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Abstract Little is known about the biological functions of neuron-specific enolase (NSE) as a specific biomarker for small-cell lung cancer (SCLC). Herein, we elucidate the effect and mechanism of NSE on SCLC stem cell-like characteristics. Upregulated NSE expression was observed in spheroid cells. The gain-of-function and loss-of-function approaches demonstrated that modulation of NSE positively regulated cell proliferation, drug resistance, spherical clone formation, tumor growth, and stem cell-like characteristics of SCLC cells. Mechanistic studies revealed that NSE might downregulate the expression of neuroblastoma suppressor of tumorigenicity 1 (NBL1) by interacting with NBL1, thereby attenuating the competitive inhibitory effect of NBL1 on BMP2 and enhancing the interaction between BMP2 and BMPR1A; this, in turn, may activate the BMP2/Smad/ID1 pathway and promote SCLC stem cell-like characteristics. Moreover, overexpression of NBL1or knockdown of BMP2 rescued the NSE-induced stem cell-like characteristics. In clinical specimens, NSE expression was positively associated with ALDH1A1 expression and negatively correlated with NBL1 expression. High NSE and ALDH1A1 expressions and low NBL1 expression were correlated with poor prognosis in patients with SCLC. In summary, our study demonstrated that NSE promoted stem cell-like characteristics of SCLC via NBL1 and the activation of the BMP2/Smad/ID1 pathway.

Amending soil with biochar can reduce the toxic effects of heavy metals (HM) on plants and the soil. However, the effects of different concentrations of biochar on the properties and microbial activities in lead (Pb)-contaminated soils are unclear. In this study, two Pb concentrations were set (low, 1000 mg/kg; high, 5000 mg/kg), and five corn straw biochar (CSB) concentrations (0, 2.5, 5, 10 and 15%) were used to determine the response of the growth and rhizosphere of red clover (Trifolium pretense L.) (in terms of soil properties and bacteria) to CSB and Pb application. The results showed that 5% CSB better alleviated the toxicity of Pb on the shoot length of red clover, the biomass increased by 74.55 and 197.76% respectively and reduced the enrichment factor (BCF) and transport factor (TF) of red clover. Pb toxicity reduced soil nutrients, catalase (CAT), acid phosphatase (ACP) and urease activity, while the addition of CSB increased soil pH, soil organic matter (SOM) content and soil enzyme activity. 16S rDNA amplicon sequencing analysis showed that Pb toxicity reduced the diversity of rhizosphere bacteria in red clover and reduced the relative abundance of plant growth-promoting rhizobacteria such as Gemmatimonas, Devosia and Bryobacter. Spearman correlation analysis showed that the addition of alkaline CSB restored the relative abundance of rhizobacteria positively correlated with pH, such as Chitinophaga, Sphingomonas, Devosia and Pseudomonas, and thus restored the rhizosphere soil environment. This study demonstrates that 5% CSB can better alleviate the toxicity of Pb to red clover and soil. We also provide a theoretical basis for the subsequent use of beneficial bacteria to regulate the repair efficiency of red clover.

Background and objectiveLifestyle modifications aimed at weight loss have been introduced as a cornerstone of nonalcoholic fatty liver disease (NAFLD) management. However, very few patients follow the doctor's prescription to change their lifestyle to achieve weight loss in the real world. The purpose of this study was to use the Health Action Process Approach (HAPA) model to examine the factors that affect adherence to lifestyle prescriptions among patients with NAFLD.MethodsSemi-structured interviews were conducted with patients with NAFLD. Reflexive thematic analysis and framework analysis were used to determine naturally identified themes and allocate them to theoretically driven domains.ResultsThirty adult patients with NAFLD were interviewed, and the identified themes were mapped directly onto the constructs of the HAPA model. This study revealed that key barriers to adhering to lifestyle prescriptions are related to the coping strategy and outcome expectation constructs of the HAPA model. For physical activity, conditional limits, lack of time, symptoms such as fatigue and poor physical fitness, and fear of sports injury are the primary barriers. Barriers to diet are mainly diet environment, mental stress, and food cravings. Key facilitators for adherence to lifestyle prescriptions include developing simple and specific action plans, coping strategies to flexibly deal with obstacles and difficulties, receiving regular feedback from doctors to improve self-efficacy, and using regular tests and behavior recording to enhance action control.ConclusionsFuture lifestyle intervention programs should pay particular attention to the planning, self-efficacy, and action control-related constructors of the HAPA model to promote the adherence of patients with NAFLD to lifestyle prescriptions.

ObjectiveTo compare the effects of five hypoxia-inducible factor-prolyl hydroxylase domain inhibitors (HIF-PHIs), two erythropoiesis-stimulating agents (ESAs), and placebo on iron metabolism in renal anemia patients with non-dialysis-dependent chronic kidney disease (NDD-CKD).MethodFive electronic databases were searched for studies. Randomized controlled clinical trials comparing HIF-PHIs, ESAs, and placebo in NDD-CKD patients were selected. The statistical program used for network meta-analysis was Stata/SE 15.1. The main outcomes were the change in hepcidin and hemoglobin (Hb) levels. The merits of intervention measures were predicted by the surface under the cumulative ranking curve method.ResultsOf 1,589 original titles screened, data were extracted from 15 trials (3,228 participants). All HIF-PHIs and ESAs showed greater Hb level–raising ability than placebo. Among them, desidustat demonstrated the highest probability of increasing Hb (95.6%). Hepcidin [mean deviation (MD) = -43.42, 95%CI: -47.08 to -39.76], ferritin (MD= -48.56, 95%CI: -55.21 to -41.96), and transferrin saturation (MD = -4.73, 95%CI: -5.52 to -3.94) were decreased, while transferrin (MD = 0.09, 95%CI: 0.01 to 0.18) and total iron-binding capacity (MD = 6.34, 95%CI: 5.71 to 6.96) was increased in HIF-PHIs versus those in ESAs. In addition, this study observed heterogeneity in the ability of HIF-PHIs to decrease hepcidin. Compared with darbepoetin, only daprodustat (MD = –49.09, 95% CI: –98.13 to –0.05) could significantly reduce hepcidin levels. Meanwhile, daprodustat also showed the highest hepcidin-lowering efficacy (84.0%), while placebo was the lowest (8.2%).ConclusionFor NDD-CKD patients, HIF-PHIs could ameliorate functional iron deficiency by promoting iron transport and utilization, which may be achieved by decreasing hepcidin levels. Interestingly, HIF-PHIs had heterogeneous effects on iron metabolism.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=242777, Identifier CRD42021242777.

Background and objectivesAlzheimer’s disease (AD) has an insidious onset, the early stages are easily overlooked, and there are no reliable, rapid, and inexpensive ancillary detection methods. This study analyzes the differences in handwriting kinematic characteristics between AD patients and normal elderly people to model handwriting characteristics. The aim is to investigate whether handwriting analysis has a promising future in AD auxiliary screening or even auxiliary diagnosis and to provide a basis for developing a handwriting-based diagnostic tool.Materials and methodsThirty-four AD patients (15 males, 77.15 ± 1.796 years) and 45 healthy controls (20 males, 74.78 ± 2.193 years) were recruited. Participants performed four writing tasks with digital dot-matrix pens which simultaneously captured their handwriting as they wrote. The writing tasks consisted of two graphics tasks and two textual tasks. The two graphics tasks are connecting fixed dots (task 1) and copying intersecting pentagons (task 2), and the two textual tasks are dictating three words (task 3) and copying a sentence (task 4). The data were analyzed by using Student’s t-test and Mann–Whitney U test to obtain statistically significant handwriting characteristics. Moreover, seven classification algorithms, such as eXtreme Gradient Boosting (XGB) and Logistic Regression (LR) were used to build classification models. Finally, the Receiver Operating Characteristic (ROC) curve, accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and Area Under Curve (AUC) were used to assess whether writing scores and kinematics parameters are diagnostic.ResultsKinematic analysis showed statistically significant differences between the AD and controlled groups for most parameters (p

IntroductionSugar-sweetened beverage (SSB) intake is associated with an increased risk of cardiometabolic diseases. However, evidence regarding associations of artificially sweetened beverages (ASBs) and fruit juices with cardiometabolic diseases is mixed. In this study, we aimed to investigate the association between the SSB, ASB and fruit juice consumption with the incidence of cardiometabolic conditions and mortality.MethodsRelevant prospective studies were identified by searching PubMed, Web of Science, Embase, and Cochrane Library until December 2022 without language restrictions. The pooled relative risk (RR) and 95% confidence intervals (CIs) were estimated for the association of SSBs, ASBs, and fruit juices with the risk of type 2 diabetes (T2D), cardiovascular disease (CVD), and mortality by using random-effect models.ResultsA total of 72 articles were included in this meta-analysis study. Significantly positive associations were observed between the consumption of individual beverages and T2D risk (RR: 1.27; 95% CI: 1.17, 1.38 for SSBs; RR: 1.32; 95% CI: 1.11, 1.56 for ASBs; and RR:0.98; 95% CI: 0.93, 1.03 for fruit juices). Moreover, our findings showed that intakes of SSBs and ASBs were significantly associated with risk of hypertension, stroke, and all-cause mortality (RR ranging from 1.08 to 1.54; all p

Immune checkpoint inhibitors (ICIs), such as programmed death-1 (PD-1), programmed death-ligand 1 (PD-L1), cytotoxic T lymphocyte antigen 4 (CTLA-4) antibodies, etc, have revolutionized cancer treatment strategies, including non-small cell lung cancer (NSCLC). While these immunotherapy agents have achieved durable clinical benefits in a subset of NSCLC patients, they bring in a variety of immune-related adverse events (irAEs), which involve cardiac, pulmonary, gastrointestinal, endocrine and dermatologic system damage, ranging from mild to life-threatening. Thus, there is an urgent need to better understand the occurrence of irAEs and predict patients who are susceptible to those toxicities. Herein, we provide a comprehensive review of what is updated about the clinical manifestations, mechanisms, predictive biomarkers and management of ICI-associated toxicity in NSCLC. In addition, this review also provides perspective directions for future research of NSCLC-related irAEs.

Rapid urbanization has profoundly changed ability of ecosystem to supply welfare and resulted a series of environmental issues, in turn, such results not only affected the economic growth, but also the quality of sustainable development. Therefore, deeply understanding the interaction between ecosystem service (ES) supply and urbanization is of great significance. As a case study of northern China, we attempt to build an effective framework to evaluate past and future states of the interaction between ES supply and urbanization from quantification spatiotemporal pattern of coupling coordination degree (CD), decoupling path exploration, driving factor analysis to grey prediction model construction. It tries to better improve the interaction between ES supply and urbanization, as well as provide some effective policies for local condition. Results showed that the synthesis coefficient of urbanization (URSC) and CD has been significantly improved from 1995 to 2020 at province scale, while the synthesis coefficient of ES supply (ESSC) and decoupling index score are fluctuating. All of indicators revealing differences between the west and east regions. The east region has the highest levels of ESSC, URSC, CD and decoupling index score during the last twenty-five years. The driving factors including annual precipitation (Precipitation), normalized difference vegetation index (NDVI), cropland area (Cropland), grassland area (Grassland), unused land area (Unused land) all have a spatiotemporal impact on the CD with divergent significances, among which the effect of NDVI is the most significant. Finally, the grey prediction model was applied to predict the ESSC, URSC, CD and decoupling index in the future. The findings reveal a growing state for ESSC and CD in province scale, while a decline state of URSC. Based on the aforementioned results, some scientific policies were proposed for different regions to improve sustainable development.

BackgroundOverweight and obesity are multifactorial conditions that are prevalent in developing and developed countries. They are emerging as a significant public health concern among healthcare workers (HCWs). We aimed to estimate the prevalence of overweight and obesity and their associated factors among HCWs in the Gaza Strip.MethodsA cross-sectional study was conducted to recruit 1,850 HCWs aged 22 years and older. Interviews were carried out to collect sociodemographic information, nutritional information, and physical activity. Anthropometric measurements [height, weight, and waist circumference] were conducted with the HCWs. The body mass index was computed to determine the prevalence of overweight and obesity. Chi-square, t-test, and one-way ANOVA were used to compare the variables, and logistic regression was used to examine the associated factors of overweight and obesity.ResultsThe combined prevalence of overweight and obesity among HCWs was 65%. The result of logistic regression showed the risk of being overweight and obesity increased within the age group of 40–49 years (OR = 3.20; 95% CI: 2.37–4.32; P < 0.001). Male participants had more risk of obesity than female participants (OR = 1.77; 95% CI: 1.45–2.15). Married participants had a significantly higher risk of being overweight and obese (OR = 2.52; 95% CI: 2.05–3.28; P = 0.001). Increased monthly income was significantly associated with the risk of being overweight and obese (OR = 2.16; 95% CI: 1.22–3.83; P = 0.008). In addition, hypertension (OR = 2.49; 95% CI: 1.65–3.78; P < 0.001) and type 2 diabetes (OR = 2.42; 95% CI: 1.21–4.85; P= 0.012) were associated with overweight and obesity. Finally, a family history of NCDs was associated with overweight and obesity (OR = 1.69; 95% CI: 1.38–2.07; P < 0.001).ConclusionThis study showed a high prevalence of overweight and obesity among HCWs. Age, monthly income, marital status, known hypertension, type 2 diabetes, and eating habits were associated with the prevalence of overweight and obesity compared to other variables that were not associated with overweight and obesity such as profession, vegetables, fruit consumption, and physical activity. Urgent action is needed to tackle overweight and obesity among HCWs.

Cardiac fibrosis is a serious public health problem worldwide that is closely linked to progression of many cardiovascular diseases (CVDs) and adversely affects both the disease process and clinical prognosis. Numerous studies have shown that the TGF-β/Smad signaling pathway plays a key role in the progression of cardiac fibrosis. Therefore, targeted inhibition of the TGF-β/Smad signaling pathway may be a therapeutic measure for cardiac fibrosis. Currently, as the investigation on non-coding RNAs (ncRNAs) move forward, a variety of ncRNAs targeting TGF-β and its downstream Smad proteins have attracted high attention. Besides, Traditional Chinese Medicine (TCM) has been widely used in treating the cardiac fibrosis. As more and more molecular mechanisms of natural products, herbal formulas, and proprietary Chinese medicines are revealed, TCM has been proven to act on cardiac fibrosis by modulating multiple targets and signaling pathways, especially the TGF-β/Smad. Therefore, this work summarizes the roles of TGF-β/Smad classical and non-classical signaling pathways in the cardiac fibrosis, and discusses the recent research advances in ncRNAs targeting the TGF-β/Smad signaling pathway and TCM against cardiac fibrosis. It is hoped, in this way, to give new insights into the prevention and treatment of cardiac fibrosis.

Chimeric antigen receptor (CAR) engineering of natural killer (NK) cells is an attractive research field in tumor immunotherapy. While CAR is genetically engineered to express certain molecules, it retains the intrinsic ability to recognize tumor cells through its own receptors. Additionally, NK cells do not depend on T cell receptors for cytotoxic killing. CAR-NK cells exhibit some differences to CAR-T cells in terms of more precise killing, numerous cell sources, and increased effectiveness in solid tumors. However, some problems still exist with CAR-NK cell therapy, such as cytotoxicity, low transfection efficiency, and storage issues. Immune checkpoints inhibit immune cells from performing their normal killing function, and the clinical application of immune checkpoint inhibitors for cancer treatment has become a key therapeutic strategy. The application of CAR-T cells and immune checkpoint inhibitors is being evaluated in numerous ongoing basic research and clinical studies. Immune checkpoints may affect the function of CAR-NK cell therapy. In this review, we describe the combination of existing CAR-NK cell technology with immune checkpoint therapy and discuss the research of CAR-NK cell technology and future clinical treatments. We also summarize the progress of clinical trials of CAR-NK cells and immune checkpoint therapy.

In the background of global climate change and rapid urbanization, extreme climate events are frequent, and highly urbanized areas flooding problems are becoming increasingly prominent. It becomes important to develop qualitative scenario storylines to assess future flooding risk in a changing environment over the highly urbanized areas. In this study, the future (2030–2050) flood risk in the Pearl River Delta (PRD) region of China was assessed based on the MaxEnt model. We have developed four future scenarios under different emission conditions based on the representative concentration pathways (RCPs) and the shared socio-economic pathways (SSPs). The MaxEnt model was trained by using flood hazard sample point data and flood risk indicators, meanwhile, food risk prediction with high accuracy was obtained. We analyzed the influencing factors of flood risk and predicted the flood risk of the PRD under four future scenarios. According to the results, there is a significant increase in the size and proportion of high flood risk areas in most scenarios. Flood risk under scenario SSP5-RCP8.5 are expected to be the most serious in the future. Population density (POPD) and Gross domestic product density (GDPD) have the highest explanatory power for flood risk. This study predict the changes of flood risk under the combined influence of climate change and human activities, and hoped to provide a reference for future planning and disaster mitigation construction in PRD cities.

Ultrasound and deep eutectic supramolecular polymers (DESP) is a novel combination of green extraction method for phytochemicals. In this study, a new type of green extractant was developed: DESP. It is a derivative of deep eutectic solvent (DES) and was prepared by supramolecular polymer unit β-cyclodextrin (β-CD) as hydrogen bond acceptor (HBA) and organic acid as hydrogen bond donor (HBD). The current work focuses on the use of ultrasonic-assisted (UAE) DESP extraction of polyphenolic compounds (PCs) from bayberry. The experimental results showed that DESP synthesized with β-CD and lactic acid (LA) in a ratio of 1:1 (w/w %) had the best extraction effect. And by using a three-level factor experiment and the response surface method, the predicted TPC content is very close to the actual content (28.85 ± 1.27 mg GAE/g). The DESP extract including PCs were further used as plasticizer for chitosan (CS) to prepare highly active green biofilms (DESP-CS). It is possible to reduce the tedious procedures for separating biologically active substances from DESP. The experiment proved that the prepared films have good mechanical properties, plastic deformation resistance, thermal stability and antioxidant activity.

Acute myeloid leukemia (AML) is prone to drug-resistant relapse with a low 5-year survival rate. New therapeutic modalities are sorely needed to provide hope for AML relapse patients. Herein, we demonstrated a specific inhibitor of type 4 phosphodiesterase (PDE4), Zl-n-91, could significantly reduce the proliferation of AML cells, block DNA replication process, and increase AML cell death. Zl-n-91 also impeded the growth of subcutaneous xenograft and prolonged the survival of the MLL-AF9-driven AML model. Bioinformatic analysis revealed that elevated mitochondrial gene signatures inversely correlate with the survival of AML patients; and importantly, Zl-n-91 strongly suppressed the function of mitochondria. In addition, this PDE4 inhibitor induced alterations in multiple signaling pathways, including the reduction of β-catenin activity. Stimulation of the Wnt/β-catenin pathway could attenuate the inhibitory effect of Zl-n-91 on AML cell proliferation as well as mitochondrial function. Taken together, we revealed for the first time that targeting PDE4 activity could attenuate mitochondrial function through a Wnt/β-catenin pathway, which in turn would block the growth of AML cells. Specific PDE4 inhibitors can potentially serve as a new treatment modality for AML patients.

Abstract Background Recent studies have shown that the excitatory amino acid transporters (EAATs) are associated with schizophrenia. The aim of this study was to investigate the relationship between the polymorphism of EAAT1 and EAAT2 genes and schizophrenia in Chinese Han population. Methods A total of 233 patients with schizophrenia and 342 healthy controls were enrolled. Two SNPs in EAAT1 gene (rs2269272, rs2731880) and four SNPs in EAAT2 gene (rs12360706, rs3088168, rs12294045, rs10836387) were genotyped by SNaPshot. Clinical features were collected using a self-made questionnaire. Psychotic symptoms of patients were measured by the Positive and Negative Syndrome Scale (PANSS), and patients’ cognitive function was assessed by Matrics Consensus Cognitive Battery (MCCB). Results Significant difference in allelic distributions between cases and controls was confirmed at locus rs12294045 (Ρ = 0.004) of EAAT2 gene. Different genotypes of rs12294045 were associated with family history (P = 0.046), in which patients with CT genotype had higher proportion of family history of psychosis. The polymorphism of rs12294045 was related to working operational memory (LNS: P = 0.016) and verbal learning function (HVLT-R: P = 0.042) in patients in which CT genotype had lower scores. However, these differences were no longer significant after Bonferroni correction. Conclusions Our study showed that the polymorphism of rs12294045 in EAAT2 gene may be associated with schizophrenia in Chinese Han population. CT genotype may be one of the risk factors for family history and cognitive deficits of patients.

Abstract Background Cancer screening provides the opportunity to detect cancer early, ideally before symptom onset and metastasis, and offers an increased opportunity for a better prognosis. The ideal biomarkers for cancer screening should discriminate individuals who have not developed invasive cancer yet but are destined to do so from healthy subjects. However, most cancers lack effective screening recommendations. Therefore, further studies on novel screening strategies are urgently required. Methods We used a simple suboptimal inoculation melanoma mouse model to obtain ‘pre-diagnostic samples’ of mice with macroscopic melanomas. High-throughput sequencing and bioinformatic analysis were employed to identify differentially expressed RNAs in platelet signatures of mice injected with a suboptimal number of melanoma cells (eDEGs) compared with mice with macroscopic melanomas and negative controls. Moreover, 36 genes selected from the eDEGs via bioinformatics analysis were verified in a mouse validation cohort via quantitative real-time PCR. LASSO regression was utilized to generate the prediction models with gene expression signatures as the best predictors for occult tumor progression in mice. Results These RNAs identified from eDEGs of mice injected with a suboptimal number of cancer cells were strongly enriched in pathways related to immune response and regulation. The prediction models generated by 36 gene qPCR verification data showed great diagnostic efficacy and predictive value in our murine validation cohort, and could discriminate mice with occult tumors from control group (area under curve (AUC) of 0.935 (training data) and 0.912 (testing data)) (gene signature including Cd19, Cdkn1a, S100a9, Tap1, and Tnfrsf1b) and also from macroscopic tumor group (AUC of 0.920 (training data) and 0.936 (testing data)) (gene signature including Ccr7, Cd4, Kmt2d, and Ly6e). Conclusions Our proof-of-concept study provides evidence for potential clinical relevance of blood platelets as a platform for liquid biopsy-based early detection of cancer.

Abstract Background Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is the main factor that leads to the deterioration of the disease. Currently, the diagnosis of AECOPD mainly relies on clinical manifestations, good predictors or biomarkers are lacking. We aim to reveal specific biomarkers and potential pathogenesis of AECOPD and provide a research basis for the diagnosis and treatment. Methods Four patients with AECOPD, four patients with stable COPD, and five control subjects were enrolled for RNA sequencing and KEGG analysis. The mRNA level of target genes was verified by quantitative real-time PCR (qPCR) with an expanded sample size (30 patients with AECOPD, 27 patients with stable COPD, and 35 control subjects). ELISA and immunofluorescence were used to identify the target proteins. Furthermore, the expression and function of WNT/β-catenin signaling pathway were assessed in animal models of COPD. Results RNA sequencing showed that 54 genes were up-regulated and 111 genes were down-regulated in the AECOPD. Differentially expressed genes were mainly enriched in WNT signaling pathway, et al. QPCR revealed that multi-genes of the WNT/β-catenin signaling were significantly down-regulated in AECOPD (P

The atmospheric oxidation of dimethyl sulfide affects the Earth’s climate, but the intricate pathways of this complex reaction are still not fully described. Here, the authors use an optimized flash pyrolysis method for gas-phase generation of the methylthio radical to study its O2-oxidation via matrix-isolation spectroscopy, and unambiguously identify two peroxyl radical intermediates.

Abstract Background Gestational diabetes mellitus (GDM) seriously affects the health of mothers and babies, and there are still no effective early diagnostic markers. Therefore, it is necessary to find diagnostic biomarkers for screening GDM in early pregnancy. Circular RNA (circRNA) is more stable than linear RNA, and can be encapsulated in exosomes and participate in the pathological process of various diseases, which makes it a better candidate biomarker for various diseases. In this study, we attempted to identify the exosomal circRNA biomarkers for detecting early GDM. Methods We performed microarray analysis to compare the plasma exosomal circRNA expression profiles of three GDM patients 48 h before and 48 h after delivery. The repeatability of the expression of circRNAs were randomly validated by RT-PCR analysis. Pearson correlation analysis was applied to evaluate the correlation between circRNAs and OGTT level. ROC curve was established to assess the diagnostic value of circRNAs for GDM at different stages. Results Plasma exosomal hsa_circRNA_0039480 and hsa_circRNA_0026497 were highly expressed in GDM patients before delivery (P

Chronic apical periodontitis (CAP) is a disease with characteristics of inflammation and bone loss. In this study, our objective was to examine the function of small extracellular vesicles (sEVs) obtained from milk in encouraging osteogenic differentiation and inhibiting inflammation by miR-21 in CAP. The expression of miR-21 was detected using qRT-PCR in human CAP samples. The impact of miR-21 on the process of osteogenic differentiation was investigated using CCK-8, qRT-PCR, immunofluorescence staining, and Western blot analysis. The evaluation of RAW 264.7 cell polarization and the assessment of inflammatory factor expression were conducted through qRT-PCR. The influence of sEVs on MC3T3-E1 cells and RAW 264.7 cells was examined, with a particular emphasis on the involvement of miR-21. In human CAP samples, a decrease in miR-21 expression was observed. MiR-21 increased the expression of osteogenesis-related genes and M2 polarization genes while decreasing the expression of M1 polarization genes and inflammatory cytokines. Treatment with milk-derived sEVs also promoted osteogenesis and M2 polarization while inhibiting M1 polarization and inflammation. Conversely, the addition of miR-21 inhibitors resulted in opposite effects. Our results indicated that sEVs derived from milk had a positive effect on bone formation and activation of anti-inflammatory (M2) macrophages and simultaneously reduced inflammation by regulating miR-21 in CAP.

The sodium smelting of vanadium–titanium magnetite (VTM) can realize a multi-component comprehensive utilization of VTM. To broaden the application of the vanadium-bearing pig iron produced through this process, it is imperative to maintain the titanium content in molten iron at a very low level. In this study, the effects of temperature, the added amounts of sodium carbonate and anthracite, and the smelting time on the titanium content of molten iron were investigated using thermodynamic calculations and experiments. The results indicate that the introduction of sodium carbonate makes the reduction reaction of VTM a relatively low-temperature smelting system. In the smelting process, the Ti content in molten iron increases with the increase in temperature and decreases with the addition of sodium carbonate, while the amount of anthracite added has little effect on it. The appropriate technological parameters were determined as temperature: 1150–1250 °C, smelting time: ≥2 h, anthracite consumption: 25–35%, and sodium carbonate consumption: ≥60%. In addition, it was determined that the Ti impurities in the V-bearing pig iron were mainly (Ti,V)(C,N), CaTiO3, and Na2TiO3. All results obtained from this work contribute to the comprehensive utilization of VTM, and also provide theoretical support for the sodium smelting of VTM.

Solar-driven interfacial evaporation and purification is a promising solar energy conversion technology to produce clean water or solve water scarcity. Although wood-based photothermal materials have attracted particular interest in solar water purification and desalination due to their rapid water supply and great heat localization, challenges exist given their complicated processing methods and relatively poor stability. Herein, we propose a facile approach for fabricating a bilayered wood-poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (wood-PEDOT:PSS) hydrogel interfacial evaporator by direct drop-casting and dry-annealing. Benefiting from the unique combined merits of the wood-PEDOT:PSS hydrogel evaporator, i.e., excellent light absorption (~99.9%) and efficient photothermal conversion of nanofibrous PEDOT:PSS and the strong hydrophilicity and fast water transport from wood, the as-fabricated bilayered wood-PEDOT:PSS hydrogel evaporator demonstrates a remarkably high evaporation rate (~1.47 kg m−2 h−1) and high energy efficiency (~75.76%) at 1 kW m−2. We further demonstrate the practical applications of such an evaporator for sewage purification and desalination, showing outstanding performance stability and partial salt barrier capability against a continuous 10-day test in simulated seawater and an ultrahigh ion removal rate of 99.9% for metal ion-containing sewage. The design and fabrication of such novel, efficient wood-based interfacial evaporators pave the way for large-scale applications in solar water purification.

When intelligent mobile robots perform global path planning in complex and narrow environments, several issues often arise, including low search efficiency, node redundancy, non-smooth paths, and high costs. This paper proposes an improved path planning algorithm based on the rapidly exploring random tree (RRT) approach. Firstly, the target bias sampling method is employed to screen and eliminate redundant sampling points. Secondly, the adaptive step size strategy is introduced to address the limitations of the traditional RRT algorithm. The mobile robot is then modeled and analyzed to ensure that the path adheres to angle and collision constraints during movement. Finally, the initial path is pruned, and the path is smoothed using a cubic B-spline curve, resulting in a smoother path with reduced costs. The evaluation metrics employed include search time, path length, and the number of sampling nodes. To evaluate the effectiveness of the proposed algorithm, simulations of the RRT algorithm, RRT-connect algorithm, RRT* algorithm, and the improved RRT algorithm are conducted in various environments. The results demonstrate that the improved RRT algorithm reduces the generated path length by 25.32% compared to the RRT algorithm, 26.42% compared to the RRT-connect algorithm, and 4.99% compared to the RRT* algorithm. Moreover, the improved RRT algorithm significantly improves the demand for reducing path costs. The planning time of the improved RRT algorithm is reduced by 64.96% compared to that of the RRT algorithm, 40.83% compared to that of the RRT-connect algorithm, and 27.34% compared to that of the RRT* algorithm, leading to improved speed. These findings indicate that the proposed method exhibits a notable improvement in the three crucial evaluation metrics: sampling time, number of nodes, and path length. Additionally, the algorithm performed well after undergoing physical verification with an insect-like mobile robot in a real environment featuring narrow elevator entrances.

The objective of this study was to evaluate the effects of potato vine and leaf mixed silage (PVS) on rumen fermentation and the microbe in ruminants and to improve the utilization of PVS resources in ruminants through in vitro gas production and feeding trials. The experiment was divided into three groups: PVS1 (50% corn + 50% potato vine and leaf silage), PVS2 (75% potato vine and leaf + 15% rice straw + 10% cornmeal silage) and whole-plant corn silage (CS). The in vitro gas production results showed that there was a significant reduction in PVS groups in the indexes of total gas (p < 0.05) and CH4 production (p < 0.05). The digestibility of dry matter (p < 0.05), neutral detergent fiber (NDF) (p < 0.05), and acid detergent fiber (ADF) (p < 0.05) at 48 h were decreased in the PVS group. For the rumen fermentation indexes, the pH (p < 0.05), microbial crude protein (MCP) (p < 0.05), and acetate to propionate (p < 0.05) showed an increase in the PVS group, but a decrease in the total volatile fatty acid concentration (p < 0.05). In the feeding trial, different silages in diets had no significant effect on the rumen fermentation indexes (p > 0.05). In the rumen microbe composition, the PVS diet significantly reduced the abundance of Prevotella (p < 0.05) compared with the CS diet group. The PVS2 diet significantly increased the abundance of the Lachnospiraceae_XPB1014_group (p < 0.05) and Bacteroidales_bacterium_Bact_22 (p < 0.05) compared with the CS diet group. In conclusion, PVS had no negative effect on rumen fermentation characteristics and rumen microbial flora and could significantly reduce rumen gas production compared to CS, positively mitigating animal husbandry CH4 emissions and environmental protection.

Cyanobacteria are ever-present, mainly flourishing in aquatic environments and surviving virtually in other habitats. The microbiota of indoor dust on the pre-filter of heating, ventilation, and air-conditioning (HVAC) systems, which reflect indoor microbial contamination and affect human health, has attracted attention. Contemporary studies on cyanobacteria deposited on the pre-filter of HVAC remain scant. By the culture-independent approach of qPCR and high throughput sequencing technologies, our results documented that the cyanobacterial concentrations were highest in autumn, occurred recurrently, and were about 2.60 and 10.57-fold higher than those in winter and summer. We proposed that aquatic and terrestrial cyanobacteria contributed to the pre-filter of HVAC by airborne transportation produced by wave breaks, bubble bursts, and soil surface by wind force, owing to the evidence that cyanobacteria were commonly detected in airborne particulate matters. The cyanobacteria community structure was characterized in Shanghai, where Chroococcidiopsaceae, norank_cyanobacteriales, Nostocaceae, Paraspirulinaceae, and others dominated the dust on the pre-filter of HVAC. Some detected genera, including Nodularia sp., Pseudanabaena sp., and Leptolyngbya sp., potentially produced cyanobacterial toxins, which need further studying to determine their potential threat to human health. The present work shed new insight into cyanobacteria distribution in the specific environment besides aquatic habitats.

The coexistence of temperature changes and air pollution poses a severe global environmental issue, exacerbating health burdens. The aim of this study was to clarify the combined effects of ambient PM2.5 and cold exposure on the development of metabolic disorders. Male C57BL/6 mice were randomly divided into four groups: TN-FA, TN-PM, TC-FA and TC-PM. The mice were then exposed to concentrated PM2.5 or filtered air (FA) under normal (22 °C) or cold (4 °C) environment conditions for 4 weeks. Metabolic-disorder-related indicators, blood pressure, serous lipids, fasting blood glucose and insulin, energy metabolism, mitochondria and protein expression in tissues were detected for comprehensively assessing metabolic disorder. The results showed that, compared to being exposed to PM2.5 only, when mice were exposed to both PM2.5 and the cold (non-optimal), they exhibited more significant metabolic disorders regarding glucose tolerance (p < 0.05), insulin resistance (p < 0.05), lipid metabolism, adipocytes (p < 0.01) and mitochondrial function. This study suggested that a cold environment might substantially exacerbate PM2.5-induced metabolic disorder. The interaction between temperature changes and air pollution implied that implementing the necessary environment-related policies is a critical and complex challenge.

In some geographically challenging areas (such as deserts, seas, and forests) where direct connectivity to a terrestrial network is difficult, space communication is the only option. In these remote locations, Internet of Space Things (IoST) applications can also be used successfully. In this paper, the proposed payload for IoST applications demonstrates how an Automatic Identification System (AIS) and a fire detection system can be used effectively. A space mission based on efficient and low-cost communication can use a constellation of nanosatellites to better meet this need. These two applications, which use a constellation of nanosatellites, can provide relevant university-level data in several countries as an effective policy for the transfer of space technology in an educational initiative project. To enhance educational participation and interest in space technology, this paper shares the lessons learned from the project feasibility study based on an in-depth design of a nanosatellite with several analyses (data budget, link budget, power budget, and lifetime estimation). Lastly, this paper highlights by experiments the development and application of a cost-effective sensor node for fire detection and the use of GPS to enable AIS capabilities in the IoST framework.

Abstract Background To evaluate the efficacy of hormone replacement therapy in relieving oral symptoms in postmenopausal women presenting with genitourinary symptoms along with oral dryness. Methods A case–control study was conducted after selecting 60 postmenopausal women. Oral dryness status of all the patients was evaluated with the help of questionnaire related to oral dryness. These subjects were divided into case group and control group on the basis of response to questionnaire of oral dryness. Unstimulated saliva samples were obtained and analyzed for estimation of salivary estradiol levels by enzyme linked immune sorbent assay technique. After analyzing the result of salivary estradiol levels, case group was subjected to hormone replacement therapy (HRT). The patients were followed up for their response towards oral dryness as well as salivary estradiol levels after the therapy. Results The mean salivary estradiol level before HRT was significantly more among control group as compared to case group (p value

Abstract Background The lncRNA H19 is believed to act as an oncogene in various types of tumors and is considered to be a therapeutic target and diagnostic marker. However, the role of the lncRNA H19 in regulating the radiosensitivity of non-small cell lung cancer (NSCLC) cells is unknown. Methods The expression profiles of lncRNAs in NSCLC were explored via transcriptome sequencing. CCK-8, EdU incorporation and clonogenic survival assays were conducted to evaluate the proliferation and radiosensitivity of NSCLC cells. Flow cytometry and Western blotting were conducted to measure the level of apoptosis. The binding relationship between the lncRNA H19 and miR-130a-3p was determined by a dual-luciferase reporter assay. A binding relationship was also identified between miR-130a-3p and With-No-Lysine Kinase 3 (WNK3). Results Expression patterns of lncRNAs revealed that the lncRNA H19 was upregulated in radioresistant NSCLC (A549-R11) cells compared with A549 cells. Knockdown of the lncRNA H19 enhanced the sensitivity of NSCLC cell lines to X-ray and carbon ion irradiation. Mechanistically, the lncRNA H19 serves as a sponge of miR-130a-3p, which downregulates WNK3 expression. The lncRNA H19–miR-130a-3p–WNK3 axis modulates radiosensitivity by regulating apoptosis in NSCLC cell lines. Conclusion Knockdown of the lncRNA H19 promotes the sensitivity of NSCLC cells to X-ray and carbon ion irradiation. Hence, the lncRNA H19 might function as a potential therapeutic target that enhances the antitumor effects of radiotherapy in NSCLC.

Abstract Cyanidin‐3‐O‐glucoside (C3G) is a kind of water‐soluble pigment widely existing in many plants. It has strong antioxidant and anti‐inflammatory activities. However, C3G cannot exist stably for a long time because of the phenolic hydroxyl groups in its structure. Liposome technology could improve the stability and bioavailability of compounds. Based on our previous studies, C3G liposomes prepared by ethanol injection method have a certain stability in two weeks of storage. In this study, THP‐1 macrophages treated with C3G and C3G liposomes can reduce the levels of inflammatory‐related factors, such as tumor necrosis factor‐a (TNF‐a), interleukin (IL)‐1β, IL‐6, and IL‐8, stimulated by lipopolysaccharide (LPS). Further studies showed that the LPS induction could increase the level of phosphorylated nuclear transcription factor NF‐κB and phosphorylated IkBa, while C3G and C3G liposomes could inhibit the expression of phosphorylated proteins. Moreover, C3G and C3G liposomes could protect macrophages from apoptosis. In conclusion, C3G prepared by liposome technology exhibits anti‐inflammatory activity, which provides a theoretical basis for the food industry to study functional food.

Niobium has a wide range of application in various industries such as materials, alloy, and electronic industry. To improve the use of ilmenorutile in China's Bayan Obo deposit, a novel process of extracting niobium, titanium, and iron from ilmenorutile by NaOH roasting-H2SO4 leaching process (NRHLP) was proposed. The influences of roasting and leaching temperature, roasting and leaching time, molar ratio of NaOH-to-ilmenorutile, leaching mass ratio of liquid-to-solid, and the H2SO4 concentration on the extraction of niobium were systematically investigated. The results demonstrate that this process is efficient. The optimized reaction parameters were as follows: roasting temperature, 550 °C; molar ratio of NaOH-to-ilmenorutile, 2.6; roasting time, 120 min; leaching mass ratio of liquid-to-solid, 4.0; leaching temperature, 90 °C; the H2SO4 concentration, 60 wt.%; leaching time, 2 h. Under these optimum circumstances, the maximum niobium and titanium recovery can reach 96.68%. In addition, a new phase containing niobium and titanium is confirmed and proved.

The identification of prognostic and therapeutic biomarkers is essential to reduce morbidity and mortality from lung adenocarcinoma (LUAD). This study aimed to identify a reliable prognostic and therapeutic biomarker for LUAD using integrated bioinformatics. Based on the cancer genome atlas (TCGA) and genome-tissue expression (GTEx) analyses, KIF20A has been identified as the hub gene. Following validation using a series of cohorts, survival analysis, meta-analysis, and univariate Cox analysis was conducted. ESTIMATE and CIBERSORT algorithms were then used to study the association of KIF20A with the tumor microenvironment (TME) and the percentage of tumor-infiltrating immune cells (TICs). In vitro experiments were conducted to determine the function of KIF20A. Finally, there was a negative association between the expression of the KIF20A and overall survival, progression-free survival, and disease-free survival, which was confirmed by meta-analysis and COX analysis. Furthermore, KIF20A also had a potential role of altering the TME and TICs proportions in LUAD. Validations in vitro were performed on A549 and PC-9 cell lines, and we found that the knockdown of KIF20A exhibited inhibitory effects on cell proliferation, resulted in cell cycle arrest during the G2/M phase, and induced cellular apoptosis. Our study demonstrated that KIF20A could be utilized as a reliable prognostic marker and treatment target for LUAD. However, further studies are required to validate these findings.

BackgroundLoop-mediated isothermal amplification (LAMP) is a novel nucleic acid amplification method using only one type of enzyme that can amplify DNA with high specificity, efficiency and rapidity under isothermal conditions. Chips for Complicated Infection Detection (CCID) is based on LAMP. This study translate CCID into clinical application and evaluate its diagnostic value for pneumonia.MethodsEighty one older patients with pneumonia were prospectively enrolled from January 1 to July 23, 2021, and 57 sputum/airway secretion and 35 bronchoalveolar lavage fluid samples were collected and analyzed by CCID and conventional microbiological tests (CMTs). Samples were collected, transported, monitored, and managed by a multidisciplinary team using a sample management information system.ResultsCCID turnaround time was 50 min, and the detection limit was 500 copies/reaction. The percentage of positive samples was significantly higher using CCID than CMTs, especially for Klebsiella pneumoniae (odds ratio [OR], 9.0; 95% confidence interval [CI], 1.1–70.5; p

IntroductionEpidemiological studies have suggested that dietary factors, especially high consumption of high glycaemic index carbohydrates and sugars, may trigger or exacerbate the progression of type 1 diabetes. We aimed to provide experimental evidence to confirm this relevance and to explore the underlying mechanisms.MethodsNOD mice were given sustained high-glucose drinking or glucose-free water and observed for the incidence of type 1 diabetes and islet inflammation. RNAseq was performed to detect the transcriptome changes of the NOD islet beta cell line NIT-1 after high glucose treatment, and mass spectrometry was performed to detect the proteome changes of NIT-1-cells-derived sEVs.ResultsSustained high glucose drinking significantly aggravates islet inflammation and accelerates the onset of type 1 diabetes in NOD mice. Mechanistically, high glucose treatment induces aberrant ER stress and up-regulates the expression of autoantigens in islet beta cell. Moreover, high glucose treatment alters the proteome of beta-cells-derived sEVs, and significantly enhances the ability of sEVs to promote DC maturation and stimulate immune inflammatory response.DiscussionThis study provides evidence for negative effect of high glucose intake as a dietary factor on the pathogenesis of type 1 diabetes in genetically predisposed individuals. Therefore, avoiding high sugar intake may be an effective disease prevention strategy for children or adults susceptible to type 1 diabetes.

Proton exchange membrane water electrolyzer (PEMWE) represents a promising technology for the sustainable production of hydrogen, which is capable of efficiently coupling to intermittent electricity from renewable energy sources (e.g., solar and wind). The technology with compact stack structure has many notable advantages, including large current density, high hydrogen purity, and great conversion efficiency. However, the use of expensive electrocatalysts and construction materials leads to high hydrogen production costs and limited application. In this review, recent advances made in key materials of PEMWE are summarized. First, we present a brief overview about the basic principles, thermodynamics, and reaction kinetics of PEMWE. We then describe the cell components of PEMWE and their respective functions, as well as discuss the research status of key materials such as membrane, electrocatalysts, membrane electrode assemblies, gas diffusion layer, and bipolar plate. We also attempt to clarify the degradation mechanisms of PEMWE under a real operating environment, including catalyst degradation, membrane degradation, bipolar plate degradation, and gas diffusion layer degradation. We finally propose several future directions for developing PEMWE through devoting more efforts to the key materials.

3D-graphene foam electrodes (Gii-Sens) immersed in a phosphate buffer solution of pH 7 are shown to generate hydrogen peroxide at a significantly faster rate in the presence of a nanoparticulate polymer of intrinsic microporosity (PIM-1). The effect is demonstrated to be associated at least in part with oxygen binding into PIM-1 under triphasic conditions. The release of the oxygen at the electrode|solution interface quadruples H2O2 production. Generator–collector experiments are performed with a graphene foam disk generator and a platinum disk electrode collector to allow in situ detection of hydrogen peroxide and oxygen.

Alterations in the global brain gray matter volume (gGMV) and global functional connectivity density (gFCD) play a pivotal role in the cognitive impairment and further deterioration in schizophrenia. This study aimed to assess the correlation between alterations in the gGMV and gFCD at baseline (ΔgGMV and ΔgFCD), and the subsequent alterations of cognitive function in schizophrenia patients after 2-year antipsychotic treatment. Global-brain magnetic resonance imaging scans were acquired from 877 drug-naïve, first-episode schizophrenia patients at baseline and after two years of antipsychotic treatment with adequate dosage and duration, and 200 healthy controls. According to ΔgGMV at baseline, schizophrenia patients were divided into mild, moderate, and severe alteration groups. The MATRICS consensus cognitive battery and Global Deficit Score (GDS) were used to assess cognitive impairment. We found that ΔgGMV and ΔgFCD at baseline were significantly correlated with the severity of the cognitive deterioration (ΔGDS). The correlation coefficient indicated a significant positive correlation between baseline ΔgFCD and subsequent cognitive deterioration, with a relatively stronger relation in the mild alteration group (r = 0.31). In addition, there was a significant positive correlation between baseline ΔgGMV and subsequent cognitive deterioration, with a stronger relation in the moderate and severe alteration groups (r = 0.303; r = 0.302, respectively). Our results showed that ΔgGMV and ΔgFCD are correlated with the severity of cognitive deterioration after completion of a 2-year antipsychotic treatment in schizophrenia patients. These findings suggest that baseline alterations in gGMV and gFCD hold potential for predicting subsequent cognitive decline in schizophrenia.

The occurrence of heavy menstrual bleeding (HMB) induced by pharmacological agents has been reported in young adult women. This study aimed to investigate a possible association between the occurrence rates of HMB and different treatment methods such as antidepressant agents alone and in combination with other pharmacological agents. The examined cohort included young women (age 18–35 years, n = 1,949) with bipolar disorder (BP) or major depressive disorder (MDD). Menstruation history for 24 months was recorded and evaluated according to pictorial blood loss assessment charts of HMB. Multivariate analyses were conducted to determine odds ratios (ORs) and 95% confidence intervals. The examined antidepressant agents had varying ORs for patients with BP vs. those with MDD. For example, the ORs of venlafaxine-induced HMB were 5.27 and 4.58 for patients with BP and MDD, respectively; duloxetine-induced HMB, 4.72 and 3.98; mirtazapine-induced HMB, 3.26 and 2.39; fluvoxamine-induced HMB, 3.11 and 2.08; fluoxetine-induced HMB, 2.45 and 1.13; citalopram-induced HMB, 2.03 and 1.25; escitalopram-induced HMB, 1.85 and 1.99; agomelatine-induced HMB, 1.45 and 2.97; paroxetine-induced HMB, 1.19 and 1.75; sertraline-induced HMB, 0.88 and 1.13; reboxetine-induced HMB, 0.45 and 0.45; and bupropion-induced HMB, 0.33 and 0.37, in each case. However, when antidepressant agents were combined with valproate, the OR of HMB greatly increased, with distinct profiles observed for patients with BP vs. those with MDD. For example, the ORs of HMB induced by venlafaxine combined with valproate were 8.48 and 6.70 for patients with BP and MDD, respectively; for duloxetine, 5.40 and 4.40; mirtazapine, 5.67 and 3.73; fluvoxamine, 5.27 and 3.37; fluoxetine, 3.69 and 4.30; citalopram, 5.88 and 3.46; escitalopram, 6.00 and 7.55; agomelatine, 4.26 and 5.65; paroxetine, 5.24 and 3.25; sertraline, 4.97 and 5.11; reboxetine, 3.54 and 2.19; and bupropion, 4.85 and 3.46, in each case. In conclusion, some antidepressant agents exhibited potential risks of inducing HMB. Therefore, a combined prescription of antidepressant agents and valproate should be carefully considered for young women with HMB.

Farmers’ entrepreneurial income is related to poverty alleviation and common prosperity. The clan network is an important social capital for farmers. However, research on effects of this relationship is still scant. We classifies farmers’ social capital as endowed social capital such as clan networks and leapfrogging social capital that needs to be operated. Using the data of CFPS 2010–2018 in China, this study investigates the influence of clan networks and farmers’ entrepreneurial income. Based on the social capital theory, we adopt a semilogarithmic model, and propensity score matching method for robustness checks. The results show that the clan network, as an endowed social capital of farmer, has a significant and positive effect on entrepreneurial income for both men and women. And the clan network has the greatest impact on middle-income farmers. Our results have important implications for policymakers in other developing economies who seek to increase farmers’ income.

Accurately quantifying the spatiotemporal patterns in ecosystem service (ES)11 ES-Ecosystem service. supply and demand and their coupling coordination dynamics, as well as identifying the spatial heterogeneity of the influencing factors for coupling coordination degree are necessary for regional sustainable development. This study used the Ulansuhai Basin in Inner Mongolia Province of China as a case to quantify the supply, demand, and supply-demand ratio of ES (meat production, grain production, carbon storage, water yield, nitrogen purification, and phosphorus purification) from 2000 to 2020. The synthesized coefficient of ES supply (ESCI)22 ESCI-Synthesized coefficient of ES supply. and demand (ESDI),33 ESDI-Synthesized coefficient of ES demand. the match degree of total supply and demand (MD),44 MD-Match degree of total ES supply and demand. and the coupling coordination degree (CD)55 CD-Coupling coordination degree between total ES supply and demand. were taken as indices to explore the relationship between the ESCI and ESDI and the coordination relationships. A mixed effects model was used to determine the spatial heterogeneity response of CD to different influencing factors. The results showed that the total ES supply in the Ulansuhai Basin always met the demand. The area with the highest ESCI was always observed in the Urad Front Banner, while Linhe district had the highest ESDI. Although incoordination improved from mild to superior from 2000 to 2020 at the basin scale, significant spatial variations were observed at the county scale. In addition, the variation in CD was significantly correlated with population, followed by precipitation, and cropland area. The findings comprehensively explore the match and coordination between ES supply and demand, and the spatial heterogeneity of the effects of the influencing factors on CD. Our study can contribute to the formulation of future policies for regional ecological restoration and sustainable development.

Abstract Mesenchymal stem-cell-derived small extracellular vesicles (MSC-EVs), as a therapeutic agent, have shown great promise in the treatment of neurological diseases. To date, the neurorestorative effects and underlying mechanism of MSC-EVs in Alzheimer’s disease (AD) are not well known. Herein, we aimed to investigate the action of MSC-EVs on the neuronal deficits in β-amyloid protein (Aβ)-stimulated hippocampal neurons, or AD cell (SHSY5Y cell lines) and animal (APPswe / PS1dE9 mice) models. In the present study, the cell and AD models received a single-dose of MSC-EVs, and were then assessed for behavioral deficits, pathological changes, intracellular calcium transients, neuronal morphology alterations, or electrophysiological variations. Additionally, the nuclear factor E2-related factor 2 (Nrf2, a key mediator of neuronal injury in AD) signaling pathway was probed by western blotting in vitro and in vivo models of AD. Our results showed that MSC-EVs therapy improved the cognitive impairments and reduced the hippocampal Aβ aggregation and neuronal loss in AD mice. Markedly, EV treatment restored the calcium oscillations, dendritic spine alterations, action potential abnormalities, or mitochondrial changes in the hippocampus of AD models. Also, we found that the Nrf2 signaling pathway participated in the actions of MSC-EVs in the cell and animal models. Together, these data indicate that MS-EVs as promising nanotherapeutics for restoration of hippocampal neuronal morphology and function in APP / PS1 mice, further highlighting the clinical values of MSC-EVs in the treatment of AD.

ABSTRACT Importance The Coronavirus disease 2019 (COVID‐19) global pandemic poses a considerable challenge for pediatricians. Objective This study aimed to identify the epidemiological characteristics and clinical features of pediatric patients with COVID‐19 in China. Methods This multicenter retrospective study included pediatric patients from 46 hospitals in China, covering 12 provinces and two municipalities. Epidemiological, demographic, clinical, laboratory, treatment, and outcome data were analyzed. Results In total, 211 pediatric patients with COVID‐19 were included in this study. The median age was 7.0 years (range: 22 days to 18 years). Approximately 16.3% of the patients exhibited asymptomatic infections, 23.0% had upper respiratory tract infections, and 60.7% had pneumonia, including two with severe pneumonia and one with critical illness. Approximately 78.7% of the pediatric patients occurred in familial clusters. The most three common symptoms or signs at onset in children with COVID‐19 were fever (54.5%), cough (49.3%), and pharyngeal congestion (20.8%). Only 17.6% of the patients presented with decreased lymphocyte count, whereas 13.6% had increased lymphocyte count. Among the patients with pneumonia who exhibited abnormal chest computed tomography findings, 18.2% (23/127) of the patients had no other symptoms. Generally, the chest radiographs showed abnormalities that affected both lungs (49.6%); ground‐glass opacity (47.2%) was the most common manifestation. The cure and improvement rates were 86.7% (183/211) and 13.3% (28/211), respectively. Only one patient with an underlying condition received invasive mechanical ventilation; none of the patients died. Interpretation Similar to adults, children of all age groups are susceptible to COVID‐19. Fortunately, most pediatric patients have mild symptoms or remain asymptomatic, despite the high incidence of pneumonia. Decreased proportions of white blood cells and lymphocytes are less frequent in children than in adults.

To make use of scrap perovskite titanium slag to produce metatitanic acid, a new method based on the high efficiency decomposition ability of sulfuric–chloric mixture acid (SCMA) has been proposed. Because Al is one of the most common elements existing in its raw state, Al3+ has become the main impurity in titanium solutions after decomposition, which affects the performance of related products. Consequently, the role of Al on the thermal hydrolysis of Ti in the SCMA solution was investigated in this study. With the addition of Al3+, a lower hydrolysis ratio was obtained at a low reaction temperature (130 °C). Moreover, the particles of metatitanic acid displayed a ball-shaped morphology and narrow particle distribution with a D50 of 1.4–2.0 μm. According to the crystal structures of Al3+, it is presumed that the priority order of ligand is SO42−>H2O>Cl−. The addition of Al3+ increases the growth rate of the a- and b-axes but reduces the growth rate of the c-axis. The results presented here confirm the influence of Al3+ in the control of nucleation and growth process during the hydrolysis to achieve qualified metatitanic acid products.

Abstract Pelvic radiotherapy is the key treatment for pelvic malignancies, usually including pelvic primary tumour lesions and lymphatic drainage areas in the pelvic region. Therefore, the intestinal tract in the radiation field is inevitably damaged, a phenomenon clinically referred to as radiation enteritis, and diarrhoea is the most common clinical symptom of radiation enteritis. Therefore, it is necessary to study the mechanism of radiation-induced diarrhoea. It has been found that the gut microbiome plays an important role in the development of diarrhoea in response to pelvic radiotherapy, and the species and distribution of intestinal microbiota are significantly altered in patients after pelvic radiotherapy. In this study, we searched for articles indexed in the Cochrane Library, Web of Science, EMBASE and PubMed databases in English and CNKI, Wanfang data and SINOMED in Chinese from their inception dates through 13 March 2020 to collect studies on the gut microbiome in pelvic radiotherapy patients. Eventually, we included eight studies: one study report on prostatic carcinoma, five studies on gynaecological carcinoma and two papers on pelvic carcinomas. All studies were designed as self-controlled studies, except for one that compared toxicity to nontoxicity. The results from all the studies showed that the diversity of intestinal flora decreased during and after pelvic radiotherapy, and the diversity of intestinal flora decreased significantly in patients with diarrhoea after radiotherapy. Five studies observed that the community composition of the gut microbiota changed at the phylum, order or genus level before, during, and after pelvic radiotherapy at different time points. In addition, the composition of the gut microbiota before radiotherapy was different between patients with postradiotherapy diarrhoea and those without diarrhoea in five studies. However, relevant studies have not reached consistent results regarding the changes in microbiota composition. Changes in the intestinal flora induced by pelvic radiotherapy and their relationship between changes in intestinal flora and the occurrence of radiation-induced diarrhoea (RID) are discussed in this study, providing a theoretical basis for the causes of RID after pelvic radiotherapy.

Abstract Background Residents’ preference for primary health care (PHC) determined their utilization of PHC. This study aimed to assess the determinants of PHC service preference among the residents and the trend in PHC service preference over time in China. Methods We employed the nationally representative longitudinal data from 2012 to 2018 based on the China Family Panel Studies. The analysis framework was guided by the Andersen model of health service utilization. We included a total of 12,508 individuals who have been successfully followed up in the surveys of 2012, 2014, 2016, and 2018 without any missing data. Logistic regressions were performed to analyze potential predictors of PHC preference behavior. Results The results indicated that individuals’ socio-economic circumstances and their health status factors were statistically significant determinants of PHC preference. Notably, over time, the residents’ likelihood of choosing PHC service represented a decreasing trend. Compare to 2012, the likelihood of PHC service preference decreased by 18.6% (OR, 0.814; 95% CI, 0.764–0.867) in 2014, 30.0% (OR, 0.700; 95% CI, 0.657–0.745) in 2016, and 34.9% (OR, 0.651; 95% CI, 0.611–0.694) in 2018. The decrease was significantly associated with the changes in residents’ health status. Conclusions The residents’ likelihood of choosing PHC service represented a decreasing trend, which was contrary to the objective of China’s National Health Reform in 2009. We recommend that policymakers adjust the primary service items in PHC facilities and strengthen the coordination of service between PHC institutions and higher-level hospitals.

Abstract Aims/Introduction Differentially expressed microribonucleic acids (miRNAs) in the placenta and circulating exosomes are of diagnostic value for gestational diabetes mellitus (GDM). In a cross‐sectional study, we identified miRNAs expressed both in the placenta and circulating exosomes of pregnant women with GDM, and estimated their diagnostic value. Materials and Methods Next‐generation sequencing was used to identify miRNAs in the placenta that were differentially expressed between GDM and normal glucose tolerance pregnancies. Quantitative polymerase chain reaction was used to validate the identified targets. Western blot and transmission electron microscopy were used to validate exosomes. Univariate logistic regression analysis was used to establish diagnostic models based on miRNAs expression, and the diagnostic value was estimated using the receiver operator characteristic curve. Results We identified 157 dysregulated miRNAs in the placental tissue obtained from GDM pregnancies. Of these, miRNA‐125b was downregulated (P