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Abstract Background Sleep remains a cornerstone for sociopsychological well-being, but it is in decline, especially among today’s youth. Simultaneously, engagement with social media is escalating. Research has identified a link between social networking sites use and sleep problems; however, the nature and direction of the relations remain obscure. Therefore, it is imperative to pursue longitudinal research to elucidate this correlation and guide suitable intervention practices. The present study aimed to examine the reciprocal relationship between social networking sites use and sleep problems. Methods By adopting a three-stage cross-lagged design across four time points, assessment results from 194 university students were gathered at four-week intervals. Results The findings indicate that (1) Social networking sites use was significantly greater in females than in males at all four time points, while sleep problems were significantly greater in females than in males at Time 3 and Time 4. (2) Sleep problems at the second time point serve as a positive predictor of subsequent social networking sites use at the third time point. (3) Social networking sites use at the initial time point could marginally significantly predict sleep problems at the fourth time point. Conclusions This study elucidates the dynamic relationship between social networking sites use and sleep problems across an academic term, suggesting the need for temporally tailored interventions.

Abstract Mucus injury associated with goblet cell (GC) depletion constitutes an early event in inflammatory bowel disease (IBD). Using single-cell sequencing to detect critical events in mucus dysfunction, we discover that the Kazal-type serine protease inhibitor SPINK4 is dynamically regulated in colitic intestine in parallel with disease activities. Under chemically induced colitic conditions, the grim status in Spink4-conditional knockout mice is successfully rescued by recombinant murine SPINK4. Notably, its therapeutic potential is synergistic with existing TNF-α inhibitor infliximab in colitis treatment. Mechanistically, SPINK4 promotes GC differentiation using a Kazal-like motif to modulate EGFR-Wnt/β-catenin and -Hippo pathways. Microbiota-derived diacylated lipoprotein Pam2CSK4 triggers SPINK4 production. We also show that monitoring SPINK4 in circulation is a reliable noninvasive technique to distinguish IBD patients from healthy controls and assess disease activity. Thus, SPINK4 serves as a serologic biomarker of IBD and has therapeutic potential for colitis via intrinsic EGFR activation in intestinal homeostasis.

Radiation-induced heart disease (RIHD), characterized by severe oxidative stress and immune dysregulation, is a serious condition affecting cancer patients undergoing thoracic radiation. Unfortunately, clinical interventions for RIHD are lacking. Selenium (Se) is a trace element with excellent antioxidant and immune-modulatory properties. However, its application in heart radioprotection remains challenging. Herein, we developed a novel bioactive Cordyceps militaris-based Se oral delivery system (Se@CM), which demonstrated superior radioprotection effects in vitro against X-ray-induced damage in H9C2 cells through suppressing excessive ROS generation, compared to the radioprotectant Amifostine. Moreover, Se@CM exhibited exceptional cardioprotective effects in vivo against X-ray irradiation, reducing cardiac dysfunction and myocardial fibrosis by balancing the redox equilibrium and modulating the expression of Mn-SOD and MDA. Additionally, Se@CM maintained immuno-homeostasis, as evidenced by the upregulated population of T cells and M2 macrophages through modulation of selenoprotein expression after irradiation. Together, these results highlight the remarkable antioxidant and immunity modulation properties of Se@CM and shed light on its promising application for cardiac protection against IR-induced disease. This research provides valuable insights into developing effective strategies for preventing and managing RIHD.

Abstract Background Cognitive impairment is a recognized fundamental deficit in individuals diagnosed with schizophrenia (SZ), bipolar II disorder (BD II), and major depressive disorder (MDD), among other psychiatric disorders. However, limited research has compared cognitive function among first-episode drug-naïve individuals with SZ, BD II, or MDD. Methods This study aimed to address this gap by assessing the cognitive performance of 235 participants (40 healthy controls, 58 SZ patients, 72 BD II patients, and 65 MDD patients) using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) before and after 12 weeks of treatment in SZ, BD II, and MDD patients. To clarify, the healthy controls only underwent RBANS testing at baseline, whereas the patient groups were assessed before and after treatment. The severity of symptoms in SZ patients was measured using the Positive and Negative Syndrome Scale (PANSS), and depression in BD II and MDD patients was assessed using the Hamilton Depression Scale-24 items (HAMD-24 items). Results Two hundred participants completed the 12-week treatment period, with 35 participants dropping out due to various reasons. This group included 49 SZ patients, 58 BD II patients, and 53 MDD patients. Among SZ patients, significant improvements in immediate and delayed memory were observed after 12 weeks of treatment compared to their initial scores. Similarly, BD II patients showed significant improvement in immediate and delayed memory following treatment. However, there were no significant differences in RBANS scores for MDD patients after 12 weeks of treatment. Conclusions In conclusion, the findings of this study suggest that individuals with BD II and SZ may share similar deficits in cognitive domains. It is important to note that standardized clinical treatment may have varying degrees of effectiveness in improving cognitive function in patients with BD II and SZ, which could potentially alleviate cognitive dysfunction.

PurposeWe aimed to explore the prognostic significance of collagen content in solitary fibrous tumors (SFTs) of the central nervous system (CNS) and preliminarily investigate its relationship with magnetic resonance imaging (MRI) features of SFTs.MethodsCollagen content was identified using Masson’s trichrome staining, and quantitatively assessed. Radiomic methods were applied to extract quantitative MRI features of SFTs, which were then analyzed in relation to collagen content.ResultsThe collagen content in CNS SFTs was categorized into high- and low-content groups, with a cutoff value of 6%. Survival analysis indicated a positive correlation between collagen content and overall survival (OS). In multivariate Cox regression analysis, incorporating factors such as mitosis, necrosis, Ki67, and collagen content and other indicators, collagen content emerged as an independent prognostic factor. Collagen content demonstrated a negative correlation with tumor histological phenotype, Ki67, WHO grade, mitosis, necrosis, and brain invasion. Additionally, the signal intensity of SFTs on T2-weighted imaging (T2WI) decreased with increasing collagen content. Radiomics analysis identified 1,702 features from each patient’s region of interest, with 12 features showing significant differences between the high and low collagen content groups. Among the quantitative parameters and radiomic models, the combined T1- and T2WI models exhibited the highest diagnostic performance.ConclusionThese findings suggest that collagen content is an independent prognostic risk factor for OS. Furthermore, combined radiomic models based on T1-and T2WI sequences may offer a more comprehensive, objective, and accurate assessment of collagen content in CNS SFTs.

Taste quality is one of the most important indicators for assessing the quality of rice. However, there has been a lack of systematic studies investigating the impact factors of taste quality. In this study, chromosomal segment substitution lines (CSSLs) with notable differences in physicochemical properties were obtained by screening the CSSL population. A correlation analysis between the physicochemical properties and the taste qualities of rice revealed that amylose and protein content are significantly negatively correlated with the taste value of both freshly cooked and rehydrated instant rice. The alkali spreading value (ASV) had limited impact on the taste value of rice, but low-ASV rice is more resistant to cooking. Grain chalkiness played a critical role in maintaining the integrity of freshly cooked rice and instant rice grains after rehydration. In summary, our study provides crucial insights and guidance for rice breeding, with the goal of developing excellent quality and enhancing the processing of instant rice.

IntroductionMutations in the protein WD repeat structural domain 26 (WDR26, MIM 617424) have been identified as the cause of autosomal dominant Skraban-Deardorff syndrome, a rare genetic disorder characterized by intellectual disability (ID), developmental delay (DD), hypotonia, epilepsy, infant feeding difficulties, gait abnormalities and distinctive facial features. The objective of this study is to investigate the genetic factors that may contribute to the development of Skraban-Deardorff syndrome in affected individuals.MethodsIn this study, we used whole-exome sequencing (WES) to analyze pathogenic and likely pathogenic variants in two unrelated Chinese patients with DD and ID. We confirmed the origin of the variants by conducting Sanger sequencing and classified them according to ACMG/AMP guidelines.ResultsHere, two novel de novo variants (c.1797delC(p.His599fs*11) and c.1414C>T(p.Gln472*)) in the WDR26 gene have been identified in two Chinese patients with Skraban-Deardorff syndrome. These patients exhibit a range of symptoms, including varying degrees of ID, DD, speech delay, an abnormal wide-foot and/or stiff-legged gait, facial dysmorphism, behavioural abnormalities, with or without seizures.ConclusionsIn this study, We report two unrelated Chinese patients with Skraban-Deardorff syndrome caused by novel de novo pathogenic variants of the WDR26 gene. These patients showed a clinical phenotype similar to that of patients with the WDR26 variant. Compared to reported cases with WDR26 pathogenic variants, patient 2 presented a novel complication of severe behavioural problems, including hyperactivity, social anxiety, self-mutilation, impulsivity and violent behaviour. This research broadens the range of genetic and clinical features of Skraban-Deardorff syndrome. In addition, the symptoms may become more pronounced as the patient ages. Furthermore, our report highlights the clinical diversity of Skraban-Deardorff syndrome. The findings may assist healthcare professionals in providing more accurate genetic testing and counselling to affected families and improving the overall management of the condition.

Summary: Increasing evidence indicates that immunotherapy is hindered by a hostile tumor microenvironment (TME) featured with deprivation of critical nutrients and pooling of immunosuppressive metabolites. Tumor cells and immunosuppressive cells outcompete immune effector cells for essential nutrients. Meanwhile, a wide range of tumor cell-derived toxic metabolites exerts negative impacts on anti-tumor immune response, diminishing the efficacy of immunotherapy. Nanomedicine with excellent targetability offers a novel approach to improving cancer immunotherapy via metabolically reprogramming the immunosuppressive TME. Herein, we review recent strategies of enhancing immunotherapeutic effects through rewiring tumor metabolism via nanomedicine. Attention is drawn on immunometabolic tactics for immune cells and stromal cells in the TME via nanomedicine. Additionally, we discuss future directions of developing metabolism-regulating nanomedicine for precise and efficacious cancer immunotherapy.

Owing to the fragile ecological environment and the prominent human–land conflict relationship, the competition between land multifunctionality in the karst region has increased. In this context, the coordination and stability of production–living–ecological space (PLES) have been severely affected, and the scientific diagnosis of PLES conflict characteristics can provide an important basis for optimizing national land allocation. Using land use data, this study used a spatial conflict measurement model to examine the spatial and temporal variations of PLES conflicts across mountain–basin areas of various geomorphological in karst types. Meanwhile, the factors influencing their evolution were also investigated. The study results showed that the ecological space (ES) area was the largest in the study area and had an increasing trend from 2010 to 2020. PLES conflicts were dominated by stable and controllable, and light conflicts, and the overall conflict level had increased. Influenced by the natural environment, socioeconomics, and policies, there were significant differences in the development of PLES conflicts in the mountain–basin areas. The conflict level in the basin area was higher than in the mountain area. The intensity of PLES conflicts in the mountain–basin areas in the karst valleys geomorphic types and in the mountain areas in the karst fault basin showed a decreasing trend. The level of conflicts in the mountain–basin areas in the karst plateau, karst peak–cluster depression, karst trough valley geomorphic and in the basin area of the karst fault basin geomorphic type showed an increasing trend. There were also common evolutionary characteristics for PLES conflicts in mountain–basin areas. The findings have provided a reference to support differentiated land management and decision-making in karst areas, which can contribute to the strategic sustainable development at the regional level.

Immunotherapy represents a promising strategy for cancer treatment that utilizes immune cells or drugs to activate the patient’s own immune system and eliminate cancer cells. One of the most exciting advances within this field is the targeting of neoantigens, which are peptides derived from non-synonymous somatic mutations that are found exclusively within cancer cells and absent in normal cells. Although neoantigen-based therapeutic vaccines have not received approval for standard cancer treatment, early clinical trials have yielded encouraging outcomes as standalone monotherapy or when combined with checkpoint inhibitors. Progress made in high-throughput sequencing and bioinformatics have greatly facilitated the precise and efficient identification of neoantigens. Consequently, personalized neoantigen-based vaccines tailored to each patient have been developed that are capable of eliciting a robust and long-lasting immune response which effectively eliminates tumors and prevents recurrences. This review provides a concise overview consolidating the latest clinical advances in neoantigen-based therapeutic vaccines, and also discusses challenges and future perspectives for this innovative approach, particularly emphasizing the potential of neoantigen-based therapeutic vaccines to enhance clinical efficacy against advanced solid tumors.

ABSTRACTPreviously, we reported a cohort of Japanese encephalitis (JE) patients with Guillain–Barré syndrome. However, the evidence linking Japanese encephalitis virus (JEV) infection and peripheral nerve injury (PNI) remains limited, especially the epidemiology, clinical presentation, diagnosis, treatment, and outcome significantly differ from traditional JE. We performed a retrospective and multicenter study of 1626 patients with JE recorded in the surveillance system of the Chinese Center for Disease Control and Prevention, spanning the years 2016–2020. Cases were classified into type 1 and type 2 JE based on whether the JE was combined with PNI or not. A comparative analysis was conducted on demographic characteristics, clinical manifestations, imaging findings, electromyography data, laboratory results, and treatment outcomes. Among 1626 laboratory confirmed JE patients, 230 (14%) were type 2 mainly located along the Yellow River in northwest China. In addition to fever, headache, and disturbance of consciousness, type 2 patients experienced acute flaccid paralysis of the limbs, as well as severe respiratory muscle paralysis. These patients presented a greater mean length of stay in hospital (children, 22 years [range, 1–34]; adults, 25 years [range, 0–183]) and intensive care unit (children, 16 years [range, 1–30]; adults, 17 years [range, 0–102]). The mortality rate was higher in type 2 patients (36/230 [16%]) compared to type 1 (67/1396 [5%]). The clinical classification of the diagnosis of JE may play a crucial role in developing a rational treatment strategy, thereby mitigating the severity of the disease and potentially reducing disability and mortality rates among patients.

Abstract Human‐induced disturbances such as dam construction and regulation have led to widespread alterations in hydrological processes and thus substantially influence plant characteristics in the hydro‐fluctuation zones (HFZs). To reveal utilization of limited resources and mechanisms of inter‐specific competition and species co‐existence of plant communities based on niche breadth and overlap under the different HFZs of the Three Gorges Reservoir (TGR) in China, we conducted a field investigation with 368 quadrats on the effects of hydrological alterations on plant diversity and niche characteristics. The results showed anti‐seasonal flooding precipitated the gradual disappearance of the original diverse niches, resulting in the reduction of plant species richness and functional diversity and more obvious competition among plant species with similar resource requirements. Annuals, perennials and shrubs accounted for 71.23%, 27.39% and 1.37%, respectively, suggesting that annuals and flood‐tolerant riparian herbs were favored under such novel flooding conditions. A consistent increase in species number, Shannon‐Wiener diversity index and Simpson dominance index with altitude was inconsistent with hump‐shaped diversity–disturbance relationship of the intermediate disturbance hypothesis, while the opposite trend was observed for the Pielou evenness index. This species distribution pattern might be caused by several synergetic attributes (e.g., the submergence depth, plant tolerant capacity to flooding, life form, dispersal mode and inter‐specific competition). Vegetation types shifted from xerophytes to mesophytes and eventually to hygrophytes with the increasing flooding time in the HFZs. Hydrological alterations proved to be the paramount driver of vegetation distribution in the different HFZs. The niche analysis provided the first insights on the mechanisms of resource utilization and inter‐specific competition, of which annuals could germinate quickly after soil drainage to achieve the greatest competitive advantages and occupy a larger niche space than other plants. Vegetation was still in the early stage of primary succession in the novel riparian forests. Therefore, vegetation restoration strategies should be biased towards herbaceous plants, due to annuals with better environmental adaptability, supplemented by shrubs and small trees. To establish a complete reference system for vegetation restoration, natural vegetation monitory plots in the different succession stages should be established in the different HFZs of the TGR, and their environmental conditions, community structures and inter‐specific relationships further analyzed.

Abstract Background Default mode network (DMN) is one of the most recognized resting‐state networks in major depressive disorder (MDD). However, the homogeneity of this network in MDD remains incompletely explored. Therefore, this study aims to determine whether there is abnormal network homogeneity (NH) of the DMN in MDD patients. At the same time, correlations between clinical variables and brain functional connectivity are examined. Methods We enrolled 42 patients diagnosed with MDD and 42 HCs. A variety of clinical variables were collected, and data analysis was conducted using the NH and independent component analysis methods. Results The study shows that MDD patients have higher NH values in the left superior medial prefrontal cortex (MPFC) and left posterior cingulate cortex (PCC) compared to HCs. Additionally, there is a positive correlation between NH values of the left superior MPFC and Eysenck Personality Questionnaire values. NH values of the left PCC are positively linked to CHOL levels, LDL levels, and utilization scores. However, these correlations lose significance after the Bonferroni correction. Conclusion Our findings indicate the presence of abnormal DMN homogeneity in MDD, underscoring the significance of DMN in the pathophysiology of MDD. Simultaneously, the study provides preliminary evidence for the correlation between clinical variables and brain functional connectivity.

The present study utilized the spared nerve injury (SNI) to create a mouse model of depression to investigate the impact of esketamine on depressive-like behaviors, on the expression of PSD-95 and CRMP2 proteins, and on changes in neuronal dendritic spine plasticity in the prefrontal cortex (PFC). Depressive-like behavioral tests were performed 1 h after esketamine treatment, and the PFC tissues were obtained on the fourth day after completing the behavioral tests. Then, dendritic spine density and morphology in the PFC were measured using Golgi staining, and CRMP2 and PSD-95 proteins were obtained from PFC tissue by western blotting. The results of this study showed that esketamine significantly increased the immobility time in the forced swimming test and tail suspension test. In the open field test, esketamine increased the time spent in the open arms, the time spent in the central area, and the total distance covered. It also increased the protein expression levels of CRMP2 and PSD-95 in addition to the total and mature dendritic spine density of the PFC in SNI-depressed mice. Esketamine can significantly improve depression-like behaviors in SNI-depressed mice and promote an increase in dendritic spine density and maturation in the PFC. These effects may be associated with changes in CRMP2 and PSD-95 expression.

Water scarcity and water-related soil erosion are severely exacerbated by inappropriate human activities and global climate change. Hence, to find a suitable technology to mitigate drought and soil erosion, three consecutive field experiments were conducted to explore the impact of ridge-furrow cropping with biochar amendment on soil water storage, runoff, sediment yield, soil nutrient losses, alfalfa (Medicago sativa L) fodder yield, crop water productivity (WPc), and economic benefit from 2019 to 2021. This experiment was conducted in a split-plot design, taking biochar amendment patterns (no biochar amendment and biochar amendment at a rate of 3× 104 kg ha−1) as a main plot and ridge-furrow technologies (traditional planting, open-ridging, and tied-ridging) as a split-plot. The combination of biochar amendment with ridge-furrow technology, especially tied-ridging technology, increased soil water storage, and captured runoff, sediment, and related soil nutrient losses, consequently increasing alfalfa fodder yield, WPc, and income. During this study, compared to traditional planting, open-ridging depicted an increase in soil water storage by a range of 9.8–39.6 mm, an alfalfa fodder yield boost ranging from 9.8% to 38.6%, and a WPc increase ranging from 0.1 to 16.5 kg ha−1 mm−1. On the other hand, tied-ridging showed greater improvements with soil water storage increasing by 29.1–65.1 mm, alfalfa fodder yield growing by 11.6–44.4%, and WPc advancing by 0.9–17.5 kg ha−1 mm−1. The mean decrease in runoff, sediment, and nutrients (total nitrogen, total phosphorus, and organic matter) loss for open-ridging was 17.9%-37.7%, 46.4%-75.5%, and 40.4%-75.3%, respectively, while for tied-ridging, it was 22.3%-55.5%, 62.1%-87.6%, and 49.0%-87.3%, respectively. Compared to no biochar amendment, soil water storage, alfalfa fodder yield, and WPc for biochar amendment increased by 9.1%-20.4%, 5.8%-52.7%, and 4.6–7.8 kg ha−1 mm−1, respectively, while runoff, sediment, and nutrients loss for biochar amendment decreased by 32.2%-40.9%, 25.5%-55.5%, and 35.9%-53.3%, respectively. Structural equation modeling analysis indicated that the significant direct effect of biochar amendment and ridge-furrow technology on WPc was 0.20 and 0.62, respectively, whereas the significant direct effect of runoff and actual crop evapotranspiration on alfalfa fodder yield was −0.40 and 0.94, respectively. Tied-ridge cropping combined with biochar addition was a highly suggested approach for addressing soil erosion and enhancing alfalfa fodder yields in the Loess Plateau in China. This technology could mitigate soil water scarcity and soil erosion, and give farmers the confidence to invest in this technology in dryland regions.

Sit-to-stand transition phase identification is vital in the control of a wearable exoskeleton robot for assisting patients to stand stably. In this study, we aim to propose a method for segmenting and identifying the sit-to-stand phase using two inertial sensors. First, we defined the sit-to-stand transition into five phases, namely, the initial sitting phase, the flexion momentum phase, the momentum transfer phase, the extension phase, and the stable standing phase based on the preprocessed acceleration and angular velocity data. We then employed a threshold method to recognize the initial sitting and the stable standing phases. Finally, we designed a novel CNN-BiLSTM-Attention algorithm to identify the three transition phases, namely, the flexion momentum phase, the momentum transfer phase, and the extension phase. Fifteen subjects were recruited to perform sit-to-stand transition experiments under a specific paradigm. A combination of the acceleration and angular velocity data features for the sit-to-stand transition phase identification were validated for the model performance improvements. The integration of the CNN, Bi-LSTM, and Attention modules demonstrated the reasonableness of the proposed algorithms. The experimental results showed that the proposed CNN-BiLSTM-Attention algorithm achieved the highest average classification accuracy of 99.5% for all five phases when compared to both traditional machine learning algorithms and deep learning algorithms on our customized dataset (STS-PD). The proposed sit-to-stand phase recognition algorithm could serve as a foundation for the control of wearable exoskeletons and is important for the further development of intelligent wearable exoskeleton rehabilitation robots.

Abstract Alphaviruses are arboviruses transmitted by mosquitoes and are pathogenic to humans and livestock, causing a substantial public health burden. So far, several receptors have been identified for alphavirus entry; however, they cannot explain the broad host range and tissue tropism of certain alphaviruses, such as Getah virus (GETV), indicating the existence of additional receptors. Here we identify the evolutionarily conserved low-density lipoprotein receptor (LDLR) as a new cell entry factor for GETV, Semliki Forest virus (SFV), Ross River virus (RRV) and Bebaru virus (BEBV). Ectopic expression of LDLR facilitates cellular binding and internalization of GETV, which is mediated by the interaction between the E2-E1 spike of GETV and the ligand-binding domain (LBD) of LDLR. Antibodies against LBD block GETV infection in cultured cells. In addition, the GST-LBD fusion protein inhibits GETV infection both in vitro and in vivo. Notably, we identify the key amino acids in LDLR-LBD that played a crucial role in viral entry; specific mutations in the CR4 and CR5 domain of LDLR-LBD reduce viral entry to cells by more than 20-fold. These findings suggest that targeting the LDLR-LBD could be a potential strategy for the development of antivirals against multiple alphaviruses.

Abstract Disulfidptosis, the demise of cells caused by the abnormal breakdown of disulfide bonds and actin in the cytoprotein backbone, has attracted attention in studies concerning disulfide-related cell death and its potential implications in cancer treatment. This study utilized bioinformatics to detect disulfidptosis associated lncRNA prognostic markers (DALPMs) with Uterine Corpus Endometrial Carcinoma (UCEC)-related to investigate the correlation between these indicators and the tumor immune microenvironment. The RNA sequencing data and somatic mutation information of patients with UCEC were obtained from the Cancer Genome Atlas (TCGA) database. Patients were randomly divided into Train and Test groups. The findings revealed a potential prognostic model comprising 14 DALPMs. Both univariate and multivariate Cox analyses demonstrated that the model-derived risk score functioned as a standalone prognostic indicator for patients. Significant disparities in survival outcomes were observed between the high- and low-risk groups as defined by the model. Differences in tumor mutational burden (TMB), tumor immune dysfunction and exclusion (TIDE), and tumor microenvironment (TME) stromal cells between patients of the high- and low-risk groups were also observed. The forecast model comprising long non-coding RNAs (lncRNAs) associated with disulfidptosis can effectively anticipate patients' prognoses.

Benzene is a known contributor to human leukaemia through its toxic effects on bone marrow cells, and epigenetic modification is believed to be a potential mechanism underlying benzene pathogenesis. However, the specific roles of N6-methyladenosine (m6A), a newly discovered RNA post-transcriptional modification, in benzene-induced hematotoxicity remain unclear. In this study, we identified self-renewing malignant proliferating cells in the bone marrow of benzene-exposed mice through in vivo bone marrow transplantation experiments and Competitive Repopulation Assay. Subsequent analysis using whole transcriptome sequencing and RNA m6A methylation sequencing revealed a significant upregulation of RNA m6A modification levels in the benzene-exposed group. Moreover, RNA methyltransferase METTL14, known as a pivotal player in m6A modification, was found to be aberrantly overexpressed in Lin-Sca-1+c-Kit+ (LSK) cells of benzene-exposed mice. Further analysis based on the GEO database showed a positive correlation between the expression of METTL14, mTOR, and GFI and benzene exposure dose. In vitro cellular experiments, employing experiments such as western blot, q-PCR, m6A RIP, and CLIP, validated the regulatory role of METTL14 on mTOR and GFI1. Mechanistically, continuous damage inflicted by benzene exposure on bone marrow cells led to the overexpression of METTL14 in LSK cells, which, in turn, increased m6A modification on the target genes’ (mTOR and GFI1) RNA. This upregulation of target gene expression activated signalling pathways such as mTOR-AKT, ultimately resulting in malignant proliferation of bone marrow cells. In conclusion, this study offers insights into potential early targets for benzene-induced haematologic malignant diseases and provides novel perspectives for more targeted preventive and therapeutic strategies.

IntroductionRemimazolam (RMZ) is a novel intravenous sedative drug of ultra-short benzodiazepine. The optimal dose of RMZ plus butorphanol for sedation during first trimester artificial abortion is unknown. Therefore, the present study aimed to evaluate the median effective dose (ED50) of RMZ combined with different doses of butorphanol on the sedative effect for first-trimester artificial abortion.MethodsSixty-one female patients were randomly assigned to Group B10 (31 patients) and Group B15 (30 patients). RMZ was administered 5 min after IV butorphanol at doses of 10 μg/kg (Group B10) and 15 μg/kg (Group B15). Cervical dilatation at the time of using a cervical dilating rod, if the patient has body movement and affects the gynecologist’s operation, we define it as “Ineffective.” Therefore, the dose of RMZ was increased in the next patient. Otherwise, it was defined as “Effective,” and the dose of RMZ was reduced in the next patient. According to the pre-experiment, the first dose of RMZ in the first patient was 0.35 mg/kg, and the adjacent geometric dose ratio was 0.9. The centered isotonic regression was performed to determine the ED50 of RMZ. The total RMZ dose administered, recovery time, and anesthesia-related adverse events were all recorded.ResultsThe ED50 (90% CI) of RMZ was 0.263 (0.215–0.310) mg/kg in Group B10, and 0.224 (0.191–0.261) mg/kg in Group B15, respectively. The recovery time in Group B10 was significantly shorter than in Group B15 (9.8 ± 2.3 vs. 12.5 ± 3.6 min, p ≤ 0.001). There was no significant difference in the incidence rate of all anesthesia-related adverse events between the two groups (p > 0.05).ConclusionThe ED50 of RMZ combined with a 10 μg/kg or 15 μg/kg dose of butorphanol was 0.263 and 0.224 mg/kg during painless first trimester artificial abortion. However, RMZ combined with a 10 μg/kg dose of butorphanol seems to have a shorter recovery time.Clinical trial registrationhttps://www.chictr.org.cn/bin/project/edit?pid=166623.

This study delves into Ulcerative colitis (UC), a persistent gastrointestinal disorder marked by inflammation and ulcers, significantly elevating colorectal cancer risk. The emergence of single-cell RNA sequencing (scRNA-seq) technology has opened new avenues for dissecting the intricate cellular dynamics and molecular mechanisms at play in UC pathology. By analyzing scRNA-seq data from individuals with UC, our study has revealed a consistent enhancement of inflammatory response pathways throughout the course of the disease, alongside detailing the characteristics of endothelial cell damage within colitis environments. A noteworthy finding is the downregulation of Phospholysine Phosphohistidine Inorganic Pyrophosphate Phosphatase (LHPP), which exhibited a inversely correlate with STAT3 expression levels. The markedly reduced expression of LHPP in both the tissues and plasma of UC patients positions LHPP as a compelling target for therapeutic intervention. Our findings highlight the pivotal role LHPP could play in moderating inflammation, spotlighting its potential as a crucial molecular target in the quest to understand and treat UC.

Context: Sanchi promotes wound healing by repressing fibroblast proliferation. Objective: This study examined the effect of Sanchi on keratinocytes (KCs) and microvascular endothelial cells (MECs) and rats with skin injury. Materials & methods: Hydrogels containing different concentrations of Sanchi extract were prepared to observe wound closure over 10 days. SD rats were divided into the control, Hydrogel, 5% Hydrogel, 10% Hydrogel, 10% Hydrogel + Ad5-NC, and 10% Hydrogel + Ad5-IL1B groups. KCs and MECs were induced with H2O2 for 24 h. Cell viability, apoptosis, and the levels of inflammation- and oxidative stress-related factors were examined. The effect of IL1B on wound healing was also evaluated. Results: Compared to the Control group (83% ± 7.4%) or Hydrogel without Sanchi extract (84% ± 8.5%), Hydrogel with 5% (95% closure ± 4.0%) or 10% Sanchi extract (98% ± 1.7%) accelerated wound healing in rats and attenuated inflammation and oxidative stress. Hydrogels containing Sanchi extract increased collagen deposition and CD31 expression in tissues. H2O2 (100 μM) induced injury in KCs and MECs, whereas Sanchi rescued the viability of KCs and MECs. Sanchi inhibited cell inflammation and oxidative stress and decreased apoptosis. As Sanchi blocked the NFκB pathway via IL1B, IL1B mitigated the therapeutic effect of Sanchi. Discussion and conclusion: Sanchi demonstrated therapeutic effects on wound healing in rats by promoting KCs and MECs activity. These findings provide valuable information for the clinical application of Sanchi, which needs to be validated in future clinical trials.

Abstract Sirtuin 1 (SIRT1) is a histone/protein deacetylase in the cellular response to inflammatory, metabolic, and oxidative stressors. We previously reported that myeloid SIRT1 regulates the inflamed liver’s canonical pyroptosis cell death pathway. However, whether/how hepatocyte SIRT1 is engaged in programmed cell death in the cold-stressed liver remains uncertain. Here, we undertook translational studies in human and mouse orthotopic liver transplantation (OLT) to interrogate the significance of hepatocyte-specific SIRT1 in cold-stored donor livers and liver grafts after reperfusion. In the clinical arm of sixty human OLT patients, hepatic SIRT1 levels in cold-preserved donor livers correlated with the anti-apoptotic Bcl-2 expression. After reperfusion, improved OLT function was accompanied by hepatic SIRT1 levels negatively associated with cleaved caspase-3 expression. In the experimental arm, we compared FLOX-control with hepatocyte-specific SIRT1-KO livers after orthotopic transplantation into WT mouse recipients, parallel with primary murine hepatocyte cultures subjected to cold activation with/without knockdown of SIRT1, GSDME, and IL18Rβ. Indeed, hepatocyte SIRT1 deficiency upregulated apoptosis and GSDME-mediated programmed cell death, deteriorating hepatocellular function and shortening OLT survival. Augmented GSDME processing, accompanied by increased secretion of IL18 by stressed hepatocytes, was prominent in SIRT1-deficient, cold-stored livers. Hepatocyte SIRT1 expression regulated anti-apoptotic Bcl-2/XIAP proteins, suppressed cold stress-triggered apoptosis, and mitigated GSDME licensing to release IL18. Notably, consistent with the ability of IL18 to depress hepatocyte SIRT1 and Bcl-2/XIAP in vitro, IL18 neutralization in vivo prevented hepatocellular damage and restored the anti-apoptotic phenotype in otherwise injury-prone SIRT1-deficient OLTs. In conclusion, this translational study identifies a novel hepatocyte SIRT1-IL18 molecular circuit as a therapeutic target in the mechanism underpinning hepatocyte death pathways in human and mouse liver transplantation.

Background: Corn peptides, a novel food prepared from corn gluten meal (CGM) by enzymatic hydrolysis or microbial fermentation, have attracted considerable interest owing to their various bioactive properties. However, the underlying mechanism of corn peptides attenuate non-alcoholic fatty liver disease (NAFLD) remains unclear. Objective: This study aimed to investigate the effect of corn peptides in NAFLD and to decipher the underlying mechanisms. Design: NAFLD was induced by a high-fat diet (HFD) for 10 weeks. Corn peptides were administered during the period. Human hepatocellular carcinomas (HepG2) cells induced by free fatty acids were used for this mechanism study. Results: Corn peptides alleviated HFD-induced histopathological changes, disorders of lipid metabolism, and mitochondrial damage. Moreover, corn peptides blocked mitophagy suppression by HFD based on the increased LC3, ATG7 expressions, as well as decreased P62 levels. Corn peptides increased the expression of proteins involved in fatty acid β-oxidation, such as PPARα and PGC-1α. Corn peptides also improved the Ser/Thr kinase PINK1 (PINK1) and the E3 ubiquitin ligase Parkin (Parkin) translocation to mitochondria, which is confirmed by immunofluorescence. Furthermore, stable knockdown of PINK1 by PINK1 SiRNA in HepG2 inhibited PINK1-Parkin-associated mitophagy and resulted in lipid accumulation. Conclusion: Corn peptides improved cell injury and ameliorated mitochondrial dysfunction and lipid accumulation via PINK1/Parkin-mediated autophagy in NAFLD. Thus, corn peptides could be a promising nutritional molecule with natural functions for preventing NAFLD.

To investigate the impact of blending natural gas with hydrogen on the combustion performance of partially premixed gas water heaters, a framelet-generated manifold (FGM) was employed for lower-order simulation of combustion processes. Coupled with the 30-step methane combustion mechanism simplified by GRI3.0, a three-dimensional computational fluid dynamics (CFD) simulation of the combustion chamber of a partially premixed gas water heater was carried out. A numerical simulation was performed to analyze the combustion process of a mixture including 0–40% natural gas and hydrogen in the combustion chamber of a partially premixed gas water heater. The results indicate that the appropriate hydrogen blending ratio for some premixed gas water heaters should be less than 20%. Furthermore, it was observed that after blending hydrogen, there was a significant increase in the combustion temperature of the water heater. Additionally, there was a slight increase in NOx.

A System-of-Systems (SoS) is characterized both by independence and by inter-dependency. This inter-dependency, while allowing an SoS to achieve its objectives, also means that failures can cascade throughout the SoS. An SoS needs to be resilient to deal with the impact of complex internal and external environments. In this paper, we propose a resilience analysis method of an SoS based on a hierarchy structure. Firstly, we establish a hierarchy structure, which is ranked from high to low as capability level, activity level and system level. Then, Bayesian Networks (BNs) and Dynamic Bayesian Networks (DBNs) are used to analyze the resilience of the SoS. A resilience-based system importance metric is introduced, which is used in the budget allocation optimization problem during the development domain of an SoS. This paper proposes a mathematical programming model aimed at optimizing SoS resilience by optimally using budget to the subsystem. The application of the proposed approach is demonstrated using a case study: a Next Generation Air Transportation setting. The study results provide evidence that the proposed inter-dependency analysis based on Bayesian theory and the SoS resilience design approach can assist SoS system engineers in increasing expected SoS resilience during the development domain.

Bent wood has the advantages of visually appealing and ergonomic shapes and the disadvantage of processing failure. Understanding how water and temperature influence wood bending is critical to avoid processing failure. Compared with softwood, saturated hardwood has been seldom reported in terms of bending performance at various temperature levels. In this paper, white birch and ash wood were studied in bending using a universal testing machine and a program-controlled water bath. White birch wood exhibited lower proportional limit stress, smaller modulus of elasticity (MOE), and lower failure stress, but higher proportional strain and failure strain than ash wood. At 20 °C, bending of air-dried wood on the tangential direction exhibited much smaller mechanical variation than that on the radial direction. The proportional limit stress, MOE, and failure stress of water-saturated wood were much smaller than those of air-dried wood, while failure strain was much higher. Evidenced by the almost constant proportional limit strain, plastic bending deformation of water-saturated wood happened to a great extent. As the temperature elevated at 20–100 °C, MOE, proportional limit stress, and failure stress of water-saturated wood decreased while proportional limit strain, failure strain, and wood toughness increased. Variation in proportional limit strain resulting from temperature change was ignorable, evidencing that elevated temperature enhanced wood plastic deformation. Furthermore, white birch wood was more susceptible to temperature over 40 °C than ash wood in terms of toughness. Under water-saturated condition, both species exhibited excellent bending performance at relatively high temperature.

The reservoir water level fluctuation zones (RWLFZs) and the natural riparian zones (NRZs) are two riparian ecosystems with dramatically opposite hydrological rhythms that notably influence the plant guilds. However, little is known about the discrepancies of the functional traits and niche characteristics of plant guilds in the RWLFZs and NRZs under different flooding rhythms. The aims of this study were to assess the divergent influence of natural and non-seasonal hydrological fluctuations on functional traits and niche characteristics of plant guilds. The results showed that 78 vascular plant species were identified in the riparian zones of the Xiangxi River basin. The dominant species were annuals in the two riparian ecosystems and their percentage increased temporally from 65.79% in the NRZs to 67.34% in the RWLFZs. Compared with the NRZs, the specific leaf area, vegetation coverage and the aboveground biomass in the RWLFZs significantly increased by 74%, 27% and 19.6%, respectively, while the water-use efficiency of the RWLFZ decreased by 59.6% and there was no significant difference in the net photosynthetic rate between them, which showed that annuals in the RWLFZs adopted the R adaptation strategy of being fast-growing with a short lifespan and quickly acquiring and investing resources by altering leaf morphology, including expanding the leaf area. The Simpson dominance index of RWLFZs was significantly higher than that of NRZ. Thus, counter-seasonally hydrological alterations had significant effects on functional traits of dominant species in the RWFLZs. Moreover, the highly adaptable and widely distributed species with larger niche breadths and high important values usually had a higher niche overlap value in the RWLFZs than in the NRZs, which showed that the competition in the plant communities after experiencing anti-seasonal flooding was much more intraspecific than interspecific and would facilitate the expansion of species niches. Our findings imply that the species with large niche breadths and high important values should be prioritized in ecological restoration efforts in the newly formed hydro-fluctuation zones of the TGR.

Satellite edge computing (SEC) plays an increasing role in earth observation, due to its global coverage and low-latency computing service. In SEC, it is pivotal to offload diverse observation-data-processing tasks to the appropriate satellites. Nevertheless, due to the sparse intersatellite link (ISL) connections, it is hard to gather complete information from all satellites. Moreover, the dynamic arriving tasks will also influence the obtained offloading assignment. Therefore, one daunting challenge in SEC is achieving optimal offloading assignments with consideration of the dynamic delay-sensitive tasks. In this paper, we formulate task offloading in SEC with delay-sensitive tasks as a mixed-integer linear programming problem, aiming to minimize the weighted sum of deadline violations and energy consumption. Due to the limited ISLs, we propose a fully-decentralized method, called the PI-based task offloading (PITO) algorithm. The PITO operates on each satellite in parallel and only relies on local communication via ISLs. Tasks can be directly offloaded on board without depending on any central server. To further handle the dynamic arriving tasks, we propose a re-offloading mechanism based on the match-up strategy, which reduces the tasks involved and avoids unnecessary insertion attempts by pruning. Finally, extensive experiments demonstrate that PITO outperforms state-of-the-art algorithms when solving task offloading in SEC, and the proposed re-offloading mechanism is significantly more efficient than existing methods.

Abstract Background Amygdala plays an important role in schizophrenia (SC), but its mechanisms are still unclear. Therefore, we investigated the relationship between the resting-state magnetic resonance imaging (rsMRI) signals of the amygdala and cognitive functions, providing references for future research in this area. Methods We collected 40 drug-naïve SC patients and 33 healthy controls (HC) from the Third People’s Hospital of Foshan. We used rsMRI and the automatic segmentation tool to extract the structural volume and local neural activity values of the amygdala and conducted Pearson correlation analysis with the Positive and Negative Syndrome Scale (PANSS) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) scores. Finally, we compared the clinical data, as well as the volume and functional changes of the amygdala in SC patients before and after treatment. Results Compared with HC, SC had widespread cognitive impairments, significant abnormalities in left amygdala function, while the reduction in volume of SC was not significant. Further Pearson correlation analysis with Bonferroni correction showed that only Immediate memory (learning) was significantly negatively correlated with fractional amplitude of low-frequency fluctuation (FALFF, r = -0.343, p = 0.001, p’ = 0.014 (Bonferroni correction)). When compared and analyzed the data difference of SC before and after treatment, we found that immediate memory and delayed memory of SC showed varying degrees of recovery after treatment (tlearning = -2.641, plearning = 0.011; tstory memory = -3.349, pstory memory = 0.001; tlist recall = -2.071, plist recall = 0.043; tstory recall = -2.424, pstory recall = 0.018). But the brain structure and function did not recover. Conclusion There was significant dysfunction in the amygdala in SC, and after conventional treatment, the function of the amygdala did not improve with the improvement of clinical symptoms and cognitive function.

Abstract Inflammatory bowel diseases (IBDs), including ulcerative colitis, and Crohn’s disease, are intestinal disorders characterized by chronic relapsing inflammation. A large proportion of patients with IBD will progress to develop colitis-associated colorectal cancer due to the chronic intestinal inflammation. Biologic agents that target tumour necrosis factor-α, integrin α4β7, and interleukin (IL)12/23p40 have been more successful than conventional therapies in treating IBD. However, drug intolerance and loss of response are serious drawbacks of current biologics, necessitating the development of novel drugs that target specific pathways in IBD pathogenesis. One promising group of candidate molecules are bone morphogenetic proteins (BMPs), members of the TGF-β family involved in regulating morphogenesis, homeostasis, stemness, and inflammatory responses in the gastrointestinal tract. Also worth examining are BMP antagonists, major regulators of these proteins. Evidence has shown that BMPs (especially BMP4/6/7) and BMP antagonists (especially Gremlin1 and follistatin-like protein 1) play essential roles in IBD pathogenesis. In this review, we provide an updated overview on the involvement of BMPs and BMP antagonists in IBD pathogenesis and in regulating the fate of intestinal stem cells. We also described the expression patterns of BMPs and BMP antagonists along the intestinal crypt-villus axis. Lastly, we synthesized available research on negative regulators of BMP signalling. This review summarizes recent developments on BMPs and BMP antagonists in IBD pathogenesis, which provides novel insights into future therapeutic strategies.

Abstract Background Electroacupuncture (EA) is a complementary and alternative therapy which has shown protective effects on vascular cognitive impairment (VCI). However, the underlying mechanisms are not entirely understood. Methods Rat models of VCI were established with cerebral ischemia using occlusion of the middle cerebral artery or bilateral common carotid artery. The brain structure and function imaging were measured through animal MRI. miRNA expression was detected by chip and qPCR. Synaptic functional plasticity was detected using electrophysiological techniques. Results This study demonstrated the enhancement of Regional Homogeneity (ReHo) activity of blood oxygen level-dependent (BOLD) signal in the entorhinal cortical (EC) and hippocampus (HIP) in response to EA treatment. miR-219a was selected and confirmed to be elevated in HIP and EC in VCI but decreased after EA. N-methyl-D-aspartic acid receptor1 (NMDAR1) was identified as the target gene of miR-219a. miR-219a regulated NMDAR-mediated autaptic currents, spontaneous excitatory postsynaptic currents (sEPSC), and long-term potentiation (LTP) of the EC-HIP CA1 circuit influencing synaptic plasticity. EA was able to inhibit miR-219a, enhancing synaptic plasticity of the EC-HIP CA1 circuit and increasing expression of NMDAR1 while promoting the phosphorylation of downstream calcium/calmodulin-dependent protein kinase II (CaMKII), improving overall learning and memory in VCI rat models. Conclusion Inhibition of miR-219a ameliorates VCI by regulating NMDAR-mediated synaptic plasticity in animal models of cerebral ischemia.

Abstract Background At present, there is not enough evidence to prove the relationship between blood lipid and electrocardiogram (ECG) abnormalities in common mental disorders (CMD). This study aimed to explore the relationship between them, to detect and prevent arrhythmia or sudden death. Methods We collected 272 CMD patients (maintained a fixed drug dose pattern for 1 year or more), including 95 schizophrenias (SC), 90 bipolar disorders (BD) and 87 major depressive disorders (MDD), and 78 healthy controls (HC) from the Third People’s Hospital of Foshan, China. We analyzed and compared their blood lipid and ECG indicators, to clarify the relationship between them. Results 350 participants were included. There were no significant differences in age, gender, total cholesterol (TC), low density lipoprotein (LDL) and QTc (p > 0.05) among subjects. And there were significant differences in body mass index (BMI), triglyceride (TG), high density lipoprotein (HDL), heart rate, PR interval and QRS width (p

Abstract Background The prognosis of patients with small cell lung cancer (SCLC) and brain metastases (BM) was poor. This study aimed to explore the efficacy and safety of anlotinib as third‐line or above treatment in SCLC with BM. Methods This was a subgroup analysis of the ALTER1202 trial, which was a randomized, placebo‐controlled trial aimed to evaluate the role of anlotinib as third‐line treatment or above in patients with SCLC. This study included patients with BM at baseline. The efficacy and safety outcomes included progression‐free survival (PFS), overall survival (OS), central nervous system (CNS), objective response rate (ORR), CNS disease control rate (DCR), time to CNS progression, and adverse events (AEs). Results Twenty‐one and nine patients with BM were included in the anlotinib and placebo groups, respectively. The median PFS and OS were 3.8 months (95% confidence interval [CI]: 1.8–6.1) and 6.1 months (95% CI: 4.1–8.0) in the anlotinib group. Anlotinib was associated with a significant improvement in PFS (hazard ratio [HR] = 0.15, 95% CI: 0.04–0.51, p = 0.0005) and OS (HR = 0.26, 95% CI: 0.09–0.73, p = 0.0061) than placebo. Anlotinib significantly prolonged the time to CNS progression (p

Abstract Diagnosing wooden foreign bodies (WFBs) using computed tomography (CT) is often missed, leading to adverse outcomes. This study aims to reduce misdiagnoses by exploring the density variation of blood-saline mixtures in ex vivo models. Twenty Cunninghamia lanceolata sticks, selected as WFB models, were randomly assigned to five groups: a control group (saline) and four experimental groups immersed in blood-saline mixtures with varying concentrations. The samples were then placed in a constant-temperature water bath at 36.8 °C. CT scans were performed in the lowest and highest density areas, and the volume of the low-density areas was measured at the post-processing workstation. Finally, the effects of time and concentration on imaging were analyzed, and fitting curves were generated. The blood-saline mixture concentration and time significantly affected the CT number in the three areas. WFB images changed dynamically over time, with two typical imaging signs: the bull's-eye sign on the short axis images and the tram line sign on the long axis images. Fitting curves of the CT number in the lowest density areas with different concentrations can quantify imaging changes. The CT number of the lowest density areas increased with time, following a logarithmic function type, while the CT number of the highest density areas exhibited a fast-rising platform type. The volume of the low-density areas decreased over time. The time of damage caused by WFBs and the influence of varying blood and tissue fluid contents at the damaged site should be considered in the diagnosis. Imaging changes from multiple CT scans at different times can aid in diagnosis.

Abstract Background Neuropathic pain (NP) is a chronic pathological pain that affects the quality of life and is a huge medical burden for affected patients. In this study, we aimed to explore the effects of secreted phosphoprotein 1 (SPP1) on NP. Methods We established a chronic constriction injury (CCI) rat model, knocked down SPP1 via an intrathecal injection, and/or activated the extracellular signal‐regulated kinase (ERK) pathway with insulin‐like growth factor 1 (IGF‐1) treatment. Pain behaviors, including paw withdrawal threshold (PWT), paw withdrawal latency (PWL), lifting number, and frequency, were assessed. After sacrificing rats, the L4‐L5 dorsal root ganglion was collected. Then, SPP1 levels were determined using quantitative polymerase chain reaction (qPCR) and western blot analysis. The levels of interleukin (IL)‐1β, tumor necrosis factor (TNF)‐α, IL‐6, IL‐10, epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), and transforming growth factor (TGF)‐β were determined using qPCR and enzyme‐linked immunosorbent assay. The levels of ERK pathway factors were determined via western blot analysis. Results We found that CCI decreased PWT and PWL, increased the lifting number and frequency, and upregulated SPP1 levels. The loss of SPP1 reversed these CCI‐induced effects. Additionally, CCI upregulated IL‐1β, TNF‐α, IL‐6, EGF, and VEGF levels, downregulated TGF‐β levels, and activated the ERK pathway, while silencing of SPP1 abrogated these CCI‐induced effects. Moreover, IGF‐1 treatment reversed the effects of SPP1 loss. Conclusions The data indicate that silencing SPP1 attenuates NP via inactivation of the ERK pathway, suggesting that SPP1 may be a promising target for NP treatment.

Background: Empagliflozin (EMPA) ameliorates reactive oxygen species (ROS) generation in human endothelial cells (ECs) exposed to 10 % stretch, but the underlying mechanisms are still unclear. Pathological stretch is supposed to stimulate protein kinase C (PKC) by increasing intracellular calcium (Ca2+), therefore activating nicotinamide adenine dinucleotide phosphate oxidase (NOX) and promoting ROS production in human ECs. We hypothesized that EMPA inhibits stretch-induced NOX activation and ROS generation through preventing PKC activation. Methods: Human coronary artery endothelial cells (HCAECs) were pre-incubated for 2 h before exposure to cyclic stretch (5 % or 10 %) with either vehicle, EMPA or the PKC inhibitor LY-333531 or PKC siRNA. PKC activity, NOX activity and ROS production were detected after 24 h. Furthermore, the Ca2+ chelator BAPTA-AM, NCX inhibitor ORM-10962 or NCX siRNA, sodium/potassium pump inhibitor ouabain and sodium hydrogen exchanger (NHE) inhibitor cariporide were applied to explore the involvement of the NHE/Na+/NCX/Ca2+ in the ROS inhibitory capacity of EMPA. Results: Compared to 5 % stretch, 10 % significantly increased PKC activity, which was reduced by EMPA and PKC inhibitor LY-333531. EMPA and LY-333531 showed a similar inhibitory capacity on NOX activity and ROS generation induced by 10 % stretch, which was not augmented by combined treatment with both drugs. PKC-β knockdown inhibits the NOX activation induced by Ca2+ and 10 % stretch. BAPTA, pharmacologic or genetic NCX inhibition and cariporide reduced Ca2+ in static HCAECs and prevented the activation of PKC and NOX in 10%-stretched cells. Ouabain increased ROS generation in cells exposed to 5 % stretch. Conclusion: EMPA reduced NOX activity via attenuation of the NHE/Na+/NCX/Ca2+/PKC axis, leading to less ROS generation in HCAECs exposed to 10 % stretch.

Uterine corpus endometrial carcinoma (UCEC) is a common female reproductive system cancer. Cuproptosis, a new type of mitochondrial respiration-regulated cell death, is associated with several cancer types. Here, we developed a cuproptosis-associated long non-coding RNA (lncRNA) model to predict the prognosis of patients with UCEC and their response to immune-based treatments. RNA sequencing (RNA-seq) and somatic mutation data for UCEC were obtained from The Cancer Genome Atlas (TCGA) database. LncRNAs co-expressed with cuproptosis-related genes were screened. Patients were randomly divided into two groups, one of which was used as training group to build the model, while the other group served as the validation group. A prognostic model comprising 13 cuproptosis-associated lncRNAs was constructed, and each lncRNA was individually related to patient prognosis. Our model clearly distinguished between risk variables in afflicted individuals. The risk score can provide a more accurate prognostic prediction compared with other clinical covariates. Patient groups at various risk groups were different according to tumor mutational burden and tumor immune dysfunction and exclusion analysis. We identified drugs for which patient populations at various risk groups showed higher sensitivity. Our model may contribute to immune related research and clinical decision-making for optimized treatment.

Abstract Background Recently studies had showed that the amygdala may take part in the cognitive impairment in schizophrenia (SC). However, the mechanism is still unclear, so we explored the relationship between the amygdala resting state magnetic resonance imaging (rsMRI) signal and cognitive function, to provide a reference for the follow-up study. Methods We collected 59 drug-naïve SCs and 46 healthy controls (HCs) from the Third People’s Hospital of Foshan. The rsMRI technique and automatic segmentation tool were used to extract the volume and functional indicators of the SC’s amygdala. The Positive and Negative Syndrome Scale (PANSS) was used to assess the severity of the disease, and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was used to assess cognitive function. Pearson correlation analysis was used to compare the relationship between the structural and functional indicators of the amygdala and PANSS and RBANS. Results (1) There was no significant difference between SC and HC in age, gender and years of education. Compared with HC, the PANSS score of SC increased and the RBANS score decreased significantly. Meanwhile, the left amygdala volume decreased (t=-3.675, p

The microscopic pore structure of tight sandstone reservoirs significantly influences the characteristics of CO2 flooding after water flooding. This research was conducted using various techniques such as casting thin sections, high-pressure mercury injection, scanning electron microscopy, nuclear magnetic resonance (NMR) testing, and a self-designed high-temperature and high-pressure microscopic visualization displacement system. Three types of cores with different pore structures were selected for the flooding experiments and the microscopic visualization displacement experiments, including CO2 immiscible flooding, near-miscible flooding, and miscible flooding after conventional water flooding. The characteristics of CO2 flooding and the residual oil distribution after water flooding were quantitatively analyzed and evaluated. The results show the following: (1) During the water flooding process, the oil produced from type I and type III samples mainly comes from large and some medium pores. Oil utilization of all pores is significant for type II samples. The physical properties and pore types have a greater impact on water flooding. Type I and II samples are more suitable for near-miscible flooding after water flooding. Type III samples are more suitable for miscible flooding after water flooding. (2) In CO2 flooding, oil recovery increases gradually with increasing pressure for all three types of samples. Type II core samples have the highest recovery. Before miscibility, the oil recovered from type I and type II samples is primarily from large pores; however, oil recovery mainly comes from medium pores when reaching miscibility. As for the type III samples, the oil produced in the immiscible state mainly comes from large and medium pores, and the enhanced oil recovery mainly comes from medium and small pores after reaching the near-miscible phase. (3) It can be seen from the microscopic residual oil distribution that oil recovery will increase as the petrophysical properties of the rock model improve. The oil recovery rate of near-miscible flooding after water flooding using the type II model is up to 68.11%. The oil recovery of miscible flooding after water flooding with the type III model is the highest at 74.57%. With increasing pressure, the proportion of flake residual oil gradually decreases, while the proportion of droplet-like and film-like residual oil gradually increases. Type II samples have a relatively large percentage of reticulated residual oil in the near-miscible stage.

ObjectivePropofol-opioids are the most common drug combination and can reduce the dose of propofol and the incidence of adverse events in painless artificial abortion. We hypothesized that butorphanol may reduce the median effective dose (ED50) of propofol, propofol injection pain, and postoperative uterine contraction pain.MethodsThis was a randomized, double-blind, controlled study. A total of 54 female patients, who had ASA I or II, aged 18–49 years, undergoing painless artificial abortion, were randomly assigned into two groups, namely, Group P (propofol) and Group PB (propofol plus 10 μg/kg butorphanol). According to the pre-experiment, the initial dose of propofol for the P and PB groups was 3 and 2.5 mg/kg, respectively, with a dose gradient of 0.25 mg/kg. The ED50 of propofol was analyzed using probit regression analysis. The total propofol dose consumed, recovery time, and anesthesia-related adverse events were also recorded.ResultsThere were 25 and 29 patients in the P and PB groups, respectively. The ED50 (95% CI) of propofol for artificial abortion were 2.477 (2.186–2.737) and 1.555 (1.173–1.846) mg/kg in the P and PB groups, respectively. The total propofol dose consumed was (150.7 ± 21.7) mg and (110.4 ± 28.2) mg in the P and PB groups, respectively (P < 0.001). Compared with the P group, injection-site pain (76 vs. 20.7%) and uterine contraction pain (72 vs. 6.9%) in the PB group had a significant decrease (P < 0.001).ConclusionCombination of propofol with 10 μg/kg butorphanol reduced the ED50 of propofol and decreased the incidence of propofol injection-site pain and postoperative uterine contraction pain during painless artificial abortion compared with propofol alone.Clinical trial registrationhttps://www.chictr.org.cn/showproj.html?proj=166610, identifier: ChiCTR2200059795.

Vascular cognitive impairment not dementia (VCIND) is one of the three subtypes of vascular cognitive impairment (VCI), with cognitive dysfunction and symptoms ranging between normal cognitive function and vascular dementia. The specific mechanisms underlying VCIND are still not fully understood, and there is a lack of specific diagnostic markers in clinical practice. With the rapid development of magnetic resonance imaging (MRI) technology, structural MRI (sMRI) and functional MRI (fMRI) have become effective methods for exploring the neurobiological mechanisms of VCIND and have made continuous progress. This article provides a comprehensive overview of the research progress in VCIND using multimodal MRI, including sMRI, diffusion tensor imaging, resting-state fMRI, and magnetic resonance spectroscopy. By integrating findings from these multiple modalities, this study presents a novel perspective on the neuropathological mechanisms underlying VCIND. It not only highlights the importance of multimodal MRI in unraveling the complex nature of VCIND but also lays the foundation for future research examining the relationship between brain structure, function, and cognitive impairment in VCIND. These new perspectives and strategies ultimately hold the potential to contribute to the development of more effective diagnostic tools and therapeutic interventions for VCIND.

Aging-related cognitive impairment (ARCI) is rapidly becoming a healthcare priority. However, there is currently no excellent cure for it. Cognitive-exercise dual-task intervention (CEDI) is a promising method to improve ARCI, while the underlying mechanisms remain unclear. Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) are involved in the onset, development, and rehabilitation of ARCI. This study aimed to investigate the effects of CEDI and the role of regulation of the lncRNA NEAT1/miR-124–3p on the caveolin-1-PI3K/Akt/GSK3β pathway in CEDI improving cognitive function. Forty 18-month-old natural aging rats were randomly assigned to four groups: exercise training group, cognitive training group, CEDI group, and aging control group, and underwent 12 weeks of intervention. A novel object recognition test was performed to determine the cognitive function, and the hippocampus was separated three days after the behavioral tests for further molecular detection. In an in vitro study, the mouse hippocampal neuronal cell line HT22 was cultured. MiR-124–3p and lncRNA NEAT1 were over-expressed or down-expressed, respectively. The expressions of related proteins, lncRNA, and miRNA were examined by WB and/or qRT-PCR. The results showed that compared with the aging control group, the CEDI group had a higher discrimination index, and significantly decreased the expressions of lncRNA NEAT1, and the protein expressions of caveolin-1 and p-GSK3β, while significantly increased the expressions of miR-124–3p, and the protein expressions of p-PI3K and p-Akt. Inhibition of the lncRNA NEAT1 could significantly increase the protein expressions of p-PI3K and p-Akt in HT22 cells. Upregulation of miR-124–3p decreased the protein expressions of caveolin-1 and p-GSK3β, and increased the protein expressions of p-PI3K and p-Akt significantly. Inhibition of miR-124–3p had the opposite effects. Our study demonstrated that CEDI improved cognitive function in aging rats better than a single intervention. The mechanisms of cognitive improvement could be related to the regulation of the lncRNA NEAT1/miR-124–3p on the caveolin-1-PI3K/Akt/GSK3β pathway.

DNASE1L3, an enzyme highly expressed in DCs, is functionally important for regulating autoimmune responses to self-DNA and chromatin. Deficiency of DNASE1L3 leads to development of autoimmune diseases in both humans and mice. However, despite the well-established causal relationship between DNASE1L3 and immunity, little is known about the involvement of DNASE1L3 in regulation of antitumor immunity, the foundation of modern antitumor immunotherapy. In this study, we identify DNASE1L3 as a potentially new regulator of antitumor immunity and a tumor suppressor in colon cancer. In humans, DNASE1L3 is downregulated in tumor-infiltrating DCs, and this downregulation is associated with poor patient prognosis and reduced tumor immune cell infiltration in many cancer types. In mice, Dnase1l3 deficiency in the tumor microenvironment enhances tumor formation and growth in several colon cancer models. Notably, the increased tumor formation and growth in Dnase1l3-deficient mice are associated with impaired antitumor immunity, as evidenced by a substantial reduction of cytotoxic T cells and a unique subset of DCs. Consistently, Dnase1l3-deficient DCs directly modulate cytotoxic T cells in vitro. To our knowledge, our study unveils a previously unknown link between DNASE1L3 and antitumor immunity and further suggests that restoration of DNASE1L3 activity may represent a potential therapeutic approach for anticancer therapy.

Vascular cognitive impairment (VCI) is the initial stage of vascular dementia (VaD). Early diagnosis and treatment of VCI are crucial to prevent the progression of VaD. In order to gain a better understanding of VCI, this study aimed to investigate the use of advanced imaging techniques such as structural magnetic resonance imaging (sMRI) and resting-state functional magnetic resonance imaging (rs-fMRI). These techniques allow researchers to observe the structural and functional changes in the brain that are associated with VCI. Functional magnetic resonance imaging (fMRI) and sMRI techniques have been widely used in studies focusing on gray matter, brain networks, and functional abnormalities during rest. By searching and summarizing recent literature, this study has provided valuable evidence on the use of advanced imaging techniques in understanding and treating VCI. The findings from this study can aid in the development of early intervention strategies for patients with VCI, potentially slowing down or even halting the progression of VCI to full-blown VaD.

Subjective cognitive decline (SCD) is the initial stage of Alzheimer’s disease (AD). Early identification of SCD and its risk factors is of great importance for targeted interventions and for delaying the onset of AD. We reviewed the relevant literature on structural magnetic resonance imaging (sMRI), diffusion tensor imaging (DTI), functional magnetic resonance imaging (fMRI), and other techniques regarding SCD research in recent years. This study applied sMRI and fMRI techniques to explore abnormal brain structures and functions, which may help provide a basis for SCD diagnosis.

Abstract Background Most Non‐small cell lung cancer (NSCLC) patients tend to have metastases at the initial diagnosis. However, limited knowledge has been established regarding which factors, are associated with its metastases. This study aims to identify more biomarkers associated with its organ tropism metastasis and to establish models for prediction of its metastatic organs. Methods We performed targeted next‐generation sequencing (NGS) to detect genes related to lung cancer in 272 patients with primary advanced NSCLC from Northeast China. We adopted Fisher test, multivariate logistic regression analysis to identify metastasis‐related gene mutations and to establish prediction models. Results Mutations of EGFR (p = 0.0003, OR = 2.554) (especially EGFR L858R [p = 0.02, OR = 2.009]), ATM (p = 0.008, OR = 11.032), and JAK2 (p = 0.009, OR = Inf) were positively and of TP53 exon4mut (p = 0.001, OR = 0.173) was negatively correlated with lung metastasis, and those of CSF1R (p = 0.01, OR = Inf), KIT (p = 0.03, OR = 4.746), MYC (p = 0.05, OR = 7.938), and ERBB2 (p = 0.02, OR = 2.666) were positively correlated with pleural dissemination; those of TP53 (p = 0.01, OR = 0.417) was negatively, while of SMAD4 (p = 0.03, OR = 4.957) was positively correlated with brain metastasis of NSCLC. Additionally, smoking history (p = 0.004, OR = 0.004) was negatively correlated with pleural dissemination of NSCLC. Furthermore, models for prediction of lung metastasis (AUC = 0.706), pleural dissemination (AUC = 0.651), and brane metastasis (AUC = 0.629) were established. Conclusion Taken together, this study revealed nine mutant genes and smoking history associated with organ tropism metastases of NSCLC and provided three models for the prediction of metastatic organs. This study enables us to predict the organs to which non‐small cell lung cancer metastasizes before it does develop.

Abstract In clinical practice, cisplatin is the most commonly used chemotherapy drug to treat a range of malignancies. Severe ROS-regulated nephrotoxicity, however, restricts its applicability. Currently, the main mechanisms leading to cisplatin-induced nephrotoxicity in clinical settings involve hydration or diuresis. However, not all patients can be treated with massive hydration or diuretics. Therefore, it is crucial to develop a treatment modality that can effectively reduce nephrotoxicity through a foodborne route. Selenium has been reported to have strong antioxidant as well as anticancer effects when administered as spore oil. Herein, we established cellular and animal models of cisplatin-induced nephrotoxicity and synthesized spore oil-functionalized nano-selenium (GLSO@SeNPs). We found that GLSO@SeNPs inhibit the mitochondrial apoptotic pathway by maintaining oxidative homeostasis and regulating related signaling pathways (the MAPK, caspase, and AKT signaling pathways). In vivo, GLSO@SeNPs could effectively improve cisplatin-induced renal impairment, effectively maintaining oxidative homeostasis in renal tissues and thus inhibiting the process of renal injury. In addition, GLSO@SeNPs were converted into selenocysteine (SeCys2), which may exert protective effects. Furthermore, GLSO@SeNPs could effectively modulate the ratio of immune cells in kidneys and spleen, reducing the proportions of CD3+CD4+ T cells, CD3+CD8+ T cells, and M1 phenotype macrophages and increasing the proportion of anti-inflammatory regulatory T cells. In summary, in this study, we synthesized food-derived spore oil-functionalized nanomaterials, and we explored the mechanisms by which GLSO@SeNPs inhibit cisplatin-induced nephrotoxicity. Our study provides a basis and rationale for the inhibition of cisplatin-induced nephrotoxicity by food-derived nutrients.