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Abstract The apparent optimum air temperature for vegetation photosynthesis (Topt) is a key temperature parameter in terrestrial ecosystem models estimating daily photosynthesis or gross primary production (GPP, g C/m2/day). To date, most models use biome-specific Topt (Topt-biome) parameter values. Given vegetation acclimation and adaptation to local climate, site-specific Topt (Topt-site) is needed to reduce uncertainties in estimating daily GPP across the scales from site to region and the globe. Previous studies have demonstrated using the Enhanced Vegetation Index (EVI) derived from Moderate Resolution Imaging Spectroradiometer (MODIS) images and daytime air temperature data to estimate the Topt-site at the eddy covariance tower sites. This study used MODIS-derived EVI and ERA5 climate data to estimate and generate global Topt-site data products from 2000 to 2019. The Topt-site of individual pixels within a biome has large variation, which clearly cannot be represented accurately by the widely used Topt-biome. Therefore, using this global dataset of Topt-site estimates might significantly affect GPP simulation in current ecosystem models.

Abstract Background Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage destruction and inflammation. CC chemokine receptor 1 (CCR1), a member of the chemokine family and its receptor family, plays a role in the autoimmune response. The impact of BX471, a specific small molecule inhibitor of CCR1, on CCR1 expression in cartilage and its effects on OA remain underexplored. Methods This study used immunohistochemistry (IHC) to assess CCR1 expression in IL-1β-induced mouse chondrocytes and a medial meniscus mouse model of destabilization of the medial meniscus (DMM). Chondrocytes treated with varying concentrations of BX471 for 24 h were subjected to IL-1β (10 ng/ml) treatment. The levels of the aging-related genes P16INK4a and P21CIP1 were analyzed via western blotting, and senescence-associated β-galactosidase (SA-β-gal) activity was measured. The expression levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), aggrecan (AGG), and the transcription factor SOX9 were determined through western blotting and RT‒qPCR. Collagen II, matrix metalloproteinase 13 (MMP13), and peroxisome proliferator-activated receptor (PPAR)-γ expression was analyzed via western blot, RT‒qPCR, and immunofluorescence. The impact of BX471 on inflammatory metabolism-related proteins under PPAR-γ inhibition conditions (using GW-9662) was examined through western blotting. The expression of MAPK signaling pathway-related molecules was assessed through western blotting. In vivo, various concentrations of BX471 or an equivalent medium were injected into DMM model joints. Cartilage destruction was evaluated through Safranin O/Fast green and hematoxylin–eosin (H&E) staining. Results This study revealed that inhibiting CCR1 mitigates IL-1β-induced aging, downregulates the expression of iNOS, COX-2, and MMP13, and alleviates the IL-1β-induced decrease in anabolic indices. Mechanistically, the MAPK signaling pathway and PPAR-γ may be involved in inhibiting the protective effect of CCR1 on chondrocytes. In vivo, BX471 protected cartilage in a DMM model. Conclusion This study demonstrated the expression of CCR1 in chondrocytes. Inhibiting CCR1 reduced the inflammatory response, alleviated cartilage aging, and retarded degeneration through the MAPK signaling pathway and PPAR-γ, suggesting its potential therapeutic value for OA. Graphical Abstract

Abstract Blood exchange therapy, specifically Whole blood exchange (WBE), is increasingly being utilized in clinical settings to effectively treat a range of diseases. Consequently, there is an urgent requirement to establish convenient and clinically applicable animal models that can facilitate the exploration of blood exchange therapy mechanisms. Our study conducted continuous WBE in rats through femoral and tail vein catheterization using dual-directional syringe pumps. To demonstrate the applicability of continuous WBE, drug-induced hemolytic anemia (DIHA) was induced through phenylhydrazine hydrochloride (PHZ) injection. Notability, the rats of DIHA + WBE group all survived and recovered within the subsequent period. After the implementation of continuous WBE therapy day (Day 1), the DIHA + WBE group exhibited a statistically significant increase in red blood cells (RBC) (P = 0.0343) and hemoglobin (HGB) levels (P = 0.0090) compared to DIHA group. The rats in the DIHA + WBE group exhibited a faster recovery rate compared to the DIHA group, indicating the successful establishment of a continuous blood exchange protocol. This experimental approach demonstrates not just promising efficacy in the treatment of DIHA and offers a valuable tool for investigating the underlying mechanisms of blood exchange. Furthermore, it has a great potential to the advancement of biomedical research such as drug delivery exploration.

Abstract Transfer RNA (tRNA)-derived small RNAs (tsRNAs) are a new type of non-coding RNAs (ncRNAs) produced by the specific cleavage of precursor or mature tRNAs. tsRNAs are involved in various basic biological processes such as epigenetic, transcriptional, post-transcriptional, and translation regulation, thereby affecting the occurrence and development of various human diseases, including cancers. Recent studies have shown that tsRNAs play an important role in tumorigenesis by regulating biological behaviors such as malignant proliferation, invasion and metastasis, angiogenesis, immune response, tumor resistance, and tumor metabolism reprogramming. These may be new potential targets for tumor treatment. Furthermore, tsRNAs can exist abundantly and stably in various bodily fluids (e.g., blood, serum, and urine) in the form of free or encapsulated extracellular vesicles, thereby affecting intercellular communication in the tumor microenvironment (TME). Meanwhile, their abnormal expression is closely related to the clinicopathological features of tumor patients, such as tumor staging, lymph node metastasis, and poor prognosis of tumor patients; thus, tsRNAs can be served as a novel type of liquid biopsy biomarker. This review summarizes the discovery, production, and expression of tsRNAs and analyzes their molecular mechanisms in tumor development and potential applications in tumor therapy, which may provide new strategies for early diagnosis and targeted therapy of tumors.

Abstract Background Although current guidelines(ESPEN guideline: Clinical nutrition in surgery and other guidelines) recommend preoperative immunonutrition for cachectic gastric cancer patients, the strength of the recommendation is weak, and the level of evidence is low. The benefits of preoperative immunonutrition still remain controversial. Patients and methods 112 patients with gastric cancer cachexia were enrolled in the study and randomly assigned in a 1:1 ratio to receive either preoperative enteral immunonutrition support (IN, n = 56) or standard enteral nutrition support (SEN, n = 56). The primary endpoint was the incidence of infectious complications, and the secondary endpoints included the nutritional indicators, inflammatory markers, immune parameters, postoperative recovery and complications and gastrointestinal intolerance reactions. Results The incidence of postoperative infectious complications(P = 0.040) and overall complications (P = 0.049)was significantly lower in the IN group compared to the SEN group. In terms of laboratory inflammatory indexes, patients in the IN group demonstrated significantly lower levels of white blood cells (WBC), C-reactive protein (CRP), and interleukin-6 (IL-6), as well as higher levels of lymphocytes (LYMPH) and immunoglobulin A (IgA), compared to patients in the SEN group, with statistically significant differences. In terms of clinical outcomes, the IN group had a shorter duration of antibiotic use (P = 0.048), shorter hospital stay (P = 0.018), and lower total hospital costs (P = 0.034) compared to the SEN group. The IN group also experienced significantly less weight loss after surgery (P = 0.043). Conclusion Preoperative administration of immunonutrition formula has a positive impact on the incidence of infectious complications in patients with gastric cancer cachexia after surgery. It improves patients’ inflammatory and immune status, shortens hospital stays, and reduces healthcare costs. Preoperative use of immunonutrition may contribute to the improvement of prognosis in this high-risk population.

BackgroundSeveral urinary biomarkers have good diagnostic value for diabetic kidney disease (DKD); however, the predictive value is limited with the use of single biomarkers. We investigated the clinical value of Luminex liquid suspension chip detection of several urinary biomarkers simultaneously.MethodsThe study included 737 patients: 585 with diabetes mellitus (DM) and 152 with DKD. Propensity score matching (PSM) of demographic and medical characteristics identified a subset of 78 patients (DM = 39, DKD = 39). Two Luminex liquid suspension chips were used to detect 11 urinary biomarkers according to their molecular weight and concentration. The biomarkers, including cystatin C (CysC), nephrin, epidermal growth factor (EGF), kidney injury molecule-1 (KIM-1), retinol-binding protein4 (RBP4), α1-microglobulin (α1-MG), β2-microglobulin (β2-MG), vitamin D binding protein (VDBP), tissue inhibitor of metalloproteinases-1 (TIMP-1), tumor necrosis factor receptor-1 (TNFR-1), and tumor necrosis factor receptor-2 (TNFR-2) were compared in the DM and DKD groups. The diagnostic values of single biomarkers and various biomarker combinations for early diagnosis of DKD were assessed using receiver operating characteristic (ROC) curve analysis.ResultsUrinary levels of VDBP, RBP4, and KIM-1 were markedly higher in the DKD group than in the DM group (p < 0.05), whereas the TIMP-1, TNFR-1, TNFR-2, α1-MG, β2-MG, CysC, nephrin, and EGF levels were not significantly different between the groups. RBP4, KIM-1, TNFR-2, and VDBP reached p < 0.01 in univariate analysis and were entered into the final analysis. VDBP had the highest AUC (0.780, p < 0.01), followed by RBP4 (0.711, p < 0.01), KIM-1 (0.640, p = 0.044), and TNFR-2 (0.615, p = 0.081). However, a combination of these four urinary biomarkers had the highest AUC (0.812), with a sensitivity of 0.742 and a specificity of 0.760.ConclusionsThe urinary levels of VDBP, RBP4, KIM-1, and TNFR-2 can be detected simultaneously using Luminex liquid suspension chip technology. The combination of these biomarkers, which reflect different mechanisms of kidney damage, had the highest diagnostic value for DKD. However, this finding should be explored further to understand the synergistic effects of these biomarkers.

[Objective] In light of a growing number of oil and gas pipelines crossing or running near power lines,the issue of lightning overvoltage at these locations has garnered increasing attention within these two industries. [Methods] In this study,a calculation model was developed using COMSOL Multiphysics software to depict the generation mechanism of potential difference between pipelines and their anticorrosive coatings at locations where these pipelines cross or run near power lines.Simulation calculations were performed to analyze the impact of soil resistivity and soil layering on pipeline overvoltage amplitude.As a result,a pipeline overvoltage protection method was proposed,considering the dispersion of current over the grounding grids at nearby towers/poles. [Results] The simulation results confirmed the effectiveness of the proposed optimization solution in limiting the voltage,establishing its practical application value.Although the potential on the pipelines and the withstand voltage of their anticorrosive coatings were generally balanced,the difference between them was notably influenced by the direction of current dispersion from the grounding electrodes.Under typical soil resistivity conditions,the withstand voltage difference between the pipelines and their anticorrosive coatings remained within limits.Additionally,it was observed that individual lightning discharges alone were insufficient to cause breakdown in the three-layer polyethylene (3PE) anticorrosive coatings.However,the withstand potential difference did contribute to the enlargement of local damage points that already existed within the coatings.To mitigate the withstand potential difference,an effective approach is proposed involving adjustments to the included angle and relative distance between the pipelines and grounding electrodes at nearby towers/poles. [Conclusion] It is proposed to effectively reduce the potential difference between pipelines and their anticorrosive coatings by modifying the configuration and current dispersion dimensions of the grounding grids at nearby towers/poles.With proven technical feasibility and economical efficiency,the findings of this study serve as a valuable reference for the design,construction,safe operation,and maintenance of oil and gas pipelines.

Abstract Tumor-associated macrophages (TAMs), one of the most abundant immune cell types in the tumor microenvironment (TME), account for approximately 50% of the local hematopoietic cells. TAMs play an important role in tumorigenesis and tumor development through crosstalk between various immune cells and cytokines in the TME. Exosomes are small extracellular vesicles with a diameter of 50–150 nm, that can transfer biological information (e.g., proteins, nucleic acids, and lipids) from secretory cells to recipient cells through the circulatory system, thereby influencing the progression of various human diseases, including cancer. Recent studies have suggested that TAMs-derived exosomes play crucial roles in malignant cell proliferation, invasion, metastasis, angiogenesis, immune responses, drug resistance, and tumor metabolic reprogramming. TAMs-derived exosomes have the potential to be targeted for tumor therapy. In addition, the abnormal expression of non-coding RNAs and proteins in TAMs-derived exosomes is closely related to the clinicopathological features of patients with cancer, and these exosomes are expected to become new liquid biopsy markers for the early diagnosis, prognosis, and monitoring of tumors. In this review, we explored the role of TAMs-derived exosomes in tumorigenesis to provide new diagnostic biomarkers and therapeutic targets for cancer prevention.

With the new concept of computing force network being put forward, how to manage, cooperate and deploy after the integration of computing power and network has become an urgent problem for telecom operators. To better solve the problems of unified management, perceptual dispatch, and collaborative arrangement of multi-dimensional resources such as network, computing, and storage, we study from the direction of computing force network management and control. Then we investigate the overall architecture design of computing force network management and control system, the core capabilities, and the evolution of underlying network technology. Based on the principle of "the network changes with the computing force, and the network strengthens the computing force", the collaborative mode of "horizontal connection and vertical dispatch" of the computing force network is formed with the help of the management and control system capabilities. Eventually, we believe it will effectively support the development demands of computing force network business and help the development of the national "Eastern Data and Western Computing" project.

The architecture of apple trees plays a pivotal role in shaping their growth and fruit-bearing potential, forming the foundation for precision apple management. Traditionally, 2D imaging technologies were employed to delineate the architectural traits of apple trees, but their accuracy was hampered by occlusion and perspective ambiguities. This study aimed to surmount these constraints by devising a 3D geometry-based processing pipeline for apple tree structure segmentation and architectural trait characterization, utilizing point clouds collected by a terrestrial laser scanner (TLS). The pipeline consisted of four modules: (a) data preprocessing module, (b) tree instance segmentation module, (c) tree structure segmentation module, and (d) architectural trait extraction module. The developed pipeline was used to analyze 84 trees of two representative apple cultivars, characterizing architectural traits such as tree height, trunk diameter, branch count, branch diameter, and branch angle. Experimental results indicated that the established pipeline attained an R2 of 0.92 and 0.83, and a mean absolute error (MAE) of 6.1 cm and 4.71 mm for tree height and trunk diameter at the tree level, respectively. Additionally, at the branch level, it achieved an R2 of 0.77 and 0.69, and a MAE of 6.86 mm and 7.48° for branch diameter and angle, respectively. The accurate measurement of these architectural traits can enable precision management in high-density apple orchards and bolster phenotyping endeavors in breeding programs. Moreover, bottlenecks of 3D tree characterization in general were comprehensively analyzed to reveal future development.

Long noncoding RNAs (lncRNAs) have been widely proven to be involved in liver lipid homeostasis. Herein, we identify an upregulated lncRNA named lncRP11-675F6.3 in response to rapamycin treatment using a microarray in HepG2 cells. Knockdown of lncRP11-675F6.3 leads to a significant reduction in apolipoprotein 100 (ApoB100), microsomal triglyceride transfer protein (MTTP), ApoE and ApoC3 with increased cellular triglyceride level and autophagy. Furthermore, we find that ApoB100 is obviously colocalized with GFP-LC3 in autophagosomes when lncRP11-675F6. 3 is knocked down, indicating that elevated triglyceride accumulation likely related to autophagy induces the degradation of ApoB100 and impairs very low-density lipoprotein (VLDL) assembly. We then identify and validate that hexokinase 1 (HK1) acts as the binding protein of lncRP11-675F6.3 and mediates triglyceride regulation and cell autophagy. More importantly, we find that lncRP11-675F6.3 and HK1 attenuate high fat diet induced nonalcoholic fatty liver disease (NAFLD) by regulating VLDL-related proteins and autophagy. In conclusion, this study reveals that lncRP11-675F6.3 is potentially involved in the downstream of mTOR signaling pathway and the regulatory network of hepatic triglyceride metabolism in cooperation with its interacting protein HK1, which may provide a new target for fatty liver disorder treatment.

Abstract Background Studies on robotic total gastrectomy (RTG) are currently limited. This study aimed to compare the intraoperative performance as well as short‐ and long‐term outcomes of RTG and laparoscopic total gastrectomy (LTG). Methods A total of 969 patients underwent robotic (n = 161) or laparoscopic (n = 636) total gastrectomy between October 2014 and October 2021. The two groups of patients were matched 1:3 using the propensity score matching (PSM) method. The intraoperative performance as well as short‐ and long‐term outcomes of the robotic (n = 147) and the laparoscopic (n = 371) groups were compared. Results After matching, the estimated intraoperative blood loss was lower (80.51 ± 68.77 vs. 89.89 ± 66.12, p = 0.008), and the total number of lymph node dissections was higher (34.74 ± 12.44 vs. 29.83 ± 12.22, p

Abstract Objective To evaluate the multiple factors influencing the survival of elderly patients with locally advanced gastric cancer (LAGC) and develop and validate the novel nomograms for predicting the survival. Methods The clinical features of patients treated between 2000 and 2018 were collected and collated from the Surveillance, Epidemiology, and End Results (SEER) database and three medical centres in China, and the patients were randomly divided into a training cohort (3494), internal validation cohort (1497) and external validation cohort (841). Univariate and multivariate analyses of the prognostic values were performed to identify independent prognostic factors associated with overall survival (OS) and cancer-specific survival (CSS), and two nomogram models were developed. Harrell’s concordance index (C-index) and calibration curves were employed to assess discrimination and calibration. Decision curve analysis (DCA) and receiver-operating characteristic (ROC) curves were utilized to investigate the clinical usefulness. Results In the SEER database, the 5-year OS of the patients was 31.08%, while the 5-year CSS of the patients was 44.09%. Furthermore, in the external validation set, the 5-year OS of the patients was 49.58%, and the 5-year CSS of these patients was 53.51%. After statistical analysis, nine independent prognostic factors of OS and CSS were identified, including age, race, tumour size, differentiation, TNM stage, gastrectomy type, lymph node metastasis (LNM), lymph node ratio (LNR) and chemotherapy. The C‐index (approximately 0.7) and calibration curve (close to the optimal calibration line) indicated satisfactory discrimination and calibration of the nomogram. DCA and ROC curves showed that the developed nomogram was superior to TNM stage. Conclusion The novel validated nomogram could accurately predict the prognosis of individual elderly patients with LAGC and guide the selection of clinical treatment measures.

ABSTRACT: Longitudinal traits, such as milk production traits in dairy cattle, are featured by having phenotypic values at multiple time points, which change dynamically over time. In this study, we first imputed SNP chip (50–100K) data to whole-genome sequence (WGS) data in a Chinese Holstein population consisting of 6,470 cows. The imputation accuracies were 0.88 to 0.97 on average after quality control. We then performed longitudinal GWAS in this population based on a random regression test-day model using the imputed WGS data. The longitudinal GWAS revealed 16, 39, and 75 quantitative trait locus regions associated with milk yield, fat percentage, and protein percentage, respectively. We estimated the 95% confidence intervals (CI) for these quantitative trait locus regions using the logP drop method and identified 581 genes involved in these CI. Further, we focused on the CI that covered or overlapped with only 1 gene or the CI that contained an extremely significant top SNP. Twenty-eight candidate genes were identified in these CI. Most of them have been reported in the literature to be associated with milk production traits, such as DGAT1, HSF1, MGST1, GHR, ABCG2, ADCK5, and CSN1S1. Among the unreported novel genes, some also showed good potential as candidate genes, such as CCSER1, CUX2, SNTB1, RGS7, OSR2, and STK3, and are worth being further investigated. Our study provided not only new insights into the candidate genes for milk production traits, but also a general framework for longitudinal GWAS based on random regression test-day model using WGS data.

Effective and robust electrocatalysts are mainly based on innovative materials and unique structures. Herein, we designed a flakelike cobalt phosphide-based catalyst supporting on NiCo2O4 nanorods array, which in-situ grew on the nickel foam (NF) current collector, referring as N–Co2P/NiCo2O4/NF electrode. By optimizing the microstructure and electronic structure through 3D hierarchy fabrication and nitrogen doping, the catalyst features with abundant electrochemical surface area, favorable surface wettability, excellent electron transport, as well as tailored d band center. Consequently, the as-prepared N–Co2P/NiCo2O4/NF electrode exhibits an impressive HER activity with a low overpotentials of 58 mV at 10 mA cm−2, a Tafel slop of 75 mV dec−1, as well as superior durability in alkaline medium. This work may provide a new pathway to effectively improve the hydrogen evolution performance of transition metal phosphides and to develop promising electrodes for practical electrocatalysis.

ABSTRACT: Proteins are considered major effectors of sperm function. However, the proteins expressed in pigeon sperm have not been explored. Here, we collected semen from meat and racing pigeons using the electroejaculation method and identified proteins in pigeon sperm using the proteomics approach. A total of 1,641 proteins were identified in the sperm of domesticated pigeons. Of which, 1,541 proteins were reliably quantified, and gene ontology (GO) and associated bioinformatics analyses indicated that annotated proteins were linked to the oxidation-reduction process, integral component membrane, and protein binding, etc. Among quantified proteins, 1,515 and 1,507 proteins were respectively presented in White King pigeons and racing pigeons, and 1,481 proteins were shared between these 2 types of pigeons, including axonemal dynein, solute carrier, cilia- and flagella-associated protein, outer dense fiber protein, etc. Proteins in our constructed protein-protein interaction (PPI) network are involved in oxidative phosphorylation, sperm axoneme assembly, cilium-dependent cell motility, axonemal dynein complex assembly, flagellated sperm motility, etc. In conclusion, this study characterized the sperm proteome of pigeons and provided a foundation for the subsequent research screening markers for fertility evaluation of pigeons.

Introduction Gastric cancer (GC) diagnosed in the elderly population has become a serious public health problem worldwide. Given the combined effects of frailty and the consequences of cancer treatment, older individuals with GC are more likely than young patients to suffer from postoperative complications and poor clinical outcomes. Nutrition, functional capacity and psychological state-based multimodal prehabilitation, which is dominated by Enhanced Recovery After Surgery (ERAS) pathway management, has been shown to reduce postoperative complications, promote functional recovery and decrease hospitalisation time in certain malignancies. However, no previous studies have investigated the clinical application of multimodal prehabilitation in frail older patients with GC.Methods and analysis The study is a prospective, multicentre randomised controlled trial in which a total of 368 participants who meet the inclusion criteria will be randomised into either a prehabilitation group or an ERAS group. The prehabilitation group will receive multimodal prehabilitation combined with ERAS at least 2 weeks before the gastrectomy is performed, including physical and respiratory training, nutritional support, and therapy and psychosocial treatment. The ERAS group patients will be treated according to the ERAS pathway. All interventions will be supervised by family members. The primary outcome measures are the incidence and severity of postoperative complications. Secondary outcomes include survival, functional capacity and other short-term postoperative outcomes. Overall, the multimodal prehabilitation protocol may improve functional capacity, reduce the surgical stress response and concomitant systemic inflammation, and potentially modulate the tumour microenvironment to improve short-term and long-term clinical outcomes and patients’ quality of life.Ethics and dissemination All procedures and participating centres of this study were approved by their respective ethics committees (QYFYKYLL 916111920). The final study results will be published separately in peer-reviewed journals.Trial registration number NCT05352802.

Background With the aging of the population, it is essential to implement fall prevention programs for the elderly. Although China has carried out fall prevention programs sporadically, among which comprehensive fall prevention programs centered on exercise intervention are rare, and there have been no investigations about the willingness of elderly people at high risk of falls in the community to participate in comprehensive fall prevention programs. Objective To examine the intention of community-living elderly residents at high risk of falls to participate in comprehensive fall-prevention programs, and associated factors, providing a theoretical basis for the implementation of such programs. Methods By economic level and geographical location, we selected three communities from Shanghai as research settings, namely, Tangqiao Community in Pudong New Area (central urban area) , Zhaoxiang Community in Qingpu District (outer suburb) and Gangyan Community in Chongming County (outer suburb) . Elderly people aged 65 and above who participated in physical examinations in the three communities from 2018 to 2019 were invited to attend a survey using a questionnaire consisting of demographics, FROP-Com Screen, MFROP-Com Tool, self-designed fall risk questionnaire, Patient Health Questionnaire-9 (PHQ-9) , and Generalized Anxiety Disorder scale (GAD-7) . Individuals with the FROP-Com Screen scale score >3 points were identified with risk of falls, among whom those with total score of MFROP-Com Tool≥11.5 points (high risk of falls) were included finally. Results In total, 318 cases were detected with high risk of falls, among whom 62 (19.5%) thought falls were unpreventable. Slippery floor〔73 respondents (23.0%) 〕, inattention〔64 respondents (20.1%) 〕and physical discomfort〔64 respondents (20.1%) 〕were reported to be the three leading causes of falls. Two hundred and fourteen (67.3%) were willing to participate in fall prevention programs. The level of intention to participate in fall prevention programs differed significantly in the participants according to living setting, educational level, use of a walker, self-assessed sleep quality, number of chronic diseases, foot disease prevalence, exercise habits, history of falls in the past year, and cognition of whether falls can be prevented (P

Transmembrane water exchange (TWE) including transcytolemmal water exchange and transvascular water exchange is involved in many in vivo measurements and makes different contributions to the measuring results. In this study, we focus on the potential influence of TWE on the cell density parameter, intracellular water mole fraction pi, derived by dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI) which has been reported as a technique to characterize perfusion and vascularization of tissues, but its accuracy in measuring cell density (or interstitial space) has been questioned. Sixteen patients with glioblastoma multiforme (GBM) were enrolled since GBM shows strong intratumor heterogeneity in both cell density and TWE. All the subjects were collected with DCE-MRI and apparent diffusion coefficient (ADC) map. The latter was considered as a valid surrogate of cell density. Extended Tofts (eTofts) model considering TWE as infinitely large variables and shutter-speed model (SSM) considering TWE as finite ones were used to fit DCE-MRI data. Monte Carlo (MC) and finite difference (FD) methods were used to simulate the influence of TWE on DCE-MRI-derived pi and ADC, respectively. The eTofts model shows a significant overestimation of pi in comparison with SSM in GBM (P 0.05) and a weaker inter-subject negative correlation (r = −0.56, P = 0.02) were found between ADC and eTofts-derived pi. Further experimental and FD results revealed that kio made a limited contribution to ADC values in the physiological kio range in GBM, supporting ADC as a valid biomarker of cell density. These results suggest that the DCE-MRI pharmacokinetic shutter-speed model could significantly improve its accuracy in cell density estimation because of the considering transmembrane water exchange.

Abstract Field and laboratory observations indicate that the frictional behaviors of faults depend on hydrothermal conditions. We extend the microphysical Chen‐Niemeijer‐Spiers (CNS) model to hydrothermal conditions by using the observed temperature variation of indentation hardness to infer the temperature dependence of a microphysical parameter aμ∼. This parameter is assumed constant in previous versions of the CNS model. A simple spring‐slider system is used to simulate the fault system and investigate the steady‐state frictional behaviors of wet granite gouges. Our numerical results quantitatively reproduce experimental data showing the frictional‐plastic transition. The results also describe the transition from velocity‐strengthening at low temperatures (370°C). In our extended CNS model, these results suggest that the dominant shear deformation mechanism does transition from frictional granular flow to fully plastic creep with increasing temperature.

We aimed to investigate the changes in the levels of high-molecular-weight (HMW) adiponectin, adiponectin receptors, and cytokines in patients with chronic obstructive pulmonary disease (COPD), as well as their potential relationships. Forty-one patients who underwent lobectomy for lung lesions and had a clear postoperative pathological diagnosis were divided into the non-COPD (N = 23) and COPD (N = 18) groups. HMW adiponectin, cytokine, and T-cadherin levels in serum and tissues were detected by enzyme-linked immunosorbent assay. The levels of HMW adiponectin and cytokine (interleukin [IL]-6, IL-10, surfactant protein D, 4-hydroxynonenal, tumor necrosis factor-α, and C reactive protein) in the serum and tissues increased in the COPD group compared to those in the non-COPD group. Patients with COPD exhibited AdipoR1 upregulation and AdipoR2 downregulation. Although T-cadherin did not differ significantly between patients with and those without COPD, its expression was elevated during the progression from COPD with benign lung lesions to combined lung cancer. Furthermore, the HMW adiponectin levels were significantly correlated with the cytokine levels and the clinical characteristics of COPD. HMW adiponectin and its receptors affect the inflammatory process in COPD and may further contribute to the progression of the disease to malignancy.

Objective: This study aimed to explore the regulatory effect of Lactarius hatsudake polysaccharide on intestinal flora. Methods: LHP was extracted from L. hatsudake by hot water. LHP-1 and LHP-2 were further purified and characterized. The effects of LHPs on body weight and intestinal microbiome composition were studied in antibiotic-induced mice. Results: LHP-1 was mainly composed of mannose, glucose and galactose. The molar mass ratio of LHP-1 was 3.44∶61.10∶1.22. LHP-2 is mainly composed of mannose and glucose, with a molar mass ratio of 3.84∶153.00. It has a "neuronal" structure and a chain structure region. LHP intervention can restore the structure and diversity of intestinal flora by increasing beneficial bacteria such as Bacteroides and Akkermansia and reducing harmful bacteria such Enterococcus and Brevundimonas. In particular, the increase of the beneficial bacteria A. muciniphila indicates the great potential of LHP in the regulation of human intestinal flora. Conclusion: Polysaccharide from Lactarius hatsudake can improve intestinal metabolism as potential prebiotics.

In this paper, we consider the Internet Protocol(IP) network quality and study the impact of network performance factors, such as delay and packet loss on the end-to-end service quality of major accounts and overall quality of internet. We propose a unified architecture design and conduct an investigation on IP network quality monitoring and optimization solutions through a combination of Telemetry, Twamp, IFIT, Flow and other applications of new technologies. The results indicate that the deployment of proposed design can provide effective improvements in the timeliness, authenticity and reliability of monitoring data. Meanwhile, it will collect and analyze the quality data of massive packet granularity, and realize fault warning with the help of AI intelligent prediction capabilities after the deployment of design. The proposed design can both improve the quality of services, and further enhance the existing network's " autonomous driving" capabilities.

ABSTRACT: Low-coverage sequencing (LCS) followed by imputation has been proposed as a cost-effective genotyping approach for obtaining genotypes of whole-genome variants. Imputation performance is essential for the effectiveness of this approach. Several imputation methods have been proposed and successfully applied in genomic studies in human and other species. However, there are few reports on the performance of these methods in livestock. Here, we evaluated a variety of imputation methods, including Beagle v4.1, GeneImp v1.3, GLIMPSE v1.1.0, QUILT v1.0.0, Reveel, and STITCH v1.6.5, with varying sequencing depth, sample size, and reference panel size using LCS data of Holstein cattle. We found that all of these methods, except Reveel, performed well in most cases with an imputation accuracy over 0.9; on the whole, GLIMPSE, QUILT, and STITCH performed better than the other methods. For species with no reference panel available, STITCH followed by Beagle would be an optimal strategy, whereas for species with reference panel available, QUILT would be the method of choice. Overall, this study illustrated the promising potential of LCS for genomic analysis in livestock.

Ovum pick up and in vitro embryo production (OPU-IVEP) is an essential technique in the dairy industry. The production efficiency of OPU-IVEP is significantly influenced by various factors, and phenotypic and genetic characteristics are highly variable in different populations. The objectives of this study were (1) to reveal the phenotypic characteristics, including population distribution, and impacts of donor age and month on in vitro embryo production and (2) to estimate genetic parameters for five in vitro embryo production traits in Chinese Holstein cattle. A total of 7311 OPU-IVEP records of 867 Holstein heifers from August 2021 to March 2023 were collected in this study. Five in vitro embryo production traits were defined, including the number of cumulus–oocyte complexes (NCOC), the number of cleaved embryos (NCLV), the number of grade I embryos (NGE), and the proportion of NCLV to NCOC (PCLV) and NGE to NCOC (PGE). A univariate repeatability animal model was employed to estimate heritability and repeatability, and a bivariate repeatability animal model was employed to estimate the genetic correlations among five in vitro embryo production traits. It was found that the in vitro embryo production traits were significantly influenced by season, as the NGE and PGE were significantly decreased from June to August. In addition, the production efficiency of OPU-IVEP was also influenced by donor age. On the observed scale, the estimates of heritability were 0.33 for NCOC, 0.24 for NCLV, 0.16 for NGE, 0.06 for PCLV, and 0.10 for PGE, respectively. On the log-transformed scale, the estimates of heritability of NCOC, NCLV, and NGE were 0.34, 0.18, and 0.13. The genetic correlations among NCOC, NCLV, and NGE ranged from 0.61 (NCLV and NGE) to 0.95 (NCOC and NCLV), considering both scales. However, there were low genetic correlations between NCOC and proportion traits (PCLV and PGE) on both the observed scale and the log-transformed scale. In the end, the variation in Chinese Holstein cattle was found to be considerable. The EBV value and average NCOC, NGE, and PGE for the top 10% donors presented extreme differences to those for the bottom 10% donors for NCOC (24.02 versus 2.60), NGE (3.42 versus 0.36), and PGE (30.54% versus 3.46%). Overall, the results of this study reveal that in vitro embryo production traits are heritable with low to high heritability, and the count traits (NCOC, NCLV, and NGE) and proportion traits (PCLV and PGE) reflect different aspects of in vitro embryo production and should be incorporated into genetic selection for improving the embryo production efficiency of dairy cattle.

Lane detection is a vital component of intelligent driving systems, offering indispensable functionality to keep the vehicle within its designated lane, thereby reducing the risk of lane departure. However, the complexity of the traffic environment, coupled with the rapid movement of vehicles, creates many challenges for detection tasks. Current lane detection methods suffer from issues such as low feature extraction capability, poor real-time detection, and inadequate robustness. Addressing these issues, this paper proposes a lane detection algorithm that combines an online re-parameterization ResNet with a hybrid attention mechanism. Firstly, we replaced standard convolution with online re-parameterization convolution, simplifying the convolutional operations during the inference phase and subsequently reducing the detection time. In an effort to enhance the performance of the model, a hybrid attention module is incorporated to enhance the ability to focus on elongated targets. Finally, a row anchor lane detection method is introduced to analyze the existence and location of lane lines row by row in the image and output the predicted lane positions. The experimental outcomes illustrate that the model achieves F1 scores of 96.84% and 75.60% on the publicly available TuSimple and CULane lane datasets, respectively. Moreover, the inference speed reaches a notable 304 frames per second (FPS). The overall performance outperforms other detection models and fulfills the requirements of real-time responsiveness and robustness for lane detection tasks.

To investigate the maintenance effect of diaphragm-to-rib fatigue cracks via steel plate reinforcement, finite element models of different-shaped steel plates were established. Stress intensity factors at the crack tip before and after reinforcement were obtained, and the variations in stresses were studied. Polygonal steel plate reinforcements were then carried out on a real bridge based on the finite element calculation results. The changes in stress amplitudes and fatigue damage degrees at the crack tip were analyzed via the rain-flow counting method and Miner’s linear damage accumulating theory. The results show that both the polygonal steel plate and the rectangular steel plate could effectively eliminate the stress concentration and restrain the propagation of cracks. The stresses in other parts of the arc notch increased after reinforcement and polygonal steel plates had less influence. After the reinforcement in a real bridge, the cycle number of high stress amplitudes at the crack tip decreased significantly. The fatigue damage degree of the repaired part reduced by 70.1%, which verified the maintenance effect via polygonal steel plate reinforcement on diaphragm-to-rib fatigue cracks.

Abstract Background Gastric cancer, which is the fifth most common malignancy and the third most common cause of cancer-related death, is particularly predominant in East Asian countries, such as China, Japan and Korea. It is a serious global health issue that causes a heavy financial burden for the government and family. To our knowledge, there are few reports of multicentre randomized controlled trials on the utilization of CT angiography (CTA) for patients who are histologically diagnosed with gastric cancer before surgery. Therefore, we planned this RCT to verify whether the utilization of CTA can change the short- and long-term clinical outcomes. Method The GISSG 20–01 study is a multicentre, prospective, open-label clinical study that emphasises the application of CTA for patients who will undergo laparoscopic gastrectomy to prove its clinical findings. A total of 382 patients who meet the inclusion criteria will be recruited for the study and randomly divided into two groups in a 1:1 ratio: the CTA group (n = 191) and the non-CTA group (n = 191). Both groups will undergo upper abdomen enhanced CT, and the CTA group will also receive CT angiography. The primary endpoint of this trial is the volume of blood loss. The second primary endpoints are the number of retrieved lymph nodes, postoperative recovery course, hospitalization costs, length of hospitalization days, postoperative complications, 3-year OS and 3-year DFS. Discussion It is anticipated that the results of this trial will provide high-level evidence and have clinical value for the application of CTA in laparoscopic gastrectomy. Trial registration ClinicalTrials.gov , NCT04636099. Registered November 19, 2020

Primary bone diffuse large B-cell lymphoma (PB-DLBCL) has been rarely reported because of its low incidence. The optimal treatment plan for patients with relapsed/refractory PB-DLBCL remains controversial. In this study, we present a case of a 57-year-old patient with refractory PB-DLBCL to better understand this disease. The patient developed lumbosacral/low extremity pain. A lumbar magnetic resonance imaging (MRI) revealed skeletal lesions with osteolysis in L4-L5 and S1. With the failure of multi-line chemotherapy, the patient developed paralysis of both lower limbs. 18-Fluorinefluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and MRI showed new lesions in the femoral head, cervical and thoracic vertebrae. We tried to treat the patient with adjuvant radiotherapy and 10 courses of high-dose methotrexate (HD-MTX)-based monotherapy, after which the patient was able to walk and achieved complete remission (CR). To the best of our knowledge, this is the first attempt to use local radiotherapy combined with an HD-MTX regimen successfully for the treatment of refractory PB-DLBCL.

This study introduces a new method to measure high refractive index (RI) materials with irregular shapes based on optical coherent tomography (OCT) images. Since the optical path length is the critical parameter to calculate RI, image fusion, thresholding, boundary extraction, and Hough transform were adopted in a well-organized sequence to extract this parameter when analyzing OCT images. Hough transform plays a key role in target recognition and parameter extraction. Glass and diamond were used as samples to test the validity of this method. The measurement result has reasonable consistency with the standard value. The method introduced in this paper has the potential to raise the automation and intelligence level of the existing research. A bright application prospect can be expected in industrial fields, such as optical glass, jewelry, and mineral substance.

The circulation of progesterone (P4) concentrations of recipients has positive correlations with embryo survival and pregnancy success of embryo transfer (ET) in dairy cows. One strategy to improve P4 concentration is the administration of gonadotropin-releasing hormone (GnRH) or human chorionic gonadotropin (hCG), thereby inducing the formation of accessory corpus luteum (CL). This study aimed at determining the efficacy of GnRH or hCG treatment regarding embryo transfer (ET) and providing a better clinical veterinary practice guidance. A meta-analysis was conducted on the data from 2048 treated recipient cows and 1546 untreated cows. By inducing the formation of accessory CL with GnRH (100 µg), GnRH analogue Buserelin (8–10 µg), or hCG (≥1500 IU) 5–11 days after synchronized ovulation, hCG alone achieved an improvement (RR = 1.39, p < 0.05), while GnRH and GnRH analogue did not result in significant changes (RR = 1.04, p = 0.26). Treatment with GnRH or hCG 5–7 days after synchronized ovulation was associated with increased chances of pregnancy compared with later treatment (11–14 days). Owing to the treatment, the pregnancy rate of cows with very poor fertility (p < 0.05) compared with heifers (RR = 1.02, p > 0.05). Additionally, as indicated by pregnancy loss analysis, the treatment had no benefit on late embryo/early fetus survival at days 28–81. In conclusion, the induction of accessory CL with GnRH or hCG may benefit fertility and have important implications for the management of reproductive performance in the dairy industry.

Abstract Red blood cells (RBCs) stressed by high temperature are similar to senescent or damaged RBCs in pathological conditions. RBCs can be efficiently labelled with 18F-fluorodeoxyglucose (FDG). The aim of this study was to assess stressed RBCs erythrophagocytosis and organ distribution in vivo with the application of 18F-FDG PET/CT. RBCs were induced under high temperature (48 °C) to prepare stressed RBCs. Fluorescence-activated cell sorting (FACS) was used to analyse reactive oxygen species (ROS) generation, intracellular Ca2+ concentration and membrane phosphatidylserine (PS) externalization of RBCs. 18F-FDG was used to label RBCs and assess the erythrophagocytosis. Finally, 18F-FDG PET/CT was applied to reveal and measure the organ distribution of stressed RBCs in mice. Compared with untreated RBCs, stressed RBCs decreased in cell volume and increased in ROS level, intracellular Ca2+ concentration, and PS exposure. RBCs could be labelled by 18F-FDG. Stressed RBCs tended to be phagocytosed by macrophages via assessment of FACS and radioactivity. 18F-FDG PET/CT imaging showed that stressed RBCs were mainly trapped in spleen, while untreated RBCs remained in circulation system. Thus, stressed RBCs can be effectively labelled by 18F-FDG and tend to be trapped in spleen of mice as assessed by PET/CT.

Cellular and humoral immunity are both important in host defense against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although defects in SARS-CoV-2-specific T cell immunity have been found in patients with severe lung pathology, it is still largely unclear whether virus-specific T cells are sufficient for host protection. Here, we found that in a previously characterized cohort of convalescent subjects, one individual, though lacking detectable anti-viral neutralizing IgG antibodies, showed virus-specific T cell responses, both in CD4+ and CD8+ T cells. SARS-CoV-2-specific T cells in this and other individuals are maintained for up to 10 months. This study thus further supports a critical role of T cells in host defense against SARS-CoV-2, offering new insights into the design and evaluation of COVID-19 vaccines.

The year 2021 saw the development and deployment of COVID-19 vaccines at an unprecedented pace, which is a remarkable success in science and technology. COVID-19 vaccines based on different technology platforms have been given to billions of humans globally to minimize the infection and transmission of SARS-CoV-2, and most importantly, to end the COVID-19 pandemic. Here, we provide a snapshot of the current status and future challenge of COVID-19 vaccination after one year.

Aim. Patients with diabetic ketosis often exhibit albuminuria. We previously found that acute hyperglycaemia can cause nephrotoxic injury. Here, we explored whether an excessive ketone body level causes kidney injury and the potential underlying mechanism. Methods. Fifty-six type 2 diabetes without ketosis (NDK group), 81 type 2 diabetes with ketosis (DK group), and 38 healthy controls (NC group) were enrolled. Clinical data were collected before and after controlling diabetic ketosis. Beta-hydroxybutyric acid (BOHB), an AKT activator, an AKT inhibitor, or plasmids encoding DAB2 were transformed into human renal proximal tubule epithelial cells (HK-2 cells). Results. The urinary albumin-to-creatinine ratio (ACR), transferrin (TF), immunoglobulin G (IgG), Beta2-microglobulin (β2-MG), retinol-binding protein (RBP), N-acetyl-beta-glucosaminidase (NAG), and Beta-galactosidase (GAL) were higher in the DK than NC and NDK groups. The proportion of patients with an increased urinary level of TF, IgG, β2-MG, RBP, NAG, or GAL was higher in the DK group too. After controlling ketosis, urinary microalbumin, TF, IgG, β2-MG, and RBP decreased significantly. In HK-2 cells, albumin endocytosis and megalin expression decreased with increasing BOHB concentration. Compared with BOHB treatment, BOHB with AKT activator significantly increased the DAB2, megalin levels and albumin endocytosis; the AKT inhibitor treatment exhibited the opposite effects. Compared with BOHB treatment, megalin expression and albumin endocytosis were significantly increased after BOHB with DAB2 overexpression treatment. Conclusions. Patients with diabetic ketosis may suffer from glomerular and tubular injuries that recover after ketosis control. High concentrations of BOHB downregulate megalin expression by inhibiting the AKT/DAB2/megalin signalling pathway and albumin endocytosis in proximal renal tubules.

Fluid charging and formation pressure evolution are of great significance for shale gas exploration and development. Taking the Longmaxi formation shale in southeast Chongqing as the research object, the fluid activity and pressure evolution process were studied by means of thin section observation, fluid inclusion analysis and testing, and basin numerical simulation. The results show that the area of the southeast of Chongqing, the Longmaxi formation of dike filling minerals, is mainly quartz vein and calcite part of the veins and arteries, and vein body captures the rich organic inclusions in minerals, sees fgas-liquid two-phase brine inclusions and methane inclusions, combining with the temperature and salinity of brine inclusions, and shows that the area has experienced two phases of oil and gas filling, the first period of gas-liquid fluid. The second stage is gas fluid. Combined with burial history and thermal maturation history, it is found that the filling time of oil and gas is late Cretaceous and Paleocene, respectively. In the Cretaceous, the pressure coefficient of Longmaxi formation reached the maximum value of 2.2 and remained above 1.5 overpressure after pressure unloading in the later period. In terms of the frequency of inclusions, the charging amount of the first stage is relatively large, and the charging time corresponds to the peak period of the palaeo-formation pressure. At the same time, fluid charging can timely supplement the pressure after unloading, which is conducive to high and stable production of shale gas.

Diabetes Mellitus (DM) and Coronary Heart Disease (CHD) are among top causes of patient health issues and fatalities in many countries. At present, terahertz biosensors have been widely used to detect chronic diseases because of their accurate detection, fast operation, flexible design and easy fabrication. In this paper, a Zeonex-based microstructured fiber (MSF) biosensor is proposed for detecting DM and CHD markers by adopting a terahertz time-domain spectroscopy system. A suspended hollow-core structure with a square core and a hexagonal cladding is used, which enhances the interaction of terahertz waves with targeted markers and reduces the loss. This work focuses on simulating the transmission performance of the proposed MSF sensor by using a finite element method and incorporating a perfectly matched layer as the absorption boundary. The simulation results show that this MSF biosensor exhibits an ultra-high relative sensitivity, especially up to 100.35% at 2.2THz, when detecting DM and CHD markers. Furthermore, for different concentrations of disease markers, the MSF exhibits significant differences in effective material loss, which can effectively improve clinical diagnostic accuracy and clearly distinguish the extent of the disease. This MSF biosensor is simple to fabricate by 3D printing and extrusion technologies, and is expected to provide a convenient and capable tool for rapid biomedical diagnosis.

Realizing the transformation from “dual control of energy consumption” to “dual control of carbon emissions” is the inherent requirement of realizing the “dual carbon” goal. Scientific planning of the provincial decomposition method of total carbon emissions is an important content of the top-level design of carbon emissions management, and an important support for the implementation of total carbon emissions control. Based on the application research of greenhouse gas inventory in all fields, this paper conducts a full factor analysis of the total carbon emissions of the whole society, establishes a comprehensive decomposition index system, and proposes a simple and transparent provincial decomposition method of the total carbon emissions control target, which considers fairness and efficiency. The simulated decomposition results show that the decomposition method is scientific and operable and can be used as an important reference for future practical decomposition operations.

The development of adsorption materials which can efficiently isolate and enrich uranium is of great scientific significance to sustainable development and environmental protection. In this work, a novel phosphonic acid-functionalized magnetic microsphere adsorbent Fe3O4/P (GMA-MBA)-PO4 was developed by functionalized Fe3O4/P (GMA-MBA) prepared by distill-precipitation polymerization with O-phosphoethanolamine. The adsorption process was endothermic, spontaneous and kinetically followed the pseudo second-order model. The maximum uranium adsorption capacity obtained from the Langmuir model was 333.33 mg g−1 at 298 K. In addition, the adsorbent also had good acid resistance and superparamagnetic properties, which could be quickly separated by a magnetic field. XPS analysis showed that the adsorption of adsorbent mainly depended on the complexation of phosphonic acid group with uranium. This work offers a promising candidate for the application of magnetic adsorbents in the field of uranium separation and enrichment.

Cancer is one of the leading causes of mortality worldwide. In recent years, various kinds of biosensors based on optical fiber have been proposed for detection of cancer cells due to their advantages of accurate diagnosis, small size, low cost, and flexible design parameters. In the present study, a microstructure fiber (MSF) biosensor with porous-core structures was designed to detect cancer cells using a terahertz time-domain system (TDS). The fiber characteristics of the proposed MSF were optimized by adopting a finite element numerical technique and perfectly matching layer absorption boundary conditions. The numerical results show that the proposed biosensor presented an ultrahigh sensitivity for detection of cancer cells. Under the optimal condition of 0.9 THz, the relative sensitivity of the proposed structure to breast cancer cells was as high as 99.8%. Moreover, other optical fiber parameters, such as effective material loss (EML), confinement loss (CL), numerical aperture (NA), power fraction, and effective area (Aeff), were optimal according to the reported results. The proposed structure can be easily fabricated by 3D printing and flexibly applied in the fields of biomedicine and biosensing with a terahertz (THz) waveguide.

Aim: Vildagliptin (vild) improves diastolic dysfunction and is associated with a lower relative risk of major adverse cardiovascular events in younger patients. The present study aimed to evaluate whether vild prevents the development of diabetic cardiomyopathy in type 2 diabetic mice and identify its underlying mechanisms.Methods: Type 2 diabetic mouse model was generated using wild-type (WT) (C57BL/6J) and miR-21 knockout mice by treatment with HFD/STZ. Cardiomyocyte-specific miR-21 overexpression was achieved using adeno-associated virus 9. Echocardiography was used to evaluate cardiac function in mice. Morphology, autophagy, and proteins levels in related pathway were analyzed. qRT-PCR was used to detect miR-21. Rat cardiac myoblast cell line (H9c2) cells were transfected with miR-21 mimics and inhibitor to explore the related mechanisms of miR-21 in diabetic cardiomyopathy.Results: Vild restored autophagy and alleviated fibrosis, thereby enhancing cardiac function in DM mice. In addition, miR-21 levels were increased under high glucose conditions. miR-21 knockout DM mice with miR-21 knockout had reduced cardiac hypertrophy and cardiac dysfunction compared to WT DM mice. Overexpression of miR-21 aggravated fibrosis, reduced autophagy, and attenuated the protective effect of vild on cardiac function. In high-glucose-treated H9c2 cells, the downstream effectors of sprouty homolog 1 (SPRY1) including extracellular signal-regulated kinases (ERK) and mammalian target of rapamycin showed significant changes following transfection with miR-21 mimics or inhibitor.Conclusion: The results of our study indicate that vild prevents DCM by restoring autophagy through the miR-21/SPRY1/ERK/mTOR pathway. Therefore, miR-21 is a target in the development of DCM, and vild demonstrates significant potential for clinical application in prevention of DCM.

Depression is a common mental disorder that presents a considerable challenge for public health. The natural product geniposide has neuroprotective effects on depression, but the underlying mechanism behind these effects had remained undefined. The present study was designed to investigate the role of microRNAs (miRs) in this mechanism. It studied mice with depression-like behavior established by exposure to chronic unpredictable mild stress (CUMS) for 2 months. The CUMS mice were intragastrically fed with geniposide at a dose of 10 ml/kg daily for two consecutive weeks. We monitored the depression-like behaviors of the CUMS mice by the forced swimming test (FST) and tail suspension test (TST). Then, we measured the cerebral expression of miR-298-5p and NADPH oxidase 1 (Nox1) mRNA in the CUMS mice by the RT-qPCR. The targeting relationship between miR-298-5p and Nox1 was evaluated by dual-luciferase reporter gene assay. The concentrations of adenosine triphosphate (ATP) and reactive oxygen species (ROS) were determined by the CellTiter-Glo® and flow cytometry, respectively. The mitochondrial membrane potential (MMP) was detected using JC-1 staining. Moreover, the expression of inflammatory cytokines (TNF-α, IL-1β, IL-6, and TGF-β) was determined by ELISA, RT-qPCR, and western blot analysis. We found that miR-298-5p was poorly-expressed while Nox1 was highly-expressed in the brain tissues of the CUMS-induced mice. Intriguingly, Geniposide treatment reversed the behavioral abnormalities of CUMS mice, including shortened immobility time. Geniposide inhibited the Nox1 expression by increasing miR-298-5p levels. There were increased ATP content and MMP and reduced contents of ROS and inflammatory cytokines in the CUMS mice receiving geniposide treatment. Hence, this study revealed an antidepressant effect of geniposide on CUMS-induced depression-like behavior in mice by down-regulating the miR-298-5p-targeted Nox1. This highlights a novel candidate target for the treatment of depression.

AimAcute hyperglycemia is closely related to kidney injury. Oxidative stress activation and notable mitochondria damages were found under acute hyperglycemia treatment in our previous work. In the present study, we explored the dose-effect relationship and the pivotal role of mitophagy in acute hyperglycemia induced tubular injuries.MethodsForty non-diabetic SD rats were randomly divided and treated with different concentrations of hyperglycemia respectively during the 6-h clamp experiment. Renal morphological and functional alterations were detected. Rat renal tubular epithelial cells were treated with different concentrations of glucose for 6 h. Markers and the regulation pathway of mitophagy were analyzed.ResultsSignificant tubular injuries but not glomeruli were observed under both light and electron microscope after acute hyperglycemia treatment, which manifested as enlargement of tubular epithelial cells, disarrangement of epithelial cell labyrinths and swelling of mitochondria. Urinary microalbumin, β2-MG, CysC, NAG, GAL, and NGAL were increased significantly with the increase of blood glucose (P < 0.05). ROS was activated, mitochondrial membrane potential and LC3-II/LC3-I ratio were decreased but P62 and BNIP3L/Nix were increased in hyperglycemia groups (P < 0.05), which were reversed by AMPK activation or mTOR inhibition.ConclusionAcute hyperglycemia causes obvious tubular morphological and functional injuries in a dose-dependent manner. Acute hyperglycemia could inhibit mitophagy through AMPK/mTOR pathway, which would aggravate mitochondria damage and renal tubular impairment.

Depression is a major cause of disease burden and severely impairs well-being of patients around the globe. Geniposide (GP) has been revealed to play a significant role in depression treatment. Of note, RNA sequencing of this study identified highly expressed long non-coding RNA Six3os1 in response to GP treatment. Thus, we aim to explore how GP affected chronic unpredictable mild stress (CUMS)-induced depression-like behaviors in mice in vivo and in vitro and the downstream molecular mechanism related to Six3os1. The relationship of Six3os1, miR-511-3p and Fezf1 was evaluated by dual-luciferase reporter gene assay, RIP assay, and RNA pulling down assay. Ectopic expression and knockdown experiments were developed in CUMS-induced mice and neurons with or without GP treatment. In vitro experiments and behavioral tests were conducted to examine alteration of CUMS-triggered oxidative stress following different interferences. The experimental data validated that GP treatment resulted in high expression of Six3os1 and Fezf1 and poor expression of miR-511-3p in CUMS-induced neurons. Six3os1 activated the AKT signaling pathway by upregulating miR-511-3p-targeted Fezf1. Either GP treatment or overexpression of Six3os1 or Fezf1 alleviated depression-like behaviors of CUMS-induced mice. GP treatment, miR-511-3p inhibition or overexpression of Six3os1 or Fezf1 not only reduced oxidative stress in CUMS-induced mice and neurons, but also reduced CUMS-induced neuronal apoptosis. Collectively, GP treatment-mediated Six3os1 upregulation ameliorated oxidative stress of mice with depression-like behaviors via the miR-511-3p/Fezf1/AKT axis.

Graphene, a novel form of the hexagonal honeycomb two-dimensional carbon-based structural material with a zero-band gap and ultra-high specific surface area, has unique optoelectronic capabilities, promising a suitable basis for its application in the field of optical fiber sensing. Graphene optical fiber sensing has also been a hotspot in cross-research in biology, materials, medicine, and micro-nano devices in recent years, owing to prospective benefits, such as high sensitivity, small size, and strong anti-electromagnetic interference capability and so on. Here, the progress of optical fiber biochemical sensors based on graphene is reviewed. The fabrication of graphene materials and the sensing mechanism of the graphene-based optical fiber sensor are described. The typical research works of graphene-based optical fiber biochemical sensor, such as long-period fiber grating, Bragg fiber grating, no-core fiber and photonic crystal fiber are introduced, respectively. Finally, prospects for graphene-based optical fiber biochemical sensing technology will also be covered, which will provide an important reference for the development of graphene-based optical fiber biochemical sensors.

This study was conducted to investigate the feasibility of improving fertility in dairy cows via immunization against inhibin. Thirty-two cows were divided into Control (n = 11), Low-dose (n = 10) and High-dose (n = 11) groups. The High-dose and Low-dose cows were treated with 1 and 0.5 mg of the inhibin immunogen, respectively. All the cows were subjected to the Ovsynch protocol from the day of antigen administration and were artificially inseminated. Blood samples were serially collected over a 24-day period from the start of the Ovsynch protocol to 14 days after insemination. The results showed that immunization against inhibin dose-dependently increased the plasma concentrations of follicle-stimulating hormone (FSH), estradiol (E2), and activin A, but decreased progesterone (P4) concentrations in the luteal phase. Immunization also increased the plasma interferon (IFN)-τ concentrations in pregnant cows on day 14 after initial insemination. The conception rates in High-dose (45.5%) and Low-dose (40%) cows marginally increased compared to that in Control cows (27.3%), but the increases were not significant (p > 0.05). In conclusion, a single immunization against inhibin has the potential to improve conception rates, despite impaired luteal development. To further improve the reproductive performance of dairy cows, additional luteal-stimulating treatments are suggested in combination with immunization against inhibin and Ovsynch techniques.

Understanding how net primary production (NPP) and its allocation respond to climate warming is of fundamental importance in predicting ecosystem carbon (C) cycle and C-climate feedback. Especially, the optimal partitioning theory suggests that plants preferentially allocate photosynthates toward the above- or below-ground parts to acquire the limiting resources to maximize their growth rate and optimize resource use under environmental change. However, it remains elusive on how NPP allocation changes and regulates community water-use efficiency (WUEc) under climate warming. In this study, we conducted a manipulative warming experiment with three levels of warming treatments (control, + 1.5 °C and + 2.5 °C) to explore the response of NPP allocation and its regulation on WUEc in an alpine meadow. Results showed that above-ground NPP (ANPP) and below-ground NPP (BNPP) responded differently to warming. On average, W1.5 (+ 1.5 °C) and W2.5 (+ 2.5 °C) treatments increased BNPP by 28.98% and 33.28% and increased NPP by 20.05% and 38.70%, respectively, across 4 years. Whereas no consistent warming effect on ANPP was observed across years. The fraction of BNPP to total NPP (f _BNPP ) responded positively to warming under low ambient temperature and community biomass while it responded negatively under high ambient temperature and community biomass. Notably warming-induced changes in f _BNPP negatively correlated with warming-induced changes in WUEc. These results suggested that warming effect on NPP allocation was largely contextually dependent and implied important biological regulation on WUEc. The emerging trade-offs between NPP allocation and WUEc reflect adaptation strategy of plant community under climate change.

With continuous nitrogen (N) enrichment and sulfur (S) deposition, soil acidification has accelerated and become a global environmental issue. However, a full understanding of the general pattern of ecosystem belowground processes in response to soil acidification due to the impacting factors remains elusive. We conducted a meta-analysis of soil acidification impacts on belowground functions using 304 observations from 49 independent studies, mainly including soil cations, soil nutrient, respiration, root and microbial biomass. Our results show that acid addition significantly reduced soil pH by 0.24 on average, with less pH decrease in forest than non-forest ecosystems. The response ratio of soil pH was positively correlated with site precipitation and temperature, but negatively with initial soil pH. Soil base cations (Ca ^2+ , Mg ^2+ , Na ^+ ) decreased while non-base cations (Al ^3+ , Fe ^3+ ) increased with soil acidification. Soil respiration, fine root biomass, microbial biomass carbon and nitrogen were significantly reduced by 14.7%, 19.1%, 9.6% and 12.1%, respectively, under acid addition. These indicate that soil carbon processes are sensitive to soil acidification. Overall, our meta-analysis suggests a strong negative impact of soil acidification on belowground functions, with the potential to suppress soil carbon emission. It also arouses our attention to the toxic effects of soil ions on terrestrial ecosystems.