experiments were carried out to study cell viability, migrated and invasive capability. Immunohistochemical staining was used to evaluate Ki67 expression. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) was performed for macrophages metabolites analysis. Results Arg-1, IL-10, CD163, CD206, and CRNDE were significantly up-regulated in HCC tissues, M2 macrophage and M0 macrophage with CRNDE overexpressed (OV-CRNDE-M0), which downregulated in M0 macrophage with CRNDE knockdown (sh-CRNDE-M0). The conditioned medium (CM) of M2 cells and OV-CRNDE-M0 cells promoted cell viability, invasion, and migration of HCC cells, the effect was reversed by sh-CRNDE-M0 cells CM. OV-CRNDE-M0 cells promoted tumor growth, Ki67 and CD206 expression in xenograft model. 61 metabolites were detected, of which 18 metabolites changed significantly in OV-CRNDE-M0 group compared to M0 group, with 9 upregulated and 9 downregulated. KEGG analysis showed the enrichment pathways were biosynthesis, glyoxylate and dicarboxylate metabolism. SMPDB analysis showed the enrichment pathways were hypoacetylaspartia, canavan disease, and aspartate metabolism. Conclusion CRNDE regulated the metabolic reprogramming of M2 macrophage via ERK pathway, which thereby contributed to HCC proliferation, migration, and invasion.

Exosomes are extracellular vesicles naturally released from cells. Exosomes from different sources play different roles in cellular component exchange, signal transduction, and pathological development. Exosomes have distinct biological characteristics such as low immunogenicity, easy uptake by cells, crossing the blood-brain barrier, natural targeting, and easy modification. Many studies show that exosomes as drug carriers have a great application prospect in cancer therapy. In this review, we review the biogenesis, origin, biological characteristics of exosomes, and the exosome drug delivery system and its application for cancer therapy are summarized to provide a reference for the study of exosomes.

Light is a fundamental environmental factor for living organisms on earth—not only as a primary energy source but also as an informational signal. In fungi, light can be used as an indicator for both time and space to control important physiological and morphological responses. Botrytis cinerea (B. cinerea) is a devastating phytopathogenic fungus that exploits light cues to optimize virulence and the balance between conidiation and sclerotia development, thereby improving its dispersal and survival in ecosystems. However, the components and mechanisms underlying these processes remain obscure. Here, we identify a novel light-signaling component in B. cinerea, BcCfaS, which encodes a putative cyclopropane fatty-acyl-phospholipid synthase. BcCfaS is strongly induced by light at the transcriptional level and plays a crucial role in regulating photomorphogenesis. Deletion of BcCfaS results in reduced vegetative growth, altered colony morphology, impaired sclerotial development, and enhanced conidiation in a light-dependent manner. Moreover, the mutant exhibits serious defects in stress response and virulence on the host. Based on a lipidomics analysis, a number of previously unknown fungal lipids and many BcCfaS-regulated lipids are identified in B. cinerea, including several novel phospholipids and fatty acids. Importantly, we find that BcCfaS controls conidiation and sclerotial development by positively regulating methyl jasmonate (MeJA) synthesis to activate the transcription of light-signaling components, revealing for the first time the metabolic base of photomorphogenesis in fungi. Thus, we propose that BcCfaS serves as an integration node for light and lipid metabolism, thereby providing a regulatory mechanism by which fungi adapt their development to a changing light environment. These new findings provide an important target for antifungal design to prevent and control fungal disease.

Abstract Background Fructans are water-soluble carbohydrates that accumulate in wheat and are thought to contribute to a pool of stored carbon reserves used in grain filling and tolerance to abiotic stress. Results In this study, transgenic wheat plants were engineered to overexpress a fusion of two fructan biosynthesis pathway genes, wheat sucrose: sucrose 1-fructosyltransferase (Ta1SST) and wheat sucrose: fructan 6-fructosyltransferase (Ta6SFT), regulated by a wheat ribulose-1,5-bisphosphate carboxylase/oxygenase small subunit (TaRbcS) gene promoter. We have shown that T4 generation transgene-homozygous single-copy events accumulated more fructan polymers in leaf, stem and grain when compared in the same tissues from transgene null lines. Under water-deficit (WD) conditions, transgenic wheat plants showed an increased accumulation of fructan polymers with a high degree of polymerisation (DP) when compared to non-transgenic plants. In wheat grain of a transgenic event, increased deposition of particular fructan polymers such as, DP4 was observed. Conclusions This study demonstrated that the tissue-regulated expression of a gene fusion between Ta1SST and Ta6SFT resulted in modified fructan accumulation in transgenic wheat plants and was influenced by water-deficit stress conditions.

Abstract This study constructs a composite indicator system covering the core dimensions of medical equipment input and output. Based on this system, an innovative cone-constrained data envelopment analysis (DEA) model is designed. The model integrates the advantages of the analytic hierarchy process (AHP) with an improved criterion importance through intercriteria correlation (CRITIC) method to determine subjective and objective weights and employs game theory to obtain the final combined weights, which are further incorporated as constraints to form the cone-constrained DEA model. Finally, a bidirectional long short-term memory (Bi-LSTM) model with an attention mechanism is introduced for integration, aiming to provide a novel and practical model for evaluating the effectiveness of medical equipment. The proposed model has essential reference value for optimizing medical equipment management decision-making and investment strategies.

Abstract Background Fat to muscle mass ratio (FMR), a novel index integrating fat and muscle composition, has garnered attention in age-related conditions such as type 2 diabetes mellitus (T2DM) and neurodegenerative diseases. Despite this research on the relationship between FMR and cognitive impairment (CI) in T2DM remains scarce. This study aimed to investigate the sex-specific association between FMR and CI in elderly T2DM patients. Methods A total of 768 elderly (> 60 years) T2DM in-patients (356 men and 412 women) were recruited from the Department of Endocrinology at Tianjin Nankai University affiliated hospital. Bioelectrical Impedance Analysis (BIA) was used to assess body composition, and Montreal Cognitive Assessment (MoCA) was used to evaluate cognitive performance. T2DM patients were categorized into normal cognitive function (NC) and cognitive impairment (CI) groups based on MoCA scores and stratified by sex. Binary logistic regression was employed to examine the association between FMR and CI. Results Among the participants, 42.7% of men and 56.3% of women experienced cognitive deterioration. Women with CI exhibited lower body mass index (BMI) and skeletal muscle mass index (SMI), while men with cognitive disorders showed lower SMI, FMR, and higher fat mass index (FMI). FMR was consistently unrelated to cognition in females, irrespective of adjustment made. However, in males, FMR was significantly associated with an increasing risk of cognitive dysfunction after adjusting for demographic and clinical variables (OR: 1.175, 95% CI: 1.045–1.320, p = 0.007). Furthermore, for each 0.1 increase in FMR, the incidence of CI rose by 31.1% after additional adjustment for BMI. In males, the prevalence of CI increased sequentially across FMR quartiles (p

Abstract The application of chimeric antigen receptor (CAR) T cells in the management of hematological malignancies has emerged as a noteworthy therapeutic breakthrough. Nevertheless, the utilization and effectiveness of CAR-T cell therapy in solid tumors are still limited primarily because of the absence of tumor-specific target antigen, the existence of immunosuppressive tumor microenvironment, restricted T cell invasion and proliferation, and the occurrence of severe toxicity. This review explored the history of CAR-T and its latest advancements in the management of solid tumors. According to recent studies, optimizing the design of CAR-T cells, implementing logic-gated CAR-T cells and refining the delivery methods of therapeutic agents can all enhance the efficacy of CAR-T cell therapy. Furthermore, combination therapy shows promise as a way to improve the effectiveness of CAR-T cell therapy. At present, numerous clinical trials involving CAR-T cells for solid tumors are actively in progress. In conclusion, CAR-T cell therapy has both potential and challenges when it comes to treating solid tumors. As CAR-T cell therapy continues to evolve, further innovations will be devised to surmount the challenges associated with this treatment modality, ultimately leading to enhanced therapeutic response for patients suffered solid tumors.

Abstract Botrytis cinerea is one of the most destructive phytopathogenic fungi, causing significant losses to horticultural crops. As a necrotrophic fungus, B. cinerea obtains nutrients by killing host cells. Secreted cell death-inducing proteins (CDIPs) play a crucial role in necrotrophic infection; however, only a limited number have been reported. For high-throughput CDIP screening, we optimized the prokaryotic expression system and compared its efficiency with other commonly used protein expression systems. The optimized prokaryotic expression system showed superior effectiveness and efficiency and was selected for subsequent CDIP screening. The screening system verified fifty-five candidate proteins and identified two novel SGNH family CDIPs: BcRAE and BcFAT. BcRAE and BcFAT exhibited high expression levels throughout the infection process. Site-directed mutagenesis targeting conserved Ser residues abolished the cell death-inducing activity of both BcRAE and BcFAT. Moreover, the transient expression of BcRAE and BcFAT in plants enhanced plant resistance against B. cinerea without inducing cell death, independent of their enzymatic activities. Our results suggest a high-efficiency screening system for high-throughput CDIP screening and provide new targets for further study of B. cinerea-plant interactions.

Abstract Clinical translation of AAV-mediated gene therapy requires preclinical development across different experimental models, often confounded by variable transduction efficiency. Here, we describe a human liver chimeric transgene-free Il2rg −/− /Rag2 −/− /Fah −/− /Aavr −/− (TIRFA) mouse model overcoming this translational roadblock, by combining liver humanization with AAV receptor (AAVR) ablation, rendering murine cells impermissive to AAV transduction. Using human liver chimeric TIRFA mice, we demonstrate increased transduction of clinically used AAV serotypes in primary human hepatocytes compared to humanized mice with wild-type AAVR. Further, we demonstrate AAV transduction in human teratoma-derived primary cells and liver cancer tissue, displaying the versatility of the humanized TIRFA mouse. From a mechanistic perspective, our results support the notion that AAVR functions as both an entry receptor and an intracellular receptor essential for transduction. The TIRFA mouse should allow prediction of AAV gene transfer efficiency and the study of AAV vector biology in a preclinical human setting.

AbstractBreast cancer is one of the most devastating cancers that have no cure. Many therapeutic and diagnostic strategies have been extensively studied in the past decade. Cancer nanotechnology has developed as a promising approach in preclinical examinations, allowing for the early exposure of primary tumors and metastases and the efficient destruction of cancer cells. The current study aims to fabricate and analyze polymeric nanoparticles for breast cancer therapy established on a copolymeric block of α-tocopheryl polyethylene glycol 1000-b-polycaprolactone (TPGS-b-PCL) incorporating paclitaxel (PTX) (termed as T-b-P@PTX). Characterization of the physical, chemical, and structural properties and the in vitro biological activity of TPGS-b-PCL (T-b-P@PTX) obtained by the nanoprecipitation method. The in vitro cytotoxicity of the nanoparticles was explored by MTT assay using MCF-7 breast cancer cells in a time-dependent manner. The IC50 values T-b-P@PTX for MCF-7 cells 543.7 ± 2.58, 130.2 ± 3.54, 66.99 ± 3.43 in 24, 48, 72-h. Biochemical experiments showed that T-b-P@PTX has a strong ability to induce cell death and to be internalized in the MCF-7 cells. Ethidium bromide (EB)-acridine orange (AO) and nuclear DAPI staining methods investigated the morphological changes of the cells. Considering all the advantages, Paclitaxel-loaded T-b-P@PTX polymeric nanoparticle is a promising approach for treating breast cancer.

Retinoic acid is an active metabolite with significant physiological functions in human development, immunity, vision, and skin health. In recent years, research on retinoic acid in the field of kidney disorders has been increasing gradually. Yet, there is a lack of systematic bibliometric analysis of retinoic acid research in the kidney domain. This study included 1,368 articles published between 1998 and 2023 on treating kidney diseases with retinoic acid. Using the bibliometric analysis software VOSviewer and CiteSpace, we analyzed data on publication trends, contributing countries and institutions, journals and cocited journals, authors and cocited authors, cocited references, research hotspots, and frontiers. On the basis of the results of the bibliometric analysis, we identified the research efforts and their developmental trends, providing the groundwork for future research on retinoic acid.

The occurrence of bone metastasis is a grave medical concern that substantially impacts the quality of life in patients with cancer. The precise mechanisms underlying bone metastasis remain unclear despite extensive research efforts, and efficacious therapeutic interventions are currently lacking. The ability of osteoclasts to degrade the bone matrix makes them a crucial factor in the development of bone metastasis. Osteoclasts are implicated in several aspects of bone metastasis, encompassing the formation of premetastatic microenvironment, suppression of the immune system, and reactivation of quiescent tumor cells. Contemporary clinical interventions targeting osteoclasts have proven effective in mitigating bone-related symptoms in patients with cancer. This review comprehensively analyzes the mechanistic involvement of osteoclasts in bone metastasis, delineates potential therapeutic targets associated with osteoclasts, and explores clinical evidence regarding interventions targeting osteoclasts.

Background: The triglyceride-glucose (TyG) index has been recommended as a practical surrogate of insulin resistance (IR). However, the association between the TyG index and hyperuricemia among adults with hypertension remains to be elucidated. Methods: We included and analyzed 3134 HTN patients and 4233 non-HTN participants from the cross-sectional 2013–2018 U.S. National Health and Nutrition Examination Surveys (NHANES). Multivariable logistic regression and restricted cubic splines (RCS) were used to explore the association between the TyG index and hyperuricemia. Stratifed analyses were performed to assess the association in populations with different subgroups of hypertension. Results: The prevalence of hyperuricemia was higher in HTN patients (28.00 %) than in non-HTN participants (12.47 %). The multivariable logistic regression showed that the TyG index was significantly associated with hyperuricemia. After multivariable adjustment, higher TyG index levels were found to be associated with a higher prevalence of hyperuricemia in HTN patients (OR: 2.39, 95 % CI: 1.37–4.17, Ptrend 0.05). In the subgroup analysis suggested that the positive association seemed to be strong among male, alcohol use, and diabetes group (P for interaction

BackgroundNumerous observational studies have identified associations between both psoriasis (PsO) and psoriatic arthritis (PsA), and autoimmune diseases (AIDs); however, the causality of these associations remains undetermined.MethodsWe conducted a bidirectional two-sample Mendelian Randomization study to identify causal associations and directions between both PsO and PsA and AIDs, such as systemic lupus erythematosus (SLE), Crohn’s disease (CD), ulcerative colitis (UC), multiple sclerosis (MS), uveitis, bullous pemphigoid (BP), Hashimoto’s thyroiditis (HT), rheumatoid arthritis (RA), vitiligo, and ankylosing spondylitis (AS). The causal inferences were drawn by integrating results from four regression models: Inverse Variance Weighting (IVW), MR-Egger, Weighted Median, and Maximum Likelihood. Furthermore, we performed sensitivity analyses to confirm the reliability of our findings.ResultsThe results showed that CD [IVW odds ratio (ORIVW), 1.11; 95% confidence interval (CI), 1.06-1.17; P = 8.40E-06], vitiligo (ORIVW, 1.16; 95% CI, 1.05-1.28; P = 2.45E-03) were risk factors for PsO, while BP may reduce the incidence of PsO (ORIVW, 0.91; 95% CI, 0.87-0.96; P = 1.26E-04). CD (ORIVW, 1.07; 95% CI, 1.02-1.12; P = 0.01), HT (ORIVW, 1.23; 95% CI, 1.08-1.40; P = 1.43E-03), RA (ORIVW, 1.11; 95% CI, 1.02-1.21, P = 2.05E-02), AS (ORIVW, 2.18; 95% CI, 1.46-3.27; P = 1.55E-04), SLE (ORIVW, 1.04; 95% CI, 1.01-1.08; P = 1.07E-02) and vitiligo (ORIVW, 1.27; 95% CI, 1.14-1.42; P = 2.67E-05) were risk factors for PsA. Sensitivity analyses had validated the reliability of the results.ConclusionsOur study provides evidence for potential causal relationships between certain AIDs and both PsO and PsA. Specifically, CD and vitiligo may increase the risk of developing PsO, while CD, HT, SLE, RA, AS, and vitiligo may elevate the risk for PsA. Additionally, it is crucial to closely monitor the condition of PsO patients with specific AIDs, as they have a higher likelihood of developing PsA than those without AIDs. Moving forward, greater attention should be paid to PsA and further exploration of other PsO subtypes is warranted.

Summary: Lymph node metastasis (LNM) is the main metastatic pathway of cervical cancer, which is closely related to 5-year survival rate of cervical squamous cell carcinoma (CSCC), yet the underlying mechanism remains unconfirmed. In this study, we show that midkine (MDK) was highly expressed in CSCC and overexpression of MDK was associated with CSCC LNM. Functional investigations demonstrated that MDK promoted LNM by enhancing proliferation, migration and invasion capacity of cervical cancer cells, facilitating lymphangiogenesis and down-regulating the expression of tight junction proteins of human lymphatic endothelial cells (HLECs). MDK exerted these biological effects by interacting with Syndecan-1 and activating PI3K/AKT and p38 MAPK pathways. A retrospective study showed that s-MDK was related to LNM. s-MDK combined with serum-squamous cell carcinoma antigen(s-SCCA) improved the diagnostic accuracy of CSCC LNM. These findings established a new mechanism of LNM and highlighted MDK as a candidate tumor biomarker and therapeutic target in CSCC.

Objectives: 'Super-agers,' individuals over 80 with memory abilities comparable to those 20–30 years younger. The relationship between super-agers and dietary acid load (DAL) is an area that warrants further investigation. We aim to examine the link between DAL and super-agers and assess DAL's effects on cognitive functions across different age groups and cognitive domains. Design: Employing a cross-sectional analysis of the 2011–2014 National Health and Nutrition Examination Survey (NHANES) data, we utilized propensity score analysis and multivariate-adjusted regression to mitigate confounding factors. Setting: Older adults aged 60 and above in the United States. Participants: Our primary analysis encompassed 985 older adults, supplemented by a sensitivity analysis with 2,522 participants. Measurements: DAL was assessed through potential renal acid load (PRAL), estimated net acid excretion (NAEes), and net endogenous acid production (NEAP) indices. Results: Super-agers demonstrate a preference for alkaline diets, shown by their lower DAL indices. After inverse probability of treatment weighting (IPTW), multivariate-adjusted logistic regression reveals that each unit reduction in NAEes and PRAL increases the chances of being a super-ager by 3.9% and 3.0%, respectively. The DAL's impact on cognitive function becomes more pronounced with age. Lower PRAL and NAEes scores are significantly linked to higher situational memory and overall cognitive performance scores in those over 70, with these effects being even more pronounced in participants over 80. Conclusion: This research pioneers in demonstrating that super-agers prefer an alkaline diet, highlighting the potential role of alkaline diet in countering cognitive decline associated with aging.

Abstract Venn diagrams serve as invaluable tools for visualizing set relationships due to their ease of interpretation. Widely applied across diverse disciplines such as metabolomics, genomics, transcriptomics, and proteomics, their utility is undeniable. However, the operational complexity has been compounded by the absence of standardized data formats and the need to switch between various platforms for generating different Venn diagrams. To address these challenges, we introduce the EVenn platform, a versatile tool offering a unified interface for efficient data exploration and visualization of diverse Venn diagrams. EVenn (http://www.ehbio.com/test/venn) streamlines the data upload process with a standardized format, enhancing the capabilities for multimodule analysis. This comprehensive protocol outlines various applications of EVenn, featuring representative results of multiple Venn diagrams, data uploads in the centralized data center, and step‐by‐step case demonstrations. Through these functionalities, EVenn emerges as a valuable and user‐friendly tool for the in‐depth exploration of multiomics data.

BackgroundWhile observational epidemiological studies have suggested an association between gut microbiota and Behçet’s disease (BD), the causal relationship between the two remains uncertain.MethodsStatistical data were obtained from gut microbiome Genome-Wide Association Studies (GWAS) published by the MiBioGen consortium, and genetic variation points were screened as instrumental variables (IV). Mendelian randomization (MR) study was performed using inverse variance weighted (IVW), weighted median, MR-Egger regression, simple mode, and weighted mode methods to evaluate the causal relationship between gut microbiota (18,340 individuals) and BD (317,252 individuals). IVW was the main method of analysis. The stability and reliability of the results were verified using the leave-one-out method, heterogeneity test, and horizontal genetic pleiotropy test. Finally, a reverse MR analysis was performed to explore reverse causality.ResultsInverse variance weighted (IVW) results showed that the genus Parasutterella (OR = 0.203, 95%CI 0.055–0.747, p = 0.016), Lachnospiraceae NC2004 group (OR = 0.101, 95%CI 0.015–0.666, p = 0.017), Turicibacter (OR = 0.043, 95%CI 0.007–0.273, p = 0.001), and Erysipelatoclostridium (OR = 0.194, 95%CI 0.040–0.926, p = 0.040) were protective factors against BD, while Intestinibacter (OR = 7.589, 95%CI 1.340–42.978, p = 0.022) might be a risk factor for BD.ConclusionOur study revealed the causal relationship between gut microbiota and BD. The microbiota that related to BD may become new biomarkers; provide new potential indicators and targets for the prevention and treatment of BD.

ABSTRACT The causative agent of Legionnaires’ disease, Legionella pneumophila, is an environmental bacterium, that replicates in macrophages, parasitizes amoeba, and forms biofilms. L. pneumophila employs the Legionella quorum sensing (Lqs) system and the transcription factor LvbR to control various bacterial traits, including virulence and biofilm architecture. LvbR negatively regulates the nitric oxide (NO) receptor Hnox1, linking quorum sensing to NO signaling. Here, we assessed the response of L. pneumophila to NO and investigated bacterial receptors underlying this process. Chemical NO donors, such as dipropylenetriamine (DPTA) NONOate and sodium nitroprusside (SNP), delayed and reduced the expression of the promoters for flagellin (PflaA) and the 6S small regulatory RNA (P6SRNA). Marker-less L. pneumophila mutant strains lacking individual (Hnox1, Hnox2, or NosP) or all three NO receptors (triple knockout, TKO) grew like the parental strain in media. However, in the TKO strain, the reduction of PflaA expression by DPTA NONOate was less pronounced, suggesting that the NO receptors are implicated in NO signaling. In the ΔnosP mutant, the lvbR promoter was upregulated, indicating that NosP negatively regulates LvbR. The single and triple NO receptor mutant strains were impaired for growth in phagocytes, and phenotypic heterogeneity of non-growing/growing bacteria in amoebae was regulated by the NO receptors. The single NO receptor and TKO mutant strains showed altered biofilm architecture and lack of response of biofilms to NO. In summary, we provide evidence that L. pneumophila regulates virulence, intracellular phenotypic heterogeneity, and biofilm formation through NO and three functionally non-redundant NO receptors, Hnox1, Hnox2, and NosP.IMPORTANCEThe highly reactive diatomic gas molecule nitric oxide (NO) is produced by eukaryotes and bacteria to promote short-range and transient signaling within and between neighboring cells. Despite its importance as an inter-kingdom and intra-bacterial signaling molecule, the bacterial response and the underlying components of the signaling pathways are poorly characterized. The environmental bacterium Legionella pneumophila forms biofilms and replicates in protozoan and mammalian phagocytes. L. pneumophila harbors three putative NO receptors, one of which crosstalks with the Legionella quorum sensing (Lqs)-LvbR network to regulate various bacterial traits, including virulence and biofilm architecture. In this study, we used pharmacological, genetic, and cell biological approaches to assess the response of L. pneumophila to NO and to demonstrate that the putative NO receptors are implicated in NO detection, bacterial replication in phagocytes, intracellular phenotypic heterogeneity, and biofilm formation.

Abstract Diseases like obesity and intestinal inflammation diseases are accompanied by dysbiosis of the gut microbiota (DSGM), which leads to various complications, including systemic metabolic disorders. DSGM reportedly impairs the fertility of male mice; however, the regulatory mechanism is unclear. Exosomes are molecular mediators of intercellular communication, but the regulation of spermatogenesis by non‐reproductive tissue‐originated exosomes remains unknown. The present study shows that DSGM altered the miRNA expression profile of mouse circulating exosomes and impaired spermatogenesis. Moreover, the single‐cell sequencing results indicate that circulating exosomes from mice with DSGM impaired spermatogenesis, while circulating exosomes from wild mice improved spermatogenesis by promoting meiosis. Further study demonstrates that DSGM leads to abnormal upregulation of miR‐211‐5p in gut‐derived circulating exosomes, which inhibited the expression of meiosis‐specific with coiled‐coil domain (Meioc) in the testes and impaired spermatogenesis by disturbing meiosis process. In summary, this study defines the important role of gut‐derived exosomes in connecting the “gut‐testis” axis.

Background and Purpose: Sex differences in acute ischemic stroke have been widely investigated, but the difference in acute ischemic stroke patients who received intravenous thrombolysis is not well understood. The current study was to investigate the issue based on a prospective cohort. Methods: From the Intravenous Thrombolysis Registry for Chinese Ischemic Stroke within 4.5h onset (INTRECIS) cohort, a total of 953 eligible patients with acute ischemic stroke were enrolled in final analysis. Based on 3-month modified Rankin scale score (mRS), patients were classified into good outcome group (mRS 0–1) and poor outcome group (mRS 2–6). Univariate and multivariate logistic regression analyses were used to identify predictive factors for clinical outcome in male or female patients. Results: Of the 953 patients treated with intravenous thrombolysis, 314 (32.9 %) were women. At day 90, we found no significant gender differences in good outcome (72.5 % vs 65.6 %, adjusted p = 0.414). We got the same results after propensity score matching (69.5 % vs 63.4 %, adjusted p = 0.637). Furthermore, we found that initial National Institute of Health Stroke Scale (NIHSS) score (odd ratio [OR] 0.877; 95 % CI 0.847–0.909, p

The market circulation system for agricultural products in less-developed regions lags behind; it fails to meet the requirements for efficient circulation. Therefore, it is crucial to explore the dynamic relationship between the Agricultural Products Circulation (APC) service industry and circulation efficiency. Using panel data from 29 regions in China, the entropy method measured the Development Level (DL) of the APC service industry, while the non-oriented super-efficiency Slacks-Based Measure (SBM) model was employed to assess the APC efficiency. A Panel Vector Autoregressive (PVAR) model was built for estimation. The impulse response function and variance decomposition were utilized to analyze the differences in the DL of the APC service industry, circulation efficiency, and their interaction mechanism across the Western, Central, and Eastern regions of China. The findings indicate that the DL of the APC service industry and APC efficiency in the less-developed regions of the West have a positive driving effect on each other. However, the magnitude of this effect was asymmetric and transient. The APC service industry’s DL and APC efficiency are more dependent on their inertia, and no efficient two-way feedback mechanism has been formed. This study provides a reference for the construction and sustainable development of modernized APC systems in less-developed regions.

Purpose: To evaluate regional changes in the posterior corneal elevation after three laser refractive surgeries for correction of myopia of different degrees. Settings and Design: Retrospective, comparative, and non-randomized study. Methods: Two hundred patients (200 eyes) who underwent laser epithelial keratoplasty (LASEK), femtosecond-assisted laser in-situ keratomileusis (FS-LASIK), and small-incision lenticule extraction (SMILE) were included in this study. According to preoperative spherical equivalent (SE), each surgical group was divided into two refractive subgroups: low-to-moderate myopia (LM group) and high myopia (H group). The posterior corneal elevation from Pentacam Scheimpflug tomography was analyzed preoperatively and at 1 month, 3 months, 6 months, and 12 months postoperatively. Three subregions of the posterior cornea were divided in this study as the central, paracentral, and peripheral regions. Statistical Analysis Used: Generalized Estimating Equations (GEE). Results: For all three surgical groups, similar changing trends were seen in the two refractive subgroups. H group presented a larger changing magnitude than the LM group in FS-LASIK over time (P < 0.05), whereas no significant difference was noted in the two refractive subgroups of LASEK or SMILE (P > 0.05). At 12 months postoperatively, the central posterior corneal elevation returned to the preoperative level in LASEK (P > 0.05) but shifted forward significantly in FS-LASIK and SMILE (P < 0.05). Conclusion: Different posterior corneal regions respond differently to corneal refractive surgeries. LASEK, FS-LASIK, and SMILE demonstrate different trends in the regional changes in posterior corneal elevation. The corneal shape seems more stable in LASEK than in FS-LASIK and SMILE.

The great potentials of massive Multiple-Input Multiple-Output (MIMO) in Frequency Division Duplex (FDD) mode can be fully exploited when the downlink Channel State Information (CSI) is available at base stations. However, the accurate CSI is difficult to obtain due to the large amount of feedback overhead caused by massive antennas. In this paper, we propose a deep learning based joint channel estimation and feedback framework, which comprehensively realizes the estimation, compression, and reconstruction of downlink channels in FDD massive MIMO systems. Two networks are constructed to perform estimation and feedback explicitly and implicitly. The explicit network adopts a multi-Signal-to-Noise-Ratios (SNRs) technique to obtain a single trained channel estimation subnet that works well with different SNRs and employs a deep residual network to reconstruct the channels, while the implicit network directly compresses pilots and sends them back to reduce network parameters. Quantization module is also designed to generate data-bearing bitstreams. Simulation results show that the two proposed networks exhibit excellent performance of reconstruction and are robust to different environments and quantization errors.

Micro-expression recognition based on ima- ges has made some progress, yet limitations persist. For instance, image-based recognition of micro-expressions is affected by factors such as ambient light, changes in head posture, and facial occlusion. The high temporal resolution of electroencephalogram (EEG) technology can record brain activity associated with micro-expressions and identify them objectively from a neurophysiological standpoint. Accordingly, this study introduces a novel method for recognizing micro-expressions using node efficiency features of brain networks derived from EEG signals. We designed a real-time Supervision and Emotional Expression Suppression (SEES) experimental paradigm to collect video and EEG data reflecting micro- and macro-expression states from 70 participants experiencing positive emotions. By constructing functional brain networks based on graph theory, we analyzed the network efficiencies at both macro- and micro-levels. The participants exhibited lower connection density, global efficiency, and nodal efficiency in the alpha, beta, and gamma networks during micro-expressions compared to macro-expressions. We then selected the optimal subset of nodal efficiency features using a random forest algorithm and applied them to various classifiers, including Support Vector Machine (SVM), Gradient-Boosted Decision Tree (GBDT), Logistic Regression (LR), Random Forest (RF), and eXtreme Gradient Boosting (XGBoost). These classifiers achieved promising accuracy in micro-expression recognition, with SVM exhibiting the highest accuracy of 92.6% when 15 channels were selected. This study provides a new neuroscientific indicator for recognizing micro-expressions based on EEG signals, thereby broadening the potential applications for micro-expression recognition.

Abstract Both lytic and apoptotic cell death remove senescent and damaged cells in living organisms. However, they elicit contrasting pro- and anti-inflammatory responses, respectively. The precise cellular mechanism that governs the choice between these two modes of death remains incompletely understood. Here we identify Gasdermin E (GSDME) as a master switch for neutrophil lytic pyroptotic death. The tightly regulated GSDME cleavage and activation in aging neutrophils are mediated by proteinase-3 and caspase-3, leading to pyroptosis. GSDME deficiency does not alter neutrophil overall survival rate; instead, it specifically precludes pyroptosis and skews neutrophil death towards apoptosis, thereby attenuating inflammatory responses due to augmented efferocytosis of apoptotic neutrophils by macrophages. In a clinically relevant acid-aspiration-induced lung injury model, neutrophil-specific deletion of GSDME reduces pulmonary inflammation, facilitates inflammation resolution, and alleviates lung injury. Thus, by controlling the mode of neutrophil death, GSDME dictates host inflammatory outcomes, providing a potential therapeutic target for infectious and inflammatory diseases.

Abstract Although no study has directly shown the relationship between bacterial vaginosis (BV) and homocysteine (HCY), we still found some association between these two through extensive literature and data analysis. BV score was calculated by Nugent’s method, less than equal to 6 is negative and greater than equal to 7 is positive. This article describes interrelationships we mined from data extracted by NHANES regarding BV and HCY under multiple covariates. We used two cycles of NHANES 2001–2002 and 2003–2004 in our study. We included 2398 participants in our study who recently completed the interview and the MEC tests. By investigating the relationship between BV and HCY under multivariate conditions, multiple linear regression analysis was performed. These factors may have influenced the results, such as ethnicity, age, education level, body mass index (BMI), etc. Serum vitamin B12, ferritin, percentage of segmented centrioles, and number of segmented centrioles were selected as potential covariates in our study. We observed that both the coarse model and the two adjusted models showed a high correlation between HCY and BV, and the correlation was positive. In the coarse model, OR = 1.26, 95% confidence interval (CI) 1.10, 1.44, P = 0.0018); HCY was positively correlated with BV (OR = 1.19, 95% confidence interval (CI) 1.05, 1.34, P = 0.0121). Multiple linear regression analysis was used to investigate the connection between BV and HCY under multivariate settings. The results of this study indicate that HCY is positively associated with the prevalence of BV and may play an important role in the prevention and management of BV.

Urban development thrives from technology inflows, which refers to the transfer of high-value technology from various cities to local recipients. The asymmetry of technical information—rooted in the tacit knowledge inherent in technology—mandates that technology transfer is heavily dependent on interactions and communication among talented individuals. This study examines the effect of China's high-speed railway (HSR) on technology inflow, with an emphasis on talent interaction in the technology transfer process. The findings suggest that HSR mitigates cross-city commuting costs and facilitates face-to-face interactions between talent, thereby fostering an increase in technology inflows to various cities. “Talent” use HSR to transfer knowledge to cities teeming with such talent resources. Concurrently, areas with robust intellectual property rights protection witness an upsurge in intercity technology transfer via HSR. This study elucidates the macro-mechanism of urban technology flow from the perspective of public transportation offering valuable insights for technology market infrastructure and services.

Studies using source localization results have shown that cortical involvement increased in treadmill walking with brain–computer interface (BCI) control. However, the reorganization of cortical functional connectivity in treadmill walking with BCI control is largely unknown. To investigate this, a public dataset, a mobile brain–body imaging dataset recorded during treadmill walking with a brain–computer interface, was used. The electroencephalography (EEG)-coupling strength of the between-region and within-region during the continuous self-determinant movements of lower limbs were analyzed. The time–frequency cross-mutual information (TFCMI) method was used to calculate the coupling strength. The results showed the frontal–occipital connection increased in the gamma and delta bands (the threshold of the edge was >0.05) during walking with BCI, which may be related to the effective communication when subjects adjust their gaits to control the avatar. In walking with BCI control, the results showed theta oscillation within the left-frontal, which may be related to error processing and decision making. We also found that between-region connectivity was suppressed in walking with and without BCI control compared with in standing states. These findings suggest that walking with BCI may accelerate the rehabilitation process for lower limb stroke.

Background: Cancer stem-like cells (CSCs), a distinct subset recognized for their stem cell-like abilities, are intimately linked to the resistance to radiotherapy, metastatic behaviors, and self-renewal capacities in tumors. Despite their relevance, the definitive traits and importance of CSCs in the realm of oncology are still not fully comprehended, particularly in the context of clear cell renal cell carcinoma (ccRCC). A comprehensive understanding of these CSCs’ properties in relation to stemness, and their impact on the efficacy of treatment and resistance to medication, is of paramount importance. Methods: In a meticulous research effort, we have identified new molecular categories designated as CRCS1 and CRCS2 through the application of an unsupervised clustering algorithm. The analysis of these subtypes included a comprehensive examination of the tumor immune environment, patterns of metabolic activity, progression of the disease, and its response to immunotherapy. In addition, we have delved into understanding these subtypes’ distinctive clinical presentations, the landscape of their genomic alterations, and the likelihood of their response to various pharmacological interventions. Proceeding from these insights, prognostic models were developed that could potentially forecast the outcomes for patients with ccRCC, as well as inform strategies for the surveillance of recurrence after treatment and the handling of drug-resistant scenarios. Results: Compared with CRCS1, CRCS2 patients had a lower clinical stage/grading and a better prognosis. The CRCS2 subtype was in a hypoxic state and was characterized by suppression and exclusion of immune function, which was sensitive to gefitinib, erlotinib, and saracatinib. The constructed prognostic risk model performed well in both training and validation cohorts, helping to identify patients who may benefit from specific treatments or who are at risk of recurrence and drug resistance. A novel therapeutic target, SAA2, regulating neutrophil and fibroblast infiltration, and, thus promoting ccRCC progression, was identified. Conclusions: Our findings highlight the key role of CSCs in shaping the ccRCC tumor microenvironment, crucial for therapy research and clinical guidance. Recognizing tumor stemness helps to predict treatment efficacy, recurrence, and drug resistance, informing treatment strategies and enhancing ccRCC patient outcomes.