Analysis of Codon Usage Bias in the Plastid Genome of Diplandrorchis sinica (Orchidaceae).

In order to understand the bias and main affecting factors of codon usage in the plastid genome of Diplandrorchis sinica, which is a rare and endangered plant species in the Orchidaceae family, the complete plastid genome sequence of D. sinica was downloaded from the GenBank database and 20 protein-coding sequences that met the analysis requirements were finally selected. The GC content, length of the amino acid (Laa), relative synonymous codon usage (RSCU), and effective number of codon (ENC) of each gene and codon were calculated using the CodonW and EMBOSS online programs. Neutral plot analysis, ENC-plot analysis, PR2-plot analysis, and correspondence analysis were performed using Origin Pro 2024 software, and correlation analysis between various indicators was performed using SPSS 23.0 software. The results showed that the third base of the codon in the plastid genome of D. sinica was rich in A and T, with a GC3 content of 27%, which was lower than that of GC1 (45%) and GC2 (39%). The ENC value ranged from 35 to 57, with an average of 47. The codon usage bias was relatively low, and there was a significant positive correlation between ENC and GC3. There were a total of 32 codons with RSCU values greater than 1, of which 30 ended with either A or U. There were a total of nine optimal codons identified, namely, UCU, UCC, UCA, GCA, UUG, AUA, CGU, CGA, and GGU. This study indicated that the dominant factor affecting codon usage bias in the plastid genome of D. sinica was natural selection pressure, while the impact of base mutations was limited. The codon usage patterns were not closely related to gene types, and the distribution of photosynthetic system genes and ribosomal protein-coding gene loci was relatively scattered, indicating significant differences in the usage patterns of these gene codons. In addition, the codon usage patterns may not be related to whether the plant is a photosynthetic autotrophic or heterotrophic nutritional type. The results of this study could provide scientific references for the genomic evolution and phylogenetic research of plant species in the family Orchidaceae.

Identification of key genes and signaling pathways based on transcriptomic studies of aerobic and resistance training interventions in sarcopenia in SAMP8 mice.

We examined the effects of resistance and aerobic exercise on the gene expression and biometabolic processes of aging skeletal muscle in senescence-accelerated mouse/prone 8 mice, a model of sarcopenia, and compared them with senescence-accelerated mouse/resistant 1 mice acting as controls. We found that exercise improved muscle strength, endurance, fiber size, also modulated genes and pathways related to synaptic transmission, potassium transport, JAK-STAT signaling, and PI3K-Akt signaling. Our results suggested that BDNF, JAK2, RhoC, Myh6, Stat5a, Tnnc1, and other genes may mediate the beneficial effects of exercise on sarcopenia through these pathways.

Single-cell analysis of chemotherapy-resistant microenvironment identifies a chemo-response biomarker for pancreatic cancer.

Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly fatal, aggressive cancer due to limited response chemotherapy. The tumor microenvironment (TME) has emerged as a key player in the development of chemoresistance and in malignant progression. In this study, we hypothesized that chemotherapy response is predictable by chemotherapy-related cell types and their differentially expressed genes (DEGs). Methods: DEGs of chemoresistance cell types were identified via single cell analysis and Wilcoxon test. A chemotherapy response signature was established using a random forest model and validated with public datasets. Bulk cell fraction was analyzed using BayesPrism algorithms. Log-rank test was used to analyze survival of PDAC patients. Results: We found that natural killer (NK) cells, myeloid cells, and erythroid cells were highly infiltrated in chemo-resistant TME. A total of 36 chemoresistance-related DEGs of chemo-resistant cells were identified in chemo-resistant PDAC. Functional enrichment analysis showed that chemoresistance upregulated various inflammation-related pathways, including TGF-ß signaling. Based on these features, we constructed a random forest model to predict the response and survival for PDAC patients, which accurately distinguished high-risk and chemoresistant patients with significantly poorer prognosis in both the training and independent validation datasets. Cox regression analysis indicated that predicted labels were an independent prognostic factor in PDAC. Moreover, deconvolution of TME confirmed higher infiltration levels of M2 macrophage and NK cells in predicted chemoresistance. When combined with chemotherapy response related tumor mutations, the model showed excellent ability in predicting chemotherapy response and survival. Conclusions: The TME was closely associated with the chemotherapy response and prognosis of PDAC. Our TME-based random forest model predicted chemotherapy response with complementary knowledge to the response-related genetic mutations.

Advances in oligosaccharides and polysaccharides with different structures as wall materials for probiotics delivery: A review.

Probiotics are active microorganisms that are beneficial to the health of the host. However, probiotics are highly sensitive to the external environment, and are susceptible to a variety of factors that reduce their activity during production, storage, and use. Microencapsulation is an effective method that enhances probiotic activity. Macromolecules like polysaccharides, who classified as biologically active prebiotics, have attracted significant attention for their utility in probiotic microencapsulation. This article summarized the types of commonly used microencapsulation materials and their structural characteristics from the perspective of polysaccharides prebiotics. It also discussed recent advancements, probiotic-prebiotic microcapsule-based modulation of the immune system, as well as the associated limitations. Furthermore, the advantages and disadvantages of eight prebiotics as microencapsulation wall materials. The honeycomb structure of ß-glucan enhances the bioavailability of probiotics, while, fructooligosaccharide and galactooligosaccharides improve microbead structure to tightly encapsulate probiotics. The terminal reducing groups of isomaltooligosaccharides and the free hydroxyl groups in xylooligosaccharides also positively affect the structure of microcapsules. Prebiotics not only enhance the survival rate and biological activity of probiotics as embedding materials during storage, but also exert their own probiotic effects. Collectively, prebiotics holds great promise as microencapsulation materials for probiotics delivery.

Liriodendrin stimulates proliferation and milk protein synthesis of mammary epithelial cells via the PI3K-DDX18 signaling.

Liriodendrin is a lignan compound that is involved in a wide variety of physiological functions, however it is unknown whether liriodendrin plays an important role in milk production in the mammary glands. In this study, we explored the role and molecular mechanism of Liriodendrin in milk synthesis of mammary epithelial cells (MECs). Bovine MECs were treated with liriodendrin (0, 0.45, 0.9, 1.35, 1.8, and 2.25 mM) for 24 h. Liriodendrin dose-dependently increased cell number, cell cycle transition, and milk protein synthesis, as well as Cyclin D1 and mTOR phosphorylation, with the maximal effects observed at a dose of 1.35 mM. Liriodendrin increased the expression of DDX18, which mediated liriodendrin stimulation of Cyclin D1 and mTOR mRNA expression. PI3K inhibition and DDX18 knockdown experiments further confirmed that liriodendrin regulates the mRNA expression of Cyclin D1 and mTOR via the PI3K-DDX18 signaling. Mouse feeding experiment showed that liriodendrin dose-dependently promotes ß-casein and DDX18 expression in mouse mammary gland. In this study, DDX18 was found to be a novel positive regulator that plays a role in cell proliferation and synthesis of milk protein. These findings reveal that liriodendrin stimulates proliferation and milk protein synthesis of MECs via the PI3K-DDX18 signaling.

Resveratrol reversed rosiglitazone administration induced bone loss in rats with type 2 diabetes mellitus.

Rosiglitazone (RSG), as an insulin-sensitizing drug to treat type 2 diabetes mellitus (T2DM) is reported to decrease bone quality and increase bone fracture risk. The multiple off-target effects of Resveratrol (RSV), a natural specific agonist of Sirtuin1 (Sirt1) with pro-osteoblastogenesis and anti-adipogenesis effects, on bone loss in T2DM are still under discussion. In this study, successfully ovariectomized rats were fed with high-fat diet and STZ (HFD/STZ) to induced T2DM mice. RSV alone, RSG alone or co-administration of RSV and RSG were given orally to T2DM rats for 8 weeks to determine whether RSV administration had any prevention effect on T2DM osteoporosis. Bone mesenchymal stem cells (BMSCs) and bone marrow­derived macrophages (BMMs) were cultured under high glucose condition and were induced to osteoblasts or adipocytes and osteoclasts, respectively. µCT and HE staining showed that in T2DM osteoporotic rats, RSV co-administration prevents RSG induced-bone loss. ELISA results confirmed that RSV suppressed osteoclast activity and promoted osteoblast activity in diabetic osteoporosis rats and RSG-administrated diabetic osteoporosis rats. In vitro study showed that RSV significantly reversed RSG induced inhibition on osteogenesis and promotion on adiopogenesis of BMSC under high glucose (HG). Moreover, RSV significantly reverse RSG induced osteoclast formation and mature under HG. Taken together, these findings uncover a previously unappreciated anti-osteoporosis effect of concomitant treatment with RSV in RSG-administrated diabetic rats, suggesting the clinical use of RSV as an adjuvant in the treatment of T2DM for preventing or reversing RSG administration-associated bone loss.

PPARγ/NF-κB axis contributes to cold-induced resolution of experimental colitis and preservation of intestinal barrier.

BACKGROUND: Environmental stress is a significant contributor to the development of inflammatory bowel disease (IBD). The involvement of temperature stimulation in the development of IBD remains uncertain. Our preliminary statistical data suggest that the prevalence of IBD is slightly lower in colder regions compared to non-cold regions. The observation indicates that temperature changes may play a key role in the occurrence and progression of IBD. Here, we hypothesized that cold stress has a protective effect on IBD. METHODS: The cold exposure model for mice was placed in a constant temperature and humidity chamber, maintained at a temperature of 4 °C. Colitis models were induced in the mice using TNBS or DSS. To promote the detection methods more clinically, fluorescence confocal endoscopy was used to observe the mucosal microcirculation status of the colon in the live model. Changes in the colonic wall of the mice were detected using 9.4 T Magnetic Resonance Imaging (MRI) imaging and in vivo fluorescence imaging. Hematoxylin and eosin (H&E) and Immunofluorescence (IF) staining confirmed the pathological alterations in the colons of sacrificed mice. Molecular changes at the protein level were assessed through Western blotting and Enzyme-Linked Immunosorbent Assay (ELISA) assays. RNA sequencing (RNA-seq) and metabolomics (n = 18) were jointly analyzed to investigate the biological changes in the colon of mice treated by cold exposure. RESULTS: Cold exposure decreased the pathologic and disease activity index scores in a mouse model. Endomicroscopy revealed that cold exposure preserved colonic mucosal microcirculation, and 9.4 T MRI imaging revealed alleviation of intestinal wall thickness. In addition, the expression of the TLR4 and PP65 proteins was downregulated and epithelial cell junctions were strengthened after cold exposure. Intriguingly, we found that cold exposure reversed the decrease in ZO-1 and occludin protein levels in dextran sulfate sodium (DSS)- and trinitrobenzenesulfonic acid-induced colitis mouse models. Multi-omics analysis revealed the biological landscape of DSS-induced colitis under cold exposure and identified that the peroxisome proliferator-activated receptor (PPAR) signaling pathway mediates the effects of cold on colitis. Subsequent administration of rosiglitazone (PPAR agonist) enhanced the protective effect of cold exposure on colitis, whereas GW9662 (PPAR antagonist) administration mitigated these protective effects. Overall, cold exposure ameliorated the progression of mouse colitis through the PPARγ/NF-κB signaling axis and preserved the intestinal mucosal barrier. CONCLUSION: Our study provides a mechanistic link between intestinal inflammation and cold exposure, providing a theoretical framework for understanding the differences in the prevalence of IBD between the colder regions and non-cold regions, and offering new insights into IBD therapy.

A crystal capping layer for formation of black-phase FAPbI3 perovskite in humid air.

Black-phase formamidinium lead iodide (α-FAPbI3) perovskites are the desired phase for photovoltaic applications, but water can trigger formation of photoinactive impurity phases such as δ-FAPbI3. We show that the classic solvent system for perovskite fabrication exacerbates this reproducibility challenge. The conventional coordinative solvent dimethyl sulfoxide (DMSO) promoted δ-FAPbI3 formation under high relative humidity (RH) conditions because of its hygroscopic nature. We introduced chlorine-containing organic molecules to form a capping layer that blocked moisture penetration while preserving DMSO-based complexes to regulate crystal growth. We report power conversion efficiencies of >24.5% for perovskite solar cells fabricated across an RH range of 20 to 60%, and 23.4% at 80% RH. The unencapsulated device retained 96% of its initial performance in air (with 40 to 60% RH) after 500-hour maximum power point operation.

A Novel MRI-Based Paravertebral Muscle Quality (PVMQ) Score for Evaluating Muscle Quality and Bone Quality: A Comparative Study with the VBQ Score.

Purpose: This study aims to develop a novel MRI-based paravertebral muscle quality (PVMQ) score for assessing muscle quality and to investigate its correlation with the degree of fat infiltration (DFF) and the vertebral bone quality (VBQ) score of paravertebral muscles. Additionally, the study compares the effectiveness of the PVMQ score and the VBQ score in assessing muscle quality and bone quality. Methods: PVMQ scores were derived from the ratio of paravertebral muscle signal intensity (SI) to L3 cerebrospinal fluid SI on T2-weighted MRI. Image J software assessed paravertebral muscle cross-sectional area (CSA) and DFF. Spearman rank correlation analyses explored associations between PVMQ, VBQ scores, DFF, and T-scores in both genders. Receiver operating characteristic (ROC) curves compared PVMQ and VBQ scores' effectiveness in distinguishing osteopenia/osteoporosis and high paraspinal muscle DFF. Results: In this study of 144 patients (94 females), PVMQ scores were significantly higher in osteoporosis and osteopenia groups compared to normals, with variations observed between genders (P < 0.05). PVMQ showed stronger positive correlation with VBQ scores and DFF in females than males (0.584 vs 0.445, 0.579 vs 0.528; P < 0.01). ROC analysis favored PVMQ over VBQ for low muscle mass in both genders (AUC = 0.767 vs 0.718, 0.793 vs 0.718). VBQ was better for bone mass in males (0.737/0.865 vs 0.691/0.858), whereas PVMQ excelled for females (0.808/0.764 vs 0.721/0.718). Conclusion: The novel PVMQ score provides a reliable assessment of paravertebral muscle quality and shows a strong correlation with VBQ scores and DFF, particularly in females. It outperforms VBQ scores in evaluating muscle mass and offers valuable insights for assessing bone mass in females. These findings underscore the potential of the PVMQ score as a dual-purpose tool for evaluating both muscle and bone health, informing future research and clinical practice.

New geographical records and molecular investigation of the ciliate Spirostomum.

Spirostomum is a genus of large ciliates, and its species are distributed worldwide. However, there has been limited research conducted on their geographical distribution and genomics. We obtained nine samples of ciliates from eight regions in Liaoning Province, China, and conducted a study on their geographical distribution and characteristics. Morphological and second-generation high-throughput sequencing methods were applied to identify the species, and a phylogenetic tree was established to gain a deeper understanding of the geographical distribution and evolutionary relationships of Spirostomum in Northeast China. The results identified Spirostomum yagiui and Spirostomum subtilis as a newly recorded species in Northeast China region. There are now five species of Spirostomum that have been recorded in China, and new details on the genomic characteristics of Spirostomum yagiui were provided. In addition, this study also identified the main branches of Spirostomum teres and Spirostomum minus in northern China, and provided a theoretical basis for the existence of hidden species. Spirostomum yagiui is the first species in the family Spirostomidae to have undergone mitochondrial genome sequencing.

Co-Invasion of Congeneric Invasive Plants Adopts Different Strategies Depending on Their Origins.

Plant communities may be co-invaded by invasive plants, sometimes even by congeneric invasive plants (CIPs). Despite the growing understanding of co-invasion in the environment, little is known about how CIP interactions and mechanisms regulate co-invasion. Darwin's naturalisation conundrum predicts that the coexistence of closely related species is difficult due to their structural and behavioural similarities. Nevertheless, communities containing closely related species are more susceptible to being invaded because close relatives may favour similar environments; therefore, this hypothesis should be followed in the co-invasion of CIPs. To explore whether the phylogenetic relatedness and origins of invasive species to CIPs can promote or hinder co-invasion, we conducted a controlled interaction and soil-legacy greenhouse experiment to quantify the growth response of invasive plants and their congeners. We consistently found that CIPs of identical origin were more likely to co-invade compared to CIPs of distinct origins. CIPs of distinct origins exhibited an antagonistic effect on co-invasion by allelopathy. Invasive plant-conditioned soil was more conducive to the growth of CIPs of identical origin than CIPs of distinct origins. Our results revealed the different effects of invader-invader phylogenetic relatedness on co-invader success and impact, suggesting the operation of different mechanisms across co-invasion.

Enhancement of Large Language Models' Performance in Diabetes Education: Retrieval-Augmented Generation Approach.

BACKGROUND: Large language models (LLMs) demonstrated advanced performance in processing clinical information. However, commercially available LLMs lack specialized medical knowledge and remain susceptible to generating inaccurate information. Given the need for self-management in diabetes, patients commonly seek information online. We introduce the RISE framework and evaluate its performance in enhancing LLMs to provide accurate responses to diabetes-related inquiries. OBJECTIVE: This study aimed to evaluate the potential of RISE framework, an information retrieval and augmentation tool, to improve the LLM's performance to accurately and safely respond to diabetes-related inquiries. METHODS: The RISE, an innovative retrieval augmentation framework, comprises four steps: Rewriting Query, Information Retrieval, Summarization, and Execution. Using a set of 43 common diabetes-related questions, we evaluated three base LLMs (GPT-4, Anthropic Claude 2, Google Bard) and their RISE-enhanced versions. Assessments were conducted by clinicians for accuracy and comprehensiveness, and by patients for understandability. RESULTS: The integration of RISE significantly improved the accuracy and comprehensiveness of responses from all three based LLMs. On average, the percentage of accurate responses increased by 12% (122 - 107/129) with RISE. Specifically, the rates of accurate responses increased by 7% (42 - 39/43) for GPT-4, 19% (39 - 31/43) for Claude 2, and 9% (41 - 37/43) for Google Bard. The framework also enhanced response comprehensiveness, with mean scores improving by 0.44. Understandability was also enhanced by 0.19 on average. Data collection was conducted from Sept. 30, 2023, to Feb. 05, 2024. CONCLUSIONS: RISE significantly improves LLMs' performance in responding to diabetes-related inquiries, enhancing accuracy, comprehensiveness, and understandability. These improvements have crucial implications for RISE's future role in patient education and chronic illness self-management, which contributes to relieving medical resource pressures and raising public awareness of medical knowledge.

Temporal Variations in Fire Impacts on Characteristics and Composition of Soil-Derived Dissolved Organic Matter at Qipan Mountain, China.

Dissolved organic matter (DOM), the most reactive fraction of forest soil organic matter, is increasingly impacted by wildfires worldwide. However, few studies have quantified the temporal changes in soil DOM quantity and quality after fire. Here, soil samples were collected after the Qipan Mountain Fire (3-36 months) from pairs of burned and unburned sites. DOM contents and characteristics were analyzed using carbon quantification and various spectroscopic and spectrometric techniques. Compared with the unburned sites, burned sites showed higher contents of bulk DOM and most DOM components 3 months after the fire but lower contents of them 6-36 months after the fire. During the sharp drop of DOM from 3 to 6 months after the fire, carboxyl-rich alicyclic molecule-like and highly unsaturated compounds had greater losses than condensed aromatics. Notably, the burned sites had consistently higher abundances of oxygen-poor dissolved black nitrogen and fluorescent DOM 3-36 months after the fire, particularly the abundance of pyrogenic C2 (excitation/emission maxima of <250/∼400 nm) that increased by 150% before gradually declining. This study advances the understanding of temporal variations in the effects of fire on different soil DOM components, which is crucial for future postfire environmental management.

Research advances in detection of food adulteration and application of MALDI-TOF MS: A review.

Food adulteration and illegal supplementations have always been one of the major problems in the world. The threat of food adulteration to the health of consumers cannot be ignored. Food of questionable origin causes economic losses to consumers, but the potential health risks cannot be ignored. However, the traditional detection methods are time-consuming and complex. This review mainly discusses the types of adulteration and technologies used to detect adulteration. Matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) is also emphasized in the detection of adulteration and authenticity of origin analysis of various types of food (milk, meat, edible oil, etc.), and the future application direction and feasibility of this technology are analyzed. On this basis, MALDI-TOF MS was compared with other detection methods, highlighting the advantages of this technology in the detection of food adulteration. The future development prospect and direction of this technology are also emphasized.

Predicting epidemic threshold in complex networks by graph neural network.

To achieve precision in predicting an epidemic threshold in complex networks, we have developed a novel threshold graph neural network (TGNN) that takes into account both the network topology and the spreading dynamical process, which together contribute to the epidemic threshold. The proposed TGNN could effectively and accurately predict the epidemic threshold in homogeneous networks, characterized by a small variance in the degree distribution, such as Erdos-Rényi random networks. Usability has also been validated when the range of the effective spreading rate is altered. Furthermore, extensive experiments in ER networks and scale-free networks validate the adaptability of the TGNN to different network topologies without the necessity for retaining. The adaptability of the TGNN is further validated in real-world networks.

Flexible Resource Allocation-Efficient Water Use Strategies Facilitate Invasion of Invasive Vine Sicyos angulatus L.

The invasive vine Sicyos angulatus L. destroys the natural ecosystem of invaded areas. Understanding the differences in growth and development between S. angulatus and other plants is necessary to explore the invasion mechanisms of S. angulatus and implement appropriate prevention and control measures. Thus, this study compared the growth, photosynthesis, and root characteristics of invasive liana S. angulatus and other three vine plants, Ipomoea nil (L.) Roth, Ipomoea purpurea (L.), and Thladiantha dubia Bunge, at different growth stages: seedling, flowering, and fruiting. The results showed that the total biomass of S. angulatus in the fruiting stage was 3-6 times that of the other three plants, and the root biomass ratio and root-shoot ratio decreased throughout the growth stage. Throughout the growth stage, the total leaf area of S. angulatus was significantly higher than that of the other three plant types, and the specific leaf area of S. angulatus at the seedling and flowering stages was 2.5-3 and 1.4-3 times that of the other three plants, respectively. The photosynthetic rate, stomatal conductance, and transpiration rate of S. angulatus at the fruiting stage were significantly higher than those of the other three plants, and its water use efficiency was higher than that of the other three plants at the three growth stages, indicating its strong photosynthetic capacity. The root activity and root pressure of S. angulatus were also significantly higher than those of the other three plants at the seedling and flowering stages. These results show that S. angulatus flexibly allocates resources to its aboveground parts during the growth stage to ensure that the plant obtains the space necessary for its growth and development and that with the help of higher root pressure and root activity, S. angulatus can maintain higher photosynthesis and water use efficiency with fewer resources. Therefore, the prevention and control of S. angulatus requires a combination of aboveground and underground measures. Spraying conventional weedicide/herbicide and manually removing aboveground plants may lead to its resurgence.

Remote Health Management via WeChat to Improve the Quality of Life of Patients After PCI.

OBJECTIVES: The purpose of this research was to assess the effect of telehealth management via WeChat on improving the quality of life of patients after percutaneous coronary intervention (PCI). METHODS: In this study, we retrospectively collected the clinical data of 118 patients who underwent PCI and received remote health management from our hospital via WeChat from June 2021 to September 2021 (WeChat group). The clinical data of 114 patients who underwent PCI but did not receive remote health management from our hospital from September 2020 to December 2020 were also collected (conventional group). Anxiety, depression, and quality of life scale scores were compared between the 2 groups at 6 months postdischarge. RESULTS: Six months postdischarge, patients in the WeChat group had significantly lower Self-rating Anxiety Scale (SAS) (55.7 ± 7.2 vs 58.8 ± 6.4, P = .001) and Self-rating Depression Scale (SDS) (56.0 ± 5.9 vs 58.2 ± 6.2, P = .007) scores than did those in the conventional group. Compared to those in the conventional group, the patients in the WeChat group had significantly greater 6 months post-discharge The World Health Organization Quality of Life - BREF scores in the following domains: physical (14.3 ± 1.7 vs 13.1 ± 1.7, P < .001 psychological (15.2 ± 1.3 vs 13.5 ± 1.5, P < .001 social relationship (12.9 ± 1.7 vs 12.3 ± 1.8, P = .01) and environmental (12.7 ± 2.0 vs 12.0 ± 1.9, P = .006). CONCLUSION: The use of WeChat to carry out remote health management for patients who underwent PCI can be an effective way to provide high-quality hospital medical services to patients' families and can effectively alleviate patients' anxiety and depression and enhance their quality of life.

Exploration of potential novel drug targets for diabetic retinopathy by plasma proteome screening.

The aim of this study is to identify novel potential drug targets for diabetic retinopathy (DR). A bidirectional two-sample Mendelian randomization (MR) analysis was performed using protein quantitative trait loci (pQTL) of 734 plasma proteins as the exposures and clinically diagnosed DR as the outcome. Genetic instruments for 734 plasma proteins were obtained from recently published genome-wide association studies (GWAS), and external plasma proteome data was retrieved from the Icelandic Decoding Genetics Study and UK Biobank Pharma Proteomics Project. Summary-level data of GWAS for DR were obtained from the Finngen Consortium, comprising 14,584 cases and 202,082 population controls. Steiger filtering, Bayesian co-localization, and phenotype scanning were used to further verify the causal relationships calculated by MR. Three significant (p < 6.81 × 10-5) plasma protein-DR pairs were identified during the primary MR analysis, including CFH (OR = 0.8; 95% CI 0.75-0.86; p = 1.29 × 10-9), B3GNT8 (OR = 1.09; 95% CI 1.05-1.12; p = 5.9 × 10-6) and CFHR4 (OR = 1.11; 95% CI 1.06-1.16; p = 1.95 × 10-6). None of the three proteins showed reverse causation. According to Bayesian colocalization analysis, CFH (coloc.abf-PPH4 = 0.534) and B3GNT8 (coloc.abf-PPH4 = 0.638) in plasma shared the same variant with DR. All three identified proteins were validated in external replication cohorts. Our research shows a cause-and-effect connection between genetically determined levels of CFH, B3GNT8 and CFHR4 plasma proteins and DR. The discovery implies that these proteins hold potential as drug target in the process of developing drugs to treat DR.

Association of smart elderly care and quality of life among older adults: the mediating role of social support.

BACKGROUND: In the current context of ageing, the field of smart elderly care has gradually developed, contributing to the promotion of health among older adults. While the positive impact on health has been established, there is a scarcity of research examining its impact on the quality of life (QoL). This study aims to investigate the mediating role of social support in the relationship between smart elderly care and QoL among older adults. METHODS: A total of 1313 older adults from Zhejiang Province, China, participated in the study. Questionnaires were used to collect data on participants' basic demographic information, smart elderly care, social support, and QoL. The descriptive analyses of the demographic characteristics and correlation analyses of the three variables were calculated. Indirect effects were tested using bootstrapped confidence intervals (CI). RESULTS: The analysis revealed a positive association between smart elderly care and social support (ß = 0.42, p < 0.01), as well as a positive correlation between social support and QoL (ß = 0.65, p < 0.01). Notably, social support emerged as an important independent mediator (effect size = 0.28, 95% bootstrap CI 0.24 to 0.32) in the relationship between smart elderly care and QoL. CONCLUSIONS: The results of this study underscore the importance of promoting the utilization of smart elderly care and improving multi-faceted social support for older adults, as these factors positively contribute to the overall QoL.

Elastic Properties of Low-Dimensional Single-Crystalline Dielectric Oxides through Controlled Large-Area Wrinkle Generation.

Freestanding single-crystalline SrTiO3 membranes, as high-κ dielectrics, hold significant promise as the gate dielectric in two-dimensional (2D) flexible electronics. Nevertheless, the mechanical properties of the SrTiO3 membranes, such as elasticity, remain a critical piece of the puzzle to adequately address the viability of their applications in flexible devices. Here, we report statistical analysis on plane-strain effective Young's modulus of large-area SrTiO3 membranes (5 × 5 mm2) over a series of thicknesses (from 6.5 to 32.2 nm), taking advantage of a highly efficient buckling-based method, which reveals its evident thickness-dependent behavior ranging from 46.01 to 227.17 GPa. Based on microscopic and theoretical results, we elucidate these thickness-dependent behaviors and statistical data deviation with a bilayer model, which consists of a surface layer and a bulk-like layer. The analytical results show that the ∼3.1 nm surface layer has a significant elastic softening compared to the bulk-like layer, while the extracted modulus of the bulk-like layer shows a variation of ∼40 GPa. This variation is considered as a combined contribution from oxygen deficiency presenting in SrTiO3 membranes, and the alignment between applied strain and the crystal orientation. Upon comparison of the extracted elastic properties and electrostatic control capability to those of other typical gate dielectrics, the superior performance of single-crystalline SrTiO3 membranes has been revealed in the context of flexible gate dielectrics, indicating the significant potential of their application in high-performance flexible 2D electronics.