Causal relationship between multiple sclerosis and primary Sjögren's syndrome: a two-sample mendelian randomization study.

This study aims to investigate the causal relationship between primary Sjögren's syndrome (SS) and multiple sclerosis (MS) using a two-sample Mendelian randomization (MR) analysis to provide insights into their common mechanisms and implications for therapeutic strategies. We utilized data from Genome-Wide Association Studies (GWAS) for primary SS (1,290 cases and 213,145 controls) and MS (4,888 cases and 10,395 controls), restricted to European ancestry. Instrumental variables (IVs) were selected based on genetic variants associated with primary SS. The primary MR method was Inverse Variance Weighted (IVW), supplemented by MR Egger, Weighted Median, Simple Mode, and Weighted Mode algorithms to assess the bidirectional causal relationships between MS and primary SS. Sensitivity analyses, including MR-PRESSO and leave-one-out analysis, were conducted to ensure the robustness of our findings. After excluding SNPs with pleiotropic effects, 42 and 5 SNPs were identified as robust IVs for primary SS and MS, respectively. Our analysis revealed a significant protective effect of MS on primary SS, with IVW showing an OR of 0.896 (95% CI: 0.841-0.954, P = 0.001). No significant heterogeneity or horizontal pleiotropy was detected, supporting the reliability of the results. Our findings suggest a potential protective effect of MS against primary SS, indicating a negative causal association between these two autoimmune diseases. This adds valuable genetic evidence to the understanding of the complex interplay between primary SS and MS, offering new avenues for research and therapeutic interventions.

Modulation in work function of CoTe as bifunctional electrocatalyst for rechargeable zinc air battery.

The sluggish kinetics and inferior stability of oxygen electrocatalyst in rechargeable zinc air battery (ZAB) hamper its industrialization. In this work, we activate cobalt telluride (CoTe) by introduction of metallic cobalt (Co) to modulate the work function to facilitate the electron transfer from Co to CoTe during oxygen catalysis; additionally, the three-dimensional porous carbon nanosheets (3DPC) are invited to reduce the resistance towards electrolyte/oxygen diffusion. Thereby, Co-CoTe@3DPC only demands 280 mV overpotential to reach 10 mA cm-2 under alkaline oxygen evolution reaction (OER) condition, relatively lower than commercial iridium oxides (IrO2); besides, the operando electrochemical impedance spectroscopy (EIS) indicates a better resistance towards surface reconstruction than Co@3DPC leading to a superior stability. A Pt-like oxygen reduction reaction (ORR) performance, half-wave potential associated with kinetic current density, is achieved for Co-CoTe@3DPC. A maximum power density of 203 mW cm-2 is achieved and sustains for 800 h. Furthermore, the all-solid-state ZAB offers 97 mW cm-2. Theoretical calculation suggests that the incorporation of metallic Co to CoTe maintains the superb ORR activity and promotes the OER catalysis.

Application of Zinc Oxide Nanoparticles to Mitigate Cadmium Toxicity: Mechanisms and Future Prospects.

Cadmium (Cd), as the most prevalent heavy metal contaminant poses serious risks to plants, humans, and the environment. The ubiquity of this toxic metal is continuously increasing due to the rapid discharge of industrial and mining effluents and the excessive use of chemical fertilizers. Nanoparticles (NPs) have emerged as a novel strategy to alleviate Cd toxicity. Zinc oxide nanoparticles (ZnO-NPs) have become the most important NPs used to mitigate the toxicity of abiotic stresses and improve crop productivity. The plants quickly absorb Cd, which subsequently disrupts plant physiological and biochemical processes and increases the production of reactive oxygen species (ROS), which causes the oxidation of cellular structures and significant growth losses. Besides this, Cd toxicity also disrupts leaf osmotic pressure, nutrient uptake, membrane stability, chlorophyll synthesis, and enzyme activities, leading to a serious reduction in growth and biomass productivity. Though plants possess an excellent defense mechanism to counteract Cd toxicity, this is not enough to counter higher concentrations of Cd toxicity. Applying Zn-NPs has proven to have significant potential in mitigating the toxic effects of Cd. ZnO-NPs improve chlorophyll synthesis, photosynthetic efficiency, membrane stability, nutrient uptake, and gene expression, which can help to counter toxic effects of Cd stress. Additionally, ZnO-NPs also help to reduce Cd absorption and accumulation in plants, and the complex relationship between ZnO-NPs, osmolytes, hormones, and secondary metabolites plays an important role in Cd tolerance. Thus, this review concentrates on exploring the diverse mechanisms by which ZnO nanoparticles can alleviate Cd toxicity in plants. In the end, this review has identified various research gaps that need addressing to ensure the promising future of ZnO-NPs in mitigating Cd toxicity. The findings of this review contribute to gaining a deeper understanding of the role of ZnO-NPs in combating Cd toxicity to promote safer and sustainable crop production by remediating Cd-polluted soils. This also allows for the development of eco-friendly approaches to remediate Cd-polluted soils to improve soil fertility and environmental quality.

Direct Synthesis of α-Ketothioamide Derivatives through a One-Pot Reaction of Sulfur Ylides, Nitrosobenzenes, and Thioacetic Acid.

A one-pot approach has been developed for the synthesis of α-ketothioamide derivatives from sulfur ylides, nitrosobenzenes, and thioacetic acid. This protocol is carried out under mild reaction conditions in generally moderate to excellent yields without any precious catalysts, affording the derivatives with structural diversity. Additionally, a possible mechanism for this chemical transformation is proposed.

20( S )-Protopanaxatriol Improves Atherosclerosis by Inhibiting Low-Density Lipoprotein Receptor Degradation in ApoE KO Mice.

ABSTRACT: Atherosclerosis (AS) is a chronic progressive disease caused by various factors and causes various cerebrovascular and cardiovascular diseases (CVDs). Reducing the plasma levels of low-density lipoprotein cholesterol is the primary goal in preventing and treating AS. Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a crucial role in regulating low-density lipoprotein cholesterol metabolism. Panax notoginseng has potent lipid-reducing effects and protects against CVDs, and its saponins induce vascular dilatation, inhibit thrombus formation, and are used in treating CVDs. However, the anti-AS effect of the secondary metabolite, 20( S )-protopanaxatriol (20( S )-PPT), remains unclear. In this study, the anti-AS effect and molecular mechanism of 20( S )-PPT were investigated in vivo and in vitro by Western blotting, real-time polymerase chain reaction, enzyme-linked immunosorbent assay, immunofluorescence staining, and other assays. The in vitro experiments revealed that 20( S )-PPT reduced the levels of PCSK9 in the supernatant of HepG2 cells, upregulated low-density lipoprotein receptor protein levels, promoted low-density lipoprotein uptake by HepG2 cells, and reduced PCSK9 mRNA transcription by upregulating the levels of forkhead box O3 protein and mRNA and decreasing the levels of HNF1α and SREBP2 protein and mRNA. The in vivo experiments revealed that 20( S )-PPT upregulated aortic α-smooth muscle actin expression, increased the stability of atherosclerotic plaques, and reduced aortic plaque formation induced by a high-cholesterol diet in ApoE -/- mice (high-cholesterol diet-fed group). Additionally, 20( S )-PPT reduced the aortic expression of CD68, reduced inflammation in the aortic root, and alleviated the hepatic lesions in the high-cholesterol diet-fed group. The study revealed that 20( S )-PPT inhibited low-density lipoprotein receptor degradation via PCSK9 to alleviate AS.

Combined toxic effects of fluxapyroxad and multi-walled carbon nanotubes in Xenopus laevis larvae.

Carbon nanomaterials rarely exist in isolation in the natural environment, and their combined effects cannot be ignored. Multi-walled carbon nanotubes (MWCNTs) have shown tremendous potential applications in diverse fields, including pollution remediation, biomedicine, energy, and smart agriculture. However, the combined toxicities of MWCNTs and pesticides on non-target organisms, particularly amphibians, are often overlooked. Fluxapyroxad (FLX), a significant succinate dehydrogenase inhibitor fungicide, has been extensively utilized for the protection of food and cash crops and control of fungi. This raises the possibility of coexistence of MWCNTs and FLX. The objective of this study was to explore the individual and combined toxic effects of FLX and MWCNTs on the early life stages of Xenopus laevis. Embryos were exposed to varying concentrations of FLX (0, 5, and 50 µg/L) either alone or in combination with MWCNTs (100 µg/L) for a duration of 17 days. The findings indicated that co-exposure to FLX and MWCNTs worsened the inhibition of growth, liver damage, and dysregulation of enzymatic activity in tadpoles. Liver transcriptomic analysis further revealed that the presence of MWCNTs exacerbated the disturbances in glucose and lipid metabolism caused by FLX. Additionally, the combined exposure groups exhibited amplified alterations in the composition and function of the gut microflora. Our study suggests that it is imperative to pay greater attention to the agricultural applications, management and ecological risks of MWCNTs in the future, considering MWCNTs may significantly enhance the toxicity of FLX.

Causal relationship between rheumatoid arthritis and epilepsy in a European population: a univariate and multivariate Mendelian randomization study.

Background: Several previous studies have reported an association between rheumatoid arthritis (RA) and epilepsy, but the causal relationship is unclear. The aim of this study was to assess the connection between RA and epilepsy in a European population using Mendelian randomization (MR). Methods: Genome-wide association study summary data on RA and epilepsy from European populations were included. Univariate MR (UVMR) and multivariate MR were used to investigate the causal relationship between the two conditions. Three analysis methods were applied: inverse variance weight (IVW), MR-Egger, and weighted median, with IVW being the primary method. Cochran Q statistics, MR-PRESSO, MR-Egger intercept, leave-one-out test, and MR-Steiger test were combined for the sensitivity analysis. Results: UVMR showed a positive association between RA and epilepsy risk (OR=1.038, 95% CI=1.007-1.038, p=0.017) that was supported by sensitivity analysis. Further MVMR after harmonizing the three covariates of hypertension, alcohol consumption, and smoking, confirmed the causal relationship between RA and epilepsy (OR=1.049, 95% CI=1.011-1.087, p=0.010). Conclusion: This study demonstrated that RA is associated with an increased risk of epilepsy. It has emphasized that the monitoring of epilepsy risk in patients diagnosed with RA should be strengthened in clinical practice, and further studies are needed in the future to explore the potential mechanism of action connecting the two conditions.

Dorsolateral septum GLP-1R neurons regulate feeding via lateral hypothalamic projections.

OBJECTIVE: Although glucagon-like peptide 1 (GLP-1) is known to regulate feeding, the central mechanisms contributing to this function remain enigmatic. Here, we aim to test the role of neurons expressing GLP-1 receptors (GLP-1R) in the dorsolateral septum (dLS; dLSGLP-1R) that project to the lateral hypothalamic area (LHA) on food intake and determine the relationship with feeding regulation. METHODS: Using chemogenetic manipulations, we assessed how activation or inhibition of dLSGLP-1R neurons affected food intake in Glp1r-ires-Cre mice. Then, we used channelrhodopsin-assisted circuit mapping, chemogenetics, and electrophysiological recordings to identify and assess the role of the pathway from dLSGLP-1R →LHA projections in regulating food intake. RESULTS: Chemogenetic inhibition of dLSGLP-1R neurons increases food intake. LHA is a major downstream target of dLSGLP-1R neurons. The dLSGLP-1R→LHA projections are GABAergic, and chemogenetic inhibition of this pathway also promotes food intake. While chemogenetic activation of dLSGLP-1R→LHA projections modestly decreases food intake, optogenetic stimulation of the dLSGLP-1R→LHA projection terminals in the LHA rapidly suppresses feeding behavior. Finally, we demonstrate that the GLP-1R agonist, Exendin 4 enhances dLSGLP-1R →LHA GABA release. CONCLUSIONS: Together, these results demonstrate that dLS-GLP-1R neurons and the inhibitory pathway to LHA can regulate feeding behavior, which might serve as a potential therapeutic target for the treatment of eating disorders or obesity.

Crystal structure of the photosensory module from a PAS-less cyanobacterial phytochrome as Pr shows a mix of dark-adapted and photoactivated features.

Phytochromes (Phys) are a diverse collection of photoreceptors that regulate numerous physiological and developmental processes in microorganisms and plants through photointerconversion between red-light-absorbing Pr and far-red light-absorbing Pfr states. Light is detected by an N-terminal photo-sensing module (PSM) sequentially comprised of Period/ARNT/Sim (PAS), cGMP-phosphodiesterase/adenylyl cyclase/FhlA (GAF), and Phy-specific (PHY) domains, with the bilin chromophore covalently-bound within the GAF domain. Phys sense light via the Pr/Pfr ratio measured by the light-induced rotation of the bilin D-pyrrole ring that triggers conformational changes within the PSM, which for microbial Phys reaches into an output region. A key step is a ß-stranded to α-helical reconfiguration of a hairpin loop extending from the PHY domain to contact the GAF domain. Besides canonical Phys, cyanobacteria express several variants, including a PAS-less subfamily that harbors just the GAF and PHY domains for light detection. Prior 2D-NMR studies of a model PAS-less Phy from Synechococcus_sp._JA-2-3B'a(2-13) (SyB-Cph1) proposed a unique photoconversion mechanism involving an A-pyrrole ring rotation while magic-angle-spinning NMR probing the chromophore proposed the prototypic D-ring flip. To help solve this conundrum, we determined the crystallographic structure of the GAF-PHY region from SyB-Cph1 as Pr. Surprisingly, this structure differs from canonical Phys by having a Pr ZZZsyn,syn,anti bilin configuration but shifted to the activated position in the binding pocket with consequent folding of the hairpin loop to α-helical, an architecture common for Pfr. Collectively, the PSM of SyB-Cph1 as Pr displayed a mix of dark-adapted and photoactivated features whose co-planar A-C pyrrole rings support a D-ring flip mechanism.

HELQ deficiency impairs the induction of primordial germ cell-like cells.

Helicase POLQ-like (HELQ) is a DNA helicase essential for the maintenance of genome stability. A recent study identified two HELQ missense mutations in some cases of infertile men. However, the functions of HELQ in the process of germline specification are not well known and whether its function is conserved between mouse and human remains unclear. Here, we revealed that Helq knockout (Helq-/-) could significantly reduce the efficiency of mouse primordial germ cell-like cell (PGCLC) induction. In addition, Helq-/- embryonic bodies exhibited a severe apoptotic phenotype on day 6 of mouse PGCLC induction. p53 inhibitor treatment could partially rescue the generation of mouse PGCLCs from Helq mutant mouse embryonic stem cells. Finally, the genetic ablation of HELQ could also significantly impede the induction of human PGCLCs. Collectively, our study sheds light on the involvement of HELQ in the induction of both mouse and human PGCLCs, providing new insights into the mechanisms underlying germline differentiation and the genetic studies of human fertility.

Solvent-free preparation and thermocompression self-assembly: an exploration of performance improvement strategies for perovskite solar cells.

Perovskite solar cells (PSCs) exhibit sufficient technological efficiency and economic competitiveness. However, their poor stability and scalability are crucial factors limiting their rapid development. Therefore, achieving both high efficiency and good stability is an urgent challenge. In addition, the preparation methods for PSCs are currently limited to laboratory-scale methods, so their commercialization requires further research. Effective packaging technology is essential to protect the PSCs from degradation by external environmental factors and ensure their long-term stability. The industrialization of PSCs is also inseparable from the preparation technology of perovskite thin films. This review discusses the solvent-free preparation of PSCs, shedding light on the factors that affect PSC performance and strategies for performance enhancement. Furthermore, this review analyzes the existing simulation techniques that have contributed to a better understanding of the interfacial evolution of PSCs during the packaging process. Finally, the current challenges and possible solutions are highlighted, providing insights to facilitate the development of highly efficient and stable PSC modules to promote their widespread application.

Portable T-2 toxin biosensor based on target-responsive DNA hydrogel using water column height as readout.

T-2 toxin, a hazardous mycotoxin often present in cereals and products based on cereals, poses a substantial risk to humans and animals due to its high toxicity. The development of uncomplicated, quick and highly sensitive methods for detecting T-2 toxin is imperative. In this work, a portable sensing system was constructed using water column height as a readout device in combination with a controlled release system, which allows for an accurate quantitative analysis of T-2 toxin without the need for expensive instrumentation or skilled technicians. Hyaluronic acid (HA) hydrogel was constructed by double cross-linked DNA/aptamer hybrids with polyethyleneimine (PEI) and embedded with platinum nanoparticles (Pt NPs). The aptamer specifically bound to T-2 toxin in its presence, resulting in the disruption of the hydrogel and subsequent release of the Pt NPs. These Pt NPs were later mixed with a solution of H2O2 in a confined reaction flask, leading to the decomposition of H2O2 into O2. A glass capillary tube containing a column of red water had been inserted into the cap of the reaction flask, and the low solubility of O2 led to an increase in pressure within the reaction unit, causing the red water column to rise. There is a good linear correlation between the height of the capillary liquid level and the T-2 toxin concentration in the range of 20 ng/mL to 6 µg/mL. The system has been successfully used to detect T-2 toxin in samples of barley tea and corn.

Synthesis and antitumor activities of novel 3-(6-aminopyridin-3-yl)benzamide derivatives: Inducing cell cycle arrest and apoptosis via AURKB transcription inhibition.

Here, a series of 3-(6-aminopyridin-3-yl) benzamide derivatives were designed and synthesized. Cell viability assay indicated that most compounds exhibited potent antiproliferative activity against all the tested cancer cells. Among them, compound 7l displayed the best antiproliferative activity particularly in A549 cells, with an IC50 value of 0.04 ± 0.01 µM. RNA-seq analysis was employed to explore the potential pathways related to the antiproliferative activity of compound 7l. The data revealed that 7l exerted antiproliferative activity mainly by regulating cell cycle, DNA replication and p53 signaling pathway. Indeed, compound 7l induced G2/M phase arrest by AURKB transcription inhibition and resulted in cell apoptosis via p53 signaling pathway. Most importantly, compound 7l demonstrated potent antitumor activity in A549 xenograft tumor model. Collectively, 7l might be a promising lead compound for the development of new therapeutic agents for AURKB overexpressed or mutated cancers.

A superior zinc-air battery performance achieved by CoO/Fe3O4 heterostructured nanosheets.

CoO/Fe3O4 nanosheets exhibit a superior rechargeable zinc-air battery (ZAB) performance of 276 mW cm-2 and stability over 600 h. The all-solid-state ZAB also affords a high power density of 107 mW cm-2.

Physical conditioning methods for sludge deep dewatering: A critical review.

Sludge is an inevitable waste product of sewage treatment with a high water content and large volume, it poses a significant threat of secondary pollution to both water and the atmosphere without proper disposal. In this regard, dewatering has emerged as an attractive method in sludge treatment, as it can reduce the sludge volume, enhance its transportability and calorific value, and even decrease the production of landfill leachate. In recent years, physical conditioning methods including non-chemical conditioners or energy input alone, have been extensively researched for their potential to enhance sludge dewatering efficiency, such as thermal treatment, freeze-thaw, microwave, ultrasonic, skeleton builders addition, and electro-dewatering, as well as combined methods. The main objective of this paper is to comprehensively evaluate the dewatering capacity of various physical conditioning methods, and identify key factors affecting sludge dewatering efficiency. In addition, future research anticipated directions and outlooks are proposed. This work is expected to provide valuable insights for developing efficient, eco-friendly, and low-energy consumption techniques for deep sludge dewatering.

Effectiveness and Safety of Flupentixol and Melitracen Tablets for the Treatment of Patients with Persistent Idiopathic Facial Pain: A Retrospective Observational Study.

BACKGROUND: Flupentixol and melitracen are being investigated for their potential effectiveness in managing persistent idiopathic facial pain (PIFP), based on their mechanisms of action as dopamine receptor antagonists and noradrenaline/serotonin reuptake inhibitors, respectively. The efficacy and safety of flupentixol and melitracen (FM) tablets in treating PIFP were retrospectively analyzed at our hospital. OBJECTIVES: The aim of this study is to determine the effectiveness and safety of FM tablets in treating PIFP. STUDY DESIGN: Retrospective unicentric cohort design. SETTING: An academic university hospital. METHODS: A retrospective analysis was conducted on a cohort comprising 128 patients with a definite diagnoses of PIFP who were treated with FM tablets (flupentixol 0.5 mg and melitracen 10 mg tablet, >= 4 tablets/d) from January 2022 through May 2023 at an academic university hospital. Baseline conditions were statistically described, and Numeric Rating Scale (NRS-11) scores of pain levels before and during treatment were collected. Pain relief rates were calculated. Differences in baseline characteristics between responsive and unresponsive patients were evaluated using statistical tests. Additionally, the side effects experienced during treatment were summarized. RESULTS: Among the included 128 patients, 105 (82.0%) patients achieved pain relief (pain NRS-11 score reduction rate >= 50%). The median treatment onset time was 3 (1-7) days. NRS-11 scores of responsive patients at week 2, week 4, week 8, and week 12 were significantly lower than the baseline NRS-11 scores (P < 0.001), regardless of their Hamilton Depression Rating Scale score. Pain duration was the only factor that related to responsiveness (Wilcoxon rank sum test, P < 0.001; logistic regression, P = 0.001). No serious side effects that could affect patients' lives were observed during the first week of treatments. LIMITATIONS: Due to its retrospective nature, this study is limited by its lack of a randomized control. The lack of data on nonresponders who did not achieve significant pain relief hinders assessing overall change and the placebo effects'. Patients previously treated with antidepressants were excluded, making it hard to determine if FM tablets were a better treatment for PIFP. Additionally, the small sample size in a single center may be influenced by chance variation in pain relief. CONCLUSIONS: FM tablets showed its potential in the management of PIFP with considerable efficacy and safety. Early administration of FM tablets after a PIFP diagnosis may result in a high possibility of pain relief.

Deep dewatering of sludge and resource recovery of hydroxyapatite: A recyclable approach via ionic liquid biphasic system and hydrogen bonds reformation.

Deep dewatering of Waste Activated Sludge (WAS) through mechanical processes remains inefficient, primarily due to the formation of a stable hydrogen bonding network between the biopolymers and water, which consequently leads to significant water trapped by Extracellular Polymeric Substances (EPS). In this study, a novel and recyclable treatment for WAS based on Ionic Liquids (ILs) was established, named IL-biphasic aqueous system (IL-ABS) treatment. Specifically, the IL-ABS formed in WAS facilitated rapid and efficient in-situ deep dewatering while concurrently recovering hydroxyapatite. The water content decreased from an initial 98.27 % to 65.35 % with IL-ABS, formed by 1-Butyl-3-methylimidazolium bromide (BmimBr) and K3PO4 synthesized from waste H3PO4. Moreover, the recycled BmimBr maintaining the water content of the dewatered sludge consistently between 65.61 % and 67.25 % across five cycles, exhibited remarkable reproducibility. Through three-dimensional excitation-emission matrix, lactate dehydrogenase analyses and confocal laser scanning microscopy, the high concentration of BmimBr in the upper phase effectively disrupted the cells and EPS, which exposed protein and polysaccharide on the EPS surface. Subsequently, the K3PO4 in the lower phase led to an enhanced salting-out effect in WAS. Furthermore, FT-IR analysis revealed that K3PO4 disrupted the original hydrogen bonds between EPS and water. Then, BmimBr formed numerous hydrogen bonds with the sludge flocs, leading to deep dewatering and agglomeration of the sludge flocs during the unique phase separation process of IL-ABS. Notably, sludge-derived hydroxyapatite product exhibited remarkable adsorption capacity for prevalent heavy metal contaminants such as Pb2+, Cd2+ and Cu2+, with efficiencies comparable to those of commercial hydroxyapatite, thereby achieving the resource utilization of waste H3PO4. Moreover, economic calculations demonstrated the suitability of this novel treatment. This innovative treatment exhibits potential for practical applications in the non-mechanical deep dewatering of WAS.

Characterizing genetic variation on the Z chromosome in Schistosoma japonicum reveals host-parasite co-evolution.

BACKGROUND: Schistosomiasis is a neglected tropical disease that afflicts millions of people worldwide; it is caused by Schistosoma, the only dioecious flukes with ZW systems. Schistosoma japonicum is endemic to Asia; the Z chromosome of S. japonicum comprises one-quarter of the entire genome. Detection of positive selection using resequencing data to understand adaptive evolution has been applied to a variety of pathogens, including S. japonicum. However, the contribution of the Z chromosome to evolution and adaptation is often neglected. METHODS: We obtained 1,077,526 high-quality SNPs on the Z chromosome in 72 S. japonicum using re-sequencing data publicly. To examine the faster Z effect, we compared the sequence divergence of S. japonicum with two closely related species, Schistosoma haematobium and S. mansoni. Genetic diversity was compared between the Z chromosome and autosomes in S. japonicum by calculating the nucleotide diversity (π) and Dxy values. Population structure was also assessed based on PCA and structure analysis. Besides, we employed multiple methods including Tajima's D, FST, iHS, XP-EHH, and CMS to detect positive selection signals on the Z chromosome. Further RNAi knockdown experiments were performed to investigate the potential biological functions of the candidate genes. RESULTS: Our study found that the Z chromosome of S. japonicum showed faster evolution and more pronounced genetic divergence than autosomes, although the effect may be smaller than the variation among genes. Compared with autosomes, the Z chromosome in S. japonicum had a more pronounced genetic divergence of sub-populations. Notably, we identified a set of candidate genes associated with host-parasite co-evolution. In particular, LCAT exhibited significant selection signals within the Taiwan population. Further RNA interference experiments suggested that LCAT is necessary for S. japonicum survival and propagation in the definitive host. In addition, we identified several genes related to the specificity of the intermediate host in the C-M population, including Rab6 and VCP, which are involved in adaptive immune evasion to the host. CONCLUSIONS: Our study provides valuable insights into the adaptive evolution of the Z chromosome in S. japonicum and further advances our understanding of the co-evolution of this medically important parasite and its hosts.

Ethnic disparities and temporal trends in health resource allocation: a retrospective decadal analysis in Sichuan, a multi-ethnic Province of Southwest China (2009-2019).

BACKGROUND: Research on health resource allocation trends in ethnic minority and impoverished areas in China is limited since the 2009 Medical Reform. This study aimed to investigate the variations and inequalities in health resource distribution among ethnic minority, poverty-stricken, and non-minority regions in Sichuan Province, a multi-ethnic province in Southwest China, from 2009 to 2019. METHODS: The numbers of beds, doctors and nurses were retrospectively sourced from the Sichuan Health Statistics Yearbook between 2009 and 2019. All the 181 counties in Sichuan Province were categorized into five groups: Yi, Zang, other ethnic minority, poverty-stricken, and non-minority county. The Theil index, adjusted for population size, was used to evaluate health resource allocation inequalities. RESULTS: From 2009 to 2019, the number of beds (Bedp1000), doctors (Docp1000), and nurses (Nurp1000) per 1000 individuals in ethnic minority and poverty-stricken counties consistently remained lower than non-minority counties. The growth rates of Bedp1000 in Yi (140%) and other ethnic minority counties (127%) were higher than in non-minority counties (121%), while the growth rates of Docp1000 in Yi (20%) and Zang (11%) counties were lower than non-minority counties (61%). Docp1000 in 33% and 50% of Yi and Zang ethnic counties decreased, respectively. Nurp1000 in Yi (240%) and other ethnic minority (316%) counties increased faster than non-minority counties (198%). The Theil index for beds and nurses declined, while the index for doctors increased. Key factors driving increases in bed allocation include preferential policies and economic development levels, while health practitioner income, economic development levels and geographical environment significantly influence doctor and nurse allocation. CONCLUSIONS: Preferential policies have been successful in increasing the number of beds in health facilities, but not healthcare workers, in ethnic minority regions. The ethnic disparities in doctor allocation increased in Sichuan Province. To increase the number of doctors and nurses in ethnic minority and poverty-stricken regions, particularly in Yi counties, more preferential policies and resources should be introduced.

Dorsolateral septum GLP-1R neurons regulate feeding via lateral hypothalamic projections.

Objective: Although glucagon-like peptide 1 (GLP-1) is known to regulate feeding, the central mechanisms contributing to this function remain enigmatic. Here, we aim to test the role of neurons expressing GLP-1 receptors (GLP-1R) in the dorsolateral septum (dLS; dLS GLP-1R ) and their downstream projections on food intake and determine the relationship with feeding regulation. Methods: Using chemogenetic manipulations, we assessed how activation or inhibition of dLS GLP-1R neurons affected food intake in Glp1r-ires-Cre mice. Then, we used channelrhodopsin-assisted circuit mapping, chemogenetics, and electrophysiological recordings to identify and assess the role of the pathway from dLS GLP-1R neurons to the lateral hypothalamic area (LHA) in regulating food intake. Results: Chemogenetic inhibition of dLS GLP-1R neurons increases food intake. LHA is a major downstream target of dLS GLP-1R neurons. The dLS GLP-1R →LHA projections are GABAergic, and chemogenetic inhibition of this pathway also promotes food intake. While chemogenetic activation of dLS GLP-1R →LHA projections modestly decreases food intake, optogenetic stimulation of the dLS GLP-1R →LHA projection terminals in the LHA rapidly suppressed feeding behavior. Finally, we demonstrate that the GLP-1R agonist, Exendin 4 enhances dLS GLP-1R →LHA GABA release. Conclusions: Together, these results demonstrate that dLS-GLP-1R neurons and the inhibitory pathway to LHA can regulate feeding behavior, which might serve as a potential therapeutic target for the treatment of eating disorders or obesity. Highlights: Chemogenetic inhibition of dLS GLP-1R neurons boosts food intake in mice dLS GLP-1R neuron activation does not alter feeding, likely by collateral inhibition dLS GLP-1R neurons project to LHA and release GABA Activation of dLS GLP-1R →LHA axonal terminals suppresses food intake GLP-1R agonism enhances dLS GLP-1R →LHA GABA release via a presynaptic mechanism.