Search

The necrosis of pancreatic acinar cells is a key molecular event in the progression of acute pancreatitis (AP), with disturbances in mitochondrial energy metabolism considered to be a direct causative factor of acinar cell necrosis. Histidine triad nucleotide-binding protein 2 (HINT2) has been implicated in the development of various diseases, whereas its involvement in the progression of AP remains unclear. This study aims to investigate the role of HINT2 in AP. HINT2 expression in pancreatic tissues was significantly downregulated after AP. The results of glutathione-S-transferase (GST) pull-down and proteomics analyses revealed the involvement of HINT2 in regulating mitochondrial oxidative phosphorylation (OXPHOS) in AP mice. Moreover, lentivirus-mediated HINT2 overexpression not only alleviated AP-induced ATP depletion, but also relieved inflammatory responses and cell necrosis. Mechanistically, HINT2 interacted with cytochrome C oxidase II (MTCO2) to promote mitochondrial OXPHOS, thereby reducing ROS accumulation and inhibiting the activation of inflammatory signaling pathway. Besides, HINT2 act as a direct pharmacological target of Emo to elicit protective effects on AP. Importantly, Emo upregulates the expression of HINT2 and OXPHOS complex proteins and enhances the interaction between HINT2 and MTCO2. Furthermore, CRISPR/Cas9-mediated HINT2 knockout significantly impaired the protective effects of Emo against AP-induced mitochondrial energy metabolism disorders, inflammatory responses, and acinar cell necrosis. Overall, these results uncover a previously unexplored role for HINT2 in maintaining mitochondrial energy metabolism in pancreatic acinar cells and reveals novel mechanism and target for Emo-mediated AP remission.

Dichlorvos (DDVP) is an organophosphorus pesticide commonly utilized in agricultural production. Recent epidemiological studies suggest that exposure to DDVP correlates with an increased incidence of liver disease. However, data regarding the hepatotoxicity of DDVP remain limited. Additionally, the regulatory mechanisms underlying DDVP-induced liver injury have not been thoroughly investigated. In this study, we utilized Wistar rats and BRL-3A cells to establish in vivo and in vitro models for examining the effects of DDVP exposure on liver damage. Our findings indicate that DDVP impairs hepatocyte autophagy and increases ROS activity. RNA sequencing and metabolomic analyses revealed that the pathways affected by DDVP exposure in hepatocytes include ABC transporters and amino acid biosynthesis processes. Furthermore, targeting IRGM overexpression through hepatic portal vein injection of adeno-associated virus mitigated DDVP-induced liver injury. These results demonstrate that DDVP exposure induces liver damage in rats through mechanisms that are dependent on ROS and autophagy, at least in part by downregulating IRGM. Our study offers new insights into the molecular mechanisms of liver injury following organophosphate poisoning and suggests that IRGM may represent a novel therapeutic target for DDVP-induced liver injury.

BackgroundGlyphosate, as the main component of glyphosate pesticides, has been shown to have toxic effects on multiple human systems. However, the association between glyphosate and atherosclerotic cardiovascular disease (ASCVD) remains unclear. This study aims to explore the effect of glyphosate exposure on ASCVD.MethodsThis study involved 1,602 participants and employed various statistical techniques, such as multivariable logistic regression, linear fitting, mediation analysis, subgroup analysis, and sensitivity analysis, to elucidate the association between glyphosate exposure and cardiovascular diseases.ResultsCompared with the low level of glyphosate exposure, the risk of ASCVD increased significantly with high level of glyphosate exposure (OR = 2.05, 95%CI = 1.17-3.58, pConclusionIncreased exposure to glyphosate is associated with an increased risk of ASCVD, and BMI plays a mediating role in this association. In addition, glyphosate exposure is associated with a higher risk of angina, coronary heart disease, and heart attack.

BackgroundThe genetic association between psychiatric disorders and hemorrhoidal disease (HEM) is still not well known. The work aims to investigate their comorbidity at a genetic level.MethodsUtilizing recent large-scale genome-wide association studies (GWAS), we investigated the genetic overlap at the single nucleotide polymorphism (SNP), gene, and molecular level between depression and HEM, bipolar disorder (BD) and HEM, neuroticism and HEM, as well as schizophrenia (SCZ) and HEM. The cross-trait genes were validated through the utilization of transcriptome and proteome methodologies. The causal link was assessed using bidirectional two-sample Mendelian randomization analysis (MR) analysis. MRlap corrects for the potential bias in estimation caused by sample overlap.ResultsWe discovered significant positive genetic associations between these four types of psychiatric disorders and HEM. Cross-phenotypic association analyses identified shared SNPs along with 17 specific loci between psychiatric disorders and HEM. MAGMA identified a total of 2304 pleiotropic genes, several of which showed significant expression in the results of transcriptome and proteome analyses. We observed that these genes are mostly associated with the regulation of transcription factors and particular DNA binding activities. Lastly, MR analysis provided evidence supporting a correlation between these conditions.ConclusionThis study revealed a genetic correlation between four psychiatric disorders and HEM, identified pleiotropic loci, found multiple candidate genes, and confirmed causal relationships. This has enhanced our comprehension of the common genetic mechanisms of psychiatric disorders and HEM.

Macroautophagy/autophagy is an intracellular degradation pathway that has an important effect on both healthy and diseased pancreases. It protects the structure and function of the pancreas by maintaining organelle homeostasis and removing damaged organelles. A variety of pancreas-related diseases, such as diabetes, pancreatitis, and pancreatic cancer, are closely associated with autophagy. Genetic studies that address autophagy confirm this view. Loss of autophagy homeostasis (lack or overactivation) can lead to a series of adverse reactions, such as oxidative accumulation, increased inflammation, and cell death. There is growing evidence that stimulating or inhibiting autophagy is a potential therapeutic strategy for various pancreatic diseases. In this review, we discuss the multiple roles of autophagy in physiological and pathological conditions of the pancreas, including its role as a protective or pathogenic factor.

Excessive and uncontrollable inflammatory responses in alveoli can dramatically exacerbate pulmonary disease progressions through vigorous cytokine releases, immune cell infiltration and protease-driven tissue damages. It is an urgent need to explore potential drug strategies for mitigating lung inflammation. Protease-activated receptor 2 (PAR2) as a vital molecular target principally participates in various inflammatory diseases via intracellular signal transduction. However, it has been rarely reported about the role of PAR2 in lung inflammation. This study applied CRISPR-Cas9 system encoding Cas9 and sgRNA (pCas9-PAR2) for PAR2 knockout and fabricated an anionic human serum albumin-based nanoparticles to deliver pCas9-PAR2 with superior inflammation-targeting efficiency and stability (TAP/pCas9-PAR2). TAP/pCas9-PAR2 robustly facilitated pCas9-PAR2 to enter and transfect inflammatory cells, eliciting precise gene editing of PAR2 in vitro and in vivo. Importantly, PAR2 deficiency by TAP/pCas9-PAR2 effectively and safely promoted macrophage polarization, suppressed pro-inflammatory cytokine releases and alleviated acute lung inflammation, uncovering a novel value of PAR2. It also revealed that PAR2-mediated pulmonary inflammation prevented by TAP/pCas9-PAR2 was mainly dependent on ERK-mediated NLRP3/IL-1β and NO/iNOS signalling. Therefore, this work indicated PAR2 as a novel target for lung inflammation and provided a potential nanodrug strategy for PAR2 deficiency in treating inflammatory diseases.

Acute pancreatitis (AP), induced by tetracycline, a widely used antibiotic, poses significant clinical and toxicological challenges, yet its molecular mechanisms remain unclear. This study aims to promote drug toxicology strategies for the effective investigation of the putative toxicity and potential molecular mechanisms of antibiotic drugs through the study of tetracycline in AP. Using the SwissTargetPrediction, SEA Search, Super-PRED, GeneCards, Drugbank, Online Mendelian Inheritance in Man (OMIM), and Therapeutic Target Database (TTD), we identified 259 potential targets associated with tetracycline exposure and AP. Further refinement via the STRING database and Cytoscape (version 3.10.1) software highlighted 22 core targets, including TP53, TNF, and AKT1. Functional enrichment via the Database for Annotation, Visualization, and Integrated Discovery (DAVID) identified pathways through Gene Ontology (GO) terms and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, highlighting PI3K-Akt, MAPK, HIF-1, and AGE-RAGE as critical mediators in tetracycline-induced AP. Molecular docking confirmed the strong binding between tetracycline and the core targets. Overall, these findings suggest that tetracycline may affect the occurrence and progression of pancreas-related inflammation by regulating pancreatic cell apoptosis and proliferation, activating inflammatory signaling pathways, and regulating lipid metabolic pathways. This study provides a theoretical basis for understanding the molecular mechanism of tetracycline-induced AP and lays the foundation for the prevention and treatment of digestive system diseases associated with excessive exposure to tetracycline antibiotics and certain tetracyclines. In addition, our network toxicology approach has accelerated the elucidation of toxic pathways in antibiotic drugs that lack specific characteristics.

AimTo explore the association between Processed red meat (PRM) consumption and cardiovascular risk factors in Chinese adults with type 2 diabetes mellitus (T2DM).MethodsDietary survey, physical measurement, and blood biochemical examination were conducted on 316 patients with type 2 diabetes in Bengbu, China from May to July 2019. Possible confounding factors were identified by comparing between-group variability in the baseline table. To eliminate the effect of confounding factors, subgroup analysis was used to explore whether there were differences in the correlation between PRM intake status and the indicators in cardiovascular disease risk factors. A logistic regression model was used to analyze the association between PRM and the risk of abnormal levels of cardiovascular risk factors in T2DM patients. Restricted cubic spline plots were used to analyze the dose–response relationship between PRM intake and the indicators of cardiovascular disease risk factors.ResultsA total of 316 subjects were included in the study, of whom 139 (44.0%) were male and 177 (56.0%) were female. In the multiplicative interaction, there was an effect modifier for smoking (Pinteraction = 0.033) on the association between PRM intake and the risk of substandard FPG level control; sex (Pinteraction = 0.035), smoking status (Pinteraction = 0.017), and alcohol consumption (Pinteraction = 0.046) had effect modifying effects on the association between PRM intake and risk of abnormal systolic blood pressure. Sex (Pinteraction = 0.045) had an effect modifier on the association of PRM intake status with the risk of diastolic blood pressure abnormality. In addition, age had an effect modifier on the association of PRM intake status with risk of abnormal triglyceride index (Pinteraction = 0.004) and risk of abnormal HDL index (Pinteraction = 0.018). After adjusting for potential confounding variables, logistic regression showed that the OR for substandard HbA1c control in patients in the highest PRM intake group, T3 (3.4 ~ 57.2 g/d), was 1.620-fold higher than in the lowest intake, i.e., the no-intake group, T1 (0.0 ~ 0.0 g/d; OR = 2.620; 95% CI 1.198 ~ 5.732; p = 0.016). Whereas the OR for abnormal control of systolic blood pressure levels was 1.025 times higher (OR = 2.025; 95% CI 1.033 ~ 3.968; p = 0.040) in patients in the PRM low intake group T2 (0.1 ~ 3.3 g/d) than in the non-intake group T1 (0.0 ~ 0.0 g/d), the OR for substandard control of systolic blood pressure in patients in the highest group T3 (3.4 ~ 57.2 g/d) was 1.166 times higher than in the no-intake group T1 (OR = 2.166; 95% CI 1.007 ~ 4.660; p = 0.048). The OR for abnormal TG levels in patients in the highest PRM intake group T3 (3.4 ~ 57.2 g/d) was 1.095 times higher than in the no-intake group T1 (OR = 2.095; 95% CI 1.076 ~ 4.078; p = 0.030). Restricted cubic spline plots presented a nonlinear dose–response relationship between PRM intake and risk of substandard HbA1c and SBP control (P nonlinear 0.05).ConclusionPRM intake was generally low in patients with T2DM, but a nonlinear dose–response relationship between PRM intake and the risk of suboptimal control of HbA1c and SBP, with an atypical inverted U-shaped association with TC and LDL-C levels, was observed. Appropriate control of PRM intake may be important for tertiary prevention of T2DM and cardiovascular disease prevention. We need to better understand these relationships to promote improved cardiometabolism and global health.

Abstract Background Pichia pastoris is a widely utilized host for heterologous protein expression and biotransformation. Despite the numerous strategies developed to optimize the chassis host GS115, the potential impact of changes in cell wall polysaccharides on the fitness and performance of P. pastoris remains largely unexplored. This study aims to investigate how alterations in cell wall polysaccharides affect the fitness and function of P. pastoris, contributing to a better understanding of its overall capabilities. Results Two novel mutants of GS115 chassis, H001 and H002, were established by inactivating the PAS_chr1-3_0225 and PAS_chr1-3_0661 genes involved in β-glucan biosynthesis. In comparison to GS115, both modified hosts exhibited a looser cell surface and larger cell size, accompanied by faster growth rates and higher carbon-to-biomass conversion ratios. When utilizing glucose, glycerol, and methanol as exclusive carbon sources, the carbon-to-biomass conversion rates of H001 surpassed GS115 by 10.00%, 9.23%, and 33.33%, respectively. Similarly, H002 exhibited even higher increases of 32.50%, 12.31%, and 53.33% in carbon-to-biomass conversion compared to GS115 under the same carbon sources. Both chassis displayed elevated expression levels of green fluorescent protein (GFP) and human epidermal growth factor (hegf). Compared to GS115/pGAPZ A-gfp, H002/pGAPZ A-gfp showed a 57.64% higher GFP expression, while H002/pPICZα A-hegf produced 66.76% more hegf. Additionally, both mutant hosts exhibited enhanced biosynthesis efficiencies of S-adenosyl-L-methionine and ergothioneine. H001/pGAPZ A-sam2 synthesized 21.28% more SAM at 1.14 g/L compared to GS115/pGAPZ A-sam2, and H001/pGAPZ A-egt1E obtained 45.41% more ERG at 75.85 mg/L. The improved performance of H001 and H002 was likely attributed to increased supplies of NADPH and ATP. Specifically, H001 and H002 exhibited 5.00-fold and 1.55-fold higher ATP levels under glycerol, and 6.64- and 1.47-times higher ATP levels under methanol, respectively, compared to GS115. Comparative lipidomic analysis also indicated that the mutations generated richer unsaturated lipids on cell wall, leading to resilience to oxidative damage. Conclusions Two novel P. pastoris chassis hosts with impaired β-1,3-D-glucan biosynthesis were developed, showcasing enhanced performances in terms of growth rate, protein expression, and catalytic capabilities. These hosts exhibit the potential to serve as attractive alternatives to P. pastoris GS115 for various bioproduction applications.

Microbially induced calcium carbonate precipitation (MICP) is an environmentally friendly technology that improves soil permeability resistance through biocementation. In this study, 2D microscopic analysis and 3D volume reconstruction were performed on river sand after 24 cycles of bio-treatment based on stacked images and computed tomography (CT) scanning data, respectively, to extract biocementation patterns between particles. Based on the mutual validation findings of the two techniques, three patterns in the biocemented sand were identified as G-C-G, G-C, and G-G. Specifically, 2D microscopic analysis showed that G-C-G featured multi-particle encapsulation and bridging, with a pore filling ratio of 81.2%; G-C was characterized by locally coated particle layers, with a pore filling ratio of 19.7%; and the G-G was marked by sporadic filling of interparticle pores, with a pore filling ratio of 11.7%. G-C-G had the best cementation effect and permeability resistance (effective sealing rate of 68.5%), whereas G-C (effective sealing rate of 2.4%) had a relatively minor contribution to pore-filling and flow sealing. 3D volume reconstruction showed that G-C-G had the highest pore filling rate, followed by G-G and G-C. The average filling ratios of area and volume for G-C-G were 83.979% and 77.257%, respectively; for G-G 20.360% and 23.600%; and for G-C 11.545% and 11.250%. The analysis of the representative element volume (REV) was conducted, and the feasibility and reliability of the micro-scale pattern extraction results were confirmed to guide the analysis of macro-scale characteristics. The exploration of the effectiveness of cementation patterns in fluid sealing provides valuable insights into effective biocementation at the pore scale of porous media, which may inspire future research.

BackgroundPoor dietary structure plays a pivotal role in the development and progression of type 2 diabetes and is closely associated with dysbiosis of the gut microbiota. Thus, the objective of this systematic review was to assess the impact of dietary interventions on improving gut microbiota and metabolic levels in patients with type 2 diabetes.MethodsWe conducted a systematic review and meta-analysis following the PRISMA 2020 guidelines.ResultsTwelve studies met the inclusion criteria. In comparison to baseline measurements, the high-fiber diet produced substantial reductions in FBG (mean difference −1.15 mmol/L; 95% CI, −2.24 to −0.05; I2 = 94%; P = 0.04), HbA1c (mean difference −0.99%; 95% CI, −1.93 to −0.03; I2 = 89%; P = 0.04), and total cholesterol (mean difference −0.95 mmol/L; 95% CI, −1.57 to −0.33; I2 = 77%; P = 0.003); the high–fat and low–carbohydrate diet led to a significant reduction in HbA1c (mean difference −0.98; 95% CI, −1.50 to −0.46; I2 = 0%; P = 0.0002). Within the experimental group (intervention diets), total cholesterol (mean difference −0.69 mmol/L; 95% CI, −1.27 to −0.10; I2 = 52%; P = 0.02) and LDL-C (mean difference −0.45 mmol/L; 95% CI, −0.68 to −0.22; I2 = 0%; P < 0.0001) experienced significant reductions in comparison to the control group (recommended diets for type 2 diabetes). However, no statistically significant differences emerged in the case of FBG, HbA1c, HOMA-IR, and HDL-C between the experimental and control groups. The high dietary fiber diet triggered an augmented presence of short-chain fatty acid-producing bacteria in the intestines of individuals with T2DM. In addition, the high-fat and low-carbohydrate diet resulted in a notable decrease in Bacteroides abundance while simultaneously increasing the relative abundance of Eubacterium. Compared to a specific dietary pattern, personalized diets appear to result in the production of a greater variety of beneficial bacteria in the gut, leading to more effective blood glucose control in T2D patients.ConclusionDietary interventions hold promise for enhancing metabolic profiles in individuals with T2D through modulation of the gut microbiota. Tailored dietary regimens appear to be more effective than standard diets in improving glucose metabolism. However, given the limited and highly heterogeneous nature of the current sample size, further well-designed and controlled intervention studies are warranted in the future.

Gastrointestinal (GI) tumors have increasing incidence worldwide with their underlying mechanisms still not being fully understood. The use of tumor-educated platelets (TEPs) in liquid biopsy is a newly-emerged blood-based cancer diagnostic method. Herein, we aimed to investigate the genomic changes of TEPs in GI tumor development and their potential functions using network-based meta-analysis combined with bioinformatic methods. We used a total of three eligible RNA-seq datasets, which were integrated using multiple meta-analysis methods on the NetworkAnalyst website, and identified 775 DEGs (differentially expressed genes; 51 up-regulated and 724 down-regulated genes) in GI tumor relative to healthy control (HC) samples. These TEP DEGs were mostly enriched in bone marrow-derived cell types and associated with gene ontology (GO) of “carcinoma” and could affect pathways of “Integrated Cancer Pathway” and “Generic transcription pathway” respectively for highly and lowly expressed DEGs. Combined network-based meta-analysis and protein–protein interaction (PPI) analysis identified cyclin dependent kinase 1 (CDK1) and heat shock protein family A (Hsp70) member 5 (HSPA5) to be the hub genes with the highest degree centrality (DC), being up-regulated and down-regulated in TEPs, respectively. GO and Kyoto Encyclopedia of Genes and Genomes (KEGG) results showed that the hub genes were primarily related to cell cycle and division, nucleobase-containing compound and carbohydrate transport, and endoplasmic reticulum unfolded protein response. Additionally, the nomogram model suggested that the two-gene signature owns extraordinary predictive power for GI tumor diagnosis. Further, the two-gene signature was demonstrated to have potential value for metastatic GI tumor diagnosis. The expression levels of CDK1 and HSPA5 in clinical platelet samples were verified to be consistent with the results from bioinformatic analysis. This study identified a two-gene signature encompassing CDK1 and HSPA5 that can be used as a biomarker for GI tumor diagnosis and maybe even cancer-associated thrombosis (CAT)-related prognosis.

Currently, the monitoring of rocky desertification(RD) is concentrated in the karst area, whereas the study in red-bed areas is rare. In this paper, we present a multi-scale classification framework for RD monitoring based on spectral-spatial features. At the pixel scale, we explored several spectral indices based on spectral statistics and separability analysis of land cover samples. The homogeneous land covers were classified by the decision rules from the selected spectral indices (such as NDIOI, NRRI and NDGI); At the patch scale, RD classes were further distinguished by spatial decision rules based on multiple neighborhood features including proximity, linear density, and buffer distance. The method was applied on an OLI image over the red-bed area of northwestern Jiangxi, south central China, and validated using ground-based observations. The experimental results of verification and comparison are satisfactory. This work demonstrates a methodological supplement to the monitoring of red bed RD.

Abstract Background While benefits of greenness exposure to health have been reported, findings specific to lung function are inconsistent. The purpose of this study is to assess the correlations of greenness exposure with multiple lung function indicators based on chronic obstructive pulmonary disease (COPD) monitoring database from multiple cities of Anhui province in China. Methods We assessed the greenness using the annual average of normalized difference vegetation index (NDVI) with a distance of 1000-meter buffer around each local community or village. Three types of lung function indicators were considered, namely indicators of obstructive ventilatory dysfunction (FVC, FEV1, FEV1/FVC, and FEV1/FEV3); an indicator of large-airway dysfunction (PEF); indicators of small-airway dysfunction (FEF25%, FEF50%, FEF75%, MMEF, FEV3, FEV6, and FEV3/FVC). Linear mixed effects model was used to analyze associations of greenness exposure with lung function through adjusting age, sex, educational level, occupation, residence, smoking status, history of tuberculosis, family history of lung disease, indoor air pollution, occupational exposure, PM2.5, and body mass index. Results A total of 2768 participants were recruited for the investigations. An interquartile range (IQR) increase in NDVI was associated with better FVC (153.33mL, 95%CI: 44.07mL, 262.59mL), FEV1 (109.09mL, 95%CI: 30.31mL, 187.88mL), FEV3 (138.04mL, 95%CI: 39.43mL, 236.65mL), FEV6 (145.42mL, 95%CI: 42.36mL, 248.47mL). However, there were no significant associations with PEF, FEF25%, FEF50%, FEF75%, MMEF, FEV1/FVC, FEV1/FEV6, FEV3/FVC. The stratified analysis displayed that an IQR increase in NDVI was related with improved lung function in less than 60 years, females, urban populations, nonsmokers, areas with medium concentrations of PM2.5 and individuals with BMI of less than 28 kg/m2. Sensitivity analyses based on another greenness indice (enhanced vegetation index, EVI) and annual maximum of NDVI remained consistent with the main analysis. Conclusions Our findings supported that exposure to greenness was strongly related with improved lung function.

Abstract Background The aim of this study was to examine the relationship between dietary intake of folate and niacin and diabetes risk in Chinese adults. Methods This is a cross-sectional study. Demographic and anthropometric data along with information on dietary intake of vitamins were collected, and eligible participants were recruited to complete the questionnaire. A binary logistic regression analysis was conducted to examine the association between dietary intake of vitamins and diabetes risk, with adjustment for potential confounders. Non-linear dose-response relationships between dietary intake of folate and niacin and diabetes risk were also evaluated using adjusted restricted cubic splines. Results Of the 3106 eligible participants, 15.9% had diabetes. Median folate was significantly higher in diabetic patients than in controls (32.030 vs. 27.600 gμ), while median niacin was significantly lower (7.000 vs. 7.900 mg). After controlling for potential confounders, binary logistic regression analysis showed that each unit increase in folate intake was associated with a 1.002-fold increase in the risk of developing diabetes (odds ratio (OR) = 1.002; 95% confidence interval (CI) 1.000–1.004; P = 0.022), while each unit increase in niacin intake was associated with a 3.5% reduction in diabetes risk (OR = 0.965; 95% CI 0.944–0.986; P = 0.001). The plots of restricted cubic splines presented an atypical inverted U-shaped association between dietary intake of folate and diabetes risk. Conclusions Diabetic patients had a low intake of vitamins, especially the B vitamins. Dietary intake of folate and niacin tended to be independently associated with the risk of diabetes. Nevertheless, this study is observational and a large-scale randomized controlled trial is yet to be conducted, which will add to the evidence of the study results.

RNAs are involved in the crucial processes of disease progression and have emerged as powerful therapeutic targets and diagnostic biomarkers. However, efficient delivery of therapeutic RNA to the targeted location and precise detection of RNA markers remains challenging. Recently, more and more attention has been paid to applying nucleic acid nanoassemblies in diagnosing and treating. Due to the flexibility and deformability of nucleic acids, the nanoassemblies could be fabricated with different shapes and structures. With hybridization, nucleic acid nanoassemblies, including DNA and RNA nanostructures, can be applied to enhance RNA therapeutics and diagnosis. This review briefly introduces the construction and properties of different nucleic acid nanoassemblies and their applications for RNA therapy and diagnosis and makes further prospects for their development.

The use of solar energy has shown the fastest global growth of all renewable energy sources. Efforts towards careful evaluation are required to select optimal locations for the installation of photovoltaics (PV) because their effectiveness is strongly reliant on exposure to solar irradiation. Assessing the shadows cast by nearby buildings and vegetation is essential, especially at the city scale. Due to urban complexity, conventional methods using Digital Surface Models (DSM) overestimate solar irradiation in dense urban environments. To provide further insights into this dilemma, a new modeling technique was developed for integrated 3D city modeling and solar potential assessment on building roofs using light detection and ranging (LiDAR) data. The methodology used hotspot analysis to validate the workflow in both site and without-site contexts (e.g., trees that shield small buildings). Field testing was conducted, covering a total area of 4975 square miles and 10,489 existing buildings. The results demonstrate a considerable impact of large, dense trees on the solar irradiation received by smaller buildings. Considering the site’s context, a mean annual solar estimate of 99.97 kWh/m2/year was determined. Without considering the site context, this value increased by 9.3% (as a percentage of total rooftops) to 109.17 kWh/m2/year, with a peak in July and troughs in December and January. The study suggests that both factors have a substantial impact on solar potential estimations, emphasizing the importance of carefully considering the shadowing effect during PV panel installation. The research findings reveal that 1517 buildings in the downtown area of Austin have high estimated radiation ranging from 4.7 to 6.9 kWh/m2/day, providing valuable insights for the identification of optimal locations highly suitable for PV installation. Additionally, this methodology can be generalized to other cities, addressing the broader demand for renewable energy solutions.

As a sub-realm of Language Teacher Psychology (LTP), teachers’ professional agency has gained significant attention from educational practitioners and teachers. The aim is to better discern teachers’ professional development and teaching effectiveness with a view to ensuring the quality of language teaching. International literature concerning teachers’ professional agency has noted a shift from knowledge training to vocational development in relation to teachers’ experience in decision making. Yet, little research so far has scrutinized this specific issue in Chinese university settings, and the real picture of teacher agency needs further exploration. Besides, the multidimensional and complex nature of agency identifies the overwhelming research work in understanding its contents in detail based on the previous perspectives from individuals, society, and time. To this end, the ecological understanding of professional agency reframed the theoretical basis of this study, prone to explore how teachers’ experience could be examined in relation to individual capacity, resources, and structural and contextual variables. The study was conducted in Chinese university settings in response to the research gap related to understanding professional agency. Quantitative and qualitative data from questionnaires, interviews, and classroom observations with 116 university teachers in China demonstrated that the enactment of professional agency rested on the interplay between temporal contexts, teacher capacity, and beliefs, especially in the instructional community. The findings revealed that university teachers at different stages of career development manifested variability in exercising their professional agency in relation to adapting or adopting existing teaching concepts, methods, or approaches. Mounting evidence revealed some enablers and constraints in relation to formative assessment, time impact, classroom interaction, and school culture. Emphasizing the interaction between individuals’ ability and their engagement with the professional environment, the findings provide insights into theoretical implications associated with ecological theory and enhance the practical discussion about promoting professional development for novice, mid-career, and veteran English teachers at the university level.

Background: Chromosome 5 open reading frame 46 (C5ORF46), also known as antimicrobial peptide with 64 amino acid residues (AP-64) and skin and saliva-secreted protein 1 (SSSP1), belongs to the family of open reading frame genes and encodes a small exosomal protein. C5ORF46 has been implicated in antibacterial activity and associated with patient prognosis in pancreatic cancer, colorectal cancer, and stomach cancer. These findings highlight the importance of C5ORF46 in gastrointestinal (GI) tumor inception and development. However, the prognostic and immunological value of C5ORF46 in human GI tumors remains largely unknown. In this study, we sought to explore the potential value of C5ORF46 in GI tumor prognosis and immunology.Method: RNA sequencing (RNA-seq) was performed on the tumor and tumor-adjacent normal samples we collected to identify potential target genes for GI tumors. Apart from our RNA-seq data, all original data were downloaded from The Cancer Genome Atlas (TCGA) database and integrated via Strawberry Perl (v 5.32.0) and R (v 4.1.1). The differential expression of C5ORF46 was examined with Oncomine, Tumor Immune Estimation Resource (TIMER), Gene Expression Profiling Interactive Analysis (GEPIA), Cancer Cell Line Encyclopedia (CCLE), the Human Protein Atlas (HPA) and TCGA databases. The c-BioPortal database was used to investigate the genomic alterations of C5ORF46. The effect of C5ORF46 on prognosis and clinical phenotypes was explored via bioinformatics analyses on the TCGA and GEPIA databases. We used the bioinformatics analyses based on the TCGA database to analyze tumor mutational burden (TMB), microsatellite instability (MSI), tumor immune cell infiltration, and the correlations between C5ORF46 expression and several immune-related genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was carried out via the DAVID website and presented as bubble charts using ShengXinRen online tools. Gene set enrichment analysis (GSEA) was performed using R scripts based on data downloaded from the GSEA website. Immunohistochemistry (IHC) was used to validate the expression of C5ORF46 in GI tumors.Results: The results of our RNA-seq data indicated a critical role for C5ORF46 in colon carcinogenesis. Consistently, we demonstrated that C5ORF46 was highly expressed in tumor tissues compared to normal tissues in human GI tumors. Moreover, a strong correlation was observed between C5ORF46 expression levels and patient prognosis, staging, TMB, MSI, and immune cell infiltration. Further, C5ORF46 presented as an important regulator in the tumor microenvironment (TME) and was active in the regulation of cancer immune functions. C5ORF46 is significantly correlated with genes regulating inflammation and immune responses.Conclusion:C5ORF46 may serve as a biomarker for GI tumor prognosis and immunology. C5ORF46 could be a novel target for GI tumor immunotherapy.

Blind signature is a special type of digital signature, the signer cannot see the specific content signed. However, blindness may cause users to abuse their rights. Partial blind signature allows the signer to embed pre-negotiated public information in the blind signature without losing blindness, which can prevent users from abusing their rights. Islam et al. presented an identity-based partial blind signature scheme and claimed that it is provable secure. However, in this paper we proved that the scheme is vulnerable against the tampering attacks with public information. We then proposed a new identity-based partial blind signature scheme, showed the security proofs under the assumption that the elliptic curve discrete logarithm problem (ECDLP) is difficult. The new scheme does not use pairing operations and enjoys less computation cost.

Kennedy et al. report the pharmacological and in vivo profiling of two small molecule PAR2 inhibitors and an agonist. They conclude that while the small molecule agonist and one of the inhibitors bind to the orthosteric PAR2 binding site, the other inhibitor is a negative allosteric modulator, highlighting two distinct mechanisms of inhibition that could be targeted for future development of drugs that modulate PAR2.

Abstract Background Abnormal glucose metabolism has been suggested to be involved in the development of hypertension. This study investigated the effect of the association and potential interaction of glycosylated hemoglobin (HbA1c) and other factors on the risk of hypertension among Chinese nondiabetic adults. Methods As a cross-sectional survey, the current work deployed a questionnaire survey, anthropometric tests, and biochemical measures for each of the eligible participants. The HbA1c levels were quantified and grouped by quartiles. Correlations between HbA1c and hypertension, isolated systolic hypertension (ISH), and isolated diastolic hypertension (IDH) risk were investigated by logistic analyses. For evaluating the interactive effects, the parameters of relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index (SI) were calculated, respectively. Results In the current study, 1462 nondiabetic subjects were enrolled. In total, the prevalence rates of hypertension, ISH and IDH were 22.4, 9.6 and 4.5%, respectively. When HbA1c levels were grouped by quartile, it was revealed that the prevalence rates of hypertension and ISH were substantially elevated across groups (Pfor trend

This study adopted a positive psychology perspective to investigate positive emotion and foreign language enjoyment among Chinese as a second language (CSL) learners in an emergency remote teaching (ERT) context amid the COVID-19 pandemic. A set of 90 preparatory Chinese language students (40 males and 50 females) was assessed for their level of foreign language enjoyment using the Foreign Language Enjoyment Scale (FLES). Participles' scores on self-perceived language achievement and actual test scores were adopted as the measurement of their Chinese language proficiency. The results revealed that: (1) CSL learners experienced high level of FL enjoyment in an online learning context, (2) no significant correlation was found between FLE and leaners' actual language achievement nor between FLE and their self-perceived achievement, (3) female learners showed higher FLE than male learners and gender was found to have a significant effect on FLE-Private, (4) participants' geological location, i.e., whether in China or at home countries, significantly influenced their FLE, (5) participants' regional group was not a significant predictor of FLE, and (6) teacher-related variables and learner self-perceptions of achievement were strong predictors of FLE among CSL learners. The findings highlight the importance of teacher's role in an online learning environment and suggest that FLE may not boost performance in the short term for language beginners but is still conducive in the long run. Implications for both teachers and learners, and suggestions for future researches are provided.

With the rapid development of digitalisation, multimedia and network-based communication technology, all walks of life are undergoing change and development driven by the application of the internet to conventional industries. Especially because of the outbreak of coronavirus disease of 2019 (COVID-19), English teaching and learning modes are undergoing revolutionary changes worldwide (Wong et al., 2020). Online courses and materials have become the norm for students, and combined with offline English learning activities, an online and offline blended learning mode has ultimately emerged (Graham, 2006; Whittaker, 2013). Whereas blended learning has been considered in several contexts, it has been less investigated in the field of blended English learning mode for the listening comprehension ability and emotional experiences of young learners of Chinese English as a foreign language (EFL) while doing the tasks. Thus, this study focussed on the achievement and experience of Chinese EFL junior high school students during blended learning using Quizlet software as the online learning tool. This study aimed to explore the following: (1) the effect of the online and offline blended mode on the learning outcomes of students and (2) the experience of students while engaging with blended tasks in terms of their learning interest, attitude, and strategy use in English listening learning. A 4-month teaching intervention involving the online and offline blended mode was conducted in English listening classes. Adopting mixed-methods qualitative and quantitative research, this study examined the engagement process of two classes of students and analysed data from their English listening tests and follow-up in-depth interviews. The results suggested that the blended activity was conducive to enhancing the listening performance of students. Moreover, the attitudes of students toward English listening learning shifted from a relatively negative engagement to a more positive one. Meanwhile, the interest of students grew and their learning strategies became more diversified. These findings have implications for English teaching and learning activity design for young learners.

The COVID-19 outbreak, along with post-pandemic impact has prompted Internet Plus education to re-examine numerous facets of technology-oriented academic research, particularly Educational Big Data (EBD). However, the unexpected transition from face-to-face offline education to online lessons has urged teachers to introduce educational technology into teaching practice, which has had an overwhelming impact on teachers' professional and personal lives. The aim of this present work is to fathom which research foci construct EBD in a comprehensive manner and how positive psychological indicators function in the technostress suffered by less agentic teachers. To this end, CiteSpace 5.7 and VOSviewer were applied to examine a longitudinal study of the literature from Web of Science Core Collection with the objective of uncovering the explicit patterns and knowledge structures in scientific network knowledge maps. Thousand seven hundred and eight articles concerned with educational data that met the criteria were extracted and analyzed. Research spanning 15 years was conducted to reveal that the knowledge base has accumulated dramatically after many governments' initiatives since 2012 with an accelerating annual growth and decreasing geographic imbalance. The review also identified some influential authors and journals whose effects will continue to have future implications. The authors identified several topical foci such as data mining, student performance, learning environment and psychology, learning analytics, and application. More specifically, the authors identified the scientific shift from data mining application to data privacy and educational psychology, from general scan to specific investigation. Among the conclusions, the results highlighted the important integration of educational psychology and technology during critical periods of educational development.

Photodynamic therapy (PDT) is considered a potential treatment regimen for colorectal cancer cases (CRC). p53 signaling and the miR-124/iASPP axis play an essential role in the PDT resistance of CRC cells. PDT treatment downregulated NEAT1 expression in p53wt HCT116 and RKO cells. In these two cell lines, NEAT1 silencing enhanced the suppressive effects of PDT on cell viability and apoptosis. Within the subcutaneously implanted tumor model, NEAT1 silencing enhanced PDT-induced suppression on tumor growth. Regarding p53-deleted HCT116 cells, PDT only moderately affected cell proliferation but induced downregulation of NEAT1. NEAT1 directly targeted miR-124, acting as a ceRNA, competing with iASPP for miR-124 binding, and counteracting miR-124–mediated repression on iASPP under PDT treatment. NEAT1 silencing was enhanced, whereas miR-124 inhibition attenuated PDT effects on CRC cells; miR-124 inhibition significantly reversed the roles of NEAT1 silencing in PDT-treated CRC cells. miR-124 negatively correlated with NEAT1 and iASPP, respectively, whereas NEAT1 and iASPP positively correlated with each other. PDT downregulated c-Myc in CRC cells, and c-Myc activated the transcription of NEAT1 through the targeting of its promoter region. Within p53mut SW480 cells, PDT failed to alter cell viability and apoptosis but still downregulated c-Myc, NEAT1, and iASPP and upregulated miR-124. In p53 mutant high-abundant CRC tissues, c-Myc and NEAT1 were up-regulated, and miR-124 was downregulated. In c-Myc high-abundant CRC tissues, NEAT1 and iASPP were up-regulated, and miR-124 was downregulated. The critical role of the c-Myc/NEAT1 axis in mediating CRC response to PDT treatment via the miR-124/iASPP/p53 feedback loop was conclusively demonstrated.

Drug resistance can notably restrict clinical applications of gefitinib that is a commonly used EGFR-tyrosine kinase inhibitors (EGFR-TKIs) for non-small cell lung cancer (NSCLC). The attempts in exploring novel drug targets and reversal strategies are still needed, since gefitinib resistance has not been fully addressed. Protease-activated receptor 2 (PAR2), a G protein-coupled receptor, possesses a transactivation with EGFR to initiate a variety of intracellular signal transductions, but there is a lack of investigations on the role of PAR2 in gefitinib resistance. This study established that protease-activated receptor 2 (PAR2), actively participated in NSCLC resistant to gefitinib. PAR2 expression was significantly up-regulated when NSCLC cells or tumor tissues became gefitinib resistance. PAR2 inhibition notably enhanced gefitinib to modulate EGFR transactivation, cell viability, migration and apoptosis in gefitinib-sensitive and-resistant NSCLC cells, suggesting its reversal effects in gefitinib resistance. Meanwhile, the combination of a PAR2 inhibitor (P2pal-18S) and gefitinib largely blocked ERK phosphorylation and epithelial-mesenchymal transition (EMT) compared to gefitinib alone. Importantly, we probed its underlying mechanism and uncovered that PAR2 blockade sensitized gefitinib and reversed its resistance mainly via β-arrestin-EGFR-ERK signaling axis. These effects of PAR2 inhibition were further confirmed by the in vivo study which showed that P2pal-18S reactivated gefitinib to inhibit tumor growth via restricting ERK activation. Taken together, this study could not only reveal a new mechanism of receptor-mediated transactivation to modulate drug resistance, but also provide a novel drug target and direction for overcoming gefitinib resistance in NSCLC.

A ring signature is an anonymous signature that implements both the authentication of the message and the anonymity of the signer. In a “normal” ring signature scheme, the same signer can generate multiple ring signatures, but the verifier cannot find this fact. Linkable ring signature (LRS) solves the problem. In the setting, the identity of the signer is still anonymous, and if the same signer generates multiple ring signatures, the verifier can confirm the fact. Linkable ring signatures are applied to some actual scenarios, such as e-cash, e-voting and ad-hoc network authentication. In this paper, we presented a new identity-based linkable ring signature scheme that avoids certificate management. We then gave the security proofs in the random oracle model (ROM) and compared the efficiency of it with the previous schemes. The new scheme requires only 7 pairing operations in signing and verifying. It is the most efficient linkable ring signature in the identity-based setting.

In this article, the attitude control problem of a new-designed aerial trees-pruning robot is addressed. During the tree cutting process, the aerial trees-pruning robot will be disturbed by unknown external disturbances. At the same time, the model uncertainties will also affect the attitude controller. To overcome the above problems, an attitude controller is designed with a nonsingular fast terminal sliding mode method. First, the extended state observer is designed to estimate the modeling uncertainties and unknown disturbances. Then, the extended state observer-based nonsingular fast terminal sliding mode controller can make the tracking error of the attitude converge to zero in a finite time. Finally, a control allocation matrix switching strategy is proposed to solve the problem of the change of the aerial robot model in the cutting process. The final simulation and experimental results show that the extended state observer-based nonsingular fast terminal sliding mode controller designed in this article has good attitude control performance and can effectively overcome the modeling uncertainties and unknown disturbances. The attitude controller and control allocation matrix switching strategy ensure that the attitude angles of the aerial robot can quickly track the reference signals.

Aims. Lipid accumulation product (LAP) is put forward as a powerful marker showing the accumulation of visceral fat. The present study is aimed at (i) analyzing the predictive performances of LAP in the identification of impaired fasting glucose (IFG) in Chinese population and (ii) exploring the potentially interactive effect between LAP and other factors on IFG risk. Methods. Analysis was conducted on the data obtained from a community-based cross-sectional survey in Chinese population, and all the participants enrolled were required to complete a face-to-face questionnaire survey and related health checks. Then, for the purpose of comparing predictive values between LAP and conventional obesity indices for IFG, relevant analysis was carried out on the receiver operating characteristic (ROC) curve. The assessment of interactive effects was conducted by employing the three indicators as follows: (1) RERI (the relative excess risk due to interaction), (2) AP (attributable proportion due to interaction), and (3) SI (synergy index). Results. A total of 1777 participants (748 males and 1029 females) were involved in the final analysis. It was finally obtained that the prevalence rate of IFG was 14.1% in total, 15.5% for males and 13.1% for females, respectively. In logistic regression analysis, individuals with LAP levels in the fourth quartile had a significant higher risk of getting IFG in comparison with that of the lowest quartile (crude OR: 4.58, 95% CI: 3.01-6.98; adjusted OR: 3.81, 95% CI: 2.33-6.23). In addition, it was indicated by the ROC curve analysis that LAP showed a better performance in discriminating IFG risk than BMI in both males (Z=2.20, P=0.028) and females (Z=2.13, P=0.033). However, LAP displayed a higher predictability in comparison with WC only in females (Z=2.07, P=0.038), but not in males (Z=0.18, P=0.860). Furthermore, LAP and family history of diabetes were able to impose significant synergistic interaction on the risk of IFG, which was indicated by all the parameters in females (RERI: 2.52, 95% CI: 0.19-4.84; AP: 0.47, 95% CI: 0.20-0.74; SI: 2.39, 95% CI: 1.17-4.87) and males (RERI: 2.18, 95% CI: 0.08-4.73; AP: 0.43, 95% CI: 0.07-0.79; SI: 2.15, 95% CI: 1.03-5.45). However, none of the indicators showed significant interaction between LAP and smoking on the risk of IFG in females (RERI: 0.92, 95% CI: -2.79-4.63; AP: 0.20, 95% CI: -0.50-0.92; SI: 1.37, 95% CI: 0.42-4.52). Meanwhile, there was also no significant interaction between LAP and smoking on the risk of IFG in males as indicated by the value of SI (2.22, 95% CI: 0.80-6.21). Conclusion. It was concluded that LAP was significantly related to a higher risk of IFG in Chinese population, and its performance was superior to that of conventional obesity indices, especially in females. Apart from that, LAP with family history of diabetes may have an interactive effect that can impose a great influence on the development of IFG.

The operation of the chemical emergency supply chain may be destroyed by the risk events, such as major natural disasters and other emergencies, which can bring about the decreasing of node operating capacity. Since the relationship among the nodes, the risk of a node will be transferred between nodes, and finally spread to the entire chemical emergency supply chain. This paper establishes and analyses the risk assessment model of chemical emergency supply chain, and then taking some certain chemical emergency supply chain as an example, analyses the risk results of the chemical emergency supply chain under risk accidents, and presents the risk mitigation strategies.

Objective. To develop a quantitative analysis of multicomponents by single-marker (QAMS) method for the simultaneous determination of polar active components in Fructus Corni. Methods. Loganin was selected as the internal reference, and the relative correction factors (RCFs) of gallic acid, 5-hydroxymethyl-2-furfural, morroniside, sweroside, cornin, 7α-O-methylmorroniside, 7β-O-methylmorroniside, 7α-O-ethylmorroniside, 7β-O-ethylmorroniside, and cornuside were established. The contents of multicomponents were then calculated based on their RCFs, respectively. Contents of the 11 components were also calculated by external standard method and compared with those of the QAMS method. Results. The contents of the 11 components in 21 crude and 10 processed Fructus Corni products were measured. No significant difference was found in the quantitative results of the QAMS and external standard methods. Conclusion. QAMS could serve as an accurate and convenient method in determining the polar and active components in Fructus Corni and its processed products.