Roles of serum uric acid on the association between arsenic exposure and incident metabolic syndrome in an older Chinese population.

Growing evidences showed that heavy metals exposure may be associated with metabolic diseases. Nevertheless, the mechanism underlying arsenic (As) exposure and metabolic syndrome (MetS) risk has not been fully elucidated. So we aimed to prospectively investigate the role of serum uric acid (SUA) on the association between blood As exposure and incident MetS. A sample of 1045 older participants in a community in China was analyzed. We determined As at baseline and SUA concentration at follow-up in the Yiwu Elderly Cohort. MetS events were defined according to the criteria of the International Diabetes Federation (IDF). Generalized linear model with log-binominal regression model was applied to estimate the association of As with incident MetS. To investigate the role of SUA in the association between As and MetS, a mediation analysis was conducted. In the fully adjusted log-binominal model, per interquartile range increment of As, the risk of MetS increased 1.25-fold. Compared with the lowest quartile of As, the adjusted relative risk (RR) of MetS in the highest quartile was 1.42 (95% confidence interval, CI: 1.03, 2.00). Additionally, blood As was positively associated with SUA, while SUA had significant association with MetS risk. Further mediation analysis demonstrated that the association of As and MetS risk was mediated by SUA, with the proportion of 15.7%. Our study found higher As was remarkably associated with the elevated risk of MetS in the Chinese older adults population. Mediation analysis indicated that SUA might be a mediator in the association between As exposure and MetS.

Regional variations of mechanical responses of IVD to 7 different motions: An in vivo study combined with FEA and DFIS.

The abnormal mechanical behaviour of a lumbar intervertebral disc (IVD) is commonly recognized as a direct indicator of intervertebral disc degeneration (IDD). However, current methods cannot evaluate the patient-specific mechanical performance of an IVD in vivo during movement. This study establishes a patient-specific (PS) model that combines the kinematics parameters of the lumbar spine obtained with a dual fluoroscopic imaging system (DFIS) and a finite-element (FE) method for the first time to reveal the mechanical behaviours of IVDs in vivo under seven motions. Three healthy participants were recruited for this study. CT images were obtained to create finite-element models of L3-L5 spine segments. Meanwhile, participants were required to take specific positions including upright standing, flexion, extension, left and right lateral bending, as well as left and right axial torsion in the DFIS. The in vivo kinematic parameters, calculated by registering the CT images with images obtained with DFIS, were considered as loading conditions in FE simulations. Significant differences of von Mises stresses and principal strains were found between PS model and GN model which employing a generalized moment as loading conditions, former resulting in up to 76.74 % lower strain than the GN model. Also, considerable differences were observed for five anatomical regions of the IVD (L3-L5). Under all motions, the stress in the centre region (nucleus pulposus) was the lowest, while the stress in the posterior region was the highest in extension motion. Therefore, activities such as stretching with an extension, should be avoided by patients with a herniated disc, in which the posterior region was the herniation site. The PS model combining in vivo kinematics and FE simulations shows the potential in the design and assessment of patient-specific implants.

Effects of Continuous Theta Burst Stimulation on Contralateral Primary Motor Cortex: A Concurrent TMS-EEG Study.

Continuous theta burst stimulation (cTBS) is a non-invasive brain stimulation technique. cTBS modulation is an effective treatment for motor dysfunction rehabilitation in post-stroke patients. However, there's currently a lack of research on the effects of cTBS stimulation on the contralesional hemisphere. To better understand the role of cTBS in motor rehabilitation, we investigated the neuroregulatory mechanisms of cTBS in the contralateral cortex using transcranial magnetic stimulation-evoked electroencephalography (TMS-EEG). In this randomized, sham-controlled, single-blind study, 18 healthy subjects received two separate stimulation conditions:cTBS or sham stimulation applied to the left M1. TMS-EEG measurements were taken before and immediately after stimulation. We investigated the TMS-evoked potentials (TEPs), evoked oscillatory responses (EOR), and phase synchronization index(PSI) of TMS-EEG. The effects of cTBS were analyzed using two-way repeated measures analysis of variance (RMANOVA). There was a significant "cTBS condition×time" interaction effect on the theta and gamma bands of EOR, as well as on inter-hemisphere PSI (inter-PSI) and global PSI in both cTBS stimulation conditions. (theta:F=4.526,p=0.041;gamma:F=5.574,p=0.024;inter-PSI:F=5.028,p=0.032;global PSI:F=5.129,p=0.030).After real cTBS modulation, the energy in the theta and gamma frequency bands was significantly higher than before (theta: F=5.747, p=0.022; gamma: F=5.545, p=0.024). The inter-PSI and global PSI significantly increased after real cTBS modulation (inter-PSI: F=6.209, p=0.018; global PSI: F=6.530, p=0.015). cTBS modulation significantly increased EOR and PSI in contralateral brain regions, thereby enhancing cortical excitability and cortical functional connectivity throughout the brain. This provides a theoretical basis for cTBS neuromodulation in stroke patients.

Paternal metformin use and risk of congenital malformations in offspring in Norway and Taiwan: population based, cross national cohort study.

OBJECTIVE: To evaluate the association between paternal metformin use and risk of congenital malformations in offspring. DESIGN: Population based, cross national cohort study. SETTING: Norway and Taiwan. PARTICIPANTS: 619 389 offspring with paternal data during the period of sperm development (three months before pregnancy) in the Norwegian cohort during 2010-21 and 2 563 812 in the Taiwanese cohort during 2004-18. MAIN OUTCOME MEASURES: The primary outcome was any congenital malformation, and the secondary outcome was organ specific malformations, classified according to the European surveillance of congenital anomalies guidelines. Relative risks were estimated with an unadjusted analysis and with analyses restricted to the cohort of men with type 2 diabetes mellitus and those using overlap propensity score weighting to control for severity of diabetes and other potential confounders. Sibling matched comparisons were conducted to account for genetic and lifestyle factors. Relative risk estimates for Norwegian and Taiwanese data were pooled using a random effects meta-analytical approach. RESULTS: Paternal data on metformin use during the period of sperm development was available for 2075 (0.3%) offspring in Norway and 15 276 (0.6%) offspring in Taiwan. Among these offspring, 104 (5.0%) in Norway and 512 (3.4%) in Taiwan had congenital malformations. Increased risks of any congenital malformation associated with paternal metformin use were observed in the unadjusted analysis and attenuated with increasing control of confounding. The relative risks of any malformations with paternal metformin use were 1.29 (95% confidence interval 1.07 to 1.55) in Norway and 1.08 (0.99 to 1.17) in Taiwan in the unadjusted analysis and 1.20 (0.94 to 1.53) and 0.93 (0.80 to 1.07), respectively, in the analysis restricted to fathers with type 2 diabetes mellitus. In the overlap propensity score weighting analysis restricted to fathers with type 2 diabetes mellitus, the relative risks were 0.98 (0.72 to 1.33) in Norway and 0.87 (0.74 to 1.02) in Taiwan, resulting in a pooled estimate of 0.89 (0.77 to 1.03). No associations were observed between paternal metformin use and any organ specific malformations. These findings were consistent in sibling matched comparisons and sensitivity analyses. CONCLUSIONS: The findings suggest that paternal use of metformin during the period of sperm development is not associated with congenital malformations in offspring, including organ specific malformations. Metformin can therefore continue to be considered a suitable initial oral agent for managing glucose levels in men with type 2 diabetes mellitus who plan on having children.

Follistatin drives neuropathic pain in mice through IGF1R signaling in nociceptive neurons.

Neuropathic pain is a debilitating chronic condition that lacks effective treatment. The role of cytokine- and chemokine-mediated neuroinflammation in its pathogenesis has been well documented. Follistatin (FST) is a secreted protein known to antagonize the biological activity of cytokines in the transforming growth factor-ß (TGF-ß) superfamily. The involvement of FST in neuropathic pain and the underlying mechanism remain largely unknown. Here, we report that FST was up-regulated in A-fiber sensory neurons after spinal nerve ligation (SNL) in mice. Inhibition or deletion of FST alleviated neuropathic pain and reduced the nociceptive neuron hyperexcitability induced by SNL. Conversely, intrathecal or intraplantar injection of recombinant FST, or overexpression of FST in the dorsal root ganglion (DRG) neurons, induced pain hypersensitivity. Furthermore, exogenous FST increased neuronal excitability in nociceptive neurons. The biolayer interferometry (BLI) assay and coimmunoprecipitation (co-IP) demonstrated direct binding of FST to the insulin-like growth factor-1 receptor (IGF1R), and IGF1R inhibition reduced FST-induced activation of extracellular signal-regulated kinase (ERK) and protein kinase B (AKT), as well as neuronal hyperexcitability. Further co-IP analysis revealed that the N-terminal domain of FST exhibits the highest affinity for IGF1R, and blocking this interaction with a peptide derived from FST attenuated Nav1.7-mediated neuronal hyperexcitability and neuropathic pain after SNL. In addition, FST enhanced neuronal excitability in human DRG neurons through IGF1R. Collectively, our findings suggest that FST, released from A-fiber neurons, enhances Nav1.7-mediated hyperexcitability of nociceptive neurons by binding to IGF1R, making it a potential target for neuropathic pain treatment.

Effect of electroacupuncture on the intestinal flora-short chain fatty acid metabolism axis in simple obesity rats. / ç”µé’ˆå¯¹å•çº¯æ€§è‚¥èƒ–ç—‡å¤§é¼ è‚ é“èŒç¾¤-çŸ­é“¾è„‚è‚ªé ¸ä»£è°¢è½´çš„å½±å“.

OBJECTIVES: To observe the effect of electroacupuncture (EA) on the intestinal flora-short chain fatty acids (SCFAs) metabolism axis in rats with simple obesity, so as to explore the underlying mechanism of EA in reducing obesity. METHODS: Male SD rats were randomly divided into control group, model group and EA group, with 6 rats in each group. The obesity model was established by feeding the rats with high-fat diet. Rats in the EA group were treated with EA at "Quchi" (LI11) and "Zusanli" (ST36) for 15 min, once daily for 21 consecutive days. The changes of body weight were observed every other day. H.E. staining was used to observe the pathological changes of adipose tissue and liver. The blood lipid content was detected by automatic biochemical analyzer. The diversity of intestinal flora in rat feces was analyzed by 16S rRNA high-throughput sequencing. The content of SCFAs in rat feces was detected by ultra-high performance liquid chromatography-electrospray ionization-mass spectrometry (UPLC-ESI-MS/MS). The correlation between the relative abundance of fecal intestinal flora and the content of SCFAs in rats was analyzed by Pearson method. RESULTS: Compared with the control group, the body weight of rats, the serum total cholesterol (TC) and triglyceride (TG) were significantly increased (P<0.01) in the model group. The results of 16S rRNA sequencing showed that, at the genus level the relative abundance of Bacteroides, Butyrivibrio and Roseburia in were decreased significantly(P<0.05), while that of the Lachnospiraceae_NK4A136_group increased(P<0.05). After the intervention, compared with the model group, the body weight, serum TC and TG contents of rats in the EA group were significantly decreased (P<0.05, P<0.01)；the results of 16S rRNA sequencing showed that, the relative abundance of the Bacteroidota phylum significantly increased (P<0.01) and Firmicutes decreased (P<0.01) at the phylum level, and at the genus level the relative abundances of Bacteroides, Butyrivibrio and Roseburia significantly increased (P<0.01, P<0.05)；the contents of acetic acid and propionic acid in SCFAs significantly increased (P<0.01). H.E. staining showed an increase of the diameter of adipocytes, with obvious lipid droplets and inflammatory infiltration in the model group, which was relatively milder in the EA group. PCoA analysis showed that there were significant differences in the structure of intestinal flora between the control group and the model group, as well as the model group and the EA group. At the phylum level, the relative abundance of Bacteroidota was positively correlated with acetic acid and propionic acid contents, with that of Firmicutes negatively correlated with acetic acid and propionic acid contents (P<0.001). At the genus level, the relative abundances of Bacteroides, Streptococcus and Butyricimonas were positively correlated with acetic acid content (P<0.01, P<0.05), and the relative abundances of Bacteroides, Streptococcus and Roseburia were positively correlated with propionic acid content (P<0.001, (P<0.05). CONCLUSIONS: EA can improve the disorder of lipid metabolism in obese rats by improving the disorder of intestinal flora-SCFAs metabolic axis, thus playing a role in inhibiting obesity.

VvbHLH036, a basic helix-loop-helix transcription factor regulates the cold tolerance of grapevine.

Cold stress is an adverse environmental factor that limits the growth and productivity of horticulture crops such as grapes (Vitis vinifera). In this study, we identified a grapevine cold-induced basic helix-loop-helix (bHLH) transcription factor (VvbHLH036). Overexpression and CRISPR/Cas9-mediated knockout (KO) of VvbHLH036 enhanced and decreased cold tolerance in grapevine roots, respectively. Transcriptome analysis of VvbHLH036-overexpressed roots identified threonine synthase (VvThrC1) as a potential downstream target of VvbHLH036. We confirmed that VvbHLH036 could bind the VvThrC1 promoter and activate its expression. Both the transcripts of VvThrC1 and the content of threonine were significantly induced in the leaves and roots of grapevine under cold treatment compared to controls. Conversely, these dynamics were significantly suppressed in the roots of CRISPR/Cas9-induced knockout of VvbHLH036. These observations support the regulation of threonine accumulation by VvbHLH036 through VvThrC1 during cold stress in grapevine. Furthermore, overexpression and CRISPR/Cas9-mediated knockout of VvThrC1 also confirmed its role in regulating threonine content and cold tolerance in transgenic roots at low temperature. Exogenous threonine treatment increased cold tolerance and reduced the accumulation of superoxide anions and hydrogen peroxide in grapevine leaves. Together, these findings point to the pivotal role of VvbHLH036 and VvThrC1 in the cold stress response in grapes by regulating threonine biosynthesis.

Revealing the links between hair metal(loids) and alterations in blood pressure among children in e-waste recycling areas through urinary metabolomics.

Hypertension is prevalent in e-waste recycling areas, and elevated blood pressure in children significantly increases the risk of hypertension in adulthood. However, the associations and toxic pathways between chronic exposure to metal(loids) and elevated blood pressure are rarely investigated. In this study, we measured the levels of 29 hair metal(loids) (chronic exposure biomarkers) and blood pressure in 667 susceptible children from an e-waste recycling area to explore their relationships. Paired urine metabolomics analysis was also performed to interpret potential mechanistic pathways. Results showed that the hypertension prevalence in our recruited children (13.0 %) exceeded the average rate (9.5 %) for Chinese children aged 6-17 years. The top five abundant metal(loids), including lead, strontium, barium, and zinc, demonstrated the most profound associations with elevated systolic blood pressure. Quantile g-computation, weighted quantile sum, and Bayesian kernel machine regression analysis jointly demonstrated a significant association between chronic exposure to metal(loids) mixture and systolic blood pressure. Interestingly, selenium showed significant antagonistic interactions with these four metals, suggesting that supplementing selenium may help children resist the elevated blood pressure induced by metal(loids) exposure. Increased metal(loids) and blood pressure levels were significantly linked to changes in urine metabolomics. Structural equation model indicated that androsterone glucuronide and N-Acetyl-1-aspartylglutamic acid were the significant mediators of the associations between metal(loids) and blood pressure, with mediation effects of 77.4 % and 29.0 %, respectively, suggesting that androsterone glucuronide and N-Acetyl-1-aspartylglutamic acid may be involved in the development of metal-induced blood pressure elevating effect. Girls were more vulnerable to metal(loids)-induced hormonal imbalance, especially androsterone glucuronide, than boys. Chronic exposure to metal(loids) at e-waste recycling sites may contribute to elevated blood pressure in children through disrupting various metabolism pathways, particularly hormonal balance. Our study provides new insights into potential mechanistic pathways of metal(loids)-induced changes in children's blood pressure.

Effect of frailty on effectiveness and safety of GLP-1 receptor agonists versus SGLT2 inhibitors in people with type 2 diabetes in Taiwan: a retrospective, nationwide, longitudinal study.

BACKGROUND: GLP-1 receptor agonists and SGLT2 inhibitors are increasingly being used in people with type 2 diabetes on the basis of findings from randomised clinical trials; however, little is known of whether clinical outcomes are affected by frailty in real-world settings. We aimed to compare the clinical effectiveness and safety of GLP-1 receptor agonists and SGLT2 inhibitors in managing type 2 diabetes, with a specific focus on stratifying people by their frailty status. METHODS: In this retrospective, nationwide, longitudinal study, we identified people (aged ≥20 years) with type 2 diabetes who newly initiated either a GLP-1 receptor agonist or an SGLT2 inhibitor during the period Jan 1, 2017 to Dec 31, 2019 from the Taiwan National Health Insurance database. Individuals were excluded if they had been diagnosed with cancer, received dialysis for kidney failure, or had prescriptions for a GLP-1 receptor agonist or an SGLT2 inhibitor, within 1 year before the index date. Mortality data were collected from the Taiwan National Death Registry. Eligible individuals were categorised into three frailty subgroups-fit, mild frailty, and moderate or severe frailty-on the basis of the multimorbidity frailty index. Propensity score matching (1:1) was used to balance covariates between recipients of GLP-1 receptor agonists and SGLT2 inhibitors among each frailty subgroup. Clinical outcomes of interest included three-point major adverse cardiovascular events (non-fatal acute myocardial infarction, non-fatal stroke, and fatal cardiovascular disease), all-cause mortality, hospitalisation for heart failure, dialysis or renal transplant, severe diabetic foot complications, retinopathy, hospitalisation for severe hyperglycaemia, and hospitalisation for severe hypoglycaemia. The association between the use of a GLP-1 receptor agonist versus an SGLT2 inhibitor and the risk of the outcomes of interest among each frailty subgroup was examined using a subdistribution hazard model. FINDINGS: We identified 320 210 people with type 2 diabetes, of whom 280 163 met the eligibility criteria, who initiated either a GLP-1 receptor agonist (n=22 968; mean age 57·7 years [SD 13·9], 11 338 [49·4%] were female, and 11 630 [50·6%] were male) or SGLT2 inhibitor (n=257 195; mean age 58·8 years [12·3], 107 988 [42·0%] were female, and 149 207 [58·0%] were male) during 2017-19. After matching, 11 882, 7210, and 3414 pairs of GLP-1 receptor agonist and SGLT2 inhibitor users were assigned in the fit, mild frailty, and moderate or severe frailty subgroups. All clinical outcomes were comparable between users of GLP-1 receptor agonists and SGLT2 inhibitors among each frailty subgroup, except for a higher risk of hospitalisation for severe hyperglycaemia with GLP-1 receptor agonists than with SGLT2 inhibitors in the mild frailty subgroup (subdistribution hazard ratio 1·25 [95% CI 1·13-1·38]; p<0·0001) and a higher risk of dialysis or renal transplant with GLP-1 receptor agonists than with SGLT2 inhibitors in the fit (2·43 [1·82-3·23]; p<0·0001), mild frailty (3·93 [3·03 -5·09]; p<0·0001), and moderate or severe frailty (2·60 [2·03-3·31]; p<0·0001) subgroups. INTERPRETATION: Formulating clear and updated guidelines on the use of GLP-1 receptor agonists and SGLT2 inhibitors according to frailty status could improve management of type 2 diabetes. FUNDING: Ministry of Education, Taiwan.

The inertial-based gait normalcy index of dual task cost during turning quantifies gait automaticity improvement in early-stage Parkinson's rehabilitation.

BACKGROUND: The loss of gait automaticity is a key cause of motor deficits in Parkinson's disease (PD) patients, even at the early stage of the disease. Action observation training (AOT) shows promise in enhancing gait automaticity. However, effective assessment methods are lacking. We aimed to propose a novel gait normalcy index based on dual task cost (NIDTC) and evaluate its validity and responsiveness for early-stage PD rehabilitation. METHODS: Thirty early-stage PD patients were recruited and randomly assigned to the AOT or active control (CON) group. The proposed NIDTC during straight walking and turning tasks and clinical scale scores were measured before and after 12 weeks of rehabilitation. The correlations between the NIDTCs and clinical scores were analyzed with Pearson correlation coefficient analysis to evaluate the construct validity. The rehabilitative changes were assessed using repeated-measures ANOVA, while the responsiveness of NIDTC was further compared by t tests. RESULTS: The turning-based NIDTC was significantly correlated with multiple clinical scales. Significant group-time interactions were observed for the turning-based NIDTC (F = 4.669, p = 0.042), BBS (F = 6.050, p = 0.022) and PDQ-39 (F = 7.772, p = 0.011) tests. The turning-based NIDTC reflected different rehabilitation effects between the AOT and CON groups, with the largest effect size (p = 0.020, Cohen's d = 0.933). CONCLUSION: The turning-based NIDTC exhibited the highest responsiveness for identifying gait automaticity improvement by providing a comprehensive representation of motor ability during dual tasks. It has great potential as a valid measure for early-stage PD diagnosis and rehabilitation assessment. Trial registration Chinese Clinical Trial Registry: ChiCTR2300067657.

Thiazole Functionalization of Thiosemicarbazone for Cu(II) Complexation: Moving toward Highly Efficient Anticancer Drugs with Promising Oral Bioavailability.

In this work, we report the synthesis of a new thiosemicarbazone-based drug of N'-(di(pyridin-2-yl)methylene)-4-(thiazol-2-yl)piperazine-1-carbothiohydrazide (HL) featuring a thiazole spectator for efficient coordination with Cu(II) to give [CuCl(L)]2 (1) and [Cu(NO3)(L)]2 (2). Both 1 and 2 exhibit dimeric structures ascribed to the presence of di-2-pyridylketone moieties that demonstrate dual functions of chelation and intermolecular bridging. HL, 1, and 2 are highly toxic against hepatocellular carcinoma cell lines Hep-G2, PLC/PRF/5, and HuH-7 with half maximal inhibitory concentration (IC50) values as low as 3.26 nmol/mL (HL), 2.18 nmol/mL (1), and 2.54 × 10-5 nmol/mL (2) for PLC/PRF/5. While the free ligand HL may elicit its anticancer effect via the sequestration of bio-relevant metal ions (i.e., Fe3+ and Cu2+), 1 and 2 are also capable of generating cytotoxic reactive oxygen species (ROS) to inhibit cancer cell proliferation. Our preliminary pharmacokinetic studies revealed that oral administration (per os, PO) of HL has a significantly longer half-life t1/2 of 21.61 ± 9.4 h, nearly doubled as compared with that of the intravenous (i.v.) administration of 11.88 ± 1.66 h, certifying HL as an effective chemotherapeutic drug via PO administration.

Multi-trajectories in different domains of social supports and subjective motoric cognitive risk syndrome: a 16-year group-based multi-trajectory analysis.

OBJECTIVE: The aim of this study was to examine the longitudinal relationships between the trajectories of distinct subtypes of various domains of social supports and risk of subjective motoric cognitive risk (MCR) syndrome. DESIGN: Longitudinal cohort study. SETTING AND PARTICIPANTS: 2,279 participants in the Taiwan Longitudinal Study on Aging (TLSA) between 1999 and 2011. METHOD: A group-based multi-trajectory modeling (GBMTM) was implemented to identify distinct trajectory subtypes within various social support domains, encompassing social networks, emotional support, instrumental support, as well as working and economic status. Logistic regression models were then utilized to evaluate the associations between these trajectory subtypes and the risk of subjective MCR. RESULTS: Among 2,279 participants, GBMTM identified four distinct trajectory subtypes: "low social support" (n = 371), "medium social support " (n = 862), "high social support" (n = 292), and "high social support with employment" (n = 754). The incidence rates of subjective MCR for these groups were 9.4%, 9.0%, 4.1%, and 0.8%, respectively. After adjusting for age, sex, education level, and comorbidities, both "low social support" (adjusted odds ratio (aOR) 4.07, 95% CI [1.60-10.34]) and "medium social support" (aOR 3.10, 95% CI [1.26-7.66]) were significantly associated with an increased risk of subjective MCR compared to the "high social support with employment" group. CONCLUSIONS AND IMPLICATIONS: The current study demonstrates that social support significantly reduces the risk of subjective MCR, with lower support levels correlating to higher risk, necessitating further intervention studies to confirm the link between social support and risk of subjective MCR.

Predicting Continuous Locomotion Modes via Multidimensional Feature Learning from sEMG.

Walking-assistive devices require adaptive control methods to ensure smooth transitions between various modes of locomotion. For this purpose, detecting human locomotion modes (e.g., level walking or stair ascent) in advance is crucial for improving the intelligence and transparency of such robotic systems. This study proposes Deep-STF, a unified end-to-end deep learning model designed for integrated feature extraction in spatial, temporal, and frequency dimensions from surface electromyography (sEMG) signals. Our model enables accurate and robust continuous prediction of nine locomotion modes and 15 transitions at varying prediction time intervals, ranging from 100 to 500 ms. Experimental results showcased Deep-STP's cutting-edge prediction performance across diverse locomotion modes and transitions, relying solely on sEMG data. When forecasting 100 ms ahead, Deep-STF achieved an improved average prediction accuracy of 96.60%, outperforming seven benchmark models. Even with an extended 500ms prediction horizon, the accuracy only marginally decreased to 93.22%. The averaged stable prediction times for detecting next upcoming transitions spanned from 31.47 to 371.58 ms across the 100-500 ms time advances. Although the prediction accuracy of the trained Deep-STF initially dropped to 71.12% when tested on four new terrains, it achieved a satisfactory accuracy of 92.51% after fine-tuning with just 5 trials and further improved to 96.27% with 15 calibration trials. These results demonstrate the remarkable prediction ability and adaptability of Deep-STF, showing great potential for integration with walking-assistive devices and leading to smoother, more intuitive user interactions.

Metformin alleviates cryoinjuries in porcine oocytes by reducing membrane fluidity through the suppression of mitochondrial activity.

Plasma membrane damage in vitrified oocytes is closely linked to mitochondrial dysfunction. However, the mechanism underlying mitochondria-regulated membrane stability is not elucidated. A growing body of evidence indicates that mitochondrial activity plays a pivotal role in cell adaptation. Since mitochondria work at a higher temperature than the constant external temperature of the cell, we hypothesize that suppressing mitochondrial activity would protect oocytes from extreme stimuli during vitrification. Here we show that metformin suppresses mitochondrial activity by reducing mitochondrial temperature. In addition, metformin affects the developmental potential of oocytes and improves the survival rate after vitrification. Transmission electron microscopy results show that mitochondrial abnormalities are markedly reduced in vitrified oocytes pretreated with metformin. Moreover, we find that metformin transiently inhibits mitochondrial activity. Interestingly, metformin pretreatment decreases cell membrane fluidity after vitrification. Furthermore, transcriptome results demonstrate that metformin pretreatment modulates the expression levels of genes involved in fatty acid elongation process, which is further verified by the increased long-chain saturated fatty acid contents in metformin-pretreated vitrified oocytes by lipidomic profile analysis. In summary, our study indicates that metformin alleviates cryoinjuries by reducing membrane fluidity via mitochondrial activity regulation.

Changing Reimbursement Criteria on Anti-VEGF Treatment Patterns Among Wet Age-Related Macular Degeneration and Diabetic Macular Edema Patients: An Interrupted Time Series Analysis.

BACKGROUND: To evaluate the impact of reimbursement criteria change on the utilization pattern of anti-vascular endothelial growth factor (anti-VEGF) among patients with wet age-related macular degeneration (wAMD) and diabetic macular edema (DME) separately in Taiwan. METHODS: An interrupted time series analysis (ITSA) was performed using Taiwan's National Health Insurance (NHI) database, and patients with wAMD or DME diagnosis at the first injection of anti-VEGF agents was identified from 2011 to 2019. The outcome of interest was treatment gaps between injections of anti-VEGF. This outcome was retrieved quarterly, and the study period was divided into three phases in wAMD (two criteria changed in August 2014 [intervention] and December 2016 [intervention]) and two phases in DME (three consecutive criteria changed in 2016 [intervention]). Segmented regression models adjusted for autocorrelation were used to estimate the change in level and the change in slope of the treatment gaps between each anti-VEGF injection. RESULTS: The treatment gaps between each anti-VEGF injection decreased from 2011 to 2019. The cancellation of the annual three needles limitation was associated with significantly shortened treatment gaps between the third and fourth needles (wAMD change in level: -228 days [95% CI -282, -173], DME change in level: -110 days [95% CI -141, -79]). The treatment gap between the fifth and sixth needles revealed a similar pattern but without significant change in DME patients. Other treatment gaps revealed considerable change in slopes in accordance with criteria changes. CONCLUSION: This is the first nationwide study using ITSA to demonstrate the impact of reimbursement policy on treatment gaps between each anti-VEGF injection. After canceling the annual limitation, we found that the treatment gaps significantly decreased among wAMD and DME patients. The shortened treatment gaps might further link to better visual outcomes according to previous studies. The different impacts from criteria changes can assist future policy shaping. Future studies were warranted to explore whether such changes are associated with the benefits of visual effects.

Schnurri-3 inhibition rescues skeletal fragility and vascular skeletal stem cell niche pathology in the OIM model of osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is a disorder of low bone mass and increased fracture risk due to a range of genetic variants that prominently include mutations in genes encoding type I collagen. While it is well known that OI reflects defects in the activity of bone-forming osteoblasts, it is currently unclear whether OI also reflects defects in the many other cell types comprising bone, including defects in skeletal vascular endothelium or the skeletal stem cell populations that give rise to osteoblasts and whether correcting these broader defects could have therapeutic utility. Here, we find that numbers of skeletal stem cells (SSCs) and skeletal arterial endothelial cells (AECs) are augmented in Col1a2oim/oim mice, a well-studied animal model of moderate to severe OI, suggesting that disruption of a vascular SSC niche is a feature of OI pathogenesis. Moreover, crossing Col1a2oim/oim mice to mice lacking a negative regulator of skeletal angiogenesis and bone formation, Schnurri 3 (SHN3), not only corrected the SSC and AEC phenotypes but moreover robustly corrected the bone mass and spontaneous fracture phenotypes. As this finding suggested a strong therapeutic utility of SHN3 inhibition for the treatment of OI, a bone-targeting AAV was used to mediate Shn3 knockdown, rescuing the Col1a2oim/oim phenotype and providing therapeutic proof-of-concept for targeting SHN3 for the treatment of OI. Overall, this work both provides proof-of-concept for inhibition of the SHN3 pathway and more broadly addressing defects in the stem/osteoprogenitor niche as is a strategy to treat OI.

Piperidine-based ionic liquid additive with electrostatic shielding and redox activity enabling advanced lithium-oxygen batteries.

Here, we propose a piperidine-based ionic liquid additive. The electrostatic shielding effect of the piperidine cation (PP13+) effectively inhibits the growth of lithium dendrites. Simultaneously, the redox activity of the bromine anion synergistically reduces the overpotential. This approach significantly improves the cycling performance of lithium-oxygen batteries.

Medical students' preferences for asynchronous online or face-to-face learning strategies in learning gross anatomy and neuroanatomy during the COVID-19 pandemic.

Gross anatomy and neuroanatomy are fundamental subjects in medical education. However, learning different anatomical terms and understanding the complexity of the subjects are often challenging for medical students. At National Taiwan University, the 2020-2021 cohort adopted a face-to-face (F2F) learning strategy for gross anatomy and neuroanatomy lecture and laboratory courses until May 17, 2021. After the aforementioned date, the same cohort learned the rest of the gross anatomy and neuroanatomy courses via asynchronous online learning. This study aimed to evaluate the benefits of and students' preferences for F2F and asynchronous online learning strategies in learning gross anatomy and neuroanatomy. A survey with closed-ended and open-ended questions was used to quantitatively and qualitatively explore medical students' learning preferences for two teaching strategies in gross anatomy and neuroanatomy. The results identified different learning preferences among students in learning gross anatomy and neuroanatomy-satisfied with both learning strategies, satisfied with only F2F learning strategy, satisfied with only asynchronous online learning strategy, and satisfied with neither learning strategy. The survey results with closed-ended and open-ended questions showed that medical students preferred F2F learning for anatomical laboratory courses but favored asynchronous online learning for neuroanatomical laboratory courses. In addition, medical students considered peer discussion more critical in learning gross anatomy than neuroanatomy. These findings provide valuable information about medical students' preference for gross anatomy and neuroanatomy courses, which anatomy teachers can consider when planning to enhance their curriculum in the future.

Co-Invasion of Congeneric Invasive Plants Adopts Different Strategies Depending on Their Origins.

Plant communities may be co-invaded by invasive plants, sometimes even by congeneric invasive plants (CIPs). Despite the growing understanding of co-invasion in the environment, little is known about how CIP interactions and mechanisms regulate co-invasion. Darwin's naturalisation conundrum predicts that the coexistence of closely related species is difficult due to their structural and behavioural similarities. Nevertheless, communities containing closely related species are more susceptible to being invaded because close relatives may favour similar environments; therefore, this hypothesis should be followed in the co-invasion of CIPs. To explore whether the phylogenetic relatedness and origins of invasive species to CIPs can promote or hinder co-invasion, we conducted a controlled interaction and soil-legacy greenhouse experiment to quantify the growth response of invasive plants and their congeners. We consistently found that CIPs of identical origin were more likely to co-invade compared to CIPs of distinct origins. CIPs of distinct origins exhibited an antagonistic effect on co-invasion by allelopathy. Invasive plant-conditioned soil was more conducive to the growth of CIPs of identical origin than CIPs of distinct origins. Our results revealed the different effects of invader-invader phylogenetic relatedness on co-invader success and impact, suggesting the operation of different mechanisms across co-invasion.