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Abstract Diabetic vascular complications attract increased attention due to their high morbidity, mortality and disability rate. Comprehensive and in-depth exploration of the etiology and pathogenesis of diabetic vascular complications is important for diagnosis and treatment. Endothelial extracellular vesicles (EVs) serve as potential intercellular communicators, transmitting biological information from the donor cell to the recipient cell, exerting both harmful and beneficial effects on vascular function. Endothelial EVs are new diagnostic and therapeutic targets and biomarkers in diabetic vascular complications. This review summarizes the biogenesis and release of endothelial EVs, as well as isolation and characterization methods, and discusses the role of endothelial EVs in the maintenance of vascular homeostasis along with their contributions to vascular dysfunction. Finally, the article illustrates the impact of endothelial EVs on the pathogenesis of diabetic vascular complications and evaluates their potential as therapeutic tools and diagnostic markers in diabetic vascular complications.

Abstract Many studies have focused on the effects of small molecules, such as amino acids, on metabolism under hypoxia. Recent findings have indicated that phenylalanine levels were markedly elevated in adaptation to chronic hypoxia. This raises the possibility that phenylalanine treatment could markedly improve the hypoxic endurance. However, the importance of hypoxia-regulated phenylalanine is still unclear. This study investigates the role of phenylalanine in hypoxia adaptation using a hypoxic zebrafish model and multi-omics analysis. We found that phenylalanine-related metabolic pathways are significantly up-regulated under hypoxia, contributing to enhanced hypoxic endurance. Phenylalanine treatment reduced ROS levels, improved mitochondrial oxygen consumption rate (OCR), and extracellular acidification rate (ECAR) in hypoxic cells. Western blotting revealed increased phenylalanine uptake via L-type amino transporters (LAT1), activating the LKB1/AMPK signaling pathway. This activation up-regulated peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) and the Bcl-2/Bax ratio, while down-regulating uncoupling protein 2 (UCP2), thereby improving mitochondrial function under hypoxia. This is the first comprehensive multi-omics analysis to demonstrate phenylalanine’s crucial role in hypoxia adaptation, providing insights for the development of anti-hypoxic drugs. Graphical Abstract

Background/objective: Physical activity (PA) self-efficacy plays a crucial role in maintaining and enhancing PA behaviors in children. However, the effectiveness of eHealth interventions in boosting PA self-efficacy among children remains uncertain. Furthermore, which behavior change techniques (BCTs) used in eHealth interventions can positively influence children's PA self-efficacy needs further exploration for designing tailored eHealth interventions. Therefore, this systematic review and meta-analysis aimed to identify the effectiveness of eHealth interventions and BCTs in promoting children's PA self-efficacy. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a comprehensive search was conducted across six databases (PubMed, Web of Science, EBSCOhost, Ovid, SPORTDiscus, PsycINFO) up to January 8, 2024. Inclusion criteria included randomized controlled trials (RCT), quasi-experimental, and two-group experiments that examined the effect of eHealth interventions on PA self-efficacy among healthy children aged 0–18 years. The Physiotherapy Evidence Database (PEDro) scale was utilized to assess the risk of bias. Random effects meta-analysis was performed to determine the effectiveness of eHealth interventions and BCTs in selected studies. Results: Sixteen studies were screened, including 6020 participants with an average age of 11.58 years (SD = 2.87). The result showed small but significant intervention effects with high heterogeneity (I2 = 92.34 %) for postintervention PA self-efficacy (Hedges’ g = 0.315; 95 % CI = 0.069, 0.562, p = .012). Two BCTs were significantly associated with enhanced PA self-efficacy: instruction on performing the behavior (p = .003) and behavior demonstration (p = .036). Additionally, studies that adopted social support (unspecified) a nd prompt/cues were significantly less effective than studies that did not use these BCTs (p = .001). Conclusions: The findings showed that eHealth interventions positively affect children's PA self-efficacy. This review is the pioneer in focusing on BCTs in eHealth interventions for children. The insights gained provide valuable knowledge about tailored BCTs incorporated into eHealth interventions that promote children's PA self-efficacy. Trial registration: International Prospective Register of Systematic Review (PROSPERO): CRD42024512058.

Abstract Astrocytes act as immune cells that can produce a series of chemokines to attract large numbers of leucocytes to the lesion site, where they contribute to excessive inflammation following spinal cord injury (SCI). However, the relevant regulatory mechanism involved in chemokine production by astrocytes has not been fully elucidated. In the present study, we examined the correlation between C-C motif chemokine ligand 5 (CCL5) and high mobility group box-1 protein (HMGB1) in a T8–T10 spinal cord contusion model. Our results revealed that SCI-induced CCL5 protein levels increased synchronously with the increase in HMGB1. Administration of an HMGB1-neutralizing antibody significantly reduced the protein expression of CCL5 in the context of SCI. An in vitro study revealed that HMGB1 binding with TLR2/4 receptors potently facilitates the production of CCL5 by astrocytes by activating the intracellular ERK/JNK-mediated NF-κB pathway. Furthermore, the HMGB1-induced release of CCL5 from astrocytes is involved in promoting microglia/macrophage accumulation and M1 polarization. The inhibition of HMGB1 activity reduces microglia/macrophage infiltration by decreasing the expression of CCL5 and improves motor functional recovery following SCI. Our results provide insights into the new functions of HMGB1-mediated astrocytic CCL5 production, which elicits inflammatory cell recruitment to the site of injury; this recruitment is associated with excessive inflammation activation. These data may provide a new therapeutic strategy for central nervous system (CNS) inflammation.

Abstract Background The patent foramen ovale (PFO) and interatrial block (IAB) are associated with cryptogenic stroke (CS). However, the role of the interaction between PFO and IAB in CS remains unclear. Methods This case–control study enrolled 256 patients with CS and 156 individuals without a history of stroke or transient ischemic attack. IAB was defined as P wave duration > 120 ms. PFO was evaluated by contrast transesophageal echocardiography, and classified as no-PFO, low-risk PFO and high-risk PFO. Multiplicative and additive interaction analysis were used to assess the interaction between PFO and IAB in CS. Results Multiplicative interaction analysis unveiled a significant interaction between IAB and low-risk PFO in CS (OR for interaction = 3.653, 95% CI, 1.115–12.506; P = 0.037). Additive interaction analysis indicated that 68.4% (95% CI, 0.333–1.050; P

Abstract The components and sources of dissolved organic matter (DOM) in urban water bodies are extremely complicated due to multiple environmental and anthropogenic factors. The comprehensive analysis of the DOM molecular composition is crucial for deep understanding their reactivities, environmental behaviors, and fates in aquatic ecosystems, thereby improving our ability to monitor and protect aquatic systems. In this study, ultraviolet–visible spectroscopy (UV–Vis) and excitation-emission matrix fluorescence spectroscopy (EEM) were combined with Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) to investigate the optical and molecular characteristics of DOM in the Yongding River (YDH) and Beiyun River (BYH), two typical urban rivers with distinct landscapes and anthropogenic influences in Beijing, China. Results showed that DOM in BYH was mainly composed of proteins from microbial and sewage sources with low aromaticity, molecular weight, and abundant saturated labile compounds, along with a significant presence of anthropogenic surfactants. Whereas the YDH was primarily composed of humic substances from plant- and soil-derived terrestrials, with higher aromaticity humification, unsaturation and refractory compounds. In addition, due to the accumulation of refractory compounds, the concentration of DOC and the degree of organic pollution increased from upstream to downstream of the rivers, manifested as an increase in humification and molecular weight at the molecular level. Our results confirmed that landscape urbanization broadly modified the structure of DOM to be more aliphatic and saturated. The findings of this study will provide important insights into the chemdiverse molecular composition of DOM undergoing different influences from human activities and provide significant guidance for water quality management in urban river ecosystems. Graphical Abstract

During emergency evacuation, it is crucial to accurately detect and classify different groups of evacuees based on their behaviours using computer vision. Traditional object detection models trained on standard image databases often fail to recognise individuals in specific groups such as the elderly, disabled individuals and pregnant women, who require additional assistance during emergencies. To address this limitation, this study proposes a novel image dataset called the Human Behaviour Detection Dataset (HBDset), specifically collected and annotated for public safety and emergency response purposes. This dataset contains eight types of human behaviour categories, i.e. the normal adult, child, holding a crutch, holding a baby, using a wheelchair, pregnant woman, lugging luggage and using a mobile phone. The dataset comprises more than 1,500 images collected from various public scenarios, with more than 2,900 bounding box annotations. The images were carefully selected, cleaned and subsequently manually annotated using the LabelImg tool. To demonstrate the effectiveness of the dataset, classical object detection algorithms were trained and tested based on the HBDset, and the average detection accuracy exceeds 90 %, highlighting the robustness and universality of the dataset. The developed open HBDset has the potential to enhance public safety, provide early disaster warnings and prioritise the needs of vulnerable individuals during emergency evacuation.

How do transportation upgrades affect structural transformation in the labor market in developing countries? We focus on a specific case, Benin’s Djougou-N’dali Road Improvement Project conducted between 2004 and 2010, and estimate its effects on changes in the composition of workers by sector. Our difference-in-differences estimates suggest evidence of structural transformation in the labor market: the road improvement project leads to a relative increase in the proportion of workers in the industrial sector by 3.9 percentage points, representing a 30-percent increase. This is accompanied by a sharp decrease in the proportion of agricultural workers and an overall insignificant decrease in the proportion of service workers. These labor market effects are spatially heterogeneous: changes in agricultural workers and service workers are significant only in rural and urban areas, respectively, while both two types of areas see an increase in the proportion of industrial workers. Besides, these effects are significant only for female workers. Our findings present direct labor market effects of transportation upgrades through job switches across sectors, while other labor market mechanisms cannot explain structural transformation.

ABSTRACTThe rising prevalence and detrimental impact of inflammatory diseases have spurred the exploration of novel therapeutic approaches to tackle these conditions. Fuzi, lateral root of Aconitum carmichaelii Debx. has been used as a traditional Chinese medicine (TCM) for the treatment of inflammatory diseases for a long time. This article provides a comprehensive review of the medicinal applications, anti-inflammatory constituents, analytical techniques for detecting anti-inflammatory components, molecular mechanisms, and anti-inflammatory effects of Fuzi and its formulas. The information on Fuzi was collected from a variety of resources including classical works on Chinese herbal medicine, scientific databases (PubMed, Google Scholar, ACS, Web of Science, Science Direct, CNKI), TCMSP, NCBI, PubChem databases and others. About 122 compounds were isolated and identified from Fuzi, with alkaloids constituting the primary constituents that demonstrate potent anti-inflammatory activity. Specifically, among the identified compounds, there was one C-18 type, nineteen C-19 type, four C-20 type diterpenoid alkaloids, one other alkaloid, and 6 non-alkaloid constituents, all of which exhibited noteworthy anti-inflammatory and pain-alleviating properties in both in vivo and in vitro models of inflammation. These effects were mainly attributed to the reduction of pro-inflammatory cytokines, including IL-1, TNF-α, NO, IL-Iβ, and IL-6, as well as the inhibition of MAPK, NF-κB or PI3K/Akt signaling pathways, which effectively suppressed the inflammatory response and alleviated pain. Additionally, the anti-inflammatory effects were also achieved through the regulation of TLR4 expression and its downstream factors, or by modulating the homeostasis of the gut microbiota.

Background: High perforation risk hinders the widespread adoption of ESD for colorectal neoplasms. This study was performed to determine the risk factors of colorectal endoscopic submucosal dissection (ESD)-induced perforation and develop a predictive model. Methods: A total of 1046 colorectal neoplasms in 1011 patients were retrospectively enrolled from January 2011 to December 2021, in a single tertiary center as the derivation cohort. We identified independent risk factors for perforation using univariate analysis and multi-variate logistic regression. A nomogram was developed based on the logistic regression model and prospectively applied to 266 colorectal neoplasms as the validation cohort. The performance of the predictive model was evaluated with the receiver operating characteristic curve, calibration plot, and decision curve analysis. Results: Independent pre-operative factors for colorectal ESD-induced perforation were tumor located in the left colon [odds ratio (OR) 2.39, P = 0.040], size ≥ 40 mm (OR 3.36, P < 0.001), ≥2/3 circumference (OR 7.55, P = 0.004), located across folds (OR 6.26, P < 0.001), and laterally spreading tumor (non-granular type, OR 2.34, P = 0.029; granular type, OR 2.46, P = 0.021). The nomogram model incorporating the pre-operative factors performed well in both the derivation and validation cohorts (areas under the curve of 0.750 and 0.806, respectively). Decision curve analysis demonstrated that the clinical benefit of the nomogram was favorable. Conclusions: The novel nomogram, developed and prospectively validated, incorporating tumor size, location, and morphology can successfully predict perforation during ESD for colorectal neoplasms.

Inefficient drug penetration hurdled by the stroma in the tumor tissue leads to a diminished therapeutic effect for drugs and a reduced infiltration level of immune cells. Herein, we constructed a PEGylated dendritic epirubicin (Epi) prodrug (Epi-P4D) to regulate the metabolism of cancer-associated fibroblasts (CAFs), thus enhancing Epi penetration into both multicellular tumor spheroids (MTSs) and tumor tissues in mouse colon cancer (CT26), mouse breast cancer (4T1) and human breast cancer (MDA-MB-231) models. Enhanced cytotoxicity against CT26 MTSs and remarkable antitumor efficacy of Epi-P4D were ascribed to reduced fibronectin, α-SMA, and collagen secretion. Besides, thinning of the tumor tissue stroma and efficient eradication of tumor cells promoted the immunogenic cell death effect for dendritic cell (DC) maturation and subsequent immune activation, including elevating the CD4+ T cell population, reducing CD4+ and CD8+ T cell hyperactivation and exhaustion, and amplifying the natural killer (NK) cell proportion and effectively activating them. As a result, this dendritic nanomedicine thinned the stroma of tumor tissues to enhance drug penetration and facilitate immune cell infiltration for elevated antitumor efficacy.

Our focus in this study was on examining the convergence problem of a novel method, inspired by the Ulm-Chebyshev-like Cayley transform method, which was designed to solve the inverse eigenvalue problems (IEPs) with multiple eigenvalues. Compared with other existing methods, the proposed method has higher convergence order and/or requires less operations. Under the assumption that the relative generalized Jacobian matrices at a solution are nonsingular, the proposed method was proved to be convergent with cubic convergence. Experimental findings demonstrated the practicality and efficiency of the suggested approaches.

Objective: To investigate whether melatonin (MT) secretion in different parts of the gastrointestinal tract (GIT) exhibits seasonal variations and its correlation with immune regulation. Methods: Sixty Sprague-Dawley rats were divided into control and model groups, and the pineal gland was removed in the model group. Stomach, jejunum, ileum, and colon tissues were obtained during the spring equinox, summer solstice, beginning of autumn, autumn equinox, and winter solstice. The levels of MT, MT receptors (MR), arylalkylamine N-acetyltransferase (AANAT), hydroxyindole-O-methyltransferase (HIOMT), interleukin-2 (IL-2), and interleukin-10 (IL-10) in the GIT were measured using enzyme-linked immunosorbent assay. Results: Except for the stomach, the jejunum, ileum, and the colon showed seasonal tendencies in MT secretion. In the control group, MT secretion in the jejunum and ileum was the highest in the long summer, and colonic MT secretion was the highest in winter. In the model group, MT levels in the colon were highest in the summer. The seasonal rhythms of the MR, AANAT, HIOMT, IL-2, and IL-10 in the colon were roughly similar to those of MT, and changed accordingly after pinealectomy. Conclusions: Gastrointestinal MT secretion is related to seasonal changes, and MT secretion in each intestinal segment is influenced by different seasons. The biological effects of MT in the gut are inextricably linked to the mediation of MR, and a hormone-receptor linkage exists between MT and MR. The effect of seasonal changes on the gastrointestinal immune system may be mediated through the regulation of seasonal secretion of MT.

At present, the controllable parameters of micro turbojet engines in engineering applications are mainly speed-fuel flow (hereinafter referred to as flow) control, in which closed-loop proportional–integral–derivative (PID) control is mostly used to achieve a stable control of engine speed under slow engine conditions. For the optimal adjustment of PID parameters, this paper designs an improved evolutionary strategy for the self-tuning of control parameters in the engine speed and flow control system and formulates an improved PI controller based on a neural network. The simulation experimental results show that the method can realistically achieve stable and fast control of the engine under above slow conditions.

Abstract Purpose Since May 2022, Mpox has spread extensively outside of Africa, posing a serious threat to the health of people globally, and particularly to the men who have sex with men (MSM) population. Chongqing, a province in Southwest China, has relatively large MSM and people living with HIV (PLWH) populations, presenting conditions conducive to the wide dissemination of Mpox. In this study, we investigated the clinical characteristics of Mpox patients among MSM and PLWH in Chongqing, aiming to inform the development of targeted prevention, control, and treatment strategies for Mpox. Method We evaluated the clinical characteristics, travel history, time of onset, distribution and number of skin lesions of Mpox patients admitted to the Chongqing Public Health Medical Center between September 2022 and October 2023. Meanwhile, a series of clinical samples were collected and the pathogen of interest was identified as Mpox virus using quantitative polymerase chain reaction (qPCR). The results were presented in the form of cycle thresholds (Ct), which help to approximate the quantification of viral load. Results As of October 11, 2023, the Chongqing Public Health Medical Center reported a total of nine Mpox virus infections. All the patients identified were male and belonged to the MSM population, among whom seven (77.8%) were living with HIV, and maintained a preserved immune system while achieving viral suppression via effective ART. We observed no discernible clinical differences between MSM with Mpox with or without HIV, and no fatalities were recorded. Viral loads were observed to be higher in samples taken from the skin than those from the throat, nasopharynx, blood, or semen. Conclusion In this retrospective study, the clinical manifestations of MPXV infection appeared consistent among MSM patients, regardless of HIV status. Elevated MPXV viral loads in the skin and mucosal tissues, particularly at genital and anal sites, indicate that transmission is more likely to occur via direct physical contact as opposed to respiratory pathways or through exposure to bodily fluids.

Abstract Background Liguzinediol (Lig) has emerged as a promising candidate for mitigating Doxorubicin (DOX)-induced cardiotoxicity, a significant limitation in the clinical application of this widely used antineoplastic drug known for its efficacy. This study aimed to explore the effects and potential mechanisms underlying Lig’s protective role against DOX-induced cardiotoxicity. Methods C57BL/6 mice were treated with DOX. Cardiac function changes were observed by echocardiography. Cardiac structure changes were observed by HE and Masson staining. Immunofluorescence was applied to visualize the cardiomyocyte apoptosis. Western blotting was used to detect the expression levels of AMP-activated protein kinase (AMPK), sirtuin 3 (SIRT3), Caspase-3 and gasdermin E N-terminal fragment (GSDME-N). These experiments confirmed that Lig had an ameliorative effect on DOX-induced cardiotoxicity in mice. Results The results demonstrated that Lig effectively countered myocardial oxidative stress by modulating intracellular levels of reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD). Lig reduced levels of creatine kinase (CK) and lactate dehydrogenase (LDH), while ameliorating histopathological changes and improving electrocardiogram profiles in vivo. Furthermore, the study revealed that Lig activated the AMPK/SIRT3 pathway, thereby enhancing mitochondrial function and attenuating myocardial cell apoptosis. In experiments with H9C2 cells treated with DOX, co-administration of the AMPK inhibitor compound C (CC) led to a significant increase in intracellular ROS levels. Lig intervention reversed these effects, along with the downregulation of GSDME-N, interleukin-1β (IL-1β), and interleukin-6 (IL-6), suggesting a potential role of Lig in mitigating Caspase-3/GSDME-mediated pyroptosis. Conclusion The findings of this study suggest that Lig effectively alleviates DOX-induced cardiotoxicity through the activation of the AMPK/SIRT3 pathway, thereby presenting itself as a natural product with therapeutic potential for preventing DOX-associated cardiotoxicity. This novel approach may pave the way for the development of alternative strategies in the clinical management of DOX-induced cardiac complications.

Summary: Di (2-ethylhexyl) phthalate (DEHP) is an environmental endocrine disruptor and commonly used as a plasticizer. Exposure to DEHP and its active metabolite mono-2-ethylhexyl phthalate (MEHP) can lead to adverse health consequences; however, the toxic mechanism is remains unclear. In this research, male and female rats were exposed to DEHP and MEHP by oral gavage for 60 consecutive days. Pathological analysis revealed that DEHP and MEHP exposure could affect liver, heart, kidney, and testis tissues, as well as alter biochemical indicators. Metagenomics (16S rRNA gene sequencing) analysis indicated that DEHP and MEHP could reduce the diversity and alter the composition of the gut microbiota. Toxic exposure also affected the levels of short chain fatty acids (SCFAs), with noticeable variations between genders. Metabolomic analysis revealed that DEHP and MEHP could influence bile acids, amino acids, hormones, and lipids. These results demonstrate that exposure to DEHP and MEHP can induce toxicity in rats via the gut-liver axis.

This review examines the complexities of Type 2 Diabetes Mellitus (T2DM), focusing on the critical role of integrating omics technologies with traditional experimental methods. It underscores the advancements in understanding the genetic diversity of T2DM and emphasizes the evolution towards personalized treatment modalities. The paper analyzes a variety of omics approaches, including genomics, methylation, transcriptomics, proteomics, metabolomics, and intestinal microbiomics, delineating their substantial contributions to deciphering the multifaceted mechanisms underlying T2DM. Furthermore, the review highlights the indispensable role of non-omics experimental techniques in comprehending and managing T2DM, advocating for their integration in the development of tailored medicine and precision treatment strategies. By identifying existing research gaps and suggesting future research trajectories, the review underscores the necessity for a comprehensive, multidisciplinary approach. This approach synergistically combines clinical insights with cutting-edge biotechnologies, aiming to refine the management and therapeutic interventions of T2DM, and ultimately enhancing patient outcomes. This synthesis of knowledge and methodologies paves the way for innovative advancements in T2DM research, fostering a deeper understanding and more effective treatment of this complex condition.

BackgroundHand function assessment heavily relies on specific task scenarios, making it challenging to ensure validity and reliability. In addition, the wide range of assessment tools, limited and expensive data recording, and analysis systems further aggravate the issue. However, smartphones provide a promising opportunity to address these challenges. Thus, the built-in, high-efficiency sensors in smartphones can be used as effective tools for hand function assessment. ObjectiveThis review aims to evaluate existing studies on hand function evaluation using smartphones. MethodsAn information specialist searched 8 databases on June 8, 2023. The search criteria included two major concepts: (1) smartphone or mobile phone or mHealth and (2) hand function or function assessment. Searches were limited to human studies in the English language and excluded conference proceedings and trial register records. Two reviewers independently screened all studies, with a third reviewer involved in resolving discrepancies. The included studies were rated according to the Mixed Methods Appraisal Tool. One reviewer extracted data on publication, demographics, hand function types, sensors used for hand function assessment, and statistical or machine learning (ML) methods. Accuracy was checked by another reviewer. The data were synthesized and tabulated based on each of the research questions. ResultsIn total, 46 studies were included. Overall, 11 types of hand dysfunction–related problems were identified, such as Parkinson disease, wrist injury, stroke, and hand injury, and 6 types of hand dysfunctions were found, namely an abnormal range of motion, tremors, bradykinesia, the decline of fine motor skills, hypokinesia, and nonspecific dysfunction related to hand arthritis. Among all built-in smartphone sensors, the accelerometer was the most used, followed by the smartphone camera. Most studies used statistical methods for data processing, whereas ML algorithms were applied for disease detection, disease severity evaluation, disease prediction, and feature aggregation. ConclusionsThis systematic review highlights the potential of smartphone-based hand function assessment. The review suggests that a smartphone is a promising tool for hand function evaluation. ML is a conducive method to classify levels of hand dysfunction. Future research could (1) explore a gold standard for smartphone-based hand function assessment and (2) take advantage of smartphones’ multiple built-in sensors to assess hand function comprehensively, focus on developing ML methods for processing collected smartphone data, and focus on real-time assessment during rehabilitation training. The limitations of the research are 2-fold. First, the nascent nature of smartphone-based hand function assessment led to limited relevant literature, affecting the evidence’s completeness and comprehensiveness. This can hinder supporting viewpoints and drawing conclusions. Second, literature quality varies due to the exploratory nature of the topic, with potential inconsistencies and a lack of high-quality reference studies and meta-analyses.

Scale effects significantly affect the rationality and accuracy of ecological models, so temporal and spatial scales are included in the construction and application of ecological studies. However, few ecological pattern analyses focus on both of these scales simultaneously, which is especially important in terms of synchrony. In this study, based on fishery catch data and simulated data, we propose a framework for coupled space-time scale analysis and reveal possible deficiencies in conventional scale studies. We verified the feasibility and reliability of the scheme using simulated data with different combinations of temporal and spatial scales. The results showed that our scheme can simultaneously identify and localize scale features in the variation in species spatial-temporal patterns, specifically regarding the synchrony and amplitude of temporal dynamics (or spatial patterns) of multiple sites (or times). Our scheme revealed that spatial scales had an important effect on the intrinsic 13-year scale features, which significantly improved our understanding of global Rajiformes fishery dynamics. This showed that the spatial-temporal patterns and scale features obtained based on the coupled space-time scale analysis were complete and more accurate. At the same time, our scheme correctly identified complex pattern structures, such as data stratification and multiple combinations of time and space scales, which can reduce possible errors in practical applications. This scheme can be applied to the identification and prediction of the spatial-temporal patterns in biodiversity in the future and will help in formulating effective policies promoting sustainable fishery resources management and comprehensive conservation of endangered marine species.

Background: Microglia-mediated inflammation is a critical factor in the progression of ischemic stroke. Consequently, mitigating excessive microglial activation represents a potential therapeutic strategy for ischemic injury. Thymol, a monophenol derived from plant essential oils, exhibits diverse beneficial biological activities, including anti-inflammatory and antioxidant properties, with demonstrated protective effects in various disease models. However, its specific effects on ischemic stroke and microglial inflammation remain unexplored. Methods: Rodent transient middle cerebral artery occlusion (tMCAO) model was established to simulate ischemic stroke. TTC staining, modified neurological function score (mNSS), and behavioral tests were used to assess the severity of neurological damage. Then immunofluorescence staining and cytoskeleton analysis were used to determine activation of microglia. Lipopolysaccharide (LPS) was utilized to induce the inflammatory response of primary microglia in vitro. Quantitative real-time polymerase chain reaction (qRT-PCR), western blot, and enzyme-linked immunosorbent assay (ELISA) were performed to exam the expression of inflammatory cytokines. And western blot was used to investigate the mechanism of the anti-inflammatory effect of thymol. Results: In this study, we found that thymol treatment could ameliorate post-stroke neurological impairment and reduce infarct volume by mitigating microglial activation and pro-inflammatory response (IL-1β, IL-6, and TNF-α). Mechanically, thymol could inhibit the phosphorylation of phosphatidylinositol-3-kinase (PI3K), sink serine/threonine kinase (Akt), and mammalian target of rapamycin (mTOR), thereby suppressing the activation of nuclear factor-κB (NF-κB). Conclusions: Our study demonstrated that thymol could reduce the microglial inflammation by targeting PI3K/Akt/mTOR/NF-κB signaling pathway, ultimately alleviating ischemic brain injury. These findings suggest that thymol is a promising candidate as a neuroprotective agent against ischemic stroke.

The prevalence of dyslipidemia is increasing, and it has become a significant global public health concern. Some studies have demonstrated contradictory relationships between urinary metals and dyslipidemia, and the combined effects of mixed urinary metal exposure on dyslipidemia remain ambiguous. In this study, we examined how individual and combined urinary metal exposure are associated with the occurrence of dyslipidemia. According to the data from the 2018–2019 baseline survey database of the China Multi-Ethnic Cohort (CMEC) Study, a population of 9348 individuals was studied. Inductively coupled plasmamass spectrometry (ICP-MS) was used to measure 21 urinary metal concentrations in the collected adult urinary samples. The associations between urinary metals and dyslipidemia were analyzed by logistic regression, weighted quantile sum regression (WQS), and quantile-based g-computation (qgcomp), controlled for potential confounders to examine single and combined effects. Dyslipidemia was detected in 3231 individuals, which represented approximately 34.6 % of the total population. According to the single-exposure model, Al and Na were inversely associated with the risk of dyslipidemia (OR = 0.95, 95 % CI: 0.93, 0.98; OR = 0.89, 95 % CI: 0.83, 0.95, respectively), whereas Zn, Ca, and P were positively associated (OR = 1.69, 95 % CI: 1.42, 2.01; OR = 1.12, 95 % CI: 1.06, 1.18; OR = 1.21, 95 % CI: 1.09, 1.34, respectively). Moreover, Zn and P were significantly positively associated even after adjusting for these metals, whereas Al and Cr were negatively associated with the risk of dyslipidemia. The results of the WQS and qgcomp analyses showed that urinary metal mixtures were positively associated with the risk of dyslipidemia (OR = 1.26, 95 % CI: 1.15, 1.38; OR = 1.09, 95 % CI: 1.01, 1.19). This positive association was primarily driven by Zn, P, and Ca. In the sensitivity analyses with collinearity diagnosis, interaction, and stratified analysis, the results remained, confirming the reliability of the study findings. In this study, the individual and combined effects of urinary Zn, P, and Ca on dyslipidemia were determined, which provided novel insights into the link between exposure to metals and dyslipidemia.

Abstract The aim of this study was to determine the role of lncRNA PART1 and downstream FUT6 in tumorigenesis and progression of head and neck cancer (HNC). Bioinformatics analysis and qRT-PCR revealed that lncRNA PART1 was expressed at low levels in HNC patients. The proliferation, apoptosis, migration and flow cytometry results showed that low expression of lncRNA PART1 inhibited apoptosis and promoted HNC cell migration and proliferation. In addition, animal experiments have also shown that low expression of lncRNA PART1 can promote tumor growth. LncRNA PART1 overexpression promoted apoptosis and inhibited HNC cell migration and proliferation. Through bioinformatics analysis, FUT6 was found to be expressed at low levels in HNC and to be correlated with patient survival. Immunohistochemical and qRT-PCR results revealed that FUT6 was underexpressed in tumour tissues and HNC cells. Cell and animal experiments showed that overexpression of FUT6 could inhibit tumour proliferation and migration. Bioinformatics analysis revealed that lncRNA PART1 was positively correlated with FUT6. By qRT-PCR and western blot, we observed that after knockdown of lncRNA PART1, both the mRNA and protein expression levels of FUT6 were reduced. The above results indicated that lncRNA PART1 and FUT6 play an important role in HNC, and that lncRNA PART1 affected the development of tumor by downstream FUT6.

Abstract Jinlida granule (JLD) is a Traditional Chinese Medicine (TCM) formula used for the treatment of type 2 diabetes mellitus (T2DM). However, the mechanism of JLD treatment for T2DM is not fully revealed. In this study, we explored the mechanism of JLD against T2DM by an integrative pharmacology strategy. Active components and corresponding targets were retrieved from Traditional Chinese Medicine System Pharmacology (TCMSP), SwissADME and Bioinformatics Analysis Tool for Molecular Mechanisms of Traditional Chinese Medicine Database (BATMAN-TCM) database. T2DM-related targets were obtained from Drugbank and Genecards databases. The protein–protein interaction (PPI) network was constructed and analyzed with STRING (Search Toll for the Retrieval of Interacting Genes/proteins) and Cytoscape to get the key targets. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genomes (KEGG) enrichment analyses were performed with the Database for Annotation, Visualization and Integrated Discovery (DAVID). Lastly, the binding capacities and reliability between potential active components and the targets were verified with molecular docking and molecular dynamics simulation. In total, 185 active components and 337 targets of JLD were obtained. 317 targets overlapped with T2DM-related targets. RAC-alpha serine/threonine-protein kinase (AKT1), tumor necrosis factor (TNF), interleukin-6 (IL-6), cellular tumor antigen p53 (TP53), prostaglandin G/H synthase 2 (PTGS2), Caspase-3 (CASP3) and signal transducer and activator of transcription 3 (STAT3) were identified as seven key targets by the topological analysis of the PPI network. GO and KEGG enrichment analyses showed that the effects were primarily associated with gene expression, signal transduction, apoptosis and inflammation. The pathways were mainly enriched in PI3K-AKT signaling pathway and AGE-RAGE signaling pathway in diabetic complications. Molecular docking and molecular dynamics simulation verified the good binding affinity between the key components and targets. The predicted results may provide a theoretical basis for drug screening of JLD and a new insight for the therapeutic effect of JLD on T2DM.

Since the catalytic activity of most nanozymes is still far lower than the corresponding natural enzymes, there is urgent need to discover novel highly efficient enzyme-like materials. In this work, Co3V2O8 with hollow hexagonal prismatic pencil structures were prepared as novel artificial enzyme mimics. They were then decorated by photo-depositing Ag nanoparticles (Ag NPs) on the surface to further improve its catalytic activities. The Ag NPs decorated Co3V2O8 (ACVPs) showed both excellent oxidase- and peroxidase-like catalytic activities. They can oxidize the colorless 3,3’,5,5’-tetramethylbenzidine rapidly to induce a blue change. The enhanced enzyme mimetic activities can be attributed to the surface plasma resonance (SPR) effect of Ag NPs as well as the synergistic catalytic effect between Ag NPs and Co3V2O8, accelerating electron transfer and promoting the catalytic process. ACVPs were applied in constructing a colorimetric sensor, validating the occurrence of the Fenton reaction, and disinfection, presenting favorable catalytic performance. The enzyme-like catalytic mechanism was studied, indicating the chief role of ⋅O2- radicals in the catalytic process. This work not only discovers a novel functional material with double enzyme mimetic activity but also provides a new insight into exploiting artificial enzyme mimics with highly efficient catalytic ability.

Abstract Ensemble learning has the potential to enhance the efficacy of feeble classifiers significantly and is increasingly being utilized in Twitter bot detection. Previous methods have utilized stacking techniques to train the primary classifiers, implementing cross-validation to mitigate overfitting and enhance predictive accuracy. However, cross-validation substantially amplifies the computation time associated with stacking. To overcome this challenge, this paper presents a novel approach, the Simplified Stacking Graph Neural Network (SStackGNN), specifically designed for the detection of social bots. Our methodology leverages the power of Graph Neural Networks (GNNs) as base classifiers, enabling effective capturing of inter-account interactions. In addition, a Multilayer Perceptron (MLP) serves as a secondary classifier, amalgamating the outcomes of the foundational classifiers to generate final predictions, thereby enhancing the predictive performance of the GNNs. Instead of relying on cross-validation and distinct base classifier structures, we employ node-level, edge-level, and feature-level graph data augmentation techniques to acquire diverse foundational classifiers. This approach significantly alleviates the computational complexity while achieving superior performance. Experimental results demonstrate that our proposed SStackGNN outperforms other approaches.

Abstract Glycogen storage disease type Ib (GSD-Ib) is a rare inborn error of glycogen metabolism caused by mutations in SLC37A4. Patients with GSD-Ib are at high risk of developing inflammatory bowel disease (IBD). We evaluated the efficacy of empagliflozin, a renal sodium‒glucose cotransporter protein 2 (SGLT2) inhibitor, on colonic mucosal healing in patients with GSD-associated IBD. A prospective, single-arm, open-label clinical trial enrolled eight patients with GSD-associated IBD from Guangdong Provincial People's Hospital in China from July 1, 2022 through December 31, 2023. Eight patients were enrolled with a mean age of 10.34 ± 2.61 years. Four male and four female. The endoscopic features included deep and large circular ulcers, inflammatory hyperplasia, obstruction and stenosis. The SES-CD score significantly decreased at week 48 compared with before empagliflozin. Six patients completed 48 weeks of empagliflozin therapy and endoscopy showed significant improvement or healing of mucosal ulcers, inflammatory hyperplasia, stenosis, and obstruction. One patient had severe sweating that required rehydration and developed a urinary tract infection. No serious or life-threatening adverse events. This study suggested that empagliflozin may promote colonic mucosal healing and reduce hyperplasia, stenosis, and obstruction in children with GSD-associated IBD.

Abstract Biodegradability is a crucial indicator to evaluate the sustainability of leather. Herein, a rapid method for biodegradation test in an aqueous medium by measuring biochemical oxygen demand was used to determine the biodegradability of leather from different tanning methods, tanning conditions and process stages. In addition, the difference in biodegradability between leather and leather-like synthetic materials were investigated. Chrome-free tanned leather showed higher degree of biodegradation and faster biodegradation rate than chrome tanned leather. Among them, leathers tanned with biomass-based tanning agents were much easier to biodegrade because the crosslinking network of tanned leather constructed with biomass was more susceptible to microbial attack. The enhancement of tanning effects through changing tanning methods and conditions (such as tanning agent dosage, pH and temperature) resulted in the decline of leather biodegradability. Future development of novel chrome-free tanning technologies should balance between these two aspects. The biodegradability of leather from tanning to post-tanning to finishing showed a stepwise decrease because various chemicals were applied and bound to leather during processing. Even so, finished leather still possessed significantly higher biodegradability compared to leather-like PU and microfiber synthetic materials, demonstrating superior environmental sustainability of natural leather. The results are expected to provide support for the evaluation of the ecological properties of leather and green upgrade of the leather industry. Graphical abstract

The continuous process of urbanization and climate change has led to severe urban heat island (UHI) effects. Constructing parks with cooling capabilities is considered an effective measure to alleviate UHI effects. However, most studies only quantify the cooling effect from a maximum value perspective, lacking a measure of temperature diffusion in space. This study combines the perspectives of maximum value and accumulation to define a cold island index, quantifying the cooling effect of 40 urban parks in the main urban area of Xi'an city. The results show that, on average, urban parks can reduce the surrounding environment by approximately 2.3℃, with a cooling range of about 127.1ha, which is three times the park area. Different factors drive the measurement of the cooling effect using different cold island indexes, but all indexes are highly correlated with green space area. There are significant differences in the cooling effect among different types of parks, and overall, ecological parks have the best cooling effect. The directional spread of internal cold islands in parks is most related to park shape, while external spread is related to surrounding green spaces. The research results have practical value in the construction of parks with cooling effects and the sustainable development of cities in urban planning processes..

Abstract SEMA7A belongs to the Semaphorin family and is involved in the oncogenesis and tumor progression. Aberrant glycosylation has been intricately linked with immune escape and tumor growth. SEMA7A is a highly glycosylated protein with five glycosylated sites. The underlying mechanisms of SEMA7A glycosylation and its contribution to immunosuppression and tumorigenesis are unclear. Here, we identify overexpression and aberrant N-glycosylation of SEMA7A in head and neck squamous cell carcinoma, and elucidate fucosyltransferase FUT8 catalyzes aberrant core fucosylation in SEMA7A at N-linked oligosaccharides (Asn 105, 157, 258, 330, and 602) via a direct protein‒protein interaction. A glycosylated statue of SEMA7A is necessary for its intra-cellular trafficking from the cytoplasm to the cytomembrane. Cytokine EGF triggers SEMA7A N-glycosylation through increasing the binding affinity of SEMA7A toward FUT8, whereas TGF-β1 promotes abnormal glycosylation of SEMA7A via induction of epithelial–mesenchymal transition. Aberrant N-glycosylation of SEMA7A leads to the differentiation of CD8+ T cells along a trajectory toward an exhausted state, thus shaping an immunosuppressive microenvironment and being resistant immunogenic cell death. Deglycosylation of SEMA7A significantly improves the clinical outcome of EGFR-targeted and anti-PD-L1-based immunotherapy. Finally, we also define RBM4, a splice regulator, as a downstream effector of glycosylated SEMA7A and a pivotal mediator of PD-L1 alternative splicing. These findings suggest that targeting FUT8-SEMA7A axis might be a promising strategy for improving antitumor responses in head and neck squamous cell carcinoma patients.

Abstract Background Scedosporium apiospermum (S. apiospermum) belongs to the asexual form of Pseudallescheria boydii and is widely distributed in various environments. S. apiospermum is the most common cause of pulmonary infection; however, invasive diseases are usually limited to patients with immunodeficiency. Case presentation A 54-year-old Chinese non-smoker female patient with normal lung structure and function was diagnosed with pulmonary S. apiospermum infection by metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF). The patient was admitted to the hospital after experiencing intermittent right chest pain for 8 months. Chest computed tomography revealed a thick-walled cavity in the upper lobe of the right lung with mild soft tissue enhancement. S. apiospermum was detected by the mNGS of BALF, and DNA sequencing reads were 426. Following treatment with voriconazole (300 mg q12h d1; 200 mg q12h d2-d20), there was no improvement in chest imaging, and a thoracoscopic right upper lobectomy was performed. Postoperative pathological results observed silver staining and PAS-positive oval spores in the alveolar septum, bronchiolar wall, and alveolar cavity, and fungal infection was considered. The patient’s symptoms improved; the patient continued voriconazole for 2 months after surgery. No signs of radiological progression or recurrence were observed at the 10-month postoperative follow-up. Conclusion This case report indicates that S. apiospermum infection can occur in immunocompetent individuals and that the mNGS of BALF can assist in its diagnosis and treatment. Additionally, the combined therapy of antifungal drugs and surgery exhibits a potent effect on the disease.

Abstract Type 2 diabetes mellitus (T2DM) poses a significant global health burden. This is particularly due to its macrovascular complications, such as coronary artery disease, peripheral vascular disease, and cerebrovascular disease, which have emerged as leading contributors to morbidity and mortality. This review comprehensively explores the pathophysiological mechanisms underlying these complications, protective strategies, and both existing and emerging secondary preventive measures. Furthermore, we delve into the applications of experimental models and methodologies in foundational research while also highlighting current research limitations and future directions. Specifically, we focus on the literature published post-2020 concerning the secondary prevention of macrovascular complications in patients with T2DM by conducting a targeted review of studies supported by robust evidence to offer a holistic perspective.

Pepper is a key agricultural crop susceptible to accumulating heavy metals like cadmium (Cd) and barium (Ba), posing significant health risks. To address these issues, this study investigated the effects of foliar applications of fulvic acid (FA), Zn-fulvic acid (Zn-FA), and Fe-fulvic acid (Fe-FA) on Ba and Cd uptake in pepper tissues, as well as their impact on nutritional quality, biomass, and leaf enzyme activity. Results indicated that Fe-FA application significantly reduced Cd and Ba in pepper fruit by 25 % and 93 %, respectively. Additionally, Fe-FA enhanced pepper growth, increasing vitamin C and phenolic compounds by 136 % and 13 %, respectively. Metabolomics analysis revealed that Fe-FA application up-regulated 857 metabolites and down-regulated 1045 metabolites. Furthermore, Fe-FA primarily influenced amino acid, carbohydrate, and lipid metabolism, promoting pepper growth. These findings suggest that Fe-FA foliar application offers a promising strategy for reducing Ba and Cd accumulation in pepper fruits while enhancing its nutritional quality.

Stress-induced immunosuppression (SIIS) is one of the most common problems in intensive poultry production, which can cause immunized chickens to still develop diseases and bring huge losses to production. Recently, adipose tissue, as an immunomodulatory organ, has become a hot topic of attention. However, the function and mechanism of adipose tissue involved in SIIS and its influence on the immune response are still unclear. In this study, we dynamically analyzed the correlations between the T cells migration and change of sphingosine-1-phosphate receptor 1 (S1PR1) gene in adipose tissue using chicken models with different immune states, and further explored the regulatory mechanisms and application. The results showed that SIIS could significantly change the expressions of lymphocytes migration related S1PR1 gene, and SIIS could inhibit the Newcastle disease virus (NDV) immune response partially by affecting the migration and proliferation of TCRα+ T cells in adipose tissue. Moreover, the miR-145-5p/S1PR1 pathway was a potential key mechanism to regulate T cells migration in adipose tissue, and circulating miR-145-5p had potential value as a molecular marker. This research can provide innovative reference for in-depth studying the immunoregulatory function and mechanism of adipose tissue.

ABSTRACTThe evolution and future trajectory of island shorelines, amidst global climate change, are of increasing concern to governments, communities and researchers worldwide. However, the field of island studies is often hampered by a lack of data and inconsistent methodologies, leading to an inadequate understanding of the processes driving shoreline changes on islands within the context of climate change. This research aims to bridge this gap by analyzing islands in Southeast Asia, the Indian Ocean and the Mediterranean Sea from 1990 to 2020 using remote sensing. Of over 13,000 islands examined, approximately 12% experienced significant shifts in shoreline positions. The total shoreline length of these islands approaches 200,000 km, with 7.57% showing signs of landward erosion and 6.05% expanding seaward. Human activities, particularly reclamation and land filling, were identified as primary drivers of local shoreline transformations, while natural factors have a comparatively minor impact. Moreover, the ongoing rise in sea levels is identified as an exacerbating factor for coastal erosion rather than the primary cause. Drawing from these findings, we propose several adaptive measures for islands in response to climate change. Taken together, this research provides comprehensive data and a basis for decision-making for sustainable development of island territories.

Temporomandibular joint osteoarthritis (TMJ-OA) is usually caused by increased friction at the joint interface, excessive release of inflammatory factors and catabolic enzymes, and free radical accumulation, which can lead to accelerated degradation and damage of cartilage. In this study, we develop a biological metabolism-inspired injectable hydrogel crosslinking by hydrazide modified hyaluronic acid (HA-HYD), aldehyde modified hyaluronic acid (HA-ALD), and ε-polylysine coated catalase-mimic nanozyme (mesoporous manganese cobalt oxide). Herein, this nanozyme-reinforced hydrogel with outstanding and durable reactive oxygen species (ROS) depletion capability and biocompatibility can alleviate the oxidative stress microenvironment, improve cell viability and proliferation, as well as up-regulate chondrogenic related gene expression and cartilage matrix formation of chondrocytes in vitro. Intra-articular administration of this engineered hydrogel can effectively scavenge endogenous over-expressed ROS to ameliorate the harsh microenvironment in the cavity of TMJ-OA. The nanozyme-reinforced hydrogel reduced proinflammatory cytokines (TNF-α, IL-1β, and IL-6) and enhance anti-inflammatory cytokines (IL-10) expression, induced polarization of synovial macrophages towards M2 phenotype, alleviated structural damage to the cartilage and subchondral bone of the condyle, thus reducing cartilage matrix destruction and protect cartilage in osteoarthritis. In summary, the bioinspired nanozyme-reinforced hydrogels might be used as a promising ROS scavenger for treatment of TMJ-OA.

ObjectiveGastrointestinal dysfunction are often associated with type 2 diabetes mellitus (T2DM), a complicated metabolic illness. Contributing factors have been proposed, including genetic predisposition, gene environmental, and lifestyle interactions, but the pathophysiology remains unknown.MethodsWe aim to explore the possible causes behind gastrointestinal dysfunction caused by type 2 diabetes in this study. A comprehensive analysis of the gastric sinus metabolome, transcriptome, and proteome in db/db mice with gastrointestinal dysfunction was conducted.ResultsThe model group of mice had considerably lower small intestine propulsion and gastric emptying rates, higher blood glucose levels, and were significantly obese compared to the control group. We identified 297 genes, 350 proteins, and 1,001 metabolites exhibiting significant differences between db/db and control mice (p < 0.05). Moreover, multi-omics analysis revealed that the genes, proteins, and metabolites in the T2DM-induced gastroenteropathy mice group were involved in arachidonic acid metabolism, glycerophospholipid metabolism and vitamin digestion and absorption. Specifically, Cbr3, Etnppl, and Apob were the major mRNAs associated with T2DM-induced gastrointestinal dysfunction, while Cyp2b10, Cyp2b19, Pgs1, Gpat3, Apoa4, and Tcn2 were the major proteins associated with T2DM-induced gastrointestinal injury, and 16(R)-HET, 5-HETE, LysoPC (22:0), and Pantothenic acid were the major metabolites associated with T2DM-induced gastrointestinal disorders.ConclusionThe mechanism of action of diabetic gastroenteropathy may be related to vitamin digestion and absorption, glycerophospholipid metabolism, and arachidonic acid metabolism.

Abstract Patients with glycogen storage disease type Ib (GSD‐Ib) frequently have inflammatory bowel disease (IBD). however, the underlying etiology remains unclear. Herein, this study finds that digestive symptoms are commonly observed in patients with GSD‐Ib, presenting as single or multiple scattered deep round ulcers, inflammatory pseudo‐polyps, obstructions, and strictures, which differ substantially from those in typical IBD. Distinct microbiota profiling and single‐cell clustering of colonic mucosae in patients with GSD are conducted. Heterogeneous oral pathogenic enteric outgrowth induced by GSD is a potent inducer of gut microbiota immaturity and colonic macrophage accumulation. Specifically, a unique population of macrophages with high CCL4L2 expression is identified in response to pathogenic bacteria in the intestine. Hyper‐activation of the CCL4L2‐VSIR axis leads to increased expression of AGR2 and ZG16 in epithelial cells, which mediates the unique progression of IBD in GSD‐Ib. Collectively, the microbiota‐driven pathomechanism of IBD is demonstrated in GSD‐Ib and revealed the active role of the CCL4L2‐VSIR axis in the interaction between the microbiota and colonic mucosal immunity. Thus, targeting gut dysbiosis and/or the CCL4L2‐VISR axis may represent a potential therapy for GSD‐associated IBD.

Mitochondrial damage has a particular impact on the immune system and tumor microenvironment, which can trigger cell stress, an inflammatory response, and disrupt immune cell function, thus all of which can accelerate the progression of the tumor. Therefore, it is of essence to comprehend how the immune system function and the tumor microenvironment interact with mitochondrial dysfunction for cancer treatment. Preserving the integrity of mitochondria or regulating the function of immune cells, such as macrophages, may enhance the efficacy of cancer therapy. Future research should concentrate on the interactions among mitochondria, the immune system, and the tumor microenvironment to identify new therapeutic strategies.

Background: Lung adenocarcinoma (LUAD) is the commonest subtype of primary lung cancer. A comprehensive analysis of the association of immunity with amino acid metabolism in LUAD is critical for understanding the disease. Methods: The present study examined LUAD and noncancerous cases from the TCGA database. Differentially expressed genes (DEGs) between LUAD and noncancerous tissues were detected by analyzing processed expression profiles. We cross-referenced the up-regulated DEGs with Immune and Amino Acid Metabolism-related genes (I&AAMGs), resulting in Immune and Amino Acid Metabolism related differentially expressed genes (IAAAMRDEGs). The STRING database was employed to analyze PPI on IAAAMRDEGs, obtaining excavated hub genes, whose biological processes, molecular functions and cellular components were examined with GO/KEGG. Potential mechanisms related to LUAD were investigated by GSEA and GSVA. A prognostic model was built by LASSO-COX analysis, taking into consideration risk scores and prognostic factors to determine biomarkers affecting LUAD occurrence and prognosis. Results: Totally 377 genes were detected at the intersection of upregulated DEGs and I&AAMGs. Analysis of PPI on these 377 IAAAMRDEGs yielded 17 hub genes. A LASSO regression analysis was utilized to assess the prognostic values of the 17 hub genes. Validation using the combined dataset confirmed 4 genes, e.g., polo-like kinase (PLK1), Ribonucleotide Reductase Subunit M2 (RRM2), Thyroid Hormone Receptor Interactor 13 (TRIP13), and Hyaluronan-Mediated Motility Receptor (HHMR). The model's accuracy was further assessed by ROC curve analysis and the COX model. In addition, immunohistochemical staining obtained from the HPA database, revealed enhanced PLK1 expression in LUAD samples. Conclusion: LUAD pathogenesis is highly associated with immunity and amino acid metabolism. The PLK1, RRM2, TRIP13, and HMMR genes have prognostic values for LUAD. PLK1 upregulation in LUAD might be involved in tumorigenesis by modulating the cell cycle and represents a potential prognostic factor in clinic.

Abstract Children are generally susceptible to COVID-19, and infection with COVID-19 may cause serious harm to children. COVID-19 vaccination is an effective way to prevent infection at present, and many factors affect children's COVID-19 vaccination. This study aimed to explore the effects of perceived social support and health literacy on hesitancy towards first and second vaccine dose. This cross-sectional study was conducted in the Minhang District of Shanghai, China, in October 2022. A total of 1150 parents of preschool children from 10 kindergartens participated. The survey encompassed four sections, capturing data on sociodemographic attributes, health literacy, perceived social support, and parental COVID-19 vaccine hesitancy. Health literacy was measured using a self-designed questionnaire consisting of four dimensions. Perceived social support was assessed using the MSPSS questionnaire. Hierarchical multiple logistic regression was used to examine the relationship between the independent variables and parental hesitancy towards the first and second doses of COVID-19 vaccine. Parental hesitancy rate for the first dose of the COVID-19 vaccine was 69.6%, and for the second dose, it was 33.1%. The final integrated model showed that parental hesitancy towards the first and the second dose of COVID-19 vaccine was associated with parental educational level, allergy in children, information decision-making and information comprehension ability, perceived social support from family and friends. Health literacy and perceived social support are influence factors for parental hesitancy towards COVID-19 vaccine for preschool children. The findings will provide insights for future intervention studies on COVID-19 vaccine hesitancy and inform the development of vaccination policies.

Abstract Background This study aims to assess the influence of early serum phosphate fluctuation on the short-term prognosis of sepsis patients. Methods This retrospective study used the Medical Information Mart for Intensive Care IV database to analyze serum phosphate levels in sepsis patients within 3 days of ICU admission. According to the absolute value of delta serum phosphate (the maximum value minus the minimum value of serum phosphorus measured within three days), the patients were divided into four groups, 0–1.3, 1.4–2.0, 2.1–3.1, and ≥ 3.2 mg/dl. Meanwhile, the direction of delta serum phosphate was compared. With the serum phosphate change group of 0–1.3 mg/dl as the reference group, the relationship between delta serum phosphate and in-hospital mortality and 28-day mortality was analyzed by multivariate Logistics regression analysis. Results The study involved 1375 sepsis patients. Serum phosphate changes (0–1.3, 1.4–2.0, 2.1–3.1, and ≥ 3.2 mg/dl) correlated with in-hospital and 28-day mortality variations (p = 0.005, p = 0.008). Much higher serum phosphate fluctuation elevated in-hospital and 28-day mortality. Compared to the 0–1.3 mg/dl change group, adjusted odds ratios (OR) in other groups for in-hospital mortality were 1.25 (0.86–1.81), 1.28 (0.88–1.86), and 1.63 (1.10–2.43), and for 28-day mortality were 1.21 (0.86–1.72), 1.10 (0.77–1.57), and 1.49 (1.03–2.19). Under the trend of increasing serum phosphate, the ORs of in-hospital mortality and 28-day mortality in ≥ 3.2 mg/dl group were 2.52 and 2.01, respectively. Conclusion In conclude, the delta serum phosphate ≥ 3.2 mg/dl was associated with in-hospital mortality and 28-day mortality in patients with sepsis.

Abstract Systemic immune monitoring is a crucial clinical tool for disease early diagnosis, prognosis and treatment planning by quantitative analysis of immune cells. However, conventional immune monitoring using flow cytometry faces huge challenges in large-scale sample testing, especially in mass health screenings, because of time-consuming, technical-sensitive and high-cost features. However, the lack of high-performance detection platforms hinders the development of high-throughput immune monitoring technology. To address this bottleneck, we constructed a generally applicable DNA framework signal amplification platform (DSAP) based on post-systematic evolution of ligands by exponential enrichment and DNA tetrahedral framework-structured probe design to achieve high-sensitive detection for diverse immune cells, including CD4+, CD8+ T-lymphocytes, and monocytes (down to 1/100 μl). Based on this advanced detection platform, we present a novel high-throughput immune-cell phenotyping system, DSAP, achieving 30-min one-step immune-cell phenotyping without cell washing and subset analysis and showing comparable accuracy with flow cytometry while significantly reducing detection time and cost. As a proof-of-concept, DSAP demonstrates excellent diagnostic accuracy in immunodeficiency staging for 107 HIV patients (AUC > 0.97) within 30 min, which can be applied in HIV infection monitoring and screening. Therefore, we initially introduced promising DSAP to achieve high-throughput immune monitoring and open robust routes for point-of-care device development.

Abstract Classical fungal mutant strains obtained by mutagenesis have helped to elucidate fundamental metabolic pathways in the past. In the filamentous fungus Neurospora crassa, the gluc-1 strain was isolated long ago and characterized by its low level of β-glucosidase activity, which is essential for the degradation of cellulose, the most abundant biopolymer on Earth and the main polymeric component of the plant cell wall. Based on genomic resequencing, we hypothesized that the causative mutation resides in the β-glucosidase gene gh3-3 (bgl6, NCU08755). In this work, growth patterns, enzymatic activities and sugar utilization rates were analyzed in several mutant and overexpression strains related to gluc-1 and gh3-3. In addition, different mutants affected in the degradation and transport of cellobiose were analyzed. While overexpression of gh3-3 led to the recovery of β-glucosidase activity in the gluc-1 mutant, as well as normal utilization of cellobiose, the full gene deletion strain Δgh3-3 was found to behave differently than gluc-1 with lower secreted β-glucosidase activity, indicating a dominant role of the amino acid substitution in the point mutated gh3-3 gene of gluc-1. Our results furthermore confirm that GH3-3 is the major extracellular β-glucosidase in N. crassa and demonstrate that the two cellodextrin transporters CDT-1 and CDT-2 are essential for growth on cellobiose when the three main N. crassa β-glucosidases are absent. Overall, these findings provide valuable insight into the mechanisms of cellulose utilization in filamentous fungi, being an essential step in the efficient production of biorefinable sugars from agricultural and forestry plant biomass.

Abstract Two-dimensional (2D) materials have drawn immense interests in scientific and technological communities, owing to their extraordinary properties and their tunability by gating, proximity, strain and external fields. For electronic applications, an ideal 2D material would have high mobility, air stability, sizable band gap, and be compatible with large scale synthesis. Here we demonstrate air stable field effect transistors using atomically thin few-layer PdSe2 sheets that are sandwiched between hexagonal BN (hBN), with large saturation current > 350 μA/μm, and high field effect mobilities of ~ 700 and 10,000 cm2/Vs at 300 K and 2 K, respectively. At low temperatures, magnetotransport studies reveal unique octets in quantum oscillations that persist at all densities, arising from 2-fold spin and 4-fold valley degeneracies, which can be broken by in-plane and out-of-plane magnetic fields toward quantum Hall spin and orbital ferromagnetism.

The application of Mg-based electrochemical energy storage materials in high performance supercapacitors is an essential step to promote the exploitation and utilization of magnesium resources in the field of energy storage. Unfortunately, the inherent chemical properties of magnesium lead to poor cycling stability and electrochemical reactivity, which seriously limit the application of Mg-based materials in supercapacitors. Herein, in this review, more than 70 research papers published in recent 10 years were collected and analyzed. Some representative research works were selected, and the results of various regulative strategies to improve the electrochemical performance of Mg-based materials were discussed. The effects of various regulative strategies (such as constructing nanostructures, synthesizing composites, defect engineering, and binder-free synthesis, etc.) on the electrochemical performance and their mechanism are demonstrated using spinel-structured MgX2O4 and layered structured Mg-X-LDHs as examples. In addition, the application of magnesium oxide and magnesium hydroxide in electrode materials, MXene's solid spacers and hard templates are introduced. Finally, the challenges and outlooks of Mg-based electrochemical energy storage materials in high performance supercapacitors are also discussed.

Abstract Background Cadmium (Cd) pollution in agricultural soils has become a priority environmental concern globally. A reasonable application of passivators is critical to address the problem. In this study, we examined the remediation effects of rice husk biochar (rBC) and sepiolite (Sep) as single and combined (rBC + Sep) treatments on Cd pollution in a weakly alkaline soil using three maize cultivars (Liyu 16, Zhengdan 958, and Sanbei 218) as test crops. We also explained the mechanisms involved in the remediation effects. Results The pseudo-second-order kinetic equation and Langmuir model could well describe the adsorption process of rBC + Sep for Cd2+. Compared with the control treatment (CK), soil available Cd concentration decreased by 29.51–36.34% under rBC + Sep treatment (p 0.05). Conclusions The application of 0.2% rBC + 0.5% Sep composite passivation material to weakly alkaline Cd-contaminated soil can effectively reduce the Cd concentration of soil and maize.