Search

Background: Emerging evidence suggests that minimal acute kidney injury (stage 1 AKI) is associated with increased hospital mortality rates. However, for those who do not meet the AKI diagnostic criteria, whether a small increase in serum creatinine (SCr) levels is associated with an increased mortality rate in elderly patients is not known. Therefore, we aimed to investigate small elevations in SCr of

Background: Premature ovarian insufficiency (POI), a modifiable cause of infertility with substantial implications for women's well-being, prompts the exploration of efficacious adjunctive treatments. Acupuncture emerges as a promising therapeutic avenue; however, the nuanced effects of acupuncture in POI warrant more comprehensive investigation. The intricate mechanisms dictating individualized responses remain elusive. This trial seeks to assess the effectiveness of acupuncture as an adjunctive treatment for POI, concurrently delving into the impact of transcriptome analysis on peripheral blood to unravel the underpinnings of these individual variations. The overarching objective is to enrich our comprehension of acupuncture's therapeutic potential in the context of POI, with a view to advancing holistic patient care. Methods/design: Constituting an open-label, nested case-control study, this research endeavors to enroll 108 women diagnosed with POI. Participants will be randomly assigned in a 1:1 ratio to either the study group or the control group, each comprising 54 subjects. Ten patients from each group meeting specific criteria will partake in transcriptome analysis. An additional 10 subjects meeting the study criteria will form a healthy control group. The study group will exclusively undergo acupuncture treatment, while the control group will solely receive Fenmutong. Acupuncture sessions, administered thrice weekly across three menstrual cycles from the fifth day of menstruation, constitute the intervention. Primary outcome measurement rests on Follicle-Stimulating Hormone (FSH) levels, supplemented by secondary assessments encompassing biometric features, hormone biomarkers, anxiety and depression scores, and transcriptome analysis. Baseline measurements precede intervention, with post-intervention evaluations following. The study endeavors to discern specific genes linked to individualized responses to acupuncture. Data analysis, employing SPSS 25.0 software, incorporates a meticulous examination of peripheral blood samples for transcriptome analysis. The investigation aspires to shed light on genetic determinants influencing the effects of acupuncture on women with POI, thereby fostering elevated standards in patient care and management. Discussion: This study pivots on the principal objective of scrutinizing the efficacy of acupuncture as an adjunctive treatment for POI. Beyond effectiveness, it undertakes an exploration of the intricate mechanisms underlying the diverse responses exhibited by individuals in the context of acupuncture, augmenting the depth of understanding in this therapeutic domain.

Metagenomic shotgun sequencing data can identify microbes and their proportions. But metagenomic shotgun data profiling results obtained from multiple projects using different reference databases are difficult to compare and apply meta-analysis. Our work aims to create a novel collection of human gut prokaryotic genomes, named Microbiome Collection Navigator (MBCN). 2379 human gut metagenomic samples are screened, and 16,785 metagenome-assembled genomes (MAGs) are assembled using a standardized pipeline. In addition, MAGs are combined with the representative genomes from public prokaryotic genomes collections to cluster, and pan-genomes for each cluster's genomes are constructed to build Kraken2 and Bracken databases. The databases built by MBCN are more comprehensive and accurate for profiling metagenomic reads comparing with other collections on simulated reads and virtual bio-projects. We profile 1082 human gut metagenomic samples with MBCN database and organize profiles and metadata on the web program. Meanwhile, using MBCN as a reference database, we also develop a unified, standardized, and systematic metagenomic analysis pipeline and platform, named MicrobiotaCN (http://www.microbiota.cn) and common statistical and visualization tools for microbiome research are integrated into the web program. Taken together, MBCN and MicrobiotaCN can be a valuable resource and a powerful tool that allows researchers to perform metagenomic analysis by a unified pipeline efficiently.

Background: Acute myocardial infarction (AMI) is a leading cause of mortality worldwide, with reduced elastin/collagen ratios exacerbating cardiac dysfunction due to collagen-rich scar tissue replacing necrotic myocardial cells. This study aims to evaluate pirfenidone's therapeutic effect on early cardiac function post-AMI and elucidate its impact on the elastin/collagen ratio. Methods: Sprague-Dawley rats were divided into four groups: Sham, AMI, AMI treated with PBS (AMI-PBS), and AMI treated with pirfenidone (AMI-PFD) (n=12 each). AMI was induced via coronary artery ligation. The AMI-PFD and AMI-PBS groups received pirfenidone and PBS for 14 days, respectively. Cardiac function, fibrosis, serum cytokines, collagen and elastin content, and their ratios were assessed. Cardiac fibroblasts (CFs) from neonatal rats were categorized into control, hypoxia-induced (LO), LO+PBS, and LO+PFD groups. ELISA measured inflammatory factors, and RT-PCR analyzed collagen and elastin gene expression. Results: The AMI-PFD group showed improved cardiac function and reduced serum interleukin-1β (IL-1β), IL-6, and transforming growth factor-β (TGF-β). Type I and III collagen decreased by 22.6 % (P=0.0441) and 34.4 % (P=0.0427), respectively, while elastin content increased by 79.4 % (P=0.0126). E/COLI and E/COLIII ratios rose by 81.1 % (P=0.0026) and 88.1 % (P=0.0006). CFs in the LO+PFD group exhibited decreased IL-1β, IL-6, TGF-β, type I and III collagen, with increased elastin mRNA, enhancing the elastin/collagen ratio. Conclusion: Pirfenidone enhances cardiac function by augmenting the early elastin/collagen ratio post-AMI.

Significal challenges exist to bacterial infection wound healing. The bacterial infection and inflammation generated by oxidative stress inevitably hinder the process of wound healing. Ag6Cu2 nanoclusters in this study were successfully prepared and displayed excellent physiological stability. Noticeably, Ag6Cu2 nanoclusters exhibited efficient therapeutic potentials for accelerating the process of wound healing, which had good biosafety under the appropriate concentration. The treatment of Ag6Cu2 was able to suppress the bacterial proliferation by destructing the bacterial, resulting in the secondary release of bacterial contents and to exert anti-inflammatory properties via scavenging the overproduction of reactive oxygen species and upregulating the expression of Nrf2 as well as its downstream genes including HO-1 and NQO1. In-vivo studies further validated the efficient therapeutic effects of Ag6Cu2 nanoclusters by inhibiting the activation of the cascade of inflammatory factors and the proliferation of bacteria as a novel agent in a nano scale for accelerating the process of wound healing.

Neurodegenerative disorders are chronic conditions that progressively damage and destroy parts of the nervous system, and are currently considered permanent and incurable. Alternative strategies capable of effectively healing neuronal damage have been actively pursued. Here, we report the neuroprotective effects of baicalin (BA) combined with plasma-activated medium (PAM) against glutamate-induced excitotoxicity in SH-SY5Y cells. Through in vitro assays, the cell viability, inflammation, apoptosis, and oxidative stress were evaluated. The co-application of BA and PAM significantly enhanced cell viability, reduced pro-inflammatory markers (TNF-α and NF-κB), decreased apoptotic proteins (Bax and Caspase-3) and boosted antioxidative defenses (increased SOD activity and lowered ROS levels). This study confirms the potential of combining BA with PAM as an effective therapeutic strategy for mitigating the effects of excitotoxicity. PAM is a promising adjunct and potential drug delivery method in neuroprotective therapy, providing a new avenue for developing treatments for diseases characterized by neuronal damage.

For patients with disorders of consciousness (DoC), accurate assessment of residual consciousness levels and cognitive abilities is critical for developing appropriate rehabilitation interventions. In this study, we investigated the potential of electrooculography (EOG) in assessing language processing abilities and consciousness levels. Patients’ EOG data and related electrophysiological data were analysed before and after explicit language learning. The results showed distinct differences in vocabulary learning patterns among patients with varying levels of consciousness. While minimally conscious patients showed significant neural tracking of artificial words and notable learning effects similar to those observed in healthy controls, whereas patients with unresponsive wakefulness syndrome did not show such effects. Correlation analysis further indicated that EOG detected vocabulary learning effects with comparable validity to electroencephalography, reinforcing the credibility of EOG indicator as a diagnostic tool. Critically, EOG also revealed significant correlations between individual patients’ linguistic learning performance and their Oromotor/verbal function as assessed through behavioural scales. In conclusion, this study explored the differences in language processing abilities among patients with varying consciousness levels. By demonstrating the utility of EOG in evaluating consciousness and detecting vocabulary learning effects, as well as its potential to guide personalised rehabilitation, our findings indicate that EOG indicators show promise as a rapid, accurate and effective additional tool for diagnosing and managing patients with DoC.

Introduction: Esophageal cancer is increasingly recognized as a significant global malignancy. The main pathological subtype of this cancer is esophageal squamous cell carcinoma (ESCC), which displays a higher degree of malignancy and a poorer prognosis. Reactive oxygen species (ROS) play a critical role in modulating the immune response to tumors, and understanding the regulation of ROS in ESCC could lead to novel and improved therapeutic strategies for ESCC patients. Methods: A consensus matrix derived from genes involved in the ROS pathway revealed two subtypes of ROS. These subtypes were categorized as ROS-active or ROS-suppressive based on their level of ROS activity. The heterogeneity among the different ROS subtypes was then explored from various perspectives, including gene function, immune response, genomic stability, and immunotherapy. In order to assess the prognosis and the potential benefits of immunotherapy, a ROS activity score (RAS) was developed using the identified ROS subtypes. In vitro experiments were performed to confirm the impact of core RAS genes on the proliferative activity of esophageal cancer cell lines. Results: Two distinctive subtypes of ROS were identified. The first subtype, referred to as ROS-active, exhibited elevated ROS activity, enhanced involvement in cancer-associated immune pathways, and increased infiltration of effector immune cells. The second subtype, named ROS-suppressive, demonstrated weaker ROS activity but displayed more pronounced dysregulation in the cell cycle and a denser extracellular matrix, indicating malignant characteristics. Genomic stability, particularly in terms of copy number variation (CNV) events, differed between the two ROS subtypes. By developing a RAS model, reliable risk assessment for overall survival (OS) in patients with ESCC was achieved, and the model demonstrated strong predictive capabilities in real-world immunotherapy cohorts. Moreover, the core gene LDLRAD1 within the RAS model was found to enhance proliferative activity in esophageal cancer cell lines. Conclusion: Based on the ROS pathway, we successfully identified two distinct subtypes in ESCC: the ROS-active subtype and the ROS-suppressive subtype. These subtypes were utilized to evaluate prognosis and the sensitivity to immunotherapy.

Lung adenocarcinoma (LUAD) is the leading cause of cancer death worldwide, with high incidence and low survival rates. Nicotinic acetylcholine receptors play an important role in the progression of LUAD. In this study, a screening of 17 nicotinic acetylcholine receptor allosteric agents revealed that spinosad effectively suppressed the proliferation of LUAD cells. The experiments demonstrated that spinosad induced cell cycle arrest in the G1 phase and stimulated apoptosis, thereby impeding the growth of LUAD and enhancing the responsiveness to gefitinib in vitro and vivo. Mechanistic insights obtained through transcriptome sequencing, Co-IP, and protein immunoblots indicated that spinosad disrupted the interaction between CHRNA5 and EGFR, thereby inhibiting the formation of downstream complexes and activation of the EGFR signaling pathway. The supplementation of exogenous acetylcholine showed to mitigate the inhibition of LUAD cell proliferation induced by spinosad. This study elucidates the therapeutic effects and mechanisms of spinosad in LUAD, and offers a theoretical and experimental foundation for novel LUAD treatments.

Objective: Dendrobin A, a typical active ingredient of the traditional Chinese medicine Dendrobium nobile, has potential clinical application in cancer treatment; however, its effect and mechanism in anti-hepatocellular carcinoma (HCC) remain unsolved. Method: The effects of Dendrobin A on the viability, migration, invasion, cycle, apoptosis, and epithelial-mesenchymal transition of HepG2 and SK-HEP-1 cells were verified by in vitro experiments. mRNA sequencing was performed to screen the differentially expressed genes (DEGs) of HCC cells before and after Dendrobin A treatment, following GO enrichment and KEGG signaling pathway analyses. Mechanistically, molecular docking was used to evaluate the binding of Dendrobin A with proteins p65 and p50, before further verifying the activation of nuclear factor kappa-B (NF-κB) signaling. Finally, the antiproliferative effect of Dendrobin A on HCC cells was explored through animal experiments. Results: Dendrobin A arrested cell cycle, induced apoptosis, and inhibited proliferation, migration, invasion, and blocked epithelial-mesenchymal transition in HepG2 and SK-HEP-1 cells. mRNA sequencing identified 830 DEGs, involving various biological processes. KEGG analysis highlighted NF-κB signaling. Molecular docking revealed strong binding of Dendrobin A with p65 and p50 proteins, and western blotting confirmed reduced levels of p-p65 and p-p50 in HCC cells post Dendrobin A treatment. NF-κB agonist PMA reversed Dendrobin A-inhibited cell proliferation migration and invasion. In vivo experiments showed that Dendrobin A inhibited HCC cell growth. Conclusion: Our findings suggest that Dendrobin A exhibits anti-HCC properties by inhibiting the activation of the NF-κB pathway. These results provide a scientific basis for utilizing Dendrobium nobile in anti-HCC therapies.

Electric vehicle (EV) charging station (CS) congestion is highly dependent on the EV owner’s behavior and their selected CS as charging choice. A fixed pricing strategy causes some CSs to be congested with EVs waiting in line to charge, while there are some other CSs with available electric plugs, which adversely affects both charging station operator (CSO) revenue and EV users’ welfare. To solve this problem, this paper presents a dynamic pricing strategy aimed at conducting EVs from congested CSs to the uncongested ones through controlling the charging prices of CSs at different times. The problem is formulated as a scenario-based stochastic optimization with the objective of maximizing overall revenue of the CSO. Moreover, an attraction function model is developed to quantify the charging choice of the EV owners by considering the effective parameters of CSs in EV charging choice decisions. QGIS software is used in this work to formulate a realistic modeling for CS locations and EV routes to calculate the distances from EVs to CSs. Three scenarios are designed to evaluate the performance of the proposed framework and to compare the results with the fixed pricing approach. The results indicate that the proposed dynamic pricing strategy mitigates the congestion of CSs while facilitating an increased number of charged EVs up to 48% as well as increasing the overall revenue of the CSO.

Constipation symptoms of Parkinson's disease (PD) seriously reduce the quality of life of patients and aggravate the development of the disease, but current treatment options still cannot alleviate the progress of constipation. Electroacupuncture (EA) is a new method for the treatment of constipation, which can effectively treat the symptoms of constipation in PD patients. However, the specific regulatory mechanisms of EA in the treatment of constipation symptoms in PD remain unclear. The aim of this study is to investigate the therapeutic effect of EA on PD constipation rats and its regulatory mechanism. A rotenone (ROT)-induced gastrointestinal motility disorder model was used to simulate the pathological process of constipation in PD. The results showed that EA could effectively promote gastrointestinal peristalsis, reduce α-synuclein accumulation in substantia nigra and colon and colonic injury in rats after ROT administration. Mechanistically, EA activation of the central-cholinergic pathway increases acetylcholine release in the colon. At the same time, EA up-regulated the co-expression of enteric glial cells (EGCs) and α7 nicotinic acetylcholine receptor (α7nAChR). EA increased the expression of choline acetyltransferase (ChAT), neuronal nitric oxide synthase (nNOS), and tyrosine hydroxylase (TH) in the colon of PD rats. Further mechanistic studies showed that EA increased the expression of glial cell-derived neurotrophic factor (GDNF), GFRa1 and p-AKT in colon tissues. The present study confirmed that EA upregulates α7nAChR through a central-cholinergic mechanism to promote GDNF release from EGCs, thereby protecting intestinal neurons and thereby improving gastrointestinal motility.

Background: Patient-ventilator asynchrony (PVA) frequently occurs in mechanically ventilated patients within the ICU and has the potential for harm. Depending solely on the health care team cannot accurately and promptly identify PVA. To address this issue, our team has developed a cloud-based platform for monitoring mechanical ventilation (MV), comprising the PVA-RemoteMonitor system and the 24-h MV analysis report. We conducted a survey to evaluate physicians' satisfaction and acceptance of the platform in 14 ICUs. Methods: Data from medical records, clinical information systems, and ventilators were uploaded to the cloud platform and underwent data processing. The data were analyzed to monitor PVA and displayed in the front-end. The 24-h analysis report for MV was generated for clinical reference. Critical care physicians in 14 hospitals' ICUs that involved in the platform participated in a questionnaire survey, among whom 10 physicians were interviewed to investigate physicians’ acceptance and opinions of this system. Results: The PVA-RemoteMonitor system exhibited a high level of specificity in detecting flow insufficiency, premature cycle, delayed cycle, reverse trigger, auto trigger, and overshoot, with sensitivities of 90.31 %, 98.76 %, 99.75 %, 99.97 %, 100 %, and 99.69 %, respectively. The 24-h analysis report supplied essential data about PVA and respiratory mechanics. 86.2 % (75/87) of physicians supported the application of this platform. Conclusions: The PVA-RemoteMonitor system accurately identified PVA, and the MV analysis report provided guidance in controlling PVA. Our platform can effectively assist ICU physicians in the management of ventilated patients.

Decabromodiphenyl ether (BDE-209) is an organic compound that is widely used in rubber, textile, electronics, plastics and other industries. It has been found that BDE-209 has a destructive effect on the reproductive system of mammals. However, the effect of BDE-209 exposure on oocyte quality and whether there is a viable salvage strategy have not been reported. Here, we report that murine oocytes exposed to BDE-209 produce a series of meiostic defects, including increased fragmentation rates and decreased PBE. Furthermore, exposure of oocytes to BDE-209 hinders mitochondrial function and disrupts mitochondrial integrity. Our observations show that supplementation with NMN successfully alleviated the meiosis impairment caused by BDE-209 and averted oocyte apoptosis by suppressing ROS generation. In conclusion, our findings suggest that NMN supplementation may be able to alleviate the oocyte quality impairment induced by BDE-209 exposure, providing a potential strategy for protecting oocytes from environmental pollutant exposure.

In order to investigate the shear behavior of coral aggregate reinforced concrete beam (CARCB), the different concrete strength, steel types affect the shear behavior of CARCB was studied, the calculation formula of shear capacity (Vcs) and numerical analysis model of CARCB was proposed. The results show that: All kinds of CARCB have inclined section suitable reinforcement failure, the failure law of CARCB and ordinary aggregate reinforced concrete beam (OARCB) was basically the same. Considering stirrups corrosion and nonlinear mechanical properties characteristic of coral aggregate concrete (CAC), the Vcs calculation formula of CARCB was proposed, and its applicability in C25 ∼ C60 CARCB was verified, its accuracy was 26% and 34% higher than GB50010–2020 and JGJ/T 12–2019, respectively. A numerical analysis model suitable for describing the shear behavior of CARCB was proposed based on K&C (Karagozian & Case) theory, and its applicability in C25 ∼ C60 CARCB was verified, it was found that this model can well describe the whole process of CARCB inclined section failure, and the errors between simulated and measured values of Vcr, Vcs and midspan deflection are 0∼18%. In addition, the Vcs obtained by the numerical model is 3% more accurate than the calculation formula, indicating that the numerical model can effectively distinguish the variation law of shear behavior of CARCB.

Background: This study aimed to explore the longitudinal associations of rumination with suicidal ideation and suicide attempts in individuals with major depressive disorder (MDD). Methods: Participants were derived from the Depression Cohort in China study (DCC). Those who completed at least one follow-up visit during the 12 months were included in the analysis. Dimensions of rumination including brooding and reflection were each measured using five items of the Ruminative Responses Scale. Suicidal ideation was assessed using the Beck Scale for Suicide Ideation. Suicide attempts were also assessed and all were analyzed with generalized estimating equations. Results: Our final sample included 532 participants aged 18 to 59 years (mean [SD], 26.91 [6.94] years) consisting of 148 (27.8%) males and 384 (72.2%) females. After adjusting for temporal trend and potential confounders, individuals with higher levels of reflection were more likely to report suicidal ideation (AOR =1.11, 95% CI:1.01–1.22). However, no statistically significant association was found between brooding and suicidal ideation (AOR =1.06, 95% CI:0.96–1.17). Conversely, individuals with higher levels of brooding were more likely to report suicide attempts (AOR =1.13, 95% CI:1.02–1.24), while no statistically significant association was observed between reflection and suicide attempts (AOR =0.91, 95% CI:0.82–1.01). Conclusion: Rumination reflects a disturbance in cognitive emotional processing and manifests in different dimensions. Our findings suggest that high levels of reflection and brooding may be associated with a higher likelihood of having suicidal ideation and suicide attempts, respectively. However, it should be interpreted with caution, given that effect sizes are small.

In this work, a multiphase reinforced non-equiatomic Al0.5CrFeNi2.5Si0.25 high-entropy alloy (HEA) was prepared by vacuum induction melting. The effect of heat-treatment temperature (1023, 1123, 1323, and 1473 K) on the microstructure, mechanical properties, and wear behavior are systematically investigated. The results indicate that the as-cast and annealed alloys are composed of face-centered cubic (FCC) and body-centered cubic (BCC) structures accompanied by microscale and nanoscale precipitated phases. To be specific, the FCC matrix is enriched in the L12 phase, and BCC particles and σ phases are observed in the B2 matrix. The microstructure of Al0.5CrFeNi2.5Si0.25 HEAs consists of dendritic region (DR) and inter-dendritic (ID) region before and after annealing. The phases and microstructure did not change. After annealing, the size of the Cr-rich BCC particles is reduced. The L12 phase has a density per unit area that first increases and then decreases, reaching its highest density at 1123 K. With the annealing temperature rising, the nanohardness increases slightly and then decreases, reaching a peak value of about 6.29 GPa at 1123 K. The Al0.5CrFeNi2.5Si0.25 HEA annealed at 1123 K also exhibits the lowest specific wear rate of 2.43 × 10−4 mm3/Nm, which is decreased by 23.5% compared to the as-cast one.

Researchers have been challenged to improve the protective performance of composite armor materials. Herein, pure Al and Cu foils were used as raw materials and composited concurrently using ultrasonic additive manufacturing technology to study their microstructure and properties. A scanning electron microscope and universal testing machine were used to systematically study the microstructure and tensile properties of the material. Furthermore, the dynamic mechanical properties were investigated using Hopkinson rods, and the propagation law of shock waves in laminated composites was explored based on the theory of propagation of one-dimensional elastic waves in cyclic layered media. The results showed that ultrasonic solidification of the Al/Cu stacked composite interface between the generation revealed no new phases, and the mechanical bonding in the tensile experiment exhibited a maximum tensile strength of 167 MPa for the Al/Cu stacked composites. In the dynamic impact experiment, with the increase of air pressure, the strength of the material also increases, and its compressive strength can reach up to 813 MPa, while the energy absorption efficiency decreases, and the energy absorption efficiency can reach up to 80%. Analysis of the attenuation process of the shock wave in the laminated composites revealed that reaching five cyclic layers of the Al/Cu laminated composites reduced the intensity attenuation ratio can reach 63% of the total number of circulating layers, and the energy attenuation ratio can reach 77% of the total number of circulating layers, thus reaching an overall optimum material performance.

Er/Zr and Sc/Zr were added into 5xxx series alloy to prepare welding wires, and the welding wires with the different compositions were used to weld 6xxx extruded alloy. The effects of different alloying additions on the microstructure and properties of welded joints were investigated. The results show that Al3(Sc1-x, Zrx) particles in the Al–Mg-Sc-Zr alloy welding wire can be used as heterogeneous nucleation site, which can effectively refine the grain structure and reduce the flow of low melting point elements to the PMZ of the joint. Compared with Al–Mg and Al–Mg–Er–Zr welding wire, the grain refinement in WZ is improved by 20.5 % and 13.8 %, and that in FZ is improved by 35.0 % and 8.1 %. At the same time, the refined grain structure can effectively eliminate the stress concentration of the joint and reduce the probability of liquation cracks. The joint welded by Al–Mg-Sc-Zr wire possesses the highest ultimate tensile strength of 249 MPa, while the joints welded by Al–Mg-Sc-Zr wire and Al–Mg wire possess ultimate tensile strength of 159 MPa and 128 MPa, respectively.

The effects of selective laser melting (SLM) parameters on the formability, microstructure, and mechanical properties of Zr-containing Al–1Cu–1Mg–3Mn alloys were investigated. It was observed that, under different energy density, the type, shape, volume, and number of defects were different. At a lower energy density, cracks and irregular holes occurred, and with an increase in the energy density, the holes gradually became spherical. The mechanism diagram for the hole formation was drawn, and the reason for crack formation was described. The microstructure of the specimen was made of equiaxed and columnar grains, and Al2Cu and Al6Mn precipitates were found both at the grain boundaries and inside the grains. The electron backscattered diffraction (EBSD) indicated that the large columnar grains in the centre primarily exhibited the {001} and {101} orientations. In the equiaxed grain region, the grain orientation along {111} was enhanced. A hardness test revealed that the hardness of cross section and longitudinal section of the alloy was basically the same. When the energy density was 3.06 J/mm2, the tensile and yield strength of the alloy were 434 MPa and 336 MPa, respectively, and the elongation was 4.8 %.

Extraction of color and texture features of buildings from high-resolution remote sensing images often encounters the problems of interference of background information and varying target scales. In addition, most of the current attention mechanisms focus on building key feature selection for building extraction optimization, but ignore the influence of the complex background. Hence, we propose incorporating a novel reverse attention module into the network. The innovative module enables the model to selectively extract crucial building features while suppressing the impact of intricate background noise. It mitigates the influence of uniform spectral and structurally similar heterogeneous background targets on building segmentation and extraction. As a result, the overall generalizability of the model is improved. The reverse attention can also emphasize and amplify the specific details pertaining to the boundaries of the target. Furthermore, we couple a new multi-branch convolution block into the encoder, integrating dilated convolutions with multiple dilation rates. Compared to other methods that use only one multi-scale module to extract multi-scale information from high-level features, we use different receptive field convolutions to simultaneously capture multi-scale targets from multi-level features, effectively improving the ability of the model to extract multi-scale building features. The experimental findings demonstrate that our proposed multi-branch reverse attention semantic segmentation network achieves IoU of 90.59% and 81.79% on the well-known WHU building and Inria aerial image datasets, respectively.

CO2 is one of the most important greenhouse gases (GHGs) in the earth’s atmosphere. Since the industrial era, anthropogenic activities have emitted excessive quantities of GHGs into the atmosphere, resulting in climate warming since the 1950s and leading to an increased frequency of extreme weather and climate events. In 2020, China committed to striving for carbon neutrality by 2060. This commitment and China’s consequent actions will result in significant changes in global and regional anthropogenic carbon emissions and therefore require timely, comprehensive, and objective monitoring and verification support (MVS) systems. The MVS approach relies on the top-down assimilation and inversion of atmospheric CO2 concentrations, as recommended by the Intergovernmental Panel on Climate Change (IPCC) Inventory Guidelines in 2019. However, the regional high-resolution assimilation and inversion method is still in its initial stage of development. Here, we have constructed an inverse system for carbon sources and sinks at the kilometer level by coupling proper orthogonal decomposition (POD) with four-dimensional variational (4DVar) data assimilation based on the weather research and forecasting–greenhouse gas (WRF-GHG) model. Our China Carbon Monitoring and Verification Support at the Regional level (CCMVS-R) system can continuously assimilate information on atmospheric CO2 and other related information and realize the inversion of regional and local anthropogenic carbon emissions and natural terrestrial ecosystem carbon exchange. Atmospheric CO2 data were collected from six ground-based monitoring sites in Shanxi Province, China to verify the inversion effect of regional anthropogenic carbon emissions by setting ideal and real experiments using a two-layer nesting method (at 27 and 9 km). The uncertainty of the simulated atmospheric CO2 decreased significantly, with a root-mean-square error of CO2 concentration values between the ideal value and the simulated after assimilation was close to 0. The total anthropogenic carbon emissions in Shanxi Province in 2019 from the assimilated inversions were approximately 28.6% (17%–38%) higher than the mean of five emission inventories using the bottom-up method, showing that the top-down CCMVS-R system can obtain more comprehensive information on anthropogenic carbon emissions.

Polymorphic phase transition in metallic materials under high pressure is a critical aspect of dynamic properties and has been attracting a great interest. Despite the extensive researches have been made on understanding of this phase transition in traditional single-principal element alloys, little is known about the phase transition in recently emergent multi-principal medium and high entropy alloys, especially compressed under high strain rates. In this work, based on molecular dynamic simulations, three impact loading strategies with distinct loading paths, such as single-shock, double-shock and ramp-wave loading are carried out on the single crystalline CoCrNi medium-entropy alloy (MEA) to investigate the phase transition under high strain-rate compression. Careful characterizations show that the phase transition of CoCrNi MEA is loading-path dependent, as evidenced by the significant differences in macroscopic pressure evolution and microscopic structural phase transition among the samples under various thermodynamic paths. An intriguing pressure “overshoot” is found and demonstrated as the characteristic of the critical structural phase transition from face-centered cubic (FCC) structure to hexagonal-close-packed (HCP) structure mediated by body-centered cubic (BCC) like clusters. We show that such loading-path dependence is attributed to the strain rate and temperature rise in the loading process, which control the evolution of microstructure and deformation field. The inherent correlation between the atomistic process of phase transition and loading strategies results in polymorphic phase transition under high strain rates. These findings shed new light on the nature of impact phase transition of multi-principal alloys.

ABSTRACT: Environmental pollution poses a significant challenge to the poultry industry, leading to substantial losses and adverse effects on the health, production, and performance of avian species. In recent years, there has been growing interest in exploring natural compounds with potential protective effects against cadmium (Cd)-induced toxicity. Luteolin (LUT), a flavonoid found in various plants, has been studied for its antioxidant, anti-inflammatory, and cytoprotective properties. In this study, Su green shell grass chickens were divided into 4 groups: control, LUT (150 mg LUT), Cd (100 mg CdCl2), and Cd + LUT (100 mg CdCl2 + 150 mg LUT) groups for 1 month, respectively. The present study revealed that LUT maintained the morphology and functional activity of the liver and intestine. LUT alleviated Cd-induced impairment in the liver and intestinal biochemical indicators, suppressed Cd-induced liver fibrosis, mitigated liver and intestinal tissue damage. Additionally, LUT reduced oxidative stress and regulated the Cd-induced impairment in trace elements of the liver and intestine. Furthermore, LUT reduced Cd-induced liver inflammation, restored Cd-induced intestinal barrier function, and normalized Cd-induced serum proteins, including changes in the content of glutamyltranspeptidase. Moreover, LUT maintained Cd-induced disruption of gut microbiota and alleviated bacterial dysbiosis. Overall, these findings suggest that LUT holds promise as a potential therapeutic agent for mitigating the adverse effects of Cd-induced toxicity in poultry, by preserving liver and intestinal health, reducing oxidative stress, inflammation, and restoring gut microbiota balance.

ABSTRACT: A recently discovered environmental contaminant, microplastics (MP) are capable of amassing within the body and pose a grave threat to the health of both humans and animals. It is widely acknowledged that the combination of cadmium (Cd), a hazardous heavy metal, and microplastics produces synergistic deleterious effects. Nevertheless, the mechanism by which co-exposure to polyvinyl chloride microplastics (PVC-MP) and Cd damages the liver of avian females is unknown. Globally prevalent and the subject of extensive research in mammals, nonalcoholic fatty liver disease (NAFLD) is a chronic liver condition. However, the mechanisms underlying injury to the avian digestive system caused by NAFLD remain unknown. Two months of co-exposure to Cd and PVC-MPs, pure water, solitary Cd exposure, single microplastics exposure, and pure water were administered to female Muscovy ducks in this study. The objective of this research was to examine whether the co-exposure of duck liver to PVC-MPs and Cd-induced oxidative stress resulted in NAFLD and subsequent apoptosis of hepatic cells. The study's findings showed that hepatocyte shape and functional activity were negatively impacted by PVC-MP and Cd buildup in liver tissues. Reduced liver organ coefficients, increased alanine aminotransferase (ALT) content, and ultrastructural damage to hepatocyte nuclei and mitochondria are indicators of this. These results point to a possible impairment in liver function. phosphoenolpyruvate carboxykinase 1 (PCK1) deficiency activates the protein kinase B/phosphatidylinositol 3-kinase (PI3K/AKT) pathway in the livers of female reproductive ducks that have been damaged by oxidative stress. This stimulation induces lipid deposition, fibrosis, and glycogen accumulation, which ultimately results in hepatocyte apoptosis. In summary, our research provides evidence that PVC-MPs cause oxidative harm to the liver, which subsequently results in fibrosis of liver tissue, hepatic glucolipid metabolism, and ultimately apoptosis.

In recent years, immunotherapy has emerged as an effective approach for treating tumors, with programmed cell death ligand 1 (PD-L1)/programmed cell death protein-1 (PD-1) immune checkpoint blockade (ICB) being a promising strategy. However, suboptimal therapeutic efficacy limits its clinical benefit. Understanding the regulation mechanism of PD-L1 expression is crucial for improving anti-PD-L1/PD-1 therapy and developing more effective tumor immunotherapy. Previous studies have revealed that resistance to PD-L1/PD-1 blockade therapy arises from the upregulation of CD38 on tumor cells induced by ATRA and IFN-β, which mediates the inhibition of CD8+ T cell function through adenosine receptor signaling, thereby promoting immune evasion.Yet, the precise role of CD38 in regulating PD-L1 on malignant tumor cells and its impact on CD8+ T cells through PD-L1 remain unclear. Here, we demonstrate that CD38 is highly expressed in malignant tumors (lung cancer, nasopharyngeal carcinoma, cervical cancer) and upregulates PD-L1 protein expression, impairing CD8+ T cell function. Mechanistically, CD38 phosphorylates GSK3β via the adenosine-activated cAMP-PKA signaling pathway, leading to GSK3β inactivation and enhanced PD-L1 stability and expression, facilitating tumor immune escape. Furthermore, we identify PRMT5 as a novel CD38-interacting molecule that symmetrically dimethylates CD38 arginine position 58, augmenting PD-L1 stability and expression through the ADO-cAMP-GSK3β signaling axis. This inhibits CD8+ T cell-mediated tumor cell killing, enabling tumor cells to evade immune surveillance. Our findings suggest that targeting the CD38 R58 site offers a new avenue for enhancing anti-PD-L1/PD-1 therapy efficacy in tumor treatment.

Objective: This study aims to explore the application of radiographic imaging and image recognition algorithms, particularly AlexNet and ResNet, in classifying malignancies for spinal bone tumors. Methods: We selected a cohort of 580 patients diagnosed with primary spinal osseous tumors who underwent treatment at our hospital between January 2016 and December 2023, whereby 1532 images (679 images of benign tumors, 853 images of malignant tumors) were extracted from this imaging dataset. Training and validation follow a ratio of 2:1. All patients underwent X-ray examinations as part of their diagnostic workup. This study employed convolutional neural networks (CNNs) to categorize spinal bone tumor images according to their malignancy. AlexNet and ResNet models were employed for this classification task. These models were fine-tuned through training, which involved the utilization of a database of bone tumor images representing different categories. Results: Through rigorous experimentation, the performance of AlexNet and ResNet in classifying spinal bone tumor malignancy was extensively evaluated. The models were subjected to an extensive dataset of bone tumor images, and the following results were observed. AlexNet: This model exhibited commendable efficiency during training, with each epoch taking an average of 3 s. Its classification accuracy was found to be approximately 95.6 %. ResNet: The ResNet model showed remarkable accuracy in image classification. After an extended training period, it achieved a striking 96.2 % accuracy rate, signifying its proficiency in distinguishing the malignancy of spinal bone tumors. However, these results illustrate the clear advantage of AlexNet in terms of proficiency despite a lower classification accuracy. The robust performance of the ResNet model is auspicious when accuracy is more favored in the context of diagnosing spinal bone tumor malignancy, albeit at the cost of longer training times, with each epoch taking an average of 32 s. Conclusion: Integrating deep learning and CNN-based image recognition technology offers a promising solution for qualitatively classifying bone tumors. This research underscores the potential of these models in enhancing the diagnosis and treatment processes for patients, benefiting both patients and medical professionals alike. The study highlights the significance of selecting appropriate models, such as ResNet, to improve accuracy in image recognition tasks.

With the rapid development of power technology and the complexity of power system equipment, efficient and accurate assessment of the quality and condition of electric power equipment oil (EPEO) has become particularly critical. EPEO is an important factor to ensure the stable operation of power equipment, and its quality and state directly affect the safety and reliability of equipment. However, there are many challenges with traditional oil measuring techniques, which often rely on destructive testing, which not only increases maintenance costs, but can also cause damage to the equipment itself. In the face of these limitations, there is an urgent need to study new oil detection technologies and methods to meet the high standards of modern power systems for high efficiency, non-destructive and comprehensive analytical capabilities. In this paper, a new EPEO measuring technique based on multivariable impedance spectroscopy (MIS) is proposed. Through in-depth analysis of oil's impedance response characteristics under electric field excitation with different frequency., a new approach is provided for the comprehensive evaluation of oil's performance. MIS technology not only has the characteristics of non-destructive testing, ensuring the non-destructive measuring of EPEO, but also its rapid response and real-time analysis ability significantly improves the monitoring efficiency. Based on the proposed MIS detection method, a detection system and experimental prototype which can detect and evaluate the performance and quality of power oil more accurately are designed. Compared with the traditional measuring device, the measuring device utilized in this method can employ three variables. Specifically, it covers a frequency range for the detectable excitation signal spanning from 1 to 100 kHz, an amplitude range from 0.1 to 11.7 V, and a temperature range from −100 °C to 100 °C. The MIS detection method has the capability to identify a variety of parameters, including the dielectric constant, volume resistivity, and dielectric loss factor, among others. This method encompasses a broader spectrum of parameters compared to traditional detection methods, which typically focus on one or two detectable indicators. The correctness and feasibility of the proposed multivariable impedance spectrum detection technique are verified, which provides a new way for the comprehensive evaluation of oil's performance.

The study aims to provide an up-to-date review at the advancements of the investigations on the ethnopharmacology, phytochemistry, pharmacological effect and exploitation and utilizations of Zanthoxylum L. Besides, the possible tendency and perspective for future research of this plant are discussed, as well. This article uses “Zanthoxylum L.” “Zanthorylum bungeanum” as the keywords and collects relevant information on Zanthoxylum L. plants through electronic searches (Elsevier, PubMed, ACS, Web of Science, Science Direct, CNKI, Google Scholar), relevant books, and classic literature about Chinese herb. The plants of this genus are rich in volatile oils, alkaloids, amides, lignans, coumarins and organic acids, and has a wide range of pharmacological activities, including but not limited to anti-inflammatory, analgesic, anti-tumor, hypoglycemic, hypolipidemic, antioxidant and anti-infectious. This article reviewed both Chinese and international research progress on the active ingredients and pharmacological activities of Zanthoxylum L. as well as the applications of this genus in the fields of food, medicinal and daily chemicals, and clarified the material basis of its pharmacological activities. Based on traditional usage, phytochemicals, and pharmacological properties, of Zanthoxylum L. species, which indicate that they possess diverse bioactive metabolites with interesting bioactivities. Zanthoxylum L. is a potential medicinal and edible plant with diverse pharmacological effects. Due to its various advantages, it may have vast application potential in the food and medicinal industries and daily chemicals. Nonetheless, the currently available data has several gaps in understanding the herbal utilization of Zanthoxylum L. Thus, further research into their toxicity, mechanisms of actions of the isolated bioactive metabolites, as well as scientific connotations between the traditional medicinal uses and pharmacological properties is required to unravel their efficacy in therapeutic potential for safe clinical application.

The aim of this study was to explore the formation of volatile lipid oxidation products by the lipoxygenase (LOX)-hydroperoxide lyase (HPL)-mediated pathway in oat, barley and soy bean. LOX activity was found only in barley and soy bean samples, but the lipase and HPL activity was detected in all samples. HPL showed particularly high activity with 13-hydroperoxides, while the activity was quite low when using 9-hydroperoxides, especially in the oat and barley. The optimum pH for HPL in different samples was similar, i.e., pH 6–7. In this condition, the volatile compounds formed dramatically with aldehydes and furans as the dominant products. Furthermore, a remarkable enzymatic degradation of lipids occurred during the preparation of food models with highly refined rapeseed oil (RO) and rapeseed oil fatty acid (ROFA) emulsions, where the ROFAs were more prone to oxidation than RO. This study shows the significance of lipid-degrading enzymes in plant-food flavour formation.

In fisheries, hypoxia stress is one of the most common environmental stresses that often cause significant harm and losses to the aquaculture industry. The liver is the most important metabolic organ of the body, which is involved in energy metabolism, synthesizes various physiologically active substances, and is an important target organ for hypoxia in fish. This study investigated how acute hypoxia stress induces liver injury and mortality of Hexagrammos otakii. During the hypoxia treatment, reactive oxygen species (ROS), a metabolic intermediary made by the mitochondrial respiratory chain, are highly accumulated, the level of lipid peroxidation increased significantly in the liver tissue. The vacuolation of liver histiocyte is enhanced due to hypoxia. The downstream gene hypoxia-inducible factor (HIF)-1 can react to the elevated ROS in liver tissue. HIF-1α expression levels greatly increase when hypoxia is applied, which prompts the activation of the nlrp3/caspase-1/il-1β and caspase-3/gsdme pathway and encourages the inflammation and pyroptosis of the liver. After reoxygenation, nlrp3/caspase-1/il-1β pathway are reactivated and cause liver damage in H. otakii. In conclusion, it has been shown that hypoxia-stress modulates the expression of HIF-1 through an increase in ROS production, which then encourages the activation of the nlrp3/caspase-1/il-1β and caspase-3/gsdme pathway to cause liver injury. This research sheds fresh light on the mechanism of hypoxia-induced pyroptosis and demonstrates the usefulness of the ROS-HIF-1 signaling pathway as a possible therapeutic target to halt the progression of hypoxia-induced illnesses.

Water, energy, and food are essential for human survival, and the production and consumption of these three resources are closely related. In the backdrop of limited resources and constantly expanding demand, the collaborative security of the water-energy-food nexus (WEF-nexus) is under serious threat. It is of great practical significance to study the adaptive management countermeasures of the collaborative security of the WEF-nexus in the Yangtze River Economic Belt (YREB) and to quantitatively evaluate the implementation sequence of relevant management countermeasures to improve the collaborative security and promote the sustainable development of the WEF-nexus. This study first establishes an evaluation indicator system for the collaborative security of the WEF-nexus in the YREB by utilizing the pressure-state-response (PSR) model. Then, the CRITIC and TOPSIS methods are used to determine the weight of indicators and the collaborative security level of the WEF-nexus in each province and city. The state transition matrix is determined based on the transition at the collaborative security level. Finally, based on the barrel theory to make up for shortcomings, the adaptive management countermeasures of provinces and cities with low collaborative safety levels are studied by combining the Bellman optimal equation. By comparing the expected returns of the same countermeasure in different implementation sequences and conducting quantitative research on the implementation sequence of adaptive management countermeasures, targeted policy suggestions are proposed based on regional characteristics, providing a reference for strategic decision-making of relevant resources in the YREB and improving regional WEF-nexus collaborative security. The results show that: (1) For Jiangxi, improving the water conservancy engineering regulation and storage capacity and other ways in a particular order can effectively improve the collaborative security level of nexus. (2) For Hunan, increasing the investment proportion of agriculture, forestry and water conservancy and resource exploration intensity and other means in a particular order can effectively improve the collaborative security level of the nexus. (3)For Sichuan, increasing the water-saving irrigation rate according to a particular order and other ways can effectively improve the collaborative security level of nexus.

Background: The lack of an efficient way to screen patients who are responsive to immunotherapy challenges PD1/CTLA4-targeting cancer treatment. Immunotherapeutic efficacy cannot be clearly determined by peripheral blood analyses, tissue gene markers or CT/MR value. Here, we used a radionuclide and imaging techniques to investigate the novel dual targeted antibody cadonilimab (AK104) in PD1/CTLA4-positive cells in vivo. Methods: First, humanized PD1/CTLA4 mice were purchased from Biocytogen Pharmaceuticals (Beijing) Co., Ltd. to express hPD1/CTLA4 in T-cells. Then, mouse colon cancer MC38-hPD-L1 cell xenografts were established in humanized mice. A bispecific antibody targeting PD1/CTLA4 (AK104) was labeled with radio-nuclide iodine isotopes. Immuno-PET/CT imaging was performed using a bispecific monoclonal antibody (mAb) probe 124I-AK104, developed in-house, to locate PD1+/CTLA4+ tumor-infiltrating T cells and monitor their distribution in mice to evaluate the therapeutic effect. Results: The 124I-AK104 dual-antibody was successfully constructed with ideal radiochemical characteristics, in vitro stability and specificity. The results of immuno-PET showed that 124I-AK104 revealed strong hPD1/CTLA4-positive responses with high specificity in humanized mice. High uptake of 124I-AK104 was observed not only at the tumor site but also in the spleen. Compared with PD1- or CTLA4-targeting mAb imaging, 124I-AK104 imaging had excellent standard uptake values at the tumor site and higher tumor to nontumor (T/NT) ratios. Conclusions: The results demonstrated the potential of translating 124I-AK104 into a method for screening patients who benefit from immunotherapy and the efficacy, as well as the feasibility, of this method was verified by immuno-PET imaging of humanized mice.

Operators in thermal hazardous environments are more susceptible to burns during physical motion due to the potential deformation of thermal protective clothing. To study the influence of fabric deformation on heat transfer, a model of a three-layer thermal protective fabric system with stretching and compression deformation throughout the heat exposure and cooling phases was established and coupled with a skin heat transfer model to predict skin burns. Changes in the thermophysical properties of the fabric with deformation and skin tissue based on body location were considered. To verify the accuracy of the model, a modified radiant protective performance tester capable of simulating fabric deformation was applied. The relative error between the prediction results of the model and the experimental results does not exceed 4.68 %. The results demonstrate that stretching or compression deformation of the fabric increases heat transfer to the skin, and compression deformation generates a greater thermal hazard by accelerating the discharge of stored energy. Fabric deformation accelerates skin burns in all body parts, especially in the arms and legs. The findings of this research can provide a theoretical basis for understanding the frequent occurrence of skin burns associated with body motion and provide guidance for the design of thermal protective clothing to enhance the partial thermal protective performance.

Gut microbes are crucial for human health, which are usually accumulated in urban wastewater systems. Seven wastewater treatment plants in Australia with distinct population obesity rates between 18% and 33% were selected for wastewater sampling and analysis. Human gut microbiome were detected using metagenomic sequencing to investigate their associations with the community obesity rate. To unravel this complex relationship, a range of algorithm models, including linear discriminant analysis effect size (LEfSe), similarity percentage analysis (SIMPER), statistical analysis of metagenomic profiles (STAMP), linear models for microarray and RNA-Seq data analysis (LIMMA), Relief, ratio approach for identifying differential abundance (RAIDA), least absolute shrinkage and selection operator (LASSO), support vector machine (SVM), Boruta, DESeq2 and analysis of compositions of microbiomes with bias correction (ANCOM-BC), were used to identify potential bacterial biomarkers for obesity in the wastewater microbiome. Among these algorithm models, LEfSe, LIMMA, SIMPER and SVM are effective in identifying multiple microbial biomarkers. Specific human gut microbes, including Ruminococcus_E, Agathobacter, Fusicatenibacter, Anaerobutyricum, Blautia_A and Neisseria, were identified as potential consensus microbial biomarkers for obesity in the population. A high obesity rate is mainly characterized by a high abundance of pathogenic bacteria and microorganisms associated with xenobiotic biodegradation and metabolism, endocrine and metabolic diseases, and transcription pathways. This study underscores the innovative potential of leveraging human gut microbes in wastewater as biomarkers for monitoring obesity levels across communities, offering a novel, cost-effective, and indirect approach to public health surveillance.

Background & Aims: A high human cytomegalovirus (HCMV) infection rate accompanied by an increased level of bile duct damage is observed in the perinatal period. The possible mechanism was investigated. Methods: A total of 1,120 HCMV-positive and 9,297 HCMV-negative children were recruited, and depending on age, their liver biochemistry profile was compared. Fetal and infant biliary epithelial cells (F-BECs and I-BECs, respectively) were infected with HCMV, and the differences in cells were revealed by proteomic analysis. Protein–protein interactions were examined by coimmunoprecipitation and mass spectrometry analyses. A murine cytomegalovirus (MCMV) infection model was established to assess treatment effects. Results: Perinatal HCMV infection significantly increased the level of bile duct damage. Neonatal BALB/c mice inoculated with MCMV showed obvious inflammation in the portal area with an abnormal bile duct structure. Proteomics analysis showed higher CD14 expression in F-BECs than in I-BECs. CD14 siRNA administration hindered HCMV infection, and CD14-knockout mice showed lower MCMV-induced bile duct damage. HCMV infection upregulated CD55 and poly ADP-ribose polymerase-1 (PARP-1) expression in F-BECs. Coimmunoprecipitation and mass spectrometry analyses revealed formation of the CD14–CD55 complex. siRNA-mediated inhibition of CD55 expression reduced sCD14-promoted HCMV replication in F-BECs. In MCMV-infected mice, anti-mouse CD14 antibody and PARP-1 inhibitor treatment diminished cell death, ameliorated bile duct damage, and reduced mortality. Conclusions: CD14 facilitates perinatal HCMV infection in BECs via CD55, and PARP-1-mediated cell death was detected in perinatal cytomegalovirus-infected BECs. These results provide new insight into the treatment of perinatal HCMV infection with bile duct damage. Impact and implications: Perinatal human cytomegalovirus (HCMV) infection is associated with bile duct damage, but the underlying mechanism is still unknown. We discovered that CD14 expression is increased in biliary epithelial cells during perinatal HCMV infection and facilitates viral entry through CD55. We also detected PARP-1-mediated cell death in perinatal HCMV-infected biliary epithelial cells. We showed that blocking CD14 or inhibiting PARP-1 reduced bile duct damage and mortality in a mouse model of murine cytomegalovirus infection. Our findings provide a new insight into therapeutic strategies for perinatal HCMV infection.

ABSTRACT: Micro-organisms on the eggshell surface of affect the quality of the egg. Sometimes, these microbes even pose a serious threat to the health of the egg's consumer. Bacterial 16S rDNA and fungal internal transcribed spacer region were sequenced to analyze the microbial diversity on the shell surface of the eggs collected from 4 distinct regions of China: Guyuan (GY; 1.5 million hens), Langfang (LF; 0.1 million hens), Beihai (BH; 1.2 million hens), and Dongguan (DG; 0.2 million hens). The results showed a higher bacterial and fungal abundance on the eggs collected from the northern and southern China farms, respectively. The dominant bacterial phylum detected across all egg samples was Firmicutes. In addition, the shell surfaces of the DG and LF samples harbored abundant levels of Proteobacteria. The dominant fungal phyla detected across all egg samples were Ascomycota and Basidiomycota. The bacterial compositions on eggshell surfaces differed significantly across all geographic regions, and the fungal composition differed significantly between samples collected from the southern and northern farms (P < 0.05). The abundance and composition of microbial colonies on the eggshell surface varied based on their geographical location (climate and environment) and farming scale (management). Our findings provide an important reference for optimizing the cleaning and disinfection methods for fresh eggs collected from different sources.

Straw mulching incorporation has a wide range of environmental benefits that make it an effective practice for sustainable agro-ecosystem in the semi-arid regions. There is an urgent need to improve the 13C-photosynthates distribution, water use efficiency (WUE) and maize canopy characteristics under the diverse tillage practices with straw mulched management strategies for sustainable intensification of maize production. The field study consists of three diverse tillage systems (RT: rotary tillage; CT, conventional tillage; MT, minimum tillage) with three straws mulching (NS: no straw mulch; SS: straw mulch on the soil surface; SI: straw incorporated into the soil) were assessed under the ridge-furrow rainfall harvesting system. Our results showed that the rotary tillage with straw incorporated into the soil significantly reduces the ET rate (11 %), and leaf rolling index; as a result considerably improves LAI, LEI, 13C-photosynthates distribution, N accumulation, and above ground biomass under various growth stages. The RTSI treatment significantly improved soil water storage, soil organic carbon (52 %, SOC), soil C storage (39 %, SCS), and NPK nutrients uptake (70 %, 62 %, and 69 %) of maize than observed for the rest of all other treatments, respectively. The RTSI treatment improves soil water balance, grain yield (53 %), biomass yield (37 %), WUEg (51 %), WUEb (35 %), nutrients uptake, and mitigating soil water depletion than the MTNS treatment. Although RTSS can achieve optimal soil water storage in the short term, RTSI has a great potential in improving soil carbon stability, canopy characteristics, soil water storage, and WUE, contributing to sustainable and intensive corn production in agricultural ecosystems in semi-arid regions.

Background: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder, characterized by progressive limb weakness, dysphagia, dysphonia, and respiratory failure due to degeneration of upper and lower motor neurons. The pathogenesis of ALS is still unclear. Neuroinflammation has been found to be involved in its development and progression. Cytokines play a significant role in the inflammatory process. This study aims to identify novel biomarkers that may assist in the diagnosis of ALS. Methods: In Fujian Medical University Union Hospital and Huashan Hospital Fudan University, two independent centers, we prospectively recruited 50 ALS patients, and 41 healthy controls (25 ALS and 26 controls in the first stage and 25 ALS and 15 controls in the validation stage). An 18-plex Luminex kit was used to screen the serum cytokines levels in the first stage. Commercial ELISA kits were used to measure the levels of target cytokines in the validation stage. A single-molecule array HD-X platform was applied to assess the levels of serum neurofilament light chain (NFL). Results: The levels of serum IL-18 were markedly increased in patients with ALS in the first stage (p = 0.016). The ROC curve showed an area under the curve at 0.695 (95% CI 0.50–0.84) in distinguishing ALS patients from healthy controls. The IL-21 was decreased in elderly patients when grouped by 55 years old (the medium age). Furthermore, the IL-5, IL-13, IL-18, and NFL had a positive relationship with the disease progression of ALS. We also found that serum IL-18 was markedly increased in ALS patients in the validation stage (167.67 [148.25–175.59] vs 116.44 [102.43–122.19]pg/ml, p

Prostate cancer (PCa) is witnessing a concerning rise in incidence annually, with the androgen receptor (AR) emerging as a pivotal contributor to its growth and progression. Mounting evidence underscores the AR’s ability to recruit cofactors, influencing downstream gene transcription and thereby fueling the proliferation and metastasis of PCa cells. Although, clinical strategies involving AR antagonists provide some relief, managing castration resistant prostate cancer (CRPC) remains a formidable challenge. Thus, the need of the hour lies in unearthing new drugs or therapeutic targets to effectively combat PCa. This review encapsulates the pivotal roles played by coactivators and corepressors of AR, notably androgen receptor-associated protein (ARA) and steroid receptor Coactivators (SRC) in PCa. Our data unveils how these cofactors intricately modulate histone modifications, cell cycling, SUMOylation, and apoptosis through their interactions with AR. Among the array of cofactors scrutinised, such as ARA70β, ARA24, ARA160, ARA55, ARA54, PIAS1, PIAS3, SRC1, SRC2, SRC3, PCAF, p300/CBP, MED1, and CARM1, several exhibit upregulation in PCa. Conversely, other cofactors like ARA70α, PIASy, and NCoR/SMRT demonstrate downregulation. This duality underscores the complexity of AR cofactor dynamics in PCa. Based on our findings, we propose that manipulating cofactor regulation to modulate AR function holds promise as a novel therapeutic avenue against advanced PCa. This paradigm shift offers renewed hope in the quest for effective treatments in the face of CRPC’s formidable challenges.

Transforming growth factor-β1 (TGF-β1) is essential for cartilage regeneration, but its susceptibility to enzymatic denaturation and high cost limit its application. Herein, we report Ac-LIANAKGFEFEFKFK-NH2 (LKP), a self-assembled peptide nanofiber hydrogel that can mimic the function of TGF-β1. The LKP hydrogel is simple to synthesize, and in vitro experiments confirmed its good biocompatibility and cartilage-promoting ability. However, LKP hydrogels suffer from poor mechanical properties and are prone to fragmentation; therefore, we prepared a series of injectable hydrogel composite scaffolds (SF-GMA/LKP) by combining LKP with glycidyl methacrylate (GMA)-modified silk fibroin (SF). SF-GMA/LKP composite scaffolds instantaneously induced in-situ filling of cartilage defects and, at the same time, relied on the interaction between LKP and SF-GMA interaction to prolong the duration of action of LKP. The SF-GMA/LKP10 and SF-GMA/LKP20 composite scaffolds had the best effect on neocartilage and subchondral bone reconstruction. This composite hydrogel scaffold can be used for high-quality cartilage repair.

The aim of this study was to investigate the possible molecular mechanism of Scutellaria baicalensis Georgi stems and leaves flavonoids (SSF) in Alzheimer's disease (AD). The active ingredients of SSF and their targets were identified via network pharmacology and bioinformatics analysis. To test the successful establishment of a rat model of AD by Aβ25-35 combined with RHTGF-β1 and AlCl3, the Morris water maze test was used. To intervene, three different doses of SSF were administered. The model group and the control group were included among the parallel groups. A shuttle box test, immunohistochemistry, an enzyme-linked immunosorbent assay, qPCR and Western blot were performed to verify the results. Based on the intersection of genes among AD disease targets, SSF component targets, and differentially expressed genes in the single cell dataset GSE138852 and bulk-seq dataset GSE5281, nine genes related to the action of SSF on AD were identified. SSF have an important anti-AD pathway in the cAMP signaling pathway. SSF can ameliorate the conditioned memory impairment, augment Brdu protein expression and cAMP content; and differentially regulate the mRNA and protein expressions of GPCR, Gαs, AC1, PKA, and VEGF. The cAMP-PKA-CREB pathway in the SSF may mediate the ability of the SSF to ameliorate the composite-induced memory loss and nerve regeneration in rats induced by composite Aβ.

Background: Human umbilical cord mesenchymal stem cells (UC-MSCs) are one of the most extensively researched stem cell types due to their potential for multi-lineage differentiation, secretion of regenerative factors, modulations of immunological activities, and the release of regenerative substances and influence immunological processes. Since UC-MSCs must be cultivated on a large scale for clinical use, selecting the appropriate storing passage, such as the usage-based passage of UC-MSCs, is critical for long-term autologous or allogeneic usage. Long-term cultivation of stem cells, on the other hand, causes them to lose their pluripotent differentiation capacity. As a result, distinguishing between high and low passages of UC-MSCs and identifying the particular variations associated with stem cells and their modes of action is essential for regenerative medicine. Therefore, we investigated the biological features and transcriptional changes of UC-MSCs over passages. Methods: UC-MSCs were isolated from the tissues of the human umbilical cord, and UC-MSCs from five passages (P1, P3, P5, P10 and P15) with three repetitions were compared and identified based on morphology, cell markers, differentiation capacity, and aging-related characteristics. It was previously assumed that the phenotype of cells before the P10 passage was stable, defined as early passage, and that culture could be continued until the 15th passage, defined as late passage. Next, the five passages of UC-MSCs were sequenced using high-throughput complete transcriptome sequencing. Fuzzy C-Means Clustering (FCM) and Weighted Gene Co-expression Network Analysis (WGCNA) were used to find hub genes, and gene silencing was performed to investigate the impact of missing genes on the stemness of UC-MSC cells. Results: UC-MSCs of different passages displayed similar surface markers, including CD73, CD105, CD90, CD34, CD45 and HLA-DR. However, the proliferation time of late-phase UC-MSCs was longer than that of early-phase UC-MSCs, and the expression of the senescence-associated (SA)-β-gal staining marker was higher. At the same time, pluripotency markers (NANOG, OCT4, SOX2 and KIF4A) were down-regulated, and the multi-differentiation potential was reduced. Meanwhile, KIFC1 and UBE2C were down-regulated in late-phase UC-MSCs, which were involved in the maintenance of stemness. Conclusions: KIFC1 and UBE2C were highly expressed in early-UC-MSCs and showed a downward gradient trend with cell expansion in vitro. They regulated UC-MSC proliferation, colony sphere formation, multiple differentiation, stemness maintenance, and other biological manifestations. Therefore, they are anticipated to be new biomarkers for UC-MSCs quality identification in regenerative medicine applications.

In this study, we delved into the safety profile of alpelisib, an FDA-approved treatment for hormone receptor-positive, HER2-negative, PIK3CA-mutated advanced or metastatic breast cancer, and PIK3CA-Related Overgrowth Spectrum (PROS). Despite its approval, real-world, long-term safety data is lacking. Our research scrutinizes the FDA database to assess alpelisib 's safety. We retrospectively analyzed data from April 2019 to June 2023 using four algorithms. Among 7,609,450 reports, 6692 implicated alpelisib as the primary suspected drug, uncovering adverse events (AEs) across 26 organ systems. Notably, we identified 21 previously unlisted AEs. Furthermore, differences in AEs emerged between patients with PIK3CA-mutated breast cancer and those with PROS. This study provides vital insights for healthcare professionals to navigate AEs in clinical practice and informs future research for enhancing alpelisib 's safety profile.

Common tyrosinase (TYR) inhibitors used in cosmetics, such as hydroquinone, kojic acid, and arbutin, can cause side effects including erythema, skin peeling, and dryness. Therefore, the development of natural whitening agents that offer excellent permeability, minimal irritation, and high safety has become a primary focus in the field of TYR inhibitors. In this study, we demonstrate that White birch sap (WBS), within a safe concentration range, effectively reduces TYR activity and melanin content in both B16F10 mouse melanoma cells and zebrafish larvae. Importantly, WBS exhibits minimal irritation to neutrophils in fluorescent zebrafish and does not affect the behavior of adult zebrafish. Furthermore, WBS downregulates the gene expression levels of microphthalmia-associated transcription factor, TYR, tyrosinase-related protein-1, and tyrosinase-related protein-2 in B16F10 cells. In conclusion, our research confirms that WBS, a naturally derived substance, offers high safety and mild effects, making it a promising candidate for a skin-whitening agent.

Summary: DNA demethylase TET2 was related with lung function. However, the precise role of TET2 in cigarette smoke (CS)-induced apoptosis of airway epithelium cells, and the mechanisms involved, have yet to be elucidated. Here, we showed that CS decreased TET2 protein levels but had no significant effect on its mRNA levels in lung tissues of chronic obstructive pulmonary disease (COPD) patients and CS-induced COPD mice model and even in airway epithelial cell lines. TET2 could inhibit CS-induced apoptosis of airway epithelial cell in vivo and in vitro. Moreover, we identified ubiquitin-specific protease 21 (USP21) as a deubiquitinase of TET2 in airway epithelial cells. USP21 interacted with TET2 and inhibited CSE-induced TET2 degradation. USP21 downregulated decreased TET2 abundance and further reduced the anti-apoptosis effect of TET2. Thus, we draw a conclusion that the USP21/TET2 axis is involved in CS-induced apoptosis of airway epithelial cells.

The capability of 5, 10, 15 mM γ-aminobutyric acid (GABA) to improve the postharvest quality and antioxidant system of strawberry was evaluated in this study. The application of GABA had no effect on fruit skin color and firmness. The weight loss in fruits treated with 10 mM GABA was significantly lower than the control. GABA treatments resulted in higher levels of total soluble sugar, titratable acid, SOD and CAT activities with 10 mM being the most significant effect. Specifically, 10 mM GABA significantly induced the accumulation of fructose, oxalic acid, and succinic acid. Besides, GABA application increased the content of total anthocyanins and total flavonoids, and DPPH radical scavenging activity in fruits. The GABA-treated fruits especially at 5 mM and 10 mM displayed less ROS and MDA. These data suggested that application of 10 mM GABA might be a promising strategy to improve the postharvest marketability of strawberry.

Objective: Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disease associated with a high incidence of complications in the mid and late stages of gestation. This study investigates differences in the composition of intestinal flora among pregnant women diagnosed with ICP, employing Illumina MiSeq high-throughput sequencing technology. Methods: This case-control study obtained patient data from the hospital information system (HIS) and the laboratory information system (LIS). Fecal samples were collected from 25 pregnant women who did not undergo intestinal preparation before delivery between December 2020 and March 2021. Whole-genome analysis was performed. PCR was used to amplify the 16S rRNA V3–V4 variable region, which was then sequenced. Alpha and beta diversity were computed, and the maternal intestinal flora's abundance and composition characteristics were analyzed. Differences in intestinal flora between the two sample groups were examined. Results: Bacteroides and Proteobacteria exhibited positive correlations with TBIL and IBIL. Betaproteobacteria, Gammaproteobacteria, and Erysipeiotrichi showed positive correlations with TBIL, IBIL, and DBIL, while Lactobacillus, Delftia, and Odoribacter demonstrated positive correlations with ALT. Conclusion: The ICP group displayed significantly higher levels of total bile acid and ALT compared to the control group. The intestinal flora composition comprised four primary phyla: Firmicutes, Actinobacteria, Bacteroidetes, and Proteobacteria. ICP patients exhibited a lower relative abundance of intestinal flora across different levels of community composition when compared to the control group. Specific correlations between certain intestinal flora and clinical liver parameters were identified.

Personalized repair of bone defects remains a tremendous clinical challenge. Developing 3D-printed bioceramics with excellent osteogenic potential is an effective therapeutic strategy to overcome this challenge. In this study, we prepared composite bioceramics (designated as CSC-DBM) with immunomodulatory, vascularization, and osteogenesis based on calcium silicate (CS) bioceramics, calcium sulfate (CSH), and decalcified bone matrix (DBM). CSC-DBM bioceramics has an unmatched biomineralization potential due to the synergistic promotion of CS and CSH. Meanwhile, CSC-DBM bioceramics could effectively modulate the immune response, induce M2 macrophage polarization, promote vascular regeneration, and further enhance new bone formation. In summary, this composite bioceramics made of CS bioceramics, CSH, and DBM can provide a new solution for bone defect repair in the clinic.