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Human bone marrow mesenchymal stem cells (HBMSCs) can promote new bone formation. Previous studies have proven the ability of long non-coding RNAs (lncRNAs) to modulate the osteogenic differentiation of mesenchymal stem cells. However, the molecular mechanism modulated by lncRNAs in affecting the osteogenic differentiation of HBMSCs remains largely unknown. Thus, this study aims to reveal the role of lncRNA ubiquitin-specific peptidase 2 antisense RNA 1 (USP2-AS1) in regulating the osteogenic differentiation of HBMSCs and investigate its regulatory mechanism. Through bioinformatics analysis and RT-qPCR, we confirmed that USP2-AS1 expression was increased in HBMSCs after culturing in osteogenic differentiation medium (OM-HBMSCs). Moreover, we uncovered that knockdown of USP2-AS1 inhibited the osteogenic differentiation of HBMSCs. Further exploration indicated that USP2-AS1 positively regulated the expression of its nearby gene USP2. Mechanistically, USP2-AS1 recruited lysine demethylase 3A (KDM3A) to stabilize ETS proto-oncogene 1 (ETS1), transcription factor that transcriptionally activated USP2. Additionally, USP2-induced Wnt/β-catenin signalling pathway activation via deubiquitination of β-catenin protein. In summary, our study proved that lncRNA USP2-AS1 facilitates the osteogenic differentiation of HBMSCs by targeting KDM3A/ETS1/USP2 axis to activate the Wnt/β-catenin signalling pathway.

It is well known that crossbreds show many advantages over purebreds in improving calf health traits, but the immunological factors responsible for this heterosis remain largely unclear. The objective of this study was to compare the cellular immune responses and antibodies of Holstein (HO) and Montbéliarde-sired × Holstein (MH) F1 generation female calves, and investigate the effects of crossbreeding on the immunity. Fifty three-month-old healthy female calves (25 HO, 25 MH) were selected meticulously in a farm with the same criteria. Subsequently, complete blood count, flow cytometric analysis of T cell subsets and intracellular IFN-γ production, as well as indirect ELISA analysis of antibodies were performed in order to determine the immune profiles of the two groups of calves. We found that MH calves had higher percentage and number of CD4+ and CD8+ T cells than HO calves in the peripheral blood (p

Abstract Arginine methylation of histones plays a critical role in regulating gene expression. The writers (methyltransferases) and readers of methylarginine marks are well-known, but the erasers–arginine demethylases–remain mysterious. Here we identify Myc-induced nuclear antigen 53 (Mina53), a jumonji C domain containing protein, as an arginine demethylase for removing asymmetric di-methylation at arginine 3 of histone H4 (H4R3me2a). Using a photoaffinity capture method, we first identify Mina53 as an interactor of H4R3me2a. Biochemical assays in vitro and in cells characterize the arginine demethylation activity of Mina53. Molecular dynamics simulations provide further atomic-level evidence that Mina53 acts on H4R3me2a. In a transgenic mouse model, specific Mina53 deletion in neural stem/progenitor cells prevents H4R3me2a demethylation at distinct genes clusters, dysregulating genes important for neural stem/progenitor cell proliferation and differentiation, and consequently impairing the cognitive function of mice. Collectively, we identify Mina53 as a bona fide H4R3me2a eraser, expanding the understanding of epigenetic gene regulation.

Abstract Nickel-rich layered oxides are one of the most promising positive electrode active materials for high-energy Li-ion batteries. Unfortunately, the practical performance is inevitably circumscribed by the structural deterioration deriving from the Ni/Li antisite disorder, leading to severe capacity loss and life attenuation. Herein, we propose an economical and facile rejuvenation strategy by employing the magneto-electrochemical synergistic activation targeting the positive electrode in assembled Li-ion batteries. This approach induces a transition of Ni3+ from high-spin to low-spin, reducing the super-exchange interaction of Ni-O-transition metal (TM). Meanwhile, electrochemical reaction drives Li+ from the host material and promotes Ni3+ to reoccupy TM layer, recovering intrinsic Li site and extending cycle life. The strategy demonstrates that low-quality positive electrodes can be converted to high-quality ones. Notably, the method can revitalize an aged Li-ion pouch cell (SiC||NCM811, 8 Ah nominal capacity) via optimizing cation occupancy and increase its capacity by 10% from 6.49 to 7.14 Ah at 1 C, illustrating the benefits of the upcycling process.

Abstract Germinal center (GC) formation, which is an integrant part of humoral immunity, involves energy-consuming metabolic reprogramming. Rag-GTPases are known to signal amino acid availability to cellular pathways that regulate nutrient distribution such as the mechanistic target of rapamycin complex 1 (mTORC1) pathway and the transcription factors TFEB and TFE3. However, the contribution of these factors to humoral immunity remains undefined. Here, we show that B cell-intrinsic Rag-GTPases are critical for the development and activation of B cells. RagA/RagB deficient B cells fail to form GCs, produce antibodies, and to generate plasmablasts during both T-dependent (TD) and T-independent (TI) humoral immune responses. Deletion of RagA/RagB in GC B cells leads to abnormal dark zone (DZ) to light zone (LZ) ratio and reduced affinity maturation. Mechanistically, the Rag-GTPase complex constrains TFEB/TFE3 activity to prevent mitophagy dysregulation and maintain mitochondrial fitness in B cells, which are independent of canonical mTORC1 activation. TFEB/TFE3 deletion restores B cell development, GC formation in Peyer’s patches and TI humoral immunity, but not TD humoral immunity in the absence of Rag-GTPases. Collectively, our data establish the Rag GTPase-TFEB/TFE3 pathway as a likely mTORC1 independent mechanism to coordinating nutrient sensing and mitochondrial metabolism in B cells.

Abstract Background Polyploid giant cancer cells (PGCCs) have properties of cancer stem cells (CSCs). PGCCs with daughter cells (PDCs) undergo epithelial–mesenchymal transition and show enhanced cellular plasticity. This study aimed to elucidate the mechanisms underlying the osteo/chondrogenic-like differentiation of PDCs, which may be exploited therapeutically by transdifferentiation into post-mitotic and functional cells. Methods Cobalt chloride was used to induce PGCC formation in MDA-MB-231 and HEY cells, and PDCs were cultured in osteo/chondrogenic differentiation media. Alcian blue staining was used to confirm osteo/chondrogenic differentiation, and the cell cycle was detected using flow cytometry. The expression of osteo/chondrogenic differentiation-related proteins was compared, and a co-immunoprecipitation assay was used to demonstrate the interactions between proteins. Bioinformatic analysis was used to explore the regulatory mechanism of osteo/chondrogenic differentiation, and a dual-luciferase reporter assay was performed to validate the interaction between transcriptional factors and target genes. Animal xenograft models were used to confirm the osteo/chondrogenic differentiation of PDCs. Results When cultured in osteo/chondrogenic medium, the stemness of PDCs decreased, and the expression of osteo/chondrogenic-related markers increased. This osteo/chondrogenic-like process was regulated by the transforming growth factor-β pathway in a time-dependent manner. A concurrent increase in the expression of histone acetyltransferase p300 and the transcription factor CCCTC-binding factor (CTCF) was observed. Co-immunoprecipitation assays revealed that p300 acetylated the osteo/chondrogenic marker RUNT-related transcription factor 2 (RUNX2). Analysis of chromatin immunoprecipitation sequencing datasets revealed that both CTCF and histone H3 lysine 27 acetylation (H3K27ac) were enriched in the promoter region of E1A-associated protein p300 (P300). The four predicted binding sites for CTCF and P300 were validated using dual-luciferase reporter assays. We examined the interaction between CTCF and H3K27ac and found that these two proteins had a combined effect on the transactivation of P300. Conclusion CTCF, in synergy with H3K27ac, amplified the expression of P300, facilitating acetyl group transfer to RUNX2. This acetylation stabilized RUNX2 and promoted osteo/chondrogenic differentiation, thereby reducing the incidence of PDC malignancies.

Abstract Background Uveal melanoma (UM) is a rare and deadly eye cancer with high metastatic potential. Despite the predominance of malignant cells within the tumor microenvironment, the heterogeneity and underlying molecular features remain to be fully characterized. Methods We analyzed single-cell transcriptomic profiling of 37,660 malignant cells from 17 UM tumors. A consensus non-negative factorization algorithm was used to decipher transcriptional programs underlying tumor cell-intrinsic heterogeneity. Tumor-infiltrated immune cells were computationally estimated from bulk transcriptomes and bioinformatics methods. A gene signature was derived for subtyping and prognostic stratification and validated in multicenter cohorts. Results ScRNA-seq analysis revealed the existence of diverse subpopulations and transcriptional variability among malignant cells within and between tumors. Furthermore, we observed that the heterogeneity of malignant cell states and compositions correlated with genomic, immunological, and clinical characteristics. By identifying gene expression programs associated with malignant cell heterogeneity at the single cell level, UM samples were classified into two distinct intra-tumoral subtypes (ITMHlo and ITMHhi) with different prognoses and immune microenvironments. Finally, a machine learning-derived 9-gene signature was developed to translate single-cell information into bulk tissue transcriptomes for patient stratification and was validated in multicenter cohorts. Conclusions Our study provides insight into understanding the intra-tumoral heterogeneity of UM and its potential impact on patient stratification.

Abstract The PI3K/Akt pathway is overexpressed in nearly 50% of hepatocellular carcinomas and inhibits apoptosis by promoting the expression of antiapoptotic genes. Serine protease inhibitors have been shown to induce apoptosis in hepatoma cells by downregulating SPINK13 in the PI3K/Akt pathway. In this study, SPINK13 was expressed in lentiviral vectors. Changes in signaling pathway adapter proteins, apoptosis regulatory proteins, cell cycle regulatory proteins, and the biological behavior of hepatocellular carcinoma were observed in cell and nude mouse xenograft models. The underlying mechanism of endogenous SPINK13-induced apoptosis in hepatocellular carcinoma cells was explored via transcriptomics. As a result, endogenous SPINK13 might inhibit the activity of Furin protease, downregulate the Notch1/Hes1 pathway in a binding manner, activate the direct effector PTEN, inhibit Akt phosphorylation, inactivate the downstream PI3K/Akt pathway, and ultimately lead to mitochondrial apoptosis and cell cycle arrest in hepatoma cells. Therefore, the Notch1/Hes1/PTEN pathway may act upstream of SPINK13 to downregulate the PI3K/Akt signaling pathway. Our study helps elucidate the underlying mechanism of SPINK13 in anti-hepatocellular carcinoma and lays a theoretical foundation for the development of novel therapeutic serine protease inhibitors.

Abstract Economic growth has brought about escalating environmental challenges. The purist of socioeconomic and environmental coordination necessitates a deep understanding of their interplay. Therefore, a game theory stepwise-cluster factorial coupling coordination model (GSFCM) has been developed to investigate the spatial and temporal patterns and driving forces of socioeconomic and environmental coordination in the Yangtze River Delta Region. Results reveal an upward in socioeconomic and environmental status from 2015 to 2020. All 41 cities in the region show progress towards coordination, coupled with spatial inequalities. Hangzhou, Shanghai, and Zhoushan demonstrate the highest coupling coordination degree (CCD), while Bozhou, Suzhou, and Fuyang located in Anhui exhibit the lowest levels. Socioeconomic factors contribute 82.98% to the enhancement of CCD, environmental factors contribute 11.05%, and their interaction accounts for 5.92%. Main drivers influencing CCD include Gross Domestic Product (GDP) per capita, the proportion of the added value of tertiary industry, PM2.5 concentration, and their interactions. Policy related to regional collaboration, industrial upgrades, and investment in environmental infrastructure are recomended to achieve a harmonious balance between economic growth and environmental protection. These insights are expected to support policy decisions in sustainable development of the region.

ObjectiveIt is vital to detect and track ships during coastal monitoring and ship navigation over long distances in complex circumstances. However, due to their small size and unclear features, they can be readily confused with shorelines, noise, and rocks, making them sometimes difficult to spot immediately. To address this issue, a novel ship detection method called ShipDet is proposed which significantly improves performance through the design of a dedicated backbone network, improved feature extraction process, and constrained microscopic detection heads. MethodFirst, this method constructs a feature fusion and extraction network that is highly sensitive to small objects by integrating the Swin Transformer module (STR) with the classic CSPDarknet53 network. This enhances the correlation between small target features and the environment, establishing associations between ships and waterways, ships and other ships, and ships and coastlines, while suppressing irrelevant information. Subsequently, considering the uneven distribution and minor scale variations of ship targets in the dataset, two detection layers are retained to reduce model parameters and further enhance model performance. Moreover, the method employs the SCYLLA-IoU (SIoU) loss function to constrain the detection heads, thereby reducing regression freedom and improving detection accuracy and robustness. ResultsTo validate the proposed method, a dataset called 2023ships is established which consists of up to 9 000 samples covering various scenarios such as inland rivers, coastal areas, daytime, nighttime, and foggy weather. During testing, the proposed method demonstrates superior overall ship detection performance compared to other algorithms, with a mAP of 92.9%, a precision rate of 92.1%, and a parameter size of 35 366 310. ConclusionThe proposed method can greatly benefit the fields of maritime monitoring and intelligent navigation.

Abstract Background The Covid-19 pandemic has affected all areas of society, including students. However, medical students have faced many challenges due to direct contact with patients. The present study was conducted with the aim of investigating and comparing the quality of life (QoL), anxiety and mindfulness between Iranian medical and non-medical students during the COVID-19 pandemic. Method Five hundred and six students (both medical and non-medical students) participated in the study from August to October 2022 with a convenience sampling method. The data were collected using an online questionnaire including a demographic form, the QoL Questionnaire (WHOQOL- BREF), the Generalized Anxiety Disorder 7-item survey (GAD‐7) and the Relaxation/Meditation/Mindfulness Tracker t-Persian version survey (RMMt-P). Pearson correlation and independent t-test and multivariate linear regression were used to determine the relationship between the study variables. Results The samples included 272 medical students and 234 non-medical students with a mean age of 21.99 ± 3.46 and 24.17 ± 6.54 years respectively. Most of the medical and non-medical students were female, single and had a bachelor’s degree. The mean scores of medical and non-medical students’ QoL during the COVID-19 pandemic were 57.86 ± 13.26 and 56.75 ± 14.42, respectively which indicates the higher quality of life of medical students. Anxiety and mindfulness predicted 29% of the variance of the QoL in the medical students, while anxiety and mindfulness and having a chronic disease predicted 30% of the variance of the QoL in the non-medical students. No significant difference existed in the QoL and its subscales during the COVID-19 pandemic between medical and non-medical students (p > 0.05). There was a significant difference in terms of anxiety (p = 0.02) and mindfulness (p = 0.03) between medical and non-medical students during the prevalence of COVID-19. Discussion and conclusion The findings of the present study indicated that medical students exhibited lower levels of anxiety and higher levels of mindfulness. Therefore, interventions aimed at reducing anxiety and increasing mindfulness among non-medical students are necessary. It is recommended that preventive approaches and psychological interventions to improve students’ quality of life become an integral part of crisis response during the COVID-19 pandemic. Additionally, reducing anxiety and enhancing mindfulness can improve the quality of education and professional performance of medical students, while also contributing to their mental well-being and effective clinical communication.

Abstract Drug-resistant epilepsy with frequent seizures are considered to undergo surgery to become seizure-free, but seizure-free rates have not dramatically improved, partly due to imprecise intervention locations. To address this clinical need, we construct effective connectivity to reveal epilepsy brain dynamics. Based on the propagation path captured by the high order effective connectivity, calculate the control centrality evaluation scheme of the excised area. We used three datasets: simulation dataset, clinical dataset, and public dataset. The epileptogenic propagation network was quantified by calculating high-order effective connection to obtain accurate propagation path, based on this, combined with the outdegree index for virtual resection. By removing electrodes and recalculating control centrality, we quantify each electrode or region’s control centrality to evaluate the virtual resection scheme. Three datasets obtained consistent results. We track the accurate propagation path and find the obvious inflection points occurring during the excision process. The minimum intervention targets were obtained by comparing different schemes without recurrence. The clinical data with multiple seizures found that after resection, the brain reaches a stable state and is less likely to continue spreading. By quantitative analysis of control centrality to evaluate the possible excision scheme, finally we obtain the best intervention area for epilepsy, which assist in developing surgical plans.

Abstract Background Pseudouridine (Ψ), a C5-glycoside isomer of uridine, stands as one of the most prevalent RNA modifications in all RNA types. Distinguishing from the C-N bond linking uridine to ribose, the link between Ψ and ribose is a C-C bond, endowing Ψ modified RNA distinct properties and functions in various biological processes. The conversion of uridine to Ψ is governed by pseudouridine synthases (PUSs). RNA pseudouridylation is implicated in cancer biology and therapeutics. Objectives In this review, we will summarize the methods for detecting Ψ, the process of Ψ generation, the impact of Ψ modification on RNA metabolism and gene expression, the roles of dysregulated Ψ and pseudouridine synthases in cancers, and the underlying mechanism. Methods We conducted a comprehensive search of PubMed from its inception through February 2024. The search terms included “pseudouridine”; “pseudouridine synthase”; “PUS”; “dyskerin”; “cancer”; “tumor”; “carcinoma”; “malignancy”; “tumorigenesis”; “biomarker”; “prognosis” and “therapy”. We included studies published in peer-reviewed journals that focused on Ψ detection, specific mechanisms involving Ψ and PUSs, and prognosis in cancer patients with high Ψ expression. We excluded studies lacking sufficient methodological details or appropriate controls. Results Ψ has been recognized as a significant biomarker in cancer diagnosis and prognosis. Abnormal Ψ modifications mediated by various PUSs result in dysregulated RNA metabolism and impaired RNA function, promoting the development of various cancers. Overexpression of PUSs is common in cancer cells and predicts poor prognosis. PUSs inhibition arrests cell proliferation and enhances apoptosis in cancer cells, suggesting PUS-targeting cancer therapy may be a potential strategy in cancer treatment. Discussion High Ψ levels in serum, urine, and saliva may suggest cancer, but do not specify the type, requiring additional lab markers and imaging for accurate diagnosis. Standardized detection methods are also crucial for reliable results. PUSs are linked to cancer, but more researches are needed to understand their mechanisms in different cancers. Anticancer treatments targeting PUSs are still under developed.

Abstract The majority of viruses classified as pandemic threats are enveloped viruses which enter the cell through receptor-mediated endocytosis and take advantage of endosomal acidification to activate their fusion machinery. Here we report that the endosomal fusion of low pH-requiring viruses is highly dependent on TRPM7, a widely expressed TRP channel that is located on the plasma membrane and in intracellular vesicles. Using several viral infection systems expressing the envelope glycoproteins of various viruses, we find that loss of TRPM7 protects cells from infection by Lassa, LCMV, Ebola, Influenza, MERS, SARS-CoV-1, and SARS-CoV-2. TRPM7 ion channel activity is intrinsically necessary to acidify virus-laden endosomes but is expendable for several other endosomal acidification pathways. We propose a model wherein TRPM7 ion channel activity provides a countercurrent of cations from endosomal lumen to cytosol necessary to sustain the pumping of protons into these virus-laden endosomes. This study demonstrates the possibility of developing a broad-spectrum, TRPM7-targeting antiviral drug to subvert the endosomal fusion of low pH-dependent enveloped viruses.

Abstract Background The association between uric acid and pulmonary embolism(PE) remains controversial, and there has been limited investigation into how uric acid influences pulmonary embolism across different age groups. Our study aimed to elucidate the relationship between uric acid levels and pulmonary embolism, considering variations across age groups. Methods A total of 368 patients who underwent computed tomography pulmonary angiography from July 2018 to May 2022 were included in the analysis. Subsequently, the cohort was stratified by age, with separate univariate and multivariate logistic regression analyses conducted for the elderly (aged ≥ 60 years) and non-elderly (aged

Abstract Background Secretory carrier membrane proteins (SCAMPs) form a family of integral membrane proteins and play a crucial role in mediating exocytosis in both animals and plants. While SCAMP genes have been studied in several plant species, their functions in cotton, particularly in response to abiotic stress, have not yet been reported. Results In this study, a total of 53 SCAMP genes were identified in G. arboreum, G. raimondii, G. hirsutum, and G. barbadense. These genes were classified into five groups based on a phylogenetic analysis with SCAMPs from Arabidopsis thaliana. The main factor driving the expansion of the SCAMP gene family in G. hirsutum is tandem and segmental duplication events. Using MEME, in addition to the conserved SCAMP domain, we identified 3–13 other domains in each GhSCAMP. The cis-element analysis suggested that GhSCAMPs were widely involved in cotton growth and development, and responses to abiotic stresses. RNA sequencing (RNA-Seq) and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) results showed that most GhSCAMPs were expressed highly in many tissues and had differential expression responses to drought, cold, and heat stresses. Knock-down of GhSCAMP2 and GhSCAMP4 by virus-induced gene silencing (VIGS) lead to a salt-sensitive phenotype and had a lower content of CAT, POD, and SOD. Conclusions This study identified SCAMP genes in four cotton species, enhancing our understanding of the potential biological functions of SCAMPs. Additionally, we demonstrated that GhSCAMP2 and GhSCAMP4 positively regulate cotton tolerance to salt stress.

Lithium element enrichment is widely observed in the coal-bearing series of the Late Permian Heshan Formation in Shanglin, Guangxi, which has potential economic value and research significance. In this study, a multi-proxy study was conducted for evaluating major elements, trace elements, zircon U–Pb dating, and zircon trace elements from the lithium mineralization layers to characterize the spatial distribution, elemental geochemical characteristics, and provenance of lithium mineralization layers of the Late Permian Heshan Formation coal-bearing series in the Wanfu mining area, Shanglin, Guangxi. Thirty four samples were selected from lithium mineralization layers in order to determine major elements and trace elements. Moreover, the zircon U–Pb dating and zircon trace elements of one sample was investigated. The study reveals that four sets of lithium mineralization layers, namely I, II, III, and IV, are developed from bottom to top in the Heshan Formation coal-bearing series from the Wanfu mining area, Shanglin, Guangxi. According to the order of lithium content from high to low, it is divided into lithium mineralization layers I, III, II and IV. Compared with average values for world claystone, the lithium mineralization layer I are highly enriched in Li, the II and III is enriched in Li, and the IV is slightly enriched in Li. The analysis of Al2O3–TiO2, La/Sc-Th/Co and V–Ni–Th×10 diagrams indicate that most of the samples of lithium mineralization layer I, III and IV fall close to the acidic volcanic rocks field, while a few samples of lithium mineralization layer I fall near the intermediate volcanic rocks field. Therefore, it is inferred that the lithium mineralization layers of the Heshan Formation in Shanglin, Guangxi are dominated by sediments derived from the acidic and intermediate volcanic rocks. The Zircon U–Pb dating, Th/Nb-Hf/Th and Th/U–Nb/Hf tectonic setting discrimination diagrams of zircon trace elements, rare earth elements analysis, and Al2O3–TiO2, La/Sc−Th/Co, V–Ni–Th×10 and Nb/Y–Zr/TiO2 source rock discrimination diagrams indicate that the lithium mineralization layers of the Heshan Formation coal-bearing series in the Wanfu mining area mainly come from acidic and intermediate volcanic rocks related to the Emeishan Igneous Province and the Paleo-Tethys Permian magmatic arc.

Abstract Background Gene methylation and the immune-related tumor microenvironment (TME) are highly correlated in tumor progression and therapeutic efficacy. Although both of them can be used to predict the clinical outcomes of colorectal cancer (CRC) patients, their predictive value is still unsatisfactory. Whether a combination risk model comprising these two prediction parameters performs better predictive effectiveness than independent factor is still unclear. Methylated Septin9 (mSEPT9) is an early diagnosis biomarker of CRC, in this study, we aimed to investigate mSEPT9-related biomarkers of immunosuppressive TME and identify the value of the combination risk model in predicting the clinical outcomes of CRC. Methods Immunofluorescence staining was performed to clarify the correlation between intratumoral IL-10+ Treg infiltration and mSEPT9 in peripheral blood. Survival time, response to 5-fluorouracil (5-FU)-based chemotherapy and PD-1 blockade, and the probability of recurrence or metastasis were analyzed in study (197 CRC samples) and validation (195 CRC samples) sets to evaluate the efficacy of combination risk model. Potential mechanisms were explored by mRNA sequencing. Results Hypermethylated SEPT9 in the peripheral blood of patients with CRC (stage I-III, and stage IV with resectable M1) before radical resection was positively correlated with high intratumoral IL-10+ Treg infiltration. The high-risk model revealed poor overall survival and progression-free survival, inferior therapeutic response to 5-FU-based chemotherapy and PD-1 blockade, and high probability of recurrence or metastasis. The underlying mechanisms may be associated with the increase in mSEPT9 and mediation of IL-10 via methionine metabolic reprogramming-induced infiltration of IL-10+ Tregs in the TME, which promotes tumor progression and resistance to 5-FU-based chemotherapy and PD-1 blockade. Conclusions The combination risk model of peripheral mSETP9 and intratumoral IL-10+ Treg infiltration in CRC can effectively predict prognosis, responsiveness to 5-FU-based chemotherapy and PD-1 blockade, and the probability of recurrence or metastasis. Therefore, this model can be used for precision treatment of CRC.

Abstract Autophagy is a cellular homeostatic mechanism characterized by cyclic degradation. It plays an essential role in maintaining cellular quality and survival by eliminating dysfunctional cellular components. This process is pivotal in various pathophysiological processes. Benign prostatic hyperplasia (BPH) is a common urological disorder in middle-aged and elderly men. It frequently presents as lower urinary tract symptoms due to an increase in epithelial and stromal cells surrounding the prostatic urethra. The precise pathogenesis of BPH is complex. In recent years, research on autophagy in BPH has gained significant momentum, with accumulating evidence indicating its crucial role in the onset and progression of the disease. This review aims to outline the various roles of autophagy in BPH and elucidate potential therapeutic strategies targeting autophagy for managing BPH.

The interfacial interaction between HMX molecules and coating materials is the key to the safety performance of explosives and has received extensive attention. However, screening suitable coating agents to enhance the interfacial effect to obtain high-energy and low-sensitivity explosives has long been a major challenge. In this work, HMX-PEI/rGO/g-C3N4 (HPrGC) composites were innovatively prepared by a multi-level coating strategy of two-dimensional graphite rGO and g-C3N4. The g-C3N4 used for desensitization has a rich π-conjugated system and shows outstanding ability in reducing friction sensitivity. The hierarchical structure of HPrGC formed by electrostatic self-assembly and π-π stacking can effectively dissipate energy accumulation under heat and mechanical stimulation through structural evolution, thus exhibiting a prominent synergistic desensitization effect on HMX. The results show that rGO/g-C3N4 coating has no effect on the crystal structure and chemical structure of HMX. More importantly, the perfect combination of g-C3N4 and rGO endows HPrGC with enhanced thermal stability and ideal mechanical sensitivity (IS: 21 J, FS: 216 N). Obviously, the new fabrication of HPrGC enriches the variety of desensitizer materials and helps to deepen the understanding of the interaction between explosives and coatings.

Abstract Background Postoperative hypoxemia and pulmonary complications remain a frequent event after on-pump cardiac surgery and mostly characterized by pulmonary atelectasis. Surfactant dysfunction or hyposecretion happens prior to atelectasis formation, and sigh represents the strongest stimulus for surfactant secretion. The role of sigh breaths added to conventional lung protective ventilation in reducing postoperative hypoxemia and pulmonary complications among cardiac surgery is unknown. Methods The perioperative sigh ventilation in cardiac surgery (E-SIGHT) trial is a single-center, two-arm, randomized controlled trial. In total, 192 patients scheduled for elective cardiac surgery with cardiopulmonary bypass (CPB) and aortic cross-clamp will be randomized into one of the two treatment arms. In the experimental group, besides conventional lung protective ventilation, sigh volumes producing plateau pressures of 35 cmH2O (or 40 cmH2O for patients with body mass index > 35 kg/m2) delivered once every 6 min from intubation to extubation. In the control group, conventional lung protective ventilation without preplanned recruitment maneuvers is used. Lung protective ventilation (LPV) consists of low tidal volumes (6–8 mL/kg of predicted body weight) and positive end-expiratory pressure (PEEP) setting according to low PEEP/FiO2 table for acute respiratory distress syndrome (ARDS). The primary endpoint is time-weighted average SpO2/FiO2 ratio during the initial post-extubation hour. Main secondary endpoint is the severity of postoperative pulmonary complications (PPCs) computed by postoperative day 7. Discussion The E-SIGHT trial will be the first randomized controlled trial to evaluate the impact of perioperative sigh ventilation on the postoperative outcomes after on-pump cardiac surgery. The trial will introduce and assess a novel perioperative ventilation approach to mitigate the risk of postoperative hypoxemia and PPCs in patients undergoing cardiac surgery. Also provide the basis for a future larger trial aiming at verifying the impact of sigh ventilation on postoperative pulmonary complications. Trial registration ClinicalTrials.gov NCT06248320. Registered on January 30, 2024. Last updated February 26, 2024.

This study aims to evaluate and analyze the differences in sleep quality among epilepsy patients of different genders to provide a reference for determining the influencing factors of sleep quality based on logistic multiple regression analysis. A retrospective analysis was conducted on the clinical data of 220 epilepsy patients admitted to our hospital from May 2022 to November 2023. The patients were divided into low-quality and high-quality sleep groups. Data were obtained using a general information questionnaire survey and the Pittsburgh Sleep Quality Index (PSQI). The average PSQI score for male patients was 12.89 ± 3.13, while for female patients, it was 9.26 ± 2.60. The PSQI score for male patients was significantly higher than that for female patients (p < 0.05). Moreover, the influencing factors for sleep quality in epilepsy patients included gender, annual income, medical insurance, frequency of epilepsy onset and medication use. Male epilepsy patients suffer from poorer sleep quality compared to female patients. Factors such as gender, annual income, medical insurance, seizure frequency and medication use significantly affect sleep quality in epilepsy patients. It could be recommended that patients adhere to medical advice for managing epilepsy and that healthcare authorities enhance awareness and policy support to reduce seizures and improve patients’ quality of life.

Abstract Fusarium oxysporum is an asexual filamentous fungus that causes vascular wilt in hundreds of crop plants and poses a threat to public health through Fusariosis. F. oxysporum f. sp. conglutinans strain Fo5176, originally isolated from Brassica oleracea, is pathogenic to Arabidopsis, making it a model pathosystem for dissecting the molecular mechanisms underlying host-pathogen interactions. Assembling the F. oxysporum genome is notoriously challenging due to the presence of repeat-rich accessory chromosomes. Here, we report a gap-free genome assembly of Fo5176 using PacBio HiFi and Hi-C data. The 69.56 Mb assembly contained 18 complete chromosomes, including all centromeres and most telomeres (20/36), representing the first gap-free genome sequence of a pathogenic F. oxysporum strain. In total, 21,460 protein-coding genes were annotated, a 26.3% increase compared to the most recent assembly. This high-quality reference genome for F. oxysporum f. sp. conglutinans Fo5176 provides a valuable resource for further research into fungal pathobiology and evolution.

Abstract Telomerase reverse transcriptase (Tert) has been found to have a protective effect on telomeric DNA, but whether it could improve the repair of reactive oxygen species (ROS)-induced DNA damage and promote myocardial regenerative repair after myocardial infarction (MI) by protecting telomeric DNA is unclear. The immunofluorescence staining with TEL-CY3 and the TeloTAGGG Telomerase PCR ELISA kit were used to show the telomere length and telomerase activity. The heart-specific Tert-deletion homozygotes were generated by using commercial Cre tool mice and flox heterozygous mice for mating. We measured the telomere length and telomerase activity of mouse cardiomyocytes (CMs) at different days of age, and the results showed that they were negatively correlated with age. Overexpressed Tert could enhance telomerase activity and lengthen telomeres, thereby repairing the DNA damage induced by ROS and promoting CM proliferation in vitro. The in vivo results indicated that enhanced Tert could significantly improve cardiac function and prognosis by alleviating CM DNA damage and promoting angiogenesis post-MI. In terms of mechanism, DNA pulldown assay was used to identify that nuclear ribonucleoprotein A2B1 (hnRNPA2B1) could be an upstream regulator of Tert in CMs. Overexpressed Tert could activate the NF-κB signaling pathway in CMs and bind to the VEGF promoter in the endothelium to increase the VEGF level. Further immunoblotting showed that Tert protected DNA from ROS-induced damage by inhibiting ATM phosphorylation and blocking the Chk1/p53/p21 pathway activation. HnRNPA2B1-activated Tert could repair the ROS-induced telomeric DNA damage to induce the cell cycle re-entry in CMs and enhance the interaction between CMs and endothelium, thus achieving cardiac regenerative repair after MI.

Abstract Background Postoperative respiratory adverse events are the most common perioperative complications in pediatric anesthesia, particularly prevalent in children undergoing tonsillectomy and adenoidectomy, with an incidence rate as high as 50%. The choice of anesthetic induction regimen directly influences the incidence of respiratory adverse events during the induction period. However, this effect seems to have minimal impact on postoperative outcomes. The occurrence rate of postoperative respiratory adverse events is likely more closely associated with the anesthetic maintenance phase, yet this relationship remains uncertain at present. Methods The objective of this study was to assess the impact of different anesthetic maintenance regimens on postoperative respiratory adverse events in pediatric patients undergoing tonsillectomy and adenoidectomy. The AmPRAEC study is a multicenter, randomized, double-blind controlled trial. A total of 717 pediatric patients were recruited from 12 medical centers and randomly assigned to three groups: group A (intravenous maintenance group, receiving propofol infusion); group B (intravenous-inhalational combination group, maintained with 1% sevoflurane combined with propofol); and group C (inhalational maintenance group, maintained with 2–3% sevoflurane inhalation). The primary outcome measure was the incidence rate of postoperative respiratory adverse events. Discussion This clinical trial aims to elucidate the impact of various anesthetic maintenance regimens on postoperative respiratory adverse events in pediatric patients. The outcomes of this study are anticipated to facilitate anesthesiologists in devising more comprehensive perioperative management strategies, enhancing comfort, and improving the clinical outcomes for this patient population. Trial registration Chinese Clinical Trial Registry ( http://www.chictr.org.cn ) ChiCTR2300074803. Registered on August 16, 2023.

Abstract Hydrogen production by seawater electrolysis is significantly hindered by high energy costs and undesirable detrimental chlorine chemistry in seawater. In this work, energy-saving hydrogen production is reported by chlorine-free seawater splitting coupling tip-enhanced electric field promoted electrocatalytic sulfion oxidation reaction. We present a bifunctional needle-like Co3S4 catalyst grown on nickel foam with a unique tip structure that enhances the kinetic rate by improving the current density in the tip region. The assembled hybrid seawater electrolyzer combines thermodynamically favorable sulfion oxidation and cathodic seawater reduction can enable sustainable hydrogen production at a current density of 100 mA cm−2 for up to 504 h. The hybrid seawater electrolyzer has the potential for scale-up industrial implementation of hydrogen production by seawater electrolysis, which is promising to achieve high economic efficiency and environmental remediation.

Abstract B cells and the antibodies they produce are critical in host defense against pathogens and contribute to various immune-mediated diseases. B cells responding to activating signals in vitro release extracellular vesicles (EV) that carry surface antibodies, yet B cell production of EVs that express antibodies and their function in vivo is incompletely understood. Using transgenic mice expressing the Cre recombinase in B cells switching to IgG1 to induce expression of fusion proteins between emerald green fluorescent protein (emGFP) and the EV tetraspanin CD63 as a model, we identify emGFP expression in B cells responding to foreign antigen in vivo and characterize the emGFP+ EVs they release. Our data suggests that emGFP+ germinal center B cells undergoing immunoglobulin class switching to express IgG and their progeny memory B cells and plasma cells, also emGFP+, are sources of circulating antigen-specific IgG+ EVs. Furthermore, using a mouse model of influenza virus infection, we find that IgG+ EVs specific for the influenza hemagglutinin antigen protect against virus infection. In addition, crossing the B cell Cre driver EV reporter mice onto the Nba2 lupus-prone strain revealed increased circulating emGFP+ EVs that expressed surface IgG against nuclear antigens linked to autoimmunity. These data identify EVs loaded with antibodies as a novel route for antibody secretion in B cells that contribute to adaptive immune responses, with important implications for different functions of IgG+ EVs in infection and autoimmunity.

Abstract Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a promising therapeutic target to reduce lipids. In 2020, we reported a chimeric camelid-human heavy chain antibody VHH-B11-Fc targeting PCSK9. Recently, it was verified that VHH-B11 binds one linear epitope in the PCSK9 hinge region. To enhance its druggability, we have developed a novel biparatopic B11-H2-Fc Ab herein. Thereinto, surface plasmon resonance (SPR) confirmed the epitope differences in binding-PCSK9 among VHH-B11, VHH-H2 and the approved Repatha. Additionally, SPR revealed the B11-H2-Fc exhibits an avidity of approximately 0.036 nM for PCSK9, representing a considerable increase compared to VHH-B11-Fc (~ 0.69 nM). Moreover, we found the Repatha and B11-H2-Fc exhibited > 95% PCSK9 inhibition efficiency compared to approximately 48% for the VHH-Fc at 7.4 nM (P 0.05). These findings provide the first evidence of the efficacy of a novel Ab targeting PCSK9 in the field of lipid-lowering drugs.

BackgroundThe interaction between the human breast milk microbiota and human milk oligosaccharides (HMOs) plays a crucial role in the healthy growth and development of infants. We aimed to clarify the link between the breast milk microbiota and HMOs at two stages of lactation.MethodsThe microbiota and HMOs of 20 colostrum samples (C group, 1–5 days postpartum) and 20 mature milk samples (S group, 42 days postpartum) collected from postpartum mothers were analyzed using 16S rRNA gene high-throughput sequencing and high-performance liquid chromatography–tandem mass spectrometry.ResultThe total average HMO content was significantly higher in the C group than in the S group (6.76 ± 1.40 g/L vs. 10.27 ± 2.00 g/L, p

Huajiao water (HW) has a wide range of applications in the new food service industry. However, few process and flavor studies have been conducted on HW. The aim of this study was to investigate the effect of boiling process on HW flavor as well as the mechanisms by which important aroma compounds affect the flavor. The results showed that HW-20 min had better flavor quality and typical flavor of Huajiao. Boiling time mainly affected the content of terpenoid, which subsequently affected the overall flavor of HW. Compared to dried Huajiao (DH), HW had significantly lower volatile compounds. Limonene and linalool were abundant volatile compounds in DH and HW. Finally, the potential degradation pathways of limonene and linalool were summarized based on model experiments and isotopic tracer techniques, respectively. This study provided a feasible solution for the investigation of the transformation pathway and the flavor regulation of HW in industry.

Objectives: To assess the diagnostic value of tuberculosis-secreted Ag85B, ESAT-6 and CFP10 in pulmonary tuberculosis. Method: Immunohistochemical (IHC) and acid-fast staining were performed, the detection efficiency of the two methods were analysed with chi-square test. Results: Acid-fast staining demonstrated a sensitivity of (18/69, 26.09%) and a specificity of 100%. IHC staining for Ag85B, ESAT-6 and CFP10 was positive in all 18 cases with positive acid-fast staining and additionally positive in 25,36 and 30 cases, respectively, that were acid-fast-negative. The sensitivities of IHC staining for Ag85B, ESAT-6 and CFP10 were 62.32%, 78.26% and69.57%, respectively, while their specificities were 86.57%, 85.07% and 91.04%, respectively. Joint antigen analysis revealed that simultaneous positivity for two or three of Ag85B, ESAT-6 and CFP10 increased specificity (95.52% to 100%) but decreased sensitivity (49.28% to 62.31%). The presence of any one of the three antigens elevated sensitivity (81.16% to 88.41%) but lowered specificity (68.66% to 77.61%). Specificity reached 100% for concurrent positivity of all three antigens, while a sensitivity of 88.41% was observed for positivity of any one antigen. Conclusions: Ag85B, ESAT-6, and CFP10 exhibits greater sensitivity in pulmonary tuberculosis and combined antigen testing enhances the diagnostic accuracy.

BackgroundVitamin D, an essential fat-soluble micronutrient, exerts diverse physiological effects including the regulation of calcium ion homeostasis, modulation of immune response, and enhancement of resistance against infectious pathogens. Empirical investigations have elucidated an association between inadequate levels of vitamin D and adverse clinical outcomes in critically ill cohorts, with a noteworthy prevalence of vitamin D deficiency observed among patients afflicted with acute kidney injury (AKI). In the context of this retrospective inquiry, our aim was to assess the potential correlation between vitamin D supplementation administered during admission to the intensive care unit (ICU) and the improvement of outcomes specifically in cases of severe AKI.MethodsThis study utilized data from the Medical Information Mart for Intensive Care IV (MIMIC-IV), a repository of ICU patient records from Beth Israel Deaconess Medical Center (BIDMC) in the United States. We focused on patients diagnosed with epsis-associated acute kidney injury (SA-AKI), dividing them into those who received vitamin D supplementation during their ICU admission and those who did not. Our primary analysis evaluated in-hospital mortality using various statistical methods, such as Kaplan–Meier survival curves, Cox proportional hazards regression models, and subgroup analyses. To enhance the robustness of our findings, we used propensity score matching (PSM) to reduce potential biases. Secondary outcomes included 28-day, 90-day mortality rates and norepinephrine-free days at 28 days.ResultsIn this investigation, a cohort of 11,896 individuals diagnosed with SA-AKI was studied. Among them, 2,724 patients received vitamin D supplementation (the vitamin D group) while 9,172 did not (the no-vitamin D group). Kaplan–Meier survival analysis indicated a significant difference in survival probabilities between the two cohorts. Upon adjusting for potential confounders using Cox regression modeling, a notably decreased risk of hospitalization and ICU mortality was observed in the vitamin D group compared to the no-vitamin D group, with an adjusted risk ratio for in-hospital mortality of 0.56 (95% CI: 0.5–0.63). These findings were consistent following PSM and subsequent adjustments for propensity score, pairwise algorithm (PA), and overlapping weights (OW) analyses, yielding hazard ratios ranging from 0.53 to 0.59, all with p-values

Background The purpose of this study was to clinically evaluate the safety and effectiveness of the electromagnetic navigation (EMN) system designed for computed tomography (CT)-guided synchronous percutaneous lung biopsy and microwave ablation (MWA) of pulmonary nodules.Methods This prospective, single-center, single-arm clinical cohort study was conducted in Beijing Hospital from March 2023 to May 2023. Patients who underwent CT-guided synchronous percutaneous lung biopsy and MWA via the EMN system were prospectively enrolled in our study. All the interventional procedures were performed by the same interventional radiologist. The technical success rate, the technical efficacy rates of biopsy and MWA were assessed as the primary outcomes. Preoperative, intraoperative, and postoperative variables were also recorded and analyzed for each patient.Results A total of 48 patients were enrolled in the study. The technical success rate was 100%. The technical efficacy rate of biopsy was 95.8% (46/48), and the technical efficacy rate of WMA was 100% (48/48) with no recurrence during follow-up. The total and subpleural needle trajectory length and distance error were 8.3 ± 2.6 cm, 3.6 ± 1.6 cm, and 1.84 ± 1.08 mm, respectively. The median numbers of needle adjustments and CT acquisitions were 1 (range 1–3) and 3 (range 3–5), respectively. The time to reach the target and procedure time were 4.4 ± 1.7 and 19.7 ± 5.2 min, respectively. The dose length product was 748.8 ± 221.8 mGy*cm. The median postoperative hospital stay was 1 (range 1–7) days. No major complications (grade ≥3) occurred and only seven minor complications (14.6%) occurred, including six cases of pneumothorax and one case of hemoptysis. The radiologists achieved high satisfaction scores after surgery.Conclusion The EMN system is feasible, safe and effective for CT-guided synchronous percutaneous lung biopsy and MWA of pulmonary nodules.

Rabies is a lethal zoonotic disease that threatens human health. As the only viral surface protein, the rabies virus (RABV) glycoprotein (G) induces main neutralizing antibody (Nab) responses; however, Nab titre is closely correlated with the conformation of G. Virus-like particles (VLP) formed by the co-expression of RABV G and matrix protein (M) improve retention and antigen presentation, inducing broad, durable immune responses. RABV nucleoprotein (N) can elicit humoral and cellular immune responses. Hence, we developed a series of nucleoside-modified RABV mRNA vaccines encoding wild-type G, soluble trimeric RABV G formed by an artificial trimer motif (tG-MTQ), membrane-anchored prefusion-stabilized G (preG). Furthermore, we also developed RABV VLP mRNA vaccine co-expressing preG and M to generate VLPs, and VLP/N mRNA vaccine co-expressing preG, M, and N. The RABV mRNA vaccines induced higher humoral and cellular responses than inactivated rabies vaccine, and completely protected mice against intracerebral challenge. Additionally, the IgG and Nab titres in RABV preG, VLP and VLP/N mRNA groups were significantly higher than those in G and tG-MTQ groups. A single administration of VLP or VLP/N mRNA vaccines elicited protective Nab responses, the Nab titres were significantly higher than that in inactivated rabies vaccine group at day 7. Moreover, RABV VLP and VLP/N mRNA vaccines showed superior capacities to elicit potent germinal centre, long-lived plasma cell and memory B cell responses, which linked to high titre and durable Nab responses. In summary, our data demonstrated that RABV VLP and VLP/N mRNA vaccines could be promising candidates against rabies.

Background: Psoriatic patients tend to develop metabolic syndrome (MS). MS accelerates psoriasis, but the exact molecular mechanisms are poorly understood.Objectives: We aim to investigate the impact of leptin on keratinocyte insulin sensitivity and explore its underlying molecular mechanism, which might play a role in the pathogenesis of this disease.Methods: ELISA and immunohistochemistry were applied respectively to detect the level of leptin in serum and in lesion of psoriatic patients with and without MS. The HaCaT cell line was cultured and western-blot assay was performed to assess the change of insulin sensibility. q-PCR and western-blot assay were applied to detect the SOCS3 expressions. Knockdown of SOCS3 were generated in HaCaT cell line by siRNA. Leptin and insulin were treated for 6 days and K10 expression was evaluated by western-blot assay.Results: Patients with MS had higher level of leptin in serum and lesions than their counterparts without MS. Serum levels of leptin was negatively correlated to PASI decline index in psoriatic patients. Long-term treatment of leptin induced insulin resistance in HaCaT cell line, as indicated by elevated expression of p-IRS-1 (ser636) and lower p-PKB (ser473). Leptin treatment up-regulated the mRNA and protein expression of SOCS3. Knockdown of SOCS3 blocked the effect of leptin-induced insulin resistance. Leptin treatment attenuated insulin-elicited K10 expression.Conclusions: Leptin induces insulin resistance by upregulating SOCS3 and give rise to differentiation disorder of keratinocyte. Insulin resistance may serve as a target for anti-psoriatic therapies.

Achieving the dual goals of improving water quality and reducing carbon emissions requires a systematic study of the combined effects of economic and environmental policies on industrial systems. A CGE-IWCR model is developed to examine the long-term evolution of industrial economic and environmental responses in the Yangtze River Economic Belt (YREB) under varying levels of carbon and water pollution taxes. The CGE-IWCE model offers several advantages: i) under the dual tax (carbon and water pollution tax) interventions, it can effectively forecast industrial CO2 and water pollution emissions driven by both macro and local factors from 2025 to 2060; ii) it quantitatively captures the interactions between various policy interventions, thereby providing guidance for comprehensive regional policy formulation. It is discovered that in the double-tax scenario, various combinations of carbon and water pollution taxes significantly impact direct carbon emissions and direct water pollution emissions, and from local consumption, imports, and exports in industrial sectors. Among them, the dual pressure of high carbon and water pollution taxes, which significantly raise production costs. In addition, increasing the carbon tax from 10 ¥/tonne to 50 ¥/tonne, the water pollution equivalent (WPE) reduction rate rises from 20.79% to 52.67% with the increase in the carbon tax from 2050 to 2060, when the water pollution tax is low. Between 2025 and 2060, the carbon tax plays a significant role in influencing the total industrial output change rate in YREB. from 2025 to 2060, the water pollution tax will play a more significant role in CO2 reduction in YREB’s industrial sector. The results will offer decision-making support for water pollution reduction and carbon mitigation in the YREB’s industrial sector, quantitatively identify the interactions between the dual taxes, and provide new insights for analyzing the impacts of pollution reduction and carbon mitigation policies.

ABSTRACT Background The increasing incidence of endometrial cancer (EC) has highlighted the need for improved early detection methods. This study aimed to develop and validate a novel DNA methylation classifier, EMPap, for EC detection using cervical scrapings. Methods EMPap incorporated the methylation status of BHLHE22 and CDO1, along with age and body mass index (BMI), into a logistic regression model to calculate the endometrial cancer methylation (EM) score for identifying EC in cervical scrapings. We enrolled 1297 patients with highly suspected EC, including 196 confirmed EC cases, and assessed the EMPap performance in detecting EC. Results EMPap demonstrated robust diagnostic accuracy, with an area under the curve of 0.93, sensitivity of 90.3%, and specificity of 89.3%. It effectively detected EC across various disease stages, grades, and histological subtypes, and consistently performed well across patient demographics and symptoms. EMPap correctly identified 87.5% of the type II ECs and 53.8% of premalignant lesions. Notably, compared with transvaginal ultrasonography (TVS) in patients with postmenopausal bleeding, EMPap exhibited superior sensitivity (100% vs. 82.0%) and specificity (85.2% vs. 38.5%). In asymptomatic postmenopausal women, EMPap maintained high sensitivity (89.5%) and negative predictive value (NPV) (98.3%). Conclusions This study demonstrated the potential of EMPap as an effective tool for EC detection. Despite the limited sample size, EMPap showed promise for identifying type II EC and detecting over 50% of premalignant lesions. As a DNA methylation classifier, EMPap can reduce unnecessary uterine interventions and improve diagnosis and outcomes.

In recent years, with rapid societal advancement and profound transformations in knowledge production, doctoral students are increasingly facing significant time pressures. These pressures not only stem from an escalation in research tasks but also from urgent demands for innovative outputs. Grounded in Affective Events Theory, this study explores the dual impact of time pressure on the innovative behaviors of doctoral students in China. It specifically examines how challenge and hindrance time pressures affect doctoral students’ innovative behavior through the mediating role of research self-efficacy and the moderating role of supervisor support. This research employed SPSS 26.0 and Mplus 8.3 for statistical analysis, analyzing multi-time point data collected from 452 Chinese doctoral students between May and August 2023. The results reveal that challenge time pressure significantly positively impacts doctoral students’ innovative behavior, while hindrance time pressure has a significant negative impact. Furthermore, research self-efficacy partially mediates the relationship between both challenge and hindrance time pressures and innovative behavior. In this process, the moderating role of supervisor support is significant, enhancing the positive effects of challenge time pressure and mitigating the negative impacts of hindrance time pressure, highlighting the importance of supervisor support in optimizing the impact of time pressure and promoting doctoral students’ innovative behavior. These findings not only enrich the theoretical framework in the field of time pressure research but also provide practical guidance for universities and supervisors on how to support doctoral students in effectively managing time pressure and fostering their innovation.

Micro light-emitting diode (Micro-LED) is a highly promising technology in the field of new displays, with the mass transfer process involved in its manufacturing process widely regarded as a major barrier to their further development. This study adopts laser transfer technology as the primary solution, using ablation-type transfer release materials that improve chip utilization rates over blister-type release materials. In addition, measurement of the laser transfer parameters, inspection, and laser repair technology are combined to achieve a transfer yield of about 100% to the carrier substrate and a cumulative transfer displacement of less than 1 µm in the Micro-LED inverted chip array. Furthermore, cleaning agents were used to remove adhesive residue from the receiving substrate after transfer, improving the bonding yield between the chip and the thin film transistor driver circuit board. This study provides a feasible solution for Micro-LED mass transfer, which could boost its further development toward commercial application.

Abstract Solution‐processed fluorescent organic light‐emitting diodes (OLEDs) are believed to be favorable for low‐cost, large‐area, and flexible displays but still suffer from the limited external quantum efficiency (EQE) below 5%. Herein, we demonstrate the EQE breakthrough by introducing a donor–acceptor type thermally activated delayed fluorescence (TADF) polymer as the sensitizer for the typical green‐emitting fluorescent dopants. Benefitting from their matched energy alignment, the unwanted trap‐assisted recombination directly on fluorescent dopant is prevented to avoid the additional loss of triplet excitons. Indeed, triplet excitons are mainly formed on the polymeric TADF sensitizer via a Langevin recombination and then spin‐flipped to singlet excitons due to the good upconversion capability. Followed by an efficient Förster energy transfer, both singlet and triplet excitons can be harvested by fluorescent dopants, leading to a promising solution‐processed green hyperfluorescence with a record‐high EQE of 21.2% (72.2 cd/A, 59.7 lm/W) and Commission Internationale de L'Eclairage coordinates of (0.32, 0.59). The results clearly highlight the great potential of solution‐processed fluorescent OLEDs based on TADF polymers as the sensitizer.

ABSTRACT Aims and objective To investigate the impact of acupuncture on post‐stroke cognitive impairment (PSCI). Background PSCI is a major barrier to stroke patients’ rehabilitation, and acupuncture is one of the treatments. However, the benefit of acupuncture on PSCI is unclear. Design A meta‐analysis and systematic review of randomized controlled trials (RCTs). Methods Up to February 1, 2024, databases in PubMed, MEDLINE, Scopus, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, VIP, and Wanfang Data were searched. The risk of bias was investigated using the Cochrane Handbook for systematic reviews of treatments. Random‐effect and fix‐effect models were used to report the effects. Results There were 29 randomized clinical trials with 2477 participants included. The findings demonstrated that the Mini‐Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) scores were higher in the acupuncture group than medicine group (mean difference [MD] = 1.74, 95% confidence interval (CI) CI [1.26, 2.23], I2 = 59%, p

Objective: To evaluate the clinical efficacy of internal limiting membrane (ILM) peeling combined with perimacular hole massage versus ILM flap insertion in the management of patients with idiopathic macular holes was conducted. Methods: 35 patients (total of 35 eyes) with idiopathic macular holes (with hole diameters ranging from 366 to 1430 μm) were divided into two groups—Group A consisted of 20 eyes that underwent pars plana vitrectomy (PPV) combined with ILM peeling and perimacular hole massage, while Group B comprised 15 eyes that underwent PPV combined with ILM flap insertion. Subsequent follow-up examinations were performed at 1 week, 1 month, and 3 months post-surgery. The study also involved a comparison of best corrected visual acuity (BCVA) and optical coherence tomography (OCT) classifications between both the patient groups. Results: The macular hole closure rates in Group A were 60 %, while in Group B, the closure rate was 93 %. There was significant difference in hiatus healing rate between the two groups (t = 4.843, p = 0.048). The difference in BCVA at 3 months post-operation between the two groups was statistically significant (t = 3.221, p = 0.003). Three months post-operatively, the BCVA in Group B demonstrated improvement compared to the pre-operative BCVA, with a statistically significant difference (p > 0.05). Three months post-operatively, the BCVA in Group A demonstrated improvement compared to the pre-operative BCVA, but this difference was not statistically significant (p > 0.05). Conclusion: The combination of PPV with ILM flap insertion demonstrates favorable therapeutic efficacy in the treatment of idiopathic macular holes, leading to improved visual acuity.

The Junggar Basin is an important coal-bearing basin in northwestern China. The coalfield in the east of the Junggar basin is an important part of the large Xinjiang coal base, and contains rich coal resources. In this study, we undertook a multi-proxy study evaluating trace elements, macerals and vitrinite maximum reflectance from coal seams B0, B1 and B2 of the middle Jurassic Xishanyao Formation to characterize paleoredox and paleosalinity conditions of coal-forming swamp and atmospheric oxygen level and paleoclimate during coal-forming period in the eastern Junggar Basin. 220 coal samples were selected from coal seams B0, B1 and B2 in order to determine trace elements. Moreover, macerals and vitrinite maximum reflectance of 16 coal samples was investigated. Compared with average values for world low-rank coals, the coal seams B0, B1 and B2 of the middle Jurassic Xishanyao Formation in the eastern Junggar Basin are slightly enriched in Sr, in addition, the coal seam B0 is also slightly enriched in Co. The analysis of Ni/Co-V/Cr and Ni/Co-Mo diagrams indicates that swamp was in oxic and dysoxic condition, which infers that the water in swamp has strong activity and high free oxygen content. According to B/Ga ratio analysis, the paleosalinity of swamp gradually increases from coal seam B0 to coal seam B1 and then to coal seam B2. The high paleosalinity of swamp during coal-forming period of coal seam B2 may be caused by an increase in the evaporation of water, which also indicates that the paleoclimate was relatively dry and hot during this period. The Sr/Cu ratios in coal seams B0, B1 and B2 reveal that the paleoclimate experienced a gradual transition from relatively warm and humid condition to relatively dry and hot condition from bottom to top during the Xishanyao Formation coal-forming period. The inertinite content varies from 40.4% to 57.2% with an average of 48.5% in coal seams B0, B1, and B2. Inferred atmospheric oxygen concentration in the middle Jurassic, as estimated from inertinite contents, were ～27.7%, which is much higher than the minimum required for sustained combustion.

ABSTRACT Importance It remained unclear that the efficacy comparison between low‐dose immune tolerance induction (LD‐ITI) incorporating immunosuppressants (IS) when severe hemophilia A (SHA) patients had inhibitor‐titer ≥200 Bethesda Units (BU)/mL (LD‐ITI‐IS200 regimen) and LD‐ITI combining with IS when SHA patients had inhibitor‐titer ≥40 BU/mL (LD‐ITI‐IS40 regimen). Objective To compare the efficacy of the LD‐ITI‐IS200 regimen with that of the LD‐ITI‐IS40 regimen for SHA patients with high‐titer inhibitors. Methods A prospective cohort study on patients receiving LD‐ITI‐IS200 compared to those receiving LD‐ITI‐IS40 from January 2021 to December 2023. Both received LD‐ITI [FVIII 50 IU/kg every other day]. IS (rituximab + prednisone) was added when peak inhibitor tier ≥200 BU/mL in the LD‐ITI‐IS200 regimen and ≥40 BU/mL in the LD‐ITI‐IS40 regimen. Success is defined as a negative inhibitor plus FVIII recovery ≥66% of the expected. Results We enrolled 30 patients on LD‐ITI‐IS200 and 64 patients on LD‐ITI‐IS40, with similar baseline clinical characteristics. A lower IS‐use rate was discovered in the LD‐ITI‐IS200 regimen compared to the LD‐ITI‐IS40 regimen (30.0% vs. 62.5%). The two regimens (LD‐ITI‐IS200 vs. LD‐ITI‐IS40) had similar success rate (70.0% vs. 79.7%), median time to success (9.4 vs. 10.6 months), and annualized bleeding rate during ITI (3.7 vs. 2.8). The cost to success was lower for LD‐ITI‐IS200 than for LD‐ITI‐IS40 (2107 vs. 3256 US Dollar/kg). Among patients with peak inhibitor‐titer 40–199 BU/mL, 10 non‐IS‐using (on LD‐ITI‐IS200 regimen) and 28 IS‐using (on LD‐ITI‐IS40 regimen) had similar success rates (70.0% vs. 78.6%) and time to success (9.0 vs. 8.8 months). Interpretation In LD‐ITI, IS are not necessary for inhibitor titer

Abstract Background The subjective sign of a serious pandemic in human work and life is mathematical neural tinnitus. fNIRS (functional near-infrared spectroscopy) is a new non-invasive brain imaging technology for studying the neurological activity of the human cerebral cortex. It is based on neural coupling effects. This research uses the fNIRS approach to detect differences in the neurological activity of the cerebral skin in the sound stimulation mission in order to better discriminate between the sensational neurological tinnitus. Methods In the fNIRS brain imaging method, 14 sensorineural tinnitus sufferers and 14 healthy controls listened to varied noise and quiet for fNIRS data collection. Linear fitting was employed in MATLAB to eliminate slow drifts during preprocessing and event-related design analysis. The false discovery rate (FDR) procedure was applied in IBM SPSS Statistics 26.0 to control the false positive rate in multiple comparison analyses. Results When the ill group and the healthy control group were stimulated by pink noise, there was a significant difference in blood oxygen concentration (P

Rockburst are often encountered in tunnel construction due to the complex geological conditions. To study the influence of unloading rate on rockburst, gneiss rockburst experiments were conducted under three groups of unloading rates. A high-speed photography system and acoustic emission (AE) system were used to monitor the entire process of rockburst process in real-time. The results show that the intensity of gneiss rockburst decreases with decrease of unloading rate, which is manifested as the reduction of AE energy and fragments ejection velocity. The mechanisms are proposed to explain this effect: (i) The reduction of unloading rate changes the crack propagation mechanism in the process of rockburst. This makes the rockbursts change from the tensile failure mechanism at high unloading rate to the tension-shear mixed failure mechanism at low unloading rate, and more energy released in the form of shear crack propagation. Then, less strain energy is converted into kinetic energy of fragments ejection. (ii) Less plate cracking degree of gneiss has taken shape due to decrease of unloading rate, resulting in the destruction of rockburst incubation process. The enlightenments of reducing the unloading rate for the project are also described quantitatively. The rockburst magnitude is reduced from the medium magnitude at the unloading rate of 0.1 MPa/s to the slight magnitude at the unloading rate of 0.025 MPa/s, which was judged by the ejection velocity.

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 The generation of alkyl radical from C(sp3)−H substrates via hydrogen atom abstraction represents a desirable yet underexplored strategy in alkylation reaction since involving common concerns remain adequately unaddressed, such as the harsh reaction conditions, limited substrate scope, and the employment of noble metal- or photo-catalysts and stoichiometric oxidants. Here, we utilize the synergistic strategy of photoredox and hydrogen atom transfer (HAT) catalysis to accomplish a general and practical functionalization of unactived C(sp3)−H centers with broad reaction scope, high functional group compatibility, and operational simplicity. A combination of validation experiments and density functional theory reveals that the N-centered radicals, generated from free N − H bond in a stepwise electron/proton transfer event, are the key intermediates that enable an intramolecular 1,5-HAT or intermolecular HAT process for nucleophilic carbon-centered radicals formation to achieve heteroarylation, alkylation, amination, cyanation, azidation, trifluoromethylthiolation, halogenation and deuteration. The practical value of this protocol is further demonstrated by the gram-scale synthesis and the late-stage functionalization of natural products and drug derivatives.