In-situ-grown multidimensional Cu-doped Co1-xS2@MoS2 on N-doped carbon nanofibers as anode materials for high-performance alkali metal ion batteries.

Transition metal sulfides with the high theoretical capacity and low cost have been considered as advanced anode candidate for alkali metal ion batteries, but suffered from unsatisfactory electrical conductivity and huge volume expansion. Herein, a multidimensional structure Cu-doped Co1-xS2@MoS2 in-situ-grown on N-doped carbon nanofibers (denoted as Cu-Co1-xS2@MoS2 NCNFs) have been elaborately constructed for the first time. The bimetallic zeolitic imidazolate framework CuCo-ZIFs were encapsulated in the one-dimensional (1D) NCNFs through an electrospinning route and then on which the two-dimensional (2D) MoS2 nanosheets were in-situ grown via a hydrothermal process. The architecture of 1D NCNFs can effectively shorten ion diffusion path and enhance electrical conductivity. Besides, the formed heterointerface between MOF-derived binary metal sulfides and MoS2 can provide extra active centers and accelerate reaction kinetics, which guarantee a superior reversibility. As expected, the resulting Cu-Co1-xS2@MoS2 NCNFs electrode delivers excellent specific capacity of Na-ion batteries (845.6 mAh/g at 0.1 A/g), Li-ion batteries (1145.7 mAh/g at 0.1 A/g), and K-ion batteries (474.3 mAh/g at 0.1 A/g). Therefore, this innovative design strategy will bring a meaningful prospect for developing high-performance multi-component metal sulfides electrode for alkali metal ion batteries.

A multicenter, prospective, randomized controlled trial of intracranial hemorrhage risk of intensive statin therapy in patients with acute ischemic stroke combined with cerebral microbleeds (CHRISTMAS): Study protocol.

Background: Low serum levels of major lipid markers have been proved to be significantly associated with increased risks of hemorrhagic stroke (HS) and cerebral microbleeds (CMBs). However, there is no lipid modification guideline telling us how to maintain a balance between the prevention of ischemic stroke recurrence and the prevention of hemorrhagic events, especially in patients with acute ischemic stroke (AIS) and CMBs. Aim: The Intracranial Hemorrhage Risk of Intensive Statin Therapy in Patients with Acute Ischemic Stroke combined with Cerebral Microbleeds (CHRISTMAS) trial evaluates the risk of intracranial hemorrhage (i.e., HS and CMBs) of high-dose statin therapy in patients with AIS combined with CMBs. Methods and design: This is an investigator-initiated, multicenter, prospective, randomized controlled clinical trial design. Up to 344 eligible patients will be consecutively randomized to receive high-dose or low-dose atorvastatin in 1:1 ratio in 5 stroke centers in China. Outcomes: CHRISTMAS trial has co-primary outcomes, namely, hemorrhage risk: the incidence of HS and the changes in degree of CMBs until the end of 36-month follow-up. Discussion: The primary hypothesis of this study is that an excessive reduction in serum lipid levels by an intensive statin therapy in AIS patients with CMBs can increase the risk of intracranial hemorrhage. This study will shed light on new clinical decisions regarding the long-term serum lipid management in these patients with dilemma in clinical practice. Clinical trial registration: Clinicaltrials.gov, identifier: NCT05589454.

Ginsenoside Rg1 in neurological diseases: From bench to bedside.

Ginseng has been used in China as a superior medicinal material for thousands of years that can nourish the five internal organs, calm the mind and benefit wisdom. Due to its anti-inflammatory, antioxidant and neuroprotective activities, one of the active components of ginseng, ginsenoside Rg1, has been extensively investigated in the remedy of brain disorders, especially dementia and depression. In this review, we summarized the research progress on the action mechanisms of Rg1 ameliorating depression-like behaviors, including inhibition of hyperfunction of hypothalamic-pituitary-adrenal (HPA) axis, regulation of synaptic plasticity and gut flora. Rg1 may alleviate Alzheimer's disease in the early phase, as well as in the middle-late phases through repairing dendrite, axon and microglia- and astrocyte-related inflammations. We also proposed that Rg1 could regulate memory state (the imbalance of working and aversive memory) caused by distinct stimuli. These laboratory studies would further the clinical trials on Rg1. From the prospective of drug development, we discussed the limitations of the present investigations and proposed our ideas to increase permeability and bioavailability of Rg1. Taken together, Rg1 has the potential to treat neuropsychiatric disorders, but a future in-depth investigation of the mechanisms is still required. In addition, drug development will benefit from the clinical trials in one specific neuropsychiatric disorder.

Association Between Plasma Apolipoprotein M With Alzheimer's Disease: A Cross-Sectional Pilot Study From China.

Background: Recent evidence of genetics and metabonomics indicated a potential role of apolipoprotein M (ApoM) in the pathogenesis of Alzheimer's disease (AD). Here, we aimed to investigate the association between plasma ApoM with AD. Methods: A multicenter, cross-sectional study recruited patients with AD (n = 67), age- and sex-matched cognitively normal (CN) controls (n = 73). After the data collection of demographic characteristics, lifestyle risk factors, and medical history, we examined and compared the plasma levels of ApoM, tau phosphorylated at threonine 217 (p-tau217) and neurofilament light (NfL). Multivariate logistic regression analysis was applied to determine the association of plasma ApoM with the presence of AD. The correlation analysis was used to explore the correlations between plasma ApoM with cognitive function [Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA)], activities of daily living (ADL), and the representative blood-based biomarkers (plasma p-tau217 and NfL). Receiver operating characteristic (ROC) analysis and Delong's test were used to determine the diagnostic power of plasma ApoM. Results: Plasma ApoM and its derived indicators (ratios of ApoM/TC, ApoM/TG, ApoM/HDL-C, and ApoM/LDL-C) were significantly higher in AD group than those in CN group (each p < 0.0001). After adjusted for the risk factors of AD, the plasma ApoM and its derived indicators were significantly associated with the presence of AD, respectively. ApoM (OR = 1.058, 95% CI: 1.027-1.090, p < 0.0001), ApoM/TC ratio (OR = 1.239, 95% CI: 1.120-1.372, p < 0.0001), ApoM/TG ratio (OR = 1.064, 95% CI: 1.035-1.095, p < 0.0001), ApoM/HDL-C ratio (OR = 1.069, 95% CI: 1.037-1.102, p < 0.0001), and ApoM/LDL-C ratio (OR = 1.064, 95% CI:1.023-1.106, p = 0.002). In total participants, plasma ApoM was significantly positively correlated with plasma p-tau217, plasma NfL, and ADL (each p < 0.0001) and significantly negatively correlated with MMSE and MoCA (each p < 0.0001), respectively. In further subgroup analyses, these associations remained in different APOEϵ 4 status participants and sex subgroups. ApoM/TC ratio (ΔAUC = 0.056, p = 0.044) and ApoM/TG ratio (ΔAUC = 0.097, p = 0.011) had a statistically remarkably larger AUC than ApoM, respectively. The independent addition of ApoM and its derived indicators to the basic model [combining age, sex, APOEϵ 4, and body mass index (BMI)] led to the significant improvement in diagnostic power, respectively (each p < 0.05). Conclusion: All the findings preliminarily uncovered the association between plasma ApoM and AD and provided more evidence of the potential of ApoM as a candidate biomarker of AD.

Memantine Promotes Bactericidal Effect of Neutrophils Against Infection with Pseudomonas aeruginosa and Its Drug-Resistant Strain, by Improving Reactive Oxygen Species Generation.

Pseudomonas aeruginosa is an opportunistic pathogen, which usually presents multiple antibiotic resistance. Host-directed therapy involves modulating the host defense system and the interplay between innate and adaptive immunity is a new strategy for designing anti-infection drugs. Memantine (MEM), a drug used to treat Alzheimer's disease, has a good inhibitory effect on neonatal mice with Escherichia coli-associated bacteremia and meningitis; however, the inhibitory effect and mechanisms of MEM against P. aeruginosa infection remain unclear. Here, we investigated whether MEM could inhibit P. aeruginosa infection and explored the potential mechanisms. MEM significantly promoted the bactericidal effect of neutrophils against P. aeruginosa and its drug-resistant strain. The combination index of MEM and amikacin (AMK) was <1. In vivo experiments showed that the bacteremia and inflammation severities in the MEM-treated group were less than those in the untreated group, and the bacterial load in the organs was significantly less than that in the control group. Combining MEM with the reactive oxygen species (ROS) inhibitor, N-acetyl-l-cysteine, weakened the anti-infective effect of MEM. MEM increased the expression of NADPH p67phox and promoted neutrophilic ROS production. Deleting the p67phox gene significantly weakened the effects of MEM on ROS generation and improving bactericidal effect of neutrophils. In conclusion, MEM promoted the bactericidal effect of neutrophils against P. aeruginosa and its drug-resistant strain, and had a synergistic antibacterial effect when combined with AMK. MEM may exert its anti-infective effects by promoting neutrophilic bactericidal activity via increasing the expression level of p67phox and further stimulating ROS generation.