Analysis of necroptosis-related prognostic genes and immune infiltration in idiopathic pulmonary fibrosis

BackgroundIPF is an undetermined, progressive lung disease. Necroptosis is a type of programmed apoptosis, which involved in the pathogenesis of lung diseases like COPD and ARDS. However, necroptosis in IPF have not been adequately studied. This study aimed to investigate the necroptosis in IPF and the relationship between necroptosis and immune infiltration, to construct a prognostic prediction model of IPF based on necroptosis-related genes.MethodsGSE110147 was downloaded from the GEO database and utilized to analyze the expression of necroptosis-related differentially expressed genes (NRDEGs). Then NRDEGs were used to construct protein-protein interaction (PPI) networks in the STRING database, and Cytoscape software was used to identify and visualize hub genes. Necroptosis-related prognosticgenes were explored in GSE70866, and a prognostic prediction model was constructed. The ImmuCellAI algorithm was utilized to analyze the landscape of immune infiltration in GSE110147. The single-cell RNA sequencing dataset GSE122960 was used to explore the association between necroptosis and type II alveolar epithelial cells (AT II) in IPF. The GSE213001 and GSE93606 were used for external validation. The expression of prognostic genes was quantified using RT-qPCRin the IPF A549 cell model, and was further verified by western blotting in the bleomycin-induced pulmonary fibrosis mouse model.ResultsIt was observed that necroptosis-related signaling pathways were abundantly enriched in IPF. 29 NRDEGs were screened, of which 12 showed consistent expression trends in GSE213001. Spearman correlation analysis showed that the expression of NRDEGs was positively correlated with the infiltration of proinflammatory immune cells, and negatively correlated with the infiltration of anti-inflammatory immune cells. NRDEGs, including MLKL, were highly expressed in AT II of fibrotic lung tissue. A necroptosis-related prediction model was constructed based on 4 NRDEGsby the cox stepwise regression. In the validation dataset GSE93606, the prognostic prediction model showed good applicability. The verification results of RT-qPCR and western blotting showed the reliability of most of the conclusions.ConclusionsThis study revealed that necroptosis existed in IPF and might occur in AT II. Necroptosis was associated with immune infiltration, suggesting that necroptosis of AT II might involve in IPF by activating immune infiltration and immune response

RP-HPLC DETERMINATION OF GINSENOSIDES RG1 AND RB1 IN PANAX GINSENG FRUITS

Background: At present, there has been a lot of research at home and abroad on the roots, stems and leaves of Panax Ginseng as well as their extracts, but the fruits of Panax Ginseng have been relatively little studied. Materials and Methods: To establish a method for determination of ginsenosides Rg1 and Rb1 in Panax Ginseng fruits. RP-HPLC method is adopted, column used is a ZOBAX SB-C18 column (4.6 mm × 250 mnl, 5 μm), mobile phase A is water, and B is acetonitrile, gradient elution conditions are: 0~20 min (A:B 20:80), 20~60 min (A:B 20~35: 80~65); and detection wavelength 203 nm. Results: Ginsenosides Rgl and Rb1 have good linear relationships within the ranges of 1.04~10.40 μg and 0.50~5.00 μg, respectively, and r is 0.9998 and 0.9997; reproducibility and recovery of the method are both in line with requirements. Conclusion: The method established is simple, accurate and fast, which is suitable for the simultaneous determination of ginsenosides Rg1 and Rb1 in Panax Ginseng fruits

Global attractivity of an almost periodic N-species nonlinear ecological competitive model

AbstractBy using comparison theorem and constructing suitable Lyapunov functional, we study the following almost periodic nonlinear N-species competitive Lotka–Volterra model:x˙i(t)=xi(t)[ri(t)−∑j=1Naij(t)xjαij(t)−∑j=1Nbij(t)xjαij(t−τij(t))−∑j=1Ncij(t)xiαii(t)xjαij(t)]. A set of sufficient conditions is obtained for the existence and global attractivity of a unique positive almost periodic solution of the above model. As applications, some special competition models are studied again, our new results improve and generalize former results. Examples and their simulations show the feasibility of our main results

Interfacial mechanical properties of graphene on randomly rough PET substrate surface: A molecular dynamics study

In this work, molecular dynamics (MD) simulations are performed to create a series of polyethylene terephthalate (PET) substrates with random roughness, and the morphological characteristics and interfacial bonding of graphene on the real rough PET surface are first simulated. The results show that the interfacial mechanical behavior of graphene freely adhered to the PET roughness is influenced by the surface profile. Besides causing the non-conformal contact, the rough surface hinders the propagation of bending waves from the graphene corner regions during the adhesion and weakens their overlap. The increased surface roughness weakens interfacial adhesion and inhibits interfacial sliding, leading to the formation of larger morphological defects such as wrinkles. Furthermore, the measurement of the interfacial adhesion energy of graphene/PET substrate is achieved by the shaft loaded blister test (SLBT), which for the first time is used to simulate the interfacial debonding of graphene on rough PET surfaces. For low surface roughness, interfacial adhesion dominates the debonding behavior and the blister boundary preferentially extends along the interfacial defect area. For high surface roughness, the increasingly serious non-conformal contact makes the blister more likely to instability and enter the stage where normal and shear interactions are coupled

Systemic Inflammatory Response Index (SIRI) is associated with all-cause mortality and cardiovascular mortality in population with chronic kidney disease: evidence from NHANES (2001–2018)

ObjectiveTo examine the correlation between SIRI and the probability of cardiovascular mortality as well as all-cause mortality in individuals with chronic kidney disease.MethodsA cohort of 3,262 participants from the US National Health and Nutrition Examination Survey (NHANES) database were included in the study. We categorized participants into five groups based on the stage of chronic kidney disease. A weighted Cox regression model was applied to assess the relationship between SIRI and mortality. Subgroup analyses, Kaplan–Meier survival curves, and ROC curves were conducted. Additionally, restricted cubic spline analysis was employed to elucidate the detailed association between SIRI and hazard ratio (HR).ResultsThis study included a cohort of 3,262 individuals, of whom 1,535 were male (weighted proportion: 42%), and 2,216 were aged 60 or above (weighted proportion: 59%). Following adjustments for covariates like age, sex, race, and education, elevated SIRI remained a significant independent risk factor for cardiovascular mortality (HR=2.50, 95%CI: 1.62-3.84, p<0.001) and all-cause mortality (HR=3.02, 95%CI: 2.03-4.51, p<0.001) in CKD patients. The restricted cubic spline analysis indicated a nonlinear relationship between SIRI and cardiovascular mortality, with SIRI>1.2 identified as an independent risk factor for cardiovascular mortality in CKD patients.ConclusionHeightened SIRI independently poses a risk for both all-cause and cardiovascular mortality in chronic kidney disease patients, with potentially heightened significance in the early stages (Stage I to Stage III) of chronic kidney disease

Targeting MCL-1 sensitizes human esophageal squamous cell carcinoma cells to cisplatin-induced apoptosis

Abstract Background Esophageal squamous cell carcinoma (ESCC) is one of the most lethal malignancies in China and is an exceptionally drug-resistant tumor with a 5-year survival rate less than 15%. Cisplatin is the most commonly used conventional chemotherapeutic drug for the treatment of ESCC, but some patients have a poor response to cisplatin-based chemotherapy. New strategies that could enhance chemosensitivity to cisplatin are needed. Methods We used reverse transcription-RCR (RT-PCR), immunoblot, immunohistochemical (IHC) staining, anchorage-dependent and -independent growth assays, co-immunoprecipitation (Co-IP) assay, RNA interference and in vivo tumor growth assay to study the expression of MCL-1 in ESCCs and the response of ESCC cells to cisplatin. Results The present study showed that MCL-1 expression was significantly increased in ESCC tissues compared to normal adjacent tissues and was associated with depth of invasion and lymph node metastasis. Knockdown of MCL-1 produced significant chemosensitization to cisplatin in association with caspase-3 activation and PARP cleavage in KYSE150 and KYSE510 cells. The selective MCL-1 inhibitor UMI-77 caused dissociation of MCL-1 from the proapoptotic protein BAX and BAK, and enhanced KYSE150 and KYSE510 cells to cisplatin-induced apoptosis accompanied by caspase-3 activation and PARP cleavage. Conclusions The current study suggests that MCL-1 contributes to the development of ESCC and is a promising therapeutic target for chemosensitization of ESCC cells to cisplatin. This might provide a scientific basis for developing effective approaches to treat the subset of ESCCs patients with MCL-1 overexpression

DataSheet_1_Systemic Inflammatory Response Index (SIRI) is associated with all-cause mortality and cardiovascular mortality in population with chronic kidney disease: evidence from NHANES (2001–2018).zip

ObjectiveTo examine the correlation between SIRI and the probability of cardiovascular mortality as well as all-cause mortality in individuals with chronic kidney disease.MethodsA cohort of 3,262 participants from the US National Health and Nutrition Examination Survey (NHANES) database were included in the study. We categorized participants into five groups based on the stage of chronic kidney disease. A weighted Cox regression model was applied to assess the relationship between SIRI and mortality. Subgroup analyses, Kaplan–Meier survival curves, and ROC curves were conducted. Additionally, restricted cubic spline analysis was employed to elucidate the detailed association between SIRI and hazard ratio (HR).ResultsThis study included a cohort of 3,262 individuals, of whom 1,535 were male (weighted proportion: 42%), and 2,216 were aged 60 or above (weighted proportion: 59%). Following adjustments for covariates like age, sex, race, and education, elevated SIRI remained a significant independent risk factor for cardiovascular mortality (HR=2.50, 95%CI: 1.62-3.84, p1.2 identified as an independent risk factor for cardiovascular mortality in CKD patients.ConclusionHeightened SIRI independently poses a risk for both all-cause and cardiovascular mortality in chronic kidney disease patients, with potentially heightened significance in the early stages (Stage I to Stage III) of chronic kidney disease.</p