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To address the issue of the difficulty in implementing non-invasive continuous blood pressure measurement technology in China, this study developed a high-performance synchronous electrocardiogram (ECG) and photoplethysmography (PPG) signal acquisition system. A PC-based human-computer interaction software platform was constructed, and continuous blood pressure measurement-related algorithms were integrated. Multiple feature parameters such as pulse wave transit time based on synchronous ECG and PPG signals were extracted, enabling non-invasive continuous blood pressure measurement. To verify the measurement accuracy of the system, tests and comparative verifications were carried out. The results demonstrated that the system could meet the requirements of relevant standards and have good application value.

Objective: To evaluate the protective effect and possible mechanism of dandelion jujube juice on D-galactose-induced liver injury in Sprague Dawley (SD) rats. Methods: D-galactose was intraperitoneally injected into the rats at a dose of 500 mg/kg for six weeks to establish a chronic liver injury model. These rats treated with D-galactose were then randomly divided into model group and dandelion jujube juice group (treated with 10 mL/kg·d of dandelion jujube juice by intragastric administration for 28 d). The liver index was calculated, and the pathological changes in liver tissue were observed using HE staining and oil red O staining. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in serum, malondialdehyde (MDA) content and catalase (CAT) activity in liver tissue were determined by corresponding assay kit. Western blot analysis was used to detect the protein expression, including Kelch like epichlorohydrin associated protein 1 (Keap1), nuclear factor E2 related factor 2 (Nrf2), heme oxygenase-1 (HO-1), BCL2 associated X (Bax), and B-cell lysoma-2 (Bcl-2) proteins in liver tissue. Results: Compared with the blank group, the liver index and liver lipid deposition area were increased in the model group. In addition, the model group showed a significant increase in the levels of serum ALT (P

Abstract Background Radiation-induced intestinal injury (RIII) interrupts the scheduled processes of abdominal and pelvic radiotherapy (RT) and compromises the quality of life of cancer survivors. However, the specific regulators and mechanisms underlying the effects of RIII remain unknown. The biological effects of RT are caused primarily by DNA damage, and ataxia telangiectasia mutated (ATM) is a core protein of the DNA damage response (DDR). However, whether ATM is regulated by deubiquitination signaling remains unclear. Methods We established animal and cellular models of RIII. The effects of ubiquitin-specific protease 15 (USP15) on DNA damage and radion-induced intestinal injury were evaluated. Mass spectrometry analysis, truncation tests, and immunoprecipitation were used to identify USP15 as a binding partner of ATM and to investigate the ubiquitination of ATM. Finally, the relationship between the USP15/ATM axes was further determined via subsequent experiments. Results In this study, we identified the deubiquitylating enzyme USP15 as a regulator of DNA damage and the pathological progression of RIII. Irradiation upregulates the expression of USP15, whereas pharmacological inhibition of USP15 exacerbates radiation-induced DNA damage and RIII both in vivo and in vitro. Mechanistically, USP15 interacts with, deubiquitinates, and stabilises ATM via K48-linked deubiquitination. Notably, ATM overexpression blocks the effect of USP15 genetic inhibition on DNA damage and RIII progression. Conclusions These findings describe ATM as a novel deubiquitination target of USP15 upon radiation-induced DNA damage and intestinal injury, and provides experimental support for USP15/ATM axis as a potential target for developing strategies that mitigate RIII.

Abstract Background Blocking the RhoA/ROCK II/MLC 2 (Ras homolog gene family member A/Rho kinase II/myosin light chain 2) signaling pathway can initiate neuroprotective mechanisms against neurological diseases such as stroke, cerebral ischemia, and subarachnoid hemorrhage. Nevertheless, it is not clear whether and how disrupting the RhoA/ROCK II/MLC 2 signaling pathway changes the pathogenic processes of the blood–brain barrier (BBB) after intracerebral hemorrhage (ICH). The present investigation included the injection of rat caudal vein blood into the basal ganglia area to replicate the pathophysiological conditions caused by ICH. Methods Scalp acupuncture (SA) therapy was performed on rats with ICH at the acupuncture point “Baihui”‐penetrating “Qubin,” and the ROCK selective inhibitor fasudil was used as a positive control to evaluate the inhibitory effect of acupuncture on the RhoA/ROCK II/MLC 2 signaling pathway. Post‐assessments included neurological deficits, brain edema, Evans blue extravasation, Western blot, quantitative polymerase chain reaction, and transmission electron microscope imaging. Results We found that ROCK II acts as a promoter of the RhoA/ROCK II/MLC 2 signaling pathway, and its expression increased at 6 h after ICH, peaked at 3 days, and then decreased at 7 days after ICH, but was still higher than the pre‐intervention level. According to some experimental results, although 3 days is the peak, 7 days is the best time point for acupuncture treatment. Starting from 6 h after ICH, the neurovascular structure and endothelial cell morphology around the hematoma began to change. Based on the changes in the promoter ROCK II, a 7‐day time point was selected as the breakthrough point for treating ICH model rats in the main experiment. The results of this experiment showed that both SA at “Baihui”‐penetrating “Qubin” and treatment with fasudil could improve the expression of endothelial‐related proteins by inhibiting the RhoA/ROCK II/MLC 2 signaling pathway and reduce neurological dysfunction, brain edema, and BBB permeability in rats. Conclusion This study found that these experimental data indicated that SA at “Baihui”‐penetrating “Qubin” could preserve BBB integrity and neurological function recovery after ICH by inhibiting RhoA/ROCK II/MLC 2 signaling pathway activation and by regulating endothelial cell–related proteins.

Intracerebral hemorrhage (ICH) is a non traumatic hemorrhage that occurs in a certain part of the brain. It usually leads to brain cell damage. According to a large number of experimental research, oxidative stress is an important pathophysiological processes of cerebral hemorrhage. In this paper, we aim to determine how changes in oxidative stress biomarkers indicate the damage degree of cerebral hemorrhage, and to explore and summarize potential treatments or interventions. We found that patients with cerebral hemorrhage are characterized by increased levels of oxidative stress markers, such as total malondialdehyde (MDA), F2 isoprostaglandin, hydroxynonenal, myeloperoxidase and protein hydroxyl. Therefore, the changes of oxidative stress caused by ICH on these markers can be used to evaluate and diagnose ICH, predict its prognosis, and guide preventive treatment to turn to antioxidant based treatment as a new treatment alternative.

Global warming has accelerated glacier retreat, subsequently leading to the formation of glacial lakes in high-altitude mountainous regions. These lakes represent emerging ecological water systems and could potentially pose significant hazards. Observations of these systems are constrained by their remote locations and the lack of cost-effective monitoring methods, resulting in limited understanding of their dynamics. In this study, we synchronized surveillance monitoring with in-situ water quality measurements at a typical high-altitude glacial lake on the Qinghai-Tibet Plateau. We aim to use images from surveillance cameras to estimate the turbidity parameter, a key indicator of changes in the water environment and the impacts of climate change on high-altitude ecosystems. We segmented RGB images and applied regression modeling with field-measured water turbidity data, and then used deep learning models to accurately estimates turbidity levels and their changes. Our study demonstrates the potential of RGB imagery and deep learning for the long-term, continuous, and high-resolution monitoring of water quality in remote glacial lakes. It presents a novel and cost-effective approach for monitoring these newly emerged and swiftly changing water systems at high altitudes, offering a significant advancement in tracking environmental changes in these critical high mountain regions.

IntroductionSoil acidification imperils soil health and hinders the agricultural sustainability. As being more tolerant than bacteria to soil acidification, so it would be more meaningful for agricultural management and crop yield to characterize fungal community in acidic soils and manifest its key drivers.MethodThis study investigated the composition and diversity of fungal communities and its key driving factors by collecting 90 soil samples from the acidic region of Jiaodong Peninsula China, spanning 3 × 104 km2.ResultsThe results indicated that most soil pH values ranged from 5.01 to 6.42, and the exchangeable acidity (EA) content raised significantly (p < 0.01) along with soil acidic degree increasing. However, no significant differences were found in fungal community diversity and composition among various soil samples, which were all predominantly habited with the phyla of Ascomycota and Basidiomycota. Results of the linear discriminant analysis effect size (LEfSe) analysis revealed that saprophytic fungi were biomarkers of the slightly acidic soil (pH 6.0–6.5), including Nectriaceae, Thielavia, Nectria, Haematonectria, and unclassified Microascaceae, while plant pathogenic fungi, such as Didymellaceae, were biomarkers of the soils pH < 5.5. Similarly, the FUNGuild results also indicated that saprophytic fungi and pathogenic fungi were the dominant functional guilds in the investigated acidic soils, accounting for 66% of the total fungal communities. Redundancy analysis (RDA) revealed that soil pH as well as nitrate nitrogen (NO3−-N) and total nitrogen (TN) significantly associated with fungal community at the phylum level, whilst soil pH was the only factor significantly linked to individual fungal classes (p < 0.01 or 0.05). The further Mantel test analysis and structural equation modeling (SEM) suggested that, in contrast to the negative and directive driving of soil pH on fungal communities' variation, the specific plant pathogenic fungi, Gibberella and Didymellaceae, were significantly and positively associated with soil acidic characteristics (p < 0.05).DiscussionThese findings highlighted that, in addition to modulating the variation of soil fungal community, soil acidification might prime some plant pathogens development. So that, more attentions should be focused on impact of soil acidification on fungal ecology, as well as plant pathogenic fungi.

ObjectiveLimb ischemia–reperfusion injury caused by repeated tourniquet application usually leads to acute kidney injury, adversely affecting patient prognosis. This study aimed to investigate the renoprotective effect of remote ischemic preconditioning (RIPC) in patients undergoing extremity surgery with repeated tourniquet application.Methods64 patients were enrolled and randomly divided into an RIPC group and a control group, with 32 patients in each. Pretreatment was administered before surgery, and baseline characteristics were collected. Perioperative surgical characteristics, renal biomarkers, oxidative stress markers, inflammatory factors, and postoperative conditions were recorded.Results2 participant were excluded from each group, leaving 30 patients per group. There were no significant differences between the two groups regarding baseline characteristics and perioperative surgical characteristics (p > 0.05). Compared to the control group, the RIPC group showed a significant decrease in BUN and SCr at 48 h postoperatively (p

Abstract The field of semiconductor surface‐enhanced Raman scattering (SERS) substrates has experienced significant advancements, leading to a wide range of applications in several fields. However, the quest for new ultra‐sensitive semiconductor SERS materials is still of utmost importance. In this regard, an efficient and novel substrate, F4TCNQ/MoS2 heterostructure is introduced, assisted by V‐shaped aluminum anodic oxide (AAO) nanocavities with different depths. Utilizing the efficient charge transfer of organic/inorganic semiconducting heterostructure and the photoconfinement capability of the nanocavity structure of the AAO nanotemplate, excellent stability, fast sensing, enhanced Raman, and photodegradation activities are achieved. Due to its unique 3D structure, the optimized F4TCNQ/MoS2/AAO with 1500 nm depth achieves ultra‐high sensitivity detection of 9.0×10−16 M for conventional probe molecules. Furthermore, precise detection of water contaminants is observed for the first time with a V‐shaped heterostructure due to combined organic/inorganic features that differ significantly from conventional MoS2 structures or other metal/inorganic or inorganic/inorganic semiconductors. This research presents a novel and versatile strategy for SERS and demonstrates its diverse potential performance in practical applications.

The higher order structure (HOS) of monoclonal antibodies (mAbs) is an important quality attribute with strong contribution to clinically relevant biological functions and drug safety. Due to the multi-faceted nature of HOS, the synergy of multiple complementary analytical approaches can substantially improve the understanding, accuracy, and resolution of HOS characterization. In this study, we applied one- and two-dimensional (1D and 2D) nuclear magnetic resonance (NMR) spectroscopy coupled with chemometric analysis, as well as circular dichroism (CD), differential scanning calorimetry (DSC), and fluorescence spectroscopy as orthogonal methods, to characterize the impact of methionine (Met) oxidation on the HOS of an IgG1 mAb. We used a forced degradation method involving concentration-dependent oxidation by peracetic acid, in which Met oxidation is site-specifically quantified by liquid chromatography-mass spectrometry. Conventional biophysical techniques report nuanced results, in which CD detects no change to the secondary structure and little change in the tertiary structure. Yet, DSC measurements show the destabilization of Fab and Fc domains due to Met oxidation. More importantly, our study demonstrates that 1D and 2D NMR and chemometric analysis can provide semi-quantitative analysis of chemical modifications and resolve localized conformational changes with high sensitivity. Furthermore, we leveraged a novel 15N-Met labeling technique of the antibody to directly observe structural perturbations at the oxidation sites. The NMR methods described here to probe HOS changes are highly reliable and practical in biopharmaceutical characterization.

Abstract Background Gender equality and the gender income gap in medicine are long-standing global problems. Although gender-related differences have been widely studied in developed countries, they remain unclear in underdeveloped regions. In 2010, China initiated a national compulsory service program (CSP) to train qualified general practitioners in rural and remote areas. This study aimed to evaluate gender income differences for early career CSP and non-CSP (NCSP) graduates in underdeveloped areas. Methods A cohort study was conducted with 3620 CSP and NCSP graduates from four medical universities in Central and Western China. Baseline surveys and six follow-up surveys were conducted between 2015 and 2022. Incomes, including monthly mean income and proportion of performance-based income, were measured as the key outcome variables. Multivariate linear regression models were used to identify the gender income gap. Results NCSP graduates had higher average monthly incomes than CSP graduates. In the seventh year after graduation, the average monthly income for NCSP graduates was 7859 CNY while was 5379 CNY for CSP graduates. After controlling for demographic characteristics, the gender monthly income gap for CSP graduates was expanded from the fourth year (3.0%) to the sixth year (5.9%) after graduation, and that for NCSP graduates was expanded from the fifth year (11.9%) to the seventh year (16.3%) after graduation. Regarding performance-based income, it was 58.9% for NCSP graduates and 45.8% for CSP graduates in the seventh year after graduation. After controlling for performance-based income proportion, the gender income gap was reduced from 5.9 to 4.0% in the sixth year after graduation for CSP graduates, and from 16.3 to 14.4% for NCSP graduates in the seventh year after graduation. Conclusion An extensive and ever-increasing gender income gap exists among young doctors in the early stages of their careers in underdeveloped areas of China. The high proportion of performance-based income among men is one of the main explanations for the observed difference. A more explicit compensation system must be established to enhance support for female health workers.

Abstract Objectives This study aims to describe the differences in body composition among different body parts of the elderly in the community and its relationship with sarcopenia. Methods Elderly people aged ≥65 underwent bioelectric impedance analysis testing and were categorized into a sarcopenia group, possible sarcopenia group, and control group. The characteristics of body composition indicators in different parts and their relationship with different stages of sarcopenia were analyzed. Results The sarcopenia group illustrated the lowest values of FFM, FFM%, BFM, BFM%, ICW, and limb PhA, along with higher ECW/TBW in the trunk and left leg compared to the control group. The possible sarcopenia group showed lower FFM% in limbs and trunk, and higher BFM% compared to the control group. Gender differences in elderly body composition were observed, with an increase in BFM% in various body parts posing a risk factor for possible sarcopenia in elderly males, whereas an increase in BFM% except in the left arm was a protective factor for sarcopenia in elderly females. Conclusion The body composition of the elderly in the community varied significantly in different stages of sarcopenia and genders, which correlated with sarcopenia.

Abstract. Objectives. This study aims to not only investigate the prevalence of social alienation among elderly patients undergoing radical prostatectomy for prostate cancer but also identify the contributing factors. Materials and methods. A total of 245 elderly patients diagnosed with prostate cancer and undergoing radical prostatectomy at a tertiary care general hospital in Jinan were included in this study. To assess the patients, several questionnaires were used. These included the General Situation Questionnaire, General Alienation Scale, Social Impact Scale, Modified Memorial Anxiety Scale for Prostate Cancer, and Perceived Social Support Scale. Pearson correlation analysis was conducted to examine the relationships between variables, whereas multiple linear regression was used to identify the factors influencing social alienation among patients who underwent radical prostatectomy. Results. Patients who underwent radical prostatectomy had a mean total score of 44.13 ± 7.24 on the Social Alienation Scale. The results of the Pearson correlation analysis indicated that social alienation showed an inverse association with social support (r = −0.627, p < 0.05) and positive associations with age, disease stigma, and anxiety (r = 0.325, 0.575, 0.421, all p’s < 0.01) among patients who underwent radical prostatectomy. The findings from multiple linear regression analysis demonstrated that educational level, age, urinary incontinence, disease stigma, anxiety, and social support significantly influenced social alienation among elderly patients who underwent radical prostatectomy (p < 0.05). Conclusions. Elderly patients who undergo radical prostatectomy often experience social alienation. This study found that social alienation was associated with factors such as educational level, age, urinary incontinence, social support, anxiety, and disease stigma. Consequently, healthcare providers should actively monitor the degree of social alienation in elderly patients after radical prostatectomy and provide suitable psychological care to facilitate positive social reintegration and alleviate their feelings of social alienation.

Aberrant changes in the gut microbiota are implicated in many diseases, including inflammatory bowel disease (IBD). Gut microbes produce diverse metabolites that can shape the immune system and impact the intestinal barrier integrity, indicating that microbe-mediated modulation may be a promising strategy for preventing and treating IBD. Although fecal microbiota transplantation and probiotic supplementation are well-established IBD therapies, novel chemical agents that are safe and exert strong effects on the gut microbiota are urgently needed. Herein, we report the total synthesis of heudelotinone and the discovery of 5S-heudelotinone (an enantiomer) as a potent agent against experimental colitis that acts by modulating the gut microbiota. 5S-Heudelotinone alters the diversity and composition of the gut microbiota and increases the concentration of short-chain fatty acids (SCFAs); thus, it regulates the intestinal immune system by reducing proinflammatory immune cell numbers, and maintains intestinal mucosal integrity by modulating tight junctions (TJs). Moreover, 5S-heudelotinone (2) ameliorates colitis-associated colorectal cancer (CAC) in an azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced in situ carcinoma model. Together, these findings reveal the potential of a novel natural product, namely, 5S-heudelotinone, to control intestinal inflammation and highlight that this product is a safe and effective candidate for the treatment of IBD and CAC.

The concentration of end-tidal carbon dioxide is one of the important indicators for evaluating whether the human respiratory system is normal. Accurately detecting of end-tidal carbon dioxide is of great significance in clinical practice. With the continuous promotion of the localization of end-tidal carbon dioxide monitoring technology, its application in clinical practice in China has become increasingly widespread in recent years. The study is based on the non-dispersive infrared method and comprehensively elaborates on the detection principle, gas sampling methods, key technologies, and technological progress of end-tidal carbon dioxide detection technology. It comprehensively introduces the current development status of this technology and provides reference for application promotion and further improvement.

In response to climate change, the reduction of carbon emissions during agricultural production has garnered increasing global focus. This study takes high-standard farmland construction (HSFC) implemented in 2011 as the standard natural experiment and adopts the continuous differences-in-differences (DID) model to explore the impact and internal mechanism of HSFC on agricultural carbon emissions based on a panel data of 31 provinces, municipalities, and autonomous regions in China from 2003 to 2021. The results show that HSFC can effectively reduce the carbon emissions in agricultural production, and the average annual reduction can reach 53.8%. The effects of HSFC on agriculture carbon emissions could be associated with reducing agricultural fossil energy consumption and reducing agricultural chemical use. Further, the heterogeneity study shows that the carbon reduction effect of HSFC was mainly reflected in non-major grain-producing areas, while there was no significant impact in major grain-producing areas. Policymakers should unswervingly continue to promote HSFC, considering their own economic and geographical conditions. This study can provide valuable information and references for developing countries similar to China to formulate policies on agricultural carbon reduction.

Extant studies have empirically tested the main two behavior responses following ostracism: prosocial or antisocial. Few studies have investigated the relationship between ostracism and social withdrawal. According to the temporal need-threat model and the self-verification theory, the present study aimed to examine the influence mechanism of ostracism on social withdrawal, especially the mediating role of self-esteem and the moderating role of rejection sensitivity. A total of 1,315 Chinese high school students (52.6% female) completed a written questionnaire. Results showed that ostracism was positively correlated with social withdrawal. Ostracism not only directly predicted social withdrawal, but also indirectly affected social withdrawal by threatening adolescents’ self-esteem. High rejection sensitivity may help aggravate adolescents’ self-esteem threaten perceive from ostracism. Adolescents with high rejection sensitivity felt a greater threat to self-esteem when ostracized. Findings suggest a new direction for understanding individuals’ responses to ostracism.

Abstract Aloperine (ALO), a quinolizidine‐type alkaloid isolated from a natural Chinese herb, has shown promising antitumor effects. Nevertheless, its common mechanism of action and specific target remain elusive. Here, it is demonstrated that ALO inhibits the proliferation and migration of non‐small cell lung cancer cell lines in vitro and the tumor development in several mouse tumor models in vivo. Mechanistically, ALO inhibits the fusion of autophagosomes with lysosomes and the autophagic flux, leading to the accumulation of sequestosome‐1 (SQSTM1) and production of reactive oxygen species (ROS), thereby inducing tumor cell apoptosis and preventing tumor growth. Knockdown of SQSTM1 in cells inhibits ROS production and reverses ALO‐induced cell apoptosis. Furthermore, VPS4A is identified as a direct target of ALO, and the amino acids F153 and D263 of VPS4A are confirmed as the binding sites for ALO. Knockout of VPS4A in H1299 cells demonstrates a similar biological effect as ALO treatment. Additionally, ALO enhances the efficacy of the anti‐PD‐L1/TGF‐β bispecific antibody in inhibiting LLC‐derived subcutaneous tumor models. Thus, ALO is first identified as a novel late‐stage autophagy inhibitor that triggers tumor cell death by targeting VPS4A.

Rivers originating from the Himalayas play a crucial role as primary water sources for a significant proportion of the population in Asia downstream. This paper presents a comprehensive synthesis of hydrogeochemical data, incorporating major ions and trace elements from 153 papers spanning 2000 to 2023, with a detailed analysis of 20 papers specific to Nepal Himalayan rivers. To bridge the research gap due to sparse data, we aimed to enhance inclusivity by amalgamating both seasonal and one-time datasets, computing mean values for singular instances, and employing grand means for multiple seasonal data points. Our findings highlight varied research attention across different river basins, with the eastern Koshi Basin receiving extensive attention, while the middle Gandaki and Bagmati Basins garner moderate attention, and data scarcity observed in the western Karnali Basin. Predominant ionic composition, notably Ca2+ and HCO3–, reflect lithological influences, primarily driven by rock weathering. Although anthropogenic impacts remain minimal in most basins, certain lowland areas with higher population densities exhibit increasing significance. Trace element contamination, notably Cd, Cu, Sr, and Zn, poses ongoing threats, both from natural and anthropogenic sources. Water quality assessments conducted for agricultural and drinking suitability indicated good status, except in the densely polluted urban Bagmati stem. Health and ecological risks are low, as determined by pollution indices such as Pi, NPI, HI, and CI. The Bagmati River's middle segment, with high population density and moderate agricultural activity, shows pronounced anthropogenic footprints, while downstream areas exhibited greater impacts. Additionally, this article proposes the potential use of a Water Quality Index tool to comprehensively assess water quality across all parameters in Himalayan water bodies, providing a roadmap for future environmental conservation in the Himalayas. This pioneering review represents a significant effort to understand Himalayan rivers geochemistry on a large geographical scale and emphasizes the need for integrated observation and consideration of river water quality across the entire Himalayan region, from high mountains to lowlands.

IntroductionPeriodontitis, a common chronic inflammatory disease, significantly impacted oral health. To provide novel biological indicators for the diagnosis and treatment of periodontitis, we analyzed public microarray datasets to identify biomarkers associated with periodontitis.MethodThe Gene Expression Omnibus (GEO) datasets GSE16134 and GSE106090 were downloaded. We performed differential analysis and robust rank aggregation (RRA) to obtain a list of differential genes. To obtain the core modules and core genes related to periodontitis, we evaluated differential genes through enrichment analysis, correlation analysis, protein-protein interaction (PPI) network and competing endogenous RNA (ceRNA) network analysis. Potential biomarkers for periodontitis were identified through comparative analysis of dual networks (PPI network and ceRNA network). PPI network analysis was performed in STRING. The ceRNA network consisted of RRA differentially expressed messenger RNAs (RRA_DEmRNAs) and RRA differentially expressed long non-coding RNAs (RRA_DElncRNAs), which regulated each other’s expression by sharing microRNA (miRNA) target sites.ResultsRRA_DEmRNAs were significantly enriched in inflammation-related biological processes, osteoblast differentiation, inflammatory response pathways and immunomodulatory pathways. Comparing the core ceRNA module and the core PPI module, C1QA, CENPK, CENPU and BST2 were found to be the common genes of the two core modules, and C1QA was highly correlated with inflammatory functionality. C1QA and BST2 were significantly enriched in immune-regulatory pathways. Meanwhile, LINC01133 played a significant role in regulating the expression of the core genes during the pathogenesis of periodontitis.ConclusionThe identified biomarkers C1QA, CENPK, CENPU, BST2 and LINC01133 provided valuable insight into periodontitis pathology.

Objective: Prostate cancer, marked by a high incidence and mortality rate, presents a significant challenge, especially in the context of castration-resistant prostate cancer (CRPC) with limited treatment options due to drug resistance. This study aims to explore the anti-tumor effects of Xihuang Pills (XHP) on CRPC, focusing on metabolic reprogramming and the Wnt/β-catenin pathway. Methods: In vitro and in vivo biofunctional assays were employed to assess the efficacy and mechanisms of XHP. Subcutaneous xenografts of PC3 in mice served as an in vivo model to evaluate XHP's anti-tumor activity. Tumor volume, weight, proliferation, and apoptosis were monitored. Various assays, including CCK8, TUNEL assay, QRT-PCR, and Western Blotting, were conducted to measure metabolic reprogramming, proliferation, apoptosis, and cell cycle in prostate cancer cells. RNA-seq analysis predicted XHP's impact on prostate cancer, validating the expression of Wnt/β-catenin-related proteins and mRNA. Additionally, 58 compounds in XHP were identified via LC-MS/MS, and molecular docking analysis connected these compounds to key genes. Results: In vitro and in vivo experiments demonstrated that XHP significantly inhibited CRPC cell viability, induced apoptosis, and suppressed invasion and migration. mRNA sequencing revealed differentially expressed genes, with functional enrichment analysis indicating modulation of key biological processes. XHP treatment downregulated Wnt signaling pathway-related genes, including CCND2, PRKCG, and CCN4. Moreover, XHP effectively inhibited glucose uptake and lactate production, leading to reduced HIF-1α and glycolytic enzymes (GLUT1, HK2, PKM2), suggesting its potential in attenuating the Warburg effect. Molecular docking analysis suggested a plausible interaction between XHP's active compounds and Wnt1 protein, indicating a mechanism through which XHP modulates the Wnt/β-catenin pathway. Conclusion: XHP demonstrated remarkable efficacy in suppressing the growth, proliferation, apoptosis, migration, and invasiveness of prostate tumors. The interaction between XHP's active constituents and Wnt1 was evident, leading to the inhibition of Wnt1 and downstream anti-carcinogenic factors, thereby influencing the β-catenin/HIF-1α-mediated glycolysis.

The overuse of fossil fuels has created a dual challenge for humanity, namely energy and environmental concerns. Excessive carbon emissions have resulted in a range of global climate issues. It’s of great practical significance to capture the excessive carbon dioxide emissions and convert them into high value-added chemicals or fuels. Methane is an important carrier for chemical bond energy storage due to its high mass calorific value. Carbon dioxide methanation is a promising process for reducing carbon dioxide emissions. This review introduces recent research progress on carbon dioxide methanation using thermal catalytic, bioconversion, photocatalytic, and electrocatalytic technologies. A dual-function integrated design integrating carbon dioxide capture and methanation is proposed, which not only realizes on-site capture and utilization, but also improves the manufacturability and economic benefits of the entire process.

Abstract Background Feminization of health workforce has been globally documented, but it has not been investigated in China. This study aims to analyze changes in the gendered composition of health workforce and explore the trend in different types of health workforce, health organizations and majors within China’s health system. Methods The data were collected from China Health Statistical Yearbook from 2002 to 2020. We focused on health professionals including doctors, nurses, and pharmacists in health organizations. Trend analysis was employed to examine the change in the ratio of female health workforce over 18 years. The estimated average annual percent change (AAPC) was estimated, and the reciprocals of variances for the female ratios were used as weights. Results In China, health professionals increased from 4.7 million in 2002 to 10.68 million in 2020. Health professionals per 1000 population increased from 3.41 in 2002 to 7.57 in 2020. The ratio of female health professionals significantly increased from 63.85% in 2002 to 72.4% in 2020 (AAPC = 1.04%, 95% CI 0.96–1.11%, P

Abstract Mitochondria are key cytoplasmic organelles in eukaryotic cells that generate adenosine triphosphate (ATP) through the electron transport chain and oxidative phosphorylation. Mitochondrial DNA (mtDNA) copy number (mtDNAcn) is considered a biomarker for both mitochondrial quantity and function as well as cellular oxidative stress level. Previous epidemiologic findings revealed that weight gain, higher body mass index (BMI), smoking, and high insulinemic potential of lifestyle were associated with lower leukocyte mtDNAcn. Carnitines are a group of compounds that play a critical role in energy production. We quantified the associations of plasma L-carnitine levels with leukocyte mtDNAcn. We then examined the association between mtDNAcn and L-carnitine (HMDB0000062) in 538 U.S. men without cancers, diabetes, or cardiovascular disease at blood collection from the Health Professionals Follow-Up Study (HPFS). We found a significant inverse association between L-carnitine and mtDNAcn (ρ = −0.1, P = 0.02). This implies that the carnitine metabolic pathway may be associated with mitochondrial function and oxidative stress.

The genus Ilex belongs to the sole family and is the single genus within the order Aquifoliales, exhibiting significant phenotypic diversity. However, the genetic differences underlying these phenotypic variations have rarely been studied. In this study, collinearity analyses of three Ilex genomes, Ilex latifolia Thunb., Ilex polyneura (Hand.-Mazz.) S. Y. Hu, and Ilex asprella Champ. ex Benth., indicated a recent fusion event contributing to the reduction of chromosomes in I. asprella. Comparative genome analyses showed slight differences in gene annotation among the three species, implying a minimal disruption of genes following chromosomal fusion in I. asprella. Comprehensive annotation of transposable elements (TEs) revealed that TEs constitute a significant portion of the Ilex genomes, with LTR transposons being predominant. TEs exhibited an inverse relationship with gene density, potentially influencing gene regulation and chromosomal architecture. TE insertions were shown to affect the conformation and binding sites of key genes such as 7-deoxyloganetin glucosyltransferase and transmembrane kinase (TMK) genes, highlighting potential functional impacts. The structural variations caused by TE insertions suggest significant roles in the evolutionary dynamics, leading to either loss or gain of gene function. This study underscores the importance of TEs in shaping the genomic landscape and evolutionary trajectories of Ilex species.

Abstract Background China initiated a health system reform in 2009 to achieve Universal Health Coverage (UHC) by 2020. While the effectiveness of health-system reforms has been studied, equity in health-service utilization and financial burden remains underexplored. This study evaluated whether the health system reform has improved the equity in utilization and financial burden of health services among patients with hypertension in China. Methods We obtained data from four waves of the China Health and Retirement Longitudinal Study (CHARLS) conducted between 2011 and 2018. The main outcome variables were outpatient and inpatient service utilization rates and catastrophic health expenditure (CHE) for patients with hypertension. The Standardized Concentration Index (CI) was used to measure the changing equity in health service utilization and affordability. Results Outpatient service utilization was relatively equal among patients with varying socioeconomic statuses (SESs) (CI: 0.041 in 2011 and 0.064 in 2018). Inpatient service utilization inequity improved from CI 0.144 in 2011 to CI 0.066 in 2018. CHE incidence increased from 15.6% in 2011 to 24.2% in 2018. CI for CHE declined from -0.069 in 2011 to -0.012 in 2015 but increased to -0.063 in 2018. Conclusions Health insurance expansion and poverty alleviation policies promoted equity in inpatient service utilization for hypertensive patients. However, the financial burden for the poor requires further attention through reimbursement policy adjustments for outpatient services in primary care settings.

Abstract Background China has made intensive efforts to eliminate extreme poverty by 2020. This paper aims to evaluate the changes in health service needs, utilization, and medical expenses for poor people during the poverty alleviation period. Methods The study used data from national health services surveys in 2013 and 2018. The poor people were identified and certified by the local government. Health service needs, utilization, medical expenses, and reimbursement rates were analyzed and compared between 2013 and 2018, between the poor and the non-poor groups. Results People living in poverty were usually elderly, illiterate, and unemployed. The poor people had a significantly higher two-week morbidity rate and a higher prevalence of chorionic non-communicable diseases than the non-poor group. For both the poor and non-poor, health service needs increased between 2013 and 2018. Accordingly, the poor people had more use of outpatient and inpatient services. The annual inpatient admission rates were 20.8% and 13.1% for the poor and non-poor, respectively, in 2018. The average medical expenses per inpatient admission were much lower for the poor than for the non-poor. Out-of-pocket (OOP) payment share decreased from 41.9% to 2013 to 31.9% in 2018 for the poor, while for the non-poor, the OOP rate was much higher (45.4%) and had no significant changes between the two surveys. The reduction in the OOP share occurred mostly in rural areas. Conclusions Poverty alleviation in China may have positive effect in improving poor people’s access to health services, and reducing their financial burden due to illness and health service utilization.

ObjectiveInvestigate the impact of combined computerized cognitive training and occupational therapy on individuals with mild cognitive impairment (MCI).MethodsWe randomly assigned 118 MCI patients into two groups: a combined intervention group (n = 37) and a control group (n = 81), the latter receiving standard nursing care. The intervention group additionally underwent 12 weeks of computerized cognitive training and occupational therapy. Blind assessors evaluated cognitive performance, anxiety, depression, and daily living activities before the intervention, post-intervention, and at a 3-month follow-up.ResultsRepeated-measures analysis of variance showed that the sMoCA scores, HAMA scores, and ADL scores of the experimental group at T2 (post-intervention) and T3 (3-month follow-up) were higher than those of the control group, and the difference was statistically significant (p

Objectives The aim of this study was to assess the quality of tuberculosis (TB) care for the whole course and assess factors that affect completing treatment.Design This is an observational retrospective study using chart abstraction for the whole course of TB care conducted at two underserved provinces in China.Setting The study was conducted from June 2021 to July 2021. All medical records (outpatient and inpatient) for the whole course (6–8 months) of patients with TB newly registered from July 2020 to December 2020 were reviewed and abstracted using predetermined checklists.Participants A total of 268 outpatient medical records and 126 inpatient records were included.Primary and secondary outcome measures The primary outcome included diagnostic quality, treatment quality and management quality. The secondary outcome was completing treatment.Results For diagnostic quality, 94.2% of the diagnosis were based on adequate evidence. For treatment quality, 240 (91.6%) outpatients and 100 (85.5%) inpatients took the standard chemotherapy regimens. 234 (87.3%) patients completed treatment. 85.1% of the inpatients prescribed with second-line drugs were inappropriate. For management quality, 128 (47.9%) patients received midterm assessments, but only 47 (19.7%) received sufficient services for the whole course. Patients with TB symptoms were 1.8 times more likely to complete treatment (p=0.011).Conclusion Patients with TB received high-quality diagnosis and treatment services, but low-quality whole-course management. Integration of medical and public health services should be strengthened to improve whole-course quality.

The junctional epithelium (JE) serves a crucial protective role in the periodontium. High glucose-related aging results in accelerated barrier dysfunction of the gingival epithelium, which may be associated with diabetic periodontitis. Metformin, an oral hypoglycemic therapeutic, has been proposed as a anti-aging agent. This study aimed to clarify the effect of metformin on diabetic periodontitis and explore its mechanism in ameliorating senescence of JE during hyperglycemia. The db/db mice was used as a diabetic model mice and alterations in the periodontium were observed by hematoxylin-eosin staining and immunohistochemistry. An ameloblast-like cell line (ALC) was cultured with high glucose to induce senescence. Cellular senescence and oxidative stress were evaluated by SA-β-gal staining and Intracellular reactive oxygen species (ROS) levels. Senescence biomarkers, P21 and P53, and autophagy markers, LC3-II/LC3-I, were measured by western blotting and quantitative real-time PCR. To construct a stable SIRT1 (Sirtuin 1) overexpression cell line, we transfected ALCs with lentiviral vectors overexpressing the mouse SIRT1 gene. Cellular senescence was increased in the JE of db/db mice and the periodontium was destroyed, which could be alleviated by metformin. Moreover, oxidative stress and cellular senescence in a high glucose environment were reduced by metformin in in-vitro assays. The autophagy inhibitor 3-MA and SIRT1 inhibitor EX-527 could dampen the effects of metformin. Overexpression of SIRT1 resulted in increased autophagy and decreased oxidative stress and cellular senescence. Meanwhile, AMPK (AMP-activated protein kinase) inhibition reversed the anti-senescence effects of metformin. Overall, these results suggest that metformin alleviates periodontal damage in db/db mice and cellular senescence in ALCs under high glucose conditions via the AMPK/SIRT1/autophagy pathway.

Abstract Background Laparoscopic minimally invasive surgery has become the primary treatment for ventral hernias. The laparoscopic intraperitoneal on lay mesh (IPOM) plus approach for abdominal wall hernias is the most used procedure, while extended view totally extraperitoneal (e‑TEP) repair is a newer option. This study aimed to compare the effectiveness and complications of the 2 procedures for abdominal wall hernias repair. Methods This was a retrospective and comparative single-center study done at The Second Clinical Medical College, Jinan University Hospital (Shenzhen People’s Hospital), Shenzhen, China. The study included patients with a 2 to 6 cm abdominal wall defect who underwent hernia repair from January 2022 to December 2022. Patients’ baseline characteristics, hernia features, operative time, blood loss, postoperative pain level, and total hospitalization expenses were extracted from the medical records and compared between patients who underwent the IPOM plus and e-TEP repair. Results A total of 53 patients were included: 22 in the e-TEP group and 31 in IPOM plus group. Patient demographic characteristics were similar between the 2 groups. The operation time of the e-TEP groups was significantly longer than the IPOM plus (98.5 ± 10.7 min vs. 65.9 ± 7.3 min, P

Abstract Immobilized microbial technology has been widely used in wastewater treatment, but it has been used less frequently for soil remediation, particularly in sites that are co-contaminated with organic compounds and heavy metals. In addition, there is limited knowledge on the efficiency of remediation and microbial preferences to colonize the immobilized carriers. In this study, biochar immobilized with Sphingobium abikonense was introduced to remediate soils that were co-contaminated with phenanthrene (PHE) and copper (Cu), and the mechanisms of microbial assemblage were investigated. The immobilized microbial biochar maintained a degradation rate of more than 96% in both the first (0–6 d) and second (6–12 d) contamination periods. The addition of biochar increased the proportion of Cu bound to organic matter, and Fe–Mn oxide bound Cu in the soil. In addition, both Cu and PHE could be adsorbed into biochar pellets in the presence or absence of immobilized S. abikonense. The presence of biochar significantly increased the abundance of bacteria, such as Luteibacter, Bordetella and Dyella, that could degrade organic matter and tolerate heavy metals. Notably, the biochar could specifically select host microbes from the soil for colonization, while the presence of S. abikonense affected this preference. The autonomous selection facilitates the degradation of PHE and/or the immobilization of Cu in the soil. These results provide a green approach to efficiently and sustainably remediate soil co-contaminated with PHE and Cu and highlight the importance of microbial preference colonized in immobilized carriers. Graphical Abstract

Cracks are a common defect in civil infrastructures, and their occurrence is often closely related to structural loading conditions, material properties, design and construction, and other factors. Therefore, detecting and analyzing cracks in civil infrastructures can effectively determine the extent of damage, which is crucial for safe operation. In this paper, Web of Science (WOS) and Google Scholar were used as literature search tools and “crack”, “civil infrastructure”, and “computer vision” were selected as search terms. With the keyword “computer vision”, 325 relevant documents were found in the study period from 2020 to 2024. A total of 325 documents were searched again and matched with the keywords, and 120 documents were selected for analysis and research. Based on the main research methods of the 120 documents, we classify them into three crack detection methods: fusion of traditional methods and deep learning, multimodal data fusion, and semantic image understanding. We examine the application characteristics of each method in crack detection and discuss its advantages, challenges, and future development trends.

Zhonghua Gate Castle is on the tentative list for Chinese World Cultural Heritage. Due to long-term sunshine, rain erosion, and man-made damage, its surface appears to have different degrees of cracks and other diseases. This paper centers on Zhonghua Gate Castle; terrestrial laser scanning is used to obtain the exterior wall point cloud data. A crack detection method based on point cloud data curved surface reconstruction is proposed. It involves data preprocessing, crack detection, and the analysis of crack features. This method initially uses data preprocessing techniques to improve data quality. These techniques include removing ground points and super-voxel segmentation. Subsequently, local surface reconstruction was employed to address the issue of missing point cloud data within cracks and the Euclidean clustering algorithm was used for precise crack identification. The article provides a detailed analysis of the geometric characteristics of cracks. They involve the calculation of length, width, and area. The results of the experiment demonstrate that the method could successfully identify cracks and extract geometric features and has millimeter-level accuracy compared to actual crack sizes.

Cyclin B (CYCB) is a regulatory subunit of cyclin-dependent kinase (CDK), the concentration of which fluctuates to regulate cell cycle progression. Extensive studies have been performed on cyclins in numerous species, yet the evolutionary relationships and biological functions of the CYCB family genes in Brassica napus remain unclear. In this study, we identified 299 CYCB genes in 11 B. napus accessions. Phylogenetic analysis suggests that CYCB genes could be divided into three subfamilies in angiosperms and that the CYCB3 subfamily members may be a newer group that evolved in eudicots. The expansion of BnaCYCB genes underwent segmental duplication and purifying selection in genomes, and a number of drought-responsive and light-responsive cis-elements were found in their promoter regions. Additionally, expression analysis revealed that BnaCYCBs were strongly expressed in the developing seed and silique pericarp, as confirmed by the obviously reduced seed size of the mutant cycb3;1 in Arabidopsis thaliana compared with Col-0. This study provides a comprehensive evolutionary analysis of CYCB genes as well as insight into the biological function of CYCB genes in B. napus.

A new biphase tandem redox electrolyte system is designed by immobilizing imidazolium iodide on Co, N‐doped carbon electrode in conjunction with polysulfide redox mediator in aqueous solution. Due to its biphasic feature, this redox system is enabled to separate the redox reactions in different phases, and hence, prevent the intertwined problem of redox reactions that occurred in one‐phase tandem redox system. Investigations show that the biphase redox system can efficiently accelerate electron reduction, and thereby inhibit charge recombination. Consequently, quantum dot (QD)‐sensitized solar cell fabricates using this biphase tandem redox together with CdSe QD‐sensitized photoanode achieved a high cell efficiency of 6.85% at 100 mW cm2 simulated AM 1.5, showing about 33% increment as compared to the traditional pure polysulfide‐based device (5.14%). The encouraging results indicate that the utilization of biphase tandem electrolytes can be an efficient way to improve the performance of sensitized solar cells.

Recent studies have indicated that gut microbiota-mediated oxidative stress is significantly associated with intestinal diseases such as colorectal cancer, ulcerative colitis, and Crohn’s disease. The level of reactive oxygen species (ROS) has been reported to increase when the gut microbiota is dysregulated, especially when several gut bacterial metabolites are present. Although healthy gut microbiota plays a vital role in defending against excessive oxidative stress, intestinal disease is significantly influenced by excessive ROS, and this process is controlled by gut microbiota-mediated immunological responses, DNA damage, and intestinal inflammation. In this review, we discuss the relationship between gut microbiota and intestinal disease from an oxidative stress perspective. In addition, we also provide a summary of the most recent therapeutic approaches for preventing or treating intestinal diseases by modifying gut microbiota.

Background and objectiveSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has broad tissue tropism and high transmission, which are likely to perpetuate the pandemic. The study aim to analyze the clinicopathogenic characteristics in paediatric patients.MethodsIn this single-centre study, we retrospectively included all confirmed cases infected by SARS-CoV-2 infection at Xi’an Children's Hospital, China, from 1 December to 31 December 2022. The demographic, clinical, laboratory, and radiological features of the patients were analysed.ResultsA total of 4,520 paediatric patients with SARS-CoV-2 omicron variant infections were included. Of these, 3,861 (85.36%) were outpatients, 659 (14.64%) were hospitalised patients, and nine patients (0.20%) died. Of the nine patients who died, five were diagnosed with acute necrotising encephalopathy (ANE). The most common symptoms were fever in 4,275 (94.59%) patients, cough in 1,320 (29.20%) patients, convulsions in 610 (13.50%) patients, vomiting in 410 (9.07%) patients, runny nose/coryza in 277 (6.13%) patients, hoarseness of voice in 273 (6.04%) patients. A blood cell analysis showed a slight elevation of monocytes (mean: 11.14 ± 0.07%). The main diagnoses for both outpatients and inpatients were respiratory infection with multisystem manifestations.ConclusionsA high incidence of convulsions is a typical characteristic of children infected with SARS-CoV-2. Five of the nine COVID-19 fatalities were associated with ANE. This indicates that nervous system damage in children with SARS-CoV-2 infection is more significant.

BackgroundThere is a paucity of evidence regarding the definition of the quality of primary health care (PHC) in China. This study aims to evaluate the PHC quality for chronic diseases in rural areas based on a modified conceptual framework tailored to the context of rural China.MethodsThis comprehensive study, involving a patient survey, a provider survey and chart abstraction, and second-hand registered data, was set in three low-resource counties in rural China from 2021 to 2022. Rural patients with hypertension or type 2 diabetes, and health care workers providing care on hypertension or diabetes were involved. The modified PHC quality framework encompasses three core domains: a competent PHC system (comprehensiveness, accessibility, continuity, and coordination), effective clinical care (assessment, diagnosis, treatment, disease management, and provider competence), and positive user experience (information sharing, shared decision-making, respect for patient's preferences, and family-centeredness). Standardized PHC quality score was generated by arithmetic means or Rasch models of Item Response Theory.ResultsThis study included 1355 patients, 333 health care providers and 2203 medical records. Ranging from 0 (the worst) to 1 (the best), the average quality score for the PHC system was 0.718, with 0.887 for comprehensiveness, 0.781 for accessibility, 0.489 for continuity, and 0.714 for coordination. For clinical care, average quality was 0.773 for disease assessment, 0.768 for diagnosis, 0.677 for treatment, 0.777 for disease management, and 0.314 for provider competence. The average quality for user experience was 0.727, with 0.933 for information sharing, 0.657 for shared decision-making, 0.936 for respect for patients' preferences, and 0.382 for family-centeredness. The differences in quality among population subgroups, although statistically significant, were small.ConclusionThe PHC quality in rural China has shown strengths and limitations. We identified large gaps in continuity of care, treatment, provider competence, family-centeredness, and shared decision-making. Policymakers should invest more effort in addressing these gaps to improve PHC quality.

Background: Liver transplantation (LTx) is the most effective treatment for end-stage liver diseases. Gut microorganisms influence the host physiology. We aim to profile the dynamics of gut microbiota in the perioperative period and a 1-year follow-up of LTx recipients in Northeast China.Methods: A total of 257 fecal samples were longitudinally collected from 85 LTx patients using anal swabs from pre-LTx to 1-year post-LTx. A total of 48 fecal samples from end-stage liver disease patients without LTx served as the control. 16S rRNA sequencing was used to analyze gut microbiota diversity, bacterial genera, phenotype classification, and metabolic pathways.Results: The diversity of gut microbiota decreased significantly after transplantation, accompanied by a profound change in the microbial structure, which is characterized by increased abundance of facultative anaerobic bacteria dominated by g_Enterococcus and reduced anaerobic bacteria composition. Predicted functional analysis also revealed disturbances in the metabolic pathway of the gut microbiota. After LTx, the diversity of microbiota gradually recovered but to a less preoperative level after 1 year of recovery. Compared with pre-transplantation, the microbiome structure was characterized by an increase in Acidaminococcus and Acidithiobacillus after 1 year of transplantation.Conclusion: LTx and perioperative treatment triggered gut microbial dysbiosis. The gut microbiota was restructured after LTx to near to but significantly differed from that of pre-LTx.

Abstract Sestrins are a small gene family of pleiotropic factors whose actions promote cell adaptation to a range of stress conditions. In this report we disclose the selective role of Sestrin2 (SESN2) in dampening aerobic glycolysis to adapt to limiting glucose conditions. Removal of glucose from hepatocellular carcinoma (HCC) cells inhibits glycolysis associated with the downregulation of the rate-limiting glycolytic enzyme hexokinase 2 (HK2). Moreover, the accompanying upregulation of SESN2 through an NRF2/ATF4-dependent mechanism plays a direct role in HK2 regulation by destabilizing HK2 mRNA. We show SESN2 competes with insulin like growth factor 2 mRNA binding protein 3 (IGF2BP3) for binding with the 3′-UTR region of HK2 mRNA. Interactions between IGF2BP3 and HK2 mRNA result in their coalescence into stress granules via liquid-liquid phase separation (LLPS), a process which serves to stabilize HK2 mRNA. Conversely, the enhanced expression and cytoplasmic localization of SESN2 under glucose deprivation conditions favors the downregulation of HK2 levels via decreases in the half-life of HK2 mRNA. The resulting dampening of glucose uptake and glycolytic flux inhibits cell proliferation and protect cells from glucose starvation-induced apoptotic cell death. Collectively, our findings reveal an intrinsic survival mechanism allowing cancer cells to overcome chronic glucose shortages, also providing new mechanistic insights into SESN2 as an RNA-binding protein with a role in reprogramming of cancer cell metabolism.

Abstract Background Increasing attention has recently been devoted to the anaerobic ammonium oxidation (anammox) in eutrophic lakes due to its potential key functions in nitrogen (N) removal for eutrophication control. However, successful enrichment of anammox bacteria from lake sediments is still challenging, partly due to the ecological interactions between anammox and denitrifying bacteria across such enrichment with lake sediments remain unclear. Results This study thus designed to fill such knowledge gaps using bioreactors to enrich anammox bacteria with eutrophic lake sediments for more than 365 days. We continuously monitored the influent and effluent water, measured the anammox and denitrification efficiencies, quantified the anammox and denitrifying bacteria, as well as the related N cycling genes. We found that the maximum removal efficiencies of NH4 + and NO2 − reached up to 85.92% and 95.34%, respectively. Accordingly, the diversity of anammox and denitrifying bacteria decreased significantly across the enrichment, and the relative dominant anammox (e.g., Candidatus Jettenia) and denitrifying bacteria (e.g., Thauera, Afipia) shifted considerably. The ecological cooperation between anammox and denitrifying bacteria tended to increase the microbial community stability, indicating a potential coupling between anammox and denitrifying bacteria. Moreover, the nirS-type denitrifiers showed stronger coupling with anammox bacteria than that of nirK-type denitrifiers during the enrichment. Functional potentials as depicted by metagenome sequencing confirmed the ecological interactions between anammox and denitrification. Metagenome-assembled genomes-based ecological model indicated that the most dominant denitrifiers could provide various materials such as amino acid, cofactors, and vitamin for anammox bacteria. Cross-feeding in anammox and denitrifying bacteria highlights the importance of microbial interactions for increasing the anammox N removal in eutrophic lakes. Conclusions This study greatly expands our understanding of cooperation mechanisms among anammox and denitrifying bacteria during the anammox enrichment with eutrophic lake sediments, which sheds new insights into N removal for controlling lake eutrophication. Video Abstract

Abstract The freshwater leech Whitmania pigra (W. pigra) Whitman (Annelida phylum) is a model organism for neurodevelopmental studies. However, molecular biology research on its embryonic development is still scarce. Here, we described a series of developmental stages of the W. pigra embryos and defined five broad stages of embryogenesis: cleavage stages, blastocyst stage, gastrula stage, organogenesis and refinement, juvenile. We obtained a total of 239.64 Gb transcriptome data of eight representative developmental phases of embryos (from blastocyst stage to maturity), which was then assembled into 21,482 unigenes according to our reference genome sequenced by single-molecule real-time (SMRT) long-read sequencing. We found 3114 genes differentially expressed during the eight phases with phase-specific expression pattern. Using a comprehensive transcriptome dataset, we demonstrated that 57, 49 and 77 DEGs were respectively related to morphogenesis, signal pathways and neurogenesis. 49 DEGs related to signal pathways included 30 wnt genes, 14 notch genes, and 5 hedgehog genes. In particular, we found a cluster consisting of 7 genes related to signal pathways as well as synapses, which were essential for regulating embryonic development. Eight genes cooperatively participated in regulating neurogenesis. Our results reveal the whole picture of W. pigra development mechanism from the perspective of transcriptome and provide new clues for organogenesis and neurodevelopmental studies of Annelida species.

Fish blood tends to coagulate due to its specialized characteristics. In general, the detection of blood physiological indices using anticoagulants reflects normal physiological status. However, the selection and application of anticoagulants have no uniform standards because of the specificity and diversity of fish species. In the present study, the effects of three different anticoagulants (sodium heparin, K2EDTA, and sodium citrate) were investigated on coagulation, blood cell type, hematological parameters (white blood cells, red blood cells, hematocrit, and hemoglobin), and plasma cortisol and glucose contents in turbot during acute hypoxic stress. The choice of anticoagulants may result in significant differences in turbot blood physiology and chemistry. To supply technological support in turbot hematological research and best-practice aquaculture, this study compared the effects of three common anticoagulants between normal dissolved oxygen and acute hypoxic states. The recirculating aquaculture system is the main culture model for turbot; water temperature and dissolved oxygen levels are important environmental factors, especially in high-density industrial systems. Sufficient oxygen is key to maintaining normal metabolism in turbot. Experimental procedures were designed for control and treatment groups, each group had three parallels, and 54 turbots were studied in all. In the control group, 200 mg/L MS-222 was used to anesthetize a specimen before collecting 5 mL of blood from the caudal vein; the blood was transferred through a needle and vacuum tubes containing three different anticoagulants, then the vacuum tubes were stored for evaluation after 6 h and 12 h. In the treatment group, nitrogen gas was used to rapidly reduce the concentration of dissolved oxygen in the container to (1.2±0.3) mg/L (measured with a dissolved oxygen meter), after which the same procedure of anesthesia and blood collection was conducted. For blood cell type and morphology studies, the Giemsa staining method was used to make blood smears. The original solution of Giemsa was diluted before use. The slide was sterilized before a drop of blood was placed on one side of the slide; one edge of a cover glass was placed in contact with the drop of blood and pushed to the opposite side of the slide at a constant velocity; the slide was then fixed with methanol for 10~15 min and stained for 15~30 min. The smears were washed and dried after staining. Finally, the stained smears were observed under a Leica microscope to determine blood cell morphology, and images were taken. Blood samples were divided into two parts for detecting physiological and biochemical indices: one was centrifuged at 3500 r/min for 10 min, and the supernatant was stored at –80℃ for the detection of plasma glucose and cortisol content using commercial kits. The residual blood samples were stored in a refrigerator at 4℃ for the detection of physiological indices using an automatic blood cell analyzer. The anticoagulant effect of K2EDTA was most effective under a normal dissolved oxygen state, and the anticoagulant effect of K2EDTA and heparin sodium were most effective after 6 h and 12 h of exposure to acute hypoxia stress, respectively. In addition to coagulation, blood cell morphology showed that binucleate cells occurred through sodium heparin, eosinophils, and basophils through sodium citrate and basophils through K2EDTA in the control. Three nucleus abnormality types were identified in the smears: micronucleus cells, binucleate cells, and erythroplastids. Binucleate cells were found using sodium heparin in the control group. In addition, binucleate cells were observed under three different anticoagulants in the treatment group, and micronucleus cells and erythroplastids were observed in the treatment group. The hematological index showed that the number of white blood cells was significantly increased by treatment with three anticoagulants during acute hypoxic stress (P < 0.05), and the number of red blood cells and hemoglobin content was significantly increased by treatment with K2EDTA and sodium heparin (P < 0.05). However, they were significantly reduced after treatment with sodium citrate. In addition, the plasma glucose and cortisol content were significantly increased when subjected to acute hypoxic stress, but the content of sodium heparin was significantly lower than that of both sodium citrate and K2EDTA. In summary, K2EDTA showed less blood coagulation than other anticoagulants, sodium heparin caused binucleate cells and decreased plasma glucose and cortisol, and sodium citrate affected the number of red blood cells and hemoglobin content. K2EDTA is the more promising anticoagulant compared to sodium heparin and sodium citrate for blood analysis of turbot and promotes the precision of turbot hematological studies under acute hypoxic conditions.

Belligobio pengxianensis is a small fish endemic to the upper Yangtze River of China. In this study, the complete mitochondrial genome of B. pengxianensis is determined for the first time, and it should become a reference sequence to aid in species identification, biodiversity monitoring and conservation. The mitogenome has overall length of 16,610 bp and AT content of 55.23%, including 13 protein-coding genes, two ribosomal RNAs, 22 transfer RNAs, and one non-coding control region. The results of phylogenetic analyses show that B. pengxianensis is nested within the genus Hemibarbus.

Abstract Background The repair of white matter injury is of significant importance for functional recovery after ischemic stroke, and the up-regulation of triggering receptors expressed on myeloid cells 2 (TREM2) after ischemic stroke is neuroprotective and implicated in remyelination. However, the lack of effective therapies calls for the need to investigate the regenerative process of remyelination and the role of rehabilitation therapy. This study sought to investigate whether and how moderate physical exercise (PE) promotes oligodendrogenesis and remyelination in rats with transient middle cerebral artery occlusion (tMCAO). Methods Male Sprague–Dawley rats (weighing 250–280 g) were subjected to tMCAO. AAV-shRNA was injected into the lateral ventricle to silence the Trem2 gene before the operation. The rats in the physical exercise group started electric running cage training at 48 h after the operation. The Morris water maze and novel object recognition test were used to evaluate cognitive function. Luxol fast blue staining, diffusion tensor imaging, and electron microscopy were used to observe myelin injury and repair. Immunofluorescence staining was applied to observe the proliferation and differentiation of oligodendrocyte precursor cells (OPCs). Expression of key molecules were detected using immunofluorescence staining, quantitative real-time polymerase chain reaction, Western blotting, and Enzyme-linked immunosorbent assay, respectively. Results PE exerted neuroprotective efects by modulating microglial state, promoting remyelination and recovery of neurological function of rats over 35 d after stroke, while silencing Trem2 expression in rats suppressed the aforementioned effects promoted by PE. In addition, by leveraging the activin-A neutralizing antibody, we found a direct beneficial effect of PE on microglia-derived activin-A and its subsequent role on oligodendrocyte differentiation and remyelination mediated by the activin-A/Acvr axis. Conclusions The present study reveals a novel regenerative role of PE in white matter injury after stroke, which is mediated by upregulation of TREM2 and microglia-derived factor for oligodendrocytes regeneration. PE is an effective therapeutic approach for improving white matter integrity and alleviating neurological function deficits after ischemic stroke.

Abstract Recurrence and metastasis are the main causes of breast cancer (BRCA)-related death and remain a challenge for treatment. In-depth research on the molecular mechanisms underlying BRCA progression has been an important basis for developing precise biomarkers and therapy targets for early prediction and treatment of progressed BRCA. Herein, we identified FERM domain-containing protein 3 (FRMD3) as a novel potent BRCA tumor suppressor which is significantly downregulated in BRCA clinical tissue and cell lines, and low FRMD3 expression has been closely associated with progressive BRCA and shortened survival time in BRCA patients. Overexpression and knockdown experiments have revealed that FRMD3 significantly inhibits BRCA cell proliferation, migration, and invasion in vitro and suppresses BRCA xenograft growth and metastasis in vivo as well. Mechanistically, FRMD3 can interact with vimentin and ubiquitin protein ligase E3A(UBE3A) to induce the polyubiquitin-mediated proteasomal degradation of vimentin, which subsequently downregulates focal adhesion complex proteins and pro-cancerous signaling activation, thereby resulting in cytoskeletal rearrangement and defects in cell morphology and focal adhesion. Further evidence has confirmed that FRMD3-mediated vimentin degradation accounts for the anti-proliferation and anti-metastasis effects of FRMD3 on BRCA. Moreover, the N-terminal ubiquitin-like domain of FRMD3 has been identified as responsible for FRMD3-vimentin interaction through binding the head domain of vimentin and the truncated FRMD3 with the deletion of ubiquitin-like domain almost completely loses the anti-BRCA effects. Taken together, our study indicates significant potential for the use of FRMD3 as a novel prognosis biomarker and a therapeutic target of BRCA and provides an additional mechanism underlying the degradation of vimentin and BRCA progression.

Abstract Background Multimorbidity is posing an enormous burden to health systems, especially for primary healthcare system. While primary care teams (PCTs) are believed to have potentials to improve quality of primary health care (PHC), less is known about their impact on the quality of care for people with multimorbidity. We assessed the characteristics of PCTs and their impact on the quality of care for people with multimorbidity and the mechanisms. Methods We searched PubMed, MEDLINE, EMBASE, ProQuest for published studies from January 2000 to October 2021 for studies in English. Following through PRISMA guidelines, two reviewers independently abstracted data and reconciled by consensus with a third reviewer. Titles, abstracts, and full texts were evaluated to identify relevant studies. Studies were categorized by types of interventions, the impact of interventions on outcome measures, and mechanisms of interventions. Results Seventeen studies (13 RCT, 3 cohort studies, and 1 non-randomized trial) were identified. PCTs were summarized into three types—upward PCTs, downward PCTs and traditional PCTs according to the skill mix. The upward PCTs included primary care workers and specialists from upper-level hospitals, downward PCTs involving primary care workers and lay health workers, and traditional PCTs involving physicians and care managers. PCTs improved patients’ mental and psychological health outcomes greatly, and also improved patients’ perceptions towards care including satisfaction with care, sense of improvement, and patient-centeredness. PCTs also improved the process of care and changed providers’ behaviors. However, PCTs showed mixed effects on clinical outcome measures. Conclusions PCTs have improved mental and psychological health outcomes, the process of care, patients’ care experiences, and satisfaction towards care for patients with multimorbidity. The effect of PCTs on clinical outcomes and changes in patient behaviors need to be further explored.