IL-27 signalling promotes adipocyte thermogenesis and energy expenditure.

Thermogenesis in brown and beige adipose tissue has important roles in maintaining body temperature and countering the development of metabolic disorders such as obesity and type 2 diabetes1,2. Although much is known about commitment and activation of brown and beige adipose tissue, its multiple and abundant immunological factors have not been well characterized3-6. Here we define a critical role of IL-27-IL-27Rα signalling in improving thermogenesis, protecting against diet-induced obesity and ameliorating insulin resistance. Mechanistic studies demonstrate that IL-27 directly targets adipocytes, activating p38 MAPK-PGC-1α signalling and stimulating the production of UCP1. Notably, therapeutic administration of IL-27 ameliorated metabolic morbidities in well-established mouse models of obesity. Consistently, individuals with obesity show significantly decreased levels of serum IL-27, which can be restored after bariatric surgery. Collectively, these findings show that IL-27 has an important role in orchestrating metabolic programs, and is a highly promising target for anti-obesity immunotherapy.

Physiological, Epigenetic, and Transcriptome Analyses Provide Insights into the Responses of Wheat Seedling Leaves to Different Water Depths under Flooding Conditions.

Flooding stress, including waterlogging and submergence, is one of the major abiotic stresses that seriously affects the growth and development of plants. In the present study, physiological, epigenetic, and transcriptomic analyses were performed in wheat seedling leaves under waterlogging (WL), half submergence (HS), and full submergence (FS) treatments. The results demonstrate that FS increased the leaves' hydrogen peroxide (H2O2) and malondialdehyde (MDA) contents and reduced their chlorophyll contents (SPAD), photosynthetic efficiency (Fv/Fm), and shoot dry weight more than HS and WL. In addition, FS increased catalase (CAT) and peroxidase (POD) activities more than HS and WL. However, there were no significant differences in the contents of H2O2, MDA, SPAD, and Fv/Fm, and the activities of superoxide dismutase (SOD) and POD between the HS and WL treatments. The changes in DNA methylation were related to stress types, increasing under the WL and HS treatments and decreasing under the FS treatment. Additionally, a total of 9996, 10,619, and 24,949 genes were differentially expressed under the WL, HS, and FS treatments, respectively, among which the 'photosynthesis', 'phenylpropanoid biosynthesis', and 'plant hormone signal transduction' pathways were extensively enriched under the three flooding treatments. The genes involved in these pathways showed flooding-type-specific expression. Moreover, flooding-type-specific responses were observed in the three conditions, including the enrichment of specific TFs and response pathways. These results will contribute to a better understanding of the molecular mechanisms underlying the responses of wheat seedling leaves to flooding stress and provide valuable genetic and epigenetic information for breeding flood-tolerant varieties of wheat.

Comparative transcriptomic and epigenetic analyses reveal conserved and divergent regulatory pathways in barley response to temperature stresses.

DNA methylation and histone modification enable plants to rapidly adapt to adverse temperature stresses, including low temperature (LT) and high temperature (HT) stress. In this study, we conducted physiological, epigenetic, and transcriptomic analyses of barley seedlings grown under control (22°C), mild low temperature (MLT, 14°C) and HT (38°C) conditions to elucidate the underlying molecular mechanisms. Compared to MLT, HT implies greater deleterious effects on barley seedlings' growth. The methylation-sensitive amplification polymorphism analysis showed that MLT induced more DNA methylation and HT more DNA demethylation compared to control. Besides, the higher levels of H3K9ac and H3K4me3 under HT compared to MLT stresses might lead to the loosening of chromatin and, subsequently, the activation of gene expression. Consistently, the transcriptome analysis revealed that there were more differentially expressed genes (DEGs) in plants subjected to HT stress than MLT stress compared to control. The common and unique pathways of these DEGs between MLT and HT were also analyzed. Transcription factors, such as ERF, bHLH, NAC, HSF, and MYB, were most involved in MLT and HT stress. The underlying gene regulation networks of epigenetic modulation-related genes were further explored by weight gene co-expression network analysis. Our study provides new insights into the understanding of epigenetic regulation responses to temperature stress in barley, which will lead to improved strategies for the development of cold- and heat-tolerant barley varieties for sustainable barley production in a climate-changing world.

[Effects of two common acellular methods on the physicochemical properties of dermal acellular matrix].

At present, acellular matrix is an effective replacement material for the treatment of skin damage, but there are few systematic evaluation studies on its performance. The experimental group of this study used two decellularization methods to prepare the matrix: one was the acellular matrix which sterilized with peracetic acid first (0.2% PAA/4% ethanol solution) and then treated with hypertonic saline (group A), the other was 0.05% trypsin/EDTA decellularization after γ irradiation (group B); and the control group was soaked in PBS (Group C). Then physical properties and chemical composition of the three groups were detected. Hematoxylin eosin (HE) staining showed that the acellular effect of group B was good. The porosity of group A and B were both above 84.9%. In group A, the compressive modulus of elasticity was (9.94 ± 3.81) MPa, and the compressive modulus of elasticity was (12.59 ± 5.50) MPa in group B. There was no significant difference between group A or B and group C. The total content of collagen in acellular matrix of group A and B was significantly lower than that of group C (1. 662 ± 0.229) mg/g, but there was no significant difference in the ratio of collagen Ⅰ/Ⅲ between group B and group C. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) showed that there was no significant difference in microstructure. Qualitative detection of fibronectin and elastin in each group was basically consistent with that in group C. Therefore, acellular matrix of group B had better performance as scaffold material. The experimental results show that the acellular matrix prepared by γ-ray sterilization and decellularization of 0.05% Trypsin enzyme/EDTA could be used for the construction of tissue-engineered skin. It could also provide reference for the preparation and mounting of heterogeneous dermal acellular matrix. It was also could be used for electrostatic spinning or three-dimensional printed tissue engineered skin scaffold which could provide physical and chemical parameters for it.

Andrographolide mitigates cardiac apoptosis to provide cardio-protection in high-fat-diet-induced obese mice.

Excessive intake of high fat diet (HFD) and associated obese conditions are critical contributors of cardiac diseases. In this study, an active metabolite andrographolide from Andrographis paniculata was found to ameliorate HFD-induced cardiac apoptosis. C57/BL6 mouse were grouped as control (n = 9), obese (n = 8), low dose (25 mg/kg/d) andrographolide treatment (n = 9), and high dose (50 mg/kg/d) andrographolide treatment (n = 9). The control group was provided with standard laboratory chow and the other groups were fed with HFD. Andrographolide was administered through oral gavage for 1 week. Histopathological analysis showed increase in apoptotic nuclei and considerable cardiac-damages in the obese group signifying cardiac remodeling effects. Further, Western blot results showed increase in pro-apoptotic proteins and decrease in the proteins of IGF-1R-survival signaling. However, feeding of andrographolide significantly reduced the cardiac effects of HFD. The results strongly suggest that andrographolide supplementation can be used for prevention and treatment of cardiovascular disease in obese patients.

Insulin Degludec in People with Type 2 Diabetes in China: A Non-interventional, Retrospective Chart Review Study (CN-TREAT).

INTRODUCTION: Insulin degludec (degludec), an ultra-long-acting basal insulin analogue, provides equivalent glycemic control to other basal insulin analogues, with lower risk of hypoglycemia and flexible dosing. Chinese TREsiba AudiT (CN-TREAT) investigated outcomes with degludec in people with type 2 diabetes (T2D) in routine clinical practice in China. METHODS: This was a retrospective chart review study in adults with T2D initiating or switching to degludec at 50 sites in China between January 2020 and July 2021. The primary endpoint was change in glycated hemoglobin (HbA1c) from baseline to end of study (EOS; week 20). Secondary endpoints included change from baseline to EOS in fasting plasma glucose (FPG), self-measured plasma glucose (SMPG), daily insulin dose, and rate of hypoglycemia. RESULTS: Data from 936 participants were included (499 insulin-naïve; 437 insulin-experienced). Mean (95% confidence interval [CI]) HbA1c change from baseline to EOS was - 1.48%-points (- 1.57; - 1.38; P < 0.0001) overall: - 1.95%-points (- 2.08; - 1.81; P < 0.0001) in insulin-naïve participants and - 0.95%-points (- 1.08; - 0.82; P < 0.0001) in insulin-experienced participants. Mean (95% CI) changes in FPG and SMPG were - 2.27 mmol/L (- 2.69; - 1.85; P < 0.0001) and - 2.89 mmol/L (- 3.52; - 2.25; P < 0.0001), respectively, with similar reductions in insulin-naïve and insulin-experienced subgroups. Rate of hypoglycemia did not change statistically significantly from baseline to EOS overall, or in insulin-experienced participants, except when adjusted for baseline hypoglycemia. Basal insulin dose did not change statistically significantly in insulin-experienced participants. CONCLUSION: In routine clinical practice in China, initiation or switching to degludec was associated with improvements in glycemic control in people with T2D, with no increased risk of hypoglycemia. TRIAL REGISTRATION: ClinialTrials.gov, NCT04227431.

Pioglitazone Hydrochloride Extends the Lifespan of Caenorhabditis elegans by Activating DAF-16/FOXO- and SKN-1/NRF2-Related Signaling Pathways.

Pioglitazone hydrochloride (PGZ), a nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist, is a universally adopted oral agent for the treatment of type 2 diabetes (T2D). Previous studies reported that PGZ could ameliorate the symptoms of aging-related diseases and Alzheimer's disease. However, whether PGZ participates in aging regulation and the underlying mechanism remain undetermined. Here, we found that PGZ significantly prolonged the lifespan and healthspan of Caenorhabditis elegans (C. elegans). We found that a variety of age-related pathways and age-related genes are required for PGZ-induced lifespan extension. The transcription factors DAF-16/FOXO, HSF-1, and SKN-1/NRF2, as well as the nuclear receptors DAF-12 and NHR-49, all functioned in the survival advantage conferred by PGZ. Moreover, our results demonstrated that PGZ induced lifespan extension through the inhibition of insulin/insulin-like signaling (IIS) and reproductive signaling pathways, as well as the activation of dietary restriction- (DR-) related pathways. Additionally, our results also indicated that beneficial longevity mediated by PGZ is linked to its antioxidative activity. Our research may provide a basis for further research on PGZ, as an anti-T2D drug, to interfere with aging and reduce the incidence of age-related diseases in diabetic patients.

Application of dynamic magnetic resonance imaging information technology in adjuvant chemotherapy for breast cancer.

In order to study the application of dynamic magnetic resonance imaging information technology in breast cancer adjuvant chemotherapy, female patients diagnosed with breast cancer in The People's Hospital of Shanxi Province are selected as research objects. Dynamic enhanced magnetic resonance imaging scans are performed to compare pathological changes by hematoxylin and eosin staining. The dynamic NMR morphological changes are used to evaluate the efficacy of neoadjuvant chemotherapy. Semi-quantitative analysis is used to compare the TIC types of lesions, and the changes in quantitative analysis parameters are used to evaluate the efficacy. The results show that in the dynamic magnetic resonance imaging technique, the effective group (RECIST standard is CR and PR) has statistically significant changes in the quantitative analysis parameters Ktrans and Kep before and after neoadjuvant chemotherapy. Ktrans and Kep are used in neoadjuvant chemotherapy for breast cancer. The assessment is consistent with the morphological RECIST criteria assessment and can be used for qualitative diagnosis of breast tumors.

Females with Type 2 Diabetes Mellitus Are Prone to Diabetic Retinopathy: A Twelve-Province Cross-Sectional Study in China.

AIMS: To investigate the distribution of diabetic retinopathy (DR) by sex in patients with type 2 diabetes mellitus (T2DM) in a twelve-province cross-sectional study in China. METHODS: Patients with T2DM, whose ages were ≥18 years, were recruited from 76 cities/counties in 12 provinces in mainland China between January 2015 and December 2018. All participants received a standardized interview, eye examinations, and digital fundus photography. The presence and severity of DR were diagnosed and classified by retina specialists according to the DR domestic typing method. RESULTS: A total of 12,766 participants (5963 males and 6803 females) were eligible for this study. The total prevalence of DR was 30.1%. Females exhibited a significantly higher prevalence of DR than males (31.1% vs. 29.0%, P = 0.011). A multivariate logistic regression analysis confirmed that female sex was an independent predictor for a higher prevalence of DR after adjusting for age, the duration of diabetes, economic status, and the presence of hypertension (OR: 1.096, 95% CI: 1.013-1.186, P = 0.023). Even after stratification by the diabetic duration, age, and economic status, female sex was still independently associated with the presence of DR in patients whose T2DM history was more than 10 years, whose ages were over 60 years, or who were in a relatively intermediate economic area. CONCLUSION: Females had a higher prevalence of DR than males in T2DM patients with a diabetic history of more than 10 years, ages over 60 years, or a relatively intermediate economic status.