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Abstract Excessive glucocorticoid (GC) action is linked to various metabolic disorders. Recent findings suggest that disrupting skeletal GC signaling prevents bone loss and alleviates metabolic disorders in high-fat diet (HFD)-fed obese mice, underpinning the neglected contribution of skeletal GC action to obesity and related bone loss. Here, we show that the elevated expression of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), the enzyme driving local GC activation, and GC signaling in osteoblasts, are associated with bone loss and obesity in HFD-fed male mice. Osteoblast-specific 11β-HSD1 knockout male mice exhibit resistance to HFD-induced bone loss and metabolic disorders. Mechanistically, elevated 11β-HSD1 restrains glucose uptake and osteogenic activity in osteoblast. Pharmacologically inhibiting osteoblastic 11β-HSD1 by using bone-targeted 11β-HSD1 inhibitor markedly promotes bone formation, ameliorates glucose handling and mitigated obesity in HFD-fed male mice. Taken together, our study demonstrates that osteoblastic 11β-HSD1 directly contributes to HFD-induced bone loss, glucose handling impairment and obesity.

Abstract Hyperuricemia, characterized by elevated levels of serum uric acid (SUA), is linked to a spectrum of commodities such as gout, cardiovascular diseases, renal disorders, metabolic syndrome, and diabetes, etc. Significantly impairing the quality of life for those affected, the prevalence of hyperuricemia is an upward trend globally, especially in most developed countries. UA possesses a multifaceted role, such as antioxidant, pro-oxidative, pro-inflammatory, nitric oxide modulating, anti-aging, and immune effects, which are significant in both physiological and pathological contexts. The equilibrium of circulating urate levels hinges on the interplay between production and excretion, a delicate balance orchestrated by urate transporter functions across various epithelial tissues and cell types. While existing research has identified hyperuricemia involvement in numerous biological processes and signaling pathways, the precise mechanisms connecting elevated UA levels to disease etiology remain to be fully elucidated. In addition, the influence of genetic susceptibilities and environmental determinants on hyperuricemia calls for a detailed and nuanced examination. This review compiles data from global epidemiological studies and clinical practices, exploring the physiological processes and the genetic foundations of urate transporters in depth. Furthermore, we uncover the complex mechanisms by which the UA induced inflammation influences metabolic processes in individuals with hyperuricemia and the association with its relative disease, offering a foundation for innovative therapeutic approaches and advanced pharmacological strategies.

ObjectiveUltimate frisbee can lead to severe sports injuries, especially joint injuries in the lower limbs, such as knee meniscus injuries. This study examines the impact of personalized exercise therapy on knee meniscus injuries in ultimate frisbee players in the Lingnan region of China.MethodsSeventy-six patients with confirmed meniscal injuries participated in the study, divided into an intervention group (n = 38) and a control group (n = 38). The control group received standard treatment, including drug therapy and physical therapy. The intervention group received standard treatment plus a personalized exercise regimen based on FITT-VP (frequency, intensity, time, type, volume, and progression) principles, incorporating strength training, aerobic exercise, flexibility training, neuromuscular training, and aquatic exercise. This program was monitored and adjusted over a six-month period through both online and offline methods. The primary outcomes were joint range of motion (ROM), thigh circumference atrophy index (TCAI), Lysholm Rating Scale (LRS) scores, and visual analog scores (VAS). The secondary outcome was the International Knee Documentation Committee (IKDC) score. Data were collected before the intervention, and at 1 month and 6 months after the intervention. Statistical analysis was conducted using SPSS 24.0 and GraphPad 10.0, with a significance level set at α = 0.05.ResultsAfter 1 month, the intervention group showed significantly better results in ROM (116.67 ± 9.063), LRS score (86.316 ± 3.750), and IKDC score (80.473 ± 5.421) compared to the control group (111.784 ± 4.778, 82.579 ± 3.818, and 77.684 ± 4.430, respectively) (p

Summary: Articular cartilage degeneration may lead to osteoarthritis (OA) during the aging process, but its underlying mechanism remains unknown. Here, we found that chondrocytes exhibited an energy metabolism shift from glycolysis to oxidative phosphorylation (OXPHOS) during aging. Parkin regulates various cellular metabolic processes. Reprogrammed cartilage metabolism by Parkin ablation decreased OXPHOS and increased glycolysis, with ameliorated aging-related OA. Metabolomics analysis indicated that lauroyl-L-carnitine (LLC) was decreased in aged cartilage, but increased in Parkin-deficient cartilage. In vitro, LLC improved the cartilage matrix synthesis of aged chondrocytes. In vivo, intra-articular injection of LLC in mice with anterior cruciate ligament transaction (ACLT) ameliorated OA progression. These results suggest that metabolic changes are regulated by Parkin-impaired cartilage during aging, and targeting this metabolomic changes by supplementation with LLC is a promising treatment strategy for ameliorating OA.

Abstract Background Osteosarcoma (OS) is one of most commonly diagnosed bone cancer. Circular RNAs (circRNAs) are a class of highly stable non-coding RNA, the majority of which have not been characterized functionally. The underlying function and molecular mechanisms of circRNAs in OS have not been fully demonstrated. Method Microarray analysis was performed to identify circRNAs that are differentially-expressed between OS and corresponding normal tissues. The biological function of circKEAP1 was confirmed in vitro and in vivo. Mass spectrometry and western blot assays were used to identify the circKEAP1-encoded protein KEAP1-259aa. The molecular mechanism of circKEAP1 was investigated by RNA sequencing and RNA immunoprecipitation analyses. Results Here, we identified a tumor suppressor circKEAP1, originating from the back-splicing of exon2 of the KEAP1 gene. Clinically, circKEAP1 is downregulated in OS tumors and associated with better survival in cancer patients. N6-methyladenosine (m6A) at a specific adenosine leads to low expression of circKEAP1. Further analysis revealed that circKEAP1 contained a 777 nt long ORF and encoded a truncated protein KEAP1-259aa that reduces cell proliferation, invasion and tumorsphere formation of OS cells. Mechanistically, KEAP1-259aa bound to vimentin in the cytoplasm to promote vimentin proteasome degradation by interacting with the E3 ligase ARIH1. Moreover, circKEAP1 interacted with RIG-I to activate anti-tumor immunity via the IFN-γ pathway. Conclusion Taken together, our findings characterize a tumor suppressor circKEAP1 as a key tumor suppressor regulating of OS cell stemness, proliferation and migration, providing potential therapeutic targets for treatment of OS.

The aim of this study is to accurately extract the dielectric parameters of building materials through nondestructive measurement methods. The ultrawideband (UWB) measurement system is used to capture echoes from marble targets in the frequency range of 2.5–15 GHz, and the reflection coefficient is derived using a time window separation technique. By combining the particle swarm optimization (PSO) algorithm, the dielectric parameters of the marble targets are successfully inverted. Research results show that the relative dielectric constant extracted under three different incident angle conditions ranges from 5.370 to 5.545, and the conductivity ranges from 0.00429 to 0.00515 S/m. The root mean square error (RMSE) between the theoretically calculated reflection coefficient and the measured reflection coefficient ranges from 0.013 to 0.025, while the RMSE ranges from 0.047 to 0.066 if the dielectric parameters recommended by ITU-R P.2040-3 are used, thus confirming the accuracy and reliability of the proposed method for dielectric parameters extraction.

To solve the problem of lack of validation for exchanging messages in BGP, a inter-domain routing mechanism, which consisted of a reputation evaluation mechanism and a reputation-based BGP optimal routing algorithm, was proposed.The reputation evaluation mechanism used a distributed autonomous system (AS) alliance architecture, which divided node routing behavior in detail.The service domain and observation weight were used as indicators to quantify the impact of node behavior.By designing a feedback mechanism, the reputation value not only reflected the good and bad of nodes, but also reflected the node’s resistance to malicious attacks.The reputation-based BGP routing selection algorithm adds a “security” policy to the existing routing selection algorithm by filtering routes containing low-reputation nodes and selecting the best route among high reputation routes.The experimental results show that the proposed mechanism outperform most existing reputation mechanisms by avoiding routes with vulnerable nodes and restraining the propagation of illegal routes, thereby providing a more secure inter-domain routing environment.

Abstract Background In response to an aging population, the Chinese government implemented the three-child policy in 2021 based on the comprehensive two-child policy. With the implementation of the new birth policy, people’s maternal and child health (MCH) needs will also increase. The allocation and fairness of MCH human resources directly affect people’s access to MCH services. The purpose of this study is to analyze the allocation of health human resources in Chinese maternal and child health care institutions, evaluate the fairness of the allocation, to provide a reference for the rational allocation of MCH human resources. Methods The data of health technicians, licensed (assistant) physicians, and registered nurses in maternal and child health care institutions nationwide from 2016 to 2020 were included. The health resource density index (HRDI) is used to evaluate the allocation level of MCH human resources. The Gini coefficient (G) and Theil index (T) are used to evaluate the fairness of the allocation of MCH human resources from the perspectives of population and geographic area. Results From 2016 to 2020, the average annual growth rate of the number of health technicians, licensed (assistant) physicians, and registered nurses in Chinese maternal and child health care institutions was 7.53, 6.88, and 9.12%, respectively. The Gini coefficient (G) of the three types of MCH human resources allocated by population were all below 0.23, and the Gini coefficient (G) allocated by geographical area were all above 0.65. The Theil index (T) of the three types of MCH human resources allocated by population was all lower than 0.06, and the Theil index (T) allocated by geographical area was all higher than 0.53. In addition, the three types of MCH human resources allocated by population and geographic area contributed more than 84% of the Theil index within the group (T intra ) to the Theil index (T). Conclusions China’s MCH human resources were fair in terms of population allocation, but unfair in terms of geographical area allocation. In the future, more attention should be paid to the geographical accessibility of MCH human resources, and the allocation of resources should comprehensively consider the two factors of serving the population and geographical area.

Ameliorating the problem of low leaching efficiency, long leaching period, and high agent consumption should be studied to efficiently exploit ion-absorbed rare earth ore resources. In this study, the surfactant sodium dodecyl sulfate (SDS) is used to enhance the leaching effect of an ion-absorbed rare earth ore by ameliorating the seepage effect for the first time. The effects of surfactant concentration, leaching agent dosage, solution flow velocity, and solution pH on the leaching rate were explored, and the mechanism of SDS was discussed. Under the optimum conditions, the addition of a small amount of SDS (mass fraction 0.04%) can increase the leaching rate by about 5%, shorten the leaching period, and reduce the consumption of the leaching agent. SDS significantly ameliorates the seepage effect of the ore body by reducing the surface tension of the leaching agent and ameliorating the wettability of the mineral surface. This effect is the main factor that improves the leaching efficiency. DFT (density functional theory) calculation results show that SDS can react with rare earth ions, which reduces the adsorption strength on clay mineral surfaces. Hence, rare earth ions are easily exchanged by ammonium ions, and mass transfer is enhanced.

Most of the imported Serck Audco pressure balanced plug valves are adopted for the bypass throttle valves, vent valves and station ESD vent valves of the block valve on the trunk line of PetroChina West-to-East Gas Pipeline. Internal leakage faults of plug valves for station ESD high-pressure venting occur frequently, but the conventional treatment appears not to be satisfactory. Through the analysis on structural characteristics of sealing and pressure balance of the imported plug valves, treatment methods such as grease filling, disassembly for maintenance, valve replacement, and return for repair were put forward based on field practical experience. The root causes of frequent internal leakage of plug valve attribute to abrasion and scratch on surface of plug valve body that may result in sealing failure. During field disassembly and maintenance, the clearance between the plug and the valve body was hard to be restored to its original state. It is hardly possible to reach the original fit accuracy after manual grinding, and the repair effect may be worse after several times of disassembly. So the disassembly and maintenance should be treated with caution. Return for repair might be able to eliminate the abrasion and scratch on the plug surface, and the internal leakage problem of the valve was verified by the site test and proved to be solvable. But for domestic plug valves or imported plug valves repaired by domestic manufacturers, the additional pressure relief nozzle at the large end of the plug is required to eliminate the plug self-locking phenomenon. The pressure relief nozzle at the large end is in direct contact with the medium fluid, and impurities cannot be prevented from entering the bottom of the large end under the working condition that the valve is used for pipeline medium containing large amounts of impurities. Research should be carried out in these aspects for the localization development of plug valves.

Evidence in animals suggests that deep brain stimulation or optogenetics can be used for recovery from disorders of consciousness (DOC). However, these treatments require invasive procedures. This report presents a noninvasive strategy to stimulate central nervous system neurons selectively for recovery from DOC in mice. Through the delivery of ultrasound energy to the ventral tegmental area, mice were aroused from an unconscious, anaesthetized state in this study, and this process was controlled by adjusting the ultrasound parameters. The mice in the sham group under isoflurane-induced, continuous, steady-state general anaesthesia did not regain their righting reflex. On insonation, the emergence time from inhaled isoflurane anaesthesia decreased (sham: 13.63±0.53 min, ultrasound: 1.5±0.19 min, p

Objectives This study attempts to analyse the impact of smoking on the income level of Chinese urban residents to provide a reference for creating informed regulations on cigarette smoking.Design A population-based cohort study.Method Two waves of panel data in 2014 and 2016 from the China Family Panel Study were used. A total of 8025 urban adults were identified. The Hausman–Taylor model was used to analyse the theoretical relationship between smoking and income.Results The percentage of current smokers decreased from 27.39% (2014) to 26.24% (2016), while the percentage of former smokers rose from 9.78% to 11.78%. The results from the Hausman–Taylor model showed that current smokers and former smokers are associated with statistically significant decrease in the income of urban residents of 37.70% and 44.00%, respectively, compared with that of non-smokers. After eliminating the impact of smoking on income, the poverty rate among urban residents decreased from 15.33% to 13.63%.Conclusions Smoking can significantly reduce the income of Chinese urban residents, resulting in immense negative impacts on Chinese society. Therefore, the government should raise the tax rate on tobacco, include smoking cessation treatment in medical insurance coverage, promote publicity campaigns on the awareness of tobacco hazards and encourage smokers to quit smoking early.

INTRODUCTION:Smoking is hazardous to health and places a heavy economic burden on individuals and their families. Clearly, smoking in China is prevalent since China is the largest consumer of tobacco in the world. Chinese smoking and nonsmoking households were compared in terms of the incidence and intensity of Catastrophic Health Expenditures (CHEs). The factors associated with catastrophic health expenditures were analyzed. METHODS:Data for this study were collected from two waves of panel data in 2011 and 2013 from the national China Health and Retirement Longitudinal Study (CHARLS). A total of 8073 households with at least one member aged above 45 were identified each year. Catastrophic health expenditure was measured by the ratio of a household's out-of-pocket healthcare payments (OOP) to the household's Capacity to Pay (CTP). A panel logit random-effects model was used to examine correlates with catastrophic health expenditure. RESULTS:The incidence of catastrophic health expenditures for Chinese households with members aged 45 and above in 2011 and 2013 were 12.99% and 15.56%, respectively. The mean gaps (MGs) were 3.16% and 4.88%, respectively, and the mean positive gaps (MPGs) were 24.36% and 31.40%, respectively. The incidences of catastrophic health expenditures were 17.41% and 20.03% in former smoking households, 12.10% and 15.09% in current smoking households, and 12.72% and 13.64% in nonsmoking households. In the panel logit regression model analysis, former smoking households (OR = 1.444, P

Background. In our previous study, mouse double minute 2 homolog (MDM2), insulin-like growth factor 1 (IGF1), signal transducer and activator of transcription 1 (STAT1), and Rac family small GTPase 1 (RAC1) were correlated with the recurrence of giant cell tumor of bone (GCT). The aim of this study is to use a large cohort study to confirm the involvement of these four genes in GCT recurrence. Methods. The expression of these four genes was detected and compared between GCT patients with or without recurrence. The correlation between the expression of these four genes and clinical characteristics was evaluated. Protein-protein interaction (PPI) network was constructed for functional enrichment analysis. Results. It showed that the expression levels of MDM2, IGF1, STAT1, and RAC1 in GCT patients with recurrence were significantly higher than those in GCT patients without recurrence (P

Glucocorticoids are the only therapy that has been demonstrated to alter the progress of Duchenne muscular dystrophy (DMD), the most common muscular dystrophy in children. However, glucocorticoids disturb skeletal muscle metabolism and hamper myogenesis and muscle regeneration. The mechanisms involved in the glucocorticoid-mediated suppression of myogenic differentiation are not fully understood. Glycogen synthase kinase-3β (GSK-3β) is considered to play a central role as a negative regulator in myogenic differentiation. Here, we showed that glucocorticoid treatment during the first 48 h in differentiation medium decreased the level of phosphorylated Ser9-GSK-3β, an inactive form of GSK-3β, suggesting that glucocorticoids affect GSK-3β activity. We then investigated whether GSK-3β inhibition could regulate glucocorticoid-mediated suppression of myogenic differentiation in vitro. Two methods were employed to inhibit GSK-3β: pharmacological inhibition with LiCl and GSK-3β gene knockdown. We found that both methods resulted in enhanced myotube formation and increased levels of muscle regulatory factors and muscle-specific protein expression. Importantly, GSK-3β inhibition attenuated glucocorticoid-induced suppression of myogenic differentiation. Collectively, these data suggest the involvement of GSK-3β in the glucocorticoid-mediated impairment of myogenic differentiation. Therefore, the inhibition of GSK-3β may be a strategy for preventing glucocorticoid-induced muscle degeneration.

This paper takes ionic rare earth ore, from Jiangxi Ganzhou Zhudong, as the research object, using indoor column leaching method to carry out optimal adjustment of the ore leaching process, investigating the effect of various process factors and result analysis of ion-type rare earth ore before leaching and after leaching. The results show that, when the raw ore about 0.056% rare earth ore, the moisture content is 4%, the ore seam height is 43mm, leaching agent concentration is 4%, leaching solution pH value is 5.0, solid-liquid ratio is 1:0.8, flow rate is 3 mL/min. We can acquire through the test that leaching rate of rare earth is 94.32%, average concentration of rare earth in leaching solution is 1.58 g/L. There are only ion exchange reaction between rare earth ions and electrolyte. Cationic polyelectrolyte is retained in leaching residue when rare earth ions is exchanged leaching. The whole leaching process did not produce other new substance. There was only ion exchange reaction, with no natural crystal texture of rare earth ore change. [ABSTRACT FROM AUTHOR]