Mild hyperthermia enhanced synergistic uric acid degradation and multiple ROS elimination for an effective acute gout therapy.

BACKGROUND: Acute gouty is caused by the excessive accumulation of Monosodium Urate (MSU) crystals within various parts of the body, which leads to a deterioration of the local microenvironment. This degradation is marked by elevated levels of uric acid (UA), increased reactive oxygen species (ROS) production, hypoxic conditions, an upsurge in pro-inflammatory mediators, and mitochondrial dysfunction. RESULTS: In this study, we developed a multifunctional nanoparticle of polydopamine-platinum (PDA@Pt) to combat acute gout by leveraging mild hyperthermia to synergistically enhance UA degradation and anti-inflammatory effect. Herein, PDA acts as a foundational template that facilitates the growth of a Pt shell on the surface of its nanospheres, leading to the formation of the PDA@Pt nanomedicine. Within this therapeutic agent, the Pt nanoparticle catalyzes the decomposition of UA and actively breaks down endogenous hydrogen peroxide (H2O2) to produce O2, which helps to alleviate hypoxic conditions. Concurrently, the PDA component possesses exceptional capacity for ROS scavenging. Most significantly, Both PDA and Pt shell exhibit absorption in the Near-Infrared-II (NIR-II) region, which not only endow PDA@Pt with superior photothermal conversion efficiency for effective photothermal therapy (PTT) but also substantially enhances the nanomedicine's capacity for UA degradation, O2 production and ROS scavenging enzymatic activities. This photothermally-enhanced approach effectively facilitates the repair of mitochondrial damage and downregulates the NF-κB signaling pathway to inhibit the expression of pro-inflammatory cytokines. CONCLUSIONS: The multifunctional nanomedicine PDA@Pt exhibits exceptional efficacy in UA reduction and anti-inflammatory effects, presenting a promising potential therapeutic strategy for the management of acute gout.

A 3-hydroxy-3-methylglutaryl-CoA synthase-based probe for the discovery of the acyltransferase-less type I polyketide synthases.

Acyltransferase (AT)-less type I polyketide synthases (PKSs) produce complex natural products due to the presence of many unique tailoring enzymes. The 3-hydroxy-3-methylglutaryl coenzyme A synthases (HCSs) are responsible for ß-alkylation of the growing polyketide intermediates in AT-less type I PKSs. In this study, we discovered a large group of HCSs, closely associated with the characterized and orphan AT-less type I PKSs through in silico genome mining, sequence and genome neighbourhood network analyses. Using HCS-based probes, the survey of 1207 in-house strains and 18 soil samples from different geographic locations revealed the vast diversity of HCS-containing AT-less type I PKSs. The presence of HCSs in many AT-less type I PKSs suggests their co-evolutionary relationship. This study provides a new probe to study the abundance and diversity of AT-less type I PKSs in the environment and microbial strain collections. Our study should inspire future efforts to discover new polyketide natural products from AT-less type I PKSs.

Lactate drives CD38 signaling to promote Epithelial-Mesenchymal Transition through Snail induction in non-small cell lung cancer cells.

CD38 is the main NADase in mammalian cells. It regulates the homeostasis of nicotinamide adenine dinucleotide (NAD+) and extracellular nucleotides. Its function plays an important role in infection and aging. However, its potential functions in tumor cells have not been fully elucidated. In the present study, we demonstrated that lactate, which is derived from tumor metabolism remodeling, upregulates the expression of CD38 through OXPHOS-driven Hippo-TAZ pathway. The highly expressed CD38 converts NAD + to adenosine through the CD203a/CD73 complex and adenosine binds and activates its receptor A2AR, inducing the expression of Snail and promoting the invasion and metastasis of lung cancer cells. This finding elucidates a new perspective on the interplay between NAD + metabolism and glycolysis in tumor development.

Effectiveness of an integrative programme in reducing hypertension incidence among the population at risk for hypertension: A community-based randomized intervention study in Shanghai, China.

Background: We aimed to evaluate the effectiveness of a community-based integrative programme in reducing hypertension incidence among populations at high risk for hypertension in Shanghai, Eastern China. Methods: We conducted a cluster-randomized intervention trial with a total of 607 participants (intervention, n = 303; control, n = 304) between October 2019 and October 2020. A total of 605 participants (intervention, n = 302; control, n = 303) completed the follow-up survey. The intervention group received an integrative programme that included health education, physician follow-up, and self-management, while the control group received usual care only. We used questionnaires to investigate risk factors, knowledge, attitudes, and behaviours regarding hypertension prevention for all participants at baseline and follow-up. We measured the incidence of hypertension according to the predefined protocol based on the national definition during the four follow-ups (only applicable to the intervention group) and the physical examination at the end of the intervention/programme/study. The difference-in-difference (DID) effects of the intervention were estimated using Generalized Estimating Equations. Results: There were no significant differences in age group, gender, and educational level between intervention and control groups at baseline. The integrative programme reduced the incidence of hypertension in the intervention group compared to the control group (odds ratio (OR) = 0.27, 95% confidence interval (CI) = 0.12-0.61). The DID analysis found that the one-year intervention has improved the level of hypertension-related knowledge and attitudes regarding diagnostic criteria, complications of hypertension, and lifestyle modification (P < 0.05). The intervention was also associated with a 3.7% increase in the behaviour change rate of "not smoking" (OR = 2.50, 95% CI = 1.45-4.30) and a 34.8% increase in the rate of "monitoring blood pressure regularly" (OR = 29.61, 95% CI = 13.02-67.35). Conclusions: The integrative programme could reduce the risk for hypertension and improve the level of hypertension-related knowledge and attitudes, affecting the formation of healthy behaviours in high-risk populations. The community-based management for high-risk groups should be scaled up and incorporated into national hypertension control programmes, which may potentially reduce the substantial burden of hypertension and cardiovascular disease in China. Registration: ISRCTN registration number: ISRCTN74154693.

Development and Validation of a Risk Score Screening Tool to Identify People at Risk for Hypertension in Shanghai, China.

Purpose: This study aimed to develop a screening tool based on a risk scoring approach that could identify individuals at high risk for hypertension in Shanghai, China. Methods: A total of 3147 respondents from the 2013 Shanghai Chronic Disease and Risk Factor Surveillance were randomly divided into the derivation group and validation group. The coefficients obtained from multivariable logistic regression were used to assign a score to each variable category. The receiver operating characteristic (ROC) curve was used to find the optimal cut-off point and to evaluate the screening performance. Results: Age, family history of hypertension, having diabetes, having dyslipidemia, body mass index, and having abdominal obesity contributed to the risk score. The area under the ROC curve was 0.817 (95% CI: 0.797-0.836). The optimal cut-off value of 20 had a sensitivity of 83.4%, and a specificity of 64.3%, demonstrating good performance. Conclusion: We developed a simple and valid screening tool to identify individuals at risk for hypertension. Early detection could be beneficial for high-risk groups to better manage their conditions and delay the progression of hypertension and related complications.

Health System Barriers and Facilitators to Delivering Additional Vaccines through the National Immunisation Programme in China: A Qualitative Study of Provider and Service-User Perspectives.

In China, there are two categories of vaccines available from the Chinese Center for Disease Control and associated public health agencies. Extended Program of Immunization (EPI) vaccines are government-funded and non-EPI vaccines are voluntary and paid for out-of-pocket. The government plans to transition some non-EPI vaccines to EPI in the coming years, which may burden public health system capacity, particularly in terms of budget, workforce, supply chains, and information systems. Our study explored vaccinator and caregiver perspectives on introducing non-EPI vaccines into routine immunization and perceived facilitators and barriers affecting this transition. We conducted a qualitative study from a realist perspective, analysing semi-structured interviews with 26 vaccination providers and 160 caregivers in three provinces, selected to represent regional socioeconomic disparities across Eastern, Central, and Western China. Data were analysed thematically, using deductive and inductive coding. Most participants were positive about adding vaccines to the national schedule. Candidate EPI vaccines most frequently recommended by participants were varicella, mumps vaccine, and hand-foot-mouth disease. Providers generally considered existing workspaces, cold-chain equipment, and funding sufficient, but described frontline staffing and vaccine information systems as requiring improvement. This is the first qualitative study to explore interest, barriers, and facilitators related to adding vaccines to China's national schedule from provider and caregiver perspectives. Findings can inform government efforts to introduce additional vaccines, by including efforts to retain and recruit vaccine programme staff and implement whole-process data management and health information systems that allow unified nationwide data collection and sharing.

[Raman spectra and its application of graphite enclaves in nephrite-jades in Xiuyan, Liaoning].

Xiuyan, Liaoning was an important locality of jade material of the Red Mountain Culture in the Neolithic Age in Chinese history where there are two types of raw material of nephrite jades, namely gravel nephrite jade (Hemo Yu in Chinese) and old nephrite jade (Lao Yu in Chinese). In the present paper, Laser Raman spectrum technique was applied to analyze the graphite enclaves in the nephrite jades of the two types of materials. The results show that the graphite enclaves in the two types of jades have different characteristics of Raman spectra, indicating that they probably were formed under different geological conditions, or originated from different ore-forming periods or were exploited from different section of ore body. Hence, laser Raman spectrum technique could be used as a supplementary measure for nondestructive detection to determine the occurrence of jades.