The establishment of either forest or grassland on degraded cropland has been proposed as an effective method for climate change mitigation because these land use types can increase soil carbon (C) ...stocks. This paper synthesized 135 recent publications (844 observations at 181 sites) focused on the conversion from cropland to grassland, shrubland or forest in China, better known as the ‘Grain‐for‐Green’ Program to determine which factors were driving changes to soil organic carbon (SOC). The results strongly indicate a positive impact of cropland conversion on soil C stocks. The temporal pattern for soil C stock changes in the 0–100 cm soil layer showed an initial decrease in soil C during the early stage (<5 years), and then an increase to net C gains (>5 years) coincident with vegetation restoration. The rates of soil C change were higher in the surface profile (0–20 cm) than in deeper soil (20–100 cm). Cropland converted to forest (arbor) had the additional benefit of a slower but more persistent C sequestration capacity than shrubland or grassland. Tree species played a significant role in determining the rate of change in soil C stocks (conifer < broadleaf, evergreen < deciduous forests). Restoration age was the main factor, not temperature and precipitation, affecting soil C stock change after cropland conversion with higher initial soil C stock sites having a negative effect on soil C accumulation. Soil C sequestration significantly increased with restoration age over the long‐term, and therefore, the large scale of land‐use change under the ‘Grain‐for‐Green’ Program will significantly increase China's C stocks.
Genomic instability is the hallmark of various cancers with the increasing accumulation of DNA damage. The application of radiotherapy and chemotherapy in cancer treatment is typically based on this ...property of cancers. However, the adverse effects including normal tissues injury are also accompanied by the radiotherapy and chemotherapy. Targeted cancer therapy has the potential to suppress cancer cells' DNA damage response through tailoring therapy to cancer patients lacking specific DNA damage response functions. Obviously, understanding the broader role of DNA damage repair in cancers has became a basic and attractive strategy for targeted cancer therapy, in particular, raising novel hypothesis or theory in this field on the basis of previous scientists' findings would be important for future promising druggable emerging targets. In this review, we first illustrate the timeline steps for the understanding the roles of DNA damage repair in the promotion of cancer and cancer therapy developed, then we summarize the mechanisms regarding DNA damage repair associated with targeted cancer therapy, highlighting the specific proteins behind targeting DNA damage repair that initiate functioning abnormally duo to extrinsic harm by environmental DNA damage factors, also, the DNA damage baseline drift leads to the harmful intrinsic targeted cancer therapy. In addition, clinical therapeutic drugs for DNA damage and repair including therapeutic effects, as well as the strategy and scheme of relative clinical trials were intensive discussed. Based on this background, we suggest two hypotheses, namely "environmental gear selection" to describe DNA damage repair pathway evolution, and "DNA damage baseline drift", which may play a magnified role in mediating repair during cancer treatment. This two new hypothesis would shed new light on targeted cancer therapy, provide a much better or more comprehensive holistic view and also promote the development of new research direction and new overcoming strategies for patients.
Radiotherapy is one of the most common countermeasures for treating a wide range of tumors. However, the radioresistance of cancer cells is still a major limitation for radiotherapy applications. ...Efforts are continuously ongoing to explore sensitizing targets and develop radiosensitizers for improving the outcomes of radiotherapy. DNA double-strand breaks are the most lethal lesions induced by ionizing radiation and can trigger a series of cellular DNA damage responses (DDRs), including those helping cells recover from radiation injuries, such as the activation of DNA damage sensing and early transduction pathways, cell cycle arrest, and DNA repair. Obviously, these protective DDRs confer tumor radioresistance. Targeting DDR signaling pathways has become an attractive strategy for overcoming tumor radioresistance, and some important advances and breakthroughs have already been achieved in recent years. On the basis of comprehensively reviewing the DDR signal pathways, we provide an update on the novel and promising druggable targets emerging from DDR pathways that can be exploited for radiosensitization. We further discuss recent advances identified from preclinical studies, current clinical trials, and clinical application of chemical inhibitors targeting key DDR proteins, including DNA-PKcs (DNA-dependent protein kinase, catalytic subunit), ATM/ATR (ataxia-telangiectasia mutated and Rad3-related), the MRN (MRE11-RAD50-NBS1) complex, the PARP (polyADP-ribose polymerase) family, MDC1, Wee1, LIG4 (ligase IV), CDK1, BRCA1 (BRCA1 C terminal), CHK1, and HIF-1 (hypoxia-inducible factor-1). Challenges for ionizing radiation-induced signal transduction and targeted therapy are also discussed based on recent achievements in the biological field of radiotherapy.
Sepsis is a systemic inflammatory response syndrome caused by infection, resulting in organ dysfunction. Sepsis‐induced acute kidney injury (AKI) is one of the most common potential complications. ...Increasing reports have shown that M1 and M2 macrophages both take part in the progress of AKI by influencing the level of inflammatory factors and the cell death, including pyroptosis. However, whether M1 and M2 macrophages regulate AKI by secreting exosome remains unknown. In the present study, we isolated the exosomes from M1 and M2 macrophages and used Western blot and enzyme‐linked immunosorbent assay (ELISA) to investigate the effect of M1 and M2 exosomes on cell pyroptosis. miRNA sequencing was used to identify the different miRNA in M1 and M2 exosomes. Luciferase reporter assay was used to verify the target gene of miRNA. We confirmed that exosomes excreted by macrophages regulated cell pyroptosis in vitro by using Western blot and ELISA. miRNA sequencing revealed the differentially expressed level of miRNAs in M1 and M2 exosomes, among which miR‐93‐5p was involved in the regulation of pyroptosis. By using bioinformatics predictions and luciferase reporter assay, we found that thioredoxin–interacting protein (TXNIP) was a direct target of miR‐93‐5p. Further in vitro and in vivo experiments indicated that exosomal miR‐93‐5p regulated the TXNIP directly to influence the pyroptosis in renal epithelial cells, which explained the functional difference between different phenotypes of macrophages. This study might provide new targets for the treatment of sepsis‐induced AKI.
Post‐synthetic modification (PSM) is an effective approach for the tailored functionalization of metal‐organic architectures, but its generalizability remains challenging. Herein we report a general ...covalent PSM strategy to functionalize PdnL2n metal‐organic cages (MOCs, n=2, 12) through an efficient Diels–Alder cycloaddition between peripheral anthracene substituents and various functional motifs bearing a maleimide group. As expected, the solubility of functionalized Pd12L24 in common solvents can be greatly improved. Interestingly, concentration‐dependent circular dichroism and aggregation‐induced emission are achieved with chiral binaphthol (BINOL)‐ and tetraphenylethylene‐modified Pd12L24, respectively. Furthermore, Pd12L24 can be introduced with two different functional groups (e.g., chiral BINOL and achiral pyrene) through a step‐by‐step PSM route to obtain chirality‐induced circularly polarized luminescence. Moreover, similar results are readily observed with a smaller Pd2L4 system.
Two PdnL2n (n=2, 12) type metal‐organic cages (MOCs) decorated with anthracene groups have been successfully functionalized by a covalent post‐synthetic modification (PSM) approach. This has led to the modified MOCs having new functions compared to the parent MOCs (e.g., concentration‐dependent chirality, aggregation‐induced emission, and chirality‐induced circularly polarized luminescence).
The matter state inside neutron stars (NSs) is an exciting problem in astrophysics, nuclear physics, and particle physics. The equation of state (EOS) of NSs plays a crucial role in the present ...multimessenger astronomy, especially after the event of GW170817. We propose a new NS EOS, "QMF18," from the quark level, which describes robust observational constraints from a free-space nucleon, nuclear matter saturation, heavy pulsar measurements, and the tidal deformability of the very recent GW170817 observation. For this purpose, we employ the quark mean-field model, which allows us to tune the density dependence of the symmetry energy and effectively study its correlations with the Love number and the tidal deformability. We provide tabulated data for the new EOS and compare it with other recent EOSs from various many-body frameworks.
Uniaxial compression tests combined with nondestructive testing techniques are performed to explore the roles of non‐isometric flaws in crack developments in brittle rocks. The acoustic emission (AE) ...rate‐process theory is adopted to analyze fracture‐related AE event rate characteristics. The full‐field optical method is applied to detect cracking modes. Experimental results show that AE activity is quite active when the matrix microcracking is dominant, while after each macrocracking event, AE activity becomes inactive because of the stress release. Multiphysical data for each tested flaw configuration faithfully confirm the rupture progressivity. The larger the flaw length ratio, the lower the peak stress (also peak axial strain and elastic modulus), as well as the more progressive the cracking process. Moreover, ultimate failure is triggered by the shear fracturing from the relatively long flaw. The short flaw is conditionally involved in ultimate failure when the stress buildup effect dominates. Finally, the fracture mechanism of brittle rocks with non‐isometric flaws is revealed.
The crack initiation, growth, wrapping and coalescence of two 3D pre-existing cross-embedded flaws in PMMA specimens under uniaxial compression are investigated. The stress–strain curves of PMMA ...specimens with 3D cross-embedded flaws are obtained. The tested PMMA specimens exhibit dominant elastic deformation and eventual brittle failure. The experimental results show that four modes of crack initiation and five modes of crack coalescence are observed. The initiations of oblique secondary crack and anti-wing crack in 3D cracking behaviors are first reported as well as the coalescence of anti-wing cracks. Moreover, two types of crack wrapping are found. Substantial wrapping of petal cracks, which includes open and closed modes of wrapping, appears to be the major difference between 2D and 3D cracking behaviors of pre-existing flaws, which are also first reported. Petal crack wraps symmetrically from either the propagated wing cracks or the coalesced wing cracks. Besides, only limited growth of petal cracks is observed, and ultimate failure of specimens is induced by the further growth of the propagated wing crack. The fracture mechanism of the tested PMMA specimens is finally revealed. In addition, the initiation stress and the peak stress versus the geometry of two 3D pre-existing cross-embedded flaws are also investigated in detail.
Photodynamic therapy (PDT) is ineffective against deeply seated metastatic tumors due to poor penetration of the excitation light. Herein, we developed a biomimetic nanoreactor (bio-NR) to achieve ...synergistic chemiexcited photodynamic-starvation therapy against tumor metastasis. Photosensitizers on the hollow mesoporous silica nanoparticles (HMSNs) are excited by chemical energy in situ of the deep metastatic tumor to generate singlet oxygen (
O
) for PDT, and glucose oxidase (GOx) catalyzes glucose into hydrogen peroxide (H
O
). Remarkably, this process not only blocks the nutrient supply for starvation therapy but also provides H
O
to synergistically enhance PDT. Cancer cell membrane coating endows the nanoparticle with biological properties of homologous adhesion and immune escape. Thus, bio-NRs can effectively convert the glucose into
O
in metastatic tumors. The excellent therapeutic effects of bio-NRs in vitro and in vivo indicate their great potential for cancer metastasis therapy.
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