Mechanistic prediction and validation of Brevilin A Therapeutic effects in Lung Cancer.

BACKGROUND: Traditional Chinese medicine (TCM) has been found widespread application in neoplasm treatment, yielding promising therapeutic candidates. Previous studies have revealed the anti-cancer properties of Brevilin A, a naturally occurring sesquiterpene lactone derived from Centipeda minima (L.) A.Br. (C. minima), a TCM herb, specifically against lung cancer. However, the underlying mechanisms of its effects remain elusive. This study employs network pharmacology and experimental analyses to unravel the molecular mechanisms of Brevilin A in lung cancer. METHODS: The Batman-TCM, Swiss Target Prediction, Pharmmapper, SuperPred, and BindingDB databases were screened to identify Brevilin A targets. Lung cancer-related targets were sourced from GEO, Genecards, OMIM, TTD, and Drugbank databases. Utilizing Cytoscape software, a protein-protein interaction (PPI) network was established. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene set enrichment analysis (GSEA), and gene-pathway correlation analysis were conducted using R software. To validate network pharmacology results, molecular docking, molecular dynamics simulations, and in vitro experiments were performed. RESULTS: We identified 599 Brevilin A-associated targets and 3864 lung cancer-related targets, with 155 overlapping genes considered as candidate targets for Brevilin A against lung cancer. The PPI network highlighted STAT3, TNF, HIF1A, PTEN, ESR1, and MTOR as potential therapeutic targets. GO and KEGG analyses revealed 2893 enriched GO terms and 157 enriched KEGG pathways, including the PI3K-Akt signaling pathway, FoxO signaling pathway, and HIF-1 signaling pathway. GSEA demonstrated a close association between hub genes and lung cancer. Gene-pathway correlation analysis indicated significant associations between hub genes and the cellular response to hypoxia pathway. Molecular docking and dynamics simulations confirmed Brevilin A's interaction with PTEN and HIF1A, respectively. In vitro experiments demonstrated Brevilin A-induced dose- and time-dependent cell death in A549 cells. Notably, Brevilin A treatment significantly reduced HIF-1α mRNA expression while increasing PTEN mRNA levels. CONCLUSIONS: This study demonstrates that Brevilin A exerts anti-cancer effects in treating lung cancer through a multi-target and multi-pathway manner, with the HIF pathway potentially being involved. These results lay a theoretical foundation for the prospective clinical application of Brevilin A.

The Impact of Problematic Internet Use on Adolescent Loneliness-Chain Mediation Effects of Social Support and Family Communication.

Purpose: To explore the relationship between adolescents' problematic Internet use and loneliness and the mediating roles of social support and family communication. Methods: A questionnaire survey of 2483 adolescents aged 12-17 years in 148 cities in China was conducted using the Problematic Internet Use Scale, the Collaborative Social Support Scale, the Family Communication Scale, and the Loneliness Scale. The data were statistically analyzed by SPSS 26.0 and validated by AMOS 28.0. Structural equation modelling (SEM) was conducted to test the effects of problematic Internet use on adolescents' loneliness and the mediating effects of perceptions of social support and family communication. Results: There was a significant positive effect of adolescents' problematic Internet use on loneliness (B-0.471, P<0.001), and the mediating effects of perceptual social support (0.003, 0.012) and family communication (0.008, 0.019) were found to play a chain effect between adolescents' problematic Internet use and loneliness, respectively. Use and feelings of loneliness played a chain mediating role (0.002, 0.006). Conclusion: This study identified the effects of adolescent problematic Internet use on loneliness and its mechanism of action, emphasized the importance of social support and family communication, and provided practical insights for improving family parenting styles and preventing and intervening in adolescent loneliness problems.

Photothermal synergistic nitric oxide controlled release injectable self-healing adhesive hydrogel for biofilm eradication and wound healing.

The development of injectable self-healing adhesive hydrogel dressings with excellent bactericidal activity and wound healing ability is urgently in demand for combating biofilm infections. Herein, a multifunctional hydrogel (QP/QT-MB) with near-infrared (NIR) light-activated mild photothermal/gaseous antimicrobial activity was developed based on the dynamic reversible borate bonds and hydrogen bonds crosslinking between quaternization chitosan (QCS) derivatives alternatively containing phenylboronic acid and catechol-like moieties in conjunction with the in situ encapsulation of BNN6-loaded mesoporous polydopamine (MPDA@BNN6 NPs). Given the dynamic reversible cross-linking feature, the versatile hybrid hydrogel exhibited injectability, flexibility, and rapid self-healing ability. The numerous phenylboronic acid and catechol-like moieties on the QCS backbone confer the hydrogel with specific bacterial affinity, desirable tissue adhesion, and antioxidant stress ability that enhance bactericidal activity and facilitate the regeneration of infection wounds. Under NIR irradiation, the QP/QT-MB hydrogels exhibited a desirable mild photothermal effect and NIR-activity controllable NO delivery, combined with the endogenous contact antimicrobial activity of hydrogel, contributing jointly to induce dispersal of biofilms and disruption of the bacterial plasma membranes, ultimately leading to bacteria inactivation and biofilm elimination. In vivo experiments demonstrated that the fabricated QP/QT-MB hydrogel platform was capable of inducing efficient eradication of the S. aureus biofilm in a severely infected wound model and accelerating infected wound repair by promoting collagen deposition, angiogenesis, and suppressing inflammatory responses. Additionally, the QP/QT-MB hydrogel demonstrated excellent biocompatibility in vitro and in vivo. Collectively, the hydrogel (QP/QT-MB) reveals great potential application prospects as a promising alternative in the field of biofilm-associated infection treatment.

Human footprints in the Global South accelerate biomass carbon loss in ecologically sensitive regions.

Human activities have placed significant pressure on the terrestrial biosphere, leading to ecosystem degradation and carbon losses. However, the full impact of these activities on terrestrial biomass carbon remains unexplored. In this study, we examined changes in global human footprint (HFP) and human-induced aboveground biomass carbon (AGBC) losses from 2000 to 2018. Our findings show an increasing trend in HFP globally, resulting in the conversion of wilderness areas to highly modified regions. These changes have altered global biomes' habitats, particularly in tropical and subtropical regions. We also found accelerated AGBC loss driven by HFP expansion, with a total loss of 19.99 ± 0.196 PgC from 2000 to 2018, especially in tropical regions. Additionally, AGBC is more vulnerable in the Global South than in the Global North. Human activities threaten natural habitats, resulting in increasing AGBC loss even in strictly protected areas. Therefore, scientifically guided planning of future human activities is crucial to protect half of Earth through mitigation and adaptation under future risks of climate change and global urbanization.

Efficacy comparison of acupuncture and balanced acupuncture combined with TongduZhengji manipulation in the treatment of acute lumbar sprain.

OBJECTIVE: To compare the curative effect of balanced acupuncture combined with TongduZhengji manipulation vs acupuncture in the treatment of acute lumbar sprain. METHODS: Clinical data of 71 patients with acute lumbar sprains in our hospital from January 2020 to December 2020 were retrospectively analyzed. Patients were divided into single group (n=35) and combined group (n=36) based on treatment methods. The single group received only acupuncture treatment, while the combined group received balanced acupuncture combined with TongduZhengji manipulation. The treatment efficacy, pain level, lumbar function and motion of the lumbar spine were compared between the two groups. RESULTS: The Visual Analogue Scale (VAS) scores of the combined group were lower than those of the single group after 3, 4, and 5 days of treatment (P<0.05). There was no significant difference in VAS scores between the two groups after 1 and 2 days of treatment (P>0.05). The Roland-Morris Disability Questionnaire (RMDQ) score of the combined group showed no significant difference compared with that of the single group after 1 and 2 days of treatment (P>0.05), and were lower than those of the single group after 3, 4, and 5 days of treatment (P<0.05). The Japanese Orthopedic Association (JOA) score of the combined group after 1, 2, and 3 days of treatment showed no significant difference compared with the single group (P>0.05), and was higher than that of the single group after 4 and 5 days of treatment (P<0.05). The Range of Motion (ROM) score of the combined group showed no significant difference compared with the single group after 1 and 2 days of treatment (P>0.05), and was lower than that of the single group after 3, 4, and 5 days of treatment (P<0.05). The total effective rate of treatment in the combined group was significantly higher than that in the single group (91.67% vs. 71.43%) (P<0.05). CONCLUSION: Compared with acupuncture alone, balanced acupuncture combined with TongduZhengji manipulation can significantly reduce the pain level and improve lumbar spine mobility as well as lumbar spine function, exhibiting better curative effect than acupuncture only.

The Spatiotemporal Distribution and Drivers of Urban Carbon Emission Efficiency: The Role of Technological Innovation.

Urban agglomerations have become the core areas for carbon reduction in China since they account for around 75% of its total emissions. Beijing-Tianjin-Hebei (BTH), Yangtze River Delta (YRD), and the Pearl River Delta (PRD), which are its most important poles of regional development and technological innovation, are key to achieving China's carbon peak emissions target. Based on the panel data of these three major urban agglomerations from 2003 to 2017, this study estimated the carbon emission efficiency (CEE) by the super-efficiency slacks-based measure (super-SBM) model and analyzed its spatiotemporal distribution pattern. The Dagum Gini coefficient was used to evaluate the difference in CEE between the three major agglomerations, while panel data models were established to analyze the impact of technological innovation on the three agglomerations. The overall CEE showed an upward trend during the study period, with significant spatial and temporal variations. Additionally, the main source of urban agglomeration difference in CEE evolved from inter-regional net differences to intensity of transvariation. While technological innovations are expected to significantly improve CEE, their effect varies among urban agglomerations. These results provide policymakers with insights on the collaborative planning of urban agglomerations and the low-carbon economy.

Evaluating the effects of air pollution control policies in China using a difference-in-differences approach.

Air pollution has caused wide concern in China, and many governance policies and plans have been implemented in recent years. Based on counterfactual quasi-natural experiments, we analyzed the implementation effects of autumn and winter air pollution control policies in the Jing-Jin-Ji region and surrounding areas using a difference-in-differences (DID) model. The control group was selected based on geographical and meteorological factors, and we analyzed the impact of the policies on six pollutants. The results show that the policies reduced air pollution overall, but not every pollutant. Due to the policy contribution, the concentrations of PM2.5 and PM10 in autumn and winter from 2017 to 2018 decreased by 6.9 % and 8.5 %, respectively. The numerical value of PM2.5, PM10, CO, and AQI in 2018-2019 decreased by 18.2 %, 7.2 %, 13.9 %, and 8.8 %, respectively. The role in the reduction of O3, SO2, and NO2 was not obvious. This work provides a research paradigm for evaluating the effects of atmospheric environment policy which can be applied to other studies and provide references for formulating additional policies.

Estimating the Decoupling between Net Carbon Emissions and Construction Land and Its Driving Factors: Evidence from Shandong Province, China.

Human activities and land transformation are important factors in the growth of carbon emissions. In recent years, construction land for urban use in China has expanded rapidly. At the same time, carbon emissions in China are among the highest in the world. However, little is known about the relationship between the two factors. This study seeks to estimate the carbon emissions and carbon sequestrations of various types of land based on the land cover data of 137 county-level administrative regions in Shandong Province, China, from 2000 to 2020.The study estimated the carbon emissions for energy consumption using energy consumption data and night-time light images, hence, net carbon emissions. The Tapio decoupling coefficient was used to analyze the decoupling between the net carbon emissions and construction land, and where the model for the decoupling effort was constructed to explore the driving factors of decoupling. The results showed that net carbon emissions in Shandong Province continued to increase, and the areas with high carbon emissions were concentrated primarily in specific districts of the province. The relationship between net carbon emissions and construction land evolved from an expansive negative decoupling type to a strong negative decoupling type. Spatially, most areas in the province featured an expansive negative decoupling, but the areas with a strong negative decoupling have gradually increased. The intensive rate of land use and efficiencies in technological innovation have restrained carbon emissions, and they have contributed to an ideal decoupling situation. Although the intensity of carbon emission and the size of the population have restrained carbon emissions, efforts towards decoupling have faded. The degree of land use has facilitated carbon emissions, and in recent years, efforts have been made to achieve an ideal decoupling. The method of estimation of net carbon emissions devised in this research can lend itself to studies on other regions, and the conclusions provide a reference for China, going forward, to balance urbanization and carbon emissions.

Observing the silent world under COVID-19 with a comprehensive impact analysis based on human mobility.

Since spring 2020, the human world seems to be exceptionally silent due to mobility reduction caused by the COVID-19 pandemic. To better measure the real-time decline of human mobility and changes in socio-economic activities in a timely manner, we constructed a silent index (SI) based on Google's mobility data. We systematically investigated the relations between SI, new COVID-19 cases, government policy, and the level of economic development. Results showed a drastic impact of the COVID-19 pandemic on increasing SI. The impact of COVID-19 on human mobility varied significantly by country and place. Bi-directional dynamic relationships between SI and the new COVID-19 cases were detected, with a lagging period of one to two weeks. The travel restriction and social policies could immediately affect SI in one week; however, could not effectively sustain in the long run. SI may reflect the disturbing impact of disasters or catastrophic events on the activities related to the global or national economy. Underdeveloped countries are more affected by the COVID-19 pandemic.

Identifying the spatial disparities and determinants of ecosystem service balance and their implications on land use optimization.

Ecosystem services (ESs) are increasingly affected by human interventions, and the ES balance between supply and demand plays a vital role in guaranteeing the expected efficacy of ecosystem restoration projects. However, the spatial disparities of ES balance, along with its determinants and spillover effects, remain unclear, constraining effective ES management and landscape planning. The aim of this study was to fill these gaps by quantifying the ES balance in the restoring Loess Plateau using an expert-based ES matrix approach and by examining the spatial associations between ES balance and driving factors via an integrated regression approach. The results showed that the county-scale ES balance was closely related to the land-use composition and population density. Geographic locations of counties with ES surplus were mainly concentrated in mountainous areas with high proportions of woodland and grassland, while urbanized land and a high population density resulted in an ES deficit. Forest and grass regeneration, due to revegetation practices, alleviated ES deficits, while rapid urbanization and population growth aggravated ES imbalance. The integrated regression approach demonstrated that the ES balance and its dependencies (i.e., landscape metrics and population density) had remarkable spatial heterogeneity and spillover effects, which should be practically considered in localized ES management and landscape optimization. Excessive agricultural reclamation and urban expansion improved grain productivity and economic profits but deteriorated landscape fragmentation, further aggravating the ES deficit. In contrast, excessive revegetation practices promoted ecosystem restoration and improved ES surplus but threatened food security. Therefore, an appropriate balanced state should be maintained for sustainable ecosystem restoration through timely and efficient policy interventions and landscape optimization.

Conjugate evaluation of sustainable carrying capacity of urban agglomeration and multi-scenario policy regulation.

The scientific evaluation of carrying capacity and the formulation of adaptive regulation policies are powerful ways to achieve sustainable development goals. In order to quantitatively and accurately diagnose the sustainable development state of urban agglomeration, this paper responds to the "Future Earth" framework; takes the carrying capacity as the breakthrough point; embeds the conjugate thought; considers the elements of the resources, the environment, the ecology, and the development; and establishes the conjugate evaluation model and the evaluation index system of sustainable carrying capacity. In order to solve the actual bottleneck problem of urban agglomeration, this work identifies the key obstacle factors, constructs the multi-scenario dynamic coupling (MSDC) model, recognizes the sensitivity policies, and proposes the adaptive regulation polices. Taking the urban agglomeration on the northern slope of the Tianshan Mountains (UANSTM) in arid areas as a case study, it was found that from 2007 to 2017, the carrying capacity gradually increased, and the sustainable development showed a benign transformation trend in the UANSTM. It will also be in a transitional stage of growth from now to 2035, and the steady development of the economy and the society and the good maintenance of the resources, the environment and the ecology are equally important. The policies on population intervention and on the management of water resources play a vital role, and the speed of economic development should be controlled throughout the whole process. The study confirms that the effective regulation is necessary for the sustainable development of the urban agglomeration in the future, and the key lies in improving technological progress and governance policy support. It is expected that this new and complete research framework for the conjugate evaluation of the sustainable carrying capacity of urban agglomeration and multi-scenario policy regulation can be applied to other regions or urban agglomerations in developing countries and can make a possible breakthrough in promoting the theoretical exploration and practice of sustainable development.

Systemic administration of mesenchymal stem cells loaded with a novel oncolytic adenovirus carrying IL-24/endostatin enhances glioma therapy.

Oncolytic adenovirus-mediated gene therapy shows promise for cancer treatment; however, the systemic delivery of oncolytic adenovirus to tumors remains challenging. Recently, mesenchymal stem cells (MSCs) have emerged as potential vehicles for improving delivery. Yet, because the oncolytic adenovirus replicates in MSCs, balancing MSC viability with viral load is key to achieving optimal therapeutic effect. We thus developed an all-in-one Tet-on system that can regulate replication of oncolytic adenovirus. Then, we loaded the novel oncolytic adenovirus carrying interleukin (IL)-24 and/or Endostatin in human umbilical cord blood-mesenchymal stem cells (hUCB-MSCs) for glioma therapy. In vitro assays demonstrated that this novel oncolytic adenovirus could efficiently replicate and kill glioma cells while sparing normal cells. Moreover, doxycycline effectively regulated oncolytic adenovirus replication in the hUCB-MSCs. The doxycycline induction group with dual expression of IL-24 and Endostatin exhibited significantly greater antitumor effects than other groups in a xenograft model of glioma. Thus, this strategy for systemic delivery of oncolytic adenovirus with its oncolytic activity controlled by a Tet-on system is a promising method for achieving antitumor efficacy in glioma, especially for metastatic tumors.

Modeling regional sustainable development scenarios using the Urbanization and Eco-environment Coupler: Case study of Beijing-Tianjin-Hebei urban agglomeration, China.

China's rapid urbanization has produced problems of excessive resource use and environmental pollution, threatening the country's sustainable development. Previous studies mainly focused on empirical observation of the interactions between urbanization and the eco-environment, mainly using econometric models which lacked detailed explanations of the coupling mechanisms between various elements. No quantitative models have been developed to describe the complex nonlinear relationships between various elements, so our understanding of urbanization and eco-environment coupling is vague, and therefore not conducive to coordinating the relationship between them. Coupling urbanization with the eco-environment allows us to simulate interactions between them and enables us to explore the most suitable scenarios for sustainable development. We designed and developed the Urbanization and Eco-environment Coupler (UEC) using system dynamics to simulate regional urbanization and eco-environment coupling and to compare different sustainable development scenarios. UEC integrates human and natural elements. It includes four urbanization submodels (the economy, society, population and construction land) and five eco-environment submodels (water, arable land, ecology, pollution and energy). UEC can fully represent the nonlinear interactions between these submodels by identifying feedback linkages. This allows us to identify an optimal sustainable regional development pattern. We chose the Beijing-Tianjin-Hebei urban agglomeration as a case study research area and obtained the following results: (1) prioritizing urbanization will accelerate economic growth and increase pollution emissions whereas prioritizing the eco-environment will negatively affect both total population and arable land; (2) when sufficient policy and technical support is directed to a particular area, urbanization may not further degrade the eco-environment; and (3) simulation results for various scenarios show that the key to guaranteeing sustainable development is improving technical and political support rather than further restricting urbanization. The UEC model is a significant aid to improving sustainable regional planning.

Prevalence of BRCA1 and BRCA2 gene mutations in Chinese patients with high-risk breast cancer.

BACKGROUND: Breast cancer is the most common cancer among women worldwide. Here, we report the prevalence of BRCA1/2 mutations in patients with high-risk breast cancer from Inner Mongolia and Jilin, China, which was a part of a nationwide project on the detection of BRCA1/2 mutations in Chinese patients with hereditary breast cancer. METHODS: According to the criteria, index patients from a total of 245 independent families were initially recruited. All 49 exons of BRCA1 and BRCA2 and adjacent noncoding regions were screened for mutations based on next-generation sequencing from collected saliva. RESULTS: We detected 17 BRCA1/2 variants in 18 of 216 (8.3%) index patients with high-risk breast cancer. Among these, seven mutations were novel, including four BRCA1 mutations (c.123_124delCAinsAT, c.5093_5096delCTAA, c.5396-2A>G, and c.2054delinsGAAGAGTAACAAGTAAGAAGAGTAACAAGAAG), and three BRCA2 mutations (c.304A>T, c.7552_7553insT, and c.9548_9549insA). The BRCA1/2 variants were identified in 14% (8/57) of the patients with triple-negative breast cancer and in 6.3% (10/159) of the patients with non-triple-negative breast cancer. There was no significant difference between the two groups (p = 0.07). A higher frequency for BRCA1 mutations was observed in patients with triple-negative breast cancer than in those with non-triple-negative breast cancer (12.3% vs. 2.5%, p = 0.004). The frequencies of the BRCA2 mutations were not significantly different between patients with triple-negative breast cancer and those with non-triple-negative breast cancer (1.8% vs. 3.8%, p = 0.46). CONCLUSION: We found that patients with triple-negative breast cancer had a higher frequency of BRCA1 mutations than those with non-triple-negative breast cancer. In this study, no significant associations between the BRCA1/2 mutation status and age, family history of breast cancer, ovarian cancer, pancreatic cancer and prostate cancer, number of primary lesions, tumor size, or lymph node metastasis were observed.

Analysis of factors related to non-sentinel lymph node metastasis in 296 sentinel lymph node-positive Chinese breast cancer patients.

OBJECTIVE: Axillary lymph node dissection (ALND) may be unnecessary in 20%-60% of breast cancer patients with sentinel lymph node (NSLN) metastasis. The aim of the present study was to review the medical records of Chinese patients with early-stage breast cancer and positive NSLN metastasis to identify clinicopathological characteristics as risk factors for non-NSLN metastasis. METHODS: The medical records of 2008 early-stage breast cancer patients who received intraoperative sentinel lymph node biopsy (SLNB) between 2006 and 2016 were retrospectively reviewed. These patients were clinically and radiologically lymph node-negative and had no prior history of receiving neoadjuvant chemotherapy or endocrinotherapy. The clinicopathological characteristics of patients with positive NSLN metastasis who underwent ALND were investigated. RESULTS: In the present study, 296 patients with positive NSLN metastases underwent ALND. Positive non-NSLN metastases were confirmed in 95 patients (32.1%). On univariate analysis, ≥ 3 positive NSLN metastases (P <0.01), NSLN macrometastases ( P = 0.023), and lymphovascular invasion (P = 0.04) were associated with non-NSLN metastasis (P <0.05). In multivariate analysis, the number of positive SLNs was the most significant predictor of non-SLN metastasis. For patients with 0, 1, 2, or 3 associated risk factors, the non-SLN metastatic rates were 11.5%, 22.5%, 35.2%, and 73.1%, respectively. CONCLUSIONS: The number of positive NSLNs, NSLN macrometastases, and lymphovascular invasion were correlated with non-SLN metastasis. The number of positive SLNs was an independent predictor for non-NSLN metastasis. When 2 or 3 risk factors were present in one patient, the probability of non-NSLN was higher than that in the American College of Surgeons Oncology Group Z0011 trial (27.3%); thus, avoiding ALND should be considered carefully.

Does economic development improve urban greening? Evidence from 289 cities in China using spatial regression models.

Significant differences in urban greening have occurred in Chinese cities, accompanied by China's rapid urbanization. However, there are relatively few studies on the spatial differentiation of urban greening in China at the city level. In addition, there is no unanimous conclusion on the main factors influencing the spatial differentiation of urban greening. Based on 2014 emission inventory data from 289 cities, the spatial differentiation pattern and spatial correlation characteristics of the urban green space ratio, urban green coverage rate, and public green area per capita were calculated and analyzed using global and local Moran's I. We then used ordinary least squares, spatial error model, spatial autoregression, and geographically weighted regression to quantify the impact and spatial variations of China's economy on urban greening. The results showed (1) a significant spatial dependence and heterogeneity existed in urban greening values, and the patterns showed influences of both the stage of economic development and spatial agglomeration; (2) regression models revealed per capita GDP had a positive effect on the urban green space ratio and public green area per capita while the urbanization rate, secondary industry, urban land, and population density had opposite effects on these two greening indexes; and (3) geographically weighted regression revealed per capita GDP had a greater influence on urban greening in the northwestern region than in the southeastern region. The study could constitute a valuable reference for mid-to-long-term green space planning policy in diverse parts of China and could further assist in coordinating the development of urban greening and economic growth.