Integration of single-cell and RNA-seq data to explore the role of focal adhesion-related genes in osteoporosis.

Integrin-based focal adhesion is one of the major mechanosensory in osteocytes. The aim of this study was to mine the hub genes associated with focal adhesion and investigate their roles in osteoporosis based on the data of single-cell RNA sequencing and RNA-sequencing. Two hub genes (FAM129A and RNF24) with the same expression trend and AUC values greater than 0.7 in both GSE56815 and GSE56116 cohorts were uncovered. The nomogram was created to predict the risk of OP based on two hub genes. Subsequently, the competing endogenous RNA network was established based on two hub genes, 14 microRNAs and five long noncoding RNAs. Meanwhile, transcription factors-hub gene network was established based on two hub genes and 14 TFs. Finally, 73 drugs were predicted, of which there were 13 drugs targeting FAM129A and 66 drugs targeting RNF24. In both mouse and human blood samples, FAM129A expression was decreased in granulocytes and RNF24 expression was increased in monocytes. In the mouse experiment, FAM129A and anti-RNF24 were found to partially alleviate the progression of osteoporosis. In conclusion, two hub genes related to focal adhesion were identified by combined scRNA-seq and RNA-seq analyses, which might supply a new insight for the treatment and evaluation of OP.

Hybrid Membrane-Camouflaged Biomimetic Immunomodulatory Nanoturrets with Sequential Multidrug Release for Potentiating T Cell-Mediated Anticancer Immunity.

Ascorbic acid (AA) has been attracting great attention with its emerging potential in T cell-dependent antitumor immunity. However, premature blood clearance and immunologically "cold" tumors severely compromise its immunotherapeutic outcomes. As such, the reversal of the immunosuppressive tumor microenvironment (TME) has been the premise for improving the effectiveness of AA-based immunotherapy, which hinges upon advanced AA delivery and amplified immune-activating strategies. Herein, a novel Escherichia coli (E. coli) outer membrane vesicle (OMV)-red blood cell (RBC) hybrid membrane (ERm)-camouflaged immunomodulatory nanoturret is meticulously designed based on gating of an AA-immobilized metal-organic framework (MOF) onto bortezomib (BTZ)-loaded magnesium-doped mesoporous silica (MMS) nanovehicles, which can realize immune landscape remodeling by chemotherapy-assisted ascorbate-mediated immunotherapy (CAMIT). Once reaching the acidic TME, the acidity-sensitive MOF gatekeeper and MMS core within the nanoturret undergo stepwise degradation, allowing for tumor-selective sequential release of AA and BTZ. The released BTZ can evoke robust immunogenic cell death (ICD), synergistically promote dendritic cell (DC) maturation in combination with OMV, and ultimately increase T cell tumor infiltration together with Mg2+. The army of T cells is further activated by AA, exhibiting remarkable antitumor and antimetastasis performance. Moreover, the CD8-deficient mice model discloses the T cell-dependent immune mechanism of the AA-based CAMIT strategy. In addition to providing a multifunctional biomimetic hybrid nanovehicle, this study is also anticipated to establish a new immunomodulatory fortification strategy based on the multicomponent-driven nanoturret for highly efficient T cell-activation-enhanced synergistic AA immunotherapy.

Polyoxometalate-Intercalated Tremella-Like CoNi-LDH Nanocomposites for Electrocatalytic Nitrite-Ammonia Conversion.

The electrocatalytic reduction of NO2- (NO2RR) holds promise as a sustainable pathway to both promoting the development of emerging NH3 economies and allowing the closing of the NOx loop. Highly efficient electrocatalysts that could facilitate this complex six-electron transfer process are urgently desired. Herein, tremella-like CoNi-LDH intercalated by cyclic polyoxometalate (POM) anion P8W48 (P8W48/CoNi-LDH) prepared by a simple two-step hydrothermal-exfoliation assembly method is proposed as an effective electrocatalyst for NO2- to NH3 conversion. The introduction of POM with excellent redox ability tremendously increased the electrocatalytic performance of CoNi-LDH in the NO2RR process, causing P8W48/CoNi-LDH to exhibit large NH3 yield of 0.369 mmol h-1 mgcat-1 and exceptionally high Faradic efficiency of 97.0% at -1.3 V vs the Ag/AgCl reference electrode in 0.1 M phosphate buffer saline (PBS, pH = 7) containing 0.1 M NO2-. Furthermore, P8W48/CoNi-LDH demonstrated excellent durability during cyclic electrolysis. This work provides a new reference for the application of POM-based nanocomposites in the electrochemical reduction of NO2- to obtain value-added NH3.

Ratiometric electrochemiluminescence sensing and intracellular imaging of ClO- via resonance energy transfer.

Electrochemiluminescence resonance energy transfer (ECL-RET) is a versatile signal transduction strategy widely used in the fabrication of chem/biosensors. However, this technique has not yet been applied in visualized imaging analysis of intracellular species due to the insulating nature of the cell membrane. Here, we construct a ratiometric ECL-RET analytical method for hypochlorite ions (ClO-) by ECL luminophore, with a luminol derivative (L-012) as the donor and a fluorescence probe (fluorescein hydrazide) as the acceptor. L-012 can emit a strong blue ECL signal and fluorescein hydrazide has negligible absorbance and fluorescence signal in the absence of ClO-. Thus, the ECL-RET process is turned off at this time. In the presence of ClO-, however, the closed-loop hydrazide structure in fluorescein hydrazide is opened via specific recognition with ClO-, accompanied with intensified absorbance and fluorescence signal. Thanks to the spectral overlap between the ECL spectrum of L-012 and the absorption spectrum of fluorescein, the ECL-RET effect is gradually recovered with the addition of ClO-. Furthermore, the ECL-RET system has been successfully applied to image intracellular ClO-. Although the insulating nature of the cell itself can generate a shadow ECL pattern in the cellular region, extracellular ECL emission penetrates the cell membrane and excites intracellular fluorescein generated by the reactions between fluorescein hydrazide and ClO-. The cell imaging strategy via ECL-RET circumvents the blocking of the cell membrane and enables assays of intracellular species. The importance of the ECL-RET platform lies in calibrating the fluctuation from the external environment and improving the selectivity by using fluorescent probes. Therefore, this ratiometric ECL sensor has shown broad application prospects in the identification of targets in clinical diagnosis and environmental monitoring.

New mechanistic understanding of osteoclast differentiation and bone resorption mediated by P2X7 receptors and PI3K-Akt-GSK3ß signaling.

OBJECTIVE: Osteoporosis is a global health issue characterized by decreased bone mass and microstructural degradation, leading to an increased risk of fractures. This study aims to explore the molecular mechanism by which P2X7 receptors influence osteoclast formation and bone resorption through the PI3K-Akt-GSK3ß signaling pathway. METHODS: An osteoporosis mouse model was generated through ovariectomy (OVX) in normal C57BL/6 and P2X7f/f; LysM-cre mice. Osteoclasts were isolated for transcriptomic analysis, and differentially expressed genes were selected for functional enrichment analysis. Metabolite analysis was performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS), and multivariate statistical analysis and pattern recognition were used to identify differential lipid metabolism markers and their distribution. Bioinformatics analyses were conducted using the Encyclopedia of Genes and Genomes database and the MetaboAnalyst database to assess potential biomarkers and create a metabolic pathway map. Osteoclast precursor cells were used for in vitro cell experiments, evaluating cell viability and proliferation using the Cell Counting Kit 8 (CCK-8) assay. Osteoclast precursor cells were induced to differentiate into osteoclasts using macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kappa-beta ligand (RANKL), and tartrate-resistant acid phosphatase (TRAP) staining was performed to compare differentiation morphology, size, and quantity between different groups. Western blot analysis was used to assess the expression of differentiation markers, fusion gene markers, and bone resorption ability markers in osteoclasts. Immunofluorescence staining was employed to examine the spatial distribution and quantity of osteoclast cell skeletons, P2X7 protein, and cell nuclei, while pit assay was used to evaluate osteoclast bone resorption ability. Finally, in vivo animal experiments, including micro computed tomography (micro-CT), hematoxylin and eosin (HE) staining, TRAP staining, and immunohistochemistry, were conducted to observe bone tissue morphology, osteoclast differentiation, and the phosphorylation level of the PI3K-Akt-GSK3ß signaling pathway. RESULTS: Transcriptomic and metabolomic data collectively reveal that the P2X7 receptor can impact the pathogenesis of osteoporosis through the PI3K-Akt-GSK3ß signaling pathway. Subsequent in vitro experiments showed that cells in the Sh-P2X7 + Recilisib group exhibited increased proliferative activity (1.15 versus 0.59), higher absorbance levels (0.68 versus 0.34), and a significant increase in resorption pit area (13.94 versus 3.50). Expression levels of osteoclast differentiation-related proteins MMP-9, CK, and NFATc1 were markedly elevated (MMP-9: 1.72 versus 0.96; CK: 2.54 versus 0.95; NFATc1: 3.05 versus 0.95), along with increased fluorescent intensity of F-actin rings. In contrast, the OE-P2X7 + LY294002 group showed decreased proliferative activity (0.64 versus 1.29), reduced absorbance (0.34 versus 0.82), and a significant decrease in resorption pit area (5.01 versus 14.96), accompanied by weakened expression of MMP-9, CK, and NFATc1 (MMP-9: 1.14 versus 1.79; CK: 1.26 versus 2.75; NFATc1: 1.17 versus 2.90) and decreased F-actin fluorescent intensity. Furthermore, in vivo animal experiments demonstrated that compared with the wild type (WT) + Sham group, mice in the WT + OVX group exhibited significantly increased levels of CTX and NTX in serum (CTX: 587.17 versus 129.33; NTX: 386.00 versus 98.83), a notable decrease in calcium deposition (19.67 versus 53.83), significant reduction in bone density, increased trabecular separation, and lowered bone mineral density (BMD). When compared with the KO + OVX group, mice in the KO + OVX + recilisib group showed a substantial increase in CTX and NTX levels in serum (CTX: 503.50 versus 209.83; NTX: 339.83 versus 127.00), further reduction in calcium deposition (29.67 versus 45.33), as well as decreased bone density, increased trabecular separation, and reduced BMD. CONCLUSION: P2X7 receptors positively regulate osteoclast formation and bone resorption by activating the PI3K-Akt-GSK3ß signaling pathway.

Effect of accelerated high-fluence riboflavin and rose bengal-mediated corneal cross-linking on resistance to enzymatic digestion.

PURPOSE: This study evaluated the effect of high-fluence accelerated corneal cross-linking on the resistance to enzymatic digestion, assessing two chromophore/light combinations: riboflavin/UV-A light (RF/UV-A) and rose bengal/green light (RB/green). METHODS: Freshly prepared ex-vivo porcine corneas (n = 189) were divided into 8 groups groups. Group A corneas were unirradiated controls without chromophore soaking (A0), or soaked with riboflavin (A1) or rose bengal (A2). Group B corneas underwent accelerated epi-off RF/UV-A CXL at fluences of 5.4 J/cm² (B1), 10 J/cm² (B2), or 15 J/cm² (B3). Group C corneas underwent accelerated epi-off RB/green CXL at fluences of either 10 J/cm² (C1) or 15 J/cm² (C2). Following CXL, all corneas were digested in 0.3% collagenase-A solution, and the time until complete dissolution was measured. RESULTS: Non-irradiated controls exposed to RF and RB enhanced corneal resistance to collagenase digestion, with RB having a stronger effect than RF. RF/UV-A-treated corneas showed significantly increased digestion resistance with increasing fluence levels. RB/green-treated corneas displayed enhanced digestion resistance with each increase in fluence up to 10 J/cm²; a 15 J/cm² fluence yielded similar digestion resistance times to a 10 J/cm² fluence, suggesting a plateau effect in accelerated RB/green CXL protocols. CONCLUSIONS: When compared to standard-fluence treatments, high-fluence accelerated epi-off CXL using both riboflavin and rose bengal significantly increases resistance to enzymatic digestion. The optimal settings for clinical protocols might be 15 J/cm² (30 mW/cm² for 8 min 20 s) for RF/UV-A and 10 J/cm² (15 mW/cm² for 11 min 7 s) for RB/Green Light.

Individual-level community-based social capital and depressive symptoms among older adults in urban China: the moderating effects of socioeconomic status.

OBJECTIVES: This study aimed to examine the moderating role of socioeconomic status in the association between community-based social capital-based on individual-level cognitive and structural social capital-and depressive symptoms among older adults in urban China. METHODS: Data were collected in 2020 through a community survey of 800 respondents aged 60 years and older living in Shijiazhuang and Tianjin. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale. Multiple-group analyses were conducted to analyze the data. RESULTS: Measurement models of cognitive social capital and structural social capital were established. Measurement invariance was established across different socioeconomic groups. Additionally, socioeconomic status significantly moderated the association between social capital and depressive symptoms. The association between cognitive social capital and depressive symptoms was statistically significant among respondents with relatively low incomes and high levels of education, whereas the association between structural social capital and depressive symptoms was significant only among those with relatively high incomes. CONCLUSION: Future social capital policies and interventions should adopt different strategies to provide services to older adults from different socioeconomic backgrounds. Furthermore, educational programs should promote the effects of cognitive social capital on depressive symptoms later in life.

Adverse childhood experiences and self-esteem among adolescents: The role of social capital and gender.

INTRODUCTION: Adverse childhood experiences have long-lasting effects on the self-esteem of adolescents. However, the extrinsic mechanism linking them to self-esteem, which is more modifiable, has rarely been examined. Therefore, this study examined the mediating roles of family, school, and peer social capital and the moderating role of gender in the association between adverse childhood experiences and adolescent self-esteem. METHODS: This study involved a cross-sectional survey of first- and second-grade students in the only high school in Wusu, Xinjiang Uygur Autonomous Region, China. Data were collected in May 2023. A sample of 2539 students (M = 16.84 years old; 55.65% female) was included. The measurement models of family, school, and peer social capital were constructed using confirmatory factor analysis. The mediating roles of the three types of social capital and the moderating role of gender were examined using mediation analysis and multiple-group analysis, respectively. RESULTS: Family, school, and peer social capital significantly mediated the relationship between adverse childhood experiences and adolescent self-esteem, and family social capital played the strongest role. Gender significantly moderated the direct effect of adverse childhood experiences on self-esteem. The direct effect was significant only among girls. CONCLUSIONS: This study underscores the protective role of social capital for self-esteem among adolescents in Northwestern China and similar areas with relatively limited social services. Comprehensive interventions promoting social capital, especially family social capital, should be conducted to enhance self-esteem among adolescents.

Tumor-infiltrating gamma delta T-cells reveal exhausted subsets with remarkable heterogeneity in colorectal cancer.

The γδT-cells recognize infected or transformed cells. However, unlike αßT-cells, γδT-cells are innate-like immune cells, with no major histocompatibility complex restriction requirements. γδT-cells are the main population of intestinal intraepithelial lymphocytes (IELs) and are associated with the antitumor immune response, particularly in colorectal cancer (CRC). Although CD8+ T-cells exhibit dysfunction and even exhaustion in the tumor microenvironment (TME), which contributes to tumor immune escape, whether the same applies to tumor-infiltrating (TI)-γδT-cells is not completely understood. Here, we sought to investigate the expression pattern of inhibitory receptors and functional state of TI-γδT-cells, and reveal the features of exhausted TI-γδT-cells in the CRC TME. We demonstrated that TI-γδT-cells exhibited exhaustion phenotypes and displayed more severe functional exhaustion than TI-CD8+ T-cells or NK-cells in the TME of CRC. In addition, scRNA-seq analysis of TI-γδT-cells revealed three exhausted subsets with remarkable heterogeneity. The presence of three heterogeneous exhausted γδT-cell (Tex) populations, including Texprog , Textran and Texterm were further confirmed by flow cytometry, on the basis of PD-1 and TIM-3 expression. Finally, we revealed that c-Maf not only contributed to γδT-cell exhaustion via upregulation of inhibitory receptors, but also involved in the exhaustion of CD8+ T and NK-cells. c-Maf may also be an important contributor to γδT-cell exhaustion in CRC patients. These findings indicated that TI-γδT-cells exhibit phenotypic and functional exhaustion in the CRC TME. The revealed features of exhausted TI-γδT-cells may provide help for understanding the mechanisms and the association of γδT-cell exhaustion with tumor development and pathogenesis.

Fabrication of Flexible Pyramid Array as SERS Substrate for Direct Sampling and Reproducible Detection.

Rapid extraction and analysis of target molecules from irregular surfaces are in high demand in the field of on-site analysis. Herein, a flexible platform used for surface-enhanced Raman scattering (SERS) based on an ordered polymer pyramid structure with half-imbedded silver nanoparticles (AgNPs) was prepared to address this issue. The fabrication includes the following steps: (1) creating inverted pyramid arrays in silicon substrate, (2) preparing a layer of AgNPs on the surface of the inverted pyramids, and (3) obtaining a substrate with an ordered polymer pyramids array with half-imbedded AgNPs by the molding method. This flexible substrate is capable of rapid extraction via a simple and convenient "paste and peel off" method. In addition, the substrate exhibits great repeatability and good sensitivity thanks to the uniformity and larger surface area of the ordered pyramids. The density of "hot spots" (local electromagnetic field with high intensity) is increased on the structured surface. Semi-imbedding silver particles in the polymer pyramids makes "hot spots" robust on the substrate. In addition, the preprepared silicon template with the inverted pyramids can be reused, which greatly reduces the production cost. With this substrate, we successfully analyzed thiram molecules on the epidermis of apples, cucumbers, and oranges, and the detection limits are 2.4, 3, and 3 ng/cm2, respectively. These results demonstrate the great potential of the substrate for in situ analysis, which can provide reference for the design of ideal SERS substrates.

Down-regulation of ALDOB during metabolic reprogramming mediates malignant behavior in hepatocellular carcinoma and insensitivity to postoperative adjuvant transarterial chemoembolization.

BACKGROUND: Postoperative transarterial chemoembolization (PA-TACE) is an effective adjuvant therapy for preventing early postoperative recurrence of hepatocellular carcinoma (HCC); however, many patients are insensitive to it. Therefore, the present study aimed to explore the in-depth reasons for PA-TACE resistance and provide a reliable basis for selecting patients who will benefit the most from PA-TACE. METHODS: The unique gene expression profiles of primary tumors from PA-TACE-sensitive or -insensitive patients were analyzed using microarray data. Combined differential expression analysis, gene set enrichment analysis (GSEA), and weighted correlation network analysis (WGCNA) were used to screen for potential drivers of PA-TACE insensitivity. The expression of ALDOB was silenced or overexpressed in hepatoma cell lines, and changes in glycolytic activity, cycle, apoptosis, and malignant biological phenotypes were observed under normoxia and hypoxia. Finally, an animal model was constructed to verify the effects of ALDOB dysregulation on the tumorigenic ability of HCC cells in vivo. RESULTS: The inhibition of ALDOB promoted the up-regulation of Ki67 expression, and glycolytic activity was significantly enhanced. Moreover, the proliferation, invasion, and migration capabilities were increased in HCC cells and even worse in hypoxia. This advantage of malignant behavior was also validated using in vivo models. CONCLUSION: Down-regulation of ALDOB may underlie the metabolic reprogramming observed in HCC by promoting the malignant behavior of HCC cells. Hypoxia and ALDOB down-regulation acted additively, which was closely related to PA-TACE insensitivity. The use of ALDOB and Ki67 as a combined marker has the potential to identify the 'PA-TACE beneficiary population'.

Selective serotonin reuptake inhibitors regulate the interrelation between 5-HT and inflammation after myocardial infarction.

BACKGROUND: Acute myocardial infarction (AMI) is a main cause of death all around the world. There is a close relationship between myocardial infarction (MI) and depression. MI patients with untreated depression had higher mortality than those without depression. Therefore, this study aimed to explore the effect of escitalopram in treating a model under MI and unpredictable chronic mild stress (UCMS). METHODS: Male C57BL/6J mice were treated with sham surgery, or MI surgery, or UCMS, or escitalopram (ES) for a consecutive two weeks. And the mice were divided into Sham group, MI group, MI + UCMS group, MI + UCMS + ES group (n = 8 in each group). After treatment, the mice went through open field test for anxiety behavior, sucrose preference test for depressive behavior. After sacrificed, the blood, heart, hippocampus, and cortex were collected. RESULTS: The escitalopram badly increased the area of cardiac fibrosis size. The sucrose preference test demonstrated that escitalopram treatment showed significant effect in improving depressive behaviors of mice under MI + UCMS. The potential mechanism involved the interrelation between 5-HT system and inflammation. MI significantly affected the level of cardiac SERT. Both UCMS and ES significantly affected the level of cortex TNF-α. UCMS significantly affected the level of cardiac IL-33. In the hippocampus tissue, TNF-α was positively correlated with SERT, and IL-10 was positively correlated with SERT. In the cortex tissue, IL-33 was positively correlated with 5-HT4R, and sST2 was positively correlated with 5-HT. CONCLUSIONS: Two-week escitalopram treatment might worsen myocardial infarction. But escitalopram could benefit depressive behaviors, which may be related with the interrelationship between the 5-HT system and inflammatory factors in the brain.

Activity engagement and cognitive function among chinese older adults: moderating roles of gender and age.

BACKGROUND: Many studies have found that engaging in activities, including physical exercise, social interaction, and cognitive training, is beneficial for preventing cognitive decline among older adults; however, the demographic differences in the association between activity engagement and cognitive functions remain understudied. This study investigates: (a) the influence of activity engagement on cognitive functions among Chinese older adults, and (b) the moderating roles of age and gender in these associations . METHODS: The data were derived from the China Health and Retirement Longitudinal Study in 2018, which included 9803 participants aged 60 or older. A multiple regression model was used to test the study hypotheses. RESULTS: Engaging in physical activity (b = 1.578, p < .001), social interaction (b = 1.199, p < .001), and cognitive activity (b = 1.468, p < .001) was positively associated with cognitive functions, whereas the effect of volunteer activities on cognitive functions was not significant (b = -.167, p = .390). Light- and moderate-intensity activities were beneficial for cognition (light: b = .847, p < .001; moderate: b = 1.189, p < .001), but vigorous-intensity activity was negatively related to cognition (b = -.767, p < .001). In addition, women and participants with advanced age appeared to benefit more from cognitive activities than their male and younger counterparts, respectively (gender: b = 1.217, p = .002; age: b = .086, p = .004). The adverse effects of vigorous-intensity activities (including agricultural work) on cognitive health were stronger for women and younger participants (gender: b = -1.472, p < .001; age: b = .115, p < .001). The protective effects of moderate-intensity activities on people's cognition increased with increasing age (b = .055, p = .012). CONCLUSIONS: The findings indicate that participating in physical, social, and cognitive activities can help older adults to maintain cognitive health. They suggest that older adults should select activities while considering activity intensity and their individual characteristics.

The roots of healthy aging: investigating the link between early-life and childhood experiences and later-life health.

Whilst early-life conditions have been understood to impact upon the health of older adults, further exploration of the field is required. There is a lack of consensus on conceptualising these conditions, and interpretation of experiences are socially and culturally dependent.To advance this important topic we invite authors to submit their research to the Collection on 'The impact of early-life/childhood circumstances or conditions on the health of older adults'.

A multiple-group analysis of social Capital and loneliness among community-dwelling older adults in urban China during the outbreak of the COVID-19 pandemic.

OBJECTIVES: The present study examined the moderating effects of family social capital on the relationship between community social capital and loneliness among older adults in urban Chinese communities during the COVID-19 outbreak period between January and March 2020.Method: We used quota sampling to recruit 472 community-dwelling older adults aged 60 years or older. A multiple-group analysis was applied to examine the proposed hypotheses.Results: Community-based cognitive social capital was significantly associated with both social and emotional loneliness among older adults with relatively low levels of family social capital. However, these associations were statistically nonsignificant among those with high family social capital levels. Community-based structural social capital was not associated with loneliness in either family social capital group.Conclusion: The findings highlight the role of cognitive social capital in reducing loneliness and support community social capital replacement theory in explaining the mechanism linking social capital to loneliness in later life in the context of the COVID-19 pandemic.

Perceptions of neighborhood environment and loneliness among older Chinese adults: the mediator role of cognitive and structural social capital.

OBJECTIVE: This study aimed to examine the mediating role of social capital in the association between perceived physical neighborhood environment and loneliness among older adults in urban China. METHOD: Data were derived from face-to-face interviews with people (n = 472) aged 60 or older in urban communities of Shanghai, China, in 2020. Loneliness was measured by the 6-item De Jong Gierveld Scale. A multiple mediator model was adopted to examine the research hypotheses. RESULTS: Cognitive social capital played a full mediation role in the association between perceived community health care (ß = -.061, p < .05), safety (ß = -.168, p < .001), recreational services (ß = -.058, p < .05), and loneliness. Structural social capital was associated with loneliness (ß = -.102, p < .05), whereas its mediator effect was not significant. Perceived transportation convenience had neither a direct nor an indirect effect on loneliness among older adults. CONCLUSION: Findings indicate that older adults' perceptions of healthcare services, safety, and recreational resources could help alleviate their loneliness via fostering cognitive social capital. Interventions improving older adults' perceptions of community health care, safety, and recreation, and their social capital level could help reduce the prevalence of loneliness.

Large-Scale Ultrafast Strain Engineering of CVD-Grown Two-Dimensional Materials on Strain Self-Limited Deformable Nanostructures toward Enhanced Field-Effect Transistors.

Strain engineering of 2D materials is capable of tuning the electrical and optical properties of the materials without introducing additional atoms. Here, a method for large-scale ultrafast strain engineering of CVD-grown 2D materials is proposed. Locally nonuniform strains are introduced through the cooperative deformation of materials and metal@metal oxide nanoparticles through cold laser shock. The tensile strain of MoS2 changes and the band gap decreases after laser shock. The mechanism of the ultrafast straining is investigated by MD simulations. MoS2 FETs were fabricated, and the field-effect mobility of devices could be increased from 1.9 to 44.5 cm2 V-1 s-1 by adjusting the strain level of MoS2. This is currently the maximum value of MoS2 FETs grown by CVD with SiO2 as the dielectric. As a large-scale and ultrafast manufacturing method, laser shock provides a universal strategy for large-scale adjustment of 2D material strain, which will help to promote the manufacturing of 2D nanoelectronic devices.

Synthesis and anti-HIV activity of non-nucleoside reverse-transcriptase inhibitor DB02 phosphate derivatives based on water-soluble optimization.

To improve the water solubility of anti-human immunodeficiency virus (HIV) agent DB02, an excellent non-nucleoside reverse-transcriptase inhibitor (NNRTI) obtained in our previous efforts, we designed and synthesized four phosphate derivatives of DB02 based on the molecular model of DB02 with RT. Here, the antiviral activity of these four derivatives was detected, leading to the discovery of compound P-2, which possessed a superior potency to the lead compound DB02 against wild-type HIV-1 and a variety of HIV-resistant mutant viruses significantly. Furthermore, the water solubility of P-2 was nearly 17 times higher than that of DB02, and the pharmacokinetic test in rats showed that P-2 demonstrate significantly improved oral bioavailablity of 14.6%. Our study showed that the introduction of a phosphate ester group at the end of the C-2 side chain of DB02 was beneficial to the improvement of its antiviral activity and pharmacokinetic properties, which provided a promising lead for the further development of S-DACOs type of NNRTIs.

Genome-Wide Identification and Expression Analysis of the SQUAMOSA Promoter-Binding Protein-like (SPL) Transcription Factor Family in Catalpabungei.

As a plant-specific transcription factor, the SPL gene family plays a critical role in plant growth and development. Although the SPL gene family has been identified in diverse plant species, there have been no genome-wide identification or systematic study reports on the SPL gene family in Catalpa bungei. In this study, we identified 19 putative SPL gene family members in the C. bungei genome. According to the phylogenetic relationship, they can be divided into eight groups, and the genes in the same group have a similar gene structure and conserved motifs. Synteny analysis showed that fragment duplication played an important role in the expansion of the CbuSPL gene family. At the same time, CbuSPL genes have cis-acting elements and functions related to light response, hormone response, growth and development, and stress response. Tissue-specific expression and developmental period-specific expression analysis showed that CbuSPL may be involved in flowering initiation and development, flowering transition, and leaf development. In addition, the ectopic expression of CbuSPL4 in Arabidopsis confirmed that it can promote early flowering and induce the expression of related flowering genes. These systematic research results will lay a foundation for further study on the functional analysis of SPL genes in C. bungei.

One-dimensional consolidation of highly saturated abandoned-soil under time-dependent stress: An analytical study.

A thorough knowledge of the consolidation behavior of highly saturated soil under time-dependent stress is essential for the design and construction of abandoned-soil dump sites in the soft soil regions of China. In this study, one-dimensional consolidation analytical solutions are derived for such soil under one-way and two-way drainage conditions, accommodating the time-dependent stress created by various dumping protocols. Representative soil samples are obtained, and consolidation tests are conducted with various saturation degrees (one-way drainage) and loading protocols (two-way drainage), to verify the consolidation equation and determine its range of applicability to various saturation degrees. The effects of layer thickness, dumping type, and compaction degree on the consolidation behaviors of highly saturated abandoned-soil dumps are investigated. The one-dimensional consolidation equation is applicable to soil with saturation degree not lower than 75% under instantaneous stress, stepped stress, and linear stress. The pore pressure distribution with depth is not symmetrical; the eccentric distance of consolidation degree increases with increasing layer thickness in the stress application stage and is approximately zero in the stress keeping stage. The pore pressure at middle of the soil layer increases with increasing layer thickness and decreases with increasing dumping rate from the completion of soil dumping. With increasing compaction degree, the middle pore pressure increases, while the surface settlement decreases. In the premise of the stability of an abandoned-soil dump, where the goals are to reduce post-construction settlement and to shorten the consolidation process of the entire soil layer, the important factors are smaller layer thickness, higher dumping rate, and larger compaction degree.