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With the development of modern rural tourism, it has become people’s spiritual demand to deeply tap the characteristic rural culture and continuously enhance the attraction of rural tourism. However, due to the complex tourism market environment, small changes in factors will affect the final result. Therefore, traditional methods cannot accurately predict the future tourism market. In view of this situation, this paper uses the mathematical algorithm of BP neural network to simulate the structure of brain neural network to deal with this kind of nonlinear relationship problem. Through the classification of complex and changeable factors, the modeling is completed systematically, and finally the effective prediction results are obtained. For the analysis of the time evolution of tourism resources development, it can be found from the policy development theory that the innovative development presents the characteristics of S-shaped curve in time; that is, the number adopted in the initial stage of development is less, then enters the rapid development period, and finally develops slowly. This study will help to solve the primary problem of balancing the positive and negative effects of rural tourism development and realizing the sustainable development of coastal villages.

Cellular senescence is a stable growth arrest that is implicated in tissue ageing and cancer. Senescent cells are characterized by an upregulation of proinflammatory cytokines, which is termed the senescence-associated secretory phenotype (SASP). NAD + metabolism influences both tissue ageing and cancer. However, the role of NAD + metabolism in regulating the SASP is poorly understood. Here, we show that nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme of the NAD + salvage pathway, governs the proinflammatory SASP independent of senescence-associated growth arrest. NAMPT expression is regulated by high mobility group A (HMGA) proteins during senescence. The HMGA–NAMPT–NAD + signalling axis promotes the proinflammatory SASP by enhancing glycolysis and mitochondrial respiration. HMGA proteins and NAMPT promote the proinflammatory SASP through NAD + -mediated suppression of AMPK kinase, which suppresses the p53-mediated inhibition of p38 MAPK to enhance NF-κB activity. We conclude that NAD + metabolism governs the proinflammatory SASP. Given the tumour-promoting effects of the proinflammatory SASP, our results suggest that anti-ageing dietary NAD + augmentation should be administered with precision. Nacarelli et al. show that the nicotinamide-phosphoribosyltransferase-regulated NAD + biogenesis pathway promotes the proinflammatory senescence-associated secretory phenotype by enhancing glycolysis and mitochondrial respiration during senescence.

R-loops are three-stranded nucleic acid structures that accumulate on chromatin in neurological diseases and cancers and contribute to genome instability. Using a proximity-dependent labeling system, we identified distinct classes of proteins that regulate R-loops in vivo through different mechanisms. We show that ATRX suppresses R-loops by interacting with RNAs and preventing R-loop formation. Our proteomics screen also discovered an unexpected enrichment for proteins containing zinc fingers and homeodomains. One of the most consistently enriched proteins was activity-dependent neuroprotective protein (ADNP), which is frequently mutated in ASD and causal in ADNP syndrome. We find that ADNP resolves R-loops in vitro and that it is necessary to suppress R-loops in vivo at its genomic targets. Furthermore, deletion of the ADNP homeodomain severely diminishes R-loop resolution activity in vitro, results in R-loop accumulation at ADNP targets, and compromises neuronal differentiation. Notably, patient-derived human induced pluripotent stem cells that contain an ADNP syndrome-causing mutation exhibit R-loop and CTCF accumulation at ADNP targets. Our findings point to a specific role for ADNP-mediated R-loop resolution in physiological and pathological neuronal function and, more broadly, to a role for zinc finger and homeodomain proteins in R-loop regulation, with important implications for developmental disorders and cancers. R-loops are three-stranded nucleic acid structures that contribute to genome instability and accumulate in neurological diseases. Here the authors identify R-loop proximal factors, which are enriched for zinc finger and homeodomain proteins, including activity-dependent neuroprotective protein (ADNP). ADNP plays a role in R-loop resolution and loss-of-function leads to R-loop accumulation.

Objective C-reactive protein-triglyceride-glucose index (CTI) has been proposed as a novel biomarker for insulin resistance and inflammation. However, the association between CTI and the risk of stroke, particularly in individuals with different glycemic status, remains unclear. Methods A total of 10,443 middle-aged and elderly participants were enrolled from the China Health and Retirement Longitudinal Study (CHARLS). The primary endpoint was the occurrence of stroke events. The CTI was calculated using the formula 0.412* Ln (CRP [mg/L]) + Ln (TG [mg/dl] × FPG [mg/dl])/2. The Kaplan–Meier curves, Cox proportional hazard models, and restricted cubic spline analysis were applied to explore the association between CTI and the risk of stroke according to gender, age and glycemic status. Results During a median follow-up of 9 years, 960 (9.2%) participants experienced a stroke. Our findings revealed a significant positive linear relationship between CTI and the occurrence of stroke. The association was similar between male and female, despite the HR tended to be higher in females (HR 1.22, 95% CI 1.09, 1.36) than males (HR 1.15, 95% CI 1.02, 1.29), and similar in middle-aged (HR 1.25, 95% CI 1.11, 1.41) and elderly participants (HR 1.12, 95% CI 1.00, 1.26). In different glycemic status, high levels of CTI were found to be linked to an increased risk of stroke in individuals with normal glucose regulation (NGR) (HR 1.33, 95% CI 1.11, 1.59) and prediabetes mellitus (Pre-DM) (HR 1.20, 95% CI 1.04, 1.39). However, this association was not observed in individuals with diabetes mellitus (DM). Conclusions Our findings revealed a significant positive linear relationship between CTI and the occurrence of stroke. The association between CTI and stroke was similar between male and female, and similar in middle-aged and elderly participants. In different glycemic status, the association was significant in individuals with NGR and Pre-DM. Graphical abstract What is currently known about this topic? CTI has been proposed as a novel biomarker for insulin resistance and inflammation. What is the key research question? What is the relationship between CTI and stroke risk under different genders, ages, and glycemic status? What is new? This is the first large-scale study to demonstrate this relationship between the CTI and stroke risk, and assessed this relationship according to gender, ages and glycemic status. How might this study influence clinical practice? Our research findings demonstrate a significant positive linear relationship between CTI and the incidence of stroke. To reduce the risk of stroke, different strategies must be adopted to manage CTI levels based on gender, age, and glycemic status.

Sucralose, a widely utilized non-caloric sweetener, is frequently added to food and beverage products as a sugar substitute aimed at lowering energy consumption and reducing obesity-related health risks. However, epidemiological studies have indicated a possible association between high intake of sucralose and increased prevalence of coronary artery disease (CAD). Prior research has demonstrated that diminished levels of circulating human endothelial progenitor cells (hEPCs) are linked to a higher risk of CAD. Although sucralose is broadly consumed, its direct biological impact on hEPCs has not been comprehensively characterized. In this study, we investigated the cellular effects of sucralose on hEPCs using a variety of in vitro techniques, including assays for viability, migration, capillary-like tube formation, lactate dehydrogenase (LDH) release-cytotoxicity assay, and protein expression profiling by Western blotting. Our results revealed that increased concentrations of sucralose significantly impaired hEPCs viability, motility, and neovasculogenic function, accompanied by increased expression of markers associated with apoptosis, inflammasome activation, and pyroptosis. Mechanistic analysis further demonstrated that sucralose strongly activated endoplasmic reticulum (ER) stress/PERK pathways in these cells. Inhibition of ER stress via 4-phenylbutyric acid (4-PBA) substantially attenuated sucralose-induced cell death and reduced the expression of pyroptosis-related proteins and inflammasome markers. Taken together, these findings suggest that sucralose disrupts hEPCs function in part by triggering ER stress, which promotes both apoptotic and pyroptotic cell death programs.

The human cytomegalovirus major immediate early proteins IE1 and IE2 are critical drivers of virus replication and are considered pivotal in determining the balance between productive and latent infection. IE1 and IE2 are derived from the same primary transcript by alternative splicing and regulation of their expression likely involves a complex interplay between cellular and viral factors. Here we show that knockdown of the host ubiquitin-dependent segregase VCP/p97, results in loss of IE2 expression, subsequent suppression of early and late gene expression and, ultimately, failure in virus replication. RNAseq analysis showed increased levels of IE1 splicing, with a corresponding decrease in IE2 splicing following VCP knockdown. Global analysis of viral transcription showed the expression of a subset of viral genes is not reduced despite the loss of IE2 expression, including UL112/113. Furthermore, Immunofluorescence studies demonstrated that VCP strongly colocalised with the viral replication compartments in the nucleus. Finally, we show that NMS-873, a small molecule inhibitor of VCP, is a potent HCMV antiviral with potential as a novel host targeting therapeutic for HCMV infection.

Synonymous recoding of RNA virus genomes is a promising approach for generating attenuated viruses to use as vaccines. Problematically, recoding typically hinders virus growth, but this may be rectified using CpG dinucleotide enrichment. CpGs are recognised by cellular zinc-finger antiviral protein (ZAP), and so in principle, removing ZAP sensing from a virus propagation system will reverse attenuation of a CpG-enriched virus, enabling high titre yield of a vaccine virus. We tested this using a vaccine strain of influenza A virus (IAV) engineered for increased CpG content in genome segment 1. Virus attenuation was mediated by the short isoform of ZAP, correlated with the number of CpGs added, and was enacted via turnover of viral transcripts. The CpG-enriched virus was strongly attenuated in mice, yet conveyed protection from a potentially lethal challenge dose of wildtype virus. Importantly for vaccine development, CpG-enriched viruses were genetically stable during serial passage. Unexpectedly, in both MDCK cells and embryonated hens’ eggs that are used to propagate live attenuated influenza vaccines, the ZAP-sensitive virus was fully replication competent. Thus, ZAP-sensitive CpG enriched viruses that are defective in human systems can yield high titre in vaccine propagation systems, providing a realistic, economically viable platform to augment existing live attenuated vaccines.

In this study, we aim to clarify the determinants of online review helpfulness concerning review depth, extremity and timeliness. Based on a meta-analysis, we examine the effects of important characteristics of reviews employing 53 empirical studies yielding 191 effect sizes. Findings reveal that review depth has a greater impact on helpfulness than review extremity and timeliness with the exception of its sub-metric of review volume, which exerts the negative influence on review helpfulness. Specifically, readability is the most important factor in evaluating review helpfulness. Furthermore, we discuss important moderators of the relationships and find interesting insights regarding website and culture background. In accordance with the results, we propose several implications for researchers and E-business firms. Our study provides a much needed quantitative synthesis of this burgeoning stream of research.

Based on the analysis of data from listed enterprises in China between 2011 and 2022, we investigate the influence of digital transformation on the governance efficiency for minority shareholders. The results show that the extent of digital transformation exert a negative effect on the agency costs incurred from related-party transactions. The mechanism examination elucidates that digital transformation augments the governance efficiency for minority shareholders by boosting attendance at shareholders’ meetings and enhancing the exit threat for minority shareholders. Subsequent analysis reveals that non-state-owned enterprises, compared to state-owned enterprises, exhibit a more pronounced effect in diminishing the second type of agency costs through digital transformation. Furthermore, the impact of digital transformation in curtailing agency costs is more significant in the eastern regions than central and western regions. The better the equity checks and balances in listed enterprises, the more effective digital transformation is in reducing agency costs. This study offers valuable insights for bolstering the governance capacity of minority shareholders in the context of digital transformation.