The Tao Hong Si Wu Decoction ameliorates diabetes-associated cognitive dysfunction by inhibiting the formation of amyloid plaques.

OBJECTIVES: The herbs in Tao Hong Si Wu Decoction (THSWD) are beneficial in the treatment of cognitive impairment. However, the underlying mechanisms of THSWD in treating diabetes-associated cognitive dysfunction (DACD) are not entirely explored. This study is aimed to investigate the therapeutic effects of THSWD in DACD model rats and the underlying mechanism. METHODS: Ultra-high-phase liquid chromatography was employed to identify the main compounds contained in the THSWD extract. DACD rat model was induced by feeding with a high-sugar and high-fat diet and injecting streptozotocin (35 mg/kg). DACD rats were gavaged with THSWD for 1 week. The learning and memory abilities of the rats were measured by using the Morris water maze. Western blotting was used to detect the changes in DACD rat targets. Statistical methods were used to evaluate the correlation between proteins. RESULTS: The results show that THSWD effectively reduced the escape latency, hippocampal neuron damage, glycosylated hemoglobin, type A1C, and blood lipid levels in DACD rats. Furthermore, DACD rats showed significantly increased amyloid precursor protein, ß-secretase, Aß1-40 , Aß1-42 , Tau phosphorylation, and advanced glycation end products (AGEs) expression. However, THSWD treatment can reverse this phenomenon. CONCLUSIONS: THSWD can improve the learning and memory abilities of DACD rats by inhibiting the expression of AEGs-AGE receptors pathway, which provides an experimental basis for the clinical application of THSWD. In addition, the experiment combines pharmacological and statistical methods, which offers a new perspective for the study of Chinese herbal medicine.

27-Hydroxycholesterol inhibits trophoblast fusion during placenta development by activating PI3K/AKT/mTOR signaling pathway.

Trophoblast cell syncytialization is essential for placental and fetal development. Abnormal trophoblast cell fusion leads to pregnancy pathologies, such as preeclampsia (PE), intrauterine growth restriction (IUGR), and miscarriage. 27-hydroxycholesterol (27-OHC) is the most abundant oxysterol in human peripheral blood synthesized by sterol 27-hydroxylase (CYP27A1) and is considered a critical mediator between hypercholesterolemia and a variety of related disorders. Gestational hypercholesterolemia was associated with spontaneous preterm delivery and low birth weight (LBW) in term infants, yet the mechanism is unclear. In this study, two trophoblast cell models and CD-1 mice were used to evaluate the effects of 27-OHC on trophoblast fusion during placenta development. Two different kinds of trophoblast cells received a dosage of 2.5, 5, or 10 uM 27-OHC. Three groups of pregnant mice were randomly assigned: control, full treatment (E0.5-E17.5), or late treatment (E13.5-E17.5). All mice received daily intraperitoneal injections of saline (control group) and 27-OHC (treatment group; 5.5 mg/kg). In vitro experiments, we found that 27-OHC inhibited trophoblast cell fusion in primary human trophoblasts (PHT) and forskolin (FSK)-induced BeWo cells. 27-OHC up-regulated the expression of the PI3K/AKT/mTOR signaling pathway-related proteins. Moreover, the PI3K inhibitor LY294002 rescued the inhibitory effect of 27-OHC. Inhibition of trophoblast cell fusion by 27-OHC was also observed in CD-1 mice. Furthermore, fetal weight and placental efficiency decreased and fetal blood vessel development was inhibited in pregnant mice treated with 27-OHC. This study was the first to prove that 27-OHC inhibits trophoblast cell fusion by Activating PI3K/AKT/mTOR signaling pathway. This study reveals a novel mechanism by which dyslipidemia during pregnancy results in adverse pregnancy outcomes.

External validation of the iScore, ASTRAL score, DRAGON score, and THRIVE score and development of a nomogram to predict outcome in patients with large vessel occlusion-acute ischemic stroke.

OBJECTIVE: This study aimed to validate the iScore, ASTRAL score, DRAGON score, and THRIVE score for assessing large vessel occlusion-acute ischemic stroke (AIS-LVO) and establish a predictive model for AIS-LVO patients that has better performance to guide clinical practice. METHODS: We retrospectively included 439 patients with AIS-LVO and collected baseline data from all of them. External validation of the iScore, ASTRAL score, DRAGON score, and THRIVE score was performed. All variables were compared between groups via univariate analysis, and the results are expressed as ORs and 95 % CIs. Independent variables with P < 0.25 were included in the multivariate logistic analysis, and statistically significant differences (P < 0.05) were identified as risk factors for prognosis in AIS-LVO patients. Receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA) were used to evaluate the predictive value of our model. RESULTS: Our external validation resulted in an iScore under the curve (AUC) of 0.8475, an ASTRAL AUC of 0.8324, a DRAGON AUC of 0.8196, and a THRIVE AUC of 0.8039. In our research, multivariate Cox regression revealed 8 independent predictors. We used a nomogram to visualize the results of the data analysis. The AUC for the training cohort was 0.8855 (95 % CI, 0.8487-0.9222), and that in the validation cohort was 0.8992 (95 % CI, 0.8496-0. 9488). CONCLUSIONS: In this study, we verified that the above scores have excellent efficacy in predicting the prognosis of AIS-LVO patients. The nomogram we developed was able to predict the prognosis of AIS-LVO more accurately and may contribute to personalized clinical decision-making and treatment for future clinical work.

The Key Effect of Carboxyl Group and CuN2 O2 Coordinate Structure for Cu, N Co-Doped Carbon Dots with Peroxidase-Like Property.

Carbon dots (CDs) with good water solubility and biocompatibility have become a research hotspot in the nano-enzyme and biomedical field. However, the problems of low catalytic activity and ambiguous catalytic site of CDs as nanozymes still need to be addressed. In this work, CDs loaded with Cu single atoms are obtained through pyrolysis, and the coordination structure and surface functional groups are regulated by adjusting the pyrolysis temperature. CDs obtained at 300 °C (named Cu-CDs-300) have the most carboxyl content and Cu is coordinated in the form of CuN2 O2 , which can better decompose H2 O2 to produce free radical and is beneficial to catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB). The vmax is 6.56*10-7  m s-1 , 6.56 times higher than that of horseradish peroxidase (HRP). Moreover, Cu-CDs-300 can effectively lead to CT26 apoptosis by generating much free radicals. This work demonstrates the synergistic effect of oxygen-containing functional groups and metal coordination structures on peroxide-like activity of CDs and provides new ideas for the design of clear active structure and high efficiency peroxide-like single atom CDs catalyst.

Hydroxysafflor yellow A protects against colitis in mice by suppressing pyroptosis via inhibiting HK1/NLRP3/GSDMD and modulating gut microbiota.

Hydroxysafflor yellow A (HSYA), a chalcone glycoside, is a component of Carthamus tinctorius L. and exerts anti-inflammatory and antioxidative effects. However, the therapeutic effect and the underlying mechanism of HSYA on ulcerative colitis is unclear. This study aimed to investigate the unexplored protective effects and underlying mechanisms of HSYA on UC. In vitro analyses showed that HSYA reduced the secretion of interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, and IL-6 and inhibited nucleotide-binding and oligomerization domain-like receptor protein 3 (NLRP3)/gasdermin D (GSDMD)-mediated pyroptosis in lipopolysaccharide/ adenosine-5'-triphosphate (LPS/ATP)-stimulated macrophages. Gas chromatography-mass spectrometry (GC-MS) profiling of intracellular metabolites showed that HSYA reduced the increased levels of glucose, glucose 6-phosphate, and lactic acid, and inhibited the increased hexokinase 1 (HK1) expression caused by LPS/ATP stimulation. HK1 shRNA transfection further confirmed that HSYA inhibited the NLRP3/GSDMD-mediated pyroptosis via HK1 downregulation. In vivo analyses showed that HSYA drastically attenuated UC symptoms by relieving body weight loss, a decline in colon length, and inflammatory infiltration in colonic tissues induced by dextran sulfate sodium (DSS). HSYA also reduced the secretion of pro-inflammatory cytokines including IL-1ß, IL-6, TNF-α, and IL-18. Moreover, HSYA inhibited HK1/NLRP3/GSDMD-mediated pyroptosis in DSS-induced colitis mice. Finally, 16S rRNA sequencing analyses of gut microbiota revealed that HSYA reversed gut microbiota dysbiosis by reducing the abundance of Proteobacteria and increasing that of Bacteroidetes. This study demonstrated that HSYA not only exerted anti-inflammatory effects by inhibiting HK1/NLRP3/GSDMD and suppressing pyroptosis but also regulated gut microbiota in mice with DSS-induced colitis. Our findings provide new experimental evidence that HSYA might be a potential candidate for treating inflammatory bowel diseases.

Reversible Single-Crystal-to-Single-Crystal Transformations between Nanoscale 2D Nanosheets and 3D Metal-Organic Frameworks.

Single-crystal-to-single-crystal (SCSC) transformations provide more possibilities for phase transitions, which have attracted great attention in crystal engineering. In this paper, we report a series of reversible SCSC transformations between nanoscale two-dimensional layered double hydroxide (LDH) crystals and three-dimensional metal-organic framework crystals. They can proceed not only in solution systems but also on the surface of solid-state polyacrylonitrile films and fibers. Specifically, reversible SCSC transformations can be carried out between nanoscale ZIF-67 and Co-LDH. The Co-LDH nanomaterials displayed excellent oxygen evolution reaction performance. This work has good universality and scalability, which provides a novel avenue for the synthesis of crystal materials and is of great significance for the recycling of resources.

Chiral Carbon Dots Derived from Serine with Well-Defined Structure and Enantioselective Catalytic Activity.

Carbon dots (C-Dots), with unique properties from tunable photoluminescence to biocompatibility, show wide applications in biotechnology, optoelectronic device and catalysis. Chiral C-Dots are expected to have strongly chirality-dependent biological and catalytic properties. For chiral C-Dots, a clear structure and quantitative structure-property relationship need to be clarified. Here, chiral C-Dots were fabricated by electrooxidation polymerization from serine enantiomers. The oxidized serine has a reversed chiral configuration to serine, which leads to the chiral C-Dots possessing inverse handedness compared with their raw materials. Electron circular dichroism spectrum, together with other diverse characterization techniques and theoretical calculations, confirmed that these chiral C-Dots (2-7 nm) have a well-defined primary structure of polycyclic dipeptide and possess a spatial structure with a c-axis of hexagonal symmetry and two cyclic dipeptides as the spatial structural unit. These chiral C-Dots also show enantioselective catalytic activity on DOPA enantiomers oxidation.

Reciprocal regulation of NRF2 by autophagy and ubiquitin-proteasome modulates vascular endothelial injury induced by copper oxide nanoparticles.

NRF2 is the key antioxidant molecule to maintain redox homeostasis, however the intrinsic mechanisms of NRF2 activation in the context of nanoparticles (NPs) exposure remain unclear. In this study, we revealed that copper oxide NPs (CuONPs) exposure activated NRF2 pathway in vascular endothelial cells. NRF2 knockout remarkably aggravated oxidative stress, which were remarkably mitigated by ROS scavenger. We also demonstrated that KEAP1 (the negative regulator of NRF2) was not primarily involved in NRF2 activation in that KEAP1 knockdown did not significantly affect CuONPs-induced NRF2 activation. Notably, we demonstrated that autophagy promoted NRF2 activation as evidenced by that ATG5 knockout or autophagy inhibitors significantly blocked NRF2 pathway. Mechanically, CuONPs disturbed ubiquitin-proteasome pathway and consequently inhibited the proteasome-dependent degradation of NRF2. However, autophagy deficiency reciprocally promoted proteasome activity, leading to the acceleration of degradation of NRF2 via ubiquitin-proteasome pathway. In addition, the notion that the reciprocal regulation of NRF2 by autophagy and ubiquitin-proteasome was further proven in a CuONPs pulmonary exposure mice model. Together, this study uncovers a novel regulatory mechanism of NRF2 activation by protein degradation machineries in response to CuONPs exposure, which opens a novel intriguing scenario to uncover therapeutic strategies against NPs-induced vascular injury and disease.

PINK1/TAX1BP1-directed mitophagy attenuates vascular endothelial injury induced by copper oxide nanoparticles.

Copper oxide nanoparticles (CuONPs) are widely used metal oxide NPs owing to their excellent physical-chemical properties. Circulation translocation of CuONPs after inhalation leads to vascular endothelial injury. Mitochondria, an important regulatory hub for maintaining cell functions, are signaling organelles in responses to NPs-induced injury. However, how mitochondrial dynamics (fission and fusion) and mitophagy (an autophagy process to degrade damaged mitochondria) are elaborately orchestrated to maintain mitochondrial homeostasis in CuONPs-induced vascular endothelial injury is still unclear. In this study, we demonstrated that CuONPs exposure disturbed mitochondrial dynamics through oxidative stress-dependent manner in vascular endothelial cells, as evidenced by the increase of mitochondrial fission and the accumulation of fragmented mitochondria. Inhibition of mitochondrial fission with Mdivi-1 aggravated CuONPs-induced mtROS production and cell death. Furthermore, we found that mitochondrial fission led to the activation of PINK1-mediated mitophagy, and pharmacological inhibition with wortmannin, chloroquine or genetical inhibition with siRNA-mediated knockdown of PINK1 profoundly repressed mitophagy, suggesting that the protective role of mitochondrial fission and PINK1-mediated mitophagy in CuONPs-induced toxicity. Intriguingly, we identified that TAX1BP1 was the primary receptor to link the ubiquitinated mitochondria with autophagosomes, since TAX1BP1 knockdown elevated mtROS production, decreased mitochondrial clearance and aggravated CuONPs-induced cells death. More importantly, we verified that urolithin A, a mitophagy activator, promoted mtROS clearance and the removal of damaged mitochondria induced by CuONPs exposure both in vitro and in vivo. Overall, our findings indicated that modulating mitophagy may be a therapeutic strategy for pathological vascular endothelial injury caused by NPs exposure.

A Longitudinal Study of Stress in New Nurses in their First Year of Employment.

Objective: This study aimed to analyze changes in occupational stress in new nurses during the first year of employment. Methods: A prospective longitudinal study was conducted from 2020 to 2021 using one questionnaire four times on 127 newly employed nurses in a tertiary general teaching hospital in the province of Fujian. Results: The results showed that new nurses had moderate to high levels of stress in all four stages, with the highest stress level at 4 and 8 months of employment and the lowest stress level at 12 months; the differences in stress scores at different time points were statistically significant (p < 0.05). The trends in each stressor dimension varied across different periods. The highest scores were for pressure caused by "time allocation and workload," which peaked in month 8. The same trend was observed for stress from "patient care" and "work environment and equipment." "Management and interpersonal relationships" scored the highest overall stress score at the start of employment before declining. The lowest stress score was from "work environment and equipment" at the start of employment, and the lowest was from "management and interpersonal relationships" from month 4 onward. Conclusion: New nurses had higher overall occupational stress during their first year of employment under different stressors. Therefore, nursing managers should actively focus on stress factors of new nurses and provide targeted interventions to help them during their training period.

Complete and rapid degradation of glyphosate with Fe3Ce1Ox catalyst for peroxymonosulfate activation at room temperature.

Glyphosate, a common broad-spectrum herbicide, is a serious environmental pollutant that causes a significant threat to humans. Hence, there is a pressing task to remove glyphosate from the environment. Here, we report an excellent Fe3Ce1Ox catalyst synthesized via the one-step co-precipitation method for activating peroxymonosulfate (PMS) to degrade glyphosate at 25 °C. As a result, glyphosate is completely degraded with a high degradation rate of 400 mg L-1·h-1, and the TOC and TN removals are 85.6% and 80.8%, respectively. As proven by systematic characterizations, the Fe-Ce synergistic effect plays a significant role in promoting PMS activation. The main reactive oxygen species for glyphosate oxidation are surface-bound SO4-· and ·OH, produced by activating PMS by electron transfer between Fe2+/Fe3+ and Ce3+/Ce4+ of Fe3Ce1Ox. In light of the products determined, the possible degradation process of glyphosate is also speculated: C-N and C-P bonds of glyphosate molecules are attacked to form aminomethylphosphonic acid (AMPA) and orthophosphate (PO43-) by surface-bound SO4-· and ·OH that continuously mineralize and dephosphorylate AMPA to generate small molecules and inorganic ions, such as H2O and PO43-. The results of this work suggest that Fe3Ce1Ox/PMS could provide a potential candidate for efficiently removing organic compounds containing nitrogen or phosphorus from wastewater.

Genome-wide identification of CNGC genes in Chinese jujube (Ziziphus jujuba Mill.) and ZjCNGC2 mediated signalling cascades in response to cold stress.

BACKGROUNDS: Cyclic nucleotide gated channels (CNGCs) play multifaceted roles in plant physiological processes, especially with respect to signalling processes, plant development, and responses to environmental stresses. However, little information is known about the CNGC family in the large cosmopolitan family Rhamnaceae, which has strong tolerance to biotic and abiotic stresses. RESULTS: In the current study, a total of 15 ZjCNGCs which located on 7 chromosomes were firstly identified in Chinese jujube (Ziziphus jujuba Mill.), the most important species of Rhamnaceae in terms of economic and ecological values. Phylogenetic analysis showed that these ZjCNGCs could be classified into four groups, ZjCNGC12 belonged to group IVA, and ZjCNGC13, 14, 15 belonged to group IVB. In addition, the paralogous and orthologous homology duplication of ZjCNGC15 occurred during the evolutionary process. The characteristics of ZjCNGCs regarding to exon-intron numbers and post-translational modifications showed diversified structures and functions. Motif composition and protein sequence analysis revealed that the phosphate-binding cassette and hinge regions were conserved among ZjCNGCs. Prediction of the cis-acting regulatory elements and expression profiles by real-time quantitative PCR analysis showed that some of the ZjCNGCs responded to environmental changes, especially ZjCNGC2, which was significantly downregulated in response to cold stress, and ZjCNGC4 was highly induced in response to cold, salt and alkaline stresses. ZjCNGC13 and 14 were highly induced in the phytoplasma-resistant cultivar and downregulated in the susceptible cultivar. Furthermore, ZjCNGC2 could be regulated by cAMP treatment, microtubule changes and interact with ZjMAPKK4, which suggested that cAMP and microtubule might play important roles in ZjCNGC2 mediated ZjMAPKK4 signalling transduction involved in cold stress. CONCLUSIONS: The identification and classification analysis of ZjCNGCs were firstly reported, and some key individual ZjCNGCs might play essential roles in the response to biotic and abiotic stresses, especially ZjCNGC2 mediated ZjMAPKK4 signalling transduction involved in cold stress. This systematic analysis could provide important information for further functional characterization of ZjCNGCs with the aim of breeding stress-resistant cultivars.

The Effects of 5,6,7,8,3',4'-Hexamethoxyflavone on Apoptosis of Cultured Human Choriocarcinoma Trophoblast Cells.

5,6,7,8,3,4'-Hexamethoxyflavone, also called nobiletin (NOB), widely found in the citrus peel, is one of the main byproducts in citrus processing. NOB is considered safe, but its safety for women during pregnancy is unknown. Therefore, the effect of NOB on apoptosis in human choriocarcinoma trophoblast cells (BeWo cells) was evaluated. Cells were divided into four groups and cultured with different concentrations of NOB (0, 10, 33, and 100 µM) for 12, 24, 36, and 48 h respectively. Cell viability was detected by CCK-8 assay, cell morphology was detected by a Cell Imaging Multi-Mode Reader, and cell cycle and apoptosis were detected by flow cytometry. Cleaved PARP level, the expressions of B cell lymphoma 2 (BCL2) family proteins, and p53 pathway proteins were detected by Western blot. The results showed that after 48 h of cell culture, the cell viability was decreased significantly, but apoptosis was significantly increased. Compared to the cells without NOB treatment, the cells treated with NOB at 10 or 33 µΜ showed no significant differences in the number of suspended cells or late apoptosis rate, except the increase of cell viability. Treatment of NOB at the concentration of 100 µM improved cell viability, attenuated apoptosis, decreased suspended cells, and did not alter the G1 phase arrest, compared with the non-NOB-treated group after 48 h of culturing. The 100 µΜ NOB treatment increased the levels of BCL2 and BCLXL, and decreased p53 accumulation in BeWo cells at 48 h, but had no effect on the expression of BAX, BAK, BAD, p21, and G1 phase arrest. These findings provide evidence that NOB (10, 33, and 100 µΜ) was safe for BeWo cells. NOB at the concentration of 100 µΜ could attenuate apoptosis in BeWo cells, which might be helpful to prevent pregnancy-related diseases caused by apoptosis.

Maltase Decorated by Chiral Carbon Dots with Inhibited Enzyme Activity for Glucose Level Control.

Carbon dots (CDs) have attracted increasing attention in disease therapy owing to their low toxicity and good biocompatibility. Their therapeutic effect strongly depends on the CDs structure (e.g., size or functional groups). However, the impact of CDs chirality on maltase and blood glucose level has not yet been fully emphasized and studied. Moreover, in previous reports, chiral CDs with targeted optical activity have to be synthesized from precursors of corresponding optical rotation, severely limiting chiral CDs design. Here, chiral CDs with optical rotation opposite to that of the precursor are facilely prepared through electrochemical polymerization. Interestingly, their chirality can be regulated by simply adjusting reaction time. At last, the resultant (+)-DCDs (700 µg mL-1 ) are employed to modify maltase in an effort to regulate the hydrolytic rate of maltose, showing an excellent inhibition ratio to maltase of 54.7%, significantly higher than that of (-)-LCDs (15.5%) in the same reaction conditions. The superior performance may be attributed to the preferable combination of DCDs with maltase. This study provides an electrochemical method to facilely regulate CDs chirality, and explore new applications of chiral CDs as antihyperglycemic therapy for controlling blood glucose levels.

Characterization and comparison of the temporal dynamics of ruminal bacterial microbiota colonizing rice straw and alfalfa hay within ruminants.

Three ruminally cannulated Holstein cows were used to characterize the dynamics of bacterial colonization of rice straw and alfalfa hay and to assess the differences in the composition and inferred gene function of the colonized microbiota between these 2 forages. Nonincubated (0h) rice straw and alfalfa hay samples and residues in nylon bags incubated for 0.5, 2, 6, 16, and 48h were analyzed for dry matter and were used for DNA extraction and MiSeq (Illumina Inc., San Diego, CA) sequencing of the 16S rRNA gene. The microbial communities that colonized the air-dried and nonincubated (0h) rice straw and alfalfa hay were both dominated by members of the Proteobacteria (contributing toward 70.47% of the 16S RNA reads generated). In situ incubation of the 2 forages revealed major shifts in the community composition: Proteobacteria were replaced within 30min by members belonging to the Bacteroidetes and Firmicutes, contributing toward 51.9 and 36.6% of the 16S rRNA reads generated, respectively. A second significant shift was observed after 6h of rumen incubation, when members of the Spirochaetes and Fibrobacteria phyla became abundant in the forage-adherent community. During the first 30min of rumen incubation, ~20.7 and 36.1% of the rice straw and alfalfa hay, respectively, were degraded, whereas little biomass degradation occurred between 30min and 2h after the rice straw or alfalfa hay was placed in the rumen. Significant differences were noted in attached bacterial community structure between the 2 forage groups, and the abundances of dominant genera Anaeroplasma, Butyrivibrio, Fibrobacter, and Prevotella were affected by the forage types. Real-time PCR results showed that the 16S rRNA copies of total bacteria attached to these 2 forages were affected by the forage types and incubation time, and higher numbers of attached bacterial 16S rRNA were observed in the alfalfa hay samples than in the rice straw from 0.5 to 16h of incubation. The metagenomes predicted by phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) revealed that the forage types significantly affected 21 metabolic pathways identified in the Kyoto Encyclopedia of Genes and Genomes, and 33 were significantly changed over time. Collectively, our results reveal a difference in the dynamics of bacterial colonization and the inferred gene function of microbiota associated with rice straw and alfalfa hay within the rumen. These findings are of great importance for the targeted improvement of forage nutrient use efficiency in ruminants.

Highly selective conversion of carbon dioxide to methane by copper single atom electrocatalysts.

Electrocatalytic carbon dioxide (CO2) reduction into high-value chemicals is one of the important solutions to the greenhouse effect and energy crisis. However, the slow kinetic process of eight electrons requires the development of efficient catalysts to improve the yields. Single atom catalysts (SACs) with high activity and selectivity have become an emerging research frontier in the field of heterogeneous catalysis. Herein, a catalyst comprised of Cu single atoms loaded on carbon substrate (Cu-NC) is developed for highly selective electrocatalytic reduction of CO2 to methane (CH4). The optimal catalyst (Cu-NC-1-4) exhibits a faradaic efficiency (FE) of over 50% for CH4 within a wide potential window from -1.3 V to -1.8 V (vs. RHE) and the highest FE of CH4 is up to 67.22% at -1.6 V (vs. RHE). Meanwhile, the product selectivity of CH4 among all the carbon products reaches 93.00%, and the activity decay can be negligible via the 70-hour-stability-test. The existence of atomic dispersed Cu-N3 sites was verified by high-angle annular dark field scanning transmission electron microscopy (HAADF-STEM) and X-ray absorption near edge structure (XANES). Density functional theory (DFT) calculations show that the effective adsorption of the key intermediate *CO on Cu-N3 sites prompts the generation of CH4.

Environmentally degradable carbon dots for inhibiting P. globosa growth and reducing hemolytic toxin.

Red tides not only destroy marine ecosystems but also pose a great threat to human health. The traditional anti-red tide materials are difficult to degrade effectively in the natural environment and there may be risks of environmental leakage and secondary pollution. Furthermore, they cannot reduce the toxicity of toxins released by algae. It is very important to prepare degradable materials that can effectively control red tide and reduce their toxins in the future. Herein, degradable CDs (De-CDs) with biocompatibility and non-toxicity is successfully prepared using the one-step electrolytic method. De-CDs can effectively inhibit P. globosa (algae associated with red tide) growth. More importantly, the De-CDs not only can attenuate the toxicity of toxins released by P. globosa, but also can be degraded under visible-light irradiation in the seawater and avoids environmental leakage. The successful preparation of De-CDs provides a new idea for degradable materials with anti-red tide algae in the future.

Metagenomic next-generation sequencing for diagnosis of infectious encephalitis and meningitis: a retrospective study of 90 patients.

BACKGROUND: Infections of the central nervous system (CNS) are potentially life-threatening and can cause serious morbidity. We evaluated the clinical value of metagenomic next-generation sequencing (mNGS) in the diagnosis of infectious encephalitis and meningitis and explored the factors affecting the results of mNGS. METHODS: Patients with suspected cases of encephalitis or meningitis who presented in Northern Jiangsu People's Hospital from 1 March 2018 to 30 September 2022 were collected. Demographic, historical, and clinical information were obtained, and cerebrospinal fluid (CSF) samples were treated with mNGS. The pathogen was identified using National Center for Biotechnology Information (NCBI) GenBank sequence data. RESULTS: Ninety-six patients were screened and finally 90 subjects enrolled. Of the 90 enrolled cases, 67 (74.4%) were diagnosed with central nervous system infections, which included 48 cases (71.6%) of viral infection, 11 (12.2%) of bacterial infection, 5 (7.5%) of mycobacterium tuberculosis, 2 (3.0%) of fungal infection, and 1 (1.5%) of rickettsia infection. From these cases, mNGS identified 40 (44.4%) true-positive cases, 3 (3.3%) false-positive case, 22 (24.4%) true-negative cases, and 25 (27.8%) false-negative cases. The sensitivity and specificity of mNGS were 61.5% and 88%, respectively. mNGS of CSF could show a higher positive rate in patients with marked CSF abnormalities, including elevated protein concentrations and monocyte counts. CONCLUSION: mNGS of CSF is an effective method for detecting infectious encephalitis and meningitis, and the results should be analyzed combined with conventional microbiological testing results.

Nobiletin, an activator of the pyruvate kinase isozyme M1/M2 protein, upregulated the glycolytic signalling pathway and alleviated depressive-like behaviour caused by artificial light exposure at night in zebrafish.

We established a zebrafish model of depression-like behaviour induced by exposure to artificial light at night (ALAN) and found that nobiletin (NOB) alleviated depression-like behaviour. Subsequently, based on the results of a 24-h free movement assay, clock gene expression and brain tissue transcriptome sequencing, the glycolysis signalling pathway was identified as a potential target through which NOB exerted antidepressant effects. Using the ALAN zebrafish model, we found that supplementation with exogenous L-lactic acid alleviated depressive-like behaviour. Molecular docking and molecular dynamics simulations revealed an inter-molecular interaction between NOB and the pyruvate kinase isozyme M1/M2 (PKM2) protein. We then used compound 3 k to construct a zebrafish model in which PKM2 was inhibited. Our analysis of this model suggested that NOB alleviated depression-like behaviour via inhibition of PKM2. In summary, NOB alleviated depressive-like behaviour induced by ALAN in zebrafish via targeting of PKM2 and activation of the glycolytic signalling pathway.

A metal-free cascaded process for efficient H2O2 photoproduction using conjugated carbonyl sites.

Carbon-based metal-free catalysts are promising green catalysts for photocatalysis and electrocatalysis due to their low cost and environmental friendliness. A key challenge in utilizing these catalysts is identifying their active sites, given their poor crystallinity and complex structures. Here we demonstrate the key structure of the double-bonded conjugated carbon group as a metal-free active site, enabling efficient O2 photoreduction to H2O2 through a cascaded water oxidation - O2 reduction process. Using ethylenediaminetetraacetic acid as a precursor, we synthesized various carbon-based photocatalysts and analyzed their structural evolution. Under the polymerization conditions of 260 °C to 400 °C, an N-ethyl-2-piperazinone-like structure was formed on the surface of the catalyst, resulting in high photocatalytic H2O2 photoproduction (2884.7 µmol g-1h-1) under visible light. A series of control experiments and theoretical calculations further confirm that the double-bond conjugated carbonyl structure is the key and universal feature of the active site of metal-free photocatalysts.