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Abstract Three-dimensional Spatial Transcriptomics has revolutionized our understanding of tissue regionalization, organogenesis, and development. However, existing approaches overlook either spatial information or experiment-induced distortions, leading to significant discrepancies between reconstruction results and in vivo cell locations, causing unreliable downstream analysis. To address these challenges, we propose ST-GEARS (Spatial Transcriptomics GEospatial profile recovery system through AnchoRS). By employing innovative Distributive Constraints into the Optimization scheme, ST-GEARS retrieves anchors with exceeding precision that connect closest spots across sections in vivo. Guided by the anchors, it first rigidly aligns sections, next solves and denoises Elastic Fields to counteract distortions. Through mathematically proved Bi-sectional Fields Application, it eventually recovers the original spatial profile. Studying ST-GEARS across number of sections, sectional distances and sequencing platforms, we observed its outstanding performance on tissue, cell, and gene levels. ST-GEARS provides precise and well-explainable ‘gears’ between in vivo situations and in vitro analysis, powerfully fueling potential of biological discoveries.

Objective To investigate the impact of succinate dehydrogenase (SDH) on the modulation of human sperm functions. Methods The isolated human sperm were co-incubated with different concentrations (10, 20, 40 mmol/L) of SDH inhibitor disodium malonate for one or two hours. The activity of the SDH was measured by commercially available reagent kit, while the protein level of the SDH catalytic subunit SDHA was determined through Western blot analysis. Sperm functions were analyzed:1)The impact of disodium malonate on important motility parameters of un-capcitated sperm including progressive motility rate (PR), total motility (TM), average pathvelocity (VAP)and the ability of capacitated sperm to penetrate viscous media were be assessed using a computer aided semen analysis system. 2) Effect of disodium malonate on sperm survival rate was evaluated using the Eosin-Nigrosin microscopy. 3) The incidence of acrosome reaction in capacitated sperm was be detected by PSA-FITC staining assay following disodium malonate treatment. Results Disodium malonate had no effect on expression of SDH catalytic subunit SHDA protein in human sperm. However, it inhibited the catalytic activity of the SDH, sperm forward motility, total motility, and the ability of sperm to penetrate viscous media. These inhibitory effects were positively correlated with the concentration of disodium malonate. Furthermore, disodium malonate had no any influence on the occurrence of spontaneous acrosome reaction in capacitated sperm. Conclusions Disodium malonate impairs human sperm motility by inhibiting succinate dehydrogenase activity.

Avian leukosis virus (ALV) is an avian oncogenic retrovirus that can impair immunological function, stunt growth and decrease egg production in avian flocks. The capsid protein (P27) is an attractive candidate for ALV diagnostics. In the present study, a new hybridoma cell (1F8) stably secreting an anti-P27 monoclonal antibody (mAb) was developed. The mAb exhibited a high affinity constant (Ka) of 8.65 × 106.0 L/mol, and it could be used for the detection of ALV-A/B/J/K strains. Moreover, a total of eight truncated recombinant proteins and five synthetic polypeptides were utilized for the identification of the B-cell epitopes present on P27. The results revealed that 218IIKYVLDRQK227 was the minimal epitope recognized by 1F8, which had never been reported before. Additionally, the epitopes could strongly react with different ALV subgroup’s specific positive serum and had a complete homology among all the ALV subgroups strains. Finally, a new sandwich ELISA method was created for the detection of ALV antigens, demonstrating increased sensitivity compared to a commercially available ELISA kit. These results offer essential knowledge for further characterizing the antigenic composition of ALV P27 and will facilitate the development of diagnostic reagents for ALV.

AbstractChrysoglossum ornatum Blume, the type species of Chrysoglossum Blume, belongs to the tribe Collabieae of the subfamily Epidendroideae of Orchidaceae. In this study, we sequenced, assembled, and analyzed the complete chloroplast genome of C. ornatum. The result showed that the complete chloroplast genome of C. ornatum was 158,175 bp in size, consisting of a large single-copy (LSC) region of 87,235 bp, a small single-copy (SSC) region of 18,384 bp, and a pair of inverted repeats (IRs) of 26,278 bp. The chloroplast genome encoded 113 unique genes, comprising 80 protein-coding genes, 29 tRNA genes, and four rRNA genes. Phylogenetic analysis inferred from the complete chloroplast genome indicated that Chrysoglossum was closely related to Collabium Blume. This study provides genomic resources helpful for further phylogenetic and biodiversity research on Chrysoglossum.

Anthocyanins, typical polyphenol compounds in grape skin, have attracted increasing interest due to their health-promoting properties. In this body of work, five representative anthocyanins (Cy-3-O-glc, Dp-3-O-glc, Pn-3-O-glc, Mv-3-O-glc, and Pt-3-O-glc) were studied using the density functional theory (DFT) to elucidate structure–radical scavenging activity in the relationship and the reaction path underlying the radical-trapping process. Based on thermodynamic parameters involved in HAT, SET-PT, and SPLET mechanisms, along with the structural attributes, it was found that the C4′ hydroxyl group mainly contributes to the radical scavenging activities of the investigated compounds. Pt-3-O-glc exhibits a good antioxidant capacity among the five compounds. The preferred radical scavenging mechanisms vary in different phases. For the Pt-3-O-glc compound, the calculations indicate the thermodynamically favoured product is benzodioxole, rather than o-quinone, displaying considerably reduced energy in double HAT mechanisms. Additionally, the thermodynamic and kinetic calculations indicate that the reaction of •OH into the 4′-OH site of Pt-3-O-glc has a lower energy barrier (7.6 kcal/mol), a higher rate constant (5.72 × 109 M−1 s−1), and exhibits potent •OH radical scavenging properties. Molecular docking results have shown the strong affinity of the studied anthocyanins with the pro-oxidant enzyme xanthine oxidase, displaying their significant role in inhibiting ROS formation.

The incidence of lung cancer, especially lung adenocarcinoma (LUAD), has recently increased. Targeted therapy and immunotherapy combined with conventional treatment have shown surprising benefits in enhancing the LUAD patient's prognosis. For the purpose of guiding treatment planning and the prognosis of LUAD, more research is required. The particular aim of this work was to establish a purine metabolism scoring (PMS) model for the purpose of individually forecasting treatment outcomes and overall survival for patients who have LUAD. Clinical and whole genome data were obtained from the TCGA-LUAD cohort via “UCSC”. The 25 driver purine metabolism-related prognostic genes were determined founded on univariate Cox regression. Then PMS was developed through stepwise LASSO Cox regression. Survival analysis indicated that patients who have PMS experienced worse outcomes. We validated the PGM2 effect on lung adenocarcinoma malignancy in in vitro experiments. Univariate as well as multivariate Cox regression suggested that PMS was an independent prognostic indicator for LUAD patients, which was confirmed in subgroup analysis. Functional assay demonstrated that immune response as well as cytotoxicity pathways have a connection with lower PMS, and patients who have low PMS possess an active immune microenvironment. Moreover, the LUAD patients who have low PMS showed greater sensitivity to immunotherapy, targeted therapy, as well as chemotherapy. Knockdown of PGM2 was discovered to decrease the proliferation, invasion, as well as migration of lung adenocarcinoma cells in an in vitro assay. Pertaining to this particular research, we created a PMS model and conducted a thorough analysis of purine metabolism in LUAD in order to determine prognosis and offer recommendations for treatment. This finding offered a fresh concept for the clinical management of LUAD and novel therapy protocols.

BackgroundEvidence shows people living with CHB even with a normal ALT (40U/L as threshold) suffer histological disease and there is still little research to evaluate the potential benefit of antiviral benefits in them.MethodsWe retrospectively examined 1352 patients who underwent liver biopsy from 2017 to 2021 and then obtained their 1-year follow-up data to analyze.ResultsALT levels were categorized into high and low, with thresholds set at >29 for males and >15 for females through Youden’s Index. The high normal ALT group showed significant histological disease at baseline (56.43% vs 43.82%, p< 0.001), and better HBV DNA clearance from treatment using PSM (p=0.005). Similar results were obtained using 2016 AASLD high normals (male >30, female >19). Further multivariate logistic analysis showed that high normal ALT (both criterias) was an independent predictor of treatment (OR 1.993, 95% CI 1.115-3.560, p=0.020; OR 2.000, 95% CI 1.055-3.793, p=0.034) Both of the models had higher AUC compared with current scoring system, and there was no obvious difference between the two models (AUC:0.8840 vs 0.8835)ConclusionMale >30 or female >19 and Male >29 or female>15 are suggested to be better thresholds for normal ALT. Having a high normal ALT in CHB provides a potential benefit in antiviral therapy.

Drug-resistant N. gonorrhoeae is an urgent threat to global public health, and vaccine development is the best long-term strategy for controlling gonorrhea. We have previously shown that adhesion and penetration protein (App) play a role in the adhesion, invasion, and reproductive tract colonization of N. gonorrhoeae. Here, we describe the immune response induced by intranasal immunization with passenger and translocator fragments of App. The recombinant App passenger and translocator fragments induced high titers of IgG and IgA antibodies in serum and vaginal washes. Antibodies produced by App passenger and the combination of passenger and translocator mediated the killing of N. gonorrhoeae via serum bactericidal activity and opsonophagocytic activity, whereas antisera from translocator-immunized groups had lower bactericidal activity and opsonophagocytic activity. The antisera of the App passenger and translocator, alone and in combination, inhibited the adhesion of N. gonorrhoeae to cervical epithelial cells in a concentration-dependent manner. Nasal immunization with App passenger and translocator fragments alone or in combination induced high levels of IgG1, IgG2a, and IgG2b antibodies and stimulated mouse splenocytes to secrete cytokines IFN-γ and IL-17A, suggesting that Th1 and Th17 cellular immune responses were activated. In vivo experiments have shown that immune App passenger and transporter fragments can accelerate the clearance of N. gonorrhoeae in the vagina of mice. These data suggest that the App protein is a promising N. gonorrhoeae vaccine antigen.

The sorption behaviors of bamboo fiber-based composites (BFC) play a critical role on its applications due to its impact on the dimensional stability and biological durability of the material. The sorption behaviors of Neosinocalamus affinis BFC with compression ratios of 1.50, 1.83 and 2.17 were studied in this project, aiming to optimize the manufacturing process of BFC to reduce the sorption of final products. It was found that the hygroscopicity of BFC samples with all three compression ratios is much lower than that of raw bamboo at all the studied relative humidity (RH) levels. The BFC manufactured with 1.50 compression ratios showed the lowest equilibrium moisture content (EMC). The sorption ability of BFC showed some increase with increasing compression ratio especially when the relative humidity (RH) was above 60%. An evolution in moisture absorption model of BFC was proposed based on the changes in its wettability, pore structures, and chemical compositions. Both introduction of phenolic formaldehyde (PF) resin and material densification reduced the water transfer pathway such as bamboo cell lumens, pits, and gaps, as well as the water absorption space in cell wall. Meanwhile, the BFC with higher compression ratio had increased difficulty to absorb water. The increase in sorption ability of BFC with higher compression ratio at high RH environment is proved to be the consequence of the higher content of its mesopore ratio resulting in increased poly-layer water content. Therefore, the RH of application occasions is critical to determine the optical compression ratio of BFC combining with other performance requirements.

AIM: To evaluate the clinical efficacy and systemic safety profile of conbercept in clinical practice on vascular endothelial growth factor (VEGF)-A, VEGF-B, and placental growth factor (PLGF) levels after intravitreal injections for the neovascular age-related macular degeneration (AMD). METHODS: Thirty-five patients (35 eyes) with neovascular AMD received intravitreal injections of conbercept treatment with pro re nata protocol. Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were detected before the intravitreal injection and at 1, 3, and 12mo after conbercept treatment. The levels of serum VEGF-A, VEGF-B, and PLGF were measured by enzyme-linked immunosorbent assay before the injection and 1 and 12mo after conbercept treatments. RESULTS: At baseline, the mean BCVA score was 39.89±14.64 letters. The mean BCVA scores were 51.03±15.78, 56.71±14.38, and 52.49±10.16 letters at 1, 3, and 12mo after conbercept treatment, and the BCVA improvements were all significant, respectively (P0.05). CONCLUSION: Conbercept intravitreal injection leads to BCVA and CRT improvement, however, it does not significantly affect systemic serum VEGF-A, VEGF-B, and PLGF levels at 1 and 12mo after intravitreal injection treating neovascular AMD.

AIM: To explore the feasibility of swept source optical coherence tomography angiography(SS-OCTA)in evaluating early retinal and choroidal microcirculation changes in patients with hypertension.METHODS:Prospective clinical study. A total of 27 patients with grade 2 or 3 essential hypertension(hypertension group)diagnosed in the Department of Cardiology of Xi'an First Hospital from July to November 2022 were included in the study. There were 14 males and 13 females. The mean age was(57.11±3.36)years. During the same period, 27 age- and sex-matched normal people without a history of hypertension were selected as the control group, including 12 males and 15 females. The average age was(55.74±2.95)years old. All patients underwent BCVA(LogMAR), intraocular pressure, axial length, slit lamp examination, fundus color photography and SS-OCTA examination. SS-OCTA was used to scan the macular area of the right eye in the range of 6×6 mm. The retina and choroid were divided into three concentric circles with diameters of 0-1 mm, 1-3 mm and 3-6 mm around the fovea according to ETDRS. Macular vessel density(VD), perfusion area(PA), retinal thickness(CMT), choroidal thickness(CT), choroidal vessel volume(CVV)and choroidal vasculr index(CVI)of the superficial capillary plexus(SCP)and the deep capillary plexus(DCP)in the macular area of 0-1 mm, 1-3 mm and 3-6 mm were analyzed and recorded. The changes in VD, PA, CMT, CT, CVV and CVI were compared between the two groups. Independent sample t-test was used to compare VD, PA, CMT and CVI between the two groups; CT, CVV and LogMAR visual acuity were analyzed by Wilcoxon signed rank test of independent samples.RESULTS:Compared with the control group, the hypertensive group had significantly lower VD in the macular area 0-3 mm(0-1 mm, t=-3.144; 1-3 mm, t=-3.611, P0.05). The CMT in the 0-1mm area of the macular area in the hypertension group was lower than that in the control group(t=-2.624, P0.05).CONCLUSION:The VD of DCP in the 0-3 mm area and the CMT in the 0-1 mm area are decreased in hypertensive patients. There were no significant differences in CT, CVV and CVI between the two groups. VD and CMT in macular DCP may be used as indicators to evaluate the early changes of retinal and choroidal microcirculation in hypertensive patients.

Background During the containment of COVID-19, the traditional face-to-face interventions conducted at the rehabilitation center were plagued by many limitations, while internet-based interventions can overcome the limitations of geographic location, working hours and transportation, with less medical costs. Objective To examine the effects of internet-based interventions on knowledge, attitude/belief and practice (KAP) toward rehabilitation exercises, physical activity (PA) level, and exercise compliance inpatients after PCI. Methods The subjects were 76 patients who received their first PCI in Department of Cardiology, Tangshan Gongren Hospital from November 2021 to June 2022. They were randomly and equally divided into two groups to receive either internet-based intervention with routine nursing (experimental group) or routine nursing (control group) . Before and three months after the intervention, the Rehabilitation Exercise Knowledge-Belief-Practice Scale for Patients with Coronary Heart Disease (REKBPCHD) , the International Physical Activity Questionnaire-Short Form (IPAQ-SF) , and Patients' Exercise Log were used to assess the KAP level, PA level, and exercise adherence, respectively. The impact of network intervention on exercise adherence in patients after PCI by univariate Logistic regression analysis. Results After 3 months of intervention, a significant increase was found in the average total score of REKBPCHD, and the average scores of the knowledge dimension, attitude dimension and practice dimension of the scale in the experimental group (P

Abstract Background Clinical practice of aerosol delivery in conjunction with respiratory support devices for critically ill adult patients remains a topic of controversy due to the complexity of the clinical scenarios and limited clinical evidence. Objectives To reach a consensus for guiding the clinical practice of aerosol delivery in patients receiving respiratory support (invasive and noninvasive) and identifying areas for future research. Methods A modified Delphi method was adopted to achieve a consensus on technical aspects of aerosol delivery for adult critically ill patients receiving various forms of respiratory support, including mechanical ventilation, noninvasive ventilation, and high-flow nasal cannula. A thorough search and review of the literature were conducted, and 17 international participants with considerable research involvement and publications on aerosol therapy, comprised a multi-professional panel that evaluated the evidence, reviewed, revised, and voted on recommendations to establish this consensus. Results We present a comprehensive document with 20 statements, reviewing the evidence, efficacy, and safety of delivering inhaled agents to adults needing respiratory support, and providing guidance for healthcare workers. Most recommendations were based on in-vitro or experimental studies (low-level evidence), emphasizing the need for randomized clinical trials. The panel reached a consensus after 3 rounds anonymous questionnaires and 2 online meetings. Conclusions We offer a multinational expert consensus that provides guidance on the optimal aerosol delivery techniques for patients receiving respiratory support in various real-world clinical scenarios.

Conclusion: In addition to drug treatment, cardiac rehabilitation guided by CPET can effectively improve blood pressure control, reduce blood pressure variability, improve cardiorespiratory function and lipid metabolism, and increase exercise endurance in patients with Grade 1 hypertension. Its efficacy is clear and safe, with clinical value for promotion.

BackgroundHyperammonemia is critical to the development of hepatic encephalopathy (HE) and is associated with mortality in end-stage liver disease. This study investigated the clinical value of ammonia variation in hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) patients.MethodsA total of 276 patients with HBV-ACLF were retrospectively recruited. Patients' ammonia levels were serially documented. Baseline ammonia, Peak ammonia (highest level), and Trough ammonia (lowest level) were particularly corrected to the upper limit of normal (AMM-ULN). The primary endpoint was 28-day mortality.ResultsThe 28-day, 3-month, and 12-month mortality rates were 19.2, 25.7, and 28.2%, respectively. A total of 51 (18.4%) patients had overt HE (grade 2/3/4). Peak AMM-ULN was significantly higher in patients with overt HE and non-survivors compared with their counterparts (P < 0.001). Following adjustment for significant confounders, high Peak AMM-ULN was an independent predictor of overt HE (hazard ratio, 1.031, P < 0.001) and 28-day mortality (hazard ratio, 1.026, P < 0.001). The cut-off of Peak AMM-ULN was 1.8, determined by using the X-tile. Patients with Peak AMM-ULN appearing on days 1–3 after admission had a higher proportion of overt HE and mortality compared to other groups. Patients with decreased ammonia levels within 7 days had better clinical outcomes than those with increased ammonia.ConclusionSerum Peak ammonia was independently associated with overt HE and mortality in HBV-ACLF patients. Serial serum ammonia may have prognostic value.

Background: Semantic segmentation is crucial in medical image diagnosis. Traditional deep convolutional neural networks excel in image classification and object detection but fall short in segmentation tasks. Enhancing the accuracy and efficiency of detecting high-level cervical lesions and invasive cancer poses a primary challenge in segmentation model development. Methods: Between 2018 and 2022, we retrospectively studied a total of 777 patients, comprising 339 patients with high-level cervical lesions and 313 patients with microinvasive or invasive cervical cancer. Overall, 1554 colposcopic images were put into the DeepLabv3+ model for learning. Accuracy, Precision, Specificity, and mIoU were employed to evaluate the performance of the model in the prediction of cervical high-level lesions and cancer. Results: Experiments showed that our segmentation model had better diagnosis efficiency than colposcopic experts and other artificial intelligence models, and reached Accuracy of 93.29 %, Precision of 87.2 %, Specificity of 90.1 %, and mIoU of 80.27 %, respectively. Conclution: The DeepLabv3+ model had good performance in the segmentation of cervical lesions in colposcopic post-acetic-acid images and can better assist colposcopists in improving the diagnosis.

In order to improve the hydrophobicity of tapioca starch, and used it as a granular emulsifier to improve the emulsification properties of myofibrillar protein (MP). In this study, a hydrophobic modification of native tapioca starch (NTS) by octenyl succinate anhydride (OSA), which produced ocentyl succinic tapioca starch (OSTS) with different modification levels and degrees of substitution (DS), and the compound emulsions were prepared using OSTS and MP. The structural changes of the OSTS were analyzed by XRD, FT-IR, SEM, and PLM, and the emulsion index (EI), emulsifying activity index (EAI), emulsion stability index (ESI), Zeta-potential, particle size distribution, sulfhydryl content, and interface protein content of the emulsions were determined. The results showed that the hydrophobic groups were successfully introduced in the tapioca starch molecules, and the hydrophobic modification treatment had basically no effect on the crystal structure type of the tapioca starch particles. The EAI and ESI of the OSTS-MP compound emulsions improved significantly (P

Objective To investigate the effect of running exercise on depression-like behaviors in chronic unpredictable stress (CUS)-induced depression mice and GABAergic interneurons, PV+ interneurons and ratio of GAD67+/PV+ cells in medial prefrontal cortex (mPFC). Methods After mouse model of depression was successfully established through CUS, these male C57BL/6 mice aged 4~6 weeks were randomly divided into control group, CUS control group and CUS+running group according to the results of sucrose preference test. The behaviors of the 3 groups were evaluated with sucrose preference test, forced swimming test and tail suspension test. The mRNA expression levels of GAD1, GAD2, PV and CCK in mPFC of mice were detected using qRT-PCR. The number of GABAergic interneurons and PV+ interneurons in mPFC of mice were quantified using immunohistochemical assay and unbiased stereological technique, and the ratio of PV+/GAD67+ cells was calculated. Results Compared with those in CUS control group, the mice from the CUS+running and control groups showed a significantly higher percentage of sucrose preference (P0.05). The mRNA level of PV, number of PV+ interneurons and ratio of PV+/GAD67+ cells in mPFC were remarkably lower in the CUS group than the CUS +running group and control group (P

In this work, a numerical method is proposed to predict the electrokinetic phenomena and combined with an experimental study of the surface charge density (ρs) and zeta potential (ζ) behavior is investigated for borosilicate immersed in KCl and NaCl electrolytes, and for imogolite immersed in KCl, CaCl2, and MgCl2 electrolytes. Simulations and experiments of the electrokinetic flows with electrolyte solutions were performed to accurately determine the electric double layer (EDL), ζ, and ρs at various electrolyte concentrations and pH. The zeta potential was experimentally determined and numerically predicted by solving the coupled governing equations of mass, species, momentum, and electrical field iteratively. Our numerical prediction shows that ζ for borosilicate develops strong nonlinear behavior with the ion concentration following a power-law. Likewise, the ρs obeys a nonlinear behavior, decreasing as the concentration increases. Moreover, for imogolite, both ζ and the ρs behave nonlinearly with the pH. The EDL for borosilicate and imogolite becomes thinner as the electrolyte concentration and pH increase; this behavior is caused by increased ρs, resulting in the higher attraction of the free charges. The reported nonlinear behavior describes more accurately the interaction of the nanoparticle surface charge with the electrolytes and its effect on the electrolyte transport properties.

Introduction Obesity is a complex and multifactorial disease that has affected many adolescents in recent decades. Clinical practice guidelines recommend exercise as the key treatment option for adolescents with overweight and obesity. However, the effects of virtual reality (VR) exercise on the physical and brain health of adolescents with overweight and obese remain unclear. This study aims to evaluate the effects of physical and VR exercises on physical and brain outcomes and explore the differences in benefits between them. Moreover, we will apply a multiomics analysis to investigate the mechanism underlying the effects of physical and VR exercises on adolescents with overweight and obesity.Methods and analysis This randomised controlled clinical trial will include 220 adolescents with overweight and obesity aged between 11 and 17 years. The participants will be randomised into five groups after screening. Participants in the exercise groups will perform an exercise programme by adding physical or VR table tennis or soccer classes to routine physical education classes in schools three times a week for 8 weeks. Participants in the control group will maintain their usual physical activity. The primary outcome will be the change in body fat mass measured using bioelectrical impedance analysis. The secondary outcomes will include changes in other physical health-related parameters, brain health-related parameters and multiomics variables.Ethics and dissemination This study was approved by the Ethics Committee of Shanghai Sixth People’s Hospital and registered in the Chinese Clinical Trial Registry. Dissemination of the findings will include peer-reviewed publications, conference presentations and media releases.Trial registration number ChiCTR2300068786.

BackgroundThe most prevalent sustained arrhythmia in medical practice, atrial fibrillation (AF) is closely associated with a high risk of cardiovascular disease. Nevertheless, the risk of AF associated with cardiovascular risk factors has not been well elucidated. We pooled all published studies to provide a better depiction of the relationship among cardiovascular risk factors with AF.MethodsStudies were searched in the MEDLINE, Web of Science, and EMBASE databases since initiation until January 15, 2022. Prospective cohort studies assessing the relationship a minimum of single cardiovascular risk factors to AF incidence were included if they contained adequate data for obtaining relative risks (RR) and 95% confidence intervals (CI). Random-effects models were utilized to perform independent meta-analyses on each cardiovascular risk factor. PROSPERO registry number: CRD42022310882.ResultsA total of 17,098,955 individuals and 738,843 incident cases were reported for data from 101 studies included in the analysis. In all, the risk of AF was 1.39 (95% CI, 1.30–1.49) for obesity, 1.27 (95% CI, 1.22–1.32) per 5 kg/m2 for increase in body mass index, 1.19 (95% CI, 1.10–1.28) for former smokers, 1.23 (95% CI, 1.09–1.38) for current smokers, 1.31 (95% CI, 1.23–1.39) for diabetes mellitus, 1.68 (95% CI, 1.51–1.87) for hypertension, and 1.12 (95% CI, 0.95–1.32) for dyslipidemia.InterpretationAdverse cardiovascular risk factors correlate with an increased risk of AF, yet dyslipidemia does not increase the risk of AF in the general population, potentially providing new insights for AF screening strategies among patients with these risk factors.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, PROSPERO identifier (CRD42022310882).

Food-borne antibiotic-resistant Campylobacter poses a serious threat to public health. To understand the prevalence and genetic characteristics of Campylobacter in Chinese local dual-purpose (meat and eggs) chickens, the genomes of 30 Campylobacter isolates, including 13 C. jejuni and 17 C. coli from Jianghan-chickens in central China, were sequenced and tested for antibiotic susceptibility. The results showed that CC-354 and CC-828 were the dominant clonal complexes of C. jejuni and C. coli, respectively, and a phylogenetic analysis showed that three unclassified multilocus sequence types of C. coli were more closely genetically related to C. jejuni than to other C. coli in this study. Of the six antibiotics tested, the highest resistance rates were to ciprofloxacin and tetracycline (100%), followed by lincomycin (63.3%), erythromycin (30.0%), amikacin (26.7%), and cefotaxime (20.0%). The antibiotic resistance rate of C. coli was higher than that of C. jejuni. The GyrA T86I mutation and 15 acquired resistance genes were detected with whole-genome sequencing (WGS). Among those, the GyrA T86I mutation and tet(O) were most prevalent (both 96.7%), followed by the blaOXA-type gene (90.0%), ant(6)-Ia (26.7%), aac(6’)-aph(3’’) (23.3%), erm(B) (13.3%), and other genes (3.3%). The ciprofloxacin and tetracycline resistance phenotypes correlated strongly with the GyrA T86I mutation and tet(O)/tet(L), respectively, but for other antibiotics, the correlation between genes and resistance phenotypes were weak, indicating that there may be resistance mechanisms other than the resistance genes detected in this study. Virulence gene analysis showed that several genes related to adhesion, colonization, and invasion (including cadF, porA, ciaB, and jlpA) and cytolethal distending toxin (cdtABC) were only present in C. jejuni. Overall, this study extends our knowledge of the epidemiology and antibiotic resistance of Campylobacter in local Chinese dual-purpose chickens.

This article proposes an infrared and water vapor channel satellite image fusion model (TCCL-DenseFuse) based on DenseNet. The infrared channel satellite image reflects the ground and cloud top infrared radiation or the distribution of temperature, and the water vapor channel satellite image reflects the spatial distribution of water vapor in the upper atmosphere. Studies have shown that infrared brightness temperature gradient and water vapor transport are closely related to tropical cyclone (TC) generation and evolution. In order to facilitate the fusion image obtained by the proposed fusion model to have a positive effect on TC monitoring and warning, the brightness temperature gradient and multiscale structural similarity in the satellite image are used to construct loss function of the proposed TCCL-DenseFuse model. The quality of the fused images is evaluated by seven objective quantitative indicators. In order to further verify the real application value of the proposed TCCL-DenseFuse model, fused images are also used to TC center location. Experimental results show that the proposed TCCL-DenseFuse fused satellite image not only contains rich information from both infrared and water vapor channels but also improves the accuracy of TC center positioning. The comprehensive performance of the proposed fusion model has certain advantages compared with similar fusion methods and can provide a reference for typhoon prevention and disaster mitigation.

Background Hemorrhagic cystitis (HC) is a severe complication of allo-HSCT, characterized by irritative symptoms of the urinary tract and a higher morbidity rate. The risk factors and prognosis of HC are still unclear.Objective The objective of this study is to identify risk factors and outcomes to improve treatment in pediatric SAA patients undergoing HSCTs in the Children's Hospital of Soochow University.Methods A total of 97 SAA patients as a cohort were enrolled from 2010 to 2019 in the Children's Hospital of Soochow University and a number of factors related to HC and outcomes were analysed. In all transplants (except UCBT), patients received a combination of G-CSF stimulated bone marrow (BM) and peripheral blood stem cell (PBSC). The minimum number of CD34 + cells is 5 × 106 cells/kg.Results Mononuclear cells dose (MNC, cut off: 8.53 × 108/kg) and grade II–IV acute graft versus host disease (aGVHD) were identified as independent risk factors for HC. Patients without HC had better overall survival (OS) than with HC (No HC: 98.6%±1.4% vs HC: 87.4% ± 6.8%, p = 0.03).Conclusion We concluded that aGVHD and MNC dose in graft might play an important role in the development of HC in pediatric SAA patients undergoing allo-HSCT. HC is also a key complication affecting the prognosis of children with SAA after allo-HSCT.

Reservoir construction alters the hydrodynamic characteristics of the flow and sediment regimes, resulting in the enhancement of the hysteresis effect between the flood and sediment peaks. In this study, a 3D numerical model was adopted to investigate the propagation characteristics of sediment peak and the management method of reservoir sediment release. The results indicate that the incoming flow rate and the storage water level have a great influence on the propagation time of the sediment peak, and the incoming flow rate has a large influence on the attenuation rate of the sediment peak while the storage water level and the incoming suspended sediment concentration have a small effect on the attenuation rate of the sediment peak. An empirical formula based on inflow rate, water level elevation, water depth and length and storage capacity of reservoirs was established to predict the lag time between the flood and sediment peaks. The asynchronous movement between the incoming flood and sediment peaks has a clear influence on the propagation characteristics of the sediment peak. The hysteresis effect of the flood and sediment peaks can be fully utilized by reservoir managers to reduce reservoir sedimentation and improve sedimentation distribution. HIGHLIGHTS The effect of the hysteresis effect of flood and sediment peaks affects the propagation characteristics of the sediment peak.; The lag time of flood and sediment peaks can be predicted based on inflow rate, water depth and length and storage capacity of reservoirs.; The hysteresis effect of the flood and sediment peaks provides an effective way to improve reservoir sedimentation.;

Objective To detect expression changes of Sfrp1 in NRK-52E cells after 5-Aza-2'deoxycytidine (5-Aza-CdR) intervention. Methods Sprague-Dawley (SD) rats were divided into normal group (NC group) and diabetic nephropathy group (DN group) randomly. The related biochemical indexes were detected after successfully modeling[1-2] for 10 weeks;kidney index (KI) was calculated; the expression of Sfrp1 in renal tissue was detected by immunohistochemistry. NRK-52E cells were divided into normal glucose group (NG, 5.5 mmol/L), high glucose group (HG, 30 mmol/L) and high glucose +5-Aza-CdR group(5-Aza-CdR group);the expressions of Sfrp1,Dnmt3a,Dnmt3b,col-Ⅲ and col-Ⅳ were detected by Western blot;the mRNA expression of Sfrp1 was detected by RT-qPCR;pearson test was used to analyze the correlation between Sfrp1 and Dnmt3a,Dnmt3b,col-Ⅲ or col-Ⅳ. Results The level of KI, blood glucose, 24 h urinary protein and creatinine in DN group were all higher than those in NC group.The expression of Sfrp1 in renal tissue of DN group was significantly lower than that of NC group.The results of in vitro experiments showed as follows:the mRNA and protein expression of Sfrp1 were decreased in HG group(P＜0.05),while the protein expressions of Dnmt3a,Dnmt3b,col-Ⅲ and col-Ⅳ in HG group were increased (P＜0.05);compared with HG group,the mRNA and protein expression of Sfrp1 was increased in 5-Aza-CdR group(P＜0.05), the protein expressions of Dnmt3a,Dnmt3b,col-Ⅲ and col-Ⅳ in 5-Aza-CdR group were decreased (P＜0.05); Sfrp1 was negatively correlated with Dnmt3a (r=-0.937, P＜0.05),Dnmt3b (r=-0.965, P＜0.05),col-Ⅲ(r=-0.694, P＜0.05) and col-Ⅳ(r=-0.888, P＜0.05). Conclusions The mechanism through which 5-Aza-2′-deoxycytidine inhibits renal fibrosis is potentially related to the reduction of Dnmt3a and Dnmt3b expression and the increase of Sfrp1 expression.

Conbercept is a novel anti-vascular endothelial growth factor drug independently developed by China. Since it was approved for clinical application by the State Food and Drug Administration of China in 2013, conbercept has shown reliable safety and efficacy in the treatment of ocular neovascular diseases such as wet age-related macular degeneration, choroidal neovascularization and macular edema. For different diseases, the treatment strategies of conbercept are different. This article mainly reviews the application progress of conbercept in ocular neovascularization related diseases including wet age-related macular degeneration, diabetic macular edema, pathologic myopia choroidal neovascularization, neovascular glaucoma, retinopathy of prematurity and corneal neovascularization, and summarizes and explores the indications, administration scheme and therapeutic effect of conbercept. It is expected that the indications of conbercept will be wider and the administration scheme will be more given, and the usage of conbercept will bring new ideas for the treatment of ocular neovascular diseases.

ObjectivePasteurella multocida is a widespread zoonotic pathogen that causes severe damage to the poultry industry. This study focused on the antibacterial effects and mechanism of action of coptisine against P. multocida.MethodsThe minimum inhibitory concentration and half maximal inhibitory concentration of coptisine against P. multocida was measured. Additionally, the effect of coptisine on growth, cell wall, activity of respiratory enzymes, soluble protein content and DNA synthesis were also analyzed. Finally, the effect of coptisine on gene transcription was determined using RNA sequencing.ResultsWe demonstrated that coptisine has a strong antibacterial effect against P. multocida, with a minimum inhibitory concentration of 0.125 mg/mL. Moreover, the measurement of the half maximal inhibitory concentration confirmed that coptisine was safe for the pathogen. The growth curve showed that coptisine inhibited bacterial growth. Measurement of alkaline phosphatase activity in the culture solution showed that coptisine affected cell wall permeability. Transmission electron microscopy revealed that coptisine chloride destroyed the cell structure. In addition, coptisine blocked the respiratory system, as measured by the levels of critical enzymes of the tricarboxylic acid cycle and glycolysis, succinate dehydrogenase and lactate dehydrogenase, respectively. Similarly, coptisine inhibited the synthesis of soluble proteins and genomic DNA. The KEGG pathway analysis of the differentially expressed genes showed that they were associated with cellular, respiratory, and amino acid metabolism, which were downregulated after coptisine treatment. Additionally, genes related to RNA degradation and the aminoacyl-tRNA pathway were upregulated.ConclusionIn this study, we demonstrated that coptisine exerts an antibacterial effect on P. multocida. These findings suggest that coptisine has a multifaceted impact on various pathways, resulting in the inhibition of P. multocida. Thus, coptisine is a potential alternative to antibiotics for the treatment of P. multocida infections in a clinical setting.

Jujuboside B (JuB), one of the main active triterpenoid saponins from the traditional Chinese medicine Ziziphus jujuba, possesses a wide range of pharmacological activities. However, it is unknown whether JuB can inhibit tumor angiogenesis, a crucial step in solid tumor growth. In this study, we found that JuB significantly inhibited the proliferation, migration, and tube formation of human umbilical vein endothelial cells in a dose-dependent manner. JuB also suppressed angiogenesis in chick embryo chorioallantoic membranes and Matrigel plugs. Moreover, through angiogenesis inhibition, JuB delayed the growth of human HCT-15 colorectal cancer xenograft in mice. Western blot assay demonstrated that JuB inhibited the phosphorylation of VEGFR2 and its key downstream protein kinases, such as Akt, FAK, Src, and PLCγ1. In conclusion, the antiangiogenic potency and molecular mechanism of JuB are revealed for the first time, indicating that this triterpene saponin may be further explored as a potential drug candidate or lead compound for antiangiogenic cancer therapy.

Objectives Acute upper gastrointestinal bleeding (UGIB) is a common reason for emergency hospital admission. Identifying low-risk patients suitable for outpatient management is a clinical and research priority. This study aimed to develop a simple risk score to identify elderly patients with UGIB for whom hospital admission is not required.Design This was a single-centre retrospective study.Setting This study was conducted at Zhongda Hospital affiliated with Southeast University in China.Participants Patients from January 2015 to December 2020 for the derivation cohort and from January 2021 to June 2022 for the validation cohort were enrolled in this study. A total of 822 patients (derivation cohort=606 and validation cohorts=216) were included in this study. Patients aged ≥65 years with coffee-grounds vomiting, melena or/and haematemesis were included in the analysis. Patients admitted but had UGIB or transferred between hospitals were excluded.Methods Baseline demographic characteristics and clinical parameters were recorded at the first visit. Data were collected from electronic records and databases. Multivariable logistic regression modelling was performed to identify predictors of safe discharge.Results 304/606 (50.2%) and 132/216 (61.1%) patients were not safely discharged in the derivation and validation cohorts, respectively. A clinical risk score of five variables was entered into UGIB risk stratification: Charlson Comorbidity Index >2, systolic blood pressure

ABSTRACT: Objectives: This study investigated the prevalence and characteristics of mcr-1-harbouring Escherichia coli isolated from chickens in central China from 2014 to 2019. Methods: A total of 1132 E. coli isolated from 1647 chicken swabs were analysed for colistin susceptibility by broth microdilution method and prevalence of mcr-1 gene by PCR. The colistin-resistant E. coli isolates were typed by multi-locus sequence typing (MLST) and tested with 12 antimicrobial agents. The transconjugation assay was conducted for the mcr-1-positive isolates using the transconjugant E. coli C600. Results: Of the 1132 E. coli isolated from chickens, 131 isolates (11.6%) exhibited colistin resistance, and 51 isolates (4.5%) were mcr-1 positive. The mcr-1-positive rate was quite low in 2014 (2.3%) and 2015 (1.7%), increased to peak in 2016 (12.6%) and 2017 (11.4%), and then decreased significantly in 2018 (1.7%) and 2019 (0.9%). The 131 colistin resistant isolates were assigned to 66 unique sequence types (STs), 27 of which contained mcr-1-positive isolates. Compared with mcr-1-negative E. coli, mcr-1-positive E. coli showed higher resistance rates to nalidixic acid, ciprofloxacin, ceftriaxone, cefotaxime, and tetracycline. Furthermore, 30 of the 51 mcr-1 positive isolates transduced their mcr-1 gene into E. coli C600, and 13 of the 30 transconjugants carried more than one replicon types. Conclusion: The mcr-1 positive rate varied enormously during 2014–2019 in central China. The ban on colistin likely decreased the dissemination of mcr-1 in E. coli isolates from chickens. Multidrug-resistant trait is observed in mcr-1 positive E. coli isolates and can be transferred into other transconjugants.

BackgroundMelanocortin-2 receptor (MC2R), a member of the G protein-coupled receptor family, is selectively activated by adrenocorticotropic hormone (ACTH). variants in MC2R are associated with family glucocorticoid deficiency 1 (FGD1).Case presentationWe first reported a Chinese family with two affected siblings with a homozygotic variant of c.712C>T/p.H238Y in MC2R, presenting with skin hyperpigmentation, hyperbilirubinemia, and tall stature. These individuals showed novel clinical features, including congenital heart defects, not been found in other FGD1 patients.ConclusionsWe reported a Chinese family with affected siblings having a homozygotic variant of c.712C>T/p.H238Y in MC2R.Our report may expand the genetic and clinical spectrum of FGD1.

Abstract Objectives To compare the predictive ability of six pre-endoscopic scoring systems (ABC, AIMS65, GBS, MAP(ASH), pRS, and T-score) for outcomes of upper gastrointestinal bleeding (UGIB) in elderly and younger patients. Methods A retrospective study of 1260 patients, including 530 elderly patients (age $$\ge$$ ≥ 65) and 730 younger patients (age

Abstract Background This study aimed to evaluate the association between homocysteine-related dietary patterns and gestational diabetes mellitus. Methods A total of 488 pregnant women at 24–28 weeks of gestation between January 2019 and December 2020 were included. Demographic characteristics, dietary intake, and multivitamin supplement intake information were collected using a food frequency questionnaire (FFQ); fasting venous blood samples were collected for serum index detection. Serum homocysteine (Hcy), folic acid, and B12 were selected as response variables, and hyperhomocysteinemia (hHcy)-related dietary patterns were extracted using the reduced rank regression.. The relationship between the score of hHcy-related dietary patterns and GDM was analyzed using a multivariate logistic regression model. Results Three hHcy-related dietary patterns were extracted. Only mode 2 had a positive and significant relationship with the risk of developing GDM. After adjusting for confounding factors, the risk of GDM was significantly increased in the highest quartile array compared with the lowest quartile of the pattern (OR = 2.96, 95% Confidence Interval: 0.939–9.356, P = 0.004). There was no significant correlation between dietary pattern 1 and GDM risk (P > 0.05). Conclusions Homocysteine-related dietary patterns were positively associated with gestational diabetes mellitus. Adjusting dietary patterns may contribute to the intervention and prevention of GDM.

RNA binding proteins can contribute to colorectal cancer (CRC) initiation and development. Here the authors show that PUMILIO proteins, PUM1 and PUM2 contribute to CRC growth by inhibiting p21 expression.

Abstract Background Avian colibacillosis is an infectious bacterial disease caused by avian pathogenic Escherichia coli (APEC). APEC causes a wide variety of intestinal and extraintestinal infections, including InPEC and ExPEC, which result in enormous losses in the poultry industry. In this study, we investigated the prevalence of InPEC and ExPEC in Central China, and the isolates were characterized using molecular approaches and tested for virulence factors and antibiotic resistance. Results A total of 200 chicken-derived E. coli isolates were collected for study from 2019 and 2020. The prevalence of B2 and D phylogenic groups in the 200 chicken-derived E. coli was verified by triplex PCR, which accounted for 50.53% (48/95) and 9.52% (10/105) in ExPEC and InPEC, respectively. Additionally, multilocus sequence typing method was used to examine the genetic diversity of these E. coli isolates, which showed that the dominant STs of ExPEC included ST117 (n = 10, 20.83%), ST297 (n = 5, 10.42%), ST93 (n = 4, 8.33%), ST1426 (n = 4, 8.33%) and ST10 (n = 3, 6.25%), while the dominant ST of InPEC was ST117 (n = 2, 20%). Furthermore, antimicrobial susceptibility tests of 16 antibiotics for those strains were conducted. The result showed that more than 60% of the ExPEC and InPEC were resistant to streptomycin and nalidixic acid. Among these streptomycin resistant isolates (n = 49), 99.76% harbored aminoglycoside resistance gene strA, and 63.27% harbored strB. Among these nalidixic acid resistant isolates (n = 38), 94.74% harbored a S83L mutation in gyrA, and 44.74% harbored a D87N mutation in gyrA. Moreover, the prevalence of multidrug-resistant (MDR) in the isolates of ExPEC and InPEC was 31.25% (15/48) and 20% (2/10), respectively. Alarmingly, 8.33% (4/48) of the ExPEC and 20% (2/10) of the InPEC were extensively drug-resistant (XDR). Finally, the presence of 13 virulence-associated genes was checked in these isolates, which over 95% of the ExPEC and InPEC strains harbored irp2, feoB, fimH, ompT, ompA. 10.42% of the ExPEC and 10% of the InPEC were positive for kpsM. Only ExPEC isolates carried ibeA gene, and the rate was 4.17%. All tested strains were negative to LT and cnf genes. The carrying rate of iss and iutA were significantly different between the InPEC and ExPEC isolates (P

Backgroud: Temporal lobe epilepsy (TLE) is associated with abnormal dynamic functional connectivity patterns, but the dynamic changes in brain activity at each time point remain unclear, as does the potential molecular mechanisms associated with the dynamic temporal characteristics of TLE. Methods: Resting-state functional magnetic resonance imaging (rs-fMRI) was acquired for 84 TLE patients and 35 healthy controls (HCs). The data was then used to conduct HMM analysis on rs-fMRI data from TLE patients and an HC group in order to explore the intricate temporal dynamics of brain activity in TLE patients with cognitive impairment (TLE-CI). Additionally, we aim to examine the gene expression profiles associated with the dynamic modular characteristics in TLE patients using the Allen Human Brain Atlas (AHBA) database. Results: Five HMM states were identified in this study. Compared with HCs, TLE and TLE-CI patients exhibited distinct changes in dynamics, including fractional occupancy, lifetimes, mean dwell time and switch rate. Furthermore, transition probability across HMM states were significantly different between TLE and TLE-CI patients (p < 0.05). The temporal reconfiguration of states in TLE and TLE-CI patients was associated with several brain networks (including the high-order default mode network (DMN), subcortical network (SCN), and cerebellum network (CN). Furthermore, a total of 1580 genes were revealed to be significantly associated with dynamic brain states of TLE, mainly enriched in neuronal signaling and synaptic function. Conclusions: This study provides new insights into characterizing dynamic neural activity in TLE. The brain network dynamics defined by HMM analysis may deepen our understanding of the neurobiological underpinnings of TLE and TLE-CI, indicating a linkage between neural configuration and gene expression in TLE. [ABSTRACT FROM AUTHOR]

Numerous single‐cell transcriptomic datasets from identical tissues or cell lines are generated from different laboratories or single‐cell RNA sequencing (scRNA‐seq) protocols. The denoising of these datasets to eliminate batch effects is crucial for data integration, ensuring accurate interpretation and comprehensive analysis of biological questions. Although many scRNA‐seq data integration methods exist, most are inefficient and/or not conducive to downstream analysis. Here, DeepBID, a novel deep learning‐based method for batch effect correction, non‐linear dimensionality reduction, embedding, and cell clustering concurrently, is introduced. DeepBID utilizes a negative binomial‐based autoencoder with dual Kullback–Leibler divergence loss functions, aligning cell points from different batches within a consistent low‐dimensional latent space and progressively mitigating batch effects through iterative clustering. Extensive validation on multiple‐batch scRNA‐seq datasets demonstrates that DeepBID surpasses existing tools in removing batch effects and achieving superior clustering accuracy. When integrating multiple scRNA‐seq datasets from patients with Alzheimer's disease, DeepBID significantly improves cell clustering, effectively annotating unidentified cells, and detecting cell‐specific differentially expressed genes. [ABSTRACT FROM AUTHOR]

Avian leukosis (AL), caused by avian leukosis virus (ALV), is a contagious tumor disease that results in significant economic losses for the poultry industry. Currently, ALV-A, B, J, and K subgroups are the most common in commercial poultry and cause possible coinfections. Therefore, close monitoring is necessary to avoid greater economic losses. In this study, a novel multiplex quantitative polymerase chain reaction (qPCR) assay was developed to detect ALV-A, ALV-B, ALV-J, and ALV-K with limits of detection of 40, 11, 13.7, and 96 copies/µL, respectively, and no cross-reactivity with other ALV subtypes and avian pathogens. We detected 852 cell cultures inoculated with clinical samples using this method, showing good consistency with conventional PCR and ELISA. The most prevalent ALV strain in Hubei Province, China, was still ALV-J (11.74%). Although single infections with ALV-A, ALV-B, and ALV-K were not found, coinfections with different subgroup strains were identified: 0.7% for ALV-A/J, 0.35% for ALV-B/J, 0.25% for ALV-J/K, and 0.12% for ALV-A/B/K and ALV-A/B/J. Therefore, our novel multiplex qPCR may be a useful tool for molecular epidemiology, clinical detection of ALV, and ALV eradication programs.

Aflatoxin B1(AFB1) is the main secondary metabolite produced by Aspergillus flavus, which is highly toxic, carcinogenic, mutagenic and teratogenic. It can induce immune imbalance in animals or humans. Penthorum chinense Pursh (PCP) is a traditional herbal plant that has been used as a hepatoprotective drug with a long history in China. Based on the theory of traditional Chinese Medicine, we prepared Penthorum chinense Pursh Compound (PCPC) by combining four herbal medicines: 5 g Penthorum chinense Pursh, 5 g Radix bupleuri, 1 g Artemisia capillaris Thunb and 1 g Radix glycyrrhizae. The role of the Penthorum chinense Pursh Compound (PCPC) in preventing AFB1-induced immune imbalance in broiler chickens was studied. A total of 180 broiler chickens were equally distributed in six groups: controls, AFB1, YCHD and high-, medium- and low-dose PCPC treatment groups. After 28 days, broilers were anesthetized, and serum spleen and thymus samples were collected for analysis. Results show that AFB1 significantly increased and decreased the relative organ weight of the spleen and thymus, respectively. Pathological section of hematoxylin/eosin (H&E) stained spleen sections showed that AFB1 resulted in splenic tissue damage. Both the serum levels of Immunoglobulin A (IgA) and Immunoglobulin G (IgG) were suppressed in the AFB1 group. IL-6 was elevated in the AFB1 group. The balance between pro-inflammatory cytokines (IFN-γ and IL-2) and anti-inflammatory cytokine (IL-4) was disturbed by AFB1. The apoptosis-related protein and JAK/STAT pathway-related gene expression indicated that AFB1-induced apoptosis via JAK/STAT pathway. PCPC has proven its immunoprotective effects by preventing AFB1-induced immune imbalance. PCPC can be applied as a novel immune-modulating medicine in broiler chickens. It can be applied as a novel immune modulator in veterinary clinical practice.

Abstract Primary lung cancer is one of the most common malignant tumors in China. Approximately 60% of lung cancer patients have distant metastasis at the initial diagnosis, so it is necessary to find new tumor markers for early diagnosis and individualized treatment. Tumor markers contribute to the early diagnosis of lung cancer and play important roles in early detection and treatment, as well as in precision medicine, efficacy monitoring, and prognosis prediction. The pathological diagnosis of lung cancer in small biopsy specimens determines whether there are tumor cells in the biopsy and tumor type. Because biopsy is traumatic and the compliance of patients with multiple biopsies is poor, liquid biopsy has become a hot research direction. Liquid biopsies are advantageous because they are nontraumatic, easy to obtain, reflect the overall state of the tumor, and allow for real-time monitoring. At present, liquid biopsies mainly include circulating tumor cells, circulating tumor DNA, exosomes, microRNA, circulating RNA, tumor platelets, and tumor endothelial cells. This review introduces the research progress and clinical application prospect of liquid biopsy technology for lung cancer.

Abstract Background Harnessing the immune system to fight cancer has led to prominent clinical successes. Strategies to stimulate innate immune effectors are attracting considerable interest in cancer therapy. Here, through conjugating multivalent Fc fragments onto the surface of mesoporous silica nanoparticles (MSN), we developed a nanoparticle-based innate immune system activator (NISA) for breast cancer immunotherapy. Methods NISA was prepared through conjugating mouse IgG3 Fc to MSN surface. Then, long-chain PEG5000, which was used to shield Fc to confer nanoparticle colloidal stability, was linked to the MSN surface via matrix metalloprotease-2 (MMP-2)-cleavable peptide (GPLGIAGQC). The activation of multiple components of innate immune system, including complement and the innate cells (macrophages and dendritic cells) and the associated anticancer effect were investigated. Results Fc fragments of NISA can be exposed through hydrolysis of long-chain PEG5000 by highly expressed MMP-2 in tumor microenvironment. Then, effective stimulation and activation of multiple components of innate immune system, including complement, macrophages, and dendritic cells were obtained, leading to efficient antitumor effect in 4T1 breast cancer cells and orthotopic breast tumor model in mice. Conclusions The antitumor potency conferred by NISA highlights the significance of stimulating multiple innate immune elements in cancer immunotherapy. Graphical Abstract

Galls are products of the hyperplasia of host plant structures induced by gall-inducing organisms and have been considered as an extended phenotype of the inducers. There is little evidence regarding the effect of host plants on gall morphology. We hypothesised that the morphology and developmental pattern of galls are different because of the different location of their stimulation, even though two kinds of inducers are close relatives. We observed that horned galls and their leaflets of their host plant, Rhus chinensis required a longer rapid growth stage than fusiform galls and Rhus potaninii leaflets. The distribution of trichomes showed positional dependence. Molecular analysis showed that in the fusiform gall, the target genes that regulate the plastochron of leaflets and serration development were hardly expressed, and CUP-SHAPED COTYLEDON-2 may be a key gene that regulates the formation of the horns. In summary, horned and fusiform galls showed a developmental pattern similar to those of their host plant leaflets. We suggest that the inducing site is important in the morphology and development of galls.

Paeoniflorin has been traditionally used to treat pain and immunologic derangement in China. However, its detailed mechanism remains to be illuminated. We investigated the mechanism by which paeoniflorin alleviates the inflammatory response in a mouse model of irritable bowel syndrome with predominant diarrhea (IBS-D). C57BL/6 wild type (WT) and miR-29a knockout (KO) mice were randomly divided into control, model, rifaximin, and paeoniflorin groups (n = 7). IBS-D model was induced by single intracolonic instillation of 0.1 mL trinitro-benzene-sulfonic acid (TNBS, 50 mg/mL) combined with restraint stress for seven consecutive days. The treatment groups received rifaximin (100 mg/kg) and paeoniflorin (50 mg/kg) via intragastric administration for seven days, respectively. The results showed that the fecal water content, fecal pellet output, visceral sensitivity, and histopathological score after paeoniflorin treatment were lower than those of the model group in both WT and miR-29a KO mice (P < 0.05). In both lineage mice, damage was observed in the colon tissues of model group, while paeoniflorin treatment partially ameliorated the tissue damage. Serum levels of DAO, DLA, IL-1β, IL-18, TNF-α, and MPO were decreased after paeoniflorin treatment (P < 0.05), with miR-29a KO mice in a lower level compared with that of WT mice. RT-PCR showed that the relative expression of miR-29a, NF-κB (p65), NLRP3, ASC, caspase-1, IL-1β, and TNF-α was downregulated while NKRF was upregulated after paeoniflorin treatment (P < 0.05). Immunohistochemistry showed that intestinal epithelial protein levels of NLRP3, ASC, and caspase-1 decreased while those of Claudin-1 and ZO-1 increased in the paeoniflorin treatment group (P < 0.05). In general, compared with WT mice, NLRP3 inflammasome pathway targets was in much lower expression level than miR-29a KO mice. In conclusion, paeoniflorin could inhibit abnormal activation of the NLRP3 inflammasome pathway by inhibiting miR-29a in IBS-D, thereby relieving the inflammatory response of the intestinal mucosa and reconstructing the intestinal epithelial barrier.

BackgroundPancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, and current therapies have limited efficacy on PDAC. The DEAH-box helicase 9 (DHX9) is widely reported to influence cell biological behavior via regulating DNA replication, genomic stability, transcription, translation, and microRNA biogenesis. However, the prognostic role of DHX9 in PDAC remains unclear. Thus, the objective of this study is to investigate the prognostic value of DHX9 expression in PDAC patients.MethodsTumor specimens from PDAC patients with surgical resection were obtained, and DHX9 was stained and analyzed in this study. Univariate and multivariate Cox regression analyses were utilized to identify independent risk factors of overall survival (OS) and recurrence-free survival (RFS). The prognostic nomograms for predicting OS and RFS were established to obtain superior predictive power.ResultsAmong the enrolled 110 patients, 61 patients were identified as having high expression of DHX9. The correlation analysis revealed that higher DHX9 expression in PDAC was prone to have advanced N stage (p = 0.010) and TNM stage (p = 0.017). For survival, the median OS (21.0 vs. 42.0 months, p < 0.001) and RFS (12.0 vs. 24.0 months, p < 0.001) of patients in the high DHX9 group were significantly shorter than those in the low DHX9 group. Within the univariate and multivariate analyses, American Joint Committee on Cancer (AJCC) N stage (p = 0.036) and DHX9 expression (p = 0.041) were confirmed as independent prognostic factors of OS, while nerve invasion (p = 0.031) and DHX9 expression (p = 0.005) were independent prognostic factors of RFS. Finally, the novel prognostic nomograms for OS and RFS were established and showed superior predictive accuracy.ConclusionThis study identified the independent prognostic value of DHX9 for RFS and OS in resected PDAC patients, and higher DHX9 expression was prone to have an earlier recurrence and shorter OS. Therefore, DHX9 may be a promising and valuable biomarker and a potential target for treating PDAC. More accurate and promising predictive models would be achieved when DHX9 is incorporated into nomograms.

Molecular peptides play an extensive range of functions in the human body. However, no previous study has performed placental peptidome profiling. In the present study, 3,941 peptides from human placental tissues were identified using peptidomics. Compared to healthy pregnant women, there were 87 and 129 differentially expressed peptides (DEPs) in the mild and severe preeclampsia groups, respectively. In the mild PE group, 55 and 34 DEPs had high and low expressions, respectively. In comparison, in the severe PE group, 82 and 47 DEPs had high and low expressions, respectively. Functional analysis of the precursor proteins of DEPs by gene ontology suggested that they are primarily involved in focal adhesion, extracellular matrix-receptor interaction, tight junction, and extracellular matrix. Network analysis using ingenuity pathway analysis software showed that the precursor proteins of DEPs were primarily related to the transforming growth factor-β (TGF-β)/Smad signaling pathway. Further molecular docking experiments showed that the AASAKKKNKKGKTISL peptide (placenta-derived peptide, PDP) derived from the precursor protein IF4B could bind to TGF-β1. Therefore, our preliminary results suggest that the actions of PDP may be mediated through the TGF-β1/Smad signaling pathway. Our results demonstrate that the placental bioactive peptides may regulate the placental function during PE progression.

Abstract Background Destruction of blood–brain barrier (BBB) ​​is one of the main mechanisms of secondary brain injury following intracerebral hemorrhage (ICH). Frizzled-7 is a key protein expressed on the surface of endothelial cells that controls vascular permeability through the Wnt-canonical pathway involving WNT1-inducible signaling pathway protein 1 (WISPI). This study aimed to investigate the role of Frizzled-7 signaling in BBB preservation after ICH in mice. Methods Adult CD1 mice were subjected to sham surgery or collagenase-induced ICH. Frizzled-7 activation or knockdown was performed by administration of Clustered Regularly Interspaced Palindromic Repeats (CRISPR) by intracerebroventricular injection at 48 h before ICH induction. WISP1 activation or WISP1 knockdown was performed to evaluate the underlying signaling pathway. Post-ICH assessments included neurobehavior, brain edema, BBB permeability, hemoglobin level, western blot and immunofluorescence. Results The brain expressions of Frizzled-7 and WISP1 significantly increased post-ICH. Frizzled-7 was expressed in endothelial cells, astrocytes, and neurons after ICH. Activation of Frizzled-7 significantly improved neurological function, reduced brain water content and attenuated BBB permeability to large molecular weight substances after ICH. Whereas, knockdown of Frizzled-7 worsened neurological function and brain edema after ICH. Activation of Frizzled-7 significantly increased the expressions of Dvl, β-Catenin, WISP1, VE-Cadherin, Claudin-5, ZO-1 and reduced the expression of phospho-β-Catenin. WISP1 knockdown abolished the effects of Frizzled-7 activation on the expressions of VE-Cadherin, Claudin-5 and ZO-1 at 24 h after ICH. Conclusions Frizzled-7 activation potentially attenuated BBB permeability and improved neurological deficits after ICH through Dvl​​/β-Catenin/WISP1 pathway. Frizzled-7 may be a potential target for the development of ICH therapeutic drugs.

Voice information processing technology is developing rapidly under the impetus of deep learning.The combination of speech synthesis and voice conversion technology can achieve real-time high-fidelity voice output of designated objects and content,and has broad application prospects in man-machine interaction,pan-entertainment and other fields.This paper aims to provide an overview of speech synthesis and voice conversion technology based on deep learning.First,this paper briefly reviews the development of speech synthesis and voice conversion technology.Next,it enumerates the common public datasets in these fields so that it is convenient for researchers to carry out related explorations.Then,it discusses the TTS models,including the classic and cutting-edge models and algorithms in terms of style,rhythm,speed,and compares their effects and development potentials respectively.Then,it reviews voice conversion by summarizing the voice conversion methods and optimization methods.Finally,it summarizes the applications and challenges of speech synthesis and voice conversion,and looks forward to their future development direction in model compression,few-shot learning and forgery detection,based on the problems faced by them in terms of model,application and regulation.