Sex Hormone-Binding Globulin and Risk of Incident Dementia in Middle-Aged to Older Women: Results from the UK Biobank Cohort Study.

INTRODUCTION: The association of serum sex hormone-binding globulin (SHBG) concentrations with dementia risk remains uncertain in middle-aged to older women. We examined associations of serum SHBG levels with incidence of all-cause dementia and its subtypes in middle-aged to older women from the large population-based UK Biobank cohort study. METHODS: Serum total SHBG levels were measured by immunoassay. The incidence of all-cause dementia and its subtypes was recorded. Cox proportional hazards models were used to calculate hazard ratios (HR) for main outcomes. RESULTS: Among 171,482 community-dwelling women (mean [SD] age was 59.9 [5.4] years, median follow-up of 11.8 years), 2,368 developed dementia, including 1,088 from Alzheimer's disease (AD), 451 from vascular dementia (VAD), and 1,609 from other dementia. After multivariable adjustments, higher serum SHBG levels were significantly associated with higher risks of all-cause dementia, AD, and other dementia (all p < 0.05). Compared to those in the lowest quartile of SHBG levels, participants in the highest quartile of SHBG levels had a higher risk of all-cause dementia (HR: 1.34; 95% confidence interval [CI]: 1.16-1.53), AD (HR: 1.32; 95% CI: 1.07-1.62), and other dementia (HR: 1.44; 95% CI: 1.21-1.70). However, this relationship was not significant for VAD (HR: 1.16; 95% CI: 0.86-1.56). CONCLUSION: These findings indicated that higher serum SHBG concentrations were independently associated with higher risks of incident all-cause dementia, as well as AD and other dementia among middle-aged to older women. No association was found for VAD.

MicroRNA Targets PAP1 to Mediate Melanization in Plutella xylostella (Linnaeus) Infected by Metarhizium anisopliae.

MicroRNAs (miRNAs) play a pivotal role in important biological processes by regulating post-transcriptional gene expression and exhibit differential expression patterns during development, immune responses, and stress challenges. The diamondback moth causes significant economic damage to crops worldwide. Despite substantial advancements in understanding the molecular biology of this pest, our knowledge regarding the role of miRNAs in regulating key immunity-related genes remains limited. In this study, we leveraged whole transcriptome resequencing data from Plutella xylostella infected with Metarhizium anisopliae to identify specific miRNAs targeting the prophenoloxidase-activating protease1 (PAP1) gene and regulate phenoloxidase (PO) cascade during melanization. Seven miRNAs (pxy-miR-375-5p, pxy-miR-4448-3p, pxy-miR-279a-3p, pxy-miR-3286-3p, pxy-miR-965-5p, pxy-miR-8799-3p, and pxy-miR-14b-5p) were screened. Luciferase reporter assays confirmed that pxy-miR-279a-3p binds to the open reading frame (ORF) and pxy-miR-965-5p to the 3' untranslated region (3' UTR) of PAP1. Our experiments demonstrated that a pxy-miR-965-5p mimic significantly reduced PAP1 expression in P. xylostella larvae, suppressed PO activity, and increased larval mortality rate. Conversely, the injection of pxy-miR-965-5p inhibitor could increase PAP1 expression and PO activity while decreasing larval mortality rate. Furthermore, we identified four LncRNAs (MSTRG.32910.1, MSTRG.7100.1, MSTRG.6802.1, and MSTRG.22113.1) that potentially interact with pxy-miR-965-5p. Interference assays using antisense oligonucleotides (ASOs) revealed that silencing MSTRG.7100.1 and MSTRG.22113.1 increased the expression of pxy-miR-965-5p. These findings shed light on the potential role of pxy-miR-965-5p in the immune response of P. xylostella to M. anisopliae infection and provide a theoretical basis for biological control strategies targeting the immune system of this pest.

Nutrient-rich hydrothermal carbon production by exogenous nutrients combined with seaweed internal water.

As a product of hydrothermal carbonization (HTC) technology, hydrothermal carbon has shown excellent application potential in soil improvement, greenhouse gas reduction and pollution remediation. Since a large amount of water and biomass are directly used as reaction media, hydrothermal carbon produced by traditional HTC possesses poor nutrient properties and accompanied by the generation of toxic and hazardous wastewater. Here, a versatile and easily scalable strategy has been demonstrated for the one-step production of industrial nutrient-rich hydrothermal carbon (NRHC) by combining the exogenous nutrients with seaweed internal water. During the reaction process, exogenous nutrients (NH4H2PO3, KNO3, CO(NH2)2) participated in the HTC reaction and were uniformly distributed on the surface of hydrothermal carbon through surface complexation precipitation, ion exchange, and electrostatic interactions. Simulations based on density functional theory revealed that NRHC produced in presence of exogenous nutrients possessed more active sites and surface charges. Moreover, the adsorbent and adsorbate were simultaneously affected by intermolecular forces, electrostatic forces, and internal energy of the system, and the thermodynamics of adsorption process was more stable. Compared with no exogenous nutrient involvement, NRHC produced by exogenous nutrients showed 2.12, 18.56, and 25.69 times increase in the N, P, and K content. The length of the seed germination root system increased by 4.3-5.9 times, which met the standards set for agricultural fertilizer. Due to increased yield per unit volume and reduced wastewater generation, the cost of NRHC production reduced by 47.83-58.23 per cent and profit enhanced by 1.56-1.68 times, as compared to traditional HTC. This low-cost streamlined process provides a new strategy for large-scale production and direct application of hydrothermal carbon.

Combined transcriptomic and proteomic analysis of developmental features in the immune system of Plutella xylostella during larva-to-adult metamorphosis.

Diamondback moth (DBM), Plutella xylostella L. (Lepidoptera: Plutellidae) is considered one of the most destructive worldwide agricultural pests and has developed various defence mechanisms to fight against the available pesticides. Understanding the host-defence system of P. xylostella is vital for developing biocontrol-based pest management strategies. Although there are several studies on P. xylostella, little is known about the changes in the immune system during the larva-to-adult metamorphosis. RNA-seq and iTRAQ investigations of P. xylostella from 2-day-old fourth instar larvae (L4D2), pupa (P0), and adult (A0) were done to understand these alterations at a molecular level. A total of 412/ 584 up-regulated and 1430/ 757 down-regulated genes/proteins between larva and pupa, 813/ 589 up-regulated and 1206/ 846 down-regulated genes/proteins between pupa and adult were identified. It was shown that the differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) expression were up-regulated during the pupation and emergence of metamorphosis. The pathway enrichment analysis demonstrated that DEGs and DEPs were mainly associated with the energy generation and metabolism and innate immunity of the insect. The expression of immune-related and developmental-related genes were significantly different during the developmental process of P. xylostella. Moreover, the expression of four focused genes, i.e., serine proteinase inhibitor (Serpin-15), prophenoloxidase activating proteinase 1 (PAP-1) and 3a (PAP-3a), Gram-negative bacteria-binding protein (GNBP-6), was different in developmental stages and after Bacillus thuringiensis HD73 and Metarhizium anisopliae infection. The phenoloxidase (PO) activity in plasma was also significantly up-regulated during the pathogen infection. Recombinant proteins PAP-1, PAP-3a, GNBP-6 could significantly trigger the PO activity in vitro, Serpin-15 could suppress the PO activity. Taken together, these results indicate that Serpin-15, PAP-1, PAP-3a, and GNBP-6 might have the potential for co-regulation of immunity and development in P. xylostella. In conclusion, this study provided the immune system dynamics in the developmental process of P. xylostella and identified four candidate genes that can serve as potential targets for pest control strategies.

Recent Advances and Future Potential of Long Non-Coding RNAs in Insects.

Over the last decade, long non-coding RNAs (lncRNAs) have witnessed a steep rise in interest amongst the scientific community. Because of their functional significance in several biological processes, i.e., alternative splicing, epigenetics, cell cycle, dosage compensation, and gene expression regulation, lncRNAs have transformed our understanding of RNA's regulatory potential. However, most knowledge concerning lncRNAs comes from mammals, and our understanding of the potential role of lncRNAs amongst insects remains unclear. Technological advances such as RNA-seq have enabled entomologists to profile several hundred lncRNAs in insect species, although few are functionally studied. This article will review experimentally validated lncRNAs from different insects and the lncRNAs identified via bioinformatic tools. Lastly, we will discuss the existing research challenges and the future of lncRNAs in insects.

Spatial distribution and migration of lead and zinc and the influence of parent materials in typical paddy soils of Hunan Province, China.

This study aimed to investigate the distribution and migration characteristics of lead (Pb) and zinc (Zn) in paddy soils in Hunan Province, China. A total of 343 soil samples from 63 profiles were collected from typical regions. The concentration, spatial distribution, and migration behaviors of Pb and Zn in the paddy soils were examined. The results showed that (1) the concentration ranges of Pb and Zn in the surface layer were 17.62-114.07 mg/kg and 44.98-146.84 mg/kg, respectively. (2) The content was higher in the middle and lower reaches of the Xiangjiang River basin horizontally and exhibited shallow enrichment characteristics vertically. (3) Pb migration was weaker than Zn migration, and the parent material had the most significant influence on Pb and Zn content in the bottom soil layer. The research results will clarify the characteristics of Pb and Zn contents in paddy soils in Hunan Province, further understand the horizontal distribution and vertical migration and transformation characteristics of Pb and Zn contents in paddy soils, and provide basic data for scientific rice cultivation and safe food production.

Association between Cardiac Outcomes and Indoxyl Sulfate Levels in Hemodialysis Patients: A Cross-Sectional Study.

OBJECTIVE: Indoxyl sulfate (IS) is a protein-bound uremic toxin that is associated with cardiovascular events and mortality in hemodialysis (HD) patients. However, the factors affecting the levels of IS are currently unclear. This study aimed to investigate the factors influencing serum IS concentrations in HD patients. METHODS: We included 100 HD patients from Guangdong Provincial People's Hospital. Baseline characteristics, including sex, age, clinical features, duration of HD, echocardiography findings, electrocardiogram results, and biochemical indicators, were collected and analyzed in relation to serum total-form IS levels. RESULTS: Among all 100 patients, serum IS levels were significantly higher in patients aged ≥60 years, males, and patients with mitral regurgitation and inadequate dialysis. Among patients aged <60 years, IS levels were significantly higher among patients with mitral regurgitation compared with those without. Furthermore, multiple linear regression analysis identified sex, age, ventricular septal thickness, and mitral regurgitation as factors independently associated with serum IS (STDß = -0.475, 0.162, -0.153, 0.142, and 0.136, respectively; all p < 0.05) adjusted for body mass index, smoking, and fasting plasma glucose. CONCLUSIONS: Male sex, age ≥60 years, ventricular septal thickness, and mitral regurgitation are factors associated with high total serum IS concentrations in Chinese HD patients. Elevated IS levels may play a role in the process of mitral regurgitation in HD patients <60 years of age.

Rapid and efficient reduction of chromate by novel Pd/Fe@biomass derived from Enterococcus faecalis.

Efficient reduction of chromate is highly desirable for its detoxification and remediation of the contaminated environment. This study described a fusion of the concepts of precious metal biorecovery and fabrication of Pd/Fe@biomass derived from simulated wastewater. The effectiveness of Pd/Fe@biomass during reduction process of Cr(VI) was evaluated by comparing with pure nZVI, E. faecalis and Pd@biomass. Results showed that Pd(II) could be recovered by E. faecalis with Fe(II) as the electron donor, and precipitation could yield nZVI anchored onto Pd-loaded E. faecalis. The nano particles (NPs) on Pd/Fe@biomass were well-dispersed, which provided 2.70 folds specific surface area comparing with nZVI. Efficient Cr(VI) reduction could be achieved at a higher catalyst dosage, the most appropriated Pd/Fe molar ratio of 2% and a wide pH range. Typically, 0.5 mM Cr(VI) could be completely reduced in 5 min driven by Pd/Fe@biomass under the conditions of dosage of 1.0 g/L and pH 3. Moreover, the mechanisms of Cr(VI) reduction by Pd/Fe@biomass were proposed, which intimately related to nZVI electron donating capacities, Pd catalysis for hydrogenation and galvanic cell effects between Fe and Pd. Therefore, Pd/Fe@biomass could be an alternative for rapid and complete reduction of Cr(VI).

Advanced glycation end products induce endothelial hyperpermeability via ß-catenin phosphorylation and subsequent up-regulation of ADAM10.

Endothelial hyperpermeability is the initial event in the development of diabetic microvascular complications, and advanced glycation end products (AGEs) are suggested to cause much of the endothelial hyperpermeability associated with diabetes mellitus, but the molecular mechanism remains to be characterized. ß-catenin reportedly plays dual functions in maintaining normal endothelial permeability by serving both as an adhesive component and a signal transduction component. Here, we found that AGEs induced the phosphorylation of ß-catenin at residues Y654 and Y142 and the endothelial hyperpermeability was reversed when the two residues were blocked. In mechanism, phosphorylation of Y654 was blocked by Src inactivation, whereas phosphorylation of Y142 was reduced by a focal adhesion kinase inhibitor. ß-catenin Y654 phosphorylation induced by AGEs facilitated the dissociation of vascular endothelial (VE)-cadherin/ß-catenin and the impairment of adherens junctions (AJs), whereas ß-catenin Y142 phosphorylation favoured the dissociation of ß-catenin and α-catenin. Further investigation revealed that ß-catenin Y142 phosphorylation was required for AGEs-mediated ß-catenin nuclear translocation, and this nuclear-located ß-catenin subsequently activated the TCF/LEF pathway. This pathway promotes the transcription of the Wnt target, ADAM10 (a disintegrin and metalloprotease 10), which mediates VE-cadherin shedding and leads to further impairment of AJs. In summary, our study showed the role of ß-catenin Y654 and Y142 phosphorylation in AGEs-mediated endothelial hyperpermeability through VE-cadherin/ß-catenin/α-catenin dissociation and up-regulation of ADAM10, thereby advancing our understanding of the underlying mechanisms of AGEs-induced microvascular hyperpermeability.

High-performance non-enzymatic catalysts based on 3D hierarchical hollow porous Co3O4 nanododecahedras in situ decorated on carbon nanotubes for glucose detection and biofuel cell application.

In this work, high-performance non-enzymatic catalysts based on 3D hierarchical hollow porous Co3O4 nanododecahedras in situ decorated on carbon nanotubes (3D Co3O4-HPND/CNTs) were successfully prepared via direct carbonizing metal-organic framework-67 in situ grown on carbon nanotubes. The morphology, microstructure, and composite of 3D Co3O4-HPND/CNTs were characterized by scanning electron microscopy, transmission electron microscopy, micropore and chemisorption analyzer, and X-ray diffraction. The electrochemical characterizations indicated that 3D Co3O4-HPND/CNTs present considerably catalytic activity toward glucose oxidation and could be promising for constructing high-performance electrochemical non-enzymatic glucose sensors and glucose/O2 biofuel cell. When used for non-enzymatic glucose detection, the 3D Co3O4-HPND/CNTs modified glassy carbon electrode (3D Co3O4-HPND/CNTs/GCE) exhibited excellent analytical performance with high sensitivity (22.21 mA mM-1 cm-2), low detection limit of 0.35 µM (S/N = 3), fast response (less than 5 s) and good stability. On the other hand, when the 3D Co3O4-HPND/CNTs/GCE worked as an anode of a biofuel cell, a maximum power density of 210 µW cm-2 at 0.15 V could be obtained, and the open circuit potential was 0.68 V. The attractive 3D hierarchical porous structural features, the large surface area, and the excellent conductivity based on the continuous and effective electron transport network in 3D Co3O4-HPND/CNTs endow 3D Co3O4-HPND/CNTs with the enhanced electrochemical performance and promising applications in electrochemical sensing, biofuel cell, and other energy storage and conversion devices such as supercapacitor. Graphical abstract High-performance non-enzymatic catalysts for enzymeless glucose sensing and biofuel cell based on 3D hierarchical hollow porous Co3O4 nanododecahedras anchored on carbon nanotubes were successfully prepared via direct carbonizing metal-organic framework-67 in situ grown on carbon nanotubes.

Effect of Ascorbic Acid on Mineral and Bone Disorders in Hemodialysis Patients: a Systematic Review and Meta-Analysis.

BACKGROUND/AIMS: Hemodialysis (HD) patients often have inadequate nutrition, especially with respect to ascorbic acid (AA). It is reported that every HD session may cause a 50%- 75% decrease in plasma AA levels. Some studies have shown that supplementation of AA can change the outcome of chronic kidney disease-mineral bone disorders (CKD-MBD), but the effect of AA on HD patients with CKD-MBD remains controversial. Consequently, we decided to perform a meta-analysis to evaluate the efficacy of AA supplementation in CKD-MBD patients requiring dialysis. METHODS: A search was conducted using Pubmed, EMBASE, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure (CNKI), Wanfang database and VIP information database up to April 2018 for all English and Chinese language publications. The main indicators of our study were changes in serum phosphate (P), calcium (Ca) and parathyroid hormone (PTH) levels after AA treatment. The efficacy of AA was evaluated by weighted mean difference (WMD) and confidence intervals (CI). Cardiovascular events, mortality and adverse events reported during the experiment were also noted. RESULTS: In total, 371 patients in six studies were involved in this meta-analysis. Compared to placebo, AA treatment had no positive effect on serum P (353 patients; WMD = -0.05; 95% CI, -0.3 to 0.2; I2 = 28%) or PTH levels (275 patients; WMD = -17.04; 95%CI, -63.79 to 29.72; I2 = 75%). The pooled mean difference of the change of Ca levels from baseline was higher in the AA therapy group versus placebo (353 patients; WMD = 0.15; 95% CI, 0.01 to 0.3; I2 = 0%). No side effects were observed. CONCLUSION: Our systematic review and meta-analysis does not support prescription of AA to HD patients with CKD-MBD. AA had no positive effect on CKD-MBD patients as it couldn't influence the serum P or PTH levels but did raise serum Ca levels in the short-term.

Ga-doped TiZnO transparent conductive oxide used as an alternative anode in blue, green, and red phosphorescent OLEDs.

X-ray diffraction was used to study the optoelectronic characteristics of Ga-doped TiZnO (GTZO) thin film and revealed increased crystallinity with annealing temperatures ranging from as-grown to 450 °C. The low thin film resistivity of 6.1 × 10(-4) Ω cm and the average high optical transmittance of 93% in the wavelength range between 350 and 800 nm make GTZO an alternative candidate for application in organic light-emitting diodes (OLEDs). Both GTZO and indium-tin-oxide (ITO) anodes are employed for the successful fabrication of blue, green, and red phosphorescent OLEDs. The similar device electrical characteristics observed could be interpreted as evidence of the effectiveness of doping Ga in TiZnO. The simplified tri-layer blue, green, and red phosphorescent OLEDs demonstrated high performance with respective maximum efficiencies of 19.0%, 14.5%, and 9.1%, representing an improvement over ITO-based OLEDs. Furthermore, the OLEDs with the GTZO anode exhibited superior performance at higher current densities, demonstrating high potential for OLED display and lighting applications.

Dynamic event-triggered consensus control for nonlinear multi-agent systems under DoS attacks.

In this paper, we investigated leader-following consensus control for nonlinear multi-agent systems (MASs) experiencing denial-of-service (DoS) attacks. We proposed a distributed control strategy incorporating an adaptive scheme and a state feedback control gain to eliminate the effects of system nonlinear dynamics and uncertainties. In addition, we introduced a dynamic event-triggered control (DETC) to minimize the utilization of communication resources. Finally, we provided simulation results to show the validity of the proposed approach.

Enhancing the Proton Exchange Membrane in Tubular Air-Cathode Microbial Fuel Cells through a Hydrophobic Polymer Coating on a Hydrogel.

The usage time of air-cathode microbial fuel cells (MFCs) is significantly influenced by the moisture content within the proton exchange membrane (PEM). Therefore, enhancing the water retention capability of the PEM by applying a hydrophobic polymer coating to its surface has extended the PEM's usage time by three times and increased MFCs' operational duration by 66%. Moreover, the hydrophobic nature of the polymer coating reduces contamination on the PEM and prevents anode liquid from permeating into the air cathode. Towards the end of MFC operation, the internal resistance of the MFC is reduced by 45%. The polymer coating effectively maintained the oxygen reduction reaction activity in the cathode. The polymer coating's ability to restrict oxygen transmembrane diffusion is demonstrated by experimental data showing a significant decrease in oxygen diffusion coefficient due to its presence. The degradation efficiency of the chemical oxygen demand from 16% to 35% increased by a factor of one.

Health screenings with a medical interpreter in a required Ambulatory Care Introductory Pharmacy Practice Experience.

BACKGROUND AND PURPOSE: This study aimed to assess second year student pharmacists' (P2) confidence in communicating with patients with limited English proficiency before and after a required community-based health screening experience. EDUCATIONAL ACTIVITY AND SETTING: All P2s were required to complete a 0.5 credit hour Ambulatory Care Introductory Pharmacy Practice Experience (IPPE). As part of this experience, P2s conducted blood pressure (BP) and blood glucose (BG) screenings with a medical interpreter at a low-income apartment building that has a large Mandarin-speaking population. Each student was required to attend one health screening event. Between September 2022 and April 2023,we administered paper questionnaires to P2s and community members to obtain feedback about the experience. Quantitative data was analyzed using descriptive statistics, chi-squared tests, and paired t-tests while a content analysis was conducted on qualitative data. FINDINGS: P2s (n = 82, 100%) conducted an average of 5.7 (SD 2.6) BP and 5.9 (SD 2.7) BG screenings per two-hour event. P2s reported higher confidence in conducting assessments, communicating via a medical interpreter, and working on a team at the end of the event. P2s agreed that it should be kept as part of the IPPE (99%). Community members (n = 55, 22%) participated in a bilingual paper-based questionnaire. Community members reported positive experiences and a desire to continue to participate. SUMMARY: At the end of the health screening event, P2s were more confident in their ability to communicate with older adult community members using translated written documents and verbally with a medical interpreter. P2s and community members supported continuation of the program.

Whole-genome sequencing of Aminobacterium sp. strain MB27-C1, isolated from the wastewater treatment plant of a steel mill.

Here, we report the complete genome sequence of Aminobacterium sp. strain MB27-C1, which was isolated from sewage sludge collected at the wastewater treatment plant of Sanming Steel Co. Ltd. in Fujian, China. The resulting genome of strain MB27-C1 is a single contig of 2,427,830 bp with 41.58% GC content.

Associations of Serum Testosterone and Sex Hormone-binding Globulin With Incident Arrhythmias in Men From UK Biobank.

CONTEXT: Sex hormones have been identified as cardiovascular risk factors, whereas the relationship between sex hormones and the risk of arrhythmias in men has not yet been well studied in the prospective cohort study. OBJECTIVE: To analyze associations of serum testosterone and SHBG concentrations and calculate free testosterone (cFT) with arrhythmias in men. METHODS: Sex hormones were measured at baseline from UK Biobank. Main outcomes were incidence of atrial fibrillation/flutter (AF), ventricular arrhythmia (VA), and bradyarrhythmia (BA). RESULTS: Of 173 498 men (aged 37-73 years, followed for 11 years), 11 368 had incident AF, 1646 had incident VA, and 4788 had incident BA. Compared with the third quartiles, the lowest category of serum testosterone was associated with increased risks of AF (hazard ratio [HR], 1.06; 95% CI, 1.00-1.12) and BA (HR, 1.11; 95% CI, 1.02-1.20) after multivariable adjustment, but no VA. Likewise, similar associations were found between cFT values and AF and BA events. Furthermore, higher levels of cFT were associated with increased risks of AF (HR, 1.07; 95% CI, 1.02-1.13) and VA (HR, 1.18; 95% CI, 1.01-1.37). Higher SHBG concentrations were associated with increased risks of AF (HR, 1.44; 95% CI, 1.34-1.54), VA (HR, 1.27; 95% CI, 1.07-1.52), and BA (HR, 1.17; 95% CI ,1.05-1.29). CONCLUSIONS: Lower levels of testosterone and cFT were associated with increased risk of AF and BA. Higher cFT levels were associated with increased risk of AF and VA. Higher SHBG levels were associated with increased risk of AF, VA, and BA.

Natural intestinal metabolite xylitol reduces BRD4 levels to mitigate renal fibrosis.

Renal fibrosis is a typical pathological change from chronic kidney disease (CKD) to end-stage renal failure, which presents significant challenges in prevention and treatment. The progression of renal fibrosis is closely associated with the "gut-kidney axis," therefore, although clinical intervention to modulate the "gut-kidney axis" imbalance associated with renal fibrosis brings hope for its treatment. In this study, we first identified the close relationship between renal fibrosis development and the intestinal microenvironment through fecal microtransplantation and non-absorbable antibiotics experiments. Then, we analyzed the specific connection between the intestinal microenvironment and renal fibrosis using microbiomics and metabolomics, screening for the differential intestinal metabolite. Potential metabolite action targets were initially identified through network simulation of molecular docking and further verified by molecular biology experiment. We used flow cytometry, TUNEL apoptosis staining, immunohistochemistry, and Western blotting to assess renal injury and fibrosis extent, exploring the potential role of gut microbial metabolite in renal fibrosis development. We discovered that CKD-triggered alterations in the intestinal microenvironment exacerbate renal injury and fibrosis. When metabolomic analysis was combined with experiments in vivo, we found that the differential metabolite xylitol delays renal injury and fibrosis development. We further validated this hypothesis at the cellular level. Mechanically, bromodomain-containing protein 4 (BRD4) protein exhibits strong binding with xylitol, and xylitol alleviates renal fibrosis by inhibiting BRD4 and its downstream transforming growth factor-ß (TGF-ß) pathway. In summary, our findings suggest that the natural intestinal metabolite xylitol mitigates renal fibrosis by inhibiting the BRD4-regulated TGF-ß pathway.

Analysis of the spatio-temporal coupling coordination mechanism supporting economic resilience and high-quality economic development in the urban agglomeration in the middle reaches of the Yangtze River.

The coupling coordination mechanism between economic resilience and high-quality economic development is clarified not only to improve the capacity of economies to withstand external shocks but also to boost the level of sustainable economic development. However, economic resilience and economic quality research are still in their infancy. This study constructs an economic resilience indicator system based on the data of 28 prefecture-level cities in the urban agglomeration in the middle reaches of the Yangtze River (UAMRYR) from 2010-2019. The entropy approach was then coupled with the coupling coordination model to determine the level of coupling coordination between the two. Finally, the geographical detector was employed to reveal the coupling coordination process and driving elements. This study demonstrates that: (1) The economic resilience and high-quality economic development of the UAMRYR are on the rise; (2) The coupling coordination degree between economic resilience and high-quality economic development is improving, with the average value increasing from 0.33 in 2010 to 0.46 in 2019, exhibiting a Core-Periphery spatial distribution pattern with Wuhan, Changsha, and Nanchang as the core; (3) The economic resilience resistance subsystem plays a substantial role in the driving influence of the coupling coordination degree, where the total retail sales of consumer goods indicator have an explanatory power of 0.8 or higher for coupled coordination. Innovation and inclusiveness thoroughly drive the coupling coordination degree among the five subsystems of high-quality economic development, where the q-value of the number of urban basic endowment insurance participants index is at least 0.9. Additionally, the interplay of the components demonstrates a complementary enhancement impact and a two-factor enhancement effect; (4) Economic resilience and high-quality economic development are complementary and provide a powerful incentive for the sustainable development of urban economic systems to achieve higher quality, more efficient, more egalitarian, and more sustainable economic development. Overall, this study improves the analysis of mechanism between economic resilience and high-quality economic development, and it provides more targeted guidance for economic development in the UARMRYR.

A system dynamics-based synergistic model of urban production-living-ecological systems: An analytical framework and case study.

Human-land coordination represents urbanization and is a key component of urban modernization. In this study, the theory of system dynamics was introduced, in which a "production-living-ecological" complex system was used based on the human-land coordination concept. Moreover, the characteristics of system dynamics of causal cycle, dynamic and sustainable development, man-land synergy, integrity and openness, and self-organization and adaptability were analyzed by dividing it into three subsystems: urban production, urban living, and urban ecological subsystems. Here, causal feedback and system structure flow diagrams were designed using causal loop diagrams and system structure flow diagrams to evaluate the causal relationships between variables and quantitatively analyzing their interactions between variables and predicting the future development of variables. Changsha City, China was selected as the case study area, where we constructed system dynamics practice equation model was then constructed to determine the interaction between the subsystems. Our findings indicate that by the year 2035 in the future, the overall trend of factors influencing the function of the subsystems such as population, GDP and built-up area are positively correlated with an increasing trend, and there are interactions between. Furthermore, these factors interact with each other, and a mutual correlation was found among the production-living-ecological functions system, Therefore, this study provides a novel perspective and exploratory practice for the study of the synergistic coupling of ecological, production, and living functions of cities and evaluating high-quality development of cities. Thus, the coupling and coordination of urban production, living and ecological functions reflects the coupling and coordination of the "people-land" relationship, which is the key to high-quality urban development.