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Abstract Metabolism reprogramming (MR) is one of the top ten hallmarks of malignant tumors. The aberrant activation of MR has been recognized as a critical contributory factor to the malignant progression of solid tumors. Moreover, various long non-coding RNAs (lncRNAs) are implicated in the aberrant activation of MR in solid tumor cells. Therefore, in this review, we mainly focus on summarizing the functional relevance and molecular mechanistic underpinnings of lncRNAs in modulating MR of solid tumors by targeting glucose metabolism, lipid metabolism, affecting mitochondrial function, and regulating interactions between tumor and non-tumor cells in tumor microenvironment. Besides, we also underscore the potential for constructing lncRNAs-centered tumor metabolic regulation networks and developing novel anti-tumor strategies by targeting lncRNAs and abnormal MR. Ultimately, this review seeks to offer new targets and avenues for the clinical treatment of solid tumors in the future.

Abstract Carboxylesterases serve as potent biocatalysts in the enantioselective synthesis of chiral carboxylic acids and esters. However, naturally occurring carboxylesterases exhibit limited enantioselectivity, particularly toward ethyl 3-cyclohexene-1-carboxylate (CHCE, S1), due to its nearly symmetric structure. While machine learning effectively expedites directed evolution, the lack of models for predicting the enantioselectivity for carboxylesterases has hindered progress, primarily due to challenges in obtaining high-quality training datasets. In this study, we devise a high-throughput method by coupling alcohol dehydrogenase to determine the apparent enantioselectivity of the carboxylesterase AcEst1 from Acinetobacter sp. JNU9335, generating a high-quality dataset. Leveraging seven features derived from biochemical considerations, we quantitively describe the steric, hydrophobic, hydrophilic, electrostatic, hydrogen bonding, and π-π interaction effects of residues within AcEst1. A robust gradient boosting regression tree model is trained to facilitate stereodivergent evolution, resulting in the enhanced enantioselectivity of AcEst1 toward S1. Through this approach, we successfully obtain two stereocomplementary variants, DR3 and DS6, demonstrating significantly increased and reversed enantioselectivity. Notably, DR3 and DS6 exhibit utility in the enantioselective hydrolysis of various symmetric esters. Comprehensive kinetic parameter analysis, molecular dynamics simulations, and QM/MM calculations offer insights into the kinetic and thermodynamic features underlying the manipulated enantioselectivity of DR3 and DS6.

Abstract African swine fever (ASF) is a highly fatal hemorrhagic disease affecting domestic pigs caused by African swine fever virus (ASFV). Genetic analysis of ASFV isolates to date has identified 24 geographically related genotypes with various subgroups, but only genotype I and II ASFVs have been reported outside Africa. ASFV genotype II and genotype I viruses were reported in China in 2018 and 2021, respectively. In this study, unique and highly conserved noncoding regions were found between MGF_505-9R and MGF_505-10R in the 188 genomes of ASFV genotypes I and II. A pair of primers was designed on the basis of this region. By optimizing the reaction system and conditions, a SYBR Green I fluorescence PCR assay that can distinguish between ASFV genotypes I and II was established, and the sensitivity, reproducibility and specificity were evaluated. The detection limit was 1 TCID50/0.1 mL for both genotypes, with no cross-reactivity observed with other common pig pathogens. The intra- and interbatch variation coefficients were both less than 1.2%. Clinical sample detection analysis revealed 47 positive cases out of 100, including 3 for genotype I and 44 for genotype II, aligning with results from the WOAH-recommended and national standard methods. The method developed in this study allows for the differentiation of ASFV genotypes I and II without the need for genome sequencing, offering a convenient and rapid approach for ASFV detection and genotype identification.

Abstract Purpose To investigate the impact and safety of canagliflozin combined with metformin on reducing cardiovascular risk in patients with type 2 diabetes mellitus (T2DM). Methods A total of 258 patients with T2DM admitted to our hospital from March 2021 to March 2022 were selected and divided into a control group and an observation group using a random number table. The control group received metformin combined with a placebo, while the observation group received canagliflozin combined with metformin therapy. All patients received drug treatment for 52 weeks. The primary endpoint of the study was major adverse cardiovascular events (MACE), including myocardial infarction, ischemic stroke, and cardiovascular death. Other study parameters included safety after medication, severe adverse reactions, levels of glycated hemoglobin (HbA1c), body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and estimated glomerular filtration rate (eGFR). Results After treatment, HbA1c, FPG, BMI, SBP, and DBP in both groups were lower than before treatment, and those indicators in the observation group were lower than those in the control group (P 0.05). Conclusion In patients with T2DM who received the canagliflozin combined with metformin, the mortality rate of cardiovascular causes was significantly reduced. Compared with metformin monotherapy, there is no significant difference in the incidence of serious adverse reactions, and the safety of medication is better, while the blood sugar, blood pressure, and weight of T2DM patients are more actively improved. For T2DM patients with high risk of cardiovascular disease, the combination of canagliflozin and metformin could have a higher benefit in cardiovascular outcomes.

Abstract There is insufficient evidence to guide dose and frequency optimization with repeated-dose ketamine for depression. This study assessed the value of symptomatic non-improvement after the first few ketamine infusions as a predictor of overall non-response in depression for early decision-making to discontinue treatment. A total of 135 individuals with major depressive disorder or bipolar disorder experiencing a current major depressive episode were administered six repeated doses of intravenous ketamine. Depressive symptoms were assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS) at baseline, 4 h after the first infusion, and 24 h after each infusion. Improvement, partial response, and response were defined as a reduction rate of ≥ 20%, 30%, and 50% in MADRS scores, respectively. This study examined the relationship between improvement (as opposed to non-improvement after each infusion or consecutive non-improvements after the first few infusions) and partial response and response after the sixth infusion. This analysis was summarized using sensitivity, specificity, and other diagnostic test parameters. The sensitivities of improvement at 24 h post-infusion 4 and improvement at 24 h post-infusion 3, vs. three consecutive non-improvements, as predictors for overall partial response and response exceeded 90%. No significant reduction in depressive symptoms was seen in non-improvers following the remaining infusions after the above-identified point. Our study suggests that non-improvement after four infusions, or more conservatively three consecutive non-improvements after three infusions, could serve as a signal of overall non-response to repeated-dose intravenous ketamine for depression and that subsequent treatments would not be warranted.

Abstract Background The prevalence of obesity is escalating. Previous research has concentrated on the link between frailty and obesity; however, the association between prefrailty and obesity has been less studied. Prefrailty screening and intervention may prevent or postpone frailty in older persons. Objective The study was to investigate into the relationship between prefrailty and several obesity indicators in Chinese community-dwelling older individuals. Methods This research employed the Frailty Screening Index to investigate the frailty phenotype of people living in Shanghai. Bioelectrical impedance analysis was used for evaluating body composition. Results There were 510 participants (39.0%) with high visceral adipose areas. Participants with a high visceral adipose area showed a higher risk of prefrailty (adjusted OR, 1.53; 95% CI, 1.19–1.96), according to multivariate models. When body mass index (BMI) and visceral fat area (VFA) were combined, it was discovered that having an overweight BMI with normal VFA was a protective factor for prefrailty (corrected OR, 0.62; 95% CI, 0.43–0.90), but having a normal weight but excess VFA increased the risk of prefrailty (corrected OR, 1.87; 95% CI, 1.15–3.03). Conclusion Visceral fat obesity is an independent risk factor for prefrailty in Chinese older adults. Implementing targeted interventions, such as dietary modifications, increased physical activity, and other lifestyle changes, could play a crucial role in reducing the risk of prefrailty and improving overall health outcomes in this population.

Objective To explore the enrichment conditions and main controlling factors of shale gas in the Lower Wuerhe Formation of the Permian System in the Junggar Basin, the Lower Wuerhe Formation in the Dongdaohaizi Sag was selected as the research object. Methods Based on the data of outcrop, core, well logging, well-calibrated seismic reflections and the technologies of total organic carbon (TOC) content determination, whole-rock X-ray diffraction, gas adsorption (N2, CO2), the distribution characteristics, organic matter development characteristics, reservoir characteristics, and gas bearing characteristics of the Lower Wuerhe Formation shale were studied. Results The results show that: (1) The organic matter of the Lower Wuerhe Formation shale is dominated by Ⅱ2 and Ⅲ types and shows an average TOC content of 1.58%. The average vitrinite reflectance (Ro) of organic matter is 1.46%, which indicates the mature stage. The average thickness of the source rock is 75 m. Summarily, the source rock is good and has a high gas potential. The basin simulation results show an average shale gas content of 1.89 m3/t in the Lower Wuerhe Formation. (2) The pores and microfractures in shale reservoirs are highly developed, and gas is primarily adsorbed in micropores and mesopores. The average porosity and permeability are 6.10% and 0.27×10-3 μm2 respectively, which are favourable for shale gas accumulation. (3) The shale has a high clay mineral content, with an average of 29.6%, providing a significant specific surface area and enhancing the gas adsorption capacity of the shale. Additionally, the average brittle mineral content is 50.9%, indicating good frackability. (4) Moreover, the shale reservoir exhibits a relatively large pressure coefficient of 1.58, indicating the favourable conservation conditions. The analysis of the regional tectonic-sedimentary environment and geochemical parameters indicates that the main factors controlling shale gas accumulation in the Lower Wuerhe Formation of the Dongdaohaizi Sag are geochemical parameters and preservation conditions. The key factors influencing shale gas accumulation include the high thermal evolution maturity of organic matter, large shale thickness, high TOC content, and good preservation conditions. These conditions suggest that the favourable area for shale gas exploration and development in the Dongdaohaizi Sag is located in the northeastern slope area of the sag's abdomen. Conclusion The results of this research reveal the enrichment conditions and main controlling factors of shale gas in the Lower Wuerhe Formation in the Dongdaohaizi Sag, which has reference value for deep oil and gas exploration in the abdominal area of the Junggar Basin.

Abstract The RATIONALE-306 study revealed that patients with advanced or metastatic oesophageal squamous cell carcinoma (OSCC) could benefit from treatment with tislelizumab plus chemotherapy. This study aimed to evaluate the cost-effectiveness of tislelizumab plus chemotherapy for treating OSCC from the perspective of the Chinese healthcare system. Partitioned survival model estimated the cost-effectiveness of tislelizumab plus chemotherapy compared with chemotherapy alone for treating OSCC using RATIONALE-306 data. Costs and utilities were obtained from local databases and published studies. Costs, quality-adjusted life-years (QALYs), life-years, incremental cost-effectiveness ratios (ICER), incremental net health benefits (INHB), and incremental net monetary benefits (INMB) were outcomes. Price simulation were conducted at the willingness-to-pay (WTP) threshold. Sensitivity and subgroup analyses were performed to assess model robustness. Compared with chemotherapy alone, tislelizumab plus chemotherapy yielded an ICER of USD 27,896/QALY, gained an additional 0.414 QALYs and 0.751 life-years, and increased the cost by USD 11,560. Probabilistic sensitivity analysis revealed that tislelizumab plus chemotherapy was cost-effective at the WTP of USD 38,258/QALY with probability of 94.43%. When the price in China was less than USD 3.714 per mg, the price simulation results indicated that tislelizumab plus chemotherapy was cost-effective at a WTP threshold of USD 38,258. Tislelizumab plus chemotherapy yielded an INHB of 0.112 QALYs and an INMB of USD 4,279 compared with chemotherapy alone at a WTP threshold of USD 38,258. Based on the sensitivity analyses, the above results were stable. A general trend was observed for subgroups with better survival benefits related to a higher probability of cost-effectiveness. From the Chinese healthcare perspective, tislelizumab plus chemotherapy is more cost-effective than chemotherapy alone as a first-line therapy for OSCC. These findings can help clinicians make optimal clinical decisions and assist decision-makers in evaluating the cost-effectiveness of tislelizumab in clinical practice.

Abstract Patients with PD-L1-positive esophageal squamous-cell carcinoma (ESCC) were significantly more likely to survive when treated with serplulimab plus cisplatin plus 5-fluorouracil (serplulimab-CF). At this point, it is unknown whether this expensive therapy is cost-effective. From the Chinese healthcare system's perspective, we aimed to evaluate serplulimab-CF versus CF alone for cost-effectiveness. A partitioned survival model was constructed based on the ASTRUM-007 trial. Quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER) were calculated. A further analysis of subgroups and scenarios was conducted. The willingness to pay (WTP) threshold of $38,258/QALY or $84,866/QALY is defined as three times the per capita gross domestic product value of the general region or affluent region. Compared with CF alone, in the overall (scenario 1), patients with PD-L1 expression level of 1 ≤ CPS

Abstract To achieve high-efficiency combustion of heavy fuel oil (HFO), this study investigated the combustion characteristics of methanol/HFO droplets with methanol content from 10 to 30% using the suspension method under ambient temperature from 923 to 1023 K. The combustion of methanol/HFO droplets was summarized as a two-phase process consisting of six typical stages, emphasizing liquid phase. Especially, the fluctuation evaporation stage, induced by frequent and intense puffing, was identified as prominent character. Both the ignition delay and lifetime of HFO and methanol/HFO droplets decreased with increasing ambient temperatures. For the methanol/HFO droplet, the ignition delay and droplet lifetime increased with the increasing methanol content. Prominently, compared to HFO, HM10 had the most significant reduction in droplet lifetime and TINL under the same operating conditions, which indicated that the addition of 10% methanol accelerated the combustion process and reduced soot generation. Additionally, the thermos-dynamic characteristics of methanol/HFO droplets were investigated. Puffing was primarily attributed to superheating of methanol and pyrolysis of heavy components in HFO, which resulted in active and passive rupture of bubbles. Similarity and maximum deformation were employed to qualitatively distinguish between them. The obtained findings aimed to develop a promising alternative fuel to reduce emissions and preserve energy.

Abstract Huanglian Jiedu Decoction (HJD) is a well-known Traditional Chinese Medicine formula that has been used for liver protection in thousands of years. However, the therapeutic effects and mechanisms of HJD in treating drug-induced liver injury (DILI) remain unknown. In this study, a total of 26 genes related to both HJD and DILI were identified, which are corresponding to a total of 41 potential active compounds in HJD. KEGG analysis revealed that Tryptophan metabolism pathway is particularly important. The overlapped genes from KEGG and GO analysis indicated the significance of CYP1A1, CYP1A2, and CYP1B1. Experimental results confirmed that HJD has a protective effect on DILI through Tryptophan metabolism pathway. In addition, the active ingredients Corymbosin, and Moslosooflavone were found to have relative strong intensity in UPLC-Q-TOF-MS/MS analysis, showing interactions with CYP1A1, CYP1A2, and CYP1B1 through molecule docking. These findings could provide insights into the treatment effects of HJD on DILI.

Abstract Semantic communication and spectrum sharing are pivotal technologies in addressing the perennial challenge of scarce spectrum resources for the sixth-generation (6G) communication networks. Notably, scant attention has been devoted to investigating semantic resource allocation within spectrum sharing semantic communication networks, thereby constraining the full exploitation of spectrum efficiency. To mitigate interference issues between primary users and secondary users while augmenting legitimate signal strength, the introduction of Intelligent Reflective Surfaces (IRS) emerges as a salient solution. In this study, we delve into the intricacies of resource allocation for IRS-enhanced semantic spectrum sharing networks. Our focal point is the maximization of semantic spectral efficiency (S-SE) for the secondary semantic network while upholding the minimum quality of service standards for the primary semantic network. This entails the joint optimization of parameters such as semantic symbol allocation, subchannel allocation, reflective coefficients of IRS elements, and beamforming adjustment of secondary base station. Recognizing computational intricacies and interdependence of variables in the non-convex optimization problem formulated, we present a judicious approach: a hybrid intelligent resource allocation approach leveraging dueling double-deep Q networks coupled with the twin-delayed deep deterministic policy. Simulation results unequivocally affirm the efficacy of our proposed resource allocation approach, showcasing its superior performance relative to baseline schemes. Our approach markedly enhances the S-SE of the secondary network, thereby establishing its prowess in advancing the frontiers of semantic spectrum sharing (S-SE).

Marine fisheries are a critical component of the marine economy. Examining the changes in the economic resilience of marine fisheries allows for identifying potential development risks and supports informed decision-making to optimize growth patterns and mitigate risks. This study applied the CRITIC-based combined weights model to calculate China’s Marine Fisheries Economic Resilience (MFER). It investigated the temporal and spatial evolution of MFER and analyzed the influencing factors using the Geographical Detector and a Two-way fixed-effects model. Furthermore, the future development trends of MFER were predicted using the Markov chain. The results show that the overall MFER in China’s coastal provinces increased steadily from 2001 to 2020. Second, MFER exhibits a clear pattern, with low-value regions improving and high-value areas shifting toward medium- and low-value provinces. Fourth, the trajectory of the MFER center is moving from north to south, with high-value regions expanding in the same direction. Fourth, factors such as EDL, TEC, SPE, and SYS positively impact MFER, while OPE has a negative effect. Finally, the results of the Markov chain indicate that the current development state of MFER is relatively stable, with evidence of club convergence. However, the probability of maintaining the current development level is gradually decreasing. Based on these findings, provide suggestions for the preservation of marine economic security.

IntroductionThe hepatitis C virus (HCV) poses a major global health challenge, with its non-structural proteins being essential for viral replication and pathogenesis. Mutations in these proteins significantly contribute to drug resistance, necessitating innovative therapeutic strategies. This study aims to identify epitope-based therapeutic targets in the non-structural proteins of HCV genotype 1, employing in-depth in silico tools to counteract emerging drug resistance.MethodsWe retrieved approximately 250 sequences of each non-structural protein from the NCBI database, capturing a broad spectrum of variability and sequence alignments, variability analysis and physicochemical property analysis were conducted. We utilized the TEPITOOL server by IEDB to predict cytotoxic T lymphocyte (CTL) epitopes. Following this, we assessed the efficiency of TAP transport and proteasomal cleavage using IEDB’s combined predictor tool. The epitopes were selected based on conservancy analysis, immunogenicity, allergenicity, and presence in non-glycosylated regions, ensuring high predictive scores and suitability as vaccine candidates. Epitopes were docked with the HLA-A*02:01 allele and Toll-like receptor-3 using the ClusPro server. The immune response potential of the epitopes was evaluated through in-silico immune stimulation.ResultsThe study identified 27 potential CTL epitopes from the non-structural proteins, including NS3, NS4a, NS4b, NS5a, and NS5b. Out of these, three lead epitopes demonstrated high conservation (>90%), strong binding affinities to HLA-A*02:01 and TLR-3, and robust immune response potential. These epitopes also showed favorable characteristics such as being non-allergenic and non-glycosylated.ConclusionThis comprehensive in-silico analysis provides a promising foundation for developing an epitope-based vaccine targeting HCV non-structural proteins, offering a novel approach to overcoming drug resistance in HCV treatment.

There is limited evidence that heavy metals exposure contributes to osteoporosis. Multi-parameter scoring machine learning (ML) techniques were developed using National Health and Nutrition Examination Survey data to predict osteoporosis based on heavy metal exposure levels. For generating an optimal predictive model for osteoporosis, 12 ML models were used. Identification was carried out using the model that performed the best. For interpretation of models, Shapley additive explanation (SHAP) methods and partial dependence plots (PDP) were integrated into a pipeline and incorporated into the ML pipeline. By regressing osteoporosis on survey cycles, logistic regression was used to evaluate linear trends in osteoporosis over time. For the purpose of training and validating predictive models, 5745 eligible participants were randomly selected into training and testing set. It was evident from the results that the gradient boosting decision tree model performed the best among the predictive models, attributing to an accuracy rate of 89.40 % in the testing set. Based on the model results, the area under the curve and F1 score were 0.88 and 0.39, respectively. As a result of the SHAP analysis, urinary Co, urinary Tu, blood Cd, and urinary Hg levels were identified as the most influential factors influencing osteoporosis. Urinary Co (0.20–6.10 μg/mg creatinine), urinary Tu (0.06–1.93 μg/mg creatinine), blood Cd (0.07–0.50 μg/L), and urinary Hg (0.06–0.75 μg/mg creatinine) levels displayed a distinctive upward trend with risk of osteoporosis as values increased. Our analysis revealed that urinary Co, urinary Tu, blood Cd, and urinary Hg played a significant role in predictability.

ObjectiveThis study aimed to explore the effect of moxibustion at Governor Vessel (GV) acupoints, including Baihui (GV 20), Shenting (GV 24) and Dazhui (GV 14) for 14 days on glial vascular unit (GVU) in rats with multiple microinfarctions (MMI), and to explore its action mechanism.MethodsThe effect and mechanism of moxibustion on vascular dementia (VD) were studied in MMI rats by means of behavioral and molecular biology experiments.ResultsRats receiving MMI showed impairment of memory function, reduction of cerebral blood flow, damage of blood-brain barrier (BBB) integrity and increased brain mass. MMI also increased neuronal degeneration in the hippocampus. Notably, levels of glial fibrillary acidic protein (GFAP) and complement component 3 significantly increased, but those of Connexin43 (CX43) and platelet derived growth factor receptor β (PDGFRβ) significantly decreased in the hippocampus of the rats receiving MMI. Moxibustion, as well as oxiracetam (ORC) treatment improved memory function and neuronal degeneration, ameliorated BBB integrity, increased cerebral blood flow and decreased brain mass. In addition, moxibustion as well as oxiracetam (ORC) treatment reduced the decrease of CX43 protein and increased PDGFRβ protein level in the hippocampus of MMI rats. Moreover, moxibustion treatment reversed MMI-induced increase of the GFAP/CX43 ratio in vascular structural units. Importantly, after PDGFRβ inhibition, VD rats treated with moxibustion had impaired learning and memory, decreased cerebral blood flow, and BBB disruption.ConclusionMoxibustion treatment at various GV acupoints improved cerebral blood flow and repaired BBB function in rats with MMI, likely through protecting GVU.

ObjectiveThe purpose of this study was to observe the relationship between objectively measured levels of physical activity and cognitive impairment (CI) in the presence or absence of diabetes in middle-aged and elderly hemodialysis patients.MethodsIn this multicenter cross-sectional study, 339 clinically stable hemodialysis patients (210 males; mean age: 67.38 ± 8.07 years) aged ≥55 years were included from 7 dialysis units in Shanghai, China. The Chinese version of the Modified Mini-Mental State Examination (MMSE) was used to assess the CI. The duration of physical activity at different intensities, including moderate to vigorous physical activity (MVPA) as well as light physical activity (LPA), was measured using a triaxial accelerometer (ActiGraph GT3X+, Pensacola, FL, USA). Logistic regression and multiple linear regression were used for analyses.ResultsThe prevalence of CI was higher in hemodialysis patients with comorbid diabetes (24.3%). In diabetic patients, MVPA (increase per 10 min/day) was negatively associated with CI after adjusting for covariates [(OR = 0.89, 95%CI = 0.79–0.99), p = 0.042]. However, no significant association between physical activity and CI was found in non-diabetic hemodialysis patients. Further analyses revealed that MVPA was positively associated with temporal orientation, attention and calculation and recall in diabetic hemodialysis patients.ConclusionPhysical activity was associated with CI in diabetic hemodialysis patients rather than the non-diabetes group. This study is important for early differential diagnosis of CI and improvement of cognitive status in hemodialysis patients.

Background Both diabetes and osteoporosis have developed into major global public health problems due to the increasing aging population. It is crucial to screen populations at higher risk of developing osteoporosis for disease prevention and management in postmenopausal women with type 2 diabetes (T2D). This study aims to quantitatively investigate the association between risk factors and bone mineral density (BMD) and develop a self-assessment tool for early osteoporosis screening in postmenopausal women with T2D. Methods We retrospectively enrolled 1,309 postmenopausal women with T2D. Linear regression methods were used to assess the association between risk factors and BMD. Additionally, a multivariate logistic regression analysis was performed to identify independent risk factors associated with osteoporosis. Utilizing the logistic regression machine learning algorithm, we developed an osteoporosis screening tool that categorizes the population into three risk regions based on age and body mass index (BMI), indicating low, moderate, and high prevalence of osteoporosis in the age-BMI plane. Results Older age and lower BMI were independently associated with decreased BMD. The BMD at the total hip, femur neck, and lumbar spine differed by 12.9, 10.9, and 15.5 mg/cm2 for each 1 unit increase in BMI, respectively. Both age and BMI were identified as independent predictors of osteoporosis. The osteoporosis screening tool was developed by using two straight lines with equations of BMI = 0.56 * age−4.12 and BMI = 0.56 * age−10.88; there were no significant differences in the prevalence of osteoporosis among the training, internal test, and external test datasets in the low-, moderate-, and high-risk regions. Conclusion We have successfully developed and validated a self-assessment tool for early osteoporosis screening in postmenopausal women with T2D for the first time. BMI was identified as a significant modifiable risk factor. Our study may improve awareness of osteoporosis and is valuable for disease prevention and management for postmenopausal women with T2D.

BackgroundThe relationship between vitamin D and depression has garnered significant attention in recent years. However, the efficacy of vitamin D in ameliorating depression among specific subgroups of older patients remains controversial. This study aimed to assess the impact of vitamin D supplementation on depressive symptoms and the prevalence of depression in older adults. Additionally, the study sought to examine potential moderating factors, including differences among population subgroups and various supplementation strategies.MethodsA systematic literature search was conducted in the databases PubMed, EMBASE, Web of Science, and the Cochrane Library up to March 2024. The RevMan 5.3 software was utilized to calculate the standardized mean difference (SMD) and to evaluate the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. The objective was to determine the efficacy of vitamin D supplementation in alleviating depressive symptoms or treating depression in older adults.ResultsThis meta-analysis encompassed eleven studies, comprising a total of 21,561 participants. The findings did not indicate a statistically significant therapeutic benefit of vitamin D supplementation for depression in older patients [SMD: −0.10; 95% CI: (−1.19, 0.00); p = 0.05]. Subgroup analyses revealed that the efficacy of vitamin D intervention in geriatric depression correlated with several factors, including baseline serum 25(OH)D levels, the dosage of the intervention, gender, and the initial presence of depressive symptoms or a diagnosis of depression.ConclusionThe current evidence is insufficient to conclusively establish the significant efficacy of vitamin D supplementation in alleviating depressive symptoms among older patients. Consequently, additional randomized controlled trials are warranted to further validate the relationship between vitamin D supplementation and depression in the older adults.

ObjectiveTo explore the value of dual-accelerated simultaneous multi-slice (SMS) imaging in diffusion tensor imaging (DTI) of glioma.MethodsThirty-four patients with glioma who underwent magnetic resonance imaging (MRI) in our hospital from January 2022 to March 2023 were randomly selected. The results of dual-accelerated SMS-DTI and conventional DTI were retrospectively analyzed. All patients were scanned using a uMR790 3.0T MRI scanner, and the scanning technicians followed a predefined sequence to ensure consistency in scan parameters. The images were subjectively evaluated using a Likert 5-point scoring system. Objective evaluation was performed by measuring the required values of the images with b-value = 1000 s/mm2, primarily measuring the signal intensity in the tumor region and the contralateral normal brain white matter region. The standard deviation values were used to calculate the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) in the same encoding direction as the background noise. The number of generated fiber pathways, fractional anisotropy (FA), and mean diffusivity (MD) were measured and analyzed using post-processing software. The relative FA (rFA) and relative MD (rMD) were calculated.ResultsThe results of conventional DTI and SMS-accelerated DTI were compared. In terms of subjective evaluation, including overall image quality, tumor edge clarity, and magnetic sensitivity artifacts, both techniques showed no significant differences, indicating comparable diagnostic performance in anatomical visualization. In terms of objective evaluation and quantitative parameter measurement, there were statistically significant differences in SNR and CNR values, with slightly lower values in the dual-accelerated SMS-DTI compared with conventional DTI, a significant reduction in scanning time can be achieved through a slight loss in image quality. The number of fiber pathways and the rFA and rMD values did not show typical differences between the two techniques. The correlation between these measures was highly similar, with no significant differences observed.ConclusionThe application of dual-accelerated simultaneous multi-slice imaging in DTI of glioma is feasible.

Abstract Long‐range thalamocortical communication is central to anesthesia‐induced loss of consciousness and its reversal. However, isolating the specific neural networks connecting thalamic nuclei with various cortical regions for state‐specific anesthesia regulation is challenging, with the biological underpinnings still largely unknown. Here, simultaneous electroencephalogram‐fuctional magnetic resonance imaging (EEG‐fMRI) and deep brain stimulation are applied to the intralaminar thalamus in macaques under finely‐tuned propofol anesthesia. This approach led to the identification of an intralaminar‐driven network responsible for rapid arousal during slow‐wave oscillations. A network‐based RNA‐sequencing analysis is conducted of region‐, layer‐, and cell‐specific gene expression data from independent transcriptomic atlases and identifies 2489 genes preferentially expressed within this arousal network, notably enriched in potassium channels and excitatory, parvalbumin‐expressing neurons, and oligodendrocytes. Comparison with human RNA‐sequencing data highlights conserved molecular and cellular architectures that enable the matching of homologous genes, protein interactions, and cell types across primates, providing novel insight into network‐focused transcriptional signatures of arousal.

Abstract The precise mechanism underlying the therapeutic effects of dihydroartemisinin (DHA) in alleviating colitis remains incompletely understood. A strong correlation existed between the elevation of glial fibrillary acidic protein (GFAP)+/S100 calcium binding protein B (S100β)+ enteric glial cells (EGCs) in inflamed colonic tissues and the disruption of the intestinal epithelial barrier (IEB) and gut vascular barrier (GVB) observed in chronic colitis. DHA demonstrated efficacy in restoring the functionality of the dual gut barrier while concurrently attenuating intestinal inflammation. Mechanistically, DHA inhibited the transformation of GFAP+ EGCs into GFAP+/S100β+ EGCs while promoting the differentiation of GFAP+/S100β+ EGCs back into GFAP+ EGCs. Furthermore, DHA induced apoptosis in GFAP+/S100β+ EGCs by inducing cell cycle arrest at the G0/G1 phase. The initial mechanism is further validated that DHA regulates EGC heterogeneity by improving dysbiosis in colitis. These findings underscore the multifaceted therapeutic potential of DHA in ameliorating colitis by improving dysbiosis, modulating EGC heterogeneity, and preserving gut barrier integrity, thus offering promising avenues for novel therapeutic strategies for inflammatory bowel diseases.

Purpose: Liver-expressed antimicrobial peptide-2 (LEAP2) is identified as an endogenous antagonist and inverse agonist of the growth hormone secretagogue receptor type 1a (GHSR1a), its effect on the GHSR1a is contrary to the role of GHRELIN. Growth hormone (GH) is a crucial hormone for early development. Previous studies report that LEAP2 dose-dependently attenuates ghrelin-induced GH secretion, and Leap2-knockout mice exhibit increased plasma GH levels after GHRELIN administration. Clinical data revealed a possible correlation between LEAP2 and height development. However, the role of LEAP2 in early development remains unclear. This study aimed to investigate the role of LEAP2 in early development using leap2 mutant zebrafish larvae as a model. Method: We analyzed the conservation of LEAP2 peptide across multiple species and generated leap2 mutants in zebrafish by CRISPR-Cas9, dynamically observed and measured the growth and development of zebrafish larvae from fertilization to 5 day post fertilization (dpf). In situ hybridization, transcriptome sequencing, quantitative real-time PCR and Western blot were used to detect the expression levels of GH and its signaling in early stage of embryonic development. Result: Our data demonstrate that zebrafish with a knockout of the leap2 gene display a significant increase in hatching rate, body length, and the distance between their eyes, all without visible developmental defects in the early stages of development. In addition, both RNA and protein analyses revealed a significant increase in GH expression in leap2 mutant. Conclusion: In general, this study demonstrates that LEAP2 regulates the expression of GH during early development, particularly influencing body length.

Background The correlation between hearing loss (HL) and physical performance in patients receiving maintenance hemodialysis (MHD) remains poorly investigated. This study explored the association between HL and physical performance in patients on MHD. Methods This multicenter cross-sectional study was conducted between July 2020 and April 2021 in seven hemodialysis centers in Shanghai and Suzhou, China. The hearing assessment was performed using pure-tone average (PTA). Physical performance was assessed using the Timed Up and Go Test (TUGT), handgrip strength, and gait speed. Results Finally, 838 adult patients (male, 516 [61.6%]; 61.2 ± 2.6 years) were enrolled. Among them, 423 (50.5%) had mild to profound HL (male, 48.6% and female, 53.4%). Patients with HL had poorer physical performance than patients without HL (p < 0.001). TUGT was positively correlated with PTA (r = 0.265, p < 0.001), while handgrip strength and gait speed were negatively correlated with PTA (r = –0.356, p < 0.001 and r = –0.342, p < 0.001, respectively). Physical performance in patients aged

Abstract Background Freezing stress is one of the major abiotic stresses that causes extensive damage to plants. LEA (Late embryogenesis abundant) proteins play a crucial role in plant growth, development, and abiotic stress. However, there is limited research on the function of LEA genes in low-temperature stress in Brassica napus (rapeseed). Results Total 306 potential LEA genes were identified in B. rapa (79), B. oleracea (79) and B. napus (148) and divided into eight subgroups. LEA genes of the same subgroup had similar gene structures and predicted subcellular locations. Cis-regulatory elements analysis showed that the promoters of BnaLEA genes rich in cis-regulatory elements related to various abiotic stresses. Additionally, RNA-seq and real-time PCR results indicated that the majority of BnaLEA family members were highly expressed in senescent tissues of rapeseed, especially during late stages of seed maturation, and most BnaLEA genes can be induced by salt and osmotic stress. Interestingly, the BnaA.LEA6.a and BnaC.LEA6.a genes were highly expressed across different vegetative and reproductive organs during different development stages, and showed strong responses to salt, osmotic, and cold stress, particularly freezing stress. Further analysis showed that overexpression of BnaA.LEA6.a increased the freezing tolerance in rapeseed, as evidenced by lower relative electrical leakage and higher survival rates compared to the wild-type (WT) under freezing treatment. Conclusion This study is of great significance for understanding the functions of BnaLEA genes in freezing tolerance in rapeseed and offers an ideal candidate gene (BnaA.LEA6.a) for molecular breeding of freezing-tolerant rapeseed cultivars.

Abstract Background and purpose Interstitial lung disease (ILD) represents a significant complication of rheumatoid arthritis (RA) that lacks effective treatment options. This study aimed to investigate the intrinsic mechanism by which resveratrol attenuates rheumatoid arthritis complicated with interstitial lung disease through the AKT/TMEM175 pathway. Methods We established an arthritis model by combining chicken type II collagen and complete Freund’s adjuvant. Resveratrol treatment was administered via tube feeding for 10 days. Pathological changes in both the joints and lungs were evaluated using HE and Masson staining techniques. Protein expression of TGF-β1, AKT, and TMEM175 was examined in lung tissue. MRC-5 cells were stimulated using IL-1β in combination with TGF-β1 as an in vitro model of RA-ILD, and agonists of AKT, metabolic inhibitors, and SiRNA of TMEM175 were used to explore the regulation and mechanism of action of resveratrol RA-ILD. Results Resveratrol mitigates fibrosis in rheumatoid arthritis-associated interstitial lung disease and reduces oxidative stress and inflammation in RA-ILD. Furthermore, resveratrol restored cellular autophagy. When combined with the in vitro model, it was further demonstrated that resveratrol could suppress TGF-β1 expression, and reduce AKT metamorphic activation, consequently inhibiting the opening of AKT/MEM175 ion channels. This, in turn, lowers lysosomal pH and enhances the fusion of autophagosomes with lysosomes, ultimately ameliorating the progression of RA-ILD. Conclusion In this study, we demonstrated that resveratrol restores autophagic flux through the AKT/MEM175 pathway to attenuate inflammation as well as fibrosis in RA-ILD by combining in vivo and in vitro experiments. It further provides a theoretical basis for the selection of therapeutic targets for RA-ILD. Graphical Abstract

Abstract Depression is a serious psychiatric illness that causes great inconvenience to the lives of elderly individuals. However, the diagnosis of depression is somewhat subjective. Nontargeted gas chromatography (GC)/liquid chromatography (LC)–mass spectrometry (MS) was used to study the plasma metabolic profile and identify objective markers for depression and metabolic pathway variation. We recruited 379 Chinese community-dwelling individuals aged ≥ 65. Plasma samples were collected and detected by GC/LC‒MS. Orthogonal partial least squares discriminant analysis and a heatmap were utilized to distinguish the metabolites. Receiver operating characteristic curves were constructed to evaluate the diagnostic value of these differential metabolites. Additionally, metabolic pathway enrichment was performed to reveal metabolic pathway variation. According to our standard, 49 people were included in the depression cohort (DC), and 49 people age- and sex-matched individuals were included in the non-depression cohort (NDC). 64 metabolites identified via GC‒MS and 73 metabolites identified via LC‒MS had significant contributions to the differentiation between the DC and NDC, with VIP values > 1 and p values

Urban growth has accelerated significantly in recent decades, categorized into two spatial patterns: adjacent and outlying growth. Traditional Cellular Automata (CA)-based models excel at simulating adjacent growth but exhibit limitations in modeling outlying growth, which can be summarized into two issues: 1) the overestimation of neighborhood effects caused by models’ excessive dependence on neighboring cell states; and 2) the ignorance of spatial heterogeneity in the relative importance of land suitability and neighborhood effects on urban growth. To address these problems, a novel CA model with Separate Extraction and Adaptive Fusion of land suitability and neighborhood effects (SEAF-CA) is proposed. In this model, a dual-path convolution structure is employed to extract spatial features from driving factors and cell states; geographical coordinates of each cell then input into a multilayer perceptron to derive spatially varying weights for feature fusion. Finally, the derived conversion probability is integrated with CA to simulate urban growth. Land use data collected from 2000 to 2020 in Wuhan are selected to evaluate the proposed model. Experimental results illustrate that SEAF-CA outperforms three typical CA models, achieving the closest outlying growth proportion to reality and the highest simulation accuracy. In addition, the source code of SEAF-CA is now available at GitHub (https://github.com/ohXu/SEAF-CA).

Abstract Multidimensional health function impairments are common in older patients with chronic kidney disease (CKD). The purpose of this study was to explore whether the risk or severity of geriatric syndrome increased with a decline in renal function. This survey was conducted for CKD patients aged ≥ 60 years and hospitalized at West China Hospital of Sichuan University (Center of Gerontology and Geriatrics, Nephrology, and Endocrinology) and Chengdu Kangfu Kidney Disease Hospital from September 01, 2013 to June 30, 2014. Patients underwent multidimensional individualized assessments by trained doctors. Logistic regression analysis found that the risk of assisted walking (P = 0.001) and urinary incontinence (P = 0.039) increased with a decline in renal function. Regression analysis revealed that the scores of activities of daily living (P = 0.024), nutritional status (P = 0.000), total social support (P = 0.014), and objective support (P = 0.000) decreased with a decline in renal function.

Abstract Chiral recognition of amino acids is very important in both chemical and life sciences. Although chiral recognition with luminescence has many advantages such as being inexpensive, it is usually slow and lacks generality as the recognition module relies on structural complementarity. Here, we show that one single molecular-solid sensor, L-phenylalanine derived benzamide, can manifest the structural difference between the natural, left-handed amino acid and its right-handed counterpart via the difference of room-temperature phosphorescence (RTP) irrespective of the specific chemical structure. To realize rapid and reliable sensing, the doped samples are obtained as nanocrystals from evaporation of the tetrahydrofuran solutions, which allows for efficient triplet-triplet energy transfer to the chiral analytes generated in situ from chiral amino acids. The results show that L-analytes induce strong RTP, whereas the unnatural D-analytes produce barely any afterglow. The method expands the scope of luminescence chiral sensing by lessening the requirement for specific molecular structures.

Abstract In the CheckMate 651 study, nivolumab plus ipilimumab versus EXTREME (cisplatin/carboplatin + cetuximab + fluorouracil) regimen was compared for effectiveness. It is not known whether these immunotherapy agents are cost-effective for recurrent or metastatic squamous cell carcinomas of the head and neck (R/M SCCHN). The purpose of this study was to compare the cost-effectiveness of nivolumab plus ipilimumab with EXTREME in the first-line setting from the standpoint of third-party payers in the United States. The projecting of costs and outcomes over 15 years was done using a three-state partitioned survival model discounted by 3% per year. Long-term extrapolation of CheckMate 651 was used to model progression-free survival and overall survival (OS). The incremental net health benefit (INHB), incremental net monetary benefit (INMB), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER) were calculated. The uncertainty and stability of the model were accounted for via one-way and probabilistic sensitivity analyses. As compared with nivolumab plus ipilimumab, EXTREME was associated with an increase of 0.154 life-years and 0.076 QALYs, as well as a cost increase of $572 per patient. The corresponding ICERs were $7545/QALY along with the values of INMB and INHB were $113,267 and 0.076 QALYs, respectively, at a willingness to pay (WTP) threshold of $150,000/QALY. The probability of nivolumab plus ipilimumab being cost-effective was > 99% in patients with combined positive score (CPS) ≥ 1, CPS 1–19, or CPS ≥ 20. Moreover, hazard ratio for OS and body weight were the most sensitive parameters for the model. According to sensitivity analyses, these results were generally robust. In overall populations with R/M SCCHN, the EXTREME regimen is cost-effective compared with nivolumab plus ipilimumab. Given a WTP threshold of $150,000 per QALY, the probability of the EXTREME regiment being cost-effective compared with nivolumab and ipilimumab, was 64%. Importantly, there was heterogeneity in the cost-effectiveness probabilities, based on primary sites and expression levels of PD-L1. Therefore, tailored treatment based on individual patient and clinical characteristics, remains important, and may impact the cost-effectiveness of the regimens under study.

Background: Diabetic foot is a major complication of diabetes. The bone transverse transport method could be applied in clinics for treatment, which could improve the metabolism of the tissues via lasting distraction forces. However, the process’ specific regulating mechanism is still unknown. Methods: Based on the notion that the healing of bones involves the recruitment of calcium ions, in this study, we established the model of tibial cortex transverse transport (TTT) on rats and then used tissue immunologic detection, such as the double fluorescent staining to explore the expression of the calcium channels’ calcium release-activated calcium modulator 1 (Orai1)/stromal interaction molecule 1 (STIM1), which belong to the store-operated calcium entry (SOCE) signaling pathways on the tissues around the bone transport area. By using the laser capture microdissection (LCM) tool, we acquired samples of tissues around the bone and endeavored to identify pivotal protein molecules. Subsequently, we validated the functions of key protein molecules through in vitro and in vivo experiments. Results: After protein profile analysis, we found the differentially expressed key protein osteopontin (OPN). The in vitro experiments verified that, being stimulated by OPN, the migration, proliferation, and angiogenesis of human umbilical vein endothelial cells (HUVEC) were observed to be enhanced. The activation of Orai1/STIM1 might increase the activity of endothelial nitric oxide synthase (eNOS) and its effect on releasing nitric oxide (NO). Subsequently, the migration and proliferation of the HUVECs are improved, which ultimately accelerates wound healing. These signaling pathway was also observed in the OPN-stimulated healing process of the skin wound surface of diabetic mice. Conclusion: This study identifies the molecular biological mechanism of OPN-benefited the migration and proliferation of the HUVECs and provides ideas for searching for new therapeutic targets for drugs that repair diabetes-induced wounds to replace invasive treatment methods. The translational potential of this article: The OPN is highly expressed in the tissues surrounding the TTT bone transfer area, which may possibly stimulate the activation of eNOS to increase NO release through the SOCE pathway mediated by Orai1/STIM1. This mechanism may play a significant role in the angiogenesis of diabetic foot's wounds promoted by TTT, providing new therapeutic strategies for the non-surgical treatment for this disease.

Abstract Background Delays in malaria treatment can not only lead to severe and even life-threatening complications, but also foster transmission, putting more people at risk of infection. This study aimed to investigate the factors influencing treatment delays among malaria patients and their health-seeking behaviour. Methods The medical records of 494 patients diagnosed with malaria from 6 different malaria-endemic provinces in China were analysed. A bivariate and multivariable regression model was used to investigate the association between delays in seeking treatment and various factors. A Sankey diagram was used to visualize the trajectories of malaria patients seeking medical care. Total treatment delays were categorized as patient delays and doctor delays. Results The incidence of total delays in seeking malaria treatment was 81.6%, of which 28.4% were delayed by patients alone and 34.8% by doctors alone. The median time from the onset of symptoms to the initial healthcare consultation was 1 day. The median time from the initial healthcare consultation to the conclusive diagnosis was 2 day. After being subjected to multiple logistic regression analysis, living in central China was less likely to experience patient delays (OR = 0.43, 95% CI 0.24–0.78). The factors significantly associated with the lower likelihood of doctor delays included: age between 30 to 49 (OR = 0.43, 95% CI 0.23–0.81), being single/divorce/separated (OR = 0.48, 95% CI 0.24–0.95), first visiting a county-level health institution (OR = 0.25, 95% CI 0.14–0.45), first visiting a prefectural health institution (OR = 0.06, 95% CI 0.03–0.12) and first visiting a provincial health institution (OR = 0.05, 95%CI 0.02–0.12). Conversely, individuals with mixed infections (OR = 2.04, 95% CI 1.02–4.08) and those experiencing periodic symptoms (OR = 1.71, 95% CI 1.00–2.92) might face increased doctor delays. Furthermore, higher financial burden and complications were found to be associated with patient delays. Doctor delays, in addition to incurring these two consequences, were associated with longer hospital stays. Conclusion There was a substantial delay in access to health care for malaria patients before China was certified malaria free. Region, marital status, periodic symptoms and the level of health institutions were factors contributing to delays in treatment-seeking among malaria patients.

Abstract Background Untargeted metabolomics can be used to expand our understanding of the pathogenesis of sarcopenia. However, the metabolic signatures of sarcopenia patients have not been thoroughly investigated. Herein, we explored metabolites associated with sarcopenia by untargeted gas chromatography (GC)/liquid chromatography (LC)–mass spectrometry (MS) and identified possible diagnostic markers. Methods Forty-eight elderly subjects with sarcopenia were age and sex matched with 48 elderly subjects without sarcopenia. We first used untargeted GC/LC–MS to analyze the plasma of these participants and then combined it with a large number of multivariate statistical analyses to analyze the data. Finally, based on a multidimensional analysis of the metabolites, the most critical metabolites were considered to be biomarkers of sarcopenia. Results According to variable importance in the project (VIP > 1) and the p-value of t-test (p

Abstract Background The purpose of this study was to explore the separate and combined associations of obstructive sleep apnea (OSA) risk and sleep duration with ideal cardiovascular health metrics in hemodialysis (HD) patients. Methods 470 HD participants (average: 59.48 ± 12.89 y, 281 men) were included in this study. Sleep duration was measured as self-reported average sleep time during the previous month. The OSA risk was assessed using the STOP-BANG questionnaire. Participants were divided into three groups based on the number of ideal cardiovascular health (CVH) metrics: 0–2,3–4, and 5–7. Ordinal logistic regression was conducted to model the associations of CVH metrics with sleep duration, OSA risk, and their combined effects by adjusting for specific covariates. Results After adjusting for covariates, short sleep duration (

AbstractAlthough there have been tremendous improvements in the production and storage of platelets, platelet transfusion refractoriness (PTR) remains a serious clinical issue that may lead to various severe adverse events. The burden of supplying platelets is worsened by rising market demand and limited donor pools of compatible platelets. Antibodies against platelet antigens are known to activate platelets through FcγR-dependent or complement-activated channels, thereby rapidly eliminating foreign platelets. Recently, other mechanisms of platelet clearance have been reported. The current treatment strategy for PTR is to select appropriate and compatible platelets; however, this necessitates a sizable donor pool and technical assistance for costly testing. Consolidation of these mechanisms should be of critical significance in providing insight to establish novel therapeutics to target immunological platelet refractoriness. Therefore, the purposes of this review were to explore the modulation of the immune system over the activation and elimination of allogeneic platelets and to summarize the development of alternative approaches for treating and avoiding alloimmunization to human leukocyte antigen or human platelet antigen in PTR.

Soil thermal conductivity (λ) is required to investigate coupled heat and water transport in disciplines such as agriculture, hydrology and engineering. Parameterization schemes or models of λ are also the critical input parameter for various numerical simulation programs like the widely used HYDRUS, one of the most commonly used models for mimicking water, heat, and solute transport. However, λ has not received enough attention in HYDRUS, and it remains unclear how different λ schemes affect the simulated soil water and thermal regimes. Thus, we programmed 24 λ schemes (including two built-in schemes) used in mainstream land surface, hydrological, and soil–vegetation–atmosphere transfer models into HYDRUS-1D (freezing module) to assess the effects of different λ schemes on soil temperature and water content simulations under freezing–thawing. The results showed that the 24 λ schemes performed differently in the simulation of soil temperature within 1 m below ground, with eight λ schemes, i.e., de Vries 1963 scheme/DV1963 (R=0.99), Camillo and Schmugge 1981/CS1981 scheme (R=0.98), Desborough and Pitman 1998/DP1998 scheme (R=0.97), Cass et al. 1984/CS1984 scheme (R=0.96), Shmakin 1998/SA1998 scheme (R=0.95), Dharssi et al. 2009/DI2009 scheme (R=0.95), Becker et al. 1992/BB1992 scheme (R=0.95), Hubrechts 1998/HL1998 scheme (R=0.94), performing superiorly to the built-in λ schemes. This study highlights the importance of choosing appropriate λ schemes in soil water and heat simulations.

Abstract Reliable detection of hydrogen (H2) leakage at low temperatures (e.g.,

IntroductionEltrombopag (EPAG), a thrombopoietin receptor agonist, was approved for the treatment of severe aplastic anemia (SAA) combined with immunosuppressive therapy (IST). However, EPAG contains a typical biphenyl structure, which causes liver function damage.MethodsTwenty patients with SAA who were intolerant or refractory to EPAG were enrolled in a multicenter prospective registry of the Chinese Eastern Collaboration Group of Anemia (ChiCTR2100045895) from October 2020 to June 2023.ResultsEight patients who were ineffective to EPAG, six with kidney impairment, and nine with abnormal liver function (two with concomitant liver and kidney impairment) were converted to avatrombopag (AVA) therapy with the median duration of AVA treatment was 6 (3-24) months. 17 cases (85%) achieved trilineage hematological response (HR): complete remission (CR) in 3 cases (15%), good partial remission (GPR) in 4 cases (20%), partial remission (PR) in 10 cases (50%), and no response (NR) in 3 cases (15%). The median time to response was 1.7 (0.5-6.9) months, with 16 cases (94%) achieving response within six months and 17 cases (100%) within 12 months. 9 cases (50%) achieved transfusion independence. AVA converted treatment was associated with higher neutrophil counts (0.8×109/L vs 2.2×109/L, p=0.0003), platelet counts (11×109/L vs 39×109/L, p=0.0008), hemoglobin count (59g/L vs 98g/L, p=0.0002), red cell count (1.06×1012/L vs 2.97×1012/L, p=0.001), and absolute reticulocyte count (31.99 ×109/L vs 67.05×109/L p=0.0004) were all significantly elevated compared with the pre-treatment level. After the conversion to AVA therapy, liver and kidney function indexes were maintained within the normal range, no AVA related grade 2 or higher adverse events occurred, and no thrombotic events occurred.ConclusionThe conversion to AVA was an optimal choice for patients with SAA who were EPAG intolerant or refractory.Clinical trial registrationhttp://www.chictr.org.cn/showproj.html?proj=125480, identifier ChiCTR2100045895.

IntroductionSport anxiety not only impacts the performance of college athletes but also influences their psychological well-being. The psychological well-being of sports students is crucial for both academic performance and competition, as they need to balance their academic performance with professional athletic training.MethodBased on self-determination theory, this study examines the relationship between various factors in sport anxiety (somatic anxiety, worry, and concentration disruption) and subjective happiness, as well as the mediating role of need satisfaction in this relationship. A total of 835 college athletic students participated in the study, completing the Sport Anxiety Scale-2, Basic Psychological Needs Satisfaction Scale-in General, and Subjective Happiness Scale.ResultsAn analysis of gender differences revealed that female participants scored significantly higher on somatic anxiety (t = −2.21, df = 833, p = 0.028, Cohen’s d = −0.155) and worry (t = −3.17, df = 833, p = 0.002, Cohen’s d = −0.223) compared to males. In the analysis by sport type, participants engaged in team sports scored significantly higher on somatic anxiety (t = 2.70, df = 833, p = 0.007, Cohen’s d = 0.187), Worry (t = 1.97, df = 833, p = 0.049, Cohen’s d = 0.136), and concentration disruption (t = 2.73, df = 833, p = 0.007, Cohen’s d = 0.189) than those in individual sports. Additionally, in the analysis by grade level, freshman college athletes exhibited significantly lower sport anxiety compared to sophomore athletes [F(4, 830) = 4.06, p = 0.003, ηp2=0.019]. The mediation analysis revealed that concentration disruption in sport anxiety is significantly and negatively related to subjective happiness. Additionally, need satisfaction (competence, autonomy, and relatedness) mediates the relationship between worry, as well as concentration disruption in sport anxiety and subjective happiness.DiscussionFuture research should build on the current study by employing longitudinal designs and integrating multiple objective measures to further explore the relationship between sport anxiety and subjective happiness.

Aims: This study explored the molecular and biologic mechanisms underlying the association between circadian rhythm disorders (CRD) and increased risk for hepatocellular carcinoma (HCC). Background: CRD are linked to increased risk for HCC, but the molecular and biologic mechanisms underlying this association are limited.ObjectiveThe study constructed and validated a CRD related gene model as an independent prognostic factor for HCC, providing insight into the molecular mechanisms linking CRD to increased HCC risk and identifying potential indicators for the efficacy of immunotherapy and anticancer drugs. This helps provide important clues for personalized treatment strategies for HCC patients. Methods: Gene sets correlated with circadian rhythm were obtained from the Molecular Signatures Database (MSigDB) to intersect with differentially expressed genes (DEGs) between tumor samples and control samples in The Cancer Genome Atlas (TCGA) and HCCDB18 from Hepatocellular Carcinoma Cell DataBase (HCCDB). The CRD related gene model was developed by univariate Cox and stepwise multivariate analysis. Immune checkpoint blockade (ICB) therapy and anticancer drugs were analyzed using the tumor immune dysfunction and exclusion (TIDE) and pRRophetic, respectively. Seurat determined the cell type of HCC by analyzing single-cell data, and malignant cells were identified using Copykat. To detect the mRNA levels of genes in the CRD related gene model, quantitative real-time polymerase chain reaction (qRT-PCR) was carried out. Results: The activity of circadian rhythm in HCC tissue was significantly lower than that in control tissue. Subsequently, EZH2, IMPDH2, TYMS and SERPINE1 were selected to construct the CRD related gene model, which was an independent factor for HCC prognosis. Notably, low-risk patients had lower levels of immune cell infiltration and lower TIDE scores compared to high-risk patients with HCC, indicating that patients with a low risk may derive more benefit from immunotherapy. IMPDH2, TYMS and SERPINE1 expressed significantly higher in malignant cells than in benign epithelial cells. Conclusions: This study presents a CRD related gene model to reveal the molecular perspective of the dependent mechanism of the association between CRD and cancer, which provides a potential indicator for understanding the preclinical efficacy of ICB and anticancer drugs.

Viral diseases pose a major threat to salmonids aquaculture, and mixed infections against salmonids are common. Early detection and identification of viral pathogens are crucial for effective prevention and control measures. This study used samples of infectious hematopoietic necrosis virus (IHNV), infectious pancreatic necrosis virus (IPNV), infectious salmon anemia virus (ISAV), salmonid alphavirus (SAV), and viral hemorrhagic septicemia virus (VHSV) to evaluate a multiplex RT-PCR assay developed for the simultaneous detection of these viruses. A liquid chip technique combined with multiplex RT-PCR was developed. The RT-PCR amplification products were tested using a liquid chip probe. The sensitivity of the assay system was evaluated using 10-fold serial dilutions of RNA extracted from IHNV, IPNV, ISAV, SAV, and VHSV with concentrations of 0.1, 0.4, 2, 0.9, and 1.6 pg µL−1, respectively. The assay was highly specific for these different viruses owing to the use of two nested degenerate primers and one probe. No cross-reactions occurred among the viruses nor did any non-specific reactions occur with other pathogens. The proposed method can be used for rapid, accurate, sensitive, and simultaneous detection of five salmon and trout viruses, thereby contributing to the rapid and accurate quarantine of aquatic animal samples.

BackgroundUntargeted metabonomics has provided new insight into the pathogenesis of sarcopenia. In this study, we explored plasma metabolic signatures linked to a heightened risk of sarcopenia in a cohort study by LC-MS-based untargeted metabonomics.MethodsIn this nested case–control study from the Adult Physical Fitness and Health Cohort Study (APFHCS), we collected blood plasma samples from 30 new-onset sarcopenia subjects (mean age 73.2 ± 5.6 years) and 30 healthy controls (mean age 74.2 ± 4.6 years) matched by age, sex, BMI, lifestyle, and comorbidities. An untargeted metabolomics methodology was employed to discern the metabolomic profile alterations present in individuals exhibiting newly diagnosed sarcopenia.ResultsIn comparing individuals with new-onset sarcopenia to normal controls, a comprehensive analysis using liquid chromatography-mass spectrometry (LC-MS) identified a total of 62 metabolites, predominantly comprising lipids, lipid-like molecules, organic acids, and derivatives. Receiver operating characteristic (ROC) curve analysis indicated that the three metabolites hypoxanthine (AUC=0.819, 95% CI=0.711–0.927), L-2-amino-3-oxobutanoic acid (AUC=0.733, 95% CI=0.598–0.868) and PC(14:0/20:2(11Z,14Z)) (AUC= 0.717, 95% CI=0.587–0.846) had the highest areas under the curve. Then, these significant metabolites were observed to be notably enriched in four distinct metabolic pathways, namely, “purine metabolism”; “parathyroid hormone synthesis, secretion and action”; “choline metabolism in cancer”; and “tuberculosis”.ConclusionThe current investigation elucidates the metabolic perturbations observed in individuals diagnosed with sarcopenia. The identified metabolites hold promise as potential biomarkers, offering avenues for exploring the underlying pathological mechanisms associated with sarcopenia.

Human induced pluripotent stem cell (hiPSC)-derived mesenchymal stem cells (iMSCs) are ideal candidates for the production of standardised and scalable bioengineered bone grafts. However, stable induction and osteogenic differentiation of iMSCs pose challenges in the industry. We developed a precise differentiation method to produce homogeneous and fully differentiated iMSCs. In this study, we established a standardised system to prepare iMSCs with increased osteogenic potential and improved bioactivity by introducing a CHIR99021 (C91)-treated osteogenic microenvironment (COOME). COOME enhances the osteogenic differentiation and mineralisation of iMSCs via canonical Wnt signalling. Global transcriptome analysis and co-culturing experiments indicated that COOME increased the pro-angiogenesis/neurogenesis activity of iMSCs. The superior osteogenic differentiation and mineralisation abilities of COOME-treated iMSCs were also confirmed in a Bio3D module generated using a polycaprolactone (PCL) and cell-integrated 3D printing (PCI3D) system, which is the closest model to in vivo research. This COOME-treated iMSCs differentiation system offers a new perspective for generating highly osteogenic, bioactive, and anatomically matched grafts for clinical applications. Statement of significance: Although human induced pluripotent stem cell-derived MSCs (iMSCs) are ideal seed cells for synthetic bone implants, the challenges of stable induction and osteogenic differentiation hinder their clinical application. This study established a standardised system for the scalable preparation of iMSCs with improved osteogenic potential by combining our precise iMSC differentiation method with the CHIR99021 (C91)-treated osteocyte osteogenic microenvironment (COOME) through the activation of canonical Wnt signalling. Moreover, COOME upregulated the pro-angiogenic and pro-neurogenic capacities of iMSCs, which are crucial for the integration of implanted bone grafts. The superior osteogenic ability of COOME-treated iMSCs was confirmed in Bio3D modules generated using PCL and cell-integrated 3D printing systems, highlighting their functional potential in vivo. This study contributes to tissue engineering by providing insights into the functional differentiation of iMSCs for bone regeneration.