Cancer is the most prevalent cause of death globally, and radiotherapy is considered the standard of care for most solid tumors, including lung, breast, esophageal, and colorectal cancers and ...glioblastoma. Resistance to radiation can lead to local treatment failure and even cancer recurrence.
In this review, we have extensively discussed several crucial aspects that cause resistance of cancer to radiation therapy, including radiation-induced DNA damage repair, cell cycle arrest, apoptosis escape, abundance of cancer stem cells, modification of cancer cells and their microenvironment, presence of exosomal and non-coding RNA, metabolic reprogramming, and ferroptosis. We aim to focus on the molecular mechanisms of cancer radiotherapy resistance in relation to these aspects and to discuss possible targets to improve treatment outcomes.
Studying the molecular mechanisms responsible for radiotherapy resistance and its interactions with the tumor environment will help improve cancer responses to radiotherapy. Our review provides a foundation to identify and overcome the obstacles to effective radiotherapy.
The sharp increase of plant genome and transcriptome data provide valuable resources to investigate evolutionary consequences of gene duplication in a range of taxa, and unravel common principles ...underlying duplicate gene retention.
We survey 141 sequenced plant genomes to elucidate consequences of gene and genome duplication, processes central to the evolution of biodiversity. We develop a pipeline named DupGen_finder to identify different modes of gene duplication in plants. Genes derived from whole-genome, tandem, proximal, transposed, or dispersed duplication differ in abundance, selection pressure, expression divergence, and gene conversion rate among genomes. The number of WGD-derived duplicate genes decreases exponentially with increasing age of duplication events-transposed duplication- and dispersed duplication-derived genes declined in parallel. In contrast, the frequency of tandem and proximal duplications showed no significant decrease over time, providing a continuous supply of variants available for adaptation to continuously changing environments. Moreover, tandem and proximal duplicates experienced stronger selective pressure than genes formed by other modes and evolved toward biased functional roles involved in plant self-defense. The rate of gene conversion among WGD-derived gene pairs declined over time, peaking shortly after polyploidization. To provide a platform for accessing duplicated gene pairs in different plants, we constructed the Plant Duplicate Gene Database.
We identify a comprehensive landscape of different modes of gene duplication across the plant kingdom by comparing 141 genomes, which provides a solid foundation for further investigation of the dynamic evolution of duplicate genes.
To clarify the influence of a pre-ageing treatment on precipitation behaviors in the AA7075 aluminum alloys with ultrafine grain (UFG) structure, the alloys were pre-aged prior to a room temperature ...rolling process (PA + RTR). The precipitation kinetics in PA + RTR alloys during isothermal heat treatment at 100 °C were systematically investigated by transmission electron microscopy (TEM), small angle X-ray scattering (SAXS), and Vickers hardness measurements compared to its counterpart without pre-ageing treatment (i.e. RTR). Results reveal the pre-ageing treatment can lead to a higher dislocation density (22.8 × 1014 m−2) and a larger concentration of Mg (~12.85 at.%) and Zn (~8.33 at.%) atoms in the vicinity of dislocation, which causes a considerable increase in the size and volume fraction of the precipitates in PA + RTR alloy. Specially, our study shows, for the first time, that many GPII zones come from second nucleating in PA + RTR alloy at 108 h, which may ascribe to the pre-ageing treatment. More importantly, the pre-ageing treatment not only makes both two hardness peaks of PA + RTR alloy appeared ahead of but also higher than those of RTR alloy, by virtue of the enhanced precipitation kinetics in PA + RTR alloy.
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•Due to pre-ageing treatment the higher dislocation density and atoms concentration can accelerate precipitation kinetics.•A large number of GPII zones could be precipitated second time because of the higher dislocation.•The GPII zones are relative stable with its feature size at around 5 nm in ultrafine-grained alloys.•Under an enhanced precipitation kinetics, the hardness peaks appeared earlier by ~80% after pre-ageing treatment.
The high-temperature solid-phase approach was used to synthesize Eu3+-doped SrMo0.5W0.5O4 phosphors, whose morphological structure and luminescence properties were then characterized by XRD, SEM, ...FT-IR, excitation spectra, emission spectra, and fluorescence decay curves. The results reveal that the best phosphor synthesis temperature was 900 °C and that the doping of Eu3+ and charge compensators (K+, Li+, Na+, NH4+) had no effect on the crystal phase change. SrMo0.5W0.5O4:Eu3+ has major excitation peaks at 273 nm, 397 nm, and 464 nm, and a main emission peak at 615 nm, making it a potential red fluorescent material to be used as a down converter in UV LEDs (273 nm and 397 nm) and blue light LEDs (464 nm) to achieve Red emission. The emission spectra of Sr1−yMo0.5W0.5O4:yEu3+(y = 0.005, 0.01, 0.02, 0.05, 0.07) excited at 273 were depicted, with the Eu3+ concentration increasing the luminescence intensity first increases and then decreases, the emission peak intensity of SrMo0.5W0.5O4:Eu3+ achieves its maximum when the doping concentration of Eu3+ is 1%, and the critical transfer distance is calculated as 25.57 Å. When various charge compensators such as K+, Li+, Na+, and NH4+ are added to SrMo0.5W0.5O4:Eu3+, the NH4+ shows the best effect with the optimal doping concentration of 3wt%. The SrMo0.5W0.5O4:Eu3+,NH4+ color coordinate is (0.656,0.343), which is close to that of the ideal red light (0.670,0.333).
Neutrophil elastase (NE), a major protease in the primary granules of neutrophils, is involved in microbicidal activity. NE is an important factor promoting inflammation, has bactericidal effects, ...and shortens the inflammatory process. NE also regulates tumor growth by promoting metastasis and tumor microenvironment remodeling. However, NE plays a role in killing tumors under certain conditions and promotes other diseases such as pulmonary ventilation dysfunction. Additionally, it plays a complex role in various physiological processes and mediates several diseases. Sivelestat, a specific NE inhibitor, has strong potential for clinical application, particularly in the treatment of coronavirus disease 2019 (COVID-19). This review discusses the pathophysiological processes associated with NE and the potential clinical applications of sivelestat.
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•NE plays a role in several human diseases.•Sivelestat, a selective NE inhibitor, has various clinical applications (particularly in COVID-19).•More studies are needed to identify more diseases associated with NE.•Additional studies to identify more clinical uses of sivelestat are also needed.
Abstract Background Diabetic retinopathy (DR) is the leading cause of blinding eye disease among working adults and is primarily attributed to the excessive proliferation of microvessels, which leads ...to vitreous hemorrhage and retinal traction, thereby significantly impairing patient vision. NSUN2-mediated RNA m 5 C methylation is implicated in various diseases, and in this investigation, we focused on elucidating the impact of NSUN2 on the regulation of the expression of the downstream gene MUC1, specifically through RNA m 5 C methylation, on the progression of DR. Method Utilizing Microarray analysis, we examined patient vitreous fluid to pinpoint potential therapeutic targets for DR. Differential expression of NSUN2 was validated through qRT-PCR, Western blot, and immunofluorescence in human tissue, animal tissue, and cell model of DR. The relationship between NSUN2 and DR was explored in vitro and in vivo through gene knockdown and overexpression. Various techniques, such as MeRIP-qPCR and dot blot, were applied to reveal the downstream targets and mechanism of action of NSUN2. Results The levels of both NSUN2 and RNA m 5 C methylation were significantly elevated in the DR model. Knockdown of NSUN2 mitigated DR lesion formation both in vitro and in vivo. Mechanistically, NSUN2 promoted MUC1 expression by binding to the RNA m 5 C reader ALYREF. Knockdown of ALYREF resulted in DR lesion alterations similar to those observed with NSUN2 knockdown. Moreover, MUC1 overexpression successfully reversed a series of DR alterations induced by NSUN2 silencing. Conclusions NSUN2 regulates the expression of MUC1 through ALYREF-mediated RNA m 5 C methylation, thereby regulating the progression of DR and providing a new option for the treatment of DR in the future.
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•Distinct functional rhizobacteria clusters assist sedum in responding to Pb stress.•Diverse clusters assist AE to better adapt Pb stress and enhance Pb absorption.•Clusters driven ...growth promotion and Pb activation enhance plant Pb accumulation.•Highly specialized clusters reduce Pb stress for NAE by phosphorus-dissolving.•Stronger selection effect may lead to vulnerable community under extreme Pb stress.
Lead (Pb) contamination presents a widespread environmental plague. Sedum alfredii is widely used for soil phytoremediation owing to its capacity to extract heavy metals, such as Pb. Although efficient Pb extraction is mediated by complex interactions between the roots and rhizospheric bacteria, the mechanism by which S. alfredii recruits microorganisms under Pb stress remains unclear. The Pb-accumulating ecotype (AE) and non-accumulating ecotype (NAE) of S. alfredii recruited different rhizobacterial communities. Under Pb stress, AE rhizosphere-enriched bacteria assembled into stable-connected clusters with higher phylogenetic and functional diversity. These microbes, e.g., Flavobacterium, could release indoleacetic acid to promote plant growth and siderophores, thereby increasing Pb availability. The NAE rhizosphere-enriched functional bacteria “desperately” assembled into highly specialized functional clusters with extremely low phylogenetic diversity. These bacteria, e.g., Pseudomonas, could enhance phosphorus solubilization and Pb precipitation, thereby reducing Pb stress and plant Pb accumulation. High niche overlap level of the rhizo-enriched species raised challenges in soil resource utilization, whereas the NAE community assembly was markedly constrained by environmental “selection effect” than that of AE rhizobacterial community. These results indicate that different ecotypes of S. alfredii recruit distinct bacterial functional assemblies to drive specific plant-soil feedbacks for different survival in Pb-contaminated soils. To cope with heavy metal stress, NAE formed a highly functional and specialized but vulnerable community and efficiently blocked heavy metal absorption by plants. However, the AE community adopted a more stable and elegant strategy to promote plant growth and the accumulation of dry matter via multiple evolutionary strategies that ensured a high yield of heavy metal phytoextraction. This for the first time provides new insights into the roles of rhizosphere microbes in plant adaptations to abiotic stresses.
Pear is an important fruit crop of the Rosaceae family and has experienced two rounds of ancient whole-genome duplications (WGDs). However, whether different types of gene duplications evolved ...differently after duplication remains unclear in the pear genome. In this study, we identified the different modes of gene duplication in pear. Duplicate genes derived from WGD, tandem, proximal, retrotransposed, DNA-based transposed or dispersed duplications differ in genomic distribution, gene features, selection pressure, expression divergence, regulatory divergence and biological roles. Widespread sequence, expression and regulatory divergence have occurred between duplicate genes over the 30-45 million years of evolution after the recent genome duplication in pear. The retrotransposed genes show relatively higher expression and regulatory divergence than other gene duplication modes. In contrast, WGD genes underwent a slower sequence divergence and may be influenced by abundant gene conversion events. Moreover, the different classes of duplicate genes exhibited biased functional roles. We also investigated the evolution and expansion patterns of the gene families involved in sugar and organic acid metabolism pathways, which are closely related to the fruit quality and taste in pear. Single-gene duplications largely account for the extensive expansion of gene families involved in the sorbitol metabolism pathway in pear. Gene family expansion was also detected in the sucrose metabolism pathway and tricarboxylic acid cycle pathways. Thus, this study provides insights into the evolutionary fates of duplicated genes.
The water-sensitive effect of expansive soil (ES) poses a serious challenge to the safety and durability of infrastructure. To reduce the effect of water sensitivity on expansive soil, a new powder ...soil passivator with polyacrylic (PA) as the main component was proposed. In this paper, a series of macroscopic and microscopic tests were conducted to evaluate the water-sensitive passivation effect and mechanism of PA-ES composites. The results showed that PA significantly attenuated the water sensitivity of ES. With the increase in PA content in the PA-ES composites, the water sensitivity of the composites decreased, swelling and shrinkage deformation decreased, and the strength of the composites increased significantly. In addition, when the content of PA in the PA-ES composite is 6%, it can significantly alleviate the deformation of the composite and improve the saturated shear strength of the composite, meeting the requirements of ES engineering disposal. Finally, the results show that the mechanism of PA passivation of ES water-sensitive effect mainly includes adsorption, binding, and filling. The study shows that PA has a broad engineering application prospect as an ES passivator.
Pear (Pyrus) is a globally grown fruit, with thousands of cultivars in five domesticated species and dozens of wild species. However, little is known about the evolutionary history of these pear ...species and what has contributed to the distinct phenotypic traits between Asian pears and European pears.
We report the genome resequencing of 113 pear accessions from worldwide collections, representing both cultivated and wild pear species. Based on 18,302,883 identified SNPs, we conduct phylogenetics, population structure, gene flow, and selective sweep analyses. Furthermore, we propose a model for the divergence, dissemination, and independent domestication of Asian and European pears in which pear, after originating in southwest China and then being disseminated throughout central Asia, has eventually spread to western Asia, and then on to Europe. We find evidence for rapid evolution and balancing selection for S-RNase genes that have contributed to the maintenance of self-incompatibility, thus promoting outcrossing and accounting for pear genome diversity across the Eurasian continent. In addition, separate selective sweep signatures between Asian pears and European pears, combined with co-localized QTLs and differentially expressed genes, underline distinct phenotypic fruit traits, including flesh texture, sugar, acidity, aroma, and stone cells.
This study provides further clarification of the evolutionary history of pear along with independent domestication of Asian and European pears. Furthermore, it provides substantive and valuable genomic resources that will significantly advance pear improvement and molecular breeding efforts.
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