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The remarkable prevalence of pyrazole scaffolds in a versatile array of bioactive molecules ranging from apixaban, an anticoagulant used to treat and prevent blood clots and stroke, to bixafen, a pyrazole-carboxamide fungicide used to control diseases of rapeseed and cereal plants, has encouraged both medicinal and organic chemists to explore new methods in developing pyrazole-containing compounds for different applications. Although numerous synthetic strategies have been developed in the last 10 years, there has not been a comprehensive overview of synthesis and the implication of recent advances for treating neurodegenerative disease. This review first presents the advances in pyrazole scaffold synthesis and their functionalization that have been published during the last decade (2011–2020). We then narrow the focus to the application of these strategies in the development of therapeutics for neurodegenerative diseases, particularly for Alzheimer’s disease (AD) and Parkinson’s disease (PD).

The Zhangxuan Basin serves as an ecological barrier and water conservation area for Beijing, the capital of China. Clarifying the hydrochemical evolution of groundwater in this region is essential for the effective management of groundwater resources and the protection of ecological security. In this study, based on data regarding chemistry and level of shallow groundwater from 2016 to 2022, hydrogeochemical analysis methods and geostatistical techniques were applied to investigate the hydrochemical evolution and genesis mechanisms of groundwater under the influence of human activities. The results showed that: (1) From 2016 to 2022, the groundwater remained predominantly characterized by Ca2+ and HCO3-, with the primary hydrochemical type unchanged as HCO3-Ca·Mg. (2) From 2016 to 2022, an overall decreasing trend in hydrochemical components was observed, alongside an increase in HCO3-Na type groundwater. Spatially, along the direction of groundwater flow, a general trend of increasing hydrochemical components was noted, with a significant rise in HCO3-Na type groundwater. (3) The spatiotemporal distribution and evolution of hydrochemistry were influenced by water-rock interactions, lithological characteristics, groundwater flow patterns, and human activities. Along the groundwater flow direction, lithological particles became finer, enhancing forward cation exchange and leaching, with the dissolution of silicate and carbonate minerals intensifying. In localized areas, the hydrochemical components were influenced by the extraction of groundwater source areas and the discharge of industrial waste.

Both over-exploitation and exploitation reduction of groundwater can alter the conditions of groundwater recharge and discharge, thereby impacting the overall quality of groundwater. This study utilizes hydrogeochemical methods and statistical analysis to explore the spatial and temporal evolution characteristics and influencing factors of groundwater chemistry in the saline-freshwater funnel area of Hengshui City under exploitation reduction. The results showed that: With the exception of the deep freshwater funnel area in the western region, which exhibits a trend of water quality deterioration (Cl − accounted for more than 25%), groundwater quality in the other funnel areas demonstrates an improving trend (HCO accounted for more than 25%). The origins of hydrochemical components in the groundwater of the two types of funnel areas are influenced by rock weathering. Only the shallow saline water funnel area in the eastern region is impacted by evaporation. And groundwater hydraulic conditions play a distinct role in controlling the evolution of water chemistry in different types of funnel areas. It is mainly manifested in changing the water-rock reaction speed in the two types of funnel areas and diluting the groundwater ion concentration in the funnel area.

A demand exists for user-friendly patient-reported outcome measures for patients with inflammatory bowel disease (IBD). The IBD-Control Questionnaire has been recently developed to assess overall disease control from the patient's view but has not been available in China. Translation and cultural adaption of the IBD-Control into Chinese was conducted through four steps (forward translation, backward translation, expert panel, and pilot testing). Afterwards, a prospective validation study was conducted from February 2022 to February 2023. The translated IBD-Control, Short Health Scale, EQ-5D-5L, and disease activity measurements using either the Physician Global Assessment and Simple Clinical Colitis Activity Index or the Crohn's Disease Activity Index were used. Acceptability, test-retest reliability, internal consistency, content validity, convergent validity, structural validity, discriminant ability, and receiver operating characteristic curves were analyzed. Questionnaires were completed by 150 participants with IBD (31 with Crohn's disease [CD] and 119 with ulcerative colitis [UC]). The Cronbach's alpha coefficient was 0.823 for the IBD-Control-8 scale. The correlations between individual item and total score varied from 0.485 to 0.892 among CD patients and from 0.588 to 0.712 among UC patients. The S-CVI/Ave was 0.98. Convergent validity analyses exhibited moderate to strong correlations between other measurements and IBD-Control-8-subscore (0.555-0.675) or IBD-Control VAS (0.503-0.671). Test-retest analysis showed that the mean scores were 75.23±17.33 versus 72.10±14.99 (r = 0.894, p<0.01) for VAS scores and 12.75±3.49versus 12.80±3.29 for IBD-Control-8 subscore (r = 0.963, p<0.01), respectively. The IBD-Control-8-subscore and IBD-Control-VAS exhibited significant discriminative capability among the PGA categories (ANOVA, p < .001). The ROC analysis revealed an optimal cut-off point for the IBD-Control-8 subscore of 14 points (sensitivity: 70.9%, specificity 83.5%), versus a cut-off of 70 on the IBD-Control VAS score (sensitivity: 84.4%, specificity 69.3%). The Chinese IBD-Control proves to be a disease-specific, reliable, and valid tool for revealing overall disease control from the patient's viewpoint. Both healthcare professionals and patients may find it to be a useful patient-reported outcome measurement for triaging IBD patients in China or complementing routine care.

Iodine and fluoride are essential trace elements for human health, with both deficiency and excess intake impacting well-being. This study investigates the groundwater funnel area in eastern Hengshui City, utilizing groundwater level and hydrochemical data from 2014 to 2022. Hydrogeochemical methods were employed to comprehensively analyze the evolution characteristics and causes of iodine and fluoride concentrations in the funnel area. The results show: (1) After the implementation of groundwater exploitation reduction (GER) (post-2014), the mean concentration of I⁻ in the study area’s shallow groundwater (SG) decreased from 0.17 mg/L to 0.16 mg/L. Conversely, the mean concentration of F⁻ increased from 1.00 mg/L to 1.12 mg/L. In the deep groundwater (DG), the mean concentration of I⁻ rose from 0.17 mg/L to 0.19 mg/L, and the mean concentration of F⁻ increased from 1.99 mg/L to 2.90 mg/L. (2) In 2014, the concentrations of I⁻ and F⁻ in SG increased progressively from the recharge area to the discharge area along the groundwater flow. By 2018 and 2022, the concentrations of I⁻ and F⁻ in the recharge area had become higher than those in the discharge area. Between 2014 and 2022, the concentrations of I⁻ and F⁻ in DG progressively increased from the recharge area to the discharge area along the groundwater flow. (3) Before and after GER, the primary sources of I⁻ and F⁻ in both SG and DG remained consistent. Nevertheless, prolonged GER and recharge have altered the groundwater hydraulic conditions, pH, redox environment, HCO₃⁻ concentration, Ca 2+ concentration, and cation exchange processes. These changes have led to the evolution of I⁻ and F⁻ concentrations.

Background Spinal cord injury (SCI) can cause destructive neurological dysfunctions. Objectives The present study investigates the role and mechanism of methyltransferase like 3 (METTL3) in neural functional recovery post-SCI. Results SCI mice showed neurological function impairment, with significantly elevated METTL3 expression and m 6 A content. METTL3 inhibition improved motor and sensory injury in SCI mice, alleviated tissue injury, up-regulated BDNF, GDNF, and IL-10 levels, and down-regulated IL-1β and TNF-α levels. Mechanistically, METTL3 mediated m 6 A modification of USP4 mRNA and enhanced YTHDF2 enrichment on USP4 mRNA, thus reducing USP4 mRNA stability and expression. Combined experiments confirmed that METTL3 exacerbated neurological impairment in SCI mice by reducing USP4 expression. Conclusion METTL3-dominated m 6 A modification enhances YTHDF2 enrichment on USP4 mRNA and thereby reduces USP4 mRNA stability, eventually aggravating neurological impairment in SCI mice.

To enhance the development efficiency of medium–deep geothermal resources in cold regions, this study focuses on a coaxial borehole heat exchanger (CBHE) located in Dapuzi Town, Xining City, Qinghai Province. Based on field-scale heat exchange experiments, a three-dimensional numerical model of the CBHE was developed using COMSOL Multiphysics 6.2, incorporating both conductive heat transfer in the surrounding geological formation and convective heat transfer within the wellbore. The model was calibrated and validated against measured data. On this basis, the effects of wellhead injection flow rate, injection temperature, and the thermal conductivity of the inner pipe on heat exchange performance were systematically analyzed. The results show that in cold regions with high altitudes (2000–3000 m) and medium–deep low-temperature geothermal reservoirs (68.8 °C), using a coaxial heat exchange system for space heating delivers good heat extraction performance, with a maximum average power output of 282.37 kW. Among the parameters, the injection flow rate has the most significant impact on heat extraction. When the flow rate increases from 10 m3/h to 30 m3/h, the heat extraction power increases by 57.58%. An increase in injection temperature helps suppress thermal short-circuiting and improves the effluent temperature, but excessively high temperatures lead to a decline in heat extraction. Additionally, increasing the thermal conductivity of the inner pipe significantly intensifies thermal short-circuiting and reduces overall heat exchange capacity. Under constant reservoir conditions, the thermal influence radius expands with both depth and operating time, reaching a maximum of 10.04 m by the end of the heating period. For the CBHE system in Dapuzi, maintaining an injection flow rate of 20–25 m3/h and an injection temperature of approximately 20 °C can achieve an optimal balance between effluent temperature and heat extraction.

Bristol stool form 1 and 2 is an important predictor of inadequate bowel preparation. To evaluate the efficacy of supplemental preparation in bowel cleansing quality among patients with Bristol stool form 1 and 2, as well as the feasibility of tailored bowel preparation guided by Bristol stool form scale. Patients with Bristol stool form 1 and 2 from 3 Chinese tertiary hospitals randomly received either 2 L PEG-ELP (group A) or 10 mg bisacodyl plus 2 L PEG-ELP (group B); patients with Bristol stool form 3 to 7 received 2 L PEG-ELP (group C) for bowel preparation. The primary endpoint is the rate of adequate bowel reparation for the whole colon. The adequate bowel preparation rate for separate colon segments, the polyp detection rate (PDR), tolerability, acceptability, sleeping quality and compliance were evaluated as secondary endpoints. 700 patients were randomized. In per-protocol analysis, patients in group B attained significantly higher successful preparation rate than group A (88.7% vs. 61.2%, p<0.001) and similar with group C (88.7% vs. 85.0%, p = 0.316). The PDR in group B was significantly higher than group A (43.2% vs. 25.7%, p<0.001). Acceptability was much higher in group B and C. 10 mg bisacodyl plus 2 L PEG-ELP can significantly improve both bowel preparation quality and PDR in patients with Bristol stool form 1 and 2. Bristol stool form scale may be an easy and efficient guide for tailored bowel preparation before colonoscopy.

Antimicrobial peptides (AMPs) are important mediators of intestinal immune surveillance. However, the regional heterogeneity of AMPs and its regulatory mechanisms remain obscure. Here, we clarified the regional heterogeneity of intestinal AMPs at the single-cell level, and revealed a cross-lineages AMP regulation mechanism that bile acid dependent transcription factors (BATFs), NR1H4 , NR1H3 and VDR , regulate AMPs through a ligand-independent manner. Bile acids regulate AMPs by perturbing cell differentiation rather than activating BATFs signaling. Chromatin accessibility determines the potential of BATFs to regulate AMPs at the pre-transcriptional level, thus shaping the regional heterogeneity of AMPs. The BATFs-AMPs axis also participates in the establishment of intestinal antimicrobial barriers of fetuses and the defects of antibacterial ability during Crohn’s disease. Overall, BATFs and chromatin accessibility play essential roles in shaping the regional heterogeneity of AMPs at pre- and postnatal stages, as well as in maintenance of antimicrobial immunity during homeostasis and disease. Wang et al. clarify the regional heterogeneity of intestinal AMPs and identify that chromatin accessibility determines the potential of BATFs to regulate AMPs at the pre-transcriptional level, thus shaping the regional heterogeneity of AMPs.

Hypertension is a global health issue, and a reduced exercise capacity is unavoidable for older people. According to recent clinical studies, the intestinal microbiota play a crucial role in the pathogenesis of many human diseases. We investigated whether specific alterations in the gut microbiota contribute to the reduced exercise capacity of elderly patients with hypertension. This study enrolled 56 subjects, and all patients performed a cardiopulmonary exercise test and underwent fecal bacteria sequencing (16 s ribosomal RNA V4 region). According to peak oxygen uptake values, patients were divided into three groups (Weber A  = 19, Weber B  = 20, and Weber C  = 17). The alpha diversity was not significantly different among the three groups. Regarding the beta diversity, Weber A samples were separate from the other two groups in the nonmetric multidimensional scaling ordination plot (ANOSIM pairwise comparisons generated an R  > 0.5; p  < 0.05). The abundance of Betaproteobacteria, Burkholderiales, Alcaligenaceae, Faecalibacterium and Ruminococcaceae was diminished in subjects with a reduced exercise capacity (LDA score > 4.0). Escherichia coli are a primary producer of trimethylamine and inflammation in the human gut, and the abundance of this bacteria was increased in patients with a reduced exercise capacity (LDA score > 4.0). On the other hand, Lachnospiraceae- Eubacterium_hallii _group, Lachnospiraceae- Lachnoclostridium , Lachnospiraceae- Blautia - Ruminococcus _sp__5_1_39BFAA, and Ruminococcaceae- Faecalibacterium belong to the order Clostridiales that are likely to produce short-chain fatty acids (LDA score > 4.0), and some of these species were enriched in the Weber B or Weber C group in multiple comparisons. Our data pointed to an altered gut microbiota as a potential contributor to the pathogenesis and progression of the reduced exercise capacity of elderly patients with hypertension.