A comprehensive study of SARS-CoV-2 main protease (Mpro) inhibitor-resistant mutants selected in a VSV-based system.

Nirmatrelvir was the first protease inhibitor specifically developed against the SARS-CoV-2 main protease (3CLpro/Mpro) and licensed for clinical use. As SARS-CoV-2 continues to spread, variants resistant to nirmatrelvir and other currently available treatments are likely to arise. This study aimed to identify and characterize mutations that confer resistance to nirmatrelvir. To safely generate Mpro resistance mutations, we passaged a previously developed, chimeric vesicular stomatitis virus (VSV-Mpro) with increasing, yet suboptimal concentrations of nirmatrelvir. Using Wuhan-1 and Omicron Mpro variants, we selected a large set of mutants. Some mutations are frequently present in GISAID, suggesting their relevance in SARS-CoV-2. The resistance phenotype of a subset of mutations was characterized against clinically available protease inhibitors (nirmatrelvir and ensitrelvir) with cell-based, biochemical and SARS-CoV-2 replicon assays. Moreover, we showed the putative molecular mechanism of resistance based on in silico molecular modelling. These findings have implications on the development of future generation Mpro inhibitors, will help to understand SARS-CoV-2 protease inhibitor resistance mechanisms and show the relevance of specific mutations, thereby informing treatment decisions.

Spatiotemporal analysis of the food-related carbon emissions of China: Regional heterogeneity and the urban‒rural divide.

As the world's largest carbon emitter of food systems, China's goal of carbon neutrality cannot be achieved without addressing the issue of food GHGs. Given the knowledge gap in subnational spatiotemporal research on China's food carbon emissions, especially drivers of regional heterogeneity and the urban‒rural divide, this study uses the household metabolism approach, the gray correlation, and logarithmic mean Divisia index decomposition to assess food-related carbon emissions (FCEs) in China, conducts urban‒rural comparisons and quantifies emission drivers across 31 provinces/regions from 1990 to 2022. The data are sourced from authentic and credible government departments. The results indicate a notable increase in FCEs in most provinces for urban regions following periods of slight decline (1990-2001), sharp increase (2001-2016), and slow growth (2016-2022). In contrast, there has been a more pronounced increase in most provinces for rural regions following a phase of slow growth (1990-2002), a marked decline (2002-2012), and a sharp rise (2012-2022). Among others, per capita carbon emissions from plant-based foods decreased from 345.79 kg in 1990 to 262.70 kg in 2022, whereas emissions from animal-based foods increased from 90.78 kg to 284.39 kg over the same period, suggesting that dietary changes have been a major contributor. Clustering based on the gray correlation further confirms the large interprovincial heterogeneity and significant urban‒rural divide. Regardless of cluster and stage, affluence consistently and significantly drives the growth of FCEs in urban/rural areas, whereas food consumption intensity consistently and significantly contributes to this reduction. The Engel coefficient reduces carbon emissions by a large amount, and the carbon emission factor increases urban/rural FCEs, albeit by a small amount. Consumption willingness reduces FCEs in urban areas but increases FCEs in rural areas in most stages. These findings can aid policy-makers in designing emission reduction policies tailored to the local context.

Complete genome of Streptococcus agalactiae strain XM_1.

Streptococcus agalactiae can cause a variety of human diseases, posing a deadly threat especially in the case of infections in newborns. A strain of Streptococcus agalactiae, designated as XM_1, was isolated from a newborn with severe clinical symptoms. Here, the genome sequence of Streptococcus agalactiae strain XM_1 is presented.

Incorporating nanosilver with glass ionomer cement-A literature review.

OBJECTIVES: The objectives of this study were to retrieve and review studies that incorporated nanosilver with GIC and summarise the evidence regarding the properties of nanosilver-modified GIC. MATERIALS AND METHODS: Two independent researchers performed a literature search using the keywords (nanosilver OR nano-silver OR (nano silver) OR (silver nanoparticles)) AND (GIC OR (glass ionomer cement) OR (glass ionomer cements)) in PubMed, Web of Science and ScienceDirect. RESULTS: A total of 368 articles were identified. After removing duplicate results, titles and abstracts were screened for eligibility. Full texts of publications that investigated the manufacture and properties of nanosilver-modified GIC were retrieved and analysed. Finally, 21 studies were included. CONCLUSIONS: All of the studies reviewed in this investigation included the incorporation of nanosilver in GIC. The proportions of nanosilver added into GIC varied from 0.05 % to 50 %. Thirteen studies investigated the antimicrobial properties of nanosilver-modified GIC; all studies supported that adding nanosilver enhanced antimicrobial effectiveness. Nineteen studies reported the mechanical properties including compressive strength, flexure strength, tensile strength, and microhardness of nanosilver-modified GIC; but the results were inconclusive. Four studies tested the bonding strength of nanosilver-modified GIC to dentine and found that adding nanosilver would not influence the bonding property of GIC. Some studies explored fluoride release level, colour stability, and cytotoxicity of nanosilver-modified GIC; but the results were all inconclusive. CLINICAL SIGNIFICANCE: This literature review is the first study to retrieve and summarise the findings and evidence regarding nanosilver-modified GIC research. It can provide clinicians with clinically relevant information about novel GIC materials that can be used in their treatment decisions.

Highly specific SARS-CoV-2 main protease (Mpro) mutations against the clinical antiviral ensitrelvir selected in a safe, VSV-based system.

In the SARS-CoV-2 pandemic, the so far two most effective approved antivirals are the protease inhibitors nirmatrelvir, in combination with ritonavir (Paxlovid) and ensitrelvir (Xocova). However, antivirals and indeed all antimicrobial drugs are sooner or later challenged by resistance mutations. Studying such mutations is essential for treatment decisions and pandemic preparedness. At the same time, generating resistant viruses to assess mutants is controversial, especially with pathogens of pandemic potential like SARS-CoV-2. To circumvent gain-of-function research with non-attenuated SARS-CoV-2, a previously developed safe system based on a chimeric vesicular stomatitis virus dependent on the SARS-CoV-2 main protease (VSV-Mpro) was used to select mutations against ensitrelvir. Ensitrelvir is clinically especially relevant due to its single-substance formulation, avoiding drug-drug interactions by the co-formulated CYP3A4 inhibitor ritonavir in Paxlovid. By treating VSV-Mpro with ensitrelvir, highly-specific resistant mutants against this inhibitor were selected, while being still fully or largely susceptible to nirmatrelvir. We then confirmed several ensitrelvir-specific mutants in gold standard enzymatic assays and SARS-CoV-2 replicons. These findings indicate that the two inhibitors can have distinct viral resistance profiles, which could determine treatment decisions.

AKAP95 regulates ubiquitination and degradation of cyclin Ds/Es, influencing the G1/S transition of lung cancer cells.

A-kinase anchoring protein 95 (AKAP95) functions as a scaffold for protein kinase A. Prior work by our group has shown that AKAP95, in coordination with Connexin 43 (Cx43), modulates the expression of cyclin D and E proteins, thus affecting the cell cycle progression in lung cancer cells. In the current study, we confirmed that AKAP95 forms a complex with Cx43. Moreover, it associates with cyclins D1 and E1 during the G1 phase, leading to the formation of protein complexes that subsequently translocate to the nucleus. These findings indicate that AKAP95 might facilitate the nuclear transport of cyclins D1 and E1. Throughout this process, AKAP95 and Cx43 collectively regulate the expression of cyclin D, phosphorylate cyclin E1 proteins, and target their specific ubiquitin ligases, ultimately impacting cell cycle progression.

Dissecting and tracing the gut microbiota of infants with botulism: a cross sectional and longitudinal study.

Background: Infant botulism is caused by botulinum neurotoxin (BoNT), which is mainly produced by Clostridium botulinum. However, there is a lack of longitudinal cohort studies on infant botulism. Herein, we have constructed a cross-sectional and longitudinal cohort of infants infected with C. botulinum. Our goal was to reveal the differences in the intestinal microbiota of botulism-infected and healthy infants as well as the dynamic changes over time through multi-omics analysis. Methods: We performed 16S rRNA sequencing of 20 infants' stools over a period of 3 months and conducted whole genome sequencing of isolated C. botulinum strains from these laboratory-confirmed cases of infant botulism. Through bioinformatics analysis, we focused on the changes in the infants' intestinal microbiota as well as function over time series. Results: We found that Enterococcus was significantly enriched in the infected group and declined over time, whereas Bifidobacterium was significantly enriched in the healthy group and gradually increased over time. 18/20 isolates carried the type B 2 botulinum toxin gene with identical sequences. In silico Multilocus sequence typing found that 20\u00B0C. botulinum isolates from the patients were typed into ST31 and ST32. Conclusion: Differences in intestinal microbiota and functions in infants were found with botulism through cross-sectional and longitudinal studies and Bifidobacterium may play a role in the recovery of infected infants.

Exogenous Glucose Interferes with Antimicrobial-Mediated ROS Accumulation and Bacterial Death.

Glucose is widely used in the reconstitution of intravenous medications, which often include antimicrobials. How glucose affects antimicrobial activity has not been comprehensively studied. The present work reports that glucose added to bacteria growing in a rich medium suppresses the bactericidal but not the bacteriostatic activity of several antimicrobial classes, thereby revealing a phenomenon called glucose-mediated antimicrobial tolerance. Glucose, at concentrations corresponding to blood-sugar levels of humans, increased survival of Escherichia coli treated with quinolones, aminoglycosides, and cephalosporins with little effect on minimal inhibitory concentration. Glucose suppressed a ROS surge stimulated by ciprofloxacin. Genes involved in phosphorylated fructose metabolism contributed to glucose-mediated tolerance, since a pfkA deficiency, which blocks the formation of fructose-1,6-bisphosphate, eliminated protection by glucose. Disrupting the pentose phosphate pathway or the TCA cycle failed to alter glucose-mediated tolerance, consistent with an upstream involvement of phosphorylated fructose. Exogenous sodium pyruvate or sodium citrate reversed glucose-mediated antimicrobial tolerance. Both metabolites bypass the effects of fructose-1,6-bisphosphate, a compound known to scavenge hydroxyl radical and chelate iron, activities that suppress ROS accumulation. Treatment with these two compounds constitutes a novel way to mitigate the glucose-mediated antimicrobial tolerance that may exist during intravenous antimicrobial therapy, especially for diabetes patients.

Bafi A1 inhibits nano-copper oxide-induced mitochondrial damage by reducing the release of copper from lysosomes.

This study demonstrated that both copper oxide nanoparticles (CuO-NPs) and copper nanoparticles (Cu-NPs) can cause swelling, inflammation, and cause damage to the mitochondria of alveolar type II epithelial cells in mice. Cellular examinations indicated that both CuO-NPs and Cu-NPs can reduce cell viability and harm the mitochondria of human bronchial epithelial cells, particularly Beas-2B cells. However, it is clear that CuO-NPs exhibit a more pronounced detrimental effect compared with Cu-NPs. Using bafilomycin A1 (Bafi A1), an inhibitor of lysosomal acidification, was found to enhance cell viability and alleviate mitochondrial damage caused by CuO-NPs. Additionally, Bafi A1 also reduces the accumulation of dihydrolipoamide S-acetyltransferase (DLAT), a marker for mitochondrial protein toxicity, induced by CuO-NPs. This observation suggests that the toxicity of CuO-NPs depends on the distribution of copper particles within cells, a process facilitated by the acidic environment of lysosomes. The release of copper ions is thought to be triggered by the acidic conditions within lysosomes, which aligns with the lysosomal Trojan horse mechanism. However, this association does not seem to be evident with Cu-NPs.

[Identification and visual analysis of ginsenosides in multi-steamed roots of Panax quinquefolium based on UPLC-Q-TOF-MS/MS and MALDI-MSI].

This study aims to investigate the component variations and spatial distribution of ginsenosides in Panax quinquefolium roots during repeated steaming and drying. Ultra performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS/MS) was employed to identify the ginsenosides in the root extract. Matrix-assisted laser desorption/ionization mass spectrometry imaging(MALDI-MSI) was employed to visualize the spatial distribution and spatiotemporal changes of prototype ginsenosides and metabolites in P. quinquefolium roots. The UPLC results showed that 90 ginsenosides were identified during the steaming process of the roots, and polar ginsenosides were converted into low polar or non-polar ginsenosides. The content of prototype ginsenosides decreased, while that of rare ginsenosides increased, which included 20(S/R)-ginsenoside Rg_3, 20(S/R)-ginsenoside Rh_2, and ginsenosides Rk_1, Rg_5, Rs_5, and Rs_4. MALDI-MSI results showed that ginsenosides were mainly distributed in the epidermis and phloem. As the steaming times increased, ginsenosides were transported to the xylem and medulla. This study provides fundamental information for revealing the changes of biological activity and pharmacological effect of P. quinquefolium roots that are caused by repeated steaming and drying and gives a reference for expanding the application scope of this herbal medicine.

Dose-response relationship of levodopa with dyskinesia in Parkinson's disease: A systematic review and meta-analysis.

Despite existing evidence linking dyskinesia to levodopa, the primary treatment for Parkinson's, the dose-response relationship and risk factors remain uncertain. In this study, the risk for dyskinesia in patients with Parkinson's disease receiving levodopa was evaluated via meta-analysis and meta-regression approaches to examine dyskinesia risk factors more reliably and improve treatment strategies and patient care. The PubMed and Embase databases were searched to identify randomized controlled trials comparing levodopa with other anti-Parkinson's drugs published in English before June 31, 2023. The primary outcome was dyskinesia, and a risk of bias assessment was performed. In total, 24 studies met the inclusion criteria; 21 had a low risk of bias, and 3 had a high risk of bias. These studies included 4698 patients with Hoehn and Yahr Grade I-III Parkinson's disease. Our meta-analysis showed that the risk of dyskinesia was higher for levodopa than for other anti-Parkinson's drugs (odds ratio: 2.52 [95% confidence interval: 1.84-3.46]). Dyskinesia was not related to age (slope coefficient: 0.185 [0.095]; P = 0.061), disease duration (slope coefficient: 0.011 [0.018]; P = 0.566), or treatment duration (slope coefficient: 0.008 [0.007]; P = 0.216). The mean levodopa equivalent dose (slope coefficient: 0.004 [0.001]; P = 0.001) in the experimental group and the differences in drug doses between the experimental and control groups were correlated with the risk of dyskinesia. Results of randomized controlled trials supported an association between the levodopa dose and dyskinesia in patients with Parkinson's disease. Compared with levodopa users, users of other anti-Parkinson's drugs had a lower incidence of dyskinesia. Age, disease duration, and treatment duration were not correlated with dyskinesia. These findings suggest that anti-Parkinson's drugs other than levodopa, particularly in cases of early-stage Parkinson's disease, should be considered to reduce the risk of dyskinesia.

Alterations of sleep deprivation on brain function: A coordinate-based resting-state functional magnetic resonance imaging meta-analysis.

BACKGROUND: Sleep deprivation is a prevalent issue that impacts cognitive function. Although numerous neuroimaging studies have explored the neural correlates of sleep loss, inconsistencies persist in the reported results, necessitating an investigation into the consistent brain functional changes resulting from sleep loss. AIM: To establish the consistency of brain functional alterations associated with sleep deprivation through systematic searches of neuroimaging databases. Two meta-analytic methods, signed differential mapping (SDM) and activation likelihood estimation (ALE), were employed to analyze functional magnetic resonance imaging (fMRI) data. METHODS: A systematic search performed according to PRISMA guidelines was conducted across multiple databases through July 29, 2023. Studies that met specific inclu-sion criteria, focused on healthy subjects with acute sleep deprivation and reported whole-brain functional data in English were considered. A total of 21 studies were selected for SDM and ALE meta-analyses. RESULTS: Twenty-one studies, including 23 experiments and 498 subjects, were included. Compared to pre-sleep deprivation, post-sleep deprivation brain function was associated with increased gray matter in the right corpus callosum and decreased activity in the left medial frontal gyrus and left inferior parietal lobule. SDM revealed increased brain functional activity in the left striatum and right central posterior gyrus and decreased activity in the right cerebellar gyrus, left middle frontal gyrus, corpus callosum, and right cuneus. CONCLUSION: This meta-analysis consistently identified brain regions affected by sleep deprivation, notably the left medial frontal gyrus and corpus callosum, shedding light on the neuropathology of sleep deprivation and offering insights into its neurological impact.

A Novel Rotavirus Reverse Genetics Platform Supports Flexible Insertion of Exogenous Genes and Enables Rapid Development of a High-Throughput Neutralization Assay.

Despite the success of rotavirus vaccines, rotaviruses remain one of the leading causes of diarrheal diseases, resulting in significant childhood morbidity and mortality, especially in low- and middle-income countries. The reverse genetics system enables the manipulation of the rotavirus genome and opens the possibility of using rotavirus as an expression vector for heterologous proteins, such as vaccine antigens and therapeutic payloads. Here, we demonstrate that three positions in rotavirus genome-the C terminus of NSP1, NSP3 and NSP5-can tolerate the insertion of reporter genes. By using rotavirus expressing GFP, we develop a high-throughput neutralization assay and reveal the pre-existing immunity against rotavirus in humans and other animal species. Our work shows the plasticity of the rotavirus genome and establishes a high-throughput assay for interrogating humoral immune responses, benefiting the design of next-generation rotavirus vaccines and the development of rotavirus-based expression platforms.

L-glutamine protects against enterohemorrhagic Escherichia coli infection by inhibiting bacterial virulence and enhancing host defense concurrently.

IMPORTANCE: The type 3 secretion system (T3SS) was obtained in many Gram-negative bacterial pathogens, and it is crucial for their pathogenesis. Environmental signals were found to be involved in the expression regulation of T3SS, which was vital for successful bacterial infection in the host. Here, we discovered that L-glutamine (Gln), the most abundant amino acid in the human body, could repress enterohemorrhagic Escherichia coli (EHEC) T3SS expression via nitrogen metabolism and therefore had potential as an antivirulence agent. Our in vitro and in vivo evidence demonstrated that Gln could decline EHEC infection by attenuating bacterial virulence and enhancing host defense simultaneously. We repurpose Gln as a potential treatment for EHEC infection accordingly.

Vaccination with a replication-defective cytomegalovirus vaccine elicits a glycoprotein B-specific monoclonal antibody repertoire distinct from natural infection.

Human Cytomegalovirus (HCMV) is the leading infectious congenital infection globally and the most common viral infection in transplant recipients, therefore identifying a vaccine for HCMV is a top priority. Humoral immunity is a correlate of protection for HCMV infection. The most effective vaccine tested to date, which achieved 50% reduction in acquisition of HCMV, was comprised of the glycoprotein B protein given with an oil-in-water emulsion adjuvant MF59. We characterize gB-specific monoclonal antibodies isolated from individuals vaccinated with a disabled infectious single cycle (DISC) CMV vaccine, V160, and compare these to the gB-specific monoclonal antibody repertoire isolated from naturally-infected individuals. We find that vaccination with V160 resulted in gB-specific antibodies that bound homogenously to gB expressed on the surface of a cell in contrast to antibodies isolated from natural infection which variably bound to cell-associated gB. Vaccination resulted in a similar breadth of gB-specific antibodies, with binding profile to gB genotypes 1-5 comparable to that of natural infection. Few gB-specific neutralizing antibodies were isolated from V160 vaccinees and fewer antibodies had identifiable gB antigenic domain specificity compared to that of naturally-infected individuals. We also show that glycosylation of gB residue N73 may shield binding of gB-specific antibodies.

[Comparison on blood-prostate barrier permeability of tanshinone extract and corresponding major monomers].

In this study, the transmittance of tanshinone Ⅱ_A(Tan Ⅱ_A) and cryptotanshinone(CTS) through the blood-prostate barrier and their distributions in the prostate tissue were compared between tanshinone extract(Tan E) treatment group and the corresponding monomer composition group under the equivalent dose conversion in vitro and in vivo. First, the human prostate epithelial cell line RWPE-1 was cultured in vitro for 21 days for the establishment of a blood-prostate barrier model, and the transmission of Tan Ⅱ_A and CTS through the barrier model was investigated after administration of Tan E and corresponding single active components. Second, SD rats were administrated with 700 mg·kg~(-1) Tan E, 29 mg·kg~(-1) CTS, and 50 mg·kg~(-1) Tan Ⅱ_A by gavage, and plasma and prostate tissue samples were collected at the time points of 2, 4, 8, 12, and 24 h. The Tan Ⅱ_A and CTS concentrations in the samples were determined. The results showed that in the cell model, the cumulative transmission amounts of CTS and Tan Ⅱ_A in the extract at each time point were higher than those of the corresponding single active components(P<0.01). In rats, after the administration of Tan E, the concentrations of Tan Ⅱ_A and CTS in rat plasma and prostate were higher than those of the corresponding single active components. This study demonstrated that the coexisting components in Tan E promoted the penetration of its main pharmacological components Tan Ⅱ_A and CTS through the blood-prostate barrier. The findings provide a theoretical and experimental basis for the application of Tan E in the clinical treatment of prostate-related diseases.

Safety, efficacy, and immunogenicity of a replication-defective human cytomegalovirus vaccine, V160, in cytomegalovirus-seronegative women: a double-blind, randomised, placebo-controlled, phase 2b trial.

BACKGROUND: A vaccine that prevents cytomegalovirus (CMV) infection in women could reduce the incidence of congenital CMV infection, a major cause of neurodevelopmental disability. We aimed to assess the safety and efficacy of a replication-defective investigational CMV vaccine, V160, in CMV-seronegative women. METHODS: This phase 2b, randomised, double-blind, placebo-controlled study was conducted at 90 sites in seven countries (USA, Finland, Canada, Israel, Spain, Russia, and Australia). Eligible participants were generally healthy, CMV-seronegative, non-pregnant, 16-35-year-old women of childbearing potential with exposure to children aged 5 years or younger. Participants were randomly assigned using central randomisation via an interactive response technology system 1:1:1 to one of three groups: V160 three-dose regimen (V160 at day 1, month 2, and month 6), V160 two-dose regimen (V160 on day 1, placebo at month 2, and V160 at month 6), or placebo (saline solution at day 1, month 2, and month 6). The primary outcomes were the efficacy of three doses of V160 in reducing the incidence of primary CMV infection during the follow-up period starting 30 days after the last dose of vaccine using a fixed event rate design, and the safety and tolerability of the two-dose and three-dose V160 regimens. We planned to test the efficacy of a two-dose regimen of V160 in reducing the incidence of primary CMV infection only if the primary efficacy hypothesis was met. Analyses for the primary efficacy endpoint were performed on the per-protocol efficacy population; safety analyses included all randomly assigned participants who received study vaccine. The primary efficacy hypothesis was tested at prespecified interim and final analyses. The study was ongoing and efficacy data continued to accrue at the time of final testing of the primary efficacy hypothesis. Vaccine efficacy was re-estimated after final testing of the primary efficacy hypothesis based on all available efficacy data at end of study. This trial is registered at ClinicalTrials.gov (NCT03486834) and EudraCT (2017-004233-86) and is complete. FINDINGS: Between April 30, 2018, and Aug 30, 2019, 7458 participants were screened, of whom 2220 were randomly assigned to the V160 three-dose group (n=733), V160 two-dose group (n=733), or placebo group (n=734). A total of 523 participants in the V160 three-dose group and 519 in the placebo group were included in the final hypothesis testing. Of these, there were 11 cases of CMV infection in the V160 three-dose group and 20 cases in the placebo group. The vaccine efficacy for the V160 three-dose group was 44·6% (95% CI -15·2 to 74·8) at the final testing of the primary efficacy hypothesis, a result corresponding to failure to demonstrate the primary efficacy hypothesis. On the basis of this result, the study was terminated for futility. The re-estimate of vaccine efficacy for the V160 three-dose group based on all available efficacy data at end of study (556 participants in the V160 three-dose group and 543 in the placebo group) was 42·4% (95% CI -13·5 to 71·1). A total of 728 participants in the V160 three-dose group, 729 in the V160 two-dose group, and 732 in the placebo group were included in the safety analyses. The most common solicited injection-site adverse event was injection-site pain (680 [93%] in the V160 three-dose group, 659 [90%] in the V160 two-dose group, and 232 [32%] in the placebo group). The most common solicited systemic adverse event was fatigue (457 [63%] in the V160 three-dose group, 461 [63%] in the V160 two-dose group, and 357 [49%] in the placebo group). No vaccine-related serious adverse events or deaths were reported. INTERPRETATION: V160 was generally well tolerated and immunogenic; however, three doses of the vaccine did not reduce the incidence of primary CMV infection in CMV-seronegative women compared with placebo. This study provides insights into the design of future CMV vaccine efficacy trials, particularly for the identification of CMV infection using molecular assays. FUNDING: Merck Sharp & Dohme, a subsidiary of Merck & Co, Rahway, NJ, USA (MSD).

Hybrid Crosslinked Solid Polymer Electrolyte via In-Situ Solidification Enables High-Performance Solid-State Lithium Metal Batteries.

Solid-state lithium-metal batteries constructed by in-situ solidification of cyclic ether are considered to be a critical strategy for the next generation of solid-state batteries with high energy density and safety. However, the poor thermal/electrochemical stability of linear polyethers and severe interfacial reactions limit its further development. Herein, in-situ ring-opening hybrid crosslinked polymerization is proposed for organic/inorganic hybrid polymer electrolyte (HCPE) with superior ionic conductivity of 2.22 × 10-3 S cm-1 at 30 °C, ultrahigh Li+ transference number of 0.88, and wide electrochemical stability window of 5.2 V. These allow highly stable lithium stripping/plating cycling for over 1000 h at 1 mA cm-2 , which also reveal a well-defined interfacial stabilization mechanism. Thus, HCPE endows assembled solid-state lithium-metal batteries with excellent long-cycle performance over 600 cycles at 2 C (25 °C) and superior capacity retention of 92.1%. More importantly, the proposed noncombustible HCPE opens up a new frontier to promote the practical application of high safety and high energy density solid-state batteries via in-situ solidification.

Black phosphorus quantum dots induced ferroptosis in lung cell via increasing lipid peroxidation and iron accumulation.

Black Phosphorus Quantum Dots (BP-QDs) have potential applications in biomedicine. BP-QDs may enter the body through the respiratory tract during grinding and crushing production and processing, causing respiratory toxicity. Ferroptosis is an oxidative, iron-dependent form of cell death. Here, respiratory toxicity of BP-QDs has been validated in mice and human bronchial epithelial cells. After 24 h of exposure to different doses (4-32 µg/mL) of BP-QDs, intracellular lipid peroxidation and iron overload occurred in Beas-2B cells. After 4 times exposures by noninvasive tracheal instillation at four doses [0, 0.25, 0.5 and 1 (mg/kg/48h)], all animals were sacrificed, organs were removed, processed for pathological examination and molecular analysis. Iron overload, glutathione (GSH) depletion and lipid peroxidation in the lung tissue of mice in the exposure group. Furthermore, based on the ferroptosis-associated protein and mRNA expression, it was hypothesized that BP-QDs induced ferroptosis through increasing intracellular free iron and polyunsaturated fatty acid synthesis. By comparing with previous studies, we speculate that primary cells generally are more sensitive to BP-QDs-induced damage than cancer cells. In summary, findings in the present study confirmed that BP-QDs induce ferroptosis via increasing lipid peroxidation and iron accumulation in vitro and in vivo.

Composition of Sphagnum palustre L. extracts using different extraction methods.

Sphagnum palustre L. is a Chinese herbal medicine with a long history, however, few studies have been performed on its chemical composition and active effects. In this study, we investigated the composition and antibacterial and antioxidant capacities of extracts obtained from Sphagnum palustre L. phytosomes extracted with conventional solvents (water, methanol, and ethanol) and two different hydrogen bond donors (citric acid and 1,2-propanediol) modified with choline chloride-type deep eutectic solvents (DESs). The results show that Sphagnum palustre extracts contained 253 compounds, including citric acid, ethyl maltol, and thymol. The highest total phenolic content (TPC) was obtained with a DES extraction method combining 1,2-propanediol and choline chloride (39.02 ± 7.08 mg gallic acid equivalent/g dried weight (DW). This shows the composition of Sphagnum palustre as a natural product and the application of DESs in the extraction of active ingredients, demonstrating the potential of peat moss extracts in cosmetics and health products.