Use of tumor markers in distinguishing lung adenocarcinoma-associated malignant pleural effusion from tuberculous pleural effusion.

BACKGROUND: The distinction between lung adenocarcinoma-associated malignant pleural effusion (MPE) and tuberculous pleural effusion (TPE) continues to pose a challenge. This study sought to assess the supplementary value of tumor markers in enabling a differential diagnosis. METHODS: Data concerning tumor markers, which included carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), cancer antigen 153 (CA153), cancer antigen 724 (CA724), neuron-specific enolase (NSE), cytokeratin19 fragment (Cyfra21-1), and squamous cell carcinoma antigen (SCCA), in both serum and pleural effusion samples, were retrospectively compiled from lung adenocarcinoma-associated MPE and TPE patients. A comparative analysis of tumor marker concentrations between the two groups was performed to assess diagnostic utility, followed by a multiple logistic regression to control for confounding variables. RESULTS: While gender, serum CA125 and SCCA, and pleural effusion SCCA manifested comparability between the groups, distinctions were noted in patient age and the concentration of other tumor markers in serum and pleural effusion, which were notably elevated in the MPE group. Multiple logistic regression demonstrated a positive association between the risk of lung adenocarcinoma-associated MPE and levels of CEA and CA153 in serum and pleural effusion, as well as Cyfra21-1 in serum (P < 0.05). The odds ratio for CEA surpassed that of CA153 and Cyfra21-1. CONCLUSIONS: CEA and CA153 in serum and pleural effusion, and Cyfra21-1 in serum emerge as biomarkers possessing supplementary diagnostic value in distinguishing lung adenocarcinoma-associated MPE from TPE. The diagnostic efficacy of CEA is superior to CA153 and Cyfra21-1. Conversely, the utility of CA125, CA724, NSE, and SCCA appears constrained.

N-Fluorosulfonyl Guanidine: An Entry to N-Guanyl Sulfamides and Sulfamates.

Here, we present the straightforward synthesis of N-fluorosulfonyl guanidine (1) from two industrial feedstocks, guanidine hydrochloride and sulfuryl fluoride (SO2F2), using SuFEx chemistry. Compound 1 exhibits excellent stability under ambient conditions and displays unique SuFEx reactivity toward amines and phenols to generate N-guanyl sulfamides and sulfamates that have rarely been accessed. Notably, water serves as an effective solvent in this process. Our protocol provides a reliable pathway for the synthesis and investigation of these novel guanidine-containing molecules.

An inulin-based glycovesicle for pathogen-targeted drug delivery to ameliorate salmonellosis.

The gut microbiota plays a significant role in the pathogenesis and remission of inflammatory bowel disease. However, conventional antibiotic therapies may alter microbial ecology and lead to dysbiosis of the gut microbiome, which greatly limits therapeutic efficacy. To address this challenge, novel nanomicelles that couple inulin with levofloxacin via disulfide bonds for the treatment of salmonellosis were developed in this study. Owing to their H2S-responsiveness, the nanomicelles can target the inflamed colon and rapidly release levofloxacin to selectively fight against enteric pathogens. Moreover, the embedded inulin can serve as prebiotic fiber to increase the amount of Bifidobacteria and Lactobacilli in mice with salmonellosis, thus maintaining the intestinal mechanical barrier and regulating the balance of the intestinal flora. Therefore, multifunctional nanomicelles had a better curative effect than pure levofloxacin on ameliorating inflammation in vivo. The pathogen-targeted glycovesicle represents a promising drug delivery platform to maximize the efficacy of antibacterial drugs for the treatment of inflammatory bowel disease.

The competitive mechanism of EZH1 and EZH2 in promoting oral squamous cell carcinoma.

Enhancer of Zeste Homolog 1 (EZH1) and Enhancer of Zeste Homolog 2 (EZH2) are the key components of polycomb repressive complex 2 (PRC2); however, the roles of these proteins in oral squamous cell carcinoma (OSCC) have yet to be elucidated. In this study, we aimed to determine the respective roles of these proteins in OSCC by investigating the expression levels of EZH1 and EZH2 in OSCC tissues (N = 63) by immunohistochemistry. In addition, we used lentiviruses to construct stable OSCC cell lines that overexpressed EZH1 and EZH2. Then, we investigated these cell lines for cell viability, colony formation capacity, stemness, and epithelial-mesenchymal transition (EMT). Binding competition between EZH1 and EZH2 with PRC2 was further evaluated using Co-immunoprecipitation (Co-IP). Compared with normal tissues, the expression levels of EZH2 in OSCC tissues was up-regulated, while the expression of EZH1 was down-regulated. EZH2 enhanced cell viability, colony formation capacity, stemness, and EMT, while EZH1 did not. Furthermore, analysis indicated that EZH1 and EZH2 bound competitively to PRC2 and influenced the methylation status of H3K27. In conclusion, our findings verified that EZH1 and EZH2 play opposing roles in OSCC and that EZH1 and EZH2 compete as the key component of PRC2, thus affecting the characteristics of OSCC via the methylation of H3K27.

Favorable effects of open surgery on patients with extensive skull base osteoradionecrosis through a personalized sequential approach: A case series.

The present study aimed to investigate outcomes following open surgery for extensive skull base ORN. Open surgery through a personalized sequential approach was employed to deal with five cases of extensive skull base ORN. Two patients with mild cases underwent regional debridement and sequestrectomy, and three patients with severe cases underwent extensive resection with reconstruction using free anterolateral thigh (ALT) flap. Biological glues and vascularized flaps were used for obturation of the skull base bony defect to prevent postoperative cerebrospinal fluid (CSF) leakage. The infections were controlled by antibiotic administrations which strictly followed the principles of antimicrobial stewardship (AMS). As results, both regional debridement plus sequestrectomy and extensive resection achieved satisfied outcomes in all patients. No severe complications and delayed hospitalization occurred. During the follow-up period (8-19 months), all patients were alive, pain free, without crusting or purulent discharge, and no sequestration or CSF leakage occurred. In conclusion, a personalized sequential approach including open surgery, pedicled/vascularized free flap reconstruction and AMS was advocated for patients with extensive skull base ORN.

Compliant gait control method based on CVSLIP-FF model for biped robot walking over uneven terrain.

Bipedal walking over uneven terrain remains a challenging task due to the environmental complexity and unavoidable landing impact. To realize the stable and robust walking of biped robots, this paper proposes a compliant gait control method, which focuses on walking compliance and conducts research on two levels. In the gait generation level, a Continuous-Variable Spring-Loaded Inverted Pendulum with Finite-sized Foot (CVSLIP-FF) model is provided with the consideration of the ankle joint and compliant spring-loaded leg. Then, a CVSLIP-FF based gait generation pattern with relevant walking strategies is provided to enhance the mobility of biped robots. In the joint control level, an ankle joint admittance control strategy is applied to achieve compliant robot-environment interaction. Experimental results indicate that compared with the traditional SLIP model, the proposed method performs better adaptability to uneven terrain with a 217.77% improvement, and enables biped robots to cope with slight unknown disturbance.

Recent advancements in the discovery of small-molecule non-nucleoside inhibitors targeting SARS-CoV-2 RdRp.

The RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 plays a pivotal role in the life cycle of the novel coronavirus and stands as a significant and promising target for anti-SARS-CoV-2 drugs. Non-nucleoside inhibitors (NNIs), as a category of compounds directed against SARS-CoV-2 RdRp, exhibit a unique and highly effective mechanism, effectively overcoming various factors contributing to drug resistance against nucleoside inhibitors (NIs). This review investigates various NNIs, including both natural and synthetic inhibitors, that closely interacting with the SARS-CoV-2 RdRp with valid evidences from in vitro and in silico studies.

Efficient biosynthesis of creatine by whole-cell catalysis from guanidinoacetic acid in Corynebacterium glutamicum.

Creatine is a naturally occurring derivative of an amino acid commonly utilized in functional foods and pharmaceuticals. Nevertheless, the current industrial synthesis of creatine relies on chemical processes, which may hinder its utilization in certain applications. Therefore, a biological approach was devised that employs whole-cell biocatalysis in the bacterium Corynebacterium glutamicum, which is considered safe for use in food production, to produce safe-for-consumption creatine. The objective of this study was to identify a guanidinoacetate N-methyltransferase (GAMT) with superior catalytic activity for creatine production. Through employing whole-cell biocatalysis, a gamt gene from Mus caroli (Mcgamt) was cloned and expressed in C. glutamicum ATCC 13032, resulting in a creatine titer of 3.37 g/L. Additionally, the study employed a promoter screening strategy that utilized nine native strong promoters in C. glutamicum to enhance the expression level of GAMT. The highest titer was achieved using the P1676 promoter, reaching 4.14 g/L. The conditions of whole-cell biocatalysis were further optimized, resulting in a creatine titer of 5.42 g/L. This is the first report of successful secretory creatine expression in C. glutamicum, which provides a safer and eco-friendly approach for the industrial production of creatine.

Micro X-ray fluorescence (µ-XRF) methodology for quantitative elemental imaging of Al-Zn-Mg-Cu alloys with varying chemical compositions.

The preparation and characterization of Al-Zn-Mg-Cu alloys with varying chemical compositions are helpful for rapid screening of the optimal compositions in the research and development of new materials. The traditional testing methods cannot accurately determine the composition gradient in samples because they have a low spatial resolution or are semi-quantitative and time-consuming. The micro X-ray fluorescence (µ-XRF) methodology has been used for the elemental imaging of Al-Zn-Mg-Cu alloys with varying chemical compositions. The experimental conditions, including testing voltages, testing currents and the dwell time for each pixel, were optimized systematically to improve the repeatability and accuracy of the µ-XRF methodology. The quantitative elemental imaging of an Al-Zn-Mg-Cu alloy rod sample using µ-XRF was performed, and the results were validated by conducting spark optical emission spectroscopy. The limits of detection of µ-XRF for Zn, Mg, and Cu were 0.007 wt%, 0.068 wt%, and 0.002 wt%, respectively. This versatile elemental imaging technique provided an effective means for the component analysis and process evaluation of alloy samples with a composition gradient and thus for research and development of new materials.

Amygdalin and exercise training exert a synergistic effect in improving cardiac performance and ameliorating cardiac inflammation and fibrosis in a rat model of myocardial infarction.

This study investigated the effects of amygdalin (AMY, a cyanogenic glycoside widely distributed in the fruits and seeds of Rosaceae plants) on cardiac performance and ventricular remodeling in a rat model of myocardial infarction (MI). We also investigated whether the combination of AMY with exercise training (ExT) has a beneficial synergistic effect in treating MI rats. MI was induced by the ligation of the left anterior descending coronary artery in male SD rats. ExT or AMY treatment was started 1 week after MI and continued for 1 week (short-term) or 8 weeks (long-term). Cardiac function was evaluated by echocardiographic and hemodynamic parameters. Heart tissues were harvested and subjected to 2,3,5-triphenyl-tetrazolium chloride, Masson's trichrome, hematoxylin-eosin, and immunohistochemical staining. Gene expression was determined by quantitative polymerase chain reaction. Western blot gave a qualitative assessment of protein levels. AMY or ExT improved cardiac function and reduced infarct size in MI rats. AMY or ExT also suppressed myocardial fibrosis and attenuated inflammation in the infarct border zone of hearts from MI rats, as evidenced by inhibition of collagen deposition, inflammatory cell infiltration, and pro-inflammatory markers (interleukin 1ß, interleukin 6, tumor necrosis factor-α, and cyclooxygenase 2). Notably, the effects of AMY combined with ExT were superior to those of AMY alone or ExT alone. Mechanistically, these beneficial functions were correlated with the inhibition of MI-induced activation of the transforming growth factor-ß/Smad pathway. Collectively, AMY and ExT exert a synergistic effect on improving cardiac performance and ameliorating cardiac inflammation and fibrosis after MI, and the effects of long-term intervention were better than short-term intervention.

Post-Transcriptional Regulator RBM47 Stabilizes FBXO2 mRNA to Advance Osteoarthritis Development: WGCNA Analysis and Experimental Validation.

Osteoarthritis (OA) is a common chronic joint degenerative disease and a major cause of disability in the elderly. However, the current intervention strategies cannot effectively improve OA, and the pathogenesis of OA remains elusive. The present study identified RNA binding motif protein 47 (RBM47) as an upstream modulator of key dysregulation gene co-expression module based on weighted gene co-expression network analysis (WGCNA) analysis and least absolute shrinkage and selection operator (Lasso) modeling. Subsequently, data from real-time quantitative PCR and western blot analysis revealed that RBM47 was upregulated in OA models in vivo and in vitro compared with normal controls. Functional analysis results from the MTT assay, flow cytometry, evaluation of LDH activities and inflammatory mediators, and western blot analysis of extracellular matrix (ECM) proteins, showed that RBM47 knockdown significantly alleviated inflammation, apoptosis, and ECM degradation in interleukin 1ß (IL-1ß)-treated chondrocytes. Mechanistically, RBM47 bound to F box only protein 2 (FBXO2) and stabilized FBXO2 messenger RNA (mRNA) to promote the phosphorylation of signal transducer and activator of transcription 3 (STAT3) in chondrocytes. Results from the recovery assay showed that the re-activation of STAT3 signaling by overexpressing FBXO2 or STAT3 counteracted the alleviating effect of RBM47 downregulation on IL-1ß-induced inflammation, apoptosis, and ECM degradation. Altogether, our findings illustrate that RBM47 stabilizes FBXO2 mRNA to advance OA development by activating STAT3 signaling, which enhances our understanding of the molecular regulatory mechanisms underlying the development of OA.

The association between victims' vulnerable and grandiose narcissism and grudge holding.

Two nonexperimental studies were conducted to test how and why transgression victims' narcissism influences their grudge holding, using undergraduate students and a community sample of adults, respectively. Study 1 tested the association between victims' vulnerable narcissism and grudge holding, including emotional persistence, perceived longevity, and disdain toward the transgressor. It also tested the extent to which victims' grandiose narcissism moderated the association. Study 2 was conducted to replicate Study 1 and test whether victims' rumination about the transgression mediated the moderated association. Overall, those with higher degrees of grandiosity showed a positive relation between vulnerable narcissism and reported emotional persistence (Studies 1 and 2) and perceived longevity (Study 2). Finally, rumination explained the moderated relation (Study 2).

Investigation of 3D printing of toddler foods with special shape and function based on fenugreek gum and flaxseed protein.

The practicability of using corn and flaxseed protein as printing inks for manufacture of printed products specifically designed for toddlers as a dysphagia diet with high precision and special shapes with addition of fenugreek gum (FGG) was investigated. 3D printing was used to process grains and dysphagia-compatible food (corn) into a dietary product with attractive appearance which was also easy to swallow. Rheological measurements shown that appropriate amount of flaxseed protein (FP, 0-10 %) can reduce the stickiness and yield strength of printing material. Based on FTIR measurements, FP weakened the hydrogen bond strength of inks, but it was still an important gradient for the formation of the ink suitable for precision 3D printing. The TPA results shown that the addition of FP (0-10 %) remarkably reduced both the stickiness and hardness of the ink. These results shown that compared with the control group, materials with FGG additions possessed higher printing accuracy and self-supporting ability. Ink with 5 % FP content exhibited the best printability and swallowability, while ink with 10 % FP content had the lowest viscosity and hardness, but it was not suitable for 3D printing. 3D printing of objects printed using Ink-C (5%FP and 0.8 %FGG) showed high support characteristic and attractive appearance. According to the international IDDSI testing standards, Ink-C (5%FP and 0.8 %FGG), Ink-E (15%FP and 0.8 %FGG), and Ink-F (20%FP and 0.8 %FGG) were defined as level 5-minced and moist foods.

Incidence of lumbar spondylolysis in athletes with low back pain: A systematic evaluation and single-arm meta-analysis.

BACKGROUND: Low back pain (LBP) is a common chief complaint from athletes. Lumbar spondylolysis (LS) is a common sport injury. Severe LS is likely to cause spinal instability, resulting in lumbar spondylolisthesis or lumbar disc herniation, and even damage to the spinal nerve roots. The incidence of LS is approximately 5% in the adult population, and nearly half of young athletes with LBP are diagnosed with LS. This meta-analysis analyzed the incidence of LS in athletes with LBP. METHODS: PubMed, Embase, Cochrane (Cochrane Central Register of Controlled Trials), and Web of Science databases were systematically searched for published case report and retrospective analyses related to the topic from the date of database creation to January 1,2023. Relevant literature was screened and information extracted, and risk of bias was assessed for included studies using the methodological index for non-randomized-studies scale. Single-arm Meta-analysis was performed using R4.04 software. Heterogeneity was quantified by Cochran Q test and Higgins I2. Funnel plots were used to visualize publication bias, and Egger test and Begg test were used to statistical tests. RESULTS: A total of 9 studies (835 patients) were included in this study. Meta-analysis revealed that the prevalence of LS in athletes with LBP was estimated at 41.7%, [95% CI = (0.28-0.55)], but this prevalence varied considerably with the gender and age of the athletes. CONCLUSION: The estimated prevalence of LS in athletes with LBP is 41.7%, and future correlations between the prevalence of LS in adolescent athletes worldwide need to be assessed from different perspectives, including biomechanical, hormonal, anatomical, behavioral, and gender differences.

SPDEF enhances cancer stem cell-like properties and tumorigenesis through directly promoting GALNT7 transcription in luminal breast cancer.

BACKGROUND: Luminal breast cancer (BC) is the predominant subtype of breast cancer with a sustained risk of late recurrence and death. Understanding the molecular mechanisms for the oncogenesis of luminal BC would improve the prognosis for this large subset of patients. SPDEF was reported to be dysregulated in breast cancers. However, the biological functions and underlying molecular mechanism of SPDEF in luminal BC remains largely unknown. The aim of the present study was to elucidate the potential roles of SPDEF underlying subtype-specific functions in BC, especially in luminal subtypes. METHODS: The expressions and clinicopathological characteristics of SPDEF in luminal BC patients were evaluated bioinformatically. In vitro and in vivo assays were performed to investigate the oncogenic function and stemness maintenance of SPDEF in luminal BC. Chromatin immunoprecipitation (ChIP) and dual luciferase reporter assays were conducted to determine the transcription regulation of GALNT7 by SPDEF. GALNT7 levels in serum from luminal BC patients were further detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: SPDEF is markedly upregulated in luminal BC and positively associated with tumor progression and poor prognosis. Furthermore, we confirmed that SPDEF enhanced the proliferation, migration, invasion and stemness of luminal BC cells in vitro as well the tumorigenicity in vivo. Mechanistically, we demonstrated the stimulative effect of SPDEF on the progression and stemness of luminal BC, which is mediated by its directly transcriptional target GALNT7. Clinically, we verified that the GALNT7 can be used as a noninvasive diagnostic marker. Noteworthy, the combined detection of serum GALNT7 and traditional tumor markers can enhance diagnostic accuracy thus is of vital importance in the early diagnosis of luminal BC. CONCLUSIONS: Our study reveals a novel mechanism by which SPDEF transcriptionally activates GALNT7 via directly binding to its promoter to promote cell proliferation, motility and stemness, and led to luminal BC tumorigenesis and poor prognosis.

AL-SAR: Active Learning for Skeleton-Based Action Recognition.

Action recognition from temporal multivariate sequences of features, such as identifying human actions, is typically approached by supervised training as it requires many ground truth annotations to reach high recognition accuracy. Unsupervised methods for the organization of sequences into clusters have been introduced, however, such methods continue to require annotations to associate clusters with actions. The challenges in annotation necessitate an effective classification methodology that minimizes the required number of labels. Active learning (AL) approaches have been proposed to address these challenges and were able to establish robust results on image classification. Such approaches are not directly applicable to sequences, since for sequences, the variations are in both spatial and temporal domains. In this brief, we introduce a novel method for AL for sequences, called "AL-SAR", which combines unsupervised training with sparsely supervised annotation. In particular, AL-SAR employs a multi-head mechanism for robust uncertainty evaluation of the latent space learned by an encoder-decoder framework. It aims to iteratively select a sparse set of samples, which annotation contributes the most to the disentanglement of the latent space. We evaluate our system on common benchmark datasets with multiple sequences and actions, such as NW-UCLA, NTU RGB + D 60, and UWA3D. Our results indicate that AL-SAR coupled with encoder-decoder network outperforms other AL methods coupled with the same network structure.

The novel peptide athycaltide-1 attenuates Ang II-induced pathological myocardial hypertrophy by reducing ROS and inhibiting the activation of CaMKII and ERK1/2.

Pathological myocardial hypertrophy initially develops as an adaptive response to cardiac stress, which can be induced by many diseases. It is accompanied by adverse cardiovascular events, including heart failure, arrhythmias, and death. The purpose of this research was to explore the molecular mechanism of a novel peptide Athycaltide-1 (ATH-1) in the treatment of Ang II-induced pathological myocardial hypertrophy. In this study, the mRNA of Control group, Ang II group, ATH-1 group and Losartan group mice were sequenced by high-throughput sequencing technology. The results showed that the differentially expressed genes (DEGs) were significantly enriched in cell response to oxidative stress, regulation of reactive oxygen species metabolism and calmodulin binding. Then, the oxidation level of mouse hearts and H9c2 cardiomyocytes in each group and the expression of key proteins of CaMKII/HDAC/MEF2C and ERK1/2 signaling pathways were detected to preliminarily verify the positive effect of ATH-1. At the same time, the effect of ATH-1 was further determined by adding reactive oxygen species (ROS) inhibitor N-acetylcysteine (NAC) and CaMKII inhibitor AIP in vitro. The results showed that ATH-1 could significantly reduce the level of oxidative stress in hypertrophic cardiomyocytes and inhibiting the activation of CaMKII and ERK1/2.

Signatures of superconductivity near 80 K in a nickelate under high pressure.

Although high-transition-temperature (high-Tc) superconductivity in cuprates has been known for more than three decades, the underlying mechanism remains unknown1-4. Cuprates are the only unconventional superconductors that exhibit bulk superconductivity with Tc above the liquid-nitrogen boiling temperature of 77 K. Here we observe that high-pressure resistance and mutual inductive magnetic susceptibility measurements showed signatures of superconductivity in single crystals of La3Ni2O7 with maximum Tc of 80 K at pressures between 14.0 GPa and 43.5 GPa. The superconducting phase under high pressure has an orthorhombic structure of Fmmm space group with the [Formula: see text] and [Formula: see text] orbitals of Ni cations strongly mixing with oxygen 2p orbitals. Our density functional theory calculations indicate that the superconductivity emerges coincidently with the metallization of the σ-bonding bands under the Fermi level, consisting of the [Formula: see text] orbitals with the apical oxygen ions connecting the Ni-O bilayers. Thus, our discoveries provide not only important clues for the high-Tc superconductivity in this Ruddlesden-Popper double-layered perovskite nickelates but also a previously unknown family of compounds to investigate the high-Tc superconductivity mechanism.

Effects of Yijinjing combined with resistance training on body fat distribution and hepatic lipids in middle-aged and older people with prediabetes mellitus: A randomized controlled trial.

PURPOSE: This randomized controlled trial aimed to study the effects of Yijinjing plus Elastic Band Resistance exercise on intrahepatic lipid (IHL), body fat distribution, glucolipid metabolism and biomarkers of inflammation in middle-aged and older people with pre-diabetes mellitus (PDM). PARTICIPANTS AGESND METHODS: 34 PDM participants (mean age, 62.62 ± 4.71 years; body mass index [BMI], 25.98 ± 2.44 kg/m2) were randomly assigned to the exercise group (n = 17) or control group (n = 17). The exercise group performed moderate-intensity Yijinjing and Elastic Band Resistance training 5 times per week for 6 months. The control group maintained their previous lifestyle. We measured body composition (body weight and body fat distribution), IHL, plasma glucose, lipid and the homeostatic model assessment of insulin resistance (HOMA-IR), inflammatory cytokines at baseline and 6 months. RESULTS: Compared with baseline, exercise significantly reduced IHL (reduction of 1.91 % ± 2.61 % vs an increase of 0.38 % ± 1.85 % for controls; P = 0.007), BMI (reduction of 1.38 ± 0.88 kg/m2 vs an increase of 0.24 ± 1.02 kg/m2 for controls; P = 0.001), upper limb fat mass, thigh fat mass and whole body fat mass. Fasting glucose, HOMA-IR, plasma total cholesterol (TC), and triglyceride (TG) were decreased in the exercise group (P < 0.05). There were no effects of exercise on liver enzyme levels and inflammatory cytokines. The decrease in IHL was positively correlated with the decreases in BMI, body fat mass and HOMA-IR. CONCLUSION: Six months of Yijinjing and resistance exercise significantly reduced hepatic lipids and body fat mass in middle-aged and older people with PDM. These effects were accompanied by weight loss, improved glycolipid metabolism and insulin resistance.