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Abstract As UAVs are more and more widely used in military and civilian fields, their intelligent applications have also been developed rapidly. However, high‐precision autonomous landing is still an industry challenge. GPS‐based methods will not work in places where GPS signals are not available; multi‐sensor combination navigation is difficult to be widely used because of the high equipment requirements; traditional vision‐based methods are sensitive to scale transformation, background complexity and occlusion, which affect the detection performance. In this paper, we address these problems and apply deep learning methods to target detection in the UAV landing phase. Firstly, we optimize the backbone network of YOLOX and propose the Swin Transformer based YOLOX (Swin‐YOLOX) UAV landing visual positioning algorithm. Secondly, based on the UAV‐VPD database, a batch of actual acquisition data is added to build the UAV‐VPDV2 database by AI annotation method. And finally, the RBN data batch normalization method is used to improve the performance of the model in extracting effective features from the data. Extensive experiments have shown that the AP50 of the proposed method can reach 98.7%, which is superior to other detection models, with a detection speed of 38.4 frames/second, and can meet the requirements of real‐time detection.

Abstract. Despite quitting smoking, patients with acute coronary syndrome (ACS) still have an increased risk of cardiovascular events. Clonal hematopoiesis of indeterminate potential (CHIP), which may be induced by smoking, has been identified to be associated with the development of coronary artery disease. However, it is unclear whether CHIP has a detrimental effect on the poor prognosis of ACS patients even after smoking cessation. This single-center, prospective cohort study will recruit 1,029 ACS patients undergoing complete percutaneous coronary intervention. The enrolled patients will be categorized into 3 groups based on their smoking status at admission: current smoker, non-smoker, and previous smoker. Previous smokers are defined as patients who have quit smoking for at least 1 year before experiencing the index ACS event. Whole-exome sequencing will be performed to identify the occurrence of CHIP in each patient. The primary endpoint is major adverse cardiovascular and cerebrovascular events, defined as a composite of cardiac death, non-fatal myocardial infarction, ischemia-driven revascularization, hospitalization for heart failure, and ischemic stroke. The association between CHIP and the primary endpoint will be determined by using Cox proportional hazard regression. This study aims to investigate the association among smoking cessation, CHIP, and the prognosis of ACS patients to provide new insights into the impact of CHIP on ACS patients, particularly among those who have quit smoking. The results will be published following the STROBE in a peer-reviewed scientific journal (Trial registration number: NCT04987268).

Abstract In the financial sector, alternatives to traditional datasets, such as financial statements and Securities and Exchange Commission filings, can provide additional ways to describe the running status of businesses. Nontraditional data sources include individual behaviors, business processes, and various sensors. In recent years, alternative data have been leveraged by businesses and investors to adjust credit scores, mitigate financial fraud, and optimize investment portfolios because they can be used to conduct more in-depth, comprehensive, and timely evaluations of enterprises. Adopting alternative data in developing models for finance and business scenarios has become increasingly popular in academia. In this article, we first identify the advantages of alternative data compared with traditional data, such as having multiple sources, heterogeneity, flexibility, objectivity, and constant evolution. We then provide an overall investigation of emerging studies to outline the various types, emerging applications, and effects of alternative data in finance and business by reviewing over 100 papers published from 2015 to 2023. The investigation is implemented according to application scenarios, including business return prediction, business risk management, credit evaluation, investment risk prediction, and stock prediction. We discuss the roles of alternative data from the perspective of finance theory to argue that alternative data have the potential to serve as a bridge toward achieving high efficiency in financial markets. The challenges and future trends of alternative data in finance and business are also discussed.

Abstract TnpB proteins encoded in the IS200/IS605 family are RNA-guided endonuclease which can be harnessed in genome editing. However, the collateral nuclease activity of TnpB remains poorly understood, which limits the development of TnpB-based diagnostic tools. Here we showed that TnpB from a thermophilic archaeon exhibits enhanced collateral ssDNA cleavage activity (trans-cleavage) activated by high temperature. Mutations either in the TAM or seed sequences of the target DNA impair the trans-cleavage activity, which indicates its potential to be employed in molecular diagnostic. Importantly, by optimizing the length and the sequences of the collateral substrates, we have developed a new nucleic acid detection method based on TnpB with a sensitivity of 29 cp μl−1 in 30 min, which we name it TESD (TnpB Enable fast and Sensitive Detection). In summary, our findings illustrate the collateral nuclease activity of a TnpB from thermophiles and provide a novel platform for molecular diagnostics.

Abstract Background Tracheobronchial mucormycosis is a fatal opportunistic infection that mainly causes airway stenosis and is difficult to manage clinically. Case presentation We report a case of severe tracheal stenosis caused by tracheobronchial mucormycosis in a 37-year-old female with a history of hyperthyroidism. She developed agranulopenia after oral methimazole administration and subsequently experienced asthma with dyspnea. Bronchoscopy, sputum culture, colony mass spectrometry, and microscopic cotton orchid staining confirmed tracheobronchial mucormycosis. The patient received venous-venous extracorporeal membrane oxygenation (VV-ECMO) and prolonged intratracheal instillation of amphotericin B (AmBD), combined with amphotericin B liposome (L-AmB) and isavuconazole intravenous infusion, ultimately resulting in successful treatment. Conclusion VV-ECMO combined with prolonged intratracheal instillation of AmBD is an effective method for the treatment of tracheobronchial mucormycosis.

Abstract Background Epidemiological studies investigating the association between flavonoid intake and bone mineral density (BMD) draw inconsistent conclusions. Our study aims to investigate the association between flavonoid intake and BMD and osteoporosis and the mediating role of composite dietary antioxidant index (CDAI) in their relationship using data from the National Health and Nutrition Examination Survey (NHANES). Methods The study assessed the relationship between flavonoid intake and femur BMD and osteoporosis in 10,225 individuals from NHANES 2007–2010 and 2017–2018. Multivariable linear regression analyses were used to detect the association between flavonoid intake and femur BMD in adult Americans. Restricted cubic splines (RCS) were used to examine the nonlinear relationship between flavonoid intake and their subclasses and osteoporosis risk in individuals 20 years or older. We explored the mediating role of CDAI in the association between flavonoid intake and BMD. Results In fully adjusted multivariable regression analyses, compared with people in the first quartile, people in the fourth quartile of total flavonoid intake have a higher BMD at total femur (0.013, 95% CI: 0.004, 0.022, P = 0.001), femur neck (0.010, 95% CI: 0.004, 0.017, P = 0.001), trochanter (0.010, 95% CI: 0.004, 0.017, P = 0.001), and intertrochanter (0.012, 95% CI: 0.003, 0.020, P = 0.006). The positive relationship between flavonoid intake and femur BMD was present in both sexes. Furthermore, we found that people in the fourth quartile of total flavonoid intake have a lower risk of osteoporosis compared with the first quartile (OR = 0.686, 95% CI: 0.528–0.890, P = 0.005). RCS found a linear inverse relationship between total flavonoid intake and osteoporosis in individuals ≥ 20 years (Overall P = 0.015, nonlinear P = 0.086). Moreover, CDAI partially mediates the association of total flavonoid intake with femur BMD. Conclusions Our findings suggest that higher flavonoid intake is associated with higher BMD and lower risk of osteoporosis in Americans. Furthermore, we found distinct associations between different flavonoid subclasses and osteoporosis risk. More studies with stronger evidence are needed to explore the causal association between flavonoid intake and bone health and their underlying mechanisms.

Abstract Many plants associate with endophytic microbes that improve root phosphorus (P) uptake. Understanding the interactions between roots and endophytes can enable efforts to improve P utilization. Here, we characterize the interactions between lateral roots of endophytes in a core collection of 50 rapeseed (Brassica napus L.) genotypes with differing sensitivities to low P conditions. With the correlation analysis result between bacterial abundance and plant physiological indices of rapeseeds, and inoculation experiments on plates and soil, we identify one Flavobacterium strain (C2) that significantly alleviates the P deficiency phenotype of rapeseeds. The underlying mechanisms are explored by performing the weighted gene coexpression network analysis (WGCNA), and conducting genome-wide association studies (GWAS) using Flavobacterium abundance as a quantitative trait. Under P-limited conditions, C2 regulates fatty acid and lipid metabolic pathways. For example, C2 improves metabolism of linoleic acid, which mediates root suberin biosynthesis, and enhances P uptake efficiency. In addition, C2 suppresses root jasmonic acid biosynthesis, which depends on α-linolenic acid metabolism, improving C2 colonization and activating P uptake. This study demonstrates that adjusting the endophyte composition can modulate P uptake in B. napus plants, providing a basis for developing agricultural microbial agents.

Abstract Background A given movement requires precise coordination of multiple muscles under the control of center nervous system. However, detailed knowledge about the changing characteristics of neuromuscular control for multi-muscle coordination in post-stroke hemiplegic patients during standing is still lacking. This study aimed to investigate the hemiplegia-linked neuromuscular dysfunction during standing from the perspective of multi-muscle dynamical coordination by utilizing a novel network approach – weighted recurrence network (WRN). Methods Ten male hemiplegic patients with first-ever stroke and 10 age-matched healthy male adults were instructed to stand on a platform quietly for 30 s with eyes opened and eyes closed, respectively. The WRN was constructed based on the surface electromyography signals of 16 muscles from trunk, hips, thighs and calves. Relevant topological parameters, including clustering coefficient (C) and average shortest path length (L), were extracted to evaluate the dynamical coordination of multiple muscles. A measure of node centrality in network theory, degree of centrality (DC), was innovatively introduced to assess the contribution of single muscle in the multi-muscle dynamical coordination. The standing-related assessment metric, center of pressure (COP), was provided by the platform directly. Results Results showed that the post-stroke hemiplegic patients stood with remarkably higher similarity of muscle activation and more coupled intermuscular dynamics, characterized by higher C and lower L than the healthy subjects (p

Abstract Background It is very important to provide the correct nursing care for patients with intracerebral hemorrhage (ICH), but the level of critical care needs in patients with intracerebral hemorrhage is not clear. The purpose of this study is to establish a risk model based on the epidemiological and clinical characteristics of ICH patients, to help identify the critical care needs of ICH patients. Methods The clinical data of ICH patients from January 2018 to September 2023 were analyzed retrospectively. The full cohort was used to derive the clinical prediction model and the model was internally validated with bootstrapping. Discrimination and calibration were assessed using the area under curve (AUC) and the Hosmer-Lemeshow tests, respectively. Results 611 patients with ICH were included for model development. 61.21% (374/611) ICH patients had received critical care interventions. The influencing factors included in the model were Glasgow Coma Scale (GCS) score, intraventricular hemorrhage, past blood pressure control, systolic blood pressure on admission and bleeding volume. The model’s goodness-of-fit was evaluated, which yielded a high area under the curve (AUC) value of 0.943, indicating a good fit. For the purpose of model validation, a cohort of 260 patients with ICH was utilized. The model demonstrated a Youden’s index of 0.750, with a sensitivity of 90.56% and a specificity of 78.22%. Conclusion GCS, systolic blood pressure, intraventricular hemorrhage, bleeding volume and past blood pressure control are the main factors affecting the critical care needs of patients with ICH. This study has deduced a clinical predictive model with good discrimination and calibration to provide scoring criteria for clinical health care providers to accurately evaluate and identify the critical care needs of ICH patients, to improve the rational integration and allocation of medical resources.

Abstract Background Valvular heart disease is the third most common cardiovascular disease; it significantly diminishes patients’ quality of life and imposes burdens on individuals, families, and healthcare systems. In recent years, psycho-cardiology has emerged as a prominent field in which to explore the link between mental illness and heart disease. This mixed-method study aims to assess the effectiveness of the WCPP, which includes hospital-to-home transitional care, remote intelligent monitoring, and decision aids, in improving the physical and mental health of patients. Methods A mixed-method study was conducted at a cardiac valve interventional surgery (CVIS) center in Southwest China. A total of 154 CVIS patients participated, with the intervention group receiving the WCPP and the control group following the traditional CVIS management program. Both groups were followed up at 1, 3, 6, and 12 months. The primary outcome is measured via the Chinese version of the 36-item Short Form Health Survey (SF-36). The Secondary outcomes included the 6-min walk test (6MWT), modified Barthel index (MBI), major adverse cardiovascular events (MACE), patient satisfaction, and length of hospital stay (LOS). Additionally, qualitative research will assess the psychological state and experiences of the patients. Discussion Our study is one of the few involving patients with CVIS and the first to apply psycho-cardiology through a full-process management platform. The study population is predominantly from Southwest China and includes a diverse range of demographic and socioeconomic backgrounds. Upon completion, this study will provide valuable insights into the use of a remote, full-process management platform for CVIS patients. Trial registration Chinese Clinical Trial Registry ChiCTR2400081052. Registered on 21 February 2024. The trial complies with the SPIRIT and CONSORT guidelines.

Abstract As a powerful eukaryotic expression vector, the baculovirus expression vector system (BEVS) is widely applied to the production of heterogeneous proteins for research and pharmaceutical purposes, while optimization of BEVS remains a work in progress for membrane or secreted protein expression. In this study, the impact of the signal peptide (SP) derived from Bombyx mori nucleopolyhedrovirus (BmNPV) GP64 protein on protein expression, secretion, and the endoplasmic reticulum-associated degradation (ERAD) pathway were investigated in BmN cells and BEVS. Transient expression studies in BmN cells revealed that SP alters the localization and expression levels of recombinant proteins, reducing intracellular accumulation while enhancing secretion efficiency. Quantitative analysis demonstrated that SP-mediated secretion was markedly higher compared to controls, albeit with lower total expression levels. Further exploration into SP-mediated ERAD pathway activation showed increased expression of BiP and other ERAD-associated genes (PDI, UFD1, S1P, and ASK1), correlating with higher SP-driven protein expression levels. RNA interference (RNAi) experiments elucidated that knockdown of ERAD-associated genes enhances both the secretion efficiency of SP-guided proteins and the infectivity of BmNPV. Particularly, interference with BiP demonstrated the most pronounced effect on protein secretion enhancement. Viral infection experiments further supported these findings, showing upregulated ERAD-associated genes during BmNPV infection, indicating their role in viral protein processing and infectivity. In conclusion, this study elucidates the complex interplay between SP-mediated protein secretion, ERAD pathway activation, and viral infectivity in BmNPV-infected cells. These insights suggest strategies for optimizing recombinant protein production and viral protein processing in baculovirus expression systems, with potential implications for biotechnological and biomedical applications. Further research could refine our understanding and manipulation of protein secretion pathways in insect cell-based expression systems.

Abstract Background Carbapenem-resistant and hypervirulent Klebsiella pneumoniae (CR-hvKP) caused infections of high mortality and brought a serious impact on public health. This study aims to evaluate the epidemiology, resistance and virulence characteristics of CR-hvKP and to identify potential drivers of cross-regional transmission in different regions of China, in order to provide a basis for developing targeted prevention measures. Methods Clinical K. pneumoniae strains were collected from Jiujiang and Nanchang in Jiangxi province between November 2021 to June 2022. Clinical data of patients (age, sex, source of infection, and diagnosis) were also gathered. We characterized these strains for their genetic relatedness using PFGE, antimicrobial and virulence plasmid structures using whole-genome sequencing, and toxicity using Galleria mellonella infection model. Results Among 609 strains, 45 (7.4%) CR-hvKP were identified, while the strains. isolated from Nanchang and Jiujiang accounted for 10.05% (36/358) and 3.59% (9/251). We observed that ST11-KL64 CR-hvKP had an overwhelming epidemic dominance in these two regions. Significant genetic diversity was identified among all ST11-KL64 CR-hvKP cross-regional transmission between Nanchang and Jiujiang and this diversity served as the primary driver of the dissemination of clonal groups. Virulence genes profile revealed that ST11-KL64 CR-hvKP might harbour incomplete pLVPK-like plasmids and primarily evolved from CRKP by acquiring the hypervirulence plasmid. We found the predominance of truncated-IncFIB/IncHI1B type virulence plasmids with a 25 kb fragment deletion that encoded iroBCDN clusters. Conclusion ST11-KL64 is the most cross-regional prevalent type CR-hvKPs in Jiangxi province, which mainly evolved from CRKPs by acquiring a truncated-IncHI1B/IncFIB virulence plasmid with the deletion of iroBCDN. Stricter surveillance and control measures are urgently needed to prevent the epidemic transmission of ST11-KL64 CR-hvKP.

Abstract Telomerase reverse transcriptase promoter (TERTp) mutations are associated with non-radioiodine avidity. However, the role of these mutations in the clinical outcomes of patients with radioiodine-refractory differentiated thyroid cancer (RAIR-DTC) remains unknown. Herein, we aim to analyze gene mutations and clinical manifestations to verify TERTp’s role in driving disease progression to RAIR-DTC and clinical outcomes. Next-generation sequencing data and clinical data were obtained from 243 patients with DTC. Of the 25 patients with TERTp mutations, 80% (20/25) had RAIR-DTC. RAIR-DTC was significantly less prevalent in patients with BRAF V600E (9/143, 6.3%) than those with both BRAF V600E and TERTp mutations (14/17, 82.4%). Patients with RAIR-DTC harboring both BRAF V600E and TERTp mutations were more likely to have > 3 distant metastatic sites (85.7%, 12/14) than those with BRAF V600E alone (33.3%, 3/9). Only one patient with both BRAF V600E and TERTp mutations had non-RAIR-DTC. The time from initial radioactive iodine therapy to RAIR-DTC diagnosis was significantly shorter in patients with TERTp mutations than in those without. Patients with BRAF V600E and TERTp mutations progressed faster to RAIR-DTC than those with BRAF V600E alone (p

Abstract Background To investigate the association of vitamin D receptor (VDR) gene polymorphism with caries risk in children(

Abstract Underground rocks are generally subjected to water erosion and dynamic disturbances. To exclude the effect of clay minerals on the water–rock interaction mechanism, clay-free artificial porous rock (APR) was used to investigate the coupling effect of water saturation and loading rate on tensile behavior. Dynamic Brazilian disc experiments were performed on APR with six water saturation levels (100, 80, 60, 40, 20, and 0%) using a split Hopkinson pressure bar (SHPB) combined with a high-speed camera. The results indicated that the number of cracks in the APR specimens increased with the water saturation level during the dynamic damage process, with more radial cracks at the water saturation of 80–100%. The dynamic tensile strength (DTS) and dissipated energy density exhibited different change trends with water saturation levels under different loading rates and the rate dependence was most significant in the fully saturated state (100%). At lower loading rates, DTS initially decreased rapidly and then more slowly with increasing water saturation. At higher loading rates, DTS exhibited a ‘decrease then increase’ trend. Moreover, the water-affecting factor exhibited an overall decreasing trend with the loading rate and gradually converged to 1.0. These phenomena can be attributed to the interplay between the weakening and strengthening water-effect mechanisms based on the microstructure and water distribution in the APR specimens.

Abstract Objective The purpose of this study was to compare the analgesic effects of intercostal nerve block (ICNB) and local anesthetic infiltration (LAI) on postoperative pain and recovery following thoracoscopic resection of pulmonary bullae. Methods A total of 160 patients undergoing thoracoscopic pulmonary bullae resection were randomly assigned to receive either ICNB (n = 80) or LAI (n = 80). An experienced anesthesiologist administered ultrasound guided ICNB at the T4 and T7 levels with 5 mL of 0.375% ropivacaine hydrochloride for the ICNB group. Instead, the LAI group received 10 mL of the same concentration of ropivacaine hydrochloride at the same concentration used for ICNB for infiltration anesthesia at the incision sites. Out of the initial cohort, 146 patients completed the study (ICNB group, n = 71; LAI group, n = 75). The collected data included preoperative clinical characteristics, visual analog scale (VAS) scores for pain at various time points post-surgery (6, 12, 24, 48, and 72 h). Additionally, the Quality of Recovery-15 (QoR-15) questionnaire was administered 24 h after surgery, and sleep quality was evaluated using the Pittsburgh Sleep Quality Index (PSQI). Results No significant differences were found in drainage volume, use of additional analgesics, duration of chest tube placement, or hospital stay between the two groups. However, the ICNB group had significantly lower VAS scores and QoR-15 scores 24 h postoperatively (p

An in-depth understanding of the mechanical properties and damage and fracture mechanism of selected rocks in a diversion tunnel plays an important role in promoting the efficient construction and safety of rock blasting excavation in a diversion tunnel. To study the mechanical properties and damage evolution characteristics of selected rocks in diversion tunnels under uniaxial loading, the uniaxial compression and uniaxial splitting tests of granite and tuff were carried out. In terms of mechanical properties, the evolution characteristics of complete stress-strain curves, instantaneous modulus-strain curves, and input energy density-strain curves were analyzed. In the aspect of damage characteristics, the macroscopic and mesoscopic failure modes were analyzed and the damage fracture mechanism was revealed. Compression-shear failure mainly occurred in granite and tuff under uniaxial compression, showing the characteristics of elastic-brittle fracture failure. Both granite and tuff showed a failure mode of coexistence of “compression-shear failure zone at the loading ends” and “tension-shear failure zone in the middle” under uniaxial splitting. The compression-shear fracture of granite was relatively smooth, and the matrix and mineral particles produced fine particles due to friction in the process of shear slip. The compression-shear fracture of tuff was relatively rough and the characteristics of shear slip were not prominent enough. The fracture failure of granite and tuff was mainly caused by the common fracture of rock matrix and mineral particles. Based on the Lemaitre equivalent strain principle, the pre-peak-post-peak two-stage damage constitutive model established by Weibull statistical distribution theory can accurately describe the static stress-strain relationships of granite and tuff under uniaxial compression.

Recent studies on male infertility reveal a growing worry: more infertile men are dealing with inflammation in the testis. Analyzing testicular biopsies from infertile men highlights a significant presence of inflammation. This connection, supported by clinical and pathological evidence, emphasizes that testicular inflammation hampers sperm production, leading to lasting declines in sperm count and quality. However, the exact reasons behind male infertility due to orchitis, a type of testicular inflammation, are still uncertain. Understanding these fundamental aspects of molecular signals and cellular mechanisms in testicular inflammation is crucial. Our review delves into recent literature with a dual objective: elucidating potential mechanisms involving immune cells, non-immune cells, and cytokines that link orchitis to male infertility, while also paving the way for precise interventions and solutions to address the challenges of male infertility.

Abstract An increasing number of studies indicate that long noncoding RNAs (lncRNAs) play important roles in tumour proliferation, migration and other vital processes and are expected to become novel biomarkers for early cancer screening. The expression of the lncRNA NBR2 (adjacent breast cancer suppressor BRCA1) has been found to decrease in several cancer types. However, it is still unknown whether the lncRNA NBR2 is involved in breast cancer and autophagy. According to the Kaplan–Meier plotter survival curve analysis, the survival rate of the group with high lncRNA-NBR2 expression was higher than that of the group with low lncRNA-NBR2 expression. The suppression of cancer cell proliferation, invasion and migration by the lncRNA NBR2 has been demonstrated, suggesting that this lncRNA is involved in the development and progression of cancer. Our subsequent study revealed that the lncRNA NBR2 inhibited autophagy in breast cancer cells, and that starvation conditions enhanced this inhibitory effect. Moreover, this lncRNA changed the proliferation ability of breast cancer cells by affecting protective autophagy. The aim of this study was to investigate the link between starvation and lncRNAs by evaluating changes in autophagy-related proteins, cell proliferation and other biological processes. Together, these studies provide strategies for the early screening of breast cancer and suggest that starvation therapy can be used as a new approach for the treatment of cancer.

Abstract Thorough investigation into the laws governing frozen rock damage in high-altitude and cold regions can offer valuable insights for advancing infrastructure construction, ecological environment protection, and sustainable development on the Qinghai-Xizang Plateau. This study combined with the seasonal variation patterns of frozen rocks in the Qinghai-Xizang Plateau, and processed the rock samples using a freeze–thaw interval of -20 °C~20 °C. Uniaxial compression test was conducted based on the MTS816 rock mechanics testing system. The porosity changes of rock samples with different freeze–thaw cycles were analyzed using the MesoMR12-060 H-I nuclear magnetic response analysis system. A rock freeze–thaw load coupled damage constitutive model was derived using the Lemaitre equivalent strain theory. Research has shown that during the freezing process, the pore water inside the rock sample is affected by the phase change of water-ice, resulting in frost heave force, which further promotes the expansion of the pore walls and the initiation of new cracks. When melted, pore water migrates towards newly formed micropores, thereby affecting the changes in the pores of rock samples. The increase in porosity at the micro level weakens the mechanical parameters of rocks at the macro level. The segmented freeze–thaw damage constitutive model based on Lemaitre equivalent strain theory can well fit the experimental results involved in this study, as well as the experimental results obtained by other researchers. The compaction stage can partially reflect the changes in sandstone pore structure under freeze–thaw cycles.

Abstract Background Chimeric antigen receptor (CAR)-T therapy has emerged as a promising treatment for hematologic malignancies. However, cytopenia remains one of the most frequent and challenging adverse effects of this therapy. Methods We conducted a retrospective analysis of 26 patients with relapsed/refractory aggressive B-cell lymphoma who received CAR-T therapy at our center. Subsequently, to investigate measures to address cytopenias following CAR-T therapy, we isolated and generated murine CAR-T cells and bone marrow-derived mesenchymal stem cells (MSCs), establishing a murine syngeneic CAR-T therapy model. We assessed the impact of MSC infusion on hematopoietic recovery post-CAR-T therapy by evaluating complete blood count, bone marrow hematopoietic stem cells and their subpopulations, bone marrow histomorphology, and hematopoiesis-related genes. Results All patients experienced cytopenias to varying degrees, with complete lineage involvement in half of the patients. Grade ≥ 3 cytopenias were observed in 88.46% of the patients. CAR-T therapy was associated with a higher incidence of biphasic, late-onset, or prolonged cytopenias. Survival analysis indicated that neutropenia and lymphopenia tended to be associated with better prognosis, whereas thrombocytopenia tended to be related to poorer outcomes. Through animal experiments, we discovered that MSCs infusion boosted HSCs and their long-term subpopulations, enhancing hematopoietic recovery, particularly in the megakaryocyte lineage, and mitigating bone marrow damage. Importantly, both in vitro and in vivo experiments demonstrated that MSCs did not compromise the activity or antitumor efficacy of CAR-T cells. Conclusions Our findings propose MSCs infusion as a promising strategy to address cytopenias, particularly thrombocytopenia, after CAR-T therapy. This approach could help overcome certain limitations of cellular immunotherapy by enhancing hematopoietic recovery without compromising the efficacy of CAR-T cells. Highlights 1 Cytopenia is a frequently observed adverse effect following CAR-T therapy, and it is often characterized by biphasic and prolonged patterns. 2 MSCs play a critical role in promoting hematopoietic recovery and mitigating bone marrow damage in a murine model of CAR-T therapy 3 The activity and antitumor efficacy of CAR-T cells were not impaired by MSCs. Graphical Abstract

Abstract Dementia represents a significant global health challenge, with early screening during the preclinical stage being crucial for effective management. Traditional diagnostic biomarkers for Alzheimer’s Disease, the most common form of dementia, are limited by cost and invasiveness. Mild cognitive impairment (MCI), a precursor to dementia, is currently identified through neuropsychological tests like the Montreal Cognitive Assessment (MoCA), which are not suitable for large-scale screening. Eye-tracking technology, capturing and quantifying eye movements related to cognitive behavior, has emerged as a promising tool for cognitive assessment. Subtle changes in eye movements could serve as early indicators of MCI. However, the interpretation of eye-tracking data is challenging. This study introduced a dementia screening tool, VR Eye-tracking Cognitive Assessment (VECA), using eye-tracking technology, machine learning, and virtual reality (VR) to offer a non-invasive, efficient alternative capable of large-scale deployment. VECA was conducted with 201 participants from Shenzhen Baoan Chronic Hospital, utilizing eye-tracking data captured via VR headsets to predict MoCA scores and classify cognitive impairment across different educational backgrounds. The support vector regression model employed demonstrated a high correlation (0.9) with MoCA scores, significantly outperforming baseline models. Furthermore, it established optimal cut-off scores for identifying cognitive impairment with notable sensitivity (88.5%) and specificity (83%). This study underscores VECA’s potential as a portable, efficient tool for early dementia screening, highlighting the benefits of integrating eye-tracking technology, machine learning, and VR in cognitive health assessments.

Abstract Background Myocardial infarction with non-obstructive coronary arteries (MINOCA) is a rare cause of heart attack, which may not receive sufficient attention from patients during post-discharge treatment, especially among those with normal coronary angiography results. Case presentation We present the case of a 65-year-old woman who was readmitted to the hospital with ventricular septal rupture (VSR) complicated by ventricular aneurysm, occurring 2 weeks after myocardial infarction. During the initial admission, coronary angiography revealed normal coronary arteries, leading to a diagnosis of MINOCA. Epicardial coronary vasospasm or coronary embolism was considered as potential causes; however, the patient did not adhere to standardized treatment upon initial discharge. The delayed VSR led to a decline in cardiac function but did not result in severe hemodynamic impairment. Following correction of heart failure with medications, the patient underwent percutaneous VSR repair 19 days after diagnosis and was discharged with a favorable recovery. Conclusions The occurrence of delayed VSR complicated with ventricular aneurysm in patients with MINOCA is rare, highlighting the possibility of serious complications in MINOCA cases. Both cardioprotective therapies and cause-targeted therapies are essential in the management of patients with MINOCA.

Abstract Background and Objective Klotho is a protein that is closely related to human aging. Soluble Klotho (S-Klotho) is a circulating protein, and its level decreases in response to systemic inflammation. The relationship between the platelet/high-density lipoprotein cholesterol ratio (PHR), an emerging inflammatory index, and S-Klotho concentrations is still unclear. In addition, the mean platelet volume has been confirmed to have a significant negative association with S-Klotho concentrations, but the relationship between the platelet count (PC) and S-Klotho concentrations has not yet been reported. Methods Data from individuals who participated in the National Health and Nutrition Examination Survey (NHANES) during the five cycles from 2007 to 2016 were retrieved for analysis. Linear regression, two-piecewise linear regression, and restricted cubic spline (RCS) methods were used to analyze the associations of the PHR index and its components with S-Klotho concentrations. In addition, subgroup analysis and effect modification tests were conducted. Results A total of 11,123 participants (5463 men (48.17%)), with an average age of 56.2 years, were included. After full adjustment, the S-Klotho levels of participants in the highest quartile group of PHR (β: -51.19, 95% CI: -75.41 to -26.97, P

Abstract Plastic pollution is an emerging environmental issue, with microplastics and nanoplastics raising health concerns due to bioaccumulation. This work explored the impact of polystyrene nanoparticle (PS-NPs) exposure during prepuberty on male reproductive function post maturation in rats. Rats were gavaged with PS-NPs (80 nm) at 0, 3, 6, 12 mg/kg/day from postnatal day 21 to 95. PS-NPs accumulated in the testes and reduced sperm quality, serum reproductive hormones, and testicular coefficients. HE staining showed impaired spermatogenesis. PS-NPs disrupted the blood-testis barrier (BTB) by decreasing junction proteins, inducing inflammation and apoptosis. Transcriptomics identified differentially expressed genes related to metabolism, lysosome, apoptosis, and TLR4 signaling. Molecular docking revealed Cordycepin could compete with polystyrene for binding to TLR4. Cordycepin alleviated oxidative stress and improved barrier function in PS-NPs treated Sertoli cells. In conclusion, prepubertal PS-NPs exposure induces long-term reproductive toxicity in male rats, likely by disrupting spermatogenesis through oxidative stress and BTB damage. Cordycepin could potentially antagonize this effect by targeting TLR4 and warrants further study as a protective agent. This study elucidates the mechanisms underlying reproductive toxicity of PS-NPs and explores therapeutic strategies.

Abstract Background Rating scales and linear indices of surface electromyography (sEMG) cannot quantify all neuromuscular conditions associated with ankle-foot dysfunction in hemiplegic patients. This study aimed to reveal potential neuromuscular conditions of ankle-foot dysfunction in hemiplegic patients by nonlinear network indices of sEMG. Methods Fourteen male patients with hemiplegia and 10 age- and sex-matched healthy male adults were recruited and tested in static standing position. The characteristics of the root mean square (RMS), median frequency (MF), and three nonlinear indices, the clustering coefficient (C), the average shortest path length (L), and the degree centrality (DC), of eight groups of muscles in bilateral calves were observed. Results Compared to those of the control group, the RMS of the medial gastrocnemius (MG), flexor digitorum longus (FDL), and extensor digitorum longus (EDL) on the affected side were significantly lower (P

Abstract Accurate diagnosis of white blood cells from cytopathological images is a crucial step in evaluating leukaemia. In recent years, image classification methods based on fully convolutional networks have drawn extensive attention and achieved competitive performance in medical image classification. In this paper, we propose a white blood cell classification network called ResNeXt-CC for cytopathological images. First, we transform cytopathological images from the RGB color space to the HSV color space so as to precisely extract the texture features, color changes and other details of white blood cells. Second, since cell classification primarily relies on distinguishing local characteristics, we design a cross-layer deep-feature fusion module to enhance our ability to extract discriminative information. Third, the efficient attention mechanism based on the ECANet module is used to promote the feature extraction capability of cell details. Finally, we combine the modified softmax loss function and the central loss function to train the network, thereby effectively addressing the problem of class imbalance and improving the network performance. The experimental results on the C-NMC 2019 dataset show that our proposed method manifests obvious advantages over the existing classification methods, including ResNet-50, Inception-V3, Densenet121, VGG16, Cross ViT, Token-to-Token ViT, Deep ViT, and simple ViT about 5.5–20.43% accuracy, 3.6–23.56% F1-score, 3.5–25.71% AUROC and 8.1–36.98% specificity, respectively.

Abstract Hailstorms, characterized by their intensity, are often accompanied by strong winds and heavy rain, posing significant destructive potential. Data indicate that the economic losses caused by hail to buildings, particularly solar panels, have been increasing annually. However, research on the hail resistance of photovoltaic panels has predominantly focused on the isolated effects of hail impacts and wind loads, neglecting the coupling effects between wind and hail. In this study, a device was designed to couple both wind and hail. The effects of turbulence, hail size, and velocity on hail impact behavior were systematically studied and quantified. A predictive formula for the peak load of hail impact on structures was established. The results indicate that the impact of turbulence on hail is significant. When turbulence intensity varies with hail velocity, hail impact force increases as turbulence decreases and hail velocity increases. When both turbulence and hail diameter vary, the impact force of smaller hailstones shows less variation with increasing turbulence. According to variance analysis, hail velocity is the most significant factor affecting hail impact, followed by hail diameter and finally turbulence. The regression equation is given by $$F = - 0.624I_{{\text{u}}} + 5116.25D + 7.85V_{hail} - 259.709$$ F = - 0.624 I u + 5116.25 D + 7.85 V hail - 259.709 , where $$F$$ F represents the peak impact force in Newtons (N), $$I_{{\text{u}}}$$ I u denotes the turbulence intensity, $$D$$ D is the hail diameter in meters (m), and $$V_{hail}$$ V hail is the hail velocity in meters per second (m/s).

Abstract The Hoek–Brown (H–B) criterion has found widespread application in numerous rock engineering projects. However, its efficacy is compromised by an underestimation of rock strength due to its neglect of the influence of the intermediate principal stress ( $$\sigma_{2}$$ σ 2 ). Experimental evidence underscores the significant impact of $$\sigma_{2}$$ σ 2 . Consequently, there exists an imperative to formulate a three-dimensional (3D) criterion. In this study, a new deviatoric function with two additional parameters ( $$k$$ k and $$A$$ A ) is developed firstly, which ensure compliance with the prerequisites of smoothness and convexity. In addition, the parameters $$k$$ k and $$A$$ A are bonded with the weakening effect of the Lode angle ( $$\theta_{\sigma }$$ θ σ ) and the strengthening effect of the mean stress ( $$\sigma_{m}$$ σ m ), respectively. Then a new 3D strength criterion for rocks is proposed by combining this new deviatoric function and the triaxial compression meridian function of the original H–B criterion. Four distinct sets of test data encompassing various rock types are employed to validate the proposed criterion. The results demonstrate that the proposed criterion adeptly captures the strength characteristics of the four rock types, providing a good depiction of failure surfaces within the 3D principal stress space. Comparative analyses involve the utilization of several existing 3D H–B criteria for strength predictions. The proposed criterion exhibits superior fitting performance for all the selected rocks.

The Anqing section of the Yangtze (Changjiang) River in Anhui Province, China, is one of the most important migratory routes and distribution of the highly valued diadromous estuarine tapertail anchovy Coilia nasus. In the past, this section has suffered a severe loss of C. nasus resources caused by human activities, especially overfishing and water pollution. Since 2019, a fishing ban policy for the species in the Yangtze River has been introduced in China for resource restoration. Otoliths are calcium carbonate structures, and otolith microchemistry can provide detailed life history information that can be used to compare habitat use between different saline water bodies. To study the habitat history of C. nasus in the Anqing section of the Yangtze River after the implementation of the fishing ban, we examined the microchemical characteristics (Sr and Ca) of otoliths from the long (previously named C. ectenes) and short maxillary (previously named C. brachygnathus) types of anchovy using electron probe X-ray microanalysis (EPMA). Line-transect analysis of Sr/Ca ratios suggested that the short maxillary type of C. nasus could be divided into two groups. The otolith Sr/Ca ratios (calculated and expressed as Sr/Ca ×1, 000) of one group were always < 3.0, indicating their freshwater residency. Those of the other group had phases of low (< 3.0, believed to be indicative of a freshwater habitat) and high values (> 3.0, believed to be indicative of a brackish or seawater habitat), indicating that anchovies not only have a freshwater habitat history with low salinity but also a brackish habitat history with high salinity. The latter group of anchovies were typically anadromous C. nasus, as the Sr/Ca ratio of the otoliths of C. nasus fluctuated significantly and coincided with variations between freshwater and estuarine brackish or seawater (i.e., anchovies experienced not only freshwater habitats but also brackish water habitats at different stages of their life history). The Sr content mapping of EPMA with different color patterns for freshwater (blue), brackish water (green-yellow) and seawater (red) habitats also confirmed the results obtained from the line-transect analysis. Our results demonstrated that the population composition of C. nasus in the Anqing section of the Yangtze river became complex, and there was coexistence of freshwater resident and anadromous C. nasus in the Anqing section of the Yangtze River in Anhui Province, China (i.e., freshwater resident and anadromous short maxillary and anadromous long maxillary type C. nasus). This phenomenon may suggest a restoration of C. nasus resource diversity after the implementation of the fishing ban in the Anqing section of the Yangtze River.

Jatropha curcas L. (J. curcas), a shrub plant of the Euphorbiaceae family, has received enormous attention as a promising biofuel plant for the production of biodiesel and medical potential in ethnopharmacology. However, the tumor-promoter toxin phorbol esters present in J. curcas raise concerns for health and environmental risk as its large-scale cultivation limits the use of meal obtained after oil extraction for animal feed. Here, we determined the variation of phorbol ester profiles and contents in eight J. curcas tissues by high-performance liquid chromatography (HPLC) and found phorbol esters present in all parts of the plant except the seed shell. We showed tissue-specific patterns of accumulation of phorbol esters and associated terpenoids at the transcriptional level with high transcript levels in reproductive and young tissues. Genes involved in the same module of terpenoids biosynthesis were positively correlated. We further present diverse abiotic and biotic stresses that had different effects on the accumulation of transcripts in terpenoids shared and branched terpenoid pathways in plant seedlings. The fine-tuning of terpenoids biosynthesis may link with ecological functions in plants under extreme environments and defense against pathogens.

The load-bearing performance (LBP) of pumpable supports (PPS) is crucial for the stability of longwall pre-driven recovery room (PRR) surrounding rock. However, the unbalanced bearing coefficient (UBC)of the PPS (undertaking unequal load along the mining direction) has not been investigated. A mechanical model of the PRR was established, considering the main roof cantilever beam structure, to derive an assessment formula for the load, the failure criteria, and the UBC of the PPS. Subsequently, the generation mechanisms, and influencing factors of the UBC were revealed. Global sensitivity analysis shows that the main roof hanging length (l2) and the spacing between the PPS (r) significantly impact the UBC. A novel design of the PPS and the coupling control technology were proposed and applied to reduce the UBC of the PPS in the adjacent longwall PRR. Monitor results showed no failure of the PPS at the test site, with the UBC (ζ) reduced to 1.1 consistent with the design value (1.15) basically, fully utilizing the collaborative LBP of the PPS. Finally, the maximum roof-to-floor convergence of the PRR was 234 mm, effectively controlling the stability of the surrounding rock of the PRR and ensuring the mining equipment recovery.

In recent years, live streaming has become the mainstream way of online shopping in China. As the dominant player and performer in live streaming, streamers play a crucial role in consumers’ purchase decisions. Therefore, this study focuses on the self-presentation behavior of streamers in the context of e-commerce live streaming and explores the mechanism of its influence on consumers’ purchase intention from the perspective of persuasion knowledge. A total of 538 consumers from China participated in this anonymous survey. The results indicate that helpful and empathetic behaviors of streamers can significantly enhance consumers’ purchase intention, while derogatory, exaggerated, and flattering behaviors of streamers can significantly diminish consumers’ purchase intention. Persuasion knowledge played a mediating role and had a significant negative impact on purchase intention, while anticipated inaction regret weakened its effect on purchase intention.

This umbrella review was conducted aiming to assess the association between genetic variations and the development of diabetic retinopathy (DR) by collecting and evaluating available systematic reviews and meta-analysis results. We evaluated the methodological quality using the Measurement Tool to Assess Systematic Reviews (AMSTAR) 2.0, estimated the summary effect size by using the random effects model and calculated the 95% prediction intervals (PIs). Evidence from the included meta-analyses was graded according to established criteria as follows: convincing, highly suggestive, suggestive, weak, or not significant. This umbrella review included 32 meta-analyses of 52 candidate SNPs. The 12 selected meta-analyses were rated as “high,” 2 studies were rated as “moderate,” 11 studies were graded as “low,” and the remaining 7 studies were graded as “critically low” in terms of methodological quality. Carriers of specific genotypes and alleles of the transcription Factor 7-like 2 C/T (TCF7L2 C/T) polymorphism (rs7903146, p < 0.001) might be more susceptible to the occurrence of DR in the homozygous and recessive models, and these associations were supported by “convincing” evidence. Significant associations were also found between interleukin-6 (IL-6) -174 G/C (rs1800795; p < 0.05) or vascular endothelial growth factor (VEGF) polymorphisms (rs2010963, rs699947, rs1570360, rs2010963, rs699947, rs2146323; all p values

Abstract Background Steroid-induced osteonecrosis of femoral head (SONFH) is a severe health risk, and this study aims to identify immune-related biomarkers and pathways associated with the disease through bioinformatics analysis and animal experiments. Method Using SONFH-related datasets obtained from the GEO database, we performed differential expression analysis and weighted gene co-expression network analysis (WGCNA) to extract SONFH-related genes. A protein-protein interaction (PPI) network was then constructed, and core sub-network genes were identified. Immune cell infiltration and clustering analysis of SONFH samples were performed to assess differences in immune cell populations. WGCNA analysis was used to identify module genes associated with immune cells, and hub genes were identified using machine learning. Internal and external validation along with animal experiments were conducted to confirm the differential expression of hub genes and infiltration of immune cells in SONFH. Results Differential expression analysis revealed 502 DEGs. WGCNA analysis identified a blue module closely related to SONFH, containing 1928 module genes. Intersection analysis between DEGs and blue module genes resulted in 453 intersecting genes. The PPI network and MCODE module identified 15 key targets enriched in various signaling pathways. Analysis of immune cell infiltration showed statistically significant differences in CD8 + t cells, monocytes, macrophages M2 and neutrophils between SONFH and control samples. Unsupervised clustering classified SONFH samples into two clusters (C1 and C2), which also exhibited significant differences in immune cell infiltration. The hub genes (ICAM1, NR3C1, and IKBKB) were further identified using WGCNA and machine learning analysis. Based on these hub genes, a clinical prediction model was constructed and validated internally and externally. Animal experiments confirmed the upregulation of hub genes in SONFH, with an associated increase in immune cell infiltration. Conclusion This study identified ICAM1, NR3C1, and IKBKB as potential immune-related biomarkers involved in immune cell infiltration of CD8 + t cells, monocytes, macrophages M2, neutrophils and other immune cells in the pathogenesis of SONFH. These biomarkers act through modulation of the chemokine signaling pathway, Toll-like receptor signaling pathway, and other pathways. These findings provide valuable insights into the disease mechanism of SONFH and may aid in future drug development efforts.

Abstract The high‐value utilization of blast furnace slag (BFS) and steel slag (SS) as a valuable resource in the field of carbon reduction represents a green revolution, and also is an indispensable path toward breaking through resource and environmental constraints and achieving high‐quality, sustainable development through solid waste utilization in the steel industry. Achieving resource recycling while harnessing the untapped latent energy of resources and exploring their carbon sequestration capabilities has become a crucial avenue for further valorization through waste utilization. BFS and SS discharged from iron‐making or steel‐making furnaces carry a significant amount of latent heat, especially the calcium oxide component in SS, which gives it a unique advantage in the field of comprehensive BFS and SS utilization and carbonation‐based SS utilization. This article discusses the current research status of low‐carbon‐waste‐heat utilization in the production of microcrystalline glass, cementitious materials, functional adsorbents, and other products through front‐end modification of molten BFS and SS. This report also provides an overview of carbon capture by utilizing BFS and SS, offering insights into the research directions for subsequent heat recovery, online quality adjustment, high‐value utilization, and carbon sequestration using BFS and SS in the steel industry.

Abstract Euglena gracilis (E. gracilis), pivotal in the study of photosynthesis, endosymbiosis, and chloroplast development, is also an industrial microalga for paramylon production. Despite its importance, E. gracilis genome exploration faces challenges due to its intricate nature. In this study, we achieved a chromosome-level de novo assembly (2.37 Gb) using Illumina, PacBio, Bionano, and Hi-C data. The assembly exhibited a contig N50 of 619 Kb and scaffold N50 of 1.12 Mb, indicating superior continuity. Approximately 99.83% of the genome was anchored to 46 chromosomes, revealing structural insights. Repetitive elements constituted 58.84% of the sequences. Functional annotations were assigned to 39,362 proteins, enhancing interpretative power. BUSCO analysis confirmed assembly completeness at 80.39%. This first high-quality E. gracilis genome offers insights for genetics and genomics studies, overcoming previous limitations. The impact extends to academic and industrial research, providing a foundational resource.

Abstract Erectile dysfunction (ED) is the most prevalent consequences in men with diabetes mellitus (DM). Recent studies demonstrates that neutrophil extracellular traps (NETs) play important roles in DM and its complications. Nevertheless, whether NETs are involved in ED remains unknown. This work intended to explore the role and mechanisms of NETs in ED in the context of DM. Here, we observed that NET generation and pyroptosis were promoted in DM rats with ED compared with controls. Mechanistically, NETs facilitated NLRP3 inflammasome activation and subsequently triggered pyroptosis under high glucose stress, ultimately leading to ED. Intriguingly, DNase I (a NET degrading agent) alleviated ED and corpus cavernosum injury in DM rats. Overall, NETs might induce ED in DM by promoting NLRP3-mediated pyroptosis in the corpus cavernosum.

Abstract Background Rabies is a fatal zoonotic disease whose pathogenesis has not been fully elucidated, and vaccination is the only effective method for protecting against rabies virus infection. Most inactivated vaccines are produced using Vero cells, which are African green monkey kidney cells, to achieve large-scale production. However, there is a potential carcinogenic risk due to nonhuman DNA contamination. Thus, replacing Vero cells with human diploid cells may be a safer strategy. In this study, we developed a novel 2BS cell-adapted rabies virus strain and analysed its sequence, virulence and immunogenicity to determine its application potential as a human diploid cell inactivated vaccine. Methods and results The 2BS cell-adapted rabies virus strain 2aG4-B40 was established by passage for 40 generations and selection of plaques in 2BS cells. RNA sequence analysis revealed that mutations in 2BS cell-adapted strains were not located at key sites that regulate the production of neutralizing antibodies or virulence in the aG strain (GQ412744.1). The gradual increase in virulence (remaining above 7.0 logLD50/ml from the 40th to 55th generation) and antigen further indicated that these mutations may increase the affinity of the adapted strains for human diploid cells. Identification tests revealed that the 2BS cell-adapted virus strain was neutralized by anti-rabies serum, with a neutralization index of 19,952. PrEP and PEP vaccination and the NIH test further indicated that the vaccine prepared with the 2aG4-B40 strain had high neutralizing antibody levels (2.24 to 46.67 IU/ml), immunogenicity (protection index 270) and potency (average 11.6 IU/ml). Conclusions In this study, a 2BS cell-adapted strain of the 2aG4 rabies virus was obtained by passage for 40 generations. The results of sequencing analysis and titre determination of the adapted strain showed that the mutations in the adaptive process are not located at key sequence regions of the virus, and these mutations may enhance the affinity of the adapted strain for human diploid cells. Moreover, vaccines made from the adapted strain 2aG4-B40 had high potency and immunogenicity and could be an ideal candidate rabies virus strain for inactivated vaccine preparation.

Abstract Pregnane X receptor (PXR) has been reported to regulate glycolipid metabolism. The dysfunction of intestinal barrier contributes to metabolic disorders. However, the role of intestinal PXR in metabolic diseases remains largely unknown. Here, we show that activation of PXR by tributyl citrate (TBC), an intestinal-selective PXR agonist, improves high fat diet (HFD)-induced obesity. The metabolic benefit of intestinal PXR activation is associated with upregulation of β-1,3 galactosyltransferase 5 (B3galt5). Our results reveal that B3galt5 mainly expresses in the intestine and is a direct PXR transcriptional target. B3galt5 knockout exacerbates HFD-induced obesity, insulin resistance and inflammation. Mechanistically, B3galt5 is essential to maintain the integrity of intestinal mucus barrier. B3galt5 ablation impairs the O-glycosylation of mucin2, destabilizes the mucus layer, and increases intestinal permeability. Furthermore, B3galt5 deficiency abolishes the beneficial effect of intestinal PXR activation on metabolic disorders. Our results suggest the intestinal-selective PXR activation regulates B3galt5 expression and maintains metabolic homeostasis, making it a potential therapeutic strategy in obesity.

BackgroundThe blastocyst-stage embryo has been considered more advantageous for increasing the cumulative live birth rate (CLBR) at fresh embryo transfer (ET) compared to the cleavage-stage embryo. However, it remains uncertain whether this advantage extends to specialized subpopulations, such as women with thin endometrium (TE), who are characteristic of impaired endometrial receptivity. Thus, this study aims to evaluate the difference in the CLBR between cleavage-stage and blastocyst-stage embryos at fresh ET specifically in women with TE.MethodsA retrospective cohort comprising 1089 women from three centers, ranging from September 2017 to January 2022, was established. These women were diagnosed with TE (defined as endometrium thickness

BackgroundAcid-sensing ion channels are activated during myocardial ischemia and are implicated in the mechanism of myocardial ischemia-reperfusion injury (MIRI). Acid-sensing ion channel 3 (ASIC3), the most pH-sensitive member of the ASIC family, is highly expressed in myocardial tissues. However, the role of ASIC3 in MIRI and its precise effects on the myocardial metabolome remain unclear. These unknowns might be related to the cardioprotective effects observed with APETx2 post-conditioning.MethodRat hearts subjected to Langendorff perfusion were randomly assigned to the normal (Nor) group, ischemia/reperfusion (I/R) group, ASIC3 blockade (AP) group. Rat hearts in group AP were treated with the ASIC3-specific inhibitor APETx2 (630 nM). Molecular and morphological changes were observed to elucidate the role of ASIC3 in MIRI. Bioinformatics analyses identified differential metabolites and pathways associated with APETx2 post-conditioning.ResultsAPETx2 post-conditioning stabilized hemodynamics in the isolated rat heart model of MIRI. It also reduced myocardial infarct size, mitigated mitochondrial damage at the ultrastructural level, and improved markers of myocardial injury and oxidative stress. Further more, we observed that phosphatidylcholine, phosphatidylethanolamine, citric acid, cyanidin 5-O-beta-D-glucoside, and L-aspartic acid decreased after MIRI. The levels of these metabolites were partially restored by APETx2 post-conditioning. These metabolites are primarily involved in autophagy and endogenous cannabinoid signaling pathways.ConclusionASIC3 is potentially a key player in MIRI. APETx2 post-conditioning may improve MIRI through specific metabolic changes. This study provides valuable data for future research on the metabolic mechanisms underlying the effects of APETx2 post-conditioning in MIRI.

Modern power systems are developing rapidly, with distributed energy, energy storage devices, adjustable loads, and other flexible resources consolidated through microgrids, virtual power plants, and integrated source–network–load–storage systems. This consolidation under various balancing zone models facilitates synergistic operations and has become critical to enhancing distributed power consumption and ensuring the reliability of electricity supply. Therefore, in light of the challenges of inadequate economic efficiency, reduced accommodation of renewable energy, and poorer operational reliability in distribution networks, this study proposes a category selection and flexibility resource scheduling method that considers the differences in multiple balancing zone models and modes. Firstly, the approach establishes a multi-dimensional characteristic evaluation index and multiple balancing zone operation models. The characteristic evaluation indicators are then utilized to assess the unique properties of the balancing zone system and eliminate unreasonable operating modes. Finally, through analyzing the effectiveness and differences of various balancing zone operation modes, an optimal operation mode is selected, and a scheduling plan is formulated. We conclude that the scheduling plan optimization method considering the operation mode can realize a reasonable choice of operation modes and achieve benefit optimization.

Time-dependent vehicle routing problem with time windows (TDVRPTW) is a pivotal problem in logistics domain. In this study, a special case of TDVRPTW with temporal-spatial distance (TDVRPTW-TSD) is investigated, which objectives are to minimize the total travel time and maximize customer satisfaction while satisfying the vehicle capacity. To address it, an improved multiobjective evolutionary algorithm (IMOEA) is developed. In the proposed algorithm, a hybrid initialization strategy with two efficient heuristics considering temporal-spatial distance is designed to generate high-quality and diverse initial solutions. Then, two crossover operators are devised to broaden the exploration space. Moreover, an efficient local search heuristic combing the adaptive large neighborhood search (ALNS) and the variable neighborhood descent (VND) is developed to improve the exploration capability. Finally, detailed comparisons with several state-of-the-art algorithms are tested on a set of instances, which verify the efficiency and effectiveness of the proposed IMOEA.

Probiotics hold great potential for treating metabolic diseases such as obesity. Given the complex and multifactorial nature of these diseases, research on probiotic combination with multiple targets has become popular. Here, we choose four obesity-related targets to perform high-throughput screening, including pancreatic lipase activity, bile salt hydrolase activity, glucagon-like peptide-1 secretion and adipocyte differentiation. Then, we obtained 649 multi-strain combinations with the requirement that each must cover all these targets in principle. After in vitro co-culture and in vivo co-colonization experiments, only four (

Hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) breast cancer is the most common subtype, representing over two-thirds of new diagnoses. Adjuvant therapy, which encompasses various medications and treatment durations, is the standard approach for managing early stage HR+ HER2- breast cancer. Optimizing treatment is essential to minimize unnecessary side effects while addressing the biological variability inherent in HR+/HER2− breast cancers. Incorporating biological biomarkers into treatment decisions, alongside traditional clinical factors, is vital. Gene expression assays can identify patients unlikely to benefit from adjuvant chemotherapy, thereby refining treatment strategies and improving risk assessment. This paper reviews evidence for several genomic tests, including Oncotype DX, MammaPrint, Breast Cancer Index, RucurIndex, and EndoPredict, which assist in tailoring adjuvant therapy. Additionally, we explore the role of liquid biopsies in personalizing treatment, emphasizing the importance of considering late relapse risks and potential benefits of extended systemic therapy for HR+/HER2− breast cancer patients.

β-N-acetylglucosaminidase (NagZ), a cytosolic glucosaminidase, plays a pivotal role in peptidoglycan recycling. Previous research demonstrated that NagZ knockout significantly eradicated AmpC-dependent β-lactam resistance in Enterobacter cloacae. However, NagZ’s role in the virulence of E. cloacae remains unclear. Our study, incorporating data on mouse and Galleria mellonella larval mortality rates, inflammation markers, and histopathological examinations, revealed a substantial reduction in the virulence of E. cloacae following NagZ knockout. Transcriptome sequencing uncovered differential gene expression between NagZ knockout and wild-type strains, particularly in nucleotide metabolism pathways. Further investigation demonstrated that NagZ deletion led to a significant increase in cyclic diguanosine monophosphate (c-di-GMP) levels. Additionally, transcriptome sequencing and RT-qPCR confirmed significant differences in the expression of ECL_03795, a gene with an unknown function but speculated to be involved in c-di-GMP metabolism due to its EAL domain known for phosphodiesterase activity. Interestingly, in ECL_03795 knockout strains, a notable reduction in the virulence was observed, and virulence was rescued upon complementation with ECL_03795. Consequently, our study suggests that NagZ’s function on virulence is partially mediated through the ECL_03795→c-di-GMP pathway, providing insight into the development of novel therapies and strongly supporting the interest in creating highly efficient NagZ inhibitors.

Objective To determine the efficacy and safety of Astragalus combined with renin-angiotensin-aldosterone system (RAAS) blockers in treating stage III diabetic nephropathy (DN) by meta-analysis.Methods PubMed, Embase, Cochrane Library, Wiley, and Web of Science databases were searched for articles published between August 2007 and August 2022. Clinical studies on Astragalus combined with RAAS blockers for the treatment of stage III DN were included. Meta-analysis was performed by RevMan 5.1 and Stata 14.3 software.Results A total of 32 papers were included in this meta-analysis, containing 2462 patients from randomized controlled trials, with 1244 receiving the combination treatment and 1218 solely receiving RAAS blockers. Astragalus combined with RAAS blockers yielded a significantly higher total effective rate (TER) (mean difference [MD] 3.63, 95% confidence interval [CI] 2.59–5.09) and significantly reduced urinary protein excretion rate (UPER), serum creatinine (Scr), blood urine nitrogen (BUN) and glycosylated hemoglobin (HbAlc) levels. In subgroup analysis, combining astragalus and angiotensin receptor blocker significantly lowered fasting plasma glucose (FPG) and 24 h urinary protein (24hUTP) levels, compared with the combined astragalus and angiotensin-converting enzyme inhibitor treatment. Meanwhile, the latter significantly decreased the urinary microprotein (β2-MG). Importantly, the sensitivity analysis confirmed the study’s stability, and publication bias was not detected for UPER, BUN, HbAlc, FPG, or β2-MG. However, the TER, SCr, and 24hUTP results suggested possible publication bias.Conclusions The astragalus-RAAS blocker combination treatment is safe and improves outcomes; however, rigorous randomized, large-scale, multi-center, double-blind trials are needed to evaluate its efficacy and safety in stage III DN.

The discovery of promising cytokines and clarification of their immunological mechanisms in controlling the intracellular fate of Mycobacterium tuberculosis (Mtb) are necessary to identify effective diagnostic biomarkers and therapeutic targets. To escape immune clearance, Mtb can manipulate and inhibit the normal host process of phagosome maturation. Phagosome maturation arrest by Mtb involves multiple effectors and much remains unknown about this important aspect of Mtb pathogenesis. In this study, we found that interleukin 16 (IL-16) is elevated in the serum samples of Tuberculosis (TB) patients and can serve as a specific target for treatment TB. There was a significant difference in IL-16 levels among active TB, latent TB infection (LTBI), and non-TB patients. This study first revealed that macrophages are the major source of IL-16 production in response to Mtb infection, and elucidated that IL-16 can promote Mtb intracellular survival by inhibiting phagosome maturation and suppressing the expression of Rev-erbα which can inhibit IL-10 secretion. The experiments using zebrafish larvae infected with M. marinum and mice challenged with H37Rv demonstrated that reducing IL-16 levels resulted in less severe pathology and improved survival, respectively. In conclusion, this study provided direct evidence that Mtb hijacks the host macrophages-derived interleukin 16 to enhance intracellular growth. It is suggesting the immunosuppressive role of IL-16 during Mtb infection, supporting IL-16 as a promising therapeutic target.