Logic Circuits Based on Extended 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 re- actions 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, and 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

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 (\u27SandG exercise intervention\u27) 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 \u27SandG exercise intervention\u27 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

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 (β=0.41, p<0.01), subjective norm (β=0.28, p<0.01) and value- added service (β=0.16, p<0.01) were directly associated with enrolment intention, explaining 32% of variance in intention. Attitude was significantly influenced by loneliness (β=−0.08, p<0.05), self-efficacy (β=0.32, p<0.01) and stigma (β=−0.24, p<0.01), while subjective norm was significantly influenced by life satisfaction (β=−0.15, p<0.01) and stigma (β=−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

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

A real-world clinicopathological model for predicting pathological complete response to neoadjuvant chemotherapy in breast cancer

PurposeThis study aimed to develop and validate a clinicopathological model to predict pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in breast cancer patients and identify key prognostic factors.MethodsThis retrospective study analyzed data from 279 breast cancer patients who received NAC at Zhejiang Provincial People’s Hospital from 2011 to 2021. Additionally, an external validation dataset, comprising 50 patients from Lanxi People’s Hospital and Second Affiliated Hospital, Zhejiang University School of Medicine from 2022 to 2023 was utilized for model verification. A multivariate logistic regression model was established incorporating clinical, ultrasound features, circulating tumor cells (CTCs), and pathology variables at baseline and post-NAC. Model performance for predicting pCR was evaluated. Prognostic factors were identified using survival analysis.ResultsIn the 279 patients enrolled, a pathologic complete response (pCR) rate of 27.96% (78 out of 279) was achieved. The predictive model incorporated independent predictors such as stromal tumor-infiltrating lymphocyte (sTIL) levels, Ki-67 expression, molecular subtype, and ultrasound echo features. The model demonstrated strong predictive accuracy for pCR (C-statistics/AUC 0.874), especially in human epidermal growth factor receptor 2 (HER2)-enriched (C-statistics/AUC 0.878) and triple-negative (C-statistics/AUC 0.870) subtypes, and the model performed well in external validation data set (C-statistics/AUC 0.836). Incorporating circulating tumor cell (CTC) changes post-NAC and tumor size changes further improved predictive performance (C-statistics/AUC 0.945) in the CTC detection subgroup. Key prognostic factors included tumor size &gt;5cm, lymph node metastasis, sTIL levels, estrogen receptor (ER) status and pCR. Despite varied pCR rates, overall prognosis after standard systemic therapy was consistent across molecular subtypes.ConclusionThe developed predictive model showcases robust performance in forecasting pCR in NAC-treated breast cancer patients, marking a step toward more personalized therapeutic strategies in breast cancer

Influencing factors of psychological well-being of the non-designated hospital staff in China during the COVID-19 pandemic

Background: Recent studies report that hospital staff at the forefront of caring for COVID-19 patients experience increased psychological distress. To effectively manage the outbreak of COVID-19, China established COVID-19 designated and non-designated hospitals. To date, few studies have examined the impacts of COVID-19 on psychological health of staff working at non-designated hospitals. This study is to explore factors affecting psychological health of non-designated hospital staff in China during the COVID-19 pandemic. Methods: Data were collected through an online questionnaire between February and March 2020. The questionnaire consists of General Health Questionnaire (GHQ-20), Social Support Rating Scale (SSRS), Simplified Coping Style Questionnaire (SCSQ), sociodemographic characteristics, employment history, health status, and contact history of COVID-19. The questionnaire was distributed through hospital WeChat groups and work colleague referrals. A total of 470 non-designated hospital staff members completed the questionnaire. Multiple Linear Regression analysis was used to interpret the associations among social support, coping styles, sociodemographic factors, job roles, and psychological status. Data were analyzed using SPSS version 21.0.Results: The non-designated hospital staff differed significantly in anxiety and depression subscores of the GHQ-20 by their job roles, levels of social support, and history of mental disorders. Staff with medical job roles, good self-reported health status, no previous mental disorders, adequate social support, and positive coping styles scored lower in GHQ-20 total score, which indicated healthier psychological status. Conclusions: The results indicate that history of mental health disorders, non-medical job roles, and inadequate social support are associated with greater psychological distress. Personalized support should be provided to those who are vulnerable and in need of social and psychological support

Patient-derived iPSCs link elevated mitochondrial respiratory complex I function to osteosarcoma in Rothmund-Thomson syndrome

Rothmund-Thomson syndrome (RTS) is an autosomal recessive genetic disorder characterized by poikiloderma, small stature, skeletal anomalies, sparse brows/lashes, cataracts, and predisposition to cancer. Type 2 RTS patients with biallelic RECQL4 pathogenic variants have multiple skeletal anomalies and a significantly increased incidence of osteosarcoma. Here, we generated RTS patient-derived induced pluripotent stem cells (iPSCs) to dissect the pathological signaling leading to RTS patient-associated osteosarcoma. RTS iPSC-derived osteoblasts showed defective osteogenic differentiation and gain of in vitro tumorigenic ability. Transcriptome analysis of RTS osteoblasts validated decreased bone morphogenesis while revealing aberrantly upregulated mitochondrial respiratory complex I gene expression. RTS osteoblast metabolic assays demonstrated elevated mitochondrial respiratory complex I function, increased oxidative phosphorylation (OXPHOS), and increased ATP production. Inhibition of mitochondrial respiratory complex I activity by IACS-010759 selectively suppressed cellular respiration and cell proliferation of RTS osteoblasts. Furthermore, systems analysis of IACS-010759-induced changes in RTS osteoblasts revealed that chemical inhibition of mitochondrial respiratory complex I impaired cell proliferation, induced senescence, and decreased MAPK signaling and cell cycle associated genes, but increased H19 and ribosomal protein genes. In summary, our study suggests that mitochondrial respiratory complex I is a potential therapeutic target for RTS-associated osteosarcoma and provides future insights for clinical treatment strategies

Sustained Na⁺/H⁺ exchanger activation promotes gliotransmitter release from reactive hippocampal astrocytes following oxygen-glucose deprivation

Hypoxia ischemia (HI)-related brain injury is the major cause of long-term morbidity in neonates. One characteristic hallmark of neonatal HI is the development of reactive astrogliosis in the hippocampus. However, the impact of reactive astrogliosis in hippocampal damage after neonatal HI is not fully understood. In the current study, we investigated the role of Na +/H+ exchanger isoform 1 (NHE1) protein in mouse reactive hippocampal astrocyte function in an in vitro ischemia model (oxygen/glucose deprivation and reoxygenation, OGD/REOX). 2 h OGD significantly increased NHE1 protein expression and NHE1-mediated H+ efflux in hippocampal astrocytes. NHE1 activity remained stimulated during 1-5 h REOX and returned to the basal level at 24 h REOX. NHE1 activation in hippocampal astrocytes resulted in intracellular Na+ and Ca2+ overload. The latter was mediated by reversal of Na+/Ca2+ exchange. Hippocampal astrocytes also exhibited a robust release of gliotransmitters (glutamate and pro-inflammatory cytokines IL-6 and TNFα) during 1-24 h REOX. Interestingly, inhibition of NHE1 activity with its potent inhibitor HOE 642 not only reduced Na+ overload but also gliotransmitter release from hippocampal astrocytes. The noncompetitive excitatory amino acid transporter inhibitor TBOA showed a similar effect on blocking the glutamate release. Taken together, we concluded that NHE1 plays an essential role in maintaining H + homeostasis in hippocampal astrocytes. Over-stimulation of NHE1 activity following in vitro ischemia disrupts Na+ and Ca2+ homeostasis, which reduces Na+-dependent glutamate uptake and promotes release of glutamate and cytokines from reactive astrocytes. Therefore, blocking sustained NHE1 activation in reactive astrocytes may provide neuroprotection following HI. © 2014 Cengiz et al