Changes of masseter muscle after mandible distraction osteogenesis in patients with Hemifacial microsomia: a retrospective study.

Introduction: Mandible distraction osteogenesis (MDO) is widely used to reconstruct the mandible in patients with mild Hemifacial microsomia (HFM). However, the masseter's response to mandible distraction remains unclear. Methods: In this study, we analyze the effect of the surgical intervention on masseter muscle by a retrospective analysis. The procedure consisted of a five-day latent period, a three-week distraction period, and a six-month consolidation period. CT data were manually segmented and measured with Mimics software before surgery, within 3 months, and more than 1 year postoperatively. Masseter volume, masseter length, masseter width, and mandible ramus height were measured and analyzed using paired t-test, Pearson, and Spearman correlation analysis. Results: We included 21 patients with HFM who underwent mandible distraction osteogenesis from 2015 to 2020. The masseter volume on the affected side increased immediately after surgery from (6,505.33 ± 3,671.95) mm3 to (10,194.60 ± 5638.79) mm3, but decreased to (8,148.38 ± 3,472.57) mm3 at the second follow-up correlated to mandible ramus height (r = 0.395, P = 0.038). A similar trend was observed in changes in masseter length. Symmetry and width of masseter muscle had no longitudinal statistical significance. Discussion: Masseter muscle involvement benefits from MDO in the short term. To achieve long-term efficacy, more attention should be paid to muscle reconstruction.

Does sexual rehabilitation work for gay and bisexual prostate cancer patients? Acceptability, feasibility, and efficacy results from the Restore-2 randomized controlled trial.

PURPOSE: Sexual minority prostate cancer patients have worse health-related quality of life outcomes than heterosexual patients. We conducted the first study to test whether sexual and urinary rehabilitation tailored for sexual minority patients was acceptable, feasible, and efficacious at improving their sexual and urinary function. METHODS: Restore-2 was a 24-month randomized controlled trial of an online biopsychobehavioral rehabilitation study for sexual minority men treated for prostate cancer experiencing sexual and/or urinary problems. Participants were 401 US sexual minority men treated for prostate cancer and experiencing sexual and/or urinary problems at baseline. Intervention components included phosphodiesterase-5 inhibitors, sexual aids, a pelvic floor exercise regimen and video, a guide to good gay sex following treatment, and coaching. Quality of life assessments were completed at baseline, 3, 6, 12, 18, and 24 months. RESULTS: We confirmed good acceptability and feasibility, but only minimal improvement was observed over time and no differences were found between treatment and control arms. CONCLUSIONS: We found no evidence that the intervention improved sexual or urinary outcomes for participants. However, we confirmed excellent acceptability and feasibility for a sexual rehabilitation program tailored to sexual minority participants. In addition, participants reported enduring usage and acceptability of sexual aids (including vacuum pump, anal dilators, and penile constriction rings) as well as masturbation and pelvic floor exercises to accommodate their sexual challenges. IMPLICATIONS FOR CANCER SURVIVORS: Sexual "accommodation," rather than "rehabilitation," may be a more accurate and realistic goal for this population. Patients should be provided sexual aids to help accommodate their sexual and urinary challenges. TRIAL REGISTRATION: This study was retrospectively registered with ClinicalTrials.gov, study number: NCT03923582; date: 22/04/2019.

Enhancing Upper Limb Function and Motor Skills Post-Stroke Through an Upper Limb Rehabilitation Robot.

Cerebrovascular accidents, commonly known as strokes, represent a prevalent neurological event leading to significant upper limb disabilities, thereby profoundly affecting individuals' activities of daily living and diminishing their quality of life. Traditional rehabilitation methods for upper limb recovery post-stroke are often hindered by limitations, including therapist and patient fatigue, reliance on singular training methodologies, and lack of sustained motivation. Addressing these challenges, this study introduces an upper limb rehabilitation robot, which uses intelligent feedback motion control to improve therapeutic outcomes. The system is distinguished by its capability to adjust the direction and magnitude of force feedback dynamically, based on the detection of spastic movements during exercises, thereby offering a tailored therapeutic experience. This system is equipped with four distinct training modes, intelligent assessment of joint range of motion, and the ability to personalize training programs. Moreover, it provides an immersive interactive gaming experience coupled with comprehensive safety measures. This multifaceted approach not only elevates the engagement and interest of participants beyond traditional rehabilitation protocols but also demonstrates significant improvements in upper limb functionality and the activities of daily living among hemiplegic patients. The system exemplifies an advanced tool in upper limb rehabilitation, offering a synergistic blend of precision, personalization, and interactive engagement, thereby broadening the therapeutic options available to stroke survivors.

Immune isolation-enabled nanoencapsulation of donor T cells: a promising strategy for mitigating GVHD and treating AML in preclinical models.

BACKGROUND: In allogeneic-hematopoietic stem cell transplantation for acute myeloid leukemia (AML), donor T cells combat leukemia through the graft-versus-leukemia (GVL) effect, while they also pose a risk of triggering life-threatening graft-versus-host disease (GVHD) by interacting with recipient cells. The onset of GVHD hinges on the interplay between donor T cells and recipient antigen-presenting cells (APCs), sparking T-cell activation. However, effective methods to balance GVHD and GVL are lacking. METHODS: In our study, we crafted nanocapsules by layering polycationic aminated gelatin and polyanionic alginate onto the surface of T cells, examining potential alterations in their fundamental physiological functions. Subsequently, we established an AML mouse model and treated it with transplantation of bone marrow cells (BMCs) combined with encapsulated T cells to investigate the GVL and anti-GVHD effects of encapsulated T cells. In vitro co-culture was employed to probe the effects of encapsulation on immune synapses, co-stimulatory molecules, and tumor-killing pathways. RESULTS: Transplantation of BMCs combined with donor T cells selectively encapsulated onto AML mice significantly alleviates GVHD symptoms while preserving essential GVL effects. Encapsulated T cells exerted their immunomodulatory effects by impeding the formation of immune synapses with recipient APCs, thereby downregulating co-stimulatory signals such as CD28-CD80, ICOS-ICOSL, and CD40L-CD40. Recipient mice receiving encapsulated T-cell transplantation exhibited a marked increase in donor Ly-5.1-BMC cell numbers, accompanied by unaltered in vivo expression levels of perforin and granzyme B. While transient inhibition of donor T-cell cytotoxicity in the tumor microenvironment was observed in vitro following single-cell nanoencapsulation, subsequent restoration to normal antitumor activity ensued, attributed to selective permeability of encapsulated vesicle shells and material degradation. Moreover, the expression of apoptotic proteins and FAS-FAS ligand pathway at normal levels was still observed in leukemia tumor cells. CONCLUSIONS: Encapsulated donor T cells effectively mitigate GVHD while preserving the GVL effect by minimizing co-stimulatory signaling with APCs through early immune isolation. Subsequent degradation of nanocapsules restores T-cell cytotoxic efficacy against AML cells, mediated by cytotoxic pathways. Using transplant-encapsulated T cells offers a promising strategy to suppress GVHD while preserving the GVL effect.

8-Week Kaempferia parviflora Extract Administration Improves Submaximal Exercise Capacity in Mice by Enhancing Skeletal Muscle Antioxidant Gene Expression and Plasma Antioxidant Capacity.

Black ginger (Kaempferia parviflora) extract (KPE) is extracted from a ginger family plant grown in Thailand. The polyphenolic components have potential antioxidant effects and have been reported to enhance exercise performance. However, the impact of long-term KPE administration combined with long-term training on the endurance exercise performance of healthy individuals has not been fully studied. In this study, a healthy mouse model was used to investigate the effects of 8 weeks KPE administration and voluntary wheel running on the submaximal endurance exercise capacity and its mechanism. The results showed that 8 weeks of KPE administration significantly enhanced the submaximal endurance exercise capacity of mice and extended the daily voluntary wheel running distance. By measuring oxidative stress markers in plasma and the mRNA expression of antioxidant genes in skeletal muscle, we found that KPE significantly increased plasma antioxidant levels and activated the Nrf2 (Nuclear factor erythroid 2-related factor 2)/ARE (Antioxidant Response Element) pathway and its downstream antioxidant genes expression in skeletal muscle. These results suggest that KPE may enhance the antioxidant capacity of plasma and skeletal muscle by activating the Nrf2-ARE-centered antioxidant pathway, thereby increasing the daily running distance and improving the submaximal endurance exercise capacity of mice.

Bone assessment of the sacroiliac joint in ankylosing spondylitis: Comparison between computed tomography and zero echo time MRI.

PURPOSE: To demonstrate the clinical applicability of zero echo time magnetic resonance imaging (ZTE MRI) in bone assessment of the sacroiliac joint in ankylosing spondylitis. METHOD: Between January 2021 and November 2021, twenty-one ankylosing spondylitis patients underwent clinically indicated MRI including ZTE sequence, in addition, all patients underwent a CT scan covering the sacroiliac joints within 6 months of the MRI examination. The sensitivity, specificity, and accuracy of ZTE MRI were calculated using CT as the reference standard. Cohen's κappa tests were applied to assess the agreement of positive imaging findings (including erosions, osteosclerosis, bony cystic changes, and joint space changes) between MRI and CT as well as the inter-reader agreement for the grading of sacroiliitis in AS patients. RESULTS: There was no statistical significance between ZTE MRI and CT in detecting of ankylosing spondylitis(p＞0.05). The consistency of the diagnosis of positive imaging findings between ZTE MRI and CT was moderate to excellent (ranging from 0.611 to 0.889), and the consistency of the scores of positive imaging was good to excellent (ranging from 0.857 to 0.979). CONCLUSIONS: ZTE MRI provides "CT-like" contrast for bony changes of the sacroiliac joint in ankylosing spondylitis and could simplify and reduce costs for some AS patients when both MRI and CT are typically required.

Discovery of metabolite from the insect-derived endophytic Penicillium chrysogenum and their COX-2 inhibitory activity.

Three new N-alkylated amino acid derivatives, penichrysoamides A-C (1-3), along with a new citric acid derivative, penichrysoacid A (4), a new chromanone lactone penichrysoacid B (5), and a new amide derivative, penichrysoamide D (6), as well as seven known benzamide derivatives (7-13), were isolated from the endophytic fungus Penicillium chrysogenum derived from the insect Periplaneta americana. The structures of these compounds, including their absolute configurations, were elucidated using spectroscopic and computational techniques. Biological evaluation revealed that compounds 8-13 exhibited significant COX-2 inhibitory activity, with IC50 values ranging from 275 nM to 1350 nM.

A multi-component paclitaxel -loaded ß-elemene nanoemulsion by transferrin modification enhances anti-non-small-cell lung cancer treatment.

A multi-component paclitaxel (PTX) -loaded ß-elemene nanoemulsion by transferrin modification (Tf-PE-MEs) was developed to enhance non-small-cell lung cancer (NSCLC) treatment. After transferrin modification, the particle size of Tf-PE-MEs was (14.87 ± 1.84) nm, and the zeta potential was (-10.19 ± 0.870) mV, respectively. In vitro experiments showed that Tf-PE-MEs induced massive apoptosis in A549 cells, indicating that it had significant cytotoxicity to A549 cells. Through transferrin modification, Tf-PE-MEs accumulated at the tumor site efficiently with overexpressed transferrin receptor (TfR) on the surface of A549 cells. This will allow increasing PTX and ß-elemene concentration in the target cells, enhancing the therapeutic effect. Compared to PTX alone, Tf-PE-MEs displayed good anti-tumor efficacy and diminished systemic toxicity in vivo studies. With favourable therapeutic potential, this study provides a new strategy for the combined anticancer treatment of non-small cell lung cancer.

Comparable cognitive impairment was detected in MACS and CS and alleviated after remission of hypercortisolism in MACS.

Context: Few studies have directly compared the cognitive characteristics of patients with mild autonomous cortisol secretion (MACS) and Cushing's syndrome (CS). The effect of surgical or conservative treatment on cognitive function in patients with MACS is still unclear. Objective: To compare the differences in cognitive function between patients with MACS and CS and evaluate the effect of surgery or conservative treatment on cognitive function. Methods: We prospectively recruited 59 patients with nonfunctional adrenal adenoma (NFA), 36 patients with MACS, and 20 patients with adrenal CS who completed the global cognition and cognitive subdomains assessments. Seventeen MACS patients were re-evaluated for cognitive function after a 12-month follow-up period; of these, eleven underwent laparoscopic adrenalectomy and six received conservative treatment. Results: Patients with MACS and CS performed worse in the global cognition and multiple cognitive domains than those with NFA (all P<0.05). No statistical difference was found in cognitive functions between patients with MACS and CS. Logistic regression analysis showed that patients with MACS (odds ratio [OR]=3.738, 95% confidence intervals [CI]: 1.329-10.515, P=0.012) and CS (OR=6.026, 95% CI: 1.411-25.730, P=0.015) were associated with an increased risk of immediate memory impairment. Visuospatial/constructional, immediate and delayed memory scores of MACS patients were significantly improved at 12 months compared with pre-operation in the surgical treatment group (all P<0.05), whereas there was no improvement in the conservative treatment group. Conclusion: Patients with MACS have comparable cognitive impairment as patients with CS. Cognitive function was partially improved in patients with MACS after adrenalectomy. The current data support the inclusion of cognitive function assessment in the clinical management of patients with MACS.

Aryl Silyl Ethers Enable Preferential Ar-O bond Cleavage in Reductive Generation of Aryllithium Species.

Two-electron transfer to haloarenes constitutes one of the most reliable synthetic methodologies for the generation of aryllithiums. In addition to the conventional halides, readily available aryl ethers can function as potent substrates. However, it is known that the reductive cleavage of alkoxides is plagued by insufficient selectivity concerning the cleaving bond adjacent to the ether oxygen, resulting in decreased reliability of these alkoxyarene substrates. In the present study, we discovered that naphthalenes bearing readily installable tert-butyldimethylsilyl ethers undergo two-electron reduction with lithium metal, resulting in lithiation at the position of the original siloxy group. DFT calculations elucidated the rationale for the change in selectivity upon incorporation of the siloxy group. Our results underscore the practical utility of a siloxy group as a leaving group for reductive transformations involving electron transfer.

Chain reactions of temperature-induced egg white protein amorphous aggregates: Formation, structure and material composition of thermal gels.

Egg white protein is widely used in food, chemical, medical and other fields due to its excellent thermal gel properties. However, the regularity of egg white thermal gel (EWTG) by temperature influence is still unknown. In this study, we investigated the potential mechanism of temperature (75-95 °C, 15 min) gradient changes inducing thermal aggregation and gel formation of EWTG. The results showed that changes in textural characteristics and water holding capacity (WHC) of EWTGs depended on switching in protein aggregation morphology (spherical shape - chain shape - regiment shape) and gel network structure differences ("irregular bead-like" - "regular lamellar structure"). In addition, proteomics indicated that the generation of amorphous protein aggregates at 95 °C might be related to Mucin 5B as the aggregation core. The research revealed the EWTG formation from "whole egg white protein" to "single molecules", aiming to provide a reference for quality control in gel food processing.

Transient titin-dependent ventricular defects during development lead to adult atrial arrhythmia and impaired contractility.

Developmental causes of the most common arrhythmia, atrial fibrillation (AF), are poorly defined, with compensation potentially masking arrhythmic risk. Here, we delete 9 amino acids (Δ9) within a conserved domain of the giant protein titin's A-band in zebrafish and human-induced pluripotent stem cell-derived atrial cardiomyocytes (hiPSC-aCMs). We find that ttna Δ9/Δ9 zebrafish embryos' cardiac morphology is perturbed and accompanied by reduced functional output, but ventricular function recovers within days. Despite normal ventricular function, ttna Δ9/Δ9 adults exhibit AF and atrial myopathy, which are recapitulated in TTN Δ9/Δ9-hiPSC-aCMs. Additionally, action potential is shortened and slow delayed rectifier potassium current (I Ks) is increased due to aberrant atrial natriuretic peptide (ANP) levels. Strikingly, suppression of I Ks in both models prevents AF and improves atrial contractility. Thus, a small internal deletion in titin causes developmental abnormalities that increase the risk of AF via ion channel remodeling, with implications for patients who harbor disease-causing variants in sarcomeric proteins.

Age, sex, and APOE gene-specific associations between dynapenic obesity and dementia in a large cohort.

OBJECTIVE: To investigate the associations between dynapenic obesity and the risk of dementia, and the modifying effects of age, sex, and the APOE gene, using a large population-based cohort. METHODS: 279,884 participants aged 55 and above from the UK Biobank were included. The participants were classified into four categories based on body mass index and hand grip strength: healthy, obesity, dynapenia, and dynapenic obesity. The incident dementia was identified based on linked hospital records and death register data. Cox proportional hazards regression models were used to estimate the associations, followed by age-, sex-, and apolipoprotein E (APOE) gene-stratified analyses. RESULTS: During the median follow-up of 12.4 years, 5,170 (1.8%) participants developed dementia. Compared with the healthy group, participants with dynapenic obesity had 67% higher dementia risk (hazard ratio [HR]: 1.67, 95% confidence interval [CI]: 1.44-1.94). Compared with the healthy group, higher risks of dementia in participants with dynapenic obesity were respectively observed in male (HR: 2.03, 95% CI: 1.65-2.50), younger (<65 years, HR: 1.97, 95% CI: 1.55-2.50), and non-ε4-carrier (HR: 1.97, 95% CI: 1.60-2.44) (all P for interaction <0.05). In participants under 65 years and non-ε4-carrier, those with dynapenic obesity had the highest risk of dementia (HR: 2.63, 95% CI: 1.91-3.62), compared with the healthy group (P for second order interaction = 0.026). CONCLUSIONS: Dynapenic obesity is associated with increased risks of dementia, especially in participants under 65 years and non-ε4-carrier, suggesting the importance of managing dynapenic obesity in the prevention of cognition-related disorders.

Ecological drivers of nesting behavior in a subtropical city: An observational study on spotted doves.

Due to rapid homogenization in habitat types as a result of urbanization, some urban birds adapt their nesting strategies to changes in local habitat characteristics. Bird nesting decisions might have been mainly linked to resource constraints and ensuring reproductive success. In this study, we examined patterns of nesting behavior by spotted doves (Spilopelia chinensis) in a rapidly urbanizing area of Nanchang, China using ArcGIS 10.8, satellite tracking, camera traps, and field survey. To explore the mechanisms underlying nesting behavior in urban habitats, we assessed the correlations between nest reuse and reproductive success, and between nest reuse and nest predation. From December 2018 to December 2021, a total of 302 breeding nests were surveyed. The results revealed that the nest reuse rate was 38.08% (n = 115). Nests closer to trunk, with lower nest position and higher large-scale urbanization score tended to have higher reuse rate. In addition, nests with the higher the nest height and percent of canopy cover, and the lower small-scale urbanization score were more likely to reproduce successfully, and the reused nests also reproduce more successfully. The reproductive success associated with nest reuse was significantly higher than that associated with new nests (χ 2 = 8.461, p = .004). High degree of urbanization promoted nest reuse of spotted doves (large-scale urbanization score, z = 2.094, p = .036), which apparently enhanced their reproductive success (nest reuse, z = 2.737, p = .006). In conclusion, a nest structure with good permeability is the material basis for the nest reuse in spotted dove, while the relatively low risk of predation in urban habitat and the scarcity of nest site resources due to urbanization increase the tendency of birds to reuse old nests, which is associated with their reproductive success and evolutionary fitness.

Near-infrared fluorescent probe for ultrasensitive detection of organophosphorus pesticides and visualization of their interaction with butyrylcholinesterase in living cells.

The toxicity of organophosphorus pesticides (OPs) can catastrophically cause liver cell damage and inhibit the catalytic activity of cholinesterase. We designed and synthesized a near-infrared fluorescent probe HP-LZB with large Stokes shift which can specifically identify and detect butyrylcholinesterase (BChE) and visually explore the interaction between OPs and endogenous BChE in living cells. Fluorescence was turned on when HP-LZB was hydrolyzed into HP-LZ in the presence of BChE, and OPs could inhibit BChE's activity resulting in a decrease of fluorescence. Six OPs including three oxon pesticides (paraoxon, chlorpyrifos oxon and diazoxon) and their corresponding thion pesticides (parathion, chlorpyrifos and diazinon) were investigated. Both in vitro and cell experiments indicated that only oxon pesticides could inhibit BChE's activity. The limits of detection (LODs) of paraoxon, chlorpyrifos oxon and diazoxon were as low as 0.295, 0.007 and 0.011 ng mL-1 respectively and the recovery of OPs residue in vegetable samples was satisfactory. Thion pesticides themselves could hardly inhibit the activity of BChE and are only toxic when they are converted to their corresponding oxon form in the metabolic process. However, in this work, thion pesticides were found not be oxidized into their oxon forms in living HepG2 cells due to the lack of cytochrome P450 in hepatoma HepG2 cell lines. Therefore, this probe has great application potential in effectively monitoring OPs in real plant samples and visually exploring the interaction between OPs and BChE in living cells.

High-Throughput Proteomics Enabled by a Fully Automated Dual-Trap and Dual-Column LC-MS.

This Technical Note describes a dual-column liquid chromatography system coupled to mass spectrometry (LC-MS) for high-throughput bottom-up proteomic analysis. This system made full use of two 2-position 10-port valves and a binary pump with an integrated loading pump of a commercial LC instrument to provide successive operation of two parallel subsystems. Each subsystem consisted of a set of trap columns and an analytical column. A T-junction union was used to split the mobile phase from the loading pump into two parts. This allowed one set of columns to be washed and equilibrated, followed by the injection of the next sample, while the previous sample was eluting and being analyzed on the other set of columns, thereby greatly increasing the analysis throughput. This approach showed high reproducibility for the analysis of HeLa tryptic digests with average relative standard deviation (RSD) values of 1.75%, 6.90%, and 5.19% for the identification number of proteins, peptides, and peptide-spectrum matches (PSMs), respectively, across 10 consecutive runs. The capacity for peptide and protein identification, as well as proteome depth, of the dual-column LC system was comparable to a conventional single-column system. Due to its simple equipment requirements and set up process, this method should be highly accessible for other laboratories.

A graphene oxide-assisted protein immobilization paper-tip immunosensor with smartphone and naked eye readout for the detection of okadaic acid.

BACKGROUND: Okadaic acid (OA), as a diarrhetic shellfish poisoning, can increase the risk of acute carcinogenic or teratogenic effects for the ingestion of OA contaminated shellfish. At present, much effort has been made to graft immunoassay onto a paper substrate to make paper-based sensors for rapid and simple detection of shellfish toxin. However, the complicated washing steps and low protein fixation efficiency on the paper substrate need to be further addressed. RESULTS: A novel paper-tip immunosensor for detecting OA was developed combined with smartphone and naked eye readout. The trapezoid paper tip was consisted of quantitative and qualitative detection zones. To improve the OA antigen immobilization efficiency on the paper substrate, graphene oxide (GO)-assisted protein immobilization method was introduced. Meanwhile, Au nanoparticles composite probe combined with the lateral flow washing was developed to simplify the washing step. The OA antigen-immobilized zone, as the detection zone Ⅰ, was used for quantitative assay by smartphone imaging. The paper-tip front, as the detection zone Ⅱ, which could qualitatively differentiate OA pollution level within 45 min using the naked eye. The competitive immunoassay on the paper tip exhibited a wide linear range for detecting OA (0.02-50 ng∙mL-1) with low detection limit of 0.02 ng∙mL-1. The recovery of OA in spiked shellfish samples was in the range of 90.3 %-113.%. SIGNIFICANCE: These results demonstrated that the proposed paper-tip immunosensor could provide a simple, low-cost and high-sensitivity test for OA detection without the need for additional large-scale equipment or expertise. We anticipate that this paper-tip immunosensor will be a flexible and versatile tool for on-site detecting the pollution of marine products.

From mechanism to application: Decrypting light-regulated denitrifying microbiome through geometric deep learning.

Regulation on denitrifying microbiomes is crucial for sustainable industrial biotechnology and ecological nitrogen cycling. The holistic genetic profiles of microbiomes can be provided by meta-omics. However, precise decryption and further applications of highly complex microbiomes and corresponding meta-omics data sets remain great challenges. Here, we combined optogenetics and geometric deep learning to form a discover-model-learn-advance (DMLA) cycle for denitrification microbiome encryption and regulation. Graph neural networks (GNNs) exhibited superior performance in integrating biological knowledge and identifying coexpression gene panels, which could be utilized to predict unknown phenotypes, elucidate molecular biology mechanisms, and advance biotechnologies. Through the DMLA cycle, we discovered the wavelength-divergent secretion system and nitrate-superoxide coregulation, realizing increasing extracellular protein production by 83.8% and facilitating nitrate removal with 99.9% enhancement. Our study showcased the potential of GNNs-empowered optogenetic approaches for regulating denitrification and accelerating the mechanistic discovery of microbiomes for in-depth research and versatile applications.

Hippo-YAP/TAZ-ROS signaling axis regulates metaflammation induced by SelenoM deficiency in high-fat diet-derived obesity.

INTRODUCTION: Metabolic inflammation (metaflammation) in obesity is primarily initiated by proinflammatory macrophage infiltration into adipose tissue. SelenoM contributes to the modulation of antioxidative stress and inflammation in multiple pathological processes; however, its roles in metaflammation and the proinflammatory macrophage (M1)-like state in adipose tissue have not been determined. OBJECTIVES: We hypothesize that SelenoM could effectively regulate metaflammation via the Hippo-YAP/TAZ-ROS signaling axis in obesity derived from a high-fat diet. METHODS: Morphological changes in adipose tissue were examined by hematoxylin-eosin (H&E) staining and fluorescence microscopy. The glucose tolerance test (GTT) and insulin tolerance test (ITT) were used to evaluate the impact of SelenoM deficiency on blood glucose levels. RNA-Seq analysis, LC-MS analysis, Mass spectrometry analysis and western blotting were performed to detect the levels of genes and proteins related to glycolipid metabolism in adipose tissue. RESULTS: Herein, we evaluated the inflammatory features and metabolic microenvironment of mice with SelenoM-deficient adipose tissues by multi-omics analyses. The deletion of SelenoM resulted in glycolipid metabolic disturbances and insulin resistance, thereby accelerating weight gain, adiposity, and hyperglycemia. Mice lacking SelenoM in white adipocytes developed severe adipocyte hypertrophy via impaired lipolysis. SelenoM deficiency aggravated the generation of ROS by reducing equivalents (NADPH and glutathione) in adipocytes, thereby promoting inflammatory cytokine production and the M1-proinflammatory reaction, which was related to a change in nuclear factor kappa-B (NF-κB) levels in macrophages. Mechanistically, SelenoM deficiency promoted metaflammation via Hippo-YAP/TAZ-ROS-mediated transcriptional regulation by targeting large tumor suppressor 2 (LATS2). Moreover, supplementation with N-acetyl cysteine (NAC) to reduce excessive oxidative stress partially rescued adipocyte inflammatory responses and macrophage M1 activation. CONCLUSION: Our data indicate that SelenoM ameliorates metaflammation mainly via the Hippo-YAP/TAZ-ROS signaling axis in obesity. The identification of SelenoM as a key regulator of metaflammation presents opportunities for the development of novel therapeutic interventions targeting adipose tissue dysfunction in obesity.

Sodium chloride promotes macrophage pyroptosis and aggravates rheumatoid arthritis by activating SGK1 through GABA receptors Slc6a12.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by synovial inflammation and the production of autoantibodies. Previous studies have indicated an association between high-salt diets (HSD) and an increased risk of RA, yet the underlying mechanisms remain unclear. Macrophage pyroptosis, a pro-inflammatory form of cell death, plays a pivotal role in RA. In this study, we demonstrate that HSD exacerbates the severity of arthritis in collagen-induced arthritis (CIA) mice, correlating with macrophage infiltration and inflammatory lesions. Given the significant alterations observed in macrophages from CIA mice subjected to HSD, we specifically investigate the impact of HSD on macrophage responses in the inflammatory milieu of RA. In our in vitro experiments, pretreatment with NaCl enhances LPS-induced pyroptosis in RAW.264.7 and THP-1 cells through the p38 MAPK/NF-κB signaling pathway. Subsequent experiments reveal that Slc6a12 inhibitors and SGK1 silencing inhibit sodium-induced activation of macrophage pyroptosis and the p38 MAPK/NF-κB signaling pathway, whereas overexpression of the SGK1 gene counteracts the effect of sodium on macrophages. In conclusion, our findings verified that high salt intake promotes the progression of RA and provided a detailed elucidation of the activation of macrophage pyroptosis induced by sodium transportation through the Slc6a12 channel.