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Obesity rates have rapidly increased worldwide and obesity-related diseases such as hypertension and cardiovascular diseases have become leading factors for global morbidity and mortality. Currently, there are no effective treatments that can prevent or reverse obesity long-term, and hence the prevention of obesity-related adverse effects such as hypertension is critical. Qingda granule (QDG) is a condensed Traditional Chinese Medicine (TCM) formula that has been used clinically for treating hypertension, however, its effectiveness in obesity-induced hypertension and cardiac dysfunction remains explored. Mouse models of obesity via long-term feeding of high-fat high-fructose diet (HFFD) were established to examine the effect and mechanism of QDG in protecting against obesity-induced hypertension and cardiac dysfunction. C57BL/6 mice were fed with either normal diet or HFFD over a period of 16 weeks and administered with either saline or QDG for assessment of obesity-induced blood pressure and cardiac function. QDG administration demonstrated robust anti-hypertensive effects and significantly attenuated HFFD-induced elevations in blood pressures. Moreover, QDG treatment also demonstrated robust cardioprotective effects during obesity-induced hypertension by markedly improving cardiac function and preventing cardiac hypertrophy. QDG protected against obesity-induced hypertension and cardiac dysfunction was due to its ability to prevent adverse chronic activation of Akt signaling pathway during long-term feeding of HFFD. Long-term usage of QDG treatments exhibited no observable side effects and also completely prevented obesity-induced organ damage, demonstrating the feasibility and safety of prolonged use. Our findings thus elucidated the role of QDG in preventing obesity-induced hypertension and cardiac hypertrophy via inhibiting adverse activation of Akt signaling activation. Therefore, our study provides the theoretical basis for the utilization of QDG as both a safe and effective drug in the therapeutic treatment of metabolic diseases such as obesity-induced hypertension.

The development of radiotherapy technology improved outcomes in rectal cancer. Nevertheless, radiotherapy resistance has become a significant problem. This resistance is associated with tumor microenvironment (TME) hypoxia, cell cycle block, and related genetic alterations. We designed a novel miRNA-delivered and improved hypoxic microenvironment sensitization therapy for rectal cancer. With the protection of Zeolitic Imidazolate Framework-8 (ZIF-8) and the delivery of nano-manganese dioxide particles, the nanocomplex exhibited outstanding catalytic mimetic activity in decomposing hydrogen peroxide into oxygen, thus significantly reversing the TME hypoxia. The radiosensitizer miRNA-181a induces DNA damage directly after radiotherapy. We loaded miR181a into the MnO2@ZIF-8-polyethylene glycol nanocomplex to prevent its degradation in the circulatory system and successfully carry miR181a into the tumor. MiR181a-MnO2@ZIF-8 overcame radioresistance and enhanced therapeutic efficacy in a subcutaneous tumor model. This multiple sensitization strategy of the combined delivery of miR181a with MnO2@ZIF-8 nanoenzymes provides a promising therapeutic approach for rectal cancer.

Based on reviews and summaries of the naming schemes of fine-grained sedimentary rocks, and analysis of characteristics of fine-grained sedimentary rocks, the problems existing in the classification and naming of fine-grained sedimentary rocks are discussed. On this basis, following the principle of three-level nomenclature, a new scheme of rock classification and naming for fine-grained sedimentary rocks is determined from two perspectives: First, fine-grained sedimentary rocks are divided into 12 types in two major categories, mudstone and siltstone, according to particle size (sand, silt and mud). Second, fine-grained sedimentary rocks are divided into 18 types in four categories, carbonate rock, fine-grained felsic sedimentary rock, clay rock and mixed fine-grained sedimentary rock according to mineral composition (carbonate minerals, felsic detrital minerals and clay minerals as three end elements). Considering the importance of organic matter in unconventional oil and gas generation and evaluation, organic matter is taken as the fourth element in the scheme. Taking the organic matter contents of 0.5% and 2% as dividing points, fine grained sedimentary rocks are divided into three categories, organic-poor, organic-bearing, and organic-rich ones. The new scheme meets the requirement of unconventional oil and gas exploration and development today and solves the problem of conceptual confusion in fine-grained sedimentary rocks, providing a unified basic term system for the research of fine-grained sedimentology.

Abstract Aims To explore the correlation between cardiac‐related comorbidities, cardiac biomarkers, acute myocardial injury, and severity level, outcomes in COVID‐19 patients. Method Pubmed, Web of Science, Embase, CNKI, VIP, Wanfang, Cochrane Library databases, medRxiv, and Sinomed were reviewed systemically. Various types of clinical research reporting cardiac‐related comorbidities, cardiac biomarkers including lactate dehydrogenase (LDH), troponin I (TnI), high sensitivity troponin I (hs‐TnI), creatine kinase (CK), creatine kinase–MB (CK‐MB), myoglobin (Myo), N‐terminal pro‐b‐type natriuretic peptide (NT‐proBNP) and acute cardiac injury grouped by severity of COVID‐19 were included. Outcome measures were events and total sample size for comorbidities, acute cardiac injury, and laboratory parameters of these biomarkers. The study was performed with Stata version 15.1. Results Seventy studies, with a total of 15,354 cases were identified. The results showed that COVID‐19's severity was related to cardiovascular disease. Similar odds ratios (ORs) were achieved in hypertension except for severe versus critical group (OR = 1.406; 95% CI, 0.942–2.097; p = .095). The relative risk (RR) of acute cardiac injury is 7.01 (95% CI, 5.64–8.71) in non‐survivor cases. When compared with the different severity of cardiac biomarkers, the pool OR of CK, CK‐MB, TnI, Myo and LDH were 2.683 (95% CI, 0.83–8.671; p = .106; I2 = 0%), 2.263 (95% CI, 0.939–5.457; p = .069), 1.242 (95% CI, 0.628–2.457; p = .534), 1.756 (95% CI, 0.608–5.071; p = .298; I2 = 42.3%), 1.387 (95% CI, 0.707–2.721; p = .341; I2 = 0%) in the critical versus severe group, whose trends were not similar to other groups. The standard mean differences (SMD) of CK and TnI in the critical versus severe group were 0.09 (95% CI, −0.33 to 0.50; p = .685; I2 = 65.2%), 0.478 (95% CI, −0.183 to 1.138; p = .156; I2 = 76.7%), which means no difference was observed in the serum level of these indicators. Conclusion Most of the findings clearly indicate that hypertension, cardiovascular disease, acute cardiac injury, and related laboratory indicators are associated with the severity of COVID‐19. What is now needed are cross‐national prospectively designed observational or clinical trials that will help improve the certainty of the available evidence and treatment decisions for patients.

PURPOSETo map the magnitudes and temporal trends of chronic myeloid leukemia (CML) along with its attributable risk factors, providing the essential foundation for targeted public policies at the national, regional, and global levels.MATERIALS AND METHODSWe retrieved annual data on CML burden in 204 countries and regions from the Global Burden of Disease Study 2019 in 1990-2019. The estimated annual percentage change (EAPC) was calculated to quantify the temporal trends of CML burden by region, sex, and age group.RESULTSGlobally, the age-standardized incidence rate of CML declined weakly over the past few years (EAPC: −1.04), but the number of incident cases increased by 54.1% to 65.8 × 103 in 2019. By contrast, a dramatic drop in death and disability-adjusted life years (DALYs) rate (EAPCs: −2.55; −2.69) led to a reduction in deaths and DALYs, especially in high-income regions. In 2019, the highest age-standardized death rate was observed in Ethiopia (1.89 per 100,000). The death rate of CML was pronounced among the population age above 70 years. DALYs of CML worldwide were primarily attributable to smoking (12.2%), high body mass index (5.0%), occupational exposure to benzene (0.9%), and occupational exposure to formaldehyde (0.3%) in 2019.CONCLUSIONAlthough the mortality rate of CML has decreased significantly, the management of patients with CML cannot be neglected, especially in elders and developing regions.

Crop breeding is an important global strategy to meet sustainable food demand. CRISPR/Cas is a most promising gene-editing technology for rapid and precise generation of novel germplasm and promoting the development of a series of new breeding techniques, which will certainly lead to the transformation of agricultural innovation. In this review, we summarize recent advances of CRISPR/Cas technology in gene function analyses and the generation of new germplasms with increased yield, improved product quality, and enhanced resistance to biotic and abiotic stress. We highlight their applications and breakthroughs in agriculture, including crop de novo domestication, decoupling the gene pleiotropy tradeoff, crop hybrid seed conventional production, hybrid rice asexual reproduction, and double haploid breeding; the continuous development and application of these technologies will undoubtedly usher in a new era for crop breeding. Moreover, the challenges and development of CRISPR/Cas technology in crops are also discussed.

The morphologies and sizes of TiN inclusions in gear steel 20CrMnTi have a significant impact on its service performance. This paper selects rare earth Ce to modify TiN inclusions in 20CrMnTi. The inclusions are analyzed by SEM (scanning electron microscope), EBSD (electron back-scattered diffraction), EDS (energy disperse spectroscopy), and OTS statistical software, and Thermo-Calc software is used to calculate the inclusion formations. The inclusions of MgAlO4-Ce and CeAlO3 can be formed when rare earth Ce is added into 20CrMnTi, which becomes TiN nucleation core after precipitation. Without the addition of rare earth Ce, square TiN inclusions ranging from 2 to 5 μm account for 60% of the total inclusions in 20CrMnTi. After adding rare earth Ce, the TiN inclusions in 20CrMnTiCe account for 36.7% of the total inclusions. Due to the new phase formations of MgAlO4-TiN and CeAlO3-TiN with sizes less than 2 μm, the titanium-containing inclusions are refined. Fatigue tests are conducted on the steels before and after the addition of Ce. The average fatigue lives of 20CrMnTi do not reach 107 times, and the deviations between the maximum and minimum fatigue lives are great. Large-sized TiN are the main inclusions that affect the fatigue performance of 20CrMnTi. The average fatigue lives of 20CrMnTiCe exceed 107 times, and the deviations of the fatigue lives are smaller than those of 20CrMnTi.

Vegetation filter strips (VFSs) have always been an important measure to control agricultural soil erosion, especially in mountainous and hilly areas with more sloping farmland. To investigate the mechanism of the sediment-trapping process by VFSs, a series of tests were conducted with four gradients of flow rate, 7.5–45 L min−1 m−1, and two different sediment concentrations of 40 and 120 g L−1. The whole process of overland flow was monitored, and sediment and particle size samples from the inflow and outflow were collected and measured. The results showed that the changes in sediment concentration did not significantly affect the corresponding coefficients in the power function relationship between overland flow rate and velocity. Using the Reynolds number alone cannot effectively indicate the flow pattern of overland flow on vegetation hillslopes. The peak particle size and linear function were effective in describing the relationship between sediment particle composition and delivery rate during the sediment-trapping process by VFSs. During the sediment-trapping process, the sediment-trapping capacity of VFSs continued to decrease. The increase in sediment discharge was accompanied by a higher proportion of coarse particles. Under the same flow rate conditions, when the sediment concentration was higher, the coarse particles and their proportion also increased faster. Therefore, using only a certain particle size threshold to distinguish suspended and transported sediment may lead to inaccurate estimation of the sediment-trapping performance of VFSs. This study deepened the understanding of the mechanism of water–sediment processes on vegetation hillslopes and promoted the widespread and efficient application of VFSs management technology.

The bond between a steel reinforcement/rod and glulam plays a crucial role in the resistance and deformation capacity of timbers joints. Existing studies provide different bond–slip models for reinforcements and rods with different anchorage lengths, in which the relationship between local bond stress and global bond behaviour cannot not be established. This study presents a unified analytical method for predicting the bond–slip behaviour of ribbed bars and threaded rods along the grain using a local bond–slip model of reinforcement at the elastic and post-yield stages. In the analytical method, equilibrium, compatibility, and constitutive models for reinforcement and rods are considered. The method is verified using test data of rebars and rods with different anchorage lengths. Comparisons between the experimental and calculated results suggest that the analytical method yields reasonably good predictions of the load–slip relationship and failure mode. Furthermore, the embedment lengths required for yield and the ultimate strengths of the reinforcement and rods along the grain are determined by assuming uniform bond stress distributions over the elastic and post-yield steel segment. The average bond stress over the entire anchorage length is calculated and compared with existing equations. Design recommendations for anchorage lengths are proposed for ribbed bars and threaded rods glued in glulam.

The fundamental mechanisms of ultrafast demagnetization and magnetization recovery processes in ferromagnetic materials remain incompletely understood. The investigation of different dynamic features which depend on various physical quantities requires a more systematic approach. Here, the femtosecond laser-induced demagnetization and recovery dynamics in L10-Fe0.5Pt0.5 alloy film are studied by utilizing time-resolved magneto-optical Kerr measurements, focusing on their dependences of excitation fluence and ambient temperature over broad ranges. Ultrafast demagnetization dominated by Elliott-Yafet spin-flip scattering, and two-step magnetization recovery processes are found to be involved in all observations. The fast recovery time corresponding to spin–lattice relaxation is much shorter than that of many ferromagnets and increase with excitation fluence. These can be ascribed to the strong spin–orbit coupling (SOC) demonstrated in FePt and the reduction of transient magnetic anisotropy, respectively. Surprisingly, the demagnetization time exhibits no discernible correlation with ambient temperature. Two competitive factors are proposed to account for this phenomenon. On the other hand, the spin–lattice relaxation accelerates as temperature decreases due to enhanced SOC at lower ambient temperature. A semiquantitative analysis is given to get a visualized understanding. These results offer a comprehensive understanding of the dynamic characteristics of ultrafast demagnetization and recovery processes in iron-based materials with strong SOC, highlighting the potential for regulating the magnetization recovery process through temperature and laser fluence adjustments.

In this paper, the results of a study on the influences of different morphologies, types, and sizes of inclusions on the fatigue lives of 20CrMnTi are reported. The results show that the addition of the rare earth element Ce can lead to the formation of spherical CeAlO3-TiN inclusions in 20CrMnTi. The fatigue performance of 20CrMnTi-Ce was significantly improved compared to that of 20CrMnTi. Using the “edge-to-edge matching” crystallographic theory, CeAlO3 was validated as a suitable hetero-nucleus core for TiN, and the following best orientation relationships between them were determined: [010]TiN//[21¯1¯1] CeAlO3&(002) TiN//(112¯1)CeAlO3. The fatigue cycle times of 20CrMnTi-Ce range up to 107, and this value is higher than that of 20CrMnTi without Ce. As the size of the TiN inclusions increases, the maximum stress of the steel matrix also increases. Also, the high-stress and low-life regions noticeably increase, thus increasing the possibility of a fatigue fracture. Under the same sizes of inclusions, the high-stress and low-life regions of square TiN are larger than those of circular TiN.

Lead is the primary toxic element found in jarosite residue; it is necessary to synthesize simulated lead-containing jarosite residue (SLJS) to investigate its lead release behavior and predict the slag’s stability and potential for secondary environmental pollution. This study explores the ion release behavior, leaching toxicity, and stability of SLJS during freeze–thaw cycles with EDTA (E-FTC). Experimental results demonstrate that the release of lead, iron, and sulfate from SLJS under E-FTC is contingent upon multiple factors, including solution pH, EDTA concentration, freeze–thaw cycles, freezing temperature, and freeze–thaw mode. Specifically, employing an EDTA concentration of 200 mM, a pH of 6, a freezing temperature of −20 °C, and 12 freeze–thaw cycles, the lead release reaches 15.1 mM, accounting for 94.9% of the total lead content, while iron is negligibly released, thus enabling effective separation of lead from iron. Subsequent to E-FTC, the exchangeable lead content exhibits a substantial reduction, accompanied by a marked increase in residual lead, resulting in a remarkable 98% reduction in leaching toxicity. Moreover, the equilibrium concentration of lead in the continuous stable leaching solution is 0.13 mg/L, significantly below the lead toxicity threshold (5 mg/L). Therefore, environmental stability can be greatly enhanced. This study presents a novel approach for the safe disposal of jarosite residue under mild conditions and at low temperatures, contributing to the broader field of environmentally sustainable waste management.

Congenital macrothrombocytopenia is a genetically heterogeneous group of rare disorders. We herein report a large Chinese family presented with phenotypic variability involving thrombocytopenia and/or giant platelets. Whole genome sequencing (WGS) of the proband and one of his affected brothers identified a potentially pathogenic c.952 C > T heterozygous variant in the TUBB1 gene. This p.R318W β1-tubulin variant was also identified in three additional siblings and five members of the next generation. These findings were consistent with an autosomal dominant inheritance with incomplete penetrance. Moreover, impaired platelet agglutination in response to ristocetin was detected in the patient’s brother. Half of the family members harboring the p.R318W mutation displayed significantly decreased external release of p-selectin by stimulated platelets. The p.R318W β1-tubulin mutation was identified for the first time in a Chinese family with congenital macrothrombocytopenia using WGS as an unbiased sequencing approach. Affected individuals within the family demonstrated impaired platelet aggregation and/or release functions.

Non‐small cell lung cancer (NSCLC) is the most common subtype of lung cancer, and it is characterized by a high incidence. It is important to understand the molecular mechanisms that determine the progression and metastasis of NSCLC in order to develop more effective therapies and identify novel diagnostic indicators of NSCLC. RSPH14 has been reported to be related to multiple human diseases, including duodenal adenocarcinoma and meningiomas, but the role of RSPH14 in NSCLC remains unclear. The present study aimed to investigate the molecular function and clinical significance of RSPH14 in NSCLC. Analyses of public datasets and clinical samples demonstrated that RSPH14 expression was upregulated in NSCLC samples compared with normal samples. In addition, high RSPH14 expression was associated with a shorter overall survival time in patients with NSCLC. Notably, RSPH14 knockdown suppressed the proliferation and cell cycle progression and enhanced the apoptosis of NSCLC cells. Mechanically, tandem mass tag analysis demonstrated that RSPH14 can affect multiple processes, including the AMPK signaling pathway, calcium ion import regulation, glucose transmembrane transporter activity, and glucose transmembrane transport. Taken together, the results of the present study suggest that RSPH14 may be a promising prognostic factor and therapeutic target for NSCLC.

Abstract Background Colorectal cancer (CRC) is one of the most highly malignant tumors and has a complicated pathogenesis. A preliminary study identified syntrophin beta 1 (SNTB1) as a potential oncogene in CRC. However, the clinical significance, biological function, and underlying mechanisms of SNTB1 in CRC remain largely unknown. Thus, the present study aimed to investigate the role of SNTB1 in CRC. Methods The expression profile of SNTB1 in CRC samples was evaluated by database analysis, cDNA array, tissue microarray, quantitative real-time PCR (qPCR), and immunohistochemistry. SNTB1 expression in human CRC cells was silenced using short hairpin RNAs (shRNA)/small interfering RNAs (siRNA) and its mRNA and protein levels were assessed by qPCR and/or western blotting. Cell viability, survival, cell cycle, and apoptosis were determined by the CCK-8 assay, colony formation, and flow cytometry assays, respectively. A xenograft nude mouse model of CRC was established to validate the roles of SNTB1 in vivo. Immunohistochemistry and TUNEL staining were used to determine the expression of SNTB1, PCNA, and cell apoptosis in tissue samples. Isobaric tag for relative and absolute quantification (iTRAQ) was used to analyze the differentially expressed proteins after knockdown of SNTB1 in CRC cells. Silence of protein kinase N2 (PKN2) using si-PNK2 was performed for rescue experiments. Results SNTB1 expression was increased in CRC tissues compared with adjacent noncancerous tissues and the increased SNTB1 expression was associated with shorter overall survival of CRC patients. Silencing of SNTB1 suppressed cell viability and survival, induced cell cycle arrest and apoptosis in vitro, and inhibited the growth of CRC cells in vivo. Further elucidation of the regulation of STNB1 on CRC growth by iTRAQ analysis identified 210 up-regulated and 55 down-regulated proteins in CRC cells after SNTB knockdown. A PPI network analysis identified PKN2 as a hub protein and was up-regulated in CRC cells after SNTB1 knockdown. Western-blot analysis further confirmed that SNTB1 knockdown significantly up-regulated PKN2 protein expression in CRC cells and decreased the phosphorylation of both ERK1/2 and AKT. Moreover, rescue experiments indicated that PKN2 knockdown significantly rescued SNTB1 knockdown-mediated decrease in cell viability, survival, and increase of cell cycle arrest at G0/G1 phase and apoptosis of CRC cells. Conclusions These findings indicate that SNTB1 is overexpressed in CRC. Elevated SNTB1 levels are correlated with shorter patient survival. Importantly, SNTB1 promotes tumor growth and progression of CRC, possibly by reducing the expression of PKN2 and activating the ERK and AKT signaling pathway. Our study highlights the potential of SNTB1 as a new prognostic factor and therapeutic target for CRC.

Scirpus planiculmis, an important weed in rice and cotton fields, stresses crop growth and development, leading to yield loss. However, it is unclear how stressed plants respond to this weed. In this study, we analysed the stress effect of S. planiculmis on cotton under different weed densities, competition periods, and distribution conditions from the perspective of morphogenesis, physiological metabolism and crop yield. The effect of a low dose of herbicide on the relationship between cotton and S. planiculmis was also explored. The results showed that plant height, stem diameter, fresh weight, root length, boll number, single boll weight and yield of cotton all decreased with increasing S. planiculmis density and damage. The spatial distribution of S. planiculmis had no significant effect on plant height, stem diameter, fresh weight or root length of cotton, but crop yield loss decreased with increasing distance. S. planiculmis stress altered cotton chlorophyll, soluble protein and malondialdehyde (MDA) content, and protective enzyme activities. Compared with superoxide dismutase (SOD) and peroxidase (POD) activities, catalase (CAT) activity was increased under different S. planiculmis stress conditions. Therefore, we concluded that CAT plays a key role in protecting enzymes involved in defence responses. Under low-dose herbicide action, the activities of protective enzymes were increased, which helped cotton plants to resist S. planiculmis stress. The results revealed that regulating protective enzyme activities is important in cotton responses to S. planiculmis stress.

The fall armyworm (FAW), Spodoptera frugiperda, is a highly polyphagous lepidopteran pest, with its growth and adaptation affected by different host plants. However, little is known about the effects of host plants on ovarian development in this species. Thus, we evaluated the effects of feeding on corn (Zea mays L.) and goosegrass (Eleusine indica), on the ovarian development of S. frugiperda. Using various stages of S. frugiperda, we also evaluated the larval and pupal weights, number of eggs, and differentiation of ovarioles over time. Results showed that females fed on goosegrass had shorter ovarioles and laid less eggs than those fed on corn. Transcriptome analysis identified 3,213 genes involved in ovarian development in the fall armyworm. Of these, 881 genes were differentially expressed when fed on corn and goosegrass. The analysis also indicated that the hormone biosynthetic pathways may be involved in the reproductive system. In relation to the reproductive function, nine juvenile hormone (JH) biosynthetic genes, four 20-hydroxyecdysone (20E) biosynthetic genes, and four ovary-relevant functional genes were identified. The time course of the expression profiles of these hormone- and ovary development-related genes was measured by quantitative real-time PCR (qRT-PCR). In total, six of them showed a decreasing trend in the ovary of the FAW fed on goosegrass, while two genes showed an increasing trend. Our results showed that significant changes in the reproductive activity/ovary development in the FAW occurred in response to different diets. These results serve as bases for evaluating how optimal host plants and feeding preference affect ovarian development in the FAW.

Primary immune thrombocytopenia (ITP) is the most common acquired autoimmune bleeding disorder. Abnormally increased levels of High Mobility Group Box 1 (HMGB1) protein associate with thrombocytopenia and therapeutic outcome in ITP. Previous studies proposed that a natural inhibitor of HMGB1, 18β-glycyrrhetinic acid (18β-GA), could be used for its anti-inflammatory and immune-modulatory effects, although its ability to correct immune balance in ITP is unclear. In this study, we showed that plasma HMGB1 correlated negatively with platelet counts in ITP patients, and confirmed that 18β-GA stimulated the production of regulatory T cells (Treg), restored the balance of CD4+ T-cell subsets and enhanced the suppressive function of Treg through blocking the effect on HMGB1 in patients with ITP. HMGB1 short hairpin RNA interference masked the effect of 18β-GA in Treg of ITP patients. Furthermore, we found that 18β-GA alleviated thrombocytopenia in mice with ITP. Briefly, anti-CD61 immune-sensitized splenocytes were transferred into severe combined immunodeficient mice to induce a murine model of severe ITP. The proportion of circulating Treg increased significantly, while the level of plasma HMGB1 and serum antiplatelet antibodies decreased significantly in ITP mice along 18β-GA treatment. In addition, 18β-GA reduced phagocytic activity of macrophages towards platelets both in ITP patients and ITP mice. These results indicate that 18β-GA has the potential to restore immune balance in ITP via inhibition of HMGB1 signaling. In short, this study reveals the role of HMGB1 in ITP, which may serve as a potential target for thrombocytopenia therapy.

Lung cancer is the leading cause of cancer-related deaths worldwide. Despite the recent advent of promising new targeted therapies, lung cancer diagnostic strategies still have difficulty in identifying the disease at an early stage. Therefore, the characterizations of more sensible and specific cancer biomarkers have become an important goal for clinicians. Circular RNAs are covalently close, endogenous RNAs without 5′ end caps or 3′poly (A) tails and have been characterized by high stability, abundance, and conservation as well as display cell/tissue/developmental stage-specific expressions. Numerous studies have confirmed that circRNAs act as microRNA (miRNA) sponges, RNA-binding protein, and transcriptional regulators; some circRNAs even act as translation templates that participate in multiple pathophysiological processes. Growing evidence have confirmed that circRNAs are involved in the pathogenesis of lung cancers through the regulation of proliferation and invasion, cell cycle, autophagy, apoptosis, stemness, tumor microenvironment, and chemotherapy resistance. Moreover, circRNAs have emerged as potential biomarkers for lung cancer diagnosis and prognosis and targets for developing new treatments. In this review, we will summarize recent progresses in identifying the biogenesis, biological functions, potential mechanisms, and clinical applications of these molecules for lung cancer diagnosis, prognosis, and targeted therapy.

The rapid growth of vascular smooth muscle cells (VSMCs) represents crucial pathological changes during the development of hypertensive vascular remodeling. Although quercetin exhibits significantly therapeutic effects on antihypertension, the systematic role of quercetin and its exact mode of action in relation to the VSMCs growth and its hypertension-related networking pharmacology is not well-documented. Therefore, the effect of quercetin was investigated using networking pharmacology followed by in vitro strategies to explore its efficacy against angiotensin II (Ang II)-induced cell proliferation. Putative genes of hypertension and quercetin were collected using database mining, and their correlation was investigated. Subsequently, a network of protein-protein interactions was constructed and gene ontology (GO) analysis was performed to identify the role of important genes (including CCND1) and key signaling pathways [including cell proliferation and Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway]. We therefore further investigated the effects of quercetin in Ang II-stimulated VSMCs. This current research revealed that quercetin significantly reduced the cell confluency, cell number, and cell viability, as well as expression of proliferating cell nuclear antigen (PCNA) in Ang II-stimulated VSMCs. Mechanistic study by western blotting confirmed that quercetin treatment attenuated the activation of JAK2 and STAT3 by reducing its phosphorylation in Ang II stimulated VSMCs. Collectively, the current study revealed the inhibitory effects of quercetin on proliferation of Ang II stimulated VSMCs, by inhibiting the activation of JAK2/STAT3 signaling might be one of underlying mechanisms.

Dry eye disease (DED) is a multifactorial syndrome that commonly occurs with depression. However, therapies targeting depression-related dry eye disease are rare. In the current study, we studied the beneficial effect of a natural flavone, acacetin, in depression-associated dry eye disease by utilizing the chronic unpredictable mild stress (CUMS) depression model. Our data showed that acacetin improved the depressive behaviors in sucrose preference test (SPT), tail suspension test (TST) and forced swim test (FST); relieved the dry eye symptoms including corneal epithelial impairments, tear production decrease and goblet cell loss in CUMS mice. Acacetin also inhibited NOD-like receptor protein 3 (NLRP3) inflammasome expression levels and suppressed inflammatory responses via enhancing glycoprotein 78 (gp78)/Insulin induced gene-1 (Insig-1)-controlled NLRP3 ubiquitination in CUMS mice. Furthermore, knockdown of gp78 compromised acacetin-conferred protective efficacy in depression-related dry eye disease. In summary, our findings indicated that acacetin exerts beneficial effect in depression-associated dry eye disease, which is tightly related to gp78-mediated NLRP3 ubiquitination.

Gastric cancer (GC) is one of the most common gastrointestinal malignancies in the world. Growing evidence emphasizes the critical role of long non-coding RNA (lncRNA) in GC tumorigenesis. The aim of the research was to elucidate the effect and mechanism of Babao Dan (BBD) on lymphangiogenesis of GC in vitro and in vivo via lncRNA-ANRIL/VEGF-C/VEGFR-3 signaling axis. The present study investigated BBD significantly decreased the expression of lncRNA-ANRIL and VEGF-C in GC cells (AGS, BGC823, and MGC80–3) by using real-time quantitative polymerasechain reaction (RT-qPCR) and the secretion and expression of VEGF-C by (enzyme linked immunosorbent assay) ELISA and western blot (WB). BBD significantly inhibited the tumor xenograft of GC growth and the expression of lncRNA-ANRIL, VEGF-C, VEGFR-3 and LYVE-1 in vivo. BBD reduced serum VEGF-C level. In vitro, BBD inhibited the tube formation and decreased the cell viability, proliferation and migration of HLECs by using tube formation, MTT, Hoechst and Transwell assays. In addition, WB assay found that BBD decreased the expression levels of VEGF-C, VEGFR-3, matrix metallopeptidase 2 (MMP-2) and matrix metallopeptidase 9 (MMP-9), and RT-qPCR assay found that the mRNA expression levels of lncRNA-ANRIL, VEGF-C, VEGFR-3, MMP-2, MMP-9, CDK4, Cyclin D1, and Bcl-2 were down-regulated, and the expression of p21 and Bax were increased. Taken together, these results demonstrated that BBD inhibited lymphangiogenesis of GC in vitro and in vivo via the lncRNA-ANRIL/VEGF-C/VEGFR-3 signaling axis.

Possessed of easy access to development and fair economic benefits, medium-high maturity continental shale oil and gas have become the focus of shale oil and gas study in the future. Shale oil and gas mainly occur in pores, but studies on the pore characteristics of shale oil and gas occurrence are by no means sufficient. Focused on shale from the Middle Jurassic Lianggaoshan Formation in Well TYX, Fuling block, southeast of Sichuan Basin where a breakthrough in shale oil and gas exploration was recently achieved, this study selects core samples and conducts a series of analyses, including vitrinite reflectance analysis, kerogen microscopic examination experiment, total organic carbon (TOC) content analysis, mineral composition analysis, gas content measurement, isothermal adsorption experiment, S1 content analysis, and others. The analyses are to identify the pore characteristics of the continental medium and high maturity shale oil and gas by virtue of scanning electron microscope (SEM) with Ar-ion milling and the image processing software ImageJ. The conclusions are drawn as follows: in terms of lithofacies, medium-high maturity continental shale oil and gas mainly occur in organic-rich clay shale and organic-rich mixed shale; with regard to material composition, shale oil and gas mainly occur in organic matter, illite-smectite mixed layers and illite. Shale adsorbed gas content accounts for at most 40% of the total shale gas content and shale free gas content takes up at least 60% of the total shale gas content. Pores of solid bitumen, solid bitumen-clay mineral complex mass, clay minerals, structured vitrinite, and funginite are mostly developed in shale. Among them, the first three types of pores are the main reservoir space in shale considering their large number, good roundness, medium pore diameter, fairly good roundness of pore edges, and the complex shapes which altogether contribute to the large surface porosity.

The deeply buried carbonate reservoir of Cambrian is an important target of oil and gas exploration in the Tarim Basin. Understanding the dissolution mechanism of the deep-buried carbonate reservoir is an urgent problem to be solved. In this study, 11 carbonate samples from three types of deep reservoirs in Tarim Basin were selected as experimental objects, and the dissolution process of carbonate reservoir was simulated by using an advanced reaction system of continuous flow at high temperature and high pressure. The dissolution test of continuous flow shows that the burial depth has an effect on carbonate dissolution, with the increasing of the depths from shallow to deep, the dissolution ability of acidic fluids in carbonate rocks increases first and then decreases. A comparison of dissolution results from different lithologic samples shows that the incomplete dolomitization calcite in the diagenetic stage provides the material basis for dissolution in the later stage. The relationship between reservoir type and physical property is discussed, and it is found that the permeability of the fracture-type and pore-fracture samples increase significantly after dissolution, indicating the pre-existing pores of carbonate rocks may be critical to the formation of high-quality reservoirs in deeply buried conditions. An interesting phenomenon was found by comparing the dissolution rates of experimental samples shows that the dissolution rate of dolomite reservoir has a trend of first increasing and then decreasing under the deeply buried environment, which proves that there is an optimal dissolution range of dolomite in the deeply buried environment, which is conducive to the formation of dolomite reservoir. The genetic model of burial dissolution in deep carbonate reservoirs was established and indicated that the search for dolostone reservoirs near the Himalayan fault may be a new idea for Cambrian deep oil and gas exploration.

Hypertension has become one of the important diseases harmful to human health. In China, Qingda granule (QDG) has been used to treat hypertension for decades. Previous studies by our team have shown that oxidative stress may be one of the pathways through which QDG inhibits hypertension-induced organs injury. However, the specific molecular mechanism of its anti-hypotension and renal oxidative stress response were unclearly. This study investigated QDG’s potential protective mechanism against hypertension-induced renal injury. Mice were infused with Angiotensin Ⅱ (Ang Ⅱ, 500 ng/kg/min) or equivalent saline solution (Control) and administered oral QDG (1.145 g/kg/day) or saline for four weeks. QDG treatment mitigated the elevated blood pressure and reduced renal pathological changes induced by Ang Ⅱ. As per the RNA sequencing results, QDG affects oxidative stress signaling. In agreement with these findings, QDG significantly attenuated the Ang Ⅱ-induced increase in Nitrogen oxides 1 (NOX1) and reactive oxygen species and the decrease in superoxide dismutase in renal tissue. Additionally, QDG significantly inhibited Interleukin 6 (IL-6), Tumor necrosis factor α (TNF-α), and Interleukin 1β (IL-1β) expression in renal tissues and blocked the phosphorylation of P65 (NF-κB subunit) and IκB. These results were confirmed in vitro. Overall, QDG reduced Ang Ⅱ-induced elevated blood pressure and renal injury by inhibiting oxidative stress and inflammation caused by NOX1 and NF-κB pathways. The results of this study provide an experimental basis for the clinical application of QDG, and to open up a new direction for the clinical treatment of hypertension.

Altered microenvironmental stiffness is a hallmark of inflammation. It is sensed by the mechanically activated cation channel Piezo1 in macrophages to induce subsequent immune responses. However, the mechanism by which the mechanosensitive signals shape the metabolic status of macrophages and tune immune responses remains unclear. We revealed that Piezo1-deficient macrophages exhibit reduced aerobic glycolysis in resting or liposaccharide (LPS)-stimulated macrophages with impaired LPS-induced secretion of inflammatory cytokines in vitro. Additionally, pretreatment with the Piezo1 agonist, Yoda1, or cyclical hydrostatic pressure (CHP) upregulated glycolytic activity and enhanced LPS-induced secretion of inflammatory cytokines. Piezo1-deficient mice were less susceptible to dextran sulfate sodium (DSS)-induced colitis, whereas Yoda1 treatment aggravated colitis. Mechanistically, we found that Piezo1 activation promotes aerobic glycolysis through the Ca2+-induced CaMKII-HIF1α axis. Therefore, our study revealed that Piezo1-mediated mechanosensitive signals Piezo1 can enhance aerobic glycolysis and promote the LPS-induced immune response in macrophages.

Sialylation is a dynamically regulated modification, which commonly occurs at the terminal of glycan chains in glycoproteins and glycolipids in eukaryotic cells. Sialylation plays a key role in a wide array of biological processes through the regulation of protein–protein interactions, intracellular localization, vesicular trafficking, and signal transduction. A majority of the proteins involved in lipoprotein metabolism and atherogenesis, such as apolipoproteins and lipoprotein receptors, are sialylated in their glycan structures. Earlier studies in humans and in preclinical models found a positive correlation between low sialylation of lipoproteins and atherosclerosis. More recent works using loss- and gain-of-function approaches in mice have revealed molecular and cellular mechanisms by which protein sialylation modulates causally the process of atherosclerosis. The purpose of this concise review is to summarize these findings in mouse models and to provide mechanistic insights into lipoprotein sialylation and atherosclerosis.

Grain size effect on rock strength is a topic of great interest in geotechnical engineering. A consensus obtained from earlier laboratory tests is that rock strength generally decreases with the increase of grain size for both silicate and carbonate rocks; however, some recent numerical results conflict with such laboratory test results. To address this intriguing issue, the effect of grain size on strength of polymineralic crystalline rock with low porosity is investigated numerically using the grain-based modeling (GBM) approach in discrete element method (DEM) by interpreting micro-cracking process in response to loading. In agreement with some previous DEM simulation results, the simulated rock strength is found to increase with increasing grain size for both homogeneous and heterogeneous models, even when the number of assembled disks in one mineral grain changes. The mechanism of strength increase with increasing grain size is mainly associated with the number of assembled smooth-joint contacts along grain interfaces and the generation of grain boundary cracks in response to loading. The grain interfaces significantly weaken the integrity of the rock model, which is similar to effects of inherent defects in real rock. As the grain size increases, fewer grain interfaces are built in the model and the rock strength becomes much higher. Hence, by solely changing the mineral grain size in a model, the mechanism of grain size effect as observed in laboratory tests cannot be replicated. To address this issue, a method of degradation of grain boundary strength parameters is used to mimic the possible mechanism of grain size effect. The simulated strength using the method becomes comparable with those obtained from laboratory tests when the heterogeneity in the rock is considered. Degradation of grain boundary parameters with increasing grain size provides a plausible explanation for the grain size effect on rock strength.

AIM: To analyze the intellectual structure and recent research trends in diabetic retinopathy (DR) and unearth potential knowledge. METHODS: English DR publication included in this study was exported from the Web of Science Core Collection, and Chinese DR publication was exported from China National Knowledge Infrastructure from the establishment time of the database to 2019. CiteSpace and Microsoft Excel were used to visually analyze DR research, including analysis of the number of publications, highly cited publication analysis, spatial distribution analysis, and keyword co-occurrence analysis. RESULTS: A total of 23 795 English studies and 11 577 Chinese studies, including 2089 studies related to traditional Chinese medicine (TCM), were obtained. The data suggested the following: 1) The number of English and Chinese DR publications increased over time, and the growth rate of English publications was relatively fast. 2) The distribution of international scholars and institutions was close, while the distribution was scattered in China. Shanghai Jiao Tong University has the largest number of publications. Tien-Yin Wong was the core author with the largest number of publications. England and the United States are the core of international DR research cooperation. 3) Optical coherence tomography and risk factors are recent international research hot spots and trends. The difference is that TCM is a recent research trend under DR in China. CONCLUSION: DR has drawn an increasing amount of attention worldwide. The focus of research in this field has shifted from tertiary type DR treatment to secondary prevention strategies which focus on the screening and monitoring of disease progression. The advantages of TCM in the prevention of DR have attracted attention, and it is worth incorporating this with Western medicine to address this challenge.

Intracranial hemorrhage (ICH) is a devastating complication of immune thrombocytopenia (ITP). However, information on ICH in ITP patients under the age of 60 years is limited, and no predictive tools are available in clinical practice. A total of 93 adult patients with ITP who developed ICH before 60 years of age were retrospectively identified from 2005 to 2019 by 27 centers in China. For each case, 2 controls matched by the time of ITP diagnosis and the duration of ITP were provided by the same center. Multivariate analysis identified head trauma (OR = 3.216, 95%CI 1.296–7.979, P =.012), a platelet count ≤ 15,000/μL at the time of ITP diagnosis (OR = 1.679, 95%CI 1.044–2.698, P =.032) and severe/life-threatening bleeding (severe bleeding vs. mild bleeding, OR = 1.910, 95%CI 1.088–3.353, P =.024; life-threatening bleeding vs. mild bleeding, OR = 2.620, 95%CI 1.360–5.051, P =.004) as independent risk factors for ICH. Intraparenchymal hemorrhage (OR = 5.191, 95%CI 1.717–15.692, P =.004) and a history of severe bleeding (OR = 4.322, 95%CI 1.532–12.198, P =.006) were associated with the 30-day outcome of ICH. These findings may facilitate ICH risk stratification and outcome prediction in patients with ITP.

Abstract Pneumatic brake systems are crucial for the operation of trains. However, due to switching characteristics of on/off solenoid valves, the precise pressure control and low switching activities of valves are difficult to guarantee simultaneously during braking. To address the issue, a hybrid model predictive control (MPC) method is proposed for implementing the multi‐objective optimisation in this paper, i.e. the precise pressure tracking and the valve switching reduction. In order to model the hybrid behaviour caused by continuous dynamics of the pressure and discrete features of solenoid valves, the mixed logic dynamical system theory is applied. Then, the braking control problem is recast as a hybrid MPC problem, which jointly optimises the pressure tracking precision and the valve switching. A mixed integer linear program is formulated to solve the MPC problem in an efficient way. Both simulation and experiment results show that the accurate pressure control and low switching activities of valves can be achieved by the proposed method when compared with existing methods.

Abstract Background The provision of public adaptive coping strategies to reduce psychological tension during the ongoing COVID-19 pandemic is critical. We sought to provide evidence-based guidance for psychological intervention, exploring the potential mediating roles of three sources of social support (i.e., subjective support, family support and counselor support) between coping strategies (i.e., cognitive coping, emotional coping and behavioral coping), and anxiety among college students at the height of the pandemic in China. Methods Using the Coping Strategy Questionnaire, Social Support Questionnaire, and Self-Rating Anxiety Scale, this large-scale online study analyzed the levels of social support, coping, and anxiety among 2640 college students in China from February 21st to 24th, 2020, when the students had been isolated at home for 1 month since the lockdown of Wuhan city. Results Students reported high levels of cognitive coping, behavioral coping, and social support. They also experienced low levels of anxiety and emotional coping. Anxiety was significantly and negatively related to coping and social support. The mediating roles of three sources of social support were found between cognitive coping, behavioral coping, and anxiety, respectively. However, the effect of emotional coping on anxiety was not found to be mediated by social support. Conclusions Adopting positive coping strategies may enhance social support that in turn relieves anxiety. The effect of social support, especially family and counselor support, should arouse greater awareness in coping with the pandemic cognitively and behaviorally.

Cardiovascular diseases remain the leading cause of death worldwide, particularly ischemic heart disease (IHD). It is also classified as incurable given the irreversible damage it causes to cardiomyocytes. Thus, myocardial tissue rejuvenation following ischemia is one of the global primary research concerns for scientists. Interestingly, the mammalian heart thrives after an injury during the embryonic or neonatal period; however, this ability disappears with increasing age. Previous studies have found that specific non-coding (nc) RNAs play a pivotal role in this process. Hence, the review herein summarizes the research on cardiomyocyte regenerative medicine in recent years and sets forth the biological functions and mechanisms of the micro (mi)RNA, long non-coding (lnc)RNA, and circular (circ)RNA in the posttranscriptional regulation of cardiomyocytes. In addition, this review summarizes the roles of ncRNAs in specific species while enumerating potential therapeutic strategies for myocardial infarction.

ObjectivesPrevious studies showed conflicting results regarding peripheral vitamin D levels in ankylosing spondylitis (AS). We performed this systemic review and meta-analysis to explore whether vitamin D may influence AS process.MethodsArticles published until March 2022 were searched in databases as follows: PubMed, Web of Science, and Google Scholar. The present study included cross-sectional and case-control studies regarding vitamin D levels in patients with AS. Studies were excluded according to the following exclusion criteria: (1) we excluded studies which did not provide sufficient information regarding the comparison of vitamin D levels in AS patients and healthy controls (HC). Vitamin D levels in the two group studies should be reported or could be calculated in included studies; (2) meta-analysis, reviews and case reports. STATA 12.0 software was used to make a meta-analysis. Standard mean differences (SMDs) and 95% confidence intervals (CIs) were computed as effect size.ResultsThe present meta-analysis showed no significant difference in peripheral 1,25-dihydroxyvitamin D3 (1,25OHD) levels between AS and healthy controls (HCs) in Caucasians with a random effects model [SMD: −0.68, 95% CI (−1.90, 0.54)]. Patients with AS had lower peripheral 25-hydroxyvitamin D (25OHD) levels compared with HC with a random effects model [SMD: −0.45, 95% CI: (−0.70, −0.20)]. Patients with AS had higher peripheral C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels compared with HC in Caucasian population with random effects models [CRP: SMD: 1.08, 95% CI: (0.78, 1.37); ESR: SMD: 0.86, 95% CI: (0.39, 1.34)]. However, no significant difference in alkaline phosphatase (ALP), parathyroid hormone (PTH) or calcium levels were indicated between AS and HC in Caucasian with random effects models [ALP: SMD: 0.07, 95% CI: (−0.41, 0.55); PTH: SMD: −0.15, 95% CI: (−0.56, 0.26); calcium: SMD: −0.06, 95% CI: (−0.39, 0.26)].ConclusionIn conclusion, the study showed an inverse association between 25OHD and AS, which suggests that vitamin D may have a protective effect on AS. ESR and C-reactive protein (CRP) are important biomarkers for AS.

IntroductionFrame-based stereotactic biopsy is well-established to play an essential role in neurosurgery. In recent years, different robotic devices have been introduced in neurosurgery centers. This study aimed to compare the SINO surgical robot-assisted frameless brain biopsy with standard frame-based stereotactic biopsy in terms of efficacy, accuracy and complications.MethodsA retrospective analysis was performed on 151 consecutive patients who underwent stereotactic biopsy at Chongqing Sanbo Jiangling Hospital between August 2017 and December 2021. All patients were divided into the frame-based group (n = 47) and the SINO surgical robot-assisted group (n = 104). The data collected included clinical characteristics, diagnostic yield, operation times, accuracy, and postoperative complications.ResultsThere was no significant difference in diagnostic yield between the frame-based group and the SINO surgical robot-assisted group (95.74 vs. 98.08%, p > 0.05). The mean operation time in the SINO surgical robot-assisted group was significantly shorter than in the frame-based group (29.36 ± 13.64 vs. 50.57 ± 41.08 min). The entry point error in the frame-based group was significantly higher than in the robot-assisted group [1.33 ± 0.40 mm (0.47–2.30) vs. 0.92 ± 0.27 mm (0.35–1.65), P < 0.001]. The target point error in the frame-based group was also significantly higher than in the robot-assisted group [1.63 ± 0.41 mm (0.74–2.65) vs. 1.10 ± 0.30 mm (0.69–2.03), P < 0.001]. Finally, there was no significant difference in postoperative complications between the two groups.ConclusionRobot-assisted brain biopsy becomes an increasingly mainstream tool in the neurosurgical procedure. The SINO surgical robot-assisted platform is as efficient, accurate and safe as standard frame-based stereotactic biopsy and provides a reasonable alternative to stereotactic biopsy in neurosurgery.

BackgroundHomocysteine (Hcy) has been extensively acknowledged to be correlated with inflammation. In this study, the relationship between Hcy and hospital-acquired pneumonia (HAP) in primary intracerebral hemorrhage (pICH) was explored.MethodsWe conducted a hospital-based study on screened eligible patients with primary intracerebral hemorrhage admitted within 24 h after symptom onset from January 2019 to June 2021. The associations between Hcy and HAP and poor outcomes in pICH were investigated using univariate and multivariate logistic regression analyses. The predictive accuracy of Hcy was assessed by the receiver operating characteristic curve and the optimal cutoff value of Hcy was determined by Youden Index. The patterns and magnitudes of associations between Hcy and HAP and poor outcomes were evaluated using a restricted cubic spline (RCS).ResultsA total of 579 patients with pICH were included in the study. Hcy level was significantly higher in patients with HAP and poor outcomes (p < 0.001). The univariate and multivariate logistic regression analyses demonstrated that elevated Hcy was independently associated with both HAP and poor outcomes (p < 0.001). Furthermore, receiver operating characteristic analysis indicated that Hcy exhibited a moderate predictive accuracy for both HAP and poor outcomes after pICH. The RCS model showed that there were linear relationships between Hcy and HAP and poor outcomes.ConclusionsHigher Hcy level was independently associated with HAP and poor outcomes in patients with pICH.

Phenotypic transformation and excessive proliferation of pulmonary arterial smooth muscle cells (PASMCs) play an important role in vascular remodeling during pulmonary hypertension (PH). Magnolol (5,5′-diallyl-2,2′-dihydroxybiphenyl) is the major bioactive constituent isolated from the bark of Magnolia Officinalis, which has anti-inflammatory, antioxidant, and cardiovascular protection effects. However, the effect of magnolol on the phenotypic transformation of PASMCs is still unknown. This study aims to evaluate the effects of magnolol on the phenotypic transformation of PASMCs induced by hypoxia. In vivo, Sprague Dawley rats were exposed to hypoxia (10% O2) for four weeks to establish a PH model. The results showed that hypoxia treatment led to an increase in right ventricle systolic pressure, Fulton index, collagen production, accompanied by upregulation in the expression of collagen Ⅰ, collagen Ⅲ, OPN, PCNA, CyclinD1, p-JAK2, and p-STAT3, as well as decreases in expression of SM-22α; these changes were attenuated by magnolol. In vitro, the primary cultured PASMCs were exposed to 3% O2 for 48 h to induce phenotypic transformation. Consistent with the findings in vivo, magnolol treatment could prevent the phenotypic transformation and hyperproliferation of PASMCs induced by hypoxia, accompanied by downregulation in the expression of p-JAK2 and p-STAT3. In summary, this study demonstrated that the protective effect of magnolol on PH vascular remodeling is related to the inhibition of phenotypic transformation and hyperproliferation of PASMCs by inhibiting the JAK2/STAT3 pathway.

In this study, the degree of bleaching of multi-grain coarse quartz optically stimulated luminescence (OSL) signal of near-surface aeolian samples collected around the Tengger Desert is assessed. The single-aliquot regenerative dose (SAR) protocol and the standardized growth curve (SGC) method are applied to measure the equivalent dose (De) of these samples. The bleaching degree of the samples is assessed by investigating 1) the relationship between Ln/Tn and SAR De and 2) the SGC De distribution. Various degrees of heterogeneously-bleached multi-grain dose distributions synthetized with a numerical simulation method is further used to validate the bleaching performance of the samples. It demonstrates that the investigated samples are characterized by tight De distributions and the maximum De estimate is smaller than 1.1 Gy. The numerical simulation method which uses as input a large proportion of fully-bleached grains and a small baseline dose is able to reproduce multi-grain De distributions similar to the measured ones. We conclude that OSL signals of multi-grain coarse quartz extracted from most of the investigated aeolian samples are fully bleached before deposition.

MXene has drawn widespread attention as a potential material for electrode use in capacitive deionization (CDI). However, the applications of MXene are limited by its property of low electrical capacity. Herein, a MnO2/MXene composite was firstly evaluated in a capacitive deionization system, in which the MnO2 acts as intercalation-type pseudocapacitive electrodes to enhance the electrical capacity, and MXene provides an electron conduction highway network that improves the charge transfer of the MnO2. The result showed that the low-crystallinity MnO2 with irregular particles was well-distributed on the surface of the MXene. The desalination capacity of 30.5 mg·g−1 is achieved at a voltage window of 1.2 V, which was higher than that of the reported pure MXene and MnO2. The electrical double-layer (EDL) capacitive and the diffusion-controlled processes are the main charge storage mechanisms, and the EDL contribution provides 50.3% to the total capacitance. This result suggests a promising direction for further applying a MnO2/MXene composite in CDI.

Lead is a toxic factor in jarosite residue, and it is important to study its release behavior from simulated lead jarosite residue (LSJ) to predict the stability of the jarosite residue and its impact on the environment. This study investigated the ion release behavior, leaching toxicity, stability, and ion migration of LSJ during freeze–thaw cycling with thiourea (T-FTC). The release of lead, iron, and sulfate radicals from lead jarosite via T-FTC was influenced by several factors. Under specific conditions, the amount of lead released was 6.09 mM/L, which accounted for 38.3% of the total lead. After the T-FTC treatment, the residual lead increased, and the leaching toxicity and long-term stable equilibrium concentration of lead were reduced to 42.1 mg/L and 12.4 mg/L, respectively, which decreased by 82% and 84%, respectively and led to improved environmental stability. This study provides a novel approach for the safe disposal of jarosite residue under low-temperature and mild conditions, and the results can be used to predict the stability of jarosite residue and its secondary pollution in the environment.

Lead is the main toxic factor in jarosite residue. It is important to study the release behavior of lead from simulated lead-bearing jarosite (SLBJ) for predicting the stability of jarosite residue and its secondary pollution to the environment. To identify the technical issues and limitations associated with its safe disposal, a comprehensive analysis of the chemical, structural, and morphological characteristics of SLBJ was conducted using various detection techniques including XRF, XRD, SEM-EDS, FTIR, XPS, etc. The environmental stability of SLBJ was assessed through the toxicity characteristic leaching procedure (TCLP), Chinese standard leaching tests (CSLT), and a long-term leaching experiment (LTLE). Phase composition analysis revealed that the primary components of SLBJ are sodium jarosite and lead sulfate. TCLP and CSLT results indicated that lead content surpassed the toxicity identification standard limit by more than 47 times. Furthermore, LTLE indicated that the lead concentration surpassed the standard limit about 15 times after prolonged contact time. This study is of great significance for predicting the stability of jarosite residue and its secondary pollution to the environment.

The RNA polymerase II degradation factor Degradation Factor 1 (Def1) is important for DNA damage repair and plays various roles in eukaryotes; however, the biological role in plant pathogenic fungi is still unknown. In this study, we investigated the role of Def1 during the development and infection of the rice blast fungus Magnaporthe oryzae. The deletion mutant of Def1 displayed slower mycelial growth, less conidial production, and abnormal conidial morphology. The appressoria of Δdef1 was impaired in the penetration into host cells, mainly due to blocking in the utilization of conidial storages, such as glycogen and lipid droplets. The invasive growth of the Δdef1 mutant was also retarded and accompanied with the accumulation of reactive oxygen species (ROS) inside the host cells. Furthermore, compared with the wild type, Δdef1 was more sensitive to multiple stresses, such as oxidative stress, high osmotic pressure, and alkaline/acidic pH. Interestingly, we found that Def1 was modified by O-GlcNAcylation at Ser232, which was required for the stability of Def1 and its function in pathogenicity. Taken together, the O-GlcNAc modified Def1 is required for hyphae growth, conidiation, pathogenicity, and stress response in M. oryzae. This study reveals a novel regulatory mechanism of O-GlcNAc-mediated Def1 in plant pathogenic fungi.

The automated detection of distress such as cracks or potholes is a key basis for assessing the condition of pavements and deciding on their maintenance. A fine-grained pavement distress-detection algorithm based on integrated data using a digital twin is proposed to solve the challenges of the insufficiency of high-quality negative samples in specific scenarios An asphalt pavement background model is created based on UAV-captured images, and a lightweight physical engine is used to randomly render 5 types of distress and 3 specific scenarios to the background model, generating a digital twin model that can provide virtual distress data. The virtual data are combined with real data in different virtual-to-real ratios (0:1 to 5:1) to form an integrated dataset and used to fully train deep object detection networks for fine-grained detection. The results show that the YOLOv5 network with the virtual-to-real ratio of 3:1 achieves the best average precision for 5 types of distress (asphalt pavement MAP: 75.40%), with a 2-fold and 1.5-fold improvement compared to models developed without virtual data and with traditional data augmentation, respectively, and achieves over 40% recall in shadow, occlusion and blur. The proposed approach could provide a more reliable and refined automated method for pavement analysis in complex scenarios.

With information technology pushing the development of intelligent teaching environments, the online teaching platform emerges timely around the globe, and how to accurately evaluate the effect of the “any-time and anywhere” teacher–student interaction and learning has become one of the hotspots of today’s education research. Bullet chatting in online courses is one of the most important ways of interaction between teachers and students. The feedback from the students can help teachers improve their teaching methods, adjust teaching content, and schedule in time so as to improve the quality of their teaching. How to automatically identify the sentiment polarity in the comment text through deep machine learning has also become a key issue to be automatically processed in online course teaching. The traditional single-layer attention mechanism only enhances certain sentimentally intense words, so we proposed a sentiment analysis method based on a hierarchical attention mechanism that we called HAN. Firstly, we use CNN and LSTM to extract local and global information, gate mechanisms are used for extracting sentiment words, and the hierarchical attention mechanism is then used to weigh the different sentiment features, with the original information added to the attention mechanism concentration to prevent the loss of information. Experiments are conducted on China Universities MOOC and Tencent Classroom comment data sets; both accuracy and F1 are improved compared to the baseline, and the validity of the model is verified.

AIM: To systematically evaluate the efficacy of sodium hyaluronate combined with recombinant human epidermal growth factor(rhEGF)eye drops in the treatment of dry eye after cataract surgery in recent 5a by Meta-analysis.METHODS: The databases of CNKI, WanFang, Chongqing VIP, CBM, Cochrane Library, Pudmed and MEDLINE from January 2015 to May 2020 were searched. Meta analysis and statistical analysis were performed with Revman 5.3 software on the clinical control study of sodium hyaluronate eye drops combined with rhEGF eye drops in the treatment of dry eye after cataract surgery.RESULTS: A total of 14 randomized controlled trials involving 1 529 eyes were included. Among them, 14 studies conducted corneal fluorescein staining(FL)score after the end of treatment, the results showed that the difference was statistically significant [MD= -0.86, 95%CI(-1.07 to -0.66), P

Axial-flux permanent magnet synchronous machine (AFPMSM) enjoys the merits of high torque density and high efficiency, which make it one good candidate in the direct-drive application. The AFPMSM is usually analyzed based on the three-dimensional finite element method (3D FEM) due to its three-dimensional magnetic field distribution. However, the 3D FEM suffers large amount of calculation, time-consuming and is not suitable for the optimization of AFPMSM. Addressing this issue, a multi-layer quasi three-dimensional equivalent model of the AFPMSM is investigated in this paper, which could take the end leakage into consideration. Firstly, the multi-layer quasi three-dimensional equivalent model of the AFPMSM with single stator and single rotor is derived in details, including the equivalent processes and conversions of structure dimensions, motion conditions and electromagnetic parameters. Then, to consider the influence of end leakage on the performance, a correction factor is introduced in the multi-layer quasi three-dimensional equivalent model. Finally, the proposed multi-layer quasi three-dimensional equivalent model is verified by the 3D FEM based on an AFPMSM under different structure parameters. It demonstrates that the errors of flux linkage and average torque obtained by the multi-layer quasi three-dimensional equivalent model and 3D FEM are only around 2% although the structure parameters of the AFPMSM are varied. Besides, the computation time of one case based on the multi-layer quasi three-dimensional equivalent model is only 6 min, which is much less than that of the 3D FEM, 1.8 h, under the same conditions. Thus, the proposed multi-layer quasi three-dimensional equivalent model could be used to optimize the AFPMSM and much time could be saved by this method compared with the 3D FEM.

AbstractIn this paper, the effect of high temperature on the mechanical properties of quartz-rich sandstone was studied by true triaxial pressure experiment. The density, P-wave velocity, elastic modulus, peak stress, peak strain, and failure mode of quartz-rich sandstone before and after heat treatment were analyzed and compared. It was found that the color of quartz-rich sandstone changes greatly when heated to 500°C. In detail, the brittleness of quartz-rich sandstone gradually decreased and the ductility increased at high temperature. Although the density, P-wave velocity, and elastic modulus fluctuate, they showed a decreasing trend as a whole. In addition, the peak stress and peak strain showed an overall upward trend with the increase of temperature, and 500°C was the high-temperature failure threshold of quartz-rich sandstone. The failure mode of quartz-rich sandstone at high temperature changes from shear failure to shear-tension combined failure, and the number of cracks increases. Therefore, these research results can provide a certain reference for high-temperature underground operation.