Mechanism of the impacts of older adults social participation on their health.

Purpose: Against the background of population aging challenges in China, focusing on health, security, and social participation as core elements of positive aging, this study aims to formulate strategies for promoting the health of the older adults and reveal the pathways and trends of social participation in promoting health. Method: The study analyzed 1,015 randomly selected older adults individuals living at home in Beijing using household survey questionnaires. Drawing on group dynamics theory and structural equation modeling, the study proposed hypotheses regarding the relationships between social participation, group cohesion, and health status. Results: First, the triangular path model of social participation, group cohesion, and health status among the older adults was established. The direct path coefficient of social participation on health status was 0.15, that of social participation on group cohesion was 0.56, and that of group cohesion on health status was 0.32. The indirect path coefficient of social participation on health status through group cohesion was calculated at 0.56 × 0.32 = 0.18. Second, of the older adults age groups-younger, middle, and older-social participation's direct path effects on health status were present only in the older age group. Social participation's indirect path effects on health status through group cohesion were relatively high in all three groups, with a slight increase in the older age group. Conclusion: First, just the older adults participation in social activities serves as a benign stimulus to physical and mental health. Additionally, group cohesion formed through interaction with others during social activities encourages self-improvement behaviors, indirectly promoting health. In fact, indirect pathways of health promotion through group cohesion are stronger than direct pathways, highlighting the importance of group cohesion during social participation. Second, participation in activities alone can provide only sufficient benign stimuli for the older adults aged 80 and above, with the direct path effect of social participation on health beginning to appear only with increasing age. With age, selectivity of interaction with others decreases, and dependence increases; social participation's indirect path effect on health through group cohesion continues to grow slightly.

Establishing a human-induced pluripotent stem cell line (SMUSHi003-A) from a patient with Charcot-Marie-Tooth disease and focal segmental glomerulosclerosis.

INF2 mutations cause Charcot-Marie-Tooth disease (CMT), and /or focal segmental glomerulosclerosis (FSGS) in an autosomal dominant inheritance mode, whose underlying mechanism remainsunclear. Here, we report the generation of an iPSC line from a female patient with CMT and FSGS. The iPSC line from the patient's PBMCscarried aheterozygous INF2 deletion mutation (c.315_323delGCGCGCCGT) within the conserved E2. This line exhibited a normal karyotype, high expression of pluripotency markers, and trilineage differentiation potential. This line can be used to dissect the complex pathomechanism through further induction of differentiation into related cells and as a drug screening tool for INF2-associated diseases.

Establishing a human-induced pluripotent stem cell line SMUSHi005-A from a patient with hypophosphatemic vitamin D-resistant rickets carrying the PHEX c.1586-1586+1 delAG mutation.

Hypophosphatemic vitamin D-resistant rickets typically presents in infancy or early childhood with skeletal deformities and growth plate abnormalities. In this report, the SMUSHi005-A human induced pluripotent stem cell (hiPSC) line was successfully established from the PBMCs of a female patient carrying the PHEX mutation with c.1586-1586+1 delAG. The iPSC line has been confirmed to have a normal karyotype. The displayed cells clearly exhibit characteristics similar to embryonic stem cells, expressing pluripotency markers and demonstrating the ability to differentiate into three germ layers.

Preparation and properties of a metal-organic frameworks polymer material based on Sa-son seed gum capable of simultaneously absorbing liquid water and water vapor.

Atmospheric water harvesting (AWH) technology has attracted significant attention as an effective strategy to tackle the global shortage of freshwater resources. Work has focused on the use of hydrogel-based composite adsorbents in water harvesting and water conservation. The approaches adopted to make use of hygroscopic inorganic salts which subject to a "salting out" effect. In this study, we report the first use of modified UIO-66-NH2 as a functional steric cross-linker and Sa-son seed gum was used as polymeric substrate to construct super hygroscopic hydrogels by free radical copolymerization. The maximum water uptake on SMAGs (572 cm3·g-1) outperforms pure UIO-66-NH2 (317 cm3·g-1). Simultaneously, our first attempt to use it for anti-evaporation applications in an arid environment (Lanzhou, China) simulating sandy areas. The evaporation rate of the anti-evaporation material treated with 0.20 % super moisture-absorbent gels (SMAGs) decreased by 6.1 % over 64 h period under natural condition in Lanzhou, China. The prepared material can not only absorb liquid water but also water vapor, which can provide a new way for water collection and conservation technology. The design strategy of this material has wide applications ranging from atmospheric water harvesting materials to anti-evaporation technology.

Tick cysteine protease inhibitors suppress immune responses in mannan-induced psoriasis-like inflammation.

Protease inhibitors regulate various biological processes and prevent host tissue/organ damage. Specific inhibition/regulation of proteases is clinically valuable for treating several diseases. Psoriasis affects the skin in the limbs and scalp of the body, and the contribution of cysteine and serine proteases to the development of skin inflammation is well documented. Cysteine protease inhibitors from ticks have high specificity, selectivity, and affinity to their target proteases and are efficient immunomodulators. However, their potential therapeutic effect on psoriasis pathogenesis remains to be determined. Therefore, we tested four tick cystatins (Sialostatin L, Sialostatin L2, Iristatin, and Mialostatin) in the recently developed, innate immunity-dependent mannan-induced psoriasis model. We explored the effects of protease inhibitors on clinical symptoms and histological features. In addition, the number and percentage of immune cells (dendritic cells, neutrophils, macrophages, and γδT cells) by flow cytometry, immunofluorescence/immunohistochemistry and, the expression of pro-inflammatory cytokines (TNF-a, IL-6, IL-22, IL-23, and IL-17 family) by qPCR were analyzed using skin, spleen, and lymph node samples. Tick protease inhibitors have significantly decreased psoriasis symptoms and disease manifestations but had differential effects on inflammatory responses and immune cell populations, suggesting different modes of action of these inhibitors on psoriasis-like inflammation. Thus, our study demonstrates, for the first time, the usefulness of tick-derived protease inhibitors for treating skin inflammation in patients.

Generation of a human induced pluripotent stem cell line (SMUSHi002-A) from an ALS patient carrying a heterozygous mutation c.1562G > A in the FUS gene.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. Affected patients experience gradual loss of their spinal cord and cortical motor neurons with consequent muscle weakness and emaciation, and eventual respiratory failure. The pathogenesis of ALS remains largely unknown although the FUS (sarcoma fusion gene) gene is known to be one of the major pathogenic genes. We have generated an induced pluripotent stem cell line SMUSHi002-A from an ALS patient who carries a heterozygous mutation c.1562G > A in FUS. This cell line will serve as a useful model to investigate disease pathogenesis and develop potential therapeutic approaches for ALS.

FS145, the first flea-derived disintegrin, inhibits angiogenesis through specifically binding integrin αvß3.

FS145, a protein containing a WGD motif, was previously described from the salivary transcriptome of the flea Xenopsylla cheopis. Nevertheless, its biological function and complete structure are still uncertain. Herein, FS145 was confirmed to adopt a common αßß structure with the WGD motif exposed on its surface and located right at the top of a loop composed of residues 72-81. Furthermore, FS145 dose-dependently inhibited the proliferation, adhesion, migration, and tube formation of HUVECs by not only binding to integrin αvß3 but also by subsequently inactivating the FAK/Src/MAPK pathway along with the reduction of the expression of MMP-2, MMP-9, VEGFA, bFGF, Ang2, Tie2, HIF-1α, and FAK. Moreover, FS145 also inhibited aortic vessel sprout and showed strong anti-angiogenic activities as assessed ex vivo, by employing the rat aortic ring assay, chick embryo chorioallantoic membrane, and zebrafish embryo models. Altogether, our results suggest that FS145 suppresses angiogenesis ex vivo and in vitro by blocking integrin αvß3. The current study reveals the first anti-angiogenesis disintegrin with WGD motif from invertebrates and provides a beneficial pharmacological activity to inhibit abnormal angiogenesis.

Cath-KP, a novel peptide derived from frog skin, prevents oxidative stress damage in a Parkinson's disease model.

Parkinson's disease (PD) is a neurodegenerative condition that results in dyskinesia, with oxidative stress playing a pivotal role in its progression. Antioxidant peptides may thus present therapeutic potential for PD. In this study, a novel cathelicidin peptide (Cath-KP; GCSGRFCNLFNNRRPGRLTLIHRPGGDKRTSTGLIYV) was identified from the skin of the Asiatic painted frog ( Kaloula pulchra). Structural analysis using circular dichroism and homology modeling revealed a unique αßß conformation for Cath-KP. In vitro experiments, including free radical scavenging and ferric-reducing antioxidant analyses, confirmed its antioxidant properties. Using the 1-methyl-4-phenylpyridinium ion (MPP +)-induced dopamine cell line and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice, Cath-KP was found to penetrate cells and reach deep brain tissues, resulting in improved MPP +-induced cell viability and reduced oxidative stress-induced damage by promoting antioxidant enzyme expression and alleviating mitochondrial and intracellular reactive oxygen species accumulation through Sirtuin-1 (Sirt1)/Nuclear factor erythroid 2-related factor 2 (Nrf2) pathway activation. Both focal adhesion kinase (FAK) and p38 were also identified as regulatory elements. In the MPTP-induced PD mice, Cath-KP administration increased the number of tyrosine hydroxylase (TH)-positive neurons, restored TH content, and ameliorated dyskinesia. To the best of our knowledge, this study is the first to report on a cathelicidin peptide demonstrating potent antioxidant and neuroprotective properties in a PD model by targeting oxidative stress. These findings expand the known functions of cathelicidins, and hold promise for the development of therapeutic agents for PD.

Androcin 18-1, a novel scorpion-venom peptide, shows a potent antitumor activity against human U87 cells via inducing mitochondrial dysfunction.

Scorpion venom is a potent natural source for antitumor drug development due to the multiple action modes of anticancer components. Although the sequence of Androcin 18-1 has been identified from the transcriptome profile of the scorpion venom Androctonus bicolor, its bioactivity remains unclear. In this study, we described the antitumor mechanism whereby Androcin 18-1 inhibits the proliferation and induces apoptosis by inducing cell membrane disruption, ROS accumulation, and mitochondrial dysfunction in human U87 glioblastoma cells. Moreover, Androcin 18-1 could suppress cell migration via the mechanisms associated with cytoskeleton disorganization and MMPs/TIMPs expression regulation. The discovery of this work highlights the potential application of Androcin 18-1 in drug development for glioblastoma treatment.

Cathelicidin-HG Alleviates Sepsis-Induced Platelet Dysfunction by Inhibiting GPVI-Mediated Platelet Activation.

Platelet activation contributes to sepsis development, leading to microthrombosis and increased inflammation, which results in disseminated intravascular coagulation and multiple organ dysfunction. Although Cathelicidin can alleviate sepsis, its role in sepsis regulation remains largely unexplored. In this study, we identified Cath-HG, a novel Cathelicidin from Hylarana guentheri skin, and analyzed its structure using nuclear magnetic resonance spectroscopy. The modulatory effect of Cath-HG on the symptoms of mice with sepsis induced by cecal ligation and puncture was evaluated in vivo, and the platelet count, degree of organ damage, and microthrombosis were measured. The antiplatelet aggregation activity of Cath-HG was studied in vitro, and its target was verified. Finally, we further investigated whether Cath-HG could regulate thrombosis in vivo in a FeCl3 injury-induced carotid artery model. The results showed that Cath-HG exhibited an α-helical structure in sodium dodecyl sulfate solution and effectively reduced organ inflammation and damage, improving survival in septic mice. It alleviated sepsis-induced thrombocytopenia and microthrombosis. In vitro, Cath-HG specifically inhibited collagen-induced platelet aggregation and modulated glycoprotein VI (GPVI) signaling pathways. Dot blotting, enzyme-linked immunosorbent assay, and pull-down experiments confirmed GPVI as the target of Cath-HG. Molecular docking and amino acid residue truncations/mutations identified crucial sites of Cath-HG. These findings suggest that GPVI represents a promising therapeutic target for sepsis, and Cath-HG may serve as a potential treatment for sepsis-related thrombocytopenia and thrombotic events. Additionally, identifying Cath-HG as a GPVI inhibitor provides insights for developing novel antithrombotic therapies targeting platelet activation mediated by GPVI.