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Introduction: Valerenic acid (VA) is a unique and biologically active component in Valeriana officinalis L., which has been reported to have a regulatory effect on the cardiovascular system. However, its therapeutic effects on pathological myocardial hypertrophy (PMH) and the underlying mechanisms are undefined. Objectives: Our study aims to elucidate how VA improves PMH, and preliminarily discuss its mechanism. Methods: The efficacy of VA on PMH was confirmed by in vivo and in vitro experiments and the underlying mechanism was investigated by molecular dynamics (MD) simulations and specific siRNA interference. Results: VA enhanced cardiomyocyte fatty acid oxidation (FAO), inhibited hyper-activated glycolysis, and improved the unbalanced pyruvate-lactate axis. VA could significantly improve impaired mitochondrial function and reduce the triglyceride (TG) in the hypertrophic myocardium while reducing the lactate (LD) content. Molecular mechanistic studies showed that VA up-regulated the expression of peroxisome proliferator-activated receptor-α (PPARα) and downstream FAO-related genes including CD36, CPT1A, EHHADH, and MCAD. VA reduced the expression of ENO1 and PDK4, the key enzymes in glycolysis. Meanwhile, VA improved the pyruvate-lactate axis and promoted the aerobic oxidation of pyruvate by inhibiting LDAH and MCT4. MD simulations confirmed that VA can bind with the F273 site of PPARα, which proposes VA as a potential activator of the PPARα. Conclusion: Our results demonstrated that VA might be a potent activator for the PPARα-mediated pathway. VA directly targets the PPARα and subsequently promotes energy metabolism to attenuate PMH, which can be applied as a potentially effective drug for the treatment of HF.

Accurate snow depth (SD) monitoring is crucial for understanding climate change and managing water resources. However, due to the sparse distribution of meteorological stations and the limited accuracy of passive microwave remote sensing data, the retrieval accuracy of large-scale snow depth in regions with complex terrain and variable climate conditions has faced significant challenges. To address this issue, this paper proposes a large-scale snow depth retrieval method based on point-surface fusion technology with the Random Forest (RF) model. The method integrates ground-based snow depth measurements with passive microwave brightness temperature data using the RF algorithm and incorporates geographic coordinates, elevation, brightness temperature, brightness temperature gradient differences, and time variables for each grid cell in Alaska, which significantly improves the accuracy and spatial resolution of the large-scale snow depth retrieval. Five-fold cross-validation results show the model exhibits excellent fitting performance (R $^{2} =0.9627$ , MAE =4.6 cm, RMSE =10.08 cm), particularly demonstrating strong robustness in sparse meteorological stations. The results indicate that the proposed method effectively captures the spatiotemporal variations in snow depth across Alaska from 2008 to 2016, providing valuable technical support for snow depth monitoring and climate change research in cold regions.

Background: Cholestasis plays a critical role in sepsis-associated liver injury (SALI). Intestine-derived fibroblast growth factor 19 (FGF19) is a key regulator for bile acid homeostasis. However, the roles and underlying mechanisms of FGF19 in SALI are still unclear. Methods: We conducted a case–control study that included 58 pediatric patients aged from 1 month to 14-years-old diagnosed with sepsis at Shanghai Children's Hospital from January to December 2018 and 30 healthy individuals. The serum FGF19 levels of these patients with sepsis were analyzed and compared with those of healthy controls. Recombinant human FGF19 was intravenously injected in mice once a day for 7 days at a dose of 0.1 mg/kg body weight before lipopolysaccharide (LPS) treatment. Liver bile acid profiles and the gene expression involved in bile acid homeostasis were investigated in the mice groups. Metabolomic data were further integrated and analyzed using Ingenuity Pathways Analysis (IPA) software. In the in vitro analysis using HepG2 cells, the influence of FGF19 pretreatment on reactive oxygen species (ROS) production and mitochondrial dysfunction was analyzed. Compound C (CC), an inhibitor of AMP-activated protein kinase (AMPK) activation, was used to confirm the roles of AMPK activation in FGF19-mediated hepatoprotective effects. Results: Serum FGF19 levels were significantly lower in children with sepsis than in healthy controls (115 pg/mL vs. 79 pg/mL, P=0.03). Pre-administration of recombinant human FGF19 alleviated LPS-induced acute liver injury (ALI) and improved LPS-induced cholestasis in mice. Moreover, FGF19 directly reversed LPS-induced intracellular ROS generation and LPS-decreased mitochondrial membrane potential in vitro and in vivo, resulting in hepatoprotection against LPS-induced apoptosis. More importantly, the inhibition of AMPK activity partially blocked the protective effects of FGF19 against LPS-induced oxidative stress and mitochondrial dysfunction. Conclusions: Intestine-derived FGF19 alleviates LPS-induced ALI via improving bile acid homeostasis and directly suppressing ROS production via activating the AMPK signaling pathway.

This investigation elucidates the spatiotemporal dynamics of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation following myocardial infarction (MI), a process that has not been fully characterized. We revealed early activation of the NLRP3 inflammasome in mice with MI and characterized its dynamic temporal expression. Notably, the knockout and inhibition of Nlrp3 expression were found to significantly mitigate infarct size and enhance cardiac function. Furthermore, our analysis of the spatial characteristics of inflammasome activation revealed predominant activation in macrophages and subsequent activation in fibroblasts on the third day post-MI. To elucidate the nexus between macrophage-associated NLRP3 inflammasome activation and myocardial fibrosis, we employed targeted metabolomics analyses of inflammatory oxylipins, small interfering RNA (siRNA) interference experiments, and various molecular assays. These findings revealed that macrophage-associated inflammasome activation facilitates the conversion of fibroblasts into myofibroblasts via the 15-hydroxy-5,8,11,13-eicosatetraenoic acid (15-HETE)-mediated small mother against decapentaplegic (Smad) pathway. Additionally, both mass spectrometry imaging (MSI) and targeted metabolomics analyses confirmed the significant increase in 15-HETE levels in mice with MI and in patients with MI and acute coronary syndrome (ACS). Our comprehensive dataset suggests that NLRP3 inflammasome activation in MI is characterized by distinct temporal and spatial patterns. These insights mark a significant advancement toward precise MI prevention and treatment strategies, particularly early myocardial fibrosis intervention.

Chimeric antigen receptor (CAR) T cells have encouraging results in the treatment of hematological malignancies. However, CAR-T therapy still faces numerous challenges against solid tumors, such as hepatocellular carcinoma (HCC), owing to heterogeneous antigen expression in tumor cells, limited persistence of CAR-T cells, etc. Therefore, to treat HCC more effectively, we connected the molecular receptor NKBB to a second-generation glypican-3 (GPC3) CAR to construct GC3328z-NKBB CAR-T cells, which have double specific targets of GPC3 and NKG2DLs (natural killer group 2, member D ligands), dual co-stimulation of CD28 and 41BB, and a single CD3ζ chain. Our study showed that the molecular receptor NKBB conferred GPC3 CAR-T cells with enhanced migration and infiltration abilities towards HCC, higher central memory T (TCM) cell proportion and proliferation capacity, and reduced exhaustion level. GC3328z-NKBB CAR-T cells exhibited improved cytotoxicity against HCC cells and prolonged persistence. The cathepsin L/interleukin-17 (CTSL/IL-17) axis contributed to the superior anti-HCC activity of GC3328z-NKBB CAR-T cells. Overall, the molecular receptor NKBB significantly increased the persistence of GPC3 CAR-T cells, and GC3328z-NKBB CAR-T cells possessed potent anti-HCC activity in mice, providing a new strategy for the potential improvement of adoptive T cell therapy in the treatment of HCC.

Schwann cells, as crucial regenerative cells, possess the ability to facilitate axon growth following peripheral nerve injury. However, the regeneration efficiency dominated by Schwann cells is impaired by factors such as the severity of peripheral nervous injury, aging, and metabolic disease. Cause the limitations of clinical treatments, it is necessary to urgently search for new substances that could reinforce the functionality of Schwann cells and promote nerve regeneration. We represented the first evidence that isoviolanthin possesses the capability to enhance Schwann cell proliferation and migration. Then, transcriptome sequencing was employed to examine the Differential Expressed Genes (DEGs), resulting in the identification of 193 DEGs. Following this, the expression levels of the top 5 up-regulated genes were confirmed through RT-qPCR, with Fhl3 demonstrating the most significant up-regulation. Schwann cells were transduced with virus particles made in HEK-293T/17 cells by transfection with lentivirus packaging plasmids containing Fhl3. A notable enhancement in Schwann cell proliferation and migration was observed following transduction. Furthermore, the Fhl3-up group exhibited a significant upregulation of Vimentin expression compared to the control group. These results suggested that isoviolanthin plays a positive role in enhancing Schwann cells' activity via increasing Fhl3 expression, and the mechanism may be related to the EMT(epithelial-mesenchymal transition)-like process.

ObjectiveFor a long time, the dispute about whether improved glycemic control can bring significant benefits has remained unresolved. We aimed to investigate the association of time spent in different fasting glucose target ranges with cardiovascular risk and all-cause mortality in a population with type 2 diabetes (T2DM).MethodA total of 3460 T2DM patients in the Kailuan cohort were included in this study. The Time in Target Range (TITRE) was calculated as the proportion of time that fasting blood glucose (FBG) was within the usual glycemic control range and the intensive glycemic control range between 2006 and 2016. The Cox proportional hazards regression model analyzed the relationship between TITRE, defined by different glucose ranges, and cardiovascular disease and all-cause mortality.ResultsDuring a median follow-up of 4.23 years, a total of 360 CVDs and 238 deaths were recorded. After correcting for traditional risk factors, we observed that in the conventional blood glucose control group, each increase of 1 standard deviation in TITRE was associated with a 23% (HR, 0.77; 95%CI, 0.68-0.87) reduction in CVD risk and a 20% reduction in all-cause mortality (HR, 0.80; 95%CI, 0.69-0.92). Similar results were also observed in the intensified blood glucose control group. In the conventional blood glucose control group, participants with TITRE of 50% or more had an absolute incidence rate of CVD of 16.77%, whereas in the intensified blood glucose control group, participants with TITRE of 50% or more had an absolute incidence rate of CVD of 11.82%.ConclusionsIn patients with type 2 diabetes, achieving near-normal blood glucose levels appears to significantly reduce the risk of diabetes-related cardiovascular outcomes.

This study aimed to isolate and characterize Seselopsis Tianschanica Schischk Polysaccharide (STSP), a natural functional ingredient, and to develop a compound fermented beverage of nutritional and health combining STSP with highland barley. Firstly, the STSP was isolated and characterized with ultrasound-assisted enzymatic method and chromatography, and analyzed the structural features of polysaccharide STSP-1. Then, a compounded fermented beverage integrating Tibet STSP and highland barley was created, with technology and flavor substances studied. Five kinds of organic acids, 18 kinds of amino acids, and 57 kinds of volatile flavor compounds were determined by GC–MS and HPLC, and quantified significantly enhancing the overall flavor profile of the compound drink-fermented. Moreover, it exhibited higher hydroxyl radical scavenging capacity (IC50 value was 42.68 μL) compared to conventional highland barley drink. This research is expected to provide a theoretical foundation for the utilization of STSP in the functional food industry and other industries.

Abstract Passivation materials play a crucial role in a wide range of high-efficiency, high-stability photovoltaic applications based on crystalline silicon and state-of-the-art perovskite materials. Currently, for perovskite photovoltaic, the mainstream passivation strategies routinely rely on crystalline materials. Herein, we have invented a new amorphous (lysine)2PbI2 layer-enhanced halide perovskite. By utilizing a solid phase reaction between PbI2 and lysine molecule, an amorphous (lysine)2PbI2 layer is formed at surface/grain boundaries in the perovskite films. The amorphous (lysine)2PbI2 with fewer dangling bonds can effectively neutralize surface/interface defects, achieving an impressive efficiency of 26.27% (certified 25.94%). Moreover, this amorphous layer not only reduces crystal lattice stress but also functions as a barrier against the decomposition of organic components, leading to suppressed de-structuring of perovskite and highly stable perovskite solar cells.

Abstract Sepsis is characterized by a metabolic disorder of amino acid occurs in the early stage; however, the profile of serum amino acids and their alterations associated with the onset of sepsis remain unclear. Thus, our objective is to identify the specific kinds of amino acids as diagnostic biomarkers in pediatric patients with sepsis. Serum samples were collected from patients with sepsis admitted to the pediatric intensive care unit (PICU) between January 2019 and December 2019 on the 1st, 3rd and 7th day following admission. Demographic and laboratory variables were also retrieved from the medical records specified times. Serum amino acid concentrations were detected by UPLC-MS/MS system. PLS-DA (VIP > 1.0) and Kruskal-Wallis test (p

Objective: This study aimed to investigate the potential of fibroblast activation protein (FAP) as a biomarker in the progression of oral leukoplakia (OLK) carcinogenesis. This was achieved by evaluating FAP expression at different levels of the organisation, namely oral normal mucosa (NM), OLK, and oral squamous cell carcinoma (OSCC). Materials and methods: Altogether, 88 paraffin-embedded tissue samples were examined, including 55 cases of OLK, 13 cases of OSCC, and 20 cases of NM (control group). An exhaustive investigation was performed to examine FAP expression in NM, OLK, and OSCC tissues via immunohistochemistry (IHC). The relationship between FAP expression and clinical pathologic characteristics was analysed. Reverse transcription-polymerase chain reaction (RT-PCR) and western blot (WB) also proved the expression of FAP in NM, OLK, and OSCC cells. Aberrant FAP expression in OLK and OSCC was explored using in vitro experiments. Results: Immunohistochemical results showed that high FAP expression was significantly correlated with histopathologic grade (P = .038) but not correlated with age, sex, or region (P = .953, .622, and .108, respectively). The expression level of FAP in NM tissues (0.15 ± 0.01) was minimal, whereas it was observed in OLK (0.28 ± 0.04) and OSCC (0.39 ± 0.02) tissues with a noticeable increase in expression levels (P < .001). The expression level of FAP in OLK with severe abnormal hyperplasia (S-OLK) tissues (0.33 ± 0.04) was significantly higher than in OLK with mild abnormal hyperplasia (MI-OLK, 0.26 ± 0.02) and OLK with moderate abnormal hyperplasia (MO-OLK, 0.28 ± 0.03) tissues (P < .001 and P = .039, respectively). The results of RT-PCR illustrated that the relative expression of FAP mRNA in OLK cells (2.63 ± 0.62) was higher than in NM cells (0.87 ± 0.14), but lower than in OSCC cells (5.63 ± 1.06; P = .027 and .012, respectively). FAP expression was minimal in NM cells (0.78 ± 0.06), modest in OLK cells (1.04 ± 0.06), and significantly elevated in OSCC cells (1.61 ± 0.09) based on the results of WB (P < .001). Conclusions: Significant variations in FAP expression were observed in NM, OLK, and OSCC tissues and cells. These findings revealed that FAP may be a reliable biomarker for the early diagnosis and evaluation of OLK carcinogenesis.

Abstract Background Triple‐negative breast cancer (TNBC) is distinguished by a significant likelihood of distant recurrence and an unfavourable prognosis. However, the underlying molecules and mechanisms have not been fully elucidated. Methods We investigated the expression profile and clinical relevance of chaperonin‐containing TCP1 subunit 6A (CCT6A) in TNBC. We performed cell function assays on TNBC cells with CCT6A knockdown or overexpression. To further explore the mechanism of action of CCT6A, RNA sequencing and co‐immunoprecipitation–mass spectrometry analyses were utilized. Rescue and ubiquitination assays evaluated the impact of TRIM21‐mediated CCT6A ubiquitination and degradation on TNBC progression in vitro and in vivo. Finally, we studied the potential of Ipatasertib, a pharmacological AKT inhibitor, and/or anti‐PD1 therapy in inhibiting TNBC progression. Results Elevated CCT6A expression in TNBC patients was associated with an adverse prognosis and lymph node metastasis. Mechanistically, CCT6A facilitated cell migration, invasion, epithelial‐mesenchymal transition and proliferation by activating the phosphatidylinositol 3‐kinase (PI3K)/AKT pathway. The TRIM21 RING domain is an E3 ligase, facilitating the K48‐linked ubiquitination‐mediated degradation of CCT6A, thereby impeding TNBC progression. Moreover, in the tumour tissues of the CCT6A‐overexpressing mice, the quantity of CD8+ T cells and the concentration of secreted interferon‐gamma were decreased, whereas in the group double‐overexpression of CCT6A and TRIM21, they were elevated; the opposite was observed in the knockdown and double‐knockdown groups. Ipatasertib demonstrated enhanced efficacy in inhibiting cell proliferation, invasion and migration in TNBC cells ectopically expressing CCT6A. When Ipatasertib and anti‐PD1 therapies were combined, both the tumour volume and mass exhibited a notable reduction, while the expression of CD45+CD8+ T cells increased, and that of CD45+CD4+CTLA4+ and CD45+CD4+PD1+ T cells decreased. Conclusions Our findings indicate that TRIM21 inhibits TNBC progression by facilitating the K48‐linked ubiquitination‐mediated degradation of CCT6A via the PI3K/AKT signalling pathway. This highlights the potential of Ipatasertib and/or anti‐PD1 as therapeutic strategies, particularly for TNBC patients overexpressing CCT6A. Key points Chaperonin TCP1 subunit 6A (CCT6A) plays an oncogenic role in triple‐negative breast cancer (TNBC) through the AKT signaling pathway. TRIM21 facilitated K48‐linked ubiquitination‐mediated degradation of CCT6A, thereby impeding TNBC progression. Our study collectively underscores the potential of Ipatasertib in conjunction with anti‐PD1 therapy as a promising strategy to counteract CCT6A/AKT hyperactivity‐driven TNBC progression.

ABSTRACT Background Non‐invasive brain stimulation (NIBS) has attracted significant attention as it has been proven to be effective in facilitating upper limb motor recovery in patients with stroke. This meta‐analysis evaluates the efficacy of dual‐site non‐invasive brain stimulation (DS‐NIBS) in improving upper extremity motor function after stroke. Methods A PRISMA systematic search was conducted for randomized controlled trials. Two authors independently extracted data, and the quality of included studies was assessed. Results Ten studies were included in the current review. DS‐NIBS demonstrated a significant effect on upper extremity motor function impairment. However, only two studies showed no clear effects of DS‐tDCS on upper extremity motor function after stroke. Due to the limited number of studies, the effects of DS‐NIBS remain inconclusive. Finding This review found evidence for the relatively higher efficacy of DS‐NIBS on post‐stroke upper extremity motor function impairment, compared to the sham and SS‐NIBS. Additionally, DS‐TMS was found to generate better improvement than DS‐tDCS.

Background: The variations in non-coding RNA alterations and the host immune response between patients with bacterial and non-bacterial sepsis, along with their clinical characteristics, are largely unknown. Methods: The landscape of long non-coding RNA (lncRNA) and mRNA in whole blood cells from pediatric patients with bacterial sepsis or non-bacterial sepsis were characterized using an Arraystar human LncRNA microarray. Weighted correlation network analysis (WGCNA) were conducted to identify immune-related LncRNA-mRNA signatures. Least absolute shrinkage and selection operator (Lasso) regression and Ridge regression analysis were employed to develop a specific LncRNA-mRNA signature, serving as a discriminant classifier for bacterial and non-bacterial sepsis in children. Results: A total of 33 differentially expressed lncRNAs and 52 mRNAs were identified in pediatric patients with either bacterial sepsis or non-bacterial sepsis. Among these, 69 lncRNAs and mRNAs were pinpointed using WGCNA and found to be significantly correlated with clinical parameters. Further intersection analysis identified 12 lncRNAs and 16 mRNAs as immune-related signature for discerning bacterial infections in children with sepsis. Additionaly, the lncRNA-mRNA co-expression network highlighted the key lncRNAs (AC090159.1 and AC080129.2) and mRNAs (S100A8 and TCF7L2) as an infection score model. Lasso regression analysis revealed that this infection score model achieved an area under the received operating curve (AUROC) of 0.96 in the training set and 0.86 in the validation set. Ultimately, the expression levels of these 4 key lncRNAs and mRNAs showed significant correlation with CRP or PCT levels. Conclusion: The machine learning model, developed utilizing key lncRNAs (AC090159.1 and AC080129.2) and mRNAs (S100A8 and TCF7L2), demonstrates robust discrimination and calibration capabilities for distinguishing between bacterial and non-bacterial sepsis in children.

Integrins are a family of cell surface membrane receptors and play a crucial role in facilitating bidirectional cell signaling. Integrin α2 (ITGA2) is expressed across a range of cell types, including epithelial cells, platelets, megakaryocytes, and fibroblasts, where it functions as a surface marker and it is implicated in the cell movements. The most recent findings have indicated that ITAG2 has the potential to function as a novel regulatory factor in cancer, responsible for driving tumorigenesis, inducing chemoresistance, regulating genomic instability and remodeling tumor microenvironment. Hence, we primarily focus on elucidating the biological function and mechanism of ITGA2 within the digestive tumor microenvironment, while highlighting its prospective utilization as a therapeutic target for cancer therapy.

Citrus melanose, caused by Diaporthe citri, is one of the most prevalent and important fungal diseases of citrus crops globally. However, the overuse of chemical fungicides for disease control has an adverse impact on citrus production. In contrast, biological control agents (BCAs) are environmentally friendly and have become essential tools for plant disease control. In the present study, Bacillus subtilis M23, a strain isolated from healthy citrus leaves, significantly suppressed the mycelial growth of D. citri, the causal agent of citrus melanose, in vitro. The fermentation broth of B. subtilis M23 also exhibited good antifungal activity against D. citri on citrus plants in greenhouse and field experiments. Lipopeptides (LPs) produced by M23 exhibited excellent antifungal activity against D. citri, with a 50 % effective concentration (EC50) of approximately 1.00 and 0.28 μg/mL for inhibition of mycelial growth and conidial germination, respectively. LP biosynthesis genes were identified in the M23 genome using a PCR assay. Notably, LP extracts significantly reduced the formation of pycnidia and ATP biosynthesis in D. citri. Comparative transcriptome analysis revealed significant differences in the expression of genes associated with fungal vacuole, oxidoreductase activity and endopeptidase activity in D. citri treated with B. subtilis M23. Both RNA-seq and RT-qPCR analysis provided similar results on the expression of selected genes. Collectively, our data provided convincing data supporting the biocontrol potential of B. subtilis M23 for the management of citrus melanose.

BackgroundIn recent years, the problem of cognitive impairment in the elderly has become increasingly prominent. Understanding the research trend of influencing factors of mild cognitive impairment, and provide reference for medical staff to early screening of the elderly with mild cognitive impairment.ObjectiveThrough the visual analysis of the influence factors of the elderly with mild cognitive impairment, the current research status was discussed.MethodsThe relevant literature in the field of influencing factors of mild cognitive impairment in the elderly included in the Web of Science core collection database from 2013 to 2022 was searched. Using software such as Cite Space and VOS viewer to visually analyze literature citations, country, keywords, and development trends.ResultsA total of 547 relevant literatures were included, and the number of publications showed an increasing trend in the past ten years. The United States ranked first in both the number of published papers (157) and centrality (0.34), and the United States and China had a greater influence on the influencing factors of mild cognitive impairment. Alzheimer’s disease, cognitive decline, the elderly, risk factors, are the research hotspot in this field.ConclusionCognitive decline will affect the autonomy of the elderly. Cognitive frailty, MRI is the forefront of MCI research, to understand the research hotspots and frontiers in this field, to conduct early screening and intervention guidance for people with mild cognitive impairment, so as to delay the occurrence of Alzheimer’s disease, and reduce the pressure on family caregivers and society.

BackgroundRobot-assisted hand function therapy is pivotal in the rehabilitation of patients with stroke; however, its therapeutic mechanism remains elusive. Currently, research examining the impact of robot-assisted hand function therapy on brain function in patients with stroke is scarce, and there is a lack of studies investigating the correlation between muscle activity and alterations in brain function.ObjectiveThis study aimed to investigate the correlation between forearm muscle movement and brain functional activation by employing the synchronized use of functional near-infrared spectroscopy and surface electromyography methods. Moreover, it sought to compare neural activity patterns during different rehabilitation tasks and refine the mechanism of robot-assisted hand function therapy for post-stroke hand function impairments.MethodsStroke patients with hand dysfunction underwent three sessions of robot-assisted hand function therapy within 2 weeks to 3 months of onset. The fNIRS-sEMG synchronous technique was used to observe brain function and forearm muscle activation. Ten participants were randomly assigned to receive mirror, resistance, or passive rehabilitation training. During the intervention, cortical and muscle activation information was obtained using fNIRS and electromyographic signals. The primary outcomes included changes in oxyhemoglobin concentration and root mean square of surface electromyography.ResultsCompared to the resting state, the Oxy-Hb concentration in the brain regions involved in three rehabilitation tasks with robot-assisted hand function therapy significantly increased (p

Abstract During harvesting, storage, transportation, and processing, potato (Solanum tuberosum L.) tubers undergo greening after exposure to light, leading to the accumulation of toxic glycoside alkaloids, resulting in quality deterioration and economic losses. However, the underlying mechanisms are unclear. This study compared the transcriptome and proteome differences among four potato cultivars during the light-induced greening process, identifying 3,751 unique proteins (high confidence; ≥91.7%). The levels of enzymes involved in steroidal glycoalkaloid biosynthesis varied among the cultivars. In addition, coexpression network analysis of the transcriptomic data identified the transcription factor MYB113 (Soltu.DM.10G020780.1) as a potential positive regulator of steroidal glycoalkaloid biosynthesis. The dual-luciferase assay revealed that StMYB113 could bind to the promoters of steroidal glycoalkaloid biosynthesis-related genes and activate them. The transgenic lines overexpressing Solanum tuberosum L. Myb domain protein (StMYB113) exhibited greater mRNA abundance of these genes and elevated levels of steroidal glycoalkaloids. This study provided a theoretical basis for exploring the impact of light on the synthesis of solanine in potatoes.

Xiangzao brine is a special flavored food produced by the natural fermentation of Huangjiu lees. To clarify fermentation time on its quality, this study integrated flavoromics analysis, macro-genomics, and polypeptide omics to analyze the volatile flavor components, microbial species, and flavor peptide distributions of four groups of samples (XZ-1Y, XZ-2Y, XZ-3Y, and XZ-4Y) fermented for 1–4 years. The results showed that the samples fermented for 1 year had the highest contents of umami amino acids and umami peptides, and the samples fermented for 4 years had the highest contents of organic acids and fruity components. In addition, 42 volatile flavor components and 532 peptides were identified, including 393 umami taste peptides and only 37 bitter taste peptides. Correlation analysis showed that ethyl lactate and furfural were positively correlated with the abundance of Nocardioides and Stenotrophomonas, respectively. The abundance of Pseudomonas was positively correlated with four previously unreported umami peptides (FATPR, RELER, FNLERP, and RSSFLGQ) screened by molecular docking. This study provides a reference for the flavor metabolism regulation of Xiangzao brine.

BackgroundAbnormal brain activation patterns in patients with knee osteoarthritis (KOA) at rest have been revealed, but it is unclear how brain activation patterns change during movement. This study aimed to investigate the alterations in brain activation patterns in KOA patients during knee isokinetic movement, and the correlation between cortical activity changes and pain severity and dysfunction.MethodsEighteen patients with KOA and 18 healthy controls (HC) were recruited, and to performed the knee isokinetic test with three speeds. Functional near-infrared spectroscopy (fNIRS) was used to detect the cerebral cortex hemodynamics changes of primary somatosensory (S1), primary motor (M1) and somatosensory association cortex (SAC) in the region of interest (ROI) during movement. Then, we evaluated potential correlations between M1, S1 and SAC values and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and visual analog scale (VAS) scores.ResultsThe results showed that peak torque of knee extension in KOA patients was significantly smaller than that in HC. For HC, unilateral knee movement activated bilateral ROIs. The contralateral activation was dominant, showing the phenomenon of high contralateral activation. For KOA patients, there were no statistical difference in the activation level between the left and right of the cerebral cortex, with both sides showing lower activation levels compared to HC. Further analysis found that the contralateral M1, S1, and SAC of the affected knee in KOA patients were significantly lower than those in HC, while no difference was found on the ipsilateral side. Moreover, during isokinetic movement at 180°/s, VAS score in KOA patients was negatively correlated with the activation level of the contralateral S1 and M1 values, and WOMAC was negatively correlated with the activation level of the contralateral M1 value.ConclusionContralateral activation of the sensorimotor cortex exists during unilateral knee movement, but in KOA patients, this contralateral cortical activation is suppressed. Furthermore, the clinical pain and dysfunction in KOA patients are associated with activation levels of specific brain regions. These findings can provide a better understanding of KOA brain science and are expected to contribute to the development of central intervention for the disease.

IntroductionReactive oxygen species (ROS) generation is a common disease defense mechanism in plants. However, it is unclear whether Citrus host activates defense response against Diaporthe citri causing citrus melanose disease by producing ROS, and the underlying molecular mechanisms are unknown.MethodsDAB staining and RNA-Seq technology were used to compare the active oxygen burst and differential gene expression, respectively, in uninfected and infected Citrus sinensis leaves at different time points during D. citri infection in vivo. The functions of CsRBOH (a significant DEG) were confirmed in N. benthamiana through the Agrobacterium-mediated transient expression system.ResultsDAB staining indicated that C. sinensis initiated defense against D. citri infection within 24 h by generating ROS. Illumina sequencing revealed 25,557 expressed genes of C. sinensis. The most upregulated DEGs (n = 1,570) were identified 72 h after fungal inoculation (sample denoted as CD72). In the CD72 vs. Cs (samples at 0 h after fungal inoculation) comparison, the KEGG pathway category with the highest number of genes (n = 62) and most significant enrichment was Protein processing in endoplasmic reticulum, followed by Glutathione metabolism and MAPK signaling pathway-plant. GO analysis revealed that the DEGs of CD72 vs. Cs related to active oxygen burst and chitin recognition were significantly grouped into the regulation of biological processes and molecular functions, with GO terms including response to ROS, response to fungus, and oxidoreductase activity. Remarkably, CsRBOH was significantly enriched in the GO and KEGG analyses, and its expression pattern in qRT-PCR and DAB staining results were consistent. Among the 63 ROS-related DEGs, HSP genes and genes associated with the peroxidase family were highly significant as revealed by protein–protein interaction networks. Furthermore, ROS accumulation, cell death, and upregulation of defense-related genes were observed in N. benthamiana leaves with CsRBOH expressed through the Agrobacterium-mediated transient expression system.ConclusionOur findings suggested that C. sinensis activates CsRBOH and ROS-related genes, leading to ROS accumulation to resist the invasion by D. citri. This study laid the foundation for future research on molecular mechanisms and breeding of C. sinensis cultivars resistant to citrus melanose.

Introduction: Chemotherapy resistance remains a significant challenge in the treatment of pancreatic adenocarcinoma (PDAC), particularly in relation to gemcitabine (Gem), a commonly used chemotherapeutic agent. MicroRNAs (miRNAs) are known to influence cancer progression and chemoresistance. This study investigates the association between miRNA expression profiles and gemcitabine resistance in PDAC.Methods: The miRNA expression profiles of a gemcitabine-sensitive (GS) PDAC cell line, MIA PaCa-2, and its gemcitabine-resistant (GR) progeny, MIA PaCa-2 GR, were analyzed. miRNA sequencing (miRNA-seq) was employed to identify miRNAs expressed in these cell lines. Differential expression analysis was performed, and Ingenuity Pathway Analysis (IPA) was utilized to elucidate the biological functions of the differentially expressed miRNAs.Results: A total of 1867 miRNAs were detected across both cell lines. Among these, 97 (5.2%) miRNAs showed significant differential expression between the GR and GS cell lines, with 65 (3.5%) miRNAs upregulated and 32 (1.7%) miRNAs downregulated in the GR line. The most notably altered miRNAs were implicated in key biological processes such as cell proliferation, migration, invasion, chemosensitization, alternative splicing, apoptosis, and angiogenesis. A subset of these miRNAs was further analyzed in patient samples to identify potential markers for recurrent tumors.Discussion: The differential miRNA expression profiles identified in this study highlight the complex regulatory roles of miRNAs in gemcitabine resistance in PDAC. These findings suggest potential targets for improving prognosis and tailoring treatment strategies in PDAC patients, particularly those showing resistance to gemcitabine. Future research should focus on validating these miRNAs as biomarkers for resistance and exploring their therapeutic potential in overcoming chemoresistance.

Mitochondria are important organelles in cells for energy production, and mitochondrial damage caused by various reasons is an important factor promoting disease progression. Mitochondrial damage involves structural damage and mitochondrial DNA damage, which are closely related to the occurrence and development of respiratory system diseases. In recent years, a large number of studies have confirmed the significant role of mitochondrial damage in the progression of respiratory system diseases, which may be an important target for the treatment of respiratory system diseases with traditional Chinese medicine (TCM). This article reviews the role of TCM in regulating mitochondrial damage for intervention in respiratory system diseases such as chronic obstructive pulmonary disease, lung cancer, pulmonary fibrosis, acute lung injury, asthma, and pneumonia, aiming to provide a basis for the study of the pathogenesis and drug action targets of respiratory system diseases.

Neuroscientists have recognized the importance of astrocytes in regulating neurological function and their influence on the release of glial transmitters. Few studies, however, have focused on the effects of general anesthetic agents on neuroglia or astrocytes. Astrocytes can also be an important target of general anesthetic agents as they exert not only sedative, analgesic, and amnesic effects but also mediate general anesthetic-induced neurotoxicity and postoperative cognitive dysfunction. Here, we analyzed recent advances in understanding the mechanism of general anesthetic agents on astrocytes, and found that exposure to general anesthetic agents will destroy the morphology and proliferation of astrocytes, in addition to acting on the receptors on their surface, which not only affect Ca2+ signaling, inhibit the release of brain-derived neurotrophic factor and lactate from astrocytes, but are even involved in the regulation of the pro- and anti-inflammatory processes of astrocytes. These would obviously affect the communication between astrocytes as well as between astrocytes and neighboring neurons, other neuroglia, and vascular cells. In this review, we summarize how general anesthetic agents act on neurons via astrocytes, and explore potential mechanisms of action of general anesthetic agents on the nervous system. We hope that this review will provide a new direction for mitigating the neurotoxicity of general anesthetic agents.

Abstract The zinc finger transcription factor gene, CASZ1/Castor (Castor zinc finger 1), initially identified in Drosophila, plays a critical role in neural, cardiac, and cardiovascular development, exerting a complex, multifaceted influence on cell fate and tissue morphogenesis. During neurogenesis, CASZ1 exhibits dynamic expression from early embryonic development to the perinatal period, constituting a key regulator in this process. Additionally, CASZ1 controls the transition between neurogenesis and gliomagenesis. During human cardiovascular system development, CASZ1 is essential for cardiomyocyte differentiation, cardiac morphogenesis, and vascular morphology homeostasis and formation. The deletion or inactivation of CASZ1 mutations can lead to human developmental diseases or tumors, including congenital heart disease, cardiovascular disease, and neuroblastoma. CASZ1 can be used as a biomarker for disease prevention and diagnosis as well as a prognostic indicator for cancer. This review explores the unique functions of CASZ1 in tissue morphogenesis and associated diseases, offering new insights for elucidating the molecular mechanisms underlying diseases and identifying potential therapeutic targets for disease prevention and treatment.

Abstract Background Prolonged length of stay in post-anesthesia care unit (PLOS in PACU) is a combination of risk factors and complications that can compromise quality of care and operating room efficiency. Our study aimed to develop a nomogram to predict PLOS in PACU of patients undergoing elective surgery. Methods Data from 24017 patients were collected. Least absolute shrinkage and selection operator (LASSO) was used to screen variables. A logistic regression model was built on variables determined by a combined method of forward selection and backward elimination. Nomogram was designed with the model. The nomogram performance was evaluated with the area under the receiver operating characteristic curve (AUC) for discrimination, calibration plot for consistency between predictions and actuality, and decision curve analysis (DCA) for clinical application value. Results A nomogram was established based on the selected ten variables, including age, BMI < 21 kg/m2, American society of Anesthesiologists Physical Status (ASA), surgery type, chill, delirium, pain, naloxone, operation duration and blood transfusion. The C-index value was 0.773 [95% confidence interval (CI) = 0.765 - 0.781] in the development set and 0.757 (95% CI = 0.744-0.770) in the validation set. The AUC was > 0.75 for the prediction of PLOS in PACU. The calibration curves revealed high consistencies between the predicted and actual probability. The DCA showed that if the threshold probability is over 10% , using the models to predict PLOS in PACU and implement intervention adds more benefit. Conclusions This study presented a nomogram to facilitate individualized prediction of PLOS in PACU for patients undergoing elective surgery.

Pullulan is a high-value biopolymer synthesized by Aureobasidium pullulans through the fermentation of starch and sugars. It finds extensive applications in food, packaging, biomedicine, and other sectors. However, the high production costs significantly limit the development and application of pullulan. Consequently, there is an urgent need to identify high-quality fermentation substrates. In recent years, the rapid growth of Huangjiu industry has led to the generation of waste Huangjiu lees, which not only contribute to environmental pollution but also represent a significant waste of resources. As a result, the resource utilization of Huangjiu lees has garnered considerable attention. In this study, Huangjiu lees were employed as raw materials for fermentation to produce pullulan. Following fermentation of Huangjiu lees powder with the primary strain Aureobasidium pullulans LL1, the yield of pullulan was notably reduced. Through adaptive evolution, an evolved strain, Aureobasidium pullulans AP9, was isolated, demonstrating enhanced efficiency in producing pullulan from Huangjiu lees. The impact of Huangjiu lees on pullulan biosynthesis was elucidated via transcriptome analysis. Fermentation conditions were optimized using a single-factor approach, and a multi-strain staged fermentation strategy involving Aspergillus niger and Aureobasidium pullulans was employed to further enhance pullulan yield. Under optimal conditions, the pullulan yield reached 22.06 g/L, with a molecular weight of 1.04 × 106 Da. This study underscores the significant potential of utilizing Huangjiu lees for pullulan production and offers valuable insights for the resource utilization of this byproduct.

In this study, we investigate the volatility spillover effects across uncertainty indices (Infectious Disease Equity Market Volatility Tracker (IDEMV) and Geopolitical Risk Index (GPR)), carbon emissions, crude oil, natural gas, and green assets (green bonds and green stock) under extreme market conditions based on the quantile connectedness approach. The empirical findings reveal that the total and directional connectedness across green assets and other variables in extreme market conditions is much higher than that in the median, and there is obvious asymmetry in the connectedness measured at the extreme lower and upper quantiles. Our findings suggest that the uncertainty caused by COVID-19 has a more significant impact on green assets than the uncertainty related to the Russia–Ukraine war under normal and extreme market conditions. Furthermore, we discover that the uncertainty indices are more important in predicting green asset volatility under extreme market conditions than they are in the normal market. Finally, we observe that the dynamic total spillover effects in the extreme quantiles are significantly higher than those in the median.

When children enter adolescence, their personality traits easily give rise to psychological reactance (PR). PR involves a desire for autonomy and independence, as well as an aversion to parental and social rules and restrictions. Factors that influence PR include physiological, familial, and social aspects. However, most studies on adolescent noncompliance have primarily focused on rebellious behavior. Little research has examined motivational state reactance, although its interaction with environmental perception can significantly affect adolescents’ lives. This study aimed to explore the relationship between the perceived friendliness of the community environment and cognitive processing at different quality of life (QoL) levels in relation to PR among adolescents. Propensity score matching was performed on a sample of 3546 adolescents, collected in Sanya, China. The results show that child-friendly communities (CFCs) had a significantly negative impact on adolescents’ PR levels. Additionally, QoL had a moderating effect, meaning that the higher the QoL, the stronger the role of a CFC in alleviating PR. In contrast to claims that PR is determined by temperament or character profiles, this study reveals the importance of environmental shaping through triadic reciprocal determinism and a focus on the key role of the community environment.

Abstract Different microorganisms can produce different proteases, which can adapt to different industrial requirements such as pH, temperature, and pressure. Salt-tolerant proteases (STPs) from microorganisms exhibit higher salt tolerance, wider adaptability, and more efficient catalytic ability under extreme conditions compared to conventional proteases. These unique enzymes hold great promise for applications in various industries including food, medicine, environmental protection, agriculture, detergents, dyes, and others. Scientific studies on microbial-derived STPs have been widely reported, but there has been little systematic review of microbial-derived STPs and their application in high-salt conventional soybean fermentable foods. This review presents the STP-producing microbial species and their selection methods, and summarizes and analyzes the salt tolerance mechanisms of the microorganisms. It also outlines various techniques for the isolation and purification of STPs from microorganisms and discusses the salt tolerance mechanisms of STPs. Furthermore, this review demonstrates the contribution of modern biotechnology in the screening of novel microbial-derived STPs and their improvement in salt tolerance. It highlights the potential applications and commercial value of salt-tolerant microorganisms and STPs in high-salt traditional soy fermented foods. The review ends with concluding remarks on the challenges and future directions for microbial-derived STPs. This review provides valuable insights into the separation, purification, performance enhancement, and application of microbial-derived STPs in traditional fermented foods. Graphical Abstract

Abstract The significance of waterlogged archaeological wood (WAW) lies in its profound informational value, encompassing historical, cultural, artistic, and scientific aspects of human civilization, and therefore need to be properly studied and preserved. In this study, the utilization of near-infrared (NIR) spectroscopy is employed as a predictive tool for assessing the hardness value of WAW. Given the submerged burial conditions, waterlogged wooden heritage frequently undergo substantial degradation in their physical and mechanical properties. The mechanical properties of waterlogged wooden heritage are essential for evaluating their state of preservation and devising appropriate conservation and restoration strategies. However, conventional methods for testing mechanical properties are limited by factors such as the availability of adequate sample size and quantity, adherence to the “principle of minimum intervention,” and cost considerations. NIR spectroscopy is a non-destructive, rapid, sensitive, and low-cost analytical technique with great potential for application in this area. In this study, two large and significant ancient Chinese shipwrecks were investigated. One hundred ninety-seven samples were collected and analyzed using NIR spectroscopy and a portable C-type shore hardness testing method. A partial least squares (PLS) regression model was developed to predict the hardness of the WAW. The model was optimized and validated using different preprocessing methods and spectral ranges. The results indicate that the best models were obtained with first derivatives + multiple scattering corrections (MSC) and first derivatives + standard normal variate (SNV) preprocessing in the 1000–2100 nm spectral range, both with an R 2 c of 0.97, a root mean squared error of correction (RMSEC) of 2.39 and 2.40, and a standard error of correction (SEC) of 2.40 and 2.41. Furthermore, they exhibited an R 2 v of 0.89 and 0.87, a root mean squared error of cross-validation (RMSECV) of 4.43 and 4.67, a standard error of cross-validation (SECV) of 4.45 and 4.68, and RPD values of 3.02 and 2.88, respectively. A coefficient of determination of the established prediction model (R 2 p) of 0.89 with a relative standard deviation for prediction (RSD) of 6.9%

IntroductionStreptococcus suis is one of the porcine pathogens that have recently emerged as a pathogen capable of causing zoonoses in some humans. Patients infected with S. suis can present with sepsis, meningitis, or arthritis. Compared to common pathogens, such as Meningococcus, Streptococcus pneumoniae, and Haemophilus influenzae, S. suis infections in humans have been reported only rarely.MethodsThis case report described a 57-year-old man who presented with impaired consciousness and fever following several days of backache. He was a butcher who worked in an abattoir and had wounded his hands 2 weeks prior. The patient was dependent on alcohol for almost 40 years. S. suis was detected in the cerebrospinal fluid by metagenomic next-generation sequencing. Although he received adequate meropenem and low-dose steroid therapy, the patient suffered from bilateral sudden deafness after 5 days of the infection. The final diagnosis was S. suis meningitis and sepsis.ResultsThe patient survived with hearing loss in both ears and dizziness at the 60-day follow-up.DiscussionWe reported a case of S. suis infection manifested as purulent meningitis and sepsis. Based on literature published worldwide, human S. suis meningitis shows an acute onset and rapid progression in the nervous system. Similar to bacterial meningitis, effective antibiotics, and low-dose steroids play important roles in the treatment of human S. suis meningitis.

ObjectivesOur objective was to compare the effectiveness of TXA in improving recurrence in patients with chronic subdural hematoma (CSDH).MethodsEligible randomized controlled trials (RCTs), prospective trials and retrospective cohort studies were searched in PubMed, Cochrane Library, Embase, and CNKI from database inception to December 2023. After the available studies following inclusion and exclusion criteria were screened, the main outcome measures were strictly extracted. Reman v5.4. was used to assess the overall recurrence rate. A random-effects model was used to assess pooled ORs, with the Mantel–Haenszel estimation method applied. Cochran Q (Chi-square) test and I2 statistics were used to assess inter-study heterogeneity. Funnel plots were used to evaluate publication bias.ResultsFrom the 141 articles found during initial citation screening, 9 literatures were ultimately included in our study. Our NMA results illustrated that patients with newly diagnosed Chronic subdural hematoma revealed a significantly improved recurrence rate when patients were treated with Tranexamic acid (OR: 0.33; 95% CI 0.26–0.41; p

Objective: Oxygen and hemodynamic management are important for providing a sufficient adequate oxygen-containing blood to the organs for septic patients. In present study, we aimed to explore the application of sequential respiratory support (SRS) and the association of SRS with the outcome of septic patients who needed continuous renal replacement therapy (CRRT). Methods: We extracted the medical information of septic patients who received CRRT within 24 h of intensive care unit (ICU) admission from the MIMIC-III v1.4. SRS was defined as receiving firstly oxygen therapy followed by mechanical ventilation (MV) within 24 h of admission to ICU. The propensity score matching (PSM) was performed to compare the differences in clinical characteristics and outcomes of patients with or without SRS. Finally, we developed logistic regression models to analyze the effects of SRS on hospital mortality. Results: A total of 181 patients entered in this study, and there were 80 patients undergoing MV including SRS group (n = 61) and non-SRS group (n = 19). In the multivariate logistic regression, the value of SRS was associated with the lower risk of hospital mortality adjusted by minimum systolic BP (SBP), maximum lactate, vasopressor use, and sequential organ failure assessment (SOFA) score or Logistic Organ Dysfunction System (LODS) scores within the first 24 h of ICU stay. After PSM adjusted by SBP, maximum lactate, vasopressor use, SOFA, and LODS, there were 31 patients in SRS group with a and 18 cases in non-SRS group, displaying a significantly lower hospital mortality in SRS group than that in patients without SRS (19.4 % vs. 83.3 %, P

Abstract Biological membranes often play important functional roles in biomimetic drug delivery systems. We discover that the circulation time and targeting capability of biological membrane coated nanovehicles can be significantly improved by reducing cholesterol level in the coating membrane. A proof-of-concept system using cholesterol-reduced and PD-1-overexpressed T cell membrane to deliver a photothermal agent and a STING agonist is thus fabricated. Comparing with normal membrane, this engineered membrane increases tumor accumulation by ~2-fold. In a melanoma model in male mice, tumors are eliminated with no recurrence in >80% mice after intravenous injection and laser irradiation; while in a colon cancer model in male mice, ~40% mice are cured without laser irradiation. Data suggest that the engineered membranes escape immune surveillance to avoid blood clearance while keeping functional surface molecules exposed. In summary, we develop a simple, effective, safe and widely-applicable biological membrane modification strategy. This “subtractive” strategy displays some advantages and is worth further development.

Abstract Circular RNA HIPK3 (circHIPK3) mediates the progression of multiple cancers, including bladder cancer, by regulating cell migration, autophagy and epithelial mesenchymal transition. However, the mechanism by which circHIPK3 regulates autophagy in bladder cancer cells remains unclear. Autophagy is a common self-protection mechanism in eukaryotic cells and is essential for cell survival and death regulation. However, it is unclear whether circHIPK3 affects the level of autophagy in bladder cancer through binding proteins, and the potential regulatory mechanism is unknown. Here, we found that circHIPK3 levels were significantly lower and autophagy-related proteins were significantly upregulated in bladder cancer cells and tissues compared to normal controls. CircHIPK3 downregulation promoted bladder cancer cell proliferation, while circHIPK3 overexpression inhibited proliferation. CircHIPK3 overexpression significantly suppressed autophagy in bladder cancer cells. Overexpression of circHIPK3 did not affect VCP protein expression but inhibited the VCP/Beclin 1 interaction. VCP also stabilized Beclin 1 and promoted autophagy in bladder cancer cells by downregulating ataxin-3. Thus, circHIPK3 may play an important role in bladder cancer by inhibiting VCP-mediated autophagy.

Abstract Self-experience consistency has an important effect on life satisfaction; however, the underlying mechanism of this relationship remains unclear. This study aims to examine why self-experience consistency is related to increased life satisfaction. To do so, we investigated the relationships between self-experience consistency, the need for relatedness, Zhong-yong thinking, and life satisfaction in a sample of 456 undergraduate students. We also tested a moderated mediation model examining Zhong-yong thinking as a moderator. The results suggest that self-experience consistency related to life satisfaction was due, in part, to an increased need for relatedness. However, interpretation of this finding is limited by the use of cross-sectional data. Furthermore, Zhong-yong thinking moderated the self-experience consistency—need for relatedness link, such that the link was stronger for individuals with high/moderate levels of Zhong-yong thinking. Overall, these findings address a major gap in the positive psychology literature. Finally, implications for research are discussed.

Abstract The aberrant expression of microRNA (miRNA) is closely associated with various pathological processes, such as the development of gastric cancer. High-efficiency quantification of miRNAs is significant for the diagnosis, prognosis, and treatment of cancers. However, the sensitive and reliable detection of miRNA remains a huge challenge. We depict here a novel fluorescent approach for sensitive and label-free miRNA detection by exploiting a designed detection scaffold to integrate the catalytic hairpin assembly and primer exchange reaction (PER). In this method, the detection scaffold that is constructed based on the hybridization between two hairpin structure probes (H1 probe and H2 probe), is capable of specifically recognizing target miRNA and activating signal amplification, and the PER process transcribes numerous G-rich sequences to induce ThT-based label-free signal generation. Based on the efficient signal amplification strategy and label-free signal generation mode, the method exhibits a wide detection range of 7 orders of magnitude and a high repeatability (coefficient of variation, 2.76%), implying that the proposed approach will be a robust tool in quantification of miRNA and early diagnosis of disease. Graphical abstract

Abstract Background Ketamine is administered in the perioperative period for its benefits in analgesia, anti-agitation and anti-depression when administered at a small dose. However, it is not clear whether the intra-operative administration of ketamine would affect emergence under sevoflurane anesthesia. To investigate this effect, we designed this trial. Methods In this randomized, double-blind, placebo-controlled study, we enrolled 44 female patients aged 18–60 who were scheduled to elective laparoscopic gynecological surgeries. All patients were randomly assigned to saline or s-ketamine group. In s-ketamine group, patients received 0.125 mg/kg s-ketamine 30 min after the start of surgery. In saline group, patients were administered the same volume of saline. Sevoflurane and remifentanil were used to maintain general anesthesia. The primary outcome was emergence time. We also assessed postoperative agitation, cognitive function, and delirium. In addition, we collected and analyzed prefrontal electroencephalogram (EEG) during and after general anesthesia. Results There were no significant differences in emergence time between s-ketamine group and saline group (10.80 ± 3.77 min vs. 10.00 ± 2.78 min, P = 0.457). Neither postoperative agitation (4 [3, 4] vs. 4 [3, 4], P = 0.835) nor cognitive function (25.84 ± 2.69 vs. 25.55 ± 2.19, P = 0.412) differed between groups. No postoperative delirium was observed in either group. Subanesthetic s-ketamine resulted in active EEG with decreased power of slow (-0.35 ± 1.13 dB vs. -1.63 ± 1.03 dB, P = 0.003), delta (-0.22 ± 1.11 dB vs. -1.32 ± 1.09 dB, P = 0.011) and alpha (-0.31 ± 0.71 dB vs. -1.71 ± 1.34 dB, P = 0.0003) waves and increased power of beta-gamma bands (-0.30 ± 0.89 dB vs. 4.20 ± 2.08 dB, P

Previous research has established a correlation between PM2.5 exposure and aging-related cardiovascular diseases, primarily in blood vessels. However, the impact of PM2.5 on cardiomyocyte aging remains unclear. In this study, we observed that extractable organic matter (EOM) from PM2.5 exposure led to cellular senescence in H9c2 cardiomyoblast cells, as characterized by an increase in the percentage of β-galactosidase-positive cells, elevated expression levels of p16 and p21, and enhanced H3K9me3 foci. EOM also induced cell cycle arrest at the G1/S stage, accompanied by downregulation of CDK4 and Cyclin D1. Furthermore, EOM exposure led to a significant elevation in intracellular reactive oxygen species (ROS), mitochondrial ROS, and DNA damage. Supplementation with the antioxidant NAC effectively attenuated EOM-induced cardiac senescence. Our findings also revealed that exposure to EOM activated the aryl hydrocarbon receptor (AhR) signaling pathway, as evidenced by AhR translocation to the nucleus and upregulation of Cyp1a1 and Cyp1b1. Importantly, the AhR antagonist CH223191 effectively mitigated EOM-induced oxidative stress and cellular senescence. In conclusion, our results indicate that PM2.5-induced AhR activation leads to oxidative stress, DNA damage, and cell cycle arrest, leading to cardiac senescence. Targeting the AhR/ROS axis might be a promising therapeutic strategy for combating PM2.5-induced cardiac aging.

The purpose of this study is to explore nonlinear and threshold effects of traffic statuses and road geometries, as well as their interactions, on traffic accident severity. In contrast to earlier research that primarily defined road alignment qualitatively as straight or curved, flat or slope, this study focused on the design elements of road geometry at accident locations. Additionally, this study considers the traffic conditions on the day of the accident, rather than the average annual traffic data as previous studies have done. To achieve this, we collected road design documents, traffic-related data, and 2023 accident data from the Suining section of the G42 Expressway in China. Using this dataset, we tested the classification performance of four machine learning models, including eXtreme Gradient Boosting, Gradient Boosted Decision Tree, Random Forest, and Light Gradient Boosting Machine. The optimal Random Forest model was employed to identify the key factors infulencing traffic accident severity, and the partial dependence plot was introduced to visualize the relationship between severity and various single and two-factor variables. The results indicate that the percentage of trucks, daily traffic volume, slope length, road grade, curvature, and curve length all exhibit significant nonlinear and threshold effects on accident severity. This reveals sepecific road and traffic features associated with varying levels of accident severity along the highway section examined in this study. The findings of this study will provide data-driven recommendations for highway design and daily safety management to reduce the severity of traffic accidents.

ABSTRACT Human adenovirus (HAdV) type 7 and type 55 infections cause more severe pneumonia than type 3 infections. However, the underlying mechanisms remain unclear. This study provided evidence linking the receptor-binding protein, fiber, to the stronger virulence of HAdV-55 and HAdV-7. Wild-type HAdV-7 and HAdV-55 produced larger plaques and grew more efficiently, resulting in a higher viral yield than HAdV-3. The recombinant knobs of HAdV-55 and HAdV-7 had higher binding affinities with desmoglein 2 (DSG2) than the HAdV-3 knob. Fiber-chimeric rAdV3E-K7 and rAdV3E-K55 were generated by replacing the knob of recombinant HAdV-3 (rAd3E) with knobs from HAdV-7 and HAdV-55, respectively. Full-length fiber-replaced rAd5-F3, rAd5-F7, and rAd5-F55 were generated from replication-defective HAdV-5. The replication and infectivity of these adenoviruses were compared using passage and primary cell and DSG2-humanized mouse models. Both rAdV3E-K7 and rAdV3E-K55 produced larger plaques and adsorbed more efficiently than rAd3E in A549 cells and primary human bronchial epithelial cells. Additionally, rAd5-F7 and rAd5-F55 showed stronger infectivity than rAd5-F3. Finally, rAdV3E-K7 and rAdV3E-K55 infections contributed to slightly more but not significant severe pneumonia than rAd3E in the humanized mouse model. In summary, higher binding affinities of fibers with DSG2 lead to higher infection efficiency of HAdV-7 and HAdV-55 compared to HAdV-3. This study provides new insights into the mechanisms of differential pathogenicity between HAdV types. It may have implications for the surveillance of highly pathogenic adenovirus strains and the development of novel adenovirus vectors and vaccines. IMPORTANCE HAdV-3, -7, and -55 are the predominant types causing acute respiratory disease outbreaks and can lead to severe and fatal pneumonia in children and adults. In recent years, emerging or re-emerging strains of HAdV-7 and HAdV-55 have caused multiple outbreaks globally in both civilian and military populations, drawing increased attention. Clinical studies have reported that HAdV-7 and HAdV-55 cause more severe pneumonia than HAdV-3. This study aimed to investigate the mechanisms explaining the higher severity of HAdV-7 and HAdV-55 infection compared to HAdV-3 infection. Our findings provided evidence linking the receptor-binding protein fiber to stronger infectivity of the strains mentioned above by comparing several fiber-chimeric or fiber-replaced adenoviruses. Our study improves our understanding of adenovirus infection and highlights potential implications, including in novel vector and vaccine development.

Recurring episodes of fever characterize tumor necrosis factor receptor-associated periodic syndrome (TRAPS) which is autosomal dominant. The primary symptoms of patients with TRAPS include prolonged fever, abdominal pain, muscle pain, and skin rashes. The prevalence of TRAPS appeared higher in Western countries than in Asian countries. Herein, we present the case of a 13-year-old girl who experienced intermittent fever for 8 years, with episodes that occur every 2 years. The patient demonstrated periodic fever, headache, vomiting, rash, and elevated inflammatory marker levels during the disease course. A heterozygous C55Y mutation was identified via a direct DNA sequencing of her genomic DNA. This mutation is located in exon 4 of TNFRSF1A. Genetic studies of her sister and mother revealed that they possessed the C55Y heterozygous mutation without demonstrating any clinical signs, while the father did not. Further, we conducted a thorough assessment of the literature and compiled the information from the eight TRAPS case series.

We propose two simple regression models of Pearson correlation coefficient of two normal responses or binary responses to assess the effect of covariates of interest. Likelihood-based inference is established to estimate the regression coefficients, upon which bootstrap-based method is used to test the significance of covariates of interest. Simulation studies show the effectiveness of the method in terms of type-I error control, power performance in moderate sample size and robustness with respect to model mis-specification. We illustrate the application of the proposed method to some real data concerning health measurements.

The container terminal handling system plays an important role in marine transportation, and improving its efficiency has become a big challenge. Therefore, this paper proposes an analytical method that combines a Petri net with simulation tools. Firstly, the container terminal handling system is abstracted into a Petri net system according to the internal logic of the handling process. Next, eigenvalues of the correlation matrix are calculated to analyse the effectiveness of the Petri net system. Then, the Petri net system is simulated using the Extend-Sim software. The result suggests that, after optimising, the handling capacity of the berth is clearly improved. Using the Petri net and simulation tools together to analyse the container terminal system is the innovation and the most important aspect of this paper. Because the combination of a Petri net and simulation can not only ensure the reliability of the model but also optimise the container terminal handling system more intuitively.

The high spatial-temporal variability of soil moisture necessitates monitoring at a high resolution in order to improve our understanding of Earth system processes. Current large-scale soil moistures inferred from the microwave satellites have limited spatial resolution, typically in the range of tens of kilometers. Recent studies have revealed that synthetic aperture radar (SAR) backscatter exhibits qualitative relationships with soil moisture, suggesting the potential for large-scale high-resolution mapping of soil moisture. Here, we proposed a method for directly estimating soil moisture content based on the advanced integral equation model and Mironov dielectric model. The approach involves establishing a series of semiempirical models, independent of preceding surface roughness determination, using two Envisat advanced synthetic aperture radar (ASAR) alternating polarization (AP) model precision products. We generate a time series of high-resolution soil moisture using Envisat ASAR AP data acquired from 2004 to 2011, with an uncertainty of approximately 0.05 m3/m3. Our soil moisture retrievals demonstrate very good agreement with European Space Agency Climate Change Initiative soil moisture products and the European Centre for Medium-Range Weather Forecasts ERA5 reanalysis hourly products, even in the absence of synchronous ground measurements. Furthermore, our study reveals good temporal coherence between drought and heavy rainfall events, and SAR-derived soil moisture, which suggests a potential to capture heavy rainfall and drought events. We conclude that SAR-derived soil moisture is a more direct and efficient method in quantifying soil moisture at a high spatial resolution, making it more suitable for watershed scale hydrological studies.

Schizophrenia is a heterogeneous mental disorder with unknown etiology or pathological characteristics. Microstate analysis of the electroencephalogram (EEG) signal has shown significant potential value for clinical research. Importantly, significant changes in microstate-specific parameters have been extensively reported; however, these studies have ignored the information interactions within the microstate network in different stages of schizophrenia. Based on recent findings, since rich information about the functional organization of the brain can be revealed by functional connectivity dynamics, we use the first-order autoregressive model to construct the functional connectivity of intra- and intermicrostate networks to identify information interactions among microstate networks. We demonstrate that, beyond abnormal parameters, disrupted organization of the microstate networks plays a crucial role in different stages of the disease by 128-channel EEG data collected from individuals with first-episode schizophrenia, ultrahigh-risk, familial high-risk, and healthy controls. According to the characteristics of the microstates of patients at different stages, the parameters of microstate class A are reduced, those of class C are increased, and the transitions from intra- to intermicrostate functional connectivity are gradually disrupted. Furthermore, decreased integration of intermicrostate information might lead to cognitive deficits in individuals with schizophrenia and those in high-risk states. Taken together, these findings illustrate that the dynamic functional connectivity of intra- and intermicrostate networks captures more components of disease pathophysiology. Our work sheds new light on the characterization of dynamic functional brain networks based on EEG signals and provides a new interpretation of aberrant brain function in different stages of schizophrenia from the perspective of microstates.

Land subsidence has become a challenging problem with urbanization and underground exploitation. The land subsidence in Wuhan, China, was inferred from 47 Sentinel-1A images acquired between June 2015 to October 2020 based on Synthetic Aperture Radar (SAR) Interferometric Point Target Analysis (IPTA) technology. Results show that significant subsidence mainly occurred in Houhu, Qinshan, Baishazhou, and Zhuankou areas, and the most significant subsidence occurred in Baishazhou, reaching an annual subsidence rate of 41.0 mm/a with accumulated subsidence of 219.4 mm., The subsidence was more significant in the carbonate solution zone with the overlying Holocene strata compared to the rest carbonate karst belts. Analysis shows thatland building construction is a major reason for land subsidence in Wuhan. The construction of subway underground stations is another factor causing land subsidence. The effect of water level fluctuations of the Yangtze River on long-term trends is negligible. Our study provides further insight into the temporal-spatial pattern of Wuhan’s displacements and suggests that the land subsidence should be continuously monitored for alleviation of potential destructive hazards, especially during the period of construction of a land building, such as residential, public facilities, and subway.

Parkinson's disease (PD) has been showed perfusion and neural activity alterations in specific regions, such as the motor and visual networks; however, the clinical significance of coupling changes is still unknown. To identify how neurovascular coupling changes during the pathophysiology of PD, patients and healthy controls underwent multiparametric magnetic resonance imaging to measure neural activity organization of segregation and integration using amplitude of low-frequency fluctuation (ALFF) and functional connectivity strength (FCS), and measure vascular responses using cerebral blood flow (CBF). Neurovascular coupling was calculated as the global CBF-ALFF and CBF-FCS coupling and the regional CBF/ALFF and CBF/FCS ratio. Correlations and dynamic causal modeling was then used to evaluate relationships with disease-alterations to clinical variables and information flow. Neurovascular coupling was impaired in PD with decreased global CBF-ALFF and CBF-FCS coupling, as well as decreased CBF/ALFF in the parieto-occipital cortex (dorsal visual stream) and CBF/FCS in the temporo-occipital cortex (ventral visual stream); these decouplings were associated with motor and non-motor impairments. The distinctive patterns of neurovascular coupling alterations within the dorsal and ventral visual streams of the visual system could potentially provide additional understanding into the pathophysiological mechanisms of PD.