Biomimetic nanoplatform with microbiome modulation and antioxidant functions ameliorating insulin resistance and pancreatic ß-cell dysfunction for T2DM management.

Insulin resistance and pancreatic ß-cell dysfunction are the main pathogenesis of type 2 diabetes mellitus (T2DM). However, insulin therapy and diabetes medications do not effectively solve the two problems simultaneously. In this study, a biomimetic oral hydrogen nanogenerator that leverages the benefits of edible plant-derived exosomes and hydrogen therapy was constructed to overcome this dilemma by modulating gut microbiota and ameliorating oxidative stress and inflammatory responses. Hollow mesoporous silica (HMS) nanoparticles encapsulating ammonia borane (A) were used to overcome the inefficiency of H2 delivery in traditional hydrogen therapy, and exosomes originating from ginger (GE) were employed to enhance biocompatibility and regulate intestinal flora. Our study showed that HMS/A@GE not only considerably ameliorated insulin resistance and liver steatosis, but inhibited the dedifferentiation of islet ß-cell and enhanced pancreatic ß-cell proportion in T2DM model mice. In addition to its antioxidant and anti-inflammatory effects, HMS/A@GE augmented the abundance of Lactobacilli spp. and tryptophan metabolites, such as indole and indole acetic acid, which further activated the AhR/IL-22 pathway to improve intestinal-barrier function and metabolic impairments. This study offers a potentially viable strategy for addressing the current limitations of diabetes treatment by integrating gut-microbiota remodelling with antioxidant therapies.

Gastrodin alleviates diabetic peripheral neuropathy by regulating energy homeostasis via activating AMPK and inhibiting MMP9.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is a serious complication of diabetes that lacks effective treatment. Gastrodin, the primary bioactive compound derived from Rhizoma Gastrodiae, has a long history in treating epilepsy and various central nervous system disorders. However, its effect on DPN remains uncertain. PURPOSE: This study aims to explore the therapeutic potential and underlying mechanisms of gastrodin in the treatment of DPN. METHOD: DPN model rats were induced with streptozotocin (STZ) injection and divided into four groups receiving either gastrodin at two doses (30 and 60 mg kg-1 per day), α-lipoic acid (positive drug, 60 mg kg-1 per day), or placebo. Healthy rats were administrated with placebo. The administrations began eight weeks post-STZ injection and continued for six weeks. Following a comprehensive evaluation of the neuroprotective effects, a systematic pharmacology-based approach was subsequently employed to investigate the underlying mechanism of gastrodin in vivo and in vitro. RESULTS: Gastrodin was demonstrated to effectively enhance peripheral nerve function and reduce pathological damages in DPN rats. Furthermore, gastrodin facilitated the expression of remyelination-related proteins and mitigated oxidative stress in DPN rats. Transcriptomic analysis indicated that the modulation of energy metabolism was pivotal in the neuroprotective effect of gastrodin, corroborated by targeted metabolomic analysis using high-performance ion chromatography coupled with mass spectrometry. Using network pharmacology analysis, 12 potential targets of gastrodin were identified. Among these, matrix metallopeptidase 9 (MMP9) was further validated as the primary target through molecular docking and cellular thermal shift assays. Functional Analysis of the potential targets underscored the pivotal role of AMPK signaling, and gastrodin demonstrated the capability to activate AMPK and inhibit MMP9 in vivo. In vitro studies further found that gastrodin enhanced antioxidant capacity and mitochondrial function of high glucose-cultured rat Schwann cells RSC96 in an AMPK-dependent manner. Inhibition of AMPK hindered the decrease of MMP9 induced by gastrodin in vitro. CONCLUSION: This study revealed the new role of gastrodin in alleviating DPN by restoring the homeostasis of energy metabolism through activating AMPK and inhibiting MMP9. These findings highlight gastrodin's potential as a novel therapeutic candidate against DPN, and underscores an appealing strategy of regulating energy metabolism for DPN therapy.

The effect of extracellular polymeric substances on the distribution and transmission of antibiotic resistance genes treating antibiotic wastewater via microbial electrolysis cells.

Microbial electrolysis cells (MEC) have emerged as a prominent technology for the treatment of antibiotics-containing wastewater in recent years. However, there remains a dearth of comprehensive exploration regarding the influence of extracellular polymers substances (EPS) on the distribution and transmission of antibiotic resistance genes (ARGs) in MEC. In this study, we quantified the distribution of ARGs in MEC by Fluorescence quantitative polymerase chain reaction and explored with emphasis on impact of EPS component on ARGs transmission at under different concentrations of roxithromycin. Results showed that the absolute abundance of ARGs in the electrode biofilm was 1-2 orders of magnitude higher than that in the anolyte. Specifically, EPS-associated ARGs accounted for 2.31%-11.18% of ARGs in electrode biofilm. The presence of elevated roxithromycin concentration led to electroactive microorganisms (Geobacter and Geothrix) as potential hosts of ARGs. In addition, both protein and polysaccharide content in the electrode biofilm increased with increasing roxithromycin concentration and showed positive correlations with EPS-associated ARGs. Fluorescence quenching experiments further elucidated that tryptophan and tyrosine residues in EPS could bind to ARGs effectively, contributing the hindering the ARGs transmission between hosts. Therefore, increased EPS content within electrode biofilm could reduce the concentration of ARGs present in anolyte while also influencing ARGs distribution throughout MEC. This study provides valuable insights into the distribution of ARGs in MEC systems and the role of EPS in regulating ARGs migration.

The application of endoscopic purse-string suture in refractory non-variceal gastrointestinal bleeding:a multicenter study (with video).

BACKGROUND AND AIMS: Non-variceal gastrointestinal bleeding is a common medical emergency. Endoscopic hemostasis is recommended and some patients experienced rebleeding after conventional endoscopic hemostasis. Originally, the purse-string suture (PSS) was employed for lesion closure during endoscopic mucosal resection (EMR). We aimed to learn whether endoscopic PSS is effective in controlling the refractory bleeding. METHODS: We retrospectively collected data of patients who underwent endoscopic PSS for refractory non-variceal gastrointestinal bleeding from 3 hospitals. Clinical success was defined as no recurrent bleeding, and patients were discharged according to medical advice. RESULTS: From October 2017 to May 2024, 36 patients who received PSS treatments were included. 83.3% (30/36) of patients achieved clinical success. In refractory upper gastrointestinal bleeding, the clinical success rate was 81.25% (26/32), and it was 100% (4/4) in lower gastrointestinal bleeding. CONCLUSION: The endoscopic PSS is effective in treating refractory non-variceal gastrointestinal bleeding.

Bibliometric analysis of research on spinal cord and sacral neuromodulation in spinal cord injury.

STUDY DESIGN: Qualitative studies. OBJECTIVES: Spinal cord injury (SCI) is one of the most devastating injuries to the central nervous system that places a major burden on society. Neuromodulation technology involving spinal cord stimulation (SCS) and sacral nerve modulation (SNM) is a promising technique for patients with SCI. However, there has been no bibliometric analysis of research in this field to date. SETTING: Not applicable. METHODS: Systematic analyses of countries, institutions, authors, journals, co-cited documents, keywords, genes and diseases were performed. Related gene and disease data from the citexs platform were also reviewed. A total of 7437 articles on SCS and SNM in SCI were retrieved from the Web of Science database. The search time was limited to 1985-01-01 to 2022-12-31. RESULTS: We identified a significant increase in research output on SCS and SNM in SCI in recent years, with a concentrated period of high publication activity. Multiple publications were identified on neuropathic pain, electronic stimulation, TNF, BDNF and STAT3 gene expression, indicating that complications and potential therapeutic strategies for SCI are a key focus in the field. CONCLUSION: Our study provides insights that may help to advance scientific research and potentially improve outcomes in patients with SCI.

Transformation of mulberry polyphenols by Lactobacillus plantarum SC-5: Increasing phenolic acids and enhancement of anti-aging effect.

Fermentation can transform bioactive compounds in food and improve their biological activity. This study aims to explore the transformation of polyphenols in mulberry juice and the improvement of its anti-aging effect. The results demonstrated that Lactobacillus plantarum SC-5 transformed anthocyanin in mulberry juice into more phenolic acids, especially improved 2-hydroxy-3-(4-hydroxyphenyl) propanoic acid from 4.16 ± 0.06 to 10.07 ± 0.03. In the D-gal-induced mouse model, fermented mulberry juice significantly raised the abundance of Bifidobacteriaceae (303.7 %) and Lactobacillaceae (237.2 %) and Short-chain fatty acids (SCFAs) in intestine, further reducing the level of oxidative stress (12.3 %). Meanwhile, the expression of Sirtuin 1 (SIRT1) and Brain-derived neurotrophic factor (BDNF) increased, which protected the integrity of hippocampal tissue. Morris water maze results approved that fermented mulberry juice improved cognitive ability in aging mice (30.3 %). This study provides theoretical support for the view that fermentation is an effective means of developing functional foods.

A Comprehensive Analysis Exploring the Impact of an Immunogenic Cell Death-Related Panel for Ovarian Cancer.

Ovarian cancer (OV) is a malignant tumor that ranks first among gynecological cancers, thus posing a significant threat to women's health. Immunogenic cell death (ICD) can regulate cell death by activating the adaptive immune system. Here, we aimed to comprehensively characterize the features of ICD-associated genes in ovarian cancer, and to investigate their prognostic value and role in the response to immunotherapy. After analyzing datasets from The Cancer Genome Atlas, we utilized weighted gene coexpression network analysis to screen for hub genes strongly correlated with ICD genes in OV, which was subsequently validated with OV samples from the Gene Expression Omnibus (GEO) database. A prognostic risk model was then constructed after combining univariate, multivariate Cox regression and LASSO regression analysis to recognize nine ICD-associated molecules. Next, we stratified all OV patients into two subgroups according to the median value. The multivariate Cox regression analysis showed that the risk model could predict OV patient survival with good accuracy. The same results were also found in the validation set from GEO. We then compared the degree of immune cell infiltration in the tumor microenvironment between the two subgroups of OV patients, and revealed that the high-risk subtype had a higher degree of immune infiltration than the low-risk subtype. Additionally, in contrast to patients in the high-risk subgroup, those in the low-risk subgroup were more susceptible to chemotherapy. In conclusion, our research offers an independent and validated model concerning ICD-related molecules to estimate the prognosis, degree of immune infiltration, and chemotherapy susceptibility in patients with OV.

Enhanced Predefined-Time Control for Spacecraft Attitude Tracking: A Dynamic Predictive Approach.

This study presents a predefined-time control strategy for rigid spacecraft, employing dynamic predictive techniques to achieve robust and precise attitude tracking within predefined time constraints. Advanced predictive algorithms are used to effectively mitigate system uncertainties and environmental disturbances. The main contributions of this work are introducing adaptive global optimization for period updates, which relaxes the original restrictive conditions; ensuring easier parameter adjustments in predefined-time control, providing a nonconservative upper bound on system stability; and developing a continuous, robust control law through terminal sliding mode control and predictive methods. Extensive simulations confirm the control scheme reduces attitude tracking errors to less than 0.01 degrees at steady state, demonstrating the effectiveness of the proposed control strategy.

Ultra-high-precision pneumatic force servo system based on a novel improved particle swarm optimization algorithm integrating Gaussian mutation and fuzzy theory.

In this study, an ultra-high-precision pneumatic force servo system (UPFSS) is proposed. On the one hand, a novel air-floating pneumatic cylinder (AFPC) with an air-floating piston capable of independent air supply and exhaust is developed for this system, and its special flow channel design allows the air-floating piston to be suspended in the cylinder without being constrained by the pressure in the chambers. The friction force of the AFPC is less than 0.0049 N. On the other hand, a leakage chamber is constructed to simulate the clearance between the air-floating piston and the cylinder wall, and a fuzzy proportional integral (FPI)-based pressure control system (PCS) is designed for the simulated leakage chamber. Furthermore, a novel particle swarm optimization algorithm integrating Gaussian mutation and fuzzy theory (IGF-PSO) is presented. After testing, the IGF-PSO algorithm is found to have outstanding optimization performance. Then, the parameters of the FPI controller are optimized through the IGFPSO algorithm. Experimental comparisons reveal that the steady-state error achieved by the parameter-optimized pressure controller in response to the leakage condition is about 38 % smaller than that achieved by the pressure controller with parameters obtained using the trial-and-error method. Finally, the UPFSS is tested by using the optimized PCS to supply compressed air to the chamber of the AFPC. The results show that the UPFSS achieves a steady-state error of no more than 0.0279 N in the continuous step response within the range of 240 N.

Customized Vascular Repair Microenvironment: Poly(lactic acid)-Gelatin Nanofibrous Scaffold Decorated with bFGF and Ag@Fe3O4 Core-Shell Nanowires.

Vascular defects caused by trauma or vascular diseases can significantly impact normal blood circulation, resulting in serious health complications. Vascular grafts have evolved as a popular approach for vascular reconstruction with promising outcomes. However, four of the greatest challenges for successful application of small-diameter vascular grafts are (1) postoperative anti-infection, (2) preventing thrombosis formation, (3) utilizing the inflammatory response to the graft to induce tissue regeneration and repair, and (4) noninvasive monitoring of the scaffold and integration. The present study demonstrated a basic fibroblast growth factor (bFGF) and oleic acid dispersed Ag@Fe3O4 core-shell nanowires (OA-Ag@Fe3O4 CSNWs) codecorated poly(lactic acid) (PLA)/gelatin (Gel) multifunctional electrospun vascular grafts (bAPG). The Ag@Fe3O4 CSNWs have sustained Ag+ release and exceptional photothermal capabilities to effectively suppress bacterial infections both in vitro and in vivo, noninvasive magnetic resonance imaging (MRI) modality to monitor the position of the graft, and antiplatelet adhesion properties to promise long-term patency. The gradually released bFGF from the bAPG scaffold promotes the M2 macrophage polarization and enhances the recruitment of macrophages, endothelial cells (ECs) and fibroblast cells. This significant regulation of diverse cell behavior has been proven to be beneficial to vascular repair and regeneration both in vitro and in vivo. Therefore, this study supplies a method to prepare multifunctional vascular-repair materials and is expected to represent a significant guidance and reference to the development of biomaterials for vascular tissue engineering.

CTRP6 alleviates endometrial fibrosis by regulating Smad3 pathway in intrauterine adhesion†.

Intrauterine adhesion (IUA) is manifestations of endometrial fibrosis and excessive extracellular matrix deposition. C1q/tumor necrosis factor-related protein-6 (CTRP6) is a newly identified adiponectin paralog which has been reported to modulate the fibrosis process of several diseases; however, the endometrial fibrosis function of CTRP6 remains unknown. Our study aimed to assess the role of CTRP6 in endometrial fibrosis and further explore the underlying mechanism. Here, we found that the expression of CTRP6 was downregulated in the endometrial tissues of IUA. In vitro experiments demonstrated the reduced level of CTRP6 in facilitated transforming growth factor-ß1 (TGF-ß1)-induced human endometrial stromal cells (HESCs). In addition, CTRP6 inhibited the expression of α-smooth muscle actin (α-SMA) and collagen I in TGF-ß1-treated HESCs. Mechanistically, CTRP6 activated the AMP-activated protein kinase (AMPK) and protein kinase B (AKT) pathway in HESCs, and AMPK inhibitor (AraA) or PI3K inhibitor (LY294002) pretreatment abolished the protective effect of CTRP6 on TGF-ß1-induced fibrosis. CTRP6 markedly decreased TGF-ß1-induced Smad3 phosphorylation and nuclear translocation, and AMPK or AKT inhibition reversed these effects. Notably, CTRP6-overexpressing treatment alleviated the fibrosis of endometrium in vivo. Therefore, CTRP6 ameliorates endometrial fibrosis, among which AMPK and AKT are essential for the anti-fibrotic effect of CTRP6 via the Smad3 pathway. Taken together, CTRP6 may be a potential therapeutic target for the treatment of intrauterine adhesion.

Diabetic peripheral neuropathy and glycemic variability assessed by continuous glucose monitoring: A systematic review and meta-analysis.

Continuous glucose monitoring (CGM)-derived metrics have been used to accurately assess glycemic variability (GV) to facilitate management of diabetes mellitus, yet their relationship with diabetic peripheral neuropathy (DPN) is not fully understood. We performed a systematic review and meta-analysis to evaluate the association between GV metrics and the risk of developing DPN. Nine studies totaling 3,649 patients with type 1 and type 2 diabetes mellitus were included. A significant association was found between increased GV, as indicated by metrics including standard deviation (SD) with OR and 95% CI of 2.58 (1.45-4.57), mean amplitude of glycemic excursions (MAGE) with OR and 95% CI of 1.90 (1.01-3.58), mean of daily difference (MODD) with OR and 95% CI of 2.88 (2.17-3.81) and the incidence of DPN. Our findings support a link between higher GV and an increased risk of DPN in patients with diabetes. These findings highlight the potential of GV metrics as indicators for the development of DPN, advocating for their inclusion in diabetes management strategies to potentially mitigate neuropathy risk. Longitudinal studies with longer observation periods and larger sample sizes are necessary to validate these associations across diverse populations.

Mediation Mendelian randomisation study on the effects of shift work on coronary heart disease and traditional risk factors via gut microbiota.

Background: Epidemiological evidence suggests that there is an increased risk of coronary heart disease (CHD) related to jobs involving shift work (JSW), but the causality of and mechanism underlying such a relationship remain unclear. Therefore, we aimed to explore the relationship between JSW and CHD, investigating both causality and potential mediating factors. Methods: We performed univariate, multivariate, and mediation Mendelian randomisation (MR) analyses using data from large genome-wide association studies focussed on JSW and CHD, as well as data on some CHD risk factors (type 2 diabetes, hypertension, obesity, and lipids measurement) and 196 gut microbiota taxa. Single-nucleotide polymorphisms significantly associated with JSW acted as instrument variables. We used inverse-variance weighting as the primary method of analysis. Results: Bidirectional MR analysis indicated a robust effect of JSW on increased CHD risk; however, the existence of CHD did not affect the choice of JSW. We identified a mediating effects of type 2 diabetes and hypertension in this relationship, accounting for 11.89% and 14.80% of the total effect of JSW on CHD, respectively. JSW were also causally associated with the risk of type 2 diabetes and hypertension and had an effect on nine microbial taxa. The mediating influence of the Eubacterium brachy group at the genus level explained 16.64% of the total effect of JSW on hypertension. We found limited evidence for the causal effect of JSW on obesity and lipids measurements. Conclusions: Our findings suggest a causal effect of JSW on CHD, diabetes, and hypertension. We also found evidence for a significant connection between JSW and alterations in the gut microbiota. Considering that certain microbial taxa mediated the effect of JSW on hypertension risk, targeting gut microbiota through therapeutics could potentially mitigate high risks of hypertension and CHD associated with JSW.

Guild-level signature of gut microbiome for diabetic kidney disease.

Current microbiome signatures for chronic diseases such as diabetic kidney disease (DKD) are mainly based on low-resolution taxa such as genus or phyla and are often inconsistent among studies. In microbial ecosystems, bacterial functions are strain specific, and taxonomically different bacteria tend to form co-abundance functional groups called guilds. Here, we identified guild-level signatures for DKD by performing in-depth metagenomic sequencing and conducting genome-centric and guild-based analysis on fecal samples from 116 DKD patients and 91 healthy subjects. Redundancy analysis on 1,543 high-quality metagenome-assembled genomes (HQMAGs) identified 54 HQMAGs that were differentially distributed among the young healthy control group, elderly healthy control group, early-stage DKD patients (EDG), and late-stage DKD patients (LDG). Co-abundance network analysis classified the 54 HQMAGs into two guilds. Compared to guild 2, guild 1 contained more short-chain fatty acid biosynthesis genes and fewer genes encoding uremic toxin indole biosynthesis, antibiotic resistance, and virulence factors. Guild indices, derived from the total abundance of guild members and their diversity, delineated DKD patients from healthy subjects and between different severities of DKD. Age-adjusted partial Spearman correlation analysis showed that the guild indices were correlated with DKD disease progression and with risk indicators of poor prognosis. We further validated that the random forest classification model established with the 54 HQMAGs was also applicable for classifying patients with end-stage renal disease and healthy subjects in an independent data set. Therefore, this genome-level, guild-based microbial analysis strategy may identify DKD patients with different severity at an earlier stage to guide clinical interventions. IMPORTANCE: Traditionally, microbiome research has been constrained by the reliance on taxonomic classifications that may not reflect the functional dynamics or the ecological interactions within microbial communities. By transcending these limitations with a genome-centric and guild-based analysis, our study sheds light on the intricate and specific interactions between microbial strains and diabetic kidney disease (DKD). We have unveiled two distinct microbial guilds with opposite influences on host health, which may redefine our understanding of microbial contributions to disease progression. The implications of our findings extend beyond mere association, providing potential pathways for intervention and opening new avenues for patient stratification in clinical settings. This work paves the way for a paradigm shift in microbiome research in DKD and potentially other chronic kidney diseases, from a focus on taxonomy to a more nuanced view of microbial ecology and function that is more closely aligned with clinical outcomes.

Altered ocular surface microbiota in obesity: a case-control study.

Purpose: This study aimed to investigate the composition of ocular surface microbiota in patients with obesity. Methods: This case-control study, spanning from November 2020 to March 2021 at Henan Provincial People's Hospital, involved 35 patients with obesity and an equivalent number of age and gender-matched healthy controls. By employing 16S rRNA sequencing, this study analyzed the differences in ocular surface microbiota between the two groups. The functional prediction analysis of the ocular surface microbiota was conducted using PICRUSt2. Results: The alpha diversity showed no notable differences in the richness or evenness of the ocular surface microbiota when comparing patients with obesity to healthy controls (Shannon index, P=0.1003). However, beta diversity highlighted significant variances in the microbiota composition of these two groups (ANOSIM, P=0.005). LEfSe analysis revealed that the relative abundances of Delftia, Cutibacterium, Aquabacterium, Acidovorax, Caulobacteraceae unclassified, Comamonas and Porphyromonas in patients with obesity were significantly increased (P<0.05). Predictive analysis using PICRUSt2 highlighted a significant enhancement in certain metabolic pathways in patients with obesity, notably xenobiotics metabolism via cytochrome P450 (CYP450), lipid metabolism, and the oligomerization domain (NOD)-like receptor signaling pathway (P<0.05). Conclusions: Patients with obesity exhibit a distinct ocular surface core microbiome. The observed variations in this microbiome may correlate with increased activity in CYP450, changes in lipid metabolism, and alterations in NOD-like receptor signaling pathways.

Defense Regulatory Network Associated with circRNA in Rice in Response to Brown Planthopper Infestation.

The brown planthopper (BPH), Nilaparvata lugens (Stål), a rice-specific pest, has risen to the top of the list of significant pathogens and insects in recent years. Host plant-mediated resistance is an efficient strategy for BPH control. Nonetheless, BPH resistance in rice cultivars has succumbed to the emergence of distinct virulent BPH populations. Circular RNAs (circRNAs) play a pivotal role in regulating plant-environment interactions; however, the mechanisms underlying their insect-resistant functions remain largely unexplored. In this study, we conducted an extensive genome-wide analysis using high-throughput sequencing to explore the response of rice circRNAs to BPH infestations. We identified a total of 186 circRNAs in IR56 rice across two distinct virulence groups: IR-IR56-BPH (referring to IR rice infested by IR56-BPH) and IR-TN1-BPH, along with a control group (IR-CK) without BPH infestation. Among them, 39 circRNAs were upregulated, and 43 circRNAs were downregulated in the comparison between IR-IR56-BPH and IR-CK. Furthermore, in comparison with IR-CK, 42 circRNAs exhibited upregulation in IR-TN1-BPH, while 42 circRNAs showed downregulation. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that the targets of differentially expressed circRNAs were considerably enriched in a multitude of biological processes closely linked to the response to BPH infestations. Furthermore, we assessed a total of 20 randomly selected circRNAs along with their corresponding expression levels. Moreover, we validated the regulatory impact of circRNAs on miRNAs and mRNAs. These findings have led us to construct a conceptual model that circRNA is associated with the defense regulatory network in rice, which is likely facilitated by the mediation of their parental genes and competing endogenous RNA (ceRNA) networks. This model contributes to the understanding of several extensively studied processes in rice-BPH interactions.

NEDD4 lactylation promotes APAP induced liver injury through Caspase11 dependent non-canonical pyroptosis.

Caspase-11 detection of intracellular lipopolysaccharide mediates non-canonical pyroptosis, which could result in inflammatory damage and organ lesions in various diseases such as sepsis. Our research found that lactate from the microenvironment of acetaminophen-induced acute liver injury increased Caspase-11 levels, enhanced gasdermin D activation and accelerated macrophage pyroptosis, which lead to exacerbation of liver injury. Further experiments unveiled that lactate inhibits Caspase-11 ubiquitination by reducing its binding to NEDD4, a negative regulator of Caspase-11. We also identified that lactates regulated NEDD4 K33 lactylation, which inhibits protein interactions between Caspase-11 and NEDD4. Moreover, restraining lactylation reduces non-canonical pyroptosis in macrophages and ameliorates liver injury. Our work links lactate to the exquisite regulation of the non-canonical inflammasome, and provides a basis for targeting lactylation signaling to combat Caspase-11-mediated non-canonical pyroptosis and acetaminophen-induced liver injury.

Mechanical strength changes of combustible municipal solid waste components during their early pyrolysis stage and mechanism analysis.

Implementation of municipal solid waste (MSW) source segregation leads to a more convenient recycle of combustible MSW components. Textiles, plastics and papers are commonly available combustible components in MSW. Their shredding is conducive to resources recovery. But these components usually have high tensile strengths and are difficult to shred. To understand their mechanical strength changes in their early pyrolysis stage will help to address this problem. In this study, a universal electronic testing machine was used to determine the breaking strengths of the materials including cotton towel, polyethylene glycol terephthalate (PET), ivory board (IB), kraft paper (KP) and wool scarf in the temperature range of 30-250°C under N2 atmosphere, and the mechanisms of their strength changes were explored. The reaction force field molecular dynamics (ReaxFF-MD) simulation was used to explain the decomposition behaviours of different sugar groups of hemicellulose in cotton and paper and the change of van der Waals energy of wool during their early pyrolysis stages. The results showed that breaking strengths of all the combustible MSW components reduced as the temperature increased. The breaking strength of PET was found to have the highest descent rate with increasing temperature, then the descent rates of wool and cotton came as the second and third, respectively. Compared with cotton, the breaking strengths of KP and IB decreased more slowly. As the temperature increased, the breaking strength of cotton reduced mainly due to the decomposition of the glucuronic acid in hemicellulose, and the reduction was characterized by CO2 release. The breaking strength reduction of PET was caused by its molecular chain being relaxed. The breaking strength reduction of wool was firstly caused by the decrease in the van der Waals energy between its molecules, and then caused by molecular chain breaking. In addition, in order to understand the influence of material size on the breaking strength change during thermal treatment, the breaking strengths of cotton yarn bundles were correlated with their yarn number and temperature. This study lays the foundation for understanding changes in mechanical strengths of combustible MSW components during their early pyrolysis stage.

Interplay of Systemic Immune-Inflammation Index and Serum Klotho Levels: Unveiling a New Dimension in Rheumatoid Arthritis Pathology.

Aim: The association between the systemic immune-inflammation index (SII) and serum Klotho concentrations (pg/ml) in patients with rheumatoid arthritis (RA) has not been elucidated. The purpose of this study was to clarify the relationship between the SII and serum Klotho concentrations in RA patients. Methods: All data come from the National Health and Nutrition Examination Survey (NHANES) database in the United States, which included 982 RA patients (age range: 40 to 79 years). The measurement data of the SII and serum Klotho are all from the NHANES mobile examination centre. We constructed a multivariate linear regression model to evaluate the association between the SII and serum Klotho levels in RA patients and conducted a subgroup analysis to test the stability of the statistical results. Results: Multivariate linear regression results indicated a negative linear relationship between the SII and serum Klotho concentrations in RA patients (ß = -6.33, 95% CI [confidence interval]: -10.15 to -2.53). Compared to the quartile 1 group, the quartile 4 group was associated with significantly lower (P<0.001) serum Klotho concentrations (ß = -120.93, 95% CI: -174.84 to -67.02). Compared with the quartile 1 group, with the increase in the SII, the ß value showed a decreasing trend (P trend < 0.001). The subgroup analysis showed that none of the covariates affected the stability of these results (all P for interaction ≥ 0.05). Conclusion: There is a significant negative linear association between the SII and serum Klotho concentrations in RA patients. The SII can serve as a predictive indicator of serum Klotho concentrations in RA patients, and Klotho may be a potential anti-inflammatory target for RA treatment.