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This study aimed to investigate the association between sanitary toilets and health poverty vulnerability among rural western Chinese adults aged 45 years and older. Using data from the 'Rural Household Health Inquiry Survey' conducted in 2022, a three-stage feasible generalized least squares method was employed to calculate health poverty vulnerability. Propensity score matching (PSM) and mediation effect analysis were used to assess the association between sanitary toilets and health poverty vulnerability among rural western Chinese adults aged 45 years and older and the mechanisms underlying this impact. This study revealed that the use of sanitary toilets was significantly associated with decreased health poverty vulnerability in adults over 45 years of age. Heterogeneity analysis revealed that this effect was more pronounced among males (β = -0.0375, P

IntroductionPostoperative cognitive dysfunction (POCD) is a common complication following surgery. Electroacupuncture (EA), manual acupuncture (MA), transcutaneous electrical acupoint stimulation (TEAS), and cognitive training (CT) can effectively maintain or improve the postoperative cognitive function of patients. However, it remains unclear which therapy is the most effective. Therefore, this network meta-analysis aims to compare and rank the efficacy of these non-pharmacological therapies for POCD to identify the optimal therapy.Methods and analysisA systematic search will be conducted across seven databases (PubMed, Cochrane Library, EMBASE, Web of Science, CINAHL, AMED, and PsycINFO) for articles published between January 2000 and November 2023. Two reviewers will independently conduct study selection and data extraction. The primary outcome will be the changes in the overall cognitive function before and after the intervention. The secondary outcome will be the incidence of POCD. The risk of bias will be assessed using the revised Risk of Bias Assessment Tool. Pairwise and Bayesian network meta-analyses will be performed using RevMan, STATA, and Aggregate Data Drug Information System statistical software. Additionally, the quality of evidence will be assessed using the Grading of Recommendations Assessment, Development, and Evaluation guidelines. Ethics and dissemination: The results will be disseminated to peer-reviewed journals or conferences.Trial registrationPROSPERO registration number: CRD42023454028.

In the task of emotion inference, a common issue is the lack of common sense knowledge, particularly in the context of dialogue, where traditional research has failed to effectively extract structural features, resulting in lower accuracy in emotion inference. To address this, this paper proposes a dialogue emotion inference model based on Common Sense Enhancement and Graph Model (CEICG). This model integrates external common sense with graph model techniques by dynamically constructing nodes and defining diverse edge relations to simulate the evolution of dialogue, thereby effectively capturing the structural and semantic features of the conversation. The model employs two methods to incorporate external common sense into the graph model, overcoming the limitations of previous models in understanding complex dialogue structures and the absence of external knowledge. This strategy of integrating external common sense significantly enhances the model's emotion inference capabilities, improving the understanding of emotions in dialogue. Experimental results demonstrate that the CEICG model outperforms six existing baseline models in emotion inference tasks across three datasets.

Currently, depression is the predominant mental illness impacting adolescents, causing severe damage to their overall health. Engaging in physical exercise can not only aid in restoring adolescent physical well-being but also function as a strategy to prevent depression and lower suicide rates. Drawing upon data from the China Education Panel Survey (CEPS) conducted between 2014 and 2015, this study delves into the effects of physical exercise on alleviating depressive symptoms among adolescent students and explores the underlying mechanisms through the lens of parent-child interactions and peer relationships. The mediation effect tests indicate that physical exercise can mitigate adolescent depression by reinforcing parent-child bonds and improving peer connections. Parents and educational institutions should judiciously plan the time for adolescents to engage in both academic pursuits and physical activities, and they should encourage greater participation in sports among adolescents through various means, thereby maximizing the beneficial role of physical exercise in ameliorating adolescent depression.

Septic Cardiomyopathy (SCM) is a syndrome of acute cardiac dysfunction in septic patients, unrelated to cardiac ischemia. Multiomics studies including transcriptomics and proteomics have provided new insights into the mechanisms of SCM. In here, a rat model of SCM was established by intraperitoneal injection of lipopolysaccharide (LPS). Biomarkers of SCM were characterized via a multi-omics analysis. The differentially expressed (DE) mRNAs predominantly appeared in pathways linked to the immune response, inflammatory response, and the complement and coagulation cascades, while DE proteins were mainly enriched in pathways associated with the complement and coagulation cascades. On this basis, the integrated analysis was performed between transcriptome and proteome. The potential biomarkers were further verified by RT-qPCR and WB. The current proteotranscriptomic research has furnished a valuable dataset and fresh perspectives that will enhance our comprehension of the development of SCM. This, in turn, is expected to expedite the formulation of novel approaches for the prevention and management of SCM in patients.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes Coronavirus Disease 2019 (COVID-19), which can result in severe disease, often characterised by a 'cytokine storm' and the associated acute respiratory distress syndrome. However, many infections with SARS-CoV-2 are mild or asymptomatic throughout the course of infection. Although blood biomarkers of severe disease are well studied, less well understood are the inflammatory signatures in lung tissues associated with mild disease or silent infections, wherein infection and inflammation are rapidly resolved leading to sequelae-free recovery. Herein we described RNA-Seq and histological analyses of lungs over time in an omicron BA.1/K18-hACE2 mouse infection model, which displays these latter features. Although robust infection was evident at 2 days post infection (dpi), viral RNA was largely cleared by 10 dpi. Acute inflammatory signatures showed a slightly different pattern of cytokine signatures compared with severe infection models, and where much diminished 30 dpi and absent by 66 dpi. Cellular deconvolution identified significantly increased abundance scores for a number of anti-inflammatory pro-resolution cell types at 5/10 dpi. These included type II innate lymphoid cells, T regulatory cells, and interstitial macrophages. Genes whose expression trended downwards over 2-66 dpi included biomarkers of severe disease and were associated with 'cytokine storm' pathways. Genes whose expression trended upward during this period were associated with recovery of ciliated cells, AT2 to AT1 transition, reticular fibroblasts and innate lymphoid cells, indicating a return to homeostasis. Very few differentially expressed host genes were identified at 66 dpi, suggesting near complete recovery. The parallels between mild or subclinical infections in humans and those observed in this BA.1/K18-hACE2 mouse model are discussed with reference to the concept of "protective inflammation".

There is different administration routes of triamcinolone acetonide (TA) administration for macular edema, but the efficacy ranking remains unclear. The purpose of this study is to assess the efficacy of different administration routes of TA employed in macular edema. PubMed, Medline, Embase, and Cochrane Central Register of Controlled Trials were systematically searched for published articles comparing macular edema in patients with triamcinolone acetonide in different administration. The sparse network was evaluated using a random-effects model and consistency model within the Bayesian framework, utilizing the multinma package in R. The evidence was assessed based on the Grading of Recommendations. Assessment, Development, and Evaluation (GRADE) criteria. A total of 1138 citations were identified by our search, of which 20 RCTs enrolled 892 eyes. The network showed that intravitreal triamcinolone acetonide (IVTA) was associated with a statistically significant better best corrected visual acuity (BCVA) at the 12th week compared to placebo (MD: − 0.15, 95% CI: − 0.30 to − 0.01, P < 0.05), which was moderate-quality evidence. IVTA and suprachoroidal triamcinolone acetonide (SCTA) were both associated with a statistically significant reduction in central macular thickness (CMT) at the 12th week, which was moderate evidence. The probabilities of rankings and SUCRA demonstrated that sub-Tenon's infusion of triamcinolone acetonide (STiTA) might be the worst. SCTA and IVTA were proven to be the best administration routes for improving BCVA and reducing CMT. In addition, STiTA was less advisable than other administration routes of triamcinolone acetonide according to the rankings and SUCRA. [ABSTRACT FROM AUTHOR]

Introduction: Postoperative cognitive dysfunction (POCD) is a common complication following surgery. Electroacupuncture (EA), manual acupuncture (MA), transcutaneous electrical acupoint stimulation (TEAS), and cognitive training (CT) can effectively maintain or improve the postoperative cognitive function of patients. However, it remains unclear which therapy is the most effective. Therefore, this network meta-analysis aims to compare and rank the efficacy of these non-pharmacological therapies for POCD to identify the optimal therapy. Methods and analysis: A systematic search will be conducted across seven databases (PubMed, Cochrane Library, EMBASE, Web of Science, CINAHL, AMED, and PsycINFO) for articles published between January 2000 and November 2023. Two reviewers will independently conduct study selection and data extraction. The primary outcome will be the changes in the overall cognitive function before and after the intervention. The secondary outcome will be the incidence of POCD. The risk of bias will be assessed using the revised Risk of Bias Assessment Tool. Pairwise and Bayesian network meta-analyses will be performed using RevMan, STATA, and Aggregate Data Drug Information System statistical software. Additionally, the quality of evidence will be assessed using the Grading of Recommendations Assessment, Development, and Evaluation guidelines. Ethics and dissemination: The results will be disseminated to peer-reviewed journals or conferences. Trial registration: PROSPERO registration number: CRD42023454028. [ABSTRACT FROM AUTHOR]

In the task of emotion inference, a common issue is the lack of common sense knowledge, particularly in the context of dialogue, where traditional research has failed to effectively extract structural features, resulting in lower accuracy in emotion inference. To address this, this paper proposes a dialogue emotion inference model based on Common Sense Enhancement and Graph Model (CEICG). This model integrates external common sense with graph model techniques by dynamically constructing nodes and defining diverse edge relations to simulate the evolution of dialogue, thereby effectively capturing the structural and semantic features of the conversation. The model employs two methods to incorporate external common sense into the graph model, overcoming the limitations of previous models in understanding complex dialogue structures and the absence of external knowledge. This strategy of integrating external common sense significantly enhances the model's emotion inference capabilities, improving the understanding of emotions in dialogue. Experimental results demonstrate that the CEICG model outperforms six existing baseline models in emotion inference tasks across three datasets. [ABSTRACT FROM AUTHOR]

Currently, depression is the predominant mental illness impacting adolescents, causing severe damage to their overall health. Engaging in physical exercise can not only aid in restoring adolescent physical well-being but also function as a strategy to prevent depression and lower suicide rates. Drawing upon data from the China Education Panel Survey (CEPS) conducted between 2014 and 2015, this study delves into the effects of physical exercise on alleviating depressive symptoms among adolescent students and explores the underlying mechanisms through the lens of parent-child interactions and peer relationships. The mediation effect tests indicate that physical exercise can mitigate adolescent depression by reinforcing parent-child bonds and improving peer connections. Parents and educational institutions should judiciously plan the time for adolescents to engage in both academic pursuits and physical activities, and they should encourage greater participation in sports among adolescents through various means, thereby maximizing the beneficial role of physical exercise in ameliorating adolescent depression. [ABSTRACT FROM AUTHOR]

Septic Cardiomyopathy (SCM) is a syndrome of acute cardiac dysfunction in septic patients, unrelated to cardiac ischemia. Multiomics studies including transcriptomics and proteomics have provided new insights into the mechanisms of SCM. In here, a rat model of SCM was established by intraperitoneal injection of lipopolysaccharide (LPS). Biomarkers of SCM were characterized via a multi-omics analysis. The differentially expressed (DE) mRNAs predominantly appeared in pathways linked to the immune response, inflammatory response, and the complement and coagulation cascades, while DE proteins were mainly enriched in pathways associated with the complement and coagulation cascades. On this basis, the integrated analysis was performed between transcriptome and proteome. The potential biomarkers were further verified by RT-qPCR and WB. The current proteotranscriptomic research has furnished a valuable dataset and fresh perspectives that will enhance our comprehension of the development of SCM. This, in turn, is expected to expedite the formulation of novel approaches for the prevention and management of SCM in patients. [ABSTRACT FROM AUTHOR]

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes Coronavirus Disease 2019 (COVID-19), which can result in severe disease, often characterised by a 'cytokine storm' and the associated acute respiratory distress syndrome. However, many infections with SARS-CoV-2 are mild or asymptomatic throughout the course of infection. Although blood biomarkers of severe disease are well studied, less well understood are the inflammatory signatures in lung tissues associated with mild disease or silent infections, wherein infection and inflammation are rapidly resolved leading to sequelae-free recovery. Herein we described RNA-Seq and histological analyses of lungs over time in an omicron BA.1/K18-hACE2 mouse infection model, which displays these latter features. Although robust infection was evident at 2 days post infection (dpi), viral RNA was largely cleared by 10 dpi. Acute inflammatory signatures showed a slightly different pattern of cytokine signatures compared with severe infection models, and where much diminished 30 dpi and absent by 66 dpi. Cellular deconvolution identified significantly increased abundance scores for a number of anti-inflammatory pro-resolution cell types at 5/10 dpi. These included type II innate lymphoid cells, T regulatory cells, and interstitial macrophages. Genes whose expression trended downwards over 2–66 dpi included biomarkers of severe disease and were associated with 'cytokine storm' pathways. Genes whose expression trended upward during this period were associated with recovery of ciliated cells, AT2 to AT1 transition, reticular fibroblasts and innate lymphoid cells, indicating a return to homeostasis. Very few differentially expressed host genes were identified at 66 dpi, suggesting near complete recovery. The parallels between mild or subclinical infections in humans and those observed in this BA.1/K18-hACE2 mouse model are discussed with reference to the concept of "protective inflammation". [ABSTRACT FROM AUTHOR]

This study aimed to investigate the association between sanitary toilets and health poverty vulnerability among rural western Chinese adults aged 45 years and older. Using data from the 'Rural Household Health Inquiry Survey' conducted in 2022, a three-stage feasible generalized least squares method was employed to calculate health poverty vulnerability. Propensity score matching (PSM) and mediation effect analysis were used to assess the association between sanitary toilets and health poverty vulnerability among rural western Chinese adults aged 45 years and older and the mechanisms underlying this impact. This study revealed that the use of sanitary toilets was significantly associated with decreased health poverty vulnerability in adults over 45 years of age. Heterogeneity analysis revealed that this effect was more pronounced among males (β = -0.0375, P<0.05), those aged 60–74 years (β = -0.0476, P<0.05), and households with middle income (β = -0.0590, P<0.01). Mediation effect analysis identified total household income (a×b = -0.0233, P<0.05), household size (a×b = -0.0181, P<0.01), number of household laborers (a×b = -0.0107, P<0.01), and registered poor households (a×b = -0.0081, P<0.01) as the mediating factors between sanitary toilets and health poverty vulnerability. The provision of sanitary toilets has been instrumental in mitigating health-related poverty among middle-aged and elderly people residing in rural areas. By improving household livelihood capital, the vulnerability of these individuals to health-related poverty can be significantly reduced. [ABSTRACT FROM AUTHOR]

In the mining process of working face, the additional stress generated by the fault changes the law of roadway deformation and failure as well as the law of overburden failure. Aiming at the influence of the fault in the mining process of working face, this study introduced the geological strength index (GSI) to analyze the stress distribution in the elastic-plastic zone of the surrounding rock of the roadway. And similar experiments under different engineering backgrounds were combined to study the characteristics of overburden movement and stress evolution. Based on the conclusions obtained, the roadway support scheme was designed. This study shows that, compared with ordinary mining, through-the-fault mining causes slippage and dislocation of the fault, the load of the overburden is transferred to both sides of the fault, and the stress near the fault accumulates abnormally. The "three zones" characteristics of the overburden movement disappear, the subsidence pattern is changed from "trapezoid" to "inverted triangle", and the influence distance of the advanced mining stress on the working face is extended from 20m to 30m. The instability range of roadway surrounding rock is exponentially correlated with the rupture degree of the surrounding rock. Through the introduction of GSI, the critical instability range of roadway surrounding rock is deduced to be 2.32m. According to the conclusion, the bolt length and roadway reinforced support length are redesigned. Engineering application shows that the deformation rate of the roadway within 60 days is controlled below 0.1~0.5mm/d, the deformation amount is controlled within 150mm, and the roadway deformation is controlled, which generally meets the requirements of use. The research results provide guidance and reference for similar roadway support.

Recent research suggests that syntactic priming in language comprehension—the facilitated processing of repeated syntactic structures—arises from the expectation for syntactic repetition due to rational adaptation to the linguistic environment. To further evaluate the generalizability of this expectation adaptation account in cross-linguistic syntactic priming and explore the influence of second language (L2) proficiency, we conducted a self-paced reading study with Chinese L2 learners of English by utilizing the sentential complement-direct object (SC-DO) ambiguity. The results showed that participants exposed to clusters of SC structures subsequently processed repetitions of this structure more rapidly (i.e., larger priming effects) than those exposed to the same number of SC structures but spaced in time, despite the prime and target being in two different languages (Chinese and English). Furthermore, this difference in priming strength was more pronounced for participants with higher L2 (English) proficiency. These findings demonstrate that cross-linguistic syntactic priming is consistent with the expectation for syntactic repetition that rationally adapts to syntactic clustering properties in surrounding bilingual environments, and such adaptation is enhanced as L2 proficiency increases. Taken together, our study extends the expectation adaptation account to cross-linguistic syntactic priming and integrates the role of L2 proficiency, which can shed new light on the mechanisms underlying syntactic priming, bilingual shared syntactic representations and expectation-based sentence processing. [ABSTRACT FROM AUTHOR]

Clearing out zombie firms is a critical challenge for both developed and developing countries. This article draws upon data from Chinese listed SOEs to examine the impact of mixed-ownership reform on zombie firms. The findings indicate that non-state-owned shareholders participating in mixed-ownership reform by appointing directors can help reduce the possibility of SOEs becoming zombie firms, while participating in mixed-ownership reform through shareholding is not significant. Moreover, the impact of mixed-ownership reform on zombie firms is more pronounced for firms in competitive industries and firms located in the eastern region of China. Mechanism analysis reveals that the reduction of inefficient investment has a positive mediating effect between mixed-ownership reform and zombie firms. [ABSTRACT FROM AUTHOR]

The fall armyworm (Spodoptera frugiperda) is a major economic pest in the United States and has recently become a significant concern in African and Asian countries. Due to its increased resistance to current management strategies, including pesticides and transgenic corn, alternative management techniques have become more necessary. Currently, silicon (Si) is being used in many pest control systems due to its ability to increase plant resistance to biotic and abiotic factors and promote plant growth. The current experiments were carried out at the College of Plant Protection, Gansu Agricultural University, Lanzhou, China, to test the effect of Si on lifetable parameters and lipase activity of fall armyworm and vegetative and physiological parameters of maize plants. Two sources of Si (silicon dioxide: SiO2 and potassium silicate: K2SiO3) were applied on maize plants with two application methods (foliar application and soil drenching). The experiment results revealed that foliar applications of SiO2 and K2SiO3 significantly (P≤0.05) increased mortality percentage and developmental period and decreased larval and pupal biomass of fall armyworm. Similarly, both Si sources significantly (P≤0.05) reduced lipase activity of larvae, and fecundity of adults, whereas prolonged longevity of adults. Among plant parameters, a significant increase in fresh and dry weight of shoot, stem length, chlorophyll content, and antioxidant activity was observed with foliar applications of Si. Root fresh and dry weight was significantly (P ≤ 0.05) higher in plants treated with soil drenching of SiO2 and K2SiO3. Moreover, SiO2 performed better for all parameters as compared to K2SiO3 and control treatment. The study conclusively demonstrated a significant negative effect on various biological parameters of fall armyworm when plants were treated with Si, so it can be a promising strategy to control this pest.

Cadmium (Cd) is a toxic non-essential element, while calcium (Ca) is an essential element with high chemical similarity to Cd. Dietary intake is the major Cd exposure pathway for non-smokers. A multi-concentration dietary intervention experiment was designed to explore the optimum concentration of Ca in diet with obvious protective effects against the toxicity of livers and kidneys induced by Cd in mice. The mice were divided into six groups with different concentrations of Cd and Ca in their food: control-group (no Cd or Ca), Ca-group (100 g/kg Ca, without Cd), Cd-group (2 mg/kg Cd, without Ca), CaL+Cd-group (2 mg/kg Cd, 2 g/kg Ca), CaM+Cd-group (2 mg/kg Cd, 20 g/kg Ca) and CaH+Cd-group (2 mg/kg Cd, 100 g/kg Ca). The organ indexes, oxidative stress biomarkers, lesions and Cd concentrations were detected after a 30-day exposure period. Results showed that serum Aspartate Aminotransferase (AST) level in CaH+Cd-group was significantly lower than that in Cd-group, while close to that in control-group. The contents of Serum Blood Urea Nitrogen (BUN) in different groups showed the same trend. Concentrations of all oxidative stress biomarkers (GSH-Px, SOD, CAT, GSH and MDA) in CaH+Cd-group were close to the normal levels of control-group while significantly different from those in Cd-group. The only exception was the Malondialdehyde (MDA) levels in kidneys. This study suggests that Ca plays a protective role in relieving the Cd-induced toxicity of livers and kidneys and a concentration of 100 g/kg for Ca in diet showed the best protective effects. These findings could provide a clue for further studies concerning human diet intervention for Cd control.

BackgroundAmong patients with acute respiratory failure requiring prolonged mechanical ventilation, tracheostomies are typically placed after approximately 7 to 10 days. Yet half of patients admitted to the intensive care unit receiving tracheostomy will die within a year, often within three months. Existing mortality prediction models for prolonged mechanical ventilation, such as the ProVent Score, have poor sensitivity and are not applied until after 14 days of mechanical ventilation. We developed a model to predict 3-month mortality in patients requiring more than 7 days of mechanical ventilation using deep learning techniques and compared this to existing mortality models.MethodsRetrospective cohort study. Setting: The Medical Information Mart for Intensive Care III Database. Patients: All adults requiring ≥ 7 days of mechanical ventilation. Measurements: A neural network model for 3-month mortality was created using process-of-care variables, including demographic, physiologic and clinical data. The area under the receiver operator curve (AUROC) was compared to the ProVent model at predicting 3 and 12-month mortality. Shapley values were used to identify the variables with the greatest contributions to the model.ResultsThere were 4,334 encounters divided into a development cohort (n = 3467) and a testing cohort (n = 867). The final deep learning model included 250 variables and had an AUROC of 0.74 for predicting 3-month mortality at day 7 of mechanical ventilation versus 0.59 for the ProVent model. Older age and elevated Simplified Acute Physiology Score II (SAPS II) Score on intensive care unit admission had the largest contribution to predicting mortality.DiscussionWe developed a deep learning prediction model for 3-month mortality among patients requiring ≥ 7 days of mechanical ventilation using a neural network approach utilizing readily available clinical variables. The model outperforms the ProVent model for predicting mortality among patients requiring ≥ 7 days of mechanical ventilation. This model requires external validation.

Soybean [Glycine max (L.) Merr.] is a crop of great interest worldwide. Exploring molecular approaches to increase yield genetic gain has been one of the main challenges for soybean breeders and geneticists. Agronomic traits such as maturity, plant height, and seed weight have been found to contribute to yield. In this study, a total of 250 soybean accessions were genotyped with 10,259 high-quality SNPs postulated from genotyping by sequencing (GBS) and evaluated for grain yield, maturity, plant height, and seed weight over three years. A genome-wide association study (GWAS) was performed using a Bayesian Information and Linkage Disequilibrium Iteratively Nested Keyway (BLINK) model. Genomic selection (GS) was evaluated using a ridge regression best linear unbiased predictor (rrBLUP) model. The results revealed that 20, 31, 37, and 23 SNPs were significantly associated with maturity, plant height, seed weight, and yield, respectively; Many SNPs were mapped to previously described maturity and plant height loci (E2, E4, and Dt1) and a new plant height locus was mapped to chromosome 20. Candidate genes were found in the vicinity of the two SNPs with the highest significant levels associated with yield, maturity, plant height, seed weight, respectively. A 11.5-Mb region of chromosome 10 was associated with both yield and seed weight. Overall, the accuracy of GS was dependent on the trait, year, and population structure, and high accuracy indicates that these agronomic traits can be selected in molecular breeding through GS. The SNP markers identified in this study can be used to improve yield and agronomic traits through the marker-assisted selection and GS in breeding programs.

Background: Traditional Chinese medicine (TCM) has been garnering ever-increasing worldwide attention as the herbal extracts and formulas prove to have potency against disease. Fuzhengjiedu San (FZJDS), has been extensively used to treat viral diseases in pigs, but its bioactive components and therapeutic mechanisms remain unclear. Methods: In this study, we conducted an integrative approach of network pharmacology and experimental study to elucidate the mechanisms underlying FZJDS's action in treating porcine reproductive and respiratory syndrome virus (PRRSV). We constructed PPI network and screened the core targets according to their degree of value. GO and KEGG enrichment analyses were also carried out to identify relevant pathways. Lastly, qRT-PCR, flow cytometry and western blotting were used to determine the effects of FZJDS on core gene expression in PRRSV-infected monkey kidney (MARC-145) cells to further expand the results of network pharmacological analysis. Results: Network pharmacology data revealed that quercetin, kaempferol, and luteolin were the main active compounds of FZJDS. The phosphatidylinositol-3-kinase (PI3K)/Akt pathway was deemed the cellular target as it has been shown to participate most in PRRSV replication and other PRRSV-related functions. Analysis by qRT-PCR and western blotting demonstrated that FZJDS significantly reduced the expression of P65, JNK, TLR4, N protein, Bax and IĸBa in MARC-145 cells, and increased the expression of Bcl-2, consistent with network pharmacology results. This study provides that FZJDS has significant antiviral activity through its effects on the PI3K/AKT signaling pathway. Conclusion: We conclude that FZJDS is a promising candidate herbal formulation for treating PRRSV and deserves further investigation. [ABSTRACT FROM AUTHOR]

Inclusions containing TAR DNA binding protein 43 (TDP-43) are a pathological hallmark of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). One of the disease-specific features of TDP-43 inclusions is the aberrant phosphorylation of TDP-43 at serines 409/410 (pS409/410). Here, we developed rabbit monoclonal antibodies (mAbs) that specifically detect pS409/410-TDP-43 in multiple model systems and FTD/ALS patient samples. Specifically, we identified three mAbs (26H10, 2E9 and 23A1) from spleen B cell clones that exhibit high specificity and sensitivity to pS409/410-TDP-43 peptides in an ELISA assay. Biochemical analyses revealed that pS409/410 of recombinant TDP-43 and of exogenous 25 kDa TDP-43 C-terminal fragments in cultured HEK293T cells are detected by all three mAbs. Moreover, the mAbs detect pS409/410-positive TDP-43 inclusions in the brains of FTD/ALS patients and mouse models of TDP-43 proteinopathy by immunohistochemistry. Our findings indicate that these mAbs are a valuable resource for investigating TDP-43 pathology both in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Unregulated protein-tyrosine kinase signaling is a common feature of AML, often involving mutations in Flt3 and overexpression of myeloid Src-family kinases (Hck, Fgr, Lyn). Here we show that high-level expression of these Src kinases predicts poor survival in a large cohort of AML patients. To test the therapeutic benefit of Flt3 and Src-family kinase inhibition, we used the pyrrolopyrimidine kinase inhibitor A-419259. This compound potently inhibits Hck, Fgr, and Lyn as well as Flt3 bearing an activating internal tandem duplication (ITD). Flt3-ITD expression sensitized human TF-1 myeloid cells to growth arrest by A-419259, supporting direct action on the Flt3-ITD kinase domain. Cells transformed with the Flt3-ITD mutants D835Y and F691L were resistant to A-419259, while co-expression of Hck or Fgr restored inhibitor sensitivity to Flt3-ITD D835Y. Conversely, Hck and Fgr mutants with engineered A-419259 resistance mutations decreased sensitivity of TF-1/Flt3-ITD cells. To investigate de novo resistance mechanisms, A-419259-resistant Flt3-ITD+ AML cell populations were derived via long-term dose escalation. Whole exome sequencing identified a distinct Flt3-ITD kinase domain mutation (N676S/T) among all A-419259 target kinases in each of six independent resistant cell populations. These studies show that Hck and Fgr expression influences inhibitor sensitivity and the pathway to acquired resistance in Flt3-ITD+ AML.

Training systems generally alter tree architecture, which modulates light microclimate within the canopy, for the purpose of improving photosynthetic efficiency and fruit quality. Gene expression quantification is one of the most important methods for exploring the molecular mechanisms underlying the influence of training systems on pear photosynthesis, and suitable reference genes for gene expression normalization are a prerequisite for this method. In this study, the expression stability of nine common and four novel candidate genes were evaluated in 14 different pear leaf samples in two training systems, including those at four developmental stages (training_period) and from different parts of the trees (training_space), using two distinct algorithms, geNorm and NormFinder. Our results revealed that SKD1 (Suppressor of K+ Transport Growth Defect1)/ YLS8 (Yellow Leaf Specific 8) and ARM (Armadillo) were the most stable single reference genes for the 'training_period' and 'training_space' subsets, respectively, although these single genes were not as stable as the optimal pairs of reference genes, SKD1+YLS8 and ARM+YLS8, respectively. Furthermore, the expression levels of the PpsAPX (Ascorbate peroxidase) gene showed that the arbitrary use of reference genes without previous testing could lead to misinterpretation of data. This work constitutes the first systematic analysis regarding the selection of superior reference genes in training system studies, facilitating the elucidation of gene function in pear and providing valuable information for similar studies in other higher plants.

Hypertriglyceridaemia is one of the most common causes of severe acute pancreatitis (SAP). However, the association between elevated triglycerides (TG) level in hospital stay and outcome in SAP patients with normal TG level at admission has not been clearly demonstrated. This retrospective study assessed the serum TG levels of patients with SAP admitted to the intensive care unit (ICU) in 2017. Variables with a statistically significant association with the incidence of in-hospital TG elevation, as determined by univariate analysis, were analysed using a logistic regression model to predictors. Of the 99 patients included in the study, TG levels were within the normal range in 59 (59.59%) patients at admission. Among patients with normal TG level when admitted to ICU, 28 (47.46%) experienced at least one episode of TG level elevation during their ICU stay. Elevated TG level in hospitalization is associated with an increased length of ICU stay, as well as increased mortality. In addition to other factors, propofol usage was independently associated with the occurrence of in-hospital-TG elevation. To conclude, we retrospectively investigated the incidence, outcome, and risk factors for in-hospital TG elevation events in SAP patients admitted to the ICU. We found a high incidence of both preexisting and in-hospital-acquired TG elevation in SAP patients admitted to the ICU. The TG elevation that occurred during the ICU stay was associated with worse outcomes and long-term hospitalization of the ICU. Propofol usage was independently associated with the TG elevation occurrence in the ICU.

This study addresses the question of whether native Mandarin Chinese speakers process and comprehend subject-extracted relative clauses (SRC) more readily than object-extracted relative clauses (ORC) in Mandarin Chinese. Presently, this has been a hotly debated issue, with various studies producing contrasting results. Using two eye-tracking experiments with ambiguous and unambiguous RCs, this study shows that both ORCs and SRCs have different processing requirements depending on the locus and time course during reading. The results reveal that ORC reading was possibly facilitated by linear/temporal integration and canonicity. On the other hand, similarity-based interference made ORCs more difficult, and expectation-based processing was more prominent for unambiguous ORCs. Overall, RC processing in Mandarin should not be broken down to a single ORC (dis)advantage, but understood as multiple interdependent factors influencing whether ORCs are either more difficult or easier to parse depending on the task and context at hand.

Follicular atresia mainly results from the apoptosis of granulosa cells (GCs). Whilst our previous investigations examined the role of chi-miR-4110 in regulating ovarian function, the present study detected the role of chi-miR-4110 in GC development. We transfected caprine GCs cultured in vitro with chi-miR-4110 mimics. Results revealed that chi-miR-4110 decreased mRNA and protein levels of Smad2 by targeting its 3'-untranslated region (3'UTR). FoxC1 and Sp1 mRNA and protein levels markedly increased, whereas those of bHLHe22 significantly decreased (P

C-peptide has been reported to be a marker of subclinical atherosclerosis in type 2 diabetes mellitus (T2DM) patients, whereas its role in coronary artery disease (CAD) has not been clarified, especially in diabetics with differing body mass indices (BMIs).This cross-sectional study included 501 patients with T2DM. First, all subjects were divided into the following two groups: CAD and non-CAD. Then, binary logistic regression was used to determine the risk factors for CAD for all patients. To clarify the role of obesity, we re-divided all subjects into two additional groups (obese and non-obese) based on BMI. Finally, binary logistic regression was used to determine the risk factors for CAD for each weight group.The patients with CAD showed a higher BMI and fasting C-peptide level in addition to an increased prevalence of traditional risk factors for CAD, such as hypertension, insulin resistance, higher cholesterol, cysteine-C (Cys-C) and lower estimated glomerular filtration rate (eGFR). Logistic regression analysis showed that fasting C-peptide (OR=1.513, p=0.005), insulin treatment (OR=1.832, p=0.027) hypertension (OR=1.987, p=0.016) and hyperlipidemia (OR=4.159, p

Abdominal aortic aneurysm (AAA) is frequently lethal and has no effective pharmaceutical treatment, posing a great threat to human health. Previous bioinformatics studies of the mechanisms underlying AAA relied largely on the detection of direct protein-protein interactions (level-1 PPI) between the products of reported AAA-related genes. Thus, some proteins not suspected to be directly linked to previously reported genes of pivotal importance to AAA might have been missed. In this study, we constructed an indirect protein-protein interaction (level-2 PPI) network based on common interacting proteins encoded by known AAA-related genes and successfully predicted previously unreported AAA-related genes using this network. We used four methods to test and verify the performance of this level-2 PPI network: cross validation, human AAA mRNA chip array comparison, literature mining, and verification in a mouse CaPO4 AAA model. We confirmed that the new level-2 PPI network is superior to the original level-1 PPI network and proved that the top 100 candidate genes predicted by the level-2 PPI network shared similar GO functions and KEGG pathways compared with positive genes.

MicroRNAs (miRNAs) are short, non-coding single-strand RNA molecules that play important roles in plant growth, development and stress responses. Flowering time affects the seed yield and quality of soybean. However, the miRNAs involved in the regulation of flowering time in soybean have not been reported until recently. Here, high-throughput sequencing and qRT-PCR were used to identify miRNAs involved in soybean photoperiodic pathways. The first trifoliate leaves of soybean that receive the signal of light treatment were used to construct six libraries (0, 8, and 16 h under short-day (SD) treatment and 0, 8, and 16 h under long-day (LD) treatment). The libraries were sequenced using Illumina Solexa. A total of 318 known plant miRNAs belonging to 163 miRNA families and 81 novel predicted miRNAs were identified. Among these, 23 miRNAs at 0 h, 65 miRNAs at 8 h and 83 miRNAs at 16 h, including six novel predicted miRNAs at 8 h and six novel predicted miRNAs at 16 h, showed differences in abundance between LD and SD treatments. Furthermore, the results of GO and KEGG analyses indicated that most of the miRNA targets were transcription factors. Seven miRNAs at 0 h, 23 miRNAs (including four novel predicted miRNAs) at 8 h, 16 miRNAs (including one novel predicted miRNA) at 16 h and miRNA targets were selected for qRT-PCR analysis to assess the accuracy of the sequencing and target prediction. The results indicated that the expression patterns of the selected miRNAs and miRNA targets showed no differences between the qRT-PCR and sequencing results. In addition, 23 miRNAs at 0 h, 65 miRNAs at 8 h and 83 miRNAs at 16 h responded to day length changes in soybean, including six novel predicted miRNAs at 8 h and six novel predicted miRNAs at 16 h. These results provided an important molecular basis to understand the regulation of flowering time through photoperiodic pathways in soybean.

Osteosarcoma is the most frequent type of malignant bone tumor in children and adolescents and is associated with a high propensity for lung metastasis. Recent experiments have indicated that PLA2G16 contributes to osteosarcoma progression and metastasis in both mouse and human osteosarcoma cell lines. The aim of this study was to compare the expression of PLA2G16 in non-metastatic and metastatic osteosarcomas to determine whether PLA2G16 expression can serve as a biomarker of osteosarcoma prognosis and metastasis.Quantitative real-time PCR was used to examine PLA2G16 mRNA in primary osteosarcoma patients (18 patients without metastases and 17 patients with metastases), and immunohistochemistry (IHC) staining of PLA2G16 was performed on tissue microarrays from 119 osteosarcoma patients. Tumor metastatic behavior and survival of the patients were followed up for a minimum of 36 months and a maximum of 171 months. The prognostic value of PLA2G16 expression was evaluated by the Kaplan-Meier method and a log-rank test. Multivariate Cox regression analysis was used to identify significant independent prognostic factors.Osteosarcoma patients with metastasis showed a higher expression of PLA2G16 at both the mRNA and protein levels (both at P values< 0.05) than did patients without metastasis. Osteosarcoma patients with positive IHC staining of PLA2G16 expression at primary sites had shorter overall survival and metastasis-free survival (both at P values

The influence of age on the performance of percent free prostate-specific antigen (%fPSA) in diagnosing prostate cancer (PCa) in East Asians is controversial. We tested the diagnostic performance of %fPSA in a multi-center biopsy cohort in China and identified the proper age-specific cutoff values to avoid unnecessary biopsies.Consecutive patients with a prostate-specific antigen (PSA) level of 4.0-10.0 ng/ml or 10.1-20.0 ng/ml who underwent transrectal ultrasound-guided or transperineal prostate biopsy were enrolled from 22 Chinese medical centers from Jan 1, 2010 to Dec 31, 2013. The diagnostic accuracy of PSA and %fPSA was determined using the area under the receiver operating characteristic (ROC) curve (AUC). Age-specific cutoff values were calculated using ROC curve analysis.The median %fPSA was much lower in younger patients compared with older patients with a PSA level of 4.0-10.0 ng/ml or 10.1-20.0 ng/ml. The AUC of %fPSA was higher than PSA only in older patients. In patients aged 50 to 59 years, %fPSA failed to improve the diagnosis compared with PSA in these two PSA ranges. Age-specific cutoff values were 24%, 27% and 32% for patients aged 60-69, 70-79 and ≥80 years, respectively, to reduce unnecessary biopsies in men with PSA levels of 4.0-10.0 ng/ml to detect 90% of all PCa.The effectiveness of %fPSA is correlated with age in the Chinese population. Age-specific cutoff values would help avoid unnecessary biopsies in the Chinese population.

The influence of environmental attitudes on environmental behaviors has long been discussed. However, few studies have addressed the foundation of such attitudes. In the present study, we explored primitive belief underlying environmental attitudes, i.e., connections with nature, and its relationship with pro-environmental behaviors. Specifically, we used scales, a computerized Implicit Association Test, and a situational simulation experiment to examine both explicit and implicit connections with nature, both deliberate and spontaneous environmental behaviors, and to find correlations between environmental connectedness and environmental behaviors. Results showed that explicit connectedness was positively correlated with deliberate environmental behaviors, while implicit connectedness was positively correlated with spontaneous environmental behaviors. Additionally, explicit and implicit connectedness was independent of each other. In conclusion, the current study confirms the positive role played by connections with nature in promoting environmental behavior, and accordingly suggests means to encourage pro-environmental behavior by enhancing people's connectedness to nature.

The D3-Creatine (D3Cr) dilution method is a direct and accurate measure of skeletal muscle mass. In this study, we examined the association of D3Cr muscle mass with measures of insulin-glucose homeostasis in community dwelling postmenopausal women. Additionally, we examined association of sarcopenic obesity, defined as low D3Cr muscle mass and high percent body fat, with fasting plasma glucose, insulin, hemoglobin A1c and insulin resistance. Insulin resistance was measured by the homeostatic measure of insulin resistance (HOMA-IR). This pilot study included 74 participants (mean age = 82.3 years) from the Women's Health Initiative-Buffalo site. The D3Cr method was initiated at a clinic visit and used to measure muscle mass via remote urine sample collection. Descriptive and graphical approaches and age-adjusted linear regression models were used to analyze study data. We examined muscle mass as an absolute value (kg) and scaled to body weight (D3Cr muscle mass/kg). There was an inverse relationship between skeletal muscle mass, and impaired insulin-glucose homeostasis. Women with low muscle mass had higher levels of insulin (uIU/mL; β = -0.40; 95% CI: -0.79, -0.01), fasting plasma glucose (mg/dL; β = -0.1; 95% CI: -0.2, 0.03), HbA1c (%; β = -2.30; 95% CI: -5.7, 1.1), and calculated homeostatic model of insulin resistance, HOMA-IR, (β = -1.49; 95% CI: -2.9, -0.1). Sarcopenic obesity was common in this population of women; 41% of participants were categorized as having low muscle mass and high percent body fat. Results demonstrate that D3Cr muscle mass is independently associated with measures of insulin-glucose homeostasis, but obesity is a stronger predictor of insulin resistance than muscle mass. [ABSTRACT FROM AUTHOR]

Typically, most nephropathies can be categorized as complex human diseases in which the cumulative effect of multiple minor genes, combined with environmental and lifestyle factors, determines the disease phenotype. Thus, multi-target drugs would be more likely to facilitate comprehensive renoprotection than single-target agents. In this study, functional chemical-protein association analysis was performed to retrieve multi-target drugs of high pathway wideness from the STITCH 3.1 database. Pathway wideness of a drug evaluated the efficiency of regulation of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways in quantity. We identified nine experimentally validated renoprotectants that exerted remarkable impact on KEGG pathways by targeting a limited number of proteins. We selected curcumin as an illustrative compound to display the advantage of multi-pathway drugs on renoprotection. We compared curcumin with hemin, an agonist of heme oxygenase-1 (HO-1), which significantly affects only one KEGG pathway, porphyrin and chlorophyll metabolism (adjusted p = 1.5×10-5). At the same concentration (10 µM), both curcumin and hemin equivalently mitigated oxidative stress in H2O2-treated glomerular mesangial cells. The benefit of using hemin was derived from its agonistic effect on HO-1, providing relief from oxidative stress. Selective inhibition of HO-1 completely blocked the action of hemin but not that of curcumin, suggesting simultaneous multi-pathway intervention by curcumin. Curcumin also increased cellular autophagy levels, enhancing its protective effect; however, hemin had no effects. Based on the fact that the dysregulation of multiple pathways is implicated in the etiology of complex diseases, we proposed a feasible method for identifying multi-pathway drugs from compounds with validated targets. Our efforts will help identify multi-pathway agents capable of providing comprehensive protection against renal injuries.

BACKGROUND:Most (70%) epithelial ovarian cancers (EOCs) are diagnosed late. Non-invasive biomarkers that facilitate disease detection and predict outcome are needed. The microRNAs (miRNAs) represent a new class of biomarkers. This study was to identify and validate plasma miRNAs as biomarkers in EOC. METHODOLOGY/PRINCIPAL FINDINGS:We evaluated plasma samples of 360 EOC patients and 200 healthy controls from two institutions. All samples were grouped into screening, training and validation sets. We scanned the circulating plasma miRNAs by TaqMan low-density array in the screening set and identified/validated miRNA markers by real-time polymerase chain reaction assay in the training set. Receiver operating characteristic and logistic regression analyses established the diagnostic miRNA panel, which were confirmed in the validation sets. We found higher plasma miR-205 and lower let-7f expression in cases than in controls. MiR-205 and let-7f together provided high diagnostic accuracy for EOC, especially in patients with stage I disease. The combination of these two miRNAs and carbohydrate antigen-125 (CA-125) further improved the accuracy of detection. MiR-483-5p expression was elevated in stages III and IV compared with in stages I and II, which was consistent with its expression pattern in tumor tissues. Furthermore, lower levels of let-7f were predictive of poor prognosis in EOC patients. CONCLUSIONS/SIGNIFICANCE:Our findings indicate that plasma miR-205 and let-7f are biomarkers for ovarian cancer detection that complement CA-125; let-7f may be predictive of ovarian cancer prognosis.

AIM: To investigate the role of neurotensin (NTS) in hepatocellular carcinoma (HCC) sub- grouping and the clinical and pathological significance of activation of NTS/IL-8 pathway in HCC. METHODS: The genome-wide gene expression profiling were conducted in 10 pairs of cancer tissues and corresponding normal adjacent tissues samples using Affymetrix GeneChip® Human Genome U133 Plus 2.0 microarray to screen differentially expressing genes and enrich dysfunctional activated pathways among different HCC subgroups. The levels of NTS protein and multiple inflammation and epithelial mesenchymal transition (EMT) related proteins, including IL-8, VEGF, MMP9, CD68, E-Cadherin, β-Catenin and Vimentin were examined in 64 cases of paraffin-embedded HCC samples using immunohistochemistry (IHC) staining method. The clinical outcome and overall survival (OS) were compared. RESULTS: A subgroup of HCC characterized by up-regulated NTS expression was accompanied by up-regulated inflammatory responses and EMT. The direct interaction between NTS and IL-8 was identified by pathway enrichment analysis. Significantly increased IL-8 protein was confirmed in 90.91% of NTS(+) HCC samples and significantly positively correlated to the levels of NTS protein in cancer tissues (P = 0.036), which implied activation of NTS/IL-8 pathway in HCC. The levels of VEGF and MMP9 correlated with co-expression of NTS and IL-8. Increased infiltration of CD68(+) macrophages and more cancer cells displaying EMT features were found in NTS(+)IL-8(+) samples. The co-expression of NTS and IL-8 in cancer significantly correlated with the clinical outcomes, as the mortality rate of NTS(+)IL-8(+) HCC patients is 2.5-fold higher than the others after the surgery (P = 0.022). Accordingly, the OS of NTS(+)IL-8(+) HCC patients significantly decreased who are under a higher hazard of death at an expected hazard ratio (HR) of 3.457. CONCLUSION: Dysfunctional activation of the NTS/IL-8 pathway was detected in HCC which is associated with increased inflammatory response in microenvironment, enhanced EMT in cancer, and worse prognosis in HCC patients.

Coal workers' pneumoconiosis (CWP), resulting from the inhalation of silica-containing coal mine dust, is characterized by fibrosing nodular lesions that eventually develop into progressive pulmonary fibrosis. Recently, it has been hypothesized that inflammasomes could have a crucial role in the host response to silica and recent studies show that the inflammasome contributes to inflammation and pulmonary fibrosis. NLRP3, CARD8 are components of the NLRP3 inflammasome, which triggers caspase 1-mediated IL-1β and IL-18 release. In the present study, we investigated whether common single nucleotide polymorphisms (SNPs) in inflammasome genes are associated with CWP.We performed an association study analyzing 3 NLRP3, 1 CARD8, 1 IL-1β, 2 IL-18 SNPs in a case-control study of 697 CWP and 694 controls. Genotyping was carried out by the TaqMan method.The NLRP3 rs1539019 TT genotype was associated with a significantly increased risk of CWP (adjusted odds ratio (OR) = 1.39, 95% confidence interval (CI) = 1.07-1.81), compared with the GG/GT genotype, in particular among smokers (adjusted OR = 1.67, 95%CI = 1.15-2.42). In addition, the polymorphism was significantly associated with risk of CWP patients with stage I.This is the first report showing an association between the NLRP3 rs1539019 polymorphism and CWP, and suggests that this polymorphism may confer increased risk for the development of the disease. Further studies are warranted to confirm our findings.