Search

Abstract Coronavirus disease 2019 (COVID‐19) pandemic has caused millions of deaths. The risk of COVID‐19 spreading still exists after the deconfinement act, Omicron became the dominant variant. Although N6‐methyladenosine (m6A) regulators has been reported to affect the pathogenicity of COVID‐19, their mechanism in the progression of lung injury in COVID‐19 patients remain elusive. Here we show the landscape and specific mechanisms of m6A regulators in lung tissues through single‐nucleus RNA sequencing (snRNA‐Seq) data sets of 116,252 cells, and the external validation was performed using data from another snRNA‐Seq data. The m6A reader IGF2BP2 was specifically upregulated in alveolar type I (AT1) cells, resulting in impaired lung regeneration. ALKBH5 expression upregulation in macrophages, impairing immune responses. Moreover, WTAP markedly upregulated in fibroblasts, leading to pulmonary fibrosis. In addition, m6A regulators dysregulation induced aberrant cell–cell communication in pulmonary tissue and mediated ligand–receptor interactions across diverse cell types in lung tissues by activating the TGF‐β signaling pathway. Overall, these results indicated that the upregulation of m6A regulators in alveolar cells, myeloid cells, and fibroblasts may induce pulmonary injury in patients. The development of m6A‐regulator inhibitors could be as one potential antifibrotic drugs for COVID‐19.

IntroductionMicrobial pathogens invade various human organs, including the oral cavity. Candida albicans (C.a) and Streptococcus mutans (S.m) served respectively as representative oral pathogenic fungi and bacteria to stimulate dental pulp stem cells (DPSCs) and to screen the DPSC subcluster that specifically responded to fungal infection.MethodsDPSCs were obtained from the impacted third molars of six healthy subjects. Then, cells were mixed and divided into three samples, two of which were stimulated with C.a and S.m, respectively; the third sample was exposed to cell medium only (Ctrl). Single-cell mRNA sequencing analysis of treated DPSCs was performed.ResultsDPSCs were composed of four major clusters of which one, DPSC.7, exhibited unique changes compared to those of other subclusters. The DPSC.7 cell percentage of the C.a sample was twice those of the Ctrl and S.m samples. DPSC.7 cells expressed genes associated with the response to reactive oxygen species (ROS) response. DPSC.7 subgroup cells established characteristic aggregation under the stimulation of different pathogens in UMAP. The MAPK/ERK1/2 and NF-κB pathways were up-regulated, DUSP1/5/6 expressions were suppressed, FOS synthesis was activated, the immune-related pathway was induced, and the levels of cytokines, including IL-6 and CCL2, were up-regulated in DPSC.7 cells when stimulated with C.a.ConclusionsOur study analyzed the cellular and molecular properties of DPSCs infected by oral fungi and bacteria with single-cell RNA sequencing. A subcluster of DPSCs responded specifically to infections with different pathogens, activating the MAPK and NF-κB pathways to induce immune responses via the ROS pathway. This suggests novel treatment strategies for fungal infections.

The brain has traditionally been considered an “immune-privileged” organ lacking a lymphatic system. However, recent studies have challenged this view by identifying the presence of the glymphatic system and meningeal lymphatic vessels (MLVs). These discoveries offer new opportunities for waste clearance and treatment of central nervous system (CNS) diseases. Various strategies have been developed based on these pathways, including modulation of glymphatic system function, enhancement of meningeal lymphatic drainage, and utilization of these routes for drug delivery. Consequently, this review explores the developmental features and physiological roles of the cerebral lymphatic system as well as its significance in various CNS disorders. Notably, strategies for ameliorating CNS diseases have been discussed with a focus on enhancing glymphatic system and MLVs functionality through modulation of physiological factors along with implementing pharmacological and physical treatments. Additionally, emphasis is placed on the potential use of the CNS lymphatic system in drug delivery while envisioning future directions in terms of mechanisms, applications, and translational research.

Abstract Metabolic factors play a critical role in the development of digestive system cancers (DSCs), and East Asia has the highest incidence of malignant tumors in the digestive system. We performed a two-sample Mendelian randomization analysis to explore the associations between 19 metabolism-related lifestyle and clinical risk factors and DSCs, including esophageal, gastric, colorectal, hepatocellular, biliary tract, and pancreatic cancer. The causal association was explored for all combinations of each risk factor and each DSC. We gathered information on the instrumental variables (IVs) from various sources and retrieved outcome information from Biobank Japan (BBJ). The data were all from studies of east Asian populations. Finally, 17,572 DSCs cases and 195,745 controls were included. Our analysis found that genetically predicted alcohol drinking was a strong indicator of gastric cancer (odds ratio (OR) = 0.95; 95% confidence interval (CI): 0.93–0.98) and hepatocellular carcinoma (OR = 1.11; 95% CI: 1.05–1.18), whereas coffee consumption had a potential protective effect on hepatocellular carcinoma (OR = 0.69; 95% CI: 0.53–0.90). Triglyceride was potentially associated with a decreased risk of biliary tract cancer (OR = 0.53; 95% CI: 0.34–0.81), and uric acid was associated with pancreatic cancer risk (OR = 0.59; 95% CI: 0.37–0.96). Metabolic syndrome (MetS) was associated with esophageal and gastric cancer. Additionally, there was no evidence for a causal association between other risk factors, including body mass index, waist circumference, waist-to-hip ratio, educational levels, lipoprotein cholesterol, total cholesterol, glycine, creatinine, gout, and Graves’ disease, and DSCs. The leave-one-out analysis revealed that the single nucleotide polymorphism (SNP) rs671 from the ALDH2 gene has a disproportionately high contribution to the causal association between alcohol drinking and gastric cancer and hepatocellular carcinoma, as well as the association between coffee consumption and hepatocellular carcinoma. The present study revealed multiple metabolism-related lifestyle and clinical risk factors and a valuable SNP rs671 for DSCs, highlighting the significance of metabolic factors in both the prevention and treatment of DSCs.

Abstract Purpose To explore a novel biopsy scheme for prostate cancer (PCa), and test the detection rate and pathological agreement of standard systematic (SB) + targeted (TB) biopsy and novel biopsy scheme. Methods Positive needles were collected from 194 patients who underwent SB + TB (STB) followed by radical prostatectomy (RP). Our novel biopsy scheme, targeted and regional systematic biopsy (TrSB) was defined as TB + regional SB (4 SB-needles closest to the TB-needles). The McNemar test was utilized to compare the detection rate performance for clinical significant PCa (csPCa) and clinical insignificant PCa (ciPCa). Moreover, the accuracy, positive predictive value (PPV) and negative predictive value (NPV) were investigated. The agreement between the different biopsy schemes grade group (GG) and RP GG were assessed. The concordance between the biopsy and the RP GG was evaluated using weighted κ coefficient analyses. Results In this study, the overall detection rate for csPCa was 83.5% (162 of 194) when SB and TB were combined. TrSB showed better NPV than TB (97.0% vs. 74.4%). Comparing to STB, the TB-detection rate of csPCa had a significant difference (p 0.999). For ciPCa, the overall detection rate was 16.5% (32 of 194). TrSB showed better PPV (96.6% vs. 83.3%) and NPV (97.6% vs. 92.9%) than TB. Comparing to STB, the detection rate of both schemes showed no significant difference (p = 0.077 and p = 0.375). All three schemes GG showed poor agreement with RP GG (TB: 43.3%, TrSB: 46.4%, STB: 45.9%). Using weighted κ, all three schemes showed no difference (TB: 0.48, TrSB: 0.51, STB: 0.51). In our subgroup analysis (PI-RADS = 4/5, n = 154), all three schemes almost showed no difference (Weighted κ: TB-0.50, TrSB-0.51, STB-0.50). Conclusion Our novel biopsy scheme TrSB (TB + 4 closest SB needles) may reduce 8 cores of biopsy compared with STB (standard SB + TB), which also showed better csPCa detection rate than TB only, but the same as STB. The pathological agreement between three different biopsy schemes (TB/TrSB/STB) GG and RP GG showed no difference.

Abstract The pathogenesis of Parkinson’s disease (PD) is strongly associated with neuroinflammation, and type I interferons (IFN-I) play a crucial role in regulating immune and inflammatory responses. However, the specific features of IFN in different cell types and the underlying mechanisms of PD have yet to be fully described. In this study, we analyzed the GSE157783 dataset, which includes 39,024 single-cell RNA sequencing results for five PD patients and six healthy controls from the Gene Expression Omnibus database. After cell type annotation, we intersected differentially expressed genes in each cell subcluster with genes collected in The Interferome database to generate an IFN-I-stimulated gene set (ISGs). Based on this gene set, we used the R package AUCell to score each cell, representing the IFN-I activity. Additionally, we performed monocle trajectory analysis, and single-cell regulatory network inference and clustering (SCENIC) to uncover the underlying mechanisms. In silico gene perturbation and subsequent experiments confirm NFATc2 regulation of type I interferon response and neuroinflammation. Our analysis revealed that microglia, endothelial cells, and pericytes exhibited the highest activity of IFN-I. Furthermore, single-cell trajectory detection demonstrated that microglia in the midbrain of PD patients were in a pro-inflammatory activation state, which was validated in the 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model as well. We identified transcription factors NFATc2, which was significantly up-regulated and involved in the expression of ISGs and activation of microglia in PD. In the 1-Methyl-4-phenylpyridinium (MPP+)-induced BV2 cell model, the suppression of NFATc2 resulted in a reduction in IFN-β levels, impeding the phosphorylation of STAT1, and attenuating the activation of the NF-κB pathway. Furthermore, the downregulation of NFATc2 mitigated the detrimental effects on SH-SY5Y cells co-cultured in conditioned medium. Our study highlights the critical role of microglia in type I interferon responses in PD. Additionally, we identified transcription factors NFATc2 as key regulators of aberrant type I interferon responses and microglial pro-inflammatory activation in PD. These findings provide new insights into the pathogenesis of PD and may have implications for the development of novel therapeutic strategies.

Abstract Background Expenditure of healthcare services has been growing over the past decades. Lean and agile are two popular paradigms that could potentially contain cost and improve proficiency of the healthcare system. However no systematic review was found on leagilty in the healthcare research. This study aims at synthesizing the extant literature of leagility in the healthcare area to consolidate its potential and identify research gaps for future study in the field. Methods A systematic literature review is conducted following the PRISMA checklist approach. Studies were searched in multiple databases. The selection of articles was executed by dual-scanning of two researchers to ensure quality of data and relevance to the topic. Scientific articles published between January 1999 and November 2023 concerning leagile healthcare are analysed using Microsoft Excel and VOSviewer (version 1.6.18). Results Out of 270 articles identified from the inclusion and exclusion criteria, 24 were included in the review. A total of 11 target areas were identified in leagility applications in healthcare. Success and limiting factors of leagile healthcare were classified into macro and micro aspects and further categorized into six dimensions: policy, organization, human resources, marketing, operation management and technology. Moreover, four research gaps were revealed and suggestions were provided for future study. Conclusion Leagility in the healthcare context is still being in its infancy. Few empirical validation was found in leagile healthcare literature. Further exploration into the application of theory in various sectors under the scope of healthcare is appealed for. Standardization and modularization, leadership support, skillfulness of professionals and staff training are the factors most frequently mentioned for a successful implementation of leagility in the healthcare sector.

Abstract Takotsubo syndrome (TTS), commonly referred to as "broken heart syndrome," is a distinctive form of acute and reversible heart failure that primarily affects young to middle-aged individuals, particularly women. While emotional or physical stressors often trigger TTS, rare cases have been linked to interventional procedures for congenital heart disease (CHD). Despite its recognition, the exact causes of TTS remain elusive. Research indicates that dysregulation in autonomic nerve function, involving sympathetic and parasympathetic activities, plays a pivotal role. Genetic factors, hormonal influences like estrogen, and inflammatory processes also contribute, unveiling potential gender-specific differences in its occurrence. Understanding these multifaceted aspects of TTS is crucial for refining clinical approaches and therapies. Continued research efforts will not only deepen our understanding of this syndrome but also pave the way for more targeted and effective diagnostic and treatment strategies. In this report, we conduct an in-depth analysis of a case involving a TTS patient, examining the illness progression and treatment procedures. The aim of this analysis is to enhance the understanding of TTS among primary care physicians. By delving into this case, we aspire to prevent misdiagnosis of typical TTS cases that patients may present, thereby ensuring a more accurate diagnosis and appropriate treatment.

Abstract Anthropogenic climate change (ACC) strengthens the global terrestrial water cycle (TWC) through increases in annual total precipitation (PRCPTOT) over global land. While the increase in the average global terrestrial PRCPTOT has been attributed to ACC, it is unclear whether this is equally true in dry and wet regions, given the difference in PRCPTOT changes between the two climatic regions. Here, we show the increase in PRCPTOT in dry regions is twice as fast as in wet regions of the globe during 1961–2018 in both observations and simulations. This faster increase is projected to grow with future warming, with an intensified human-induced TWC in the driest regions of the globe. We show this phenomenon can be explained by the faster warming and precipitation response rates as well as the stronger moisture transport in dry regions under ACC. Quantitative detection and attribution results show that the global increase in PRCPTOT can no longer be attributed to ACC if dry regions are excluded. From 1961–2018, the observed PRCPTOT increased by 5.63%~7.39% (2.44%~2.80%) over dry (wet) regions, and as much as 89% (as little as 5%) can be attributed to ACC. The faster ACC-induced TWC in dry regions is likely to have both beneficial and detrimental effects on dry regions of the globe, simultaneously alleviating water scarcity while increasing the risk of major flooding.

Abstract Background A stable public health workforce plays an indispensable role in the realization of the goal of health for all. However, there is an exodus of public health workers from the Centers for Disease Control and Prevention (CDC). Given the limited evidence on the mechanisms shaping turnover intention (TI) among public health workers, the study aims to investigate the triggering mechanisms of high and low turnover intention by combining job demands, job resources, and personal resources through a set theory perspective based on the Job-Demand-Resources (JD-R) model. Methods The cross-sectional study was conducted from September 7 to 18, 2020 at district (county) level CDC in Liaoning Province, China. A total of 584 public health professionals were included. Overcommitment, effort, social respect, occupational identity, job rewards, self-efficacy, and psychological resilience were included in the study as configuration factors. The data were gathered through an online questionnaire and were analyzed using multiple regression and fuzzy-set Qualitative Comparative Analysis (fsQCA). Results Social respect (B = -0.682, P

At present, osteoarthritis stands as one of the most prevalent degenerative musculoskeletal diseases globally. The inherent lack of self-healing capacity in articular cartilage presents a considerable obstacle in treating osteoarthritis. Tissue engineering emerged as a promising strategy for the regeneration of osteochondral defects. Collagen, a primary component of bone and cartilage, stands out as a widely utilized natural material in osteochondral tissue engineering. Among various collagen types, Type I and type II collagen are notably prominent in this field. This review initially summarizes the advantageous and disadvantageous properties of type I/II collagen in osteochondral tissue engineering, proceeds to introduce their applications in this context, and concludes with a prospective outlook on the future development of type I/II collagen's applications.

Spinal cord injury (SCI) is a severe event that occurs in the central nervous system (CNS). Long noncoding RNAs (lncRNAs) have already been proven to play key roles in different diseases of the CNS. Nevertheless, the roles of messenger RNAs (mRNAs) and lncRNAs one week after SCI remain to be elucidated. We established a rat model of SCI and examined the differential levels of mRNAs and lncRNAs, and then, the differentially expressed mRNAs (DE mRNAs) and lncRNAs (DE lncRNAs) were investigated. Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of DE lncRNAs and mRNAs were subsequently carried out to explore crucial biological processes and signaling pathways. Moreover, we constructed protein–protein interaction (PPI) networks, the STRING database, and identified the 10 high degree core nodes. We also established a co-expression network by calculating the correlation between lncRNA expression profile and mRNA expression profile. The identified DE lncRNAs and DE mRNAs may potentially be critical targets for the diagnosis and treatment of SCI in the future. Abbreviations: SCI: spinal cord injury; CNS: central nervous system; YLDs: years of life lived with disability; lncRNAs: long noncoding RNAs; mRNAs: messenger RNAs; DE: differentially expressed; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; GSEA: gene set enrichment analysis; RIN: Renewable Identification Number; PCA: principal component analysis; PPI: protein–protein interaction; MF, molecular function; BP: biological process; CC: cellular component; MCODE: molecular complex detection

Remote sensing observations and artificial intelligence algorithms have emerged as key components for crop yield estimation at various scales during the past decades. However, the utilization of multi-source satellite data and machine learning for estimating aggregated crop yield at the regional level in Europe has been only scarcely explored. Our study aims to bridge this research gap by focusing on the district-level spring barley yield estimation in southern Sweden from 2017 to 2022. We developed an estimation method with the random forest (RF) approach using four satellite-derived products along with two climate variables. These variables were used individually and in combinations as inputs for the RF approach. The results showed that vegetation indices (VIs) outperformed solar-induced chlorophyll fluorescence (SIF) in barley yield estimation, while combining VIs and SIF variables achieved the highest model performance (R2 = 0.77, RMSE = 488 kg/ha). The inclusion of climate variables generally had little added contributions to the model performance. Importantly, barley yield prediction could be achieved two months prior to harvest, using monthly VIs and SIF data from April and May. Our study demonstrated the feasibility of using freely accessible satellite data and the machine learning approach for estimating crop yield at the pan-European regional level. We expect that our proposed methodology can be extended to different crop types and regional-scale crop yield estimation in Europe, benefiting national and local authorities in making agricultural productivity decisions.

PurposeThe development of multiple system diseases is increased by obesity. However, the connection between obesity and developmental disabilities (DDs) in children is unclear. As an obesity index, the weight-adjusted waist index (WWI) assessed fat distribution and muscle mass. In this study, we examined the correlation between WWI and DDs among children 6 to 17 years of age.MethodsThis study used data from the National Health and Nutrition Examination Survey database (NHANES) covering 2003 to 2018, which included the data of 17,899 participants between 6 and 17 years of age. Data regarding their waist circumference, weight, and DDs were collected via physical examinations and questionnaire, respectively. A person’s WWI is calculated by dividing their waist circumference by their weight squared. The correlation between WWI and DDs was studied using weighted multiple logistic regression models. Additionally, a sensitivity analysis was conducted utilizing a generalized additive model and smooth curve fitting.ResultsAfter adjusting for all covariates, WWI was positively related to DDs in children ages 6-17. Based on the sensitivity analysis, the correlation between the WWI and prevalence of DDs remained consistent across subgroups. Additionally, there was a J-shaped correlation between the WWI and the prevalence of DDs in children ages 6 through 11.ConclusionChildren 6–17 years of age with a high WWI were at greater risk for DDs; however, the causal relationships and potential mechanisms require further exploration.

Background/purpose(s)The continuously increasing carbapenem resistance within Enterobacterales and Pseudomonas poses a threat to public health, nevertheless, the molecular characteristics of which in southern China still remain limited. And carbapenemase identification is a key factor in effective early therapy of carbapenem-resistant bacteria infections. We aimed to determine the molecular characteristics of these pathogens and compare commercial combined disc tests (CDTs) with the modified carbapenem inactivation method (mCIM) and EDTA-CIM (eCIM) in detecting and distinguishing carbapenemases using whole genome sequencing (WGS).MethodsA total of 78 Enterobacterales, 30 Pseudomonas were obtained from two tertiary hospitals in southern China. Susceptibility tests were conducted using an automated VITEK2 compact system with confirmation via the Kirby–Bauer method. The WGS was conducted on all clinical isolates and the molecular characteristics were analyzed by screening the whole genome sequences. CDTs with or without cloxacillin, mCIM, and eCIM, were performed and compared by taking WGS results as the benchmark.ResultsA total of 103 carbapenem non-susceptible and 5 carbapenem susceptible bacteria were determined, with Klebsiella pneumoniae (42.7%), Pseudomonas aeruginosa (23.3%) and Escherichia coli (18.4%) being most prevalent. Carbapenemase genes were detected in 58 (56.3%) of the 103 carbapenem-non-susceptible clinical isolates, including 46 NDM, 6 KPC, 3 IMP, 1 IPM+VIM,1NDM+KPC, and 1 OXA-181. Carbapenemase-producing isolates were detected more frequently in Enterobacterales (76.3%). Among K. pneumoniae, the major sequence types were st307 and st11, while among E. coli and P. aeruginosa, the most prevalent ones were st410 and st242 respectively. For carbapenemase detection in Enterobacterales, the mCIM method achieved 100.00% (95% CI, 92.13–100.00%) sensitivity and 94.44% (70.63–99.71%) specificity (kappa, 0.96); for Pseudomonas, detection sensitivity was 100% (5.46–100.00%), and 100% (84.50–100.00%) specificity (kappa, 0.65). Commercial CDT carbapenemase detection sensitivity for Enterobacterales was 96.49% (86.84–99.39%), and 95.24% (74.13–99.75%) specificity (kappa, 0.90); for Pseudomonas, carbapenemase detection sensitivity was 100.00% (5.46–100.00%) and 37.93% (21.30–57.64%) specificity (kappa, 0.04). When cloxacillin testing was added, CDT specificity reached 84.61% (64.27–94.95%).ConclusionThe molecular epidemiology of carbapenem-non-susceptible isolates from pediatric patients in Southern China exhibited distinctive characteristics. Both the mCIM–eCIM combination and CDT methods effectively detected and differentiated carbapenemases among Enterobacterales isolates, and the former performed better than CDT among Pseudomonas.

ABSTRACT This study aims to elucidate additional mutation loci associated with fluoroquinolone (FQ) resistance and evaluate the discriminatory capacity of mutation loci and allele mutation frequencies in identifying FQ-resistant Mycobacterium tuberculosis (MTB) isolates. A random selection of isolates was extracted from an ongoing collection. Drug resistance was determined using the resazurin microtiter assay (REMA) as the gold standard. Mutation loci and the burden of mutations in the quinolone resistance-determining region (QRDR) were elucidated through whole-genome sequencing (WGS). Novel amino acid mutations, namely, G520D and G520T, were identified in the gyrB and associated with FQ resistance. In the context of distinguishing FQ-resistant isolates, the AUC for the QRDR mutation frequency burden (0.969) surpassed that of the mutation locus (0.929), and this difference was statistically significant (P = 0.03). Furthermore, using the resistance mutation locus as a reference, setting the QRDR mutation frequency burden threshold at 1.31% resulted in a 3.60% increase in the accuracy of classifying FQ-resistant isolates (NRI = 3.60%, P < 0.001). The QRDR mutation frequency burden appears to offer superior diagnostic efficacy in discriminating FQ-resistant isolates compared to qualitative detection of mutant loci.IMPORTANCEFluoroquinolone (FQ) drugs are recommended as second-line drugs for the treatment of multidrug-resistant tuberculosis. With the massive use of FQ drugs in the clinical treatment of tuberculosis (TB), there is an increasing rate of drug resistance to FQ drugs. In this study, we identified and demonstrated novel amino acid mutations associated with FQ resistance in Mycobacterium tuberculosis (MTB), and we quantified the mutation sites and identified the quinolone resistance-determining region (QRDR) mutation frequency burden as a novel diagnostic method for FQ resistance. We hope that the results of this study will provide data support and a theoretical basis for the rapid diagnosis of FQ-resistant MTB.

Colorectal cancer is one of the most common malignancies and ranks second in terms of cancer-related mortality worldwide due to its metastasis, drug resistance, and reoccurrence. High-mobility gene group A2 (HMGA2) is overexpressed in colorectal cancer, contributing to the aggressiveness of tumor malignance, and promotes drug resistance in many types of cancer. However, the underlying molecular mechanism of HMGA2 is yet to be elucidated. In this study, we showed that HMGA2 is overexpressed in colorectal cancer tissue, and knockdown of HMGA2 significantly inhibited colorectal cancer cell growth and migratory capability. HMGA2 regulates the cancer cell response to a widely used anti-cancer drug, paclitaxel (PTX). HMGA2 knockdown increased cell death, whereas HMGA2 overexpression decreased cell death after PTX treatment. Furthermore, lower reactive oxygen species (ROS) levels and mitochondrial potential were detected in HMGA2 overexpression cells after PTX treatment. However, HMGA2 knockdown produced the opposite effect. RNA sequencing showed a p53 signaling pathway-dependent regulation in HMGA2 knockdown cells. Combined with p53 inhibitors and HMGA2 knockdown, a synergetic effect of more cell death was observed in colorectal cancer cells after PTX treatment. Thus, we showed that HMGA2 can activate p53 signaling to regulate colorectal cancer cell death after PTX treatment. Altogether, our results reveal novel insights into the molecular mechanisms underlying HMGA2-mediated cancer cell resistance against PTX and highlight the potential of targeting HMGA2 and p53 signaling for the therapeutic investigation of colorectal cancer.

Abstract Background The shortage of public health personnel and the uneven distribution between urban and rural areas are thorny issues in China. Master of public health (MPH) is an integral part of public health human resources in the future, and it is of far-reaching significance to discuss their work preferences. The present study wants to investigate the job preference of MPH, understand the relative importance of different job attributes, and then put forward targeted incentive measures. Methods Discrete choice experiment (DCE) was used to evaluate the job preference of MPHs in two medical colleges in Liaoning Province. Attributes include employment location, bianzhi, working environment, career development prospects, work value and monthly income. Thirty-six choice sets were developed using a fractional factorial design. Mixed logit models were used to analysis the DCE data. Results The final sample comprised 327 MPHs. All the attributes and levels included in the study are statistically significant. Monthly income is the most important factor for MPHs. For non-economic factors, they value career development prospects most, followed by the employment location. Respondents’ preferences are heterogeneous and influenced by individual characteristics. Subgroup analysis showed that respondents from different family backgrounds have different job preferences. Policy simulation suggested that respondents were most sensitive to a salary increase, and the combination of several non-economic factors can also achieve the same effect. Conclusions Economic factors and non-economic factors significantly affect the job preference of MPHs. To alleviate the shortage and uneven distribution of public health personnel, more effective policy intervention should comprehensively consider the incentive measures of the work itself and pay attention to the individual characteristics and family backgrounds of the target object.

Abstract Ferroptosis is an iron-dependent cell death mechanism involving the accumulation of lipid peroxides. As a critical regulator, glutathione peroxidase 4 (GPX4) has been demonstrated to be downregulated in epilepsy. However, the mechanism of ferroptosis in epilepsy remains unclear. In this study, bioinformatics analysis, analysis of epilepsy patient blood samples and cell and mouse experiments revealed strong associations among epilepsy, ferroptosis, microRNA-211-5p and purinergic receptor P2X 7 (P2RX7). P2RX7 is a nonselective ligand-gated homotrimeric cation channel, and its activation mainly increases neuronal activity during epileptic seizures. In our study, the upregulation of P2RX7 in epilepsy was attributed to the downregulation of microRNA (miR)-211-5p. Furthermore, P2RX7 has been found to regulate GPX4/HO-1 by alleviating lipid peroxidation induced by suppression of the MAPK/ERK signaling pathway in murine models. The dynamic decrease in miR-211-5p expression induces hypersynchronization and both nonconvulsive and convulsive seizures, and forebrain miR-211-5p suppression exacerbates long-lasting pentylenetetrazole-induced seizures. Additionally, in this study, induction of miR-211-5p expression or genetic-silencing of P2RX7 significantly reduced the seizure score and duration in murine models through the abovementioned pathways. These results suggest that the miR-211-5p/P2RX7 axis is a novel target for suppressing both ferroptosis and epilepsy.

In the present study, we investigated the intervention effects of a purified Polygonatum cyrtonema polysaccharide (PCP) on high-fat diet (HFD)-induced atherosclerosis in male and female LDLr−/− mice. Results showed that HFD caused severe dyslipidemia, atherosclerotic lesions, oxidative damages and inflammation in male and female mice, and these effects seemed to be more pronounced in males than in females. However, the above variations could be dose-dependently reversed by PCP treatment, and the intervention effects on males were greater than those on females. Nuclear factor kappa-B (NF-κB), mitogen-activated protein kinase (MAPKs) and protein kinase B (Akt) are 3 pivotal signaling pathways mediating the development of atherosclerosis. Consistently, PCP was also found to significantly decrease the phosphorylation of p65, p38, extracellular-regulated kinase 1/2 (ERK1/2) and Akt, and increase the protein expression of inhibitor of NF-κB (IκB) in the aortas of male and female mice induced by HFD. Taken together, these findings indicated that PCP could be effective for the prevention of atherosclerosis, and the intervention effect of PCP on male mice was more obvious than that of female mice.

Abstract Background Staphylococcus aureus, one of the most prevalent opportunistic pathogens, mainly colonizes the nasal cavity and is a risk factor for severe infections. Virulence factors and accessory gene regulator (agr) are key to the severity and diversity of staphylococcal infection. In this study, we aimed to characterise S. aureus agr-types and virulence genes and correlated them with genetic background and antibiotic-resistant phenotypes. Results Agr types were identified in 704 isolates (98.5%), with only 11 isolates were negative for agr type. Most of our isolates were classified as agr type I, followed by types III, II and IV. The enterotoxin c gene (sec) was detected in 48.6% of isolates, showing the highest prevalence among the five enterotoxin genes detected. The positivity rates for the lukS/F-PV and tsst genes were 4% and 2.2%, respectively, while neither sed nor SasX were detected. ST45, ST59, ST338, ST188, ST6, ST7, ST22, ST25, ST398, and ST944 belonged to agr I group, while ST5 and ST15 belonged to agr II group. ST30 and ST1 were classified into agr III group, and ST121 was assigned into agr IV group. The tsst gene was found exclusively within agr I and III types belonging to ST7 and ST30 isolates, while the lukS/F-PV was predominantly carried by agr I type isolates primarily within CC59 and CC22 clones. Among the methicillin-resistant S. aureus (MRSA) isolates, 89.7% belonged to agr I group, and 97.8% of rifampicin-resistant or intermediate isolates were assigned to agr I group. MRSA isolates harboured more tested virulence genes compared to methicillin-susceptible S. aureus isolates. Conclusions We characterized the distributions of agr types and eight major virulence genes of 715 S. aureus isolates, and our findings revealed clear associations between agr types and STs, as well as virulence genes, and drug resistant phenotypes.

Abstract Mitochondrial DNA plays a critical role in the pathophysiological process of inflammation. However, the relationship between mitochondrial DNA copy number (mtDNA-CN) and inflammatory bowel diseases (IBD) remains poorly understood. We conducted a comprehensive Mendelian randomization (MR) using three instrumental variables (IVs) to explore the causal associations between mtDNA-CN and IBD, including Crohn's disease (CD), ulcerative colitis (UC). MR-Egger regression, weighted median, inverse-variance weighted (IVW), and weighted mode methods were used to evaluate the potential causal associations. The robustness of the IVW estimates was determined using the leave-one-out sensitivity test. A meta-analysis was conducted to pool the results from the three sets of IVs. Upon analysis, the findings of the current study revealed that genetically predicted mtDNA-CN was not associated with IBD (CD + UC) and UC. The results of MR analyses between mtDNA-CN and CD risk were inconsistent by using three sets of IVs. After a meta-analysis, we found that genetically predicted mtDNA-CN was associated with CD risk (odds ratio = 2.09; 95% confidence interval: 1.37–3.18). This finding was also confirmed by multivariable MR analyses and remained robust when tested with the leave-one-out sensitivity test. In conclusion, genetically predicted mtDNA-CN was found to be associated with CD risk. Therefore, mtDNA levels in the blood could potentially be used as a marker for CD risk assessment. Further studies are needed to elucidate the underlying mechanisms and validate the results of this study.

Healthcare researchers are increasingly utilizing smartphone sensor data as a scalable and cost-effective approach to studying individualized health-related behaviors in real-world settings. However, to develop reliable and robust digital behavioral signatures that may help in the early prediction of the individualized disease trajectory and future prognosis, there is a critical need to quantify the potential variability that may be present in the underlying sensor data due to variations in the smartphone hardware and software used by large population. Using sensor data collected in real-world settings from 3000 participants’ smartphones for up to 84 days, we compared differences in the completeness, correctness, and consistency of the three most common smartphone sensors—the accelerometer, gyroscope, and GPS— within and across Android and iOS devices. Our findings show considerable variation in sensor data quality within and across Android and iOS devices. Sensor data from iOS devices showed significantly lower levels of anomalous point density (APD) compared to Android across all sensors (p < 1 × 10−4). iOS devices showed a considerably lower missing data ratio (MDR) for the accelerometer compared to the GPS data (p < 1 × 10−4). Notably, the quality features derived from raw sensor data across devices alone could predict the device type (Android vs. iOS) with an up to 0.98 accuracy 95% CI [0.977, 0.982]. Such significant differences in sensor data quantity and quality gathered from iOS and Android platforms could lead to considerable variation in health-related inference derived from heterogenous consumer-owned smartphones. Our research highlights the importance of assessing, measuring, and adjusting for such critical differences in smartphone sensor-based assessments. Understanding the factors contributing to the variation in sensor data based on daily device usage will help develop reliable, standardized, inclusive, and practically applicable digital behavioral patterns that may be linked to health outcomes in real-world settings.

The interaction between woody plants and mycorrhizal fungi is an important biological interaction; however, the driving factors behind the diversity of mycorrhizal trees formed through the symbiosis of mycorrhizal fungi and woody plants remain unclear. In this study, we collected and compiled the woody plant data of 34 forest dynamic plots containing 3350 species from habitats around the world and divided them into AM and EcM trees. We tested the contribution of AM and EcM trees to tree diversity and its components in forest communities worldwide. Our results showed that AM trees rather than EcM trees affect the tree diversity of forest communities, and that the diversity of AM trees has a significant latitudinal gradient pattern. Climate variables, especially temperature, are strongly correlated with the diversity patterns for AM trees rather than EcM trees. Topography is the most significant factor affecting the diversity of EcM trees. Our findings highlight the importance of AM trees for the tree diversity of forest communities worldwide. Our findings have important implications for understanding the response of complex woody plant communities with different types of mycorrhizal symbiosis to climate change.

Pinus massoniana Lamb. is an evergreen conifer; however, some current-year seedlings exhibit “winter reddening” at the onset of winter. The biological significance of this reddening is unclear. We examine the physiological responses of needles during the reddening process and explore the relationships between physiological traits and seeding cold resistance. Based on needle color, we recognize non-reddened, partially reddened, and fully reddened needle stages. As reddening progresses, chlorophyll fluorescence parameters (maximum light energy conversion efficiency of photosystem II (PSII) photochemistry, PSII potential activity, effective photosynthetic quantum yield, non-photochemical and photochemical quenching coefficients, and actual quantum yield of PSII photochemistry) decrease, reducing photosynthetic efficiency. Concurrently, the proportion of regulated energy dissipation in quantum yield of PSII decreases, and that of PSII non-regulated energy dissipation increases. Antioxidant enzyme activities (catalase and peroxidase) and osmoregulatory substances (soluble sugars and proteins and proline) increase, and malondialdehyde levels and relative cell damage at 4 °C and −10 °C gradually increase. Although P. massoniana seedlings adapt to low-temperature environments as their needles redden by increasing antioxidant enzyme activities and osmoregulatory substances and by adjusting photosynthetic efficiency and light energy distribution, cell membrane damage persists. Cold resistance in P. massoniana seedlings is not fully established during winter reddening.

Petunia hybrida is an economically important ornamental plant species. Branching in ornamental plants is closely associated with their ornamental traits, and branching is a significant agronomic trait in petunia, which shapes plant architecture and production cost. Although there are few studies regarding the involvement of the SPEAR genes in lateral branch development, they are known to regulate the development of plant organs. The PhSPEAR1 gene in petunia, an ortholog of Arabidopsis SPEAR1, was isolated for study. According to the results of real-time quantitative PCR (qRT-PCR), PhSPEAR1 was primarily expressed in the roots. The fluorescence signal indicated that PhSPEAR1 was localized in the nucleus and cytoplasm. An increase in PhSPEAR1 expression was induced by cytokinin or decapitation. Overexpression of PhSPEAR1 increased lateral branches in Arabidopsis. Based on our findings, PhSPEAR1 participates significantly in the regulation of branch number in petunia.

High mobility group box 1 (HMGB1) is a nuclear DNA-binding protein with a dual role in cancer, acting as an oncogene and a tumor suppressor. This protein regulates nucleosomal structure, DNA damage repair, and genomic stability within the cell, while also playing a role in immune cell functions. This review comprehensively evaluates the biological and clinical significance of HMGB1 in cancer, including its involvement in cell death and survival, its potential as a therapeutic target and cancer biomarker, and as a prosurvival signal for the remaining cells after exposure to cytotoxic anticancer treatments. We highlight the need for a better understanding of the cellular markers and mechanisms involved in the involvement of HMGB1in cancer, and aim to provide a deeper understanding of its role in cancer progression.

Ureteral stenting is a common clinical procedure for the treatment of upper urinary tract disorders, including conditions such as urinary tract infections, tumors, stones, and inflammation. Maintaining normal renal function by preventing and treating ureteral obstruction is the primary goal of this procedure. However, the use of ureteral stents is associated with adverse effects, including surface crusting, bacterial adhesion, and lower urinary tract symptoms (LUTS) after implantation. Recognizing the need to reduce the complications associated with permanent ureteral stent placement, there is a growing interest among both physicians and patients in the use of biodegradable ureteral stents (BUS). The evolution of stent materials and the exploration of different stent coatings have given these devices different roles tailored to different clinical needs, including anticolithic, antibacterial, antitumor, antinociceptive, and others. This review examines recent advances in BUS within the last 5 years, providing an in-depth analysis of their characteristics and performance. In addition, we present prospective insights into the future applications of BUS in clinical settings.

Chronic kidney disease (CKD) is a progressive disorder characterized by structural and functional changes in the kidneys, providing a global health challenge with significant impacts on mortality rates. Extracellular vesicles (EVs), are vital in the physiological and pathological processes associated with CKD. They have been shown to modulate key pathways involved in renal injury, including inflammation, fibrosis, apoptosis, and oxidative stress. Currently, the application research of EVs in the diagnosis and treatment of CKD is highly prevalent. However, there is currently a lack of standardized guidelines for their application, and various methodologies have advantages and limitations. Consequently, we present an comprehensive summary elucidating the multifaceted involvement of EVs in both physiological and pathological aspects in CKD. Furthermore, we explore their potential as biomarkers and diverse therapeutic roles in CKD. This review provides an overview of the current state of research on application of EVs in the diagnosis and therapeutic management of CKD.

Soil carbon content prediction based on hyperspectral images can achieve large-scale spatial measurement, which has the advantages of wide coverage and fast information collection, is more suitable for field data collection. However, the research on soil carbon content prediction based on hyperspectral images mainly focuses on feature extraction of spectral information, ignoring the spatial information, and cannot well reveal the intrinsic structural characteristics of data. Aiming at the lack of spatial features consideration in hyperspectral images, soil carbon content prediction methods based on multi-scale feature fusion are proposed by hyperspectral image. At the same time of extracting spectral features from hyperspectral images, the spatial information is used for the first time and a multi-scale spectral and spatial feature network (SpeSpaMN) is designed. In the SpeSpaMN, the multi-scale spectral feature network (SpeMN) is constructed to extract spectral features, the multi-scale spatial feature network (SpaMN) is constructed to extract spatial features. The two networks are fused by using the complementary relationship between different scale features to achieve soil carbon content prediction based on multi-scale feature fusion. The results showed that SpeSpaMN had the best results compared to other methods, followed by the method of SpeMN. The RPD of Inland, Aoshan Bay and Jiaozhou Bay samples based on SpeSpaMN were increased by 47.36%, 37.96% and 4.30% respectively. This paper can effectively solve the problem of the deep fusion of spatial and spectral features in the soil carbon content prediction by hyperspectral image, so as to improve the accuracy and stability of soil carbon content prediction.

Heterosis is widely used in crop production, but phenotypic dominance and its underlying causes in soybeans, a significant grain and oil crop, remain a crucial yet unexplored issue. Here, the phenotypes and transcriptome profiles of three inbred lines and their resulting F1 seedlings were analyzed. The results suggest that F1 seedlings with superior heterosis in leaf size and biomass exhibited a more extensive recompilation in their transcriptional network and activated a greater number of genes compared to the parental lines. Furthermore, the transcriptional reprogramming observed in the four hybrid combinations was primarily non-additive, with dominant effects being more prevalent. Enrichment analysis of sets of differentially expressed genes, coupled with a weighted gene co-expression network analysis, has shown that the emergence of heterosis in seedlings can be attributed to genes related to circadian rhythms, photosynthesis, and starch synthesis. In addition, we combined DNA methylation data from previous immature seeds and observed similar recompilation patterns between DNA methylation and gene expression. We also found significant correlations between methylation levels of gene region and gene expression levels, as well as the discovery of 12 hub genes that shared or conflicted with their remodeling patterns. This suggests that DNA methylation in contemporary hybrid seeds have an impact on both the F1 seedling phenotype and gene expression to some extent. In conclusion, our study provides valuable insights into the molecular mechanisms of heterosis in soybean seedlings and its practical implications for selecting superior soybean varieties.

Background: Many researchers have investigated the use of Chinese herbs to delay the progression of chronic kidney disease (CKD) through their effects on colonic microflora and microbiota-derived metabolites. However, whether FuZhengHuaYuJiangZhuTongLuo (FZHY) has effects that are similar to those of AST-120 on CKD needs to be elucidated. Methods: In this study, we compared the effects of FZHY and AST-120 on the colonic microbiota and plasma metabolites in the CKD rat model. We developed a unilateral ureteral obstruction (UUO)-induced CKD rat model and then administered FZHY and AST-120 to these model rats. Non-targeted metabolomic LC-MS analysis, 16S rRNA sequencing, and histopathological staining were performed on plasma, stool, and kidney tissues, respectively, and the joint correlation between biomarkers and metabolites of candidate bacteria was analyzed. Results: Our results showed that administering FZHY and AST-120 effectively ameliorated UUO-induced abnormal renal function and renal fibrosis and regulated the composition of microbiota and metabolites. Compared to the UUO model group, the p_Firmicutes and o_Peptostreptococcales_Tissierellales were increased, while 14 negative ion metabolites were upregulated and 21 were downregulated after FZHY treatment. Additionally, 40 positive ion metabolites were upregulated and 63 were downregulated. On the other hand, AST-120 treatment resulted in an increase in the levels of g_Prevotellaceae_NK3B31_group and f_Prevotellaceae, as well as 12 upregulated and 23 downregulated negative ion metabolites and 56 upregulated and 63 downregulated positive ion metabolites. Besides, FZHY increased the levels of candidate bacterial biomarkers that were found to be negatively correlated with some poisonous metabolites, such as 4-hydroxyretinoic acid, and positively correlated with beneficial metabolites, such as l-arginine. AST-120 increased the levels of candidate bacterial biomarkers that were negatively correlated with some toxic metabolites, such as glycoursodeoxycholic acid, 4-ethylphenol, and indole-3-acetic acid. Conclusion: FZHY and AST-120 effectively reduced kidney damage, in which, the recovery of some dysregulated bacteria and metabolites are probably involved. As their mechanisms of regulation were different, FZHY might play a complementary role to AST-120 in treating CKD.

Summary: Background: The therapeutic effectiveness of the empirical and unselected use of oral rehydration salts (ORS) on postural tachycardia syndrome (POTS) is not satisfactory in children. Therefore, looking for suitable predictors of the therapeutic effects of ORS before treatment is extremely necessary to implement individualised treatment for paediatric patients with POTS. Methods: A retrospective case-control analysis of 130 patients (aged 5–18 years) who suffered from POTS with a 3-month treatment of ORS was conducted. A nomogram model was developed in the training set (n = 87) to predict the therapeutic response to ORS. Univariate analysis and logistic regression were applied to select the most useful predictors. ROC curves were applied to evaluate the discriminative performance of the nomogram model. The nomogram was then evaluated by calibration curves and the Hosmer–Lemeshow (H-L) test. The results were further validated using 1000 bootstrap resamples. External validation was performed in an independent validation set (n = 43). Findings: Among the ten variables with significant differences between the responders and non-responders in univariate analysis, five variables were found to be independently associated factors for ORS therapeutic efficacy among POTS children in the further logistic regression, including mean corpuscular haemoglobin concentration (MCHC), mean corpuscular volume (MCV), mean arterial pressure (MAP) at the first minute of the upright position, urine specific gravity (SG), and P-wave voltage peaking ratio (PWP). The nomogram model was established in the training set (AUC 0.926 [95% CI: 0.865–0.988], yielding a sensitivity of 87.8% and a specificity of 86.8%). The calibration curves showed good agreement between the prediction of the nomogram and actual observation in both the training and validation sets. The nomogram also effectively predicted the external validation set (sensitivity 82.1%, specificity 73.3%, and accuracy 79.1%). Interpretation: We established a feasible and high-precision nomogram model to predict the efficacy of ORS, which would help implement individualised treatment for children with POTS. Funding: This study was supported by National High-Level Hospital Clinical Research Funding (Multi-centre Clinical Research Project of Peking University First Hospital) (2022CR59).

Study region: The study region was the Tuojiang River, a tributary of the upper Yangtze River. Study focus: Sediment phosphorus (P) release remains unclear in the Tuojiang River in Southwest China. The sediments were collected from the upper, middle, and lower reaches of the Tuojiang River in this study. The potential of sediment P release (percentage saturation of zero equilibrium P concentration, EPCsat) was determined by isotherm experiments. The influential factors and mechanisms on sediment P release were explored. New hydrological insights for the region: The sediment mainly acted as a source to release P. Phosphorus bound by Fe oxides (Fe-P), organic matter (OM), water temperature (T), and the P content originally adsorbed on sediment (Q0) were the most influential factors on the EPCsat. The pH, T, or disturbance had the greatest effect on the content of exchangeable P (Ex-P), organic P (Org-P), and Fe-P. FeCl3 has an inhibitory effect on sediment P release. Fe-P mainly participates in the sediment P release process. The release kinetics were well fitted to the pseudo-second-order model. These results obtained could help to understanding the P pollution status of sediment, improve our knowledge of the sediment P release mechanisms and provide significant information for further management of P pollution in sediment.

Abstract Background Cisplatin (CDDP) is a common anticancer drug whose side effects limit its clinical applications. Tannins (TA) are plant-derived polyphenols that inhibit tumor growth in different types of cancer. Here, we evaluated the anticancer effect of TA combined with CDDP on lung cancer cell lines (GLC-82 and H1299) and investigated the underlying molecular mechanism of endoplasmic reticulum (ER) stress-induced apoptosis. Methods Cell lines were treated with CDDP, TA, and CDDP + TA, and the effect of the combination was assessed using MTT assay and observed under light and fluorescence microscopes. Cell apoptosis was detected by flow cytometry, and the levels of ERS apoptosis pathway related genes were valuated by qRT-PCR and western blotting. The effects of the drug combination on the tumors of nude mice injected with H1299 cells were investigated, and the expression of key factors in the ER stress apoptotic pathway was investigated. Results The combination of CDDP and TA significantly inhibited lung cancer cell viability indicating a synergistic antitumoral effect. The mRNA and protein expression levels of key ER stress factors in the CDDP + TA group were considerably higher than those in the CDDP and TA groups, the tumor volume in tumor-bearing mice was the smallest, and the number of apoptotic cells and the protein expression levels of the key ER stress in the combination group were considerably higher. Conclusions The combination of TA and CDDP may produce synergistic antitumoral effects mediated by the PERK-ATF4-CHOP apoptotic axis, suggesting a novel adjuvant treatment for lung cancer.

Abstract Rapid economic growth has given rise to the urgent demand for more efficient waste recycling systems. An innovative smart recycling bin is proposed that automatically separates urban waste to increase the recycling rate. Over 1800 recycling waste images were collected and combined with an existing public dataset to train neural network classification models for two embedded systems, one incorporating a Jetson Nano and the other a K210 unit. The model developed reached an accuracy of 93.99% on the Jetson Nano and 94.61% on the K210. A user interface application was also designed to collect feedback from users during their interaction with the smart bin. In terms of power consumption, the system employing the Jetson Nano consumed 4.7 W, representing a 30% reduction in power consumption compared to previous work, while the K210 required just 0.89 W of power to operate. In summary, our work demonstrated a small‐scale, fully functional prototype of an energy‐efficient, high‐accuracy smart recycling bin, with the potential of commercialisation for the purpose of improving urban waste recycling.

Soil microorganisms are a crucial component of forest ecosystems because of their involvement in the decomposition of organic matter and nutrient cycling and their influence on plant growth and development. Soil type is a fundamental characteristic of soil. In the transitional forest regions from subtropical to temperate zones in China, various soil types can be found, including yellow-brown soils, brown soils, and cinnamon soils. However, the composition and distribution patterns of soil bacterial and fungal communities in different soil types remain uncertain. This study selected a 4.8-hectare plot in Baiyun Mountain Forest National Park, China. To explore the spatial distribution and ecological processes of soil microbial communities across three different soil types, Illumina sequencing was conducted. Results showed that the composition and assembly of bacterial and fungal communities varied substantially among different soil types. Bacteria were more influenced by environmental factors than fungi. Fungal communities consistently demonstrated greater stability compared to bacterial communities across the three soil types. Light was the main environmental factor driving the variation in the assembly of microbial communities among different soil types. This study demonstrates that there are differences in the composition and structure of soil microbial communities among different soil types, providing important insights into the management and sustainable development of soil microorganisms in temperate forests.

Tumors of the central nervous system (CNS) are severe and refractory diseases with poor prognosis, especially for patients with malignant glioblastoma and brain metastases. Currently, numerous studies have explored the potential role of bacteria and intestinal flora in tumor development and treatment. Bacteria can penetrate the blood–brain barrier (BBB), targeting the hypoxic microenvironment at the core of tumors, thereby eliminating tumors and activating both the innate and adaptive immune responses, rendering them promising therapeutic agents for CNS tumors. In addition, engineered bacteria and derivatives, such as bacterial membrane proteins and bacterial spores, can also be used as good candidate carriers for targeted drug delivery. Moreover, the intestinal flora can regulate CNS tumor metabolism and influence the immune microenvironment through the “gut–brain axis”. Therefore, bacterial anti-tumor therapy, engineered bacterial targeted drug delivery, and intervention of the intestinal flora provide therapeutic modalities for the treatment of CNS tumors. In this paper, we performed a comprehensive review of the mechanisms and therapeutic practices of bacterial therapy for CNS tumors and discussed potential future research directions in this field.

Spinal cord injury (SCI) causes motor, sensory and automatic impairment due to rarely axon regeneration. Developing effective treatment for SCI in the clinic is extremely challenging because of the restrictive axonal regenerative ability and disconnection of neural elements after injury, as well as the limited systemic drug delivery efficiency caused by blood spinal cord barrier. To develop an effective non-invasive treatment strategy for SCI in clinic, we generated an autologous plasma exosome (AP-EXO) based biological scaffold where AP-EXO was loaded with neuron targeting peptide (RVG) and growth-facilitating peptides (ILP and ISP). This scaffold can be targeted delivered to neurons in the injured area and elicit robust axon regrowth across the lesion core to the levels over 30-fold greater than naïve treatment, thus reestablish the intraspinal circuits and promote motor functional recovery after spinal cord injury in mice. More importantly, in ex vivo, human plasma exosomes (HP-EXO) loaded with combinatory peptides of RVG, ILP and ISP showed safety and no liver and kidney toxicity in the application to nude SCI mice. Combining the efficacy and safety, the AP-EXO-based personalized treatment confers functional recovery after SCI and showed immense promising in biomedical applications in treating SCI. It is helpful to expand the application of combinatory peptides and human plasma derived autologous exosomes in promoting regeneration and recovery upon SCI treatment.

Abstract Background Early studies have shown a relationship between activities of daily living (ADL) disability and depressive symptoms in older people. However, discussions on the direction of this relationship are insufficient. The study’s objective was to assess the reciprocal relationship between ADL disability and depressive symptoms among middle-aged and older Chinese people. Method Data was collected in four waves of a nationwide survey, the China Health and Retirement Longitudinal Study (CHARLS), which was carried out in 2011, 2013, 2015, and 2018. In total, this study included 4,124 participants aged ≥ 45 years at baseline. A summing score of the eleven items for basic activities of daily living (BADL) and instrumental activities of daily living (IADL) was calculated to indicate the degree of ADL disability. The 10-item Centre for Epidemiological Studies Depression Scale (CESD-10) was adopted to measure depressive symptoms. The reciprocal relationship between ADL disability and depressive symptoms was tested by cross-lagged models. Result At baseline, 911 (22.1%) participants were classified as having difficulties with ADL, and the prevalence of depressive symptoms was 34.4% (1,418). Among middle-aged and older people in China, there was a significant reciprocal and longitudinal relationship between ADL disability and depressive symptoms. People who had difficulty with ADL faced a higher risk of depressive symptoms, and those who suffered from depressive symptoms were accompanied by an increase in ADL disability in the following years. The subgroup analysis on age also showed that ADL disability was reciprocally and longitudinally related to depressive symptoms. However, only women showed similar results in the subgroup analysis on gender. Conclusion This study shows that ADL disability is bi-directionally related to depressive symptoms in middle-aged and older Chinese people over time. The results suggest we should identify ADL disability and bad psychological conditions in time to prevent subsequent mutual damage among middle-aged and older Chinese people, a vulnerable group rising in the future.

Abstract Background The treatment of insomnia, which is the most common sleep disorder, includes drug and behavioral treatment, but each treatment measure has its limitations. So new treatment method needs to be taken to improve the treatment effect. MN supplementation is a potential promising new method for the treatment of insomnia, resulting in a rising need for methodological research towards verifying its efficacy. Methods/design We describe a proposal for a multicenter, patient-assessor-blinded, randomized controlled trial with two parallel arms. A total of 400 chronic insomnia patients will be allocated 1:1 to the intervention group (treatment with oral NMN 320 mg/day) or control group (treatment with oral placebo). All subjects are clinical chronic insomnia patients who meet all inclusion criteria. All subjects are treated by taking NMN or placebo. The primary outcome is the score on the Pittsburgh Sleep Quality Index (PSQI). Secondary outcomes are the score on the Insomnia Severity Index (ISI) and Epworth Sleeping Scale (ESS), the total sleep time (TST), sleep efficiency (SE), sleep latency, and REM sleep latency to assess sleep quality changes. Subjects are assessed at two time points: baseline and follow-up. The duration of the clinical trial is 60 days. Discussion This study will provide more evidence on the effects of NMN on improving sleep quality among patients with chronic insomnia. If proven effective, NMN supplement can be used as a new treatment for chronic insomnia in the future. Trial registration Chinese Clinical Trial Registry (chictr.org.cn) ChiCTR2200058001. Registered on 26 March 2022.

Abstract N1-Methyladenosine (m1A) is an abundant modification of transcripts, plays important roles in regulating mRNA structure and translation efficiency, and is dynamically regulated under stress. However, the characteristics and functions of mRNA m1A modification in primary neurons and oxygen glucose deprivation/reoxygenation (OGD/R) induced remain unclear. We first constructed a mouse cortical neuron OGD/R model and then used methylated RNA immunoprecipitation (MeRIP) and sequencing technology to demonstrate that m1A modification is abundant in neuron mRNAs and dynamically regulated during OGD/R induction. Our study suggests that Trmt10c, Alkbh3, and Ythdf3 may be m1A-regulating enzymes in neurons during OGD/R induction. The level and pattern of m1A modification change significantly during OGD/R induction, and differential methylation is closely associated with the nervous system. Our findings show that m1A peaks in cortical neurons aggregate at both the 5’ and 3’ untranslated regions. m1A modification can regulate gene expression, and peaks in different regions have different effects on gene expression. By analysing m1A-seq and RNA-seq data, we show a positive correlation between differentially methylated m1A peaks and gene expression. The correlation was verified by using qRT-PCR and MeRIP-RT-PCR. Moreover, we selected human tissue samples from Parkinson’s disease (PD) and Alzheimer’s disease (AD) patients from the Gene Expression Comprehensive (GEO) database to analyse the selected differentially expressed genes (DEGs) and differential methylation modification regulatory enzymes, respectively, and found similar differential expression results. We highlight the potential relationship between m1A modification and neuronal apoptosis following OGD/R induction. Furthermore, by mapping mouse cortical neurons and OGD/R-induced modification characteristics, we reveal the important role of m1A modification in OGD/R and gene expression regulation, providing new ideas for research on neurological damage.

ObjectiveTo explore the relationship between outdoor lighting and sports and the development of myopia, and to analyze the effects of outdoor lighting and exercise on the diopter of children with normal vision and myopia, so as to provide guidance for the prevention and treatment of myopia in children and adolescents in the future.MethodsA total of 201 children were divided into two groups according to myopia or not. Each group was randomly divided into 4 groups: outdoor exercise group, outdoor control group, indoor exercise group and indoor control group. Among them, the outdoor exercise group and indoor exercise group received moderate and high intensity aerobic exercise 3 times a week for 60 min each time for 12 months, while the outdoor control group and indoor control group had normal study and life during the corresponding period of time. No additional exercise intervention. At the end of the experiment, the diopter of each group was compared.ResultsThe diopter of all groups with normal vision and myopia decreased significantly after the experiment (p

Cerebral ischaemiareperfusion injury is an important pathological process in nervous system diseases during which neurons undergo oxygenglucose deprivation and reoxygenation (OGD/R) injury. No study has used epitranscriptomics to explore the characteristics and mechanism of injury. N6methyladenosine (m6A) is the most abundant epitranscriptomic RNA modification. However, little is known about m6A modifications in neurons, especially during OGD/R. m6A RNA immunoprecipitation sequencing (MeRIPseq) and RNA-sequencing data for normal and OGD/R-treated neurons were analysed by bioinformatics. MeRIP quantitative real-time polymerase chain reaction was used to determine the m6A modification levels on specific RNAs. We report the m6A modification profiles of the mRNA and circRNA transcriptomes of normal and OGD/R-treated neurons. Expression analysis revealed that the m6A levels did not affect m6A mRNA or m6A circRNA expression. We found crosstalk between m6A mRNAs and m6A circRNAs and identified three patterns of m6A circRNA production in neurons; thus, distinct OGD/R treatments induced the same genes to generate different m6A circRNAs. Additionally, m6A circRNA biogenesis during distinct OGD/R processes was found to be time specific. These results expand our understanding of m6A modifications in normal and OGD/R-treated neurons, providing a reference to explore epigenetic mechanisms and potential treatments for OGD/R-related diseases.

Abstract The relationship between High-mobility group box 1 (HMGB1) and febrile seizures (FS) in children remains unclear. This study aimed to apply meta-analysis to reveal the correlation between HMGB1 levels and FS in children. Databases including PubMed, EMBASE, Web of science, Cochrane library, CNKI, SinoMed and WanFangData were searched for relevant studies. Pooled standard mean deviation and 95% confidence interval were calculated as effect size since the random-effects model was used when I2 > 50%. Meanwhile, between-study heterogeneity was determined by performing subgroup and sensitivity analyses. A total of 9 studies were finally included. Meta-analysis showed that the children with FS had significantly higher HMGB1 levels compared with healthy children and children with fever but no seizures (P15 min were higher than those with duration ≤15min (P0.05). Finally, children with FS who converted to epilepsy exhibited higher HMGB1 levels than those who did not convert to epilepsy (P