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Abstract D-dimer is a biomarker of coagulation and fibrinolytic system activation in response to the hypercoagulable state of the body. The research aimed to analyze the value of D-dimer in the prognosis of patients with dilated cardiomyopathy (DCM). Patients admitted to our center for the first time with DCM were enrolled consecutively. The clinical characteristics variables were obtained from the electronic medical record system, and the prognostic information was obtained using telephone return visits and a review of repeated hospitalization records. Univariate and multivariate Cox regression was used to explore the association of D-dimer with all-cause mortality. Smooth curve fitting, threshold saturation effect analysis, and subgroup analysis were performed. Ultimately, 534 patients were included. After a follow-up of the enrolled patients, 485 patients obtained prognostic information, of which 159 died from all causes, and the main cause of death was heart failure (89/159), the sudden death accounted for about 17%. The independent positive association between D-dimer and all-cause mortality remained unchanged in both unadjusted and adjusted Cox regression models. In the fully adjusted model, each standard deviation increase in D-dimer was associated with a 14% increase in all-cause mortality (HR = 1.14; 95% CI: 1.02 ~ 1.27; P

Abstract The rapid recombination of photoinduced charge carriers in semiconductors fundamentally limits their application in photocatalysis. Herein, we report that a superlattice interface and S-scheme heterojunction based on Mn0.5Cd0.5S nanorods can significantly promote ultrafast charge separation and transfer. Specifically, the axially distributed zinc blende/wurtzite superlattice interfaces in Mn0.5Cd0.5S nanorods can redistribute photoinduced charge carriers more effectively when boosted by homogeneous internal electric fields and promotes bulk separation. Accordingly, S-scheme heterojunctions between the Mn0.5Cd0.5S nanorods and MnWO4 nanoparticles can further accelerate the surface separation of charge carriers via a heterogeneous internal electric field. Subsequent capture of the photoelectrons by adsorbed H2O is as fast as several picoseconds which results in a photocatalytic H2 evolution rate of 54.4 mmol·g−1·h−1 without any cocatalyst under simulated solar irradiation. The yields are increased by a factor of ~5 times relative to control samples and an apparent quantum efficiency of 63.1% at 420 nm is measured. This work provides a protocol for designing synergistic interface structure for efficient photocatalysis.

Abstract Reliable traffic flow data is not only crucial for traffic management and planning, but also the foundation for many intelligent applications. However, the phenomenon of missing traffic flow data often occurs, so we propose an imputation model for missing traffic flow data to overcome the randomness and instability bands of traffic flow. First, k-means clustering is used to classify road segments with traffic flow belonging to the same pattern into a group to utilize the spatial characteristics of roads fully. Then, the LSTM networks optimized with an attention mechanism are used as the base learner to extract the temporal dependence of the traffic flow. Finally, the AdaBoost algorithm is used to integrate all the LSTM-attention networks into a reinforced learner to impute the missing data. To validate the effectiveness of the proposed model, we use the PeMS dataset for validation, we impute the data with missing data rate from 10 to 60% under three missing modes, and we use multiple baseline models for comparison, which confirms that our proposed model improves the stability and accuracy of imputing the missing data of the traffic flow with different scenarios.

Abstract Background Respiratory diseases impose an immense health burden worldwide. Epidemiological studies have revealed extensive disparities in the incidence and severity of respiratory tract infections between men and women. It has been hypothesized that there might also be a nasal microbiome axis contributing to the observed sex disparities. Results Here, we study the nasal microbiome of healthy young adults in the largest cohort to date with 1593 individuals, using shotgun metagenomic sequencing. We compile the most comprehensive reference catalog for the nasal bacterial community containing 4197 metagenome-assembled genomes and integrate the mycobiome, to provide a valuable resource and a more holistic perspective for the understudied human nasal microbiome. We systematically evaluate sex differences and reveal extensive sex-specific features in both taxonomic and functional levels in the nasal microbiome. Through network analyses, we capture markedly higher ecological stability and antagonistic potentials in the female nasal microbiome compared to the male’s. The analysis of the keystone bacteria reveals that the sex-dependent evolutionary characteristics might have contributed to these differences. Conclusions In summary, we construct the most comprehensive catalog of metagenome-assembled-genomes for the nasal bacterial community to provide a valuable resource for the understudied human nasal microbiome. On top of that, comparative analysis in relative abundance and microbial co-occurrence networks identify extensive sex differences in the respiratory tract community, which may help to further our understanding of the observed sex disparities in the respiratory diseases.

Abstract Background Breast cancer brain metastasis (BCBM) is associated with poor survival outcomes and reduced quality of life. The Graded Prognostic Assessment (GPA) score model serves as a well-established tool for predicting the prognosis of BCBM. Notably, the presence of extracranial metastasis (ECM) is considered as a significant prognostic factor in the breast GPA model. This study aims to further refine other features of ECM to enhance the prognostic prediction for BCBM. Methods This study included all inpatients diagnosed with BCBM at the Cancer Hospital, Chinese Academy of Medical Sciences, from January 2010 to July 2021. Baseline characteristics of patients were compared based on features of ECM, including the presence, number, location, and control status of metastases. Overall survival (OS) were compared using the Kaplan–Meier method with log-rank tests. Cox regression analyses were conducted to identify significant prognostic factors. The aforementioned ECM features were incorporated into the original Breast-GPA model to enhance its prognostic accuracy. The concordance index (C-index) and restricted mean survival time (RMST) were utilized to evaluate and compare the predictive accuracy of the updated and original survival models. Results 284 patients with BCBM were included in the study. Kaplan–Meier survival curves suggested that patients without ECM when diagnosed with BCBM showed better survival (p = 0.007). In the subgroups with ECM, more than 3 organs involved, both bone and visceral metastasis and progressive ECM portended dismal OS (p = 0.003, 0.001 and

Abstract Palbociclib is a CDK4/6 inhibitor approved for the treatment of breast cancer by suppressing cell proliferation. However, monotherapy with palbociclib was discouraging in prostate cancer, calling for a mechanism-based effective therapy. In this study, we reported in prostate cancer that palbociclib is a potent sensitizer of ferroptosis, which is worked out by downregulating the expression of TRIB3, a gene highly expressed in prostate cancer. Specifically, TRIB3 knockdown augmented the response of prostate cancer cells to ferroptosis inducers, whereas, TRIB3 overexpression rescued prostate cancer cells from palbociclib-induced ferroptosis. Mechanistically, TRIB3 inhibition by palbociclib resulted in downregulation of SOX2, which subsequently led to compromised expression of SLC7A11, a cystine/glutamate antiporter that counteracts ferroptosis. Functionally, a combined treatment of palbociclib with ferroptosis inducer significantly suppressed prostate cancer growth in a xenograft tumor model. Together, these results uncover an essential role of TRIB3/SOX2/SLC7A11 axis in palbociclib-induced ferroptosis, suggesting palbociclib a promising targeted therapy in combine with ferroptosis induction for the treatment of prostate cancer.

Abstract Background We conducted a systematic review and meta-analysis to assess the risk of respiratory adverse effects in patients with solid tumors treated with immune checkpoint inhibitors (PD-1, PD-L1 and CTLA-4 inhibitors) in combination with radiation therapy. Methods We selected eligible studies through the following databases: PubMed, Embase, Cochrane Library, and Clinicaltrials ( https://clinicaltrials.gov/ ). The data was analyzed by using Rstudio. Results Among 3737 studies, 26 clinical trials, including 2670 patients, were qualified for the meta-analysis. We evaluated the incidence rates of adverse respiratory events, including cough, pneumonia, upper respiratory tract infections, and others: grades 1–5 cough, 0.176 (95%CI: 0.113–0.274, I2 = 92.36%); grades 1–5 pneumonitis, 0.118 (95%CI: 0.067–0.198, I2 = 88.64%); grades 1–5 upper respiratory tract infection, 0.064 (95%CI: 0.049–0.080, I2 = 0.98%); grades 3–5 cough, 0.050 (95%CI: 0.012–0.204, I2 = 8.90%); grades 3–5 pneumonitis, 0.052 (95%CI: 0.031–0.078, I2 = 83.86%); grades 3–5 upper respiratory tract infection, 0.040 (95%CI: 0.007–0.249, I2 = 45.31%). Conclusions Our meta-analysis demonstrated that ICI combined with radiotherapy for solid tumors can produce respiratory adverse effects. ICIs combination treatment, a tumor located in the chest, is more likely to cause adverse reactions, and SBRT treatment and synchronous treatment will bring less incidence of adverse reactions. This study provide insights for clinicians to balance the risks of radiotherapy in the course of treating oncology patients.

Abstract The electron injection and transport behavior are of vital importance to the performance of quantum-dot light-emitting diodes. By simultaneously measuring the electroluminescence-photoluminescence of the quantum-dot light-emitting diodes, we identify the presence of leakage electrons which leads to the discrepancy of the electroluminescence and the photoluminescence roll-off. To trace the transport paths of the leakage electrons, a single photon counting technique is developed. This technique enables us to detect the weak photon signals and thus provides a means to visualize the electron transport paths at different voltages. The results show that, the electrons, except those recombining within the quantum-dots, leak to the hole transport layer or recombine at the hole transport layer/quantum-dot interface, thus leading to the reduction of efficiency. By reducing the amount of leakage electrons, quantum-dot light-emitting diode with an internal power conversion efficiency of over 98% can be achieved.

Abstract Background RNA sequencing is a vital technique for analyzing RNA behavior in cells, but it often suffers from various biases that distort the data. Traditional methods to address these biases are typically empirical and handle them individually, limiting their effectiveness. Our study introduces the Gaussian Self-Benchmarking (GSB) framework, a novel approach that leverages the natural distribution patterns of guanine (G) and cytosine (C) content in RNA to mitigate multiple biases simultaneously. This method is grounded in a theoretical model, organizing k-mers based on their GC content and applying a Gaussian model for alignment to ensure empirical sequencing data closely match their theoretical distribution. Results The GSB framework demonstrated superior performance in mitigating sequencing biases compared to existing methods. Testing with synthetic RNA constructs and real human samples showed that the GSB approach not only addresses individual biases more effectively but also manages co-existing biases jointly. The framework’s reliance on accurately pre-determined parameters like mean and standard deviation of GC content distribution allows for a more precise representation of RNA samples. This results in improved accuracy and reliability of RNA sequencing data, enhancing our understanding of RNA behavior in health and disease. Conclusions The GSB framework presents a significant advancement in RNA sequencing analysis by providing a well-validated, multi-bias mitigation strategy. It functions independently from previously identified dataset flaws and sets a new standard for unbiased RNA sequencing results. This development enhances the reliability of RNA studies, broadening the potential for scientific breakthroughs in medicine and biology, particularly in genetic disease research and the development of targeted treatments.

Abstract Pantoea stewartii subsp. stewartii (Pnss), is the bacterial causal agent of Stewart’s wilt of sweet corn. Disease symptoms include systemic wilting and foliar, water-soaked lesions. A Repeat-in-toxin (RTX)-like protein, RTX2, causes cell leakage and collapse in the leaf apoplast of susceptible corn varieties and is a primary mediator of water-soaked lesion formation in the P. stewartii-sweet corn pathosystem. RTX toxins comprise a large family of proteins, which are widely distributed among Gram-negative bacteria. These proteins are generally categorized as cellulolysins, but the Biofilm-Associated Proteins (Bap) subfamily of RTX toxins are implicated in surface adhesion and other biofilm behaviors. The Pnss RTX2 is most phylogenetically related to other Bap proteins suggesting that Pnss RTX2 plays a dual role in adhesion to host surfaces in addition to mediating the host cell lysis that leads to water-soaked lesion formation. Here we demonstrated that RTX2 localizes to the bacterial cell envelope and influences physiochemical properties of the bacterial cell envelope that impact bacterial cell length, cell envelope integrity and overall cellular hydrophobicity. Interestingly, the role of RTX2 as an adhesin was only evident in absence of exopolysaccharide (EPS) production suggesting that RTX2 plays a role as an adhesin early in biofilm development before EPS production is fully induced. However, deletion of rtx2 severely impacted Pnss’ colonization of the xylem suggesting that the dual role of RTX2 as a cytolysin and adhesin is a mechanism that links the apoplastic water-soaked lesion phase of infection to the wilting phase of the infection in the xylem.

Abstract Background With the aging population, the increasing prevalence of chronic non-communicable diseases, and the diversified needs for primary health care (PHC) medicines, it is necessary to rethink the functional role of the supply of PHC medicines. This study aims to evaluate the supply of PHC medicines and the status of meeting PHC medicine needs. Methods The mixed-methods study was conducted to evaluate the supply of PHC medicines in Shandong Province. In the quantitative study, survey questionnaires were distributed to county hospitals, township hospitals, and patients, and a prescription review was performed in township hospitals. In the qualitative study, semi-structured interviews were conducted with the pharmacy managers, physicians, and patients in county hospitals, township hospitals, and village clinics. A senior pharmacist from a tertiary hospital who has rich experience on the indications for medicine use, accompanied us on a visit to inspect the PHC pharmacies to survey medicine equipment with a professional perspective. Results Quantitative analysis revealed that 211 county hospitals and 1,581 township hospitals participated in the survey, revealing the median annual frequency of medicine shortages of 5.0 times for county hospitals and 2.0 times for township hospitals. Of the 6,323 patient medication surveys, after excluding 152 patients not involved in medication use, 945 (15.3%) indicated medicine shortages, with half of these attributable to institutions lacking required medicines (52.8%). On average, the prescription qualified rate of 37 township hospitals was 72.2%. Four final themes emerged during the qualitative data analysis: (1) Supply of PHC medicines; (2) Solutions to the shortage of off-list medicines; (3) Appropriateness of PHC medicines list; (4) Pharmacist workforce development and pharmacy services. Conclusions The discrepancy between patients’ need for PHC medicine and present medicine supply is noteworthy. It is suggested that governments should optimize the existing lists to adequately meet patient medicine needs and prioritize medicines for chronic diseases, which is also particularly important for developing countries. Integrated health care may be a novel strategy to establish unified medicines list and achieve uniform pharmaceutical services in PHC.

In patients with Alzheimer’s disease, gamma-glutamyl transferase 5 (GGT5) expression has been observed to be downregulated in cerebrovascular endothelial cells. However, the functional role of GGT5 in the development of Alzheimer’s disease remains unclear. This study aimed to explore the effect of GGT5 on cognitive function and brain pathology in an APP/PS1 mouse model of Alzheimer’s disease, as well as the underlying mechanism. We observed a significant reduction in GGT5 expression in two in vitro models of Alzheimer’s disease (Aβ1–42–treated hCMEC/D3 and bEnd.3 cells), as well as in the APP/PS1 mouse model. Additionally, injection of APP/PS1 mice with an adeno-associated virus encoding GGT5 enhanced hippocampal synaptic plasticity and mitigated cognitive deficits. Interestingly, increasing GGT5 expression in cerebrovascular endothelial cells reduced levels of both soluble and insoluble amyloid-β in the brains of APP/PS1 mice. This effect may be attributable to inhibition of the expression of β-site APP cleaving enzyme 1, which is mediated by nuclear factor-kappa B. Our findings demonstrate that GGT5 expression in cerebrovascular endothelial cells is inversely associated with Alzheimer’s disease pathogenesis, and that GGT5 upregulation mitigates cognitive deficits in APP/PS1 mice. These findings suggest that GGT5 expression in cerebrovascular endothelial cells is a potential therapeutic target and biomarker for Alzheimer’s disease.

Abstract This study introduces a novel self-supervised learning method for single-frame subtraction and vessel segmentation in coronary angiography, addressing the scarcity of annotated medical samples in AI applications. We pretrain a U-Net model on a large dataset of unannotated coronary angiograms using an image-to-image translation framework, then fine-tune it on a limited set of manually annotated samples. The pretrained model excels at comprehensive single-frame subtraction, outperforming existing DSA methods. Fine-tuning with just 40 samples yields a Dice coefficient of 0.828 for vessel segmentation. On the public XCAD dataset, our model sets a new state-of-the-art benchmark with a Dice coefficient of 0.755, surpassing both unsupervised and supervised learning approaches. This method achieves robust single-frame subtraction and demonstrates that combining pretraining with minimal fine-tuning enables accurate coronary vessel segmentation with limited manual annotations. We successfully apply this approach to assist physicians in visualizing potential vascular stenosis sites during coronary angiography. Code, dataset, and a live demo will be available available at: https://github.com/newfyu/DeepSA .

Traditional designs and developments of bone biomaterials mostly concentrate on the positive regulation of osteoblast lineage cells, but often ignore the importance of immune responses and the equilibrium between bone resorption mediated by osteoclasts and bone formation mediated by osteoblasts. Immune dysregulation is associated with an imbalance between pro-inflammatory and anti-inflammatory processes, which may influence the efficacy of bone therapy. Therefore, implanted biomaterials should appropriately and precisely modulate subsequent immune responses. Magnesium (Mg) has been used to fabricate various Mg alloys for bone repair because of its favorable attributes such as osteogenic potential, immune regulation characteristics, biodegradability, and biocompatibility. Various basic research and clinical trials have been already conducted in many countries to explore the physical properties of Mg-containing implants and their clinical outcomes in bone fracture and defect repair. Therefore, this review summarizes the immune response to Mg-containing implants, and further organizes the current research and development progress of Mg-containing implants. The review aims to offer an overview of the current knowledge on immunomodulation of Mg-containing implants and future challenges in their clinical application, which could provide further insight in the development of better strategies for the treatment of bone defect and fracture.

Abstract Purpose A practical noninvasive method is needed to identify lymph node (LN) status in breast cancer patients diagnosed with a suspicious axillary lymph node (ALN) at ultrasound but a negative clinical physical examination. To predict ALN metastasis effectively and noninvasively, we developed an artificial intelligence-assisted ultrasound system and validated it in a retrospective study. Methods A total of 266 patients treated with sentinel LN biopsy and ALN dissection at Peking Union Medical College & Hospital(PUMCH) between the year 2017 and 2019 were assigned to training, validation and test sets (8:1:1). A deep learning model architecture named DeepLabV3 + was used together with ResNet-101 as the backbone network to create an ultrasound image segmentation diagnosis model. Subsequently, the segmented images are classified by a Convolutional Neural Network to predict ALN metastasis. Results The area under the receiver operating characteristic curve of the model for identifying metastasis was 0.799 (95% CI: 0.514–1.000), with good end-to-end classification accuracy of 0.889 (95% CI: 0.741–1.000). Moreover, the specificity and positive predictive value of this model was 100%, providing high accuracy for clinical diagnosis. Conclusion This model can be a direct and reliable tool for the evaluation of individual LN status. Our study focuses on predicting ALN metastasis by radiomic analysis, which can be used to guide further treatment planning in breast cancer.

Abstract Echovirus 30 (E30), a member of the species B Enterovirus family, is a primary pathogen responsible for aseptic meningitis and encephalitis. E30 is associated with severe nervous system diseases and is a primary cause of child illness, disability, and even mortality. However, the mechanisms underlying E30-induced brain injury remain poorly understood. In this study, we used a neonatal mouse model of E30 to investigate the possible mechanisms of brain injury. E30 infection triggered the activation of microglia in the mouse brain and efficiently replicated within HMC3 cells. Subsequent transcriptomic analysis revealed inflammatory activation of microglia in response to E30 infection. We also detected a significant upregulation of polo-like kinase 1 (PLK1) and found that its inhibition could limit E30 infection in a sucking mouse model. Collectively, E30 infection led to brain injury in a neonatal mouse model, which may be related to excessive inflammatory responses. Our findings highlight the intricate interplay between E30 infection and neurological damage, providing crucial insights that could guide the development of interventions and strategies to address the severe clinical manifestations associated with this pathogen.

Abstract Cu catalyses electrochemical CO2 reduction to valuable multicarbon products but understanding the structure-function relationship has remained elusive due to the active Cu sites being heterogenized and under dynamic re-construction during electrolysis. We herein coordinate Cu with six phenyl-1H-1,2,3-triazole derivatives to form stable coordination polymer catalysts with homogenized, single-site Cu active sites. Electronic structure modelling, X-ray absorption spectroscopy, and ultraviolet–visible spectroscopy show a widely tuneable Cu electronics by modulating the highest occupied molecular orbital energy of ligands. Using CO diffuse reflectance Fourier transform infrared spectroscopy, in-situ Raman spectroscopy, and density functional theory calculations, we find that the binding strength of *CO intermediate is positively correlated to highest occupied molecular orbital energies of the ligands. As a result, we enable a tuning of C–C coupling efficiency—a parameter we define to evaluate the efficiency of C2 production—in a broad range of 0.26 to 0.86. This work establishes a molecular platform that allows for studying structure-function relationships in CO2 electrolysis and devises new catalyst design strategies appliable to other electrocatalysis.

Abstract Backgroud Type II congenital pulmonary airway malformation (CPAM) is a rare pulmonary microcystic developmental malformation. Surgical excision is the primary treatment for CPAM, although maternal steroids and betamethasone have proven effective in reducing microcystic CPAM. Disturbed intercellular communication may contribute to the development of CPAM. This study aims to investigate the expression profile and analyze intercellular communication networks to identify genes potentially associated with type II CPAM pathogenesis and therapeutic targets. Methods RNA sequencing (RNA-seq) was performed on samples extracted from both the cystic area and the adjacent normal tissue post-surgery in CPAM patients. Iterative weighted gene correlation network analysis (iWGCNA) was used to identify genes specifically expressed in type II CPAM. Single-cell RNA-seq (scRNA-seq) was integrated to unveil the heterogeneity in cell populations and analyze the communication and interaction within epithelial cell sub-populations. Results A total of 2,618 differentially expressed genes were identified, primarily enriched in cilium-related biological process and inflammatory response process. Key genes such as EDN1, GPR17, FPR2, and CHRM1, involved in the G protein-coupled receptor (GPCR) signaling pathway and playing roles in cell differentiation, apoptosis, calcium homeostasis, and the immune response, were highlighted based on the protein-protein interaction network. Type II CPAM-associated modules, including ciliary function-related genes, were identified using iWGCNA. By integrating scRNA-seq data, AGR3 (related to calcium homeostasis) and SLC11A1 (immune related) were identified as the only two differently expressed genes in epithelial cells of CPAM. Cell communication analysis revealed that alveolar type 1 (AT1) and alveolar type 2 (AT2) cells were the predominant communication cells for outgoing and incoming signals in epithelial cells. The ligands and receptors between epithelial cell subtypes included COLLAGEN genes enriched in PI3K-AKT singaling and involved in epithelial to mesenchymal transition. Conclusions In summary, by integrating bulk RNA-seq data of type II CPAM with scRNA-seq data, the gene expression profile and critical signaling pathways such as GPCR signaling and PI3K-AKT signaling pathways were revealed. Abnormally expressed genes in these pathways may disrupt epithelial-mesenchymal transition and contribute to the development of CPAM. Given the effectiveness of prenatal treatments of microcystic CPAM using maternal steroids and maternal betamethasone administration, targeting the genes and signaling pathways involved in the development of CPAM presents a promising therapeutic strategy.

Abstract Traditional open head and neck surgery often leaves permanent scars, significantly affecting appearance. The emergence of surgical robots has introduced a new era for minimally invasive surgery. However, the complex anatomy of the head and neck region, particularly the oral and maxillofacial areas, combined with the high costs associated with established systems such as the da Vinci, has limited the widespread adoption of surgical robots in this field. Recently, surgical robotic platform in China has developed rapidly, exemplified by the promise shown by the KangDuo Surgical Robot (KD-SR). Although the KD-SR has achieved some results comparable to the da Vinci surgical robot in urology and colorectal surgery, its performance in complex head and neck regions remains untested. This study evaluated the feasibility, effectiveness, and safety of the newly developed KD-SR-01, comparing it with standard endoscopic systems in head and neck procedures on porcine models. We performed parotidectomy, submandibular gland resection, and neck dissection, collected baseline characteristics, perioperative data, and specifically assessed cognitive workload using the NASA-TLX. None of the robotic procedures were converted to endoscopic or open surgery. The results showed no significant difference in operation time between the two groups (P = 0.126), better intraoperative bleeding control (P = 0.001), and a significant reduction in cognitive workload (P

Abstract Closed chest drainage is typically necessary following Lobar and Sublobar resections to evacuate gases and fluids from the thoracic cavity, eliminate residual pleural space for lung expansion, and maintain negative pressure. Currently, three conventional closed chest drainage systems are commonly employed: single-chamber, double-chamber, and triple-chamber systems; each system has its own advantages and disadvantages. Despite the emergence of digital drainage systems in recent years, their high cost hinders their widespread adoption. Based on this premise, our research team has achieved a patent for a micro air pump-integrated chest closed drainage bottle, which has been further developed into a novel device integrating a three-chamber system with negative pressure control and power supply capabilities. This device enables patients undergoing perioperative lung procedures to ambulate freely while simultaneously receiving chest suction therapy—a concept that theoretically promotes rapid postoperative recovery. Moreover, this device offers economic benefits and holds potential for clinical implementation (particularly in economically underdeveloped regions). In this article, we modified the thoracic closed drainage device based on our patent and presented this novel thoracic closed drainage device after 3D printing and assembly.

Abstract Background This study investigates the distribution and characteristics of linezolid and vancomycin susceptibilities among Enterococcus faecalis (E. faecalis) and Enterococcus faecium (E. faecium) and explores the underlying resistance mechanisms. Methods A total of 2842 Enterococcus clinical isolates from patients were retrospectively collected, and their clinical data were further analyzed. The minimum inhibitory concentrations (MICs) of vancomycin and linezolid were validated by broth dilution method. The resistance genes optrA, cfr, vanA, vanB and vanM were investigated using polymerase chain reaction (PCR). Housekeeping genes and resistance genes were obtianed through whole-genome sequencing (WGS). Results Of the 2842 Enterococcus isolates, 88.5% (2516) originated from urine, with E. faecium accounted for 60.1% of these. The vanA gene was identified in 27/28 vancomycin resistant Enterococcus (VRE) isolates, 4 of which carried both vanA and vanM genes. The remaining strain was vanM positive. The optrA gene was identified in all E. faecalis isolates among linezolid resistant Enterococcus (LRE). E. faecium showed a higher multiple antibiotic resistance index (MAR index) compared to E. faecalis. The multi-locus sequence typing (MLST) showed the sequence type of E. faecium mainly belongs to clonal complex (CC) 17, nearly E. faecalis isolates analyzed were differentiated into 7 characteristics of sequence types (STs), among which ST16 of CC16 were the major lineage. Conclusion Urine was the primary source of VRE and LRE isolates in this study. E. faecium showed higher levels of resistance compared to E. faecalis. OptrA gene was detected in 91.6% of LRE, which could explain linezolid resistance, and van genes were detected in all vancomycin resistant Enterococcus strains, while vanA was a key resistance mechanism in VRE identified in this study.

【Objective】As one of the four major nutrients required by plants, sulfur is a crucial for plant growth and development, playing a pivotal role in enhancing plant resistance against both biotic and abiotic stresses. Sulfate transporters (SULTR) serve as primary regulators in the absorption and transport of sulfate in plants, playing an irreplaceable role in this process. The understanding of the fundamental characteristics and expression patterns of CaSULTR genes could help to provide theoretical support for advancing researches on SULTR in peppers.【Method】Based on the pepper genome, members of the epper CaSULTR gene family were identified at the whole-genome level. A comprehensive analysis of their physicochemical properties, conserved Motifs and gene structures was conducted. By utilizing publicly available transcriptome data and qPCR technology, the expression patterns of CaSULTR genes under various hormone stress conditions were analyzed. Additionally, differentially expressed genes were cloned for further investigation.【Result】A total of 13 CaSULTR genes were identified and designated as CaSULTR1;1~1;3, CaSULTR2;1~2;2, CaSULTR3;1~3;7 and CaSULTR4;1. These genes were distributed on seven chromosomes in pepper, with amino acid lengths ranging from 641 to 947 aa, molecular weights from 69.65 to 104.36 kD, and isoelectric points between 8.42 to 9.62. Characterized by the hydrophobicity, CaSULTR proteins were classified into four subgroups (Ⅰ-Ⅳ), with subgroup Ⅲ containing the highest number of members. Within the same subgroup, members exhibited relatively small differences in physicochemical properties, and Motifs and gene structures were relatively conserved. With the exception of CaSULTR2;1 and CaSULTR2;2, all members possessed Motif 5. Tissue expression analysis indicated that CaSULTR genes may be involved in the development of organs such as leaves, fruits and flowers, with CaSULTR4;1 exhibiting expression in leaves, roots and stems. Expression profile analysis under hormone stress, coupled with qPCR results, revealed significant up-regulation of CaSULTR1;1 and CaSULTR3;4 under hormone induction.【Conclusion】The expression patterns of CaSULTR genes under hormone stress are identified, suggesting that of CaSULTR1;1 and CaSULTR3;4 may be involved in the regulation of sulfur metabolism by exogenous hormones.

Abstract Respiratory diseases constitute a major health problem for ruminants, resulting in considerable economic losses throughout the world. Parainfluenza type 3 virus (PIV3) is one of the most important respiratory pathogens of ruminants. The pathogenicity and phylogenetic analyses of PIV3 virus have been reported in sheep and goats. However, there are no recent studies of the vaccination of sheep or goats against PIV3. Here, we developed a purified inactivated ovine parainfluenza virus type 3 (OPIV3) vaccine candidate. In addition, we immunized sheep with the inactivated OPIV3 vaccine and evaluated the immune response and pathological outcomes associated with OPIV3 TX01 infection. The vaccinated sheep demonstrated no obvious symptoms of respiratory tract infection, and there were no gross lesions or pathological changes in the lungs. The average body weight gain significantly differed between the vaccinated group and the control group (P

Abstract The timely detection and management of hemorrhagic shock hold paramount importance in clinical practice. This study was designed to establish a nomogram that may facilitate early identification of hemorrhagic shock in pediatric patients with multiple-trauma. A retrospective study was conducted utilizing a cohort comprising 325 pediatric patients diagnosed with multiple-trauma, who received treatment at the Children's Hospital, Zhejiang University School of Medicine, Zhejiang, China. For external validation, an additional cohort of 144 patients from a children's hospital in Taizhou was included. The model's predictor selection was optimized through the application of the Least Absolute Shrinkage and Selection Operator (LASSO) regression. Subsequently, a prediction nomogram was constructed using multivariable logistic regression analysis. The performance and clinical utility of the developed model were comprehensively assessed utilizing various statistical metrics, including Harrell's Concordance Index (C-index), receiver operating characteristic (ROC) curve analysis, calibration curve analysis, and decision curve analysis (DCA). Multivariate logistic regression analysis identified systolic blood pressure (ΔSBP), platelet count, activated partial thromboplastin time (APTT), and injury severity score (ISS) as independent predictors for hemorrhagic shock. The nomogram constructed using these predictors demonstrated robust predictive capabilities, as evidenced by an impressive area under the curve (AUC) value of 0.963. The model's goodness-of-fit was assessed using the Hosmer–Lemeshow test (χ2 = 10.023, P = 0.209). Furthermore, decision curve analysis revealed significantly improved net benefits with the model. External validation further confirmed the reliability of the proposed predictive nomogram. This study successfully developed a nomogram for predicting the occurrence of hemorrhagic shock in pediatric patients with multiple trauma. This nomogram may serve as an accurate and effective tool for timely and efficient management of children with multiple trauma.

Abstract Conventionally, non-orthogonal multiple access (NOMA) has traditionally been implemented separately from orthogonal multiple access (OMA), aiming to improve the capacity of multi-user systems. However, a recent study has ventured beyond this conventional approach by integrating OMA and NOMA proportionally within the same system. In spite of these advancements, the consideration towards optimizing multi-user systems remains incomplete especially when user service requirements vary significantly. Therefore, this paper explores a novel layered device-to-device (D2D) partial NOMA (P-NOMA) scheme, which introduces a hybrid power-domain access method into multi-user systems. The analysis primarily focuses on evaluating both the system performance and the impact of various parameters on it. In contrast to conventional fully overlapped NOMA signals, P-NOMA signals are partially overlapped with an overlap rate that can be determined based on quality-of-service (QoS) requirements. Simulation results demonstrate that judicious utilization of P-NOMA can effectively enhance overall system performance, particularly in terms of sum rate (SR) metrics, while also flexibly accommodating diverse QoS requirements for multiple users.

Grid-based recommendation algorithms view users and items as abstract nodes, and the information utilised by the algorithm is hidden in the selection relationships between users and items. Although these relationships can be easily handled, much useful information is overlooked, resulting in a less accurate recommendation algorithm. The aim of this paper is to propose improvements on the standard substance diffusion algorithm, taking into account the influence of the user’s rating on the recommended item, adding a moderating factor, and optimising the initial resource allocation vector and resource transfer matrix in the recommendation algorithm. An average ranking score evaluation index is introduced to quantify user satisfaction with the recommendation results. Experiments are conducted on the MovieLens training dataset, and the experimental results show that the proposed algorithm outperforms classical collaborative filtering systems and network structure based recommendation systems in terms of recommendation accuracy and hit rate.

Background: Pirfenidone (PFD) is commonly applied for antifibrotic treatment in patients with idiopathic pulmonary fibrosis but has rarely been studied in cases with connective tissue disease-associated interstitial lung diseases (CTD-ILDs). Objectives: We aimed to examine the efficacy of PFD in patients with CTD-ILD based on real-world data. Design: A retrospective cohort study. Methods: This study assessed the clinical features of CTD-ILD patients with or without a 6-month PFD treatment. A linear mixed effects model was employed to evaluate the effectiveness of PFD in alleviating lung function changes. Differences in response to PFD were analyzed based on CTD subtype, imaging classification, and pattern of pulmonary function at baseline. Results: A total of 289 patients with CTD-ILD were included, with 155 (53.6%) receiving PFD treatment and the remaining constituting the control group. Patients with the usual interstitial pneumonia (UIP) pattern were more likely to receive PFD treatment, and a relatively lower proportion of cases in the PFD group received immunosuppressive therapies compared to the control group ( p

Apoptosis is a crucial pathological process in myocardial ischemia/reperfusion injury (MIRI). Verapamil (Ver), normally used to treat hypertension or heart rhythm disorders, also attenuates MIRI. The potential of Ver to inhibit apoptosis and thereby attenuate MIRI remains unclear, as does the mechanism. We established an in vivo mouse ischemia/reperfusion (I/R) model by occlusion of the left anterior descending coronary. To construct a hypoxia/reoxygenation model in vitro, H9c2 cardiomyocytes were immersed in a hypoxic buffer in a hypoxia/anaerobic workstation. Ver significantly improved cardiac function and reduced myocardial infarction size in I/R mice, while decreasing apoptosis. Both in vivo and in vitro, application of Ver activated the JAK2/STAT3 signaling pathway and elevated Bcl-2 expression, while decreasing Bax and cleaved caspase-3 levels. Treatment with AG490, a JAK2 inhibitor, partially counteracted the anti-apoptotic and the cardioprotective effect of Ver. Thus, we conclude that Ver alleviates MIRI by reducing apoptosis via the JAK2/STAT3 signaling pathway activation. These findings provide a novel mechanism of Ver in the treatment of MIRI.

ABSTRACT The circadian oscillation of gut microbiota plays vital roles in the normal physiology and health of the host. Although the diurnal oscillation of intestinal bacteria has been extensively studied, little relevant work has been done on intestinal fungi. Besides, the rhythmic correlations between bacterial and fungal microbes are also scarcely reported. Here, we investigated the diurnal oscillations of bacterial and fungal communities in male cynomolgus monkeys by performing 16S rRNA and ITS amplicon sequencing. As for bacterial genera, we found that the relative abundance of Prevotella, norank_f_Eubacterium_coprostanoligenes_group, and Peptococcus underwent significant changes at ZT12 (19:00) and exhibited obvious rhythmic oscillations. Consequently, most of the bacterial functions varied at ZT12 and were positively correlated with the bacterial genera norank_f_Eubacterium_coprostanoligenes_group and Prevotella. Among the fungal genera, the relative abundance of Aspergillus and Talaromyces decreased at ZT18 (1:00) and showed slight rhythmic oscillations. As for the fungal function, the undefined saprotroph showed slight rhythmic oscillation and was positively correlated with the fungal genus Aspergillus. Notably, we characterized the correlations between intestinal bacteria and fungi every 6 h over the course of a day and found that the bacterial and fungal microbes interacted closely, with the most bacteria–fungi interactions occurring at ZT12. Our study contributed to a more comprehensive understanding of the diurnal oscillation patterns of bacterial and fungal microbes in male cynomolgus monkeys and uncovered their correlations during a diurnal cycle.IMPORTANCEThe rhythmic oscillation of gut microbiota can impact the physiology activity and disease susceptibility of the host. Until now, most of the studies are focused on bacterial microbes, ignoring other components of gut microbes, such as fungal microbes (mycobiota). Besides, only few studies have addressed the rhythmic correlations between gut bacteria and fungi. Here, we analyzed the rhythmic oscillations of bacterial and fungal communities in male cynomolgus monkeys by performing 16S rRNA and ITS amplicon sequencing. Apart from identifying the rhythmically oscillated bacterial and fungal microbes, we conducted the correlation analysis between these two microbial communities and found that the intestinal bacteria and fungi exhibited close interactions rhythmically, with the most interactions occurring at ZT12. Thus, our study not only investigated the rhythmic oscillations of gut bacterial and fungal communities in male cynomolgus monkeys but also uncovered their rhythmic interactions.

It is of great value to develop effective methods for accurately and simultaneously detecting ascorbic acid (AA) and dopamine (DA) in the field of biochemistry. This work reports a nonenzymatic electrochemical sensor for the simultaneous detection of AA and DA by employing a Co-modified MCM-41 (CoMCM-41) mesoporous molecular sieve as an efficient electrocatalytic material, which was synthesized by a two-step hydrothermal method. Subsequently, the high structural organization of the CoMCM-41 mesoporous structure was characterized, and the electrocatalytic performance of CoMCM-41 toward AA and DA oxidation was then evidenced by the catalytic effect of different electrodes modified with or without CoMCM-41. By virtue of the superior electrocatalytic activity of the CoMCM-41, a much wider peak potential difference (ΔEpa) of 310 mV was obtained for the oxidation of AA and DA in their mixture solution, and the parameters that influenced the electrochemical signals of the modified electrode were also optimized. Under optimal conditions, a good linear response to AA and DA was observed on the CoMCM-41 modified electrode. For individual detection of AA and DA, the linear ranges were 7 ~ 105 μM and 5 ~ 110 μM respectively, while the linear response range was 20 ~ 100 μM for simultaneous detection of AA and DA. Satisfactory recovery results were obtained when the fabricated sensor was applied to determine AA in orange juice and DA in madopar pill samples.

Abstract Gut microbiota dysbiosis has been implicated in rheumatoid arthritis (RA) and influences disease progression. Although molecular and culture‐independent studies revealed RA patients harbored a core microbiome and had characteristic bacterial species, the lack of cultured bacterial strains had limited investigations on their functions. This study aimed to establish an RA‐originated gut microbial biobank (RAGMB) that covers and further to correlates and validates core microbial species on clinically used and diagnostic inflammation and immune indices. We obtained 3200 bacterial isolates from fecal samples of 20 RA patients with seven improved and 11 traditional bacterial cultivation methods. These isolates were phylogenetically identified and selected for RAGMB. The RAGMB harbored 601 bacterial strains that represented 280 species (including 43 novel species) of seven bacterial phyla. The RAGMB covered 93.2% at species level of medium‐ and high‐abundant (relative abundances ≥0.2%) RA gut microbes, and included four rare species of the phylum Synergistota. The RA core gut microbiome was defined and composed of 20 bacterial species. Among these, Mediterraneibacter tenuis and Eubacterium rectale were two species that statistically and significantly correlated with clinically used diagnostic indices such as erythrocyte sedimentation rate (ESR) and IL‐10. Thus, M. tenuis and E. rectale were selected for experimental validation using DSS‐treated and not DSS‐treated mice model. Results demonstrated both M. tenuis and E. rectale exacerbated host inflammatory responses, including shortened colon length and increased spleen weight, decreased IL‐10 and increased IL‐17A levels in plasma. Overall, we established the RAGMB, defined the RA core microbiome, correlated and demonstrated core microbial species effected on host inflammatory and immune responses. This work provides diverse gut microbial resources for future studies on RA etiology and potential new targets for new biomedical practices.

The contamination of aquatic environments by organic dye contaminants in industrial wastewater has attracted widespread global attention. The heterogeneous Fenton-like process presents an attractive method for degrading dye pollutants, especially when such reactions are conducted under neutral pH. In this study, Fe2O3/MnO2 composite was employed as a novel heterogeneous catalyst for activating hydrogen peroxide (H2O2) to oxidize and subsequently degrade methylene blue (MB) under neutral pH. Multiple characterization results have confirmed the presence of MnO2 and Fe2O3 as the primary phases of the synthesized compound catalyst. Degradation experiments have demonstrated that the degradation efficiency of MB approaches 100% under the conditions of H2O2 concentration of 0.30% and Fe2O3/MnO2 amount of 0.888 g/L. Furthermore, the Fe2O3/MnO2 catalyst exhibits consistent and outstanding catalytic activity within a broad pH range from 5 to 9 benefiting from the strong interface interaction in Fe2O3/MnO2. The investigation into the kinetics of the Fenton-like reaction indicates that the catalytic degradation of MB by Fe2O3/MnO2 in conjunction with H2O2 follows pseudo-first-order kinetics. Moreover, supplementary scavenging experiments have demonstrated the crucial role played by hydroxyl radicals (·OH) in the catalytic oxidation mechanism of MB. This study offers a promising catalyst for the treatment of dye-containing wastewater under neutral pH condition.

BackgroundThe status of sentinel lymph nodes is crucial for prognosis and treatment decisions in breast cancer patients. This study aimed to evaluate the predictive value of combined methylene blue and indocyanine green for sentinel lymph node metastasis in breast cancer.MethodsThis prospective cohort study enrolled 90 clinically node-negative breast cancer patients. Methylene blue and indocyanine green were injected locally before surgery. Sentinel lymph nodes were grouped based on fluorescence intensity and methylene blue staining. A binary logistic regression model was established using 285 lymph node groups to predict metastatic risk.ResultsA total of 475 lymph nodes were identified, with 33 being metastatic. The metastatic risk reached 70% for partially blue-stained and weakly fluorescent lymph nodes between 1-2 cm. The model revealed associations between lymph node size, dye staining patterns, and metastatic risks (P

Rock masses in deep engineering are often subjected to high geothermal effect, and blasting is a key technique for deep rock excavation. It is crucial to study the dynamic characteristics of fractured rock masses under high geothermal conditions and blasting excavation. This paper focuses on fractured gabbro, examining the effects of high temperatures on its surface chromaticity and mass. Dynamic splitting tests were conducted using a Split Hopkinson Pressure Bar (SHPB) apparatus, and the microstructure was analyzed with scanning electron microscopy (SEM). The results indicate that: (1) High temperatures significantly affect the surface chromaticity and mass of gabbro samples. (2) Elevated temperatures lead to the progression from a microstructure with no noticeable microcracks to the development of extensive microcracks and mineral particle fragmentation. (3) The impacts of high temperatures on the splitting strength, peak strain, and dynamic elastic modulus of gabbro samples reach a critical point around 500 °C. At this temperature, the strengthening effect of high temperature is evident, whereas at 800 °C, these properties significantly decrease due to extensive mineral crystal fragmentation and microcrack expansion, weakening the sample's strength, stiffness, and deformation resistance. (4) From 25 °C to 600 °C, the fissure angle significantly influences the splitting strength, peak strain, and dynamic elastic modulus of gabbro. Although the fissure angle still impacts these properties at 800 °C, the overall effect of high temperature is more pronounced. (5) The failure of fractured gabbro samples is primarily characterized by tensile and shear failures, with the crack initiation angle closely related to the fissure angle.

To investigate the correlation between the difference of secondary metabolites and the disease-resistance activity of different varieties of Congou black tea. Among a total of 657 secondary metabolites identified, 183 metabolites had anti-disease activity, 113 were key active ingredients in traditional Chinese medicine (TCM), 73.22% had multiple anti-disease activities, and all were mainly flavonoids and phenolic acids. The main enriched metabolic pathways were phenylpropanoid biosynthesis, biosynthesis of secondary metabolites, flavonoid biosynthesis, and metabolic pathways. Flavonoid and phenolic acid secondary metabolites were more correlated with anti-disease activity and key active TCM ingredients. Conclusion: The types of JGY and Q601 Congou black tea of the relative contents show large differences in secondary metabolites. Flavonoid and phenolic acid secondary metabolites were identified as the primary factors contributing to the variation in secondary metabolites among different varieties of Congou black tea. These compounds also exhibited a stronger correlation with disease resistance activity.

Background Seed hypocotyl germination signifies the initiation of the life cycle for plants and represents a critical stage that heavily influences subsequent plant growth and development. While previous studies have established the melatonin (MEL; N-acetyl-5-methoxytrytamine) effect to stimulate seed germination of some plants, its specific role in peony germination and underlying physiological mechanism have yet to be determined. This study aims to evaluate the MEL effect for the hypocotyl germination of peony seeds, further ascertain its physiological regulation factors. Methods In this work, seeds of Paeonia ostia ‘Fengdan’ were soaked into MEL solution at concentrations of 50, 100, 200, and 400 µM for 48 h and then germinated in darkness in incubators. Seeds immersed in distilled water without MEL for the same time were served as the control group. Results At concentrations of 100 and 200 µM, MEL treatments improved the rooting rate of peony seeds, while 400 µM inhibited the process. During seed germination, the 100 and 200 µM MEL treatments significantly reduced the starch concentration, and α-amylase was the primary amylase involved in the action of melatonin. Additionally, compared to the control group, 100 µM MEL treatment significantly increased the GA3 concentration and radicle thickness of seeds, but decreased ABA concentration. The promotion effect of 200 µM MEL pretreatment on GA1 and GA7 was the most pronounced, while GA4 concentration was most significantly impacted by 50 µM and 100 µM MEL. Conclusion Correlation analysis established that 100 µM MEL pretreatment most effectively improved the rooting rate characterized by increasing α-amylase activity to facilitate starch decomposition, boosting GA3 levels, inhibiting ABA production to increase the relative ratio of GA3 to ABA. Moreover, MEL increased radicle thickness of peony seeds correlating with promoting starch decomposition and enhancing the synthesis of GA1 and GA7.

Background: To date, a large number of studies have shown correlations between environmental variables and pediatric asthma in short-term lag time. However, their results are inconsistent. Therefore, we aimed to evaluate the short-term impact of environmental variables on daily pediatric asthma patients’ visits (DPAPV) in Hangzhou, China, and find the most important risk factor. Methods: Generalized additive distribution lag non-linear model (GAM-DLNM) was applied to explore the effect of environmental variables on DPAPV in single- and multi-variable models in Hangzhou, China from 2014 to 2021. Then, risk factors of pediatric asthma were selected (p

Objective: To analyze and validate differential genes in the cytokine-cytokine receptor interaction CCRI pathway in laryngeal squamous cell carcinoma (LSCC) using bioinformatics and Mendelian randomization (MR) to find potential biomarkers for LSCC. Methods: Five sets of LSCC-related gene chips were downloaded from the GEO database, and four sets of combined datasets were randomly selected as the test set and one set as the validation set to screen for differential genes in the CCRI pathway; two-way Mendelian randomization was performed to analyze the causal relationship between cytokine receptor as the exposure factor and LSCC as the outcome variable; and the causal relationship was analyzed by DGIdb, Miranda, miRDB, miRWalk, TargetScan, spongeScan, and TISIDB databases to analyze the relationship between differential genes and drugs, immune cell infiltration, and mRNA-miNA-lncRNA interactions. Results: A total of 7 differentially expressed genes CD27, CXCL2, CXCL9, INHBA, IL6, CXCL11, and TNFRSF17 were screened for enrichment in the CCRI signaling pathway; MR analysis showed that the CCRI receptor was a risk factor for LSCC (IVW: OR = 1.629, 95 % CI:1.060–2.504, P = 0.026); Seven differential genes were correlated with drugs, immune cells and mRNA-miNA-lncRNA, respectively; the CCRI differential gene expression analysis in the validation set was consistent with the test set results. Conclusion: This study provided CCRI differential gene expression by bioinformatics, and MR analysis demonstrated that cytokine receptors are risk factors for LSCC, providing new ideas for the pathogenesis and therapeutic targets of LSCC.

We report a case of acute myeloid leukemia (AML) with retinoic acid receptor gamma (RARG) rearrangement, exhibiting clinical, morphological, and immunophenotypic features similar to classic acute promyelocytic leukemia (APL). RNA sequencing analysis of the patient’s bone marrow samples revealed the presence of nucleoporin 98 (NUP98)-RARG caused by translocation. AML with RARG rearrangement is insensitive to all-trans retinoic acid (ATRA) and arsenic trioxide. The patient received azacitidine therapy after failing ATRA and standard 3 + 7 therapy (idarubicin and cytarabine) and achieved complete remission. Conclusively, this acute myeloid leukemia subtype may benefit from azacitidine.

Human beings are living longer than ever before and aging is accompanied by an increased incidence of motor deficits, including those associated with the neurodegenerative conditions, Parkinson's disease (PD) and Huntington's disease (HD). However, the biological correlates underlying this epidemiological finding, especially the functional basis at the synapse level, have been elusive. This study reveals that motor skill performance examined via rotarod, beam walking and pole tests is impaired in aged mice. This study, via electrophysiology recordings, further identifies an aging-related reduction in the efficacy of inhibitory synaptic transmission onto dorsolateral striatum (DLS) indirect-pathway medium spiny neurons (iMSNs), i.e., a disinhibition effect on DLS iMSNs. In addition, pharmacologically enhancing the activity of DLS iMSNs by infusing an adenosine A2A receptor (A2AR) agonist, which presumably mimics the disinhibition effect, impairs motor skill performance in young mice, simulating the behavior in aged naïve mice. Conversely, pharmacologically suppressing the activity of DLS iMSNs by infusing an A2AR antagonist, in order to offset the disinhibition effect, restores motor skill performance in aged mice, mimicking the behavior in young naïve mice. In conclusion, this study identifies a functional inhibitory synaptic plasticity in DLS iMSNs that likely contributes to the aging-related motor skill deficits, which would potentially serve as a striatal synaptic basis underlying age being a prominent risk factor for neurodegenerative motor deficits.

One possible way to enhance the power density of electric vehicle (EV) powertrains is by utilizing temperature-sensitive permanent magnet synchronous motors (PMSMs) managed through liquid cooling. The management of benefits and costs from EV PMSM liquid cooling versus power are carried out for energy system output power (ESOP) increase. This study examines the effects of optimizing flow rate into housing water jackets (HWJ) and implementing compound shaft water (SWJ) cooling as management strategies using numerical multiphysics simulations and experiments. The PMSM with higher temperature at higher speed shows larger profit space brought by enhanced cooling. The optimized HWJ flow rate is a highly-efficient strategy to increase ESOP when overall pumping efficiency e1 for HWJ is less than 5 %, increasing more than 5.6 %, 2.1 % and 2.4 % ESOP at 1500, 3500, and 7000 rpm continuous working point. ESOP is insensitive to the condition of HWJ flow rate below 6 L/min or e1 over 30 %. The SWJ cooling is proved to be a low-cost and high-yield energy management strategy roughly independent of SWJ flow rate and EV's cooling system arrangement. ESOP is further increased by up to 3.9 %, 6.2 % and 4.4 % with SWJ cooling at 1500, 3500, and 7000 rpm.

Abstract In order to make magnesium alloys better used in aviation, electronic information and other fields, it is necessary to improve their corrosion resistance and wave absorption properties. In this paper, a composite coating with corrosion resistance and wave absorption properties was prepared on magnesium alloy by micro-arc oxidation-organic coating technology. An organic absorbing coating with a thickness of about 40 μm was sprayed on the MAO coating containing Yb2O3 nanoparticles. Among them, the absorbing fillers in the organic coating are mainly SiO2 and α-Fe2O3. Three different mass ratios of SiO2 and α-Fe2O3 were set to 20%, 22.5% and 25%, respectively, to prepare three different MAO/SiO2@α-Fe2O3 organic composite coatings. The morphology, roughness, microstructure and chemical composition of the organic composite coating are characterized. The results show that after coating the organic composite coating, the roughness of the coating is significantly reduced, and the compactness and interlayer adhesion of the coating are significantly improved. The electrochemical test and SKPFM test of the organic composite coating were carried out. The results showed that with the increase of the mass ratio of SiO2 and α-Fe2O3, the corrosion resistance and stability of the organic composite coating increased, and the Volta potential also gradually moved up. The microwave absorbing properties of organic composite coatings were studied by vector network analyzer. The results show that the microwave absorbing properties of the coatings are positively correlated with the mass ratio of SiO2 and α-Fe2O3.

Abstract Background The presence of mesenchymal stem cells has been confirmed in some solid tumors where they serve as important components of the tumor microenvironment; however, their role in cancer has not been fully elucidated. The aim of this study was to investigate the functions of mesenchymal stem cells isolated from tumor tissues of patients with non-small cell lung cancer. Results Human lung cancer-derived mesenchymal stem cells displayed the typical morphology and immunophenotype of mesenchymal stem cells; they were nontumorigenic and capable of undergoing multipotent differentiation. These isolated cells remarkably enhanced tumor growth when incorporated into systems alongside tumor cells in vivo. Importantly, in the presence of mesenchymal stem cells, the ability of peripheral blood mononuclear cell-derived natural killer and activated T cells to mediate tumor cell destruction was significantly compromised. Conclusion Collectively, these data support the notion that human lung cancer-derived mesenchymal stem cells protect tumor cells from immune-mediated destruction by inhibiting the antitumor activities of natural killer and T cells.

Abstract Visual information is important for accurate spatial coding and memory-guided navigation. As a crucial area for spatial cognition, the medial entorhinal cortex (MEC) harbors diverse spatially tuned cells and functions as the major gateway relaying sensory inputs to the hippocampus containing place cells. However, how visual information enters the MEC has not been fully understood. Here, we identify a pathway originating in the secondary visual cortex (V2) and directly targeting MEC layer 5a (L5a). L5a neurons served as a network hub for visual processing in the MEC by routing visual inputs from multiple V2 areas to other local neurons and hippocampal CA1. Interrupting this pathway severely impaired visual stimulus-evoked neural activity in the MEC and performance of mice in navigation tasks. These observations reveal a visual cortical-entorhinal pathway highlighting the role of MEC L5a in sensory information transmission, a function typically attributed to MEC superficial layers before.

Abstract Background Pulmonary hypertension (PH) is a progressive disease characterized by pulmonary vascular remodeling. Increasing evidence indicates that endothelial-to-mesenchymal transition (EndMT) in pulmonary artery endothelial cells (PAECs) is a pivotal trigger initiating this remodeling. However, the regulatory mechanisms underlying EndMT in PH are still not fully understood. Methods Cytokine-induced hPAECs were assessed using RNA methylation quantification, qRT-PCR, and western blotting to determine the involvement of N6-methyladenosine (m6A) methylation in EndMT. Lentivirus-mediated silencing, overexpression, tube formation, and wound healing assays were utilized to investigate the function of METTL3 in EndMT. Endothelial-specific gene knockout, hemodynamic measurement, and immunostaining were performed to explore the roles of METTL3 in pulmonary vascular remodeling and PH. RNA-seq, RNA Immunoprecipitation-based qPCR, mRNA stability assay, m6A mutation, and dual-luciferase assays were employed to elucidate the mechanisms of RNA methylation in EndMT. Results The global levels of m6A and METTL3 expression were found to decrease in TNF-α- and TGF-β1-induced EndMT in human PAECs (hPAECs). METTL3 inhibition led to reduced endothelial markers (CD31 and VE-cadherin) and increased mesenchymal markers (SM22 and N-cadherin) as well as EndMT-related transcription factors (Snail, Zeb1, Zeb2, and Slug). The endothelial-specific knockout of Mettl3 promoted EndMT and exacerbated pulmonary vascular remodeling and hypoxia-induced PH (HPH) in mice. Mechanistically, METTL3-mediated m6A modification of kruppel-like factor 2 (KLF2) plays a crucial role in the EndMT process. KLF2 overexpression increased CD31 and VE-cadherin levels while decreasing SM22, N-cadherin, and EndMT-related transcription factors, thereby mitigating EndMT in PH. Mutations in the m6A site of KLF2 mRNA compromise KLF2 expression, subsequently diminishing its protective effect against EndMT. Furthermore, KLF2 modulates SM22 expression through direct binding to its promoter. Conclusions Our findings unveil a novel METTL3/KLF2 pathway critical for protecting hPAECs against EndMT, highlighting a promising avenue for therapeutic investigation in PH.

The purpose of this study is to explore the possibility of gold tailings as an alternative to natural river sand for preparing concrete, to solve the problems of rapid increase in gold tailings and insufficient natural river sand stock. Additionally, gold tailings upgraded by centrifugal separation are compared with untreated gold tailings. The performances and modification mechanisms of gold tailings on the mechanical strength and durability performance of concrete were investigated. The results demonstrate that concrete composed of gold tailings exhibits commendable mechanical and durability properties, with the optimal replacement level of natural river sand being 30%. Replacing river sand with gold tailings enhances the compressive and split tensile strengths of concrete, reduces water absorption, and improves its resistance to freeze-thaw cycles and chloride ion permeability, primarily owing to the pozzolanic activity and filling effect of the gold tailings. The upgrading of gold tailings not only changed altered the particle size but also changed the active SiO2 and Al2O3 content, thus, further enhancing the mechanical and durability of concrete. The study establishes that utilizing gold tailings in construction can serve as a viable substitute for river sand, thereby mitigating potential environmental repercussions associated with gold tailings. The findings hold promise for diminishing the reliance on river sand, thereby markedly enhancing resource sustainability.

Abstract Background Diabetic cardiomyopathy (DCM) poses a growing health threat, elevating heart failure risk in diabetic individuals. Understanding DCM is crucial, with fibroblasts and endothelial cells playing pivotal roles in driving myocardial fibrosis and contributing to cardiac dysfunction. Advances in Multimodal single-cell profiling, such as scRNA-seq and scATAC-seq, provide deeper insights into DCM’s unique cell states and molecular landscape for targeted therapeutic interventions. Methods Single-cell RNA and ATAC data from 10x Multiome libraries were processed using Cell Ranger ARC v2.0.1. Gene expression and ATAC data underwent Seurat and Signac filtration. Differential gene expression and accessible chromatin regions were identified. Transcription factor activity was estimated with chromVAR, and Cis-coaccessibility networks were calculated using Cicero. Coaccessibility connections were compared to the GeneHancer database. Gene Ontology analysis, biological process scoring, cell-cell communication analysis, and gene-motif correlation was performed to reveal intricate molecular changes. Immunofluorescent staining utilized various antibodies on paraffin-embedded tissues to verify the findings. Results This study integrated scRNA-seq and scATAC-seq data obtained from hearts of WT and DCM mice, elucidating molecular changes at the single-cell level throughout the diabetic cardiomyopathy progression. Robust and accurate clustering analysis of the integrated data revealed altered cell proportions, showcasing decreased endothelial cells and macrophages, coupled with increased fibroblasts and myocardial cells in the DCM group, indicating enhanced fibrosis and endothelial damage. Chromatin accessibility analysis unveiled unique patterns in cell types, with heightened transcriptional activity in myocardial cells. Subpopulation analysis highlighted distinct changes in cardiomyocytes and fibroblasts, emphasizing pathways related to fatty acid metabolism and cardiac contraction. Fibroblast-centered communication analysis identified interactions with endothelial cells, implicating VEGF receptors. Endothelial cell subpopulations exhibited altered gene expressions, emphasizing contraction and growth-related pathways. Candidate regulators, including Tcf21, Arnt, Stat5a, and Stat5b, were identified, suggesting their pivotal roles in DCM development. Immunofluorescence staining validated marker genes of cell subpopulations, confirming PDK4, PPARγ and Tpm1 as markers for metabolic pattern-altered cardiomyocytes, activated fibroblasts and endothelial cells with compromised proliferation. Conclusion Our integrated scRNA-seq and scATAC-seq analysis unveils intricate cell states and molecular alterations in diabetic cardiomyopathy. Identified cell type-specific changes, transcription factors, and marker genes offer valuable insights. The study sheds light on potential therapeutic targets for DCM.