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The eastern uplift of the Junggar Basin has great coalbed methane (CBM) exploration potential. CBM selection and evaluation will provide scientific guidance and direction for CBM exploration in the region. Utilizing well logging data, core analysis test results, and seismic data, well-seismic calibration and seismic profile interpretation were carried out. Connecting-well profiles and thickness distribution maps for coal seams in the Jurassic Xishanyao and Badaowan formations were compiled. The study analyzed main accumulation factors, including gas source, basic characteristics of coal rocks, reservoir physical properties, gas content, and preservation conditions. The results show that: ① Coal seams of the Xishanyao Formation are distributed continuously in the Wucaiwan-Wutongwozi sags to the north of the Shaqi Uplift, while to the south of the Shaqi Uplift, the seams are mainly distributed in the Jimusaer-Jinan sags. Coal seams of the Badaowan Formation are strongly segmented and mainly distributed in parts of the sags. ② This region contains self-sourced biogenic gas from coal seams, low-maturity thermogenic gas, and high-maturity deep-seated exogenous gas. ③ The organic components in coal rocks are mainly inertinite, followed by vitrinite with small amounts of exinite. The vitrinite reflectance (Ro) in coal rocks is low (0.39%-0.47%), indicating low-rank coal. CBM mainly consists of N2, CO2, and CH4, with N2 being the dominant component. The combustible gas (CH4) content is low relative to the total gas content in coal rocks. ④ CBM enrichment and accumulation models include piedmont fault depression, deep depression, and open slope gas escape models. ⑤ Evaluation parameters and classification standards were established. The Wucaiwan, Wutongwozi, Jimusaer, and Jinan sags are favorable areas for CBM exploration. The Shazhang fault-fold belt and the Shiqiantan Sag are moderately favorable areas. The Shishugou and Gucheng sags are unfavorable areas.

Abstract Background Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease with poor prognosis, nomogram model for its prognosis and acute exacerbation was constructed. Methods Two hundred and sixty eight patients with IPF were grouped with different severity according to fibrosis area, serum Club cell secretory protein 16(CC16) was compared between these groups. All patients were randomly divided into training and testing sets. COX regression and LASSO algorithm were used to screen featured characteristics. Then nomogram models were constructed, ROC curve, calibration curve and decision curve analysis(DCA) were conducted to evaluate the performance of model. Expression of CC16 were detected in fibrotic human lung tissues, bronchoalveolar lavage fluid (BALF) and Bleomycin(BLM)-treated mouse lung tissues and serums. Results Serum CC16 gradually increased with the severity of fibrosis, and was especially high in AE-IPF group. CC16 and diffusion capacity for carbon monoxide (DLCO) were screened as characteristic variables to construct nomogram model for IPF prognosis. The survival was significantly lower in high-risk group scored by the model. The area under ROC curves(AUCs) for 1-year and 2-year mortality prediction were 0.866 and 0.916, respectively. This model performed better than gender-age-physiology (GAP) index for predicting 2-year and 3-year mortality. Another nomogram model for acute exacerbation of IPF based on CC16, Krebs von den Lungen-6(KL-6) and DLCO was developed, the AUC was 0.815. Expression of CC16 obviously up-regulated in fibrotic lung tissues, BALF and BLM-treated mice lung tissues and serums. Conclusions The nomogram model based on CC16 performed good predictive ability for prognosis and acute exacerbation of IPF.

The nervous and immune systems are crucial in fighting infections and inflammation and in maintaining immune homeostasis. The immune and nervous systems are independent, yet tightly integrated and coordinated organizations. Numerous molecules and receptors play key roles in enabling communication between the two systems. Transient receptor potential vanilloid subfamily member 1 (TRPV1) is a non-selective cation channel, recently shown to be widely expressed in the neuroimmune axis and implicated in neuropathic pain, autoimmune disorders, and immune cell function. TRPV1 is a key bridge in neuroimmune interactions, allowing for smooth and convenient communication between the two systems. Here, we discuss the coordinated cross-talking between the immune and nervous systems and the functional role and the functioning manner of the TRPV1 involved. We suggest that TRPV1 provides new insights into the collaborative relationship between the nervous and immune systems, highlighting exciting opportunities for advanced therapeutic approaches to treating neurogenic inflammation and immune-mediated diseases.

Background: The complex correlation between Adverse Childhood Experiences (ACEs) and the emergence of Conduct Disorder (CD) requires in-depth examination to inform targeted interventions and support strategies fitted to the unique context of Chinese children. This study explored the correlation between Adverse Childhood Experiences and Conduct Disorder among children in China.Methods: We employed a cross-sectional design to examine the population within Fujian Province, China. A total of 168 participants were recruited by cluster random sampling method on February 9, 2023. The Strengths and Difficulties Questionnaire (SDQ) and Adverse Childhood Experience International Questionnaire (ACE-IQ) were applied for data collection. IBM SPSS version 25 was applied for data analysis to conduct a multiple regression analysis. Pearson correlations and multiple linear regression were also used to analyze the data.Results: Adverse childhood experience (Mean±SD=2.208±2.08) and conduct disorder (Mean±SD=1.77±1.35) were investigated. Based on the results, there was a positive correlation between physical neglect (r=0.302, P

Abstract The applications of hydrogels have expanded significantly due to their versatile, highly tunable properties and breakthroughs in biomaterial technologies. In this review, we cover the major achievements and the potential of hydrogels in therapeutic applications, focusing primarily on two areas: emerging cell-based therapies and promising non-cell therapeutic modalities. Within the context of cell therapy, we discuss the capacity of hydrogels to overcome the existing translational challenges faced by mainstream cell therapy paradigms, provide a detailed discussion on the advantages and principal design considerations of hydrogels for boosting the efficacy of cell therapy, as well as list specific examples of their applications in different disease scenarios. We then explore the potential of hydrogels in drug delivery, physical intervention therapies, and other non-cell therapeutic areas (e.g., bioadhesives, artificial tissues, and biosensors), emphasizing their utility beyond mere delivery vehicles. Additionally, we complement our discussion on the latest progress and challenges in the clinical application of hydrogels and outline future research directions, particularly in terms of integration with advanced biomanufacturing technologies. This review aims to present a comprehensive view and critical insights into the design and selection of hydrogels for both cell therapy and non-cell therapies, tailored to meet the therapeutic requirements of diverse diseases and situations.

Nitrogen is an indispensable element in the growth and development stages of various crops, as well as an important component of soil nutrients. It plays an important role in farmland ecosystems. Studying the spatial distribution of soil total nitrogen (STN) is essential for improving the efficiency of soil fertility management and for a better understanding of the soil nitrogen cycle. In the study, the STN content data of surface soil (0–20 cm) were obtained from 19,119 sampling sites within an area of 7.47 × 104 km2 based on a multi-purpose regional geochemical survey established in Zhejiang Province, China, from 2002 to 2018. The spatial distribution and main driving factors of STN were determined using the random forest model. The results showed that the average STN content in the topsoil of the Zhejiang Province was 1.48 g⋅kg−1. Among the different land-use types, grassland soil had the highest STN content of 1.55 g⋅kg−1, and alfisol had the highest STN content of 2.59 g⋅kg−1. The spatial distribution of STN content was high in the northern part and low in the southern part of the study area. The results of the random forest analysis showed that nitrogen deposition, pH, and mean annual precipitation (MAP) were the most important factors influencing the spatial variability of STN. The STN content exhibited a nonlinear decrease with an increase in pH and MAP and a nonlinear increase with an increase in nitrogen deposition. This study provides decision-makers with synthesized information on the spatial variability of STN and its driving factors in Zhejiang Province, which is important for accurately grasping the spatial distribution characteristics of STN to implement precision agriculture management measures.

Rotenone (ROT), a widely used natural pesticide, has an uncertain effect on reproductive toxicity. In this study, we used 20 mice distributed randomly into four groups, with each group receiving ROT doses of 0, 2, 4, and 8 mg/kg/day for 28 days. The results demonstrated that ROT induced significant testicular damage, including impaired spermatogenesis, inhibition of testosterone synthesis, and apoptosis of Leydig cells. Additionally, ROT disrupted the normal ultrastructure of the endoplasmic reticulum (ER) in testicular tissue, leading to ER stress in Leydig cells. To further explore whether ROT-induced apoptosis in Leydig cells is related to ER stress, the mouse Leydig cell line (TM3 cells) was treated with ROT at 0, 250, 500, and 1000 nM. ROT inhibited TM3 cell viability, induced cytotoxicity, and reduced testosterone content in the culture supernatants. Furthermore, ROT treatment triggered apoptosis in TM3 cells by activating ER stress and the PERK-eIF2α-CHOP signalling pathway. Pre-treatment of TM3 cells exposed to ROT with the ER stress inhibitor 4-phenylbutyric acid (4-PBA) alleviated these effects, decreasing apoptosis and preserving testosterone levels. Further intervention with the PERK inhibitor GSK2606414 reduced ROT-induced apoptosis and testosterone reduction by inhibiting PERK activity. In summary, ROT-induced male reproductive toxicity is specifically driven by apoptosis, with the PERK-eIF2α-CHOP signalling pathway activated by ER stress playing a crucial role in the apoptosis of Leydig cells triggered by ROT.

Renal fibrosis is a common pathological manifestation of chronic kidney disease （CKD）. Since the process of renal drug delivery is rather complex, there is currently no effective remedy for reversing renal fibrosis （RF）. Nanotechnology has been widely applied in the field of medicine and its targeting applications bring new hopes for managing RF. Currently numerous studies are aimed at developing delivery systems of targeting specific renal regions, cells or proteins. This review summarized the current diagnoses of RF, different targeting strategies and potential nano-preparations of plant extracts for treating RF.

Abstract Idiopathic pulmonary fibrosis (IPF) is a life-threatening interstitial lung disease. Identifying biomarkers for early diagnosis is of great clinical importance. The epididymis protein 4 (HE4) is important in the process of inflammation and fibrosis in the epididymis. Its prognostic value in IPF, however, has not been studied. The mRNA and protein levels of HE4 were used to determine the prognostic value in different patient cohorts. In this study, prognostic nomograms were generated based on the results of the cox regression analysis. We identified the HE4 protein level increased in IPF patients, but not the HE4 gene expression. The increased expression of HE4 correlated positively with a poor prognosis for patients with IPF. The HR and 95% CI were 2.62 (1.61–4.24) (p

BackgroundHyperuricemia (HUA) is a glo\bal public health problem. The etiology of HUA is complex and efficient and accurate assessment metrics are still lacking when conducting large-scale epidemiologic screening. The aim of this study was to evaluate the association of the triglyceride glucose (TyG) index, TyG-body mass index (BMI), TyG-waist-to-height ratio (WHtR) with the risk of HUA.MethodsBased on data collected from the National Health and Nutrition Examination Survey (NHANES) in the United States and the China Health and Aging Longitudinal Study (CHARLS) in China, a total of 14,286 U.S. adults and 4,620 Chinese adults were included in the analysis. The study examined the levels of TyG, TyG-BMI, TyG-WHtR, and TyG-WC. Multivariate logistic regression was utilized to investigate the relationships between these variables and hyperuricemia (HUA), separately. Additionally, the study used restricted cubic splines (RCS) to explore the linear associations of TyG, TyG-BMI, TyG-WHtR, TyG-WC, and HUA, separately.ResultsThe NHANES results showed that TyG [Q2, 1.58(1.26, 1.98); Q3, 2.36 (1.94, 2.88); Q4, 3.21 (2.61, 3.94)], TyG-BMI [Q2, 2.14 (1.74, 2.65); Q3, 3.38 (2.74, 4.17); Q4, 6.70 (5.55, 8.02)], TyG-WHtR [Q2, 1.92 (1.56, 2.36); Q3, 3.14 (2.56, 3.85); Q4, 6.28 (5.12, 7.69)], TyG-WC [Q2, 2.32 (1.85, 2.90); Q3, 3.51 (2.84, 4.34); Q4, 7.32 (5.95, 9.02)] were identified as risk factors for hyperuricemia (HUA). Similarly, the CHARLS results, when fully adjusted for covariates, indicated that TyG [Q4, 2.36 (1.08, 5.15)], TyG-BMI [Q3, 2.60 (1.05, 6.41); Q4, 3.70 (1.64, 8.32)], TyG-WHtR (Q4, 2.84 (1.23, 6.55), TyG-WC [Q4, 2.85 (1.23, 6.5)] were also risk factors for HUA. The predictive ability of each indicator for the risk of developing HUA was stronger in women than in men. Furthermore, there was an observed nonlinear relationship between TyG, TyG-BMI, TyG-WHtR, TyG-WC, and HUA in both the NHANES and CHARLS datasets (P-nonlinearity < 0.05).ConclusionThese findings suggest that TyG, TyG-BMI, TyG-WHtR and TyG-WC are associated with an increased risk of HUA. They are potential indicators for screening HUA status in the general population in China and the United States.

BackgroundThe Geriatric Nutritional Risk Index (GNRI) is a straightforward and objective tool for nutritional screening in older patients and has been demonstrated to possess prognostic predictive value in several diseases. Nonetheless, there is a lack of research on the nutritional risk associated with brain abscess in the older. This study aimed to evaluate the prevalence of nutritional risk among these patients by GNRI and to investigate its potential prognostic value for clinical outcomes.Materials and methodsFrom August 2019 to April 2023, 100 older patients diagnosed with brain abscess were enrolled in this single-center prospective cohort study, which evaluated the prognostic value of the Geriatric Nutritional Risk Index (GNRI) in elderly brain abscess patients. Data collected included demographic, and clinical characteristics at admission and calculated the GNRI, and the Glasgow Outcome Scale (GOS) score 6 months post-discharge. A GOS score of 5 was considered indicative of a good recovery, whereas scores ranging from 1 to 4 were classified as poor recovery.ResultsThe results revealed that 48% of older brain abscess patients were at risk of malnutrition according to the GNRI. These patients had significantly higher post-admission C-reactive protein (CRP) levels (p = 0.017), more comorbidities (p

Background: Severe intracerebral hemorrhage (ICH) is the most devastating subtype of stroke resulting in high mortality and disability. At present, the development of targeted treatments to minimize the high morbidity and mortality is limited partly due to the lack of a severe ICH animal model. In this study, we aimed to establish an accurate severe ICH model in rats and examine the pathological and physiological changes associated with ICH. Methods: A rat model of severe ICH model was established by intrastriatal injection of autologous blood using different blood volumes (ICH 100 µL group, ICH 130 µL group, ICH 160 µL group, ICH 170 µL group, and ICH 180 µL group). The mortality was assessed during the 28-day post-ICH period. Short- and long-term neurological deficits were evaluated using the Longa method, foot fault, falling latency, and Morris water maze tests. Brain water content, hematoma volume, hemoglobin content, and magnetic resonance imaging were assessed to determine the extent of brain injury. Immunofluorescence staining was conducted to examine microglial activation and neuronal apoptosis. Hematoxylin and eosin (H&E) staining, lung water content, and western blotting were used to assess lung injury following ICH. Results: The mortality of ICH rats increased significantly with an increase in autologous blood injection. The 28-day mortality in the 100 µL, 130 µL, 160 µL, 170 µL, and 180 µL ICH groups were 5%, 20%, 40%, 75%, and 100%, respectively. A significantly higher 28-day mortality was observed in the ICH 160 µL group compared to the ICH 100 µL group. The ICH 160 µL group exhibited significantly increased neurological deficits, brain edema, hematoma volume, and hemoglobin content compared to the sham group. Compared with the sham operation group, the activation of microglia and neuronal death in ICH 160 µL rats increased. The use of H&E staining and western blotting demonstrated that disruption of the intra-alveolar structure, alveolar edema, and infiltration of inflammatory cells and cytokines into the lung tissue were more severe in the ICH 160 µL group than the sham group. Conclusions: A severe ICH model in rats was successfully established using an injection of autologous blood at a volume of 160 µL. This model may provide a valuable tool to examine the pathological mechanisms and potential therapeutic interventions of severe ICH.

This paper introduces a pioneering approach that combines ex situ synthesis with advanced manufacturing to develop ZIF-67-PA12 Nylon composites with mixed-matrix membranes (MMMs), with the goal of enhancing hydrogen storage systems. One method involves producing MOF-PA12 composite powders through an in situ process, which is then commonly used as a base powder for powder bed fusion (PBF) to fabricate various structures. However, developing the in situ MOF-PA12 matrix presents challenges, including limited spreadability and processability at higher MOF contents, as well as reduced porosity due to pore blockage by polymers, ultimately diminishing hydrogen storage capacity. To overcome these issues, PBF is employed to form PA12 powder into films, followed by the ex situ direct synthesis of ZIF-67 onto these substrates at loadings exceeding those typically used in conventional MMM composites. In this study, ZIF-67 mass loadings ranging from 2 to 30 wt.% were synthesized on both PA12 powder and printed film substrates, with loadings on printed PA12 films extended up to 60 wt.%. ZIF-67-PA12-60(f) demonstrated a hydrogen capacity of 0.56 wt.% and achieved 1.53 wt.% for ZIF-67-PA12-30(p); in comparison, PA12 exhibited a capacity of 0.38 wt.%. This was undertaken to explore a range of ZIF-67 Metal–organic frameworks (MOFs) to assess their impact on the properties of the composite, particularly for hydrogen storage applications. Our results demonstrate that ex situ-synthesized ZIF-67-PA12 composite MMMs, which can be used as a final product for direct application and do not require the use of in situ pre-synthesized powder for the PBF process, not only retain significant hydrogen storage capacities, but also offer advantages in terms of repeatability, cost-efficiency, and ease of production. These findings highlight the potential of this innovative composite material as a practical and efficient solution for hydrogen storage, paving the way for advancements in energy storage technologies.

Sepsis causes significant morbidity and mortality worldwide, most surviving patients show acute or chronic mental disorders, which are known as sepsis-associated encephalopathy (SAE). SAE involves many pathological processes, including the blood-brain barrier (BBB) damage. The BBB is located at the interface between the central nervous system and the surrounding environment, which protects the central nervous system (CNS) from the invasion of exogenous molecules, harmful substances or microorganisms in the blood. Recently, a growing number of studies have indicated that the BBB destruction was involved in SAE and played an important role in SAE-induced brain injury. In the present review, we firstly reveal the pathological processes of SAE such as the neurotransmitter disorders, oxidative stress, immune dysfunction and BBB destruction. Moreover, we introduce the structure of BBB, and describe the immune cells including microglia and astrocytes that participate in the BBB destruction after SAE. Furthermore, in view of the current research on non-coding RNAs (ncRNAs), we explain the regulatory mechanism of ncRNAs including long noncoding RNAs (lncRNAs), microRNAs (miRNAs) and circular RNAs (circRNAs) on BBB in the processes of SAE. Finally, we propose some challenges and perspectives of regulating BBB functions in SAE. Hence, on the basis of these effects, both immune cells and ncRNAs may be developed as therapeutic targets to protect BBB for SAE patients.

Cyfluthrin (Cy) is a widely used pyrethroid insecticide. There is growing evidence that Cy can cause damage to the nervous, reproductive, and immune systems, but there is limited evidence on the potential effects of maternal Cy exposure on offspring. A model of maternal Cy exposure was used to assess its neurobehavioral effects on young-adult offspring. We found that gestational Cy exposure affected pregnancy outcomes and fetal development, and that offspring showed impairments in anxiety as well as learning and memory, accompanied by impairments in hippocampal synaptic ultrastructure and synaptic plasticity. In addition, the IP3R-GRP75-VDAC1 apoptogenic pathway was also upregulated, and in vitro models showed that inhibition of this pathway alleviated neuronal apoptosis as well as synaptic plasticity damage. In conclusion, maternal Cy exposure during pregnancy can cause neurobehavioral abnormalities and synaptic damage in offspring, which may be related to neuronal apoptosis induced by activation of the IP3R-GRP75-VDAC1 pathway in the hippocampus of offspring. Our findings provide clues to understand the neurotoxicity mechanism of maternal Cy exposure to offspring during pregnancy.

Abstract Objective Interstitial lung disease (ILD) is a severe complication of connective tissue disease (CTD) that can significantly impact patients' prognosis and quality of life. However, the current diagnostic arena lacks reliable biomarkers for detecting and monitoring the progression and exacerbation of CTD-ILD. This study aimed to investigate the clinical value of 12 serum cytokines in the diagnosis of CTD-ILD and prediction of the risk of acute exacerbation (AE) in this disease. Methods This study was a cross-sectional investigation. Ninety-one hospitalized CTD patients were allocated into two groups: CTD-ILD group (n = 61) and CTD-non-ILD group (n = 30), and 30 sex-age matched healthy volunteers were enrolled as controls. The serum concentrations of interferon (IFN)-α, IFN-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17A, and IL-1β were measured by Luminex suspension arrays. Logistic regression was employed to determine the significance of variables in the occurrence of AE-CTD-ILD. A nomogram was constructed to visualize the independent variables. Results Elevated levels of IL-6, IL-8, and TNF-α were observed and compared in the CTD-ILD group with CTD-non-ILD (all P

Progress in medicine such as the use of anti-infective drugs and development of the advanced life support equipment has greatly improved the survival rate of patients with sepsis. However, the incidence of sepsis-related diseases is increasing. These include severe neurologic and psychologic disorders, cognitive decline, anxiety, depression, and post-traumatic stress disorder. Cerebral dysfunction occurs via multiple interacting mechanisms, with different causative pathogens having distinct effects. Because sepsis-related diseases place a substantial burden on patients and their families, it is important to elucidate the underlying pathophysiologic mechanisms to develop effective treatments.

Accurate and prompt determination of fire types is essential for effective firefighting and reducing damage. However, traditional methods such as smoke detection, visual analysis, and wireless signals are not able to identify fire types. This paper introduces FireSonic, an acoustic sensing system that leverages commercial speakers and microphones to actively probe the fire using acoustic signals, effectively identifying fire types. By incorporating beamforming technology, FireSonic first enhances signal clarity and reliability, thus mitigating signal attenuation and distortion. To establish a reliable correlation between fire type and sound propagation, FireSonic quantifies the heat release rate (HRR) of flames by analyzing the relationship between fire-heated areas and sound wave propagation delays. Furthermore, the system extracts spatiotemporal features related to fire from channel measurements. The experimental results demonstrate that FireSonic attains an average fire type classification accuracy of 95.5% and a detection latency of less than 400 ms, satisfying the requirements for real-time monitoring. This system significantly enhances the formulation of targeted firefighting strategies, boosting fire response effectiveness and public safety.

Spatial–temporal variation in soil organic carbon is an important factor for national targets to mitigate climate change and land degradation impacts. In this research, we took Guangdong Province of China as the study area, evaluated the spatial–temporal distributions of soil organic carbon using data from three China Geochemical Baseline projects (conducted in 2009, 2016, and 2023, respectively), and quantified the main driving factors of spatial–temporal variations in soil organic carbon using the random forest algorithm, further predicting the density and inventories of soil organic carbon. The results demonstrate that the mean value of SOC in Guangdong in 2009 was 0.81%; in 2016 it was 1.13%; and in 2023 it was 1.02%. The inventories of soil organic carbon (0–30 cm) in Guangdong Province were 0.61 Pg in 2009, 0.74 Pg in 2016, and 0.62 Pg in 2023. Soil in Guangdong acted as a carbon sink from 2009 to 2023 as a whole, and the most important driving force behind spatial–temporal variations in soil organic carbon was temperature, followed by precipitation and vegetation cover.

Peripheral nerve remodeling and sensitization are involved in cancer-related bone pain. As a member of the transforming growth factor-β class, bone morphogenetic protein 2 (BMP2) is recognized to have a role in the development of the neurological and skeletal systems. Our previous work showed that BMP2 is critical for bone cancer pain (BCP) sensitization. However, the mechanism remains unknown. In the current study, we demonstrated a substantial increase in BMP2 expression in the dorsal root ganglia (DRG) in a rat model of BCP. Knockdown of BMP2 expression ameliorated BCP in rats. Furthermore, the DRG neurons of rats with BCP expressed higher levels of calcitonin gene-related peptide (CGRP), and BCP was successfully suppressed by intrathecal injection of a CGRP receptor blocker (CGRP8-37). Downregulation of BMP2 expression reduced the expression of CGRP in the DRG of rats with BCP and relieved pain behavior. Moreover, we revealed that upregulation of CGRP expression in the DRG may be induced by activation of the BMPR/Smad1 signaling pathway. These findings suggest that BMP2 contributes to BCP by upregulating CGRP in DRG neurons via activating BMPR/Smad1 signaling pathway and that therapeutic targeting of the BMP2-Smad1-CGRP pathway may ameliorate BCP in the context of advanced cancer.

Ulcerative colitis (UC) is a gastrointestinal disease with an unknown etiology that severely affects patients' quality of life. Acupuncture and moxibustion therapies are effective in the treatment of UC, but existing systematic reviews (SRs) and meta-analyses (MAs) on this subject have variable methodological and outcome quality. Therefore, this study aimed to summarize and evaluate the evidence of existing SRs and MAs to provide more reliable evidence for clinical practice. Data were extracted from seven databases through systematic search and evaluated in terms of the methodological quality, reporting quality, risk of bias, and quality of evidence using the AMSTAR-2, PRISMA, ROBIS, and GRADE systems, respectively. Ten studies were finally included, and all of them showed many problems with the overall design and quality of outcomes. Because of the lack of high-quality evidence to support the findings from the existing studies, we should take this conclusion with caution and strictly implement the registration, design, and implementation of trials based on evidence to provide high-quality results in future studies.

This paper proposes a probabilistic hazard assessment model for debris flows considering the uncertainties of multiple influencing factors based on copula approaches. Fifty-nine rainfall-induced debris flows occurred between 2001 and 2009 in Taiwan are taken as an illustrative example to validate the proposed approaches. A copula-based probabilistic model is developed to model the joint probability distribution of debris-flow volume V and its influencing factors (e.g., rainfall intensity, RI and landslide area, AL). The developed model is then used to make probabilistic prediction of debris-flow volume for a specific hazard level, and compared with the empirical approaches. The proposed probabilistic model is also used to develop the exceedance probability charts of quantities for a specific debris-flow basin. Results show that the developed V–RI–AL probabilistic model can provide reasonable estimates of debris-flow volume in Taiwan for a specific probability level of 0.94, and show better predictive performance than the empirical relationships by using an independent debris-flow dataset in Taiwan for validation. The developed multivariate joint probabilistic model can also provide the exceedance probability of debris flows through considering the uncertainties of debris flow and its influencing factors, providing a preliminary reference for hazard assessment of the debris flows.

Abstract Introduction The prognosis of anti‐MDA5 antibody‐positive dermatomyositis/clinically amyopathic dermatomyositis‐associated interstitial lung disease (MDA5‐DM/CADM‐ILD) is poor. This study was to evaluate the effect of serum soluble CD206 (sCD206), a biomarker of macrophage activation, on predicting the interstitial lung disease (ILD) deterioration and prognosis for MDA5‐DM/CADM‐ILD. Methods Forty‐one patients diagnosed with MDA5‐DM/CADM‐ILD were retrospectively included. The clinical data were analyzed. Serum sCD206 levels were measured in 41 patients and 30 healthy controls. The relation between sCD206 levels and ILD deterioration was assessed. Receiver operating characteristic (ROC) curve was generated to determine the optimal cut‐off value of sCD206 for predicting outcome. The association between sCD206 and survival was examined. Results The median serum sCD206 level in patients was significantly higher than healthy controls (464.1 ng/mL vs. 349.1 ng/mL, P = 0.002). In DM/CADM patients, the sCD206 level was significantly higher in patients with acute/subacute interstitial lung disease (AILD/SILD) than those with chronic interstitial lung disease (CILD) (539.2 ng/mL vs. 309.4 ng/mL, P = 0.005). The AUC of sCD206 was 0.885 for predicting mortality (95% CI 0.779–0.990). Patients were divided into two groups: sCD206 high level group (≥400 ng/mL) and sCD206 low level group (

BackgroundResearch on non-target organ damage of biological pesticides has attracted much attention. Rotenone exposure may be far beyond the occupational environment, and the exposureduring pregnancy may be increased through bioaccumulation, fruit or vegetable residues, and other forms of oral intake. At present, the effects of rotenone on placental development and its mechanism are still unknown. ObjectiveTo investigate the developmental damage of rat placenta and evaluate the expression levels of glycogen synthase kinase (GSK-3β) and beta catenin (β-catenin) followed by rotenone exposure through the placental barrier during pregnancy, as well as to propose possible associated mechanisms. MethodsEighteen sexually mature SD female infertile rats without specific pathogens were selected and divided into three groups: blank control group (0.9% saline), corn oil group, and rotenone group (corn oil + 2 mg·kg−1 rotenone) by random number method, six female animals in each group. Another six male rats were selected and mated to the female rats at night with a female to male ratio of 3:1 per cage. Pregnant rats were given 0.9% saline, corn oil, and 2 mg·kg−1 rotenone preparation by isovolumetric gavage once daily for the entire gestation period (19 d), and their conditions were observed after the last dose. The pregnant rats were anesthetized, and the size of the placenta and blood perfusion were detected by ultrasound the next day of the last dose of rotenone. Then, 3 pregnant rats in each group were sacrificed immediately and the placenta and umbilical cord tissues were dissected. The remaining 9 pregnant rats gave birth naturally, and the fetuses were observed for developmental evaluation and weighed. The histopathological changes of umbilical cord and placenta were observed by hematoxylin-eosin staining. The reactive oxygen species levels of placenta tissues were detected by flow cytometry. The Ca2+-ATPase activity of placenta tissues was detected by colorimetric method. The localization and levels of GSK-3β and β-catenin expression of placenta were detected by immunohistochemistry. The p-GSK-3β/GSK-3β and p-β-catenin/β-catenin protein expression in placental tissues were measured by Western blotting. ResultsNo injury or death was recorded during the pregnant rats receiving rotennon administration. Adverse pregnancy outcomes such as fetal absorption and postpartum stillbirth were found in the rotenone group, and the weight of the fetal mice decreased (P

Abstract Background Sepsis-associated encephalopathy (SAE) is a common and severe complication of sepsis. While several studies have reported the proteomic alteration in plasma, urine, heart, etc. of sepsis, few research focused on the brain tissue. This study aims at discovering the differentially abundant proteins in the brains of septic rats to identify biomarkers of SAE. Methods The Prague-Dawley rats were randomly divided into sepsis (n = 6) or sham (n = 6) groups, and then the whole brain tissue was dissected at 24 h after surgery for further protein identification by Quantitative iTRAQ LC-MS/MS Proteomics. Ingenuity pathway analysis, Gene ontology knowledgebase, and STRING database are used to explore the biological significance of proteins with altered concentration. Results Among the total of 3163 proteins identified in the brain tissue, 57 were increased while 38 were decreased in the sepsis group compared to the sham group. Bioinformatic analyses suggest that the differentially abundant proteins are highly related to cellular microtubule metabolism, energy production, nucleic acid metabolism, neurological disease, etc. Additionally, acute phase response signaling was possibly activated and PI3K/AKT signaling was suppressed during sepsis. An interaction network established by IPA revealed that Akt1, Gc-globulin, and ApoA1 were the core proteins. The increase of Gc-globulin and the decrease of Akt1 and ApoA1 were confirmed by Western blot. Conclusion Based on the multifunction of these proteins in several brain diseases, we first propose that Gc-globulin, ApoA1, PI3K/AKT pathway, and acute phase response proteins (hemopexin and cluster of alpha-2-macroglobulin) could be potential candidates for the diagnosis and treatment of SAE. These results may provide new insights into the pathologic mechanism of SAE, yet further research is required to explore the functional implications and clinical applications of the differentially abundant proteins in the brains of sepsis group.

Abstract Background To compare the characteristics of corneal thickness measurements among the RTVue, Casia-2, and Pentacam in patients with mild-to-moderate keratoconus. Methods We recruited 46 eyes of 46 patients diagnosed with mild-to-moderate keratoconus at our hospital between January and March 2022. The central corneal thickness (CCT) and thinnest corneal thickness (TCT) were measured using two optical coherence tomography (OCT) instruments (RTVue and Casia-2) and the more conventional Pentacam. Differences and correlations between the CCTs and TCTs, based on the device and influencing factors, were explored. Results The CCTs were highly consistent among the groups (p = 0.434) and correlated with one another (p 0.05). Multivariate analysis identified that the TCT measurement difference between the RTVue and Pentacam was related to the difference between the CCT and TCT (b = 0.490, 95% confidence interval [CI]: 0.033 to 0.948, p = 0.036), whereas the difference between the Casia-2 and Pentacam was related to the anterior radius for curvature (A) grade (b = 3.9, 95% CI: 1.753 to 6.074, p = 0.001), corneal pachymetry at the thinnest (C) grade (b = − 7.875, 95% CI: − 11.404 to − 4.346, p

Regenerated rice, characterized by single planting and double harvesting, saves labor and costs, significantly contributing to global food security. Hyperspectral imaging technology, which integrates image and spectral data, provides comprehensive, non-destructive, and pollution-free vegetation canopy analysis, making it highly effective for crop nutrient diagnosis. In this study, we selected two varieties of regenerated rice for field trials. Hyperspectral images were captured during key growth stages (flush, grouting, and ripening) of both the first and regenerated seasons. Utilizing a two-dimensional convolutional neural network (2D-CNN) as a deep feature extractor and a fully connected layer for nitrogen content prediction, we developed a robust model suitable for estimating nitrogen content in regenerated rice. The experimental results demonstrate that our method achieves a mean squared error (MSE) of 0.0008, significantly outperforming the back-propagation (BP) network and multiple linear regression by reducing the MSE by 0.0151 and 0.0247, respectively. It also surpasses the one-dimensional convolutional neural network (1D-CNN) by 0.003. This approach ensures accurate nitrogen content prediction throughout the growth cycle of regenerated rice, aiding in yield and economic benefit enhancement.

Abstract Background The mortality of extensively drug-resistant Gram-negative (XDR GN) bacilli-induced ventilator-associated pneumonia (VAP) is extremely high. The purpose of this study was to compare the efficacy and safety of inhaled (IH) plus intravenous (IV) polymyxin B versus IV polymyxin B in XDR GN bacilli VAP patients. Methods A retrospective multi-center observational cohort study was performed at eight ICUs between January 1st 2018, and January 1st 2020 in China. Data from all patients treated with polymyxin B for a microbiologically confirmed VAP were analyzed. The primary endpoint was the clinical cure of VAP. The favorable clinical outcome, microbiological outcome, VAP-related mortality and all-cause mortality during hospitalization, and side effects related with polymyxin B were secondary endpoints. Favorable clinical outcome included clinical cure or clinical improvement. Results 151 patients and 46 patients were treated with IV polymyxin B and IH plus IV polymyxin B, respectively. XDR Klebsiella pneumoniae was the main isolated pathogen (n = 83, 42.1%). After matching on age (± 5 years), gender, septic shock, and Apache II score (± 4 points) when polymyxin B was started, 132 patients were included. 44 patients received simultaneous IH plus IV polymyxin B and 88 patients received IV polymyxin B. The rates of clinical cure (43.2% vs 27.3%, p = 0.066), bacterial eradication (36.4% vs 23.9%, p = 0.132) as well as VAP-related mortality (27.3% vs 34.1%, p = 0.428), all-cause mortality (34.1% vs 42.0%, p = 0.378) did not show any significant difference between the two groups. However, IH plus IV polymyxin B therapy was associated with improved favorable clinical outcome (77.3% vs 58.0%, p = 0.029). Patients in the different subgroups (admitted with medical etiology, infected with XDR K. pneumoniae, without bacteremia, with immunosuppressive status) were with odd ratios (ORs) in favor of the combined therapy. No patient required polymyxin B discontinuation due to adverse events. Additional use of IH polymyxin B (aOR 2.63, 95% CI 1.06, 6.66, p = 0.037) was an independent factor associated with favorable clinical outcome. Conclusions The addition of low-dose IH polymyxin B to low-dose IV polymyxin B did not provide efficient clinical cure and bacterial eradication in VAP caused by XDR GN bacilli. Keypoints Additional use of IH polymyxin B was the sole independent risk factor of favorable clinical outcome. Patients in the different subgroups were with HRs substantially favoring additional use of IH polymyxin B. No patients required polymyxin B discontinuation due to adverse events.

Abstract Background Neuroinflammation is a crucial factor in the development of secondary brain injury after intracerebral hemorrhage (ICH). Irisin is a newly identified myokine that confers strong neuroprotective effects in experimental ischemic stroke. However, whether this myokine can exert neuroprotection effects after ICH remains unknown. This study aimed to investigate the impact of irisin treatment on neuroinflammation and neuronal apoptosis and the underlying mechanism involving integrin αVβ5/AMPK pathway after ICH. Methods Two hundred and eighty-five adult (8-week-old) male C57BL/6 mice were randomly assigned to sham and ICH surgery groups. ICH was induced via intrastriatal injection of autologous blood. Irisin was administered intranasally at 30 min after ICH. To elucidate the underlying mechanism, cilengitide (a selective integrin αVβ5 inhibitor) and dorsomorphin (a selective phosphorylated AMPK inhibitor) were administered before irisin treatment. The short- and long-term neurobehavior tests, brain edema, quantitative-PCR, western blotting, Fluoro-Jade C, TUNEL, and immunofluorescence staining were performed to assess the neurofunctional outcome at the level of molecular, cell, histology, and function. Results Endogenous irisin and its receptor, integrin αVβ5, were increased, peaked at 24 h after ICH. irisin post-treatment improved both short- and long-term neurological functions, reduced brain edema after ICH. Interestingly, integrin αVβ5 was mainly located in the microglia after ICH, and irisin post-treatment inhibited microglia/macrophage pro-inflammatory polarization and promoted anti-inflammatory polarization. Moreover, irisin treatment inhibited neutrophil infiltration and suppressed neuronal apoptotic cell death in perihematomal areas after ICH. Mechanistically, irisin post-treatment significantly increased the expression of integrin αVβ5, p-AMPK and Bcl-2, and decreased the expression of IL-1β, TNF-α, MPO, and Bax following ICH. The neuroprotective effects of irisin were abolished by both integrin αVβ5 inhibitor cilengitide and AMPK inhibitor dorsomorphin. Conclusions This study demonstrated that irisin post-treatment ameliorated neurological deficits, reduced brain edema, and ameliorated neuroinflammation and neuronal apoptosis, at least in part, through the integrin αVβ5/AMPK signaling pathway after ICH. Thus, irisin post-treatment may provide a promising therapeutic approach for the early management of ICH.

Abstract Background This study aimed to evaluate the clinical outcomes and assess preoperative characteristics that may predict outcomes in keratoconus 1 year after accelerated transepithelial corneal cross-linking (ATE-CXL). Methods This prospective study included 93 eyes of 84 consecutive keratoconus patients with 1-year follow-up after ATE-CXL. Preoperative characteristics included corneal astigmatism, anterior chamber depth, anterior chamber volume, radius of curvature, posterior elevation, central corneal thickness (CCT), thinnest corneal thickness, steepest meridian keratometry, flattest meridian keratometry, and the maximum keratometry (Kmax). Data were obtained preoperatively and at 1, 3, 6, and 12 months postoperatively. The patient eyes were grouped into 3 subgroups according to CCT and Kmax values to observe the changes of keratoconus progression. Results All patients were successfully operated without complications at any follow-up time point. Mean changes of Kmax from baseline at 6 and 12 months were − 0.60 ± 2.21 D (P = 0.011) and − 0.36 ± 1.58 D (P = 0.030), respectively. Eyes with a thinner CCT and higher Kmax values exhibited a tendency for topographic flattening of ≥1.0 D (P = 0.003; P = 0.003). In the subgroup comparison, the Kmax values decreased significantly at 6 and 12 months after ATE-CXL in the group with CCT ≤ 450 μm (P = 0.018 and P = 0.045); the Kmax values of the group with Kmax > 65.0 D decreased significantly at 6 months postoperatively (P = 0.025). Conclusion ATE-CXL is a safe and effective treatment for keratoconus patients. Patients with thinner CCT and higher Kmax values are more likely to benefit from ATE-CXL.

In this study, the regional spatial-temporal variability of cadmium (Cd) in the topsoil of Guangxi, China from 2010 to 2016 was studied from data obtained from the China Geochemical Baseline Project (CGB Ⅰ and CGB Ⅱ). The driving forces of natural and anthropogenic variables were quantitatively analyzed using a geographically and temporally weighted regression model. The results showed that 1) soil Cd was highly enriched in 2010 and in soils of Hechi city in northwest Guangxi, a non-ferrous metal mining and metallurgy area, ~17% of the samples exceeded the soil contamination risk limit. In contrast, in 2016, the topsoil Cd content decreased significantly, with 7% of sites exceeding the soil risk limit. 2) Multiple factors jointly influenced the regional spatial variability of Cd. pH and organic carbon were found to be the main factors influencing Cd content and were strongly spatially correlated with Cd. Anthropogenic activities, including mining and industrial emissions, resulted in significant Cd enrichment in local areas, whereas agricultural and domestic pollutants were relatively weakly correlated with Cd. The weathering products of carbonates were significantly enriched in Cd; thus, the geological background played a significant role in the spatial variability of Cd. Soil-forming factors, including temperature, precipitation, and elevation influenced the spatial distribution of Cd, especially in the Cd background area. 3) Anthropogenic activities were the key factors influencing temporal changes in Cd. Mining caused significant enrichment of Cd in CGB Ⅰ, while industrial emissions were the primary factor for Cd enrichment in CGB Ⅱ. In addition, natural factors also played an important role; the increased Normalized Difference Vegetation Index suggested reduced desertification and reduction of soil erosion in the watershed and in pollutants transported from upstream.

Accurate delineation of debris-flow-endangered areas (e.g., the maximum runout distance) is a necessary prerequisite for the debris-flow risk assessment and countermeasures design. Recently, machine-learning models have been proved to be an effective tool in predicting debris-flow parameters. However, existing machine-learning models are generally developed based on a very limited number of observation data, which may result in the predictive model overfitting or underfitting. How to develop a robust model for accurate forecasting of debris-flow-endangered areas still remains a difficult task. This paper proposes a hybrid method for predicting debris-flow hazard zone by integrating machine-learning algorithms and an empirical regression model. The proposed method takes the calculated maximum runout distance obtained from the empirical model as supplementary inputs to increase the amount of training data to construct hybrid machine-learning models. Three commonly used machine-learning models (i.e., multivariate adaptive regression splines (MARS), random forest (RF), and support vector machine (SVM)) are developed based on the training datasets of a specific debris basin. Then, these three machine-learning models are combined with an empirical relationship developed using the same training datasets to generate corresponding hybrid models. Finally, the performance metrics (i.e., coefficient of determination (R2), root-mean-square error (RMSE), and mean absolute error (MAE)) of the proposed hybrid models are comprehensively investigated and compared with the single predictive model (i.e., MARS, RF, SVM, and the empirical model) under fivefold cross-validation. The proposed method is illustrated using 134 channelized debris-flow events in Sichuan province, China. Results show that compared with the three individual machine-learning models, hybridization of machine-learning algorithms and the empirical model results in R2, RMSE, and MAE improved by 70.5%, 32.9%, and 41.1%, respectively. In contrast to the empirical model, the R2, RMSE, and MAE value of the proposed hybrid models are improved by 29.6%, 22.3%, and 32.5%, respectively. The proposed hybrid models generally perform better than the single machine-learning and the empirical model, providing a promising tool for accurate forecasting of a debris-flow-endangered area.

Abstract Background Wilson disease (WD) is a rare genetic disorder of copper metabolism. Differences in copper tissue accumulation lead to various clinical manifestations, including some atypical presentations. The complex clinical features of WD make diagnosis challenging, delaying the best chance for treatment. Case presentation We report a case of a 26-year-old man with nephritis-range proteinuria and elevated serum creatinine. The renal pathology indicated immunoglobulin A (IgA) nephropathy and tubular injury, which was inconsistent with glomerular lesions. Cirrhosis was also detected by imaging examination. Considering both kidney injury and liver damage, WD was suspected. Based on results showing abnormal copper metabolism, corneal Kayser–Fleischer rings, and genetic disorders in the ATP7B gene, the patient was finally diagnosed with WD. After treatment with oral penicillamine, zinc sulfate and losartan, the patient showed alleviation of both WD and nephropathy after 3 years of follow-up. He maintained a good quality of daily life. Conclusion This case highlights that unexplained neurological and liver symptoms in patients with IgA nephropathy can be clues for WD.

Bone cancer pain (BCP) is one of the most common types of pain in cancer patients which compromises the patient’s functional status, quality of life, and survival. Central hyperalgesia has increasingly been identified as a crucial factor of BCP, especially in the medial prefrontal cortex (mPFC) which is the main cortical area involved in the process of pain and consequent negative emotion. To explore the genetic changes in the mPFC during BCP occurrence and find possible targets for prediction, we performed transcriptome sequencing of mPFC in the BCP rat model and found a total of 147 differentially expressed mRNAs (DEmRNAs). A protein-protein interaction (PPI) network revealed that the DEmRNAs mainly participate in the inflammatory response. Meanwhile, microglia and astrocytes were activated in the mPFC of BCP rats, further confirming the presence of neuroinflammation. In addition, Gene Ontology (GO) analysis showed that DEmRNAs in the mPFC are mainly involved in antigen processing, presentation of peptide antigen, and immune response, occurring in the MHC protein complex. Besides, the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that DEmRNAs are mainly enriched in the pathways of phagosome, staphylococcus aureus infection, and antigen processing, in which MHCII participate. Furthermore, immunostaining showed that MHCII is mainly located in the microglia. Microglia are believed to be involved in antigen processing, a key cause of BCP. In vivo, minocycline (MC) treatment inhibits the activation of microglia and reduces the expression of MHCII and proinflammatory cytokines, thereby alleviating BCP and pain-related anxiety. Taken together, our study identified differentially expressed genes in the BCP process and demonstrated that the activation of microglia participates in the inflammatory response and antigen process, which may contribute to BCP.

Abstract Background Cases of concurrent immunoglobulin A nephropathy (IgAN) and IgG4-related tubulointerstitial nephritis (IgG4-TIN) are rare and previous case reports have lacked important data. KDIGO suggests a treatment with systemic glucocorticoids in IgAN patients. Glucocorticoids are recommended as the first-line therapy for IgG4-TIN. The use of tacrolimus as a long-term maintenance treatment has not been described. We report the case of a man who developed IgAN and IgG4-TIN without abnormalities in extra-renal tissue, without renal function abnormalities or impairment as well, and was treated by tacrolimus as a long-term maintenance during 45 months follow-up. Case presentation A 56-year-old Chinese man first presented to our hospital with the chief complaint of foamy urine for 1 year and hematuria for 3 months, with a medical history of hypertension. Testing revealed a notable increase in serum IgG4 level without abnormalities in renal function or imaging, or in dysfunction other organs. Renal biopsy showed mesangial extracellular matrix proliferation, increased mesangial cell numbers and infiltration of plasma cells. Immunofluorescence showed mesangial positivity for IgA and C3. Immunohistochemistry staining showed widespread IgG4 and increased CD38 and CD138 expression. Electron microscopy showed immune complexes located on the tubular basement membrane. He was diagnosed with IgAN and IgG4-TIN. He received glucocorticoids, leflunomide and tacrolimus to induce remission. He was given tacrolimus as long-term maintenance treatment. When tacrolimus was temporarily withdrawn, proteinuria recurred. After resuming tacrolimus therapy, he again entered complete remission. After 45 months of therapy, he remains in complete remission and the serum IgG4 level is normal. Conclusions The finding of concurrent IgAN and IgG4-TIN without abnormalities in renal function, imaging or extra-renal tissue is rare and their coexistence may be coincidental. Long-term treatment with tacrolimus proved effective and he has remained in remission during 45 months follow-up.

Bedload sediment transport is critical in the natural river environmental and ecological system. It is quite challenging to measure the bedload sediment transport rate in rivers with any degree of accuracy. In this study, the authors developed the Gravel Pressure and Voice Synchronous observation system (GPVS) to estimate the bedload sediment transport rate in rivers. The core of the GPVS includes an underwater high-fidelity audio recorder and pressure sensor. The audio recorder is intended to monitor the low bedload sediment transport rate, whereas the pressure sensor is utilized to detect relatively substantial bedload sediment transport. The GPVS is tested by running flume experiments with natural gravel to evaluate the system’s reliability and feasibility. Results reveal that the GPVS has a very high sensitivity for detecting bedload transport. When the bedload sediment transport rate is relatively low, the audio recorder can measure it quantitatively, showing that the system is not impacted by ambient noise.

Supercapacitors are regarded as reliable energy storage devices to alleviate the energy crisis and environmental pollution. However, the relatively low capacitance and low energy density limit the practical application of supercapacitors. In this context, boron carbon nitride (BCN) nanomaterials have been extensively studied in the past decade due to their chemical and thermal stability, high mechanical strength, as well as tunable bandgap. The specific capacitance and energy density of supercapacitors can be significantly improved by fabricating nanostructured BCN-based electrode materials. In this review, the recent advances in the application of BCN-based materials in supercapacitors is presented. Strategies such as structure design, porosity/defect engineering, and hybrid nanostructure construction to boost the electrochemical performance of BCN-based materials are provided and, finally, promising research directions for novel energy storage materials are proposed.

Central nervous system (CNS) injuries, including traumatic brain injury (TBI), intracerebral hemorrhage (ICH) and ischemic stroke, are the most common cause of death and disability around the world. As the most common modification on ribonucleic acids (RNAs), N6-methyladenosine (m6A) modification has recently attracted great attentions due to its functions in determining the fate of RNAs through changes in splicing, translation, degradation and stability. A large number of studies have suggested that m6A modification played an important role in brain development and involved in many neurological disorders, particularly in CNS injuries. It has been proposed that m6A modification could improve neurological impairment, inhibit apoptosis, suppress inflammation, reduce pyroptosis and attenuate ferroptosis in CNS injuries via different molecules including phosphatase and tensin homolog (PTEN), NLR family pyrin domain containing 3 (NLRP3), B-cell lymphoma 2 (Bcl-2), glutathione peroxidase 4 (GPX4), and long non-coding RNA (lncRNA). Therefore, m6A modification showed great promise as potential targets in CNS injuries. In this article, we present a review highlighting the role of m6A modification in CNS injuries. Hence, on the basis of these properties and effects, m6A modification may be developed as therapeutic agents for CNS injury patients.

PurposeAnti-gamma-aminobutyric-acid type B receptor (anti-GABABR) encephalitis is a rare autoimmune condition caused by the presence of GABABR antibodies in the limbic system. However, its clinical features and prognostic factors are poorly understood. In this study, we aimed to explore factors that affect the response to first-line treatment in patients with anti-GABABR encephalitis.MethodsThirty-four patients with an initial diagnosis of anti-GABABR encephalitis were retrospectively enrolled from December 2015 to June 2021. Clinical features and experimental data recorded within 24 h of admission were extracted from the patients’ medical records. The modified Rankin Scale (mRS) was utilized to assess disease severity at admission and functional recovery after immunotherapy. Independent prognostic factors were determined by ordinal logistic regression analysis.ResultsOf the 34 anti-GABABR encephalitis patients, 12 (35%) presented with cancer; all of these patients had lung cancer. According to multivariate regression analysis, the cancer group exhibited a decrease in the peripheral blood absolute lymphocyte count (ALC) (odds ratio [OR]: 0.063, 95% confidence interval [CI]: 0.006-0.639, P=0.019) and hyponatremia (OR: 9.268, 95% CI: 1.054-81.502, 0.045). In addition, the neutrophil/lymphocyte ratio (NLR), monocyte/lymphocyte ratio (MLR) and platelet/lymphocyte ratio (PLR) did not significantly differ according to mRS scores in patients receiving first-line treatment. No patients with mild or moderate mRS scores (0-2) at admission developed symptoms after treatment; in contrast, only 11 patients with a severe mRS scores (≥3, 11/18) experienced symptom alleviation. Ordinal regression analysis indicated that worse prognosis was associated with pulmonary infection (OR=9.885, 95% CI: 1.106-88.323, P=0.040) and baseline mRS scores (OR= 24.047, 95% CI: 3.294-175.739, P=0.002) in the adjusted model.ConclusionOur findings demonstrate that pulmonary infection and baseline mRS scores are independent risk factors for poor prognosis in patients with anti-GABABR encephalitis after first-line treatment. ALC and hyponatremia are potential biomarkers for anti-GABABR encephalitis cases accompanied by lung cancer.

Abstract The liver plays an important role in lipid and glucose metabolism. Here, we show the role of human antigen R (HuR), an RNA regulator protein, in hepatocyte steatosis and glucose metabolism. We investigated the level of HuR in the liver of mice fed a normal chow diet (NCD) and a high-fat diet (HFD). HuR was downregulated in the livers of HFD-fed mice. Liver-specific HuR knockout (HuRLKO) mice showed exacerbated HFD-induced hepatic steatosis along with enhanced glucose tolerance as compared with control mice. Mechanistically, HuR could bind to the adenylate uridylate-rich elements of phosphatase and tensin homolog deleted on the chromosome 10 (PTEN) mRNA 3′ untranslated region, resulting in the increased stability of Pten mRNA; genetic knockdown of HuR decreased the expression of PTEN. Finally, lentiviral overexpression of PTEN alleviated the development of hepatic steatosis in HuRLKO mice in vivo. Overall, HuR regulates lipid and glucose metabolism by targeting PTEN.

Live cell imaging of mitochondrial cristae is challenged by the unsuitability of current fluorescent probes and high phototoxicity. Here the authors develop a squarine variant probe (MitoESq-635) that is capable of longitudinal imaging of cristae with STED with minimal phototoxicity.

BackgroundDifferential diagnosis of patients with suspected infections is particularly difficult, but necessary for prompt diagnosis and rational use of antibiotics. A substantial proportion of these patients have non-infectious diseases that include malignant tumors. This study aimed to explore the clinical value of metagenomic next-generation sequencing (mNGS) for tumor detection in patients with suspected infections.MethodsA multicenter, prospective case study involving patients diagnosed with suspected infections was conducted in four hospitals in Shanghai, China between July 2019 and January 2020. Based upon mNGS technologies and chromosomal copy number variation (CNV) analysis on abundant human genome, a new procedure named Onco-mNGS was established to simultaneously detect pathogens and malignant tumors in all of the collected samples from patients.ResultsOf 140 patients screened by Onco-mNGS testing, 115 patients were diagnosed with infections; 17 had obvious abnormal CNV signals indicating malignant tumors that were confirmed clinically. The positive percent agreement and negative percent agreement of mNGS testing compared to clinical diagnosis was 53.0% (61/115) and 60% (15/25), vs. 20.9% (24/115) and 96.0% (24/25), respectively, for conventional microbiological testing (both P

BackgroundBartter syndrome (BS) type II is a rare autosomal recessive renal tubular disorder caused by mutations in the KCNJ1 gene, which encodes the apical renal outer medullary potassium (ROMK) channel in the thick ascending limb (TAL) of Henle’s loop. BS type II is typically considered as a disorder of infancy and seldom seen in adults.Case PresentationA 34-year-old woman was admitted with generalized body numbness and hand convulsions, without growth retardation. Laboratory tests revealed hypokalemic metabolic alkalosis, hyperreninemic hyperaldosteronism, and nephrocalcinosis. She was misdiagnosed during the initial diagnosis process and was finally diagnosed with late-onset BS type II via genetic testing through next-generation sequencing combined with Sanger sequencing. A novel compound heterozygous p.Leu207Ile/p. Cys308Arg variant in exon 5 of the KCNJ1 gene from her parents was identified and speculated to be a potential pathogenic gene variation.ConclusionWe report a case of late-onset BS type II with a novel compound heterozygous mutation in KCNJ1. Both variants are novel and have never been reported. Our report will have a significant impact on the diagnosis of BS in other patients without typical clinical presentations and emphasizes the importance of genetic investigation.

Real-time sweat monitoring is vital for athletes in order to reflect their physical conditions, quantify their exercise loads, and evaluate their training results. Therefore, a multi-modal sweat sensing system with a patch-relay-host topology was developed, which consisted of a wireless sensor patch, a wireless data relay, and a host controller. The wireless sensor patch can monitor the lactate, glucose, K+, and Na+ concentrations in real-time. The data is forwarded via a wireless data relay through Near Field Communication (NFC) and Bluetooth Low Energy (BLE) technology and it is finally available on the host controller. Meanwhile, existing enzyme sensors in sweat-based wearable sports monitoring systems have limited sensitivities. To improve their sensitivities, this paper proposes a dual enzyme sensing optimization strategy and demonstrates Laser-Induced Graphene (LIG)-based sweat sensors decorated with Single-Walled Carbon Nanotubes (SWCNT). Manufacturing an entire LIG array takes less than one minute and costs about 0.11 yuan in materials, making it suitable for mass production. The in vitro test result showed sensitivities of 0.53 μA/mM and 3.9 μA/mM for lactate and glucose sensing, and 32.5 mV/decade and 33.2 mV/decade for K+ and Na+ sensing, respectively. To demonstrate the ability to characterize personal physical fitness, an ex vivo sweat analysis test was also performed. Overall, the high-sensitivity lactate enzyme sensor based on SWCNT/LIG can meet the requirements of sweat-based wearable sports monitoring systems.

As we move away from internal combustion engines to tackle climate change, the importance of hydrogen-powered vehicles and polymer electrolyte membrane fuel cell (PEMFC) technology has dramatically increased. In the present study, we aimed to determine the optimal configuration for the power output of a PEMFC system using computational fluid dynamics (CFD) modelling to analyse variations of the primary serpentine design of gas flow channels. This helps improve efficiency and save on valuable materials used, reducing potential carbon emissions from the production of hydrogen vehicles. Different numbers of serpentine gas channels were represented with various spacing between them, within the defined CFD model, to optimise the gas channel geometry. The results show that the optimum configuration was found to have 11 serpentine channels with a spacing of 3.25 mm. In this optimum configuration, the ratio between the channel width, channel spacing, and serpentine channel length was found to be 1:2.6:38 for PEMFCs. Furthermore, the inclusion of fillets to the bends of the serpentine gas channels was found to have a negative effect on the overall power output of the fuel cell. Moreover, the optimisation procedures with respect to the number of gas channels and the spacing revealed an optimal power density exceeding 0.65 W/cm2.

Purpose: To investigate the safety and efficacy of topography-guided transepithelial accelerated corneal collagen cross-linking for low refractive error correction in patients with keratoconus.Methods: This was a prospective self-controlled study. Eighteen patients (18 eyes) were enrolled and assessed at 6 visits (pre-operation, 1 w, 1 month, 3 months, 6 months, and 1 year postoperatively). The examination at every visit included analysis of uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA), corneal topography, and corneal endothelial cell counts. Data are expressed as mean ± standard deviation (SD). The p-value was determined using repeated-measures analysis of variance.Results: No complications occurred in any eye during 1 year follow-up period. At each visit after the operation, the corneal K values and spherical equivalent (SE) were reduced, while the visual acuity values were increased compared with those preoperatively, although these results were not statistically significant (p > 0.05). UCVA of nearly 1/3 of the patients was enhanced by at least 3 lines at each follow-up visit. During the whole follow-up, corneal endothelial cell counts were stable (p > 0.05). Regarding topography, part of the corneal cone was flattened after the operation.Conclusion: Topography-guided transepithelial-accelerated corneal collagen cross-linking is safe and may correct low refractive error in keratoconus treatment. Further studies and improvements are required in this regard.

Stroke is a devastating disease with high mortality and disability rates. Previous research has established that mitochondria, as major regulators, are both influenced by stroke, and further regulated the development of poststroke injury. Mitochondria are involved in several biological processes such as energy generation, calcium homeostasis, immune response, apoptosis regulation, and reactive oxygen species (ROS) generation. Meanwhile, mitochondria can evolve into various quality control systems, including mitochondrial dynamics (fission and fusion) and mitophagy, to maintain the homeostasis of the mitochondrial network. Various activities of mitochondrial fission and fusion are associated with mitochondrial integrity and neurological injury after stroke. Additionally, proper mitophagy seems to be neuroprotective for its effect on eliminating the damaged mitochondria, while excessive mitophagy disturbs energy generation and mitochondria-associated signal pathways. The balance between mitochondrial dynamics and mitophagy is more crucial than the absolute level of each process. A neurovascular unit (NVU) is a multidimensional system by which cells release multiple mediators and regulate diverse signaling pathways across the whole neurovascular network in a way with a high dynamic interaction. The turbulence of mitochondrial quality control (MQC) could lead to NVU dysfunctions, including neuron death, neuroglial activation, blood–brain barrier (BBB) disruption, and neuroinflammation. However, the exact changes and effects of MQC on the NVU after stroke have yet to be fully illustrated. In this review, we will discuss the updated mechanisms of MQC and the pathophysiology of mitochondrial dynamics and mitophagy after stroke. We highlight the regulation of MQC as a potential therapeutic target for both ischemic and hemorrhagic stroke.

Abstract Immune checkpoint inhibitors (ICIs) have shown significant efficacy in various solid tumors, but only a small subgroup of patients benefit from them because of immune resistance. Oncorine (formerly H101), a recombinant human adenovirus type 5, has direct anticancer properties and enhances cell‐mediated immune responses. At present, few studies on the role of Oncorine in reversing resistance to ICIs have been reported. Here, we present a case with recurrent non‐small cell lung cancer (NSCLC). The patient developed resistance to nivolumab therapy. After trying immunotherapy plus chemotherapy or antiangiogenesis therapy, the patient only obtained a transient response. The patient then received experimental treatment with Oncorine together with nivolumab and anlotinib. She experienced symptomatic improvement with a performance status score of 1, and achieved stable disease despite partial lung tissue necrosis. This was a successful exploration of oncolytic viruses reversing immune resistance.