Progranulin mitigates intestinal injury in a murine model of necrotizing enterocolitis by suppressing M1 macrophage polarization.

Neonatal necrotizing enterocolitis (NEC) is a critical digestive disorder frequently affecting premature infants. Characterized by intestinal inflammation caused by activated M1 macrophages, modulation of macrophage polarization is considered a promising therapeutic strategy for NEC. It has been demonstrated that the growth factor-like protein progranulin (PGRN), which plays roles in a number of physiological and pathological processes, can influence macrophage polarization and exhibit anti-inflammatory characteristics in a number of illnesses. However, its role in NEC is yet to be investigated. Our research showed that the levels of PGRN were markedly elevated in both human and animal models of NEC. PGRN deletion in mice worsens NEC by encouraging M1 polarization of macrophages and escalating intestinal damage and inflammation. Intravenous administration of recombinant PGRN to NEC mice showed significant survival benefits and protective effects, likely due to PGRN's ability to inhibit M1 polarization and reduce the release of pro-inflammatory factors. Our findings shed new light on PGRN's biological role in NEC and demonstrate its potential as a therapeutic target for the disease.

Proteins extracted from pearl oyster (Pinctada martensii) with efficient accelerated wound healing in vitro through promoting cell proliferation, migration, and collagen formation.

Ethnopharmacological relevance: Pearl oyster (Pinctada martensii) is used in Chinese traditional medicine use in photoprotective, anti-inflammatory, and wound treatment.Aim of the study: This study explored whether the mucus protein of Pearl oyster (protein of Pinctada martensii, PMP) affects human skin fibroblast (HSF) proliferation, migration, collagen-related gene expression related to collagen formation, and in vivo healing effects. Materials and methods: The PMP component was analyzed by LC-MS/MS. The cell viability was evaluated using a CCK-8 kit. The expression genes were measured by reverse transcription polymerase chain reaction. A full-thickness excisional wounding model in Sprague-Dawley (SD) rats was used to test the repairing effect of PMP in vivo, and Hematoxylin-Eosin (H&E) and Masson's Trichrome staining were applied to evaluate skin structure. Results: The components of PMP were identified using LC-MS/MS proteomics, and a total of 3023 proteins were detected. The results of PMP-treated HSF showed that PMP effectively promoted cell proliferation by 1.6-fold and cell migration by 1.5-fold at a concentration of 1 mg/mL. Additionally, PMP treatment up-regulated the expression levels of collagen-related genes COL1A1, COL3A1, and MMP-1 in fibroblasts. Furthermore, PMP was applied in the therapy of full-thickness excisional wounds in rats. The results demonstrated that PMP significantly accelerated wound healing time, resulted in the recovery of dermal and epithelial thickness, and stimulated collagen regeneration. The regenerated skin closely resembled the structure of normal skin. Conclusions: These findings provide solid evidence supporting the potential of PMP as a promising candidate for the treatment of skin wounds.

The severity of NEC is ameliorated by prostaglandin E2 through regulating intestinal microcirculation.

Prostaglandin E2 (PGE2) is implicated in intestinal inflammation and intestinal blood flow regulation with a paradoxical effect on the pathogenesis of necrotizing enterocolitis (NEC), which is not yet well understood. In the current study, we found that PGE2, EP4, and COX-2 varied at different distances from the most damaged area in the terminal ileum obtained from human infants with NEC. PGE2 administration alleviated the phenotype of experimental NEC and the intestinal microvascular features in experimental NEC, but this phenomenon was inhibited by eNOS depletion, suggesting that PGE2 promoted intestinal microcirculatory perfusion through eNOS. Furthermore, PGE2 administration increased the VEGF content in MIMECs under TNFα stress and promoted MIMEC proliferation. This response to PGE2 was involved in eNOS phosphorylation and nitric oxide (NO) production and was blocked by the EP4 antagonist in vitro, suggesting that targeting the PGE2-EP4-eNOS axis might be a potential clinical and therapeutic strategy for NEC treatment. The study is reported in accordance with ARRIVE guidelines ( https://arriveguidelines.org ).

NAMPT inhibition relieves intestinal inflammation by regulating macrophage activation in experimental necrotizing enterocolitis.

Nicotinamide phosphoribosyl transferase (NAMPT) is associated with various NAD+ -consuming enzymatic reactions. The precise role in intestinal mucosal immunity in necrotizing enterocolitis (NEC) is not well defined. Here, we examined whether NAMPT inhibition by the highly specific inhibitor FK866 could alleviate intestinal inflammation during the pathogenesis of NEC. In the present study, we showed that NAMPT expression was upregulated in the human terminal ileum of human infants with NEC. FK866 administration attenuated M1 macrophage polarization and relieved the symptoms of experimental NEC pups. FK866 inhibited intercellular NAD+ levels, macrophage M1 polarization, and the expression of NAD+ -dependent enzymes, such as poly (ADP ribose) polymerase 1 (PARP1) and Sirt6. Consistently, the capacity of macrophages to phagocytose zymosan particles, as well as antibacterial activity, were impaired by FK866, whereas NMN supplementation to restore NAD+ levels reversed the changes in phagocytosis and antibacterial activity. In conclusion, FK866 reduced intestinal macrophage infiltration and skewed macrophage polarization, which is implicated in intestinal mucosal immunity, thereby promoting the survival of NEC pups.

Involvement of HIF1 stabilization and VEGF signaling modulated by Grx-1 in murine model of bronchopulmonary dysplasia.

Hypoxia inducible factor (HIF)-1α could be stabilized by Grx1 deletion, which is implicated critical in the pathogenesis of bronchopulmonary dysplasia (BPD). Until now, the stabilization of HIF-1α by glutathionylation to regulate the pulmonary microcirculation in BPD is not well addressed. In this study, we investigated whether the HIF-1α stabilization modulated by Grx1 ablation could ameliorate the pathological changes in the mouse model of BPD, including angiogenesis and alveolar formation. We found that depletion of Grx1 increased levels of GSH-protein adducts, which was associated with the improvement in the numbers of alveoli, the capillary density in the pulmonary microcirculation and the survival rate in the littermates with hyperoxic exposure. Grx1 ablation could promote HIF-1α glutathionylation by increasing GSH adducts to stabilize HIF-1α and to induce VEGF-A production in the lung tissue. The above phenotype of capillary density and VEGF-A production was removed by the pharmacological administration of YC-1, the HIF-1α inhibitor, suggesting the HIF-1α dependent manner for pulmonary microcirculatory perfusion. These data indicate that HIF-1α stabilization plays an critical role in modification pulmonary microcirculatory perfusion, which is associated with the pathological damage under hyperoxic conditions, suggesting that targeting with HIF-1α stabilization should be a potential clinical and therapeutic strategy for BPD treatment.

High-Throughput Screen of Natural Compounds and Biomarkers for NSCLC Treatment by Differential Expression and Weighted Gene Coexpression Network Analysis (WGCNA).

Lung cancer is known as the leading cause which presents the highest fatality rate worldwide; non-small-cell lung cancer (NSCLC) is the most prevalent type of lung carcinoma with high severity and affects 80% of patients with lung malignancies. Up to now, the general treatment for NSCLC includes surgery, chemotherapy, and radiotherapy; however, some therapeutic drugs and approaches could cause side effects and weaken the immune system. The combination of conventional therapies and traditional Chinese medicine (TCM) significantly improves treatment efficacy in lung cancer. Therefore, it is necessary to investigate the chemical composition and underlying antitumor mechanisms of TCM, so as to get a better understanding of the potential natural ingredient for lung cancer treatment. In this study, we selected 78 TCM to treat NSCLC cell line (A549) and obtained 92 transcriptome data; differential expression and WGCNA were applied to screen the potential natural ingredient and target genes. The sample which was treated with A. pierreana generated the most significant DEG set, including 6130 DEGs, 2479 upregulated, and 3651 downregulated. KEGG pathway analyses found that four pathways (MAPK, NF-kappa B, p53, and TGF-beta signaling pathway) were significantly enriched; 16 genes were significantly regulated in these four pathways. Interestingly, some of them such as EGFR, DUSP4, IL1R1, IL1B, MDM2, CDKNIA, and IDs have been used as the target biomarkers for cancer diagnosis and therapy. In addition, classified samples into 14 groups based on their pharmaceutical effects, WGCNA was used to identify 27 modules. Among them, green and darkgrey were the most relevant modules. Eight genes in the green module and four in darkgrey were identified as hub genes. In conclusion, we screened out three new TCM (B. fruticose, A. pierreana, and S. scandens) that have the potential to develop natural anticancer drugs and obtained the therapeutic targets for NSCLC therapy. Our study provides unique insights to screen the natural components for NSCLC therapy using high-throughput transcriptome analysis.

Methodology of an exercise intervention program using social incentives and gamification for obese children.

BACKGROUND: Traditional exercise [supervised exercise (SE)] intervention has been proved to be one of the most effective ways to improve metabolic health. However, most exercise interventions were on a high-cost and small scale, moreover lacking of the long-term effect due to low engagement. On the other hand, it was noteworthy that gamification and social incentives were promising strategies to increase engagement and sustain exercise interventions effects; as well as mobile technologies such as WeChat also can provide an appropriate platform to deploy interventions on a broader, low-cost scale. Thus, we aim to develop a novel exercise intervention ('S&G exercise intervention') that combines SE intervention with gamification and social incentives design through WeChat, with the aim of improving metabolic health and poor behaviors among overweight and obesity children. METHODS: We propose a randomized controlled trial of a 'S&G exercise intervention' among 420 overweight and obese children who have at least one marker of metabolic syndrome. Children will be randomized to control or intervention group in a 1:1 ratio. The exercise intervention package includes intervention designs based on integrated social incentives and gamification theory, involving targeted essential volume and intensity of activity (skipping rope) as well as monitoring daily information and providing health advice by WeChat. Participants will undertake assessments at baseline, at end of intervention period, in the follow-up time at months 3,6,12. The primary outcome is outcome of metabolic health. Secondary outcomes include behavioral (e.g., diary physical activity, diet) and anthropometric measures (e.g., body fat rate and muscle mass). DISCUSSIONS: This will be the first study to design an exercise intervention model that combines traditional supervised exercise (SE) intervention with gamification and social incentives theory through WeChat. We believed that this study could explore a low-cost, easy-to-popularize, and effective exercise intervention model for improving metabolic health and promote healthy among obese children. Furthermore, it will also provide important evidence for guidelines to prevent and improve metabolic health and health behaviors. TRIAL REGISTRATION: 10-04-2019;Registration number: ChiCTR1900022396 .

Using Gamification and Social Incentives to Increase Physical Activity and Related Social Cognition among Undergraduate Students in Shanghai, China.

Gamification and social incentives are promising strategies to increase the effectiveness of web-based physical activity (PA) interventions by improving engagement. In this study, we designed a PA intervention integrating gamification and social incentives based on the most popular social networking service in China, WeChat. A controlled trial involving 52 Chinese undergraduate students was implemented to evaluate the effectiveness of the intervention. Subjects in the intervention group received a 7-week intervention. PA behavior and related social cognitive variables according to the theory of planned behavior were measured at the baseline and after the intervention. Daily physical activity duration was measured during the intervention. The results showed that PA-related subjective norms, perceived behavior control, and intention, as well as self-reported vigorous physical activity and moderate physical activity in the intervention group, were increased after the intervention, compared with the control group (p <0.05). During the intervention, perceived daily physical activity duration in the intervention group was on the rise, while it declined in the control group (p <0.001). The findings indicate that WeChat-based intervention integrating gamification and social incentives could effectively increase subjectively measured PA and related social cognition among Chinese undergraduate students and that it is a promising way to ameliorate the problem of insufficient PA among youths.

Sexual compulsivity and its relationship with condomless sex among unmarried female migrant workers in Shanghai, China: a cross-sectional study.

BACKGROUND: Individuals with high sexual compulsivity are preoccupied with their sexual desire to such an extent that it interferes with their normal daily life and can inhibit self-control. Previous studies have found a close association between sexual compulsivity and condomless sex among different populations; however, no studies have investigated this among unmarried female migrant workers in China. This study aimed to validate the Sexual Compulsivity Scale (SCS) for appropriate use and examine the association between sexual compulsivity and condomless sex in this target population. METHODS: In 2015, we recruited 1325 unmarried female migrant workers in Shanghai, China. Information about sociodemographics, sexual compulsivity, and condomless sex were collected using a structured questionnaire. Exploratory factor analysis and reliability analysis were performed to validate the Chinese version of the SCS. Multiple logistic regression analyses were used to examine the association between sexual compulsivity and condomless sex. RESULTS: The prevalence of condomless sex in the previous 6 months was 66.8% among all participants. The SCS was proven internally consistent for the overall scale (Cronbach's α = 0.89), and two factors, Social Disruptiveness (Cronbach's α = 0.87) and Perceived Self-Control (Cronbach's α = 0.84), were extracted. With mean total score of 18.25 (standard deviation = 4.94) after adjusting for significant sociodemographic factors, the SCS total scores (adjusted odds ratio [AOR] = 1.04, 95% confidence interval [CI] = 1.02-1.07) and two subscale scores (AOR = 1.07, 95% CI = 1.02-1.13; AOR = 1.06, 95% CI = 1.02-1.10) were all related to inconsistent condom use with partners in the previous 6 months. CONCLUSIONS: The Chinese version of the SCS was found to be well adaptable for use among unmarried Chinese female migrant workers and a potential predictor for condomless sex. In addition to safe sex interventions, counselling on managing sexually compulsivity should also be provided in this population.

What factors influence older people's intention to enrol in nursing homes? A cross-sectional observational study in Shanghai, China.

OBJECTIVES: Given the increasing need of long-term care and the low occupancy rate of nursing homes in Shanghai, this study attempts to explore what factors influence older people's intention to enrol in nursing homes. DESIGN: A cross-sectional observational study based on the theory of reasoned action was conducted. Survey data were collected from subjects during face-to-face interviews. Structural equation modelling was employed for data analysis. SETTING: This study was conducted in six community health service centres in Shanghai, China. Two service centres were selected in urban, suburban and rural areas, respectively. PARTICIPANTS: A total of 641 Shanghai residents aged over 60 were surveyed. RESULTS: Structural equation modelling analysis showed that the research model fits the data well (χ2/df=2.948, Comparative Fit Index=0.972 and root mean squared error of approximation =0.055). Attitude (ß=0.41, p<0.01), subjective norm (ß=0.28, p<0.01) and value-added service (ß=0.16, p<0.01) were directly associated with enrolment intention, explaining 32% of variance in intention. Attitude was significantly influenced by loneliness (ß=-0.08, p<0.05), self-efficacy (ß=0.32, p<0.01) and stigma (ß=-0.24, p<0.01), while subjective norm was significantly influenced by life satisfaction (ß=-0.15, p<0.01) and stigma (ß=-0.43, p<0.01). CONCLUSIONS: This study advances knowledge regarding the influencing factors of older people's intention to enrol in nursing homes. It suggests that Chinese older persons' perceived stigma has the strongest indirect effect on their intention to enrol in nursing homes. This is unique to the Chinese context and has practical implications for eldercare in China and other Asian countries with similar sociocultural contexts.

[Materiamedica literature study on medicinal properties and utility of four kinds of Alpinia Chinese medicines].

In order to explore the correlation between the medicinal properties，efficacy and application in the same genetic relationship，explain the scientific connotation of the medicinal properties and effects of traditional Chinese medicines(TCM)，promote the academic development of the theory of traditional Chinese medicines，and provide reference for the research and development of the traditional Chinese medicines of a same genus. In this paper, a literature study of ancient and modern works of Chinese herbal medicine was conducted to investigate the correlation between the properties, meridians tropism, efficacy and application of Alpinia officinarum， A. katsumadai， Galangae Fructus and Alpinae Oxyphyllae Fructus, four kinds of Alpinia Chinese medicines．The results showed that the similar properties of these four kinds of Alpinia Chinese medicines included that they were acrid, warm,and mainly getting into the spleen and stomach channels; the similar efficacies included that dispelling cold，relieving pain，warming stomach，anti-nausea，anti-diarrheal，reinforcing spleen to promote digestion and other effects; in application aspects, the similarities were that they were all mainly used in treatment of catching cold or spleen deficiency induced by abdominal pain，vomiting，diarrhea,diet indigestion, etc. indicating that phylogenetic relationship was closely related with the herbal properties, efficacy and application. It is an effective way to explore，collate and research traditional Chinese medicine by using plant phylogenetic relationships in exploring the internal relations and laws of TCM theories，material bases, pharmacological effects and clinical applications, also with a strong maneuverability to explain their scientific connotation.

Logic circuits based on molecular spider systems.

Spatial locality brings the advantages of computation speed-up and sequence reuse to molecular computing. In particular, molecular walkers that undergo localized reactions are of interest for implementing logic computations at the nanoscale. We use molecular spider walkers to implement logic circuits. We develop an extended multi-spider model with a dynamic environment wherein signal transmission is triggered via localized reactions, and use this model to implement three basic gates (AND, OR, NOT) and a cascading mechanism. We develop an algorithm to automatically generate the layout of the circuit. We use a kinetic Monte Carlo algorithm to simulate circuit computations, and we analyze circuit complexity: our design scales linearly with formula size and has a logarithmic time complexity.