Comprehensive multiscale analysis of lactate metabolic dynamics in vitro and in vivo using highly responsive biosensors.

As a key glycolytic metabolite, lactate has a central role in diverse physiological and pathological processes. However, comprehensive multiscale analysis of lactate metabolic dynamics in vitro and in vivo has remained an unsolved problem until now owing to the lack of a high-performance tool. We recently developed a series of genetically encoded fluorescent sensors for lactate, named FiLa, which illuminate lactate metabolism in cells, subcellular organelles, animals, and human serum and urine. In this protocol, we first describe the FiLa sensor-based strategies for real-time subcellular bioenergetic flux analysis by profiling the lactate metabolic response to different nutritional and pharmacological conditions, which provides a systematic-level view of cellular metabolic function at the subcellular scale for the first time. We also report detailed procedures for imaging lactate dynamics in live mice through a cell microcapsule system or recombinant adeno-associated virus and for the rapid and simple assay of lactate in human body fluids. This comprehensive multiscale metabolic analysis strategy may also be applied to other metabolite biosensors using various analytic platforms, further expanding its usability. The protocol is suited for users with expertise in biochemistry, molecular biology and cell biology. Typically, the preparation of FiLa-expressing cells or mice takes 2 days to 4 weeks, and live-cell and in vivo imaging can be performed within 1-2 hours. For the FiLa-based assay of body fluids, the whole measuring procedure generally takes ~1 min for one sample in a manual assay or ~3 min for 96 samples in an automatic microplate assay.

Dorsomedial hypothalamus-raphe pallidus-cardiac sympathetic pathway mediates electroacupuncture intervention of stress-induced tachycardia.

Electroacupuncture at Neiguan point (PC6) effectively ameliorates tachycardia. However, very little is known about the neural pathway mechanism underlying the effect of electroacupuncture at PC6 in stress-induced tachycardia. Here, we investigate whether there exists a dorsomedial hypothalamus (DMH)-raphe pallidus (RP)-heart pathway to mediate the effect of electroacupuncture at PC6. The virus tracing results show that the heart is innervated by the neurons in DMH and RP, and the neurons of DMH project to RP. Chemogenetic inhibition of RP projecting DMH neurons reverses the cardiac autonomic imbalance and tachycardia induced by stress. Of note, immunofluorescence results show that the neural activity of DMH and RP is inhibited by electroacupuncture at PC6 accompanied with improved cardiac autonomic imbalance and tachycardia under stress. Moreover, chemogenetic inhibition of RP projecting DMH neurons cannot affect autonomic nervous activity and heart rate of stress rats after administrating electroacupuncture at PC6.NEW & NOTEWORTHY Our study suggests that this dorsomedial hypothalamus (DMH)-raphe pallidus (RP)-cardiac sympathetic pathway involves in the improvement of cardiac dysfunction associated with stress by administrating electroacupuncture at PC6, thus providing beneficial information for the development of therapeutic strategies to prevent stress-induced cardiovascular diseases, and insight into neural pathway basis for electroacupuncture at PC6 intervention of cardiac dysfunction.

Impacts of glutamate, an exercise-responsive metabolite on insulin signaling.

AIMS: Disruption of the insulin signaling pathway leads to insulin resistance (IR). IR is characterized by impaired glucose and lipid metabolism. Elevated levels of circulating glutamate are correlated with metabolic indicators and may potentially predict the onset of metabolic diseases. Glutamate receptor antagonists have significantly enhanced insulin sensitivity, and improved glucose and lipid metabolism. Exercise is a well-known strategy to combat IR. The aims of our narrative review are to summarize preclinical and clinical findings to show the correlations between circulating glutamate levels, IR and metabolic diseases, discuss the causal role of excessive glutamate in IR and metabolic disturbance, and present an overview of the exercise-induced alteration in circulating glutamate levels. MATERIALS AND METHODS: A literature search was conducted to identify studies on glutamate, insulin signaling, and exercise in the PubMed database. The search covered articles published from December 1955 to January 2024, using the search terms of "glutamate", "glutamic acid", "insulin signaling", "insulin resistance", "insulin sensitivity", "exercise", and "physical activity". KEY FINDINGS: Elevated levels of circulating glutamate are correlated with IR. Excessive glutamate can potentially hinder the insulin signaling pathway through various mechanisms, including the activation of ectopic lipid accumulation, inflammation, and endoplasmic reticulum stress. Glutamate can also modify mitochondrial function through Ca2+ and induce purine degradation mediated by AMP deaminase 2. Exercise has the potential to decrease circulating levels of glutamate, which can be attributed to accelerated glutamate catabolism and enhanced glutamate uptake. SIGNIFICANCE: Glutamate may act as a mediator in the exercise-induced improvement of insulin sensitivity.

Surgical treatment of severe benign tracheal stenosis.

OBJECTIVE: To present clinical experiences regarding surgical treatment of patients with severe cicatricial tracheal stenosis. PATIENTS AND METHODS: From January 2008 to March 2020, 14 patients underwent tracheal resection and reconstruction under general anesthesia. Nine cases had cervical tracheal stenosis and five cases had thoracic tracheal stenosis. The mean diameter and length of strictured trachea was 0 - 8 mm with a mean of 4.5 ± 2.4 mm and 1 - 3 cm with a mean of 1.67 ± 0.63 cm, respectively. General anesthesia and mechanical ventilation were performed in ten cases and four patients underwent femoral arteriovenous bypass surgery due to severe stenosis. End-to-end anastomosis of trachea was performed in 13 cases and the anastomosis between trachea and cricothyroid membrane was performed in one case. Absorbable and unabsorbable sutures were used for the anterior and posterior anastomoses, respectively. Postoperative neck anteflexion was maintained by a suture between the chin and superior chest wall. The relevant data of the 14 patients were retrospectively reviewed, and the operation time, blood loss, postoperative hospital stay, postoperative complications and follow-up were retrieved. RESULTS: There was no intraoperative death. The length of resected trachea ranged from 1.5 to 4.5 cm with a mean of 1.67 ± 0.63 cm. Operation time ranged from 50 - 450 min with a mean of 142.8 ± 96.6 min and intraoperative hemorrhage ranged from 10 - 300 ml with a mean of 87.8 ± 83.6 ml. Follow-up period ranged from 5 to 43 months with a mean of 17.9 ± 10.6 months. None of the patients had recurrent laryngeal nerve paralysis during postoperative follow-up. Ten cases were discharged uneventfully. Anastomosis stenosis occurred in three cases who received interventional therapies. Bronchopleurocutaneous fistula occurred in one patient after 6 days postoperatively and further treatment was declined. CONCLUSION: The strategies of anesthesia, mechanical ventilation, identification of stenosis lesion, the "hybrid" sutures and postoperative anteflexion are critical to be optimized for successful postoperative recovery.

Metabolic crosstalk between skeletal muscle cells and liver through IRF4-FSTL1 in nonalcoholic steatohepatitis.

Inter-organ crosstalk has gained increasing attention in recent times; however, the underlying mechanisms remain unclear. In this study, we elucidate an endocrine pathway that is regulated by skeletal muscle interferon regulatory factor (IRF) 4, which manipulates liver pathology. Skeletal muscle specific IRF4 knockout (F4MKO) mice exhibited ameliorated hepatic steatosis, inflammation, and fibrosis, without changes in body weight, when put on a nonalcoholic steatohepatitis (NASH) diet. Proteomics analysis results suggested that follistatin-like protein 1 (FSTL1) may constitute a link between muscles and the liver. Dual luciferase assays showed that IRF4 can transcriptionally regulate FSTL1. Further, inducing FSTL1 expression in the muscles of F4MKO mice is sufficient to restore liver pathology. In addition, co-culture experiments confirmed that FSTL1 plays a distinct role in various liver cell types via different receptors. Finally, we observed that the serum FSTL1 level is positively correlated with NASH progression in humans. These data indicate a signaling pathway involving IRF4-FSTL1-DIP2A/CD14, that links skeletal muscle cells to the liver in the pathogenesis of NASH.

Insulin Glargine is More Suitable Than Exenatide in Preventing Muscle Loss in Non-Obese Type 2 Diabetic Patients with NAFLD.

AIM: This study investigated the effects of insulin glargine and exenatide on the muscle mass of patients with newly diagnosed type 2 diabetes (T2DM) and nonalcoholic fatty liver disease (NAFLD). METHODS: We performed a post-hoc analysis of our previously study, a 24-week randomized controlled multicenter clinical trial (ClinicalTrials.gov, NCT02303730). Seventy-six patients were randomly assigned 1:1 to receive insulin glargine or exenatide treatment. The changes in psoas muscle area (PMA) (mm2) were obtained with the cross-sectional Dixonfat magnetic resonance images at the fourth lumber vertebra. RESULTS: There were no significant differences in age, BMI, gender, and PMA in insulin glargine and exenatide groups at baseline. After treatment, PMA tended to increase by 13.13 (-215.52, 280.80) mm2 in the insulin glargine group and decrease by 149.09 (322.90-56.39) mm2 in the exenatide group (both p>0.05). Subgroup analysis showed a 560.64 (77.88, 1043.40) (mm2) increase of PMA in the insulin group relative to the Exenatide group in patients with BMI<28 kg/m2 (p0.031) after adjusting for gender, age, and research center. Interaction analysis showed an interaction between BMI and treatment (p0.009). However, no interaction was observed among subgroups with a BMI≥28 kg/m2 or with different genders and ages. CONCLUSION: Compared to exenatide, insulin glargine can relativity increase PMA in patients with T2DM having BMI<28 kg/m2 and NAFLD.

Skeletal muscle-specific DJ-1 ablation-induced atrogenes expression and mitochondrial dysfunction contributing to muscular atrophy.

BACKGROUND: DJ-1 is a causative gene for Parkinson's disease. DJ-1-deficient mice develop gait-associated progressive behavioural abnormalities and hypoactive forearm grip strength. However, underlying activity mechanisms are not fully explored. METHODS: Western blotting and quantitative real-time polymerase chain reaction approaches were adopted to analyse DJ-1 expression in skeletal muscle from aged humans or mice and compared with young subjects. Skeletal muscle-specific-DJ-1 knockout (MDKO) mice were generated, followed by an assessment of the physical activity phenotypes (grip strength, maximal load capacity, and hanging, rotarod, and exercise capacity tests) of the MDKO and control mice on the chow diet. Muscular atrophy phenotypes (cross-sectional area and fibre types) were determined by imaging and quantitative real-time polymerase chain reaction. Mitochondrial function and skeletal muscle morphology were evaluated by oxygen consumption rate and electron microscopy, respectively. Tail suspension was applied to address disuse atrophy. RNA-seq analysis was performed to indicate molecular changes in muscles with DJ-1 ablation. Dual-luciferase reporter assays were employed to identify the promoter region of Trim63 and Fbxo32 genes, which were indirectly regulated by DJ-1 via the FoxO1 pathway. Cytoplasmic and nuclear fractions of DJ-1-deleted muscle cells were analysed by western blotting. Compound 23 was administered into the gastrocnemius muscle to mimic the of DJ-1 deletion effects. RESULTS: DJ-1 expression decreased in atrophied muscles of aged human (young men, n = 2; old with aged men, n = 2; young women, n = 2; old with aged women, n = 2) and immobilization mice (n = 6, P < 0.01). MDKO mice exhibited no body weight difference compared with control mice on the chow diet (Flox, n = 8; MDKO, n = 9). DJ-1-deficient muscles were slightly dystrophic (Flox, n = 7; MDKO, n = 8; P < 0.05), with impaired physical activities and oxidative capacity (n = 8, P < 0.01). In disuse-atrophic conditions, MDKO mice showed smaller cross-sectional area (n = 5, P < 0.01) and more central nuclei than control mice (Flox, n = 7; MDKO, n = 6; P < 0.05), without alteration in muscle fibre types (Flox, n = 6; MDKO, n = 7). Biochemical analysis indicated that reduced mitochondrial function and upregulated of atrogenes induced these changes. Furthermore, RNA-seq analysis revealed enhanced activity of the FoxO1 signalling pathway in DJ-1-ablated muscles, which was responsible for the induction of atrogenes. Finally, compound 23 (an inhibitor of DJ-1) could mimic the effects of DJ-1 ablation in vivo. CONCLUSIONS: Our results illuminate the crucial of skeletal muscle DJ-1 in the regulation of catabolic signals from mechanical stimulation, providing a therapeutic target for muscle wasting diseases.

Designing Intracellular Compartments for Efficient Engineered Microbial Cell Factories.

With the rapid development of synthetic biology, various kinds of microbial cell factories (MCFs) have been successfully constructed to produce high-value-added compounds. However, the complexity of metabolic regulation and pathway crosstalk always cause issues such as intermediate metabolite accumulation, byproduct generation, and metabolic burden in MCFs, resulting in low efficiencies and low yields of industrial biomanufacturing. Such issues could be solved by spatially rearranging the pathways using intracellular compartments. In this review, design strategies are summarized and discussed based on the types and characteristics of natural and artificial subcellular compartments. This review systematically presents information for the construction of efficient MCFs with intracellular compartments in terms of four aspects of design strategy goals: (1) improving local reactant concentration; (2) intercepting and isolating competing pathways; (3) providing specific reaction substances and environments; and (4) storing and accumulating products.

Lipid Profiling Reveals Lipidomic Signatures of Weight Loss Interventions.

Obesity is an epidemic all around the world. Weight loss interventions that are effective differ from each other with regard to various lipidomic responses. Here, we aimed to find lipidomic biomarkers that are related to beneficial changes in weight loss. We adopted an untargeted liquid chromatography with tandem mass spectrometry (LC-MS/MS) method to measure 953 lipid species for Exercise (exercise intervention cohort, N = 25), 1388 lipid species for LSG (laparoscopic sleeve gastrectomy cohort, N = 36), and 886 lipid species for Cushing (surgical removal of the ACTH-secreting pituitary adenomas cohort, N = 25). Overall, the total diacylglycerol (DG), triacylglycerol (TG), phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphatidylserine (PS), and sphingomyelin (SM) levels were associated with changes in BMI, glycated hemoglobin (HbA1c), triglyceride, and total cholesterol according to weight loss interventions. We found that 73 lipid species changed among the three weight loss interventions. We screened 13 lipid species with better predictive accuracy in diagnosing weight loss situations in either Exercise, LSG, or Cushing cohorts (AUROC > 0.7). More importantly, we identified three phosphatidylcholine (PC) lipid species, PC (14:0_18:3), PC (31:1), and PC (32:2) that were significantly associated with weight change in three studies. Our results highlight potential lipidomic biomarkers that, in the future, could be used in personalized approaches involving weight loss interventions.

Effect of initiative pulmonary bullectomy on the risk of post-operative pneumothorax in patients with esophageal carcinoma: a propensity score-matched analysis.

Background: Postoperative pneumothorax can lead to additional invasive intervention and extended hospitalization. The effect of initiative pulmonary bullectomy (IPB) during the esophagectomy on preventing postoperative pneumothorax remains controversial. This study evaluated the efficacy and safety of IPB in patients who underwent minimally invasive esophagectomy (MIE) for esophageal carcinoma complicated by ipsilateral pulmonary bullae. Methods: Data from 654 consecutive patients with esophageal carcinoma who underwent MIE from January 2013 to May 2020 were retrospectively collected. A total of 109 patients who had a definite diagnosis of ipsilateral pulmonary bullae were recruited and classified into two groups: the IPB group and the control group (CG). Propensity score matching (PSM, match ratio =1:1), incorporating preoperative clinical features, was used to compare the perioperative complications and analyze efficacy and safety between IPB and control group. Results: The incidences of postoperative pneumothorax in the IPB and control groups was 3.13% and 40.63% respectively, with a significant difference (P<0.001). Logistic analyses indicated that removing ipsilateral bullae was associated with a lower risk (OR 0.030; 95% CI: 0.003-0.338; P=0.005) of incident postoperative pneumothorax. No significant difference was found between the two groups in terms of the incidence of anastomotic leakage (6.25% vs. 3.13%, P=1.000), arrhythmia (3.13% vs. 3.13%, P=1.000), chylothorax (0% vs. 3.13%, P=1.000) and other common complications. Conclusions: In esophageal cancer patients with ipsilateral pulmonary bullae, IPB performed in the same anesthesia process is an effective and safe method for the prevention of postoperative pneumothorax, allowing for a shorter postoperative rehabilitation time, and it does not exert unfavorable effects on complications.

Electroacupuncture intervention on stress-induced cardiac autonomic imbalance in rats involves corticotropin-releasing hormone system activity.

Autonomic imbalance is a core aspect of stress response that strongly correlates to cardiovascular diseases. Enhanced activity of the central corticotropin-releasing hormone (CRH) system may result in autonomic imbalance to cause cardiovascular responses in a stress state. Electroacupuncture at PC6 acupoints has been demonstrated to prevent and treat cardiovascular diseases. In this study, we aim to demonstrate the protective role of electroacupuncture at PC6 in ameliorating cardiac autonomic imbalance and investigate the underlying mechanisms in immobilization stress rats. Four groups were subjected. Immobilization stress was applied to three groups. And the rats in two electroacupuncture-intervened groups exerted electroacupuncture at PC6 or tail respectively. Then, we performed ECG recording for heart rate variability (HRV) analysis, and rats were sacrificed after experiments for biological analysis. HRV analysis indicated that electroacupuncture at PC6 improved the enhanced low-frequency band of the power spectrum (LF), the reduced high-frequency band of the power spectrum (HF), and the enhanced LF/HF ratio caused by immobilization stress. Besides, electroacupuncture at PC6 significantly decreased phosphorylated tyrosine hydroxylase expression and increased acetylcholine esterase expression in heart of immobilization stress rats. Furthermore, electroacupuncture at PC6 significantly decreased CRH level and CRH 1 type receptor and CRH 2 type receptor (CRHR2) expressions in the rostral ventrolateral medulla (RVLM), and CRH level and CRHR2 expression in the nucleus of the solitary tract (NTS) of immobilization stress rats. Our findings suggest that electroacupuncture at PC6 can ameliorate stress-induced cardiac autonomic imbalance by modulating the CRHergic input in the RVLM and NTS.

Muscle PARP1 inhibition extends lifespan through AMPKα PARylation and activation in Drosophila.

Poly(ADP-ribose) polymerase-1 (PARP1) has been reported to play an important role in longevity. Here, we showed that the knockdown of the PARP1 extended the lifespan of Drosophila, with particular emphasis on the skeletal muscle. The muscle-specific mutant Drosophila exhibited resistance to starvation and oxidative stress, as well as an increased ability to climb, with enhanced mitochondrial biogenesis and activity at an older age. Mechanistically, the inhibition of PARP1 increases the activity of AMP-activated protein kinase alpha (AMPKα) and mitochondrial turnover. PARP1 could interact with AMPKα and then regulate it via poly(ADP ribosyl)ation (PARylation) at residues E155 and E195. Double knockdown of PARP1 and AMPKα, specifically in muscle, could counteract the effects of PARP1 inhibition in Drosophila. Finally, we showed that increasing lifespan via maintaining mitochondrial network homeostasis required intact PTEN induced kinase 1 (PINK1). Taken together, these data indicate that the interplay between PARP1 and AMPKα can manipulate mitochondrial turnover, and be targeted to promote longevity.

Exercise-induced microbial changes in preventing type 2 diabetes.

The metabolic benefits associated with long-term physical activity are well appreciated and growing evidence suggests that it involves the gut microbiota. Here we re-evaluated the link between exercise-induced microbial changes and those associated with prediabetes and diabetes. We found that the relative abundances of substantial amounts of diabetes-associated metagenomic species associated negatively with physical fitness in a Chinese athlete students cohort. We additionally showed that those microbial changes correlated more with handgrip strength, a simple but valuable biomarker suggestive of the diabetes states, than maximum oxygen intake, one of the key surrogates for endurance training. Moreover, the causal relationships among exercise, risks for diabetes, and gut microbiota were explored based on mediation analysis. We propose that the protective roles of exercise against type 2 diabetes are mediated, at least partly, by the gut microbiota.

Hypoxia as a Double-Edged Sword to Combat Obesity and Comorbidities.

The global epidemic of obesity is tightly associated with numerous comorbidities, such as type II diabetes, cardiovascular diseases and the metabolic syndrome. Among the key features of obesity, some studies have suggested the abnormal expansion of adipose-tissue-induced local endogenous hypoxic, while other studies indicated endogenous hyperoxia as the opposite trend. Endogenous hypoxic aggravates dysfunction in adipose tissue and stimulates secretion of inflammatory molecules, which contribute to obesity. In contrast, hypoxic exposure combined with training effectively generate exogenous hypoxic to reduce body weight and downregulate metabolic risks. The (patho)physiological effects in adipose tissue are distinct from those of endogenous hypoxic. We critically assess the latest advances on the molecular mediators of endogenous hypoxic that regulate the dysfunction in adipose tissue. Subsequently we propose potential therapeutic targets in adipose tissues and the small molecules that may reverse the detrimental effect of local endogenous hypoxic. More importantly, we discuss alterations of metabolic pathways in adipose tissue and the metabolic benefits brought by hypoxic exercise. In terms of therapeutic intervention, numerous approaches have been developed to treat obesity, nevertheless durability and safety remain the major concern. Thus, a combination of the therapies that suppress endogenous hypoxic with exercise plans that augment exogenous hypoxic may accelerate the development of more effective and durable medications to treat obesity and comorbidities.

Neoadjuvant immunotherapy combined with chemotherapy significantly improved patients' overall survival when compared with neoadjuvant chemotherapy in non-small cell lung cancer: A cohort study.

Background: Programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitors displayed considerable advantages in neoadjuvant therapy of non-small cell lung cancer (NSCLC), but the specific application of neoadjuvant immunotherapy has not been well determined, and the long-term prognostic data of neoadjuvant immunochemotherapy combined with surgical resection of NSCLC remains limited. In this study, we intended to assess the efficacy of the neoadjuvant therapy of the PD-1 inhibitor and long-term prognosis in patients with resectable NSCLC. Methods: We retrospectively analyzed NSCLC surgical patients treated with neoadjuvant therapy in our hospital, and divided them into a neoadjuvant chemotherapy group and a neoadjuvant immunotherapy combined with chemotherapy group. The propensity score matching method was used to evaluate the effectiveness of immunotherapy combined with chemotherapy in the treatment of resectable lung cancer, and the long-term prognosis of these two groups was compared. Results: A total of 62 cases were enrolled, including 20 patients (20/62, 32.26%) in the immunotherapy group and 42 patients (42/62, 67.74%) in the chemotherapy group. The clinical baseline data of these two groups were balanced. In the immunotherapy group, all patients had tumor regression in imaging finding (tumor regression ratio: 11.88% - 75.00%). In the chemotherapy group, 30 patients had tumor regression (tumor regression ratio: 2.70% - 58.97%). The R0 removal rates of cancers were comparable between the immunotherapy group and chemotherapy group (19/20, 95.00% vs. 39/42, 92.86%, P=1.000). The two groups were balanced in complete minimally invasive surgery, pneumonectomy, operative duration, blood loss, postoperative complications, and hospital stay. The immunotherapy group had more sleeve resection (36.84% vs. 10.26%, p=0.039) including bronchial sleeve and vascular sleeve, higher pathological complete response (pCR) rate (57.89% vs. 5.13%, P<0.001) and major pathologic response (MPR) rate (78.95% vs. 10.26%, P<0.001). There were no differences in survival curves for: smoker and non-smoker, squamous cell carcinoma and adenocarcinoma, or right lung cancer and left lung cancer. Moreover, patients who achieved MPR (including pCR) had significantly better overall survival (OS) and disease-free survival (DFS). Patients in immunotherapy group had significantly better OS and longer DFS than those in chemotherapy group. Conclusions: In conclusion, neoadjuvant immunotherapy combined with chemotherapy can provide better OS and DFS and improving pCR and MPR rates by shrinking tumors.This study has been registered in the Chinese Clinical Trial Registry, number ChiCTR2200060433. http://www.chictr.org.cn/edit.aspx?pid=170157&htm=4.

Plasma Metabolomics Reveals ß-Glucan Improves Muscle Strength and Exercise Capacity in Athletes.

The present study aimed to assess the changes in muscle strength and plasma metabolites in athletes with ß-glucan supplementation. A total of 29 athletes who met the inclusion criteria were recruited for this study (ChiCTR2200058091) and were randomly divided into a placebo group (n = 14) and ß-glucan group (n = 15). During the trial, the experimental group received ß-glucan supplementation (2 g/d ß-glucan) for 4 weeks and the control group received an equal dose of placebo supplementation (0 g/d ß-glucan), with both groups maintaining their regular diet and exercise habits during the trial. The athletes' exercise performance, muscle strength, and plasma metabolome changes were analyzed after 4 weeks of ß-glucan supplementation. The results showed a significant increase in mean grip strength (kg), right hand grip strength (kg), left triceps strength (kg), and upper limb muscle mass (kg) in the experimental group after the 4-week intervention compared to the preintervention period (p < 0.05). A comparison of the difference between the two groups after the intervention showed that there were significant differences between the control group and the experimental group in mean grip strength (kg) and right-hand grip strength (kg) (p < 0.05). Athletes in the experimental group showed significant improvements in 1 min double rocking jump (pcs), VO2max (ml/kg-min) (p < 0.05). The ß-glucan intake increased the creatine-related pathway metabolites in plasma. Overall, these results suggest that 4 weeks of ß-glucan supplementation can improve muscle strength in athletes, with the potential to increase aerobic endurance and enhance immune function, possibly by affecting creatine-related pathways.

The roles of PARK gene family in myopathy.

The causative gene family of Parkinson's disease, PARK, plays important roles in the regulation of skeletal myopathy and is also involved in multiple biological processes, such as the modification of motor neurons, the transmission of nerve signals at the nerve-muscle junction, the regulation of skeletal muscle energy metabolism and mitochondrial quality, and the expression of myogenesis factors. PARK gene family regulates skeletal muscle mass, functions through a multi-level regulatory system, and plays a key role in the occurrence and development of skeletal myopathy. In this review, we summarize the structural characteristics, functions, and research of the PARK gene family in skeletal myopathy, providing a theoretical foundation and future research direction for in-depth study of the molecular mechanism for skeletal myopathy and giving references to further study on the role of PARK family in the development, the pathology, clinical diagnosis, and treatment of skeletal myopathy.

Proteomics and Organoid Culture Reveal the Underlying Pathogenesis of Hashimoto's Thyroiditis.

Hashimoto's thyroiditis (HT) is an autoimmune disease, and its incidence continues to rise. Although scientists have studied this disease for many years and discovered the potential effects of various proteins in it, the specific pathogenesis is still not fully comprehended. To understand HT and translate this knowledge to clinical applications, we took the mass spectrometric analysis on thyroid tissue fine-needle puncture from HT patients and healthy people in an attempt to make a further understanding of the pathogenesis of HT. A total of 44 proteins with differential expression were identified in HT patients, and these proteins play vital roles in cell adhesion, cell metabolism, and thyroxine synthesis. Combining patient clinical trial sample information, we further compared the transient changes of gene expression regulation in HT and papillary thyroid carcinoma (PTC) samples. More importantly, we developed patient-derived HT and PTC organoids as a promising new preclinical model to verify these potential markers. Our data revealed a marked characteristic of HT organoid in upregulating chemokines that include C-C motif chemokine ligand (CCL) 2 and CCL3, which play a key role in the pathogenesis of HT. Overall, our research has enriched everyone's understanding of the pathogenesis of HT and provides a certain reference for the treatment of the disease.

Central 5-HTR2C in the Control of Metabolic Homeostasis.

The 5-hydroxytryptamine 2C receptor (5-HTR2C) is a class G protein-coupled receptor (GPCR) enriched in the hypothalamus and the brain stem, where it has been shown to regulate energy homeostasis, including feeding and glucose metabolism. Accordingly, 5-HTR2C has been the target of several anti-obesity drugs, though the associated side effects greatly curbed their clinical applications. Dissecting the specific neural circuits of 5-HTR2C-expressing neurons and the detailed molecular pathways of 5-HTR2C signaling in metabolic regulation will help to develop better therapeutic strategies towards metabolic disorders. In this review, we introduced the regulatory role of 5-HTR2C in feeding behavior and glucose metabolism, with particular focus on the molecular pathways, neural network, and its interaction with other metabolic hormones, such as leptin, ghrelin, insulin, and estrogens. Moreover, the latest progress in the clinical research on 5-HTR2C agonists was also discussed.

Cost-effectiveness evaluation of robotic-assisted thoracoscopic surgery versus open thoracotomy and video-assisted thoracoscopic surgery for operable non-small cell lung cancer.

BACKGROUND: This study aimed to evaluate the cost-effectiveness of robotic-assisted thoracoscopic surgery (RATS) over open thoracotomy (OT) and video-assisted thoracoscopic surgery (VATS) for operable non-small cell lung cancer (NSCLC) from the perspective of Chinese healthcare payer. METHODS: The Markov decision model was developed to assess the 5-year costs and quality-adjusted life year (QALY) of RATS versus OT and VATS for operable NSCLC patients. The propensity-matched cohorts were generated from our clinical center to determine the surgical costs and complication rates. An individual patient data meta-analysis was conducted to estimate model probabilities of progression and survival risks. Other model inputs were abstracted from available studies. The primary outcome was incremental cost-effectiveness ratios (ICERs). RESULTS: RATS contributed to an incremental 0.28 QALYs at an additional cost of $3,104.82, making for an ICER of $10,967.41 per QALY versus OT. Robotic approach harvested an incremental 0.05 QALYs at an additional cost of $4006.86, making for an ICER of $80324.98 per QALY over VATS. RATS shown a same cost-effectiveness probability (0.50) versus OT and VATS at a willing-to-pay (WTP) threshold of $12,000 per QALY and $75,800 per QALY, respectively. The probabilities of cost-effectiveness for RATS were 0.64 and 0.21 at a presupposed WTP threshold of $ 30,000 per QALY versus OT and VATS, respectively. CONCLUSIONS: RATS was evaluated to be cost-effective versus OT for patients with operable NSCLC from the perspective of Chinese healthcare payer. To the contrary, robotic approach was associated with less cost-effective than VATS.