A randomized, double-blind, placebo-controlled phase I clinical trial of rotavirus inactivated vaccine (Vero cell) in a healthy adult population aged 18-49 years to assess safety and preliminary observation of immunogenicity.

We conducted a phase I, randomized, double-blind, placebo-controlled trial including healthy adults in Sui County, Henan Province, China. Ninety-six adults were randomly assigned to one of three groups (high-dose, medium-dose, and low-dose) at a 3:1 ratio to receive one vaccine dose or placebo. Adverse events up to 28 days after each dose and serious adverse events up to 6 months after all doses were reported. Geometric mean titers and seroconversion rates were measured for anti-rotavirus neutralizing antibodies using microneutralization tests. The rates of total adverse events in the placebo group, low-dose group, medium-dose group, and high-dose group were 29.17 % (12.62 %-51.09 %), 12.50 % (2.66 %-32.36 %), 50.00 % (29.12 %-70.88 %), and 41.67 % (22.11 %-63.36 %), respectively, with no significant difference in the experimental groups compared with the placebo group. The results of the neutralizing antibody assay showed that in the adult group, the neutralizing antibody geometric mean titer at 28 days after full immunization in the low-dose group was 583.01 (95 % confidence interval [CI]: 447.12-760.20), that in the medium-dose group was 899.34 (95 % CI: 601.73-1344.14), and that in the high-dose group was 1055.24 (95 % CI: 876.28-1270.75). The GMT of serum-specific IgG at 28 days after full immunization in the low-dose group was 3444.26 (95 % CI: 2292.35-5175.02), that in the medium-dose group was 6888.55 (95 % CI: 4426.67-10719.6), and that in the high-dose group was 7511.99 (95 % CI: 3988.27-14149.0). The GMT of serum-specific IgA at 28 days after full immunization in the low-dose group was 2332.14 (95 % CI: 1538.82-3534.45), that in the medium-dose group was 4800.98 (95 % CI: 2986.64-7717.50), and that in the high-dose group was 3204.30 (95 % CI: 2175.66-4719.27). In terms of safety, adverse events were mainly Grades 1 and 2, indicating that the safety of the vaccine is within the acceptable range in the healthy adult population. Considering the GMT and positive transfer rate of neutralizing antibodies for the main immunogenicity endpoints in the experimental groups, it was initially observed that the high-dose group had higher levels of neutralizing antibodies than the medium- and low-dose groups in adults aged 18-49 years. This novel inactivated rotavirus vaccine was generally well-tolerated in adults, and the vaccine was immunogenic in adults (ClinicalTrials.gov number, NCT04626856).

Cognitive Functions and Subjective Hearing in Cochlear Implant Users.

Background and Objectives: : A cochlear implant (CI) is an effective prosthetic device used to treat severe-to-profound hearing loss. The present study examined cognitive function in CI users by employing a web-based cognitive testing platform, i.e., BrainCheck, and explored the correlation between cognitive function and subjective evaluation of hearing. Subjects and Methods: : Forty-two CI users (mean age: 58.90 years) were surveyed in the subjective evaluation of hearing, and 20/42 participated in the BrainCheck cognitive tests (immediate recognition, Trail Making A, Trail Making B, Stroop, digit symbol substitution, and delayed recognition). As controls for cognitive function, young normal-hearing (YNH, mean age=23.83 years) and older normal-hearing (ONH, mean age=52.67 years) listener groups were subjected to Brain- Check testing. Results: : CI users exhibited poorer cognitive function than the normal hearing groups in all tasks except for immediate and delayed recognition. The highest percentage of CI users who had "possible" and "likely" cognitive impairment, based on BrainCheck scores (ranging from 0-200), was observed in tests assessing executive function. The composite cognitive score across domains tended to be related to subjective hearing (p=0.07). Conclusions: : The findings of the current study suggest that CI users had a higher likelihood of cognitive impairment in the executive function domain than in lower-level domains. BrianCheck online cognitive testing affords a convenient and effective tool to self-evaluate cognitive function in CI users.

Honokiol suppress the PD-L1 expression to improve anti-tumor immunity in lung cancer.

Lung cancer is a serious health issue globally, and current treatments have proven to be inadequate. Therefore, immune checkpoint inhibitors (ICIs) that target the PD-1/PD-L1 pathway have become a viable treatment option in lun cancer. Honokiol, a lignan derived from Magnolia officinalis, has been found to possess anti-inflammatory, antioxidant, and antitumor properties. Our research found that honokiol can effectively regulate PD-L1 through network pharmacology and transcriptome analysis. Cell experiments showed that honokiol can significantly reduce PD-L1 expression in cells with high PD-L1 expression. Molecular docking, cellular thermal shift assay (CETSA) and Bio-Layer Interferometry (BLI)indicated that Honokiol can bind to PD-L1. Co-culture experiments on lung cancer cells and T cells demonstrated that honokiol mediates PD-L1 degradation, stimulates T cell activation, and facilitates T cell killing of tumor cells. Moreover, honokiol activates CD4 + and CD8 + T cell infiltration in vivo, thus suppressing tumor growth in C57BL/6 mice. In conclusion, this study has demonstrated that honokiol can inhibit the growth of lung cancer by targeting tumor cell PD-L1, suppressing PD-L1 expression, blocking the PD-1/PD-L1 pathway, and enhancing anti-tumor immunity.

Effects of the seedling tray overlapping for seed emergence mode on emergence characteristics and growth of rice seedlings.

Seedling mode plays a crucial role in the rice production process, as it significantly affects the growth and development of seedlings. Among the various seedling modes, the seedling tray overlapping for seed emergence mode (STOSE mode) has been demonstrated to be effective in enhancing seedling quality. However, the impact of this mode on the germination and growth of seeds with varying plumpness remains uncertain. To investigate the effect of the STOSE mode on seedling emergence characteristics, growth uniformity, and nutrient uptake of seeds with varying plumpness levels, we conducted a study using super early rice Zhongzao 39 (ZZ39) as the test material. The seeds were categorized into three groups: plumped, mixed, and unplumped. The results indicated that the STOSE mode significantly improved the seedling rate for all types of seeds in comparison to the seedling tray nonoverlapping for seed emergence mode (TSR mode). Notably, the unplumped seeds exhibited the most pronounced enhancement effect. The soluble sugar content of the seeds increased significantly after 2 days of sowing under the STOSE mode, whereas the starch content exhibited a significant decrease. Furthermore, the STOSE mode outperformed the TSR mode in several aspects including seedling growth uniformity, aboveground dry matter mass, root traits, and nutrient uptake. Overall, the STOSE mode not only promoted the germination and growth of plumped and mixed seeds but also had a more pronounced impact on unplumped seeds.

Metalation of metal-organic frameworks: fundamentals and applications.

Metalation of metal-organic frameworks (MOFs) has been developed as a prominent strategy for materials functionalization for pore chemistry modulation and property optimization. By introducing exotic metal ions/complexes/nanoparticles onto/into the parent framework, many metallized MOFs have exhibited significantly improved performance in a wide range of applications. In this review, we focus on the research progress in the metalation of metal-organic frameworks during the last five years, spanning the design principles, synthetic strategies, and potential applications. Based on the crystal engineering principles, a minor change in the MOF composition through metalation would lead to leveraged variation of properties. This review starts from the general strategies established for the incorporation of metal species within MOFs, followed by the design principles to graft the desired functionality while maintaining the porosity of frameworks. Facile metalation has contributed a great number of bespoke materials with excellent performance, and we summarize their applications in gas adsorption and separation, heterogeneous catalysis, detection and sensing, and energy storage and conversion. The underlying mechanisms are also investigated by state-of-the-art techniques and analyzed for gaining insight into the structure-property relationships, which would in turn facilitate the further development of design principles. Finally, the current challenges and opportunities in MOF metalation have been discussed, and the promising future directions for customizing the next-generation advanced materials have been outlined as well.

Efficacy and safety analysis of immunotherapy in non-small cell lung cancer patients with MET alterations.

BACKGROUND: Mesenchymal epithelial transition factor (MET) is a rare oncologic driver gene, and information on immunotherapy for non-small cell lung cancer (NSCLC) patients with this driver gene is limited. Here we evaluate the efficacy and safety of immune checkpoint inhibitors (ICI) under different therapeutic regimen for NSCLC patients with MET alterations. METHODS: From June 2019 to December 2023, we assessed the efficacy and toxicity of ICIs in 42 NSCLC patients with MET alterations. Survival curves were plotted using the Kaplan-Meier method and the Cox proportional hazards model applied for univariate and multivariate analyses. We assessed the size of target lesion according to RECIST v1.1, and objective response rate (ORR) was defined as the sum of complete response (CR) and partial response (PR), disease control rate (DCR) as the sum of CR, PR, and disease stable. RESULTS: A total of 42 NSCLC patients with MET alterations were included in this retrospective study, 10 was MET 14 skipping mutation and 32 was MET amplification. The ORR for ICI treatment was 30.95% and the DCR was 71.43%. Median progression-free survival (mPFS) and median overall survival (OS) were 4.40 and 13.97 months, respectively. There exists statistical differences between the mPFS of ICI monotherapy and combine ICI therapy (2.8 vs 7.8 months, p = 0.022). The incidence of drug-related adverse reactions was 47.62%, mainly bone marrow suppression (14.28%), immune-related pneumonia (7.14%), and liver function impairment (7.14%), and six patients (14.28%) experiencing grade 3 or above adverse events. CONCLUSION: NSCLC patients with MET alterations can benefit from immunotherapy, especially the patients treated by combined ICI therapy. However, special attention should be paid to the occurrence of grade 3/4 adverse reactions while using the combined ICI therapy.

Protective Effects and Mechanisms of Esculetin against H2O2-Induced Oxidative Stress, Apoptosis, and Pyroptosis in Human Hepatoma HepG2 Cells.

Oxidative stress plays a crucial role in the pathogenesis of many diseases. Esculetin is a natural coumarin compound with good antioxidant and anti-inflammatory properties. However, whether esculetin can protect HepG2 cells through inhibiting H2O2-induced apoptosis and pyroptosis is still ambiguous. Therefore, this study aimed to investigate the protective effects and mechanisms of esculetin against oxidative stress-induced cell damage in HepG2 cells. The results of this study demonstrate that pretreatment with esculetin could significantly improve the decrease in cell viability induced by H2O2 and reduce intracellular ROS levels. Esculetin not only apparently reduced the apoptotic rates and prevented MMP loss, but also markedly decreased cleaved-Caspase-3, cleaved-PARP, pro-apoptotic protein (Bax), and MMP-related protein (Cyt-c) expression, and increased anti-apoptotic protein (Bcl-2) expression in H2O2-induced HepG2 cells. Meanwhile, esculetin also remarkably reduced the level of LDH and decreased the expression of the pyroptosis-related proteins NLRP3, cleaved-Caspase-1, Il-1ß, and GSDMD-N. Furthermore, esculetin pretreatment evidently downregulated the protein expression of p-JNK, p-c-Fos, and p-c-Jun. Additionally, anisomycin, a specific activator of JNK, blocked the protection of esculetin against H2O2-induced HepG2 cells apoptosis and pyroptosis. In conclusion, esculetin can protect HepG2 cells against H2O2-induced oxidative stress, apoptosis, and pyroptosis via inhibiting the JNK signaling pathway. These findings indicate that esculetin has the potential to be used as an antioxidant that improves oxidative stress-related diseases.

Nitroreductase-responsive nanoparticles for in situ fluorescence imaging and synergistic antibacterial therapy of bacterial keratitis.

As bacterial keratitis progresses rapidly, prompt intervention is necessary. Current diagnostic processes are time-consuming and invasive, leading to improper antibiotics for treatment. Therefore, innovative strategies for diagnosing and treating bacterial keratitis are urgently needed. In this study, Cu2-xSe@BSA@NTRP nanoparticles were developed by loading nitroreductase-responsive probes (NTRPs) onto Cu2-xSe@BSA. These nanoparticles exhibited integrated fluorescence imaging and antibacterial capabilities. In vitro and in vivo experiments showed that the nanoparticles produced responsive fluorescence signals in bacteria within 30 min due to an interaction between the released NTRP and bacterial endogenous nitroreductase (NTR). When combined with low-temperature photothermal therapy (PTT), the nanoparticles effectively eliminated E. coli and S. aureus, achieved antibacterial efficacy above 95% and facilitated the re-epithelialization process at the corneal wound site in vivo. Overall, the Cu2-xSe@BSA@NTRP nanoparticles demonstrated potential for rapid, noninvasive in situ diagnosis, treatment, and visualization assessment of therapy effectiveness in bacterial keratitis.

Rejuvenating classical brain electrophysiology source localization methods with spatial graph Fourier filters for source extents estimation.

EEG/MEG source imaging (ESI) aims to find the underlying brain sources to explain the observed EEG or MEG measurement. Multiple classical approaches have been proposed to solve the ESI problem based on different neurophysiological assumptions. To support clinical decision-making, it is important to estimate not only the exact location of the source signal but also the extended source activation regions. Existing methods may render over-diffuse or sparse solutions, which limit the source extent estimation accuracy. In this work, we leverage the graph structures defined in the 3D mesh of the brain and the spatial graph Fourier transform (GFT) to decompose the spatial graph structure into sub-spaces of low-, medium-, and high-frequency basis. We propose to use the low-frequency basis of spatial graph filters to approximate the extended areas of brain activation and embed the GFT into the classical ESI methods. We validated the classical source localization methods with the corresponding improved version using GFT in both synthetic data and real data. We found the proposed method can effectively reconstruct focal source patterns and significantly improve the performance compared to the classical algorithms.

Allometric Growth Pattern and Hunger Tolerance of Hemibarbus maculatus Bleeker Larvae.

To clarify the allometric growth pattern and hunger tolerance of Hemibarbus maculatus Bleeker larvae, the morphological lengths of their functional organs were measured continuously and their primary feeding rates under a state of starvation were studied. A control group and starvation group were set up for this study, and 10 larvae were sampled from each group every day in order to study their allometric growth pattern and starvation tolerance. The results indicated that the Hemibarbus maculatus larvae opened their mouths for feeding at 4 days after hatching, and that the yolk sac disappeared completely at 11 days after hatching. The Hemibarbus maculatus larvae preferentially developed their heads, fins, and eyes, related to the functions of feeding, balancing, and swimming, in order to cope with complex environments. The growth inflection points for the head length, pectoral fin length, dorsal fin length, eye diameter, eye spacing, snout length, and body height were characterized by total lengths of 10.93 mm, 11.67 mm, 11.67 mm, 13.17 mm, 16.53 mm, 15.13 mm, and 15.13 mm, respectively. Prior to and following the inflection point, positive allometric growth was observed in all organs. After the inflection point, the dorsal fin continued to maintain positive allometric growth, while the others changed to isometric allometric growth. A growth inflection point was not observed for trunk length or the lengths of the tail and anal fins. The trunk length always maintained negative allometry, while the tail and anal fin lengths were reversed. The growth inflection point of the tail length was at a total length of 13.68 mm. Before and after the growth inflection point, negative and isometric allometric growths were observed, respectively. According to the relationship between the total length and number of days after hatching, the growth inflection point of the Hemibarbus maculatus larvae was concentrated at TL = 10.93-16.53 mm, which was observed 14-20 days after hatching. The point of no return for the Hemibarbus maculatus larvae was 12-13 days after hatching, and the ratio of days after hatching in the mixed trophic period to the endotrophic period was 1.75, indicating that the larvae had strong hunger tolerance. Therefore, when considering a water temperature of 22.66 ± 1.56 °C, 4-5 days after hatching is the best time to cultivate in the pond, and it should not be carried out later than 12 days after hatching.

Edoxaban for stroke prevention in atrial fibrillation and factors associated with dosing: patient characteristics from the prospective observational ETNA-AF-China registry.

Real-world data on effectiveness and safety of a single non-vitamin K antagonist oral anticoagulant in the Chinese population with atrial fibrillation (AF) are limited. This study reports characteristics of patients treated with edoxaban and factors associated with dosing patterns from routine care in China. ETNA-AF-China (NCT04747496) is a multicentre, prospective, observational study enrolling edoxaban-treated patients from four economic regions with a targeted 2-year follow-up. Of the 4930 patients with AF (mean age: 70.2 ± 9.5 years; male, 57.1%), the mean creatinine clearance (CrCl), CHA2DS2-VASc, and HAS-BLED scores were 71.2 mL/min, 2.9, and 1.6. Overall, 6.4% of patients were perceived as frail by investigators. Available label dose reduction criteria (N = 4232) revealed that 3278 (77.5%) patients received recommended doses and 954 (22.5%) non-recommended doses. Northeast (53.0%) and West (43.1%) regions had the highest prescriptions of 60 mg and 30 mg recommended doses, respectively. Non-recommended 30 mg doses were more frequently prescribed in patients with antiplatelet use and history of heart failure than recommended 60 mg. Multivariate analysis identified advanced age as the strongest associated factor with non-recommended doses. Frailty had the strongest association with 30 mg except for age, and history of TIA was the most relevant factor associated with 60 mg. In conclusion, patients in the ETNA-AF-China study were predominantly aged 65 years and older, had mild-to-moderate renal impairment and good label adherence. Advanced age was associated with non-recommended doses, with frailty most common for non-recommended 30 mg and a history of TIA for the non-recommended 60 mg dose.

Flexible-center Hat Complete Electrode Model for EEG Forward Problem.

OBJECTIVE: This study aims to develop a more realistic electrode model by incorporating the non-uniform distribution of electrode contact conductance (ECC) and the shunting effects, to accurately solve EEG forward problem (FP). METHODS: Firstly, a hat function is introduced to construct a more realistic hat-shaped distribution (HD) for ECC. Secondly, this hat function is modified by applying two parameters - offset ratio and offset direction - to account for the variability in ECC's center and to develop the flexible-center HD (FCHD). Finally, by integrating this FCHD into the complete electrode model (CEM) with the shunting effects, a novel flexible-center hat complete electrode model (FCH-CEM) is proposed and used to solve FP. RESULTS: Simulation experiments using a realistic head model demonstrate the necessity of FCHCEM and its potential to improve the accuracy of the FP solution compared to current models, i.e., the point electrode model (PEM) and CEM. And compared to PEM, it has better performance under coarse mesh conditions (2 mm). Further experiments indicate the significance of considering shunting effects, as ignoring them results in larger errors than coarse mesh when the average contact conductance is large (). CONCLUSION: The proposed FCH-CEM has better accuracy and performance than PEM and complements CEM in finer meshes, making it necessary for coarse meshes. SIGNIFICANCE: This study proposes a novel model that enhances electrode modeling and FP accuracy, and provides new ideas and methods for future research.

Cathepsin B serves as a potential prognostic biomarker and correlates with ferroptosis in rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a long-term, systemic, and progressive autoimmune disorder. It has been established that ferroptosis, a type of iron-dependent lipid peroxidation cell death, is closely associated with RA. Fibroblast-like synoviocytes (FLS) are the main drivers of RA joint destruction, and they possess a high concentration of endoplasmic reticulum structure. Therefore, targeting ferroptosis and RA-FLS may be a potential treatment for RA. METHODS: Four machine learning algorithms were utilized to detect the essential genes linked to RA, and an XGBoost model was created based on the identified genes. SHAP values were then used to visualize the factors that affect the development and progression of RA, and to analyze the importance of individual features in predicting the outcomes. Moreover, WGCNA and PPI were employed to identify the key genes related to RA, and CIBERSORT was used to analyze the correlation between the chosen genes and immune cells. Finally, the findings were validated through in vitro cell experiments, such as CCK-8 assay, lipid peroxidation assay, iron assay, GSH assay, and Western blot. RESULTS: Bioinformatics and machine learning were employed to identify cathepsin B (CTSB) as a potential biomarker for RA. CTSB is highly expressed in RA patients and has been found to have a positive correlation with macrophages M2, neutrophils, and T cell follicular helper cells, and a negative correlation with CD8 T cells, monocytes, Tregs, and CD4 memory T cells. To investigate the effect of CTSB on RA-FLS from RA patients, the CTSB inhibitor CA-074Me was used and it was observed to reduce the proliferation and migration of RA-FLS, as indicated by the accumulation of lipid ROS and ferrous ions, and induce ferroptosis in RA-FLS. CONCLUSIONS: This study identified CTSB, a gene associated with ferroptosis, as a potential biomarker for diagnosing and managing RA. Moreover, CA-074Me, a CTSB inhibitor, was observed to cause ferroptosis and reduce the migratory capacity of RA-FLS.

PVB exerts anti-inflammatory effects by inhibiting the activation of MAPK and NF-κB signaling pathways and ROS generation in neutrophils.

Pinaverium bromide (PVB) has been shown to protect mice against sepsis, which is predominantly attributed to PVB-mediated anti-inflammatory effects by inhibiting primed neutrophils to produce proinflammatory cytokines. However, the underlying mechanism(s) by which PVB affects neutrophils remains unknown. In this study, we report that treatment with PVB either before or after LPS stimulation attenuated IL-1ß and TNF-α expression at both mRNA and protein levels in LPS-activated murine neutrophils. Further experiments revealed that PVB inhibited the phosphorylation of ERK, JNK, and IκBα in LPS-stimulated murine neutrophils. Moreover, PVB reduced reactive oxygen species (ROS) levels via regulating NADPH oxidase 2 (NOX2) activity, as represented by inhibiting p47phox translocation from the cytoplasm to the cellular membrane. Importantly, PVB significantly attenuated IL-1ß, TNF-α, IL-6, CXCL1 production in both LPS-stimulated low density neutrophils (LDNs) and normal density neutrophils (NDNs) isolated from septic patients. Collectively, we demonstrated that PVB exerts anti-inflammatory effect by attenuating ROS generation and suppressing the activation of MAPK and NF-κB signaling pathways, suggesting that PVB may act as a potential therapeutic agent for sepsis by inhibiting neutrophil priming and activation.

Ursolic acid induces apoptosis and pyroptosis in Reh cells by upregulating of the JNK signalling pathway based on network pharmacology and experimental validation.

Objective: To explore the mechanism of ursolic acid (UA) against acute B lymphoblastic leukaemia (B-ALL) based on network pharmacological analysis, molecular docking and experimental verification. Methods: The core targets, functional processes, and biological pathways of UA in B-ALL were predicted by network pharmacology and molecular docking. The efficacy and mechanism of UA against B-ALL were verified through in vitro experiments such as cell viability assays, CCK-8 assays, LDH assays, AO/EB staining, flow cytometry, and Western blot assays. Results: Network pharmacology analysis of the core targets indicated that the effects of UA on B-ALL were related to programmed cell death (apoptosis and pyroptosis). Molecular docking results showed that FOS, CASP8, MAPK8, IL-1ß and JUN were the key targets of UA against B-ALL. The MTS assay showed that UA decreased the viability of Reh cells in a concentration- and time-dependent manner. Cellular and Western blot experiments found that UA induced Reh cell apoptosis and pyroptosis by upregulating the JNK signalling pathway. Conclusions: Our findings demonstrated that UA could induce Reh cell apoptosis and pyroptosis by activating the JNK signalling pathway to exert anti-B-ALL effects. This indicates that UA may become a potential drug for the effective treatment of B-ALL.

A preliminary investigation of the regulatory effect of acupuncture on hippocampal circHDAC2/miR-3065/SLC30A3 axis in CIRI rats. / å¤§é¼ æµ·é©¬ç»„ç»‡circHDAC2/miR-3065/SLC30A3è½´å‚ä¸Žé’ˆåˆºè°ƒèŠ‚è„‘ç¼ºè¡€å†çŒæ³¨æŸä¼¤çš„åˆæ­¥ç ”ç©¶.

OBJECTIVES: To explore the mechanisms of acupuncture against cerebral ischemia/reperfusion injury (CIRI) through observing the expression of circular RNA HDAC2 (circHDAC2) in the hippocampus of rats. METHODS: SD rats were randomly divided into sham-operation, model and acupuncture groups, with 13 rats in each group. The rat model of CIRI was established by middle cerebral artery occlusion. In the acupuncture group, acupuncture was delivvered at "Dazhui" (GV14), "Shuigou" (GV26) and "Baihui" (GV20), and the needles were retained for 30 min each time and acupuncture was conducted once every 12 h for a total of 7 sessions. Before and after intervention, using modified Garcia scale, the neurological function of the rats were evaluated, and TTC staining was employed to determine the cerebral infarct area. Gene chip technology was used to screen the circRNAs with differential expressions in the ischemic hippocampus, and the circRNAs with co-differential expression (co-DE circRNAs) in the model group/sham-operation group, and the acupuncture group/model group separately. Among those circRNAs, the core circRNAs were screened according to P value, fold change (FC) and gene ontology (GO) analysis；and their expressions in the ischemic hippocampus were determined using quantitative real-time PCR (qPCR). Based on the verification results, a competing endogenous RNA (ceRNA) prediction network was constructed. The expression levels of microRNA (miRNA) and mRNA with high node centrality in the prediction network were validated by qPCR. RESULTS: Before intervention, compared with the sham-operation group, the modified Garcia score of each modeling group decreased (P<0.01). After intervention, the modified Garcia score was reduced and the cerebral infarct area ratio increased (P<0.01) in the model group when compared with the sham-operation group. In the acupuncture group, the modified Garcia score was higher and the cerebral infarct area ratio lower (P<0.01) than those of the model group. The microarray results of gene chip showed that 16 co-DE circRNAs were down-regulated in the model group and up-regulated in the acupuncture group, and 7 co-DE circRNAs up-regulated in the model group and down-regulated in the acupuncture group. The core circHDAC2 and circNTRK2 were screened according to P value, FC and the enrichment number of GO entries. QPCR results showed that, compared with the sham-operation group, the expression of circHDAC2 and circNTRK2 of the ischemic hippocampal tissue was down-regulated in the model group (P<0.01)；and that of circHDAC2 and circNTRK2 up-regulated in the acupuncture group when compared with the model group (P<0.01). The relevant ceRNA regulatory network was constructed for circHDAC2 and the prediction results showed that the regulatory networks contained 12 miRNAs and 31 mRNAs. Results of verifying miRNA with high network node centrality and mRNA relevant with nerve regulation showed that, when compared with the sham-operation group, the expression levels of miR-29a, miR-29b and the solute carrier family 30 member 3 (SLC30A3) mRNA in the ischemic hippocampus were down-regulated (P<0.01)；and those of miR-3065 and mercaptopyruvate sulfurtransferase (MPST) up-regulated (P<0.01) in the model group. Compared with the model group, the expressions of miR-29a, miR-29b and SLC30A3 mRNA in the ischemic hippocampus were up-regulated (P<0.01, P<0.05), while that of miR-3065 down-regulated (P<0.05) in the acupuncture group. CONCLUSIONS: Acupuncture significantly improves the neurological function and reduces the cerebral infarct area in CIRI rats, which may be related to the regulation of hippocampal circHDAC2/miR-3065/SLC30A3 axis.

Comparative Transcriptome Combined with Morphophysiological Analyses Revealed Carotenoid Biosynthesis for Differential Chilling Tolerance in Two Contrasting Rice (Oryza sativa L.) Genotypes.

Early spring cold spells can lead to leaf chlorosis during the rice seedling greening process. However, the physiological and molecular mechanisms underlying the rice greening process under low-temperature conditions remain unknown. In this study, comparative transcriptome and morphophysiological analyses were performed to investigate the mechanisms mediating the responses of the Koshihikari (Kos) and Kasalath (Kas) rice cultivars to chilling stress. According to their growth-related traits, electrolyte leakage, and chlorophyll fluorescence parameters, Kos was more tolerant to low-temperature stress than Kas. Moreover, chloroplast morphology was more normal (e.g., oval) in Kos than in Kas at 17 °C. The comparative transcriptome analysis revealed 610 up-regulated differentially expressed genes that were common to all four comparisons. Furthermore, carotenoid biosynthesis was identified as a critical pathway for the Kos response to chilling stress. The genes in the carotenoid biosynthesis pathway were expressed at higher levels in Kos than in Kas at 17 °C, which was in accordance with the higher leaf carotenoid content in Kos than in Kas. The lycopene ß-cyclase and lycopene ε-cyclase activities increased more in Kos than in Kas. Additionally, the increases in the violaxanthin de-epoxidase and carotenoid hydroxylase activities in Kos seedlings resulted in the accumulation of zeaxanthin and lutein and mitigated the effects of chilling stress on chloroplasts. These findings have clarified the molecular mechanisms underlying the chilling tolerance of rice seedlings during the greening process.

Synthesis, structure and photoluminescence of Cu(I) complexes containing new functionalized 1,2,3-triazole ligands.

The reaction of a triazole ligand, 2-(1H-1,2,3-triazol-4-yl)pyridine (L1), with 2-bromopyridine afforded three new ligands, 2,2'-(1H-1,2,3-triazole-1,4-diyl)dipyridine (L2), 2,2'-(2H-1,2,3-triazole-2,4-diyl)dipyridine (L3) and 2,2'-(1H-1,2,3-triazole-1,5-diyl)dipyridine (L4). A series of luminescent mononuclear copper(I) complexes of these ligands [Cu(Ln)(P^P)](ClO4) [n = 1, P^P = (PPh3)2 (1); n = 1, P^P = POP (2); n = 2, P^P = (PPh3)2 (3); n = 2, P^P = POP (4); n = 3, P^P = (PPh3)2 (5); n = 3, P^P = POP (6); n = 4, P^P = (PPh3)2 (9); n = 4, P^P = POP (10)] have been obtained from the reaction of Ln with [Cu(MeCN)4]ClO4 in the presence of PPh3 and POP. L3 was also found to form dinuclear compounds [Cu2(L3)(PPh3)4](ClO4)2 (7) and [Cu2(L3)(POP)2](ClO4)2 (8). All of the Cu(I) compounds have been characterized by IR, UV/vis, CV, 1H NMR, and 31P{1H} NMR. The molecular structures of 1-3, 5, and 7 have been further determined by X-ray crystallography. In CH2Cl2 solutions, these Cu(I) complexes exhibit tunable green to orange emissions (563-621 nm) upon excitation at λex = 380 nm. In the solid state, these complexes show intense emissions and it is interesting to note that 1 and 3 are blue-light emitters. Density functional theory (DFT) calculations revealed that the lowest energy electronic transition associated with these complexes predominantly originates from metal-to-ligand charge transfer transitions (MLCT).

Slow magnetic relaxation in 8-coordinate Mn(II) compounds.

The design and synthesis of high-spin Mn(II)-based single-molecule magnets (SMMs) have not been well developed to a great extent, as compared with a large number of SMMs based on the other first row transition metal complexes. In light of our success in designing Fe(II), Co(II) and Fe(III)-based SMMs with a high coordination number of 8, it is of great interest to design Mn(II) analogues with such a strategy. In this contribution, four Mn(II) compounds, [MnII(Ln)2](ClO4)2 (1-4) were obtained from reactions of neutral tetradentate ligands, L1-L4, with hydrated MnII(ClO4)2 (L1 = 2,9-bis(carbomethoxy)-1,10-phenanthroline, L2 = 2,9-bis(carbomethoxy)-2,2'-dipyridine, L3 = N2,N9-dibutyl-1,10-phenanthroline-2,9-dicarboxamide, L4 = 6,6'-bis(2-(tert-butyl)-2H-tetrazol-5-yl)-2,2'-bipyridine). Their crystal structures have been determined by X-ray crystallography and it clearly shows that the Mn(II) centers in these compounds have an oversaturated coordination number of 8. Their magnetic properties have been investigated in detail; to our surprise, all of these Mn(II) compounds show interesting slow magnetic relaxation behaviors under an applied direct current field, although they have very small negative D values.

Psychological interventions for the prevention of depression relapse: systematic review and network meta-analysis.

Depression is highly prevalent and easily relapses. Psychological interventions are effective for the prevention of depression relapse. This systematic review and network meta-analysis aimed to compare the efficacy at the same follow-up time points of psychological interventions in depression. We searched PubMed, Embase, and PsycINFO via OVID, and the Cochrane Library published up to December 12, 2021, and PubMed up to July 1, 2022. The primary outcome was depression relapse, considering the same time points that were extracted on survival curves or relapse curves. The study protocol was registered with PROSPERO, CRD42022343327. A total of 2,871 patients were included from 25 RCTs. Mindfulness-based cognitive therapy (MBCT) was significantly better than placebo at the 3 months, the 6 months, and the 9 months at follow-up. Cognitive behavioral therapy (CBT) was significantly better than treatment as usual at the 3 months, the 9 months, the 12 months, and the 15 months at follow-up. CBT was significantly better than placebo at the 21 months and the 24 months at follow-up. Behavioral activation therapy was significantly better than placebo at the 21 months and the 24 months at follow-up. Interpersonal psychotherapy was significantly better than placebo at the 24-month follow-up. All psychological interventions included in the study were significantly better than supportive counseling most of the time. The results were robust in various sensitivity and subgroup analyses. In conclusion, MBCT had a continuous effect in preventing relapse of depression. CBT had the longest but not continuous effect in preventing relapse of depression. The effects of behavioral activation therapy and interpersonal therapy for the prevention of depression appeared late. All psychological interventions included in the study were more effective than supportive counseling. More evidence is needed from large comparative trials that provide long-term follow-up data.