Chronic hyperglycemia, a defining feature of type 2 diabetes (T2D) and related metabolic disorders, exacerbates insulin resistance and impairs muscle glucose utilization, contributing to systemic metabolic dysfunction. While skeletal muscle is the primary site for postprandial glucose uptake and plays a pivotal role in maintaining whole-body glucose homeostasis, the molecular mechanisms by which hyperglycemia induces maladaptive responses in muscle remain poorly understood. Here, PAXIP1-associated glutamate-rich protein 1 (PAGR1) is identified as a glucose-responsive regulator in skeletal muscle, whose expression is induced by high glucose levels and modulates systemic glucose homeostasis and hepatic metabolism. Using muscle-specific PAGR1-knockout mice, it is demonstrated that PAGR1 deficiency enhances insulin signaling, promotes glucose transporter 4 (GLUT4) translocation, and increases muscle glucose uptake and utilization. Mechanistically, PAGR1 directly activates the expression of TBC1 Domain Family Member 4 (TBC1D4), a RAB GTPase Activating Protein (RabGAP) known to negatively regulate GLUT4 translocation. Importantly, muscle-specific deletion of PAGR1 protects against high-fat-diet-induced insulin resistance and hepatic steatosis. These findings establish PAGR1 as a critical mediator of muscle glucose sensing and utilization, positioning it as a potential target for therapeutic strategies aimed at mitigating glucotoxicity and preventing metabolic diseases such as T2D.

OBJECTIVE:We aimed to demonstrate the effects of creatine (Cr) on osteogenic differentiation (OD) in HDPSCs. MATERIALS AND METHODS:HDPSCs were treated with Cr and an inhibitor of Cr transporter. The OD capacity was evaluated by detecting ALP staining and activity, alizarin red staining (ARS), as well as osteogenesis-related protein levels. Transcriptomic sequencing, western blotting, transmission electron microscopy, immunofluorescence staining, and autophagy-related protein marker detection were applied to illustrate the underlying mechanism. Furthermore, the impact of Cr on bone regeneration was investigated in vivo. RESULTS:We found that 1 mm of Cr effectively enhanced the OD of HDPSCs. The creatine group displayed significantly increased AMPK phosphorylation, overexpressed autophagy-related proteins, enhanced OD, and mineralization capabilities. We also found that ULK1 is the downstream molecule through which AMPK induces cellular autophagy. In vivo results demonstrated that Cr could increase the new bone formation of periodontitis. CONCLUSION:Our research discovered a new AMPK-ULK1-autophagy pathway through which Cr enhances OD in HDPSCs. Cr enhanced HDPSCs-mediated periodontal tissue regeneration in a periodontitis mouse model, providing a theoretical foundation for the study of bone repair in periodontitis.

Chronic ankle pain significantly impairs daily activities and athletic performance with osteochondral lesions of the talus (OLT) in Hepple stages IV and V, which are often causative factors. This study aimed to assess the efficacy and safety of autologous osteochondral transplantation (AOT) for the treatment of these conditions. This retrospective study was conducted from May 2020 to May 2023 at Cangzhou Traditional Chinese and Western Medicine Combined Hospital, including patients with a diagnosis of Hepple stage IV or V OLT confirmed by magnetic resonance imaging (MRI) and arthroscopy. Surgical interventions involved arthroscopic debridement, followed by AOT or limited arthrotomy based on the location and size of the lesion. Preoperative and postoperative evaluations used the Visual Analog Scale, American Orthopedic Foot and Ankle Society Ankle-Hindfoot Scale, MRI-Based Cartilage Repair Tissue Scoring, and the International Knee Documentation Committee Knee Evaluation Form. Statistical analysis was conducted using paired-sample t tests to compare the preoperative and postoperative data. Twenty patients were included, revealing significant postoperative improvements in Visual Analog Scale, American Orthopedic Foot and Ankle Society, and MRI-based cartilage repair tissue scores (P < .05). The radiographic findings suggested effective cartilage regeneration. No adverse effects were observed in the donor knee sites, as confirmed by the stable pre- and postoperative International Knee Documentation Committee Knee Evaluation Form scores. Recovery of physical abilities was achieved on average within 7.3 weeks for daily activities and 13.4 weeks for sports activities. AOT effectively treats Hepple stage IV-V OLT, improves ankle function, promotes cartilage regrowth, and allows quick resumption of daily and athletic activities without compromising donor-site integrity.

Mitochondrial proteases are emerging as key regulators of mitochondrial plasticity and acting as both protein quality surveillance and regulatory enzymes by performing highly regulated proteolytic reactions. However, it remains unclear whether the regulated mitochondrial proteolysis is mechanistically linked to cell identity switching. Here we report that cold-responsive mitochondrial proteolysis is a prerequisite for white-to-beige adipocyte cell fate programming during adipocyte thermogenic remodelling. Thermogenic stimulation selectively promotes mitochondrial proteostasis in mature white adipocytes via the mitochondrial protease LONP1. Disruption of LONP1-dependent proteolysis substantially impairs cold- or β3 adrenergic agonist-induced white-to-beige identity switching of mature adipocytes. Mechanistically, LONP1 selectively degrades succinate dehydrogenase complex iron sulfur subunit B and ensures adequate intracellular succinate levels. This alters the histone methylation status on thermogenic genes and thereby enables adipocyte cell fate programming. Finally, augmented LONP1 expression raises succinate levels and corrects ageing-related impairments in white-to-beige adipocyte conversion and adipocyte thermogenic capacity. Together, these findings reveal that LONP1 links proteolytic surveillance to mitochondrial metabolic rewiring and directs cell identity conversion during adipocyte thermogenic remodelling.

Background: IRF2BP2, a transcriptional co-factor, has emerged as a potential regulator of circulating lipid levels based on several coronary artery disease (CAD) genome-wide association studies (GWAS) studies. However, the role of IRF2BP2 in adipocytes, which regulate fat storage, energy expenditure, and fatty acid release, remains unexplored. Our aim is to investigate the role of IRF2BP2 in adipocyte function regulation. Methods: Human adipocyte stem cells (hASC) were differentiated into adipocytes for in vitro studies. We used the CRISPR system and lentiviral expression constructs to knockout (KO) and overexpress (OE) IRF2BP2. Control, IRF2BP2 KO and IRF2BP2 OE adipocytes were assessed by several methods, including RNA-seq, western blot analysis, and functional assessment of lipolysis and glucose uptake. IRF2BP2 chromatin immunoprecipitation (ChIP)-seq was performed in vitro . Adiponectin-Cre mice were crossed with Irf2bp2 flox/flox mice to generate adipocyte-specific KO (AKO) animals. We evaluated the effect of IRF2BP2 KO on adipose morphology and gene profiles. Circulating fatty acids were assessed in control and AKO mice. Results: IRF2BP2 deletion or OE in hASC-differentiated adipocytes did not affect adipocyte differentiation or glucose uptake. However, triglyceride lipolysis was markedly increased in KO cells. Conversely, IRF2BP2 OE suppressed lipolysis. RNA-seq analysis of control vs. IRF2BP2 KO or OE cells identified the enrichment of lipid catabolic pathways. Notably, IRF2BP2 KO upregulated, whereas IRF2BP2 OE downregulated the mRNA and protein levels of LIPE (i.e. hormone sensitive lipase, or HSL). Further, ChIP-seq analysis demonstrates strong binding of IRF2BP2 to a LIPE enhancer, suggesting direct regulation. In mice, Irf2bp2 AKO increased circulating fatty acids, accompanied by a reduction of adipocyte size. LIPE mRNA and protein expression in adipose tissue was also elevated. Finally, Irf2bp2 AKO induces massive adipose tissue inflammation, evidenced by F4/80 staining and chemotaxis gene markers expression. Conclusions: We established IRF2BP2, as a novel transcriptional regulator of adipocyte lipolysis, through the key lipolytic gene LIPE, which may shed light on deciphering the role of IRF2BP2 in CAD.

The extracurricular life and education of migrant children are significant to the formation of personality and values, but it has been ignored for a long time. The aim of this study is to obtain evidence supporting the theoretical argument that social work intervention in extracurricular education can have a positive impact on migrant children’s learning ability, social adaptability, personality, and interest shaping. From the perspective of practice, including participatory observation and case study method, this paper analyzes the situation of 71 migrant children in order to improve their extracurricular life quality by social work intervention. In the short term, project members have generally developed good study habits. In the long term, the academic performance is generally excellent, which is beneficial to the development of school teaching tasks. The project has an obvious beneficial impact on the academic learning ability and mental health of migrant workers’ children, especially the ability of social adaptation and the shaping of personality interests. The project helps to strengthen the sustainability of migrant children’s education.

Metabolically beneficial beige adipocytes offer tremendous potential to combat metabolic diseases. The folliculin interacting protein 1 (FNIP1) is implicated in controlling cellular metabolism via AMPK and mTORC1. However, whether and how FNIP1 regulates adipocyte browning is unclear. Here, we demonstrate that FNIP1 plays a critical role in controlling adipocyte browning and systemic glucose homeostasis. Adipocyte-specific ablation of FNIP1 promotes a broad thermogenic remodeling of adipocytes, including increased UCP1 levels, high mitochondrial content, and augmented capacity for mitochondrial respiration. Mechanistically, FNIP1 binds to and promotes the activity of SERCA, a main Ca2+ pump responsible for cytosolic Ca2+ removal. Loss of FNIP1 resulted in enhanced intracellular Ca2+ signals and consequential activation of Ca2+-dependent thermogenic program in adipocytes. Furthermore, mice lacking adipocyte FNIP1 were protected against high-fat diet-induced insulin resistance and liver steatosis. Thus, these findings reveal a pivotal role of FNIP1 as a negative regulator of beige adipocyte thermogenesis and unravel an intriguing functional link between intracellular Ca2+ dynamics and adipocyte browning.

To explore the effects of social support on the mental health of older adults in different age groups in China, and to provide reference for the development of social support policies to promote the mental health of older adults in China. This paper uses a random sampling method to conduct a questionnaire survey of 3,000 older adults aged 60 years or older in Nanjing and a dichotomous logistic regression model for empirical analysis. The two dimensions of mental health and social adjustment were used to measure the mental health status of the elderly. The results showed that the overall mental health status of the elderly in Nanjing city was more optimistic, and the nonempty nesters with male gender, higher education level, and partners were generally healthier; objective and subjective support had significant positive effects on the mental health of middle and high aged elderly, while the utilization of support had more significant effects on the health of low-aged elderly. This paper proposes that government departments should develop a localized elderly support system and social support policies adapted to the actual situation in Nanjing according to the quantitative distribution and demand characteristics of the mental health of elderly people in different age groups. The study is structured as follows: the second part contains data sources and statistical methods. The third part is the analysis of empirical results. The fourth part is the discussion and conclusion part of the article.

Adipose tissue undergoes thermogenic remodeling in response to thermal stress and metabolic cues, playing a crucial role in regulating energy expenditure and metabolic homeostasis. Endoplasmic reticulum (ER) stress is associated with adipose dysfunction in obesity and metabolic disease. It remains unclear, however, if ER stress-signaling in adipocytes mechanistically mediates dysregulation of thermogenic fat. Here we show that inositol-requiring enzyme 1α (IRE1α), a key ER stress sensor and signal transducer, acts in both white and beige adipocytes to impede beige fat activation. Ablation of adipocyte IRE1α promotes browning/beiging of subcutaneous white adipose tissue following cold exposure or β3-adrenergic stimulation. Loss of IRE1α alleviates diet-induced obesity and augments the anti-obesity effect of pharmacologic β3-adrenergic stimulation. Notably, IRE1α suppresses stimulated lipolysis and degrades Ppargc1a messenger RNA through its RNase activity to downregulate the thermogenic gene program. Hence, blocking IRE1α bears therapeutic potential in unlocking adipocytes' thermogenic capacity to combat obesity and metabolic disorders.

Objective To elucidate the neuroprotective function of metformin in suppressing propofol-induced apoptosis of HT-22 cells. Methods HT-22 cells were treated with 0, 10 or 100 μmol/L propofol, followed by determination of their proliferative ability. Subsequently, changes in proliferation and apoptosis of propofol-treated HT-22 cells induced with metformin were assessed. Apoptosis-associated genes in HT-22 cells were detected by Western blot. At last, regulatory effects of Cav-1 on propofol and metformin-treated HT-22 cells were examined. Results Propofol treatment dose-dependently decreased proliferative ability and increased apoptosis ability in HT-22 cells, which were partially blocked by metformin administration. Upregulated Bcl-2 and downregulated Bax were observed in propofol-treated HT-22 cells following metformin administration. In addition, Cav-1 level in HT-22 cells was regulated by metformin treatment. Notably, metformin reversed propofol-induced apoptosis stimulation and proliferation decline in HT-22 cells via downregulating Cav-1. Conclusion In our study, we found that propofol could induce apoptosis of HT-22 cells and metformin could rescue the apoptosis effect regulated by propofol. Then, we found that metformin protects propofol-induced neuronal apoptosis via downregulating Cav-1.

The pyrochlore-type (Sr0.6Bi0.305)(2)Bi2O7 containing Bi3+ and Bi5+ mixed valent states was first investigated as a new photocatalytic material in this work and successfully synthesized by a facile hydrothermal method. The phase structure, morphology, microstructure, elemental composition, and optical properties of samples were characterized in details. The experimental measurements combining with the first-principles calculations show that (Sr0.6Bi0.305)(2)Bi2O7 is a n-type semiconductor with a band gap of 1.25 eV. The photocatalytic activity of (Sr0.6Bi0.305)(2)Bi2O7 was evaluated by the degradation of various organic dyes. Our results show that (Sr0.6Bi0.305)(2)Bi2O7 exhibits high photocatalytic efficiency and stability under visible light irradiation. The calculated electronic density of states indicates that Bi and O atoms close to the Sr vacancy probably possess higher activity and are helpful for its photocatalytic performance.

综观高校"形势与政策"课程,目前存在着教学组织模式多元、 教学效果参差不齐、 师资力量相对不足、 考核评价激励欠缺等短板,亟需进一步改革与提升.借鉴通识教育在课程目标、 课程设置等方面成熟的理念和实践,高校"形势与政策"课程应重点在以下几方面进行改革:突出目标意识,探索教学多样模式;突出问题意识,整合教学内容资源;突出互动意识,激发教学主体活力;突出评价意识,推动课程持续发展.

高校学术交流对于提高学术起点、提高科研水平和竞争力、培养创新型人才具有重要的作用,学术交流的目的就在于实现知识共享及知识创新.本文在对高校学术交流中的知识共享的分析中,探讨了学术交流中知识共享的特征及影响因素,最后借助Nonaka的知识螺旋增长模型对高校学术交流中的知识创新路径进行了阐述,为高校提高学术交流中知识共享的效率提供了参考依据.

Background: The poor prognosis of colorectal cancer (CRC) largely results from local invasion and tumor metastases. Epithelial-mesenchymal transition (EMT) is a key step in the progression of solid tumors and plays a vital role in tumor metastasis. Recent studies demonstrate that C-X-C motif chemokine 11 (CXCL11) is involved in various cancers' progression. However, its biological activity in CRC needs deeper exploration. Methods: The level of CXCL11 in CRC tissues and cell lines was determined using the quantitative real-time PCR (qRT-PCR) assay. The MTT, colony formation, wound healing and Transwell invasion assays were applied to assess the role of CXCL11 in CRC cell gro wth, migration and invasion, in vitro, respectively. A xenograft model was constructed to analyze the function of CXCL11 in CRC cell growth in vivo. Results: CXCL11 was over-expressed in CRC tissues and cell lines. Repression of CXCL11 significantly inhibited CRC cell migration, invasion and EMT in vitro. In addition, downregulation of CXCL11 reduced CRC cell growth and metastasis in vivo. Finally, we revealed that repression of CXCL11 inhibited the metastatic ability of CRC cell in a N-cadherin dependent manner. Conclusion: In summary, this study explicates the oncogenic activities of CXCL11 in CRC cell growth and metastasis.

在应用型人才培养目标的指引下,培养德智体全面发展,具有创新意识和实践能力的、适应经济社会发展需求的应用型人力资源管理人才是目前独立学院人力资源管理专业的人才培养方向.本文从制订应用型人才培养方案的思路出发,为独立学院人力资源管理专业应用型人才培养方案的实施提出了可行的举措.

Klotho is an anti-aging protein mainly expressed in the kidney. Reduced Klotho expression closely correlates with the development and progression of chronic kidney disease (CKD). Klotho is also a downstream gene of Peroxisome Proliferation-Activated Receptor gamma (PPAR gamma), a major transcription factor whose functions are significantly affected by post-translational modifications including acetylation. However, whether PPARg acetylation regulates renal Klotho expression and function in CKD is unknown. Here we test whether renal damage and reduced Klotho expression in the adenine CKD mouse model can be attenuated by the pan histone deacetylase (HDAC) inhibitor trichostatin A. This inhibition up-regulated Klotho mainly through an enhancement of PPARg acetylation, stimulation of PPARg binding to Klotho promoter, and PPAR gamma-dependent increase in Klotho transcription, with a substantial control of the regulation occurring via PPARg acetylations on K240 and K265. Consistently trichostatin A-induced reversal of Klotho loss and renoprotective effects were abrogated in PPARg knockout mice, supporting that PPARg is an essential acetylation target for Klotho restoration and renal protection. Intriguingly, the kidneys of adenine-fed CKD mice displayed deregulated HDAC3 up-regulation. Selective HDAC3 inhibition effectively alleviated Klotho loss and kidney injury, whereas the protective effects were largely abolished when Klotho was knocked down by siRNA, suggesting that aberrant HDAC3 and Klotho loss are crucial components involved in the renal damage of mice with CKD. Our study identified an important signaling cascade and key components contributing to the pathogenesis of CKD. Thus, targeting Klotho loss by HDAC3 inhibition has promising therapeutic potential for the reduction of CKD progression.

"新工科"的提出主要基于服务新经济发展、解决人才供需矛盾和深化工程教育改革的需要,是应对知识生产模式转型开展的探索与实践,具有立足发展新经济的应用情境、学科交叉与融合、场所多元化和团队构成的异质性、链式自反性思维和多维度质量控制评估等特点,要求人才培养实现从"适应需要"到"引领发展"、从"术业有专攻"到"跨界融合"、从"理性认知"到"工程实践"、从"家国情怀"到"国际视野"的转变.

Promoting college students' self-employment, is not only the performance of college students' employment view, but also the initiative of college students to participate in social competition and constantly break through their own attempts. It is also one of the measures to alleviate the difficulty of college graduates. Based on the spirit of "double creation", this paper draws lessons from the relevant research ideas and achievements, takes Taizhou university students as the research object, analyzes the status of college students' entrepreneurial self-efficacy and expands their impact on the mechanism of college students' entrepreneurial intention, so as to provide an important theoretical basis for business policy.

思想政治理论课是高校思想政治工作的主渠道,在改进中加强、在创新中提升是高校办好思想政治理论课的基本要求.当前,高校思想政治理论课应加大教学改革力度,着力在教学理念、教学方式、教学质量等方面实现突破与提升.思想政治理论课“浸润式”教学强调教学理念的人本导向、教学题旨的全程浸沁、教学情境的精心创设、教学主体的深度体悟和教学成效的稳定持续.高校应在完善培养方案、转变师生角色、创新方式方法以及优化条件保障等方面着力推进思想政治理论课“浸润式”教学,切实提升教学的亲和力和有效性.

Rhein is an anthraquinone compound isolated from the medicinal plant rhubarb and mainly used in the clinical treatment of diabetic nephropathy. Rhein exhibits various renoprotective functions, but the underlying mechanisms are not fully determined. However, its renoprotective properties recapitulate the role of Klotho, a renal-specific antiaging protein critical for maintaining kidney homeostasis. Here we explored the connections between rhein renoprotection and Klotho in a mouse model of adenine-induced chronic kidney disease. In addition to being an impressive Klotho upregulator, rhein remarkably reversed renal Klotho deficiency in adenine-treated mice. This effect was associated with significant improvement in disturbed serum biochemistry, profibrogenic protein expression, and kidney and bone damage. Further investigation of the molecular basis of Klotho loss revealed that these kidneys displayed marked inductions of DNA methyltransferase DNMT1/DNMT3a and Klotho promoter hypermethylation, whereas rhein treatment effectively corrected these alterations. The renal protective effects of rhein were largely abolished when Klotho was knocked-down by RNA interferences, suggesting that rhein reversal of Klotho deficiency is essential for its renoprotective actions. Thus, our study clarifies how rhein regulation of Klotho expression contributes to its renoprotection and brings new insights into Klotho-targeted strategy for the treatment of kidney diseases of various etiologies.