Advances of Layered Double Hydroxide-Based Materials for Tumor Imaging and Therapy.

Layered double hydroxides (LDH) are a class of functional anionic clays that typically consist of orthorhombic arrays of metal hydroxides with anions sandwiched between the layers. Due to their unique properties, including high chemical stability, good biocompatibility, controlled drug loading, and enhanced drug bioavailability, LDHs have many potential applications in the medical field. Especially in the fields of bioimaging and tumor therapy. This paper reviews the research progress of LDHs and their nanocomposites in the field of tumor imaging and therapy. First, the structure and advantages of LDH are discussed. Then, several commonly used methods for the preparation of LDH are presented, including co-precipitation, hydrothermal and ion exchange methods. Subsequently, recent advances in layered hydroxides and their nanocomposites for cancer imaging and therapy are highlighted. Finally, based on current research, we summaries the prospects and challenges of layered hydroxides and nanocomposites for cancer diagnosis and therapy.

Eldecalcitol prevents muscle loss and osteoporosis in disuse muscle atrophy via NF-κB signaling in mice.

We investigated the effect of eldecalcitol on disuse muscle atrophy. C57BL/6J male mice aged 6 weeks were randomly assigned to control, tail suspension (TS), and TS-eldecalcitol-treated groups and were injected intraperitoneally twice a week with either vehicle (control and TS) or eldecalcitol at 3.5 or 5 ng for 3 weeks. Grip strength and muscle weights of the gastrocnemius (GAS), tibialis anterior (TA), and soleus (SOL) were determined. Oxidative stress was evaluated by malondialdehyde, superoxide dismutase, glutathione peroxidase, and catalase. Bone microarchitecture was analyzed using microcomputed tomography. The effect of eldecalcitol on C2C12 myoblasts was analyzed by measuring myofibrillar protein MHC and the atrophy markers Atrogin-1 and MuRF-1 using immunofluorescence. The influence of eldecalcitol on NF-κB signaling pathway and vitamin D receptor (VDR) was assessed through immunofluorescence, (co)-immunoprecipitation, and VDR knockdown studies. Eldecalcitol increased grip strength (P < 0.01) and restored muscle loss in GAS, TA, and SOL (P < 0.05 to P < 0.001) induced by TS. An improvement was noted in bone mineral density and bone architecture in the eldecalcitol group. The impaired oxidative defense system was restored by eldecalcitol (P < 0.05 to P < 0.01 vs. TS). Eldecalcitol (10 nM) significantly inhibited the expression of MuRF-1 (P < 0.001) and Atrogin-1 (P < 0.01), increased the diameter of myotubes (P < 0.05), inhibited the expression of P65 and P52 components of NF-κB and P65 nuclear location, thereby inhibiting NF-κB signaling. Eldecalcitol promoted VDR binding to P65 and P52. VDR signaling is required for eldecalcitol-mediated anti-atrophy effects. In conclusion, eldecalcitol exerted its beneficial effects on disuse-induced muscle atrophy via NF-κB inhibition.

Subject clustering by IF-PCA and several recent methods.

Subject clustering (i.e., the use of measured features to cluster subjects, such as patients or cells, into multiple groups) is a problem of significant interest. In recent years, many approaches have been proposed, among which unsupervised deep learning (UDL) has received much attention. Two interesting questions are 1) how to combine the strengths of UDL and other approaches and 2) how these approaches compare to each other. We combine the variational auto-encoder (VAE), a popular UDL approach, with the recent idea of influential feature-principal component analysis (IF-PCA) and propose IF-VAE as a new method for subject clustering. We study IF-VAE and compare it with several other methods (including IF-PCA, VAE, Seurat, and SC3) on 10 gene microarray data sets and eight single-cell RNA-seq data sets. We find that IF-VAE shows significant improvement over VAE, but still underperforms compared to IF-PCA. We also find that IF-PCA is quite competitive, slightly outperforming Seurat and SC3 over the eight single-cell data sets. IF-PCA is conceptually simple and permits delicate analysis. We demonstrate that IF-PCA is capable of achieving phase transition in a rare/weak model. Comparatively, Seurat and SC3 are more complex and theoretically difficult to analyze (for these reasons, their optimality remains unclear).

mRNA therapeutics for disease therapy: principles, delivery, and clinical translation.

Messenger RNA (mRNA) has become a key focus in the development of therapeutic agents, showing significant potential in preventing and treating a wide range of diseases. The COVID-19 pandemic in 2020 has accelerated the development of mRNA nucleic therapeutics and attracted significant investment from global biopharmaceutical companies. These therapeutics deliver genetic information into cells without altering the host genome, making them a promising treatment option. However, their clinical applications have been limited by issues such as instability, inefficient in vivo delivery, and low translational efficiency. Recent advances in molecular design and nanotechnology have helped overcome these challenges, and several mRNA formulations have demonstrated promising results in both animal and human testing against infectious diseases and cancer. This review provides an overview of the latest research progress in structural optimization strategies and delivery systems, and discusses key considerations for their future clinical use.

Prevalent and immunodominant CD8 T cell epitopes are conserved in SARS-CoV-2 variants.

The emergence of SARS-CoV-2 variants of concern (VOC) is driven by mutations that mediate escape from neutralizing antibodies. There is also evidence that mutations can cause loss of T cell epitopes. However, studies on viral escape from T cell immunity have been hampered by uncertain estimates of epitope prevalence. Here, we map and quantify CD8 T cell responses to SARS-CoV-2-specific minimal epitopes in blood drawn from April to June 2020 from 83 COVID-19 convalescents. Among 37 HLA ligands eluted from five prevalent alleles and an additional 86 predicted binders, we identify 29 epitopes with an immunoprevalence ranging from 3% to 100% among individuals expressing the relevant HLA allele. Mutations in VOC are reported in 10.3% of the epitopes, while 20.6% of the non-immunogenic peptides are mutated in VOC. The nine most prevalent epitopes are conserved in VOC. Thus, comprehensive mapping of epitope prevalence does not provide evidence that mutations in VOC are driven by escape of T cell immunity.

Eldecalcitol prevents muscle loss by suppressing PI3K/AKT/FOXOs pathway in orchiectomized mice.

Elderly male patients are susceptible to develop osteoporosis and sarcopenia, especially those with fragility fractures, hypogonadism, and prostate cancer with androgen deprivation therapy. However, at present, very few treatments are available for men with sarcopenia. Previous preclinical studies in ovariectomized rats have shown the promising effects of eldecalcitol in ameliorating the bone strength and muscle atrophy. We thus investigated the effects of eldecalcitol on androgen-deficient male mice. Six-week-old male mice underwent orchiectomy (ORX) or sham surgery. Mice were randomly divided into 4 groups (n = 12/per group), including 1) sham mice, 2) ORX group, 3) ORX eldecalcitol 30 ng/kg, and 4) ORX eldecalcitol 50 ng/kg. Eldecalcitol increased bone mass and strength of femur in ORX mice. Eldecalcitol 30 ng/kg dose completely rescued ORX-induced muscle weakness. The RT-qPCR showed that eldecalcitol enhanced the mRNA levels of type I and IIa fibers. The expression levels of MuRF1 and Atrogin-1 of gastrocnemius in the eldecalcitol groups were much lower than that of the ORX group. It is assumed that eldecalcitol potentially acts via PI3K/AKT/FOXOs signaling pathway. These findings provide evidence for evaluating eldecalcitol as an investigational treatment for male patients with sarcopenia and osteoporosis.

Point-of-care non-invasive enzyme-cleavable nanosensors for acute transplant rejection detection.

Accurate and non-invasive monitoring of allograft posttransplant is essential for early detection of acute cellular rejection and determines the long-term survival of the graft. Clinically, tissue biopsy is the most effective approach for diagnosing transplant rejection. Nonetheless, the procedure is invasive and potentially triggers organ failure. This work aims to design and apply GzmB-responsive nanosensors (GBRNs) that can readily size-change in graft tissues. Subsequently, we investigate the activity of serine protease granzyme B by generating a direct colorimetric urinary readout for non-invasive detection of transplant rejection in under 1 h. In preclinical heart graft mice models of transplant rejection, GBRNs were cleaved by GzmB and excreted by the kidneys via accurate nanometre-size glomerular filtration. By exploiting the catalytic activity of ultrasmall gold nanoclusters, GBRNs urinalysis promotes ultrasensitive surveillance of rejection episodes with a receiver operator characteristic curve area under the curve of 0.896 as well as a 95% confidence interval of about 0.7701-1.000. Besides, the catalytic activity of gold nanoclusters in urine can be detected at point-of-care testing to predict the immunity responses in mice with insufficient immunosuppressive therapy. Therefore, this non-invasive, sensitive, and quantitative method is a robust and informative approach for rapid and routine monitoring of transplant allografts without invasive biopsy.

A photocontrollable thermosensitive chemical spatiotemporally destabilizes mitochondrial membranes for cell fate manipulation.

Perturbations in mitochondrial membrane stability lead to cytochrome c release and induce caspase-dependent apoptosis. Using synthetic smart chemicals with changeable physicochemical properties to interfere the mitochondrial membrane stability has not yet been reported. Here we show that a thermosensitive anchor-polymer-peptide conjugate (anchor-PPC) destabilizes mitochondrial membranes upon in situ molecule changes from hydrophilic to hydrophobic, which consequently induces apoptosis in a spatiotemporally controlled manner and acts as an antitumor pharmaceutical. The anchor-PPC is composed of a thermosensitive copolymer, a photolabile linker, a hydrophilic HIV Tat-derived peptide both for cell penetration and polymer phase transition temperature (Tt) modulation, and an anchor peptide for intercalating into mitochondrial membranes. The photocontrollable anchor-PPC dehydrates and changes from being hydrophilic to hydrophobic upon photoactivation at body temperature. This cell-penetrable anchor-PPC specifically targets mitochondria and destabilizes mitochondrial membranes upon irradiation, and consequently initiates apoptosis in cells and a complex 3D tumor model. This study provides the first experimental evidence that the synthetic smart chemical can spatiotemporally control the stability of organelle membranes based on its in situ physicochemical property change.

Pharmacological Therapies for Osteoporosis: A Bayesian Network Meta-Analysis.

BACKGROUND Numerous randomized controlled trials (RCTs) have evaluated pharmacological therapies for osteoporosis. The aim of this Bayesian network meta-analysis was to compare the efficacy and safety of pharmacological therapies for osteoporosis patients. MATERIAL AND METHODS The electronic databases of PubMed, Embase, and Cochrane Library were systematically searched for eligible RCTs from their inception up to January 2021. The primary endpoints were all fractures, vertebral fractures, and non-vertebral fractures, while the secondary endpoints were fractures at hip or peripheral locations, bone mineral density (BMD) at various sites, and potential adverse events. RESULTS We included 79 RCTs reporting a total of 108 797 individuals in the final quantitative analysis. The results of network analysis indicated that romosozumab (92.1%) was the most effective in reducing the risk for all fractures, with the best therapeutic effects on vertebral fracture (97.2%) and non-vertebral fracture (88.0%). Romosozumab (92.5%) provided better therapeutic effects for the reduction of hip fracture. The best treatment agents for improving whole-body BMD (100.0%), spine BMD (95.7%), hip BMD (92.4%), femoral neck BMD (86.7%), and trochanter BMD (95.5%) were alendronate, strontium ranelate, ibandronate, risedronate, and ibandronate, respectively. Finally, the use of bazedoxifene was associated with the highest incidence of any upper-gastrointestinal event, nasopharyngitis, and back pain, while risedronate was associated with higher incidence of abdominal pain and dyspepsia. CONCLUSIONS This study found that romosozumab yielded the best effects for preventing fracture risk, while abaloparatide was the most effective in reducing the risk of vertebral fracture and non-vertebral fracture.

Rituximab-treated patients with lymphoma develop strong CD8 T-cell responses following COVID-19 vaccination.

B-cell depletion induced by anti-cluster of differentiation 20 (CD20) monoclonal antibody (mAb) therapy of patients with lymphoma is expected to impair humoral responses to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccination, but effects on CD8 T-cell responses are unknown. Here, we investigated humoral and CD8 T-cell responses following two vaccinations in patients with lymphoma undergoing anti-CD20-mAb therapy as single agent or in combination with chemotherapy or other anti-neoplastic agents during the last 9 months prior to inclusion, and in healthy age-matched blood donors. Antibody measurements showed that seven of 110 patients had antibodies to the receptor-binding domain of the SARS-CoV-2 Spike protein 3-6 weeks after the second dose of vaccination. Peripheral blood CD8 T-cell responses against prevalent human leucocyte antigen (HLA) class I SARS-CoV-2 epitopes were determined by peptide-HLA multimer analysis. Strong CD8 T-cell responses were observed in samples from 20/29 patients (69%) and 12/16 (75%) controls, with similar median response magnitudes in the groups and some of the strongest responses observed in patients. We conclude that despite the absence of humoral immune responses in fully SARS-CoV-2-vaccinated, anti-CD20-treated patients with lymphoma, their CD8 T-cell responses reach similar frequencies and magnitudes as for controls. Patients with lymphoma on B-cell depleting therapies are thus likely to benefit from current coronavirus disease 2019 (COVID-19) vaccines, and development of vaccines aimed at eliciting T-cell responses to non-Spike epitopes might provide improved protection.

Heritability of tea drinking and its relationship with cigarette smoking in the Chinese male adult twins.

The aims of this study are to estimate the contributions of genetic factors to the variation of tea drinking and cigarette smoking, to examine the roles of genetic factors in their correlation and further to investigate underlying causation between them. We included 11 625 male twin pairs from the Chinese National Twin Registry (CNTR). Bivariate genetic modelling was fitted to explore the genetic influences on tea drinking, cigarette smoking and their correlation. Inference about Causation through Examination of FAmiliaL CONfounding (ICE FALCON) was further used to explore the causal relationship between them. We found that genetic factors explained 17% and 23% of the variation in tea drinking and cigarette smoking, respectively. A low phenotypic association between them was reported (rph = 0.21, 95% confidence interval [CI]: [0.19, 0.24]), which was partly attributed to common genetic factors (rA = 0.45, 95% CI [0.19, 1.00]). In the ICE FALCON analysis with current smoking as the exposure, tea drinking was associated with his own (ßself = 0.39, 95% CI [0.23, 0.55]) and his co-twin's smoking status (ßco-twin = 0.25, 95% CI [0.10, 0.41]). Their association attenuated with borderline significance conditioning on his own smoking status (p = 0.045), indicating a suggestive causal effect of smoking status on tea drinking. On the contrary, when we used tea drinking as the predictor, we found familial confounding between them only. In conclusion, both tea drinking and cigarette smoking were influenced by genetic factors, and their correlation was partly explained by common genetic factors. In addition, our finding suggests that familial confounders account for the relationship between tea drinking and cigarette smoking. And current smoking might have a causal effect on weekly tea drinking, but not vice versa.

CuCoFe Layered double hydroxides as laccase mimicking nanozymes for colorimetric detection of pheochromocytoma biomarkers.

A laccase catalyzed colorimetric biosensing approach is promising for the detection of pheochromocytoma biomarkers, yet suffers from the poor stability of enzymes and high cost for production. Here we report for the first time an easy to produce, cheap, stable and reliable laccase-mimicking CuCoFe-LDHzyme, which can catalyze the oxidation of pheochromocytoma biomarkers to form a chromogenic product for smartphone-based colorimetric detection.

A data harmonization pipeline to leverage external controls and boost power in GWAS.

The use of external controls in genome-wide association study (GWAS) can significantly increase the size and diversity of the control sample, enabling high-resolution ancestry matching and enhancing the power to detect association signals. However, the aggregation of controls from multiple sources is challenging due to batch effects, difficulty in identifying genotyping errors and the use of different genotyping platforms. These obstacles have impeded the use of external controls in GWAS and can lead to spurious results if not carefully addressed. We propose a unified data harmonization pipeline that includes an iterative approach to quality control and imputation, implemented before and after merging cohorts and arrays. We apply this harmonization pipeline to aggregate 27 517 European control samples from 16 collections within dbGaP. We leverage these harmonized controls to conduct a GWAS of Crohn's disease. We demonstrate a boost in power over using the cohort samples alone, and that our procedure results in summary statistics free of any significant batch effects. This harmonization pipeline for aggregating genotype data from multiple sources can also serve other applications where individual level genotypes, rather than summary statistics, are required.

Relationship between the risk factors of cardiovascular disease by testing biochemical markers and young men with erectile dysfunction: a case-control study.

BACKGROUND: Erectile dysfunction (ED) shares common risk factors with cardiovascular disease (CVD), such as diabetes mellitus (DM) and dyslipidemia, but the relationship between the risk factors of CVD in biochemical markers and young men with ED age 20-40 years is not fully clarified. METHODS: A total of 289 ED outpatients (20-40 years old) were allocated under ED group, based on patients' complaints and physical examinations. According to the frequency matching ratio of 1:4, 1,155 male individuals (20-40 years old) without ED were set as control group. All participants were tested for lipid profiles including total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL), low density lipoprotein (LDL), blood glucose (BG), homocysteine (HCY), liver function including alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and renal function including uric acid (UA) and creatinine (CR). The study was designed to compare the two groups using an established binary logistic regression analysis model. The ED group was then subdivided into a younger ED group (20-30 years old) and an older ED group (31-40 years old) for further comparisons. RESULTS: After comparison, no obvious differences were found in medians of age, TC, TG, HDL, HCY, UA, and ALT in the two groups. Median LDL, BG, and CR were significantly higher and AST was much lower in the ED group (P<0.01). In binary logistic regression analysis, odds ratios (OR) for LDL, BG, CR, and AST were 1.279, 1.237, 1.026, and 0.978, respectively. The sensitivity value and specificity value were 43.25% and 72.56%, respectively. The medians of LDL, TG, and TC were higher and HDL was much lower in the older ED group, as compared with the younger group (P<0.05). No significant differences were displayed in medians of other biochemical markers in the above comparisons. CONCLUSIONS: Elevated LDL, BG, and CR were related factors of ED in young men. Lipid profile was significantly different between young men with ED aged 20-30 and 31-40 years.

Comparison of antiangina therapies in patients with coronary heart disease in China: study protocol for a multicentre, retrospective, hospital system-based study.

INTRODUCTION: China has the largest number of patients with coronary heart disease (CHD) in the world. Numerous pharmacological strategies are available for CHD in routine clinical practice. CHD-induced angina pectoris affects patients' quality of life and is a key predictor of prognosis. This study will compare the effectiveness of different antiangina treatments, particularly ATP-sensitive potassium channel (KATP) activators, in the Central China District. This proposal underpins the first comparison of antiangina therapies in patients with CHD in China using a multicentre, retrospective, hospital system-based assessment. METHODS AND ANALYSIS: This retrospective real-world study will assess the largest hospital databases in Wuhan City in Central China to evaluate outcomes including mortality, revascularisation, myocardial infarction (MI), stroke and other cardio-cerebrovascular events in patients with CHD. Data will be consecutively collected between 1 April 2009 and 31 August 2019 through the hospital information system, laboratory information system and hospital imaging system. All data will be standardised by at least three independent technicians and statisticians using International Classification of Diseases Tenth Version, ISO15189 and Specification for Drafting of Basic Dataset of Electronic Medical Record (WS445). The data will include patient demographics, physical and laboratory examinations, imaging examinations, medical history, diagnosis, treatment options and payment information. We will compare KATP activators with other antiangina drugs using propensity score matching. The primary outcome will be major adverse cardiovascular events, defined as a composite of death, MI, stroke and rehospitalisation due to angina. ETHICS AND DISSEMINATION: The current study is designed to translate research into improved care for patients. The institutional review board of Wuhan Tongji Hospital (Liao Jiazhi, Du Aiye, Chen Zhishui, Fang Feng, Yu Shiying, Liu Dong and Li Yaping) approved the study protocol (version 1.0, July 2019, approval number TJ-IRB201909112). Here we reported a protocol related to a pre-results. Data will be presented in peer-reviewed journals, social media and relevant conferences. TRIAL REGISTRATION NUMBER: ChiCTR1900027812; Pre-results.

[Analysis of Injection of Xuesaitong (lyophilized) in 30097 cases in real world].

To investigate the extensive application of Injection of Xuesaitong(lyophilized) in clinical real world study, and provide basis for clinical guidance on rational drug use and improvement of drug instructions. A prospective, multi-center, large-sample hospital centralized monitoring method was adopted to collect the general information and medication information of all patients who received Injection of Xuesaitong(lyophilized) during the study period in the respective monitoring units. Data analysis was performed using SAS 9.1 software. This study included 79 hospitals, with 30 097 patients being recruited. The patients who met the indications for stroke and hemiplegia accounted for 31.18%, those who experienced indications of chest pain and heartache accounted for 23.15%, and patients with central retinal vein occlusion indication accounted for 0.53%. The minimum single dose of Injection of Xuesaitong(lyophilized) was 20 mg, the maximum single dose was 1 000 mg, and the average single dose was(383.31±78.10) mg. 69.96% of the patients used 0.9% sodium chloride as the menstruum, 28.78% of the patients used 5% glucose as the menstruum, and 0.19% of the patients used 10% glucose as the menstruum. The minimum time for Injection of Xuesaitong(lyophilized) to dissolve is 0 min, 120 min maximally, and(14.26±13.73) min on an average basis. Patients using Injection of Xuesaitong(lyophilized) by intravenous drip accounted for 99.93%, with a slowest drip rate of 10 drops per min, fastest drip rate of 80 drops per min, and an average of(43.91±10.77) drops per min. Injection of Xuesaitong(lyophilized) was used for a minimum of 1 day and a maximum of 80 days, with an average of(8.22±5.12) days. Combined use with other injections accounted for 80.67%, 47.14% of them flushed the tube and 3.31% of them replaced infusion sets. The study found 40 cases of adverse reactions in patients with Injection of Xuesaitong(lyophilized), with an overall incidence of 0.13%(0.09% to 0.17%) for adverse reactions. In the real world application, the usage of Injection of Xuesaitong(lyophilized) basically meets the requirement of drug instructions in terms of indications, dosages, and methods of administration. However, it still needs to be improved in standardizing the selection of the menstruum, drip rate, course of treatment, and the combined usage of medicine.

[Post-marketing intensive safety monitoring of Injection of Xuesaitong (lyophilized) in 30097 cases].

To investigate the safety of Injection of Xuesaitong(lyophilized) in clinical "real world" application, including the types, incidence, as well as the severity and treatment measures of adverse reactions/adverse events. This will serve as a basis for hospitals and enterprises to develop risk control measures. A prospective, multi-center, and large-sample hospital centralized monitoring method was used to conduct post-marketing safety monitoring of Injection of Xuesaitong(lyophilized) in medical institutions nationwide. Paper case report forms were adopted to collect general information, medication and adverse reaction information of patients using Injection of Xuesaitong(lyophilized). Data analysis was performed by using SAS 9.1 software. The study included 79 hospitals with 30 097 patients. 199 cases of adverse events were found in patients administered with Injection of Xuesaitong(lyophilized), a total of 206 times. Among 199 cases, 40 of them showed adverse reactions, accounting for an overall incidence of 0.13% and 95%CI[0.09%,0.17%], which was an occasional grade. There were 38 cases of mild adverse reactions, accounting for 95.0%, 2 cases of moderate adverse reactions, accounting for 5.0%. Adverse reaction symptoms were relieved in six patients, accounting for 15.0% of the total number of adverse reactions, adverse reaction symptoms disappeared in 34 cases, with an overall percentage of 85.0%. The results of the study showed the adverse reactions in patients using Injection of Xuesaitong(lyophilized) were rare and mild, with a good prognosis. Therefore, clinical administration of Injection of Xuesaitong(lyophilized) is relatively safe.

Selective Phosphorization Boosting High-Performance NiO/Ni2Co4P3 Microspheres as Anode Materials for Lithium Ion Batteries.

Phosphorization of metal oxides/hydoxides to promote electronic conductivity as a promising strategy has attracted enormous attention for improving the electrochemical properties of anode material in lithium ion batteries. For this article, selective phosphorization from NiCo2O4 to NiO/Ni2Co4P3 microspheres was realized as an efficient route to enhance the electrochemical lithium storage properties of bimetal Ni-Co based anode materials. The results show that varying phosphorizaed reagent amount can significantly affect the transformation of crystalline structure from NiCo2O4 to intermediate NiO, hybrid NiO/Ni2Co4P3, and, finally, to Ni2Co4P3, during which alterated sphere morphology, shifted surface valance, and enhanced lithium-ion storage behavior are detected. The optimized phosphorization with 1:3 reagent mass ratio can maintain the spherical architecture, hold hybrid crystal structure, and improve the reversibly electrochemical lithium-ion storage properties. A specific capacity of 415 mAh g-1 is achieved at 100 mA g-1 specific current and maintains at 106 mAh g-1 when the specific current increases to 5000 mA g-1. Even after 200 cycles at 500 mA g-1, the optimized electrode still delivers 224 mAh g-1 of specific capacity, exhibiting desirable cycling stability. We believe that understanding of such selective phosphorization can further evoke a particular research enthusiasm for anode materials in lithium ion battery with high performances.

Characteristics and Workload of Pediatricians in China.

OBJECTIVES: Although it is widely believed that China is facing a major shortage of pediatricians, the real situation of the current national status of pediatric human resources and their working conditions has not been evaluated to date. METHODS: We administered a survey to 54 214 hospitals from all 31 provinces in mainland China from 2015 to 2016. Hospital directors of all secondary and tertiary hospitals with pediatric services and a random sample (10%) of primary hospitals provided information on number of pediatricians and their educational levels, specialties, workloads, dropout rates, and other hospital characteristics. A data set of medical resources and socioeconomic information regarding each region (1997-2016) was constructed from the Chinese National Statistics Bureau. The Gini coefficient was used to describe the geographical distributions of pediatricians and hospitals. RESULTS: There were 135 524 pediatricians in China or ∼4 pediatricians per 10 000 children. Pediatricians' average educational level was low, with ∼32% having only 3 years of junior college training after high school. The distribution of pediatricians was extremely skewed (Gini coefficient 0.61), and the imbalance of highly educated pediatricians was even more skewed (Gini coefficient 0.68). The dropout rate of pediatricians was 12.6%. Despite an increase in the Chinese government's financial investment in health over the last decade, physicians have been burdened with a greater workload. CONCLUSIONS: Uneven development of the pediatric care system, inadequately trained pediatricians, low job satisfaction, and unmet demand for pediatric care are the major challenges facing China's pediatric health care system.

Bis(propyl)-cognitin potentiates rehabilitation of treadmill exercise after a transient focal cerebral ischemia, possibly via inhibiting NMDA receptor and regulating VEGF expression.

Combination therapies may have greater efficacy compared with monotherapy in treating stroke. We investigated the molecular mechanisms by which the combination of bis(propyl)-cognitin, an uncompetitive antagonist of NMDA receptor, and treadmill exercise promote rehabilitation after ischemic stroke. Rats were distributed into 3 treatment groups: infarct/bis(propyl)-cognitin(drug only group, DO); infarct/treadmill exercise(exercise only group, EO); infarct/bis(propyl)-cognitin + treadmill exercise (drug + exercise group, DE). The DE group had further separated to 3 sub-groups to investigate the effects achieved by different time for drug administration (60 min before stroke (DE-60 m), 15 min (DE+15 m) and 60 min (DE+60 m) after stroke). Although all infarct groups improved over time, the combination of bis(propyl)-cognitin and treadmill exercise effectively enhanced motor recovery during 14-day intervention. Early drug intervention has a best recovery result, the DE+15 m group with drug intervention at 15-min after stroke had better motor recovery than DE+60 m, DO, EO and control groups. Both bis(propyl)-cognitin and treadmill exercise significantly elevated brain VEGF expression and decreased brain infarct volume at 14 day post-ischemia. Our study reveals that bis(propyl)-cognitin potentiated rehabilitation of treadmill exercise after ischemic stroke, possibly via regulating brain VEGF expression, indicating that the combination of NMDA receptor antagonists and exercise might be useful for stroke rehabilitation.