•The Very High level of ES occupied 69% of the GBA in 2020.•Urban expansion occupied 78.48% of areas provided a Very High level of ES.•There was an increasing trend of ES in old urban areas.
...Ecosystem services (ESs) have been changed significantly due to human and natural interference, especially in urban megaregions. Numerous studies have revealed the impact of urbanization on regional ecosystem service(ES). However, the research on whether urban expansion has sacrificed the areas providing high ESs, which played a crucial role in sustainable development, was poorly understood. This study analyzed the spatial variation of ES supply from 2000 to 2020 under the influence of urban expansion in the Guangdong-Hong Kong-Macao Greater Bay Area (GBA). The result showed that GBA has witnessed high-seeped urban development, and nearly 50% of urban expansion encroached on cropland, 25% on forestland, and 25% on waterbody from 2000 to 2020. Secondly, The ESs changed significantly due to urban expansion. Importantly, nearly 74.48% and 59.74% of areas that urban expansion encroached on were the ecological lands that provided a very high level of ESs from 2000 to 2010 and from 2010 to 2020, respectively. However, the direct impact of urban expansion on the ecological lands providing a very high level of ESs has been decreased. Additionally, the increase in ESs in old urban areas also has a positive role in the regional ES. This study expects to systematically assess the direct impact of urbanization on regional ES and provide scientific information on land use planning for sustainable development.
Lupus nephritis (LN) is a representative manifestation in systemic lupus erythematosus (SLE). Some studies have shown that myeloid-derived suppressor cells (MDSCs) play a vital role in the regulation ...of the SLE process. MDSC infiltration in the kidney as well as inflammation and oxidative stress provokes the acceleration and deterioration of LN. Nuclear factor E2-related factor 2 (Nrf2) is thought to be a major regulator of the antioxidant response. Baicalein is a flavonoid with known anti-inflammatory effects and antioxidant response. However, the effects of baicalein on MDSCs, inflammation, and oxidative stress are not evaluated in the development of pristane-induced LN in mice.
The renoprotective effect of baicalein was detected in a pristane-induced lupus mice model. NLRP3 inflammasome activation and NF-κB phosphorylation as well as reactive oxygen species (ROS) production and Nrf2 activation were examined. The percentages and function changes of MDSCs were measured. The possible mechanisms of the underlying effects of baicalein on ROS production and signaling pathways of Nrf2/heme-oxygenase (HO)-1, NLRP3 inflammasome, and NF-κB phosphorylation in lipopolysaccharide (LPS)-primed MDSCs were analyzed.
Baicalein reduced proteinuria and attenuated renal function impairment and renal histopathology including intrinsic cell proliferation, cellular crescents, and podocyte injury as well as glomerulonephritis activity in lupus mice. Moreover, baicalein downregulated the activation of NLRP3 inflammasome and levels of ROS or NF-κB phosphorylation, and it enhanced Nrf2 activation. Of note, baicalein inhibited the expansion of MDSCs and improved the function of MDSCs in lupus mice. Through analyzing LPS-primed MDSCs in vitro, baicalein was found to exhibit cytoprotective effects coincident with the induction of Nrf2/HO-1 signaling and the suppression of the NLRP3 inflammasome.
The data show that baicalein alleviates the symptoms of pristane-induced LN and suggest that the alleviation may be attributed to inhibition of MDSC expansion and regulation of the balance of the Nrf2/HO-1 signal and NLRP3 expression in MDSCs.
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As one of the most promising medical metal implants, magnesium (Mg) or its alloys have shown significant advantages over other candidates attributed to not only their excellent ...biodegradability and suitable mechanical properties but also their osteopromotive effects for bone applications. Prior to approval mandated by the governmental regulatory body, the access to the medical market for Mg-based implants requires a series of testing for assurance of their safety and efficacy via preclinical evaluations and clinical tests including phase 1 and 2 evaluations, and phase 3 of multi-center randomized double blind and placebo-controlled clinical trials. However, as the most widely used protocols for biosafety evaluation of medical devices, current ISO 10993 standards should be carefully reevaluated when directly applying them to predict potential health risks of degradable Mg based biomaterials via cytotoxicity tests due to the huge gap between in vitro and in vivo conditions. Therefore, instead of a direct adoption, modification of current ISO standards for in vitro cytotoxicity test is desirable and justified. The differences in sensitivities of cells to in vitro and in vivo Mg ions and the capability of in vivo circulation system to dilute local degradation products were fully considered to propose modification of current ISO standards. This paper recommended a minimal 6 times to a maximal 10 times dilution of extracts for in vitro cytotoxicity test specified in ISO 10993 part 5 for pure Mg developed as potential orthopedic implants based on literature review and our specifically designed in vitro and in vivo tests presented in the study. Our work may contribute to the progress of biodegradable metals involved translational work.
Emerging evidence suggests that long noncoding RNA (lncRNA) plays pivotal roles in regulating various biological process in human cancers. Titin-antisense RNA1 (TTN-AS1) has been regarded as a tumor ...promoting lncRNA in numerous cancers. However, the clinical significance and biological function of TTN-AS1 in lung adenocarcinoma (LUAD) remain unclear. In the present study, we revealed that the expression of TTN-AS1 was upregulated in LUAD tissues and cell lines. High TTN-AS1 expression was associated with TNM stage and lymph node metastasis of LUAD patients. In addition, high expression of TTN-AS1 was correlated with poor postoperative prognosis of LUAD patients. Knockdown of TTN-AS1 significantly inhibited the growth, proliferation, migration, and invasion ability of LUAD cells in vitro. Then, by using bioinformation analysis and luciferase reporter experiment, we identified that TTN-AS1 could function as a competing endogenous RNA (ceRNA) by sponging miR-142-5p to regulate the expression of cyclin-dependent kinase 5 (CDK5) in LUAD. Since CDK5 is a key regulator in the process of epithelial mesenchymal transition (EMT), we detected the expression of EMT-related proteins, consequently, EMT was suppressed by knockdown of TTN-AS1 while this phenomenon was rescued by miR-142-5p inhibitor. Taken above, our study revealed that TTN-AS1 played an important role in LUAD progression. TTN-AS1/miR-142-5p/CDK5 regulatory axis may serve as a novel therapeutic target in the treatment of LUAD.
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•Completely alloyed RuCu/CNFs nanoparticles are for the first time designed for Li-CO2 batteries.•Li-CO2 batteries with i-Ru4Cu1/CNFs cathode show record-high rate capability.•Li-CO2 ...batteries with i-Ru4Cu1/CNFs cathode deliver superb Coulombic efficiency of 99.3%.•This work demonstrates the exceptional activity of RuCu bimetallic nanoalloys for high-performance Li-CO2 batteries.
Rechargeable Li-CO2 batteries are attracting increasing attention due to their high energy density and ability to capture greenhouse gas CO2. However, the difficulty in decomposing electronically insulating and electrochemically sluggish Li2CO3 discharge products under low charge voltages is still a major challenge. Herein, for the first time, a composite of intermixed ruthenium-copper alloy nanoparticles uniformly anchored on carbon nanofibers (i-RuCu/CNFs) as efficient cathode electrocatalysts for Li-CO2 batteries is well designed. Remarkably, the Li-CO2 batteries with i-Ru4Cu1/CNFs cathodes can be steadily cycled for over 110 cycles without capacity decay. And they show record-high rate capability along with much decreased overpotentials of 1.45 and 1.56 V even at current densities of 1000 and 2000 mA g−1, respectively. Moreover, a high discharge capacity of 15,753 mAh g−1 is obtained for Li-CO2 batteries based on i-Ru4Cu1/CNFs, and 99.3% of discharged capacity could be reversibly charged, giving the significant Coulombic efficiency. This work demonstrates the powerfully catalytic activity of intermixed RuCu nanoalloys for easily decomposing discharge products in Li-CO2 batteries and provides more insights to design more highly efficient cathode electrocatalysts for Li-CO2 batteries and beyond.
Peri-tunnel bone loss after anterior cruciate ligament (ACL) reconstruction is often observed clinically, which may detrimentally affect tendon graft integration with surrounding bone tissue. ...Biodegradable magnesium (Mg) based fixators in terms of interference screws may be suitable for fixation of the tendon graft due to their favorable effects on promotion of new bone formation. However, the poor mechanical strength of Mg is still one of the major challenges for its clinical applications. The addition of alloying elements into Mg is one of the strategies to improve their mechanical properties. Here, we prepared magnesium (Mg)-(4 and 6 wt%) zinc (Zn)-(0.2, 0.5, 1 and 2 wt%) strontium(Sr) alloys and tested their potential for attenuating peri-tunnel bone loss in ACL reconstruction. The optimal (6 wt%) Zn and (0.5 wt%) Sr contents were screened with respect to the microstructures, mechanical properties and corrosion behavior of these alloys. As compared to pure Mg, Mg-6Zn-0.5Sr rods and screws showed significantly higher torque and torsional stiffness in both numerical and experimental analysis. The in vitro cyto-compatibility of Mg-6Zn-0.5Sr alloy was assessed with MTT test and fluorescence assay. The Mg-6Zn-0.5Sr interference screw was designed for fixation of the tendon graft to the femoral tunnel in a rabbit model of ACL reconstruction, with a commercially available poly-lactide (PLA) screw for comparison. In vivo high resolution peripheral quantitative computed tomography (HR-pQCT) scanning was performed to measure the degradation behavior of Mg-6Zn-0.5Sr interference screws and peri-tunnel bone quality at 0, 6, 12 and 16 weeks post-surgically. Mg-6Zn-0.5Sr interference screw was completely degraded within 12 weeks after surgery. The peri-tunnel bone loss was significantly attenuated in the Mg-6Zn-0.5Sr group when compared to the PLA group. Importantly, the bony ingrowth rapidly filled the cavity left by the complete degradation of Mg-6Zn-0.5Sr screws at 16 weeks. In histological analysis, more bone formation was observed in peri-tunnel region in the Mg-6Zn-0.5Sr group in comparison to the PLA group at 6 and 16 weeks after surgery. The femur-tendon graft-tibia complex was harvested at the end of week 6 and 16 post-operation for tensile testing. The maximum load to failure was significantly improved in the Mg-6Zn-0.5Sr group at week 16 post-operation. Therefore, our results indicate the potential clinical application of MgZnSr based interference screws in ACL reconstruction.
Mitogen-activated protein kinase (MAPK) cascades are highly conserved signal transduction modules, which transmit environmental signals in plant cells through stepwise phosphorylation and play ...indispensable roles in a wide range of physiological and biochemical processes. Here, we isolated and characterized a gene encoding MKK2 protein from poplar through the rapid amplification of cDNA ends (RACE). The full-length PeMKK2a gene was 1571 bp, including a 1068 bp open reading frame (ORF) encoding 355 amino acids, and the putative PeMKK2a protein belongs to the PKc_like (protein kinase domain) family (70–336 amino acids) in the PKc_MAPKK_plant subfamily and contains 62 sites of possible phosphorylation and two conserved domains, DLK and S/T-xxxxx-S/T. Detailed information about its gene structure, sequence similarities, subcellular localization, and transcript profiles under salt-stress conditions was revealed. Transgenic poplar lines overexpressing PeMKK2a exhibited higher activities of superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) than non-transgenic poplar under salt stress conditions. These results will provide insight into the roles of MAPK signaling cascades in poplar response to salt stress.
Lung cancer causes significant morbidity and mortality in China and worldwide. In China, lung cancer accounts for nearly one-fourth of all cancer deaths. Non-small cell lung cancer (NSCLC) is the ...predominant type of lung cancer, accounting for approximately 80%-85% of all lung cancer cases. Immunotherapy with immune checkpoint inhibitors (ICIs) is revolutionizing the treatment of NSCLC. Immune checkpoint molecules, including PD-1/PD-L1 and CTLA-4, can suppress immune responses by delivering negative signals to T cells. By interfering with these immunosuppressive axes, ICIs unleash antitumor immune responses, ultimately eliminating cancer cells. ICIs have demonstrated promising antitumor efficacy in NSCLC, and mounting evidence supports the use of ICIs in treatment-naïve patients with advanced NSCLC. A comprehensive overview of current and emerging ICIs for the first-line treatment of NSCLC in China will facilitate a better understanding of NSCLC immunotherapy using ICIs and optimize the clinical use of ICIs in previously untreated Chinese patients with NSCLC. Herein, we review the efficacy and safety of currently approved and investigational ICIs as the first-line treatment of NSCLC in China. We also discuss the challenges limiting more widespread use of ICIs and future directions in the first-line treatment of NSCLC using ICIs.
Understanding gene function and regulation in homeostasis and disease requires knowledge of the cellular and tissue contexts in which genes are expressed. Here, we applied four single-nucleus RNA ...sequencing methods to eight diverse, archived, frozen tissue types from 16 donors and 25 samples, generating a cross-tissue atlas of 209,126 nuclei profiles, which we integrated across tissues, donors, and laboratory methods with a conditional variational autoencoder. Using the resulting cross-tissue atlas, we highlight shared and tissue-specific features of tissue-resident cell populations; identify cell types that might contribute to neuromuscular, metabolic, and immune components of monogenic diseases and the biological processes involved in their pathology; and determine cell types and gene modules that might underlie disease mechanisms for complex traits analyzed by genome-wide association studies.
Column attached ventilation (CAV) is a new form of air distribution based on pillars widely distributed in buildings. Due to thermal buoyancy in the room, the airflow mechanism and performance of CAV ...is uncertain when it is applied for winter heating, especially in buildings with large space. In this study, a simplified three-dimensional model was established based on a shopping mall. A Computational Fluid Dynamics (CFD) method was employed to simulate the airflow in the room. Archimedes number (Ar) was used to study air distribution and ventilation performance. Results indicated that CAV could be used for room heating, and inertia force was the main driving force of the airflow. In the occupied zone, air velocity and temperature could be controlled by supply air velocity and temperature. Ar was related to air distribution and ventilation effect. In selected cases, Ar less than 2.241 × 10−3 was the prerequisite for effective air distribution. Heat removal effectiveness was linearly related to Ar, and it increased by about 0.01 when Ar reduced by 0.1. CAV saved more energy than mixing ventilation to achieve the same parameters of the occupied zone. These results provide a theoretical basis for the application of CAV in winter conditions.
•Column attached ventilation (CAV) can be used for room heating.•Archimedes number can determine whether CAV forms effective air distribution.•In the occupied zone, the inertial force dominates the CAV air distribution.•Average room temperature increases linearly with increasing supply air temperature.•CAV has a higher heat and CO2 removal effectiveness than mixing ventilation.