Ferroptosis-related gene transferrin receptor protein 1 expression correlates with the prognosis and tumor immune microenvironment in cervical cancer.

Background: Ferroptosis is a non-apoptotic iron-dependent form of cell death implicated in various cancer pathologies. However, its precise role in tumor growth and progression of cervical cancer (CC) remains unclear. Transferrin receptor protein 1 (TFRC), a key molecule associated with ferroptosis, has been identified as influencing a broad range of pathological processes in different cancers. However, the prognostic significance of TFRC in CC remains unclear. The present study utilized bioinformatics to explore the significance of the ferroptosis-related gene TFRC in the progression and prognosis of CC. Methods: We obtained RNA sequencing data and corresponding clinical information on patients with CC from The Cancer Genome Atlas (TCGA), Genotype Tissue Expression (GTEx) and Gene Expression Omnibus (GEO) databases. Using least absolute shrinkage and selection operator (LASSO) Cox regression, we then generated a multigene signature of five ferroptosis-related genes (FRGs) for the prognostic prediction of CC. We investigated the relationship between TFRC gene expression and immune cell infiltration by employing single-sample GSEA (ssGSEA) analysis. The potential functional role of the TFRC gene was evaluated through gene set enrichment analysis (GSEA). Immunohistochemistry and qPCR was employed to assess TFRC mRNA and protein expression in 33 cases of cervical cancer. Furthermore, the relationship between TFRC mRNA expression and overall survival (OS) was investigated in patients. Results: CC samples had significantly higher TFRC gene expression levels than normal tissue samples. Higher TFRC gene expression levels were strongly associated with higher cancer T stages and OS events. The findings of multivariate analyses illustrated that the OS in CC patients with high TFRC expression is shorter than in patients with low TFRC expression. Significant increases were observed in the levels of TFRC mRNA and protein expression in patients diagnosed with CC. Conclusion: Increased TFRC expression in CC was associated with disease progression, an unfavorable prognosis, and dysregulated immune cell infiltration. In addition, it highlights ferroptosis as a promising therapeutic target for CC.

Cur@ZIF-8@BA nanomaterials with pH-responsive and photodynamic therapy properties promotes antimicrobial activity.

Antimicrobial photodynamic therapy (aPDT) has emerged as a highly promising strategy for non-antibiotic treatment of infections due to its unique advantages in efficient bactericidal action and reduction of drug resistance. The natural photosensitizing properties of curcumin (Cur) are widely acknowledged; however, its limited bioavailability has impeded its practical application. In this study, we developed a nanomaterial called Cur@ZIF-8@BA by encapsulating Cur within ZIF-8 and modifying the surface with boric acid (BA). The Cur@ZIF-8@BA exhibits pH-responsive properties and enhances bacterial binding, thereby effectively promoting photodynamic therapy. Moreover, its antibacterial activity against E. coli, Staphylococcus aureus and A. baumannii is significantly increased in the presence of light compared to a dark environment. The mechanism behind this may be that BA increases the affinity of Cur@ZIF-8@BA towards bacteria, and making released Zn2+ and BA from the nanomaterial increase bacterial cell membrane permeability. This facilitates efficient delivery of Cur into bacterial cells, resulting in generation of abundant reactive oxygen species (ROS) and subsequent bactericidal activity. In conclusion, our prepared Cur@ZIF-8@BA holds great promise as a photodynamically mediated antimicrobial strategy.

A self-healing thermogelling polymer with tunable transparency based on biomolecule alginate grafting phenylboronic acid.

Thermogelling polymers with transparency, structure stability and biocompatibility are promising for biomedicine application. In this study, a thermogelling polymer P-C5PEG with tunable transparency was developed by the reaction between alternating copolymer C5PEG and chemically modified biomolecule Alg-PBA via boronic ester bonds. The sol-to-gel transition of P-C5PEG aqueous solution sensitively responded to changes in temperature, and the critical value could be adjusted between 15 and 40 °C by varying the content of C5PEG and Alg-PBA. As the weight ratio of Alg-PBA to C5PEG was over 0.3, the transparency of as-synthesized hydrogel kept above 75 % at 37 °C. Meanwhile, immersion P-C5PEG hydrogel in CaCl2 solution significantly increased its mechanical strength by 3 times due to chelation effect. The shear-resistance and self-healing properties were ensured by dynamic boronic ester bonds due to the protective effect of hydrophobic gel network. As a drug delivery, P-C5PEG hydrogel had a swelling rate of 3748.7 ± 103 % in PBS and could continuously release fluorescein sodium within 24 h. Moreover, the in vitro degradability and cytotoxicity of P-C5PEG was confirmed. Finally, the mechanisms behind the thermogelling property and tunable transparency were revealed. Overall, this thermogelling P-C5PEG polymer, with tunable transparency and thermo-responsiveness, exhibits great potential for biomedicine application.

Single-cell analysis reveals a subpopulation of adipose progenitor cells that impairs glucose homeostasis.

Adipose progenitor cells (APCs) are heterogeneous stromal cells and help to maintain metabolic homeostasis. However, the influence of obesity on human APC heterogeneity and the role of APC subpopulations on regulating glucose homeostasis remain unknown. Here, we find that APCs in human visceral adipose tissue contain four subsets. The composition and functionality of APCs are altered in patients with type 2 diabetes (T2D). CD9+CD55low APCs are the subset which is significantly increased in T2D patients. Transplantation of these cells from T2D patients into adipose tissue causes glycemic disturbance. Mechanistically, CD9+CD55low APCs promote T2D development through producing bioactive proteins to form a detrimental niche, leading to upregulation of adipocyte lipolysis. Depletion of pathogenic APCs by inducing intracellular diphtheria toxin A expression or using a hunter-killer peptide improves obesity-related glycemic disturbance. Collectively, our data provide deeper insights in human APC functionality and highlights APCs as a potential therapeutic target to combat T2D. All mice utilized in this study are male.

Metabolic regulator LKB1 controls adipose tissue ILC2 PD-1 expression and mitochondrial homeostasis to prevent insulin resistance.

Adipose tissue group 2 innate lymphoid cells (ILC2s) help maintain metabolic homeostasis by sustaining type 2 immunity and promoting adipose beiging. Although impairment of the ILC2 compartment contributes to obesity-associated insulin resistance, the underlying mechanisms have not been elucidated. Here, we found that ILC2s in obese mice and humans exhibited impaired liver kinase B1 (LKB1) activation. Genetic ablation of LKB1 disrupted ILC2 mitochondrial metabolism and suppressed ILC2 responses, resulting in exacerbated insulin resistance. Mechanistically, LKB1 deficiency induced aberrant PD-1 expression through activation of NFAT, which in turn enhanced mitophagy by suppressing Bcl-xL expression. Blockade of PD-1 restored the normal functions of ILC2s and reversed obesity-induced insulin resistance in mice. Collectively, these data present the LKB1-PD-1 axis as a promising therapeutic target for the treatment of metabolic disease.

Superlubricity Achieved by a Transparent Poly(vinylpyrrolidone) Composite Hydrogel with Glycerol Ethoxylate in Ocular Conditions.

Efficient and stable ocular lubrication is pivotal in safeguarding eye tissues from wear, especially under repetitive strain due to frequent blinking. Hydrogels have been reported to possess adjustable mechanical properties, biocompatibility, durability, and elevated water content and extensive utilization in medical fields. In this work, a kind of visible photo-cross-linking poly(vinylpyrrolidone) (PVP) hydrogel was designed and synthesized using 1-vinyl-2-pyrrolidone (NVP) and poly(ethylene glycol) diacrylate (PEGDA). To optimize the structure and improve the lubrication performance of hydrogels, we prepared and investigated glycerol ethoxylate (GE)-introduced composite hydrogels (GE/PVP). The results show that the addition of 3 wt % GE helped the hydrogel to form a uniform and dense porous matrix and reduce the frictional coefficient (COF) by over 50%, achieving superlubricity (COF ≈ 0.005). However, with the excessive increase of GE (6 wt %), the structure of the hydrogel is destroyed, inducing pore walls to thin and expand. After that, a lubrication mechanism of the GE/PVP composite hydrogel was proposed, in which the addition of GE reduced the surface tension of the hydrogel, enhanced the hydration ability of the hydrogel, and thus decreased the friction between sliding surfaces. Besides, the cytotoxicity tests show that the composite hydrogels possess good biocompatibility. Overall, the as-synthesized hydrogels hold great potential as lubricating medium for use in ocular applications.

Thermosensitive Triblock Copolymer for Slow-Release Lubricants under Ocular Conditions.

The ocular environment is crucial for a biological lubrication system. An unstable condition of tear film may cause a series of ocular diseases due to serious friction, such as dry eye syndrome, which has drawn extensive attention nowadays. In this study, an in vitro biocompatible superlubricity system, containing thermogelling copolymers (PCGA-PEG-PCGA) and slow-release lubricant (PEG 300/Tween 80), was constructed. First, the sol-gel transition temperature and gel strength of PCGA-PEG-PCGA were adjusted based on the ocular environment by regulating the length of PCGA blocks. Furthermore, the copolymer hydrogel exhibited a reliable slow-release property within 10 days and showed low cytotoxicity. Then, the superlubricity (coefficient of friction of approximately 0.005) was achieved with its released PEG 300/Tween 80 aqueous solution at the sliding velocity range of 1-100 mm s-1 and pressure range of 10-22 kPa. However, the lubrication behaviors varied, while PEG 300 chains and Tween 80 micelles were demonstrated to form a multilayer and a single layer adsorption structure on the sliding surface, respectively. On the whole, the composite lubrication systems, especially the one composed of Tween 80, showed excellent tribological properties owing to the stable slow-release and full hydration effects under ocular conditions, which hold great potential for improving ocular lubrication and maintaining human visual health.

Multi-omics analyses based on genes associated with oxidative stress and phospholipid metabolism revealed the intrinsic molecular characteristics of pancreatic cancer.

Oxidative stress (OS), which impacts lipid metabolic reprogramming, can affect the biological activities of cancer cells. How oxidative stress and phospholipid metabolism (OSPM) influence the prognosis of pancreatic cancer (PC) needs to be elucidated. The metabolic data of 35 pancreatic tumor samples, 34 para-carcinoma samples, and 31 normal pancreatic tissues were obtained from the previously published literature. Pan-cancer samples were obtained from The Cancer Genome Atlas (TCGA). And the Gene Expression Omnibus (GEO), International Cancer Genome Consortium (ICGC), ArrayExpress, and the Genotype-Tissue Expression (GTEx) databases were searched for more PC and normal pancreatic samples. The metabolites in PC were compared with normal and para-carcinoma tissues. The characteristics of the key OSPM genes were summarized in pan-cancer. The random survival forest analysis and multivariate Cox regression analysis were utilized to construct an OSPM-related signature. Based on this signature, PC samples were divided into high- and low-risk subgroups. The dysregulations of the tumor immune microenvironment were further investigated. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was conducted to investigate the expression of genes in the signature in PC and normal tissues. The protein levels of these genes were further demonstrated. In PC, metabolomic studies revealed the alteration of PM, while transcriptomic studies showed different expressions of OSPM-related genes. Then 930 PC samples were divided into three subtypes with different prognoses, and an OSPM-related signature including eight OSPM-related genes (i.e., SLC2A1, MMP14, TOP2A, MBOAT2, ANLN, ECT2, SLC22A3, and FGD6) was developed. High- and low-risk subgroups divided by the signature showed different prognoses, expression levels of immune checkpoint genes, immune cell infiltration, and tumor microenvironment. The risk score was negatively correlated with the proportion of TIL, pDC, Mast cell, and T cell co-stimulation. The expression levels of genes in the signature were verified in PC and normal samples. The protein levels of SLC2A1, MMP14, TOP2A, MBOAT2, ANLN, and SLC22A3 showed up-regulation in PC samples compared with normal tissues. After integrating metabolomics and transcriptomics data, the alterations in OSPM in PC were investigated, and an OSPM-related signature was developed, which was helpful for the prognostic assessment and individualized treatment for PC.

A TDV attention-based BiGRU network for AIS-based vessel trajectory prediction.

Automatic identification system (AIS) is a vessel-based system for the automatic broadcast and reception of vessel information, and it also supports data for trajectory prediction. Since the vessel's sailing route is flexible and changeable and the AIS broadcast is unconfirmed, the trajectory varies greatly and the original AIS data contains some noisy trajectory, which leads to low prediction accuracy and stability. Therefore, to solve the above problem, this paper proposes a trajectory prediction method based on bidirectional gate recurrent unit (BiGRU) and trajectory direction vector (TDV) with attention mechanism. This paper firstly proposes a TDV to associate latitude and longitude with the course and speed. Then the paper proposes an attention mechanism to self-adaptively update weight to the TDV in different stages to eliminate unreasonable predicted trajectory points. Finally, this paper combines the TDV attention mechanism and the BiGRU network to train a vessel trajectory prediction model.

Th1 bias of liver mucosal-associated invariant T cells promotes hepatic gluconeogenesis in type 2 diabetes mellitus.

AIMS: It is acknowledged that aberrant liver immunity contributes to the development of type 2 diabetes mellitus (T2DM). Mucosal-associated invariant T (MAIT) cells, an innate-like T-cell subset, are enriched in the human liver. Nevertheless, the characterisation and potential role of hepatic MAIT cells in T2DM remain unclear. MATERIALS AND METHODS: Fourteen newly diagnosed T2DM subjects and 15 controls received liver biopsy. The frequency and cytokine production of MAIT cells were analysed by flow cytometry. The expression of genes involved in glucose metabolism was determined in HepG2 cells co-cultured with hepatic MAIT cells. RESULTS: Compared with controls, hepatic MAIT cell frequency was significantly increased in T2DM patients (24.66% vs. 14.61%, p = 0.001). There were more MAIT cells producing interferon-γ (IFN-γ, 60.49% vs. 33.33%, p = 0.021) and tumour necrosis factor-α (TNF-α, 46.84% vs. 5.91%, p = 0.021) in T2DM than in controls, whereas their production of interleukin 17 (IL-17) was comparable (15.25% vs. 4.55%, p = 0.054). Notably, an IFN-γ+ TNF-α+ IL-17+/- producing MAIT cell subset was focussed, which showed an elevated proportion in T2DM (42.66% vs. 5.85%, p = 0.021) and positively correlated with plasma glucose levels. A co-culture experiment further indicated that hepatic MAIT cells from T2DM upregulated the gene expression of pyruvate carboxylase, a key molecule involved in gluconeogenesis, in HepG2 cells, and this response was blocked with neutralising antibodies against IFN-γ and TNF-α. CONCLUSIONS: Our data implicate an increased Th1-like MAIT cell subset in the liver of newly diagnosed T2DM subjects, which induces hyperglycaemia by promoting hepatic gluconeogenesis. It provides novel insights into the immune regulation of metabolic homoeostasis. CLINICAL TRIAL REGISTRATION NUMBER: NCT03296605 (registered at www. CLINICALTRIALS: gov on 12 October 2018).

The association between visceral adipocyte hypertrophy and NAFLD in subjects with different degrees of adiposity.

OBJECTIVE: To investigate the association between visceral adipocyte hypertrophy and the onset and development of non-alcoholic fatty liver disease (NAFLD) in subjects with different degrees of adiposity. METHODS: Omental adipose tissue and liver biopsies were collected from obese subjects. NAFLD was defined according to the NASH Clinical Research Network scoring system. Adipocyte size was measured using pathological section analysis. Adipose tissue insulin resistance (Adipo-IR) was calculated as fasting insulin (pmol/L) × fasting free fatty acid concentration (mmol/L). RESULTS: In total, 275 obese patients were enrolled, including 158 females and 58 males with NAFLD. In females, adipocyte size was significantly larger in NAFLD participants as compared to the controls (99.37 ± 14.18 vs. 84.14 ± 12.65 [Formula: see text]m, p < 0.001). Moreover, adipocyte size was larger in females with non-alcoholic steatohepatitis (NASH) as compared to those with non-alcoholic fatty liver (NAFL) (101.45 ± 12.77 vs. 95.79 ± 15.80 [Formula: see text]m, p = 0.015). Mediation analysis showed that adipocyte size impacted the NAFLD activity score through Adipo-IR (b = 0.007 [95% bootstrap CI 0.002, 0.013]). Furthermore, the females were divided into: Q1 (BMI < 32.5 kg/m2), Q2 (BMI 32.5-35.5 kg/m2), Q3 (BMI 35.5-38.8 kg/m2) and Q4 (BMI ≥ 38.8 kg/m2) according to BMI quartiles. Omental adipocyte size was larger in NAFLD subjects in Q1-Q3, but not in Q4. No similar results were observed in males. CONCLUSION: For the first time, we reported that visceral adipocyte hypertrophy was associated with the onset and progression of NAFLD in mild to moderate adiposity but not in severe obesity, which may be mediated by adipose tissue insulin resistance.

Total and methylmercury concentrations in nocturnal migratory birds passing through Mount Ailao, Southwest China.

Despite growing concerns over mercury (Hg) accumulation in birds in recent decades, little is known about Hg exposure in nocturnal migratory birds. Here, total mercury (THg) and methylmercury (MeHg) were detected in the feathers of nocturnal migratory birds (n = 286, belonging to 46 species) passing through Mount Ailao in Southwest China. The stable isotope ratios of carbon (δ13C) and nitrogen (δ15N) were also determined to clarify the effects of trophic position, foraging guild, and foraging behavior on Hg bioaccumulation. Our results show that the THg and MeHg concentrations varied by two orders of magnitude among all nocturnal migratory birds investigated, with the lowest values (THg: 0.056 mg kg-1; MeHg: 0.038 mg kg-1) in the Asian koel (Eudynamys scolopaceus) and the highest (THg: 12 mg kg-1; MeHg: 7.8 mg kg-1) in the hair-crested drongo (Dicrurus hottentottus). Waterbirds showed higher δ15N values and higher THg and MeHg concentrations than songbirds, and the Hg concentrations in piscivorous species were significantly higher than those in herbivores, omnivores, and insectivores. Significant effects of foraging guilds (Kruskal-Wallis one-way ANOVA, p < 0.001) and foraging behaviors (Kruskal-Wallis one-way ANOVA, p < 0.001) on the Hg concentrations in migratory bird feathers were detected. A risk assessment indicated that approximately 7.0% of individuals were at moderate (2.4-5.0 mg kg-1) to high (>5.0 mg kg-1) risk of Hg exposure, and were therefore vulnerable to adverse physiological and behavioral effects. A long-term monitoring campaign during the migratory period is highly recommended to better understand the bioaccumulation of Hg in these nocturnal migratory bird populations over time.

Environmental Friendly Fabrication of Porous Cement Membranes via Reusable Camphene-Based Freeze-Casting Method.

Inorganic membranes have been developed rapidly in recent years because of excellent anti-fouling performance, high mechanical strength and outstanding resistances to acid and alkali. However, the high production cost still restricts its large-scale industrial application. In this work, an environmental friendly unidirectional freezing method via introducing camphene as a reusable template was adapted to prepare porous cement membranes (PCMs). The naturally formed and highly aligned porous structures of PCMs could be divided into three parts: a dense layer, a transition layer and a supporting layer. With the solid content rising from 40 wt.% to 60 wt.%, the pore size of the PCMs decreased from 3.34 nm to 3.62 nm, the bovine serum albumin (BSA) rejection increased from 81.3% to 93.5% and water flux decreased from 346.8 L·m-2·h-1 to 167.3 L·m-2·h-1 (0.2 MPa). Significantly, the performance of PCMs was maintained; even the camphene was reused 20 times. Additionally, the recovery rate of camphene could be reached up to 97.16%. Therefore, this method is cost effective and environmental friendly, which endowed the PCMs great potential in water treatment.

Video Image Moving Target Recognition Method Based on Generated Countermeasure Network.

In order to improve the accuracy of video image moving target recognition and shorten the recognition time, a video image moving target recognition method based on a generation countermeasure network is proposed. Firstly, the image sensor is used to collect the video image and obtain the video image sequence. The Roberts operator is used for edge detection and Gaussian smoothing of the video image. Secondly, the normalization method is used to extract the key features of moving targets in video images. Finally, training is carried out alternately to generate the countermeasure network model, and the video image moving target recognition sample results are output according to the training results to realize the video image moving target recognition. The experimental results show that the highest recognition accuracy of the proposed method is 98.1%, and the longest recognition time is only 5.7 s, indicating that its recognition effect is good.

Research on Haze Image Enhancement based on Dark Channel Prior Algorithm in Machine Vision.

According to the characteristics of foggy images, such as high noise, low resolution, and uneven illumination, an improved foggy image enhancement method based on dark channel priority is proposed. First, the new algorithm refines the transmittance and optimizes the atmospheric light value and converts the restored image to HSV space. Second, the brightness V component is enhanced by MSRCR algorithm improved by bilateral filtering, and the saturation S is improved by adaptive stretching algorithm. Finally, the image is converted from HSV space to RGB space to complete image enhancement. The new method solves the problems of that the color of large area is uneven and the overall color of the image is dark when the traditional dark channel prior method is used to remove fog. The experimental results show that from subjective evaluation and quantitative analysis the new algorithm overcomes the shortcomings of noise amplification and edge blur when the conventional enhancement algorithm enhances the image. It can improve image darkening and avoid image distortion in JPEG, BMP, GIF, PNG, PSD, and TIFF formats. By comparing with other image enhancement algorithms, the improved algorithm performs better than DCP, SSR, MSR, MSRCR, and CLAHE algorithm in PSNR, SSIM, and IE evaluation indexes. It has a good effect on preserving the edge information and has good adaptability and stability for heavily polluted haze image enhancement.

Increased plasmablasts enhance T cell-mediated beta cell destruction and promote the development of type 1 diabetes.

BACKGROUND: Although type 1 diabetes (T1D) is typically described as a T cell-mediated autoimmune disease, increasing evidence for a role of B cells has emerged. However, the pivotal disease-relevant B cell subset and its contribution to islet autoimmunity remain elusive. METHODS: The frequencies and phenotypic characteristics of circulating B cell subsets were analyzed using flow cytometry in individuals with new-onset T1D, long-term T1D, type 2 diabetes, and nondiabetic controls, and also in a prospective cohort of patients receiving mesenchymal stromal cell (MSC) transplantation. NOD mice and adoptive transfer assay were used to dissect the role of the certain B cell subset in disease progression. An in-vitro coculture system of islets with immune cells was established to examine the response against islets and the underlying mechanisms. RESULTS: We identified that plasmablasts, a B cell subset at the antibody-secreting stage, were significantly increased and correlated with the deterioration of beta cell function in patients with new-onset T1D. Further, a fall of plasmablast number was associated with the preservation of beta cell function in patients who received MSC transplantation after 3 months of follow-up. Meanwhile, a gradual increase of plasmablasts in pancreatic lymph nodes during the natural progression of insulitis was observed in non-obese diabetic (NOD) mice; adoptive transfer of plasmablasts together with T cells from NOD mice accelerated diabetes onset in NOD/SCID recipients. CONCLUSIONS: Our study revealed that plasmablasts may function as antigen-presenting cells and promote the activation and proinflammatory response of CD4+ T cells, further contributing to the T cell-mediated beta cell destruction. Our results provide insights into the pathogenic role of plasmablasts in islet autoimmunity and may offer new translational strategies for inhibiting T1D development.

Effects of Early Intensive Insulin Therapy on Endothelial Progenitor Cells in Patients with Newly Diagnosed Type 2 Diabetes.

AIM: This study aimed to investigate the alteration of circulating CD34+KDR+CD133+ endothelial progenitor cells (EPCs) in patients with newly diagnosed type 2 diabetes and the mechanism of the effect of early intensive insulin therapy. METHODS: In this study, 36 patients with newly diagnosed type 2 diabetes and 22 control subjects matched by age and gender were enrolled. All of the patients with diabetes received intensive insulin therapy. The number of EPCs was assessed by flow cytometry based on the expression of CD34, CD133, and kinase insert domain-containing receptor (KDR). RESULTS: Levels of circulating CD34+KDR+CD133+ EPCs were higher in patients with diabetes compared to control subjects and significantly decreased after intensive insulin therapy. Levels of vascular endothelial growth factor (VEGF), a major contributor to EPC mobilization, were significantly higher in patients with diabetes compared to control subjects, and dramatically decreased after insulin therapy. Importantly, VEGF levels correlated with number of EPCs. Moreover, compared with control subjects, pro-inflammatory cytokines and oxidative stress were significantly higher in patients with diabetes and markedly decreased after intensive insulin therapy. CONCLUSIONS: These results showed that type 2 diabetes is associated with an increase of circulating CD34+KDR+CD133+ EPCs at the onset of diabetes, indicating increased compensatory mobilization. Additionally, early intensive insulin therapy exerts a preserving effect on EPC level partly through improving inflammation status and oxidative stress, thereby implying a putative long-term beneficial effect on vascular integrity via suspending excessive EPC exhaustion. CLINICAL TRIAL NUMBER: NCT03710811.

Peripheral Administration of NMU Promotes White Adipose Tissue Beiging and Improves Glucose Tolerance.

PURPOSE: Targeting white adipose tissue (WAT) beiging has been proposed as an effective way to increase thermogenesis and improve glucose metabolism. Neuromedin U (NMU) is a neuropeptide that could increase energy expenditure, while its effects on WAT beiging and glucose homeostasis remain to be investigated. METHODS: Male C57BL/6 mice were fed with high fat diet (HFD) to induce obesity and hyperglycemia and then treated with chronic subcutaneous injection of NMU. Body weight and food intake were recorded daily. After 14 days of injection, intraperitoneal glucose tolerance tests and 18F-fluorodeoxyglucose micro-positron emission tomography/computed tomography (18F-FDG micro-PET/CT) scans were conducted. Subcutaneous WAT (sWAT) and interscapular brown adipose tissue were collected for the evaluation of adipocyte size, expression of uncoupling protein 1 (Ucp1), and other thermogenic-related genes. Stromal vascular fraction of subcutaneous WAT was extracted for the measurement of type 2 innate lymphocytes (ILC2s) proportions. RESULTS: Glucose tolerance was markedly improved by peripherally administered NMU. Micro-PET/CT suggested that NMU promoted WAT beiging, which was further confirmed by haematoxylin and eosin (H&E) staining and immunohistochemistry. In diet-induced-obese (DIO) mice, NMU activated thermogenic-related genes in WAT. In addition, NMU stimulated ILC2s in the stromal vascular fraction of WAT. CONCLUSION: Taken together, our study indicates that peripheral administration of NMU is a potential therapeutic strategy for the promotion of WAT beiging and the improvement of impaired glucose tolerance.

Body Adiposity Index Is Predictive of Weight Loss after Roux-en-Y Gastric Bypass.

BACKGROUND/AIMS: Roux-en-Y gastric bypass (RYGB) is one of the most effective therapies for morbid obesity, yet some patients who have taken the surgery still undergo insufficient weight loss. Visceral adiposity index (VAI), lipid accumulation product (LAP), body adiposity index (BAI), and cardiometabolic index (CMI) have been regarded as clinical indicators of adiposity phenotypes that associated closely with obesity-related metabolic diseases. However, no studies have evaluated the relationship between these indexes and weight loss after bariatric surgery. In this prospective study, we aimed to evaluate whether VAI, LAP, BAI, and CMI would predict postoperative weight loss outcomes after RYGB. METHODS: This study included 38 men and 67 women who have undergone RYGB between January 2017 and May 2018 and recorded their %TWL (percent of total weight loss), %EBMIL (percent of excess body mass index loss), %EWL (percent of excess weight loss), anthropometric indices, and biochemical parameters before and 12 months after the surgery. In addition, VAI, LAP, BAI, and CMI were measured with anthropometric measures or lipid profiles using related equations and analyzed with metabolic characteristics. RESULTS: Subjects with lower BAI (<32.54 in men and 37.39 in women) displayed higher %EBMIL and %EWL 12 months after surgery. BAI was independently associated with %EWL 12 months after surgery in both men and women (both p < 0.05). The area under the receiver operating characteristic curve for BAI was significantly higher (0.773 in men and 0.818 in women) than VAI, LAP, and CMI. CONCLUSIONS: BAI serves as a reliable surrogate marker of the weight loss outcome after RYGB. The predictivity of adiposity indexes in beneficial outcomes after weight loss therapies is of important referential value for the implementation and optimization of individualized and refined weight loss treatments for obese patients.