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Abstract Background Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder associated with alterations in structural and functional coupling in gray matter. However, despite the detectability and modulation of brain signals in white matter, the structure-function coupling in white matter in autism remains less explored. Methods In this study, we investigated structural-functional coupling in white matter (WM) regions, by integrating diffusion tensor data that contain fiber orientation information from WM tracts, with functional connectivity tensor data that reflect local functional anisotropy information. Using functional and diffusion magnetic resonance images, we analyzed a cohort of 89 ASD and 63 typically developing (TD) individuals from the Autism Brain Imaging Data Exchange II (ABIDE-II). Subsequently, the associations between structural-functional coupling in WM regions and ASD severity symptoms assessed by Autism Diagnostic Observation Schedule-2 were examined via supervised machine learning in an independent test cohort of 29 ASD individuals. Furthermore, we also compared the performance of multi-model features (i.e. structural-functional coupling) with single-model features (i.e. functional or structural models alone). Results In the discovery cohort (ABIDE-II), individuals with ASD exhibited widespread reductions in structural-functional coupling in WM regions compared to TD individuals, particularly in commissural tracts (e.g. corpus callosum), association tracts (sagittal stratum), and projection tracts (e.g. internal capsule). Notably, supervised machine learning analysis in the independent test cohort revealed a significant correlation between these alterations in structural-functional coupling and ASD severity scores. Furthermore, compared to single-model features, the integration of multi-model features (i.e., structural-functional coupling) performed best in predicting ASD severity scores. Conclusion This work provides novel evidence for atypical structural-functional coupling in ASD in white matter regions, further refining our understanding of the critical role of WM networks in the pathophysiology of ASD.

Abstract Background Echocardiography-based ultrasomics analysis aids Kawasaki disease (KD) diagnosis but its role in predicting coronary artery lesions (CALs) progression remains unknown. We aimed to develop and validate a predictive model combining echocardiogram-based ultrasomics with clinical parameters for CALs progression in KD. Methods Total 371 KD patients with CALs at baseline were enrolled from a retrospective cohort (cohort 1, n = 316) and a prospective cohort (cohort 2, n = 55). CALs progression was defined by increased Z scores in any coronary artery branch at the 1-month follow-up. Patients in cohort 1 were split randomly into training and validation set 1 at the ratio of 6:4, while cohort 2 comprised validation set 2. Clinical parameters and ultrasomics features at baseline were analyzed and selected for models construction. Model performance was evaluated by area under the receiver operating characteristic curve (AUROC), area under the precision-recall curve (AUPRC) and decision curve analysis (DCA) in the training and two validation sets. Results At the 1-month follow-ups, 65 patients presented with CALs progression. Three clinical parameters and six ultrasomics features were selected to construct the model. The clinical-ultrasomics model exhibited a good predictive capability in the training, validation set 1 and set 2, achieving AUROCs of 0.83 (95% CI, 0.75–0.90), 0.84 (95% CI, 0.74–0.94), and 0.73 (95% CI, 0.40–0.86), respectively. Moreover, the AUPRC values and DCA of three model demonstrated that the clinical-ultrasomics model consistently outperformed both the clinical model and the ultrasomics model across all three sets, including the training set and the two validation sets. Conclusions Our study demonstrated the effective predictive capacity of a prediction model combining echocardiogram-based ultrasomics features and clinical parameters in predicting CALs progression in KD.

Abstract Purpose The objective of this systematic review and metaanalysis is to compare the efficacy and safety of decompression alone versus decompression plus fusion in single-level lumbar spinal stenosis with spondylolisthesis. Methods A comprehensive search of the PubMed, Embase, Cochrane Library, and Ovid Medline databases was conducted to find randomized control trials (RCTs) or cohort studies that compared decompression alone and decompression plus fusion in single-level lumbar spinal stenosis with spondylolisthesis. Operation time; reoperation; postoperative complications; postoperative Oswestry disability index(ODI) scores and scores related to back and leg pain were collected from eligible studies for meta-analysis. Results We included 3 randomized controlled trials and 9 cohort studies with 6182 patients. The decompression alone group showed less operative time(P

Abstract In March 2023, our pediatric intensive care unit (PICU) retrospectively examined six cases of pediatric necrotizing tracheobronchitis (NTB), focusing on co-infections with influenza A virus (IAV) and Staphylococcus aureus (S. aureus). This study aimed to elucidate NTB’s clinical characteristics, diagnostics, and therapeutic approaches. Diagnostics included symptom assessment, microbiological testing that confirmed all patients were positive for IAV H1N1 with a predominant S. aureus co-infection, and bronchoscopy. The patients predominantly exhibited fever, cough, and dyspnea. Laboratory analysis revealed decreased lymphocyte counts and elevated infection markers like C-reactive protein and procalcitonin. Chest computed tomography (CT) scans detected tracheobronchial obstructions in half of the cases, while bronchoscopy showed severe mucosal congestion, edema, necrosis, and purulent-hemorrhagic exudates. Treatments encompassed comprehensive strategies like oxygen therapy, intubation, bronchoscopic interventions, thoracentesis, oseltamivir, and a regimen of antibiotics. Our findings suggested potential correlations between clinical markers, notably lymphocyte count and procalcitonin, and clinical interventions such as the number of rescues and intensive care unit (ICU) duration. This research highlights the importance of early detection and the role of bronchoscopy and specific markers in assessing NTB, advocating for continued research in larger cohorts to better understand its clinical trajectory and refine treatment approaches for this challenging pediatric disease.

Abstract The dehydration process is widely recognized as a significant phenomenon in nature. Hydrogels, which are important functional materials with high water content and crosslinked networks, encounter the issue of dehydration in their practical applications. Here, we report the distinctive anisotropic dehydration modality of dynamic hydrogels, which is fundamentally different from the more commonly observed isotropic dehydration of covalent hydrogels. Xerogels derived from dynamic hydrogel dehydration will fully cover a curved substrate surface and exhibit hollow structures with internal knots, in contrast to the bulk xerogels produced by covalent hydrogel dehydration. Depending on the competing cohesion of polymer chains and the adhesion at the hydrogel-substrate interface, the previously overlooked reorganization of polymer networks within dynamic hydrogels, triggered by dehydration-induced stress, has been discovered to regulate such macroscopic structural reconstruction for dynamic hydrogel dehydration. With the attached hydrogel-substrate interface, the surface microstructures of substrates can also be engraved onto xerogels with high resolution and on a large scale. This work will greatly enhance our understanding of the soft matter dehydration process and broaden the applications of dehydration technologies using water-containing materials.

Abstract Sepsis is a critical global health concern linked to high mortality rates, often due to acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). While the gut-lung axis involvement in ALI is recognized, direct migration of gut immune cells to the lung remains unclear. Our study reveals sepsis-induced migration of γδ T17 cells from the small intestine to the lung, triggering an IL-17A-dominated inflammatory response in mice. Wnt signaling activation in alveolar macrophages drives CCL1 upregulation, facilitating γδ T17 cell migration. CD44+ Ly6C– IL-7Rhigh CD8low cells are the primary migratory subtype exacerbating ALI. Esketamine attenuates ALI by inhibiting pulmonary Wnt/β-catenin signaling-mediated migration. This work underscores the pivotal role of direct gut-to-lung memory γδ T17 cell migration in septic ALI and clarifies the importance of localized IL-17A elevation in the lung.

Abstract Background The management of systemic lupus erythematosus (SLE) during pregnancy remains a challenge currently. Identifying early predictors of adverse pregnancy outcomes in SLE patients can help to develop treatment plan and improve prognosis. The aim of this study is to explore the clinical and laboratory variables in the early pregnancy that can predict adverse neonatal and maternal outcomes, thereby facilitating the grading management of SLE. Methods A retrospective analysis was conducted on 126 pregnant women with SLE who were admitted to Zhongnan Hospital of Wuhan University between January 2017 and December 2022. All enrolled patients were diagnosed (including newly diagnosed and previously diagnosed) during first trimester of pregnancy and their clinical records, laboratory results and pregnancy outcomes were reviewed. The association between the clinical and laboratory characteristics of patients at 12 gestational age and the adverse neonatal (ANOs) as well as maternal outcomes (AMOs) were analyzed. Results A total of 117 live births (92.8%) were recorded in the study. ANOs occurred in 59 (46.8%) cases, including fetal loss in 9 cases (7.1%), preterm birth in 40 cases (31.7%), small for gestational (SGA) in 15 cases (11.9%), and complete heart block in 2 cases (1.5%). Univariate analysis showed that disease activity index (P

Abstract O6-methylguanine-DNA methyltransferase (MGMT) has been demonstrated to be an important prognostic and predictive marker in glioblastoma (GBM). To establish a reliable radiomics model based on MRI data to predict the MGMT promoter methylation status of GBM. A total of 183 patients with glioblastoma were included in this retrospective study. The visually accessible Rembrandt images (VASARI) features were extracted for each patient, and a total of 14676 multi-region features were extracted from enhanced, necrotic, “non-enhanced, and edematous” areas on their multiparametric MRI. Twelve individual radiomics models were constructed based on the radiomics features from different subregions and different sequences. Four single-sequence models, three single-region models and the combined radiomics model combining all individual models were constructed. Finally, the predictive performance of adding clinical factors and VASARI characteristics was evaluated. The ComRad model combining all individual radiomics models exhibited the best performance in test set 1 and test set 2, with the area under the receiver operating characteristic curve (AUC) of 0.839 (0.709–0.963) and 0.739 (0.581–0.897), respectively. The results indicated that the radiomics model combining multi-region and multi-parametric MRI features has exhibited promising performance in predicting MGMT methylation status in GBM. The Modeling scheme that combining all individual radiomics models showed best performance among all constructed moels.

Abstract The relationship between bone mineral density and type 2 diabetes is still controversial. The aim of this study is to investigate the relationship between type 2 diabetes mellitus (T2DM) and bone mineral density (BMD) in elderly men and postmenopausal women. The participants in this study included 692 postmenopausal women and older men aged ≥ 50 years, who were divided into the T2DM group and non-T2DM control group according to whether or not they had T2DM. The data of participants in the two groups were collected from the inpatient medical record system and physical examination center systems, respectively, of the Tertiary Class A Hospital. All data analysis is performed in SPSS Software. Compared with all T2DM group, the BMD and T scores of lumbar spines 1–4 (L1–L4), left femoral neck (LFN) and all left hip joints (LHJ) in the non-T2DM group were significantly lower than those in the T2DM group (P

Abstract Abnormal trophoblast self-renewal and differentiation during early gestation is the major cause of miscarriage, yet the underlying regulatory mechanisms remain elusive. Here, we show that trophoblast specific deletion of Kat8, a MYST family histone acetyltransferase, leads to extraembryonic ectoderm abnormalities and embryonic lethality. Employing RNA-seq and CUT&Tag analyses on trophoblast stem cells (TSCs), we further discover that KAT8 regulates the transcriptional activation of the trophoblast stemness marker, CDX2, via acetylating H4K16. Remarkably, CDX2 overexpression partially rescues the defects arising from Kat8 knockout. Moreover, increasing H4K16ac via using deacetylase SIRT1 inhibitor, EX527, restores CDX2 levels and promoted placental development. Clinical analysis shows reduced KAT8, CDX2 and H4K16ac expression are associated with recurrent pregnancy loss (RPL). Trophoblast organoids derived from these patients exhibit impaired TSC self-renewal and growth, which are significantly ameliorated with EX527 treatment. These findings suggest the therapeutic potential of targeting the KAT8-H4K16ac-CDX2 axis for mitigating RPL, shedding light on early gestational abnormalities.

Background/purpose: Artificial intelligence (AI) is reshaping clinical practice in dentistry. This study aims to provide a comprehensive overview of global trends and research hotspots on the application of AI to dentistry. Materials and methods: Studies on AI in dentistry published between 2000 and 2023 were retrieved from the Web of Science Core Collection. Bibliometric parameters were extracted and bibliometric analysis was conducted using VOSviewer, Pajek, and CiteSpace software. Results: A total of 651 publications were identified, 88.7 % of which were published after 2019. Publications originating from the United States and China accounted for 34.5 % of the total. The Charité Medical University of Berlin was the institution with the highest number of publications, and Schwendicke and Krois were the most active authors in the field. The Journal of Dentistry had the highest citation count. The focus of AI in dentistry primarily centered on the analysis of imaging data and the dental diseases most frequently associated with AI were periodontitis, bone fractures, and dental caries. The dental AI applications most frequently discussed since 2019 included neural networks, medical devices, clinical decision support systems, head and neck cancer, support vector machine, geometric deep learning, and precision medicine. Conclusion: Research on AI in dentistry is experiencing explosive growth. The prevailing research emphasis and anticipated future development involve the establishment of medical devices and clinical decision support systems based on innovative AI algorithms to advance precision dentistry. This study provides dentists with valuable insights into this field.

Backgrounds: The functional recovery after peripheral nerve injury remains unsatisfactory. This study aims to perform a comprehensive evaluation of the efficacy of Fasudil Hydrochloride at treating the sciatic nerve transection injury in rats and the mechanism involved. Materials and methods: In animal experiments, 75 Sprague Dawley rats that underwent transection and repair of the right sciatic nerve were divided into a control, Fasudil, and Fas + LY group, receiving daily intraperitoneal injection of saline, Fasudil Hydrochloride (10 mg/kg), and Fasudil Hydrochloride plus LY294002 (5 mg/kg), respectively. At day 3 after surgery, the expression of ROCK2, p-PI3K, and p-AKT in L4-5 DRG and the lumbosacral enlargement was determined using Western blotting. At day 7 and 14, axon density in the distal stump was evaluated with immunostaining using the anti-Neurofilament-200 antibody. At day 30, retrograde tracing by injecting Fluoro-gold in the distal stump was performed. Three months after surgery, remyelination was analyzed with immostaining using the anti-MPZ antibody and the transmission electron microscope; Moreover, Motion-Evoked Potential, and recovery of sensorimotor functions was evaluated with a neuromonitor, Footprint, Hot Plate and Von Frey Filaments, respectively. Moveover, the Gastrocnemius muscles were weighed, and then underwent H＆E staining, and staining of the neuromuscular junction using α-Bungarotoxin to evaluate the extent of atrophy and degeneration of the endplates in the Gastrocnemius. In vitro, spinal motor neurons (SMNs) and dorsal root ganglia (DRG) were cultured to examine the impact of Fasudil Hydrochloride and LY294002 on the axon outgrowth. Results: Three days after injury, the expression of ROCK2 increased significantly (P＜0.01), and Fasudil application significantly increased the expression of p-PI3K and p-AKT in L4-6 DRG and the lumbosacral enlargement (P

When fetuses are exposed to abnormally high levels of glucocorticoids in utero, irreversible damage to neuronal synaptogenesis occurs, leading to long-term cognitive and emotional behavioral abnormalities after birth. In this study, we investigated how maternal exposure to a novel environmental pollutant—synthetic glucocorticoid dexamethasone—affects offspring cognitive and emotional behaviors enduringly. We noted that offspring subjected to maternal dexamethasone exposure (MDE) displayed cognitive and emotional neurobehavioral deficits beginning in infancy, and these impairments persisted into adulthood. The principal mechanism involves MDE-induced damage to hippocampal neuronal synapse formation in the offspring, primarily due to a cholesterol deficiency which destabilizes neuronal membranes, thereby affecting normal synapse formation and ultimately leading to cognitive and emotional deficiencies. Specifically, we demonstrated abnormal activation of glucocorticoid receptors in hippocampal astroglial cells of MDE offspring, which triggers changes in the miR-450a-3p/HAT1/ABCG1 signaling axis, causing impaired cholesterol efflux in astroglial cells and insufficient cholesterol supply to neurons, further impairing synaptogenesis. This research not only underscores the significant impact of prenatal environmental pollutants on long-term health outcomes in offspring but also broadens our understanding of how prenatal exposure to glucocorticoids affects brain development in the progeny, providing new insights for interventions in neurodevelopmental and psychiatric disorders of fetal origin.

Abstract Reprogramming tumor‐associated macrophages (TAMs) to an inflammatory phenotype effectively increases the potential of immune checkpoint blockade (ICB) therapy. Artificial mitochondrial transplantation, an emerging and safe strategy, has made brilliant achievements in regulating the function of recipient cells in preclinic and clinic, but its performance in reprogramming the immunophenotype of TAMs has not been reported. Here, the metabolism of M2 TAMs is proposed resetting from oxidative phosphorylation (OXPHOS) to glycolysis for polarizing M1 TAMs through targeted transplantation of mannosylated mitochondria (mPEI/M1mt). Mitochondria isolated from M1 macrophages are coated with mannosylated polyethyleneimine (mPEI) through electrostatic interaction to form mPEI/M1mt, which can be targeted uptake by M2 macrophages expressed a high level of mannose receptors. Mechanistically, mPEI/M1mt accelerates phosphorylation of NF‐κB p65, MAPK p38 and JNK by glycolysis‐mediated elevation of intracellular ROS, thus prompting M1 macrophage polarization. In vivo, the transplantation of mPEI/M1mt excellently potentiates therapeutic effects of anti‐PD‐L1 by resetting an antitumor proinflammatory tumor microenvironment and stimulating CD8 and CD4 T cells dependent immune response. Altogether, this work provides a novel platform for improving cancer immunotherapy, meanwhile, broadens the scope of mitochondrial transplantation technology in clinics in the future.

Objectives Diagnosis and assessment of chronic obstructive pulmonary disease (COPD) rely extensively on spirometry, which necessitates patient cooperation. The clinical value of impulse oscillometry (IOS) as a non-volitional method in patients with COPD remains uncertain.Design This retrospective observational study was conducted using patient data from between January 2014 and December 2015.Setting Five public hospitals in China: West China Hospital, Nuclear Industry 416 Hospital, Suining Central Hospital, Affiliated Hospital, Medical College of Chengdu University and 363 Hospital.Participants The study included 6307 participants aged>40 years, comprising 2109 COPD patients and 4198 general non-COPD individuals, according to the Global Initiative for Obstructive Lung Disease (GOLD) spirometry standard. Participants with lung cancer, pulmonary tuberculosis, pneumonia or those who underwent lung resection were excluded from the study.Outcome measures and analysis Demographic data, spirometry results and IOS results were collected. Spearman’s correlation analysis was used to examine the correlation between the IOS and spirometry parameters. Receiver operating characteristic curve analysis was used to evaluate the IOS performance in COPD diagnosis and severity staging.Results Patients with COPD exhibited significant increases in Z5, R5, R20, R5−R20, Fres and Rp, but a decrease in X5 compared with non-COPD subjects (p

Background: Drug-induced dry mouth is an adverse reaction that can significantly affect the quality of life and mental state of patients. In this study, we aimed to identify the most common drugs associated with dry mouth using data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database. Methods: We accessed data from the FAERS database between the first quarter of 2004 and the first quarter of 2024. The Medical Dictionary for Regulatory Activities was used to identify reports of dry mouth, and disproportionality analyses (reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker) were performed to examine the risk signals for dry mouth and its causative drugs. Results: A total of 75,899 adverse event reports were related to dry mouth. Tiotropium bromide monohydrate (2080 cases) was associated with the majority of dry mouth cases. Disproportionality analysis revealed that the top five drugs with the highest reporting odds ratio (ROR) were darifenacin, solifenacin succinate, fesoterodine fumarate, tolterodine tartrate, and niraparib. Moreover, eight of the top 19 drugs that caused dry mouth were not identified as having major side effects in the package inserts. Conclusion: Tiotropium bromide monohydrate was the most frequently reported drug for dry mouth, whereas darifenacin had the highest ROR. Collectively, our findings emphasize the necessity for improved recognition and management of drug-induced dry mouth, particularly for medications not adequately flagged for this side effect in their labels.

Abstract Highly performance flexible strain sensor is a crucial component for wearable devices, human‐machine interfaces, and e‐skins. However, the sensitivity of the strain sensor is highly limited by the strain range for large destruction of the conductive network. Here the quasi‐1D conductive network (QCN) is proposed for the design of an ultra‐sensitive strain sensor. The orientation of the conductive particles can effectively reduce the number of redundant percolative pathways in the conductive composites. The maximum sensitivity will reach the upper limit when the whole composite remains only “one” percolation pathway. Besides, the QCN structure can also confine the tunnel electron spread through the rigid inclusions which significantly enlarges the strain‐resistance effect along the tensile direction. The strain sensor exhibits state‐of‐art performance including large gauge factor (862227), fast response time (24 ms), good durability (cycled 1000 times), and multi‐mechanical sensing ability (compression, bending, shearing, air flow vibration, etc.). Finally, the QCN sensor can be exploited to realize the human‐machine interface (HMI) application of acoustic signal recognition (instrument calibration) and spectrum restoration (voice parsing).

The study focuses on the critically endangered Dabry’s sturgeon (Acipenser dabryanus), a species on the brink of extinction in the wild. This research investigates the role of the Forkhead box protein L2 (foxl2) in the gonadal development and differentiation of this species. The foxl2 gene, known for its role in various physiological processes, including sexual maturation, is hypothesized to play a significant role in the sex differentiation of Dabry’s sturgeon. This study cloned the full-length cds sequence of the foxl2 gene and analyzed its expression across various tissues, focusing on its response to estradiol treatment. Our findings indicate that foxl2 is predominantly expressed in ovaries and shows a dose-dependent response to estradiol, suggesting its potential role in ovarian differentiation. This research underscores the importance of foxl2 in understanding reproductive biology and offers a foundation for future conservation strategies.

Sepsis, a life-threatening condition, involves complex interactions among metabolic alterations, inflammatory mediators, and host responses. This study utilized a bidirectional Mendelian randomization approach to investigate the causal relationships between 1400 metabolites and sepsis, and the mediating role of inflammatory factors. We identified 36 metabolites significantly associated with sepsis (p < 0.05), with AXIN1, FGF-19, FGF-23, IL-4, and OSM showing an inverse association, suggesting a protective role, while IL-2 exhibited a positive correlation, indicating a potential risk factor. Among these metabolites, Piperine and 9-Hydroxystearate demonstrated particularly interesting protective effects against sepsis. Piperine’s protective effect was mediated through its interaction with AXIN1, contributing to a 16.296% reduction in sepsis risk. This suggests a potential pathway where Piperine influences sepsis outcomes by modulating AXIN1 levels. 9-Hydroxystearate also exhibited a protective role against sepsis, mediated through its positive association with FGF-19 and negative association with IL-2, contributing 9.436% and 12.565%, respectively, to its protective effect. Experimental validation confirmed significantly elevated IL-2 levels and reduced FGF-19, AXIN1, piperine, and 9-hydroxyoctadecanoic acid levels in sepsis patients compared to healthy controls. Piperine levels positively correlated with AXIN1, while 9-hydroxyoctadecanoic acid levels negatively correlated with IL-2 and positively correlated with FGF-19, supporting the Mendelian randomization findings. Our findings provide insights into the molecular mechanisms of sepsis, highlighting the unique roles and contributions of specific metabolites and their interactions with inflammatory mediators. This study enhances our understanding of sepsis pathophysiology and opens avenues for targeted therapeutic interventions and biomarker development for sepsis management. However, further research is essential to validate these pathways across diverse populations and fully explore the roles of these metabolites in sepsis.

IntroductionRecent studies have emphasized the intricate connection between exercise and cognition, focusing on specific cognitive processes and their correlations with specific motor skills. However, research on the impact of the qualitative aspects of movement on both short- and long-term cognitive performance is limited. In this quasi-experimental study, we investigate the impact of a 10-week fancy rope-skipping intervention on motor coordination and selective attention of 7–9-year-old children.MethodsA total of 60 primary school students from Changbin School in Haikou participated and completed the study from October to December 2022. The 60 participants were divided into a fancy rope-skipping group and a control group. Children's motor coordination was assessed using the Körperkoordinations Test für Kinder (KTK), while selective attention was evaluated using the d2 Test of Attention. Children were assessed at baseline and after the 10-week intervention.ResultsCompared with the control group, the scores for the total KTK and for the hopping for height, jumping sideways, and moving sideways sub-items were significantly higher in the rope-skipping group after the intervention, with a significant interaction effect between time and intervention. Attention concentration improved in the rope-skipping group and had a significant interaction effect between time and intervention compared with the control group; the effects of the intervention on other aspects of selective attention were unclear.ConclusionsOur study suggests that a 10-week fancy rope-skipping intervention may potentially enhance motor coordination and selective attention accuracy in children aged 7–9 years.

ABSTRACT Mycophenolate mofetil (MMF) is commonly utilized for the treatment of neuromyelitis optica spectrum disorders (NMOSD). However, a subset of patients experience significant gastrointestinal (GI) adverse effects following MMF administration. The present study aims to elucidate the underlying mechanisms of MMF-induced GI toxicity in NMOSD. Utilizing a vancomycin-treated mouse model, we compiled a comprehensive data set to investigate the microbiome and metabolome in the GI tract to elucidate the mechanisms of MMF GI toxicity. Furthermore, we enrolled 17 female NMOSD patients receiving MMF, who were stratified into non-diarrhea NMOSD and diarrhea NMOSD (DNM) groups, in addition to 12 healthy controls. The gut microbiota of stool samples was analyzed using 16S rRNA gene sequencing. Vancomycin administration prevented weight loss and tissue injury caused by MMF, affecting colon metabolomes and microbiomes. Bacterial β-glucuronidase from Bacteroidetes and Firmicutes was linked to intestinal tissue damage. The DNM group showed higher alpha diversity and increased levels of Firmicutes and Proteobacteria. The β-glucuronidase produced by Firmicutes may be important in causing gastrointestinal side effects from MMF in NMOSD treatment, providing useful information for future research on MMF.IMPORTANCENeuromyelitis optica spectrum disorder (NMOSD) patients frequently endure severe consequences like paralysis and blindness. Mycophenolate mofetil (MMF) effectively addresses these issues, but its usage is hindered by gastrointestinal (GI) complications. Through uncovering the intricate interplay among MMF, gut microbiota, and metabolic pathways, this study identifies specific gut bacteria responsible for metabolizing MMF into a potentially harmful form, thus contributing to GI side effects. These findings not only deepen our comprehension of MMF toxicity but also propose potential strategies, such as inhibiting these bacteria, to mitigate these adverse effects. This insight holds broader implications for minimizing complications in NMOSD patients undergoing MMF therapy.

Summary: In response to corneal injury, an activation of corneal epithelial stem cells and their direct progeny the early transit amplifying (eTA) cells to rapidly proliferate is critical for proper re-epithelialization. Thus, it is important to understand how such stem/eTA cell activation is regulated. Angiotensin-converting enzyme 2 (ACE2) is predominantly expressed in the stem/eTA-enriched limbal epithelium but its role in the limbal epithelium was unclear. Single cell RNA sequencing (scRNA-seq) suggested that Ace2 involved the proliferation of the stem/eTA cells. Ace2 was reduced following corneal injury. Such reduction enhanced limbal epithelial proliferation and downregulated LCN2, a negative regulator of proliferation in a variety of tissues, via upregulating TGFA and consequently activating epidermal growth factor receptor (EGFR). Inhibition of EGFR or overexpression of LCN2 reversed the increased proliferation in limbal epithelial cells lacking ACE2. Our findings demonstrate that after corneal injury, ACE2 is downregulated, which activates limbal epithelial cell proliferation via a TGFA/EGFR/LCN2 pathway.

Acute kidney injury (AKI) is in high prevalence worldwide but with no therapeutic strategies. Programmed cell death in tubular epithelial cells has been reported to accelerate a variety of AKI, but the major pathways and underlying mechanisms are not defined. Herein, we identified that pyroptosis was responsible for AKI progression and related to ATP depletion in renal tubular cells. We found that FAM3A, a mitochondrial protein that assists ATP synthesis, was decreased and negatively correlated with tubular cell injury and pyroptosis in both mice and patients with AKI. Knockout of FAM3A worsened kidney function decline, increased macrophage and neutrophil cell infiltration, and facilitated tubular cell pyroptosis in ischemia/reperfusion injury model. Conversely, FAM3A overexpression alleviated tubular cell pyroptosis, and inhibited kidney injury in ischemic AKI. Mechanistically, FAM3A promoted PI3K/AKT/NRF2 signaling, thus blocking mitochondrial reactive oxygen species (mt-ROS) accumulation. NLRP3 inflammasome sensed the overload of mt-ROS and then activated Caspase-1, which cleaved GSDMD, pro-IL-1β, and pro-IL-18 into their mature forms to mediate pyroptosis. Of interest, NRF2 activator alleviated the pro-pyroptotic effects of FAM3A depletion, whereas the deletion of NRF2 blocked the anti-pyroptotic function of FAM3A. Thus, our study provides new mechanisms for AKI progression and demonstrates that FAM3A is a potential therapeutic target for treating AKI.

Abstract Background Despite ongoing research, the underlying causes of schizophrenia remain unclear. Aspartate and asparagine, essential amino acids, have been linked to schizophrenia in recent studies, but their causal relationship is still unclear. This study used a bidirectional two-sample Mendelian randomization (MR) method to explore the causal relationship between aspartate and asparagine with schizophrenia. Methods This study employed summary data from genome-wide association studies (GWAS) conducted on European populations to examine the correlation between aspartate and asparagine with schizophrenia. In order to investigate the causal effects of aspartate and asparagine on schizophrenia, this study conducted a two-sample bidirectional MR analysis using genetic factors as instrumental variables. Results No causal relationship was found between aspartate and schizophrenia, with an odds ratio (OR) of 1.221 (95%CI: 0.483–3.088, P-value = 0.674). Reverse MR analysis also indicated that no causal effects were found between schizophrenia and aspartate, with an OR of 0.999 (95%CI: 0.987–1.010, P-value = 0.841). There is a negative causal relationship between asparagine and schizophrenia, with an OR of 0.485 (95%CI: 0.262-0.900, P-value = 0.020). Reverse MR analysis indicates that there is no causal effect between schizophrenia and asparagine, with an OR of 1.005(95%CI: 0.999–1.011, P-value = 0.132). Conclusion This study suggests that there may be a potential risk reduction for schizophrenia with increased levels of asparagine, while also indicating the absence of a causal link between elevated or diminished levels of asparagine in individuals diagnosed with schizophrenia. There is no potential causal relationship between aspartate and schizophrenia, whether prospective or reverse MR. However, it is important to note that these associations necessitate additional research for further validation.

Abstract Quantum information is often carried in the frequency and polarization degrees of freedom (DoFs) in single photons and entangled photons. We demonstrate an approach to couple and decouple the frequency and polarization DoFs of broadband biphotons. Our approach is based on a nonlinear interferometer consisting of a linear dispersive medium and a polarization controller in between the two biphoton sources (nonlinear media). When the two DoFs are decoupled, maximally polarization-entangled biphotons are observed in the polarization DoF, while interference fringes are observed in the spectrum of the biphotons. When the two DoFs are coupled, by adjusting the polarization controller, interference fringes disappear from the spectrum and instead appear in the degree of polarization entanglement, varying between 0 and 1, depending on the signal and idler frequencies. Our approach offers a convenient means of tuning the polarization entanglement and can be employed for arbitrary biphoton polarization state generation.

Abstract Background Acute pancreatitis (AP) is a clinically common acute abdominal disease, whose pathogenesis remains unclear. The severe patients usually have multiple complications and lack specific drugs, leading to a high mortality and poor outcome. Acinar cells are recognized as the initial site of AP. However, there are no precise single-cell transcriptomic profiles to decipher the landscape of acinar cells during AP, which are the missing pieces of jigsaw we aimed to complete in this study. Methods A single-cell sequencing dataset was used to identify the cell types in pancreas of AP mice and to depict the transcriptomic maps in acinar cells. The pathways’ activities were evaluated by gene sets enrichment analysis (GSEA) and single-cell gene sets variation analysis (GSVA). Pseudotime analysis was performed to describe the development trajectories of acinar cells. We also constructed the protein–protein interaction (PPI) network and identified the hub genes. Another independent single-cell sequencing dataset of pancreas samples from AP mice and a bulk RNA sequencing dataset of peripheral blood samples from AP patients were also analyzed. Results In this study, we identified genetic markers of each cell type in the pancreas of AP mice based on single-cell sequencing datasets and analyzed the transcription changes in acinar cells. We found that acinar cells featured acinar-ductal metaplasia (ADM), as well as increased endocytosis and vesicle transport activity during AP. Notably, the endoplasmic reticulum stress (ERS) and ER-associated degradation (ERAD) pathways activated by accumulation of unfolded/misfolded proteins in acinar cells could be pivotal for the development of AP. Conclusion We deciphered the distinct roadmap of acinar cells in the early stage of AP at single-cell level. ERS and ERAD pathways are crucially important for acinar homeostasis and the pathogenesis of AP.

Abstract Purpose This study investigated and compared the effects of Gd enhancement on brain tumours with a half-dose of contrast medium at 5.0 T and with a full dose at 3.0 T. Methods Twelve subjects diagnosed with brain tumours were included in this study and underwent MRI after contrast agent injection at 3.0 T (full dose) or 5.0 T (half dose) with a 3D T1-weighted gradient echo sequence. The postcontrast images were compared by two independent neuroradiologists in terms of the signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and subjective image quality score on a ten-point Likert scale. Quantitative indices and subjective quality ratings were compared with paired Student's t tests, and interreader agreement was assessed with the intraclass correlation coefficient (ICC). Results A total of 16 enhanced tumour lesions were detected. The SNR was significantly greater at 5.0 T than at 3.0 T in grey matter, white matter and enhanced lesions (p

Crucian carp (Carassius auratus gibelio), an extensively cultivated freshwater fish, was one of the model species for the study of fish immunology. Polyclonal antibodies were advantageous molecular tools for studying teleost immune system. Specifically, polyclonal antibodies reacting with immunoglobulins (Ig) were used successfully in studies of the teleost fishes. In the present study, we produced polyclonal antibody against CH2 domains of crucian carp IgM, and measured the in vivo dynamics of IgM mRNA caused by CyHV-2 infection. The recombinant protein IgM with relative molecular weight about 53 KD was correctly expressed in prokaryotic cells. The specificity of the polyclonal antibody was evaluated by Western blotting and results revealed that the antibody not only specifically recognized crucian carp serum but also cross-reacted with grass carp serum. Quantitative RT-PCR analysis demonstrated the expression of IgM mRNA changed significantly after CyHV-2 infection. The expression of IgM in the kidney increased and reached a maximum at 6 h post-infection (hpi), while dropped to a low level at 5 days post-infection (dpi). In conclusion, the expression of IgM was significantly upregulated in the kidney of crucian carp infected with CyHV-2, indicating that IgM played a potential role in systemic immunity against viral infection. Polyclonal antibody against crucian carp IgM had certain clinical relevance, which might provide insight into the early stage of virus infection and prevention of the disease.

Introduction: Forming a bridge made of functional axons to span the lesion is essential to reconstruct the motor circuitry following spinal cord injury (SCI). Dorsal root ganglion (DRG) axons are robust in axon growth and have been proved to facilitate the growth of cortical neurons in a process of axon-facilitated axon regeneration. However, whether DRG transplantation affects the axon outgrowth of spinal motor neurons (SMNs) that play crucial roles in motor circuitry remains unclear. Methods: We investigated the axonal growth patterns of co-cultured DRGs and SMN aggregates (SMNAs) taking advantage of a well-designed 3D-printed in vitro system. Chondroitin sulphate proteoglycans (CSPG) induced inhibitory matrix was introduced to imitate the inhibitory environment following SCI. Axonal lengths of DRG, SMNA or DRG & SMNA cultured on the permissive or CSPG induced inhibitory matrix were measured and compared. Results: Our results indicated that under the guidance of full axonal connection generated from two opposing populations of DRGs, SMNA axons were growth-enhanced and elongated along the DRG axon bridge to distances that they could not otherwise reach. Quantitatively, the co-culture increased the SMNA axonal length by 32.1 %. Moreover, the CSPG matrix reduced the axonal length of DRGs and SMNAs by 46.2 % and 17.7 %, respectively. This inhibitory effect was antagonized by the co-culture of DRGs and SMNAs. Especially for SMNAs, they extended the axons across the CSPG-coating matrix, reached the lengths close to those of SMNAs cultured on the permissive matrix alone. Conclusions: This study deepens our understanding of axon-facilitated reconstruction of the motor circuitry. Moreover, the results support SCI treatment utilizing the enhanced outgrowth of axons to restore functional connectivity in SCI patients.

Meteorological disasters along highways significantly reduce road traffic efficiency. Low visibility caused by heavy fog is a severe meteorological disaster that greatly increases highway traffic accidents. Accurately predicting highway visibility and taking timely response measures can reduce the impact of meteorological disasters and improve traffic safety. We proposed an Attention-based BiLSTM-CNN (ABCNet) model, which synergized attention mechanisms with BiLSTM and CNN technologies to forecast atmospheric visibility more accurately. First, the Bi-LSTM module processed information both forward and backward, capturing intricate temporal dependencies in the model. Second, the multi-head attention mechanism following the Bi-LSTM distilled and prioritized salient features from multiple aspects of the sequence data. Third, the CNN module recognized local spatial features, and a singular attention mechanism refined the feature map after the CNN module, further enhancing the model's accuracy and predictive capability. Experiments showed that the model was accurate, effective, and significantly advanced compared to conventional models. It could fully extract the spatiotemporal characteristics of meteorological elements. The model was integrated into practical systems with positive results. Additionally, this study provides a self-collected meteorological dataset for highways in high-altitude mountainous areas.

Abstract Objective We aimed to explore the heterogeneity of neurons in heart failure with dilated cardiomyopathy (DCM). Methods Single-cell RNA sequencing (scRNA-seq) data of patients with DCM and chronic heart failure and healthy samples from GSE183852 dataset were downloaded from NCBI Gene Expression Omnibus, in which neuron data were extracted for investigation. Cell clustering analysis, differential expression analysis, trajectory analysis, and cell communication analysis were performed, and highly expressed genes in neurons from patients were used to construct a protein-protein interaction (PPI) network and validated by GSE120895 dataset. Results Neurons were divided into six subclusters involved in various biological processes and each subcluster owned its specific cell communication pathways. Neurons were differentiated into two branches along the pseudotime, one of which was differentiated into mature neurons, whereas another tended to be involved in the immune and inflammation response. Genes exhibited branch-specific differential expression patterns. FLNA, ITGA6, ITGA1, and MDK interacted more with other gene-product proteins in the PPI network. The differential expression of FLNA between DCM and control was validated. Conclusion Neurons have significant heterogeneity in heart failure with DCM, and may be involved in the immune and inflammation response to heart failure.

To synthesise the best available evidence for the effectiveness of interventions delivered in community-based rehabilitation (CBR) centers on physical fitness, for community-dwelling older adults living in Asian countries. This study is a systematic review and meta-analysis. Seven English and two Chinese electronic databases were searched for randomised controlled trials (RCTs) and quasi-experimental studies that were conducted by centers providing CBR. Independent reviewers screened, quality-appraised and extracted data. The primary outcome was physical fitness measured by validated assessment tools, including the Timed Up and Go Test (TUG) gait speed, hand grip strength, Functional Reach Test (FRT), and one-leg standing test. Assessments of activity of daily living and quality of life using tools including the Barthel Index, Short Form (SF)-12, and SF-36 were secondary outcomes. After screening 5,272 studies, 29 studies were included (16 RCTs, 13 quasi-experimental studies) from four countries. Meta-analyses found that CBR programs significantly decreased TUG time (mean difference [MD], -1.89 seconds; 95% confidence interval [95% CI], -2.84 to -0.94; I2=0%; Z=3.90, p

BackgroundType 1 diabetes mellitus (T1DM) is the most common chronic autoimmune disease among children and adolescents. Telemedicine has been widely used in the field of chronic disease management and can benefit patients with T1DM. However, existing studies lack high-level evidence related to the effectiveness of telemedicine for glycemic control in children and adolescents with T1DM. ObjectiveThis study aims to systematically review the evidence on the effectiveness of telemedicine interventions compared with usual care on glycemic control among children and adolescents with T1DM. MethodsIn this systematic review and meta-analysis, we searched PubMed, Cochrane Library, Embase, Web of Science (all databases), and CINAHL Complete from database inception to May 2023. We included randomized controlled trials (RCTs) that evaluated the effectiveness of a telemedicine intervention on glycemic control in children and adolescents with T1DM. In total, 2 independent reviewers performed the study selection and data extraction. Study quality was assessed using the Cochrane Risk of Bias 2 tool. Our primary outcome was glycated hemoglobin (HbA1c) levels. Secondary outcomes were quality of life, self-monitoring of blood glucose, the incidence of hypoglycemia, and cost-effectiveness. A random-effects model was used for this meta-analysis. ResultsOverall, 20 RCTs (1704 participants from 12 countries) were included in the meta-analysis. Only 5% (1/20) of the studies were at high risk of bias. Compared to usual care, telemedicine was found to reduce HbA1c levels by 0.22 (95% CI –0.33 to –0.10; P

IntroductionDiabetic cardiomyopathy (DCM) is predominantly distinguished by impairment in ventricular function and myocardial fibrosis. Previous studies revealed the cardioprotective properties of C1q/tumor necrosis factor-related protein 9 (CTRP9). However, whether CTRP9 affects diabetic myocardial fibrosis and its underlying mechanisms remains unclear.MethodsWe developed a type 1 diabetes (T1DM) model in CTRP9-KO mice via streptozotocin (STZ) induction to examine cardiac function, histopathology, fibrosis extent, Yes-associated protein (YAP) expression, and the expression of markers for autophagy such LC3-II and p62. Additionally, we analyzed the direct impact of CTRP9 on high glucose (HG)-induced transdifferentiation, autophagic activity, and YAP protein levels in cardiac fibroblasts.ResultsIn diabetic mice, CTRP9 expression was decreased in the heart. The absence of CTRP9 aggravated cardiac dysfunction and fibrosis in mice with diabetes, alongside increased YAP expression and impaired autophagy. In vitro, HG induced the activation of myocardial fibroblasts, which demonstrated elevated cell proliferation, collagen production, and α-smooth muscle actin (α-SMA) expression. CTRP9 countered these adverse effects by restoring autophagy and reducing YAP protein levels in cardiac fibroblasts. Notably, the protective effects of CTRP9 were negated by the inhibition of autophagy with chloroquine (CQ) or by YAP overexpression through plasmid intervention. Notably, the protective effect of CTRP9 was negated by inhibition of autophagy caused by chloroquine (CQ) or plasmid intervention with YAP overexpression.DiscussionOur findings suggest that CTRP9 can enhance cardiac function and mitigate cardiac remodeling in DCM through the regulation of YAP-mediated autophagy. CTRP9 holds promise as a potential candidate for pharmacotherapy in managing diabetic cardiac fibrosis.

Porcine epidemic diarrhea virus (PEDV) is a highly infectious pathogen that targets pig intestines to cause disease. It is globally widespread and causes huge economic losses to the pig industry. PEDV N protein is the protein that constitutes the core of PEDV virus particles, and most of it is expressed in the cytoplasm, and a small part can also be expressed in the nucleus. However, the role of related proteins in host nucleotide metabolic pathways in regulating PEDV replication have not been fully elucidated. In this study, PEDV-N-labeled antibodies were co-immunoprecipitated and combined with LC-MS to screen for host proteins that interact with N proteins. Bioinformatics analyses showed that the selected host proteins were mainly enriched in metabolic pathways. Moreover, co-immunoprecipitation and confocal microscopy confirmed that the second-largest subunit of RNA polymerase II (RPB2) and uridine phosphorylase 1 (UPP1) interacted with the N protein. RPB2 is the main subunit of RNA polymerase II and plays an important role in eukaryotic transcription. UPP1 is an enzyme that catalyzes reversible phosphorylation of uridine to uracil and ribo-1-phosphate to promote catabolism and bio anabolism. RPB2 overexpression significantly promoted viral replication, whereas UPP1 overexpression significantly inhibited viral replication. Studies on interactions between the PEDV N and host proteins are helpful in elucidating the pathogenesis and immune escape mechanism of PEDV.

BackgroundIntegrin-dependent cell adhesion and migration play important roles in systemic sclerosis (SSc). The roles of integrin activating molecules including talins and kindlins, however, are unclear in SSc.ObjectivesWe aimed to explore the function of integrin activating molecules in SSc.MethodsTranscriptome analysis of skin datasets of SSc patients was performed to explore the function of integrin-activating molecules including talin1, talin2, kindlin1, kindlin2 and kindlin3 in SSc. Expression of talin1 in skin tissue was assessed by multiplex immunohistochemistry staining. Levels of talin1 in serum were determined by ELISA. The effects of talin1 inhibition were analyzed in human dermal fibroblasts by real-time PCR, western blot and flow cytometry.ResultsWe identified that talin1 appeared to be the primary integrin activating molecule involved in skin fibrosis of SSc. Talin1 was significantly upregulated and positively correlates with the modified Rodnan skin thickness score (mRSS) and the expression of pro-fibrotic biomarkers in the skin lesions of SSc patients. Further analyses revealed that talin1 is predominantly expressed in the dermal fibroblasts of SSc skin and promotes fibroblast activation and collagen production. Additionally, talin1 primarily exerts its effects through integrin β1 and β5 in SSc.ConclusionsOverexpressed talin1 is participated in skin fibrosis of SSc, and talin1 appears to be a potential new therapeutic target for SSc.

Background This study aims to examine the relationship between functional movements and golf performance using the Golf Specific Functional Movement Screen (GSFMS). Methods This cross-sectional study included a total of 56 collegiate golfers (aged 20.89 ± 0.99 years, height of 174.55 ± 7.76 cm, and weight 68.48 ± 9.30 kg) who met the criteria, and were recruited from Hainan Normal University in June 2022. The participants’ golf motor skills (1-yard putt, 10-yard putt, 25-yard chip, 130/100-yard set shot, driver, and 9-hole stroke play) were tested and the GSFMS (e.g., pelvic tilt, pelvic rotation, and torso rotation) was used. Results There were significant weak or moderate correlations between the variables. Furthermore, a multiple linear regression analysis found that pelvic rotation and lower-body rotation abilities can significantly predict golf skill levels, which collectively explain 31.2% of the variance in golf skill levels among collegiate golfers (Adjusted R2 = 0.312, F = 2.663, p < 0.05). Standardised β values indicate that pelvic rotation (β = 0.398) has a more substantial impact on golf skill levels than lower-body rotation (β = 0.315). Conclusions This study found the weak to moderate correlations between the GSFMS and golf performance, and pelvic rotation and lower-body rotation abilities, thus predicting golf skills. Our findings provide novel insights into the relationship between functional abilities and comprehensive skill performance within the context of the Gray Cook’s Movement Pyramid model, and provide theoretical support and practical reference for collegiate golf motor-skill learning and sports injury prevention.

Objective: To investigate whether inflammatory indices, including the systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), product of platelet and neutrophil count (PPN), and lymphocyte-to-monocyte ratio (LMR), correlate with chronic obstructive pulmonary disease (COPD). Methods: This was a cross-sectional study from the National Health and Nutrition Examination Survey (NHANES) database 2007–2018. The SII, NLR, PLR, PPN and LMR were calculated based on blood cell counts and were log2-transformed. COPD was diagnosed via a questionnaire or spirometry examination. Multivariate logistic regression, sensitivity analysis, subgroup analyses, and interaction tests were performed to evaluate the relationships. Results: 23,875 participants, including 1000 COPD patients (453 diagnosed via spirometry examination, 547 diagnosed via a questionnaire), were enrolled in this study. Positive associations were observed between SII (OR 1.231, 95 % CI 1.081,1.401), NLR (OR 1.223, 95 % CI 1.064,1.405), PLR (OR 1.325, 95 % CI 1.086,1.617), PPN (OR 1.157, 95 % CI 1.031,1.298) and COPD, while a negative association was obtained between LMR and COPD (OR 0.794, 95 % CI 0.666,0.948) after covariate adjustments. When divided COPD patients into spirometry-based and questionnaire-based, only SII (OR 1.310, 95%CI 1.122,1.529), PLR (OR 1.669, 95%CI 1.272,2.191) and PPN (OR 1.218, 95%CI 1.050,1.412) significantly correlated with spirometry-based COPD, while only NLR (OR 1.303, 95%CI 1.055,1.609) and LMR (OR 0.524, 95%CI 0.406,0.677) significantly correlated with questionnaire-based COPD after covariate adjustments. Conclusion: Significant associations are observed between different inflammation indices and COPD. Heterogeneity exists between spirometry-based and questionnaire-based COPD patients. Future studies are needed to verify the results.

Abstract Intrinsic immunosuppressive tumor microenvironment (ITM) and insufficient tumor infiltration of T cells severely impede the progress of glioblastoma (GBM) immunotherapy. In this study, it is identify that inhibiting the expression of glucose transporter 1 (GLUT1) can facilitate the prevention of lactate excretion from tumor glycolysis, which significantly alleviates the lactate‐driven ITM by reducing immunosuppressive tumor‐associated macrophages (TAMs) and regulatory T cells (Tregs). Simultaneously, the findings show that the generated inflammatory cytokine IFN‐γ during immune activation aggravates the immune escape by upregulating immune checkpoint programmed death‐ligand 1 (PD‐L1) in tumor cells and TAMs. Therefore, an injectable thermogel loaded with a GLUT1 inhibitor BAY‐876 and a PD‐1/PD‐L1 blocker BMS‐1 (Gel@B‐B) for dual‐regulation of metabolism and immunity of GBM is developed. Consequently, in situ injection of Gel@B‐B significantly delays tumor growth and prolongs the survival of the orthotopic GBM mouse model. By actively exposing tumor antigens to antigen‐presenting cells, the GBM vaccine combined with Gel@B‐B is found to significantly increase the fraction of effector T cells (Th1/CTLs) in the tumor microenvironment, thereby remarkably mitigating tumor recurrence long‐term. This study may provide a promising strategy for GBM immunotherapy.

Combining inverse projection and vote accumulation methods, we propose a novel 3-D geometric reconstruction method based on inverse synthetic aperture radar image sequence for triaxially stabilized space targets. Considering that the translation of a triaxially stabilized space target results in a large angular rotation of the radar line-of-sight and an attitude adjustment rotation of the target itself, the projection relationship between the radar imaging plane and a triaxially stabilized space target is constructed first. Subsequently, we perform an inverse projection on the dominant points extracted from each imaging plane to determine the location of the 3-D candidate scatterers and assign a voting value of 1 to each position. By accumulating these vote values, we can obtain the total number of votes for the candidate scatterer position. We treat candidate 3-D scatterers with a large cumulative number of votes as actual scatterers. Thus, the target 3-D geometry can be obtained. Compared with the traditional matrix factorization-based 3-D reconstruction methods, this method is more accurate and ensures that the target pose is consistent with the actual pose. At the same time, compared with 3-D reconstruction methods based on the energy accumulation ideas, this method produces fewer false scatterers and has higher credibility. The experimental results based on the simulated point target and electromagnetic data are presented to validate the effectiveness and robustness of the proposed method.

Multiple-input-multiple-output (MIMO) synthetic aperture radar (SAR) (MIMO-SAR) has numerous potential applications in fields, such as medical diagnosis and security screening. In near-field MIMO-SAR imaging, the virtual array is typically defined as the midpoint of the transceiver array. Based on the virtual array, the multistatic data can be converted to monostatic data for imaging. However, these approaches suffer from low accuracy and cannot reconstruct large scenes, despite their small computational load. In this article, we propose a novel near-field MIMO-SAR imaging algorithm based on range compensation. The convolution between transmitting and receiving elements of the MIMO array defines the positions of virtual array's elements, with the center of the small scene selected as the reference point. The range difference between the transceiver array and the corresponding virtual array to the reference point is calculated. An approximate expression of the range difference is also derived, which can effectively reduce the computational load associated with the range compensation. The conditions for partitioning large scenes are derived by analyzing the range difference between the reference point and other scattered points with respect to the antenna elements. Based on the conditions, the large scenes are divided into blocks. The final image is obtained by a weighted sum of each block scene image. Simulation and experimental results on the designed MIMO radar near-field imaging system demonstrate that the proposed algorithm can effectively reconstruct high-resolution scene images of arbitrary size.

In saline environments, it is difficult for reinforced concrete structures to meet normal durability requirements, which in turn affects the mechanical properties of the members. In this context, this paper proposes a reinforcement method that involves wrapping corroded reinforced concrete columns with CFRP (carbon fiber reinforced polymer) cloth. By conducting axial compression tests on four specimens, key mechanical performance indicators such as failure mode, ductility, and bearing capacity during the entire stress process of the specimens were analyzed, revealing the failure mechanism of CFRP-confined corroded reinforced concrete columns. A refined finite element model of CFRP-confined corroded reinforced concrete columns was established using ABAQUS software. The influence of key parameters such as the number of CFRP wrapping layers, longitudinal reinforcement corrosion rate, and axial compression ratio on the mechanical properties of the specimens was studied, and the influence of each parameter was determined. Furthermore, a formula for the axial compression bearing capacity of CFRP-confined corroded reinforced concrete columns was proposed. The results indicate that in the presence of corroded steel reinforcement, specimens confined with CFRP undergo substantial lateral constraints during the mid to late stages of loading. This approach effectively alleviates the transverse deformation of the concrete. The specimen demonstrated yield bearing capacities and peak loads of 1441 KN and 1934 KN, respectively, representing a 2.2-fold and 2.5-fold increase compared to the non-reinforced specimen. With the increase in the transverse strain of concrete, CFRP begins to play a restraint role, and a more obvious restraint role in the failure stage of members. It is recommended to apply 1–3 layers of CFRP wrapping for a longitudinal reinforcement corrosion rate of 5%, 3–5 layers for a rate of 10%, and 6–8 layers for an overall corrosion rate of 15%. This paper establishes a theoretical framework for investigating the performance characteristics of such columns and offers technical assistance for practical engineering purposes.

Fungi are rich sources of secondary metabolites of agrochemical, pharmaceutical, and food importance, such as mycotoxins, antibiotics, and antitumor agents. Secondary metabolites play vital roles in fungal pathogenesis, growth and development, oxidative status modulation, and adaptation/resistance to various environmental stresses. LaeA contains an S-adenosylmethionine binding site and displays methyltransferase activity. The members of velvet proteins include VeA, VelB, VelC, VelD and VosA for each member with a velvet domain. LaeA and velvet proteins can form multimeric complexes such as VosA-VelB and VelB-VeA-LaeA. They belong to global regulators and are mainly impacted by light. One of their most important functions is to regulate gene expressions that are responsible for secondary metabolite biosynthesis. The aim of this mini-review is to represent the newest cognition of the biosynthetic regulation of mycotoxins and other fungal secondary metabolites by LaeA and velvet proteins. In most cases, LaeA and velvet proteins positively regulate production of fungal secondary metabolites. The regulated fungal species mainly belong to the toxigenic fungi from the genera of Alternaria, Aspergillus, Botrytis, Fusarium, Magnaporthe, Monascus, and Penicillium for the production of mycotoxins. We can control secondary metabolite production to inhibit the production of harmful mycotoxins while promoting the production of useful metabolites by global regulation of LaeA and velvet proteins in fungi. Furthermore, the regulation by LaeA and velvet proteins should be a practical strategy in activating silent biosynthetic gene clusters (BGCs) in fungi to obtain previously undiscovered metabolites.

Carassius auratus herpesvirus (CaHV) is a pathogen isolated from crucian carp (Carassius auratus) associated with high mortality. A diagnosis method that can detect the virus at an early stage, specifically and accurately, is an urgent requirement for the prevention of CaHV transmission. In the present study, a droplet digital PCR (ddPCR) method based on the tumor necrosis factor receptor (TNFR) gene was established to detect and quantify CaHV DNA with high specificity and no cross-reactions with other aquatic viruses. Skin mucus samples were collected from infected crucian carp from Day 1–8 after infection, and positive amplification was detected on the first day by ddPCR (0.54 copies/μL), whereas the presence of CaHV was not detected by routine PCR until Day 6. Tissue DNA was then collected from the head kidney of 20 fishes which were injected with CaHV and died during the experiment. The five negative samples checked by routine PCR were detected by ddPCR and real-time PCR (qPCR), respectively. The results showed that the positive detection rate of ddPCR (100%) was higher than that of qPCR (40%). The detection limit of the ddPCR was found to be 0.52 copies/μL, which was much lower than the 50.12 copies/μL determined by qPCR. Overall, ddPCR offers a highly promising diagnosis method for the absolute quantification of CaHV in carrier fish and samples from the skin mucus and head kidney with low viral concentrations.

BackgroundAcute pancreatitis (AP) is a severe digestive system disorder with a significant risk of progressing to sepsis, a major cause of mortality. Unraveling the immunological pathways in AP is essential for developing effective treatments, particularly understanding the role of specific immune cell traits in this progression.MethodsEmploying a bidirectional two-sample Mendelian Randomization (MR) approach, this study first examined the causal relationship between AP and 731 immune cell traits to identify those significantly associated with AP. Subsequently, we explored the causal associations between 731 immune cell traits and sepsis. The analysis utilized extensive genome-wide association studies (GWAS) summary datasets, with a focus on identifying common immune cell traits with statistically significant causal associations between AP and sepsis.ResultsOur investigation identified 44 immune cell traits unidirectionally associated with AP and 36 traits unidirectionally associated with sepsis. Among these, CD127 on CD28+ CD45RA- CD8+ T cells emerged as a common mediator, accounting for 5.296% of the increased risk of sepsis in AP patients. This finding highlights the significant role of specific memory CD8+ T cells in the pathophysiology of AP and its progression to sepsis.ConclusionThis study elucidates the critical role of specific immune cell traits, particularly CD127hi memory CD8+ T cells, in the progression of AP to sepsis. Our findings provide a foundation for future research into targeted immune-modulatory therapies, potentially improving patient outcomes in AP-related sepsis and offering new insights into the complex immunological dynamics of this condition.

Summary: Intricate cerebral cortex formation is orchestrated by the precise behavior and division dynamics of radial glial cells (RGCs). Endocytosis functions in the recycling and remodeling of adherens junctions (AJs) in response to changes in RGC activity and function. Here, we show that conditional disruption of ubiquitin-associated protein 1 (UBAP1), a component of endosomal sorting complex required for transport (ESCRT), causes severe brain dysplasia and prenatal ventriculomegaly. UBAP1 depletion disrupts the AJs and polarity of RGCs, leading to failure of apically directed interkinetic nuclear migration. Accordingly, UBAP1 knockout or knockdown results in reduced proliferation and precocious differentiation of neural progenitor cells. Mechanistically, UBAP1 regulates the expression and surface localization of cell adhesion molecules, and β-catenin over-expression significantly rescues the phenotypes of Ubap1 knockdown in vivo. Our study reveals a critical physiological role of the ESCRT machinery in cortical neurogenesis by regulating AJs of RGCs.

Adeno-associated virus (AAV) vectors have been widely used in therapy to treat hereditary retinal diseases. But its transduction efficiency by intravitreal injection still needs to be improved. In this study, we investigated the transduction efficiency of AAV-DJ (K137R)-GFP in different retinal cells of normal mice, as well as the therapy effection of AAV-DJ (K137R)-Rs1 on retinal function and structure in Rs1-KO mice. The intravitreal injection of AAV-DJ (K137R)-GFP demonstrated that this vector transduced cells in all layers of the retina, including the inner nuclear layer and photoreceptor layer. The intravitreal injection of AAV-DJ (K137R)-Rs1 found that 3 months post-injection of this vector improved retinal function and structure in Rs1-KO mice. Our conclusion is that AAV-DJ (K137R) vector can efficiently and safely penetrate the inner limiting membrane and transduce different layers of retinal cells in the long term, as well as being able to continuously and efficiently express target therapeutic proteins, making it a candidate therapeutic vector for X-linked retinoschisis (XLRS).

Idiopathic multicentric Castleman disease (iMCD) is a rare and cytokine storm-driven inflammatory disorder. The exact cause of iMCD is still unknown, although several hypotheses have been proposed. However, regardless of the underlying cause, the ultimate result is the activation of the inflammatory pathway, which can lead to damage in multiple organs. Currently, there have been several reports highlighting the intricate link between coronavirus disease 2019 (COVID-19) and iMCD. To better understand the impact of COVID-19-induced immune storm on iMCD, we conducted a multicenter retrospective study in three hospitals in China. A total of 28 patients with iMCD were included, among whom 25 had confirmed COVID-19 infection, and we presented 4 cases that showed different disease progression after the infection of COVID-19, including 2 who did not receive any treatment for Castleman disease before. Our findings underscore the necessity of carefully monitoring iMCD patients with COVID-19 and promptly intervening to address any changes in their condition. Besides, this study also summarized the shared cytokines between COVID-19 and iMCD. Recent studies have shown promising results in treating severe COVID-19 and iMCD using tocilizumab, an interleukin-6 receptor antagonist. Therefore, it suggests that other potential cytokine storm therapy targets that have been effective in COVID-19 may also be explored for the treatment of iMCD.

Fecal scores are crucial for assessing the digestive and gastrointestinal status of animals. The Bristol fecal scoring system is a commonly used method for the subjective evaluation of host feces, there is limited research on fecal scoring standards for fattening Hu sheep. In this study, Hu sheep were collected for rumen, rectum, and colon contents for 16S rDNA sequencing. 514 Hu sheep feces were scored based on the Bristol fecal scoring system, and production performance at each stage was measured. Finally, we developed the scoring standard of the manure of Hu sheep in the fattening period (a total of five grades). The result shows that moisture content significantly increased with higher grades (p < 0.05). We analyzed the relationship between fecal scores and production traits, blood indices, muscle nutrients, and digestive tract microorganisms. The growth traits (body weight, body height, body length, average daily gain (ADG), and average daily feed intake (ADFI) during 80–180 days), body composition traits of the F3 group, and the carcass traits were found to be significantly higher (p < 0.05) than those of the F1 and F2 groups. There was no significant difference in gastrointestinal microflora diversity among all groups (p > 0.05). Significant differences were observed in Aspartate aminotransferase, Glucose, Total bilirubin, and Red Blood Cell Count between groups (p < 0.05). The mutton moisture content in group F4 was significantly higher than in the other groups, and the protein content was also the lowest (p < 0.05). The results of the correlation analysis demonstrated that Actinobacteria, Peptostreptococcaceae, Acidaminococcales, Gammaproteobacteria, and Proteobacteria were the significant bacteria affecting fecal scores. In addition, Muribaculaceae and Oscillospiraceae were identified as the noteworthy flora affecting growth performance and immunity. This study highlights the differences in production traits and blood indicators between fecal assessment groups and the complex relationship between intestinal microbiota and fecal characteristics in Hu sheep, suggesting potential impacts on animal performance and health, which suggest strategies for improved management.

The Western Pacific region is highly vulnerable to typhoon storm surge disasters, with localized erosion posing a particularly prominent issue for coastal marine structures. The prevalence of extreme typhoon storm surges poses a significant threat to the safety of engineering projects in these areas. In this study, a parameterized wind field model with precise calculation of wind speed was employed to establish a numerical model for typhoon storm tides. Based on the Western Pacific typhoon data from 1949 to 2023, hydraulic simulations were conducted for Hangzhou Bay, Xiangshan Port, and Yueqing Bay, revealing maximum flow velocities of 4.5 m/s, 1.95 m/s, and 2.09 m/s, respectively. These velocities exceeded the maximum possible tidal flow by 0.47–1.17 m/s. Additionally, using Sun’s velocity formula, the initiation flow velocities were calculated to be 1.85 m/s, 1.81 m/s, and 2.06 m/s for the aforementioned locations. Through localized erosion tests conducted around typical bridge piers and the subsequent application of similarity criteria, the maximum depth of localized erosion in the study area was determined to range from 2.16 m to 16.1 m, which corresponds to 1.1–2.3 times the scour caused by the maximum tidal flow scenario. A comparison of the erosion test results with calculations based on several formulas demonstrated that the scour prediction formula proposed by Sun exhibited the highest accuracy. This study supplements the understanding of the impact of typhoon storm surges on bridge pier erosion and provides a scientific basis for the design of bridge foundations.