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Oxidative stress, dysbiosis, and immune dysregulation have been confirmed to play pivotal roles in the complex pathogenesis of inflammatory bowel disease (IBD). Herein, we design copper ion–luteolin nanocomplexes (CuL NCs) through a metal–polyphenol coordination strategy, which plays a multifaceted role in the amelioration of IBD. The fabricated CuL NCs function as therapeutic agents with exceptional antioxidant and anti-inflammatory capabilities because of their great stability and capacity to scavenge reactive oxygen species (ROS). It can effectively modulate the inflammatory microenvironment including facilitating the efficient reduction of pro-inflammatory cytokine levels, protecting intestinal epithelial cells, promoting mucosal barrier repair and regulating intestinal microbiota. In addition, CuL NCs have been found to enhance cellular antioxidant and anti-inflammatory capacities by regulating the nuclear factor erythroid 2–related factor 2/heme oxygenase-1 (Nrf2/HO-1) oxidative stress pathway and nuclear factor kappa B (NF-κB) signaling pathway, respectively. Notably, CuL NCs demonstrate significant prophylactic and therapeutic efficacy in mouse models with typical IBD, including ulcerative colitis (UC) and Crohn's disease (CD). This study provides a new approach for building multifaceted therapeutic platforms for natural products to treat IBD.

Abstract Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease characterized by multilineage immune dysregulation, which subsequently causes inflammation, fibrosis, and even cirrhosis of liver. Due to the limitation of traditional assays, the local hepatic immunopathogenesis of PBC has not been fully characterized. Here, we utilize single-cell RNA sequencing technology to depict the immune cell landscape and decipher the molecular mechanisms of PBC patients. We reveal that cholangiocytes and hepatic stellate cells are involved in liver inflammation and fibrosis. Moreover, Kupffer cells show increased levels of inflammatory factors and decreased scavenger function related genes, while T cells exhibit enhanced levels of inflammatory factors and reduced cytotoxicity related genes. Interestingly, we identify a liver-resident Th1-like population with JAK-STAT activation in the livers of both PBC patients and murine PBC model. Finally, blocking the JAK-STAT pathway alleviates the liver inflammation and eliminates the liver-resident Th1-like cells in the murine PBC model. In conclusion, our comprehensive single-cell transcriptome profiling expands the understanding of pathological mechanisms of PBC and provides potential targets for the treatment of PBC in patients.

ABSTRACT Aims/Introduction To investigate risk factors for diabetic peripheral neuropathy (DPN) and to explore the connection between insulin‐like growth factor‐1 (IGF‐1) and DPN in individuals with type 2 diabetes. Materials and Methods A total of 790 patients with type 2 diabetes participated in a cross‐sectional study, divided into two groups: those with DPN (DPN) and those without DPN (non‐DPN). Blood samples were taken to measure IGF‐1 levels and other biochemical markers. Participants underwent nerve conduction studies and quantitative sensory testing. Results Patients with DPN exhibited significantly lower levels of IGF‐1 compared with non‐DPN patients (P 0.05), or the temperature detection threshold (P > 0.05). Multivariate regression analysis identified diabetes duration, HbA1c, and the low levels of IGF‐1 as independent risk factors (P

Abstract Peroxyacetyl nitrate (PAN) is an important photochemical product and affects ozone (O3) formation in the troposphere. Yet, the long-term observation of PAN remains scarce, limiting the full understanding of its impacts on photochemical pollution. Here, we observed PAN from 2018 to 2022 in urban Fuzhou, Southeastern China. We found that, in contrast to upward trend of O3, PAN concentrations shown a significant decreasing trend at an average rate of −0.07 ppb/year. NO2, CO, UVB, and T contributed to the decreasing trend of PAN according to Machine learning analyses, while the effect of O3-represented atmospheric oxidation capacity on PAN was fluctuating from year to year. Chemical box model revealed active PA production and depletion in Fuzhou. Thus, despite the decreasing PAN concentration, PAN chemistry effectively promoted O3 formation by rising ROx levels, leading to increases of 2.18%–58.4% in net O3 production rate in different years. Our results provide valuable insights into the evolution of photochemical pollution in urban environments.

Abstract Background Automated test assembly (ATA) represents a modern methodology that employs data science optimization on computer platforms to automatically create test form, thereby significantly improving the efficiency and accuracy of test assembly procedures. In the realm of medical education, large-scale high-stakes assessments often necessitate lengthy tests, leading to elevated costs in various dimensions (such as examinee fatigue and expenses associated with item development). This study aims to augment the design of the medical education assessments by leveraging modern ATA approaches. Methods To achieve the objective, a four-step process employing psychometric methodologies was used to calibrate and analyze the item pool of the Standardized Competence Test for Clinical Medicine Undergraduates (SCTCMU), a nationwide summative test comprising 300 multiple-choice questions (MCQ) in China. Subsequently, two modern ATA approaches were employed to determine the optimal item combination, accounting for both statistical and content requirements specified in the test blueprint. The qualities of the assembled test form, generated using modern ATA approaches, underwent meticulous evaluation. Results Through an exploration of the psychometric properties of the SCTCMU as a foundational step, the evaluation revealed commendable quality in the item properties. Furthermore, the evaluation of the quality of assembled test form using modern ATA approaches indicated the ability to ascertain the optimal test length within the predefined measurement precision. Specifically, this investigation demonstrates that the application of modern ATA approaches can substantially reduce the test length of assembled test form, while simultaneously maintaining the required statistical and content standards specified in the test blueprint. Conclusions This study harnessed modern ATA approaches to facilitate the automatic construction of test form, thereby significantly enhancing the efficiency and precision of test assembly procedures. The utilization of modern ATA approaches offers medical educators a valuable tool to enhance the efficiency and cost-effectiveness of medical education assessment.

Background The International IgA Nephropathy (IgAN) Network developed and validated two prognostic prediction models for IgAN, one incorporating a race parameter. These models could anticipate the risk of a 50% reduction in estimated glomerular filtration rate (eGFR) or progression to end-stage renal disease (ESRD) subsequent to an IgAN diagnosis via renal biopsy. This investigation aimed to validate the International IgA Nephropathy Prediction Tool (IIgANPT) within a contemporary Chinese cohort.Methods Within this study,185 patients diagnosed with IgAN via renal biopsy at the Center for Kidney Disease, Second Affiliated Hospital of Nanjing Medical University, between January 2012 and December 2021, were encompassed. Each patient’s risk of progression was assessed utilizing the IIgANPT formula. The primary outcome, a 50% decline in eGFR or progression to ESRD, was examined. Two predictive models, one inclusive and the other exclusive of a race parameter, underwent evaluation via receiver-operating characteristic (ROC) curves, subgroup survival analyses, calibration plots, and decision curve analyses.Results The median follow-up duration within our cohort spanned 5.1 years, during which 18 patients encountered the primary outcome. The subgroup survival curves exhibited distinct separations, and the comparison of clinical and histological characteristics among the risk subgroups revealed significant differences. Both models demonstrated outstanding discrimination, evidenced by the areas under the ROC curve at five years: 0.882 and 0.878. Whether incorporating the race parameter or not, both prediction models exhibited acceptable calibration. Decision curve analysis affirmed the favorable clinical utility of both models.Conclusions Both prognostic risk evaluation models for IgAN exhibited remarkable discrimination, sound calibration, and acceptable clinical utility.

Background While renal biopsy remains the preferred diagnostic method for assessing proteinuria, hematuria, or renal failure, laparoscopic renal biopsy (LRB) can serve as an alternative for high-risk patients when percutaneous kidney biopsy (PKB) is not recommended. This study was aimed to evaluate the safety of LRB.Methods In study 1, Fourteen patients from January 2021 to January 2023 had a LRB taken for various indications, such as morbid obesity, abnormal kidney construction, uncontrolled hypertension, and coagulopathy. We also conducted a Meta-analysis of the success rate and complication rate of previous LRB in study 2.Results All the patients completed biopsies and adequate renal tissues were obtained. The success rate was 100%. The median number of glomeruli obtained was 22.5 (range:12.0, 45.0). The complication rate was 7.1% (urinary tract infection). There were no significant differences between levels of hemoglobin, serum creatinine, and urinary NAGL before and after surgery. In the meta-analysis, the success rate of operation, satisfactory rate of sample, and complication rate of surgery were 99.9%, 99.1%, and 2.6% respectively.Conclusion LRB can achieve a good success rate and specimen retrieval and does not increase the risk of complications for high-risk patients. It can present as one of the alternative methods for patients with glomerular diseases.

Background Monocyte to high-density lipoprotein cholesterol ratio (MHR) was confirmed as a novel inflammatory marker and strongly associated with the risk of several diseases. This study aimed to investigate the relationship between MHR and chronic kidney disease (CKD) in a Chinese adult population.Methods In this cross-sectional study, 232,775 community-dwelling adults in Binhai who completed health checkups in 2021 were enrolled. Participants were categorized based on the MHR quartiles. Clinical characteristics of participants across different groups were compared using one-way ANOVA, Kruskal-Wallis h-test, and Chi-squared test as appropriate. Univariate and multivariable logistic regression analyses were taken to assess the relationship between MHR and the presence of CKD, as well as its association with low estimated glomerular filtration rate (eGFR) and proteinuria. Subgroup analyses were further executed to confirm the reliability of this relationship.Results A total of 21,014 (9.0%) individuals were diagnosed with CKD. Characteristic indicators including waist circumference, body mass index (BMI), blood pressure (BP), serum uric acid (SUA), triglyceride, and fasting blood glucose (FBG) showed a gradual increase with higher MHR quartiles, whereas parameters such as age, total cholesterol, high-density lipoprotein cholesterol (HDL-C), and eGFR decreased (p

Summary: Background: Dementia among younger people is rapidly emerging as a global health concern; however, comprehensive research on its shifting burden trends remains insufficient. Methods: Data on the prevalence, incidence, mortality, and disability-adjusted life years (DALYs) associated with dementia occurring in individuals

Abstract Background To systematically analyze differences in atherosclerotic cardiovascular disease (ASCVD) burden between young and older adults. Methods We estimated the prevalence, mortality, and disability-adjusted life years (DALYs) of ASCVD, including ischemic heart disease (IHD), ischemic stroke (IS), and peripheral artery disease (PAD), in individuals aged 20–54 and > 55 years from 1990–2019, utilizing data from the 2019 Global Burden of Disease Study. The annual percentage changes (EAPCs) for age-specific prevalence, mortality, or DALY rates were calculated to quantify the temporal trends of ASCVD burden. We also analyzed population attribution fractions (PAF) of premature ASCVD mortality and DALYs for different risk factors and compared the burden of extremely premature, premature, and non-premature ASCVD cases based on clinical classifications. Results From 1990–2019, the global prevalence rates of IHD, IS, and PAD in the 20–54 years age group increased by 20.55% (from 694.74 to 837.49 per 100,000 population), 11.50% (from 439.48 to 490.03 per 100,000 population), and 7.38% (from 384.24 to 412.59 per 100,000 population), respectively. Conversely, the ASCVD prevalence in > 55years age group decreased. Adverse outcome burdens, including mortality and DALYs, varied among ASCVD subtypes. The decrease in the mortality/DALY burden of IHD and IS was lower in the 20–54 years group than in the > 55 years group. For PAD, DALYs among those aged 20–54 increased but decreased among those aged > 55 years. When grouped according to socio-demographic index (SDI) values, lower SDI regions exhibited a higher proportion of young ASCVD burden. The prevalence of young IHD, IS, and PAD in low SDI regions reached 20.70%, 40.05%, and 19.31% in 2019, respectively, compared with 12.14%, 16.32%, and 9.54%, respectively, in high SDI regions. Metabolic risks were the primary contributors to the ASCVD burden in both age groups. Increased susceptibility to ambient particulate matter pollution and inadequate control of high body-mass index and high fasting plasma glucose in young individuals may partially explain the differing temporal trends between young and older individuals. Conclusions The ASCVD burden in young individuals may become a growing global health concern, especially in areas with lower socioeconomic development levels that require more effective primary prevention strategies.

[Introduction] With the establishment of the energy Internet architecture mainly relying on new energies, HVDC transmission has become an important way of power transmission, power grids present a new characteristic of "strong DC and weak AC". Synchronous condensers have unique advantages in dealing with the issue of "strong DC and weak AC" by virtue of their dynamic performance such as fast reactive power response and strong voltage support capability. [Method] To study the application of synchronous condensers in HVDC works, this paper summarized the development of synchronous condensers, introduced the current development status of several major types of synchronous condensers in China, such as synchronous condensers for transforming thermal power units, new-generation large-capacity synchronous condensers, distributed synchronous condensers, analyzed the working principle and dynamic characteristics of synchronous condensers. Then the paper summarized the virtues of synchronous condensers when compared with other reactive power compensation devices such as SVC, the application scenarios, existing configuration strategies of large-capacity synchronous condensers and distributed synchronous condensers. [Result] Finally, a simulation model of DC transmission system with synchronous condensers is built on the PSCAD/EMTDC platform. The simulation verify the suppression capability of synchronous condensers for commutation failure at the sending end and transient overvoltage at the receiving end caused by commutation failure, as well as the dynamic reactive power compensation capability under lagging phase operation. [Conclusion] The analysis shows that synchronous condensers have adequate suppression of transient overvoltage and commutation failure and their reactive power response speed and dynamic reactive power support capability will not be affected by lagging phase operation, which contributes to their prospect of engineering application for steady-state compensation in converter stations.

Objective In situ leaching is a uranium extraction process in which a solution reacts with uranium-bearing minerals in a saturated aquifer and then uranium in the flowing solution is extracted through exchange. To understand the internal structure and seepage path of the 512 deposits, Methods representative wallrock and ore cores of the deposit were selected for CT scanning, and the pore throat parameters were obtained via image noise reduction filtering, image segmentation to extract pores, and the construction of pore network models. The changes in the absolute permeability, tortuosity and seepage velocity are simulated with Avizo software. Results The results showed that the porosity of the wallrock was 15.42%, the connected porosity was 9.61%, the ore porosity was 15.18%, the connected porosity was 13.82%, and the water permeability was better than that of the wallrock. The high-density materials in the wallrock are metal minerals, accounting for approximately 0.54%, and most of the high-density minerals in the ore are secondary uranium minerals, accounting for 1.06%. It can be fully in contact with the solution during the leaching process. Conclusion There is strong heterogeneity inside the pores, which causes the flow rate to gradually decrease in the flow path. The number of large pores connecting the wallrock and ore is greater than that of small pores, indicating that large pores are the main factors determining the degree of pore development. According to the velocity streamlines, although there is a blockage area in the wallrock and ore, the circulation area is dominant.

Objective: This study aimed to evaluate the efficacy of acupuncture in treating allergic rhinitis (AR) in animal models of the disease, and to explore the underlying mechanism of acupuncture in AR. Methods: Related literature was retrieved from multiple databases, including China National Knowledge Infrastructure (CNKI), Wan Fang databases, SinoMed databases, VIP database, PubMed, EMBASE, the Cochrane Library, up to September 2023. The inclusion criteria were focused on animal experiments that investigated the effect of acupuncture therapy on animal models of AR. Studies combining acupuncture with other Chinese medicine therapies were excluded. Data were extracted independently by two reviewers using standardized forms. A total of 75 studies were finally included. The risk of bias in individual studies was evaluated using the Systematic Review Centre for Laboratory animal Experimentation (SYRCLE) tool, and the quality of reporting was evaluated according to Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines. Meta-analyses and plotting were conducted using STATA 17.0 and RevMan 5.4. When heterogeneity was present, a random effects model was applied. Subgroup, meta-regression and sensitivity analyses were also performed. Results: The SYRCLE scores ranged from 3 to 7, and the ARRIVE scores ranged from 6.5 to 11 points. Meta-analysis results demonstrated that acupuncture could significantly down-regulate EOS counts in both blood and nasal mucosa, and reduce the serum levels of IL-5, compared to the AR model group. The results of the qualitative analysis showed that acupuncture could reduce the behavior scores of AR, down-regulate serum levels of IL-4, IgE and sIgE, as well as up-regulate IFN-γ levels. Subgroup analysis results suggested that the different interventions might contribute to the observed heterogeneity. Conclusion: Our results demonstrate that acupuncture effectively alleviates the nasal allergic symptoms in animal models, inhibits immune and inflammatory signaling transduction, and reduces the release of inflammatory mediators. This study highlights the potential of acupuncture as a promising therapeutic option for AR, however, further studies are required to fully understand its mechanisms of action.

BackgroundThyrotropin (TSH)-secreting pituitary neuroendocrine tumors (PitNETs) are recognized as a rare disease. Mixed TSH PitNETs account for 20–25% of TSH PitNETs. This study aimed to report an extremely rare case of a mixed TSH PitNET coexisting with Graves' disease (GD) and also to review the literature.Case presentationA 36-year-old male patient presented with elevated levels of free triiodothyronine (FT3), free thyroxine (FT4), and insulin-like growth factor 1 (IGF-1) but a non-suppressed thyroid-stimulating hormone (TSH) level. His anti-thyroglobulin antibody (TgAb), anti-thyroid peroxidase autoantibody (TPOAb), and thyrotropin receptor antibody (TRAb) tests were positive. Symptoms of palpitations, hyperhidrosis, heat intolerance, and irritability appeared 2 years before his admission. However, he showed neither any signs nor any symptoms of acromegaly. The contrast-enhanced pituitary magnetic resonance imaging (MRI) showed enlargement of the pituitary fossa, with an irregular abnormal signal mass. The patient underwent endoscopic pituitary tumor resection via a transsphenoidal approach. The postoperative pathology suggested a mixed pituitary adenoma. At 8 months after the surgery, the patient had a postoperative recurrence of hyperthyroidism, and methimazole (MMI) was then administered. The recurrence of the TSH PitNET was confirmed by the positron emission tomography-computed tomography (PET-CT), which was performed 11 months after the surgery, and treatment with lanreotide was initiated. Gradually, his levels of FT3, FT4, TSH, TPOAb, and TgAb became normal and the levels of TRAb and IGF-1 improved.ConclusionWhen the circulating levels of both FT4 and FT3 were upregulated, non-suppressed TSH levels and positive thyroid antibodies were found. TSH PitNETs coexisting with GD should be carefully taken into account to avoid the potential risk of treatment-induced tumor progression.

Abstract Introduction Frailty has become a worldwide health burden that has a large influence on public health and clinical practice. The incidence of frailty is anticipated to increase as the ageing population increases. Myocardial injury after noncardiac surgery (MINS) is associated with short-term and long-term mortality. However, the incidence of MINS in frail geriatric patients is unknown. Methods and analysis This prospective, multicentre, real-world observational cohort study will be conducted at 18 designated centres in China from January 2023 to December 2024, with an anticipated sample size of 856 patients aged 65 years and older who are scheduled to undergo noncardiac surgery. The primary outcome will be the incidence of MINS. MINS is defined as a fourth-generation plasma cardiac troponin T (cTnT) concentration ≥ 0.03 ng/mL exhibited at least once within 30 days after surgery, with or without symptoms of myocardial ischaemia. All data will be collected via electronic data acquisition. Discussion This study will explore the incidence of MINS in frail patients. The characteristics, predictive factors and 30-day outcomes of MINS in frail patients will be further investigated to lay the foundation for identifying clinical interventions. Clinical trial registration https://beta.clinicaltrials.gov/study/NCT05635877 , NCT05635877.

Abstract Chronic diabetic wounds are at lifelong risk of developing diabetic foot ulcers owing to severe hypoxia, excessive reactive oxygen species (ROS), a complex inflammatory microenvironment, and the potential for bacterial infection. Here we develop a programmed treatment strategy employing live Haematococcus (HEA). By modulating light intensity, HEA can be programmed to perform a variety of functions, such as antibacterial activity, oxygen supply, ROS scavenging, and immune regulation, suggesting its potential for use in programmed therapy. Under high light intensity (658 nm, 0.5 W/cm2), green HEA (GHEA) with efficient photothermal conversion mediate wound surface disinfection. By decreasing the light intensity (658 nm, 0.1 W/cm2), the photosynthetic system of GHEA can continuously produce oxygen, effectively resolving the problems of hypoxia and promoting vascular regeneration. Continuous light irradiation induces astaxanthin (AST) accumulation in HEA cells, resulting in a gradual transformation from a green to red hue (RHEA). RHEA effectively scavenges excess ROS, enhances the expression of intracellular antioxidant enzymes, and directs polarization to M2 macrophages by secreting AST vesicles via exosomes. The living HEA hydrogel can sterilize and enhance cell proliferation and migration and promote neoangiogenesis, which could improve infected diabetic wound healing in female mice.

Continuous cropping obstacles (CCOs) have increasingly become an important phenomenon affecting morel mushroom yield and quality. In this review, we summarize the current knowledge about the driving factors behind morel mushroom continuous cropping, including the increase in soil nutrients, disorder of the soil microbial structure, aggravation of diseases, and accumulation of allelochemicals and autotoxins. Furthermore, we analyze the interrelationships among these driving factors. To mitigate these adverse effects, we propose five potential strategic approaches aimed at optimizing existing interventions. This overview not only delineates the causative agents and their intricate interactions under continuous cropping scenarios but also consolidates prospective solutions to alleviate these constraints, thereby advancing our understanding and management of morel production sustainability.

The discovery of MPTP, an industrial chemical and contaminant of illicit narcotics, which causes parkinsonism in humans, non-human primates and rodents, has led to environmental pollutants exposure being convicted as key candidate in Parkinson’s disease (PD) pathogenesis. Though MPTP-induced mitochondrial dysfunction and neuroinflammation are mainly responsible for the causative issue of MPTP neurotoxicity, the underlying mechanism involved remains unclear. Here, we reveal a novel signaling mechanism of CDK5-USP30-MAVS regulating MPTP/MPP+ induced PD. MPP+ (the toxic metabolite of MPTP) treatment not only led to the increased protein levels of USP30 but also to mitophagy inhibition, mitochondrial dysfunction, and MAVS-mediated inflammation in BV2 microglial cells. Both mitophagy stimulation (Urolithin A administration) and USP30 knockdown relieved MAVS-mediated inflammation via restoring mitophagy and mitochondrial function in MPP+-induced cell model. Notably, MPTP/MPP+-induced CDK5 activation regulated USP30 phosphorylation at serine 216 to stabilize USP30. Moreover, CDK5-USP30 pathway promoted MAVS-mediated inflammation in MPTP/MPP+-induced PD model. Inhibition of CDK5 not only had a protective effect on MPP+-induced cell model of PD via suppressing the upregulation of USP30 and the activation of MAVS inflammation pathway in vitro, but also prevented neurodegeneration in vivo and alleviated movement impairment in MPTP mouse model of PD. Overall, our study reveal that CDK5 blocks mitophagy through phosphorylating USP30 and activates MAVS inflammation pathway in MPTP/MPP+-induced PD model, which suggests that CDK5-USP30-MAVS signaling pathway represents a valuable treatment strategy for PD induced by environmental neurotoxic pollutants in relation to MPTP.

Abstract Myocardial ischemia/reperfusion injury (MIRI) is the leading cause of irreversible myocardial damage. A pivotal pathogenic factor is ischemia/reperfusion (I/R)‐induced cardiomyocyte ferroptosis, marked by iron overload and lipid peroxidation. However, the impact of lipid droplet (LD) changes on I/R‐induced cardiomyocyte ferroptosis is unclear. In this study, an aggregation‐induced emission probe, TPABTBP is developed that is used for imaging dynamic changes in LD during myocardial I/R‐induced ferroptosis. TPABTBP exhibits excellent LD‐specificity, superior capability for monitoring lipophagy, and remarkable photostability. Molecular dynamics (MD) simulation and super‐resolution fluorescence imaging demonstrate that the TPABTBP is specifically localized to the phospholipid monolayer membrane of LDs. Imaging LDs in cardiomyocytes and myocardial tissue in model mice with MIRI reveals that the LD accumulation level increase in the early reperfusion stage (0–9 h) but decrease in the late reperfusion stage (>24 h) via lipophagy. The inhibition of LD breakdown significantly reduces the lipid peroxidation level in cardiomyocytes. Furthermore, it is demonstrated that chloroquine (CQ), an FDA‐approved autophagy modulator, can inhibit ferroptosis, thereby attenuating MIRI in mice. This study describes the dynamic changes in LD during myocardial ischemia injury and suggests a potential therapeutic target for early MIRI intervention.

Spider silks are natural protein-based biomaterials which are renowned for their mechanical properties and hold great promise for applications ranging from high-performance textiles to regenerative medicine. While some spiders can produce several different types of silks, most spider silk types – including pyriform and aciniform silks – are relatively unstudied. Pyriform and aciniform silks have distinct mechanical behavior and physicochemical properties, with materials produced using combinations of these silks currently unexplored. Here, we introduce an engineered chimeric fusion protein consisting of two repeat units of pyriform (Py) silk followed by two repeat units of aciniform (W) silk named Py2W2. This recombinant ∼86.5 kDa protein is amenable to expression and purification from Escherichia coli and exhibits high α-helicity in a fluorinated acid- and alcohol-based solution used to form a dope for wet-spinning. Wet-spinning enables continuous fiber production and post-spin stretching of the wet-spun fibers in air or following submersion in water or ethanol leads to increases in optical anisotropy, consistent with increased molecular alignment along the fiber axis. Mechanical properties of the fibers vary as a function of post-spin stretching condition, with the highest extensibility and strength observed in air-stretched and ethanol-treated fibers, respectively, with mechanics being superior to fibers spun from either constituent protein alone. Notably, the maximum extensibility obtained (∼157 ± 38 %) is of the same magnitude reported for natural flagelliform silks, the class of spider silk most associated with being stretchable. Interestingly, Py2W2 is also water-compatible, unlike its constituent Py2. Fiber-state secondary structure correlates well with the observed mechanical properties, with depleted α-helicity and increased β-sheet content in cases of increased strength. Py2W2 fibers thus provide enhanced materials behavior in terms of their mechanics, tunability, and fiber properties, providing new directions for design and development of biomaterials suitable and tunable for disparate applications.

Accurate inversion of remote sensing indices images with high-resolution is an important basis for extracting the surface information on fine scale and the remote sensing application with high precision. Under the background that the effect of atmospheric correction on the inversion accuracy of medium-resolution remote sensing indices has been widely concerned, the atmospheric correction method based on the synchronous atmospheric parameters retrieved from the synchronization monitoring atmospheric corrector, which is on board the high-resolution multimode integrated imaging satellite (Gao Fen Duo Mo,) platform, is proposed. The “spaceborne—airborne” synchronous imaging experiment was conducted to investigate the effect of synchronous atmospheric correction on the accuracy of high-resolution remote sensing indices images. The low-altitude synchronous remote sensing indices images were taken as the reference standard, the correlation between the normalized difference vegetation index (NDVI) and normalized difference water index (NDWI) images after synchronous atmospheric correction and the reference images are improved by 4.27% and 12.22%, respectively. The mean errors in average NDVI and NDWI value of sampling plot decreased by 0.2489 and 0.1032, respectively. The average errors in the peak value of change rate of pixel index value are reduced by 0.1194 and 0.2288 in the case of NDVI and NDWI, respectively. Compared with the results of FLAASH, the synchronous atmospheric correction method shows better performance, especially in the targets with low reflectance (the atmospheric radiation contribution is higher than the surface radiation contribution), and in the adjacent area between two different ground objects. The results demonstrate that synchronous atmospheric correction can effectively improve the inversion accuracy of high-resolution remote sensing indices images and its ability of quantitative application.

Abstract Background Non-small cell lung cancer (NSCLC) is a major pathological type of lung cancer. However, its pathogenesis remains largely unclear. MRPL35 is a regulatory subunit of the mitoribosome, which can regulate the assembly of cytochrome c oxidases and plays an important role in the occurrence of NSCLC. Methods The expression of MRPL35 in NSCLC was detected by tissue microarray and immunohistochemistry. H1299 cells were infected with lentivirus to knockdown MRPL35, and the cells were subjected to crystal violet staining to assess the results of colony formation assays. A549 cells were infected by lentiviral particles-expressing shMRPL35 or shControl, and then subcutaneously injected into nude mice. Tumorigenesis in mice was detected by in vivo imaging. The potential pathway of MRPL35 in NSCLC was assessed by Western blotting. Results MRPL35 was over-expressed in NSCLC tissue compared to para-cancerous and normal tissues. Knockdown of MRPL35 suppressed cell proliferation and decreased NSCLC progression both in vitro and in vivo. The possible molecular mechanisms were also clarified, which indicated that MRPL35 could be involved in cell apoptosis and proliferation by modulating the expression levels of CDK1, BIRC5, CHEK1, STMN1 and MCM2. Knockdown of MRPL35 activated p53 signaling pathway and inhibited cell cycle regulation. Conclusions The oncogenic role of MRPL35 in NSCLC was potentially mediated through the cell cycle regulatory genes such as BIRC5, STMN1, CDK1, CHEK1 and MCM2, as well as activation of P53 signaling pathway.

Abstract Atopic dermatitis (AD) is a common skin disease involving important immune mechanisms. There is an unmet need for a treatment for this condition. Herein, we focused on elucidating the role of Bi2-xMnxO3 nanospheres (BM) in alleviating skin inflammation in AD-like C57BL/6 mice. The BM was fabricated via sacrificial templates and its biosafety was systematically evaluated. The BM was applied topically to skin lesions of AD-like C57BL/6 mice. The phenotypic and histological changes in the skin were examined carefully. The responses of barrier proteins, inflammatory cytokines and cells to BM were evaluated in HaCaT cells and AD mouse models. The data demonstrated that BM treatment alleviated the AD phenotypes and decreased the level of inflammatory factors, while increasing the expression of the barrier proteins filaggrin/involucrin in the skin. BM effectively reduced the expression of phosphorylated STAT6, which in turn reduced the expression of GATA3, and further decreased the differentiation ratio of Th2 cells, thereby reducing the expression of IL-4. In conclusion, topical drug therapy with BM provides a safe and effective treatment modality for AD by reducing IL-4 and increasing barrier proteins. Graphical Abstract

The rising prevalence of obesity has resulted in an increased demand for innovative and effective treatment strategies. Houttuynia cordata Thunb. (H. cordata) has demonstrated promising potential in preventing obesity. However, the mechanism underlying the anti-obesity effects of H. cordata and its bioactive component, sodium houttuybonate (SH), remains unclear. Our study reveals that SH treatment promotes the browning of inguinal white adipose tissue (iWAT) and prevents the obesity induced by a high-fat diet. SH significantly mitigates ferroptosis by upregulating glutathione peroxidase 4 (Gpx4) and decreasing malondialdehyde (MDA) levels, while also enhancing superoxide dismutase (SOD) levels. Furthermore, SH promotes the phosphorylation of AMP-activated protein kinase (AMPK), which subsequently increases the expression of nuclear factor erythroid 2-related factor 2 (NRF2) and heme oxygenase-1 (HO-1) in the iWAT. However, the effects of SH were attenuated by ML385, an Nrf2 inhibitor. Collectively, our findings suggest that SH induces iWAT browning and prevents diet-induced obesity primarily through the AMPK/NRF2/HO-1 pathway by inhibiting ferroptosis.

[Introduction] Under the existing converter station reactive power compensation scheme, the synchronous condenser only provides transient reactive power support, and the AC (Alternating Current) filter undertakes steady-state reactive power compensation and adjustment tasks, with a lack of coordination scheme between the two and insufficient economy. [Method] On the basis of ensuring the dynamic characteristics of the synchronous condenser, based on the operating characteristics of the DC (Direct Current) sending and receiving end systems, firstly, a reactive power optimization scheme for the converter station was proposed, in which the regulator was used to replace a part of the part of the AC filter capacity with the regulator, and both participated in steady state reactive power compensation. Ubsequently, a two-layer reactive power adjustment strategy for the converter station was proposed according to the sequence of actions. The first layer of reactive power adjustment was undertaken by the synchronous condenser, which was realized by adjusting the output within the range of steady state operation. The second layer of reactive power adjustment was started after the first layer of reactive power adjustment, and the AC filters were switched on group by group for reactive power adjustment until the reactive power adjustment requirement of the converter station was reached. Finally, a LCC-HVDC (Line-Commutated Converter High Voltage Direct Current) system simulation model was built in PSCAD for simulation verification. [Result] The simulation results show that the reactive power compensation scheme and the two-layer reactive power adjustment strategy proposed can optimize the number of AC filter configuration groups in the converter station, reduce the frequency of AC filter switching in the converter station. [Conclusion] The proposed scheme achieves optimization of the existing LCC-HVDC converter station reactive power compensation scheme and reactive power adjustment strategy.

Abstract Objective The aim of this study was to evaluate the impact of peer role-playing on the clinical skills performance of pediatric trainees. Methods Seventy-eight clinical medicine trainees were randomly divided into a role-playing group and a traditional teaching group, with 39 students in each group. The role-playing group alternated between the roles of clinicians and patients, while the traditional teaching group received the bedside teaching mode of verbal instruction. After two weeks traineeship, mini-Clinical Evaluation Exercise(Mini-CEX) was used to evaluate the trainees’ competence in physician-patient communication and clinical practice. A questionnaire was given to the role-playing group to assess their satisfaction with the method. Results The Mini-CEX scores showed that the role-playing group had superior clinical skills (p

In order to improve the quality of wheat noodles, the compounding gels were prepared by enzymatic hydrolysis of konjac gum and carrageenan to study its effects on quality of wheat noodle. The additions of compounding gels, salt and water were selected as single factors, and cooking, texture, and sensory properties were used as evaluation indexes to optimize the processing condition of wheat noodles by response surface and principal component analysis. The optimum formula determined as follows: based on 150 g of wheat flour as 100%, the compounding gel was 3%, salt was 1% and water was 43%. Under these conditions, the improved noodles had the best comprehensive quality, with a cooking yield of 64% and a cooking loss of 4.5%. Compared with the traditional wheat noodles, the cooking yield, hardness and chewiness of the improved noodles were increased by 3.8%, 18.6% and 2.1%, respectively, whereas the cooking loss and stickiness values decreased by 7.3% and 2.9%, respectively. The comprehensive quality of noodles was improved with sensory score increasing from 69.9 to 82.9. This study showed that enzymatic konjac gum and carrageenan compound gelling agent could be used as a noodle improver to enhance the quality of wheat noodles, and the results of the study provided a certain reference for the development of konjac gum and carrageenan compound gelling agent and its application research.

Abstract Acute myeloid leukemia (AML) is one of the most common hematological malignancy that has a high recurrence rate. FIBP was reported to be highly expressed in multiple tumor types. However, its expression and role in acute myeloid leukemia remains largely unknown. The aim of this study was to clarify the role and value of FIBP in the diagnosis and prognosis, and to analyze its correlation with immune infiltration in acute myeloid leukemia by The Cancer Genome Atlas (TCGA) dataset. FIBP was highly expressed in AML samples compared to normal samples. The differentially expressed genes were identified between high and low expression of FIBP. The high FIBP expression group had poorer overall survival. FIBP was closely correlated with CD4, IL-10 and IL-2. The enrichment analysis indicated DEGs were mainly related to leukocyte migration, leukocyte cell–cell adhesion, myeloid leukocyte differentiation, endothelial cell proliferation and T cell tolerance induction. FIBP expression has significant correlation with infiltrating levels of various immune cells. FIBP could be a potential targeted therapy and prognostic biomarker associated with immune infiltrates for AML.

This study proposes an empirical ensemble equating (3E) approach that collectively selects, adopts, weighs, and combines outputs from different sources to take and combine advantage of equating techniques in various score intervals. The ensemble idea was demonstrated and tailored to the Non-Equivalent groups with Anchor Test (NEAT) equating. A simulation study based on several published settings was conducted. Three outcome measures – average bias, its absolute value, and root mean square difference – were used to evaluate the selected methods’ performance. The 3E approach outperformed other counterparts in most given conditions, while the cautions, such as tuning weights and assuming possible scenarios for using the proposed approach were also addressed.

Abstract Background Experimental and epidemiological studies have indicated an association between diabetes exposure and an increased risk of liver cancer due to nonalcoholic steatohepatitis (NASH). However, to date, no systematic study has specifically investigated the burden of NASH-related liver cancer due to exposure to high fasting plasma glucose (HFPG) levels worldwide. Methods The number and rate of deaths and disability-adjusted life years (DALYs) from HFPG-induced NASH-related liver cancer were estimated based on the results of the 2019 Global Burden of Disease Study. The estimated annual percentage changes (EAPCs) for age-standardized death or DALYs rates were calculated using a generalized linear model with a Gaussian distribution to quantify the temporal trends in the global burden of NASH-related liver cancer attributable to HFPG. The strength and direction of the association between the sociodemographic index (SDI) and death or DALY rate were measured using Spearman’s rank-order correlation. Results Globally, approximately 7.59% of all DALY and 8.76% of all mortalities of NASH-related liver cancer in 2019 were due to HFPG. The age-standardized death and DALY rates of NASH-related liver cancer attributable to HFPG increased from 1990 to 2019. The corresponding EAPCs were 0.69 (95% UI 0.48–0.89), and 0.30 (95% UI 0.05–0.56), respectively. This increasing pattern was most obvious in the high- and low-SDI regions. The age-standardized mortality and DALYs rate of NASH-related liver cancer attributable to HFPG varies considerably worldwide, with the middle SDI region having the highest death and DALY rates in 2019 (DALY 0.96 [95% UI 0.23–2.18]; death 0.05 [95% UI 0.01–0.11]). Conclusion The burden of NASH-related liver cancer attributable to HFPG has increased over the past three decades, particularly in regions with high and low SDI.

Abstract Background Renovascular hypertension (RVH) is one of the main causes of hypertensive crisis (HTN-C). It is characterized by acute onset and severe disease, and early diagnosis and treatment are difficult. The objective was to describe the characteristics of RVH and factors associated with RVH leading to HTN-C in children. At present, there are few clinical studies on RVH in children with large cases in China. Methods This study retrospectively analyzed the clinical data of inpatient children with RVH. Patients were divided into non-hypertensive crisis (non-HTN-C) group, and HTN-C group according to the first symptoms and blood pressure. Further, HTN-C were classified as hypertensive urgency (HTN-U) or hypertensive emergency (HTN-E). Results Fifty-four pediatric cases (41 boys and 13 girls) were included. 83.3% of the RVH cases were ≥ 6 years old. Three cases were classified into the non-HTN-C group. Of the 51 HTN-C cases, 18 cases were grouped as HTN-U and 33 as HTN-E. The HTN-U group were mainly asymptomatic (50.0%, 9/18) while the HTN-E group mainly presented with neurological symptoms (72.7%, 24/33). The number of unknown etiology children was 32 (59.2%). The top three known etiologies were Takayasu’s arteritis (50.0%, 11/22), congenital renal dysplasia (27.3%, 6/22) and fibromuscular dysplasia (13.6%, 3/22). As for the target organ damage of RVH, patients had a higher prevalence of left ventricular hypertrophy (71.4%, 35/49) and retinopathy (77.8%, 21/27). Conclusions Most RVH patients with HTN-C as the first symptoms, especially for males over 6 years old, should be assessed for RVH even if they were asymptomatic. Most asymptomatic patients with RVH already had target organ damage, and symptomatic patients even developed life-threatening complications. As preventive measures, routine monitoring of BP during children’s physical examinations is advised.

Abstract Atmospheric corrosion is ubiquitous in China but varies a lot among different regions covering the cold, temperate, and tropical zones. Categorizing the atmospheric corrosivity and plotting precise atmospheric corrosion map remain key interest for a variety of industries. The present work proposed an atmospheric corrosion map of China for hot-dip galvanized steels, which was constructed by inverse distance weighting (IDW) interpolation algorithm based on both the measured corrosion rates of coupons exposed at 2393 inland test stations and calculated corrosion rates from a prevalent dose-response function in 2918 sites in coastal regions. When the corrosion category was used as the criterion, the IDW interpolation algorithm of power 2 performed best. Cross-validation results confirmed that the prediction accuracy of IDW interpolation reached 85.6%. Based on the corrosion map, the categories of atmospheric corrosivity in China could be determined.

Oxidative stress induced by reactive oxygen species (ROS) is promising treatment approach for pancreatic ductal adenocarcinoma (PDAC), which is typically insensitive to conventional chemotherapy. In this study, BxPC-3 pancreatic cancer cell membrane-coated upconversion nanoparticles/ZnxMn1-xS core-shell nanoparticles (abbreviated as BUC@ZMS) were developed for tumor-targeted cancer therapy via synergistically oxidative stress and overcoming glutathione (GSH) overexpression. Using a combination of photodynamic therapy (PDT) and chemodynamic therapy (CDT), the BUC@ZMS core-shell nanoparticles were able to elicit the death of pancreatic cancer cells through the high production of ROS. Additionally, the BUC@ZMS core-shell nanoparticles could deplete intracellular GSH and increase the sensitivity of tumor cells to oxidative stress. The in vivo results indicated that BUC@ZMS nanoparticles can accumulate specifically in tumor locations and suppress PDAC without generating obvious toxicity. Thus, it was determined that the as-prepared core-shell nanoparticles would be a viable treatment option for solid malignancies.

Objectives To inform the impacts of health programmes which aimed at preventing women and children from being trapped in or returning to poverty because of illness in Yunnan, the main battlefield against poverty in China.Design The longitudinal comparative evaluation design.Data collection and analysis National and Yunnan policy documents related to maternal and child health programmes for poverty alleviation during 2015–2020 were analysed. The changes in disparities in maternal and child health system inputs, service coverage, and health outcomes between poor and non-poor areas, as well as out-of-pocket payments between poor and non-poor populations were assessed before and after 2017.Results In total 12 policies and 15 programmes related to poverty alleviation for poor women and children in Yunnan were summarised. As a result of health system strengthening in Yunnan, the densities of licensed doctors, nurses, obstetricians, midwives, township health workers and female village doctors had been increased substantially in poor areas, with the annual rates of 14.3%, 22.5%, 21.8%, 23.9%, 14.1% and 7.1% separately. Although disparities existed in some of service coverage between poor and non-poor areas, the health programmes had narrowed the gaps in utilisation of facility birth, caesarean section, prenatal screening and newborn screening across Yunnan (p

The successful large-scale cultivation of morel mushrooms (Morchella sextelata) requires a comprehensive understanding of the soil bacterial communities associated with morel-farming beds, as the interactions between fungi and bacteria play a crucial role in shaping the soil microbiome. In this study, we investigated the temporal distribution and ecological characteristics of soil bacteria associated with morel fruiting bodies at different stages, specifically the conidial and primordial stages, under two cropping regimes, non-continuous cropping (NCC) and continuous cropping (CC). Our findings revealed a significant reduction in the yield of morel primordia during the third year following 2 years of CC (0.29 ± 0.25 primordia/grid), in comparison to the NCC regime (12.39 ± 6.09 primordia/grid). Furthermore, inoculation with morel mycelia had a notable impact on soil bacterial diversity, decreasing it in the NCC regime and increasing the number of generalist bacterial members in the CC regime. The latter regime also led to the accumulation of nutrients in the soil beds, resulting in a shift from a stochastic to a deterministic process in the composition of the bacterial community, which differed from the NCC regime. Additionally, mycelial inoculation had a positive effect on the abundance of potential copiotrophic/denitrifying and N-fixing bacteria while decreasing the abundance of oligotrophic/nitrifying bacteria. Interestingly, this effect was more pronounced in the NCC regime than in the CC regime. These results suggest that the increase in potential copiotrophic/denitrifying and N-fixing bacteria facilitated the decomposition of nutrients in exogenous nutrient bags by morel mushrooms, thereby maintaining nitrogen balance in the soil. Overall, our study provides valuable insights into the interactions between morel mycelia and the associated soil bacteriome as well as the influence of different cultivation regimes on these interactions. These findings contribute to our understanding of the complex dynamics of the soil microbiome and can inform strategies for optimizing morel mushroom cultivation.

Abstract Electrical stimulation (ES), as one of the physical therapy modalities for tumors, has attracted extensive attention of researchers due to its promising efficacy. With the continuous development of material science, nanotechnology, and micro/nano processing techniques, novel electroactive nanomaterials and delicately designed devices have emerged to realize innovative ES therapies, which provide more possibilities and approaches for tumor treatment. Meanwhile, exploring the molecular biological mechanisms underlying different ES modalities affecting tumor cells and their immune microenvironment is also an unresolved hotspot emerging from the current biomedical engineering research. Focusing on the above research interests, in this review, we systematically summarized the effects of different ES parameters on the subcellular structure of tumor cells and the tumor immune microenvironment (TIME) in conjunction with the involved signaling pathways. In addition, we also reviewed the latest progress in novel self‐powered devices and electroactive nanomaterials for tumor therapy. Finally, the prospects for the development of electrostimulation tumor therapy are also discussed, bringing inspiration for the development of new physical therapy strategies in the future.

Targeted and controlled nitric oxide (NO) release is critical due to an extremely short half life and low bioavailability for treating cardiovascular diseases. To address this challenge, various sustained‐release precursors and NO donors activated by light, enzyme, or pH are developed. However, their efficacy is limited by the deep location and rapid blood flow of the heart. Herein, a platelet membrane‐coated nanoparticle (B‐P@PLT) is designed with a polymeric core loaded with BNN6, an ultrasound‐responsive NO donor, for the targeted treatment of myocardial ischemia reperfusion injury (MIRI). B‐P@PLT can specifically target the ischemic myocardium and release NO during ultrasound (US) irradiation, thereby increasing the local concentration of NO. B‐P@PLT + US shows promising results in promoting angiogenesis, reducing reactive oxygen species production, protecting cardiomyocytes both in vitro and in vivo, and ultimately decreasing cardiac injury and improving heart function in MIRI mice. These findings demonstrate a simple and noninvasive strategy for targeted delivery and controlled release of NO, highlighting its potential therapeutic application in MIRI.

Abstract Long non-coding RNAs (lncRNAs) is known to play vital roles in modulating tumorigenesis. We previously reported that LCAT1, a novel lncRNA, promotes the growth and metastasis of lung cancer cells both in vitro and in vivo. However, the underlying mechanism(s) of LCAT1 as an oncogenic regulator remains elusive. Here, we showed that LCAT1 physically interacts with and stabilizes IGF2BP2, an m6A reader protein, by preventing its degradation via autolysosomes. IGF2BP2 is overexpressed in lung cancer tissues, which is associated with poor survival of non-small cell lung cancer patients, suggesting its oncogenic role. Biologically, IGF2BP2 depletion inhibits growth and survival as well as the migration of lung cancer cells. Mechanistically, the LCAT1/IGF2BP2 complex increased the levels of CDC6, a key cell cycle regulator, by stabilizing its mRNA in an m6A-dependent manner. Like IGF2BP2, CDC6 is also overexpressed in lung cancer tissues with poor patient survival, and CDC6 knockdown has oncogenic inhibitory activity. Taken together, the LCAT1-IGF2BP2-CDC6 axis appears to play a vital role in promoting the growth and migration of lung cancer cells, and is a potential therapeutic target for lung cancer. Importantly, our finding also highlights a previously unknown critical role of LCAT1 in m6A-dependent gene regulation by preventing autolytic degradation of IGF2BP2.

C-terminal truncation of a-syn results in a more extended and exposed conformation, providing further insight into the pathological role of this truncation event in the progression of Parkinson’s disease.

Refined conditions of konjac glucomannan (KGM), physicochemical properties and structural characterization of KGM before and after refining and its blend with κ-carrageenan were explored in this study. Furthermore, the correlation between physicochemical properties of KGM and gel properties of the blend was also determined. The result showed that refined conditions of KGM were as follows: Refined ethanol concentration 60%, swelling time 2 h, swelling temperature 50 ℃. With this treatment, the glucomannan content, viscosity, brightness and whiteness of KGM were increased by 34.43%, 128.55%, 17.94% and 28.29%, respectively. Gel strength, hardness, chewiness and gumminess of its blend with κ-carrageenan were significantly increased by 47.39%, 60.47%, 55.44%, and 45.87%（P < 0.05）, respectively. The best gel properties of the blend were obtained with the enhanced hydrogen bond force, smoother and tighter gel network structure. In addition, physicochemical properties of KGM e.g. glucomannan content, viscosity, color and flavor were considered to be the key factors to improve quality of the blend gel. This study could provide an efficient and simple refined method for development of KGM and carrageenan blend with high gel strength, and lay a theoretical foundation for the industrial production of refined KGM in future.

Understanding the influence of the heavy metal cadmium (Cd) on the phyllosphere microbiome of hyperaccumulator plants is crucial for enhancing phytoremediation. The characteristics of the phyllosphere of Sedum alfredii Hance, a hyperaccumulator plant, were investigated using 16S rRNA and internal transcribed spacer amplicon sequencing of powdery mildew-infected leaves treated or untreated with Cd. The results showed that the colonization of powdery mildew caused severe chlorosis and necrosis in S. alfredii leaves, and the relative abundance of Leotiomycetes in infected leaves increased dramatically and significantly decreased phyllosphere microbiome diversity. However, S. alfredii preferentially accumulated higher concentrations of Cd in the leaves of infected plants than in uninfected plants by powdery mildew, which in turn significantly inhibited powdery mildew colonization in leaves; the relative abundance of the fungal class Leotiomycetes in infected leaves decreased, and alpha and beta diversities of the phyllosphere microbiome significantly increased with Cd treatment in the infected plants. In addition, the inter-kingdom networks in the microbiota of the infected leaves treated with Cd presented many nodes and edges, and the highest inter-kingdom modularity compared to the untreated infected leaves, indicating a highly connected microbial community. These results suggest that Cd significantly inhibits powdery mildew colonization by altering the composition of the phyllosphere microbiome in S. alfredii leaves, paving the way for efficient heavy metal phytoremediation and providing a new perspective on defense strategies against heavy metals.

AimsDiabetes mellitus (DM), one of the most common chronic diseases in China, is a risk factor for SARS-COV-2 infection and poor prognosis of COVID-19. The COVID-19 vaccine is one of the key measures to control the pandemic. However, the actual coverage of COVID-19 vaccination and associated factors remain unclear among DM patients in China. We conducted this study to investigate the COVID-19 vaccine coverage, safety, and perceptions among patients with DM in China.MethodsA cross-sectional study of a sample of 2200 DM patients from 180 tertiary hospitals in China was performed using a questionnaire developed through the Wen Juan Xing survey platform to collect information regarding their coverage, safety, and perceptions of COVID-19 vaccination. A multinomial logistic regression analysis model was performed to determine any independent relationships with COVID-19 vaccination behavior among DM patients.ResultsIn total, 1929 (87.7%) DM patients have received at least one dose COVID-19 vaccine, and 271 (12.3%) DM patients were unvaccinated. In addition, 65.2% (n = 1434) were booster vaccinated against COVID-19, while 16.2% (n = 357) were only fully vaccinated and 6.3% (n = 138) were only partially vaccinated. The prevalence of adverse effects after the first dose of vaccine, the second dose of vaccine, and the third dose of vaccine were 6.0%, 6.0%, and 4.3% respectively. Multinomial logistic regression analysis showed that DM patients complicated with immune and inflammatory diseases (partially vaccinated: OR = 0.12; fully vaccinated: OR = 0.11; booster vaccinated: OR = 0.28), diabetic nephropathy (partially vaccinated: OR = 0.23; fully vaccinated: OR = 0.50; booster vaccinated: OR = 0.30), and perceptions on the safety of COVID-19 vaccine (partially vaccinated: OR = 0.44; fully vaccinated: OR = 0.48; booster vaccinated: OR = 0.45) were all associated with the three of vaccination status.ConclusionThis study showed that higher proportion of COVID-19 vaccine coverage among patients with DM in China. The concern about the safety of the COVID-19 vaccine affected the vaccine behavior in patients with DM. The COVID-19 vaccine was relatively safe for DM patients due to all side effects were self-limiting.

An imbalance of bacteria in oral environment can lead to a variety of oral diseases, such as periodontal disease, dental caries, and peri-implant inflammation. In the long term, in view of the increasing bacterial resistance, finding suitable alternatives to traditional antibacterial methods is an important research today. With the development of nanotechnology, antibacterial agents based on nanomaterials have attracted much attention in dental field due to their low cost, stable structures, excellent antibacterial properties and broad antibacterial spectrum. Multifunctional nanomaterials can break through the limitations of single therapy and have the functions of remineralization and osteogenesis on the basis of antibacterial, which has made significant progress in the long-term prevention and treatment of oral diseases. In this review, we have summarized the applications of metal and their oxides, organic and composite nanomaterials in oral field in recent five years. These nanomaterials can not only inactivate oral bacteria, but also achieve more efficient treatment and prevention of oral diseases by improving the properties of the materials themselves, enhancing the precision of targeted delivery of drugs and imparting richer functions. Finally, future challenges and untapped potential are elaborated to demonstrate the future prospects of antibacterial nanomaterials in oral field.

Abstract Poly(l‐lactic acid) (PLLA) films have excellent piezoelectric properties, but the strong hydrophobicity of the surface makes it difficult for cells to attach there. PLLA nanofibers have good biocompatibility, but the weak piezoelectric coefficient limits the ability of the nanofibers to stimulate cell growth. Therefore, the PLLA piezoelectric film is combined with the PLLA nanofibers to make a multilayer film. In our tests, the piezoelectric output of the multilayer film ≈260 mV. In the biological experiments section, without piezoelectric stimulation, the cell length on the nanofibers is approximately twice that of the cells in the blank control group. The length of cells cultured on piezoelectric‐based stimulated nanofibers is more than twice that of cells cultured on nanofibers without piezoelectric stimulation. Therefore, it is confirmed that under the dual action of nanofiber guidance and piezoelectric stimulation, the growth rate of cells is four times faster than that in ordinary Petri dishes. Intracellular calcium imaging experiments confirmed that the concentration of Ca2+ in electrically stimulated cells is approximately twice that of ordinary cells. It is also confirmed that piezoelectric materials can complete electrical stimulation of cells in indirect contact with cells.

ObjectiveMotor recovery is crucial in stroke rehabilitation, and acupuncture can influence recovery. Neuroimaging and machine learning approaches provide new research directions to explore the brain functional reorganization and acupuncture mechanisms after stroke. We applied machine learning to predict the classification of the minimal clinically important differences (MCID) for motor improvement and identify the neuroimaging features, in order to explore brain functional reorganization and acupuncture mechanisms for motor recovery after stroke.MethodsIn this study, 49 patients with unilateral motor pathway injury (basal ganglia and/or corona radiata) after ischemic stroke were included and evaluated the motor function by Fugl–Meyer Assessment scores (FMA) at baseline and at 2-week follow-up sessions. Patients were divided by the difference between the twice FMA scores into one group showing minimal clinically important difference (MCID group, n = 28) and the other group with no minimal clinically important difference (N-MCID, n = 21). Machine learning was performed by PRoNTo software to predict the classification of the patients and identify the feature brain regions of interest (ROIs). In addition, a matched group of healthy controls (HC, n = 26) was enrolled. Patients and HC underwent magnetic resonance imaging examination in the resting state and in the acupuncture state (acupuncture at the Yanglingquan point on one side) to compare the differences in brain functional connectivity (FC) and acupuncture effects.ResultsThrough machine learning, we obtained a balance accuracy rate of 75.51% and eight feature ROIs. Compared to HC, we found that the stroke patients with lower FC between these feature ROIs with other brain regions, while patients in the MCID group exhibited a wider range of lower FC. When acupuncture was applied to Yanglingquan (GB 34), the abnormal FC of patients was decreased, with different targets of effects in different groups.ConclusionFeature ROIs identified by machine learning can predict the classification of stroke patients with different motor improvements, and the FC between these ROIs with other brain regions is decreased. Acupuncture can modulate the bilateral cerebral hemispheres to restore abnormal FC via different targets, thereby promoting motor recovery after stroke.Clinical trial registrationhttps://www.chictr.org.cn/showproj.html?proj=37359, ChiCTR1900022220.

Abstract Objective To investigate the clinical characteristics of patients with multiple endocrine neoplasia type 1 (MEN1)-related insulinoma and their relationship with specific biochemical changes and to summarize the features of treatment options for the Chinese population with this disease and the impact on long-term prognosis. Methods “MEN1” and “insulinoma” were used when searching the Peking Union Medical College Hospital (PUMCH) medical record retrieval system to obtain clinical information about patients. We identified patients diagnosed with MEN1-associated insulinoma based on endocrinological, radiological, and pathological examinations, and subsequently analyzed their clinical data. Results A total of 55 patients with MEN1-associated insulinoma were included, including 29 (52.7%) men and 26 (47.3%) women. The parathyroid gland was the most commonly affected (78.2%), followed by the pituitary gland (69.1%) and adrenal gland (16.4%). Insulinoma was the first manifestation of MEN1 in at least 23.6% (13/55) of patients. Nineteen (34.5%) patients presented with initial symptoms of hypoglycemia before the age of 22 years. Among the 24 Patients with high serum calcium (Ca) had significantly lower serum insulin levels than those with normal serum Ca levels (p

The molecular mechanisms underlying cervical carcinogenesis following integration of HPV DNA into the human genome remain elusive. Here, the authors perform long-read sequencing in 16 HPV16-positive cervical tumors and identify distinct integration types, structural variations and potential driver genes.

Abstract Background Abnormal expression of long non-coding RNAs (lncRNAs) has been shown to be associated with the pathogenesis of cancers, including colorectal cancer (CRC). It has been reported that LINC00022 is highly expressed in some typs of cancer and its overexpression indicates poor prognosis. The function of LINC00022 in CRC progression remains unclear and is mainly investigated in the present study. Methods LINC00022 expression in CRC tissues was analyzed by using the TNMplot software. LINC00022 expression in CRC cells was measured by quantitative real-time PCR. The effects of LINC00022 on the malignant behaviors of CRC cells were detected by a series of in vitro and in vivo experiments. Dual-luciferase assays were used to verify the targeting relationship between LINC00022 and miR-375-3p and between miR-375-3p and Forkhead box F1 (FOXF1), followed by the rescue experiment. Results LINC00022 was highly expressed in CRC tissues compared with paired para-carcinoma tissues (n = 41). CRC cells with LINC00022 knockdown exhibited decreased cell proliferation, migration, and invasion abilities but increased apoptosis accompanied by decreased protein levels of c-Myc, cyclin D1, cleaved caspase 3, cleaved poly(ADP-ribose) polymerase, matrix metalloproteinase (MMP) 2, and MMP9. Additionally, LINC00022 downregulation in CRC cells suppressed the tube formation of human umbilical vein endothelial cells (HUVECs) as evidenced by decreased vascular endothelial growth factor A levels in LINC00022-silenced cells. The inhibitory effect of LINC00022 knockdown on tumor growth was also observed in an in vivo model. Conversely, LINC00022 overexpression showed that opposite effect. We further demonsrtaed that LINC00022 could upregulate FOXF1 expression through sponging miR-375-3p. Moreover, miR-375-3p knockdown reversed the effects of LINC00022 down-regulation. Conclusions LINC00022 may up-regulate FOXF1 expression via competitively binding miR-375-3p, thereby promoting the development of CRC.