Comparable clinical advantages identification of three formulae on rheumatic disease using a modular-based network proximity approach.

ETHNOPHARMACOLOGICAL RELEVANCE: Herbal formulae have been used in China for thousands of years but have unclear clinical positioning and unknown characteristic indications make it difficult to determine their specific application in various diseases, which seriously hamper their clinical value. Identifying the precise clinical positioning and clinical advantages of similar formulae for related diseases is a critical issue. AIM OF THIS STUDY: To develop a methodology based on modular pharmacology to determine the clinical advantages and precise clinical position of similar formulae. MATERIALS AND METHODS: In this study, we proposed a modular-based network proximity approach to explore drug repositioning and clinical advantages of three formulae, Shirebi tablets (SRB), Yuxuebi capsules (YXB), and Wangbifukang granules (WBFK), for rheumatic disease. First, we constructed a rheumatology target network, and modules were obtained using the cluster tool molecular complex detection (MCODE). Based on the modular interaction map established by a quantitative approach for inter-module coordination and its transition (IMCC), using a targeting rate (TR) matrix to identify targeted modules of three formulae. Moreover, the network proximity Z-score and Jaccard similarity coefficient were used to identify potential optimal symptomatic indications and related diseases using three formulae. At the same time, the driver genes for SRB and gouty arthritis were identified by flow centrality and shortest distance, and the epresentative driver genes were validated by in vivo experiments. RESULTS: 32 modules were obtained using the MCODE method. 4, 4, and 14 characteristic targeted modules of SRB, YXB, and WBFK, respectively, were identified using a targeting rate (TR) matrix. Module 2, 16, and 19 were targeted by both SRB and WBFK. The common effects of SRB and WBFK focused on inflammatory response and innate immune response, YXB was found to be involved in the collagen catabolic process, transmembrane receptor protein serine/threonine kinase signaling pathway. Moreover, potential optimal symptomatic indications and representative related diseases were identified for three formulae: SRB was significantly associated with GA (Z = -20.26); YXB was significantly associated with AS (Z = -4.532), MI (Z = -29.11), RhFv (Z = -6.945), OA (Z = -39.97), and GA (Z = -13.03); and WBFK was significantly associated with MI (Z = -205.5), SLE (Z = -37.65), RhFv (Z = -42.45), and GA (Z = -17.24). Finally, 8 driver genes for SRB and gouty arthritis were identified,the representative driver genes TRAF6 and NFE2L1 were validated by in vivo experiments. CONCLUSIONS: The modular-based network proximity approach proposed in this study may provide a new perspective for the precise drug repositioning and clinical advantages of similar formulae in disease treatment.

Endotype-driven Co-module mechanisms of danhong injection in the Co-treatment of cardiovascular and cerebrovascular diseases: A modular-based drug and disease integrated analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Cardiovascular and cerebrovascular diseases are the leading causes of death worldwide and interact closely with each other. Danhong Injection (DHI) is a widely used preparation for the co-treatment of brain and heart diseases (CTBH). However, the underlying molecular endotype mechanisms of DHI in the CTBH remain unclear. AIM OF THIS STUDY: To elucidate the underlying endotype mechanisms of DHI in the CTBH. MATERIALS AND METHODS: In this study, we proposed a modular-based disease and drug-integrated analysis (MDDIA) strategy for elucidating the systematic CTBH mechanisms of DHI using high-throughput transcriptome-wide sequencing datasets of DHI in the treatment of patients with stable angina pectoris (SAP) and cerebral infarction (CI). First, we identified drug-targeted modules of DHI and disease modules of SAP and CI based on the gene co-expression networks of DHI therapy and the protein-protein interaction networks of diseases. Moreover, module proximity-based topological analyses were applied to screen CTBH co-module pairs and driver genes of DHI. At the same time, the representative driver genes were validated via in vitro experiments on hypoxia/reoxygenation-related cardiomyocytes and neuronal cell lines of H9C2 and HT22. RESULTS: Seven drug-targeted modules of DHI and three disease modules of SAP and CI were identified by co-expression networks. Five modes of modular relationships between the drug and disease modules were distinguished by module proximity-based topological analyses. Moreover, 13 targeted module pairs and 17 driver genes associated with DHI in the CTBH were also screened. Finally, the representative driver genes AKT1, EDN1, and RHO were validated by in vitro experiments. CONCLUSIONS: This study, based on clinical sequencing data and modular topological analyses, integrated diseases and drug targets. The CTBH mechanism of DHI may involve the altered expression of certain driver genes (SRC, STAT3, EDN1, CYP1A1, RHO, RELA) through various enriched pathways, including the Wnt signaling pathway.

Cultural Dimensions Moderate the Association between Loneliness and Mental Health during Adolescence and Younger Adulthood: A Systematic Review and Meta-Analysis.

Cultural factors, such as country or continent, influence the relationship between loneliness and mental health. However, less is known about how cultural dimensions moderate this relationship during adolescence and younger adulthood, even if these dimensions manifest as country or continent differences. This study aims to examine the potential influence of Hofstede's cultural dimensions on this relationship using a three-level meta-analysis approach. A total of 292 studies with 291,946 participants aged 10 to 24 were included in this study. The results indicate that cultural dimensions, such as individualism vs. collectivism, indulgence vs. restraint, power distance, and long-term vs. short-term orientation, moderated the associations between loneliness and social anxiety, stress, Internet overuse, and negative affect. The association between loneliness and mental health was not moderated by cultural dimensions, such as masculinity and uncertainty avoidance. These findings suggest that culture's influence on the association between loneliness and mental health is based on a domain-specific mechanism.

TCMFP: a novel herbal formula prediction method based on network target's score integrated with semi-supervised learning genetic algorithms.

Traditional Chinese medicine (TCM) has accumulated thousands years of knowledge in herbal therapy, but the use of herbal formulas is still characterized by reliance on personal experience. Due to the complex mechanism of herbal actions, it is challenging to discover effective herbal formulas for diseases by integrating the traditional experiences and modern pharmacological mechanisms of multi-target interactions. In this study, we propose a herbal formula prediction approach (TCMFP) combined therapy experience of TCM, artificial intelligence and network science algorithms to screen optimal herbal formula for diseases efficiently, which integrates a herb score (Hscore) based on the importance of network targets, a pair score (Pscore) based on empirical learning and herbal formula predictive score (FmapScore) based on intelligent optimization and genetic algorithm. The validity of Hscore, Pscore and FmapScore was verified by functional similarity and network topological evaluation. Moreover, TCMFP was used successfully to generate herbal formulae for three diseases, i.e. the Alzheimer's disease, asthma and atherosclerosis. Functional enrichment and network analysis indicates the efficacy of targets for the predicted optimal herbal formula. The proposed TCMFP may provides a new strategy for the optimization of herbal formula, TCM herbs therapy and drug development.

Factors contributing to spatial-temporal variations of observed oxygen concentration over the Qinghai-Tibetan Plateau.

Oxygen (O2) is the most abundant molecule in the atmosphere after nitrogen. Previous studies have documented that oxygen concentration remains nearly constant (20.946%) at all altitudes. Here we show for the first time that oxygen concentration varies significantly from earlier consensus and shows strong spatial and seasonal differences. Field observations on the Qinghai-Tibetan Plateau (QTP) indicate oxygen concentration of 19.94-20.66% (2018, n = 80), 19.98-20.78% (2019, n = 166) and 19.97-20.73% (2020, n = 176), all statistically different from earlier reports (p < 0.001) and are lower than the nearly constant. The mean oxygen concentration in summer (20.47%) is 0.31% higher than that of winter (20.16%) (n = 53) at identical locations in 2019, sampled in the Qilian Mountains, northwest QTP. We used LMG (The Lindeman, Merenda and Gold) method to estimate the relative contributions of altitude, air temperature and vegetation index (Fractional Vegetation Cover, FVC and Leaf Area Index, LAI) to oxygen concentration, which are 47%, 32% and 3% (FVC, R2 = 82%); 45%, 30% and 7% (LAI, R2 = 82%), respectively. These findings provide a new perspective for in-depth understanding on population risk in high altitude regions in the context of global climate change, to ensure the health and safety of residents and tourists in high altitude regions and promoting the stability, prosperity and sustainable development of high-altitude regions worldwide.

Rice drought risk assessment under climate change: Based on physical vulnerability a quantitative assessment method.

Drought is the most serious natural disaster causing severe damage to agriculture. Drought impacts on rice (Oryza sativa) production present a major threat to future global food security. In this paper, the Environmental Policy Integrated Climate (EPIC) model was used to simulate the growth of rice, in different periods (short-term (2019-2039), medium-term (2040-2069), long-term (2070-2099)), based on multiple Representative Concentration Pathways (RCP) scenarios. Drought intensity and rice physical vulnerability curves were assessed, based on the output parameters of EPIC, to evaluate global rice yield risk, due to drought. The results show that the average expected loss rate of global rice yield may reach 13.1% (±0.4%) in the future. The high-risk area of rice drought is mainly located in the north of 30°N. The fluctuation of rice drought risk and the proportion of increased risk areas will increase significantly. About 77.6% of the changes in rice drought risk are explained by variations in shortwave radiation (r = 0.88). Projections show that the average value of daily shortwave radiation increases by 1 W/m2 during the rice growth period, accompanied by an expected rice yield loss rate of about 12.7%. The rice drought risk methods presented in this paper provide plausible estimates of forecasting future drought risk under climate change, and address challenges of sparse data; we believe these methods can be applied to decisions for reducing drought-related crop losses and ensuring global food security.

Pulsed radiofrequency alleviated neuropathic pain by down-regulating the expression of substance P in chronic constriction injury rat model.

BACKGROUND: Pulsed radiofrequency (PRF), as a non-invasive treatment of neuropathic pain (NP), has been widely administered clinically. Previous studies have shown that PRF has the potential to improve hyperalgesia in animal models of NP. However, there have been few reports to clarify whether the mechanism of PRF treatment of NP involves intervention in the expression of substance P (SP). Therefore, this study administered PRF treatment to chronic constriction injury (CCI) model rats and observed the sciatic nerve mechanical pain threshold and SP expression in the spinal cord to explore the mechanism of PRF treatment. METHODS: A total of 96 Sprague-Dawley rats were randomly divided into the sham-surgery-sham-treatment group (S-S group), the sham-surgery-PRF group (S-P group), the CCI-sham-treatment group (C-S group), and the CCI-PRF group (C-P group). The C-S group and the C-P group underwent sciatic nerve CCI, while the other groups received a sham operation. At 14 days after the operation, the C-P group and the S-P group were treated with PRF for 300 s. We recorded the hindpaw withdrawal threshold (HWT) and the thermal withdrawal latency (TWL) of rats in the various groups at baseline, before treatment (0 days), and at 1, 7, 14, and 28 days after treatment. L4 to L6 spinal cord tissues were taken before treatment (0 days) and 1, 7, 14, and 28 days after treatment. The transcription and translation of SP were measured by quantitative polymerase chain reaction and Western blotting, respectively. RESULTS: The HWT and the TWL in the C-P group 28 days after PRF treatment were significantly higher than those in the C-S group (95% confidence interval [CI]: 5.84-19.50, P < 0.01; 95% CI: 2.58-8.69, P = 0.01). The expression of SP in the C-P group 28 days after PRF treatment was significantly lower than that in the C-S group (95% CI: 1.17-2.48, P < 0.01). CONCLUSIONS: PRF may alleviate CCI-induced NP by down-regulating the expression of SP in the spinal cord of CCI model rats.