In Situ Inorganic/Organic Protective Layer on Carbon Paper as Advanced Current Collector for Robust Li Metal Anode.

Lithium (Li) metal is regarded as the most promising anode for next-generation batteries with high energy density. However, the uncontrolled dendrite growth and infinite volume expansion during cycling seriously hinder the application of Li metal batteries (LMBs). Herein, an inorganic/organic protective layer (labeled as BPH), composed of in situ formed inorganic constituents and PVDF-HFP, is designed on the 3D carbon paper (CP) surface by hot-dipping method. The BPH layer can effectively improve the mechanical strength and ionic conductivity of the SEI layer, which is beneficial to expedite the Li-ion transfer of the entire framework and achieve stable Li plating/stripping behavior. As a result, the modified 3D CP (BPH-CP) exhibits an ultrahigh average Coulombic efficiency (CE) of ≈99.7% over 400 cycles. Further, the Li||LiFePO4 (LFP) cell exhibits an extremely long-term cycle life of over 3000 cycles at 5 C. Importantly, the full cell with high mass loading LiFePO4 (20 mg cm-2) or LiNi0.8Co0.1Mn0.1O2 (NCM, 16 mg cm-2) cathode exhibits stable cycling for 100 or 150 cycles at 0.5 C with high-capacity retention of 86.5% or 82.0% even at extremely low N/P ratio of 0.88 or 0.94. believe that this work enlightens a simple and effective strategy for the application of high-energy-density and high-rate-C LMBs.

Comparative network analysis reveals the regulatory mechanism of 1-methylcyclopropene on sugar and acid metabolisms in yellow peach stored at non-chilling temperatures.

Soluble carbohydrates and organic acids are critical determinants of fruit flavor and consumer preference, both of which are susceptible to postharvest treatments and storage conditions. While the individual effectiveness of 1-methylcyclopropene (1-MCP) and non-chilling temperature storage in delaying fruit ripening and influencing flavor development has been established, their combined effects on peach storage traits remain unexplored. This study investigated the impact of 1-MCP combined with non-chilling temperature storage on the quality and flavor attributes of yellow peach. Our results revealed that 1-MCP treatment reduced ethylene production during storage and delayed ripening and softening by down-regulating ethylene biosynthesis and signaling genes. Transcriptomic analysis indicated that 1-MCP maintained higher levels of soluble carbohydrates by up-regulating sucrose phosphate synthase (PpSPS1/2) and sorbitol dehydrogenase (PpSDH1) while down-regulating hexokinase (PpHXK1). Concurrently, 1-MCP preserved citric and malic acid levels by suppressing aconitate hydratase (PpACO1) and inducing malate dehydrogenase (PpMDH1), thereby delaying flavor degradation. Co-expression network analysis implicated ethylene response factors (PpERFs) as major regulators of sugar and acid metabolisms genes, with PpERF19 potentially functioning as a key transcriptional controller. Overall, this study verified the efficacy of combined 1-MCP and non-chilling storage for yellow peach preservation, identified key 1-MCP-modulated genes involved in sugar and acid metabolisms, and provided insights into regulating peach flavor development via postharvest approaches.

Perturbation walking effects on prefrontal cortical activation and walking performance in older women with and without osteoarthritis: a FNIRS study.

Introduction: Perturbation walking (PW) has been shown to improve gait, however its effect on the cortical control of gait might provide insights on neural mechanisms underlying falls in adults with osteoarthritis. The objective of this study is to investigate the effect of PW on prefrontal cortical (PFC) activation in older women with (OA) and without osteoarthritis (HOA). We hypothesized that there would be an increase in PFC activation during PW relative to comfortable walking (CW) and higher increase in PFC activation during PW in HOA compared to OA. Methods: Twenty community-dwelling older women (66.7 ± 5.41 years old) walked on an instrumented treadmill that provided perturbations at pseudo-random intervals between 5-25 s using a counterbalanced design. Functional Near Infrared Spectroscopy was used to quantify PFC oxygenated hemoglobin (HbO2) and deoxyhemoglobin (Hb) levels, while standing prior to the task as a baseline. A linear mixed effects model was conducted to investigate the effects of cohort (HOA vs OA), task (PW vs CW), and their interaction on HbO2 (µM) and Hb (µM) levels. Results: HbO2 and Hb levels differed significantly between CW and PW tasks for both cohorts (P < 0.001) and demonstrated significant task by cohort interaction (P < 0.05). In addition, we found changes in walking performance (stride time, stride length, stride width and stance time) during and after PW. Spearman correlation demonstrated a strong association between increased stance time, increased body mass index and decreased PFC activation during PW. No other significant results were found. Discussion: This study found increase in PFC activation during PW and gait adaptation after a short bout of PW in HOA and OA. This increase in PFC activation was higher in HOA compared to OA, particularly during PW tasks, and was consistent with theory of limitations in mobility affecting neural activation in older adults. Further work remains to examine how pain, obesity, and mobility impacts cortical control in older adults with and without osteoarthritis.

Practical feature filter strategy to machine learning for small datasets in chemistry.

Many potential use cases for machine learning in chemistry and materials science suffer from small dataset sizes, which demands special care for the model design in order to deliver reliable predictions. Hence, feature selection as the key determinant for dataset design is essential here. We propose a practical and efficient feature filter strategy to determine the best input feature candidates. We illustrate this strategy for the prediction of adsorption energies based on a public dataset and sublimation enthalpies using an in-house training dataset. The input of adsorption energies reduces the feature space from 12 dimensions to two and still delivers accurate results. For the sublimation enthalpies, three input configurations are filtered from 14 possible configurations with different dimensions for further productive predictions as being most relevant by using our feature filter strategy. The best extreme gradient boosting regression model possesses a good performance and is evaluated from statistical and theoretical perspectives, reaching a level of accuracy comparable to density functional theory computations and allowing for physical interpretations of the predictions. Overall, the results indicate that the feature filter strategy can help interdisciplinary scientists without rich professional AI knowledge and limited computational resources to establish a reliable small training dataset first, which may make the final machine learning model training easier and more accurate, avoiding time-consuming hyperparameter explorations and improper feature selection.

Lifetime physical activity influences Parkinson's disease progression.

INTRODUCTION: Past studies suggested that Parkinson's disease (PD) patients who engage in physical activity (PA) after diagnosis have slower motor progression. Here, we examine the influence of lifetime PA prior to PD onset on motor, cognitive, and overall functional decline among PD patients. METHODS: For 495 participants in the Parkinson's Environment and Gene (PEG) studies, we collected PA-related measures through interviews and quantified these using metabolic equivalents (MET) scores. PD progression was defined as time to a Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) conversion to ≥ 35 points, Hoehn and Yahr (H&Y) ≥ 3, and a 4-point decline in Mini-Mental State Examination (MMSE). We used Cox frailty models to estimate hazard ratios and inverse probability weights to account for heterogeneity by enrollment wave and censoring. RESULTS: For PD patients reporting the highest lifetime strenuous MET-h/wk (highest quartile), we estimated a lower HR for time-to-UPDRS-III-conversion (Q4 vs. Q1: HR = 0.56, 95 % CI = [0.36, 0.87]). Additionally, having engaged in any competitive sport also reduced the risk of reaching a UPDRS-III ≥ 35 points (low vs. none: HR = 0.61, 95 % CI = [0.44, 0.86]; high vs. none: HR = 0.63; 95 % CI = [0.44,0.86]); high levels of sports activities also affected progression on the H&Y scale (high vs. none: HR = 0.73; 95 % CI = [0.46,1.00]). Lifetime PA measures did not affect time-to-MMSE decline. CONCLUSION: Our study suggests that PD patients who engaged in higher levels of lifetime strenuous PA and competitive sports prior to PD diagnosis experience slower motor and overall functional decline, suggesting that lifetime PA may contribute to a physical reserve advantageous for PD patients.

Clinical efficacy and immune response of neoadjuvant camrelizumab plus chemotherapy in resectable locally advanced oesophageal squamous cell carcinoma: a phase 2 trial.

BACKGROUND: Neoadjuvant immunotherapy is under intensive investigation for esophageal squamous cell carcinoma (ESCC). This study assesses the efficacy and immune response of neoadjuvant immunochemotherapy (nICT) in ESCC. METHODS: In this phase II trial (ChiCTR2100045722), locally advanced ESCC patients receiving nICT were enrolled. The primary endpoint was the pathological complete response (pCR) rate. Multiplexed immunofluorescence, RNA-seq and TCR-seq were conducted to explore the immune response underlying nICT. RESULTS: Totally 42 patients were enrolled, achieving a 27.0% pCR rate. The 1-year, 2-year DFS and OS rates were 89.2%, 64.4% and 97.3%, 89.2%, respectively. RNA-seq analysis highlighted T-cell activation as the most significantly enriched pathway. The tumour immune microenvironment (TIME) was characterised by high CD4, CD8, Foxp3, and PD-L1 levels, associating with better pathological regression (TRS0/1). TIME was categorised into immune-infiltrating, immune-tolerant, and immune-desert types. Notably, the immune-infiltrating type and tertiary lymphoid structures correlated with improved outcomes. In the context of nICT, TIM-3 negatively influenced treatment efficacy, while elevated TIGIT/PD-1 expression post-nICT correlated positively with CD8+ T cell levels. TCR-seq identified three TCR rearrangements, underscoring the specificity of T-cell responses. CONCLUSIONS: Neoadjuvant camrelizumab plus chemotherapy is effective for locally advanced, resectable ESCC, eliciting profound immune response that closely associated with clinical outcomes.

Mechanism of neurodegeneration mediated by clonal inflammatory microglia.

Langerhans cell Histiocytosis (LCH) and Erdheim-Chester disease (ECD) are clonal myeloid disorders, associated with MAP-Kinase activating mutations and an increased risk of neurodegeneration. Surprisingly, we found pervasive PU.1+ microglia mutant clones across the brain of LCH and ECD patients with and without neurological symptoms, associated with microgliosis, reactive astrocytosis, and neuronal loss. The disease predominated in the grey nuclei of the rhombencephalon, a topography attributable to a local proliferative advantage of mutant microglia. Presence of clinical symptoms was associated with a longer evolution of the disease and a larger size of PU.1+ clones (p= 0.0003). Genetic lineage tracing of PU.1+ clones suggest a resident macrophage lineage or a bone marrow precursor origin depending on patients. Finally, a CSF1R-inhibitor depleted mutant microglia and limited neuronal loss in mice suggesting an alternative to MAPK inhibitors. These studies characterize a progressive neurodegenerative disease, caused by clonal proliferation of inflammatory microglia (CPIM), with a decade(s)-long preclinical stage of incipient disease that represent a therapeutic window for prevention of neuronal death.

Lignan Intake and Type 2 Diabetes Incidence Among US Men and Women.

Importance: Lignans are phytoestrogens abundant in Western diets and may be associated with type 2 diabetes (T2D) risk. Objective: To prospectively investigate associations between lignan intake and T2D incidence. Design, Setting, and Participants: Population-based cohort study of US men and women enrolled in the Nurses' Health Study (NHS, 1984-2018), NHSII (1991-2019), and Health Professionals Follow-Up Study (HPFS, 1986-2020), as well as 496 participants from the Men's Lifestyle Validation Study (MLVS). Participants were free of T2D, cardiovascular disease, and cancer at baseline. Data were analyzed from November 2022 to July 2023. Exposures: Total and individual lignans were assessed using a validated food frequency questionnaire, which was updated every 2 to 4 years. In the MLVS, lignan intake was measured using 2 sets of 7-day diet records (7DDRs). Main Outcomes and Measures: Incident T2D cases were confirmed using American Diabetes Association diagnostic criteria. Cox proportional hazards models were used to assess multivariable-adjusted associations. Results: The current study included 201 111 participants (mean [SD] age, 44.7 [10.1] years; 161 169 female participants [80.2%]; 2614 African American participants [1.3%], 1609 Asian participants [0.8%], 2414 Hispanic and other race or ethnicity participants [1.2%], and 194 474 White participants [96.7%]) from the HPFS, NHS, and NHSII studies. The median (IQR) total lignan intake of the highest quintile ranged from 355.1 (330.2-396.9) µg/d in NHS to 459.9 (422.2-519.5) µg/d in HPFS at the median follow-up time. Over 5 068 689 person-years, 20 291 incident cases of T2D were identified. Higher lignan intake was inversely associated with T2D incidence, except for lariciresinol. The multivariable-adjusted pooled hazard ratios (HRs) for the highest vs lowest quintiles were 0.87 (95% CI, 0.83-0.91) for total lignans, 0.72 (95% CI, 0.69-0.76) for secoisolariciresinol, 0.92 (95% CI, 0.87-0.96) for pinoresinol, 0.93 (95% CI, 0.89-0.98) for matairesinol, and 0.99 (95% CI, 0.94-1.04) for lariciresinol. Secoisolariciresinol intake exhibited a significant inverse association with T2D risk among individuals with obesity (HR, 0.75 for body mass index [BMI] ≥30; 95% CI, 0.71-0.79 vs HR, 0.82 for BMI <25; 95% CI, 0.81-0.83; P < .001 for interaction) and premenopausal women (HR, 0.67 for premenopausal women; 95% CI, 0.65-0.69 vs HR, 0.82 for the past use of hormones; 95% CI, 0.76-0.88; P = .003 for interaction). Dietary lignan assessed with 7DDRs was associated with lower HbA1c levels (percentage change range from -0.92% to 1.50%), as well as lower C-reactive protein levels and better lipid profiles. Conclusions and Relevance: This cohort study found that long-term lignan consumption was associated with a lower T2D risk, particularly among individuals with obesity and premenopausal women.

Antirheumatic drug leflunomide attenuates atherosclerosis by regulating lipid metabolism and endothelial dysfunction via DHODH/AMPK signaling pathway.

The probability of cardiovascular events has been reported lower in rheumatoid arthritis (RA) patients treated with leflunomide. However, the anti-atherosclerotic and cardiovascular protective effects and metabolism of leflunomide are not explored. In this study, we assessed the potential benefits of leflunomide on atherosclerosis and revealed the underlying mechanism. ApoE-/- mice were fed a western diet (WD) alone or supplemented with leflunomide (20 mg/kg, oral gavage, once per day) for 12 weeks. Samples of the aorta, heart, liver, serum, and macrophages were collected. We found that leflunomide significantly reduced lesion size in both en-face aortas and aortic root in WD-fed ApoE-/- mice. Leflunomide also obviously improved dyslipidemia, reduced hepatic lipid content, and improved disorders of glucose and lipid metabolism in vivo. RNA-Seq results showed that leflunomide effectively regulated the genes' expression involved in the lipid metabolism pathway. Importantly, leflunomide significantly increased the phosphorylation levels of AMPKα and acetyl-CoA carboxylase (ACC) in vivo. Furthermore, leflunomide and its active metabolite teriflunomide suppressed lipid accumulation in free fatty acid (FFA)-induced AML12 cells and improved endothelial dysfunction in palmitic acid (PA)-induced HUVECs through activating AMPK signaling and inhibiting dihydroorotate dehydrogenase (DHODH) signaling pathway. We present evidence that leflunomide and teriflunomide ameliorate atherosclerosis by regulating lipid metabolism and endothelial dysfunction. Our findings suggest a promising use of antirheumatic small-molecule drugs leflunomide and teriflunomide for the treatment of atherosclerosis and related cardiovascular diseases (CVDs).

Effects of ttk on development and courtship of male Nilaparvata lugens.

BACKGROUND: The transcription product of tramtrack (ttk) is an important transcription factor which plays many roles in the regulation of the development, differentiation and chromosome recombination of organisms. Few studies have been reported on the specific functions of ttk in other insects except Drosophila melanogaster. Our aims are to reveal the ttk effects on development and courtship of male rice pest brown planthopper (BPH), Nilaparvata lugens. RESULTS: In this study, we first assayed spatiotemporal expression of ttk in BPH, then treated the fourth nymphs of BPH with dsttk. We found most individuals died before emerging to adults, the adult eclosion rate was only 18.89%. No courtship behavior was found in individuals injected with dsttk. Further research showed that the main frequency of courtship vibration signal (CVS) 431.3 Hz in the individuals injected with dsttk was significantly higher than 223 Hz in the individuals injected with dsGFP, and female adults nearly had no response to the 431.3 Hz CVS. CONCLUSION: We found that about 81% of the 4-instar nymphs of BPH treated with dsttk died before they emerged as adults, the successfully emerged adults emitted the 431.3 Hz CVS to which female adults did not respond and lost the ability of courtship. This was first finding about the functions of ttk in rice planthopper and illustrated the potential of ttk as target for RNAi to control rice planthopper. © 2024 Society of Chemical Industry.

Tai Chi Expertise Classification in Older Adults Using Wrist Wearables and Machine Learning.

Tai Chi is a Chinese martial art that provides an adaptive and accessible exercise for older adults with varying functional capacity. While Tai Chi is widely recommended for its physical benefits, wider adoption in at-home practice presents challenges for practitioners, as limited feedback may hamper learning. This study examined the feasibility of using a wearable sensor, combined with machine learning (ML) approaches, to automatically and objectively classify Tai Chi expertise. We hypothesized that the combination of wrist acceleration profiles with ML approaches would be able to accurately classify practitioners' Tai Chi expertise levels. Twelve older active Tai Chi practitioners were recruited for this study. The self-reported lifetime practice hours were used to identify subjects in low, medium, or highly experienced groups. Using 15 acceleration-derived features from a wearable sensor during a self-guided Tai Chi movement and 8 ML architectures, we found multiclass classification performance to range from 0.73 to 0.97 in accuracy and F1-score. Based on feature importance analysis, the top three features were found to each result in a 16-19% performance drop in accuracy. These findings suggest that wrist-wearable-based ML models may accurately classify practice-related changes in movement patterns, which may be helpful in quantifying progress in at-home exercises.

Analyzing the Effect of Microbial Consortia Fermentation on the Quality of HnB by Untargeted Metabolomics.

Fermentation has been identified as an effective strategy to alter the chemical makeup of tobacco, thereby enhancing its quality. The deliberate introduction of microorganisms can hasten the fermentation process. In this research, microbial consortia harvested from the tobacco surface were utilized to enhance the tobacco quality. This enhancement also elevated several sensory attributes of HnB cigarettes, such as aroma richness, moisture, strength, and reduced irritation, achieving a sensory quality rating of 84.5. This marks a notable improvement compared to the 82 rating of the original, unfermented cigarettes. Untargeted metabolomics analysis revealed a decrease in total polyphenols and unsaturated fatty acids, while the levels of polyacids, alcohols, ketones, furans, and other compounds increased in the fermented tobacco. Additionally, KEGG pathway enrichment analysis indicated that the enhancement in tobacco quality through microbial consortia fermentation is linked to various biological pathways, with pathways related to fatty acid and amino acid degradation playing pivotal roles. The findings of this study will serve as a reference for the commercial production of HnB cigarettes, and the elucidated mechanism offers a theoretical basis for exploring microbial fermentation as a means to improve tobacco quality.

Progress in the Application of Organoids-On-A-Chip in Diseases.

With the rapid development of the field of life sciences, traditional 2D cell culture and animal models have long been unable to meet the urgent needs of modern biomedical research and new drug development. Establishing a new generation of experimental models and research models is of great significance for deeply understanding human health and disease processes, and developing effective treatment measures. As is well known, long research and development cycles, high risks, and high costs are the "three mountains" facing the development of new drugs today. Organoids and organ-on-chips technology can highly simulate and reproduce the human physiological environment and complex reactions in vitro, greatly improving the accuracy of drug clinical efficacy prediction, reducing drug development costs, and avoiding the defects of drug testing animal models. Therefore, organ-on-chips have enormous potential in medical diagnosis and treatment.

Surface Cladding Engineering via Oxygen Sulfur Distribution for Stable Electrocatalytic Oxygen Evolution Reaction.

Inevitable leaching and corrosion under anodic oxidative environment greatly restrict the lifespan of most catalysts with excellent primitive activity for oxygen production. Here, based on Fick' s Law, we present a surface cladding strategy to mitigate Ni dissolution and stabilize lattice oxygen triggering by directional flow of interfacial electrons and strong electronic interactions via constructing elaborately cladding-type NiO/NiS heterostructure with controlled surface thickness. Multiple in-situ characterization technologies indicated that this strategy can effectively prevent the irreversible Ni ions leaching and inhibit lattice oxygen from participating in anodic reaction. Combined with density functional theory calculations, we reveal that the stable interfacial O-Ni-S arrangement can facilitate the accumulation of electrons on surficial NiO side and weaken its Ni-O covalency. This would suppress the overoxidation of Ni and simultaneously fixing the lattice oxygen, thus enabling catalysts with boosted corrosion resistance without sacrificing its activity. Consequently, this cladding-type NiO/NiS heterostructure exhibits excellent performance with a low overpotential of 256 mV after 500 h. Based on Fick's law, this work demonstrates the positive effect of surface modification through precisely adjusting of the oxygen-sulfur exchange process, which has paved an innovative and effective way to solve the instability problem of anodic oxidation.

Vonoprazan and amoxicillin dual therapy for 14 days as the first-line treatment of Helicobacter pylori infection: A non-inferiority, randomized clinical trial.

BACKGROUND: We previously optimized the duration and dose of vonoprazan and amoxicillin dual therapy in China. The efficacy of vonoprazan with b.i.d. amoxicillin in comparison with vonoprazan-containing quadruple therapy as the first-line treatment of Helicobacter pylori infection has not been adequately evaluated. METHODS: In a non-inferiority, randomized clinical trial, H. pylori infected and treatment-naïve patients were randomly assigned to receive 14 days of either vonoprazan dual (vonoprazan 20 mg and amoxicillin 1 g twice daily) or quadruple therapy (vonoprazan 20 mg + amoxicillin 1 g + furazolidone 100 mg + bismuth potassium citrate 600 mg twice daily). H. pylori status was confirmed using 13C-urea breath tests or fecal antigen test. The primary outcome was the H. pylori eradication rate following vonoprazan dual and quadruple therapy at 4-12 weeks. We also compared drug compliance to either regimen and documented their side effect. RESULTS: A total of 190 subjects were randomized. The eradication rate of vonoprazan dual and quadruple therapy were 87.4% and 92.6% (p = 0.23) by intention-to-treat analysis, respectively, and 96.5% and 97.7% (p = 0.63) by per-protocol analysis, respectively. The efficacy of vonoprazan dual therapy was non-inferior to vonoprazan-containing quadruple therapy in per-protocol analysis (p < 0.001; difference: -1.2%; 90% confidence interval: -5.4% to 3.0%). CONCLUSION: Vonoprazan with b.i.d. amoxicillin for 14 days provided similar satisfactory efficacy with vonoprazan-containing quadruple therapy as a first-line H. pylori treatment in China.

A linear compensation method for inference accuracy improvement of memristive in-memory computing.

Memristive computing system (MCS), with the feature of in-memory computing capability, for artificial neural networks (ANNs) deployment showing low power and massive parallelism, is a promising alternative for traditional Von-Neumann architecture computing system. However, because of the various non-idealities of both peripheral circuits and memristor array, the performance of the practical MCS tends to be significantly reduced. In this work, a linear compensation method (LCM) is proposed for the performance improvement of MCS under the effect of non-idealities. By considering the effects of various non-ideal states in the MCS as a whole, the output error of the MCS under different conditions is investigated. Then, a mathematic model for the output error is established based on the experimental data. Furthermore, the MCS is researched at the physical circuit level as well, in order to analyze the specific way in which the non-idealities affect the output current. Finally, based on the established mathematical model, the LCM output current is compensated in real time to improve the system performance. The effectiveness of LCM is verified and showing outstanding performance in the residual neural network-34 network architecture, which is easily affected by the non-idealities in hardware. The proposed LCM can be naturally integrated into the operation processes of MCS, paving the way for optimizing the deployment on generic ANN hardware based on the memristor.

Lidocaine and risk of postoperative vomiting in children undergoing tonsillectomy: a randomised clinical trial.

The dose-response of intravenous lidocaine in preventing postoperative vomiting (POV) in children remains unclear. This study investigated whether intravenous lidocaine dose-dependently decreased POV risk within 24 h postoperatively in children undergoing tonsillectomy (with or without adenoidectomy) without severe complications. Patients aged 3-12 years (American Society of Anesthesiologists grade I-II) scheduled for elective tonsillectomy (with or without adenoidectomy) were enroled from December 2021 to March 2022. They were randomly grouped according to the lidocaine dose (A [0 mg kg-1], B [1 mg kg-1], C [1.5 mg kg-1], and D [2 mg kg-1]) and were administered the same induction protocol (sufentanil, propofol, and suxamethonium chloride). Anaesthesia was maintained with sevoflurane. The incidence of POV within 24 h postoperatively was 46, 40, 36, and 20% in groups A, B, C, and D, respectively, with significant differences between groups D and A. Postoperative analgesic rescues in groups A, B, C, and D were 62, 36, 34, and 16%, respectively, with significant differences between groups D and B, C and A, and D and A. No severe adverse events were reported. Intravenous lidocaine has a dose-dependent effect on reducing the risk of POV in children undergoing tonsillectomy (with or without adenoidectomy) without serious adverse events.Trial registration: Chinese Clinical Trial Registry, ChiCTR2100053006.

Differential white blood cell count and epigenetic clocks: a bidirectional Mendelian randomization study.

BACKGROUND: Human aging and white blood cell (WBC) count are complex traits influenced by multiple genetic factors. Predictors of chronological age have been developed using epigenetic clocks. However, the bidirectional causal effects between epigenetic clocks and WBC count have not been fully examined. METHODS: This study employed Mendelian randomization (MR) to analyze summary statistics from four epigenetic clocks involving 34,710 participants, alongside data from the Blood Cell Consortium encompassing 563,946 individuals. We primarily explored bidirectional causal relationships using the random-effects inverse-variance weighted method, supplemented by additional MR methods for comprehensive analysis. Additionally, multivariate MR was applied to investigate independent effects of WBC count on epigenetic age acceleration. RESULTS: In the two-sample univariate MR (UVMR) analysis, we observed that a decrease in lymphocyte count markedly accelerated aging according to the PhenoAge, GrimAge, and HannumAge metrics (all P < 0.01, ß < 0), though it did not affect Intrinsic Epigenetic Age Acceleration (IEAA). Conversely, an increase in neutrophil count significantly elevated PhenoAge levels (ß: 0.38; 95% CI 0.14, 0.61; P = 1.65E-03 < 0.01). Reverse MR revealed no significant causal impacts of epigenetic clocks on overall WBC counts. Furthermore, in multivariate MR, the impact of lymphocyte counts on epigenetic aging metrics remained statistically significant. We also identified a marked causal association between neutrophil counts and PhenoAge, GrimAge, and HannumAge, with respective results showing strong associations (PhenoAge ß: 0.78; 95% CI 0.47, 1.09; P = 8.26E-07; GrimAge ß: 0.55; 95% CI 0.31, 0.79; P = 5.50E-06; HannumAge ß: 0.42; 95% CI 0.18, 0.67; P = 6.30E-04). Likewise, eosinophil cell count demonstrated significant association with HannumAge (ß: 0.33; 95% CI 0.13, 0.53; P = 1.43E-03 < 0.01). CONCLUSION: These findings demonstrated that within WBCs, lymphocyte and neutrophil counts exert irreversible and independent causal effects on the acceleration of PhenoAge, GrimAge, and HannumAge. Our findings highlight the critical role of WBCs in influencing epigenetic clocks and underscore the importance of considering immune parameters when interpreting epigenetic age.

Deconvoluting Surface and Bulk Charge Storage Processes in Redox-Active Oxides by Integrating Electrochemical and Optical Insights.

Redox-active transition metal oxides (TMOs) play crucial roles in diverse energy storage and conversion technologies, such as batteries and pseudocapacitors. These materials show intricate electrochemical charge storage processes, encompassing both bulk ion-intercalation, typical of battery electrodes, and pseudocapacitive-like behavior localized near the surfaces. However, understanding the underlying mechanisms of charge storage in redox-active TMOs is challenging due to the coexistence of these behaviors. In this study, we propose an integrated approach that combines operando electrochemical and optical techniques to disentangle the contributions of bulk and surface phenomena. Using birnessite δ-MnO2-x as a model system, we account for surface pseudocapacitive-like layers and employ a refined model that incorporates both surface reactions and bulk chemical diffusion. This methodology allows us to extract essential kinetic parameters, establishing a fundamental framework for unraveling surface and bulk electrochemical processes. This advancement provides a valuable tool for the rational design of energy storage devices, enhancing our ability to tailor these materials for specific applications.

Oltipraz attenuated cerebral ischemia-reperfusion injury through inhibiting the oxidative stress and ferroptosis in mice.

Oltipraz (OPZ) is a synthetic dithiolethione and is considered a novel activator of nuclear factor E2-related factor 2 (Nrf2). Increasing evidence indicates that Nrf2 protects against cerebral ischemia/reperfusion (I/R) injury by antagonizing ferroptosis and lipid peroxidation. However, the protective effects of OPZ on cerebral I/R injury remain to be elucidated. We investigated the in vitro and in vivo neuroprotective effects of OPZ. Mice were subjected to middle cerebral artery occlusion/reperfusion (MCAO/R) to construct an in vivo model and PC12 cells were exposed to oxygen and glucose deprivation/reoxygenation (OGD/R) to establish an in vitro model. OPZ administration reduced the infarct volume and brain water content, and alleviated the neurological deficit of MCAO/R mice. Moreover, OPZ ameliorated MCAO/R-induced oxidative stress by decreasing the levels of 4-HNE and MDA and increasing the activities of SOD and GSH. We also found that OPZ ameliorated MCAO/R-induced ferroptosis by increasing SLC7A11 and GPX4 protein expression and downregulating ACSL4 protein expression. Similarly, the in vitro results revealed that OGD/R-induced oxidative stress and ferroptosis. Finally, mechanistic analysis revealed that OPZ significantly upregulated the Nrf2 expression and Nrf2 knockout (Nrf2 KO) abolished the OPZ-mediated protective effects. Taken together, these findings demonstrate that OPZ ameliorates cerebral I/R injury by suppressing the oxidative stress and ferroptosis.