PDCD4-induced oxidative stress through FGR/NF-κB axis in rectal cancer radiotherapy-induced AKI.

This study aimed to investigate the molecular mechanism of the effect of PDCD4 on radiotherapy-induced acute kidney injury (AKI) in rectal cancer through the regulation of FGR/NF-κB signaling. Differentially expressed genes were identified using Gene Expression Omnibus (GEO) datasets (GSE90627 for rectal cancer and GSE145085 for AKI) and R software. The human renal tubular epithelial cell line, HK-2, was used to establish an in vitro model of radiotherapy-induced AKI. RT-qPCR and western blotting were used to detect gene and protein expression levels, respectively. Cell proliferation and apoptosis were assessed using the CCK-8 assay and flow cytometry, respectively. The malondialdehyde and superoxide dismutase levels in the cell culture supernatants were determined. Additionally, an in vivo AKI model was established using BALB/c mice, and kidney tissue morphology, expression of the renal injury molecule KIM-1, apoptosis of renal tubular cells, and TAS and TOS in serum were evaluated. Bioinformatics analysis revealed the upregulated expression of PDCD4 in AKI. In vitro experiments demonstrated that PDCD4 induced apoptosis in renal tubular cells by promoting FGR expression, which activated the NF-κB signaling pathway and triggered an oxidative stress response. In vivo animal experiments confirmed that PDCD4 promoted oxidative stress response and radiotherapy-induced AKI through the activation of the FGR/NF-κB signaling pathway. Silencing PDCD4 attenuated radiotherapy-induced AKI. Our findings suggest that PDCD4 may induce radiotherapy-induced AKI in rectal cancer by promoting FGR expression, activating the NF-κB signaling pathway, and triggering an oxidative stress response.

Optimal site selection strategies for urban parks green spaces under the joint perspective of spatial equity and social equity.

Urban park green spaces (UPGS) are a crucial element of social public resources closely related to the health and well-being of urban residents, and issues of equity have always been a focal point of concern. This study takes the downtown area of Nanchang as an example and uses more accurate point of interest (POI) and area of interest (AOI) data as analysis sources. The improved Gaussian two-step floating catchment area (G2SFCA) and spatial autocorrelation models are then used to assess the spatial and social equity in the study area, and the results of the two assessments were coupled to determine the optimization objective using the community as the smallest unit. Finally, the assessment results are combined with the k-means algorithm and particle swarm algorithm (PSO) to propose practical optimization strategies with the objectives of minimum walking distance and maximum fairness. The results indicate (1) There are significant differences in UPGS accessibility among residents with different walking distances, with the more densely populated Old Town and Honggu Tan areas having lower average accessibility and being the main areas of hidden blindness, while the fringe areas in the northern and south-western parts of the city are the main areas of visible blindness. (2) Overall, the UPGS accessibility in Nanchang City exhibits a spatial pattern of decreasing from the east, south, and west to the center. Nanchang City is in transition towards improving spatial and social equity while achieving basic regional equity. (3) There is a spatial positive correlation between socioeconomic level and UPGS accessibility, reflecting certain social inequity. (4) Based on the above research results, the UPGS layout optimization scheme was proposed, 29 new UPGS locations and regions were identified, and the overall accessibility was improved by 2.76. The research methodology and framework can be used as a tool to identify the underserved areas of UPGS and optimize the spatial and social equity of UPGS, which is in line with the current trend of urban development in the world and provides a scientific basis for urban infrastructure planning and spatial resource allocation.

A Prolonged Artificial Nighttime-light Dataset of China (1984-2020).

Nighttime light remote sensing has been an increasingly important proxy for human activities. Despite an urgent need for long-term products and pilot explorations in synthesizing them, the publicly available long-term products are limited. A Night-Time Light convolutional LSTM network is proposed and applied the network to produce a 1-km annual Prolonged Artificial Nighttime-light DAtaset of China (PANDA-China) from 1984 to 2020. Assessments between modeled and original images show that on average the RMSE reaches 0.73, the coefficient of determination (R2) reaches 0.95, and the linear slope is 0.99 at the pixel level, indicating a high confidence in the quality of generated data products. Quantitative and visual comparisons witness PANDA-China's superiority against other NTL datasets in its significantly longer NTL dynamics, higher temporal consistency, and better correlations with socioeconomics (built-up areas, gross domestic product, population) characterizing the most relevant indicator in different development phases. The PANDA-China product provides an unprecedented opportunity to trace nighttime light dynamics in the past four decades.

Deforestation in Latin America in the 2000s predominantly occurred outside of typical mature forests.

The role of tropical forests in the global carbon budget remains controversial, as carbon emissions from deforestation are highly uncertain. This high uncertainty arises from the use of either fixed forest carbon stock density or maps generated from satellite-based optical reflectance with limited sensitivity to biomass to generate accurate estimates of emissions from deforestation. New space missions aiming to accurately map the carbon stock density rely on direct measurements of the spatial structures of forests using lidar and radar. We found that lost forests are special cases, and their spatial structures can be directly measured by combining archived data acquired before and after deforestation by space missions principally aimed at measuring topography. Thus, using biomass mapping, we obtained new estimates of carbon loss from deforestation ahead of forthcoming space missions. Here, using a high-resolution map of forest loss and the synergy of radar and lidar to estimate the aboveground biomass density of forests, we found that deforestation in the 2000s in Latin America, one of the severely deforested regions, mainly occurred in forests with a significantly lower carbon stock density than typical mature forests. Deforestation areas with carbon stock densities lower than 20.0, 50.0, and 100.0 Mg C/ha accounted for 42.1%, 62.0%, and 83.3% of the entire deforested area, respectively. The average carbon stock density of lost forests was only 49.13 Mg C/ha, which challenges the current knowledge on the carbon stock density of lost forests (with a default value 100 Mg C/ha according to the Intergovernmental Panel on Climate Change Tier 1 estimates, or approximately 112 Mg C/ha used in other studies). This is demonstrated over both the entire region and the footprints of the spaceborne lidar. Consequently, our estimate of carbon loss from deforestation in Latin America in the 2000s was 253.0 ± 21.5 Tg C/year, which was considerably less than existing remote-sensing-based estimates, namely 400-600 Tg C/year. This indicates that forests in Latin America were most likely not a net carbon source in the 2000s compared to established carbon sinks. In previous studies, considerable effort has been devoted to rectify the underestimation of carbon sinks; thus, the overestimation of carbon emissions should be given sufficient consideration in global carbon budgets. Our results also provide solid evidence for the necessity of renewing knowledge on the role of tropical forests in the global carbon budget in the future using observations from new space missions.

Governing cross-border healthcare in mainland China: a scoping review of national policies from 2002 to 2022.

This study reviews national-level policies regulating cross-border healthcare in mainland China after it acceded to the World Trade Organization (WTO). Policy documents from official websites of the State Council and 19 ministries were screened, from which 487 policy documents were analyzed. WTO's five modes of trade and WHO's six building blocks of healthcare system were used to guide the analysis of policymaking patterns, charting of policy evolution process, identification of key policy areas, differentiation of 29 detailed policy themes, and identification of major countries/regions involved in cross-border healthcare. The findings lead to four policy recommendations: (1) to establish a national-level committee to govern cross-border healthcare, (2) to build an information system to comprehensively integrate various information on cross-border healthcare consumption and provision, (3) to take more proactive policy actions in healthcare internationalization, and (4) to carry out reform experiments in key sub-national regions to fully explore various possibilities in developing and regulating cross-border healthcare.

China's carbon-neutral policies will reduce short-term PM2.5-associated excess incidence of cardiovascular diseases.

China's carbon-neutral target could have benefits for ambient fine particulate matter (PM2.5)-associated mortality. Although previous studies have researched such benefits, the potential impact on cardiovascular disease incidence burden is yet to be investigated thoroughly. Here, we first estimate the association between short-term PM2.5 exposure and the incidence of stroke and coronary heart disease (CHD) via a case-crossover study before projecting future changes in short-term PM2.5-associated excess incidence across China from 2025 to 2060 under three different emission scenarios. We find that, compared to the 2015-2020 baseline, average PM2.5 concentrations nationwide in 2060 under SSP119 (an approximation of a carbon-neutral scenario) are projected to decrease by 81.07%. The short-term PM2.5-related excess incidence of stroke and CHD is projected to be reduced to 3,352 cases (95% confidence interval: 939, 5,738)-compared with 34,485 cases under a medium-emissions scenario (SSP245)-and is expected to be accompanied by a 95% reduction in the related economic burden. China's carbon-neutral policies are likely to bring health benefits for cardiovascular disease by reducing short-term PM2.5-related incidence burden.

Electroacupuncture stimulation enhances the permeability of the blood-brain barrier: A systematic review and meta-analysis of preclinical evidence and possible mechanisms.

An important cellular barrier to maintain the stability of the brain's internal and external environment is the blood-brain barrier (BBB). It also prevents harmful substances from entering brain tissue through blood circulation while providing protection for the central nervous system. It should be noted, however, that the intact BBB can be a barrier to the transport of most drugs into the brain via the conventional route of administration, which can prevent them from reaching effective concentrations for the treatment of disorders affecting the central nervous system. Electroacupuncture stimulation has been shown to be effective at opening the BBB in a series of experimental studies. This study systematically analyzes the possibility and mechanism by which electroacupuncture opens the BBB. In PubMed, Web of Science, VIP Database, Wanfang Database, and the Chinese National Knowledge Infrastructure, papers have been published for nearly 22 years aimed at opening the BBB and its associated structures. A comparison of EB content between electroacupuncture and control was selected as the primary outcome. There were also results on vascular endothelial growth factor (VEGF), nerve growth factor (NGF), P-Glycoprotein (P-gp), Matrix Metalloproteinase 9 (MMP-9), and glial fibrillary acidic protein (GFAP). We utilized Review Manager software analysis to analyze correlations between studies with a view to exploring the mechanisms of similarity. Evans Blue infiltration forest plot: pooled effect size of 2.04, 95% CI: 1.21 to 2.87, P < 0.01. These results indicate that electroacupuncture significantly increases EB penetration across the BBB. Most studies have reported that GFAP, MMP-9, and VEGF were upregulated after treatment. P-gp expression decreased as well. Electroacupuncture can open the BBB, and the sparse-dense wave is currently the most effective electroacupuncture frequency for opening the BBB. VEGF plays an important role in opening the BBB. It is also important to regulate the expression of MMP-9 and GFAP and inhibit the expression of P-gp.

SKP2 promotes the metastasis of pancreatic ductal adenocarcinoma by suppressing TRIM21-mediated PSPC1 degradation.

Despite significant advances in diagnostic techniques and treatment approaches, the prognosis of pancreatic ductal adenocarcinoma (PDAC) is still poor. Previous studies have reported that S-phase kinase-associated protein 2 (SKP2), a subunit of the SCF E3 ubiquitin ligase complex, is engaged in the malignant biological behavior of some tumor entities. However, SKP2 has not been fully investigated in PDAC. In the present study, it was observed that high expression of SKP2 significantly correlates with decreased survival time. Further experiments suggested that SKP2 promotes metastasis by interacting with the putative transcription factor paraspeckle component 1 (PSPC1). According to the results of coimmunoprecipitation and ubiquitination assays, SKP2 depletion resulted in the polyubiquitination of PSPC1, followed by its degradation. Furthermore, the SKP2-mediated ubiquitination of PSPC1 partially depended on the activity of the E3 ligase TRIM21. In addition, inhibition of the SKP2/PSPC1 axis by SMIP004, a traditional inhibitor of SKP2, impaired the migration of PDAC cells. In summary, this study provides novel insight into the mechanisms involved in PDAC malignant progression. Targeting the SKP2/PSPC1 axis is a promising strategy for the treatment of PDAC.

Long-Range Epitaxial MOF Electronics for Continuous Monitoring of Human Breath Ammonia.

As an important biomarker, ammonia exhibits a strong correlation with protein metabolism and specific organ dysfunction. Limited by the immobile instrumental structure, invasive and complicated procedures, and unsatisfactory online sensitivity and selectivity, current medical diagnosis fails to monitor this chemical in real time efficiently. Herein, we present the successful synthesis of a long-range epitaxial metal-organic framework on a millimeter domain-sized single-crystalline graphene substrate (LR-epi-MOF). With a perfect 30° epitaxial angle and a mere 2.8% coincidence site lattice mismatch between the MOF and graphene, this long-range-ordered epitaxial structure boosts the charge transfer from ammonia to the MOF and then to graphene, thereby promoting the overall charge delocalization and exhibiting extraordinary electrical global coupling properties. This unique characteristic imparts a remarkable sensitivity of 0.1 ppb toward ammonia. The sub-ppb detecting capability and high anti-interference ability enable continuous information recording of breath ammonia that is strongly correlated with the intriguing human lifestyle. Wearable electronics based on the LR-epi-MOF could accurately portray the active protein metabolism pattern in real time and provide personal assistance in health management.

A jingmenvirus RNA-dependent RNA polymerase structurally resembles the flavivirus counterpart but with different features at the initiation phase.

Jingmenviruses are a category of emerging segmented viruses that have garnered global attention in recent years, and are close relatives of the flaviviruses in the Flaviviridae family. One of their genome segments encodes NSP1 homologous to flavivirus NS5. NSP1 comprises both the methyltransferase (MTase) and RNA-dependent RNA polymerase (RdRP) modules playing essential roles in viral genome replication and capping. Here we solved a 1.8-Å resolution crystal structure of the NSP1 RdRP module from Jingmen tick virus (JMTV), the type species of jingmenviruses. The structure highly resembles flavivirus NS5 RdRP despite a sequence identity less than 30%. NSP1 RdRP enzymatic properties were dissected in a comparative setting with several representative Flaviviridae RdRPs included. Our data indicate that JMTV NSP1 produces characteristic 3-mer abortive products similar to the hepatitis C virus RdRP, and exhibits the highest preference of terminal initiation and shorter-primer usage. Unlike flavivirus NS5, JMTV RdRP may require the MTase for optimal transition from initiation to elongation, as an MTase-less NSP1 construct produced more 4-5-mer intermediate products than the full-length protein. Taken together, this work consolidates the evolutionary relationship between the jingmenvirus group and the Flaviviridae family, providing a basis to the further understanding of their viral replication/transcription process.

Spatially heterogeneous shifts in vegetation phenology induced by climate change threaten the integrity of the avian migration network.

Phenological responses to climate change frequently vary among trophic levels, which can result in increasing asynchrony between the peak energy requirements of consumers and the availability of resources. Migratory birds use multiple habitats with seasonal food resources along migration flyways. Spatially heterogeneous climate change could cause the phenology of food availability along the migration flyway to become desynchronized. Such heterogeneous shifts in food phenology could pose a challenge to migratory birds by reducing their opportunity for food availability along the migration path and consequently influencing their survival and reproduction. We develop a novel graph-based approach to quantify this problem and deploy it to evaluate the condition of the heterogeneous shifts in vegetation phenology for 16 migratory herbivorous waterfowl species in Asia. We show that climate change-induced heterogeneous shifts in vegetation phenology could cause a 12% loss of migration network integrity on average across all study species. Species that winter at relatively lower latitudes are subjected to a higher loss of integrity in their migration network. These findings highlight the susceptibility of migratory species to climate change. Our proposed methodological framework could be applied to migratory species in general to yield an accurate assessment of the exposure under climate change and help to identify actions for biodiversity conservation in the face of climate-related risks.

Spatiotemporal trends of hemorrhagic fever with renal syndrome (HFRS) in China under climate variation.

Hemorrhagic fever with renal syndrome (HFRS) is a zoonotic disease caused by the rodent-transmitted orthohantaviruses (HVs), with China possessing the most cases globally. The virus hosts in China are Apodemus agrarius and Rattus norvegicus, and the disease spread is strongly influenced by global climate dynamics. To assess and predict the spatiotemporal trends of HFRS from 2005 to 2098, we collected historical HFRS data in mainland China (2005-2020), historical and projected climate and population data (2005-2098), and spatial variables including biotic, environmental, topographical, and socioeconomic. Spatiotemporal predictions and mapping were conducted under 27 scenarios incorporating multiple integrated representative concentration pathway models and population scenarios. We identify the type of magistral HVs host species as the best spatial division, including four region categories. Seven extreme climate indices associated with temperature and precipitation have been pinpointed as key factors affecting the trends of HFRS. Our predictions indicate that annual HFRS cases will increase significantly in 62 of 356 cities in mainland China. Rattus regions are predicted to be the most active, surpassing Apodemus and Mixed regions. Eighty cities are identified as at severe risk level for HFRS, each with over 50 reported cases annually, including 22 new cities primarily located in East China and Rattus regions after 2020, while 6 others develop new risk. Our results suggest that the risk of HFRS will remain high through the end of this century, with Rattus norvegicus being the most active host, and that extreme climate indices are significant risk factors. Our findings can inform evidence-based policymaking regarding future risk of HFRS.

Ribosomal protein S6 kinase 2 (RPS6KB2) is a potential immunotherapeutic target for cancer that upregulates proinflammatory cytokines.

BACKGROUND: Cancer is still a leading cause of mortality. Over the years, cancer therapy has undergone significant advances driven by advancements in science and technology. A promising area of drug discovery in this field involves the development of therapeutic targets for cancer treatment. The urgent need to identify new pharmacological targets arises from the impact of tumor resistance on the effectiveness of current medications. Specifically, the RPS6KB2 gene on chromosome 11 has been implicated in cell cycle regulation and exhibits higher expression levels in tumor tissue. Given this association, there is a potential for this gene to serve as a target for cancer treatment. METHODS: We conducted an analysis using the GTEx, TCGA, and CCLE databases to explore the relationship between RPS6KB2 and immune infiltration, the tumor microenvironment (TME), microsatellite instability (MSI), and more. Cell proliferation was assessed using EDU detection, while cell invasion and migration were evaluated via wound healing and Transwell assays. Additionally, western blot analysis was employed to measure expression of Bax, Bcl-2, MMP2, MMP9, PCNA, and proinflammatory factors. RESULTS: Through data analysis and molecular biology methods, our study carefully examined the potential role of RPS6KB2 in cancer therapy. The data revealed that RPS6KB2 is aberrantly expressed in most cancers and is associated with poor prognosis. Further analysis indicated its involvement in cancer cell apoptosis and migration, as well as its role in cancer immune processes. We validated the significance of RPS6KB2 in hepatocellular carcinoma (HCC), highlighting its capacity to upregulate proinflammatory cytokines. CONCLUSION: Our research indicates that RPS6KB2 is a prognostic biomarker associated with immune infiltration in cancer that can affect antitumor immunity by increasing secretion of proinflammatory factors, providing a potential drug target for cancer treatment.

Data error propagation in stacked bioclimatic envelope models.

Stacking is the process of overlaying inferred species potential distributions for multiple species based on outputs of bioclimatic envelope models (BEMs). The approach can be used to investigate patterns and processes of species richness. If data limitations on individual species distributions are inevitable, but how do they affect inferences of patterns and processes of species richness? We investigate the influence of different data sources on estimated species richness gradients in China. We fitted BEMs using species distributions data for 334 bird species obtained from (1) global range maps, (2) regional checklists, (3) museum records and surveys, and (4) citizen science data using presence-only (Mahalanobis distance), presence-background (MAXENT), and presence-absence (GAM and BRT) BEMs. Individual species predictions were stacked to generate species richness gradients. Here, we show that different data sources and BEMs can generate spatially varying gradients of species richness. The environmental predictors that best explained species distributions also differed between data sources. Models using citizen-based data had the highest accuracy, whereas those using range data had the lowest accuracy. Potential richness patterns estimated by GAM and BRT models were robust to data uncertainty. When multiple data sets exist for the same region and taxa, we advise that explicit treatments of uncertainty, such as sensitivity analyses of the input data, should be conducted during the process of modeling.

Projecting future labor losses due to heat stress in China under climate change scenarios.

Climate change is expected to increase occupational heat stress, which will lead to diminished work performance and labor losses worldwide. However, sub-regional analyses remain insufficient, especially for countries with a heterogeneous spatial distribution of working populations, industries and climates. Here, we projected heat-induced labor losses in China, by considering local climate simulations, working population characteristics and developing an exposure-response function suitable for Chinese workers. We showed that the annual heat-induced work hours lost (WHL), compared to the baseline of 21.3 billion hours, will increase by 121.1% (111.2%-131.1%), 10.8% (8.3%-15.3%), and -17.8% (-15.3%--20.3%) by the end of the century under RCP(Representative Concentration Pathways)8.5, RCP4.5, and RCP2.6, respectively. We observed an approximately linear upward trend of WHL under RCP8.5, despite the decrease in future working population. Notably, WHL will be most prominent in the southern, eastern and central regions, with Guangdong and Henan accounting for a quarter of national total losses; this is largely due to their higher temperature exposure, larger population size, and higher shares of vulnerable population in total employment. In addition, limiting global warming to 1.5 °C would yield substantial gains. Compared to RCP2.6, RCP4.5, and RCP8.5, all provinces can avoid an average of 11.8%, 33.7%, and 53.9% of annual WHL if the 1.5 °C target is achieved, which is equivalent to avoiding 0.1%, 0.6%, and 1.4% of annual GDP losses in China, respectively. This study revealed climate change will exacerbate future labor losses, and adverse impacts can be minimized by adopting stringent mitigation policies coupled with effective adaptation measures. Policymakers in each province should tailor occupation health protection measures to their circumstances.