An evolutionary game theory-based study examining the relationship between fiscal policy, stability of farmers' cooperatives, and environmentally friendly digital management.

To increase the degree of implementation of the rural revitalization strategy, it is crucial to conduct a scientific investigation of the relationship between fiscal policy, fiscal decentralization, green digital management, and contract selection. This research develops an analytical framework for the application of fiscal policy and the choice of cooperative association contracts based on the contract theory. On the basis of a theoretical analysis of the external factors that influence the choice of residents' cooperative association contract and behavior, it goes on to investigate the interest game relationship and stability of three different cooperative associations (production type, service type, and industrial chain type). Additionally, it runs an empirical test using survey information from cooperative associations in China's Gansu Province. The findings indicate that the cooperative association is more likely to select the factor contract model depending on the strength of the fiscal policy support, the union's brand influence, and the regional market share change of the primary products. Evolutionary equilibrium is inhibited by the association's input costs, but a stable contract is created more favorably the more average the cost distribution is. The stability of the contract and its detrimental effects on pro-environmental behavior are worse the more damage other residents' breaches of the contract have caused. The research findings in this paper may serve as a basis for decision-making and a source of information for encouraging the high-quality growth of cooperative groups.

A retrospective comparative cohort study: concurrent versus consolidative immunotherapy with chemoradiotherapy in EGFR- or ALK-negative unresectable stage III non-small cell lung cancer.

Background: The treatment of stage III non-small cell lung cancer (NSCLC) is very challenging because it is a heterogeneous group of diseases. This study was to investigative whether concurrent immunotherapy with chemoradiotherapy was associated with improved outcomes compared to consolidative immunotherapy following chemoradiotherapy in patients with unresectable stage III NSCLC, which may provide evidence-based medical evidence for the treatment of stage III NSCLC. Methods: A total of 78 epidermal growth factor receptor or anaplastic lymphoma kinase (EGFR/ALK) negative patients from the clinical database of the shanghai pulmonary hospital with locally advanced unresectable NSCLC and we evaluated them for baseline clinical factors, follow-up. Patients underwent concurrent immunotherapy with chemoradiotherapy or consolidative immunotherapy after chemoradiotherapy. Patients were classified based on initial site of progression (primary versus non-primary site). The study endpoints were progression-free survival (PFS) and time to death or distant metastasis (TDDM). Cox proportional hazards analysis was used to assess the factors affecting PFS and TDDM. Results: The median follow-up time for both groups was 26 months, and there was no significant difference in baseline clinical characteristics (P>0.05). The patients receiving concurrent immunotherapy (n=36) had a longer PFS than those receiving consolidative immunotherapy (n=42) (median 32.4 vs. 15.5 months; P<0.01). The TDDM was also longer in patients with concurrent immunotherapy than those with consolidative immunotherapy (median 57.3 vs. 31.0 months; P=0.01). Furthermore, in a subset of patients with initial site of progression at a non-primary-site, patients undergoing concurrent immunotherapy had longer PFS than those undergoing consolidative immunotherapy (median 22.7 vs. 11.9 months; P=0.03). Conclusions: Concurrent immunotherapy with chemoradiotherapy may be associated with improved disease progression outcomes as compared to consolidative immunotherapy following chemoradiotherapy.

Silica nanoparticles induces sperm granuloma formation and blood-epididymal barrier disruption via the p38 MAPK pathway in mice.

Previous researches have demonstrated that the silica nanoparticles (SiNPs), which are widely used in all aspects of life, are hazardous to the male reproductive system. However, the cellular and molecular mechanism underlying SiNPs toxicity to the epididymis remain unclear. In this present study, a total of 60 male mice were separated into 4 groups and then treated to SiNPs for 7 consecutive days at a dose of 0, 2.5, 10, and 20 mg/kg body weight. The results showed that SiNPs could alter the histological structure of epididymis and induce sperm granuloma formation, leading to decreased sperm quality and quantity. In addition, the ultrastructure and permeability of blood-epididymal barrier (BEB) were impaired after exposure to SiNPs, and a significant downregulation of integral membrane proteins at the BEB was detected. SiNPs were also found to raise the percentage of macrophages in the epithelium and interstitium of the epididymis, followed by increased expression of pro-inflammatory molecules including TNF α, IL-1ß, and IL-6. Meanwhile, SiNPs induced oxidative stress in epididymis, as shown by the markedly elevated generation of reactive oxygen species (ROS) and malondialdehyde (MDA) and upregulated activity of superoxide dismutase (SOD). Further study showed that SiNPs activated the p38 MAPK signaling pathway, which accelerated clathrin-mediated endocytosis of integral membrane proteins and perturb vesicular trafficking. Taken together, exposure to SiNPs could induce sperm granuloma formation and impair the integrity of BEB in mice through activating the p38 MAPK pathway.

Ethanol mediates the interaction between Caenorhabditis elegans and the nematophagous fungus Purpureocillium lavendulum.

Accurately recognizing pathogens by the host is vital for initiating appropriate immune response against infecting microorganisms. Caenorhabditis elegans has no known receptor to recognize pathogen-associated molecular pattern. However, recent studies showed that nematodes have a strong specificity for transcriptomes infected by different pathogens, indicating that they can identify different pathogenic microorganisms. However, the mechanism(s) for such specificity remains largely unknown. In this study, we showed that the nematophagous fungus Purpureocillium lavendulum can infect the intestinal tract of the nematode C. elegans and the infection led to the accumulation of reactive oxygen species (ROS) in the infected intestinal tract, which suppressed fungal growth. Co-transcriptional analysis revealed that fungal genes related to anaerobic respiration and ethanol production were up-regulated during infection. Meanwhile, the ethanol dehydrogenase Sodh-1 in C. elegans was also up-regulated. Together, these results suggested that the infecting fungi encounter hypoxia stress in the nematode gut and that ethanol may play a role in the host-pathogen interaction. Ethanol production in vitro during fungal cultivation in hypoxia conditions was confirmed by gas chromatography-mass spectrometry. Direct treatment of C. elegans with ethanol elevated the sodh-1 expression and ROS accumulation while repressing a series of immunity genes that were also repressed during fungal infection. Mutation of sodh-1 in C. elegans blocked ROS accumulation and increased the nematode's susceptibility to fungal infection. Our study revealed a new recognition and antifungal mechanism in C. elegans. The novel mechanism of ethanol-mediated interaction between the fungus and nematode provides new insights into fungal pathogenesis and for developing alternative biocontrol of pathogenic nematodes by nematophagous fungi. IMPORTANCE Nematodes are among the most abundant animals on our planet. Many of them are parasites in animals and plants and cause human and animal health problems as well as agricultural losses. Studying the interaction of nematodes and their microbial pathogens is of great importance for the biocontrol of animal and plant parasitic nematodes. In this study, we found that the model nematode Caenorhabditis elegans can recognize its fungal pathogen, the nematophagous fungus Purpureocillium lavendulum, through fungal-produced ethanol. Then the nematode elevated the reactive oxygen species production in the gut to inhibit fungal growth in an ethanol dehydrogenase-dependent manner. With this mechanism, novel biocontrol strategies may be developed targeting the ethanol receptor or metabolic pathway of nematodes. Meanwhile, as a volatile organic compound, ethanol should be taken seriously as a vector molecule in the microbial-host interaction in nature.

Comprehensive analysis of immune-related genes for classification and immune microenvironment of asthma.

OBJECTIVES: To determine the effects of immune-related genes (IRGs) and immune landscape of induced sputum, and develop novel, non-invasive diagnostic molecular therapeutic targets for asthma. METHODS: GSE76262 datasets were used to identify differentially expressed IRGs in asthma. Key IRGs were detected using a protein-protein interaction network. Receiver operating characteristic (ROC) curves were analyzed to investigate the diagnostic value of key IRGs. Gene set enrichment analysis (GSEA) was performed with WebGestalt. Single-sample gene set enrichment analysis and CIBERSORT were used to investigate the immune landscape of induced sputum. RESULTS: A total of 75 potential IRGs were associated with asthma, most of which were involved in the NF-kappa B signaling pathway. ROC analysis showed AUC values for the hub pathway ranging from 0.676-0.767, with moderate diagnostic value for asthma. We also identified IRGs-related cytokines (TNF-α, IL-1ß, IL-8 and IL-6) in 76 asthma and 91 control serum samples to further explore diagnostic efficacy, showing a cumulative AUC of 0.998 for these four related cytokines. Analysis of immune cell infiltration levels showed that follicular helper T cells, activated dendritic cells, activated mast cells and eosinophils were significantly higher and macrophages M0 and macrophages M2 were significantly reduced in sputum from patients with asthma. CONCLUSIONS: IRGs-related cytokines and immune infiltration may contribute to the diagnosis and immune classification of asthma.

The location of visceral pleural invasion in stage IB patients with non-small cell lung cancer: Comparison and prognosis.

OBJECTIVES: Recently, early-stage lung cancer has been drawing more attention, especially in screening and treatment. Visceral pleural invasion in stage IB cancer is considered as risk factor for poor prognosis. Herein, we aimed to study the distinction between the different locations of visceral pleural invasion. METHODS: In this retrospective cohort study, we summarized 58,242 patient cases that underwent surgery from 2015 to 2018 at Shanghai Chest Hospital. Of those patients, 389 met the inclusion criteria. Patients with PL3 pleural invasion were excluded. The patients were dichotomized into the interlobar pleural and peripheral pleural groups. The outcomes measured were overall survival (OS) and recurrence-free survival (RFS) rates. RESULTS: According to the initial analysis, the baseline characteristics of the two groups were largely balanced. In multivariate Cox analyses, we found that the location of visceral pleural invasion was not a risk factor for prognosis in the overall population (RFS: P = 0.726, OS: P = 0.599). However, we discovered that relative to patients with peripheral pleura invasion, those with interlobar pleura invasion, PL1 invasion, lesions with greater than 3 cm solid components, and those who underwent segmentectomy had a compromised prognosis. Additionally, tumors larger than 3 cm in size with interlobar pleura invasion showed poor prognosis in patients who underwent postoperative chemotherapy. CONCLUSIONS: In most cases, the location of tumor invasion did not worsen the postoperative prognosis of stage IB non-small cell lung cancer patients with visceral pleural invasion. However, interlobar pleural invasion still had some potential risks compared to that of peripheral pleural invasion.

Arginine Enhances Ovarian Antioxidant Capability via Nrf2/Keap1 Pathway during the Luteal Phase in Ewes.

This study evaluated the effect of arginine (Arg) on ovarian antioxidant capability during the luteal phase in ewes. A total of 108 multiparous Hu sheep at two years of age were randomly allocated to three groups: a control group (CG), a restriction group (RG), and an Arg group (AG), with six replicates per group and six ewes per replicate. Our results showed that the end body weight was significantly decreased in the RG group (p < 0.05), while the Arg addition reversed this reduction. The estrous cycle days were significantly increased in the RG group (p < 0.05), while Arg addition reversed this time extension. Compared with the control group, restricting feeding could significantly enhance the number of small follicles (SF), total follicles (TF), large corpora lutea, and the SF/TF (p < 0.05), while Arg addition reduced the number of SF and TF. However, the large follicles/TF were significantly decreased (p < 0.05), while Arg addition reversed this reduction. In addition, nutrition restriction significantly increased the malondialdehyde (MDA) level (p < 0.05), while significantly decreased the glutathione/glutathione disulfide and the activities of superoxidative dismutase, catalase, and glutathione peroxidase in the ovaries (p < 0.05). However, Arg addition reversed this enhancement of the MDA level and the reductions in these antioxidant enzymes activities. In addition, positive relationships occurred between antioxidant enzyme activities and the enzyme mRNA expressions. Meanwhile, the nuclear factor erythroid 2-related factor 2 (Nrf2) mRNA expression was positively connected with antioxidant mRNA expressions and negatively related to the Kelch-like ECH-associated protein 1 (Keap1) mRNA expression. The Nrf2 protein expression was negatively related to the Keap1 protein expression. In conclusion, nutrition restriction reduced the ovarian antioxidant capability in ewes, while this was significantly improved by Arg supplementation, which was associated with the Nrf2/Keap1 pathway.

shRNA­mediated knockdown of KNTC1 inhibits non-small-cell lung cancer through regulating PSMB8.

In view of the important roles played by Kinetochore proteins in mitosis, we believed that they may contribute to the development and progression of human cancers, which has been reported recently elsewhere. Kinetochore-associated 1 (KNTC1) participates in the segregation of sister chromatids during mitosis, the effects of which on non-small-cell lung cancer (NSCLC) remain unclear. Here, we sought to identify the biological significance of KNTC1 in NSCLC. KNTC1 protein expression in NSCLC tissues was investigated by immunohistochemistry. Lentivirus delivered short hairpin RNA (shRNA) was utilized to establish KNTC1 silence NSCLC cell lines. The effects of KNTC1 depletion on NSCLC cell proliferation, migration, apoptosis, and tumor formation were analyzed by MTT assay, wound-healing assay, transwell assay, flow cytometry assay, and in nude mouse models in vivo. After KNTC1 reduction, NSCLC cell viability, proliferation, migration, and invasion were restrained. A xenograft tumor model was also provided to demonstrate the inhibited tumorigenesis in NSCLC. In addition, the downstream mechanism analysis indicated that KNTC1 depletion was positively associated with PSMB8. The findings of the present study suggested that KNTC1 may have a pivotal role in mediating NSCLC progression and may act as a novel therapeutic target for NSCLC.

The outcomes of margin status after sleeve lobectomy for patients of non-small cell lung cancer.

BACKGROUND: Sleeve lobectomy is recognized as an alternative surgical operation to pneumonectomy because it preserves the most pulmonary function and has a considerable prognosis. In this study, we aimed to investigate the implications of residual status for patients after sleeve lobectomy. METHODS: In this retrospective cohort study, we summarized 58 242 patients who underwent surgeries from 2015 to 2018 in Shanghai Chest Hospital and found 456 eligible patients meeting the criteria. The status of R2 was excluded. The outcomes were overall survival (OS) and recurrence-free survival (RFS). We performed a subgroup analysis to further our investigation. RESULTS: After the propensity score match, the baseline characteristic was balanced between two groups. The survival analysis showed no significant difference of overall survival and recurrence-free survival between R0 and R1 groups (OS: p = 0.053; RFS: p = 0.14). In the multivariate Cox analysis, we found that the margin status was not a dependent risk factor to RFS (p = 0.119) and OS (p = 0.093). In the patients of R1, N stage and age were closely related to OS, but we did not find any significant risk variable in RFS for R1 status. In the subgroup analysis, R1 status may have a worse prognosis on patients with more lymph nodes examination. On further investigation, we demonstrated no differences among the four histological types of margin status. CONCLUSION: In our study, we confirmed that the margin status after sleeve lobectomies was not the risk factor to prognosis. However, patients with more lymph nodes resection should pay attention to the margin status.

Reproductive toxicity investigation of silica nanoparticles in male pubertal mice.

Silica nanoparticles (SiNPs), one of the most produced nanoparticles (NPs) in the world, are used in all aspects of life. The increased application of SiNPs, especially in medicine, has raised considerable concern regarding their toxicological impact. Previous studies have shown that SiNPs can pass through the reproductive barrier and cause reproductive organ dysfunction by destroying Sertoli cells, Leydig cells, and germ cells. However, little is known about the mechanism of SiNPs-induced reproductive toxicity. In the present study, 5-week-old male mice were intraperitoneally administered SiNPs per day for 1 week at a dose of 0.2 mg per mouse. The results showed that SiNPs could cause damage to the structure of the testis and the epididymis and change the reproductive organ coefficients, leading to decreases of 56.1% and 55.3% in the rates of sperm concentration and motility and an increase of 168.8% in the rate of sperm abnormality. Moreover, the serum testosterone level obviously decreased from 18.77 to 5.23 µg/ml after exposure, and the transcription statuses of some key genes involved in the synthesis and transport of testosterone in the testis were also affected. Additional experiments showed that SiNPs exposure during puberty induced oxidative stress and an inflammatory response, as shown by the changed activity of superoxide dismutase (SOD), increased contents of malondialdehyde (MDA), and excess expression of proinflammatory factors, including TNF-α and IL-1ß. Furthermore, the administration of SiNPs caused DNA damage and cell apoptosis, which were presented by the increased apoptotic cells in the sections of testis and epididymis and activation of the TNF-α/TNFR I-mediated pro-apoptotic pathway. In conclusion, these results indicate that SiNPs exposure during puberty significantly damaged the structure and function of the testis and epididymis by inducing oxidative stress and cell apoptosis. This study provides novel insight into SiNPs-induced reproductive toxicity during puberty, which warrants a more careful assessment of SiNPs before their application in juvenile supplies.

Identification of a 7-miRNA signature for predicting the prognosis of patients with lung adenocarcinoma.

The role of microRNAs (miRNAs) in tumor diagnosis and patients' prognosis has recently gained extensive research attention. This study was designed to analyze miRNA in lung adenocarcinoma (LUAD) using bioinformatics analysis and to identify novel biomarkers to predict overall survival (OS) for LUAD patients. Differential miRNA expression analysis was performed on LUAD, and normal tissues were extracted from The Cancer Genome Atlas (TCGA). Univariate Cox risk regression and least absolute shrinkage and selection operator (LASSO) Cox analysis were used to screen prognostic miRNAs and develop a risk score model. The prognostic performance of the system was examined utilizing the Kaplan-Meier and receiver operating characteristic (ROC) curves. Independent prognostic factors of LUAD were determined by multivariate Cox regression analysis. Nomogram was constructed according to the independent prognostic factors to evaluate the patients' one-, three- and five-year OS. A 7-miRNA signature based on miR-584-5p, miR-31-3p, miR-490-3, miR-4661-5p, miR-30e-5p, miR-582-5p, and miR-148a-3p was established. To categorize patients into high- and low-risk groups, the risk score was computed. The OS of the low-risk group was significantly longer than the high-risk group, and the signature showed high sensitivity and specificity in anticipating the one-, three- and five-year OS. The system was an independent factor in predicting the OS of LUAD patients and performed better when combined with the N stage in nomogram. A 7-miRNA signature developed in this study could accurately predict LUAD survival.

Silica nanoparticles cause spermatogenesis dysfunction in mice via inducing cell cycle arrest and apoptosis.

The widespread use of silica nanoparticles (SiNPs) has increased the risk of human exposure, which raised concerns about their adverse effects on human health, especially the reproductive system. Previous studies have shown that SiNPs could cause damage to reproductive organs, but the specific mechanism is still unclear. In this study, to investigate the underlying mechanism of male reproductive toxicity induced by SiNPs, 40 male mice at the age of 8 weeks were divided into two groups and then intraperitoneally injected with vehicle control or 10 mg/kg SiNPs per day for one week. The results showed that SiNPs could damage testicular structure, perturb spermatogenesis and reduce serum testosterone levels, leading to a decrease in sperm quality and quantity. In addition, the ROS level in the testis of exposed mice was significantly increased, followed by imbalance of the oxidative redox status. Further study revealed that exposure to SiNPs led to cell cycle arrest and apoptosis, as shown by downregulation of the expression of positive cell cycle regulators and the activation of TNF-α/TNFR Ⅰ-mediated apoptotic pathway. The results demonstrated that SiNPs could cause testicles injure via inducing oxidative stress and DNA damage which led to cell cycle arrest and apoptosis, and thereby resulting in spermatogenic dysfunction.

The significance of systematic lymph node dissection in surgery for early-stage non-small cell lung cancer patients aged ≤40 years.

BACKGROUND: Surgery remains the best option for treating early-stage non-small cell lung cancer (NSCLC), and lymph node dissection (LND) is an important step in this approach. However, the extent of LND in the general age population, especially in young patients, is controversial. This retrospective study aimed to investigate the correlation between systematic lymph node dissection (SLND) and prognosis in young (≤40 years) patients with stage IA NSCLC. METHODS: Clinicopathological data of 191 patients aged ≤40 years who underwent surgical pulmonary resection for stage IA NSCLC between January 2010 and December 2016 were retrospectively collected. Of the patients, 104 received SLND (SLND group), while the other 87 patients underwent sampling or no LND (non-SLND group). The disease-free survival (DFS) and overall survival (OS) curves of the patients from each group were plotted using the Kaplan-Meier method, and the correlations of the patients' clinical factors with prognosis were also analyzed. RESULTS: The median follow-up period was 55 months. During follow-up, 7 patients died, and recurrence or metastasis was detected in 16 patients. Kaplan-Meier analysis revealed no difference in DFS (P=0.132) between the SLND and non-SLND group, but a significant difference was found between the groups in OS (P=0.022). Additionally, there was no statistically pronounced difference in OS or DFS between male and female patients. Multivariate survival analysis showed that the type of SLND, as well as tumor size, is an independent prognostic factor for DFS (HR, 3.530; 95% CI, 1.120-11.119; P=0.031) and OS (HR, 13.076; 95% CI, 1.209-141.443; P=0.034). CONCLUSIONS: For young (age ≤40) stage IA NSCLC patients with pathological invasive adenocarcinoma, intraoperative SLND can improve the DFS and OS. Further studies are needed to verify the most optimal degree of LND in young patients.

Liver knockout YAP gene improved insulin resistance-induced hepatic fibrosis.

Yes-associated protein (YAP), as a co-activator of transcription factors, is a downstream protein in the Hippo signaling pathway with important functions in cell proliferation, apoptosis, invasion and migration. YAP also plays a key role in the development of CCl4-induced liver fibrosis. However, the mechanism of YAP during hepatic fibrosis progression and reversion is still unclear. Mild liver fibrosis was developed after 4 months of high-fat diet (HFD) stimulation, and we found that the YAP signaling pathway was activated. Here, we aim to reveal whether specific knockout of Yap gene in the liver can improve liver fibrosis induced by insulin resistance (IR) stimulated by HFD, and further explain its specific mechanism. We found that liver-specific Yap gene knockout improved IR-induced liver fibrosis and liver dysfunction, and this mechanism is related to the inhibition of the insulin signal pathway at the FoxO1 level. These findings provide a new insight, and Yap is expected to be a new target to reverse the early stage of liver fibrosis induced by IR.

Natural and human environment interactively drive spread pattern of COVID-19: A city-level modeling study in China.

A novel Coronavirus COVID-19 has caused high morbidity and mortality in China and worldwide. A few studies have explored the impact of climate change or human activity on the disease incidence in China or a city. The integrated study concerning environment impact on the emerging disease is rarely reported. Therefore, based on the two-stage modeling study, we investigate the effect of both natural and human environment on COVID-19 incidence at a city level. Besides, the interactive effect of different factors on COVID-19 incidence is analyzed using Geodetector; the impact of effective factors and interaction terms on COVID-19 is simulated with Geographically Weighted Regression (GWR) models. The results find that mean temperature (MeanT), destination proportion in population flow from Wuhan (WH), migration scale (MS), and WH*MeanT, are generally promoting for COVID-19 incidence before Wuhan's shutdown (T1); the WH and MeanT play a determinant role in the disease spread in T1. The effect of environment on COVID-19 incidence after Wuhan's shutdown (T2) includes more factors (including mean DEM, relative humidity, precipitation (Pre), travel intensity within a city (TC), and their interactive terms) than T1, and their effect shows distinct spatial heterogeneity. Interestingly, the dividing line of positive-negative effect of MeanT and Pre on COVID-19 incidence is 8.5°C and 1 mm, respectively. In T2, WH has weak impact, but the MS has the strongest effect. The COVID-19 incidence in T2 without quarantine is also modeled using the developed GWR model, and the modeled incidence shows an obvious increase for 75.6% cities compared with reported incidence in T2 especially for some mega cities. This evidences national quarantine and traffic control take determinant role in controlling the disease spread. The study indicates that both natural environment and human factors integratedly affect the spread pattern of COVID-19 in China.

Functional Characterization of Core Regulatory Genes Involved in Sporulation of the Nematophagous Fungus Purpureocillium lavendulum.

The nematophagous fungus Purpureocillium lavendulum is a natural enemy of plant-parasitic nematodes, which cause severe economic losses in agriculture worldwide. The production of asexual spores (conidia) in P. lavendulum is crucial for its biocontrol activity against nematodes. In this study, we characterized the core regulatory genes involved in conidiation of P. lavendulum at the molecular level. The central regulatory pathway is composed of three genes, P. lavendulumbrlA (PlbrlA), PlabaA, and PlwetA, which regulate the early, middle, and late stages of asexual development, respectively. The deletion of PlbrlA completely inhibited conidiation, with only conidiophore stalks produced. PlAbaA determines the differentiation of conidia from phialides. The deletion of PlwetA affected many phenotypes related to conidial maturation, including abscission of conidia from conidium strings, thickening of the cell wall layers, vacuole generation inside the cytoplasm, production of trehalose, tolerance to heat shock, etc. Comparative analyses showed that the upstream regulators of the core regulatory pathway of conidiation, especially the "fluffy" genes, were different from those in Aspergillus Besides their roles in conidiation, the central regulators also influence the production of secondary metabolites, such as the leucinostatins, in P. lavendulum Our study revealed a set of essential genes controlling conidiation in P. lavendulum and provided a framework for further molecular genetic studies on fungus-nematode interactions and for the biocontrol of plant-parasitic nematodes.IMPORTANCE Plant-parasitic nematodes cause serious damage to crops throughout the world. Purpureocillium lavendulum is a nematophagous fungus which is a natural enemy of nematodes and a potential biocontrol agent against plant-parasitic nematodes. The conidia play an important role during infection of nematodes. In this study, we identified and characterized genes involved in regulating asexual development of P. lavendulum We found that these genes not only regulate conidiation but also influence secondary-metabolite production. This work provides a basis for future studies of fungus-nematode interactions and nematode biocontrol.

Baihe Wuyao decoction ameliorates CCl4-induced chronic liver injury and liver fibrosis in mice through blocking TGF-ß1/Smad2/3 signaling, anti-inflammation and anti-oxidation effects.

ETHNOPHARMACOLOGICAL RELEVANCE: Baihe Wuyao decoction (BWD), a prescription of Traditional Chinese Medicines, composed of Lilium brownii var. viridulum Baker.(Lilii Bulbus) and Lindera aggregata (Sims) Kosterm. (Linderae Radix), has been used to treat epigastric pain and superficial gastritis for hundreds of years in China. Recently, some compounds obtained from Lilii Bulbus and Linderae Radix had active effects of hepatic protection or liver fibrosis alleviation. Thus, we aim to evaluate the effects of BWD on treatment of chronic liver injury and liver fibrosis induced by carbon tetrachloride (CCl4) and to elucidate the possible molecular mechanism. MATERIALS AND METHODS: Mice were treated with BWD (low, medium and high dose), diammonium glycyrrhizinate or vehicle by oral gavage once daily, simultaneously intraperitoneal injected with a single dose of CCl4 (1 µl/g body weight) twice a week for consecutive 6 weeks. Next, all mice were sacrificed after fasted 12 h, and serums and liver tissues were harvested for analysis. The hepatic injury was detected by serum biomarker assay, including aspartate aminotransferase (AST) and alanine aminotransferase (ALT). The hepatic histology and collagen were illustrated by hematoxylin-eosin staining and Sirius red staining respectively. The antioxidant capacity of liver tissues was evaluated by the contents of superoxide dismutase (SOD) and malondialdehyde (MDA) in liver homogenization. The mRNA gene or protein expressions related to fibrosis, oxidative stress and inflammation molecules were performed by real-time quantitative PCR (RT-PCR) or Western-blot. RESULTS: BWD exhibited a good hepatic protection with ameliorating liver histological changes, decreasing serum AST and ALT contents, and reducing hepatic fibrosis with stimulation ECMs (such as Collagen1 and Collagen3) degradation. BWD inhibited hepatic stellate cells (HSCs) activation, promoted matrix metalloproteinase-2 (MMP2), MMP9, and MMP12 while suppressing tissue inhibitors of matrix metalloproteinase-1 (TIMP1) expression, and blocked traditional fibrosis TGF-ß1/Smad2/3 signal pathway. Moreover, BWD exhibited anti-inflammation effect proved by the reduction of liver Interleukin-1ß (IL-1ß), TNF-α, IL-11 mRNA levels and promoted anti-oxidation effects determined by inhibition of liver MDA and iNOS levels while promoting liver SOD and Mn-SOD. CONCLUSION: BWD ameliorates CCl4-induced CLI and liver fibrosis which is correlated to its blocking TGF-ß1/Smad2/3 signaling, anti-inflammation, and anti-oxidation effects. BWD, as a small traditional prescription, is a promising treatment for CLI and liver fibrosis through multiple pharmacological targets.

Bioengineered carina reconstruction using In-Vivo Bioreactor technique in human: proof of concept study.

BACKGROUNDS: Long-segment airway defect reconstruction, especially when carina is invaded, remains a challenge in clinical setting. Previous attempts at bioengineered carina reconstruction failed within 90 days due to delayed revascularization and recurrent infection. METHODS: To establish the feasibility of carina bioengineering use In-Vivo Bioreactor technique. Uncontrolled single-center cohort study including three patients with long-segment airway lesions invading carina. Radical resection of the lesions was performed using standard surgical techniques. After resection, In-Vivo Bioreactor airway reconstruction was performed using a nitinol stent wrapped in two layers of acellularized dermis matrix (ADM). Two Port-a-Cath catheters connected to two portable peristaltic pumps were inserted between the ADM layers. The implanted bioengineered airway was continuously perfused with an antibiotic solution via the pump system. Peripheral total nucleated cells (TNCs) were harvested and seeded into the airway substitute via a Port-a-Cath twice a week for 1 month. The patients were treated as a bioreactor for in situ regeneration of their own bioengineered airway substitute. RESULTS: Three patients were included in the study (mean age, 54.7 years). The first patient underwent 8 cm long trachea and carina reconstruction, the second patient 6 cm long trachea, carina and main bronchus reconstruction. The third patient right main bronchus and carina reconstruction. Major morbidity included gastric retention and pneumonia. All three patients survived till last follow-up and bronchoscopy follow-up showed well-vascularized regenerated tissue without leakage. CONCLUSIONS: In this uncontrolled study, In-Vivo Bioreactor technique demonstrated potential to be applied for long-segment trachea, carina and bronchi reconstruction. Further research is needed to assess efficacy and safety.

Impact of environmental factors on gastric cancer: A review of the scientific evidence, human prevention and adaptation.

Globally, gastric cancer (GC) ranks fifth in prevalence and third in fatalities, and shows a distinct geographical distribution in morbidity and mortality. Such a spatial pattern indicates that environmental factors could be an important contributor to GC. We reviewed a total of 135 relevant peer-reviewed articles and other literature published 1936-2019 to investigate the scientific evidence concerning the effects of environmental factors on GC worldwide. Environmental factors affect GC from the aspects of water, soil, air, radiation, and geology. Risk factors identified include water type, water pollution, water hardness, soil type, soil pollution, soil element content, climate change, air pollution, radiation, altitude, latitude, topography, and lithology; and most of them have an adverse impact on GC. Furthermore, we found that their effects followed five common rules: (1) the leading environmental factors that affect GC incidence and mortality vary by region, (2) the same environmental factors may have different effects on GC in different regions, (3) some different environmental factors have similar effects on GC in essence, (4) different environmental factors often interact to have combined or synergistic effects on GC, and (5) environmental factors can affect human factors to have an impact on GC. Environmental factors have a great impact on GC. Human beings may prevent GC by controlling carcinogenic factors, screening high-risk populations and providing symptomatic and rehabilitative treatments. Furthermore, adaptation measures are recommended to reduce GC risk on private and public levels. Future studies should transcend existing empirical studies to develop causal relationship models and focus on vulnerable population analysis.

TRPV1 Induced Apoptosis of Colorectal Cancer Cells by Activating Calcineurin-NFAT2-p53 Signaling Pathway.

BACKGROUND/AIMS: TRPV1 is a nonselective Ca2+ channel which has recently been observed in many cancers, while its effect on cell proliferation, apoptosis, metabolism, and cancer development in colorectal cancer (CRC) is still unclear. In this study, we hypothesized that TRPV1 is a tumor suppressor in CRC development as well as the underlying mechanism. METHODS: Immunohistochemistry assay was applied to detect the expression of TRPV1 protein in CRC tissues. HCT116 cell proliferation and apoptosis were measured by CCK-8 and flow cytometry, respectively. Cellular Ca2+ concentration was measured by Fluo-4/AM-based flow cytometer. Apoptosis-related proteins were measured by Western blotting. RESULTS: In this study, we found that TRPV1 expression was significantly decreased in CRC tissues, compared with CRC-adjacent tissues and normal tissues, respectively. Then, we found that the TRVP1 agonist capsaicin treatment inhibited CRC growth and induced apoptosis by activating P53. Subsequent mechanistic study revealed that the TRPV1 induced cytosolic Ca2+ influx to regulate cell apoptosis and p53 activation through calcineurin. CONCLUSIONS: This study suggests that TRPV1 served as a tumor suppressor in CRC and contributed to the development of novel therapy of CRC.