Social environment, lifestyle, and genetic predisposition with dementia risk: A long-term longitudinal study among older adults.

BACKGROUND: The role of social environment, i.e., the aggregate effect of social determinants of health (SDOHs), in determining dementia is unclear. METHODS: We developed a novel polysocial risk score for dementia based on 19 SDOH among 5,199 participants in the Health and Retirement Study, US, to measure the social environmental risk. We used a survival analysis approach to assess the association between social environment and dementia risk in 2006-2020. We further studied the interaction between social environment and lifestyles, and explored racial disparities. RESULTS: The study participants (mean age=73.4 years, SD=8.3; 58.0% female; 11.6% African American) were followed up for an average of 6.2 years, and 1,089 participants developed dementia. Every one-point increase in the polysocial risk score (ranging from 0-10) was associated with a 21.6% higher risk (aHR=1.21, 95% CI=1.15-1.26) of developing dementia, other things being equal. Among participants with high social environmental risk, regular exercise and moderate drinking were associated with a 43-60% lower risk of developing dementia (p<0.001). In addition, African Americans were 1.3 times (aHR=2.28, 95% CI=1.96-2.66) more likely to develop dementia than European Americans, other things being equal. DISCUSSION: An adverse social environment is linked to higher dementia risk, but healthy lifestyles can partially offset the increased social environmental risk. The polysocial risk score can complement the existing risk tools to identify high-risk older populations, and guide the design of targeted social environmental interventions, particularly focusing on improving the companionship of the older people, to prevent dementia.

Natural tea polyphenol functionalized graphene anode for simultaneous power production and degradation of methyl orange dye in microbial fuel cells.

The microbial fuel cell (MFCs) has dual functions, capable of achieving dye decolorization and synchronous power generation. Despite these advantages, the MFCs have faced challenges related to low electron transfer efficiencies and limited dye treatment capacity in wastewater applications. This work introduces an innovative approach by employing reduced graphene oxide-modified carbon cloth (TP-RGO@CC) anodes, utilizing tea polyphenols as the reducing agent. This modification significantly enhances the hydrophilicity and biocompatibility of the anodes. The MFC equipped with the TP-RGO@CC anode demonstrated a remarkable increase in the maximum power density, reaching 773.9 mW m-2, representing a 22% improvement over the plain carbon cloth electrode. The decolorization rate of methyl orange (50 mg L-1, pH 7) reached 99% within 48 h. Biodiversity analysis revealed that the TP-RGO@CC anode selectively enriched electrogens producing and organic matter-degrading bacteria, promoting a dual mechanism of dye decolorization, degradation, and simultaneous electro-production at the anode. This work highlights advanced anode materials that excel in effective pollutant removal, energy conversion, and biomass reuse.

A multimodal approach using fundus images and text meta-data in a machine learning classifier with embeddings to predict years with self-reported diabetes - An exploratory analysis.

AIMS: Machine learning models can use image and text data to predict the number of years since diabetes diagnosis; such model can be applied to new patients to predict, approximately, how long the new patient may have lived with diabetes unknowingly. We aimed to develop a model to predict self-reported diabetes duration. METHODS: We used the Brazilian Multilabel Ophthalmological Dataset. Unit of analysis was the fundus image and its meta-data, regardless of the patient. We included people 40 + years and fundus images without diabetic retinopathy. Fundus images and meta-data (sex, age, comorbidities and taking insulin) were passed to the MedCLIP model to extract the embedding representation. The embedding representation was passed to an Extra Tree Classifier to predict: 0-4, 5-9, 10-14 and 15 + years with self-reported diabetes. RESULTS: There were 988 images from 563 people (mean age = 67 years; 64 % were women). Overall, the F1 score was 57 %. The group 15 + years of self-reported diabetes had the highest precision (64 %) and F1 score (63 %), while the highest recall (69 %) was observed in the group 0-4 years. The proportion of correctly classified observations was 55 % for the group 0-4 years, 51 % for 5-9 years, 58 % for 10-14 years, and 64 % for 15 + years with self-reported diabetes. CONCLUSIONS: The machine learning model had acceptable accuracy and F1 score, and correctly classified more than half of the patients according to diabetes duration. Using large foundational models to extract image and text embeddings seems a feasible and efficient approach to predict years living with self-reported diabetes.

Long-term follow-up after the treatment of impacted canines in the maxilla causing severe root resorption of the lateral incisors: two case reports.

BACKGROUND: Root resorption of adjacent teeth due to impacted canines is common, and orthodontic treatment often leads to secondary resorption or even loss of adjacent roots. Clinical reports of long-term stability after treatment are rare. CASE PRESENTATION: This study reports two cases of maxillary impacted canines resulting in severe root resorption of the adjacent lateral incisors. Surgical exposure, orthodontic retraction, and alignment of the impacted canines were successful in both cases, and the resorbed lateral incisors were stable with no significant loosening and normal pulp vitality after treatment and at the 5- and 10-year follow-up appointments. CONCLUSIONS: Light orthodontic force may be used to move adjacent teeth with root resorption due to tooth obstruction. The path and direction in which the teeth are moved must be specifically designed so that the adjacent roots are not resorbed and so long-term stability can be achieved.

Reduced Cx43 Expression Induces Autophagy through Activation of the AMPK-mTOR-ULK1 Signaling Pathway in the Common Bile Duct Ligation Rat Heart.

BACKGROUNDS: This study aimed to investigate the relationship between Cx43 expression and autophagy mediated by the AMPK-mTOR-Ulk1 signaling pathway in jaundice heart. METHODS: In this study, a jaundice model was established in common bile duct ligation (CBDL) rats. Cardiac injury was assessed using various methods including myocardial injury indicators, echocardiography, TEM, HE staining, Masson staining, IHC, and IF. We investigated the regulatory relationship between Cx43, autophagy, and the AMPK-mTOR-ULK pathway in vivo by administering autophagy agonists (Rapa), autophagy inhibitors (3-MA), and Cx43 inhibitors (Gap 26). In vitro, we observed the relationship between autophagy and the AMPK-mTOR-ULK1 pathway in cells by exposing them to the AMPK inhibitor Compound C and the AMPK activator AICAR. RESULTS: We found that CBDL induced autophagy through the AMPK-mTOR-ULK pathway, leading to the inhibition of myocardial dysfunction. Rapamycin pretreatment with CBDL3d exhibited a protective effect against myocardial injury and promoted autophagy. In contrast, 3-MA had no impact. Pretreatment with rapamycin at CBDL2w enhanced autophagy and aggravated cardiac injury; however, inhibition of autophagy using 3-MA attenuated cardiac injury. Cell viability was enhanced by AMPK inhibitors and inhibited by AMPK agonists. In addition, we observed that increased autophagy led to decreased Cx43 expression, which negatively affected cardiac function. CONCLUSIONS: CBDL induces myocardial injury in rats and activates autophagy through the AMPK-mTOR-ULK pathway, resulting in decreased Cx43 protein levels. A moderate increase in early autophagy in CBDL can improve cardiac injury, while late inhibition of autophagy can reduce myocardial injury.

The developmental origins of health and disease and intergenerational inheritance: a scoping review of multigenerational cohort studies.

Epidemiologic research has increasingly acknowledged the importance of developmental origins of health and disease (DOHaD) and suggests that prior exposures can be transferred across generations. Multigenerational cohorts are crucial to verify the intergenerational inheritance among human subjects. We carried out this scoping review aims to summarize multigenerational cohort studies' characteristics, issues, and implications and hence provide evidence to the DOHaD and intergenerational inheritance. We adopted a comprehensive search strategy to identify multigenerational cohorts, searching PubMed, EMBASE, and Web of Science databases from the inception of each dataset to June 20th, 2022, to retrieve relevant articles. After screening, 28 unique multigenerational cohort studies were identified. We classified all studies into four types: population-based cohort extended three-generation cohort, birth cohort extended three-generation cohort, three-generation cohort, and integrated birth and three-generation cohort. Most cohorts (n = 15, 53%) were categorized as birth cohort extended three-generation studies. The sample size of included cohorts varied from 41 to 167,729. The study duration ranged from two years to 31 years. Most cohorts had common exposures, including socioeconomic factors, lifestyle, and grandparents' and parents' health and risk behaviors over the life course. These studies usually investigated intergenerational inheritance of diseases as the outcomes, most frequently, obesity, child health, and cardiovascular diseases. We also found that most multigenerational studies aim to disentangle genetic, lifestyle, and environmental contributions to the DOHaD across generations. We call for more research on large multigenerational well-characterized cohorts, up to four or even more generations, and more studies from low- and middle-income countries.

Perioperative outcomes and long-term survival of cryosurgery on unresectable pancreatic cancer: a systematic review and meta-analysis.

BACKGROUND: Pancreatic cancer (PC) continues to rank as one of the deadliest forms of cancer, with the majority of patients being diagnosed with unresectable disease. The implementation of cryoablation-based comprehensive treatment is expected to lead to a reduction in tumor size and potentially achieve complete resection. However, the availability of systematic and evidence-based treatment guidelines for cryoablation in pancreatic cancer is currently limited. MATERIALS AND METHODS: A computerized search was conducted in the Medline, Embase, Cochrane Library databases, and Clinicaltrials to retrieve studies published from August 1987 to June 2023. The perioperative outcomes and long-term survival of patients with locally advanced pancreatic cancer (LAPC) or metastatic pancreatic cancer (mPC) who underwent cryosurgery were systematically collected. Heterogeneity was assessed using the Cochran's Q test, and a funnel plot was implemented to evaluate publication bias. Data were pooled and analyzed using Stata 14.0 software. The Newcastle-Ottawa Quality Assessment Form tool was employed for quality evaluation. RESULTS: 9 studies including 368 patients were identified. The pooled overall incidence rate was 4% (95%CI: 0-14%; I²=54.06%) for acute pancreatitis, 0% (95%CI: 0-0%; I²=0.0%) for delayed gastric emptying, 0% (95%CI: 0-1%; I²=0.0%) for postoperative pancreatic fistula (POPF) or bile leakage, 2% (95%CI:0-5%; I²=0.0%) for bleeding, and 4% (95%CI: 0-12%; I²=70.46%) for fever. Our subgroup analysis revealed that the percutaneous treatment group had a lower incidence of complications compared to laparotomy, but had higher incidences of POPF, bleeding, and pancreatitis than the intraoperative group. Median overall survival (OS) varied from 5 to 16.2 months. The median survival rates at 6, 12, 24, and 36 months for patients who underwent cryosurgery were as follows: 94.9%, 64.8% (range: 4.8%-63.1%), 22.80%, and 9.5%, respectively. CONCLUSION: With the advancements in cryoablation and anti-tumor therapy, cryoablation emerges as a promising treatment modality for patients with unresectable pancreatic cancer. According to existing literature, the combination of cryoablation with radioactive particle implantation or immunotherapy has demonstrated considerable efficacy and safety. However, while the majority of included data is derived from retrospective studies, it is imperative to conduct larger sample sizes or prospective trials for further validation.

Corrigendum: Genetic liability for diet-derived circulating antioxidants, oxidative stress, and risk of osteoarthritis: a Mendelian randomization study.

[This corrects the article DOI: 10.3389/fnut.2023.1233086.].

Constructing models for Crohn's disease diagnosis and prediction of infliximab non-response based on angiogenesis-related genes.

Background: Angiogenesis response plays a crucial role in the occurrence and development of Crohn's disease (CD) and may involve the mechanism of infliximab non-response. However, the role of angiogenesis-related genes in Crohn's disease has not been comprehensively studied. This study aimed to explore the expression profiles of angiogenesis-related genes in CD patients and construct models for disease diagnosis and prediction of infliximab non-response. Methods: CD-related microarray datasets were collected from the GEO database. Unsupervised consensus clustering analysis was performed based on differentially expressed angiogenesis-related genes to divide CD samples into two distinct clusters. Weighted gene co-expression network analysis (WGCNA) was conducted on the clusters to identify angiogenesis-related module. Based on the differentially expressed genes in the module, machine learning algorithms were employed to further identify hub genes and construct a disease diagnostic model. Subsequently, treatment outcome-related genes were extracted from these hub genes, and a predictive model for infliximab non-response in CD patients was ultimately built. Results: Based on angiogenesis-related genes, we identified two distinct CD clusters (C1 and C2). Compared to C1, the metabolic pathways in C2 were significantly upregulated, and there was a higher abundance of cell clusters such as M1 macrophages and plasma cells. Additionally, C2 showed a poorer response to infliximab. Furthermore, a predictive model for infliximab non-response in CD patients was constructed based on the hub genes, and it was successfully validated using an external dataset. Conclusion: Comprehensive analysis of angiogenesis-related genes revealed different clusters of CD, which exhibited differential response rates to infliximab. The construction of models provides a reference for disease diagnosis and drug selection, aiding in clinical decision-making.

MgO-modified biochar by modifying hydroxyl and amino groups for selective phosphate removal: Insight into phosphate selectivity adsorption mechanism through experimental and theoretical.

Metal oxides-modified biochars have been widely studied as promising adsorbents for removing phosphate from wastewater discharge. Yet, the low adsorption selectivity towards phosphate severely limits its potential in practical applications. In this study, MgO-modified biochar modified by hydroxyl and amino groups (OH/NH2@MBC) is developed for selective phosphorus recovery from wastewater. As major results, the OH/NH2@MBC exhibits favorable phosphate adsorption performance is superior to that of MBC resin in the presence of co-existing anions (NO3-, Cl-, HCO3- and SO42-) and natural organic matter (humic acid) even actual wastewater, suggesting its superior selectivity towards phosphate. The OH/NH2@MBC shows an excellent phosphate adsorption capacity (43.27 mg/g) and desorption ratio (82.34 %) after five cycles under the condition of anion coexistence (100 mg/L). The experimental and DFT theoretical study reveals that attaching hydroxyl and amino groups onto the MBC surface, which facilitates to inhibiting the side effects of anions (NO3-, Cl-, HCO3-, and SO42-) through Lewis acid-base sites, hydrogen bonds, and metal affinity, and preferentially select adsorption P, contributing greatly to improve phosphate adsorption selectivity. Importantly, the presence of amino and hydroxyl groups can reduce the Fermi level of OH/NH2@MgO(220) and OH/NH2@MgO(200) and improve the adsorption selection for HPO42-. This study provides an effective strategy for enhancing the adsorption selectivity of metal oxides-modified biochars towards phosphate through modifying functional groups.

Intraocular schwannoma: case series of 28 patients and literature review.

PURPOSE: Intraocular schwannoma is a rare tumour, which is often misdiagnosed. We presented the demographics and clinical characteristics of patients with intraocular schwannoma. METHODS: Retrospective case series were collected between May 2005 and July 2021 in Beijing Tongren Hospital. RESULTS: A total of 28 patients were diagnosed with intraocular schwannoma on histopathological examination of surgical specimen. The median age was 39 years (range: 12-64). Fourteen patients were female and 14 were male. Among the all subjects, 21/28 patients (75.0%) presented as visual loss, and 3/28 patients (10.7%) had visual field loss. Intraocular schwannoma presented as nonpigmented mass in the ciliary body in 12/28 cases (42.9%), in the choroid in 9/28 cases (32.1%), and in ciliochoroid in 7/28 cases (25.0%). Intraocular schwannoma was often clinically misdiagnosed as uveal melanoma, which occurred in 16/28 patients (57.1%). Tumour excision with pars plana vitrectomy was performed for all included patients. Endoresection with lens removal was performed for tumours in the choroid, while transscleral resection was performed for tumours located in ciliary body or ciliochoroid. Increased light transmission was detected in 12/28 cases (42.9%). In the consecutive follow-up (median: 73 months, range: 7-193 months), no cases of recurrence or metastatic disease were detected. CONCLUSIONS: Intraocular schwannoma is a rare benign tumour. It usually presents as nonpigmented mass, which can easily be misdiagnosed as nonpigmented uveal melanoma.

Community-based rehabilitation/community based inclusive development functioning during the COVID-19 pandemic: A secondary analysis of qualitative data.

INTRODUCTION: The coronavirus (COVID-19) became a global pandemic in March 2020 and impacted nations worldwide not only because of the disease but also because the containment measures-imposed created ripple effects for the populations in each country. The COVID-19 pandemic disproportionately affected vulnerable groups, such as persons with disabilities. This study aimed to understand the impact of COVID-19 on the function of Community-Based Rehabilitation (CBR)/Community-Based Inclusive Development (CBID) across nations and for their target communities-persons with disabilities. The current article also described some measures CBR/CBID programs took in light of service closure to facilitate access to needed services for persons with disabilities. METHODS: We conducted a secondary analysis of qualitative data to understand the impact of COVID-19 on the functioning of CBR/CBID programs and their target communities. The original qualitative data were collected through online dialogues among CBR/CBID partners across five regions of the world, facilitated for understanding of their practices on five other topics. FINDINGS: COVID-19 significantly impacted the function of CBR/CBID programs across the world. Many services were halted due to public health measures, such as maintaining social distancing or lockdowns. The COVID-19 pandemic also had a negative impact on access to health, education and livelihood support for persons with disabilities. Additionally, many people with disabilities did not have access to COVID-19 related information and services like vaccines. However, we found that technology played a significant role in revitalizing CBR/CBID programs during COVID-19. CBR/CBID service providers across five regions used online platforms to disseminate information about COVID-19. Professionals also used technology to provide rehabilitation and educational services to people with disabilities through online platforms. CONCLUSION: Our findings suggest that technology can play a vital role in continuing many services (e.g., CBR/CBID) that cannot be offered in person during crises like COVID-19. However, it is important to remember that technology may not be accessible to many individuals with disabilities, specifically those who reside in rural areas and who experience adverse situations like financial constraints. Additionally, many persons with disabilities may not have the necessary knowledge and skills to use technology. CBR personnel must consider that before adopting technology to provide services under CBR programs.

Nrf2 protein in melanoma progression, as a new means of treatment.

Melanoma is a potentially lethal form of skin cancer resulting from the unlimited proliferation of melanocytes. Melanocytic lineage appears to have a greater rate of reactive oxygen species (ROS) production, possibly as a result of exposure to ultraviolet (UV) light and the production of melanin. It has been established that nuclear factor erythroid 2-related factor 2 (Nrf2) serves as a master regulator of the cellular response to oxidative stresses. Recent research has shown that the Nrf2 and its critical negative regulator Kelch-like ECH-associated protein 1 (Keap1) are misregulated in melanoma, and the Keap1-Nrf2 pathway has emerged as a promising new target for treating and preventing melanoma. In melanoma, Nrf2 may either limit tumor growth or promote its development. This review covers a wide range of topics, including the dual functions played by the Keap1-Nrf2 signaling pathway in melanoma and the most recent targeting techniques of the Nrf2.

Mean age and body mass index at type 2 diabetes diagnosis: Pooled analysis of 56 health surveys across income groups and world regions.

BACKGROUND: Screening for type 2 diabetes mellitus (T2DM) targets people aged 35+ years and those with overweight/obesity. With mounting evidence on young-onset T2DM and T2DM patients with lean phenotypes, it is worth revising the screening criteria to include younger and leaner adults. We quantified the mean age and body mass index (BMI; kg/m2 ) at T2DM diagnosis in 56 countries. METHODS: Descriptive cross-sectional analysis of WHO STEPS surveys. We analysed adults (25-69 years) with new T2DM diagnosis (not necessarily T2DM onset) as per fasting plasma glucose ≥126 mg/dL measured during the survey. For people with new T2DM diagnosis, we summarized the mean age and the proportion of each five-year age group; also, we summarized the mean BMI and the proportion of mutually exclusive BMI categories. RESULTS: There were 8695 new T2DM patients. Overall, the mean age at T2DM diagnosis was 45.1 years in men and 45.0 years in women; and the mean BMI at T2DM diagnosis was 25.2 in men and 26.9 in women. Overall, in men, 10.3% were 25-29 years and 8.5% were 30-34 years old; in women, 8.6% and 12.5% were 25-29 years and 30-34 years old, respectively. 48.5% of men and 37.3% of women were in the normal BMI category. CONCLUSIONS: A non-negligible proportion of new T2DM patients were younger than 35 years. Many new T2DM patients were in the normal weight range. Guidelines for T2DM screening may consider revising the age and BMI criteria to incorporate young and lean adults.

Bioinspired Structural Composite Flexible Material with High Cushion Performance.

Impacts occur everywhere, and they pose a serious threat to human health and production safety. Flexible materials with efficient cushioning and energy absorption are ideal candidates to provide protection from impacts. Despite the high demand, the cushioning capacity of protective materials is still limited. In this study, an integrated bionic strategy is proposed, and a bioinspired structural composite material with highly cushioning performance is developed on the basis of this strategy. The results demonstrated that the integrated bionic material, an S-spider web-foam, has excellent energy storage and dissipation as well as cushioning performance. Under impact loading, S-spider web-foam can reduce peak impact forces by a factor of 3.5 times better than silicone foam, achieving unprecedented cushioning performance. The results of this study deepen the understanding of flexible cushioning materials and may provide new strategies and inspiration for the preparation of high-performance flexible cushioning materials.

Dietary factors in relation to the risk of cognitive impairment and physical frailty in Chinese older adults: a prospective cohort study.

PURPOSE: The study aimed to investigate the independent associations of dietary factors with cognitive impairment (CI) and physical frailty (PF) among Chinese older adults. METHODS: This study included 10,734 participants (mean age = 78.7 years) free of CI and PF at baseline from the Chinese Longitudinal Health Longevity Survey. Dietary intake was collected using a simplified food frequency questionnaire every 3-4 years. The Chinese version Mini-Mental State Examination was used to assess cognition function, participants with a score below 18 were defined as CI. PF was defined using the activities of daily living, instrumental activities of daily living, and functional limitation-related questions. The outcome was defined as the first onset of either CI or PF. Competing risk models were used to estimate the corresponding hazard ratios (HRs) and the 95% confidence intervals (95% CIs). RESULTS: During the study follow-up (mean = 8.1 years), a total of 1220 CI cases and 1451 PF cases were newly identified. Higher frequency of fruits intake was associated with a lower hazard of CI (HR = 0.75, 95% CI 0.58-0.97), whereas higher intake of preserved vegetables demonstrated an opposite association (HR = 1.23, 95% CI 1.07-1.42). In terms of PF, we observed a lower risk associated with higher meat and poultry intake (HR = 0.72, 95% CI 0.61-0.88). In particular, a significant protective association of fish and aquatic products intake with PF was observed among participants with ≥ 28 natural teeth (HR = 0.52, 95% CI 0.27-0.99). CONCLUSION: Our findings suggest divergent roles of major dietary factors in the development of CI and PF among Chinese older adults.

Maduramicin-guided nanotherapy: A polymeric micelles for targeted drug delivery in canine mammary tumors.

Canine mammary tumors (CMT) can severely compromise the life quality of the affected dogs through local recurrence, distant metastases and ultimately succumb to death. Recently, more attention has been given to the potential antimetastatic effect of maduramicin (MAD) on breast cancer. However, its poor aqueous solubility and toxicity to normal tissues limit its clinical application. Therefore, to address the drawbacks of MAD and enhance its anticancer and antimetastatic effects, MAD-loaded TPGS polymeric micelles (MAD-TPGS) were prepared by a thin-film hydration technique. The optimized MAD-TPGS exhibited excellent size distribution, stability and improved water solubility. Cellular uptake assays showed that TPGS polymer micelles could enhance drug internalization. Moreover, TPGS synergistically improved the cytotoxicity of MAD by targeting mitochondrial organelles, improving reactive oxygen species levels and reducing the mitochondrial transmembrane potential. More importantly, MAD-TPGS significantly impeded the metastasis of tumor cells. In vivo results further confirmed that, in addition to exhibiting excellent biocompatibility, MAD-TPGS exhibited greater antitumor efficacy than free MAD. Interestingly, MAD-TPGS displayed superior suppression of CMT metastasis via tail vein injection compared to oral administration, indicating its suitability for intravenous delivery. Overall, MAD-TPGS could be applied as a potential antimetastatic cancer agent for CMT.

Serum/plasma biomarkers and the progression of cardiometabolic multimorbidity: a systematic review and meta-analysis.

Background: The role of certain biomarkers in the development of single cardiometabolic disease (CMD) has been intensively investigated. Less is known about the association of biomarkers with multiple CMDs (cardiometabolic multimorbidity, CMM), which is essential for the exploration of molecular targets for the prevention and treatment of CMM. We aimed to systematically synthesize the current evidence on CMM-related biomarkers. Methods: We searched PubMed, Embase, Web of Science, and Ebsco for relevant studies from inception until August 31st, 2022. Studies reported the association of serum/plasma biomarkers with CMM, and relevant effect sizes were included. The outcomes were five progression patterns of CMM: (1) no CMD to CMM; (2) type 2 diabetes mellitus (T2DM) followed by stroke; (3) T2DM followed by coronary heart disease (CHD); (4) T2DM followed by stroke or CHD; and (5) CHD followed by T2DM. Newcastle-Ottawa Quality Assessment Scale (NOS) was used to assess the quality of the included studies. A meta-analysis was conducted to quantify the association of biomarkers and CMM. Results: A total of 68 biomarkers were identified from 42 studies, which could be categorized into five groups: lipid metabolism, glycometabolism, liver function, immunity, and others. Lipid metabolism biomarkers were most reported to associate with CMM, including TC, TGs, HDL-C, LDL-C, and Lp(a). Fasting plasma glucose was also reported by several studies, and it was particularly associated with coexisting T2DM with vascular diseases. According to the quantitative meta-analysis, HDL-C was negatively associated with CHD risk among patients with T2DM (pooled OR for per 1 mmol/L increase = 0.79, 95% CI = 0.77-0.82), whereas a higher TGs level (pooled OR for higher than 150 mg/dL = 1.39, 95% CI = 1.10-1.75) was positively associated with CHD risk among female patients with T2DM. Conclusion: Certain serum/plasma biomarkers were associated with the progression of CMM, in particular for those related to lipid metabolism, but heterogeneity and inconsistent findings still existed among included studies. There is a need for future research to explore more relevant biomarkers associated with the occurrence and progression of CMM, targeted at which is important for the early identification and prevention of CMM.

Progression and trajectory network of age-related functional impairments and their combined associations with mortality.

Age-related functional impairments (ARFIs) contribute to the loss of independence in older adults, but their progressions, interrelations, and combined relations with mortality are largely unknown. We conducted a prospective study among 17,914 participants in the Health and Retirement Study (2000-2020). The incidence rates of visual impairment, hearing impairment, physical frailty, and cognitive impairment increased exponentially with age, while those of restless sleep and depression increased relatively slowly. These ARFIs were associated with each other in temporal sequence and constituted a hazard network. We observed a dose-response relationship between the number of ARFIs and mortality risk, and the dyads involving physical frailty demonstrated the strongest associations with mortality. Our findings may assist in the identification of individuals at higher mortality risk and highlight the potential for future investigations to explore the impact of multiple ARFIs in aging.

Nanoparticles (NPs)-mediated Siglec15 silencing and macrophage repolarization for enhanced cancer immunotherapy.

T cell infiltration and proliferation in tumor tissues are the main factors that significantly affect the therapeutic outcomes of cancer immunotherapy. Emerging evidence has shown that interferon-gamma (IFNγ) could enhance CXCL9 secretion from macrophages to recruit T cells, but Siglec15 expressed on TAMs can attenuate T cell proliferation. Therefore, targeted regulation of macrophage function could be a promising strategy to enhance cancer immunotherapy via concurrently promoting the infiltration and proliferation of T cells in tumor tissues. We herein developed reduction-responsive nanoparticles (NPs) made with poly (disulfide amide) (PDSA) and lipid-poly (ethylene glycol) (lipid-PEG) for systemic delivery of Siglec15 siRNA (siSiglec15) and IFNγ for enhanced cancer immunotherapy. After intravenous administration, these cargo-loaded could highly accumulate in the tumor tissues and be efficiently internalized by tumor-associated macrophages (TAMs). With the highly concentrated glutathione (GSH) in the cytoplasm to destroy the nanostructure, the loaded IFNγ and siSiglec15 could be rapidly released, which could respectively repolarize macrophage phenotype to enhance CXCL9 secretion for T cell infiltration and silence Siglec15 expression to promote T cell proliferation, leading to significant inhibition of hepatocellular carcinoma (HCC) growth when combining with the immune checkpoint inhibitor. The strategy developed herein could be used as an effective tool to enhance cancer immunotherapy.