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Abstract It is challenging to attain strong near-infrared (NIR) emissive gold nanoclusters. Here we show a rod-shaped cluster with the composition of [Au28(p-MBT)14(Hdppa)3](SO3CF3)2 (1 for short, Hdppa is N,N-bis(diphenylphosphino)amine, p-MBT is 4-methylbenzenethiolate) has been synthesized. Single crystal X-ray structural analysis reveals that it has a rod-like face-centered cubic (fcc) Au22 kernel built from two interpenetrating bicapped cuboctahedral Au15 units. 1 features NIR luminescence with an emission maximum at 920 nm, and the photoluminescence quantum yield (PLQY) is 12%, which is 30-fold of [Au21(m-MBT)12(Hdppa)2]SO3CF3 (2, m-MBT is 3-methylbenzenethiolate) with a similar composition and 60-fold of Au30S(S‑t‑Bu)18 with a similar structure. time-dependent DFT(TDDFT)calculations reveal that the luminescence of 1 is associated with the Au22 kernel. The small Stokes shift of 1 indicates that it has a very small excited state structural distortion, leading to high radiative decay rate (k r) probability. The emission of cluster 1 is a mixture of phosphorescence and thermally activated delayed fluorescence(TADF), and the enhancement of the NIR emission is mainly due to the promotion of k r rather than the inhibition of k nr. This work demonstrates that the metal kernel and the surface structure are both very important for cluster-based NIR luminescence materials.

Abstract Background Benign prostatic hyperplasia (BPH) is the most common disease in elderly men. There is increasing evidence that periodontitis increases the risk of BPH, but the specific mechanism remains unclear. This study aimed to explore the role and mechanism of the key periodontal pathogen Porphyromonas gingivalis (P. gingivalis) in the development of BPH. Methods The subgingival plaque (Sp) and prostatic fluid (Pf) of patients with BPH concurrent periodontitis were extracted and cultured for 16S rDNA sequencing. Ligature-induced periodontitis, testosterone-induced BPH and the composite models in rats were established. The P. gingivalis and its toxic factor P. gingivalis lipopolysaccharide (P.g-LPS) were injected into the ventral lobe of prostate in rats to simulate its colonization of prostate. P.g-LPS was used to construct the prostate cell infection model for mechanism exploration. Results P. gingivalis, Streptococcus oralis, Capnocytophaga ochracea and other oral pathogens were simultaneously detected in the Pf and Sp of patients with BPH concurrent periodontitis, and the average relative abundance of P. gingivalis was found to be the highest. P. gingivalis was detected in both Pf and Sp in 62.5% of patients. Simultaneous periodontitis and BPH synergistically aggravated prostate histological changes. P. gingivalis and P.g-LPS infection could induce obvious hyperplasia of the prostate epithelium and stroma (epithelial thickness was 2.97- and 3.08-fold that of control group, respectively), and increase of collagen fibrosis (3.81- and 5.02-fold that of control group, respectively). P. gingivalis infection promoted prostate cell proliferation, inhibited apoptosis, and upregulated the expression of inflammatory cytokines interleukin-6 (IL-6; 4.47-fold), interleukin-6 receptor-α (IL-6Rα; 5.74-fold) and glycoprotein 130 (gp130; 4.47-fold) in prostatic tissue. P.g-LPS could significantly inhibit cell apoptosis, promote mitosis and proliferation of cells. P.g-LPS activates the Akt pathway through IL-6/IL-6Rα/gp130 complex, which destroys the imbalance between proliferation and apoptosis of prostate cells, induces BPH. Conclusion P. gingivalis was abundant in the Pf of patients with BPH concurrent periodontitis. P. gingivalis infection can promote BPH, which may affect the progression of BPH via inflammation and the Akt signaling pathway.

Objective: This study aimed to explore andrographolide’s mechanism of action and its protective effect on noise-induced hearing loss (NIHL). Materials and Methods: A mice animal model for NIHL was established through exposure to broadband noise at 120 dB sound pressure level for 4 h. Transcriptomics analysis and pharmacodynamic experiments were carried out. Results: Andrographolide enters the inner ear and effectively prevents hearing damage following noise exposure in the mice model for permanent hearing loss. Moreover, treatment with andrographolide inhibited the excessive activation of inflammatory factors in the cochleae of noise-exposed mice. Conclusion: Andrographolide might be a promising candidate for auditory protective drug investigation.

Abstract Background Growing evidence showed that acupuncture may improve cognitive function by reducing oxidative stress, key to the pathogenesis in vascular dementia (VaD), but this is yet to be systematically analysed. This study aimed to summarize and evaluate the effect of acupuncture on oxidative stress in animal models of VaD. Method Eight databases including PubMed, Embase, Web of Science, Cochrane library, CNKI, Wan Fang, CBM, and VIP were searched since their establishment until April 2023, for studies that reported the effect of acupuncture on oxidative stress in VaD animal models. Relevant literature was screened, and information was extracted by two reviewers. The primary outcomes were the levels of oxidative stress indicators. The methodological quality was assessed via the SYRCLE Risk of Bias Tool. Statistical analyses were performed using the RevMan and Stata software. Results In total, 22 studies with 747 animals were included. The methodology of most studies had flaws or uncertainties. The meta-analysis indicated that, overall, acupuncture significantly reduced the expression of pro-oxidants including reactive oxygen species (standardized mean differences [SMDs] = -4.29, 95% confidence interval [CI]: -6.26, -2.31), malondialdehyde (SMD = -2.27, 95% CI: -3.07, -1.47), nitric oxide (SMD = -0.85, 95% CI: -1.50, -0.20), and nitric oxide synthase (SMD = -1.01, 95% CI: -1.69, -0.34) and enhanced the levels of anti-oxidants including super oxide dismutase (SMD = 2.80, 95% CI: 1.98, 3.61), glutathione peroxidase (SMD = 1.32, 95% CI: -0.11, 2.76), and catalase (SMD = 1.31, 95% CI: 0.05, 2.58) in VaD animal models. In subgroup analyses, acupuncture showed significant effects on most variables. Only partial modelling methods and treatment duration could interpret the heterogeneity of some outcomes. Conclusion Acupuncture may inhibit oxidative stress to improve cognitive deficits in animal models of VaD. Nevertheless, the methodological quality is unsatisfactory. More high-quality research with a rigorous design and further experimental researches and clinical trials are needed to confirm these findings. Systematic review registration This study was registered in PROSPERO (CRD42023411720).

Abstract HEI10 is a conserved E3 ubiquitin ligase involved in crossover formation during meiosis, and is thus essential for both male and female gamete development. Here, we have discovered a novel allele of HEI10 in rice that produces a truncated HEI10 protein missing its N-terminal RING domain, namely sh1 (shorter hei10 1). Unlike previously reported hei10 null alleles that are completely sterile, sh1 exhibits complete male sterility but retains partial female fertility. The causative sh1 mutation is a 76 kb inversion between OsFYVE4 and HEI10, which breaks the integrity of both genes. Allelic tests and complementation assays revealed that the gamete developmental defects of sh1 were caused by disruption of HEI10. Further studies demonstrated that short HEI10 can correctly localise to the nucleus, where it could interact with other proteins that direct meiosis; expressing short HEI10 in hei10 null lines partially restores female fertility. Our data reveal an intriguing mutant allele of HEI10 with differential effects on male and female fertility, providing a new tool to explore similarities and differences between male and female meiosis.

Abstracts: Objectives: To elucidate the therapeutic effects and mechanisms of Atractylodes macrocephala extract crystallize (BZEP) and BZEP self-microemulsion (BZEPWR) on metabolic dysfunction-associated fatty liver disease (MAFLD) induced by “high sugar, high fat, and excessive alcohol consumption” based on the gut–liver axis HDL/LPS signaling pathway. Methods: In this study, BZEP and BZEPWR were obtained via isolation, purification, and microemulsification. Furthermore, an anthropomorphic MAFLD rat model of “high sugar, high fat, and excessive alcohol consumption” was established. The therapeutic effects of BZEPWR and BZEP on the model rats were evaluated in terms of liver function, lipid metabolism (especially HDL-C), serum antioxidant indexes, and liver and intestinal pathophysiology. To determine the lipoproteins in the serum sample, the amplitudes of a plurality of NMR spectra were derived via deconvolution of the composite methyl signal envelope to yield HDL-C subclass concentrations. The changes in intestinal flora were detected via 16 S rRNA gene sequencing. In addition, the gut–liver axis HDL/LPS signaling pathway was validated using immunohistochemistry, immunofluorescence, and western blot. Results: The findings established that BZEPWR and BZEP improved animal signs, serum levels of liver enzymes (ALT and AST), lipid metabolism (TC, TG, HDL-C, and LDL-C), and antioxidant indexes (GSH, SOD, and ROS). In addition, pathological damage to the liver, colon, and ileum was ameliorated, and the intestinal barrier function of the model rats was restored. At the genus level, BZEPWR and BZEP exerted positive effects on beneficial bacteria, such as Lactobacillus and norank_f__Muribaculaceae, and inhibitory effects on harmful bacteria, such as unclassified_f__Lachnospiraceae and Blautia. Twenty HDL-C subspecies were detected, and their levels were differentially increased in both BZEPWR and BZEP groups, with BZEPWR exhibiting a stronger elevating effect on specific HDL-C subspecies. Also, the gut–liver axis HDL/LPS signaling pathway was studied, which indicated that BZEPWR and BZEP significantly increased the expressions of ABCA1, LXR, occludin, and claudin-1 proteins in the gut and serum levels of HDL-C. Concomitantly, the levels of LPS in the serum and TLR4, Myd88, and NF-κB proteins in the liver were decreased. Conclusion: BZEPWR and BZEP exert restorative and reversal effects on the pathophysiological damage to the gut–liver axis in MAFLD rats, and the therapeutic mechanism may be related to the regulation of the intestinal flora and the HDL/LPS signaling pathway.

Hyperuricaemia (HUA) is a metabolic disorder characterised by high blood uric acid (UA) levels; moreover, HUA severity is closely related to the gut microbiota. HUA is also a risk factor for renal damage, diabetes, hypertension, and dyslipidaemia; however, current treatments are associated with detrimental side effects. Alternatively, Fangyukangsuan granules are a natural product with UA-reducing properties. To examine their efficacy in HUA, the binding of small molecules in Fangyukangsuan granules to xanthine oxidase (XOD), a key factor in UA metabolism, was investigated via molecular simulation, and the effects of oral Fangyukangsuan granule administration on serum biochemical indices and intestinal microorganisms in HUA-model rats were examined. Overall, 24 small molecules in Fangyukangsuan granules could bind to XOD. Serum UA, creatinine, blood urea nitrogen, and XOD levels were decreased in rats treated with Fangyukangsuan granules compared to those in untreated HUA-model rats. Moreover, Fangyukangsuan granules restored the intestinal microbial structure in HUA-model rats. Functional analysis of the gut microbiota revealed decreased amino acid biosynthesis and increased fermentation of pyruvate into short-chain fatty acids in Fangyukangsuan granule-treated rats. Together, these findings demonstrate that Fangyukangsuan granules have anti-hyperuricaemic and regulatory effects on the gut microbiota and may be a therapeutic candidate for HUA.

BackgroundOlder adults worldwide experienced heightened risks of depression, anxiety, loneliness, and poor mental well-being during the COVID-19 pandemic. During this period, digital technology emerged as a means to mitigate social isolation and enhance social connectedness among older adults. However, older adults’ behaviors and attitudes toward the adoption and use of digital technology are heterogeneous and shaped by factors such as age, income, and education. Few empirical studies have examined how older adults experiencing social and economic disadvantages perceive the learning of digital tools. ObjectiveThis study aims to examine the motivations, experiences, and perceptions toward a community-based digital intervention among older adults residing in public rental flats in a low-income neighborhood. Specifically, we explored how their attitudes and behaviors toward learning the use of smartphones are shaped by their experiences related to age and socioeconomic challenges. MethodsThis study adopted a qualitative methodology. Between December 2020 and March 2021, we conducted semistructured in-depth interviews with 19 participants aged ≥60 years who had completed the community-based digital intervention. We asked participants questions about the challenges encountered amid the pandemic, their perceived benefits of and difficulties with smartphone use, and their experiences with participating in the intervention. All interviews were audio recorded and analyzed using a reflexive thematic approach. ResultsAlthough older learners stated varying levels of motivation to learn, most expressed ambivalence about the perceived utility and relevance of the smartphone to their current needs and priorities. While participants valued the social interaction with volunteers and the personalized learning model of the digital intervention, they also articulated barriers such as age-related cognitive and physical limitations and language and illiteracy that hindered their sustained use of these digital devices. Most importantly, the internalization of ageist stereotypes of being less worthy learners and the perception of smartphone use as being in the realm of the privileged other further reduced self-efficacy and interest in learning. ConclusionsTo improve learning and sustained use of smartphones for older adults with low income, it is essential to explore avenues that render digital tools pertinent to their daily lives, such as creating opportunities for social connections and relationship building. Future studies should investigate the relationships between older adults’ social, economic, and health marginality and their ability to access digital technologies. We recommend that the design and implementation of digital interventions should prioritize catering to the needs and preferences of various segments of older adults, while working to bridge rather than perpetuate the digital divide.

Introduction Considering the increasing incidence of Alzheimer’s disease (AD) and mild cognitive impairment (MCI) worldwide, there is an urgent need to identify efficacious, safe and convenient treatments. Numerous investigations have been conducted on the use of supplements in this domain, with oral supplementation emerging as a viable therapeutic approach for AD or MCI. Nevertheless, given the multitude of available supplements, it becomes imperative to identify the optimal treatment regimen.Methods and analysis Eight academic databases and three clinical trial registries will be searched from their inception to 1 June 2023. To identify randomised controlled trials investigating the effects of supplements on patients with AD or MCI, two independent reviewers (X-YZ and Y-QL) will extract relevant information from eligible articles, while the risk of bias in the included studies will be assessed using the Rob 2.0 tool developed by the Cochrane Collaboration. The primary outcome of interest is the overall cognitive function. Pair-wise meta-analysis will be conducted using RevMan V.5.3, while network meta-analysis will be carried out using Stata 17.0 and ADDIS 1.16.8. Heterogeneity test, data synthesis and subgroup analysis will be performed if necessary. The GRADE system will be employed to assess the quality of evidence. This study is scheduled to commence on 1 June 2023 and conclude on 1 October 2023.Ethics and dissemination Ethics approval is not required for systematic review and network meta-analysis. The results will be submitted to a peer-reviewed journal or at a conference.Trial registration number PROSPERO (CRD42023414700).