Amino-Induced CO2 Spillover to Boost the Electrochemical Reduction Activity of CdS for CO Production.

A considerable challenge in CO2 reduction reaction (CO2RR) to produce high-value-added chemicals comes from the adsorption and activation of CO2 to form intermediates. Herein, an amino-induced spillover strategy aimed at significantly enhancing the CO2 adsorption and activation capabilities of CdS supported on N-doped mesoporous hollow carbon sphere (NH2-CdS/NMHCS) for highly efficient CO2RR is presented. The prepared NH2-CdS/NMHCS exhibits a high CO Faradaic efficiency (FECO) exceeding 90% from -0.8 to -1.1 V versus reversible hydrogen electrode (RHE) with the highest FECO of 95% at -0.9 V versus RHE in H cell. Additional experimental and theoretical investigations demonstrate that the alkaline -NH2 group functions as a potent trapping site, effectively adsorbing the acidic CO2, and subsequently triggering CO2 spillover to CdS. The amino modification-induced CO2 spillover, combined with electron redistribution between CdS and NMHCS, not only readily achieves the spontaneous activation of CO2 to *COOH but also greatly reduces the energy required for the conversion of *COOH to *CO intermediate, thus endowing NH2-CdS/NMHCS with significantly improved reaction kinetics and reduced overpotential for CO2-to-CO conversion. It is believed that this research can provide valuable insights into the development of electrocatalysts with superior CO2 adsorption and activation capabilities for CO2RR application.

Machine learning versus multivariate logistic regression for predicting severe COVID-19 in hospitalized children with Omicron variant infection.

With the emergence of the Omicron variant, the number of pediatric Coronavirus Disease 2019 (COVID-19) cases requiring hospitalization and developing severe or critical illness has significantly increased. Machine learning and multivariate logistic regression analysis were used to predict risk factors and develop prognostic models for severe COVID-19 in hospitalized children with the Omicron variant in this study. Of the 544 hospitalized children including 243 and 301 in the mild and severe groups, respectively. Fever (92.3%) was the most common symptom, followed by cough (79.4%), convulsions (36.8%), and vomiting (23.2%). The multivariate logistic regression analysis showed that age (1-3 years old, odds ratio (OR): 3.193, 95% confidence interval (CI): 1.778-5.733], comorbidity (OR: 1.993, 95% CI:1.154-3.443), cough (OR: 0.409, 95% CI:0.236-0.709), and baseline neutrophil-to-lymphocyte ratio (OR: 1.108, 95% CI: 1.023-1.200), lactate dehydrogenase (OR: 1.993, 95% CI: 1.154-3.443), blood urea nitrogen (OR: 1.002, 95% CI: 1.000-1.003) and total bilirubin (OR: 1.178, 95% CI: 1.005-3.381) were independent risk factors for severe COVID-19. The area under the curve (AUC) of the prediction models constructed by multivariate logistic regression analysis and machine learning (RandomForest + TomekLinks) were 0.7770 and 0.8590, respectively. The top 10 most important variables of random forest variables were selected to build a prediction model, with an AUC of 0.8210. Compared with multivariate logistic regression, machine learning models could more accurately predict severe COVID-19 in children with Omicron variant infection.

Neurological manifestations and risk factors associated with poor prognosis in hospitalized children with Omicron variant infection.

There are increasing reports of neurological manifestation in children with coronavirus disease 2019 (COVID-19). However, the frequency and clinical outcomes of in hospitalized children infected with the Omicron variant are unknown. The aim of this study was to describe the clinical characteristics, neurological manifestations, and risk factor associated with poor prognosis of hospitalized children suffering from COVID-19 due to the Omicron variant. Participants included children older than 28 days and younger than 18 years. Patients were recruited from December 10, 2022 through January 5, 2023. They were followed up for 30 days. A total of 509 pediatric patients hospitalized with the Omicron variant infection were recruited into the study. Among them, 167 (32.81%) patients had neurological manifestations. The most common manifestations were febrile convulsions (n = 90, 53.89%), viral encephalitis (n = 34, 20.36%), epilepsy (n = 23, 13.77%), hypoxic-ischemic encephalopathy (n = 9, 5.39%), and acute necrotizing encephalopathy (n = 6, 3.59%). At discharge, 92.81% of patients had a good prognosis according to the Glasgow Outcome Scale (scores ≥ 4). However, 7.19% had a poor prognosis. Eight patients died during the follow-up period with a cumulative 30-day mortality rate of 4.8% (95% confidence interval (CI) 1.5-8.1). Multivariate analysis revealed that albumin (odds ratio 0.711, 95% CI 0.556-0.910) and creatine kinase MB (CK-MB) levels (odds ratio 1.033, 95% CI 1.004-1.063) were independent risk factors of poor prognosis due to neurological manifestations. The area under the curve for the prediction of poor prognosis with albumin and CK-MB was 0.915 (95%CI 0.799-1.000), indicating that these factors can accurately predict a poor prognosis.          Conclusion: In this study, 32.8% of hospitalized children suffering from COVID-19 due to the Omicron variant infection experienced neurological manifestations. Baseline albumin and CK-MB levels could accurately predict poor prognosis in this patient population. What is Known: • Neurological injury has been reported in SARS-CoV-2 infection; compared with other strains, the Omicron strain is more likely to cause neurological manifestations in adults. • Neurologic injury in adults such as cerebral hemorrhage and epilepsy has been reported in patients with Omicron variant infection. What is New: • One-third hospitalized children with Omicron infection experience neurological manifestations, including central nervous system manifestations and peripheral nervous system manifestations. • Albumin and CK-MB combined can accurately predict poor prognosis (AUC 0.915), and the 30-day mortality rate of children with Omicron variant infection and neurological manifestations was 4.8%.

Association between triglyceride-glucose index and sarcopenia in patients with chronic inflammatory airway disease.

Objective: This research sought to explore the association between the triglyceride-glucose (TyG) index and the risk of sarcopenia in patients with chronic inflammatory airway disease (CIAD). Methods: Data were obtained from the National Health and Nutrition Examination Survey 2011-2018. Grouping was performed using TyG index tertiles and multiple logistic regression was employed to assess the correlation between TyG levels and the risk of sarcopenia. The Receiver Operating Characteristic (ROC) curve analysis was conducted to determine the prognostic value of the TyG index for sarcopenia. Linear regression analysis was utilized to elucidate the direct relationship between TyG index and sarcopenia. Additionally, the curve between the TyG and sarcopenia indices was examined using a generalized additive model. Results: The study included 981 individuals diagnosed with CIAD. After adjusting for potential confounders, a significant positive correlation was observed between TyG and sarcopenia (OR = 1.70, 95 % CI: 1.20-2.39, P = 0.002). Trend analysis using the chi-square test revealed an increase in sarcopenia prevalence concomitant with higher TyG levels (P < 0.05). Furthermore, linear regression analysis revealed a notable inverse linear association between the TyG and sarcopenia indices (ß = -0.03; 95 % CI: -0.07-0.01; P = 0.020). The ROC curves corroborated the robust predictive capacity of TyG for sarcopenia among patients with CIAD, with an AUC of 0.685 (95 % CI: 0.636-0.735, P < 0.001). Conclusion: Our research indicates a positive association between TyG and sarcopenia in CIAD patients. The TyG index may serve as a reliable marker for predicting sarcopenia risk in CIAD patients.

Early Stage Preclinical Formulation Strategies to Alter the Pharmacokinetic Profile of Two Small Molecule Therapeutics.

Early stage chemical development presents numerous challenges, and achieving a functional balance is a major hurdle, with many early compounds not meeting the clinical requirements for advancement benchmarks due to issues like poor oral bioavailability. There is a need to develop strategies for achieving the desired systemic concentration for these compounds. This will enable further evaluation of the biological response upon a compound-target interaction, providing deeper insight into the postulated biological pathways. Our study elucidates alternative drug delivery paradigms by comparing formulation strategies across oral (PO), intraperitoneal (IP), subcutaneous (SC), and intravenous (IV) routes. While each modality boasts its own set of merits and constraints, it is the drug's formulation that crucially influences its pharmacokinetic (PK) trajectory and the maintenance of its therapeutic levels. Our examination of model compounds G7883 and G6893 highlighted their distinct physio-chemical attributes. By harnessing varied formulation methods, we sought to fine-tune their PK profiles. PK studies showcased G7883's extended half-life using an SC oil formulation, resulting in a 4.5-fold and 2.5-fold enhancement compared with the IP and PO routes, respectively. In contrast, with G6893, we achieved a prolonged systemic coverage time above the desired target concentration through a different approach using an IV infusion pump. These outcomes underscore the need for tailored formulation strategies, which are dictated by the compound's innate properties, to reach the optimal in vivo systemic concentrations. Prioritizing formulation and delivery optimization early on is pivotal for effective systemic uptake, thereby facilitating a deeper understanding of biological pathways and expediting the overall clinical drug development timeline.

d-band center engineering of single Cu atom and atomic Ni clusters for enhancing electrochemical CO2 reduction to CO.

The rational design of catalysts with atomic dispersion and a deep understanding of the catalytic mechanism is crucial for achieving high performance in CO2 reduction reaction (CO2RR). Herein, we present an atomically dispersed electrocatalyst with single Cu atom and atomic Ni clusters supported on N-doped mesoporous hollow carbon sphere (CuSANiAC/NMHCS) for highly efficient CO2RR. CuSANiAC/NMHCS demonstrates a remarkable CO Faradaic efficiency (FECO) exceeding 90% across a potential range of -0.6 to -1.2 V vs. reversible hydrogen electrode (RHE) and achieves its peak FECO of 98% at -0.9 V vs. RHE. Theoretical studies reveal that the electron redistribution and modulated electronic structure-notably the positive shift in d-band center of Ni 3d orbital-resulting from the combination of single Cu atom and atomic Ni clusters markedly enhance the CO2 adsorption, facilitate the formation of *COOH intermediate, and thus promote the CO production activity. This study offers fresh perspectives on fabricating atomically dispersed catalysts with superior CO2RR performance.

Bibliometric analysis of neuroinflammation and Alzheimer's disease.

Background: Alzheimer's disease (AD) is the predominant cause of dementia on a global scale, significantly impacting the health of the elderly population. The pathogenesis of AD is closely linked to neuroinflammation. The present study employs a bibliometric analysis to examine research pertaining to neuroinflammation and AD within the last decade, with the objective of providing a comprehensive overview of the current research profile, hotspots and trends. Methods: This research conducted a comprehensive review of publications within the Science Citation Index Expanded of the Web of Science Core Collection Database spanning the years 2014 to 2024. Bibliometric analyses were performed using VOSviewer (version 1.6.19) and CiteSpace (version 6.3.R1) software to visualize data on countries, institutions, authors, journals, keywords, and references. Results: A total of 3,833 publications on neuroinflammation and AD were included from January 2014 to January 2024. Publications were mainly from the United States and China. Zetterberg, Henrik emerged as the author with the highest publication output, while Edison, Paul was identified as the most cited author. The most productive journal was Journal of Alzheimers Disease, and the most co-cited was Journal of Neuroinflammation. Research hotspot focused on microglia, mouse models, oxidative stress, and amyloid-beta through keyword analysis. Additionally, keywords such as blood-brain barrier and tau protein exhibited prolonged citation bursts from 2022 to 2024. Conclusion: This study provides a comprehensive review of the last 10 years of research on neuroinflammation and AD, including the number and impact of research findings, research hotspots, and future trends. The quantity of publications in this field is increasing, mainly in the United States and China, and there is a need to further strengthen close cooperation with different countries and institutions worldwide. Presently, research hotspots are primarily concentrated on microglia, with a focus on inhibiting their pro-inflammatory responses and promoting their anti-inflammatory functions as a potential direction for future investigations.

Efficacy and safety of butylphthalide in patients with mild cognitive impairment: a multicentre, randomised, double-blind, placebo-controlled trial (EBMCI study).

INTRODUCTION: The efficacy of multitarget neuroprotective drug DL-3-n-butylphthalide (NBP) in improving cognitive function has been confirmed in patients with vascular cognitive impairment without dementia. However, its efficacy in patients with symptomatic predementia phase of Alzheimer's disease remains uncertain. This study aims to evaluate the efficacy and safety of NBP in improving cognitive function in patients with mild cognitive impairment (MCI) through a clinical randomised controlled trail. METHODS AND ANALYSIS: This study is a 12-month, randomised, double-blind, placebo-controlled, multicentric trial, involving 270 patients with MCI. Subjects are randomly assigned to receive either NBP soft capsule (200 mg, three times per day) or placebo with an allocation ratio of 1:1. The efficacy and safety of NBP are assessed by comparing the results of neuropsychological, neuroimaging and laboratory tests between the two groups. The primary endpoint is the change in Alzheimer's Disease Assessment Scale-Cognitive Subscale after 12 months. All patients will be monitored for adverse events. ETHICS AND DISSEMINATION: This study involving human participants has been reviewed and approved by Ethics Committee of Xuan Wu Hospital (No.2017058). The participants provide their written informed consent to participate in this study. Results will be published in peer-reviewed medical journals and disseminated to healthcare professionals at local and international conferences. PROTOCOL VERSION: V 3.0, 3 September 2022. TRIAL REGISTRATION NUMBER: ChiCTR1800018362.

Generation of human induced pluripotent stem cell line (XWHNi004-A) from a male with APOE gene mutation.

Genetic polymorphism of apolipoprotein E (APOE) confers differential susceptibility to Alzheimer's disease (AD), and APOE ɛ4 variants is the most powerful risk factor for this disease. Here, we report the generation of a human induced pluripotent stem cell (iPSC) line carrying the APOE ɛ4/ɛ4 genotype from peripheral blood mononuclear cells (PBMCs) isolated from a male with a family history of AD utilizing non-integrative Sendai virus vector. The iPSC maintains their original genotype, highly express endogenous pluripotency markers, displays a normal karyotype, and retains the ability to differentiate into cells representative of the three germ layers.

Generation of induced pluripotent stem cell line (XWHNi003-A) from a female with APOE gene mutation.

Apolipoprotein E (APOE)is the gene with greatest genetic risk for Alzheimer's disease (AD). We successfully established a human induced pluripotent stem cell(iPSC) line from a woman mutated by APOE gene. The cell line was isolated from this woman's peripheral blood mononuclear cells using a non-integrated Sendai virus, which retained the original genotype, showed a normal karyotype, highly expressed pluripotent markers and could differentiate into three germ layers.