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Abstract Background & Aim There is a lack of understanding of how social anxiety may affect Internet addiction among adolescents. Based on several theories, the purpose of this study was to investigate the multiple mediating roles of loneliness and coping styles in the association between social anxiety and Internet addiction in Chinese adolescents. Methods This study used the Social Anxiety Scale, Internet Addiction Test, Loneliness Scale, and Simple Coping Style Questionnaire to investigate 1188 students in two junior high schools and senior high schools in Henan Province, China. We adopted Pearson’s correlation analysis and the PROCESS Macro Model 81 in regression analysis to explore the relationships among social anxiety, loneliness, coping styles, and Internet addiction. Results We found that social anxiety not only directly affects teenagers' Internet addiction, but also affects teenagers' Internet addiction through loneliness and coping styles. Conclusions These results emphasize the importance of improving social anxiety to reduce Internet addiction among adolescents. At the same time, it also emphasizes the need to reduce adolescents' loneliness and cultivating positive coping styles. In addition, this study has certain theoretical significance for teenagers' mental health and intervention studies on Internet addiction.

Nanomedicine‐induced cancer cell death has become a prominent area of research in the life sciences field in recent years. The concept of cuproptosis was first proposed in 2022. Copper homeostasis in organisms is tightly regulated by protein transporters and molecular chaperones. Disruptions in copper homeostasis can adversely affect mitochondrial respiration and disrupt other physiological processes, leading to cytotoxicity. Therefore, researchers have designed and refined copper‐based nanomaterials to induce cuproptosis and assess their effects on cancer treatment. While several reviews on cuproptosis exist, they primarily delve into its molecular mechanisms. This review begins with elucidating the metabolism and homeostasis of copper in the body. Subsequently, the latest advancements in copper nanomaterial‐induced cuproptosis for cancer treatment and antimicrobial purposes is summarized. Finally, a comprehensive summary and outlook on the subject is provided. The goal with this review is to assist researchers in gaining a deeper understanding of the interaction between nanomaterials and cuproptosis, thereby offering new perspectives for designing novel nanomaterials to induce cuproptosis.

Abstract Although it is known that the frequency and intensity of heatwaves are affected by the El Niño–Southern Oscillation (ENSO), unknown are the ENSO modulations on the moving properties (e.g., moving distance and speed) of spatiotemporally contiguous heatwaves. Here, we investigate the relationship between ENSO and the moving patterns of contiguous heatwaves. We show that contiguous heatwaves are likely more frequent, more persistent, and longer‐traveling, but slower‐moving during El Niño than La Niña episodes. The differences in the tropical contiguous heatwaves between El Niño and La Niña are influenced by persistent high‐pressure anomalies. During the following summers, El Niño can induce anomalous atmospheric circulation characterized by an intensified subsidence over the western North Pacific and ascending motion over the tropical Indian and Pacific Oceans. These features provide favorable conditions for the occurrence and maintenance of contiguous heatwaves.

Skin photoaging, resulting from prolonged exposure to ultraviolet radiation, is a form of exogenous aging that not only impacts the aesthetic aspect of the skin but also exhibits a strong correlation with the onset of skin cancer. Nonetheless, the safety profile of non-natural anti-photoaging medications and the underlying physiological alterations during the process of photoaging remain inadequately elucidated. Consequently, there exists a pressing necessity to devise more secure interventions involving anti-photoaging drugs. Multiple studies have demonstrated the noteworthy significance of marine biomolecules in addressing safety concerns related to anti-photoaging and safeguarding the skin. Notably, bioactive peptides have gained considerable attention in anti-photoaging research due to their capacity to mitigate the physiological alterations associated with photoaging, including oxidative stress; inflammatory response; the abnormal expression of matrix metalloproteinase, hyaluronidase, and elastase; and excessive melanin synthesis. This review provides a systematic description of the research progress on the anti-photoaging and skin protection mechanism of marine bioactive peptides. The focus is on the utilization of marine bioactive peptides as anti-photoaging agents, aiming to offer theoretical references for the development of novel anti-photoaging drugs and methodologies. Additionally, the future prospects of anti-aging drugs are discussed, providing an initial reference for further research in this field.

The angiotensin-converting enzyme (ACE) inhibitory peptide NCW derived from Mizuhopecten yessoensis has been demonstrated to have significant in vivo anti-hypertensive effects, however, its anti-hypertensive mechanism is still not fully clarified. This study established a UPLC-Q-TRAP-MS/MS-based widely targeted kidney metabolomics approach to explore the changes of kidney metabolic profiles and to clarify the anti-hypertensive mechanism of peptide NCW in spontaneously hypertensive rats (SHRs). Multivariate statistical analysis indicated that the kidney metabolic profiles were clearly separated between the SHR-NCW and SHR-Untreated groups. A total of 85 metabolites were differentially regulated, and 16 metabolites were identified as potential kidney biomarkers, e.g., 3-hydroxybutyrate, malonic acid, deoxycytidine, and L-aspartic acid. The peptide NCW might regulate kidney metabolic disorder of SHRs to alleviate hypertension by suppressing inflammation and improving nitric oxide production under the regulation of linoleic acid metabolism, folate related pathways, synthesis and degradation of ketone bodies, pyrimidine metabolism, β-alanine metabolism, and retinal metabolism.

Abstract Precipitation exhibits a pronounced seasonal cycle, of which the phase and amplitude are closely associated with water resource management. While previous studies suggested an emerged delaying phase in the past decades, whether the amplified amplitude has emerged is controversial. Using multiple observational data sets and climate simulations, here we show that the amplification of precipitation annual cycle has emerged in most global land areas since the 1980s, especially in the tropics. These amplifications are mainly driven by anthropogenic emissions, and will be further intensified by 17.6% in the future (2081–2100) under high emission scenario (Shared Socioeconomic Pathways, SSP585), and limited to 7.2% under SSP126 scenario, relative to the historical period (1982–2014). Precipitation seasonality will be amplified by 4.2% for each 1°C of global warming, which is seen in all emission scenarios. The mitigation of lower emissions is helpful for alleviating the amplification of precipitation seasonality in a warming world.

Collagen electrospun fibers are promising materials for food packaging and tissue engineering. The conventional electrospinning of collagen, however, is usually carried out by dissolving it in organic reagents, which are toxic. In this study, collagen/pullulan (COL/PUL) ultra-thin fibers were prepared by electrospinning using acetic acid as a solvent. Compared to the conventional preparation method, the proposed method is safe and does not produce toxic solvent residues. The introduction of PUL increased the degree of molecular entanglement in the solution, so the viscosity of the COL/PUL electrospun solution increased from 0.50 ± 0.01 Pa∙s to 4.40 ± 0.08 Pa∙s, and the electrical conductivity decreased from 1954.00 ± 1.00 mS/cm to 1372.33 ± 0.58 mS/cm. Scanning electron microscopy analysis confirmed that PUL improved the spinnability of COL, and smooth, defect-free COL/PUL ultra-thin fibers with diameters of 215.32 ± 40.56 nm and 240.97 ± 53.93 nm were successfully prepared at a viscosity of greater than 1.18 Pa∙s. As the proportion of PUL increased, intramolecular hydrogen bonds became the dominant interaction between COL and PUL. The intermolecular hydrogen bonding content decreased from 52.05 % to 36.45 %, and the intramolecular hydrogen bonding content increased from 46.11 % to 62.95 %. The COL was gradually unfolded, the content of α-helices decreased from 33.57 % to 25.91 % and the random coils increased from 34.22 % to 40.09 %. More than 36 % of the triple helix fraction of COL was retained by the COL/PUL ultra-thin fibers, whereas only 16 % of the triple helix fraction of COL was retained by the COL nanofibers prepared with 2.2.2-trifluoroethanol. These results could serve as a reference for the development of green food COL-based fibers.

Abstract Background The timings of reproductive life events have been examined to be associated with various psychiatric disorders. However, studies have not considered the causal pathways from reproductive behaviors to different psychiatric disorders. This study aimed to investigate the nature of the relationships between five reproductive behaviors and twelve psychiatric disorders. Methods Firstly, we calculated genetic correlations between reproductive factors and psychiatric disorders. Then two-sample Mendelian randomization (MR) was conducted to estimate the causal associations among five reproductive behaviors, and these reproductive behaviors on twelve psychiatric disorders, using genome-wide association study (GWAS) summary data from genetic consortia. Multivariable MR was then applied to evaluate the direct effect of reproductive behaviors on these psychiatric disorders whilst accounting for other reproductive factors at different life periods. Results Univariable MR analyses provide evidence that age at menarche, age at first sexual intercourse and age at first birth have effects on one (depression), seven (anxiety disorder, ADHD, bipolar disorder, bipolar disorder II, depression, PTSD and schizophrenia) and three psychiatric disorders (ADHD, depression and PTSD) (based on p

Abstract Human-perceived temperature (HPT) describes the joint effects of multiple climatic factors such as temperature and humidity. Extreme HPT events may reduce labor capacity and cause thermal discomfort and even mortality. These events are becoming more frequent and more intense under global warming, posing severe threats to human and natural systems worldwide, particularly in populated areas with intensive human activities, e.g., the North China Plain (NCP). Therefore, a fine-scale HPT dataset in both spatial and temporal dimensions is urgently needed. Here we construct a daily high-resolution (~1 km) human thermal index collection over NCP from 2003 to 2020 (HiTIC-NCP). This dataset contains 12 HPT indices and has high accuracy with averaged determination coefficient, mean absolute error, and root mean squared error of 0.987, 0.970 °C, and 1.292 °C, respectively. Moreover, it exhibits high spatiotemporal consistency with ground-level observations. The dataset provides a reference for human thermal environment and could facilitate studies such as natural hazards, regional climate change, and urban planning.

Abstract Second near-infrared (NIR-II) fluorescence imaging in the range of 1000–1700 nm has great prospects for in vivo imaging and theranostics monitoring. At present, few NIR-II probes with theranostics properties have been developed, especially the high-performance organic theranostics material remains underexploited. Herein, we demonstrate a selenium (Se)-tailoring method to develop high-efficient NIR-II imaging-guided material for in vivo cancer phototheranostics. Via Se-tailoring strategy, conjugated oligomer TPSe-based nanoparticles (TPSe NPs) achieve bright NIR-II emission up to 1400 nm and exhibit a relatively high photothermal conversion efficiency of 60% with good stability. Moreover, the TPSe NPs demonstrate their photothermal ablation of cancer cells in vitro and tumor in vivo with the guidance of NIR-II imaging. It is worth noting that the TPSe NPs have good biocompatibility without obvious side effects. Thus, this work provides new insight into the development of NIR-II theranostics agents.

Heatwaves are among the deadliest weather-related disasters. They are not only seen in summer but also may appear in spring and autumn, especially under climate warming. Although the mechanisms of summertime heatwaves have been extensively studied, how they differ from spring and autumn seasons and possibly season-dependent mechanisms of heatwaves are poorly understood. Here we examine the specific processes associated with spring, summer, and autumn heatwaves in southern China during 1961–2020. We show that heatwaves in all three seasons are intensifying in frequency, duration, and intensity, and they exhibit distinctly season-dependent circulation changes. Summer heatwaves are characterized by a warm-core high-pressure structure, while spring and autumn heatwaves exhibit a warm low pattern. Summer heatwaves are mainly triggered by the westward (eastward) extension of the western North Pacific subtropical high (South Asian high), and are accompanied by anomalous lower-level anticyclone and positive pressure anomalies. In contrast, spring and autumn heatwaves coincide with lower-than-normal pressure and anomalous southwesterly over East Asia, indicative of a weakening of the East Asian winter monsoon circulation and the Siberian high. Their developments are linked to the eastward movement of an upper-tropospheric wave-like pattern over the mid-latitudes. It is also found that autumn heatwaves are largely contributed by local preceding soil moisture deficit, in comparison to spring and summer heatwaves. Our findings contribute to a better understanding of the heatwave characteristics in different seasons and provide insights into their mitigation strategies.

Abstract Background & aims Diabetes may perceive or experience varying degrees of stigma and psychological distress. The association between diabetes-related stigma and psychological distress has been examined in many studies, but no research has used a quantitative synthesis method to investigate the severity of this association and the moderators of the relationship. Thus, we conducted a meta-analysis to quantitatively integrate previous findings to identify the magnitude of the association between stigma and psychological distress among people with diabetes. Review methods Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, we systematically searched four English academic databases (PubMed, Embase, Web of Science, and PsycINFO) and three Chinese databases (China National Knowledge Infrastructure [CNKI], WANFANG Data, China Science and Technology Journal Database [VIP]). The databases were searched from the inception of each database to the end of March 2023. The pooled correlation coefficient of the association between stigma and psychological distress among people with diabetes was calculated by a random effects model using Stata software (version 17.0), and several moderators that impacted this relationship were identified. Results Eligible studies (N = 19) with a total of 12,777 participants were analysed. The pooled correlation was high between diabetes-related stigma and psychological distress (r = 0.50, 95% CI: [0.43–0.57]). Moreover, the association was moderated by the diabetes stigma measurement tools and diabetes distress measurement tools used. However, the relationship was not moderated by type of diabetes, age, gender, geographical location, or type of stigma. Conclusions The results of the meta-analysis showed that stigma is strongly related to psychological distress among people with diabetes. Longitudinal or experimental research should be expanded in the future to further identify the causal pathways in the relationship between diabetes stigma and diabetes distress.

Adenosine-to-inosine (A-to-I) RNA editing, constituting nearly 90% of all RNA editing events in humans, has been reported to contribute to the tumorigenesis in diverse cancers. However, the comprehensive map for functional A-to-I RNA editing events in cancers is still insufficient. To fill this gap, we systematically and intensively analyzed multiple tumorigenic mechanisms of A-to-I RNA editing events in samples across 33 cancer types from The Cancer Genome Atlas. For individual candidate among ∼ 1,500,000 quantified RNA editing events, we performed diverse types of downstream functional annotations. Finally, we identified 24,236 potentially functional A-to-I RNA editing events, including the cases in APOL1, IGFBP3, GRIA2, BLCAP, and miR-589-3p. These events might play crucial roles in the scenarios of tumorigenesis, due to their tumor-related editing frequencies or probable effects on altered expression profiles, protein functions, splicing patterns, and microRNA regulations of tumor genes. Our functional A-to-I RNA editing events (https://ccsm.uth.edu/CAeditome/) will help better understand the cancer pathology from the A-to-I RNA editing aspect.

The application of organic fertilizers is one of the most important agricultural measures aimed at improving the flavor and productivity of Lycopersicon esculentum, with the granulation and coating of organic fertilizers, which can reduce seepage losses of great significance to the ecosystem. In this study, Jingcai 8 tomato was selected as the test material. Headspace solid-phase microextraction and gas chromatography–mass spectrometry (HS-SPME-GC-MS) methods were used to investigate the effects of different pelletized organic fertilizers and various coating materials on the flavor profile of the tomatoes. The results indicated that 67 volatile organic compounds (VOCs) were identified in the tomato fruits and 62 volatile compounds were identified in the leaves under different fertilizer treatments. The volatile compound content of the fruits in the BP treatment group was 35.38 μg/g, which was higher than that in other treatment groups, and the volatile compound content of the leaves was lower. A differential compound analysis with log2|fold change| ≥ 1 and variable important in projection (VIP) > 1 highlighted styrene, 3-methyl-1-butanol, and (E, E)-2,4-hexadienal as the major up-regulated compounds and methyl salicylate as the major down-regulated compound in the tomato fruit BCK (control) vs. BP. Moreover, the α-phellandrene content decreased in the tomato leaves. In addition, an analysis of the tomato fruit differential compounds and compounds with odor activity values (OAV) of ≥ 1, considering the OAV values of characteristic aroma compounds, identified key compounds affecting the flavor of the tomato fruits under the BP treatment. These included 2-nonenal, (E)-2-pentylfuran, trans-β-ionone, 1-penten-3-one, (E, E)-2,4-hexadienal, and 3-hexenol (fruity, floral, and herbaceous odors), (E, E)-2,4-heptadienal (fatty odor), and hexanal (green odor). The combined results analysis of the volatile compound content, differential compounds, and OAV values of characteristic aroma compounds aimed to clarify that the BP treatment group, which applied pelletized, large-grain organic fertilizer with polyurethane (pozzolanic + small-grain oil-coated + 2% paraffinic + 4% polyurethane) as a coating material, proved to be most effective in influencing the flavor of the tomato fruits. This finding lays the foundation for its potential commercial application in artificial orchards.

Abstract Heatwaves impose serious impacts on ecosystems, human health, agriculture, and energy consumption. Previous studies have classified heatwaves into independent daytime, independent nighttime, and compound daytime-nighttime types, and examined the long-term changes in the three types. However, the underlying mechanisms associated with the variations in different heatwave types remain poorly understood. Here we present the first investigation of the local physical processes associated with the daytime, nighttime, and compound heatwaves over the global land during 1979–2020. The results show that three heatwave types occur frequently and increasingly in most regions worldwide. Nighttime and compound heatwaves exhibit stronger increases in both frequency (the yearly number of the events) and fraction (the ratio of the yearly number of one heatwave type to the total yearly number of all types) than daytime heatwaves. Composite diagnostic analyses of local meteorological variables suggest that daytime heatwaves are associated with increased solar radiation under dry conditions and reduced cloud cover and humidity under a clear sky. In contrast, nighttime heatwaves are typically accompanied by moist conditions with increases in cloud fraction, humidity, and longwave radiation at night. These synoptic conditions for daytime and nighttime heatwaves are combined to contribute to compound heatwaves. Local divergences and moisture fluxes responsible for different heatwaves are further revealed. Positive moisture divergence anomalies are seen in most land areas for daytime and compound heatwaves, while they mainly appear in low latitudes for nighttime heatwaves. Our research provides a comprehensive understanding of the local mechanisms of different heatwave types, informing future risks and impact assessments.

Under global warming and rapid urbanization, heat extremes, ozone pollution, and their co-occurrences are emerging and posing severe risks to human health. However, possibly different characteristics of independent heat days (IHD), independent ozone pollution (IOP) and compound heat-ozone pollution (CHOP) events are unclear. In this study, we present an investigation of the spatial distribution and mechanisms associated with IHD, IOP and CHOP events during May–October in 2014–2022 by taking the Guangdong-Hong Kong-Macao Greater Bay Area (GBA) of China as an example. The results show that central GBA faces higher compound risk than northwestern and southeastern regions. IHD events are primarily driven by extremely high temperatures and accompanied by anomalous anticyclone and high pressure at both lower and upper troposphere levels, under the joint effects of the South Asian high and western North Pacific subtropical high. IOP events are predominantly accompanied by decreased cloud cover, air humidity and enhanced downward solar radiation. CHOP events are influenced by increases in both temperature and downward solar radiation. The circulation patterns of CHOP events are somewhat similar to IOP but with much stronger magnitude and faster developing process, and both are likely related to tropical cyclone activities. Our findings can strengthen the early forecasting of these extreme events and mitigate their negative impacts.

Abstract Background The high prevalence of depression among older people in China places a heavy burden on the health system. Multimorbidity, mobility limitation and subjective memory impairment are found to be risk indicators for depression. However, most studies on this topic focused on depression at a single point in time, ignoring the dynamic changes in depressive symptoms and the relationship between the trajectories and these three conditions. Therefore, we aimed to identify distinct trajectories of depressive symptoms in older people and investigate their associations with multimorbidity, mobility limitation and subjective memory impairment. Methods Data was drawn from China Health and Retirement Longitudinal Study conducted during 2011–2018. A total of 5196 participants who completed 4 visits, conducted every 2–3 years were included in this study. Group-based trajectory modeling was conducted to identify distinct trajectories of depressive symptoms z-scores. Multinomial logistic regression was used to investigate the relationships. Results Four distinct trajectories of depressive symptoms z-scores were identified, labeled as persistently low symptoms (68.69%, n = 3569), increasing symptoms (12.14%, n = 631), decreasing symptoms (14.05%, n = 730) and persistently high symptoms (5.12%, n = 266). Participants with multimorbidity had unfavorable trajectories of depressive symptoms compared with those without multimorbidity, with adjusted odds ratios (95% CIs) of 1.40 (1.15, 1.70), 1.59 (1.33, 1.90) and 2.19 (1.65, 2.90) for the increasing symptoms, decreasing symptoms and persistently high symptoms, respectively. We also observed a similar trend among participants with mobility limitations. Compared with participants who had poor subjective memory, participants with excellent/very good/good subjective memory had a lower risk of developing unfavorable trajectories of depressive symptoms. The adjusted odds ratios (95% CIs) of the increasing symptoms, decreasing symptoms and persistently high symptoms were 0.54 (0.40, 0.72), 0.50 (0.38, 0.65) and 0.48 (0.31, 0.73), respectively. Conclusions Multimorbidity, mobility limitation and subjective memory impairment were found to be potential risk factors for unfavorable depression trajectories.

In the past decade, deep learning methods have proven to be highly effective in the classification of hyperspectral images (HSI), consistently outperforming traditional approaches. However, the large number of spectral bands in HSI data can lead to interference during the learning process. To address this issue, dimensionality reduction techniques can be employed to minimize data redundancy and improve HSI classification performance. Hence, we have developed an efficient lightweight learning framework consisting of two main components. Firstly, we utilized band selection and principal component analysis to reduce the dimensionality of HSI data, thereby reducing redundancy while retaining essential features. Subsequently, the pre-processed data was input into a modified VGG-based learning network for HSI classification. This method incorporates an improved dynamic activation function for the multi-layer perceptron to enhance non-linearity, and reduces the number of nodes in the fully connected layers of the original VGG architecture to improve speed while maintaining accuracy. This modified network structure, referred to as lightweight-VGG (LVGG), was specifically designed for HSI classification. Comprehensive experiments conducted on three publicly available HSI datasets consistently demonstrated that the LVGG method exhibited similar or better performance compared to other typical methods in the field of HSI classification. Our approach not only addresses the challenge of interference in deep learning methods for HSI classification, but also offers a lightweight and efficient solution for achieving high classification accuracy.

Mizuhopecten yessoensis-derived angiotensin converting enzyme (ACE) inhibitory peptide Asn-Cys-Trp (NCW) has been found that had a significantly in vivo antihypertensive effect. However, the special mechanism of peptide NCW for lowing blood pressure has not been fully elucidated. This study aimed to screen the key targets and elucidate the antihypertensive mechanism of based on the network pharmacology and molecular docking. A total of 70 potential antihypertensive targets of peptide NCW were identified, which were mainly enriched in Regulation of blood pressure, Positive regulation of smooth muscle cell proliferation, and other biological processes; Plasma membrane, Extracellular exosome, and other cellular components; Endopeptidase activity, Zinc ion binding, and other molecular functions. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that lipid and atherosclerosis pathway, relaxin signaling pathway, and mitogen-activated protein kinase (MAPK) signaling pathway were the key pathways for peptide NCW to regulate the potential antihypertensive targets. Eleven potential key antihypertensive targets were screened via topology analysis of protein and protein interaction network, i.e., albumin (ALB), matrix metallopeptidase 9 (MMP9), MMP2, insulin like growth factor 1, AKT serine/threonine kinase 1 (IGF1), ACE, nitric oxide synthase 3 (NOS3), peroxisome proliferator activated receptor gamma (PPARG), epidermal growth factor receptor (EGFR), catalase (CAT), and renin (REN). In addition, molecular docking results showed that the peptide NCW had high affinities with these potential key antihypertensive targets, and hydrogen bonds were the key interaction forces between the peptide NCW and targets. This study provided a theoretical basis for the multi-target and multi-pathway prevention and improvement of hypertension with peptide NCW.

BackgroundHypertrophic cardiomyopathy (HCM) is the most common genetic heart disease. The purpose of this study was to evaluate the efficacy and safety of several medications and recommend better drug treatments for adults with HCM.MethodsA review of PubMed, Embase, the Cochrane Controlled Register of Trials (CENTRAL), ClinicalTrials.gov and CNKI databases was conducted for studies on the efficacy and safety of drugs for adults with HCM. A frequentist random effects model was used in this network analysis.ResultsThis network meta-analysis included 7 studies assessing seven medications, 6 studies evaluating monotherapy and 1 study evaluating combination therapy. Based on the network meta-analysis results, xiaoxinbi formula plus metoprolol (MD −56.50% [−72.43%, −40.57%]), metoprolol (MD −47.00% [−59.07%, −34.93%]) and mavacamten (MD −34.50% [−44.75%, −24.25%]) significantly reduced the resting left ventricular outflow tract gradient (LVOTG) in comparison with placebo. Resting LVOTG could also be reduced with N-acetylcysteine (NAC). The incidence of adverse drug reactions was not significantly different between the placebo group and the treatment group.ConclusionFor adults with HCM, the top 4 treatments included xiaoxinbi formula plus metoprolol, metoprolol, mavacamten and NAC.Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=374222], identifier [CRD42022374222].

Objective: Preeclampsia (PE) is a serious condition in pregnant women and hence an important topic in obstetrics. The current research aimed to recognize the potential and significant immune-related diagnostic biomarkers for PE.Methods: From the Gene Expression Omnibus (GEO) data sets, three public gene expression profiles (GSE24129, GSE54618, and GSE60438) from the placental samples of PE and normotensive pregnancy were downloaded. Differentially expressed genes (DEGs) were selected and determined among 73 PE and 85 normotensive control pregnancy samples. The DEGs were used for Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Disease Ontology (DO) enrichment analysis, and Gene Set Enrichment Analysis (GSEA). The candidate biomarkers were identified by the least absolute shrinkage and selection operator (LASSO) and support vector machine recursive feature elimination (SVM-RFE) analysis. The receiver operating characteristic curve (ROC) was applied to evaluate diagnostic ability. For further confirmation, the expression levels and diagnostic value of biomarkers in PE were verified in the GSE75010 data set (80 PE and 77 controls) and validated by qRT-RCR, Western blot, and immunohistochemistry (IHC). The CIBERSORT algorithm was used to calculate the compositional patterns of 22 types of immune cells in PE.Results: In total, 15 DEGs were recognized. The GO and KEGG analyses revealed that the DEGs were enriched in the steroid metabolic process, receptor ligand activity, GnRH secretion, and neuroactive ligand−receptor interaction. The recognized DEGs were primarily implicated in cell-type benign neoplasm, kidney failure, infertility, and PE. Gene sets related to hormone activity, glycosylation, multicellular organism process, and response to BMP were activated in PE. The LEP gene was distinguished as a diagnostic biomarker of PE (AUC = 0.712) and further certified in the GSE75010 data set (AUC = 0.850). The high expression of LEP was associated with PE in clinical samples. In addition, the analysis of the immune microenvironment showed that gamma delta T cells, memory B cells, M0 macrophages, and regulatory T cells were positively correlated with LEP expression (P < 0.05).Conclusion:LEP expression can be considered to be a diagnostic biomarker of PE and can offer a novel perspective for future studies regarding the occurrence and molecular mechanisms of PE.

BackgroundAcademic procrastination is common among college students, but there is a lack of research on the influencing mechanism of academic procrastination among nursing students. The purpose of this study was to explore the influence of parental rearing patterns on academic procrastination of nursing students, and the mediating role of causal attribution and self-efficacy.MethodsUsing Parental Bonding Instrument, Aitken Procrastination Inventory, Multidimensional Multi-Attribution Causality Scale and General Self-Efficiency Scale, the data of 683 nursing undergraduates from two universities in China were collected. Moreover, path analysis for structural equation modeling via AMOS 26.0 to evaluate mediation path model.ResultsPositive parenting style was negatively associated with academic procrastination (r = –0.350) and negative parenting style was positively associated with academic procrastination (r = 0.402). Positive parenting style directly or indirectly predicted academic procrastination through the mediating effect of internal attributional style (β = –0.10, 95% CI: –0.18 to –0.04) and self-efficacy (β = –0.07, 95% CI: –0.11 to –0.03), and this mediating effect accounted for 41.46% of the total effect. Positive parenting style directly or indirectly predicted academic delay through the mediating effect of external attributional style (β = 0.12, 95% CI: 0.07 to 0.17) and self-efficacy (β = 0.05, 95% CI: 0.03 to 0.08), and this mediating effect accounted for 42.5% of the total effect. In addition, causal attribution and self-efficacy of nursing students play a chain intermediary role between parenting style and academic procrastination.ConclusionParents should give students more care and autonomy and reduce control. In addition, educators should give students attribution training, which is helpful to improve students’ self-efficacy and reduce academic procrastination.

Introduction: The current quality evaluation of traditional Chinese medicine (TCM) is difficult to attribute to clinical efficacy due to the complexity of TCM. Zishen Yutai pill (ZYP), a well-known traditional Chinese patent medicine, has been widely used to prevent recurrent miscarriage and treat threatened abortion. However, the chemical components of ZYP are unknown, and there is no convincing quality control method applied on ZYP. Although ZYP has been found to promote endometrial receptivity and treat impending abortion, the substantial basis of the therapeutic effects is unclear. The aim of this study was to clarify the quality markers correlated with the potential medicinal activities and provide a theoretical foundation for scientific quality control and product quality improvement of ZYP.Methods: The chemical constituents of ZYP were comprehensively analyzed by offline two-dimensional liquid chromatography-mass spectrometry (2DLC-LTQ-Orbitrap-MS). The efficacy of the 27 ZYP orthogonal groups was investigated using the HTR-8/SVneo oxidative damage model and migration model in vitro, as well as the endometrial receptivity disorder mouse model and premature ovarian failure mouse model in vivo. Based on the efficacy and mass spectral results, spectrum–effect relationship analysis was used to identify the chemical components with corresponding pharmacological activities.Results: A total of 589 chemical components were found in ZYP, of which 139 were not identified in the literature. The potential quality markers for ZYP were successfully identified through orthogonal design and spectrum–effect relationship analysis. By combining mass spectrum data and pharmacological results of 27 orthogonal groups, 39 substances were identified as potential quality markers.Conclusion: The approaches used in this study will provide a feasible strategy for the discovery of quality markers with bioactivity and further investigation into the quality evaluation of TCM.

ObjectiveThe important contribution of dietary triggers to migraine pathogenesis has been recognized. However, the potential causal roles of many dietary habits on the risk of migraine in the whole population are still under debate. The objective of this study was to determine the potential causal association between dietary habits and the risk of migraine (and its subtypes) development, as well as the possible mediator roles of migraine risk factors.MethodsBased on summary statistics from large-scale genome-wide association studies, we conducted two-sample Mendelian randomization (MR) and bidirectional MR to investigate the potential causal associations between 83 dietary habits and migraine and its subtypes, and network MR was performed to explore the possible mediator roles of 8 migraine risk factors.ResultsAfter correcting for multiple testing, we found evidence for associations of genetically predicted coffee, cheese, oily fish, alcohol (red wine), raw vegetables, muesli, and wholemeal/wholegrain bread intake with decreased risk of migraine, those odds ratios ranged from 0.78 (95% CI: 0.63–0.95) for overall cheese intake to 0.61 (95% CI: 0.47–0.80) for drinks usually with meals among current drinkers (yes + it varies vs. no); while white bread, cornflakes/frosties, and poultry intake were positively associated with the risk of migraine. Additionally, genetic liability to white bread, wholemeal/wholegrain bread, muesli, alcohol (red wine), cheese, and oily fish intake were associated with a higher risk of insomnia and (or) major depression disorder (MDD), each of them may act as a mediator in the pathway from several dietary habits to migraine. Finally, we found evidence of a negative association between genetically predicted migraine and drinking types, and positive association between migraine and cups of tea per day.SignificanceOur study provides evidence about association between dietary habits and the risk of migraine and demonstrates that some associations are partly mediated through one or both insomnia and MDD. These results provide new insights for further nutritional interventions for migraine prevention.

Abstract Heatwaves detrimentally affect human health and ecosystems. While previous studies focused on either temporal changes or spatial extents of heatwaves, their spatiotemporal contiguity and propagation patterns are unclear. Here, we investigate the climatology, long-term trends, and interannual variations of spatiotemporally contiguous heatwaves across China during 1961 to 2018. Two distinct propagation patterns are identified by introducing a spatiotemporally contiguous events tracking (SCET) method and the k-means clustering. Type 1 contiguous heatwaves mostly generate over eastern China and move southwestward at shorter distances, while Type 2 heatwaves generally initiate over western China and move southeastward at longer distances, with stronger intensity, longer lifetime, and larger coverage. Since the 1960s, both types exhibit significant increases in frequency, intensity, coverage, lifetime, and traveling distances, with relatively larger magnitudes for Type 2, but significant decreases in moving speed only appear for Type 1. On interannual timescale, preceding winter El Niño prolongs the duration and slows down the moving speed of Type 1 through the western North Pacific subtropical high. Type 2 contiguous heatwaves are intensified by the negative spring North Atlantic Oscillation via the upper-atmospheric Rossby wave train.

The purpose of this study was to screen the xanthine oxidase (XO) inhibitory peptides from egg white proteins through virtual hydrolysis, in vitro activity validation, and molecular docking. The results demonstrated that tripeptide EEK from ovalbumin exhibited potent XO inhibitory activity with an IC50 value of 141 µmol/L. The molecular docking results showed that tripeptide EEK bound with the active center of XO via 3 carbon hydrogen bond interactions, 2 salt bridges, 5 conventional hydrogen bond interactions, and 4 attractive charge interactions. The residues Glu802, Phe1009, and Arg880 may play key roles in the XO catalytic reaction. Especially, the key intermolecular forces of inhibiting XO activity may be special type of hydrogen bonds including carbon hydrogen bond interactions and attraction charge interactions. The novel tripeptide EEK is potential candidates for controlling hyperuricemia.

Abstract Biomolecule-functionalized fluorescent gold nanocluster (AuNCs) have attracted a lot of attention due to good biocompatibility, stable physicochemical properties and considerable cost advantages. Inappropriate concentration of Cu2+ may cause a variety of diseases. In this study, AuNCs were synthesized in alkaline aqueous solution using bovine serum albumin (BSA) as a template. And then, the peptide CCYWDAHRDY was coupled to AuNCs. Furthermore, the fluorescence of synthesized CCYWDAHRDY-AuNCs response to Cu2+ was evaluated. As the results shown that the CCYWDAHRDY-AuNCs can sensitively detect Cu2+. After adding Cu2+ to the probe system, the fluorescence of the CCYWDAHRDY-AuNCs was quenched. The detection conditions were at pH 6 and 30 °C for 10 min, the linear relationship between Cu2+ concentration and fluorescence intensity were good in the range of 0.1 ~ 4.2 μmol/L. The regression equation was y = − 105.9x + 693.68, the linear correlation coefficient is 0.997, and the minimum detection limit was 52 nmol/L.

BackgroundImmune checkpoint inhibitors (ICIs) have changed the treatment pattern of advanced and metastatic NSCLC. A series of ICI based therapies have emerged in the first-line treatment field, but the comparative efficacy was unclear.MethodWe searched multiple databases and abstracts of major conference proceedings up to Apri1, 2022 for phase III randomised trials of advanced driver-gene wild type NSCLC patients receiving first-line therapy. Outcomes analyzed included progression free survival (PFS), overall survival (OS), and et al.ResultsThirty-two double-blind RCTs were included, involving 18,656 patients assigned to 22 ICI-based first-line regimens. A series of ICI regiments (including ICI plus chemotherapy), ICI monotherapy, doublet ICIs, doublet ICIs plus chemotherapy) emerged, and showed significant PFS and OS benefit than chemotherapy and chemotherapy + bevacizumab (BEV) for advanced wild-type NSCLC. In comprehensive terms of PFS, chemoimmunotherapy (CIT) were significantly more effective than ICI monotherapy and doublet ICIs. In terms of OS for patients with non-squamous NSCLC, pembrolizumab containing CIT was associated with a median rank of the best regimens, and followed by Atezolizumab+BEV based CIT; while for OS in patients with squamous NSCLC, Cemiplimab and sintilimab based CIT were the most effective regimens. For more than 2 years follow-up, the atezolizumab, pembrolizumab, nivolumab and durvalumab containing ICI therapy all provide a durable long-term OS benefit over chemotherapy and BEV + chemotherapy.ConclusionsThe findings of the present NMA represent the most comprehensive evidence, which might suggest or provide basis for first-line ICI therapy decision for advanced NSCLC patients without oncogenic driver mutations.

Taurine, a sulfur-containing amino acid, has a wide range of biological effects, such as bile salt formation, osmotic regulation, oxidative stress inhibition, immunomodulation and neuromodulation. Taurine has been proved to be synthesized and abundant in male reproductive organs. Recently, accumulating data showed that taurine has a potential protective effect on reproductive function of male animals. In physiology, taurine can promote the endocrine function of the hypothalamus-pituitary-testis (HPT) axis, testicular tissue development, spermatogenesis and maturation, delay the aging of testicular structure and function, maintain the homeostasis of the testicular environment, and enhance sexual ability. In pathology, taurine supplement may be beneficial to alleviate pathological damage of male reproductive system, including oxidative damage of sperm preservation in vitro, testicular reperfusion injury and diabetes -induced reproductive complications. In addition, taurine acts as a protective agent against toxic damage to the male reproductive system by exogenous substances (e.g., therapeutic drugs, environmental pollutants, radiation). Related mechanisms include reduced oxidative stress, increased antioxidant capacity, inhibited inflammation and apoptosis, restored the secretory activity of the HPT axis, reduced chromosomal variation, enhanced sperm mitochondrial energy metabolism, cell membrane stabilization effect, etc. Therefore, this article reviewed the protective effect of taurine on male reproductive function and its detailed mechanism, in order to provide reference for further research and clinical application.

Tripeptide NCW identified in Mizuhopecten yessoensis has been shown to possess in vivo antihypertensive effect. However, the poor understanding of the absorption of NCW across the membrane limits its application. In this study, we have investigated the interaction of NCW with DPPC membrane via 400 ns all-atom molecular dynamic simulation using GROMACS software. The structural variations of NCW during absorption, the location and distribution of NCW in the membrane, and the effect of NCW on the properties of membranes during simulation were analyzed to understand the dynamic behavior of NCW in DPPC membrane system. The results suggested that the structures of NCW were stable during simulation. Further, NCW could bind on the surface of the DPPC membrane and enter the hydrophobic interior of the DPPC membrane. Residue Try played an important role in the absorption of NCW across the membrane. Hydrogen bonds and hydrophobic interactions stabilized the interaction of NCW with the membrane. All the above studies analyzed the interaction mechanism between NCW and DPPC membranes at the atomic level and laid the foundation for further transmembrane studies of NCW.

ObjectiveType 2 diabetes is more common in adults, but is becoming the major concern in children and adolescent recently. This study aimed to provide additional pharmaceutical management for children and adolescents with type 2 diabetes by assessing the efficacy and safety of several glucose-lowering drugs.MethodsSearches were performed in PubMed, Medline, Ovid, Cochrane Controlled Register of Trials (CENTRAL), and ClinicalTrials.gov that reported the efficacy and safety of drugs for children and adolescents with type 2 diabetes. Pooled effects were calculated by frequentist fixed effects network meta-analyses and additive network meta-analyses.ResultsA total of 12 trials assessing eight glucose-lowering drugs were included, which compose of seven trials with monotherapy and five trials with combination therapies. Network meta-analysis results showed compared to placebo, saxagliptin+metformin (mean difference (MD) -1.91% [-2.85%, -0.97%]), liraglutide+metformin (MD -1.45% [-1.65%, -1.26%]), and liraglutide (MD -0.90% [-1.35%, -0.45%]) were the top 3 drugs that significantly reduced hemoglobin A1c (HbA1c). Sitagliptin+metformin, dapagliflozin, exenatide-2mcg, linagliptin-5mg, metformin, exenatide-5/10mcg, glimepiride, and sitagliptin also showed significant reduction in HbA1c. There were no significant differences between treatments in the incidence of adverse events, except that liraglutide+metformin had significant adverse effect such as abdominal pain. In addition, dapagliflozin, sitagliptin+metformin, and saxagliptin+metformin showed better efficacy compared with FDA-approved drugs.ConclusionsThe top 10 treatments of type 2 diabetes in children and adolescents aged 10–17 years were saxagliptin+metformin, liraglutide+metformin, liraglutide, dapagliflozin, exenatide–2 mcg, sitagliptin+metformin, linagliptin–5 mg, linagliptin–1 mg, metformin, and exenatide–5/10 mcg.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=284897, identifier CRD42021284897.

Parkinson’s disease (PD) is characterized by dopaminergic neurodegeneration and an abnormal accumulation of α-synuclein aggregates. A number of genetic factors have been shown to increase the risk of PD. Exploring the underlying molecular mechanisms that mediate PD’s transcriptomic diversity can help us understand neurodegenerative pathogenesis. In this study, we identified 9897 A-to-I RNA editing events associated with 6286 genes across 372 PD patients. Of them, 72 RNA editing events altered miRNA binding sites and this may directly affect miRNA regulations of their host genes. However, RNA editing effects on the miRNA regulation of genes are more complex. They can (1) abolish existing miRNA binding sites, which allows miRNAs to regulate other genes; (2) create new miRNA binding sites that may sequester miRNAs from regulating other genes; or (3) occur in the miRNA seed regions and change their targets. The first two processes are also referred to as miRNA competitive binding. In our study, we found 8 RNA editing events that may alter the expression of 1146 other genes via miRNA competition. We also found one RNA editing event that modified a miRNA seed region, which was predicted to disturb the regulation of four genes. Considering the PD-related functions of the affected genes, 25 A-to-I RNA editing biomarkers for PD are proposed, including the 3 editing events in the EIF2AK2, APOL6, and miR-4477b seed regions. These biomarkers may alter the miRNA regulation of 133 PD-related genes. All these analyses reveal the potential mechanisms and regulations of RNA editing in PD pathogenesis.

Abstract While it is well known that rapid urbanization poses prominent effects on regional or local temperature changes under global warming, possible impacts of urbanization on the changes in atmospheric aridity (measured by vapor pressure deficit [VPD]) are poorly understood. In this study, we provide a national investigation of the spatiotemporal changes of atmospheric aridity over China in recent decades by analyzing observations at over 2,000 weather stations across China during 1971–2017 and further quantify the effects of urbanization on the atmospheric aridity changes in different subregions. The results show that most parts of China have experienced a significant intensification of atmospheric aridity since the 1970s. Especially, stronger drying trends tend to appear in urban agglomerations with higher urbanization levels and denser population, such as Beijing‐Tianjin‐Hebei (BTH), the Yangtze River Delta (YRD), the Pearl River Delta (PRD), and the Sichuan Basin. It is estimated that urbanization contributed to more than 30% of the total increases in atmospheric aridity in urban core areas (i.e., 32.58%, 27.73%, 30.29%, 42.03%, and 37.33%, respectively, for annual, spring, summer, autumn, and winter VPD). Spatially, urbanization exerted significant amplification effects on increasing VPD in most parts of China (nearly 80% grid cells) except for few areas with higher elevation and complex topography (e.g., Qinghai‐Tibet Plateau and Xinjiang). In particular, the areas with higher urbanization (e.g., BTH, YRD, and PRD) underwent even stronger urbanization effects on amplifying atmospheric aridity. Our findings suggest that how to alleviate atmospheric aridity in future urban planning is worthy of consideration.

Rice–crab co-culture is a high-benefit eco-breeding pattern that has been extensively developed in many regions of China. However, little attention has been paid to the safety of pesticides used to control rice pests in the crab–rice co-culture system. This study monitored the actual residue levels of propiconazole in water and soil of rice–crab co-culture fields and evaluated the acute toxicity, subchronic toxicity, and bioaccumulation of propiconazole to Eriocheir sinensis. We observed that the residue level of propiconazole in paddy soil was higher than that in paddy water within 42-day field monitoring. Propiconazole demonstrated a low acute toxicity (96 h-LC50 > 100 mg/L) to E. sinensis and exhibited no obvious adverse impact on the growth of E. sinensis after exposure to 500 μg/L, which was 10 times the actual residual concentration of propiconazole in the crab–rice co-culture field. The highest bioaccumulation of propiconazole was obtained from gills, followed by the hepatopancreas and meat. These results will contribute to the guidance of scientific utilization of pesticides in the crab–rice co-culture field.

Inhibition of beta-site APP cleaving enzyme1 (BACE1) is one of the most promising therapeutic approaches for Alzheimer’s disease. To find natural products for the treatment of Alzheimer's disease, absorption, distribution, metabolism, excretion and toxicity (ADMET) properties and in vitro BACE1 inhibitory activity of the peptides isolated from egg albumin were evaluated. Then, molecular docking and molecular dynamics simulation were used to explain the molecular mechanism of the interactions between BACE1 and peptides. The IC50 value of peptide KLPGF, with satisfactory ADMET properties, against BACE1 was (8.30 ± 0.56) mmol/L. Molecular docking revealed that KLPGF contacted with the residues of BACE1’s active sites through twelve hydrogen bonds interactions, two hydrophobic interactions, one electrostatic interaction, and two Pi-cation interactions. The 5 ns molecular dynamics simulations confirmed that the structure of KLPGF with BACE1 was stable. Peptide KLPGF contacted the residues Lys321, Asp228, and Asn233 with stable hydrogen bonds. KLPGF may be a potential anti-BACE1 candidate.

Mild cognitive impairment (MCI) is a transition between normal cognition (NC) and Alzheimer’s disease (AD). Differences in cortical thickness (ΔCT) have been reported in cases that degenerate from MCI to AD. The aspects of genetic and transcriptional variation related to ΔCT are vague. In this study, using an 8-year longitudinal follow-up outcome, we investigated the genetic correlates of ΔCT in MCI subjects with degeneration from MCI to AD (MCI_AD). We employed partial least squares regression (PLSR) on brain T1-weighted magnetic resonance imaging (MRI) images of 180 participants [143 stable MCI (MCI_S) participants and 37 MCI_AD participants] and brain gene expression data from the Allen Institute for Brain Science (AIBS) database to investigate genes associated with ΔCT. We found that upregulated PLS component 1 ΔCT-related genes were enriched in chemical synaptic transmission. To verify the robustness and specificity of the results, we conducted PLSR analysis invalidation and specificity datasets and performed weighted gene co-expression network analysis instead of PLSR for the above three datasets. We also used gene expression data in the brain prefrontal cortex from the Gene Expression Omnibus (GEO) database to indirectly validate the robustness and specificity of our results. We conclude that transcriptionally upregulated genes involved in chemical synaptic transmission are strongly related to global ΔCT in MCI patients who experience degeneration from MCI to AD.

Compared with individual events, compound weather and climate extremes may impose more serious influences on natural systems and human society, especially in populated areas. In this study, we examine the changes in the compound precipitation events that follow extremely hot weather within several days during 1961–2017 in South China by taking the Guangdong Province as an example. Additionally, we assess the impacts of urbanization on these changes. It is found that extreme precipitation events in Guangdong are often preceded by hot weather, with an average fraction of 28.25%. The fraction of such compound events is even larger in more populated and urbanized areas such as the Pearl River Delta (PRD) region. Moreover, our results reveal significant increases in the frequency and fraction of the compound extreme heat and precipitation events. These increases are especially stronger in more developed areas (e.g., PRD), and their increasing trends tend to accelerate in recent decades. Furthermore, the local urbanization contributes to 40.91 and 49.38% of the increases in the frequency and fraction of the compound events, respectively. Our findings provide scientific references for policy-makers and urban planners to mitigate the influences of the compound heat and precipitation extremes by considering their increasing risks under the context of global climate change and local urbanization.

The shikimate pathway is a necessary pathway for the synthesis of aromatic compounds. The intermediate products of the shikimate pathway and its branching pathway have promising properties in many fields, especially in the pharmaceutical industry. Many important compounds, such as shikimic acid, quinic acid, chlorogenic acid, gallic acid, pyrogallol, catechol and so on, can be synthesized by the shikimate pathway. Among them, shikimic acid is the key raw material for the synthesis of GS4104 (Tamiflu®), an inhibitor of neuraminidase against avian influenza virus. Quininic acid is an important intermediate for synthesis of a variety of raw chemical materials and drugs. Gallic acid and catechol receive widespread attention as pharmaceutical intermediates. It is one of the hotspots to accumulate many kinds of target products by rationally modifying the shikimate pathway and its branches in recombinant strains by means of metabolic engineering. This review considers the effects of classical metabolic engineering methods, such as central carbon metabolism (CCM) pathway modification, key enzyme gene modification, blocking the downstream pathway on the shikimate pathway, as well as several expansion pathways and metabolic engineering strategies of the shikimate pathway, and expounds the synthetic biology in recent years in the application of the shikimate pathway and the future development direction.

Marine collagen is an ideal material for tissue engineering due to its excellent biological properties. However, the limited mechanical properties and poor stability of marine collagen limit its application in tissue engineering. Here, collagen was extracted from the skin of tilapia (Oreochromis nilotica). Collagen-thermoplastic polyurethane (Col-TPU) fibrous membranes were prepared using tilapia collagen as a foundational material, and their physicochemical and biocompatibility were investigated. Fourier transform infrared spectroscopy results showed that thermoplastic polyurethane was successfully combined with collagen, and the triple helix structure of collagen was retained. X-ray diffraction and differential scanning calorimetry results showed relatively good compatibility between collagen and TPU.SEM results showed that the average diameter of the composite nanofiber membrane decreased with increasing thermoplastic polyurethane proportion. The mechanical evaluation and thermogravimetric analysis showed that the thermal stability and tensile properties of Col-TPU fibrous membranes were significantly improved with increasing TPU. Cytotoxicity experiments confirmed that fibrous membranes with different ratios of thermoplastic polyurethane content showed no significant toxicity to fibroblasts; Col-TPU fibrous membranes were conducive to the migration and adhesion of cells. Thus, these Col-TPU composite nanofiber membranes might be used as a potential biomaterial in tissue regeneration.

Salvia miltiorrhiza Bunge is a common Chinese herbal medicine, and its major active ingredients are phenolic acids and tanshinones, which are widely used to treat vascular diseases. However, the wild form of S. miltiorrhiza possess low levels of these important pharmaceutical agents; thus, improving their levels is an active area of research. Transcription factors, which promote or inhibit the expressions of multiple genes involved in one or more biosynthetic pathways, are powerful tools for controlling gene expression in biosynthesis. Several families of transcription factors have been reported to participate in regulating phenolic acid and tanshinone biosynthesis and influence their accumulation. This review summarizes the current status in this field, with focus on the transcription factors which have been identified in recent years and their functions in the biosynthetic regulation of phenolic acids and tanshinones. Otherwise, the new insight for further research is provided. Finally, the application of the biosynthetic regulation of active ingredients by the transcription factors in S. miltiorrhiza are discussed, and new insights for future research are explored.

PurposeTriple-negative breast cancer (TNBC) is a type of breast cancer (BC) showing a high recurrence ratio and a low survival probability, which requires novel actionable molecular targets. The involvement of alternative splicing (AS) in TNBC promoted us to study the potential roles of AS events in the survival prognosis of TNBC patients.MethodsA total of 150 TNBC patients from The Cancer Genome Atlas (TCGA) were involved in this work. To study the effects of AS in the recurrence-free survival (RFS) prognosis of TNBC, we performed the analyses as follows. First, univariate Cox regression model was applied to identify RFS-related AS events. Their host genes were analyzed by Metascape to discover the potential functions and involved pathways. Next, least absolute shrinkage and selection operator (LASSO) method was used to select the most informative RFS-related AS events to constitute an AS risk factor for RFS prognosis, which was evaluated by Kaplan–Meier (KM) and receiver operating characteristic (ROC) curves in all the data and also in different clinical subgroups. Furthermore, we analyzed the relationships between splicing factors (SFs) and these RFS-related AS events to seek the possibility that SFs regulated AS events to influence RFS. Then, we evaluated the potential of these RFS-related AS events in the overall survival (OS) prognosis from all the above aspects.ResultsWe identified a total of 546 RFS-related AS events, which were enriched in some splicing and TNBC-associated pathways. Among them, seven RFS-related events were integrated into a risk factor, exhibiting satisfactory RFS prognosis alone and even better performance when combined with clinical tumor–node–metastasis stages. Furthermore, the correlation analysis between SFs and the seven AS events revealed the hypotheses that SRPK3 might upregulate PCYT2_44231_AA to have an effect on RFS prognosis and that three other SFs may work together to downregulate FLAD1_7874_RI to influence RFS prognosis. In addition, the seven RFS-related AS events were validated to be promising in the OS prognosis of TNBC as well.ConclusionThe abnormal AS events regulated by SFs may act as a kind of biomarker for the survival prognosis of TNBC.

Background Non-alcoholic steatohepatitis (NASH) is a progressive liver disease characterized by hepatic steatosis, lobular inflammation and fibrosis. Acetyl-CoA carboxylase (ACC) isoform 1 and 2 involved in de novo lipogenesis (DNL) and fatty acid oxidation have been identified as a therapeutic target in NASH. GS-0976, the inhibitor of ACC1 and ACC2, has achieved favorable therapeutic effects in clinical trials with NASH. The purpose of this study was to explore the transcriptional alterations regulated by GS-0976 in NASH. Methods C57BL/6 mice were fed on a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) or normal diet for 12 weeks. Mice were treated with or without GS-0976 (3 mg/kg per day) in the last 8 weeks. Oil Red O, Haematoxylin-eosin (H & E), and Sirius Red were used to evaluate hepatic steatosis, inflammation and fibrosis. The comparative RNA-sequencing was conducted to analyse the hepatic gene expression profiles in mice. Reverse transcription–polymerase chain reaction analysis was performed to validate the differential expression of representative genes. Results GS-0976 attenuated the steatosis, inflammation, and fibrosis of NASH in CDAHFD mouse model. High-throughput sequencing and differential gene expression analysis showed that there were 516 up-regulated genes and 525 down-regulated genes after GS-0976 treatment. Genes involved in the metabolic process, extracellular matrix formation, immune response, and angiogenesis were significantly enriched. The “Metabolic pathways” and “ECM-receptor interaction” pathways were the most significantly enriched KEGG pathways in the up-regulated and down-regulated differentially expressed genes (DEGs), respectively. Conclusions Transcriptome analysis showed that GS-0976 could regulate the expression of genes related to metabolism, inflammation and fibrosis in NASH. The global transcriptomic changes in gene expression promote the further understanding for the inhibition mechanisms of GS-0976 in NASH.

Abstract Background The challenges posed by Mycobacterium tuberculosis infection require the gradual removal of the pool of latent tuberculosis infection (LTBI). The current cell-immune-based diagnostic tests used to identify LTBI individuals have several irreversible drawbacks. In the present study, we attempted to identify novel diagnostic antigens for LTBI. Methods A high-throughput glutathione S-transferase (GST)-fusion technology was used to express over 409 TB proteins and sera from LTBI and healthy individuals was used to interrogate these GST-TB fusion proteins. Results Of 409 TB proteins, sixty-three reacted seropositive and defined the immuno-ORFeome of latent M. tuberculosis. Within the immuno-ORFeome, the rare targets were predominantly latency-associated proteins and secreted proteins, while the preferentially recognized antigens tended to be transmembrane proteins. Six of novel highly-reactive antigens had the potential to distinguish LTBI from active TB and healthy individuals. A multiple-antigen combination set was selected through analysis of various combinations. A panel of 94 archived serum samples was used to validate the diagnostic performance of the multiple-antigen combination set, which had sensitivity of 66.1% (95% CI 52.9, 77.4) and specificity of 87.5% (95% CI 70.1, 95.1). Conclusion These results provide experimental evidence of the immunogenicity of novel TB proteins that are suitable for the development of serodiagnostic tools for LTBI.

We have previously reported that Trichoderma atroviride, an endophytic fungus isolated from S. miltiorrhiza, promotes S. miltiorrhiza hairy root growth and significantly stimulates the biosynthesis of tanshinones specifically the polysaccharide fraction (PSF). However, this study only focused exclusively on six metabolites whilst ignoring changes to the whole metabolite composition of the S. miltiorrhiza hairy roots. In the present study, the dynamic metabonomic responses of S. miltiorrhiza hairy roots were investigated using ultra-high-performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMSn). UHPLC-HRMS typical total ions chromatograms (TICs) of PSF-treated hairy root samples were different from the control. Moreover, the results of principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA) and hierarchical clustering analysis (HCA) indicated that PSF-treated samples were significantly different from the control. Through the analysis of PLS-DA, a total of 114 and 99 differential metabolites were found from the positive and negative models respectively and a total of 33 differential metabolites were identified. Thus, S. miltiorrhiza hairy roots had been induced to regulate the metabolic profiling in response to PSF and the changes of the metabolic profiling contributed to promoting the biosynthesis of tanshinones notably whilst the biosynthesis of phenolic acids were slightly inhibited.

Collagen is widely used in the pharmaceutical, tissue engineering, nutraceutical, and cosmetic industries. In this study, acid-soluble collagen (ASC) and pepsin-soluble collagen (PSC) were extracted from the skin of red stingray, and its physicochemical and functional properties were investigated. The yields of ASC and PSC were 33.95 ± 0.7% and 37.18 ± 0.71% (on a dry weight basis), respectively. ASC and PSC were identified as type I collagen by Sodium Dodecyl Sulfate Polyacrylamide Gel Electrophoresis (SDS-PAGE) analysis, possessing a complete triple helix structure as determined by UV absorption, Fourier transform infrared, circular dichroism, and X-ray diffraction spectroscopy. Contact angle experiments indicated that PSC was more hydrophobic than ASC. Thermal stability tests revealed that the melting temperature of PSC from red stingray skin was higher than that of PSC from duck skin, and the difference in the melting temperature between these two PSCs was 9.24 °C. Additionally, both ASC and PSC were functionally superior to some other proteins from terrestrial sources, such as scallop gonad protein, whey protein, and goose liver protein. These results suggest that PSC from red stingray skin could be used instead of terrestrial animal collagen in drugs, foods, cosmetics, and biological functional materials, and as scaffolds for bone regeneration.

Serology-based tests for tuberculosis (TB) diagnosis, though rapid, efficient and easily implemented, have so far shown unsatisfactory levels of sensitivity and specificity, probably due to variations of the antibody response in TB patients. The number and types of seropositive antigens vary from individual to individual. The person-to-person variations of antigen recognition may be linked to genetic polymorphisms of the human leukocyte antigen (HLA) class II alleles. In the present study, we find that there is a significant increase in the frequency of HLA-DRB1*14 (P = 2.5×10-4) among subjects with high antibody response levels compared to those with low antibody levels. HLA-DRB1*15, the most frequent allelic group in the studied active TB population, positively correlates with subjects with low antibody response levels rather than subjects with high antibody response levels (P = 0.005), which indicates the loss of relevant antigens for screening of patients with this allelic group. The potential association between HLA-DRB1 allelic group and individual antigens implies that TB diagnostic yield could be improved by the addition of antigens screened at the proteome scale in infected subjects from the HLA-DRB1*15 allelic group.

[This corrects the article DOI: 10.1371/journal.pone.0161913.].

RNase H (RNH) is a pivotal domain in retrovirus to cleave the DNA-RNA hybrid for continuing retroviral replication. The crucial role indicates that RNH is a promising drug target for therapeutic intervention. However, annotated RNHs in UniProtKB database have still been insufficient for a good understanding of their statistical characteristics so far. In this work, a computational RNH model was proposed to annotate new putative RNHs (np-RNHs) in the retroviruses. It basically predicts RNH domains through recognizing their start and end sites separately with SVM method. The classification accuracy rates are 100%, 99.01% and 97.52% respectively corresponding to jack-knife, 10-fold cross-validation and 5-fold cross-validation test. Subsequently, this model discovered 14,033 np-RNHs after scanning sequences without RNH annotations. All these predicted np-RNHs and annotated RNHs were employed to analyze the length, hydrophobicity and evolutionary relationship of RNH domains. They are all related to retroviral genera, which validates the classification of retroviruses to a certain degree. In the end, a software tool was designed for the application of our prediction model. The software together with datasets involved in this paper can be available for free download at https://sourceforge.net/projects/rhtool/files/?source=navbar.