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ObjectiveFibroblast growth factor 21 (FGF21) is a secreted protein that regulates body metabolism. In recent years, many observational studies have found that FGF21 is closely related to bone mineral density and osteoporosis, but the causal relationship between them is still unclear. Therefore, this study used two-sample, mediated Mendelian randomization (MR) analysis to explore the causal relationship between FGF21 and osteoporosis and bone mineral density.MethodsWe conducted a two-sample, mediator MR Analysis using genetic data from publicly available genome-wide association studies (GWAS) that included genetic variants in the inflammatory cytokine FGF21, and Total body bone mineral density, Heel bone mineral density, Forearm bone mineral density, Femoral neck bone mineral density, osteoporosis. The main analysis method used was inverse variance weighting (IVW) to investigate the causal relationship between exposure and outcome. In addition, weighted median, simple median method, weighted median method and MR-Egger regression were used to supplement the explanation, and sensitivity analysis was performed to evaluate the reliability of the results.ResultsMR Results showed that FGF21 overexpression reduced bone mineral density: Total body bone mineral density (OR=0.920, 95%CI: 0.876-0.966), P=0.001), Heel bone mineral density (OR=0.971, 95%CI (0.949-0.993); P=0.01), Forearm bone mineral density (OR=0.882, 95%CI(0.799-0.973); P=0.012), Femoral neck bone mineral density (OR=0.952, 95%CI(0.908-0.998), P=0.039); In addition, it also increased the risk of osteoporosis (OR=1.003, 95%CI (1.001-1.005), P=0.004). Sensitivity analysis supported the reliability of these results. The effect of FGF21 overexpression on osteoporosis may be mediated by type 2 diabetes mellitus and basal metabolic rate, with mediating effects of 14.96% and 12.21%, respectively.ConclusionsOur study suggests that the overexpression of FGF21 may lead to a decrease in bone mineral density and increase the risk of osteoporosis, and the effect of FGF21 on osteoporosis may be mediated through type 2 diabetes and basal metabolic rate. This study can provide a reference for analyzing the potential mechanism of osteoporosis and is of great significance for the prevention and treatment of osteoporosis.

Abstract Objective Lumbar disc herniation (LDH) is a common spinal surgical disease. Low back and leg pain caused by LDH is the main factor leading to functional disability, which has caused a serious burden to patients and society. Osteoking can delay the progression of osteoporosis and osteoarthritis, and even has a significant effect on the prevention of deep vein thrombosis after fracture surgery. In recent years, it has been gradually used in the treatment of LDH and has received significant results. However, the underlying mechanism remains unclear. The aim of this study was to predict the mechanism of Osteoking in the treatment of LDH through network pharmacology and verify it by molecular docking method. Methods The TCMSP database was used to collect the relevant active components and targets of Osteoking, while the GeneCards, OMIM and DisGeNET databases were utilized to collect the relevant disease targets of LDH. The Venny 2.1.0 software was employed to obtain the intersecting gene targets of Osteoking and LDH. PPI network construction and core target selection were performed using Cytoscape 3.9.0 software. The Metascape database was used for GO and KEGG enrichment analysis of the relevant targets. Finally, molecular docking was conducted using AutoDock software. Results The study identified 116 potential targets and 26 core targets for the treatment of LDH with Osteoking. Pathways in cancer, Alzheimer's disease, microRNAs in cancer and the IL-17 signalling pathway were among the main involved signalling pathways. Molecular docking results demonstrated that the key targets AKT1, IL-6, ALB, TNF and IL-1β exhibited relatively stable binding activities with the main active components of Osteoking. Conclusions Osteoking can alleviate the symptoms of lumbar disc herniation through the modulation of multiple targets and signalling pathways.

The western Pacific Ocean is the global center for marine biodiversity, with high vulnerability to climate change. A better understanding of the spatiotemporal characteristics and potential drivers of compound marine heatwaves (MHWs) and low-chlorophyll (LChl) extreme events is essential for the conservation and management of local marine organisms and ecosystems. Here, using daily satellite sea surface temperature and model-based chlorophyll concentration, we find that the climatological spatial distribution of MHW-LChl events in total days, duration, and intensity exhibits heterogeneous distributions. The southwest sections of the South China Sea (WSCS) and Indonesian Seas are the hotspots for compound events, with total MHW-LChl days that are more than 2.5 times higher than in the other sub-regions. Notably, there is a trend toward more frequent (> 4.2 d/decade), stronger (> 0.5), and longer-lasting (> 1.4 d/decade) MHW-LChl occurrences in the WSCS. The occurrence of compound MHW-LChl extremes exhibits remarkable seasonal differences, with the majority of these events transpiring during winter. Moreover, there are generally statistically significant increasing trends in MHW-LChl events for all properties on both seasonal and inter-annual timescales. Furthermore, we reveal that the total days of compound MHW-LChl extremes are strongly modulated by large-scale climate modes such as the El Niño-Southern Oscillation and Dipole Mode Index. Overall, pinpointing MHW-LChl hotspots and understanding their changes and drivers help vulnerable communities in better preparing for heightened and compounded risks to marine organism and ecosystems under climate change.

In boreal summer (July–August) 2022, an unprecedented marine heatwave (MHW) occurred in the northwest Pacific Ocean (NWP), while a record-breaking terrestrial heatwave (THW) hit the Yangtze River Basin (YRB). The temperature anomalies caused by this compound MHW-THW event exceeded climatology by 2.5 standard deviations (SDs), breaking the historical record for nearly 100 years, with severe impacts on the ecosystems and social economy. To investigate the underlying causes, we explored the potential roles of anthropogenic forcing, atmospheric circulation, and ‘triple-dip’ La Niña on this compound event using the Coupled Model Intercomparison Project Phase 6 (CMIP6) multi-model simulations. Results indicate that the 2022-like compound MHW-THW event was extremely unlikely to happen without anthropogenic warming, and that such extreme heatwaves were governed by the climatic mean temperature rather than changes in temperature variability. Notably, the anticyclone circulation patterns and associated high-pressure systems (i.e. western North Pacific subtropical high (WNPSH) and South Asian high (SAH)) increase the probability of a 2022-like MHW-THW event by 3.7 times. However, the La Niña phase has no significant effect on the occurrence probability of such events. We further estimate that the 2022-like MHW-THW event will become 7.5 and 11.4 times more likely under the SSP3-7.0 scenario by the middle and end of the 21st century, respectively. This study demonstrates the contribution of anthropogenic climate change and natural variability to the occurrence of compound MHW-THW events and highlights the urgent need to build mitigation strategies for compound MHW-THW events.

The western Pacific Ocean is the global center for marine biodiversity, with high vulnerability to climate change. A better understanding of the spatiotemporal characteristics and potential drivers of compound marine heatwaves (MHWs) and low-chlorophyll (LChl) extreme events is essential for the conservation and management of local marine organisms and ecosystems. Here, using daily satellite sea surface temperature and model-based chlorophyll concentration, we find that the climatological spatial distribution of MHW-LChl events in total days, duration, and intensity exhibits heterogeneous distributions. The southwest sections of the South China Sea (WSCS) and Indonesian Seas are the hotspots for compound events, with total MHW-LChl days that are more than 2.5 times higher than in the other sub-regions. Notably, there is a trend toward more frequent (> 4.2 d/decade), stronger (> 0.5), and longer-lasting (> 1.4 d/decade) MHW-LChl occurrences in the WSCS. The occurrence of compound MHW-LChl extremes exhibits remarkable seasonal differences, with the majority of these events transpiring during winter. Moreover, there are generally statistically significant increasing trends in MHW-LChl events for all properties on both seasonal and inter-annual timescales. Furthermore, we reveal that the total days of compound MHW-LChl extremes are strongly modulated by large-scale climate modes such as the El Niño-Southern Oscillation and Dipole Mode Index. Overall, pinpointing MHW-LChl hotspots and understanding their changes and drivers help vulnerable communities in better preparing for heightened and compounded risks to marine organism and ecosystems under climate change. [ABSTRACT FROM AUTHOR]

Noncoding RNAs (ncRNAs) are involved in the pathological processes of various diseases. The aim of the present study was to verify the expression levels and the diagnostic value of two candidate ncRNAs in the blood leukocytes of patients with gestational diabetes mellitus (GDM) compared to healthy controls. The long ncRNA paired box 8 antisense 1 (Pax8-AS1) and the microRNA miR-4646 were selected, which were identified to be associated with GDM by bioinformatics analysis of a dataset from the Gene Expression Omnibus GEO database. By using reverse transcription-quantitative PCR, the expression levels of Pax8-AS1 and miR-4646 were analysed in leukocytes of patients with GDM (n=35) and normal pregnant females (n=35). The results indicated a significant decrease in the expression levels of both Pax8-AS1 and miR-4646 in patients with GDM as compared with those in the healthy controls. In the second trimester, a strong negative correlation between Pax8-AS1/miR-4646 and 2-h glucose levels was detected in patients with GDM. Receiver operating characteristic curve analysis indicated that the levels of Pax8-AS1 and miR-4646 in the second trimester of pregnancy had a significant diagnostic value with high selectivity and specificity for GDM (area under the curve values, 0.902 and 0.891, respectively; P<0.001). Overall, the present study suggested that Pax8-AS1 and miR-4646 may serve as promising diagnostic biomarkers for GDM. [ABSTRACT FROM AUTHOR]