Cost-effectiveness analysis of the tislelizumab versus docetaxel for advanced or metastatic non-small-cell lung cancer in China.

Background: Tislelizumab is the first PD-1 inhibitor in China to demonstrate superior efficacy in second-line or third-line treatment of patients with advanced or metastatic non-small-cell lung cancer (NSCLC). This study aimed to evaluate the cost-effectiveness of tislelizumab compared to docetaxel from a Chinese healthcare system perspective. Methods: A dynamic Markov model was developed to evaluate the cost-effectiveness of tislelizumab in comparison to docetaxel in second or third-line treatment. The efficacy data utilized in the model were derived from the RATIONALE-303 clinical trial, while cost and utility values were obtained from the drug data service platform and published studies. The primary outcomes of the model encompassed quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs). One-way sensitivity analysis and probabilistic sensitivity analysis were conducted to validate the robustness of the base case analysis results. Results: The tislelizumab group demonstrated a cost increase of CNY 117,473 and a gain of 0.58 QALYs compared to the docetaxel group, resulting in an ICER value of CNY 202,927 per QALY gained. Conclusion: The administration of tislelizumab in patients with advanced or metastatic NSCLC not only extends the progression-free survival (PFS) and overall survival (OS). Moreover, this treatment demonstrates a favorable cost-effectiveness profile across the Chinese population.

Double gyroid-structured electrolyte based on an azobenzene-containing monomer and its polymer.

The self-assembled structure has a significant impact on the performance of ion conductors. We prepared a new type of electrolyte with self-assembled structures from an azobenzene-based liquid crystalline (LC) monomer and its corresponding polymer. By doping different amounts of monomers and lithium salt LiTFSI, the self-assembled nanostructure of the electrolyte was changed from lamellae to double gyroid. The ionic conductivity of the azobenzene-based electrolytes with the double gyroid structure was 1.64 × 10-4 S cm-1, higher than most PEO-based polymer electrolytes. The azobenzene-based system provides a new strategy to design solid electrolytes with self-assembled structures that may be potentially used in solid-state lithium-ion batteries.

Anti­epileptic mechanism of isopimaric acid from Platycladi cacumen based on network pharmacology, molecular docking and biological validation.

Platycladi cacumen (PC) is derived from the dry twigs and leaves of Platycladi orientalis (L.) Franco and exerts anti-epileptic effects. However, its mechanism of action remains unknown. The present study explored the potential anti-epileptic components and mechanisms of PC. The primary active components and targets of PC were analyzed using network pharmacology and a lipopolysaccharide (LPS)-induced murine microglial cell line (BV2) was used to confirm anti-epileptic effects by detecting reactive oxygen species (ROS), apoptosis, inflammatory markers, cell migration and signaling pathways. A total of 13 core active components showed druggable properties, of which deoxypicrop odophyllotoxin, hinokinin and isopimaric acid (IPA) were predicted to cross the blood-brain barrier. In total, 255 potential targets of these three compounds were predicted using SwissTargetPrediction and Similarity Ensemble Approach websites and 150 were associated with epilepsy. In vitro experiments confirmed that IPA significantly inhibited LPS-induced microglial oxidative stress and inflammation by decreasing the migration area, cellular ROS content, lactate dehydrogenase release and early phase of apoptosis. IPA also increased the mRNA expression of anti-oxidative enzymes (superoxide dismutase-1 and -2) and suppressed inflammatory cytokines (interleukin-1ß and tumor necrosis factor-α). Furthermore, IPA phosphorylated AKT and mTOR proteins. Taken together, the present findings suggested that IPA is a potential anti-epileptic compound derived from PC.

Deciphering the maize gene ZmGF14-3: implications for plant height based on co-expression networks.

The evolutionary analysis showed that the GF14 family was conserved, however, there was limited evidence linking GF14s to plant height. In our investigations, we discovered a co-expression relationship between ZmGF14s and functionally characterized genes linked to plant height. In the co-expression network, we identified ZmGF14-3, a gene expression exhibiting a positive correlation with plant height in three maize varieties, we postulated that this gene could be intimately linked to plant height development. Subsequently, we cloned ZmGF14-3 from the maize B73 inbred line and overexpressed it in Arabidopsis, resulting in markedly dwarfed transgenic phenotypes. Measurements of endogenous phytohormones disclosed a significant reduction in concentrations of Gibberellic Acid 7 (GA7) and Indole-3-Acetic Acid (IAA) in the overexpressed Arabidopsis, furthermore, qPCR results highlighted a pronounced decrease in the expression levels of plant height-related genes when compared to the wild type, therefore, it is plausible to posit that ZmGF14-3 plays a pivotal role in regulating the growth and development of maize through interactions with various phytohormone-related genes. Thus, delving into the potential interactions between ZmGF14-3 and these genes holds the promise of yielding valuable insights into the molecular mechanisms underpinning plant height development in maize.

Light-Driven Electrochemical Biosensing with DNA Origami-Assisted Hybrid Nanoantenna for Fumonisin B1 Monitoring.

The electrochemical detection of biosensors is largely governed by the changes in physical properties of redox probes, which are susceptible to electrode substrate effects, inhibiting sensor sensitivity. In this work, a light-driven electrochemical biosensor based on a hybrid nanoantenna was developed for the sensitive detection of fumonisin B1 (FB1). The hybrid nanoantenna sensing interface was constructed by coupling CdSe quantum dots (QDs)-DNA nanowire and graphdiyne oxide composites loaded with methylene blue and gold nanorods (GDYO-MB-Au NRs) using a tetrahedral DNA nanostructure, which acted as a light-driven unit and an amplification unit, respectively. The hybrid nanoantenna with light-driven properties facilitated the alteration in the chemical properties of MB at the sensing interface; that is, MB was degraded under light illumination. The stripping of the CdSe QDs-DNA nanowire triggered by the binding of FB1 could degrade the light-driven capability, thereby improving the electrochemical signal through depressing MB degradation. Taking advantage of the photodegradation of MB by the hybrid nanoantenna, the developed biosensor reduced the background signal and increased the detection sensitivity. The developed biosensor exhibited a linear detection range from 0.5 fg mL-1 to 10 pg mL-1 and a detection limit down to 0.45 fg mL-1. This strategy shows great promise for the fabrication of highly sensitive electrochemical biosensors.

Association between atherogenic index of plasma and gestational diabetes mellitus: a prospective cohort study based on the Korean population.

BACKGROUND: Atherogenic index of plasma (AIP) is a non-traditional lipid parameter that can reflect the burden of atherosclerosis. A lipid profile resembling atherosclerosis emerged during pregnancy. Although lipid metabolism is pivotal in diabetes pathogenesis, there is no evidence linking AIP to gestational diabetes mellitus (GDM). Therefore, our objective was to explore the relationship between AIP and GDM and assess AIP's predictive capability for GDM. METHODS: This was a secondary analysis based on data from a prospective cohort study in Korea involving 585 single pregnant women. AIP was calculated as log10 (TG/HDL). We examined the relationship between AIP and GDM using logistic regression models, curve fitting, sensitivity analyses, and subgroup analyses. Receiver operating characteristic (ROC) analysis was also used to determine the ability of AIP to predict GDM. RESULTS: The average age of the participants was 32.06 ± 3.76 years. The AIP was 0.24 ± 0.20 on average. The GDM incidence was 6.15%. After adjustment for potentially confounding variables, AIP showed a positive linear relationship with GDM (P for non-linearity: 0.801, OR 1.58, 95% CI 1.27-1.97). The robustness of the connection between AIP and GDM was demonstrated by sensitivity analyses and subgroup analyses. An area under the ROC curve of 0.7879 (95% CI 0.7087-0.8671) indicates that AIP is an excellent predictor of GDM. With a specificity of 75.41% and sensitivity of 72.22%, the ideal AIP cut-off value for identifying GDM was 0.3557. CONCLUSIONS: This study revealed that the AIP at 10-14 weeks of gestation was independently and positively correlated with GDM risk. AIP could serve as an early screening and monitoring tool for pregnant women at high risk of GDM, thereby optimizing GDM prevention strategies. TRIAL REGISTRATION: ClinicalTrials.gov registration no. NCT02276144.

Chronic inflammation with microglia senescence at basal forebrain: impact on cholinergic deficit in Alzheimer's brain haemodynamics.

Cholinergic innervation in the brain is involved in modulating neurovascular function including cerebral blood flow haemodynamics in response to neuronal activity. Cholinergic deficit is associated with pathophysiology in Alzheimer's disease, albeit the aetiology remains to be clarified. In the current study, neocortex cerebral blood flow response to acetylcholine was evaluated by Laser-Doppler Flowmetry (LDF) in 3xTgAD Alzheimer's disease model) and wild-type mice of two age groups. The peak of cerebral blood flow to acetylcholine (i.v.) from baseline levels (% ΔrCBF) was higher in young 3xTgAD versus in wild-type mice (48.35; 95% CI:27.03-69.67 versus 22.70; CI:15.5-29.91, P < 0.05); this was reversed in old 3xTgAD mice (21.44; CI:2.52-40.35 versus 23.25; CI:23.25-39). Choline acetyltransferase protein was reduced in neocortex, while cerebrovascular reactivity to acetylcholine was preserved in young 3×TgAD mice. This suggests endogenous acetylcholine deficit and possible cholinergic denervation from selected cholinergic nuclei within the basal forebrain. The early deposition of tauopathy moieties (mutant hTau and pTau181) and its coincidence in cholinergic cell clusters (occasionaly), were observed at the basal forebrain of 3xTgAD mice including substantia innominate, nucleus Basalis of Meynert and nucleus of horizontal limb diagonal band of Broca. A prominent feature was microglia interacting tauopathy and demonstrated a variety of morphology changes particularly when located in proximity to tauopathy. The microglia ramified phenotype was reduced as evaluated by the ramification index and Fractal analysis. Increased microglia senescence, identified as SASP (senescence-associated secretory phenotype), was colocalization with p16Ink4ɑ, a marker of irreversible cell-cycle arrest in old 3xTgAD versus wild-type mice (P = 0.001). The p16Ink4ɑ was also observed in neuronal cells bearing tauopathy within the basal forebrain of 3xTgAD mice. TNF-ɑ, the pro-inflammatory cytokine elevated persistently in microglia (Pearson's correlation coefficient = 0.62) and the loss of cholinergic cells in vulnerable basal forebrain environment, was indicated by image analysis in 3xTgAD mice, which linked to the cholinergic deficits in neocortex rCBF haemodynamics. Our study revealed the early change of CBF haemodynamics to acetylcholine in 3xTgAD model. As a major effector of brain innate immune activation, microglia SASP with age-related disease progression is indicative of immune cell senescence, which contributes to chronic inflammation and cholinergic deficits at the basal forebrain. Targeting neuroinflammation and senescence may mitigate cholinergic pathophysiology in Alzheimer's disease.

Construction and validation of predictive models for intravenous immunoglobulin-resistant Kawasaki disease using an interpretable machine learning approach.

BACKGROUND: Intravenous immunoglobulin (IVIG)-resistant Kawasaki disease is associated with coronary artery lesion development. PURPOSE: This study aimed to explore the factors associated with IVIG-resistance and construct and validate an interpretable machine learning (ML) prediction model in clinical practice. METHODS: Between December 2014 and November 2022, 602 patients were screened and risk factors for IVIG-resistance investigated. Five ML models are used to establish an optimal prediction model. The SHapley Additive exPlanations (SHAP) method was used to interpret the ML model. RESULTS: Na+, hemoglobin (Hb), C-reactive protein (CRP), and globulin were independent risk factors for IVIG-resistance. A nonlinear relationship was identified between globulin level and IVIG-resistance. The XGBoost model exhibited excellent performance, with an area under the receiver operating characteristic curve of 0.821, accuracy of 0.748, sensitivity of 0.889, and specificity of 0.683 in the testing set. The XGBoost model was interpreted globally and locally using the SHAP method. CONCLUSION: Na+, Hb, CRP, and globulin levels were independently associated with IVIG-resistance. Our findings demonstrate that ML models can reliably predict IVIG-resistance. Moreover, use of the SHAP method to interpret the established XGBoost model's findings would provide evidence of IVIG-resistance and guide the individualized treatment of Kawasaki disease.

Inhibition of KIAA1429/HK1 axis enhances the sensitivity of liver cancer cells to sorafenib by regulating the Warburg effect.

N6-methyladenosine (m6A) serves as the most abundant posttranscription modification. However, the role of m6A in tumorigenesis and chemotherapeutic drugs sensitivity remains largely unclear. Present research focuses on the potential function of the m6A writer KIAA1429 in tumor development and sorafenib sensitivity in liver cancer. We found that the level of KIAA1429 was significantly elevated in liver cancer tissues and cells and was closely associated with poorer prognosis. Functionally, KIAA1429 promoted the proliferation and Warburg effect of liver cancer cells in vitro and in vivo. RNA-seq and MeRIP-seq analysis revealed the glycolysis was one of the most affected pathways by KIAA1429, and m6A-modified HK1 was the most likely targeted gene to regulate the Warburg effect. KIAA1429 depletion decreased Warburg effect and increased sorafenib sensitivity in liver cancer. Mechanistically, KIAA1429 could affect the m6A level of HK1 mRNA through directly binding with it. Moreover, KIAA1429 cooperated with the m6A reader HuR to enhance HK1 mRNA stability, thereby upregulating its expression. These findings demonstrated that KIAA1429/HK1 axis decreases the sensitivity of liver cancer cells to sorafenib by regulating the Warburg effect, which may provide a novel therapeutic target for liver cancer treatment.

Semivortex solitons and their excited states in spin-orbit-coupled binary bosonic condensates.

It is known that two-dimensional two-component fundamental solitons of the semivortex (SV) type, with vorticities (s_{+},s_{-})=(0,1) in their components, are stable ground states (GSs) in the spin-orbit-coupled (SOC) binary Bose-Einstein condensate with the contact self-attraction acting in both components, in spite of the possibility of the critical collapse in the system. However, excited states (ESs) of the SV solitons, with the vorticity set (s_{+},s_{-})=(S_{+},S_{+}+1) and S_{+}=1,2,3,..., are unstable in the same system. We construct ESs of SV solitons in the SOC system with opposite signs of the self-interaction in the two components. The main finding is stability of the ES-SV solitons, with the extra vorticity (at least) up to S_{+}=6. The threshold value of the norm for the onset of the critical collapse, N_{thr}, in these excited states is higher than the commonly known critical value, N_{c}≈5.85, associated with the single-component Townes solitons, N_{thr} increasing with the growth of S_{+}. A velocity interval for stable motion of the GS-SV solitons is found too. The results suggest a solution for the challenging problem of the creation of stable vortex solitons with high topological charges.

[Spatial and Temporal Scale Effects of Landscape Pattern on Riverine Nitrogen and Phosphorus Nutrients in the Qingshan Lake Watershed].

The influences of landscape pattern on water quality are dependent on spatial-temporal scales. However, the effects of landscape composition, landscape configuration, and landscape slope metrics on seasonal water quality at different spatial scales remain unclear. Based on the total nitrogen, total phosphorus, nitrate-N, and ammonium-N data from 26 sampling sites in the Qingshan Lake watershed, this study coupled landscape pattern analysis, redundancy analysis, and partial redundancy analysis to quantify the spatiotemporal scale effects of landscape pattern on riverine nitrogen （N） and phosphorus （P） concentrations. The results showed that： ① The explanatory ability of landscape pattern at the sub-watershed scale on riverine N and P concentrations was 6.8%-8.4% higher than that at the buffer scale, and this effect was more obvious in the dry season. ② At the sub-watershed scale, the percentage of forestland and the interspersion and juxtaposition degree of residential land had a greater influence on riverine N and P concentrations. At the buffer scale, the slope of farmland and residential land and the aggregation degree of forestland patches were the key factors affecting riverine N and P concentrations. ③ The contribution rate of landscape configuration to riverine N and P concentration variations （20.1%-36.5%） was the highest. The sensitivity of the effect of landscape configuration on riverine N and P concentrations to seasonal changes was the highest, and the effect of landscape slope on riverine N and P concentrations had the highest sensitivity to spatial scale changes. Therefore, landscape pattern-regulated non-point source pollution should be considered from a multi-scale perspective. These results can provide scientific basis for the formulation of landscape pattern optimization measures aiming at non-point source pollution control.

Pig blastocyst-like structure models from embryonic stem cells.

Pluripotent stem cells have the potential to generate embryo models that can recapitulate developmental processes in vitro. Large animals such as pigs may also benefit from stem-cell-based embryo models for improving breeding. Here, we report the generation of blastoids from porcine embryonic stem cells (pESCs). We first develop a culture medium 4FIXY to derive pESCs. We develop a 3D two-step differentiation strategy to generate porcine blastoids from the pESCs. The resulting blastoids exhibit similar morphology, size, cell lineage composition, and single-cell transcriptome characteristics to blastocysts. These porcine blastoids survive and expand for more than two weeks in vitro under two different culture conditions. Large animal blastoids such as those derived from pESCs may enable in vitro modeling of early embryogenesis and improve livestock species' breeding practices.

Gradient failure mechanism and control technology of deep roadways under the action of deviatoric stress field.

Deformation control of deep roadways is a major challenge for mine safety production. Taking a deep roadway with a burial depth of 965 m in a mine in North China as the engineering background, on-site investigation found that significant creep deformation occurred in the surrounding rock of the roadway. The original supporting U-shaped steel support failed due to insufficient supporting strength. The rock mass near the roadway experienced a transition from triaxial stress conditions to biaxial and even uniaxial stress states as a result of excavation and unloading, leading to a gradient stress distribution in the surrounding rock. From the perspective of the roadway's deviatoric stress field distribution, we investigated the gradient failure mechanism of the roadway and validated it through theoretical analysis and numerical simulations. The study found that the ratio of horizontal principal stress and vertical principal stress determines the distribution shape of the surrounding rock deviatoric stress field. The gradient distribution of the stress field in the roadway will cause time-related deformation of the roadway, which will lead to large deformation and failure of the roadway. Based on this, the control mechanism of roadway gradient failure was studied, and then a combined support technology of CFST supports with high bearing capacity was proposed.

NAD+ metabolism and therapeutic strategies in cardiovascular diseases.

Nicotinamide adenine dinucleotide (NAD+) is a central and pleiotropic metabolite involved in cellular energy metabolism, cell signaling, DNA repair, and protein modifications. Cardiovascular diseases (CVDs) are the leading cause of death worldwide. Metabolic stress and aging directly affect the cardiovascular system. Compelling data suggest that NAD + levels decrease with age, obesity, and hypertension, which are all notable risk factors for CVD. In addition, the therapeutic elevation of NAD + levels reduces chronic low-grade inflammation, reactivates autophagy and mitochondrial biogenesis, and enhances oxidative metabolism in vascular cells of humans and rodents with vascular disorders. In preclinical models, NAD + boosting can also expand the health span, prevent metabolic syndrome, and decrease blood pressure. Moreover, NAD + storage by genetic, pharmacological, or natural dietary NAD + -increasing strategies has recently been shown to be effective in improving the pathophysiology of cardiac and vascular health in different animal models, and human health. Here, we review and discuss NAD + -related mechanisms pivotal for vascular health and summarize recent experimental evidence in NAD + research directly related to vascular disease, including atherosclerosis, and coronary artery disease. Finally, we comparatively assess distinct NAD + precursors for their clinical efficacy and the efficiency of NAD + elevation in the treatment of major CVD. These findings may provide ideas for new therapeutic strategies to prevent and treat CVD in the clinic.

Ganoderic acid a decreased Aß42-induced neurotoxicity in PC12 cells by reduced mitochondrial damage.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Accumulation of ß-amyloid (Aß) in the brain has been recognized as a key factor in the onset and progression of Alzheimer's disease (AD).The accumulation of Aß in the brain catalyzes the production of reactive oxygen species (ROS), which in turn triggers oxidative damage to cellular components such as DNA, lipids, and proteins. In the present study, we investigated the protective effect of Ganoderic acid A (GA.A) against Aß42-induced apoptosis in PC12 cells. Changes in mitochondrial membrane potential indicated that GA.A treats mitochondrial dysfunction by decreasing Aß42 deposition and inhibiting neural protofiber tangle formation. Changes in intracellular Ca2+ and caspase-3 indicated that GA.A reduced mitochondrial damage by Aß42 in PC12 cells, thereby decreasing ROS accumulation and reducing Aß protofiber-induced cytotoxicity. These features suggest that GA.A has great potential as an effective neuroprotective drug in the treatment of Alzheimer's disease.

Mechanism of action of miR-15a-5p and miR-152-3p in paraquat-induced pulmonary fibrosis through Wnt/ß-catenin signaling mediation.

Background: miRNAs are small, conserved, single-stranded non-coding RNA that are typically transported by exosomes for their functional roles. The therapeutic potential of exosomal miRNAs has been explored in various diseases including breast cancer, pancreatic cancer, cholangiocarcinoma, skin diseases, Alzheimer's disease, stroke, and glioma. Pathophysiological processes such as cellular inflammation, apoptosis, necrosis, immune dysfunction, and oxidative stress are closely associated with miRNAs. Internal and external factors such as tissue ischemia, hypoxia, pathogen infection, and endotoxin exposure can trigger these reactions and are linked to miRNAs. Paraquat-induced fibrosis is a protracted process that may not manifest immediately after injury but develops during bodily recovery, providing insights into potential miRNA intervention treatments. Rationale: These findings could potentially be applied for further pharmaceutical research and clinical therapy of paraquat-induced pulmonary fibrosis, and are likely to be of great interest to clinicians involved in lung fibrosis research. Methodology: Through a literature review, we identified an association between miR-15a-5p and miR-152-3p and their involvement in the Wnt signaling pathway. This allowed us to deduce the molecular mechanisms underlying regulatory interactions involved in paraquat-induced lung fibrosis. Results: miR-15a-5p and miR-152-3p play roles in body repair processes, and pulmonary fibrosis can be considered a form of reparative response by the body. Although the initial purpose of fibrotic repair is to restore normal body function, excessive tissue fibrosis, unlike scar formation following external skin trauma, can significantly and adversely affect the body. Modulating the Wnt/ß-catenin signaling pathway is beneficial in alleviating tissue fibrosis in various diseases. Conclusions: In this study, we delineate the association between miR-15a-5p and miR-152-3p and the Wnt/ß-catenin signaling pathway, presenting a novel concept for addressing paraquat-induced pulmonary fibrosis.

Effect of Relative Protein Intake on Hypertension and Mediating Role of Physical Fitness and Circulating Fatty Acids: A Mendelian Randomization Study.

OBJECTIVE: To investigate the causal effect of protein intake on hypertension and the related mediating pathways. PATIENTS AND METHODS: Using genome-wide association study summary statistics of European ancestry, we applied univariable and multivariable Mendelian randomization to estimate the bidirectional associations of relative protein intake and related metabolomic signatures with hypertension (FinnGen: Ncase=42,857/Ncontrol=162,837; UK Biobank: Ncase=77,723/Ncontrol=330,366) and blood pressure (International Consortium of Blood Pressure: N=757,601) and two-step Mendelian randomization to assess the mediating roles of 40 cardiometabolic factors therein. Mendelian randomization estimates of hypertension from FinnGen and UK Biobank were meta-analyzed without heterogeneity. We performed the study from May 15, 2023, to September 15, 2023. RESULTS: Each 1-SD higher relative protein intake was causally associated with 69% (odds ratio, 0.31; 95% CI, 0.11 to 0.89) lower hypertension risk independent of the effects of other macronutrients, and was the only macronutrient associated with 2.21 (95% CI, 0.52 to 3.91) mm Hg lower pulse pressure, in a unidirectional manner. Higher plant protein-related metabolomic signature (glycine) was associated with lower hypertension risk and pulse pressure, whereas higher animal protein-related metabolomic signatures (leucine, isoleucine, valine, and isovalerylcarnitine [only systolic blood pressure]) were associated with higher hypertension risk, pulse pressure, and systolic blood pressure. The effect of relative protein intake on hypertension was causally mediated by frailty index (mediation proportion, 40.28%), monounsaturated fatty acids (13.81%), saturated fatty acids (11.39%), grip strength (5.34%), standing height (3.99%), and sitting height (3.61%). CONCLUSION: Higher relative protein intake causally reduces the risk of hypertension, partly mediated by physical fitness and circulating fatty acids.

Clinical Outcome Assessment of Colistin Sulfate in Children with Carbapenem-Resistant Organism Infections: First Data from China.

OBJECT: Colistin sulfate for injection (CSI) became clinically available in China in July 2019. To date, there is no published data regarding its usage in children. Our research group has been following data on the efficacy and safety of CSI in Chinese pediatric patients with carbapenem-resistant organism (CRO) infections. The purpose of this short communication is to provide a brief overview of the findings to date. METHODS: We reviewed the electronic medical records of pediatric patients (aged 9-17 years) who were administered CSI during their hospital stay at Tongji Hospital in Wuhan, China, between June 2021 and November 2023. Drug efficacy was evaluated based on clinical and microbiological outcomes, while drug safety was assessed using surveillance markers that reflect adverse reactions. RESULTS: A total of 20 patients met the inclusion criteria. The predominant pathogens were Klebsiella pneumoniae (8 strains), followed by Acinetobacter baumannii (5 strains) and Pseudomonas aeruginosa (2 strains). The clinical response rate of CSI was 85%, with a bacterial clearance rate of 79%. None of the patients experienced colistin-related nephrotoxicity or neurotoxicity during the treatment. CONCLUSION: In this real-world setting, CSI demonstrated a high level of clinical response and was well tolerated for the treatment of CRO infections in Chinese children.

An Electrolyte Engineered Homonuclear Copper Complex as Homogeneous Catalyst for Lithium-Sulfur Batteries.

Lithium-sulfur (Li-S) batteries suffer from severe polysulfide shuttle, retarded sulfur conversion kinetics and notorious lithium dendrites, which has curtailed the discharge capacity, cycling lifespan and safety. Engineered catalysts act as a feasible strategy to synchronously manipulate the evolution behaviors of sulfur and lithium species. Herein, a chlorine bridge-enabled binuclear copper complex (Cu-2-T) is in situ synthesized in electrolyte as homogeneous catalyst for rationalizing the Li-S redox reactions. The well-designed Cu-2-T provides completely active sites and sufficient contact for homogeneously guiding the Li2S nucleation/decomposition reactions, and stabilizing the lithium working interface according to the synchrotron radiation X-ray 3D nano-computed tomography, small angle neutron scattering and COMSOL results. Moreover, Cu-2-T with the content of 0.25 wt% approaching saturated concentration in electrolyte further boosts the homogeneous optimization function in really operated Li-S batteries. Accordingly, the capacity retention of the Li-S battery is elevated from 51.4% to 86.3% at 0.2 C, and reaches 77.0% at 1.0 C over 400 cycles. Furthermore, the sulfur cathode with the assistance of Cu-2-T realizes the stable cycling under the practical scenarios of soft-packaged pouch cell and high sulfur loading (6.5 mg cm-2 with the electrolyte usage of 4.5 µL mgS -1).

Sex differences in the association between plasma branched-chain amino acids and risk of ischemic stroke: A nested case-control study from China.

OBJECTIVES: The aim of this study was to investigate the prospective associations between plasma branched-chain amino acids (BCAAs) and the risk of ischemic stroke in men and women. METHODS: We conducted a nested case-control study within a community-based cohort in China. The cohort consisted of 15,926 participants in 2013-2018. A total of 321 ischemic stroke cases were identified during the follow up and individually matched with 321 controls by date of birth (±1 year) and sex. Females accounted for 55.8% (n = 358, 179 cases vs 179 controls) of the study population. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the association between plasma BCAAs and ischemic stroke risk by conditional logistic regression. RESULTS: Elevated plasma isoleucine was associated with a higher risk of ischemic stroke in women. The OR for the highest compared to the lowest quartile was 2.22 (95% CI: 1.11-4.44, P trend = 0.005) after adjustment for body mass index, education attainment, smoking, hypertension, renal function, menopause and physical activity. A similar association was found for total BCAAs (adjusted OR = 2.03, 95% CI: 1.05-3.95, P trend = 0.04). In contrast, no significant association of plasma BCAAs with ischemic stroke risk was observed in men. CONCLUSIONS: Plasma isoleucine and total BCAAs were significantly associated with ischemic stroke risk in women, but not in men, highlighting sex differences in BCAAs metabolism and stroke pathogenesis.