Genome-wide DNA methylation sequencing reveals the involvement of ferroptosis in hepatotoxicity induced by dietary exposure to food-grade titanium dioxide.

BACKGROUND: Following the announcement by the European Food Safety Authority that the food additive titanium dioxide (E 171) is unsafe for human consumption, and the subsequent ban by the European Commission, concerns have intensified over the potential risks E 171 poses to human vital organs. The liver is the main organ for food-grade nanoparticle metabolism. It is increasingly being found that epigenetic changes may play an important role in nanomaterial-induced hepatotoxicity. However, the profound effects of E 171 on the liver, especially at the epigenetic level, remain largely unknown. METHODS: Mice were exposed orally to human-relevant doses of two types of E 171 mixed in diet for 28 and/or 84 days. Conventional toxicology and global DNA methylation analyses were performed to assess E 171-induced hepatotoxicity and epigenetic changes. Whole genome bisulfite sequencing and further ferroptosis protein detection were used to reveal E 171-induced changes in liver methylation profiles and toxic mechanisms. RESULTS: Exposed to E 171 for 28 and/or 84 days resulted in reduced global DNA methylation and hydroxymethylation in the liver of mice. E 171 exposure for 84 days elicited inflammation and damage in the mouse liver, whereas 28-day exposure did not. Whole-genome DNA methylation sequencing disclosed substantial methylation alterations at the CG and non-CG sites of the liver DNA in mice exposed to E 171 for 84 days. Mechanistic analysis of the DNA methylation alterations indicated that ferroptosis contributed to the liver toxicity induced by E 171. E 171-induced DNA methylation changes triggered NCOA4-mediated ferritinophagy, attenuated the protein levels of GPX4, FTH1, and FTL in the liver, and thereby caused ferroptosis. CONCLUSIONS: Long-term oral exposure to E 171 triggers hepatotoxicity and induces methylation changes in both CG and non-CG sites of liver DNA. These epigenetic alterations activate ferroptosis in the liver through NCOA4-mediated ferritinophagy, highlighting the role of DNA methylation and ferroptosis in the potential toxicity caused by E 171 in vivo.

Synergistic effect and mechanism of monoacylglycerol lipase inhibitor and Icaritin in the treatment of ulcerative colitis.

Ulcerative colitis (UC) is a chronic, relapsing nonspecific intestinal inflammatory disease. It is difficult for a single drug to treat UC effectively and maintain long-term efficacy. There is an urgent need to find new drugs and treatment strategies. MAGL11 is a new kind of single acylglycerol lipase (MAGL) inhibitor. Icaritin (Y003) is the major metabolite of icariin in vivo. Several studies have confirmed the role of MAGL inhibitors and icariin in anti-inflammatory and regulation of intestinal stability. Therefore, this study adopted a new strategy of combining MAGL inhibitor with Icaritin to further explore the role and mechanism of drugs in the treatment of UC. Enzyme-linked immunosorbent assay (ELISA), hematoxylin-eosin staining (HE), immunohistochemical (IHC) and Western blot were used to detect the synergistic protective effects of MAGL11 and Y003 on intestinal pathological injury, intestinal mucosal permeability and inflammation in UC mice. 16S rDNA sequencing was used to detect the synergistic effect of MAGL11 and Y003 on gut microbiota. The effects of MAGL11 and Y003 combined therapy on serum and fecal metabolism of UC mice were analyzed by untargeted metabolomics. Proteomics method was applied to investigate the molecular mechanisms underlying MAGL11 and Y003 synergy in the treatment of UC. The results showed that MAGL11 and Y003 could synergistically improve the clinical symptoms, reduce intestinal inflammation and pathological damage, and improve intestinal mucosal permeability in UC mice. The mechanism study found that MAGL11 and Y003 could synergistically inhibit Toll-like receptors 4 (TLR4) / Myeloid differentiation primary response gene (Myd88)/Nuclear factor kappa-B (NF-κB) pathway and further regulate gut microbiota imbalance and metabolic disorders to treat UC.

Wide-Range Excitation-Dependent Phosphorescence of Coordination Polymers Exhibiting Dynamic Anticounterfeiting, White-Light Emission, and Antibacterial Performance.

Multicolor-tunable room-temperature phosphorescence (RTP) is attracting wide attention in optoelectronic applications. Here, we propose a coordination-oriented assembly approach to achieve wide-range RTP with a benzimidazole derivative (2,7-diazabenzimidazole, DZBIM) as a luminogen. These two compounds exhibit unexpected excitation-responsive RTP emission, and the phosphorescence emission nearly covers the entire visible region with the change of the excitation wavelength from 360 to 620 nm. To the best of our knowledge, this is the first report of coordination polymers with such a full-color-tunable RTP. Compound 1 also shows white-light emission upon excitation at 280 nm. Experimental and theoretical results demonstrate that multiple intermolecular interactions and emission centers from different aggregates are responsible for the generation of multicolor emission. The white-light emission and multiple anticounterfeiting are explored. Besides, compound 1 exhibits high antibacterial activity benefiting from efficient 1O2 generation. This work provides an efficient way to prepare a color-tunable RTP.

miR-106b-5p protects against drug-induced liver injury by targeting vimentin to stimulate liver regeneration.

Understanding the endogenous mechanism of adaptive response to drug-induced liver injury (arDILI) may discover innovative strategies to manage DILI. To gain mechanistic insight into arDILI, we investigated exosomal miRNAs in the adaptive response to toosendanin-induced liver injury (TILI) of mice. Exosomal miR-106b-5p was identified as a specific regulator of arDILI by comprehensive miRNA profiling. Outstandingly, miR-106b-5p agomir treatment alleviated TILI and other DILI by inhibiting apoptosis and promoting hepatocyte proliferation. Conversely, antagomir treatments had opposite effects, indicating that miR-106b-5p protects mice from liver injury. Injured hepatocytes released miR-106b-5p-enriched exosomes taken up by surrounding hepatocytes. Vim (encodes vimentin) was identified as an important target of miR-106b-5p by dual luciferase reporter and siRNA assays. Furthermore, single-cell RNA-sequencing analysis of toosendanin-injured mouse liver revealed a cluster of Vim + hepatocytes; nonetheless declined following miR-106b-5p cotreatment. More importantly, Vim knockout protected mice from acetaminophen poisoning and TILI. In the clinic, serum miR-106b-5p expression levels correlated with the severity of DILI. Indeed, liver biopsies of clinical cases exposed to different DILI causing drugs revealed marked vimentin expression among harmed hepatocytes, confirming clinical relevance. Together, we report mechanisms of arDILI whereby miR-106b-5p safeguards restorative tissue repair by targeting vimentin.

An integrated network pharmacology and molecular docking approach to reveal the role of Arctigenin against Cutibacterium acnes-induced skin inflammation by targeting the CYP19A1.

Acne caused by inflammation of hair follicles and sebaceous glands is a common chronic skin disease. Arctigenin (ATG) is an extract of Arctium lappa L., which has significant anti-inflammatory effects. However, the effect and mechanism of ATG in cutaneous inflammation mediated by Cutibacterium acnes (C. acnes) has not been fully evaluated. The purpose of this study was to explore the effect and potential mechanism of ATG in the treatment of acne through network pharmacology and experimental confirmation. An acne model was established by injected live C. acnes into living mice and treated with ATG. Our data showed that ATG effectively improved acne induced by live C. acnes, which was confirmed by determining ear swelling rate, estradiol concentration and hematoxylin and eosin (H&E) staining. In addition, ATG inhibited the NLRP3 inflammasome signaling pathway in mice ear tissues and reduced the secretion of pro-inflammatory cytokines IL-1ß to relieve inflammation. The results of network pharmacology and molecular docking confirmed that ATG can regulate 17ß-Estradiol (E2) levels through targeted to CYP19A1, and finally inhibited skin inflammation. Taken together, our results confirmed that ATG regulated E2 secretion by targeting CYP19A1, thereby inhibiting the NLRP3 inflammasome signaling pathway and improving inflammation levels in acne mice. This study provides a basis for the feasibility of ATG in treating acne in clinical practice.

Disorders of fatty acid metabolism and imbalance in the ratio of monounsaturated fatty acids promote the development of pulmonary fibrosis.

OBJECTIVE: Although some studies suggested that metabolic abnormalities may contribute to the development of pulmonary fibrosis, there are no studies that have reported a clear causal relationship between them, and the aim of this study was to explore the causal relationship between plasma metabolites and pulmonary fibrosis using Mendelian randomization (MR) combined with metabolomics analysis. METHODS: Firstly, we explored the causal relationship between 1400 metabolites and pulmonary fibrosis using MR analysis, and detected plasma metabolites in mice with pulmonary fibrosis using metabolomics technology, thus validating the results of MR analysis. In addition, we again used MR to explore the causal relationship between the results of the differential metabolite KEGG in metabolomics and pulmonary fibrosis. RESULTS: A total of 52 metabolites were screened for association with pulmonary fibrosis in the MR analysis of 1400 plasma metabolites with pulmonary fibrosis, based on P < 0.05 for the IVW method, with consistent OR directions for all methods. Four of them were validated in the plasma of mice with pulmonary fibrosis, namely carnitine c18:2 levels (negative correlation), Glutamine degradant levels (positive correlation), Propionylcarnitine (c3) levels (negative correlation), carnitine to palmitoylcarnitine (c16) ratio (negative correlation). In addition, KEGG analysis of plasma differential metabolites revealed that the signaling pathway of biosynthetic of unsaturated fatty acids was most affected in mice with pulmonary fibrosis, and MR analysis showed that imbalance in the ratio of monounsaturated fatty acids was significantly associated with pulmonary fibrosis. CONCLUSIONS: Our study suggests that abnormal fatty acid levels due to reduced levels of carnitine-like metabolites, and an imbalance in the ratio of monounsaturated, promote the development of pulmonary fibrosis. This study reveals the marker metabolites and metabolic pathways affecting the development of pulmonary fibrosis to provide a basis for the development of new drugs for the treatment of pulmonary fibrosis.

A viroid-derived small interfering RNA targets bHLH transcription factor MdPIF1 to regulate anthocyanin biosynthesis in Malus domestica.

Fruit colour is a critical determinant for the appearance quality and commercial value of apple fruits. Viroid-induced dapple symptom severely affects the fruit coloration, however, the underlying mechanism remains unknown. In this study, we identified an apple dimple fruit viroid (ADFVd)-derived small interfering RNA, named vsiR693, which targeted the mRNA coding for a bHLH transcription factor MdPIF1 (PHYTOCHROME-INTERACTING FACTOR 1) to regulate anthocyanin biosynthesis in apple. 5' RLM-RACE and artificial microRNA transient expression system proved that vsiR693 directly targeted the mRNA of MdPIF1 for cleavage. MdPIF1 positively regulated anthocyanin biosynthesis in both apple calli and fruits, and it directly bound to G-box element in the promoter of MdPAL and MdF3H, two anthocyanin biosynthetic genes, to promote their transcription. Expression of vsiR693 negatively regulated anthocyanin biosynthesis in both apple calli and fruits. Furthermore, co-expression of vsiR693 and MdPIF1 suppressed MdPIF1-promoted anthocyanin biosynthesis in apple fruits. Infiltration of ADFVd infectious clone suppressed coloration surrounding the injection sites in apple fruits, while a mutated version of ADFVd, in which the vsiR693 producing region was mutated, failed to repress fruit coloration around the injection sites. These data provide evidence that a viroid-derived small interfering RNA targets host transcription factor to regulate anthocyanin biosynthesis in apple.

Intravitreal Dexamethasone Implant (Ozurdex) for Ocular Toxocariasis.

This study aimed to evaluate the efficacy and safety of intravitreal dexamethasone implants in the treatment of ocular toxocariasis (OT). A retrospective analysis was performed on 6 cases in which laboratory tests diagnosed OT. All patients were administered with intravitreal dexamethasone implants with or without vitrectomy. The average follow-up time was 19.7 months. All operated eyes achieved anatomic success, and all patients' visual acuity was improved. Five of these six had a visual acuity of 20/100, and three had final acuity of 20/40 or even better. Intravitreal dexamethasone implants can be used to treat different types of OT, which not only effectively control inflammation and improve the patient's vision but also reduce the use of systemic glucocorticoids.

Incidence and influencing factors of cephalosporin-induced anaphylaxis: a multicenter cross-sectional study. / é™è„‰æ³¨å°„å¤´å­¢èŒç´ ç±»è¯ç‰©æ‚£è€ è¿‡æ•ååº”å‘ç”ŸçŽ‡åŠå ¶å½±å“å› ç´ çš„å¤šä¸­å¿ƒä¸´åºŠç ”ç©¶.

OBJECTIVES: To investigate the incidence and influencing factors of allergic reactions to cephalosporins. METHODS: A cross-sectional study of 29 medical institutions in Zhejiang Province was conducted from April 2021 to June 2021. The incidence of allergic reactions to cephalosporins was investigated. The influencing factors of cephalosporin-induced allergic reactions were analyzed by Poisson regression. RESULTS: A total of 56 155 patients were included in this study. The total incidence of allergic reactions to cephalosporin was 1.67 ‰, the highest incidences of anaphylaxis occurred in ceftizoxime (4.27‰), followed by ceftriaxone (3.49‰) and cefotaxime (2.40‰). There was no significant difference in the incidence of allergic reactions between patients with negative skin tests and those without skin tests (1.75‰ vs. 1.63‰, RR=1.07, 95%CI:0.70-1.63, P> 0.05). Poisson regression showed that body mass index (BMI) <18.5 kg/cm2 (RR=2.43, 95%CI: 1.23-4.82, P<0.01) and history of ß-lactam antibiotics allergy (RR=33.88, 95%CI: 1.47-781.12, P<0.05) increased cephalosporin-induced anaphylaxis. Compared with cefuroxime, the risk of allergic reactions was increased for ceftriaxone (RR=3.08, 95%CI: 1.70-5.59, P<0.01), ceftazidime (RR=1.89, 95%CI: 1.03-3.47, P<0.05), and ceftriaxone (RR=3.74, 95%CI: 1.64-8.50, P<0.01). CONCLUSIONS: Lower BMI and history of ß-lactam antibiotics allergy increase the risk of cephalosporin allergic reactions, and the routine skin test may not reduce the occurrence of allergic reactions to cephalosporins.

Is the Homologous Recombination Repair Mutation Defined by a 15-Gene Panel Associated with the Prognosis of Epithelial Ovarian Cancer?

BACKGROUND: There is no consensus regarding the specific genes included in the homologous recombination repair (HRR) gene panel for identifying the HRR deficiency (HRD) status and predicting the prognosis of epithelial ovarian cancer (EOC) patients. OBJECTIVE: We aimed to explore a 15-gene panel involving the HRR pathway as a predictive prognostic indicator in Chinese patients newly diagnosed with EOC. PATIENTS AND METHODS: We reviewed the previously published reports about different HRR gene panels and prespecified the 15-gene panel. The genetic testing results in a 15-gene panel from 308 EOC patients diagnosed between 2014 and 2022 from six centers were collected. The association of clinicopathologic characteristics, the use of poly (adenosine diphosphate-ribose) polymerase inhibitors (PARPis) and progression-free survival (PFS) with 15-gene panel HRR mutations (HRRm) status was assessed. RESULTS: 43.2% (133/308) of patients were determined to carry 144 deleterious HRRm, among which 68.1% (98/144) were germline mutations and 32.8% (101/308) were BRCA1/2 gene lethal mutations. The hazard ratio (HR) (95% confidence interval, CI) for PFS (HRRm v HRR wild type, HRRwt) using the 15-gene panel HRRm was 0.42 (0.28-0.64) at all stages and 0.42 (0.27-0.65) at stages IIIC-IV. However, a prognostic difference was observed only between the BRCA mutation group and the HRRwt group, not between the non-BRCA HRRm group and the HRRwt group. For the subgroups of patients not using PARPis, the HR (95% CI) was 0.41 (0.24-0.68) at stages IIIC-IV. CONCLUSIONS: This study provides evidence that 15-gene panel HRRm can predict the prognosis of EOC, of these only the BRCA1/2 mutations, not non-BRCA HRRm, contribute to prognosis prediction. Among patients without PARPis, the HRRm group presented a better PFS. This is the first study of this kind in the Chinese population.

Highly Stable and Selective Ni/ZrO2 Nanofiber Catalysts for Efficient CO2 Methanation.

Ni-based oxides are promising catalysts for CO2 methanation. However, Ni-based catalysts also have some unresolved issues and drawbacks in practical applications. The activity and selectivity of Ni-based catalysts in CO2 methanation at low temperatures still need to be improved. Here, Ni/ZrO2 nanofibers with high surface areas (up to 101.2 m2/g) were prepared by electrospinning methods. The Ni/ZrO2-ES (also named as 66Ni/ZrO2) catalyst showed excellent catalytic performance in CO2 methanation (the CO2 conversion = 81% and CH4 selectivity = 99% at 350 °C) and excellent stability for 100 h, which was better than most reported Ni/ZrO2 catalysts. However, the comparison sample Ni/ZrO2-CP prepared by the coprecipitation method had poor catalytic performance (the CO2 conversion = 54% and CH4 selectivity = 90% at 350 °C). Within 100 h, the CO2 conversion decreased to 30% and the CH4 selectivity decreased to 52%. Both EPR and O1S XPS confirmed that Ni/ZrO2 nanofibers can form more reactive oxygen species vacancies, and CO2-TPD confirmed that nanofibers had more CO2 adsorption sites compared with the control sample Ni/ZrO2-CP. In situ DRIFTS analysis showed that bidentate carbonate and monodentate carbonate were key intermediates in CO2 methanation. The catalytic performance of Ni/ZrO2 nanofiber catalysts would be attributed to higher dispersion of Ni species on the surface of nanofibers, high specific surface area (101.2 m2/g), more oxygen vacancies, more CO2 adsorption sites, and the synergistic effect between Ni nanoparticles and ZrO2 nanofibers. This work may inspire the rational design of Ni/ZrO2 nanofiber catalysts with rich oxygen vacancies for low-temperature CO2 methanation.

Encapsulation engineering of porous crystalline frameworks for delayed luminescence and circularly polarized luminescence.

Delayed luminescence (DF), including phosphorescence and thermally activated delayed fluorescence (TADF), and circularly polarized luminescence (CPL) exhibit common and broad application prospects in optoelectronic displays, biological imaging, and encryption. Thus, the combination of delayed luminescence and circularly polarized luminescence is attracting increasing attention. The encapsulation of guest emitters in various host matrices to form host-guest systems has been demonstrated to be an appealing strategy to further enhance and/or modulate their delayed luminescence and circularly polarized luminescence. Compared with conventional liquid crystals, polymers, and supramolecular matrices, porous crystalline frameworks (PCFs) including metal-organic frameworks (MOFs), covalent-organic frameworks (COFs), zeolites and hydrogen-bonded organic frameworks (HOFs) can not only overcome shortcomings such as flexibility and disorder but also achieve the ordered encapsulation of guests and long-term stability of chiral structures, providing new promising host platforms for the development of DF and CPL. In this review, we provide a comprehensive and critical summary of the recent progress in host-guest photochemistry via the encapsulation engineering of guest emitters in PCFs, particularly focusing on delayed luminescence and circularly polarized luminescence. Initially, the general principle of phosphorescence, TADF and CPL, the combination of DF and CPL, and energy transfer processes between host and guests are introduced. Subsequently, we comprehensively discuss the critical factors affecting the encapsulation engineering of guest emitters in PCFs, such as pore structures, the confinement effect, charge and energy transfer between the host and guest, conformational dynamics, and aggregation model of guest emitters. Thereafter, we summarize the effective methods for the preparation of host-guest systems, especially single-crystal-to-single-crystal (SC-SC) transformation and epitaxial growth, which are distinct from conventional methods based on amorphous materials. Then, the recent advancements in host-guest systems based on PCFs for delayed luminescence and circularly polarized luminescence are highlighted. Finally, we present our personal insights into the challenges and future opportunities in this promising field.

scRank infers drug-responsive cell types from untreated scRNA-seq data using a target-perturbed gene regulatory network.

Cells respond divergently to drugs due to the heterogeneity among cell populations. Thus, it is crucial to identify drug-responsive cell populations in order to accurately elucidate the mechanism of drug action, which is still a great challenge. Here, we address this problem with scRank, which employs a target-perturbed gene regulatory network to rank drug-responsive cell populations via in silico drug perturbations using untreated single-cell transcriptomic data. We benchmark scRank on simulated and real datasets, which shows the superior performance of scRank over existing methods. When applied to medulloblastoma and major depressive disorder datasets, scRank identifies drug-responsive cell types that are consistent with the literature. Moreover, scRank accurately uncovers the macrophage subpopulation responsive to tanshinone IIA and its potential targets in myocardial infarction, with experimental validation. In conclusion, scRank enables the inference of drug-responsive cell types using untreated single-cell data, thus providing insights into the cellular-level impacts of therapeutic interventions.

Detection of a Human Adenovirus Outbreak, Including Some Critical Infections, Using Multipathogen Testing at a Large University, September 2022-January 2023.

Background: Human adenoviruses (HAdVs) can cause outbreaks of flu-like illness in university settings. Most infections in healthy young adults are mild; severe illnesses rarely occur. In Fall 2022, an adenovirus outbreak was identified in university students. Methods: HAdV cases were defined as university students 17-26 years old who presented to the University Health Service or nearby emergency department with flu-like symptoms (eg, fever, cough, headache, myalgia, nausea) and had confirmed adenovirus infections by polymerase chain reaction (PCR). Demographic and clinical characteristics were abstracted from electronic medical records; clinical severity was categorized as mild, moderate, severe, or critical. We performed contact investigations among critical cases. A subset of specimens was sequenced to confirm the HAdV type. Results: From 28 September 2022 to 30 January 2023, 90 PCR-confirmed cases were identified (51% female; mean age, 19.6 years). Most cases (88.9%) had mild illness. Seven cases required hospitalization, including 2 critical cases that required intensive care. Contact investigation identified 44 close contacts; 6 (14%) were confirmed HAdV cases and 8 (18%) reported symptoms but never sought care. All typed HAdV-positive specimens (n = 36) were type 4. Conclusions: While most students with confirmed HAdV had mild illness, 7 otherwise healthy students had severe or critical illness. Between the relatively high number of hospitalizations and proportion of close contacts with symptoms who did not seek care, the true number of HAdV cases was likely higher. Our findings illustrate the need to consider a wide range of pathogens, even when other viruses are known to be circulating.

Identification of Hsp20 gene family in Malus domestica and functional characterization of Hsp20 class I gene MdHsp18.2b.

Heat shock protein 20 (Hsp20) is a small molecule heat shock protein that plays an important role in plant growth, development, and stress resistance. Little is known about the function of Hsp20 family genes in apple (Malus domestica). Here, we performed a genome-wide analysis of the apple Hsp20 gene family, and a total of 49 Hsp20s genes were identified from the apple genome. Phylogenetic analysis revealed that the 49 genes were divided into 11 subfamilies, and MdHsp18.2b, a member located in the CI branch, was selected as a representative member for functional characterization. Treatment with NaCl and Botryosphaeria dothidea (B. dothidea), the causal agent of apple ring rot disease, significantly induced MdHsp18.2b transcription level. Further analysis revealed that overexpressing MdHsp18.2b reduced the resistance to salt stress but enhanced the resistance to B. dothidea infection in apple calli. Moreover, MdHsp18.2b positively regulated anthocyanin accumulation in apple calli. Physiology assays revealed that MdHsp18.2b promoted H2O2 production, even in the absence of stress factors, which might contribute to its functions in response to NaCl and B. dothidea infection. Hsps usually function as homo- or heterooligomers, and we found that MdHsp18.2b could form a heterodimer with MdHsp17.9a and MdHsp17.5, two members from the same branch with MdHsp18.2b in the phylogenetic tree. Therefore, we identified 49 Hsp20s genes from the apple genome and found that MdHsp18.2b was involved in regulating plant resistance to salt stress and B. dothidea infection, as well as in regulating anthocyanin accumulation in apple calli.

Facile Solid-State Chemical Synthesis of CoMoO4 Nanorods for High-Performance Supercapacitors.

The development of electrode materials with excellent performance serves as the key for researchers to enhance the energy density of supercapacitors. Cobalt molybdate (CoMoO4) nanomaterials have been regarded as one of the most prospective electrode materials for supercapacitors due to their high theoretical capacitance and excellent electrical conductivity. In this paper, three kinds of CoMoO4 nanorods were prepared directly via simple and environmentally friendly solid-phase chemical reactions with solid inorganic salts as raw materials. According to X-ray powder diffraction (XRD) and scanning electron microscopy (SEM) test results, different reagents had certain effects on the size and morphology of CoMoO4, and these affected its electrochemical performance. In particular, the samples prepared with Co(NO3)2·6H2O as raw material took on a more uniform micromorphology, with a better crystallinity. Simultaneously, electrochemical test results showed that the samples synthesized with Co(NO3)2·6H2O presented relatively good electrical conductivity and a large specific capacitance (177 F g-1). This may be due to the nitrates reacting more slowly during the reaction and the crystals having difficulty aggregating during growth. Therefore, the structure of the prepared CoMoO4 nanomaterial was more uniform, and it was resistant to collapse during the charging and discharging process; thus, the capacitor presents the best performance.

Salvianolic acid C attenuates cerebral ischemic injury through inhibiting neuroinflammation via the TLR4-TREM1-NF-κB pathway.

BACKGROUND: Stroke is a leading cause of mortality and disability with ischemic stroke being the most common type of stroke. Salvianolic acid C (SalC), a polyphenolic compound found in Salviae Miltiorrhizae Radix et Rhizoma, has demonstrated therapeutic potential in the recovery phase of ischemic stroke. However, its pharmacological effects and underlying mechanisms during the early stages of ischemic stroke remain unclear. This study aimed to examine the potential mechanism of action of SalC during the early phase of ischemic stroke using network pharmacology strategies and RNA sequencing analysis. METHODS: SalC effects on infarct volume, neurological deficits, and histopathological changes were assessed in a mouse model of transient middle cerebral artery occlusion (tMCAO). By integrating RNA sequencing data with a cerebral vascular disease (CVD)-related gene database, a cerebral ischemic disease (CID) network containing dysregulated genes from the tMCAO model was constructed. Network analysis algorithms were applied to evaluate the key nodes within the CID network. In vivo and in vitro validation of crucial targets within the identified pathways was conducted. RESULTS: SalC treatment significantly reduced infarct volume, improved neurological deficits, and reversed pathological changes in the tMCAO mouse model. The integration of RNA sequencing data revealed an 80% gene reversion rate induced by SalC within the CID network. Among the reverted genes, 53.1% exhibited reversion rates exceeding 50%, emphasizing the comprehensive rebalancing effect of SalC within the CID network. Neuroinflammatory-related pathways regulated by SalC, including the toll-like-receptor 4 (TLR4)- triggering receptor expressed on myeloid cells 1 (TREM1)-nuclear factor kappa B (NF-κB) pathway, were identified. Further in vivo and in vitro experiments confirmed that TLR4-TREM1-NF-κB pathway was down-regulated by SalC in microglia, which was essential for its anti-inflammatory effect on ischemic stroke. CONCLUSIONS: SalC attenuated cerebral ischemic injury by inhibiting neuroinflammation mediated by microglia, primarily through the TLR4-TREM1-NF-κB pathway. These findings provide valuable insights into the potential therapeutic benefits of SalC in ischemic stroke.

Feasibility of a Mobile Health Intervention for Providing a Continuum of HIV Services for MSM: Pilot Study of the WeTest Program in 3 Cities in China.

BACKGROUND: Men who have sex with men (MSM) in China have a high risk for HIV infection but experience suboptimal rates of HIV testing and service engagement due to various social and structural barriers. We developed a mobile health (mHealth) intervention entitled "WeTest-Plus" (WeTest+) as a user-centered "one-stop service" approach for delivering access to comprehensive information about HIV risk, HIV self-testing, behavioral and biomedical prevention, confirmatory testing, treatment, and care. OBJECTIVE: The goal of the current study was to investigate the feasibility of WeTest+ to provide continuous HIV services to high-risk MSM. METHODS: Participants completed a 3-week pilot test of WeTest+ to examine acceptability, feasibility, and recommendations for improvement. Participants completed a structured online questionnaire and qualitative exit interviews facilitated by project staff. "Click-through" rates were assessed to examine engagement with online content. RESULTS: 28 participants were included, and the average age was 27.6 years (standard deviation = 6.8). Almost all participants (96.4%) remained engaged with the WeTest+ program over a 3-week observational period. The majority (92.9%) self-administered the HIV self-test and submitted their test results through the online platform. Overall click-through rates were high (average 67.9%). Participants provided favorable comments about the quality and relevance of the WeTest+ information content, the engaging style of information presentation, and the user-centered features. CONCLUSION: This pilot assessment of WeTest+ supports the promise of this program for promoting HIV self-testing and linkage to in-person services for MSM in China. Findings underscore the utility of a user-centered approach to mHealth program design.

Association of non-obstructive dyspnoea with all-cause mortality and incident chronic obstructive pulmonary disease: a systematic literature review and meta-analysis.

BACKGROUND: Controversy exists regarding the association between non-obstructive dyspnoea and the future development of chronic obstructive pulmonary disease (COPD) and mortality. Therefore, we aimed to evaluate the association of non-obstructive dyspnoea with mortality and incident COPD in adults. METHODS: We searched PubMed, Embase, and Web of Science to identify studies published from inception to 13 May 2023. Eligibility screening, data extraction, and quality assessment of the retrieved articles were conducted independently by two reviewers. Studies were included if they were original articles comparing incident COPD and all-cause mortality between individuals with normal lung function with and without dyspnoea. The primary outcomes were incident COPD and all-cause mortality. The secondary outcome was respiratory disease-related mortality. We used the random-effects model to calculate pooled estimates and corresponding 95% confidence interval (CI). Heterogeneity was determined using the I² statistic. RESULTS: Of 6486 studies, 8 studies involving 100 758 individuals fulfilled the inclusion and exclusion criteria and were included in the study. Compared with individuals without non-obstructive dyspnoea, individuals with non-obstructive dyspnoea had an increased risk of incident COPD (relative risk: 1.41, 95% CI: 1.08 to 1.83), and moderate heterogeneity was found (p=0.079, I2=52.2%). Individuals with non-obstructive dyspnoea had a higher risk of all-cause mortality (hazard ratio: 1.21, 95% CI: 1.14 to 1.28, I2=0.0%) and respiratory disease-related mortality (hazard ratio: 1.52, 95% CI: 1.14 to 2.02, I2=0.0%) than those without. CONCLUSIONS: Individuals with non-obstructive dyspnoea are at a higher risk of incident COPD and all-cause mortality than individuals without dyspnoea. Further research should investigate whether these high-risk adults may benefit from risk management and early therapeutic intervention. PROSPERO REGISTRATION NUMBER: CRD42023395192.

Screening Mutations of the Monogenic Syndromic High Myopia by Whole Exome Sequencing From MAGIC Project.

Purpose: This observational study aimed to identify mutations in monogenic syndromic high myopia (msHM) using data from reported samples (n = 9370) of the Myopia Associated Genetics and Intervention Consortium (MAGIC) project. Methods: The targeted panel containing 298 msHM-related genes was constructed and screening of clinically actionable variants was performed based on whole exome sequencing. Capillary sequencing was used to verify the identified gene mutations in the probands and perform segregation analysis with their relatives. Results: A total of 381 candidate variants in 84 genes and 85 eye diseases were found to contribute to msHM in 3.6% (335/9370) of patients with HM. Among them, the 22 genes with the most variations accounted for 62.7% of the diagnostic cases. In the genotype-phenotype association analysis, 60% (201/335) of suspected msHM cases were recalled and 25 patients (12.4%) received a definitive genetic diagnosis. Pathogenic variants were distributed in 18 msHM-related diseases, mainly involving retinal dystrophy genes (e.g. TRPM1, CACNA1F, and FZD4), connective tissue disease genes (e.g. FBN1 and COL2A1), corneal or lens development genes (HSF4, GJA8, and MIP), and other genes (TEK). The msHM gene mutation types were allocated to four categories: nonsense mutations (36%), missense mutations (36%), frameshift mutations (20%), and splice site mutations (8%). Conclusions: This study highlights the importance of thorough molecular subtyping of msHM to provide appropriate genetic counselling and multispecialty care for children and adolescents with HM.