Apoptosis and NETotic cell death affect diabetic nephropathy independently: An study integrative study encompassing bioinformatics, machine learning, and experimental validation.

OBJECTIVE: Although programmed cell death (PCD) and diabetic nephropathy (DN) are intrinsically conneted, the interplay among various PCD forms remains elusive. In this study, We aimed at identifying independently DN-associated PCD pathways and biomarkers relevant to the related pathogenesis. METHODS: We acquired DN-related datasets from the GEO database and identified PCDs independently correlated with DN (DN-PCDs) through single-sample Gene Set Enrichment Analysis (ssGSEA) as well as, univariate and multivariate logistic regression analyses. Subsequently, applying differential expression analysis, weighted gene co-expression network analysis (WGCNA), and Mfuzz cluster analysis, we filtered the DN-PCDs pertinent to DN onset and progression. The convergence of various machine learning techniques ultimately spotlighted hub genes, substantiated through dataset meta-analyses and experimental validations, thereby confirming hub genes and related pathways expression consistencies. RESULTS: We harmonized four DN-related datasets (GSE1009, GSE142025, GSE30528, and GSE30529) post-batch-effect removal for subsequent analyses. Our differential expression analysis yielded 709 differentially expressed genes (DEGs), comprising 446 upregulated and 263 downregulated DEGs. Based on our ssGSEA as well as univariate and multivariate logistic regressions, apoptosis and NETotic cell death were appraised as independent risk factors for DN (Odds Ratio > 1, p < 0.05). Next, we further refined 588 apoptosis- and NETotic cell death-associated genes through WGCNA and Mfuzz analysis, resulting in the identification of 17 DN-PCDs. Integrating protein-protein interaction (PPI) network analyses, network topology, and machine learning, we pinpointed hub genes (e.g., IL33, RPL11, and CX3CR1) as significant DN risk factors with expression corroborating in subsequent meta-analyses and experimental validations. Our GSEA enrichment analysis discerned differential enrichments between DN and control samples within pathways such as IL2/STAT5, IL6/JAK/STAT3, TNF-α via NF-κB, apoptosis, and oxidative phosphorylation, with related proteins such as IL2, IL6, and TNFα, which we subsequently submitted to experimental verification. CONCLUSION: Innovatively stemming from from PCD interactions, in this study, we discerned PCDs with an independent impact on DN: apoptosis and NETotic cell death. We further screened DN evolution- and progression-related biomarkers, i.e. IL33, RPL11, and CX3CR1, all of which we empirically validated. This study not only poroposes a PCD-centric perspective for DN studies but also provides evidence for PCD-mediated immune cell infiltration exploration in DN regulation. Our results could motivate further exploration of DN pathogenesis, such as how the inflammatory microenvironment mediates NETotic cell death in DN regulation, representing a promising direction for future research.

Identification of steroid-induced osteonecrosis of the femoral head biomarkers based on immunization and animal experiments.

BACKGROUND: Steroid-induced osteonecrosis of femoral head (SONFH) is a severe health risk, and this study aims to identify immune-related biomarkers and pathways associated with the disease through bioinformatics analysis and animal experiments. METHOD: Using SONFH-related datasets obtained from the GEO database, we performed differential expression analysis and weighted gene co-expression network analysis (WGCNA) to extract SONFH-related genes. A protein-protein interaction (PPI) network was then constructed, and core sub-network genes were identified. Immune cell infiltration and clustering analysis of SONFH samples were performed to assess differences in immune cell populations. WGCNA analysis was used to identify module genes associated with immune cells, and hub genes were identified using machine learning. Internal and external validation along with animal experiments were conducted to confirm the differential expression of hub genes and infiltration of immune cells in SONFH. RESULTS: Differential expression analysis revealed 502 DEGs. WGCNA analysis identified a blue module closely related to SONFH, containing 1928 module genes. Intersection analysis between DEGs and blue module genes resulted in 453 intersecting genes. The PPI network and MCODE module identified 15 key targets enriched in various signaling pathways. Analysis of immune cell infiltration showed statistically significant differences in CD8 + t cells, monocytes, macrophages M2 and neutrophils between SONFH and control samples. Unsupervised clustering classified SONFH samples into two clusters (C1 and C2), which also exhibited significant differences in immune cell infiltration. The hub genes (ICAM1, NR3C1, and IKBKB) were further identified using WGCNA and machine learning analysis. Based on these hub genes, a clinical prediction model was constructed and validated internally and externally. Animal experiments confirmed the upregulation of hub genes in SONFH, with an associated increase in immune cell infiltration. CONCLUSION: This study identified ICAM1, NR3C1, and IKBKB as potential immune-related biomarkers involved in immune cell infiltration of CD8 + t cells, monocytes, macrophages M2, neutrophils and other immune cells in the pathogenesis of SONFH. These biomarkers act through modulation of the chemokine signaling pathway, Toll-like receptor signaling pathway, and other pathways. These findings provide valuable insights into the disease mechanism of SONFH and may aid in future drug development efforts.

Carbon Dots with Dual-Emissive, Robust, and Aggregation-Induced Room-Temperature Phosphorescence Characteristics.

Carbon dots (CDs) with dual-emissive, robust, and aggregation-induced RTP characteristics are reported for the first time. The TA-CDs are prepared via hydrothermal treatment of trimellitic acid and exhibit unique white prompt and yellow RTP emissions in solid state under UV excitation (365 nm) on and off, respectively. The yellow RTP emission of TA-CDs powder should be resulted from the formation of a new excited triplet state due to their aggregation, and the white prompt emission is due to their blue fluorescence and yellow RTP dual-emissive nature. The RTP emission of TA-CDs powder was highly stable under grinding, which is very rare amongst traditional pure organic RTP materials. To employ the unique characteristics of TA-CDs, advanced anti-counterfeiting and information encryption methodologies (water-stimuli-response producing RTP) were preliminarily investigated.

Facile, Quick, and Gram-Scale Synthesis of Ultralong-Lifetime Room-Temperature-Phosphorescent Carbon Dots by Microwave Irradiation.

Long-lifetime room-temperature phosphorescence (RTP) materials are important for many applications, but they are highly challenging materials owing to the spin-forbidden nature of triplet exciton transitions. Herein, a facile, quick and gram-scale method for the preparation of ultralong RTP (URTP) carbon dots (CDs) was developed via microwave-assisted heating of ethanolamine and phosphoric acid aqueous solution. The CDs exhibit the longest RTP lifetime, 1.46 s (more than 10 s to naked eye) for CDs-based materials to date. The doping of N and P elements is critical for the URTP which is considered to be favored by a n→π* transition facilitating intersystem crossing (ISC) for effectively populating triplet excitons. In addition, possibilities of formation of hydrogen bonds in the interior of the CDs may also play a significant role in producing RTP. Potential applications of the URTP CDs in the fields of anti-counterfeiting and information protection are proposed and demonstrated.

Environmental health, economy, and amenities interactively drive migration patterns among China's older people.

The increasing number of older adult migrants is rapidly changing regional demographic and social structures in China. There is an urgent need to understand the spatial patterns and factors that influence older adults to migrate, especially the role of environmental health. However, this issue has been under-studied. This study focused on intra-provincial and inter-provincial older adult migrants as research subjects, estimated their spatial concentration index based on the iterative proportional fitting approach, and explored the factors influencing their migration using the GeoDetector Model. The results showed the following: (1) In 2015, more than 76% of inter-provincial older adult migrants were distributed in Eastern China, and most intra-provincial older adult migrants were scattered in sub-provincial cities. (2) Compared to factors relating to economy and amenities, environmental health by itself played a relatively weak role in the migration of older adults, but the interaction among environmental health, economy, and amenities was a key driving force of older adult migration. (3) There were significant differences in the dominant environmental health factors between inter-provincial migration and intra-provincial migration, which were temperature and altitude, respectively. Our findings can help policymakers focus on the composition of older adult migrants based on urban environmental health characteristics and rationally optimize older adult care facilities to promote supply-demand matching.

Adverse tumor events induced by ranitidine: an analysis based on the FAERS database.

BACKGROUND: Ranitidine induced tumor adverse events remains a contradictory clinical question, due to the limited evidence of tumor risk associated with ranitidine in the real world. The purpose of this study was to evaluate the association of ranitidine with all types of tumors through the FAERS database and to provide a reference for clinical use. RESEARCH DESIGN AND METHODS: Cancer cases associated with ranitidine in the FAERS database from the first quarter of 2004 to the fourth quarter of 2023 were extracted to analyze demographic characteristics, and a disproportion analysis was performed. RESULT: A total of 662,998 ranitidine-related cancer cases were screened, and the 50-59 and 60-69 groups accounted for the largest proportion. In PT signal detection, ranitidine was associated with 98 PT, including penal cancer stage II, gastric cancer stage II, et al. In terms of outcome events, adverse events were higher in men (20.65%) than in women (18.47%). CONCLUSIONS: Ranitidine may induce various tumor-related adverse reactions, especially in long-term users and elderly patients. For these patients, tumor screening should be strengthened, and long-term use of ranitidine should be avoided. Since this study cannot prove causality, further evidence is needed for prospective studies with a larger sample size.

Biomarker screening using integrated bioinformatics for the development of "normal-impaired glucose intolerance-type 2 diabetes mellitus".

Type 2 diabetes mellitus (T2DM) is a progressive disease. We utilized bioinformatics analysis and experimental research to identify biomarkers indicative of the progression of T2DM, aiming for early detection of the disease and timely clinical intervention. Integrating Mfuzz analysis with differential expression analysis, we identified 76 genes associated with the progression of T2DM, which were primarily enriched in signaling pathways such as apoptosis, p53 signaling, and necroptosis. Subsequently, using various analytical methods, including machine learning, we further narrowed down the hub genes to STK17A and CCT5. Based on the hub genes, we calculated the risk score for samples and interestingly found that the score correlated with multiple programmed cell death (PCD) pathways. Animal experiments revealed that the diabetes model exhibited higher levels of MDA and LDH, with lower expression of SOD, accompanied by islet cell apoptosis. In conclusion, our study suggests that during the progression of diabetes, STK17A and CCT5 may contribute to the advancement of the disease by regulating oxidative stress, programmed cell death pathways, and critical signaling pathways such as p53 and MAPK, thereby promoting the death of islet cells. This provides substantial evidence in support of further disease prevention and treatment strategies.

Exploring the Climate Temperature Effects on Settlement Intentions of Older Migrants: Evidence from China.

Permanent migration across provinces in China has become an important strategy for Chinese older people to respond to a temperature-unfriendly place of residence in late life. However, the relation between temperature effects and permanent settlements of older migrants remains unclear. Based on the data obtained from China Migrants Dynamic Survey, this paper examined how four temperature effects (i.e., cold effect, heat effect, temperature gap effect, and temperature zone effect) play a role in shaping older migrants' intentions to settle permanently in a destination place by conducting logistic regression analysis. Our findings show that: (1) extreme cold (rather than extreme heat or mild temperature) was found to have significant effects on settlement intentions of older people; (2) relative winter temperature between origin and destination places rather than absolute winter temperature in the destination place has a significant positive effect on the settlement intentions; (3) spatially, older migrants tend to migrate to geographically adjacent temperature zones. Our findings will inform a more effective planning and allocation of services for supporting older people by better understanding trends and intentions of older migrants.

Glucose-lowering effects of orally administered superoxide dismutase in type 2 diabetic model rats.

Superoxide dismutase (SOD) is an enzyme found in most food sources, might be a candidate to reduce oxidative damage to intestinal barrier, thereby ameliorating the vicious circle between hyperglycemia and the oxidative damage. Here we report the oral administration of SOD, liposome-embedded SOD (L-SOD), and SOD hydrolysate to type 2 diabetic model rats to confirm this hypothesis. Oxidative damage severity in model rat intestine was indicated by malondialdehyde level, GSSG/GSH ratio, and antioxidant enzyme activity. The damage was significantly repaired by L-SOD. Furthermore, blood glucose and related indexes correlated well not only with oxidative damage results but also with indexes indicating physical intestinal damage such as colon density, H&E staining, immunohistochemical analysis of the tight junction proteins occludin and ZO-1 in the colon, as well as lipopolysaccharide and related inflammatory cytokine levels. The order of the magnitude of the effects of these SOD preparations was L-SOD > SOD > SOD hydrolysate. These data indicate that orally administered SOD can exhibit glucose-lowering effect via targeting the intestine of diabetic rats and systemic lipopolysaccharide influx.

Understanding the Unmet Needs among Community-Dwelling Disabled Older People from a Linkage Perspective.

One of the challenges in response to population aging is to meet needs for elderly care among older people especially for those who want to age in their homes or communities. However, disabled older people have more challenges due to their restricted mobility to access care resources than non-disabled ones. We propose a new framework based on the changing relationship between older people and their environment, in which resource linkage in elderly care utilization is emphasized. We conducted a survey with 139 participants (i.e., older people age 60 years or over with different level of disabilities) in three types of neighborhoods in Beijing, China. By conducting a decision tree analysis under the Person-Environment Link (P-E Link) model, we (1) characterized unmet needs for elderly care (activities of daily living (ADL) and instrumental activities of daily living (IADL) assistance) among community-dwelling disabled older people; (2) found disabled older people had more unmet needs for both ADL and IADL assistance because of a lack in linkages to care resources than non-disabled ones; and (3) characterized the linkages to care resources for better supporting disabled older people to age in place, including family support, social connection, and spatial environment. Our findings help improve the Anderson behavioral model by characterizing enabling environments, which highlights that not only the availability of enabling resources but also linkages to these enabling resources play an important role in meeting needs for care among disabled older people. Our findings can also inform improvements in policy design that are targeted to reduce elderly care inequalities.

Preparation of Multicolor Photoluminescent Carbon Dots by Tuning Surface States.

The achievements of multicolor photoluminescent (PL)-emissive carbon dots (CDs), particularly red to near infrared (NIR), are critical for their applications in optoelectronic devices and bioimaging, but it still faces great challenges to date. In this study, PL emission red-shifts were observed when tartaric acid (TA) was added into m-phenylenediamine (mPD) or o-phenylenediamine (oPD) solutions as carbon sources to prepare CDs, i.e., from blue to green for mPD and from yellow-green to red for oPD. Morphology and structure analyses revealed that the increased surface oxidation and carboxylation were responsible for the red-shifts of emission, indicating that TA played a key role in tuning the surface state of CDs. These factors could be employed as effective strategies to adjust PL emissions of CDs. Consequently, multicolor PL CDs (i.e., blue-, green-, yellow-green- and red-emissive CDs) can be facilely prepared using mPD and oPD in the absence and presence of TA. Particularly, the obtained red-emissive CDs showed a high PL quantum yield up to 22.0% and an emission covering red to NIR regions, demonstrating great potentials in optoelectronic devices and bioimaging. Moreover, multicolor phosphors were further prepared by mixing corresponding CDs with polyvinylpyrrolidone (PVP), among which the blue, green, and red ones could serve as three primary color phosphors for fabricating multicolor and white light-emitting diodes (LEDs). The white LED was measured to show a Commission Internationale de L'Eclairage (CIE) 1931 chromaticity coordinate of (0.34, 0.32), a high color rendering index (CRI) of 89, and a correlated color temperature (CCT) of 5850 K, representing one of the best performances of white LEDs based on CDs.

Modeling satisfaction amongst the elderly in different Chinese urban neighborhoods.

Rapidly aging populations constitute a critical issue for researchers and policymakers across the world; the challenges of a shifting demographic structure are particularly pertinent in the case of China. Population control strategies implemented in China in the late 1970s have substantially changed the social and demographic structure of Chinese cities and the traditional role of families in caring for elderly people. To meet the growing needs of elderly residents "aging in place," age-friendly environments and new types of senior services are required and encouraged. This research examines the satisfaction of seniors in relation to the elderly services and living environments available to them, through empirical studies of six types of neighborhoods in Beijing. Using structural equation modeling (SEM), a satisfaction model under the Person-Environment Fit (P-E Fit) model framework was developed. This model considered the senior respondent's health status, economic attributes, family and social support networks, and neighborhood living environments. Social support was found to be the primary factor affecting satisfaction amongst the urban elderly in Beijing. The research also highlights the need to differentiate between different types of neighborhoods, which can differ significantly in terms of the socio-economic attributes (i.e., family structure, income, and education) of their senior residents. As such, based on the path coefficients revealed by different structural equation models of various neighborhoods, four types of neighborhoods were identified: in Type 1 neighborhoods, the neighborhood environment and the senior services provided by communities were primary factors in elderly satisfaction; in Type 2 neighborhoods, the satisfaction of inhabitants was strongly influenced by personal attributes such as health and income; Type 3 neighborhoods were residence of low-income people where the level of social support was the foremost factor; and in Type 4, social support and the environment were both essential.