Epitaxial Metal-Organic Framework-Mediated Electron Relay for H2 Detection on Demand.

Hydrogen is regarded as one of the most promising clean substitutes for fossil fuels toward a carbon-zero society. However, the safety management of the upcoming hydrogen energy infrastructure has not been fully prepared, in contrast to the well-established natural gas and gasoline systems. On the frontline is the guard post of hydrogen detectors, which need to be deployed on various structural surfaces and environmental conditions. Conventional hydrogen detectors are usually bulky and environmentally sensitive, limiting their flexible and conformal deployment to various locations, such as pipelines and valves. Herein, we demonstrate the successful synthesis of a palladium-modified epitaxial metal-organic framework (MOF) on single-layer graphene to fabricate a heterostructure material (Epi-MOF-Pd). Device based on the heterostructure demonstrates high sensitivity toward low- concentration H2 (155% resistance response to 1% H2 within 12 s, a theoretical detection limit of 3 ppm). The 25 nm epitaxial MOF acquires electrons from the Pd nanoparticles after the trace amount of H2 is chemically adsorbed and further relays the electrons to the highly conductive graphene. The Epi-MOF-Pd is both flexible and enduring, and maintains stable detection over 10 000 bending cycles. Through photolithography, device arrays with a density of 3000 units/cm2 are successfully fabricated. This versatile material provides a prospective avenue for the mass production of high-performance chemical-sensitive electronics, which could significantly improve the hydrogen safety management on demand.

Clinical characteristics of peripapillary hyperreflective ovoid mass-like structures in myopic children.

AIM: To describe the characteristics of peripapillary hyperreflective ovoid mass-like structure (PHOMS) in myopic children and to investigate factors associated with PHOMS. METHODS: This retrospective observational study included 101 eyes of 101 children (age ≤17y) with myopia. All included patients underwent comprehensive clinical examination. Optic nerve canal parameters, including disc diameter, optic nerve head (ONH) tilt angle, and border tissue angle were measured using serial enhanced-depth imaging spectral-domain optical coherence tomography (EDI-OCT). Based on the optic disc drusen consortium's definition of PHOMS, eyes were classified as PHOMS group and non-PHOMS group. PHOMS was categorized according to height. RESULTS: Sixty-seven (66.3%) eyes were found with PHOMS. Small PHOMS could only be detected by optical coherence tomography (OCT). Medium PHOMS could be seen with blurred optic disc borders corresponding to OCT. The most frequent location of PHOMS was at the nasosuperior (91%, 61 of 67 eyes) to ONH disc. The axial length and spherical equivalent were more myopic in the PHOMS group than in the non-PHOMS group (both P<0.001). ONH tilt angle was also significantly greater in PHOMS group than in non-PHOMS group [8.90 (7.16-10.54) vs 3.93 (3.09-5.25), P<0.001]. Border tissue angle was significantly smaller in PHOMS group than in non-PHOMS group [29.70 (20.90-43.81) vs 45.62 (35.18-60.45), P<0.001]. In the multivariable analysis, spherical equivalent (OR=3.246, 95%CI=1.209-8.718, P=0.019) and ONH tilt angle (OR=3.275, 95%CI=1.422-7.542, P=0.005) were significantly correlated with PHOMS. There was no disc diameter associated with PHOMS. In the linear regression analysis, border tissue angle was negatively associated with PHOMS height (ß=-2.227, P<0.001). CONCLUSION: PHOMS is associated with optic disc tilt and optic disc nasal shift in myopia. Disc diameter is not a risk factor for PHOMS. The changes in ONH caused by axial elongation facilitated an understanding of the mechanism of PHOMS.

Genetic influence on vascular smooth muscle cell apoptosis.

Vascular smooth muscle cell (VSMC) proliferation, migration, and apoptosis play important roles in many physiological processes and pathological conditions. To identify genetic influences on VSMC behavior, we measured these traits and undertook genome-wide association studies in primary umbilical artery-derived VSMCs from >2000 individuals. Although there were no genome-wide significant associations for VSMC proliferation or migration, genetic variants at two genomic loci (7p15.3 and 7q32.3) showed highly significant associations with VSMC apoptosis (P = 1.95 × 10-13 and P = 7.47 × 10-9, respectively). The lead variant at the 7p51.3 locus was associated with increased expression of the GSDME and PALS2 genes in VSMCs. Knockdown of GSDME or PALS2 in VSMCs attenuated apoptotic cell death. A protein co-immunoprecipitation assay indicated that GSDME complexed with PALS2. PALS2 knockdown attenuated activated caspase-3 and GSDME fragmentation, whilst GSDME knockdown also reduced activated caspase-3. These findings provide new insights into the genetic regulation of VSMC apoptosis, with potential utility for therapeutic development.

Gastroenteropancreatic neuroendocrine neoplasms: current development, challenges, and clinical perspectives.

Neuroendocrine neoplasms (NENs) are highly heterogeneous and potentially malignant tumors arising from secretory cells of the neuroendocrine system. Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are the most common subtype of NENs. Historically, GEP-NENs have been regarded as infrequent and slow-growing malignancies; however, recent data have demonstrated that the worldwide prevalence and incidence of GEP-NENs have increased exponentially over the last three decades. In addition, an increasing number of studies have proven that GEP-NENs result in a limited life expectancy. These findings suggested that the natural biology of GEP-NENs is more aggressive than commonly assumed. Therefore, there is an urgent need for advanced researches focusing on the diagnosis and management of patients with GEP-NENs. In this review, we have summarized the limitations and recent advancements in our comprehension of the epidemiology, clinical presentations, pathology, molecular biology, diagnosis, and treatment of GEP-NETs to identify factors contributing to delays in diagnosis and timely treatment of these patients.

Dihydroartemisinin breaks the immunosuppressive tumor niche during cisplatin treatment in Hepatocellular carcinoma.

OBJECTIVE: Hepatocellular carcinoma, characterized by high mortality rates, often exhibits limited responsiveness to conventional treatments such as surgery, radiotherapy, and chemotherapy. Therefore, identifying a sensitizer for cisplatin has become crucial. Dihydroartemisinin, known for its potent role of tumor treatment, arises as a prospective candidate for cisplatin sensitization in clinical settings. METHODS: A mouse model of liver tumor was established through chemical induction of DEN/TCPOBOP. Upon successful model establishment, ultrasound was employed to detect tumors, Hematoxylin and eosin staining was conducted for observation of liver tissue pathology, and ELISA was utilized to assess cytokine changes (IFN-γ, IL-2, IL-4, IL-10, TGF-ß, IL-1ß, CCL2, and CCL21) in peripheral blood, para-tumor tissues, and tumor tissues. The infiltration of CD8+T cells and macrophages in tumor tissue sections was detected by immunofluorescence. RESULTS: Dihydroartemisinin combined with cisplatin obviously restrained the growth of liver tumors in mice and improved the weight and spleen loss caused by cisplatin. Cisplatin treatment of liver tumor mice increased the content of CCL2 and the number of macrophages in tumor tissues and promoted the formation of an immunosuppressive microenvironment. The combination therapy decreased the content of TGF-ß in tumor tissues while increasing CCL2 levels in para-tumor tissues. Both combination therapy and cisplatin alone increased the number of CD8+T cells in tumor tissue, but there was no difference between them. CONCLUSION: Dihydroartemisinin combined with cisplatin obviously prevented the deterioration of liver tumor in hepatocellular carcinoma mice and improve the therapeutic effect of cisplatin by improving the immunosuppressive microenvironment induced by cisplatin. Our findings provide a theoretical basis for considering dihydroartemisinin as an adjuvant drug for cisplatin in the treatment of hepatocellular carcinoma in the future.

3D-printed Bi2Te3-based Thermoelectric Generators for Energy Harvesting and Temperature Response.

Thermoelectric generators (TEGs) are environmentally friendly energy harvesting technologies that hold great promise in the field of self-powered electronics and sensing. However, the current development of thermoelectric (TE) devices has largely lagged behind the development of thermoelectric materials, especially in the preparation of thermoelectric components with customizable shapes and excellent properties, which largely limits their practical applications. These issues can be effectively addressed by using 3D printing technology. Here, we print multiple p-type thermoelectric legs (pins) consecutively with this simple technique, and the printed TEGs have excellent thermal potential (288 µV K-1 at room temperature) and excellent temperature response properties, which exhibited an output voltage of 127.94 mV at a temperature difference (ΔT) of 40 K. The 3D-printed thermoelectric generator enables the collection of thermal energy. In addition, the device has excellent temperature sensing characteristics, and this temperature signal to electrical signal conversion is very rapid, which enables temperature sensing alarms in a wide temperature domain. Combining these features, an energy harvesting and electrical alarm concept for home-scale applications is proposed, which is expected to provide a diverse research idea for the application of next-generation thermoelectric devices.

Mapping global lake aquatic vegetation dynamics using 10-m resolution satellite observations.

Aquatic vegetation is crucial for improving water quality, supporting fisheries and preserving biodiversity in lakes. Monitoring the spatiotemporal dynamics of aquatic vegetation is indispensable for the assessment and protection of lake ecosystems. Nevertheless, a comprehensive global assessment of lacustrine aquatic vegetation is lacking. This study introduces an automatic identification algorithm (with a total accuracy of 94.4%) for Sentinel-2 MSI, enabling the first-ever global mapping of aquatic vegetation distribution in 1.4 million lakes using 14.8 million images from 2019 to 2022. Results show that aquatic vegetation occurred in 81,116 lakes across six continents over the past four years, covering a cumulative maximum aquatic vegetation area (MVA) of 16,111.8 km2. The global median aquatic vegetation occurrence (VO, in %) is 3.0%, with notable higher values observed in South America (7.4%) and Africa (4.1%) compared with Asia (2.7%) and North America (2.4%). High VO is also observed in lakes near major rivers such as the Yangtze, Ob, and Paraná Rivers. Integrating historical data with our calculated MVA, the aquatic vegetation changes in 170 lakes worldwide were analyzed. It shows that 72.4% (123/170) of lakes experienced a decline in aquatic vegetation from the early 1980s to 2022, encompassing both submerged and overall aquatic vegetation. The most substantial decrease is observed in Asia and Africa. Our findings suggest that, beyond lake algal blooms and temperature, the physical characteristics of the lakes and their surrounding environments could also influence aquatic vegetation distribution. Our research provides valuable information for the conservation and restoration of lacustrine aquatic vegetation.

Cryo-EM structures of Thogoto virus polymerase reveal unique RNA transcription and replication mechanisms among orthomyxoviruses.

Influenza viruses and thogotoviruses account for most recognized orthomyxoviruses. Thogotoviruses, exemplified by Thogoto virus (THOV), are capable of infecting humans using ticks as vectors. THOV transcribes mRNA without the extraneous 5' end sequences derived from cap-snatching in influenza virus mRNA. Here, we report cryo-EM structures to characterize THOV polymerase RNA synthesis initiation and elongation. The structures demonstrate that THOV RNA transcription and replication are able to start with short dinucleotide primers and that the polymerase cap-snatching machinery is likely non-functional. Triggered by RNA synthesis, asymmetric THOV polymerase dimers can form without the involvement of host factors. We confirm that, distinctive from influenza viruses, THOV-polymerase RNA synthesis is weakly dependent of the host factors ANP32A/B/E in human cells. This study demonstrates varied mechanisms in RNA synthesis and host factor utilization among orthomyxoviruses, providing insights into the mechanisms behind thogotoviruses' broad-infectivity range.

Relational Part-Aware Learning for Complex Composite Object Detection in High-Resolution Remote Sensing Images.

In high-resolution remote sensing images (RSIs), complex composite object detection (e.g., coal-fired power plant detection and harbor detection) is challenging due to multiple discrete parts with variable layouts leading to complex weak inter-relationship and blurred boundaries, instead of a clearly defined single object. To address this issue, this article proposes an end-to-end framework, i.e., relational part-aware network (REPAN), to explore the semantic correlation and extract discriminative features among multiple parts. Specifically, we first design a part region proposal network (P-RPN) to locate discriminative yet subtle regions. With butterfly units (BFUs) embedded, feature-scale confusion problems stemming from aliasing effects can be largely alleviated. Second, a feature relation Transformer (FRT) plumbs the depths of the spatial relationships by part-and-global joint learning, exploring correlations between various parts to enhance significant part representation. Finally, a contextual detector (CD) classifies and detects parts and the whole composite object through multirelation-aware features, where part information guides to locate the whole object. We collect three remote sensing object detection datasets with four categories to evaluate our method. Consistently surpassing the performance of state-of-the-art methods, the results of extensive experiments underscore the effectiveness and superiority of our proposed method.

A Novel Drug Candidate for Sepsis Targeting Heparanase by Inhibiting Cytokine Storm.

Sepsis is an infection-triggered, rapidly progressive systemic inflammatory syndrome with a high mortality rate. Currently, there are no promising therapeutic strategies for managing this disease in the clinic. Heparanase plays a crucial role in the pathology of sepsis, and its inhibition can significantly relieve related symptoms. Here, a novel heparanase inhibitor CV122 is rationally designed and synthesized, and its therapeutic potential for sepsis with Lipopolysaccharide (LPS) and Cecal Ligation and Puncture (CLP)-induced sepsis mouse models are evaluated. It is found that CV122 potently inhibits heparanase activity in vitro, protects cell surface glycocalyx structure, and reduces the expression of adhesion molecules. In vivo, CV122 significantly reduces the systemic levels of proinflammatory cytokines, prevents organ damage, improves vitality, and efficiently protects mice from sepsis-induced death. Mechanistically, CV122 inhibits the activity of heparanase, reduces its expression in the lungs, and protects glycocalyx structure of lung tissue. It is also found that CV122 provides effective protection from organ damage and death caused by Crimean-Congo hemorrhagic fever virus (CCHFV) infection. These results suggest that CV122 is a potential drug candidate for sepsis therapy targeting heparanase by inhibiting cytokine storm.

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.

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.

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.

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.

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.