Fast Na+ Kinetics and Suppressed Voltage Hysteresis Enabled by a High-Entropy Strategy for Sodium Oxide Cathodes.

O3-type layered transition metal cathodes are promising energy storage materials due to their sufficient sodium reservoir. However, sluggish sodium ions kinetics and large voltage hysteresis, which are generally associated with Na+ diffusion properties and electrochemical phase transition reversibility, drastically minimize energy density, reduce energy efficiency, and hinder further commercialization of sodium-ion batteries (SIBs). Here, this work proposes a high-entropy tailoring strategy through manipulating the electronic local environment within transition metal slabs to circumvent these issues. Experimental analysis combined with theoretical calculations verify that high-entropy metal ion mixing contributes to the improved reversibility of redox reaction and O3-P3-O3 phase transition behaviors as well as the enhanced Na+ diffusivity. Consequently, the designed O3-Na0.9Ni0.2Fe0.2Co0.2Mn0.2Ti0.15Cu0.05O2 material with high-entropy characteristic could display a negligible voltage hysteresis (<0.09 V), impressive rate capability (98.6 mAh g-1 at 10 C) and long-term cycling stability (79.4% capacity retention over 2000 cycles at 5 C). This work provides insightful guidance in mitigating the voltage hysteresis and facilitating Na+ diffusion of layered oxide cathode materials to realize high-rate and high-energy SIBs.

Tobacco retailer outside middle schools in Wuhan City and its impact on smoking behavior among students / 中国学校卫生

Objective@#To understand the distribution of tobacco retailer within 100 meters outside middle schools in Wuhan City and its impact on smoking behavior of middle school students, so as to provide basis and feasible suggestions for the development of tobacco control policy for adolescents.@*Methods@#From February to May 2023, a multi stage stratified cluster random sampling method was used to select 20 middle schools from 4 districts in Wuhan City. To investigate the distribution of tobacco retailer within 100 metres outside the school and the sale of tobacco to minors. A total of 4 882 students were surveyed using the core questions of the 2021 Chinese Adolescent Tobacco Prevalence Questionnaire. Fisher exact probability test, Chi square test and Chi square trend test were used for statistical analysis.@*Results@#Nearly 70.00% of middle schools had tobacco retailer within 100 metres, with an average of (1.10±0.97) per middle school. The awareness rate (100.00%) and labeling rate (87.50%) of licensed tobacco retailer were higher than those of non licensed tobacco retailer (33.33%, 16.67%) ( P <0.05). The rates of tried smoking, current smoking and buying cigarettes within 30 days were 7.13%, 1.99% and 2.54%, respectively. The rates of students who tried smoking ( 8.58 %), current smoking (2.29%) and buying cigarettes within 30 days (2.85%) in schools with tobacco retailer within 100 metres were higher than those in schools without tobacco retailer (3.79%, 1.28%, 1.83%)( χ 2=35.80, 5.37, 4.37 , P <0.05). And as the grade increased, the rates of tried smoking, current smoking and buying cigarettes among middle school students all showed an upward trend ( χ 2 trend =66.20, 36.10, 16.17, P <0.05).@*Conclusions@#Middle school students in Wuhan City have high tobacco availability. The findings suggest that school ban should be extended from 50 meters to 100 meters, and the regulatory authorities must strictly prohibit selling tobacco products to minors at tobacco retailer.

A multiple-step screening protocol to identify norepinephrine and dopamine reuptake inhibitors for depression.

Depression severely impairs the health of people all over the world. Cognitive dysfunction due to depression has resulted in a severe economic burden to family and society induced by the reduction of social functioning of patients. Norepinephrine-dopamine reuptake inhibitors (NDRIs) targeted with the human norepinephrine transporter (hNET) and distributed with the human dopamine transporter (hDAT) simultaneously treat depression and improve cognitive function, and they effectively prevent sexual dysfunction and other side effects. Because many patients continue to poorly respond to NDRIs, it is urgent to discover novel NDRI antidepressants that do not interfere with cognitive function. The aim of this work was to selectively identify novel NDRI candidates acting against hNET and hDAT from large compound libraries by a comprehensive strategy integrating support vector machine (SVM) models, ADMET, molecular docking, in vitro binding assays, molecular dynamics simulation, and binding energy calculation. First, 6522 compounds that do not inhibit the human serotonin transporter (hSERT) were obtained by SVM models of hNET, hDAT, and non-target hSERT with similarity analyses from compound libraries. ADMET and molecular docking were then used to identify compounds that could potently bind to the hNET and hDAT with satisfactory ADMET, and 4 compounds were successfully identified. According to their docking scores and ADMET information, 3719810 was advanced for profiling by in vitro assays as a novel NDRI lead compound due to its strongest druggability and balancing activities. Encouragingly, 3719810 performed comparative activities on two targets, with Ki values of 7.32 µM for hNET and 5.23 µM for hDAT. To obtain candidates with additional activities and balance the activities of 2 targets, 5 analogs were optimized, and 2 novel scaffold compounds were successively designed. By assessment of molecular docking, molecular dynamics simulations, and binding energy calculations, 5 compounds were validated as NDRI candidates with high activities, and 4 of them performed acceptable balancing activities acting on hNET and hDAT. This work supplied promising novel NDRIs for treatment of depression with cognitive dysfunction or other related neurodegenerative disorders, and also provided a strategy for highly efficient and cost-effective identification of inhibitors for dual targets with homologous non-targets.

Changes in the health literacy of residents aged 15-69 years in central China: A three-round cross-sectional study.

Introduction: Health literacy is an effective strategy to promote more cost-effective use of health care services and a crucial tool for preventing the spread of infectious diseases. The main objective of this study was to analyze changes in health literacy from 2019 to 2021. Methods: Data were from the latest three-round cross-sectional studies with the same study design. Results: Although the prevalence of adequate health literacy rose significantly over time, increasing from 26.9% (95% CI 20.1-33.7) in 2019 to 34.1% (32.9-35.3) in 2021, it was still at a relatively low level. The most significant decrease was observed for health skills among the three aspects and health information literacy among the six dimensions. Working as medical staff was a protective factor for adequate health literacy, health skills literacy, and health information literacy. Risk factors for adequate health literacy and health information literacy were older age and lower education level. Furthermore, adequate health information literacy was positively related to annual family income. Discussion: More practical and effective policies targeting health literacy for critical aspects and groups in Central China, are urgently needed, especially during the epidemic.

Investigating the performance of three modified activated sludge processes treating municipal wastewater in organic pollutants removal and toxicity reduction.

This study investigated the treatment performance of three types of modified activated sludge processes, i.e., anoxic/oxic (A/O), anaerobic/anoxic/oxic (A2/O) and oxidation ditch process, in treating municipal wastewater by measuring physicochemical and spectroscopic parameters, and the toxicity of the influents and effluents collected from 8 full-scale municipal wastewater treatment plants (MWTPs). The relationships between spectroscopic and physicochemical parameters of the wastewater samples and the applicability of the nematode Caenorhabditis elegans (C. elegans) bioassays for the assessment of the toxic properties of municipal wastewater were also evaluated. The results indicated that the investigated MWTPs employing any of A/O, A2/O and oxidation ditch processes could effectively control the discharge of major wastewater pollutants including biochemical oxygen demand (BOD), chemical oxygen demand, nitrogen and phosphorus. The oxidation ditch process appeared to have the advantage of removing tyrosine-like substances and presented slightly better removal efficiency of tryptophan-like fluorescent (peak T) substances than the A/O and A2/O processes. Both ultraviolet absorbance at 254nm and peak T may be used to characterize the organic load of municipal wastewater, and peak T can be adopted as a gauge of the BOD removal efficacy of municipal wastewater treatment. Using C. elegans-based oxygen consumption rate assay for monitoring municipal wastewater toxicity deserves further investigations.

Toxicity of 2,6-dichloro-1,4-benzoquinone and five regulated drinking water disinfection by-products for the Caenorhabditis elegans nematode.

Scarce toxicological data are available for 2,6-dichloro-1,4-benzoquinone (DCBQ), an emerging water disinfection by-product (DBP) that is of potential public health concern. This study investigated the effects of DCBQ on the lethality, respiration rate, and DNA damage in the Caenorhabditis elegans nematode. Meanwhile, the toxic effects of five regulated DBPs, dichloroacetic acid (DCA), trichloroacetic acid (TCA), monobromoacetic acid (MBA), dibromoacetic acid (DBA), and N-nitrosodimethylamine (NDMA), have also been evaluated. The tested DBPs increased the lethality and inhibited the respiration of C. elegans with an identical order of toxicity as follows: DCBQ>MBA>DBA>DCA>TCA>NDMA. The EC50 value (median concentration causing 50% reduction in respiration compared with untreated C. elegans) is at least 30-fold lower than the corresponding LC50 value (median lethal concentration). Exposure to DCBQ and NDMA, but not to MBA, DBA, DCA, or TCA, resulted in DNA damage to C. elegans. The study suggested that DCBQ was more potent in inducing general toxicity than some regulated DBPs, and it revealed the in vivo genotoxic effect of DCBQ. Furthermore, the C. elegans-based bioassays may provide potentially useful tools for the toxicology assessment and ranking of DBPs.

Detection of genotoxic effects of drinking water disinfection by-products using Vicia faba bioassay.

Plant-based bioassays have gained wide use among the toxicological and/or ecotoxicological assessment procedures because of their simplicity, sensitivity, low cost, and reliability. The present study describes the use of Vicia faba (V. faba) micronucleus (MN) test and V. faba comet assay in the evaluation of the genotoxic potential of disinfection by-products (DBPs) commonly found in chlorine-disinfected drinking water. Five haloacetic acids and three halogenated acetonitriles were chosen as representatives of DBPs in this study because they are of potentially great public health risk. Results of the MN test indicated that monochloroacetic acid (MCA), monobromoacetic acid (MBA), dichloroacetic acid (DCA), dibromoacetic acid (DBA), trichloroacetic acid (TCA), and trichloroacetonitrile (TCAN) caused a statistically significant increase in MN frequency in V. faba root tip cells. However, no genotoxic response was observed for dichloroacetonitrile (DCAN) and dibromoacetonitrile (DBAN). Results of the comet assay showed that all tested DBPs induced a statistically significant increase in genomic DNA damage to V. faba root tip cells. On considering the capacity to detect genomic damage of a different nature, we suggest that a combination of V. faba MN test and V. faba comet assay is a useful tool for the detection of genotoxic effects of DBPs. It is worthy of assessing the feasibility of using V. faba comet assay combined with V. faba MN test to screen for the genotoxic activity of chlorinated drinking water in future work.

Single-chain Fv-streptavidin substantially improved therapeutic index in multistep targeting directed at disialoganglioside GD2.

UNLABELLED: Multistep targeting can improve the therapeutic index of antibody-based targeting, particularly relevant to pediatric tumors where acute toxicity and late effects of treatment are major concerns. Neuroblastoma is uniquely suited for such investigations because of its abundance of surface ganglioside GD2. METHODS: 5F11scFv (scFv = single-chain variable fragment) was constructed from the variable regions of the heavy (V(H)) and kappa-light (V(L)) chain complementary DNA (cDNA) of anti-GD2 IgM hybridoma 5F11 and ligated to full-length streptavidin cDNA for expression in Escherichia coli. Purified 5F11-scFv-streptavidin (5F11-scFv-SA) was a homotetramer and showed comparable avidity to 5F11 IgM and a 30-fold improvement over monomeric scFv. Biodistribution of 5F11-scFv-SA was studied in nude mice xenografted with neuroblastoma LAN-1. Twenty-four hours after intravenous injection of 300-900 microg 5F11-scFv-SA, 150-450 microg of a thiogalactoside-containing clearing agent, (Gal-NAc)(16)-alpha-S-C(5)H(10)-NH-LC-N-Me-biotin (molecular weight, 8652), were administered intravenously, followed by approximately 2.5 microg (1.85-3.7 MBq) (111)In-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-biotin ((111)In-DOTA-biotin) intravenously 4 h later and clocked as time 0. RESULTS: Tumor uptake (percentage of injected dose per gram [%ID/g]) at 2 h was 7 %ID/g and decayed with a half-life of 72 h, whereas blood %ID/g rapidly decreased to <1/500 of that of tumor after the first 24 h. The tumor-to-nontumor (T/NT) ratio at 72 h was high (median, 106; range, 3.4 [kidney] to 1660 [blood]). When the area under the radioactivity curve was computed, the T/NT organ ratio was favorable (4.8 for kidney and 162 for blood). When human and murine tumors were surveyed, the T/NT ratio of (111)In-DOTA-biotin uptake correlated with their levels of GD2 expression as assayed by flow cytometry. Biotinylated polypeptides (bovine serum albumin and vasointestinal peptides) achieved selective tumor targeting when the multistep strategy was applied. CONCLUSION: Improvement in the T/NT ratio using pretargeting strategy may increase the efficacy and safety of scFv-based approaches in cancer therapy. Additionally, since biotinylated polypeptides can be rendered tumor selective, a large repertoire of agents can potentially be explored.

Combination therapy with Pretarget CC49 radioimmunotherapy and gemcitabine prolongs tumor doubling time in a murine xenograft model of colon cancer more effectively than either monotherapy.

Pretarget radioimmunotherapy (RIT) is a multistep strategy for cancer therapy designed to reduce nontarget organ exposure by uncoupling the tumor targeting moiety from the radioactive ligand. Using this approach, we and others have demonstrated objective responses to therapy among patients with non-Hodgkin's lymphoma, with less hematological toxicity than is typically seen at equivalent doses of conventional RIT in the same patient population. In the present study, we show that combination therapy with gemcitabine (200 mg/kg on days -1 and +1) and Pretarget RIT (400 micro Ci (90)Y-labeled DOTA-biotin on day +1) is superior to Pretarget monotherapy (400 or 800 micro Ci (90)Y) as well as to gemcitabine monotherapy in nude mice bearing established human LS174T colon cancer xenografts. For the targeting moiety, we used a murine anti-TAG-72 (CC49) single-chain Fv-streptavidin (scFvSA) fusion protein that has been shown to be safe and well-tolerated in humans. The median number of days to tumor volume doubling in the gemcitabine-only studies (200 mg/kg) was 10.4 +/- 5.5 days; in the Pretarget 400 micro Ci dose-only studies, tumor doubling time was 6.7 +/- 4.9 days; and in combination therapy studies, it was 23.9 +/- 7.2 days (P