Iron supplementation and iron accumulation promote adipocyte thermogenesis through PGC1α-ATGL-mediated lipolysis.

Iron homeostasis is essential for maintaining metabolic health and iron disorder has been linked to chronic metabolic diseases. Increasing thermogenic capacity in adipose tissue has been considered as a potential approach to regulate energy homeostasis. Both mitochondrial biogenesis and mitochondrial function are iron-dependent and essential for adipocyte thermogenic capacity, but the underlying relationships between iron accumulation and adipose thermogenesis is unclear. Firstly, we confirmed that iron homeostasis and the iron regulatory markers (e.g., Tfr1 and Hfe) are involved in cold-induced thermogenesis in subcutaneous adipose tissues using RNA-seq and bioinformatic analysis. Secondly, an Hfe (Hfe-/-)-deficient mouse model, in which tissues become overloaded with iron, was employed. We found iron accumulation caused by Hfe deficiency enhanced mitochondrial respiratory chain expression in subcutaneous white adipose in vivo and resulted in enhanced tissue thermogenesis with upregulation of PGC-1α and adipose triglyceride lipase, mitochondrial biogenesis and lipolysis. To investigate the thermogenic capacity in vitro, stromal vascular fraction from adipose tissues was isolated, followed with adipogenic differentiation. Primary adipocyte from Hfe-/- mice exhibited higher cellular oxygen consumption, associated with enhanced expression of mitochondrial oxidative respiratory chain protein, while primary adipocytes or stromal vascular fractions from WT mice supplemented with iron citrate) exhibited similar effect in thermogenic capacity. Taken together, these findings indicate iron supplementation and iron accumulation (Hfe deficiency) can regulate adipocyte thermogenic capacity, suggesting a potential role for iron homeostasis in adipose tissues.

All-optical tunable microfiber knot resonator with graphene-assisted sandwich structure.

We demonstrate an all-optical tunable microfiber knot resonator (MFKR) by direct light-graphene interaction using external vertical incidence pump laser. The 1530 nm CW pump source is employed to irradiate the sample, which can achieve the performance modulation of MFKR including transmission loss, extinction ratio, and resonant wavelength by the saturable absorption, photo-thermal, and optical Kerr effects, respectively. Compared with the MFKR with only the bottom graphene film, the tunable ranges of transmission loss and extinction ratio are increased by 69 and 125 times, respectively, which can induce a remarkable amplitude tuning. The resonant wavelength of MFKR occurs a red-shift under the irradiation of the pump light, and the red-shift range can exceed one free spectral range (FSR), which means the resonant wavelength could be tuned in the full wavelength range of the transparent window of optical fiber. It is promising for the device to be applied as an all-optical modulator, tunable optical filter, etc.

UN peacekeeper health and risk factors --- a systematic scoping review.

BACKGROUND: Conflicts, natural disasters, and complex emergencies present substantial health challenges to United Nations (UN) peacekeepers deployed in mission areas. This scoping review aims at summarizing previous research on the health of UN peacekeepers and identifies issues for further investigation. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for Scoping Reviews, we systematically searched Web of Science, PubMed, EMBASE, Scopus and China National Knowledge Infrastructure (CNKI) for English and Chinese literature published from April 1997 to November 2023. A data charting form was developed by two reviewers to extract relevant themes and provided narrative descriptions. RESULTS: We screened 1079 de-duplicated records and included 143 studies in this scoping review. There were 112 studies on the health status of UN peacekeepers, with more than half on mental health problems such as stress and anxiety. Many studies explored the health status of UN peacekeepers in African countries deployed from mainly U.S., Canada, U.K., China, Australia and Norway. There were 39 studies on the health risk factors of UN peacekeepers, including natural environmental, social environmental, psychological, behavioral lifestyle, biological factors and health service factors. There were 62 articles on the health protection of UN peacekeepers, mainly based on previous deployment experience, with a lack of theoretical guidance from global health perspectives. This scoping review found that health problems of UN peacekeepers are complicated, and whose impacts are cross-border. Social environmental factors were explored the most among health risk factors. Disease prevention measures, medical and health measures, and psychosocial measures were the main health protection for UN peacekeepers. CONCLUSIONS: This scoping review highlighted that health problems of UN peacekeepers were typical global health issues with complicated and cross-border health risk factors. Therefore, comprehensive strategies could be taken from global health perspectives, including multi-phases (before-deployment, during-deployment, and post-deployment), multi-disciplines (public health, medicine, politics, health diplomacy, and others), and multi-levels (the UN, host countries, troop-contributing countries, the UN peacekeeping team, and UN peacekeepers).

Barriers and opportunities in pancreatic cancer immunotherapy.

Pancreatic ductal adenocarcinoma (PDAC) presents a fatal clinical challenge characterized by a dismal 5-year overall survival rate, primarily due to the lack of early diagnosis and limited therapeutic efficacy. Immunotherapy, a proven success in multiple cancers, has yet to demonstrate significant benefits in PDAC. Recent studies have revealed the immunosuppressive characteristics of the PDAC tumor microenvironment (TME), including immune cells with suppressive properties, desmoplastic stroma, microbiome influences, and PDAC-specific signaling pathways. In this article, we review recent advances in understanding the immunosuppressive TME of PDAC, TME differences among various mouse models of pancreatic cancer, and the mechanisms underlying resistance to immunotherapeutic interventions. Furthermore, we discuss the potential of targeting cancer cell-intrinsic pathways and TME components to sensitize PDAC to immune therapies, providing insights into strategies and future perspectives to break through the barriers in improving pancreatic cancer treatment.

Effects of breast-fed infants-derived Limosilactobacillus reuteri and Bifidobacterium breve ameliorate DSS-induced colitis in mice.

Studies have shown that breastfeeding can reduce the risk and severity of inflammatory bowel disease (IBD) in children and adults. Probiotics in breast milk have also been isolated and their effects on IBD have been studied. However, based on current evidence, the exact efficacy and mechanisms of probiotics in the treatment of IBD cannot be determined. In this study, Bifidobacterium breve FPHC4024 (BB FPHC4024) and Limosilactobacillus reuteri FPHC2951 (LR FPHC2951) were isolated from feces of exclusively breastfed healthy infants and administered by gavage to dextran sulfate sodium (DSS)-induced IBD mice. The results showed that LR FPHC2951 improved the symptoms of DSS-induced IBD, increased the expression of interleukin (IL)-10 mRNA and upregulated the abundance of Verrucomicrobiaceae Akkermansia. Combined with Kyoto Encyclopedia of Genes and Genomes (KEGG)-based Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) function prediction results, we hypothesized that LR FPHC2951 improved DSS-induced colitis symptoms in mice by increasing of IL-10 mRNA, altering the structure of intestinal flora, and reducing proinflammatory pathways and enhancing pathways associated with anti-inflammatory and intestinal protection.

Identification of PANoptosis-related predictors for prognosis and tumor microenvironment by multiomics analysis in glioma.

PANoptosis is a newly described inflammatory programmed cell death, that highlights coordination between pyroptosis, apoptosis and necroptosis. However, the functions of PANoptosis-related genes in glioma progression still remain to be explored. This study aims to identify PANoptosis-related predictors that may be utilized for prognosis prediction and development of new therapeutic targets. Firstly, bulk and single-cell RNA-seq (scRNA-seq) data of glioma patients were extracted from TCGA, CGGA and GEO database. Genetic analysis indicates a considerably high mutation frequency of PANoptosis-related genes (PANRGs) in glioma. Consensus clustering was applied to reveal different subtypes of glioma based on PANRGs. Two PANoptosis subtypes with distinct prognostic and TME characteristics were identified. Then, with LASSO-Cox regression analysis, four PANoptosis-related predictors (MYBL2, TUBA1C, C21orf62 and KCNIP2) were determined from bulk and scRNA-seq analysis. Predictive PANRG score model was established with these predictors and its correlation with tumor microenvironment (TME) was investigated. The results showed that patients with low PANRG score, had higher infiltration of anti-tumor immune cells, higher MSI score and lower TIDE score, which are more likely to benefit from immunotherapy. Further analysis identified 16 potential drugs associated with PANoptosis-related predictors. Moreover, the expression levels of four PANoptosis-related predictors were examined in clinical samples and the results were consistent with those analyzed in the database. Besides, we also confirmed the biological functions of two oncogenic predictors (MYBL2 and TUBA1C) by cell experiments, which revealed that knockdown of MYBL2 or TUBA1C could significantly inhibit the proliferation and migration of glioma cells. These findings highlight the prognostic value and biological functions of PANRGs in glioma, which may provide valuable insights for individualized treatment.

Low-intensity pulsed ultrasound (LIPUS) promotes skeletal muscle regeneration by regulating PGC-1α/AMPK/GLUT4 pathways in satellite cells/myoblasts.

Low-Intensity Pulsed Ultrasound (LIPUS) holds therapeutic potential in promoting skeletal muscle regeneration, a biological process mediated by satellite cells and myoblasts. Despite their central roles in regeneration, the detailed mechanistic of LIPUS influence on satellite cells and myoblasts are not fully underexplored. In the current investigation, we administrated LIPUS treatment to injured skeletal muscles and C2C12 myoblasts over five consecutive days. Muscle samples were collected on days 6 and 30 post-injury for an in-depth histological and molecular assessment, both in vivo and in vitro with immunofluorescence analysis. During the acute injury phase, LIPUS treatment significantly augmented the satellite cell population, concurrently enhancing the number and size of newly formed myofibers whilst reducing fibrosis levels. At 30 days post-injury, the LIPUS-treated group demonstrated a more robust satellite cell pool and a higher myofiber count, suggesting that early LIPUS intervention facilitates satellite cell proliferation and differentiation, thereby promoting long-term recovery. Additionally, LIPUS markedly accelerated C2C12 myoblast differentiation, with observed increases in AMPK phosphorylation in myoblasts, leading to elevated expression of Glut4 and PGC-1α, and subsequent glucose uptake and mitochondrial biogenesis. These findings imply that LIPUS-induced modulation of myoblasts may culminate in enhanced cellular energy availability, laying a theoretical groundwork for employing LIPUS in ameliorating skeletal muscle regeneration post-injury. NEW & NOTEWORTHY: Utilizing the cardiotoxin (CTX) muscle injury model, we investigated the influence of LIPUS on satellite cell homeostasis and skeletal muscle regeneration. Our findings indicate that LIPUS promotes satellite cell proliferation and differentiation, thereby facilitating skeletal muscle repair. Additionally, in vitro investigations lend credence to the hypothesis that the regulatory effect of LIPUS on satellite cells may be attributed to its capability to enhance cellular energy metabolism.

Developing a conceptual framework for the health protection of United Nations peacekeepers against the COVID-19 pandemic from global health perspectives.

The coronavirus disease 2019 (COVID-19) pandemic has posed particular health risks to United Nations peacekeepers, which require prompt responses and global attention. Since the health protection of United Nations peacekeepers against the COVID-19 pandemic is a typical global health problem, strategies from global health perspectives may help address it. From global health perspectives, and referring to the successful health protection of the Chinese Anti-Ebola medical team in Liberia, a conceptual framework was developed for the health protection of United Nations peacekeepers against the COVID-19 pandemic. Within this framework, the features include multiple cross-borders (cross-border risk factors, impact, and actions); multiple risk factors (Social Determinants of Health), multiple disciplines (public health, medicine, politics, diplomacy, and others), and extensive interdepartmental cooperation. These strategies include multiple phases (before-deployment, during-deployment, and post-deployment), multi-level cooperation networks (the United Nations, host countries, troop-contributing countries, the United Nations peacekeeping team, and United Nations peacekeepers), and concerted efforts from various dimensions (medical, psychological, and social).

Long noncoding RNA SNHG6 promotes papillary thyroid cancer cells proliferation via regulating miR-186/CDK6 axis.

BACKGROUND: Papillary thyroid cancer (PTC) is a common endocrine malignancy, and its incidence rate has been increasing in recent years. Long noncoding RNAs (lncRNAs) participate in cell biological processes through a variety of regulatory ways, and play an essential role in tumor development. METHODS: This study explored the expression of lncRNA small nucleolar RNA host gene 6 (SNHG6) in PTC by bioinformatics analysis, and quantitative real-time PCR (qRT-PCR). Cell counting kit-8 (CCK-8) assay, colony formation assay, and 5-ethynyl-2'-deoxyuridine (EdU) assay were used to study the effect of SNHG6 on the proliferation of PTC cells. Luciferase reporter gene assay and western blot were used to study the mechanism. RESULTS: SNHG6 was highly expressed in PTC tissue samples and cell lines. In vitro, overexpression of SNHG6 promoted the proliferation of PTC cells, while silencing SNHG6 inhibited the proliferation of PTC cells. miR-186 is the downstream target of SNHG6. SNHG6 regulates the proliferation of PTC cells through miR-186. In addition, CDK6 is the target gene of miR-186, which can inhibit the expression of CDK6 protein. SNHG6 can promote the expression of CDK6 by regulating miR-186. CONCLUSIONS: SNHG6 is highly expressed in PTC and can promote the proliferation of PTC cells by regulating the miR-186/CDK6 axis, which is expected to become a potential therapeutic target for PTC.