Exploring the moderated mediation of stress and media use: Social support's impact on anxiety among older adults during the COVID-19 pandemic - Insights from a large-scale cross-sectional study in China.

BACKGROUND: This study aimed to assess the prevalence of anxiety symptoms among the older adults, explore whether stress mediated the association between social support and anxiety symptoms, and investigate whether media use moderated the direct or indirect effects within the mediation model. METHODS: Questionnaires and scales were employed to collect data from 1143 individuals aged 60 years and older across 120 cities in China during the COVID-19 pandemic. The collected information encompassed sociodemographic characteristics, social support, anxiety, stress, and media use. Bivariate correlations were then used to analyze the relationships among the study variables. Finally, the mediation and moderated mediation models were examined using the PROCESS macro for SPSS. RESULTS: During the COVID-19 pandemic, 40.1 % of Chinese elderly experienced anxiety. Social support exhibited a negative correlation with anxiety. And, media use positively influenced both stress and anxiety. Stress partially mediated the relationship between social support and anxiety, with a mediation effect of 50.95 %. Notably, media use moderated the association between social support and anxiety, serving as both an indirect mediator (path a: Social support - Stress: B = 0.071, 95 % CI: 0.022, 0.120) and a direct mediator (path c': Social support - Anxiety: B = -0.066, 95 % CI: -0.111, -0.022). LIMITATIONS: This study used a cross-sectional design, which restricts the ability to infer causal relationships. CONCLUSION: Social support is proven to be a potent alleviator of anxiety among the elderly. Stress partially mediated this relationship, while the indirect and direct impact of this mediation was influenced by media use. BRIEF SUMMARY: This study underscores the heightened anxiety prevalence among Chinese elderly during the COVID-19 pandemic, emphasizing the critical role of social support in mitigating these effects. It discovers that while stress acts as a mediator, media use serves as a significant moderator in this dynamic. These findings advocate for the necessity of bolstering social support networks and encouraging prudent media use to effectively manage anxiety and stress among the elderly, particularly in challenging times like a pandemic.

Decoding functional impact of epigenetic regulator mutations on ligand-receptor interaction perturbations for evaluation of cancer immunotherapy.

Cellular crosstalk mediated by ligand-receptor interactions largely complicates the tumour ecosystem, resulting in heterogeneous tumour microenvironments that affect immune response and clinical benefits from immunotherapy. Epigenetic mechanisms are pivotal to expression changes of immune-related genes and can modulate the anti-tumour immune response. However, the functional consequences of disrupted epigenetic regulators (ERs) on ligand-receptor interactions in the tumour microenvironment remain largely unexplored. Here, we proposed mutations of ERs in perturbed interactions (MERIN), a molecular network-based approach that incorporates multi-omics data, to infer the potential consequences of ER mutations on ligand-receptor interaction perturbations. Leveraging cancer genomic profiles and molecular interaction data, we comprehensively decoded the functional consequences of ER mutations on dysregulated ligand-receptor interactions across 33 cancers. The dysregulated ligand-receptor genes were indeed enriched in cancer and immune-related function. We demonstrated the potential significance of PD1-PDL1 interaction-related ER mutations in stratifying cancer patients from multiple independent data cohorts. The ER mutation group showed distinct immunological characterizations and prognoses. Furthermore, we highlighted that the ER mutations could potentially predict clinical outcomes of immunotherapy. Our computational and clinical assessment underscore the utility of MERIN for elucidating the functional relevance of ER mutations in cancer immune response, potentially aiding patients' stratification for immunotherapy.

211At radiolabeled APBA-FAPI for enhanced targeted-alpha therapy of glioma.

Fibroblast activation protein-α (FAPα) is highly expressed in tumor-associated cells and has become one of the most attractive targeting sites in cancer diagnosis and therapy. To ameliorate the rapid metabolism of FAPα inhibitor (FAPI), here, a multifunctional binding agent was introduced to simultaneously achieve 211At radiolabeling and tumor retention prolongation of corresponding radiolabeled drug. 211At-APBA-FAPI was successfully synthesized by conjugating 211At with the designed FAPI carrier in satisfactory radiochemical yield (>60 %). 211At-APBA-FAPI exhibited excellent in vitro stability, significant tumor affinity and specific killing effect on FAPα-positive U87MG cells. Molecular docking reveals that FAPI decorated with albumin binder can bind with FAPα protein via multiple intermolecular interactions with a considerable binding energy of -9.66 kcal/mol 211At-APBA-FAPI exhibits good targeting in murine xenograft models, showing obviously longer tumor retention than previously-reported radioastatinated compound. As a result, 211At-APBA-FAPI presents pronounced therapeutic effect with ignorable normal organs/tissues biotoxicity. All these indicate that introducing a multifunctional binding agent can effectively enhance the availability of FAPI for 211At conjugation and tumoricidal effect, providing vital hints for the translation of targeted-alpha therapy based on radiolabeled FAPI derivatives.

Triglyceride-rich lipoproteins cholesterol, 10-year atherosclerotic cardiovascular disease risk, and risk of myocardial infarction and ischemic stroke.

BACKGROUND: Triglyceride-rich lipoproteins cholesterol (TRLs-C) has been associated with atherosclerotic cardiovascular disease (ASCVD), even among individuals with low-density lipoprotein cholesterol in the targeted range. We assessed whether the associations of TRLs-C with myocardial infarction (MI) and ischemic stroke (IS) vary by the burden of traditional cardiovascular risk factors, as reflected by predicted 10-year risk for ASCVD. MATERIALS AND METHODS: Included were 327,899 participants from the UK Biobank who were free of MI or IS and did not receive lipid-lowering treatment at baseline. Ten-year risk for ASCVD was estimated by the Pooled Cohort Equations and was grouped as low (<7.5%), intermediate (7.5% to <20%), and high risk (≥20%). Multivariable Cox regression models were used to examine the associations of TRLs-C and triglycerides with risk of MI and IS, overall and by the 10-year risk categories. RESULTS: During a median of 12.3 years of follow-up, 8,358 incident MI and 4,400 incident IS cases were identified. Overall, higher TRLs-C was associated with a higher risk of MI (p-trend <.0001) but not IS (p-trend = 0.074). Triglycerides and non-HDL-C levels provide generally similar results. There was evidence for interactions between TRLs-C, triglycerides, non-HDL-C and 10-year ASCVD risk on risk of MI. However, the interaction was only between TRLs-C, triglycerides and10-year ASCVD risk on risk of IS. Hazard ratios (95% CIs) of MI comparing the highest with the lowest quartiles of TRLs-C, triglycerides, non-HDL-C were 2.10 (1.23-1.30), 2.02 (1.80-2.27) and 2.17 (1.93-2.44) in the low-risk group. The corresponding estimates for IS were 1.24 (1.05-1.45) 1.25 (1.06-1.47) and 1.08 (0.92-1.27) respectively. CONCLUSIONS: The associations of TRLs-C with MI and IS were significant in the low-risk group. Triglycerides and non-HDL cholesterol are roughly equivalent to TRLs-C in determining risk. These findings may have implications for more detailed risk stratification and early intervention.

Intake of dietary flavonoids in relation to overactive bladder among U.S. adults: a nutritional strategy for improving urinary health.

Background: The increasing influence of overactive bladder (OAB) on physical as well as mental health of individuals is becoming more pronounced annually, as evidenced by the urge urinary incontinence and nocturia. Symptoms in OAB patients may be influenced by inflammation and oxidative stress. Flavonoids are recognized as significant anti-inflammatory and antioxidant agents, which are commonly available in fruits, tea, vegetables, etc. Previous research has demonstrated the therapeutic potential of flavonoids and their subclasses in treating inflammation, and oxidative stress. Despite this, there remains a paucity of research exploring the potential correlation between flavonoid consumption, specifically within distinct subclasses, and OAB. Thus, our study aims to investigate the relationship between flavonoid intake and OAB to identify possible dietary interventions for OAB management. Methods: We utilized the survey data from the National Health and Nutrition Examination Survey (NHANES) and the USDA Food and Nutrient Database for Dietary Studies (FNDDS) to investigate the relationship between dietary intake of total and subclass flavonoids and the risk of OAB based on 13,063 qualified American adults. The dietary flavonoid intake was estimated from two 24-h dietary recalls. Weighted multivariate logistic regression model, quantile-based g-computation, restricted cubic spline model, and stratified analysis were used to explore the association between flavonoid intake and OAB, respectively. Results: The participants diagnosed with OAB exhibited a higher percentage of being female, older, Non-Hispanic Black, unmarried, former drinkers, having a lower annual household income, lower poverty to income ratio, lower educational attainment, and a higher likelihood of being obese and smokers. Upon adjusting for confounding factors, the weighted logistic regression models revealed that the third quartile of consumption of anthocyanidin and the second quartile of consumption of flavone were significantly associated with the reduced odds of OAB, while total flavonoid consumption did not show a significant correlation with the risk of OAB. The quantile-based g-computation model indicated that flavone, anthocyanidin and flavonol were the primary contributors to the observed negative correlation. Furthermore, the restricted cubic spline models demonstrated a J-shaped non-linear exposure-response association between anthocyanidin intake and the risk of OAB (P nonlinear = 0.00164). The stratified and interaction analyses revealed that the relationship between anthocyanidin intake and the risk of OAB was significantly influenced by age (P interaction = 0.01) and education level (P interaction = 0.01), while the relationship between flavone intake and the risk of OAB was found to vary by race (P interaction = 0.02) and duration of physical activity (P interaction = 0.05). Conclusion: Our research suggests that consuming a diet rich in flavonoid subclass anthocyanidin and flavone is associated with a reduced risk of OAB, potentially offering clinical significance in the prevention of OAB development. This underscores the importance of dietary adjustments in the management of OAB symptoms.

Evaluating plantar biomechanics while descending a single step with different heights.

Objective: This study aims to investigate the plantar biomechanics of healthy young males as they descend a single transition step from varying heights. Methods: Thirty healthy young males participated the experiment using the F-scan insole plantar pressure system in which participants made single transition steps descent from four step heights (5, 15, 25, and 35 cm), leading with their dominant or non-dominant foot. Plantar pressure data were collected for 5 s during the period between landing touchdown and standing on the ground. Landing at each step height was repeated three times, with a five-minute rest between different height trials. Results: At 5 cm and 15 cm steps, participants demonstrated a rearfoot landing strategy on both sides. However, forefoot contact was observed at heights of 25 cm and 35 cm. Parameters related to center of plantar pressure (COP) of the leading foot were significantly larger compared to the trailing foot (P < 0.001), increased with higher step heights. Vertical ground reaction forces for the biped, leading and trailing feet decreased with increasing step height (all P < 0.05). The leading foot had a higher proportion of overall and forefoot loads, and a lower proportion of rearfoot load compared to the trailing foot (P < 0.001). The overall load on the dominant side was lower than that on the non-dominant side for both the leading and trailing feet (P < 0.001). For the trailing foot, forefoot load on the dominant side was lower than that on the non-dominant side, however, the opposite result appeared in rearfoot load (P < 0.001). Upon the leading foot landing, forefoot load exceeded the rearfoot load for the dominant (P < 0.001) and non-dominant sides (P < 0.001). Upon the trailing foot landing, forefoot load was lower than the rearfoot load for the dominant (P < 0.001) and non-dominant sides (P = 0.019). Conclusion: When the characteristics of biomechanical stability are compromised by step height, landing foot, and footedness factors - due to altered foot landing strategies, changing COP, or uneven force distribution - ability to control motion efficiently and respond adaptively to the forces experienced during movement is challenged, increasing the likelihood of loss of dynamic balance, with a consequent increased risk of ankle sprains and falls.

Consumption of Total and Specific Alcoholic Beverages and Long-Term Risk of Gout Among Men and Women.

Importance: Previous studies on alcohol consumption and incident gout have mostly included men or combined both sexes, and the sex-specific associations between alcohol consumption and gout are poorly understood. Objective: To evaluate the consumption of total and specific alcoholic beverages in association with incident gout in men and women. Design, Setting, and Participants: This prospective cohort study included 401 128 participants in the UK Biobank aged 37 to 73 years who were free of gout at baseline (2006-2010). Participants were followed up through December 31, 2021, and data were analyzed between August 2023 and June 2024. Exposure: Questionnaire-based consumption of total alcohol and specific alcoholic beverages. Main Outcomes and Measures: The outcome was incident gout, identified using hospital records. Multivariable Cox proportional hazards regression models were used to estimate sex-specific hazard ratios (HRs) and 95% CIs of incident gout associated with alcohol consumption, with a particular consideration of reverse causation bias. Results: The main analysis included 179 828 men (mean [SD] age, 56.0 [8.2] years) and 221 300 women (mean [SD] age, 56.0 [8.0] years). Current drinkers showed a higher risk of gout than never drinkers among men (HR, 1.69; 95% CI, 1.30-2.18) but not among women (HR, 0.83; 95% CI, 0.67-1.03). Among current drinkers, higher total alcohol consumption was associated with a higher risk of gout among both sexes and more strongly among men than women (men: HR, 2.05 [95% CI, 1.84-2.30]; women: HR, 1.34 [95% CI, 1.12-1.61]). The most evident sex difference in the consumption of specific alcoholic beverages was observed for beer or cider (men: mean [SD], 4.2 [4.8] pints per week; women: mean [SD], 0.4 [1.1] pints per week). Consumption of champagne or white wine, beer or cider, and spirits each was associated with a higher risk of gout among both sexes, with beer or cider showing the strongest association per 1 pint per day (men: HR, 1.60 [95% CI, 1.53-1.67]; women: HR, 1.62 [95% CI, 1.02-2.57]). Some inverse associations between light to moderate consumption of specific alcoholic beverages and gout were eliminated after adjusting for other alcoholic beverages and excluding individuals who had reduced alcohol consumption for health reasons, self-reported poor health, or had cardiovascular disease, cancer, or kidney failure at baseline, or developed gout within the first 2 years of follow-up. Conclusions and Relevance: In this cohort study, higher consumption of several specific alcoholic beverages was associated with a higher risk of gout among both sexes. The sex-specific associations for total alcohol consumption may be associated with differences between men and women in the types of alcohol consumed.

[Chemical constituents from Clitocybe clavipes and their antitumor activities].

This paper aimed to study the chemical constituents from Clitocybe clavipes. Silica gel, ODS, Sephadex LH-20, and semi-p reparative HPLC were employed to separate the ethanol extract of C. clavipes. Six compounds were identified by ~1H-NMR, ~(13)CNMR,and ESI-MS as clavilactone L(1), clavilactone A(2), clavilactone B(3), clavilactone E(4), clavilactone H(5), and clav ilactone I(6). Among them, compound 1 was a new meroterpenoid with a 10-membered carbocycle connected to a hydroquinone. Theantitumor activities of compounds 1-6 were determined by the methyl thiazolyl tetrazolium(MTT) ass ay. The results showed that compounds 1-6 exerted inhibitory effects on the proliferation of human gastric cancer cells(MGC-803),human non-small cell lung cancer cells(A549), and cervical cancer cells(HeLa). Compound 1 exhibited significant inhibitory activity against MGC-803 cells, with the half maximal inhibitory concentration(IC_(50)) of 11. 76 µmol·L~(-1).

Golden 2-like Transcription Factors Regulate Photosynthesis under UV-B Stress by Regulating the Calvin Cycle.

UV-B stress can affect plant growth at different levels, and although there is a multitude of evidence confirming the effects of UV-B radiation on plant photosynthesis, there are fewer studies using physiological assays in combination with multi-omics to investigate photosynthesis in alpine plants under stressful environments. Golden 2-like (G2-like/GLK) transcription factors (TFs) are highly conserved during evolution and may be associated with abiotic stress. In this paper, we used Handy-PEA and Imaging-PAM Maxi to detect chlorophyll fluorescence in leaves of Rhododendron chrysanthum Pall. (R. chrysanthum) after UV-B stress, and we also investigated the effect of abscisic acid (ABA) on photosynthesis in plants under stress environments. We used a combination of proteomics, widely targeted metabolomics, and transcriptomics to study the changes of photosynthesis-related substances after UV-B stress. The results showed that UV-B stress was able to impair the donor side of photosystem II (PSII), inhibit electron transfer and weaken photosynthesis, and abscisic acid was able to alleviate the damage caused by UV-B stress to the photosynthetic apparatus. Significant changes in G2-like transcription factors occurred in R. chrysanthum after UV-B stress, and differentially expressed genes localized in the Calvin cycle were strongly correlated with members of the G2-like TF family. Multi-omics assays and physiological measurements together revealed that G2-like TFs can influence photosynthesis in R. chrysanthum under UV-B stress by regulating the Calvin cycle. This paper provides insights into the study of photosynthesis in plants under stress, and is conducive to the adoption of measures to improve photosynthesis in plants under stress to increase yield.

Effects of textured insoles on dynamic balance and ankle muscle activity in soccer players with and without chronic ankle instability.

BACKGROUND: Chronic ankle instability (CAI) poses challenges in sports. Textured insoles (TI) are a promising intervention for enhancing dynamic balance in CAI athletes. This study aimed to investigate the effects of TI on dynamic balance performance and ankle muscle activity in soccer players with and without CAI. METHODS: Thirty-eight soccer players (19 CAI, 19 non-CAI) participated. Participants performed a modified star excursion balance test (mSEBT) while wearing TI and standard insoles (SI). The %SEBT reach distance and electromyography (EMG) activity of tibialis anterior (TA), medial gastrocnemius (MG), and peroneus longus (PL) were measured during maximum reached in each direction of the mSEBT. RESULTS: No significant effects or interactions were found between ankle conditions (CAI vs. non-CAI) or insole types (TI vs. SI) on %SEBT reach. However, CAI players showed greater MG activity in posteromedial and posterolateral direction (P=0.04, P=0.01). CONCLUSIONS: Overall, the application of TI did not have immediate effects on dynamic balance performance or ankle muscle activity in either CAI or non-CAI soccer players. Nonetheless, CAI players seemed to employ a different ankle strategy involving the MG muscle, possibly to control stability during dynamic movement, particularly in the posteromedial and posterolateral directions.

Female reproductive factors, exogenous hormone use, and incident chronic kidney disease and end-stage renal disease.

CONTEXT: Younger women have a slower progressive loss of kidney function than age-matched men and the sex advantage diminishes after menopause, suggesting a role for female hormones in the development of kidney diseases. OBJECTIVE: To examine the relationships of numerous reproductive factors and exogenous hormone use with long-term risk of chronic kidney disease (CKD) and end-stage renal disease (ESRD) in women. METHODS: A total of 260,108 women without prevalent CKD and ESRD were included. The relationships of various reproductive factors and exogenous hormone use with incident CKD and ESRD were assessed, with multivariable adjustment for potential confounders. RESULTS: During a median of ∼12.5 years of follow-up, 8,766 CKD and 554 ESRD cases were identified. Younger age at first live birth, hysterectomy or bilateral oophorectomy before 50 years old, menopausal before 45 years old, and menopausal hormone therapy (MHT) initiated before 50 years old was associated with a higher risk of CKD. The relationships of these factors with ESRD were generally consistent with those for CKD. Each 5-year increment in menopausal age was associated with an 11% lower risk of CKD (HR = 0.89; 95% CI: 0.87, 0.91) and a 13% lower risk of ESRD (HR = 0.87; 95% CI: 0.79, 0.95). Each 5-year delay in starting MHT was associated with a 13% lower risk of CKD (HR = 0.87; 95% CI: 0.84, 0.90) and a 15% lower risk of ESRD (HR = 0.85; 95% CI: 0.73, 0.99). CONCLUSION: Several reproductive characteristics reflecting shorter cumulative exposure to endogenous estrogen or premature exposure to exogenous hormones are associated with a greater risk of CKD and ESRD in women, supporting a potential role of female hormones in renal pathophysiology.

Deciphering the environmental chemical basis of muscle quality decline by interpretable machine learning models.

BACKGROUND: Sarcopenia is known as a decline in skeletal muscle quality and function that is associated with age. Sarcopenia is linked to diverse health problems, including endocrine-related diseases. Environmental chemicals (ECs), a broad class of chemicals released from industry, may influence muscle quality decline. OBJECTIVES: In this work, we aimed to simultaneously elucidate the associations between muscle quality decline and diverse EC exposures based on the data from the 2011-2012 and 2013-2014 survey cycles in the National Health and Nutrition Examination Survey (NHANES) project using machine learning models. METHODS: Six machine learning models were trained based on the EC and non-EC exposures from NHANES to distinguish low from normal muscle quality index status. Different machine learning metrics were evaluated for these models. The Shapley additive explanations (SHAP) approach was used to provide explainability for machine learning models. RESULTS: Random forest (RF) performed best on the independent testing data set. Based on the testing data set, ECs can independently predict the binary muscle quality status with good performance by RF (area under the receiver operating characteristic curve = 0.793; area under the precision-recall curve = 0.808). The SHAP ranked the importance of ECs for the RF model. As a result, several metals and chemicals in urine, including 3-phenoxybenzoic acid and cobalt, were more associated with the muscle quality decline. CONCLUSIONS: Altogether, our analyses suggest that ECs can independently predict muscle quality decline with a good performance by RF, and the SHAP-identified ECs can be closely related to muscle quality decline and sarcopenia. Our analyses may provide valuable insights into ECs that may be the important basis of sarcopenia and endocrine-related diseases in United States populations.

Lower plasma linoleic acids as a risk factor for gout: an integrated analysis of population-based cohort and genetic data.

Background: Gout is a nutrition-related, highly prevalent inflammatory arthritis with undesirable effects on the quality of life. The relationships between circulating fatty acids (FAs) and gout remain poorly understood. Method: We included 268 174 participants with plasma FAs measured using nuclear magnetic resonance at the baseline (2006-2010) from the UK Biobank, of which 15 194 participants had repeated measures of FAs between 2012 and 2013. Cox proportional hazards models were used to assess the association of the baseline and longitudinal changes in relative levels of plasma FAs (% total FAs) with incident gout. Mendelian randomization (MR) analyses were conducted to assess the potential causality of the examined association. Results: Over a median follow-up of 12.8 years, 5160 incident cases of gout occurred. Baseline polyunsaturated fatty acids (PUFAs), n-6 PUFAs, and linoleic acids (LAs) were inversely associated with incident gout (all P-trend values < 0.0001). Baseline monounsaturated fatty acids (MUFAs), n-3 PUFAs, and docosahexaenoic acids (DHAs) were positively associated with incident gout (all P-trend values < 0.0001). Longitudinal increments of n-6 PUFAs and LAs were associated with a lower risk of subsequent gout, whereas an increment of n-3 PUFAs was associated with a higher risk. In two-sample MR analyses, genetically determined higher levels of PUFAs, n-6 PUFAs, and LAs were associated with a decreased risk of gout (all P values < 0.05). Conclusions: Our findings consistently indicate a causal relationship of elevated levels of n-6 PUFAs, especially LAs, with a reduced risk of gout.

Effectiveness and feasibility of 5G-based remote interactive ultrasound training in critical care.

BACKGROUND: Ultrasound has widely used in various medical fields related to critical care. While online and offline ultrasound trainings are faced by certain challenges, remote ultrasound based on the 5G cloud platform has been gradually adopted in many clinics. However, no study has used the 5G remote ultrasound cloud platform operating system for standardized critical care ultrasound training. This study aimed to evaluate the feasibility and effectiveness of 5G-based remote interactive ultrasound training for standardized diagnosis and treatment in critical care settings. METHODS: A 5G-based remote interactive ultrasound training system was constructed, and the course was piloted among critical care physicians. From July 2022 to July 2023, 90 critical care physicians from multiple off-site locations were enrolled and randomly divided into experimental and control groups. The 45 physicians in the experimental group were trained using the 5G-based remote interactive ultrasound training system, while the other 45 in the control group were taught using theoretical online videos. The theoretical and practical ultrasonic capabilities of both groups were evaluated before and after the training sessions, and their levels of satisfaction with the training were assessed as well. RESULTS: The total assessment scores for all of the physicians were markedly higher following the training (80.7 ± 11.9) compared to before (42.1 ± 13.4) by a statistically significant margin (P < 0.001). Before participating in the training, the experimental group scored 42.2 ± 12.5 in the critical care ultrasound competency, and the control group scored 41.9 ± 14.3-indicating no significant differences in their assessment scores (P = 0.907). After participating in the training, the experimental group's assessment scores were 88.4 ± 6.7, which were significantly higher than those of the control group (72.9 ± 10.8; P < 0.001). The satisfaction score of the experimental group was 42.6 ± 2.3, which was also significantly higher than that of the control group (34.7 ± 3.1, P < 0.001). CONCLUSION: The 5G-based remote interactive ultrasound training system was well-received and effective for critical care. These findings warrant its further promotion and application.

Knee osteoarthritis patients assessed during walking for ankle inversion movement discrimination sensitivity.

Background: Knee osteoarthritis (KOA) is a common musculoskeletal condition that affects dynamic balance control and increases the risk of falling during walking. However, the mechanisms underlying this are still unclear. Diminished ankle proprioception during walking has been found to be related to fear of falling in older adults, with a gender difference in incidence of falling. This study aimed to determine 1) whether ankle inversion proprioceptive acuity during walking is impaired in patients with KOA; and 2) whether there is any difference between genders. Methods: Thirty-two patients with KOA (F:M = 17:15, Median age = 52.5, BMI = 22.3 ± 3.0) and 34 healthy controls without KOA (HC) (F:M = 17:17; median age = 49.0, BMI = 22.5 ± 2.7) were recruited. In patients with KOA, ankle inversion proprioceptive acuity was measured on the affected side using the ankle inversion discrimination apparatus for walking (AIDAW), whilst HC were assessed on a randomly selected side. Two-way (2*2) analysis of variance (ANOVA) was performed to determine the main effects and interaction between gender and KOA condition. Results: Two-way ANOVA showed a significant KOA main effect (F = 26.6, p < 0.001, ƞp 2 = 0.3) whereby AIDAW scores during walking for individuals with KOA were significantly lower than those without KOA (KOA vs. HC: 0.746 ± 0.057 vs. 0.807 ± 0.035). There was neither a gender main effect nor interaction (both p > 0.05). Conclusion: Individuals with KOA demonstrated lower ankle proprioception scores during walking compared to their healthy counterparts, with a similar level of impairment in ankle proprioceptive acuity between male and female patients. A low score may contribute to an increased risk of falling in the KOA population. The current findings suggest the need for global concern about lower limb proprioception in the clinical management of KOA.

SCTC: inference of developmental potential from single-cell transcriptional complexity.

Inferring the developmental potential of single cells from scRNA-Seq data and reconstructing the pseudo-temporal path of cell development are fundamental but challenging tasks in single-cell analysis. Although single-cell transcriptional diversity (SCTD) measured by the number of expressed genes per cell has been widely used as a hallmark of developmental potential, it may lead to incorrect estimation of differentiation states in some cases where gene expression does not decrease monotonously during the development process. In this study, we propose a novel metric called single-cell transcriptional complexity (SCTC), which draws on insights from the economic complexity theory and takes into account the sophisticated structure information of scRNA-Seq count matrix. We show that SCTC characterizes developmental potential more accurately than SCTD, especially in the early stages of development where cells typically have lower diversity but higher complexity than those in the later stages. Based on the SCTC, we provide an unsupervised method for accurate, robust, and transferable inference of single-cell pseudotime. Our findings suggest that the complexity emerging from the interplay between cells and genes determines the developmental potential, providing new insights into the understanding of biological development from the perspective of complexity theory.

Immunosuppressive microvesicles-mimetic derived from tolerant dendritic cells to target T-lymphocytes for inflammation diseases therapy.

The utilization of extracellular vesicles (EV) in immunotherapy, aiming at suppressing peripheral immune cells responsible for inflammation, has demonstrated significant efficacy in treating various inflammatory diseases. However, the clinical application of EV has faced challenges due to their inadequate targeting ability. In addition, most of the circulating EV would be cleared by the liver, resulting in a short biological half-life after systemic administration. Inspired by the natural microvesicles (MV, as a subset of large size EV) are originated and shed from the plasma membrane, we developed the immunosuppressive MV-mimetic (MVM) from endotoxin tolerant dendritic cells (DC) by a straightforward and effective extrusion approach, in which DC surface proteins were inherited for providing the homing ability to the spleen, while αCD3 antibodies were conjugated to the MVM membranes for specific targeting of T cells. The engineered MVM carried a large number of bioactive cargos from the parental cells, which exhibited a remarkable ability to promote the induction of regulatory T cells (Treg) and polarization of anti-inflammatory M2 macrophages. Mechanistically, the elevated Treg level by MVM was mediated due to the upregulation of miR-155-3p. Furthermore, it was observed that systemic and local immunosuppression was induced by MVM in models of sepsis and rheumatoid arthritis through the improvement of Treg and M2 macrophages. These findings reveal a promising cell-free strategy for managing inflammatory responses to infections or tissue injury, thereby maintaining immune homeostasis.

Comparative Metabolomics and Transcriptome Studies of Two Forms of Rhododendron chrysanthum Pall. under UV-B Stress.

Rhododendron chrysanthum Pall. (R. chrysanthum), a plant with UV-B resistance mechanisms that can adapt to alpine environments, has gained attention as an important plant resource with the ability to cope with UV-B stress. In this experiment, R. chrysanthums derived from the same origin were migrated to different culture environments (artificial climate chamber and intelligent artificial incubator) to obtain two forms of R. chrysanthum. After UV-B irradiation, 404 metabolites and 93,034 unigenes were detected. Twenty-six of these different metabolites were classified as UV-B-responsive metabolites. Glyceric acid is used as a potential UV-B stress biomarker. The domesticated Rhododendron chrysanthum Pall. had high amino acid and SOD contents. The study shows that the domesticated Rhododendron chrysanthum Pall. has significant UV-B resistance. The transcriptomics results show that the trends of DEGs after UV-B radiation were similar for both forms of R. chrysanthum: cellular process and metabolic process accounted for a higher proportion in biological processes, cellular anatomical entity accounted for the highest proportion in the cellular component, and catalytic activity and binding accounted for the highest proportion in the molecular function category. Through comparative study, the forms of metabolites resistant to UV-B stress in plants can be reflected, and UV-B radiation absorption complexes can be screened for application in future specific practices. Moreover, by comparing the differences in response to UV-B stress between the two forms of R. chrysanthum, references can be provided for cultivating domesticated plants with UV-B stress resistance characteristics. Research on the complex mechanism of plant adaptation to UV-B will be aided by these results.

Ankle inversion proprioception measured during stair descent can identify chronic ankle instability.

BACKGROUND: Individuals with chronic ankle instability (CAI) may experience recurrent ankle sprains and symptoms during daily activities such as stair descent, where the associated proprioceptive deficit is largely unevaluated. OBJECTIVES: To evaluate the reliability and validity of an ankle inversion discrimination apparatus for stair descent, and examine whether proprioceptive scores from this apparatus are associated with patient-reported symptoms. DESIGN: Cross-sectional study. METHOD: Sixty-six participants volunteered in this study. The ankle inversion discrimination apparatus was purpose-built to assess ankle proprioception across four positions of ankle inversion (10°, 12°, 14°, and 16°) during stair descent. The Area Under the Receiver Operating Curve (AUC) was employed as the ankle proprioceptive discrimination score. RESULTS: Test-retest reliability ICC (3,1) for the whole group was 0.825, with 0.747 for the non-CAI group (95%CI = 0.331-0.920) and 0.701 for CAI (95%CI = 0.242-0.904). The CAI group performed at a significantly lower level than non-CAI on the ankle inversion discrimination apparatus for stair descent assessment (0.769 ± 0.034 vs. 0.830 ± 0.035, F = 33.786, p < 0.001). CAIT scores were strongly and significantly correlated with scores from this apparatus (Spearman's rho = 0.730, p < 0.001). CONCLUSIONS: The ankle inversion discrimination apparatus for stair descent is reliable and valid for assessing task-specific ankle proprioceptive impairments in CAI. The strong and significant relationship found between ankle proprioception during stair descent and the severity of CAI suggests that rehabilitation programs focusing on deficits in ankle inversion proprioception during stair descent may improve self-reported instability in CAI.