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Leaf anatomical traits are susceptible to environmental changes and can reflect plant adaptation strategies to the environment. Populus euphratica plays a key role in maintaining ecosystem processes and functions in arid zones, but the variations in leaf anatomical traits of Populus euphratica and their drivers at large scales remain unclear. Here, we investigated 10 leaf anatomical traits of Populus euphratica from 12 sampling sites in the arid zone of China, and explored how they were affected by geographic, climatic, and soil factors. Our results showed that these traits differed significantly between sites (P < 0.05), which was mainly determined by climate and soil factors that together explained 41.4 % of the trait variation. The impact of climate factors is the most critical, as they can directly influence the variation in leaf anatomical traits and indirectly affect trait variation by influencing soil factors. Among them, the max temperature of the warmest month (BIO5), soil available phosphorus (SAP) and soil moisture content (SM) had the most critical effect. Besides, temperature was the major influencing factor for the ratio of spongy tissue thickness to leaf thickness (SR), palisade tissue thickness (PT), the ratio of palisade tissue thickness to spongy tissue thickness (PSR), and the ratio of palisade tissue thickness to leaf thickness (CTR), while soil nutrient was the major influencing factor for leaf thickness (LT), lower epidermis thickness (LET), and spongy tissue thickness (ST). Our results provide important insights into the response of dryland forests to climate change, and suggest that climate warming and declining soil quality may have a stronger effect on Populus euphratica.

The construction of an ecological security pattern (ESP) is an important undertaking in ensuring the stability of the ecosystem and the long-term growth of humanity. Existing research, However, existing research often overlooks the quantification of policy implications in ESP development. The objective of this paper was to bridge this gap by integrating policy quantification analysis (PQA) with nature, society and into ESP construction and providing targeted ecological management recommendations. The policy texts were quantified into reusable research data, which served as a foundation for the selection of indicators and the optimization of ecological security patterns, by using machine learning techniques. The methodology “Patch-matrix-corridor” was used to create a spatially correlated ecological security pattern. Through factor analysis and Random Forest (RF), the impact of each indicator on ecological security was thoroughly examined, offering substantial support for policy development and ESP construction planning. The Guangdong-Hong Kong-Macao Greater Bay Area(GBA) was selected as the study area, the study found that: (1) The proposed framework PQA based-ESP could provide a useful eco-management tools. (2) Policy adaptability had a substantial impact on environmental security in the GBA, but the ecosystem service index has the highest impact. (3) Applying the framework, we identified a total of 1,993 km2 of ecological sources, 23 key ecological corridors, 58 general ecological corridors, and 31 ecological nodes. An improved ESP, characterized as “one circle, two bays, three rivers, multiple areas, corridors, and nodes,” was constructed in the GBA. (4) Given the multi-scale analysis, tailored ecological management policy recommendations were proposed for each city in the GBA. The study's findings offer actionable solutions for the international community facing growing ecological challenges.

Autophagy mediates PM2.5-related lung injury (LI) and is tightly linked to inflammation and apoptosis processes. IL-37 has been demonstrated to regulate autophagy. This research aimed to examine the involvement of IL-37 in the progression of PM2.5-related LI and assess whether autophagy serves as a mediator for its effects.To create a model of PM2.5-related LI, this research employed a nose-only PM2.5 exposure system and utilized both human IL-37 transgenic mice and wild-type mice. The hIL-37tg mice demonstrated remarkable reductions in pulmonary inflammation and pathological LI compared to the WT mice. Additionally, they exhibited activation of the AKT/mTOR signaling pathway, which served to regulate the levels of autophagy and apoptosis.Furthermore, in vitro experiments revealed a dose-dependent upregulation of autophagy and apoptotic proteins following exposure to PM2.5 DMSO extraction. Simultaneously, p-AKT and p-mTOR expression was found to decrease. However, pretreatment with IL-37 demonstrated a remarkable reduction in the levels of autophagy and apoptotic proteins, along with an elevation of p-AKT and p-mTOR. Interestingly, pretreatment with rapamycin, an autophagy inducer, weakened the therapeutic impact of IL-37. Conversely, the therapeutic impact of IL-37 was enhanced when treated with 3-MA, a potent autophagy inhibitor. Moreover, the inhibitory effect of IL-37 on autophagy was successfully reversed by administering AKT inhibitor MK2206. The findings suggest that IL-37 can inhibit both the inflammatory response and autophagy, leading to the alleviation of PM2.5-related LI. At the molecular level, IL-37 may exert its anti autophagy and anti apoptosis effects by activating the AKT/mTOR signaling pathway.

Subwavelength imaging plays an important role in various fields of science and technology. We propose a electro-thermally tunable hyperlens design featuring alternating graphene/metal/dielectric layers that enables subdiffraction far-field imaging with real-time amplification capabilities at terahertz frequencies. We show that one layer of graphene is able to increase the intensity of the subwavelength image of the hyperlens radiation in the near and far zones by tuning its chemical potential by the applied voltage. The proposed hyperlens is dynamically tunable with temperature changes over a wide frequency range. Simultaneous or independent electro-thermal tunability of the hyperlens opens new multifunctional possibilities for light manipulation. This improves the quality of subwavelength images for new devices in the terahertz range.

The production of reactive oxygen species (ROS) by NADPH oxidase (NOX) 2 has been linked to both insulin resistance and exercise training adaptations in skeletal muscle. This study explores the previously unexamined role of NOX2 in the interplay between diet-induced insulin resistance and exercise training (ET). Using a mouse model that harbors a point mutation in the essential NOX2 regulatory subunit, p47phox (Ncf1*), we investigated the impact of this mutation on various metabolic adaptations. Wild-type (WT) and Ncf1* mice were assigned to three groups: chow diet, 60% energy fat diet (HFD), and HFD with access to running wheels (HFD + E). After a 16-week intervention, a comprehensive phenotypic assessment was performed, including body composition, glucose tolerance, energy intake, muscle insulin signaling, redox-related proteins, and mitochondrial adaptations. The results revealed that NOX2 deficiency exacerbated the impact of HFD on body weight, body composition, and glucose intolerance. Moreover, in Ncf1* mice, ET did not improve glucose tolerance or increase muscle cross-sectional area. ET normalized body fat independently of genotype. The lack of NOX2 activity during ET reduced several metabolic adaptations in skeletal muscle, including insulin signaling and expression of Hexokinase II and oxidative phosphorylation complexes. In conclusion, these findings suggest that NOX2 mediates key beneficial effects of exercise training in the context of diet-induced obesity.

This study aimed to investigate the maternally inherited intergenerational and transgenerational effects of cadmium (Cd) exposure on steroid hormone synthesis in the ovarian granulosa cells (GCs) of offspring rats. F1 rats were obtained by mating adult female Sprague–Dawley rats with healthy adult male rats and were exposed to 0, 0.5, 2.0, and 8.0 mg/kg CdCl2 during pregnancy. The adult female rats (PND 56) were mated with healthy adult male rats to produce F2 and F3 rats. The serum progesterone (Pg) and estradiol (E2) levels of the F2 adult female rats were decreased, while those of F3 rats were significantly increased. Moreover, hormone synthesis-related genes had different expression patterns in the F2 and F3 generations. F2 and F3 rat ovarian GCs exhibited altered miRNA expression profiles and DNA methylation patterns. Validation of miRNAs that regulate hormone synthesis-related genes in the cAMP/PKA signaling pathway suggested that miR-124–3p was downregulated in F2 and F3 rats, while miR-133a-5p and miR-150–5p were upregulated in F2 rats and downregulated in F3 rats. In summary, 1) there are maternal genetic intergenerational (GCs hormone synthesis disorder) and transgenerational (GCs hormone synthesis function repair change) effects on hormone synthesis function changes in offspring GCs induced by Cd exposure during pregnancy. 2) Changes in miRNAs and DNA methylation modifications associated with the genetic effects of altered hormone synthesis function in offspring GCs induced by Cd exposure during pregnancy are important. 3) Under the current environmental level of Cd exposure, the possible risk of maternal genetic intergenerational and transgenerational effects of offspring ovarian toxicity should be strongly considered.

Soil fungal communities play a crucial role in maintaining and regulating ecosystem functions. The soil fungal structure of different plant communities in forests has been widely studied. However, the drivers of changes in soil fungal community dynamics in warm temperate secondary forests and the pathways influencing them remain to be explored. The Illumina high-throughput sequencing and FUNGuild platform were used to characterize the soil fungal diversity and community composition of six typical plant communities (JM, Juglans mandshurica; PD, Populus davidiana; QM, Quercus mongolica; MB, mixed broadleaf forest; MC, mixed conifer forest; PT, Pinus tabuliformis) in warm temperate secondary forests. The drivers of structural changes in dominant fungal taxa and functional groups were also explored. The pathways through which forest type, soil properties, altitude, climate, and plant diversity affected fungal community structure were further clarified. The results suggested that Ascomycota, Basidiomycota, and Zygomycota dominated the soil fungal communities in warm temperate secondary forests. Except for symbiotic fungi, there was no significant difference in soil fungal α-diversity among forest types. However, there were significant differences in total fungi and functional group community composition. The drivers of diversity and community composition of different soil fungal taxa in warm temperate secondary forests differed. In addition, the partial least squares path model indicated that the composition of soil fungal community in warm temperate secondary forests was directly influenced by forest type and was less dependent on soil properties. Collectively, our study highlights the importance of forest type, soil properties, and other factors (climate, altitude, plant diversity) in driving changes in soil fungal community structure.

Parkinson's disease (PD) is currently the fastest growing disabling neurological disorder worldwide, with motor and non-motor symptoms being its main clinical manifestations. The primary pathological features include a reduction in the number of dopaminergic neurons in the substantia nigra and decrease in dopamine levels in the nigrostriatal pathway. Existing treatments only alleviate clinical symptoms and do not stop disease progression; slowing down the loss of dopaminergic neurons and stimulating their regeneration are emerging therapies. Preclinical studies have demonstrated that transplantation of dopamine cells generated from human embryonic or induced pluripotent stem cells can restore the loss of dopamine. However, the application of cell transplantation is limited owing to ethical controversies and the restricted source of cells. Until recently, the reprogramming of astrocytes to replenish lost dopaminergic neurons has provided a promising alternative therapy for PD. In addition, repair of mitochondrial perturbations, clearance of damaged mitochondria in astrocytes, and control of astrocyte inflammation may be extensively neuroprotective and beneficial against chronic neuroinflammation in PD. Therefore, this review primarily focuses on the progress and remaining issues in astrocyte reprogramming using transcription factors (TFs) and miRNAs, as well as exploring possible new targets for treating PD by repairing astrocytic mitochondria and reducing astrocytic inflammation.

Cardiovascular diseases caused by atherosclerosis (AS) seriously endanger human health, which is closely related to vascular smooth muscle cell (VSMC) phenotypes. VSMC phenotypic transformation is marked by the alteration of phenotypic marker expression and cellular behaviour. Intriguingly, the mitochondrial metabolism and dynamics altered during VSMC phenotypic transformation. Firstly, this review combs VSMC mitochondrial metabolism in three aspects: mitochondrial ROS generation, mutated mitochondrial DNA (mtDNA) and calcium metabolism respectively. Secondly, we summarized the role of mitochondrial dynamics in regulating VSMC phenotypes. We further emphasized the association between mitochondria and cytoskelton via presenting cytoskeletal support during mitochondrial dynamics process, and discussed its impact on their respective dynamics. Finally, considering that both mitochondria and cytoskeleton are mechano-sensitive organelles, we demonstrated their direct and indirect interaction under extracellular mechanical stimuli through several mechano-sensitive signaling pathways. We additionally discussed related researches in other cell types in order to inspire deeper thinking and reasonable speculation of potential regulatory mechanism in VSMC phenotypic transformation.

In December 2019, the novel coronavirus disease (COVID-19) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection broke. With the gradual deepening understanding of SARS-CoV-2 and COVID-19, researchers and clinicians noticed that this disease is closely related to the nervous system and has complex effects on the central nervous system (CNS) and peripheral nervous system (PNS). In this review, we summarize the effects and mechanisms of SARS-CoV-2 on the nervous system, including the pathways of invasion, direct and indirect effects, and associated neuropsychiatric diseases, to deepen our knowledge and understanding of the relationship between COVID-19 and the nervous system.

Understanding the changes of wetlands on the Tibetan Plateau (TP) is important for action to ensure ecosystem resilience in Asia. However, mapping long-term changes of wetlands at high resolutions remains challenging. Here, we quantify the spatio-temporal changes of TP wetlands from 1990 to 2019, by combining Landsat imagery with deep learning to map TP wetlands. The deep learning model combined with transfer learning strategies achieves high classification performance using a few class samples. The validation results show that the user’s accuracy is 95.5% and the producer's accuracy is 90.1% for wetland extraction, satisfying with subsequent analysis of wetland spatio-temporal changes. Based on the wetland extraction model, we have created annual wetland map in the TP for the first time. We find that the areal extent of TP wetlands has increased by 31.2 ± 6.6 % over the past 30 years. The growth is particularly noticeable (by 22.5 ± 6.2 %) during 2015–2019. Spatially, the wetland areal extent on the Qiangtang Plateau (in the inner part of TP and as habitats of various birds and rare wild animals) and the source region of Yangtze River show the largest expansions by 55.3 ± 9.3 % and 44.0 ± 8.9 %, respectively. Such rapid wetland expansions are associated with increasing rainfall and temperature which have heterogeneous influences on wetland changes across the TP. Our findings provide evidence for the impact of climate change on wetland area. The marked wetland changes highlight that climate mitigation is a priority for high-latitude ecosystems.

The aim of this study was to explore and analyze the main features of the top 100 most-cited original articles, systematic reviews (SRs)/meta-analyses (MAs) in the field of robotic surgery, through scientometric analysis. VOSviewer and Excel 2019 were employed to conduct this scientometric study. We found that the majority of original articles (72/100) were published during the 2000s, while the majority of the top 100 most-cited SRs/MAs (91/100) during the 2010s. The USA was the most dominant country (n = 78), Henry Ford Health System was the most productive institution (n = 10), and Menon M was the largest contributing first author (n = 5) of the top 100 most-cited original articles. The USA was the most dominant country (n = 33), University of Padua was the most productive institution (n = 9), and Ficarra V was the largest contributing first author (n = 4) of the top 100 most-cited SRs/MAs. The top 100 most-cited original articles in robotic surgery have focused on the feasibility, outcomes and learning curve of robotic surgery for various neoplasms and cancers. The top 100 most-cited SRs/MAs have focused on the differences between robotic surgery and other types of surgery, with respect to the learning curve, costs, outcomes and experience in treating neoplasms, cancer and other diseases. In the future, the formation of cross-institutional and cross-disciplinary cooperation teams should be promoted and corresponding regulations and standards for specific diseases should be developed to regulate and promote the development of robotic surgery.

Background: Studies on the epidemiology and prognosis of primary breast lymphoma (PBL) are lack for low incidence. Therefore, we aimed to investigate the epidemiological characteristics of PBL and develop nomograms to predict patient survival. Methods: Data of patients who were diagnosed with PBL from 1975 to 2011 and incidence rate of PBL from 1975 to 2017 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Time-varying multivariable Cox regression analysis was performed to identify independent prognostic factors for overall survival (OS) and disease-specific survival (DSS). Nomograms were constructed based on the independent prognostic factors identified in multivariate Cox regression analysis. Results: A total of 1427 patients diagnosed with PBL were identified with the average age of 67.1 years. The overall incidence of PBL is 1.35/1,000,000 (adjusted to the United States standard population in 2000) from 1975 to 2017, with a significant upward trend by an annual percentage change (APC) of 2.91 (95%CI 2.29–3.94, P

Summary: COVID-19 outbreaks have crushed our healthcare systems, which requires clinical guidance for the healthcare following the outbreaks. We conducted retrospective cohort studies with Pearson’s pattern-based analysis of clinical parameters of 248 hospitalized patients with COVID-19. We found that dysregulated neutrophil densities were correlated with hospitalization duration before death (p = 0.000066, r = −0.45 for % neutrophil; p = 0.0001, r = −0.47 for neutrophil count). As such, high neutrophil densities were associated with mortality (p = 4.23 × 10−31 for % neutrophil; p = 4.14 × 10−27 for neutrophil count). These findings were further illustrated by a representative “second week crash” pattern and validated by an independent cohort (p = 5.98 × 10−11 for % neutrophil; p = 1.65 × 10−7 for neutrophil count). By contrast, low aspartate aminotransferase (AST) or lactate dehydrogenase (LDH) levels were correlated with quick recovery (p ≤ 0.00005). Collectively, these correlational at-admission findings may provide healthcare guidance for patients with COVID-19 in the absence of targeted therapy.

We have shown in the past studies that fine particulate matter (PM2.5) exposure increases airway hyperresponsiveness and leads to lung inflammation damage. Interleukin (IL)-37 plays a inhibitory role in inflammation activation and maintenance. However, the function of IL-37 in the above processes keep unclear. We aim to explore the role of IL-37 in PM2.5-induced airway hyperresponsiveness in this study. A nose-only PM2.5 online concentration, enrichment and exposure instrument was also applied to generate mice model of airway hyperresponsiveness. A transgenic mice strain using a CMV promoter to express human IL-37b (hIL-37tg) was obtained. PM2.5 exposure was shown to increase airway resistance, followed by lung inflammation and IL-1β, TNFα, and IL-6 release, which was inhibited by IL-37tg mice and mice administrated recombinant human IL-37 intranasally (i.n). Moreover, expression of the proliferation-related protein PCNA and migration-related proteins MMP-2, MMP-9, and Vimentin was reduced in lung tissues of IL-37tg mice and mice given recombinant human IL-37 i.n. Abnormal cell contraction, proliferation, and migration of human airway smooth muscle cells (hASMCs) incubated with PM2.5 were also decreased by IL-37 treatment. In addition, IL-37 intervention of hASMCs before PM2.5 incubation decreased cytoplasmic calcium level and expression of PCNA, MMP-2, MMP-9 and Vimentin. Finally, knockdown of the IL-37 receptor IL-1R8 gene eliminated the protective effects of IL-37 in the above responses. We conclude that IL-37 inhibits inflammation activation and disease severity of airway hyperreactivity by PM2.5 induction.

Epidemiological research has identified that exposure to fine particulate matter (PM2.5) can increase airway hyperresponsiveness (AHR) which is considered a typical characteristic of asthma. Although the effect of PM2.5 on AHR has been elucidated to a certain degree, its exact mechanism remains unclear. Bromodomain-containing protein 4 (BRD4) is recognized as a member of the bromodomain and extraterminal (BET) family, with the ability to maintain higher-order chromatin configuration and regulate gene expression programs. The primary objective of our study was to examine the role of BRD4 in AHR triggered by PM2.5, and to elucidate its possible molecular mechanism. A mouse model with AHR was established using a nose-only PM2.5 exposure system. We observed that PM2.5 enhanced AHR in the experimental group compared to the control group, and this alteration was accompanied by increased lung inflammation and BRD4 expression in bronchi-lung tissue. However, the BRD4 inhibitor (ZL0420) could alleviate the aforementioned alterations in the mouse model with PM2.5 exposure. To explore the exact molecular mechanism, we further examined the role of BRD4 in human airway smooth muscle cells (hASMCs) after exposure to PM2.5 DMSO extracts. We found that PM2.5 DMSO extracts, which promoted the contraction and migration of hASMCs, was accompanied by an increase in the levels of BRD4, kallikrein 14 (KLK14), bradykinin 2 receptor (B2R), matrix metalloproteinases2(MMP-2), matrix metalloproteinases9(MMP-9), vimentin and bradykinin (BK) secretion, while ZL0420 and BRD4 gene silencing could reverse this response. In summary, these results demonstrate that BRD4 is an important player in AHR triggered by PM2.5, and BRD4 inhibition can ameliorate AHR induced by PM2.5. In addition, PM2.5 DMSO extracts can promote the contraction and migration of hASMCs by increasing BRD4 expression.

The determinants of bacterial β-diversity across the large scale have been well explored, yet little is known that about how the driving factors of bacterial β-diversity differ between the forest and grassland in northwest China. Here, we comprehensively compared the biogeographic patterns and their drivers of bacterial communities in the forest and grassland. We also quantified the relative contribution of two components (replacement and nestedness components) to bacterial β-diversity. We found the significant distance-decay relationships in both two ecosystems, whereas more species turnover correlating with geographic distance was observed in forest ecosystems than grassland ecosystem, and the slope in the forest was significantly steeper than that in grassland. This suggests that bacterial diversity in forest and grassland soil exhibits distinct biogeographic and ecological patterns. More importantly, we found that soil bacterial β-diversity was mainly derived from replacement components in both two ecosystems, implying high proportion of endemic bacterial species distribute in dryland forest and grassland soil. Our results further demonstrated that environmental filtering have dominant effect on soil bacterial β-diversity in both forest and grassland. However, the relative roles of spatial processes varied between forest and grassland, where stochastic processes only have significant influence on soil bacterial β-diversity in forest but not in grassland. Among environmental factors, bacterial β-diversity and turnover components was mainly determined by water availability in grassland soil, but by soil pH in the forest soil. Taken together, our findings collectively suggest that differential ecological drivers underlie distinct biogeographic patterns of bacterial diversity in forest and grassland soil.

Objective: Chronic ad libitum low protein-high carbohydrate diet (LPHC) increases health- and life-span in mice. A periodized (p) LPHC regimen would be a more practical long-term human lifestyle intervention, but the metabolic benefits of pLPHC are not known. Also, the interactions between LPHC diet and exercise training have not been investigated. Presently, we aimed to provide proof-of-concept data in mice of the efficacy of pLPHC and to explore the potential interactions with concurrent exercise training. Methods: A detailed phenotypic and molecular characterization of mice undergoing different durations of 14 d LPHC (5 E% protein)/14 d control diet cycles for up to 4 months with or without concurrent access to activity wheels allowing voluntary exercise training. Results: pLPHC conferred metabolic benefits similar to chronic LPHC, including increased FGF21 and adaptive thermogenesis, obesity-protection despite increased total energy intake and improved insulin sensitivity. The improved insulin sensitivity showed large fluctuations between diet periods and was lost within 14 days of switching back to control diet. Parallel exercise training improved weight maintenance but impaired the FGF21 response to pLPHC whereas repeated pLPHC cycles progressively augmented this response. Both the FGF21 suppression by exercise and potentiation by repeated cycles correlated tightly with Nupr1 mRNA in liver, suggesting dependence on liver integrated stress response. Conclusion: These results suggest that pLPHC may be a viable strategy to promote human health but also highlight the transient nature of the benefits and that the interaction with other lifestyle-interventions such as exercise training warrants consideration. Keywords: Dietary restriction, FGF21, Periodized diet, Glucose metabolism, Obesity, Exercise, Integrated stress response

The biogeographic patterns and its drivers of plant diversity across drylands have been well documented, while the associated difference in the determinants of plant β-diversity between different growth forms remain unclear. Here, we selected 68 plots from a typical dryland region of Northwest China to explore how and to what extent different environmental and spatial factors influence plant β-diversity of different growth forms. The results showed that environmental and spatial factors were significantly correlated with whole community, shrub and herb β-diversity (P

Taxus cuspidata Siebold et Zuccarini, one of the plant species with extremely small populations in China, is listed as a first-class national key protected wild plant that urgently needs to be rescued. However, there are different viewpoints on the population status of T. cuspidata. To elucidate the current actual population status of T. cuspidata, we conducted a systematic field survey in the distribution area of T. cuspidata in China, and analyzed the size structure, sex ratio, dynamics, and threat factors of T. cuspidata populations. Our results are as follows. (1) T. cuspidata was mainly distributed in Wangqing County, Helong City, Hunchun City of Jilin Province, and Muling City of Heilongjiang Province, while seldom distributed in Liaoning Province. T. cuspidata was distributed in the broad-leaved-conifer-Korean pine mixed forest in Northeast China, mostly as sporadic single individuals or scattered small populations. The highest density of adult individuals of T. cuspidata was 20 individuals/0.1 ha in DHZ, and the highest density of regeneration individuals was 28 individuals/0.1 ha in JGL. There was a significant exponential relationship (p

Benzo[a]pyrene (BaP) widely presents in soot, tar, cigarette smoke, and has a strong carcinogenic effect. It is stable in the environment and accumulates through the biological chain. Therefore, it is of vital importance to develop a simple and rapid method to detect Bap in real environment. In this work, based on surface enhanced Raman scattering (SERS) technology, a silver nanorod (AgNR) substrate was developed for detecting BaP in river water and soil. Vibration modes of BaP’s characteristic peaks were calculated by density functional theory (DFT). The characteristic peak of BaP is at 1234 cm−1. In the range of 10 ~ 100 ppb, the characteristic peak intensity of BaP shows good linear relationship with the concentration. The limit of detection (LOD) is down to 1 ppm in river water and 10 ppm in soil, respectively. These results demonstrate the applicability of the AgNR substrate for SERS detection of BaP which present an application prospect of AgNR substrate in environmental detection.

This study investigated the effects of xyloglucan (XG) compounded inulin and XG compounded arabinoxylan on the hypoglycemic activity of mice fed with high-fat diet (HFD). Forty male ICR/KM mice were randomly divided into four groups, namely, control group, high-fat group, XG and 4% inulin supplemented in a HFD group (HFXI), and XG and 4% arabinoxylan supplemented in a HFD group (HFXA). Results showed that XI and XA supplementation decreased serum glucose level and intestinal disaccharidase activity. XI and XA decreased the level of total bile acid (TBA) in the serum and liver. Fecal TBA excretion was increased in the HFXI group, and XA treatment decreased colon digesta TBA excretion. XI treatment activated liver farnesoid X receptor (FXR) and G protein-coupled receptor 5 (TGR5). Intestinal FXR and TGR5 were activated after XA supplementation. XA increased the abundance of Verrucomicrobia, promoting Akkermansia growth, whereas XI treatment increased the abundance of gut Bifidobacterium.

The expanding role of refractive index measurement in many fields including chemistry, biology and medicine, food industry, process control, and environmental monitoring, has led to a growth of research and development efforts in this field. Optical fibers represents a very promising platform for refractive index sensing due to appealing features such as high sensitivity, small fingerprint, high degrees of integration, compatiblity in harsh environments, and potential to provide real time and remote analysis. Up to date, a wide range of fiber-optic refractive index sensors based on different configurations and mechanisms have been proposed and developed. In this paper, we aim to review the most commonly-used fiber-based refractive index sensors operating in visible and infrared regions, and briefly summarize their advantages and limitations. Furthermore, since THz waves have prominent advantages such as extended probing length, no damage to biological samples, unique fingerprint of biological samples, and non-ionizing feature, we then proceed to review the recent development of several categories of THz waveguide platforms for refractive index sensing applications. Finally, we summarize the review work and present the future perspectives of this field.

This study investigated the effects of xyloglucan (XG) on gut microbiota, bile acid metabolism, and liver injury in mice fed with high-fat diet (HFD). Thirty male ICR/KM mice were randomly divided into three groups, as follows: control group (10% fat energy); high-fat group (60% fat energy); and XG group (8% XG supplemented in a high-fat diet). The mice were sacrificed after 8 weeks, and samples were collected. XG reduced the body weight, serum, and liver lipids of high-fat mice and gut-liver axis circulation bile acid level. Liver damage and gut disorders caused by HFD were relieved after XG supplementation. The intestinal bile acid metabolism farnesoid X receptor-small heterodimer partner (FXR-SHP) pathway was up-regulated by XG. XG reduced liver damage and obesity by regulating gut microbiota to up-regulate the intestinal bile acid metabolism pathways of HFD-fed mice.

In the paper, a DNA assisted magnetic reduced graphene oxide-copper nanocomposite (mrGO-CuNCs) is proposed. Copper ions are able to accelerate the oxidation of o-phenylenediamine. The electrochemical signal of the oxidized product, 2,3-diaminobenazine, are employed to characterize the HCV DNAs. The strategy is able to sensitively detect HCV DNA over a wide linear range within the range of 0.5–10 nM and has a detection limit of 405.0 pM. Critically, it could effectively discriminate the 1b and 6 k subtypes of HCV. This assay strategy has promising applications in the early diagnosis and blood screening of HCV. Keywords: Magnetic reduced graphene oxide, Hepatitis C virus, Electrochemical measurements, Ultrasensitive detection

Horqin Sandy Land is located in the semiarid farming-pastoral ecotone of China, with a long-term history of uncontrolled livestock grazing. However, the relative effects of grazing, environmental and spatial factors on taxonomic, functional, and phylogenetic diversity has not been explored simultaneously. To test the relative importance of grazing, environmental and spatial factors in shaping alpha and beta components of taxonomic, functional, and phylogenetic diversity in semiarid sandy land, a large-scale field survey was carried out from 141 plots at 41 sites across Horqin Sandy Land. Results showed that grazing, environmental and spatial factors affected three facets of diversity in different ways at both alpha and beta scales. Taxonomic, functional, and phylogenetic diversity was shaped by environmental factors at the alpha scale, whereas phylogenetic diversity was correlated with spatial factors at the beta scale. Interestingly, beta taxonomic diversity was determined by spatially structured environmental factors and beta functional diversity was determined by environmental factors. Results showed that the ecological drivers of biodiversity may vary according to different facets and scales. Meanwhile, we also found that grazing plays an important role in structuring biodiversity in semiarid sandy land. Grazing disturbance explained more variation at the alpha scale than at the beta scale. Furthermore, the joint effect of grazing disturbance and soil fertility played an important role in shaping alpha diversity. It is worth noting that all three facets of diversity were reduced by increasing grazing intensity or decreasing soil fertility. Our results highlight that correctly managing grazing locally and unfertile site can decrease the effects of disturbance on biodiversity patterns in semiarid ecosystems. Future research should focus on taxonomic, functional, and phylogenetic diversity at various scales to determine biodiversity conservation strategies. Keywords: Alpha diversity, Beta diversity, Grazing disturbance, Horqin sandy land

HMGA2, a pivotal transcription factor, functions as a versatile regulator implicated in the progression of diverse aggressive malignancies. In this study, mass spectrometry was employed to identify ubiquitin-specific proteases that potentially interact with HMGA2, and USP48 was identified as a deubiquitinating enzyme of HMGA2. The enforced expression of USP48 significantly increased HMGA2 protein levels by inhibiting its degradation, while the deprivation of USP48 promoted HMGA2 degradation, thereby suppressing tumor invasion and metastasis. We discovered that USP48 undergoes SUMOylation at lysine 258, which enhances its binding affinity to HMGA2. Through subsequent phenotypic screening of small molecules, we identified DUB-IN-2 as a remarkably potent pharmacological inhibitor of USP48. Interestingly, the small-molecule inhibitor targeting USP48 induces destabilization of HMGA2. Clinically, upregulation of USP48 or HMGA2 in cancerous tissues is indicative of poor prognosis for patients with colorectal cancer (CRC). Collectively, our study not only elucidates the regulatory mechanism of DUBs involved in HMGA2 stability and validates USP48 as a potential therapeutic target for CRC, but also identifies DUB-IN-2 as a potent inhibitor of USP48 and a promising candidate for CRC treatment.

Background: Prolonged sitting and reduced physical activity lead to low energy expenditures. However, little is known about the joint impact of daily sitting time and physical activity on body fat distribution. We investigated the independent and joint associations of daily sitting time and physical activity with body fat among adults. Methods: This was a cross-sectional analysis of U.S. nationally representative data from the National Health and Nutrition Examination Survey 2011–2018 among adults aged 20 years or older. Daily sitting time and leisure-time physical activity (LTPA) were self-reported using the Global Physical Activity Questionnaire. Body fat (total and trunk fat percentage) was determined via dual X-ray absorptiometry. Results: Among 10,808 adults, about 54.6% spent 6 h/day or more sitting; more than one-half reported no LTPA (inactive) or less than 150 min/week LTPA (insufficiently active) with only 43.3% reported 150 min/week or more LTPA (active) in the past week. After fully adjusting for sociodemographic data, lifestyle behaviors, and chronic conditions, prolonged sitting time and low levels of LTPA were associated with higher total and trunk fat percentages in both sexes. When stratifying by LTPA, the association between daily sitting time and body fat appeared to be stronger in those who were inactive/insufficiently active. In the joint analyses, inactive/insufficiently active adults who reported sitting more than 8 h/day had the highest total (female: 3.99% (95% confidence interval (95%CI): 3.09%–4.88%); male: 3.79% (95%CI: 2.75%–4.82%)) and trunk body fat percentages (female: 4.21% (95%CI: 3.09%–5.32%); male: 4.07% (95%CI: 2.95%–5.19%)) when compared with those who were active and sitting less than 4 h/day. Conclusion: Prolonged daily sitting time was associated with increased body fat among U.S. adults. The higher body fat associated with 6 h/day sitting may not be offset by achieving recommended levels of physical activity.

Ischemia-reperfusion (I/R) injury is an inevitable pathological process in many clinical practices, such as transplantation, myocardial infarction, cerebral infarction and current treatments for I/R injury are limited. Ferroptosis is an essential pathogenic mechanism for triggering I/R injury, characterized by excess reactive oxygen species (ROS) accompanied by lipid peroxidation and increased intracellular iron concentration consistent with the mechanical manifestations of I/R. Resveratrol (RES) is a polyphenolic compound found in red wine that acts as an iron chelator, lipophilic antioxidant, and lipid peroxidation inhibitor. It helps to inhibit I/R damage by reversing ferroptosis-induced cell death, providing insights into developing therapeutic strategies for this devastating disease. In this review, we used the keywords “ferroptosis”, “resveratrol”, and “ischemia-reperfusion” in conjunction with each other, collected 1039 papers from the last decade, 114 relevant papers were screened to review the research progress on the mitigating of I/R injury through ferroptosis in Res and its future perspectives.

Low-temperature sintering Ag technology is a feasible approach employed in power electron devices. In this study, the influence of the different amounts (0, 0.03, 0.05, 0.07, 0.10, 0.20 wt%) of silicon carbide nanowires (SiC NWs) on the properties and microstructure of micro-Ag paste sintered at 250 °C without pressure has been investigated. The results exhibit that the bonding strength of the Ag-SiC joint reaches a maximum of 43.57 MPa after doping 0.07 wt% SiC NWs, with an increase of 13 % compared with pure Ag joint. This enhancement mechanism can be owed to the Orowan mechanism and the pinning effect of SiC NWs, which nail at grain boundaries that will restrain the dislocation motion of Ag grains. Meanwhile, the electrical resistivity of Ag-0.07SiC shows a minimum value of 5.20 μΩ cm, approximately 10.65 % lower than pure Ag joint. This is attributed to the well-sintered Ag network and the bridging effect of SiC NWs distributed in Ag particles. Thus, incorporating appropriate content of SiC NWs into micro-Ag paste can strengthen the mechanical performance and electrical conductivity of sintered Ag joint. It is hoped that this research could develop a new micro-Ag paste with outstanding properties that could be employed in high-power electronic devices.

Background: The emergence of drug-resistant strains of Klebsiella pneumoniae (K. pneumoniae) has become a significant challenge in the field of infectious diseases, posing an urgent need for the development of highly protective vaccines against this pathogen. Methods and results: In this study, we identified three immunogenic extracellular loops based on the structure of five candidate antigens using sera from K. pneumoniae infected mice. The sequences of these loops were linked to the C-terminal of an alpha-hemolysin mutant (mHla) from Staphylococcus aureus to generate a heptamer, termed mHla-EpiVac. In vivo studies confirmed that fusion with mHla significantly augmented the immunogenicity of EpiVac, and it elicited both humoral and cellular immune responses in mice, which could be further enhanced by formulation with aluminum adjuvant. Furthermore, immunization with mHla-EpiVac demonstrated enhanced protective efficacy against K. pneumoniae channeling compared to EpiVac alone, resulting in reduced bacterial burden, secretion of inflammatory factors, histopathology and lung injury. Moreover, mHla fusion facilitated antigen uptake by mouse bone marrow-derived cells (BMDCs) and provided sustained activation of these cells. Conclusions: These findings suggest that mHla-EpiVac is a promising vaccine candidate against K. pneumoniae, and further validate the potential of mHla as a versatile carrier protein and adjuvant for antigen design.

Human enterovirus (EV) infections can lead to various manifestations, with variable correlations between genotypes and symptoms. Human enterovirus D68 (EV-D68) was considered to be associated with acute respiratory disease and acute flaccid myelitis. In this short report, both EV-D68 and poliovirus 3 were detected in the stool of a hospitalized 5-month child who presented with acute respiratory symptoms and who was recently vaccinated with oral polio vaccine (OPV), using a metatranscriptomic high-throughput sequencing method. The nearly full-length genome sequences with complete open reading frames of EV-D68 and poliovirus 3 were assembled. One previously-reported neurovirulence-related amino acid substitution (T860N) in the EV-D68 VP1 region was observed, but the patient showed no neurological symptoms. More attention should be paid to EV-D68, and continuous multiple syndrome-based surveillance on non-polio enterovirus is called for.

Summary: Background: The dual impacts of a warming climate and population ageing lead to an increasing kidney disease prevalence, highlighting the importance of quantifying the burden of kidney disease (BoKD) attributable to high temperature, yet studies on this subject are limited. The study aims to quantify the BoKD attributable to high temperatures in Australia across all states and territories, and project future BoKD under climatic, population and adaptation scenarios. Methods: Data on disability-adjusted-life-years (DALYs) due to kidney disease, including years of life lost (YLL), and years lived with disability (YLD), were collected during 2003–2018 (baseline) across all states and territories in Australia. The temperature-response association was estimated using a meta-regression model. Future temperature projections were calculated using eight downscaled climate models to estimate changes in attributable BoKD centred around 2030s and 2050s, under two greenhouse gas emissions scenarios (RCP4.5 and RCP8.5), while considering changes in population size and age structure, and human adaptation to climate change. Findings: Over the baseline (2003–2018), high-temperature contributed to 2.7% (Standard Deviation: 0.4%) of the observed BoKD in Australia. The future population attributable fraction and the attributable BoKD, projected using RCP4.5 and RCP8.5, showed a gradually increasing trend when assuming no human adaptation. Future projections were most strongly influenced by the population change, with the high temperature-related BoKD increasing by 18.4–67.4% compared to the baseline under constant population and by 100.2–291.2% when accounting for changes in population size and age structure. However, when human adaptation was adopted (from no to partial to full), the high temperature-related BoKD became smaller. Interpretation: It is expected that increasing high temperature exposure will substantially contribute to higher BoKD across Australia, underscoring the urgent need for public health interventions to mitigate the negative health impacts of a warming climate on BoKD. Funding: Australian Research Council Discovery Program.

Carboxyamidotriazole (CAI) was initially considered a non-cytotoxic anticancer agent. However, recently, pronounced anti-inflammatory properties of CAI have been reported. Rheumatoid arthritis (RA) is an autoimmune inflammatory disease characterized by aberrant activation of signaling pathways. Therefore, this study explored the therapeutic effects and potential mechanism of action of CAI on RA in the adjuvant arthritis (AA) model. The results showed that CAI reduced the severity of arthritis in AA rats as demonstrated by inhibited hind paw swelling, reduced body weight, and decreased infiltration of joint pathological inflammatory cells. Importantly, pathological scoring of new blood vessels and immunohistochemical assays revealed that CAI inhibited pannus formation. CAI decreased the expression of pro-angiogenic growth factors, such as vascular epidermal growth factor, basic fibroblast growth factor, and metalloproteinases (MMPs), namely, MMP-1 and MMP-3 in the synovium of AA rats. Furthermore, CAI significantly reduced the increased levels of phosphorylated p38, c-Jun N-terminal kinase (JNK)1/2, and extracellular signal-regulated kinase (ERK)1/2 proteins in AA rats. In addition, the proliferation of fibroblast-like synoviocytes (FLS) was downregulated by CAI both in vivo and in vitro. In conclusion, this investigation illustrates the therapeutic effect of CAI on synovitis and erosion of articular cartilage in RA. Furthermore, the mechanism might involve inhibition of aberrantly activated mitogen-activated protein kinase signaling, as well as a decrease in pro-angiogenic factors, MMP expression, and FLS proliferation.

Summary: Background: Accelerated approval (AA) of novel anticancer drugs based on surrogacy has attracted considerable concern globally. China National Medical Products Administration (NMPA) also established a similar conditional approval (CA) program to accelerate the approval of novel drugs to address unmet medical needs. This cross-sectional study aimed to evaluate the pre-approval clinical trial evidence and potential challenge of cancer drugs receiving CA in China from policy implementation to 2022. Methods: The cancer drugs (initial and supplemental indications) granted CA between January 1, 2015 and December 31, 2022 using the public database of the NMPA were analyzed. The characteristics of the cancer drugs received CA were described. Primary efficacy endpoints and safety derived from the pre-approval clinical trial, including response rates (RR), progression-free survival (PFS), overall survival (OS), treatment-related serious adverse events (SAE) and Grade ≥3 adverse events (AEs) were quantitatively estimated by meta-analysis. Besides, the correlation between the surrogate endpoints and OS was estimated by the reported trial-level correlation analysis. Findings: The NMPA approved 72 cancer indications (56 new molecular entities) with CA between 2015 and 2022. 34 indications (47%) were also approved by the FDA or EMA. 74% (53/72) of cancer indications were based on a single-arm trial design while 26% (19/72) for randomized controlled trials. The pooled RR was 0.50 (95% CI: 0.45–0.55, I2 = 96%) with significant differences across cancer types and targets while the pooled hazard risk was 0.39 (95% CI: 0.28–0.53, I2 = 89%) for PFS and 0.67 (95% CI: 0.61–0.73, I2 = 0%) for OS. The pooled treatment-related SAE and Grade ≥3 AEs from single-arm designs resulted in 15% and 25%, respectively. In randomized controlled trials, the pooled treatment-related SAE and Grade ≥3 AEs observed in CA drugs and the control groups were comparable. Surrogate endpoints were widely used as the primary efficacy endpoints in the pre-approval pivotal clinical trials with 75% (54/72) for RR, 10% (7/72) for PFS, and 4% (3/72) for others. Of these, 27% (17/63) of the surrogate endpoints reported a trial-level correlation with OS; three reported high correlation (r ≥ 0.85), two reported moderate correlation (0.70 ≤ r

The antioxidant activity of curcumin has been extensively investigated for years. However, its molecular function mechanism remained unclear. Our preliminary study showed that curcumin downregulated miR-22-3p expression. This study aimed to address whether miR-22-3p mediated the antioxidant activity of curcumin and the possible action mechanism. The results showed that miR-22-3p repression increased the total cellular antioxidant capacity and enhanced the endogenous antioxidant enzyme system of LO2 cells. In addition, miR-22-3p-deteriorated cellular antioxidant capacity was prevented by curcumin pretreatment. Moreover, miR-22-3p inhibition significantly improved mitochondrial function and biogenesis. Further investigation demonstrated that a mitochondrial key regulator, the cardiolipin synthase gene (CRLS1), was targeted and downregulated by miR-22-3p. CRLS1 overexpression also significantly improved cellular antioxidant capacity and enhanced mitochondrial function and biogenesis in LO2 cells. Taken together, all these data suggested that miR-22-3p modulated the antioxidant effect of curcumin via targeting CRLS1, which may provide novel insights into miRNA-mediated antioxidant mechanism of curcumin.

Objective: The mechanistic target of rapamycin complex 1 (mTORC1) is a key molecule that links nutrients, hormones, and growth factors to cell growth/function. Our previous studies have shown that mTORC1 is required for β-cell functional maturation and identity maintenance; however, the underlying mechanism is not fully understood. This work aimed to understand the underlying epigenetic mechanisms of mTORC1 in regulating β-cell functional maturation. Methods: We performed Microarray, MeDIP-seq and ATAC-seq analysis to explore the abnormal epigenetic regulation in 8-week-old immature βRapKO islets. Moreover, DNMT3A was overexpressed in βRapKO islets by lentivirus, and the transcriptome changes and GSIS function were analyzed. Results: We identified two major epigenetic silencing mechanisms, DNMT3A-dependent DNA methylation and PRC2-dependent H3K27me3 modification, which are responsible for functional immaturity of Raptor-deficient β-cell. Overexpression of DNMT3A partially reversed the immature transcriptome pattern and restored the impaired GSIS in Raptor-deficient β-cells. Moreover, we found that Raptor directly regulated PRC2/EED and H3K27me3 expression levels, as well as a group of immature genes marked with H3K27me3. Combined with ATAC-seq, MeDIP-seq and ChIP-seq, we identified β-cell immature genes with either DNA methylation and/or H3K27me3 modification. Conclusion: The present study advances our understanding of the nutrient sensor mTORC1, by integrating environmental nutrient supply and epigenetic modification, i.e., DNMT3A-mediated DNA methylation and PRC2-mediated histone methylation in regulating β-cell identity and functional maturation, and therefore may impact the disease risk of type 2 diabetes.

C-type lectins are pattern recognition receptors (PRRs) involved in innate immunity. They possess one or more carbohydrate recognition domains (CRDs) belonging to Ca2+-dependent carbohydrate binding proteins. Herein, two C-type lectins were identified from the mud crab Scylla paramamosain. The open reading frame (ORF) of SpCTL-E encodes 160 amino acids including a CRD and a signal peptide, while the SpCTL-F ORF encodes a 244 amino acid polypeptide with a signal peptide and a CRD, and the key motifs for carbohydrate binding specificity are Asp-Pro-Asn (DPN) and Gln-Pro-Asp (QPD), respectively. DPN is a newly discovered motif, while QPD is typical of C-type lectins. The binding specificity toward different pathogen-associated molecular patterns (PAMPs) was analysed, and both bound three PAMPs: lipopolysaccharide (LPS), glucan (GLU) and peptidoglycan (PGN). SpCTL-F bound more strongly than SpCTL-E. SpCTL-E and SpCTL-F bound to five and seven microbial species, respectively, both agglutinated Gram-negative bacteria and fungi, and both promoted the phagocytosis activity of hemocytes toward Escherichia coli, and both enhanced the encapsulation activity of hemocytes towards Ni-NTA beads. SpCTL-E inhibited the growth of Micrococcus luteus and E. coli, while SpCTL-F also inhibited Vibrio parahaemolyticus. Thus, SpCTL-E and SpCTL-F are important PRRs with a broad nonself-recognition spectrum and play a key role in pathogen elimination.

Pickled radish is a general source of natural bioactive compounds that include phenols. Here, we used molecular docking, fluorescence quenching, circular dichroism spectroscopy and molecular dynamics simulations to identify potential inhibitors against xanthine oxidase from a library of pickled radish compounds. The most effective compounds were selected for validation through in vitro experiments including enzyme activity inhibition tests, and cell-based assays. Molecular docking results revealed that 2,6-Dihydroxyacetophenone, 4-Hydroxyphenethyl alcohol, and 4-Hydroxybenzaldehyde exhibited significant effects on xanthine oxidase inhibition. Three phenols have varying degrees of inhibition on xanthine oxidase, which is driven by hydrophobic interactions and hydrogen bonds and affects the secondary structure and hydrophobic homeostasis of xanthine oxidase. The stability of xanthine oxidase inhibition by three phenols was analyzed by molecular dynamics simulation. Finally, cellular experiments confirmed that three phenols reduced uric acid levels by inhibiting the xanthine oxidase enzyme activity of BRL 3A cells.

Objective: To determine the duration of SARS-CoV-2 persistence in quarantine hotel environments. Methods: 39 Patients confirmed by RT-PCR were included. We collected clinical features, laboratory test results, smear sample information, and quarantine room information. Genome sequencing and phylogenetic analysis were conducted. We analyzed the factors associated with environmental contamination. Result: Among 39 COVID-19 cases, 10 were asymptomatic and 37 were imported from aboard. We collected 271 swab samples from environmental surfaces related to observational patients. Eighteen swab samples from seven patients were positive. The highest contamination rates occurred on cups (100%), followed by hand sink (12.82%), toilet seat and flush (7.89%), telephone (5.56%), bedside table (5.56%), and floor drain (5.41%). The results showed that environmental surface contamination was associated with the clinical cycle threshold values for patients (P = 0.01) and the sampling interval time after the cases left their rooms (P = 0.03). The duration of environmental surface contamination was associated with the wet status of the sampling site (P = 0.01). Conclusion: Our findings showed that environmental contamination might be attributed to the viral load in the respiratory tracts of patients and the sampling interval time after the cases left their rooms. Moist surfaces were more vulnerable to remaining SARS-CoV-2 RNA-positive. Our study highlights the importance of implementing strict chemical disinfection strategies in quarantine rooms.

Background & Aims: Rapid gastric epithelial progenitor cell (EPC) proliferation and inflammatory response inhibition play key roles in promoting the repair of gastric mucosal damage. However, specific targets inducing these effects are unknown. In this study, we explored the effects of a potential target, Ankyrin repeat domain 22 (ANKRD22). Methods: An acute gastric mucosal injury model was established with Ankrd22-/- and Ankrd22+/+ mice by intragastric administration of acidified ethanol. Organoid culture and flow cytometry were performed to evaluate the effects of ANKRD22 on leucine-rich repeat-containing G-protein–coupled receptor 5–positive (Lgr5+) gastric EPC proliferation. The mechanisms by which ANKRD22 affects gastric EPC proliferation and inflammatory responses were explored by mitochondrial Ca2+ influx and immunoblotting. Candidate ANKRD22 inhibitors then were screened virtually and validated in vitro and in vivo. Results: After acute gastric mucosal injury, the number of Lgr5+ gastric EPCs was increased significantly in Ankrd22-/- mice compared with that in Ankrd22+/+ mice. Moreover, Ankrd22 knockout attenuated inflammatory cell infiltration into damaged gastric tissues. ANKRD22 deletion also reduced mitochondrial Ca2+ influx and cytoplasmic nuclear factor of activated T cells in gastric epithelial cells and macrophages, which further induced Lgr5+ gastric EPC proliferation and decreased macrophage release of tumor necrosis factor-α and interleukin 1α. In addition, a small molecule, AV023, was found to show similar effects to those produced by ANKRD22 deletion in vitro. Intraperitoneal injection of AV023 into the mouse model promoted the repair of gastric mucosal damage, with increased proliferation of Lgr5+ gastric EPCs and visible relief of inflammation. Conclusions: ANKRD22 inhibition is a potential target-based therapeutic approach for promoting the repair of gastric mucosal damage.

N6-Methyladenosine (m6A) is the most common internal modification of eukaryotic messenger RNA (mRNA) that occurred on the N6 nitrogen of adenosine. However, the roles of m6A in oral squamous cell carcinoma (OSCC) are still elusive. Here, we investigate the function and mechanism of methyltransferase-like 3 (METTL3) in OSCC tumorigenesis. Clinically, METTL3 was significantly upregulated in tissue samples and correlated with the poor prognosis of OSCC patients. Functionally, loss and gain studies illustrated that METTL3 promoted the proliferation, invasion, and migration of OSCC cells in vitro, and METTL3 knockdown inhibited tumor growth in vivo. Mechanistically, methylated RNA immunoprecipitation sequencing (MeRIP-seq) illustrated that METTL3 targeted the 3′ UTR (near to stop codon) of the c-Myc transcript to install the m6A modification, thereby enhancing its stability. Furthermore, results revealed that YTH N6-methyladenosine RNA binding protein 1 (YTH domain family, member 1 [YTHDF1]) mediated the m6A-increased stability of c-Myc mRNA catalyzed by METTL3. In conclusion, our findings herein identify that METTL3 accelerates the c-Myc stability via YTHDF1-mediated m6A modification, thereby giving rise to OSCC tumorigenesis.