Circulating levels of IL-33 are elevated by obesity and positively correlated with metabolic disorders in Chinese adults.

BACKGROUND: Interleukin-33 (IL-33) plays a pivotal role in regulating innate immune response and metabolic homeostasis. However, whether its circulating level is correlated with obesity and metabolic disorders in humans remains largely unknown. We aimed to address this gap by determining IL-33 serum level and its downstream type 2 inflammatory cytokines interleukin-5 (IL-5) and interleukin-13 (IL-13) in overweight/obese population, and analyzing the specific associations between IL-33 and obesity metabolic phenotypes. METHODS: 217 subjects were enrolled and divided into three groups: healthy control (HC) subjects, metabolically healthy overweight/obese (MHOO) subjects and metabolically unhealthy overweight/obese (MUOO) subjects. Circulating levels of IL-33, IL-5 and IL-13 were measured using ELISA analyses. Multivariate regression analyses were further performed to determine the independent association between IL-33 and obesity metabolic phenotypes. RESULTS: Circulating levels of IL-33 were significantly elevated in subjects of MUOO group compared with HC group and MHOO group, while no significant difference was observed between the latter two groups in IL-33 levels. Consistent with this, serum levels of IL-5/13 were higher in the MUOO group compared with HC and MHOO groups. After adjusted for all confounders, MUOO phenotype was significantly associated with increased IL-33 serum levels (OR = 1.70; 95% CI 1.09-2.64; p = 0.019). With the MHOO group as the reference population, higher circulating level of IL-33 was also positively associated with MUOO phenotype after adjusting for confounders (OR = 1.50; 95% CI 1.20-1.88; p = 2.91E-4). However, there was no significant association between MHOO phenotype and IL-33 levels (p = 0.942). Trend analysis further confirmed the positive correlation between MUOO phenotype and IL-33 level (p for trend = 0.019). Additionally, IL-33 was significantly and positively correlated with diastolic blood pressure (DBP), total cholesterol (TC), alanine aminotransferase (ALT), aspartate aminotransferase (AST), white blood cell (WBC), neutrophil and IL-5 only in MUOO group, while inversely correlated with high density lipoprotein cholesterol (HDL-C) in MHOO subjects. CONCLUSION: Circulating levels of IL-33 were significantly elevated in overweight/obese Chinese adults with metabolic disorders. Increased levels of IL-33 were positively associated with metabolically unhealthy overweight/obese phenotype and several metabolic syndrome risk factors.

Perinatal exposure to BDE-47 exacerbated autistic-like behaviors and impairments of dendritic development in a valproic acid-induced rat model of autism.

Perinatal exposure to polybrominated diphenyl ethers (PBDEs) may be a potential risk factor for autism spectrum disorders (ASD). BDE-47 is one of the most common PBDEs and poses serious health hazards on the central nervous system (CNS). However, effects of perinatal exposure to BDE-47 on social behaviors and the potential mechanisms are largely unexplored. Thus, we aimed to investigate whether BDE-47 exposure during gestation and lactation led to autistic-like behaviors in offspring rats in the present study. Valproic acid (VPA), which is widely used to establish animal model of ASD, was also adopted to induce autistic-like behaviors. A battery of tests was conducted to evaluate social and repetitive behaviors in offspring rats. We found that perinatal exposure to BDE-47 caused mild autistic-like behaviors in offspring, which were similar but less severe to those observed in pups maternally exposed to VPA. Moreover, perinatal exposure to BDE-47 aggravated the autistic-like behaviors in pups maternally exposed to VPA. Abnormal dendritic development is known to be deeply associated with autistic-like behaviors. Golgi-Cox staining was used to observe the morphological characteristics of dendrites in the prefrontal cortex of pups. We found perinatal exposure to BDE-47 reduced dendritic length and complexity of branching pattern, and spine density in the offspring prefrontal cortex, which may contribute to autistic-like behaviors observed in the present study. Perinatal exposure to BDE-47 also exacerbated the impairments of dendritic development in pups maternally exposed to VPA. Besides, our study also provided the evidence that the inhibition of BDNF-CREB signaling, a key regulator of dendritic development, may be involved in the dendritic impairments induced by perinatal exposure to BDE-47 and/or VPA, and the consequent autistic-like behaviors.

Sialoglycoprotein isolated from Carassius auratus eggs promotes osteogenesis by stimulating mesenchymal stem cells to commit to osteoblast differentiation.

In this study, we explore whether the pro-osteogenic effects of sialoglycoprotein from Carassius auratus eggs (Ca-SGP) involve mesenchymal stem cells (MSCs). Ovariectomized osteoporotic mice treated with Ca-SGP had increased bone formation and reduced bone marrow adipose tissue. As MSCs are common progenitors of osteoblasts and adipocytes, we isolated MSCs from Ca-SGP-treated mice and found that they tended to differentiate into osteoblasts over adipocytes confirmed by Alizarin red and Oil red O staining. This change was seen at the gene and protein level. To further explore the effect of Ca-SGP on MSCs, we isolated MSCs from healthy mice and treated them with Ca-SGP in vitro. We discovered that Ca-SGP promoted MSC differentiation to osteoblasts. In addition, Ca-SGP promoted osteogenesis and reduced the fat in marrow cavity of adolescent mice. For the first time, our results demonstrate that Ca-SGP promotes osteogenesis via stimulating MSCs to commit to osteoblasts. Graphical Abstract ᅟ.

Yogurt Alleviates Cyclophosphamide-Induced Immunosuppression in Mice through D-Lactate.

Numerous studies have investigated the immunomodulatory effects of yogurt, but the underlying mechanism remained elusive. This study aimed to elucidate the alleviating properties of yogurt on immunosuppression and proposed the underlying mechanism was related to the metabolite D-lactate. In the healthy mice, we validated the safety of daily yogurt consumption (600 µL) or D-lactate (300 mg/kg). In immunosuppressed mice induced by cyclophosphamide (CTX), we evaluated the immune regulation of yogurt and D-lactate. The result showed that yogurt restored body weight, boosted immune organ index, repaired splenic tissue, recovered the severity of delayed-type hypersensitivity reactions and increased serum cytokines (IgA, IgG, IL-6, IFN-γ). Additionally, yogurt enhanced intestinal immune function by restoring the intestinal barrier and upregulating the abundance of Bifidobacterium and Lactobacillus. Further studies showed that D-lactate alleviated immunosuppression in mice mainly by promoting cellular immunity. D-lactate recovered body weight and organ development, elevated serum cytokines (IgA, IgG, IL-6, IFN-γ), enhanced splenic lymphocyte proliferation and increased the mRNA level of T-bet in splenic lymphocyte to bolster Th1 differentiation. Finally, CTX is a chemotherapeutic drug, thus, the application of yogurt and D-lactate in the tumor-bearing mouse model was initially explored. The results showed that both yogurt (600 µL) and D-lactate (300 mg/kg) reduced cyclophosphamide-induced immunosuppression without promoting tumor growth. Overall, this study evaluated the safety, immune efficacy and applicability of yogurt and D-lactate in regulating immunosuppression. It emphasized the potential of yogurt as a functional food for immune regulation, with D-lactate playing a crucial role in its immunomodulatory effects.

Evaluating MODIS cloud-free snow cover datasets using massive spatial benchmark data in the Tibetan Plateau.

Accurate snow cover data is crucial for understanding climate change, managing water resources, and calibrating models. The MODIS (Moderate-resolution Imaging Spectroradiometer) and its cloud-free snow cover datasets are widely used, but they have not been systematically evaluated due to different benchmark data and evaluation parameters. Conventional methods using station observations as a ground truth suffer from underrepresentation and mismatches in temporal and spatial scales. This study established a scale-matched spatial benchmark dataset, compiling from 18,433 Landsat series and 11,172 Sentinel-2 images over two decades, totaling ∼1.86 billion samples and ∼320 million snow samples. We evaluated seven MODIS cloud-free snow cover datasets for seasons, elevation zones, land covers and subregions using this benchmark data. For the clear-sky part, NIEER_MODIS_SCE (MODIS snow cover extent product over China) performs best due to its use of optimal NDSI thresholds suitable for each land use type. This highlights the importance of regional customization in snow mapping algorithms, and it can be further improved in spring, forests and zone 1 by combining it with M*D10A1GL06. For the cloud removed part, one-step integrated spatiotemporal cloud removal datasets perform better than any other approach does. The second-best dataset is obtained from a simple but effective single temporal cloud removal method using nearby time information. For the whole dataset, the best NIEER_MODIS_SCE has an overall accuracy of 0.82 and snow retrieval accuracy of 84.56 %. It performs excellently in most settings but weakest in forests thus requiring more efficient strategies. This research provides new perspectives and methods for objectively assessing MODIS snow cover products and other relevant datasets. These methods can be readily extended to other regions and adapted to future satellite missions. And such findings may guide the selection of more valid snow cover data and the developing of even better snow detecting strategies.

Thromboxane A2/thromboxane A2 receptor axis facilitates hepatic insulin resistance and steatosis through endoplasmic reticulum stress in non-alcoholic fatty liver disease.

BACKGROUND AND PURPOSE: Defective insulin signalling and dysfunction of the endoplasmic reticulum (ER), driven by excessive lipid accumulation in the liver, is a characteristic feature in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Thromboxane A2 (TXA2 ), an arachidonic acid metabolite, is significantly elevated in obesity and plays a crucial role in hepatic gluconeogenesis and adipose tissue macrophage polarization. However, the role of liver TXA2 /TP receptors in insulin resistance and lipid metabolism is largely unknown. EXPERIMENTAL APPROACH: TP receptor knockout (TP-/- ) mice were generated and fed a high-fat diet for 16 weeks. Insulin sensitivity, ER stress responses and hepatic lipid accumulation were assessed. Furthermore, we used primary hepatocytes to dissect the mechanisms by which the TXA2 /TP receptor axis regulates insulin signalling and hepatocyte lipogenesis. KEY RESULTS: TXA2 was increased in diet-induced obese mice, and depletion of TP receptors in adult mice improved systemic insulin resistance and hepatic steatosis. Mechanistically, we found that the TXA2 /TP receptor axis disrupts insulin signalling by activating the Ca2+ /calcium calmodulin-dependent kinase II γ (CaMKIIγ)-protein kinase RNA-like endoplasmic reticulum kinase (PERK)-C/EBP homologous protein (Chop)-tribbles-like protein 3 (TRB3) axis in hepatocytes. In addition, our results revealed that the TXA2 /TP receptor axis directly promoted lipogenesis in primary hepatocytes and contributed to Kupffer cell inflammation. CONCLUSIONS AND IMPLICATIONS: The TXA2 /TP receptor axis facilitates insulin resistance through Ca2+ /CaMKIIγ to activate PERK-Chop-TRB3 signalling. Inhibition of hepatocyte TP receptors improved hepatic steatosis and inflammation. The TP receptor is a new therapeutic target for NAFLD and metabolic syndrome.

A Combination of Exercise and Yogurt Intake Protects Mice against Obesity by Synergistic Promotion of Adipose Browning.

Exercise exerts many beneficial effects on obesity, but the mechanism remains elusive. Here, we report a previously unidentified role of the lactate receptor GPR81 in exercise. We observed that GPR81 was significantly up-regulated in white adipose tissues (WAT) upon exercise training in both lean and obese mice. Exercise could induce thermogenesis and beige adipocyte development, whereas such an effect was markedly impaired by the deficiency of GPR81. Furthermore, the activation of GPR81 by exercise and lactate supplementation (250 or 500 mg/kg) yielded a synergistic enhancement of WAT browning and thermogenesis. Yogurt is a dairy product enriched with lactate. A combination of exercise and yogurt intake (20 g/kg) synergistically protected mice against high-fat-diet-induced obesity, as evidenced by decreased body weight, ameliorative dyslipidemia, improved glucose tolerance, and reduced hepatic steatosis. Mechanistically, lactate-GPR81 axis might aid in the norepinephrine-stimulated beige adipocyte biogenesis cascade via the Ca2+/CaMK pathway. Together, these findings reveal the critical role of lactate-GPR81 signaling in exercise-induced WAT browning and provide a new strategy for personalized diet and lifestyle interventions for obesity management.

Yogurt Alleviates Imiquimod-Induced Psoriasis by Activating the Lactate/GPR81 Signaling Axis in Mice.

In addition to colorectal cancer and metabolic syndrome, regular yogurt consumption has shown promise in improving skin inflammation. In this study, we investigated the effects and possible mechanisms of yogurt on imiquimod-induced psoriasis-like inflammation in mice. After oral administration with yogurt (18 or 36 g/kg) and/or its main metabolite lactate (250 or 500 mg/kg) for 3 days, the mice were treated with a topical dose of 62.5 mg of imiquimod (IMQ) cream for seven consecutive days. Data showed that yogurt and lactate treatment significantly reduced the severity of psoriasis-like skin lesions, excessive keratinocyte proliferation, and immune cell infiltration. Mechanistically, we found that the genetic deficiency of the lactate receptor GPR81 aggravated psoriasis-like features in mice. Activation of the lactate/GPR81 axis inhibited the degradation of IκBα, prevented the nuclear translocation of histone deacetylase 3 (HDAC3) in macrophages, and thus constrained skin inflammation. Overall, these findings suggest that yogurt consumption effectively protects against experimental psoriasis and targeting the lactate/GPR81 signaling axis could be a promising approach for psoriasis inflammation management.

Piperlongumine, a natural alkaloid from Piper longum L. ameliorates metabolic-associated fatty liver disease by antagonizing the thromboxane A2 receptor.

Metabolic dysfunction-associated fatty liver disease (MAFLD) encompasses a broad spectrum of hepatic disorders, including hyperglycemia, hepatic steatosis, and insulin resistance. Piperlongumine (PL), a natural amide alkaloid extracted from the fruits of Piper longum L., exhibited hepatoprotective effects in zebrafish and liver injury mice. This study aimed to investigate the therapeutic potential of PL on MAFLD and its underlying mechanisms. The findings demonstrate that PL effectively combats MAFLD induced by a high-fat diet (HFD) and improves metabolic characteristics in mice. Additionally, our results suggest that the anti-MAFLD effect of PL is attributed to the suppression of excessive hepatic gluconeogenesis, inhibition of de novo lipogenesis, and alleviation of insulin resistance. Importantly, the results indicate that, on the one hand, the hypoglycemic effect of PL is closely associated with CREB-regulated transcriptional coactivators (CRTC2)-dependent cyclic AMP response element binding protein (CREB) phosphorylation; on the other hand, the lipid-lowering effect of PL is attributed to reducing the nuclear localization of sterol regulatory element-binding proteins 1c (Srebp-1c). Mechanistically, PL could alleviate insulin resistance induced by endoplasmic reticulum stress by antagonizing the thromboxane A2 receptor (TP)/Ca2+ signaling, and the TP receptor serves as the potential target for PL in the treatment of MAFLD. Therefore, our results suggested PL effectively improved the major hallmarks of MAFLD induced by HFD, highlighting a potential therapeutic strategy for MAFLD.

Westerly-triggered lake-effect snowfall enhanced with climate warming over the Tibetan Plateau.

Lake-effect snowfall (LES) occurs when cold air moves across open lakes. LES is expected to occur more frequently over the TP, due to the intensified lake expansion caused by intensified global warming. Thus, there is an urgent need to comprehensively assess the LES over the TP. Here, we revealed that the LES is triggered by westerly southward shift leading to the drop in air temperature and is positively correlated with lake area, wind speed and longitude across 12 large lakes (>300 km2) based on satellite observations and reanalysis data. Using a sensitivity model simulation, we determined that large lakes in the southern TP contributed to more than 50% of the snowfall in the downwind area in 2013. Projections indicate that the westerly-triggered LES will increase under the future RCP4.5 climate warming scenario, highlighting the importance of developing adaptive policies to address the growing risks associated with future LES.

Aspirin Suppresses Hepatic Glucagon Signaling Through Decreasing Production of Thromboxane A2.

Excessive hepatic glucose production (HGP) is a major cause of fasting hyperglycemia in diabetes, and antihyperglycemic therapy takes center stage. Nonsteroidal anti-inflammatory drugs, such as acetylsalicylic acid (aspirin), reduce hyperglycemia caused by unrestrained gluconeogenesis in diabetes, but its mechanism is incompletely understood. Here, we reported that aspirin lowers fasting blood glucose and hepatic gluconeogenesis, corresponds with lower thromboxane A2 (TXA2) levels, and the hypoglycemic effect of aspirin could be rescued by TP agonist treatment. On fasting and diabetes stress, the cyclooxygenase (COX)/TXA2/thromboxane A2 receptor (TP) axis was increased in the livers. TP deficiency suppressed starvation-induced hepatic glucose output, thus inhibiting the progression of diabetes, whereas TP activation promoted gluconeogenesis. Aspirin restrains glucagon signaling and gluconeogenic gene expression (phosphoenolpyruvate carboxykinase [PCK1] and glucose-6-phosphatase [G6Pase]) through the TXA2/TP axis. TP mediates hepatic gluconeogenesis by activating PLC/IP3/IP3R signaling, which subsequently enhances CREB phosphorylation via facilitating CRTC2 nuclear translocation. Thus, our findings demonstrate that TXA2/TP plays a crucial role in aspirin's inhibition of hepatic glucose metabolism, and TP may represent a therapeutic target for diabetes.

Thromboxane A2-TP axis promotes adipose tissue macrophages M1 polarization leading to insulin resistance in obesity.

Aberrant arachidonic acid metabolism has been implicated in multiple pathophysiological conditions, and the downstream prostanoids levels are associated with adipocyte dysfunction in obesity. However, the role of thromboxane A2 (TXA2) in obesity remains unclear. We observed that TXA2, through its receptor TP, is a candidate mediator in obesity and metabolic disorders. Obese mice with upregulated TXA2 biosynthesis (TBXAS1) and TXA2 receptor (TP) expression in caused insulin resistance and macrophage M1 polarization in white adipose tissue (WAT), which can be prevented by treatment with aspirin. Mechanistically, the activation of TXA2-TP signaling axis leads to accumulation of protein kinase Cɛ (PKCɛ), thereby enhancing free fat acid (FFA) induced Toll-like receptor4 (TLR4) proinflammatory macrophage activation and the tumor necrosis factor-a (TNF-a) production in adipose tissues. Importantly, TP knockout mice reduced the accumulation of proinflammatory macrophages and adipocyte hypertrophy in WAT. Thus, our findings demonstrate that TXA2-TP axis plays a crucial role in obesity-induced adipose macrophage dysfunction, and rational targeting TXA2 pathway may improve obesity and its associated metabolic disorders in future. In this work, we establish previously unknown role of TXA2-TP axis in WAT. These findings might provide new insight into the molecular pathogenesis of insulin resistance, and indicate rational targeting TXA2 pathway to improve obesity and its associated metabolic disorders in future.

Surveillance of the Antimicrobial Susceptibility and Molecular Characteristics of Neisseria gonorrhoeae Isolates Collected in Changsha, China from 2016 to 2021.

Antibiotic treatment is critical for individuals infected with gonorrhea and preventing disease transmission. This study aimed to analyze the antimicrobial susceptibility and molecular epidemiological characteristics of Neisseria gonorrhoeae isolates in Changsha, China. A total of 271 N.gonorrhoeae isolates collected from the clinical laboratories of two hospitals between 2016 and 2021 were analyzed for antimicrobial susceptibility using the agar dilution method. N. gonorrhoeae multi-antigen sequence typing (NG-MAST) was conducted for genotyping, and phylogenetic analysis was performed using the porB and tbpB sequences. The results showed that antimicrobial resistance against ciprofloxacin, tetracycline, and penicillin was high, and these drugs are no longer recommended for the treatment of gonorrhea. All isolates were susceptible to spectinomycin. However, in 2016-2021, a total of 15 (5.5%) ceftriaxone (CRO)-resistant strains and 31 (11.4%) isolates with decreased susceptibility to CRO were found, and the resistance rate to azithromycin had reached 7.1% in 2016-2017. Epidemiologically, the mosaic penA allele was identified in all CRO-resistant isolates. Based on NG-MAST, ST5061 was the most prevalent ST. Phylogenetic analysis suggested that the resistant isolates did not cluster independently. Despite focus on the local situation, this study raises the need for better gonorrhea medication and highlights that CRO may not be adequate as first-line treatment for gonorrhea in Changsha.

The lactate receptor GPR81 mediates hepatic lipid metabolism and the therapeutic effect of metformin on experimental NAFLDs.

The lactate receptor G protein-coupled receptor 81 (GPR81) has been recently implicated in lipolysis in adipose tissue. In this study, we accidently discovered the role of GPR81 in hepatic lipid metabolism. Data clearly showed that hepatic GPR81 was markedly up-regulated in fasted mice, whereas it was severely down-regulated in obese mice. Genetic deficiency of GPR81 impaired ketogenic response, enhanced hepatic lipid accumulation, and exacerbated hepatosteatosis under acute fasting conditions. Mechanically, we demonstrated that hepatic GPR81 might function as a modulator of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), activate the downsream transcription of liver carnitine o-palmitoyltransferase 1(L-CPT1), and thereby control the influx of fatty acids into mitochondria for ß-oxidation. Importantly, metformin improved experimental nonalcoholic fatty liver disease (NAFLDs) in a GPR81-dependent manner. Collectively, GPR81 was critical for hepatic lipid homeostasis and activation of hepatic GPR81 might represent a promising strategy for the treatment of obesity and its associated metabolic disorders.

The Association Between Hyperuricemia and Obesity Metabolic Phenotypes in Chinese General Population: A Retrospective Analysis.

Purpose: Serum uric acid (UA) not only affects the development of obesity but also alters the metabolic status in obese subjects; thus we investigated the relationship between serum UA and the overweight/obese metabolic phenotypes. Methods: The demographic, biochemical, and hematological data were collected for 12,876 patients undergoing routine physical examination, and 6,912 participants were enrolled in our study. Participants were classified into four obesity metabolic phenotypes according to their BMI and the presence of metabolic syndrome: metabolically healthy overweight/obese (MHOO), metabolically healthy and normal weighted (MHNW), metabolically abnormal and overweight/obese (MAOO), and metabolically abnormal but normal weighted (MANW). Univariate and multivariate logistic regression analysis, stratified analysis, and also interaction analysis were conducted to analyze the relationship between serum UA and obesity metabolic phenotypes. Results: Multivariable logistic regression analysis showed that hyperuricemia was positively associated with MHOO, MANW, and MAOO phenotypes relative to MHNW. After adjusting for the confounding factors, the odds ratios (OR) for individuals with hyperuricemia to be MHOO, MANW, and MAOO phenotypes were 1.86 (1.42-2.45), 2.30 (1.44-3.66), and 3.15 (2.34-4.24), respectively. The ORs for having MHOO, MANW, and MAOO increased 6% [OR: 1.06 (1.05-1.07), P < 0.0001], 5% [OR: 1.05 (1.03-1.07), P < 0.0001], and 11% [OR: 1.11 (1.10-1.13), P < 0.0001] for each 10 unit (µmol/L) of increase in serum UA level. Stratification analysis as well as an interaction test showed that sex and age did not interfere with the association of hyperuricemia with each metabolic phenotype. In terms of the components of the metabolic syndrome, after adjusting for other confounding factors including all of the metabolic indicators except itself, hyperuricemia was positively associated with increased BMI [OR: 1.66 (1.32-2.09), P < 0.0001], hypertriglyceridemia [OR: 1.56 (1.21-2.02), P = 0.0006], and hypertension [OR: 1.22 (1.03-1.46), P = 0.0233], while it had no significant association with hyperglycemia and low HDL-C (all P > 0.05). Conclusion: In our study, we discovered that hyperuricemia was positively associated with MHOO, MANW, and MAOO phenotypes, and this relationship was independent of sex and age.

A low proportion n-6/n-3 PUFA diet supplemented with Antarctic krill (Euphausia superba) oil protects against osteoarthritis by attenuating inflammation in ovariectomized mice.

Osteoarthritis (OA), the most common form of arthritis, is characterized by cartilage destruction, and its incidence is much higher in the osteoporotic population. There is increasing evidence that the occurrence and development of OA are modulated by the dietary intake of polyunsaturated fatty acids (PUFA). This study investigated the effects of dietary PUFA, including n-3/n-6 PUFA proportion and the molecular form of n-3 PUFA, on OA using osteoporotic osteoarthritis dual model mice, where phospholipid type n-3 PUFA were specifically examined. The results revealed that a low proportion of n-6/n-3 PUFA in diets from 1 : 1 to 6 : 1 significantly improved the cartilage structure and inhibited articular cartilage polysaccharide loss. Furthermore, the low proportion n-6/n-3 PUFA diets inhibited the NF-κB signaling pathway by activating G-protein coupled receptor 120 (GPR120) to reduce inflammation and inhibit catabolism. Antarctic krill (Euphausia superba) oil (AKO), rich in phospholipid-type n-3 PUFA, had a better effect on OA than linseed oil (plant-derived n-3 PUFA), which may be due to peroxisome proliferator-activated receptor-gamma (PPAR γ). These findings suggested that the low proportion n-6/n-3 PUFA diets, particularly with AKO, alleviated inflammation and inhibited articular cartilage degeneration. Therefore, dietary intervention can be a potential treatment for OA.

Peptides from Euphausia superba Promote Longitudinal Bone Growth by Accelerating Growth Plate Chondrocyte Proliferation and Hypertrophy.

BACKGROUND: With the improvements in living standards, height is getting more attention. Malnutrition is one of the main causes of children's short stature; therefore, nutritional intervention in adolescence is the key to prevent short stature. The peptides from Antarctic Krill (AKPs), the ideal protein model, act in bone formation and anti-osteoporosis. However, the studies on promoting longitudinal bone growth by AKPs have not been reported. METHODS: Three-week-old male ICR mice, to construct the adolescent mice model, randomly divided into three groups: normal group, casein group (casein, 300 mg/kg·BW), and AKPs group (AKPs, 300 mg/kg·BW). After 21 days of drug administration, the effects of AKPs on serum biochemical indexes and femur histomorphology of mice, and the mechanism of AKPs promoting longitudinal bone growth was discussed. RESULTS: AKPs significantly increased longitudinal bone growth and improved bone strength. In addition, AKPs remarkably promoted proliferation and hypertrophy of chondrocytes in the growth plate. The further mechanism revealed that AKPs increased serum Growth Hormone (GH) and Insulin-Like Growth Factors-1(IGF-1) contents, which activated the downstream GH/IGF-1 axis signaling pathways. Moreover, AKPs induced the secretion and expression of bone morphogenetic protein 2 (BMP- 2) and triggered the activation of BMP2-dependent Smads signaling. AKPs also activated Wnt/ ß-catenin signaling, and synergistically activated the expression of Runt-related transcription factor 2 (Runx 2) and Osterix (OSX). CONCLUSION: AKPs promoted longitudinal bone growth by activating GH/IGF-1 axis, BMP-2/Smads and Wnt/ß-catenin pathways, suggesting AKPs to be a potential nutrient fortifier for longitudinal bone growth.

Evaluation of a Rapid and Simplified Protocol for Direct Identification of Microorganisms From Positive Blood Cultures by Using Matrix Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS).

Early and rapid identification of microorganisms is critical for reducing the mortality rate caused by bloodstream infections (BSIs). The accuracy and feasibility of directly identifying pathogens in positive blood cultures by matrix assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) has been intensely confirmed. In this study, we combined density centrifugation and extra chemical lysis-extraction to develop an optimized method in the blood culture process, which significantly improved the effectiveness of direct identification by MALDI-TOF MS. The accuracy was evaluated by 2,032 positive blood culture samples (115 species of microorganism). The overall MALDI-TOF MS based identification rate with scores ≥ 1.700 was 87.60%. 94.06% of gram-negative bacteria were identified consistently to the genus level, followed by anaerobes (93.33%), gram-positive bacteria (84.46%), and fungi (60.87%). This protocol could obtain results within 10-20 min at a cost of less than $0.1 per sample, which saved up to 24 h in identifying 87.60% of the microorganism from positive blood cultures. This rapid and simplified protocol facilitates the direct identification of microorganism in positive blood cultures, and exhibits the advantages of cost-effective, time-saving, and easy-to-use. It could provide the causative organism of the patient to clinicians in time for targeted treatment and reduce mortality.

Influence of Serum Albumin on HbA1c and HbA1c-Defined Glycemic Status: A Retrospective Study.

Background: Glycated hemoglobin (HbA1c) is commonly used in the diagnosis and evaluation of glycemic control in diabetes, and it may be influenced by several non-glycemic and glycemic factors, including albumin. This retrospective study investigated the influence of albumin on HbA1c and HbA1c-defined glycemic status. Methods: The demographic, hematological, and biochemical data were collected for 11,922 patients undergoing routine physical examination. Univariate and multivariate linear regression analyses, stratified analyses and interaction analyses, and multiple logistic regression were conducted to identify the association between albumin and HbA1c in people with different glycemic status. Results: HbA1c levels were inversely associated with serum albumin level (P < 0.0001) in all participants. Risk factors leading to the association included age > 45 years, high fasting plasma glucose (≥7.0 mmol/L), and anemia. The negative association between HbA1c and albumin was curved (P < 0.0001) and had a threshold effect in the HbA1c-defined diabetic population; the association was significantly stronger when the albumin level fell below 41.4 g/L (ß: -0.31, 95% CI: -0.45 to -0.17, P < 0.0001). A 2 g/L increase in albumin reduced the odds of HbA1c-defined dysglycemia, diabetes, and poor glycemia control by 12% to 36%, after adjustment for all possible confounders. Conclusions: HbA1c was inversely associated with albumin level in all participants, and the association was significantly stronger in people with diabetes (defined by HbA1c criteria). For diabetic patients with lower albumin level, there was an increased risk of an erroneous HbA1c-based identification and management of glycemic status.

Bioinformatic prediction of immunodominant regions in spike protein for early diagnosis of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

BACKGROUND: To contain the pandemics caused by SARS-CoV-2, early detection approaches with high accuracy and accessibility are critical. Generating an antigen-capture based detection system would be an ideal strategy complementing the current methods based on nucleic acids and antibody detection. The spike protein is found on the outside of virus particles and appropriate for antigen detection. METHODS: In this study, we utilized bioinformatics approaches to explore the immunodominant fragments on spike protein of SARS-CoV-2. RESULTS: The S1 subunit of spike protein was identified with higher sequence specificity. Three immunodominant fragments, Spike56-94, Spike199-264, and Spike577-612, located at the S1 subunit were finally selected via bioinformatics analysis. The glycosylation sites and high-frequency mutation sites on spike protein were circumvented in the antigen design. All the identified fragments present qualified antigenicity, hydrophilicity, and surface accessibility. A recombinant antigen with a length of 194 amino acids (aa) consisting of the selected immunodominant fragments as well as a universal Th epitope was finally constructed. CONCLUSION: The recombinant peptide encoded by the construct contains multiple immunodominant epitopes, which is expected to stimulate a strong immune response in mice and generate qualified antibodies for SARS-CoV-2 detection.