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BACKGROUND: Lupus nephritis (LN) is the most common and severe clinical manifestation of systemic lupus erythematosus (SLE). N6-methyladenosine (m6A) is a reversible RNA modification and has been implicated in various biological processes. However, the roles of m6A regulators in LN are not fully demonstrated. METHODS: We downloaded the kidney tissue transcriptome dataset of LN patients and normal controls from the GEO database and extracted the expression levels of m6A regulators. We constructed and compared Random Forest (RF) and Support Vector Machine (SVM) models, and subsequently selected featured genes to develop nomogram models. The m6A subtypes were identified based on significantly differentially expressed m6A regulators, and the m6A gene subtypes were identified based on m6A-associated differential genes, and the two m6A modification patterns were comprehensively evaluated. RESULTS: We obtained the GSE32591 and GSE112943 datasets from the GEO database, including 78 LN samples and 36 normal control samples. We extracted the expression levels of 20 m6A regulators. By RF analysis we identified 7 characteristic m6A regulators and constructed nomogramh models with these 7 genes. We identified two m6A subtypes based on these seven important m6A regulators, and the immune cell infiltration levels of the two subtype clusters were significantly different. We identified two more m6A gene subtypes based on m6A-associated DEGs. We calculated the m6A scores using the principal component analysis (PCA) algorithm and found that the m6A scores of m6A cluster A and gene cluster A were lower than those of m6A cluster B and gene cluster B. In addition, we found that the levels of inflammatory factors were also significantly different between m6A clusters and gene clusters. CONCLUSION: This study confirms that m6A regulators are involved in the LN process through different modes of action and provide new diagnostic and therapeutic targets for LN.
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Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Humanos , Nefrite Lúpica/genética , Adenina , AdenosinaRESUMO
INTRODUCTION: Youthful blood environment was shown to decelerate the aging process of the kidney and to attenuate senile renal fibrosis in a young-old parabiotic animal model; in addition, we identified a stem cell factor (SCF) that is closely linked with the process. This research was to investigate the effect of youthful blood environment on senile renal interstitial fibrosis and the role of SCF. METHODS: We bred SCF receptor c-Kit gene loss-of-function Wps/Wps mice and established a combination mice model that was subjected to unilateral ureteral obstructive (UUO) and parabiotic surgeries. Parabiotic mice were divided into isochronic parabiotic (young-young [Y-IP] and old-old [O-IP]) and heterochronic parabiotic (young-old [HP]) groups. UUO surgery was performed in one of the parabiotic pairs in the IP group (Y-IPuuo and O-IPuuo) and in the elderly mice in the HP group (O-HPuuo). In order to study the role of SCF/c-kit on renal interstitial fibrosis, UUO surgery was performed in wildtype (WT) and Wps/Wps mice. RESULTS: Fourteen days after UUO surgery, the kidney interstitial fibrosis area, kidney function, and the expressions of SCF/c-Kit, pNF-κB, and fibrosis-related proteins in the O-HPuuo group were significantly lower than those in the Ouuo and O-IPuuo groups. Compared with WT UUO mice, the expressions of pNF-κB and fibrosis-related proteins and the kidney function were all significantly decreased in Wps/Wps UUO mice. CONCLUSION: Youthful blood environment downregulated the expressions of SCF/c-Kit in elderly UUO mice and ameliorated UUO-induced kidney fibrosis and function loss.
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Nefropatias , Obstrução Ureteral , Camundongos , Animais , Fator de Células-Tronco/genética , Fator de Células-Tronco/metabolismo , Fator de Células-Tronco/farmacologia , Obstrução Ureteral/complicações , Obstrução Ureteral/metabolismo , Obstrução Ureteral/patologia , Nefropatias/genética , Nefropatias/metabolismo , Rim/patologia , Fibrose , Modelos Animais de DoençasRESUMO
PURPOSE: To investigate serum leptin levels in patients with type 2 diabetes mellitus (T2DM) and the relationship between leptin levels and T2DM complications and prevalence. METHODS: A total of 355 patients, 282 cases with T2DM and 73 normal controls, were recruited at 1st Medical Centre, Chinese PLA General Hospital (Beijing, China) between November 2013 and July 2014. Levels of serum leptin, biochemical markers and sexual hormones were measured, and clinical characteristics were retrieved through the electronic medical record system. RESULTS: Leptin levels in females were higher than that in males. Leptin levels in T2MD patients were positively correlated with body mass index, percent body fat, triglyceride, cystatin C homocysteine and salivary acid, and negatively correlated with glycosylated serum protein and glycosylated albumin levels. Leptin levels in males were positively correlated with systolic pressure and estradiol, and negatively correlated with testosterone and high density lipoprotein cholesterol. Sex (female) was positively correlated with the duration of disease. Leptin levels in T2DM patients with complications such as hypertension, diabetic nephropathy, diabetic peripheral neuropathy and coronary heart disease were higher than that in patients without such complications. Leptin levels in females with diabetic retinopathy and diabetic macroangiopathy were higher than that in patients without such complications, but there was no difference in males. CONCLUSIONS: Leptin has significant gender differences. Leptin levels are related to body mass index, percent body fat and sex hormone level in T2DM patients and may affect short-term blood glucose control in T2DM patients. Leptin levels are related to complications in patients with T2DM and affect the prevalence rates of complications.
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Diabetes Mellitus Tipo 2 , Retinopatia Diabética , Albuminas , Biomarcadores , Índice de Massa Corporal , HDL-Colesterol , Cistatina C , Diabetes Mellitus Tipo 2/complicações , Estradiol , Feminino , Homocisteína , Humanos , Leptina , Masculino , Poliésteres , Testosterona , TriglicerídeosRESUMO
BACKGROUD: MicroRNAs play important roles in the development and progression of many human diseases. mir-146a could significantly suppress the induction of proinflammatory cytokines IL-1ß, IL-6, TNF-α, NF-κB and chemokine MCP-1, which might play important roles in chronic pancreatitis. This study was conducted to evaluate the association between mir-146a rs2910164, a functional polymorphism in the pre-mir-146a, and chronic pancreatitis risk. METHODS: The rs2910164 genotypes were determined in 165 patients with chronic pancreatitis and 200 healthy controls who were frequency matched for age and gender. One single nucleotide polymorphism (rs2910164) was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RLFP). RESULTS: The frequency of individuals who carried [G] allele was significantly higher in cases (62.7%) than in controls (53.7%, p = 0.015), which resulted in a statistically significant pathogenic effect associated with this variant allele (OR: 1.448, CI: 1.076-1.950; p = 0.015). The GC and GG genotypes showed strong and significant increased risk for complication of chronic pancreatitis (OR = 3.668, 95%CI = 1.233-10.916, p = 0.019; OR = 5.667, 95%CI = 1.852-17.336, p = 0.002). The individuals carrying G allele confer a lower expression level of mature mir-146a. CONCLUSION: These findings suggest that the mir-146a rs2910164 may contribute to genetic susceptibility to chronic pancreatitis, and that mir-146a might be involved in chronic pancreatitis development.
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Citocinas/metabolismo , Regulação da Expressão Gênica/fisiologia , MicroRNAs/genética , Pancreatite Crônica/genética , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Idoso , Citocinas/genética , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Encarceramento do Tendão , Adulto JovemRESUMO
OBJECTIVES: To investigate the relationship between telomere length in peripheral blood white cells and cardiovascular function in a healthy, aging Han Chinese population. METHODS: In 2012, peripheral blood leukocytes were obtained from 139 healthy individuals in Beijing, China, and telomere restriction fragment (TRF) length was assayed using a digoxigenin-labeled hybridization probe in Southern blot assays. Indicators of cardiovascular function were also evaluated, including electrocardiograms (ECG), (RR, P, PR, QRS, ST and T intervals); blood pressure (BP), (SBP, DBP, PP, PPI); cardiovascular ultrasound (left ventricular ejection fraction, LVEF); mitral early and late diastolic peak flow velocity (MVE and MVA); and lipid indices (TC, TG, HDL, LDL, LCI). The relationships of these cardiovascular indictors to telomere length were evaluated. RESULTS: No correlations were found between telomere length and ECG, BP or lipid indices even after adjustment for age. Correlations were found between TFR length and some cardiovascular ultrasound indictors (D, MVEA, MVEDT, MVES, MVEL, MVEI, IMT), but these were not seen after adjusting for age. CONCLUSIONS: We did not find that leukocyte TFR length was associated with cardiovascular ultrasound indictors, ECG, BP, or lipid indices in this population of healthy Han Chinese individuals. Telomere length may serve as a genetic factor in biological aging.
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Envelhecimento/genética , Povo Asiático/genética , Leucócitos/citologia , Encurtamento do Telômero , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/fisiologia , Pressão Sanguínea , China , Colesterol/sangue , Ecocardiografia , Eletrocardiografia , Feminino , Humanos , Lipoproteínas HDL/sangue , Lipoproteínas LDL/sangue , Masculino , Pessoa de Meia-Idade , Valva Mitral/fisiopatologia , Volume Sistólico , Triglicerídeos/sangueRESUMO
A pulse forming network (PFN) is a significant component, contributing a lot to the overall dimension of pulse generators. In order to both reduce the size of PFN and improve the output waveform quality, this paper proposes a compact low-impedance PFN with a rotational symmetry structure. The PFN consists of four groups of Blumlein pulse forming units (PFUs) connected in parallel along the angular direction, and the spline curve structure is applied in each PFU, which achieves a higher space utilization rate. The theoretical maximum energy density of PFN is 6.6 J/L as the dimensions of PFN are φ500 × 138 mm. Field-circuit co-simulation is carried out based on the spatial model of PFN and the double switch modulation circuit to analyze the effects of switch delay time (time between main switch and steep discharge switch), as well as the output port position affecting the output pulse waveform. The results show that the PFN is appropriate to achieve quasi-square wave pulse modulation as the switch delay time is 290 ns with the output port positioned at the periphery. The verification experiments are also carried out. The results show that the PFN can generate a quasi-square wave pulse with an output voltage of 49.6 kV, a pulse width of 83 ns, and a peak power of 1 GW on a matched load. The output pulse exhibits a distinct flat top, with the fluctuation of the plateau being less than 3%.
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Flexible endoscopes are ideal instruments for visualizing and diagnosing the inner surfaces of organs via a minimally invasive incision. Calibrating a flexible endoscope is a troublesome yet inevitable process in image-based tools tracking. Aiming to simplify the calibration process, we propose an electromagnetic (EM)-tracked calibration approach that does not require any predefined poses of the EM sensor. A three-stage calibration protocol was presented in an extensor. First, the orientation of the endoscope tube was derived by conducting a circular rotation of the endoscope around its axis utilizing a pair of tightly bearing stands. Second, the 3D position of the endoscope tip was acquired by having the tip come into contact with a flat plane. Third, the pose model of the bending section was derived and transformed into the local coordinate system of the EM sensor attached to the endoscope handle. To assess the accuracy of the proposed calibration approach, two experiments were designed and performed. Experimental results indicate accuracies of 0.09 ± 0.06 deg and 0.03 ± 0.19 deg in the estimation of the endoscope tube orientation and 0.52 ± 0.29, 0.33 ± 0.11, and 0.29 ± 0.17 mm in the x, y, and z estimations of the endoscope tip position, respectively. The proposed approach is accurate and easy to operate, does not require the employment of custom calibration markers, and can be used not only in surgical training systems but also in the endoscopic-based tools tracking.
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Endoscópios , Endoscopia , Fenômenos Eletromagnéticos , Imagens de Fantasmas , Desenho de EquipamentoRESUMO
Background: Lupus nephritis (LN) is an autoimmune nephropathy associated with systemic lupus erythematosus. Circadian rhythms are involved in the development of several diseases, especially inflammation-related diseases, but their relationship with LN is unclear. Methods: This was an integrative bioinformatics study. The expression profile from glomeruli, tubular interstitium and renal whole tissue samples was used to assess the expression levels and relevance of circadian rhythm-related genes. To screen for circadian rhythm-related signatures, we employed the LASSO and SVM-RFE algorithms. A consensus clustering algorithm was used to classify LN patients into two circadian rhythm patterns (cluster A and cluster B). We made immune cell infiltration analysis. We used the weighted gene co-expression network analysis (WGCNA) algorithm to identify cluster-specific differentially expressed genes. Nephroseq data were used to observe the relationship between genes and renal function. Results: We found more significant differences in circadian rhythm-related gene expression in LN glomeruli compared with tubulointerstitial and whole-kidney tissues. We established a circadian rhythm-related signature consisting of eight genes that can easily distinguish LN from healthy individuals. Patients in cluster A were associated with B-cell-dominated immunity, whereas patients in cluster B were associated with T-cell-dominated immunity. As most of the patients with proliferative LN combined with membranous LN belonged to cluster B, patients in cluster B may have more severe renal pathology compared with patients in cluster A. Fifteen circadian rhythm-related genes associated with LN and LN typing were screened using the WGCNA algorithm, with COL1A2 and DOCK2 associated with renal prognosis. Conclusions: This study found that circadian rhythms are associated with the occurrence of LN, providing new ideas for the development of new LN treatment options from the perspective of circadian rhythms.
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PURPOSE: Papillary renal cell carcinoma (PRCC) is a common renal cell carcinoma. Recent studies have reported that ferroptosis is involved in the occurrence and development of tumors. Long non-coding RNAs can be used as independent biomarkers for the diagnosis and prognosis of a variety of tumors. METHODS: Gene expression profile and clinical information of patients with PRCC were obtained from The Cancer Genome Atlas (TCGA) database. Lasso penalized Cox regression and univariate Cox regression analysis were utilized for model construction. The Kaplan-Meier (K-M) and receiver operating characteristic (ROC) curves were plotted to validate the predictive effect of the prognostic signature. Immune cell infiltration and immune function were compared between the high-risk and low-risk groups. Chemotherapy sensitivity analysis was also performed. RESULTS: We constructed a prognostic signature consisting of 15 ferroptosis-related lncRNAs. The K-M curves validated the fine predictive accuracy of the prognostic signature (p < 0.001). The area under the curve (AUC) of the lncRNA signature was 0.930, exhibiting robust prognostic capacity. The high-risk group had a greater degree of immune cell infiltration than the low-risk group. Significant differences in inflammation promotion, parainflammation, and type I IFN response were noted between the low-risk and high-risk groups (p < 0.01). The expression levels of immune checkpoints including CD80, IDO1, and LAG3 were significantly higher in the high-risk group than in the low-risk group (p < 0.05). Chemotherapy sensitivity analysis showed that MNX1-AS1, ZFAS1, MIR4435-2HG, and ADAMTS9-AS1 were significantly correlated with the sensitivity of some chemotherapy drugs (p < 0.05). CONCLUSION: We demonstrated that a ferroptosis-related lncRNA prognostic signature could be a novel biomarker for PRCC.
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The development of pulsed power technology requires an electron beam accelerator with high output power and repetitive operation. A compact repetitive electron beam accelerator based on a pulse transformer and a pulse forming line of high permittivity liquid, as an essential type of one, has attracted extensive attention at the present time. In this paper, the development of a compact high energy-density electron beam accelerator, viz., HEART-20, based on a propylene carbonate (PC) forming line is presented. The accelerator HEART-20 consists of a primary energy source, a pulse transformer, a PC pulse forming line, a gas spark gap switch, and a vacuum diode. First, the operation principle of the accelerator is described. Second, the design of the accelerator's parameters is presented. A pulse transformer is developed for rapid charging of the PC-filled pulse forming line. The coupling coefficient is above 0.9, the voltage ratio is about 200, and the operation voltage is about 800 kV. Third, the energy storage characteristics of PC are investigated. The insulation characteristics of PC under positive charging voltage are found to perform better than those under negative charging voltage. The insulating strength of PC can be improved by pressurization. Finally, the development of the accelerator HEART-20 is presented. Across a vacuum diode load, it can steadily operate at a 20 GW output power in 5 Hz rep-rate. Moreover, it can drive a magnetically insulated line oscillator to produce about 2.0 GW microwave. These findings provide a good foundation for the development of a rep-rate intensive electron beam accelerator with promising applications for the future.
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Background: As genetic genetic factors are important in SLE, so screening causative genes is of great significance for the prediction and early prevention in people who may develop SLE. At present, it is very difficult to screen causative genes through pedigrees. The analytical method described herein can be used to screen causative genes for SLE and other complex diseases through pedigrees. Methods: For the first time, 24 lupus pedigrees were analyzed by combining whole exon sequencing and a variety of biological information tools including common-specific analysis, pVAAST (pedigree variant annotation, analysis and search tool), Exomiser (Combining phenotype and PPI associated analysis), and FARVAT (family based gene burden), and the causative genes of these families with lupus identified. Selected causative genes in peripheral-blood mononuclear cells (PBMCs) were evaluated by quantitative polymerase chain reaction (qPCR). Results: Cell division cycle 27 (CDC27) was screened out by common-specific analysis and Exomiser causative gene screening. FARVAT analysis on these families detected only CDC27 at the extremely significant level (false discovery rate <0.05) by three family-based burden analyses (BURDEN, CALPHA, and SKATO). QPCR was performed to detect for CDC27 in the PBMCs of the SLE family patients, sporadic lupus patients, and healthy people. Compared with the healthy control group, CDC27 expression was low in lupus patients (familial and sporadic patients) (P<0.05) and correlated with lupus activity indicators: negatively with C-reactive protein (CRP) (P<0.05) and erythrocyte sedimentation rate (P<0.05) and positively with complement C3 and C4 (P<0.05). The CDC27 expression was upregulated in PBMCs from SLE patients with reduced lupus activity after immunotherapy (P<0.05). Based on Receiver operating characteristic (ROC) curve analysis, the sensitivity and specificity of CDC27 in diagnosing SLE were 82.30% and 94.40%. Conclusion: The CDC27 gene, as found through WES combined with multiple analytical method may be a causative gene of lupus. CDC27 may serve as a marker for the diagnosis of SLE and is closely related to the lupus activity. We hope that the analytical method in this study will be used to screen causative genes for other diseases through small pedigrees, especially among non-close relatives.
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Subunidade Apc3 do Ciclossomo-Complexo Promotor de Anáfase , Lúpus Eritematoso Sistêmico , Subunidade Apc3 do Ciclossomo-Complexo Promotor de Anáfase/genética , Biomarcadores , Humanos , Leucócitos Mononucleares/metabolismo , Lúpus Eritematoso Sistêmico/genética , Curva ROC , Reação em Cadeia da Polimerase em Tempo RealRESUMO
In order to meet the application needs of gyromagnetic nonlinear transmission lines, a pulsed power generator is required to output short duration pulses with a fast rising edge in high repetitive-rate mode. In this paper, a low-impedance high-power pulsed generator based on the forming line with a built-in Tesla transformer is explored and developed. The generator includes a 14 Ω coaxial forming line, a SF6/N2 gas switch, and a resistive dummy load, which can steadily operate in 100 Hz mode and suits the needs above. The pulsed forming line adopts transformer oil as the insulation medium and has a large shell radius and short length to reduce impedance. It has been verified by CST simulation that a relatively high coupling coefficient (0.93) can be achieved when the length-radius ratio is 3.2. The maximum forming line charging voltage is -600 kV in single-shot mode, while the charging voltage is -520 kV in repetitive-rate mode. The output pulse duration is 13 ns with a 4 ns rising edge, and its amplitude for a 10 Ω load is -220 kV at a repetition rate of 100 Hz. The experimental results showed the feasibility of the low-impedance nanosecond periodically pulsed generator based on an oil forming line charged from the high-coupling Tesla transformer. These efforts expand the technical route of the pulse forming line with a built-in Tesla transformer and set a good foundation for its application in the future.
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PURPOSE: This study aimed to explore the underlying mechanisms of Shenyankangfu tablet (SYKFT) in the treatment of glomerulonephritis (GN) based on network pharmacology, machine learning, molecular docking, and experimental validation. METHODS: The active ingredients and potential targets of SYKFT were obtained through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, the targets of GN were obtained through GeneCards, etc. Perl and Cytoscape were used to construct an herb-active ingredient-target network. Then, the clusterProfiler package of R was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. We also used the STRING platform and Cytoscape to construct a protein-protein interaction (PPI) network, as well as the SwissTargetPrediction server to predict the target protein of the core active ingredient based on machine-learning model. Molecular-docking analysis was further performed using AutoDock Vina and Pymol. Finally, we verified the effect of SYKFT on GN in vivo. RESULTS: A total of 154 active ingredients and 255 targets in SYKFT were screened, and 135 targets were identified to be related to GN. GO enrichment analysis indicated that biological processes were primarily associated with oxidative stress and cell proliferation. KEGG pathway analysis showed that these targets were involved mostly in infection-related and GN-related pathways. PPI network analysis identified 13 core targets of SYKFT. Results of machine-learning model suggested that STAT3 and AKT1 may be the key target. Results of molecular docking suggested that the main active components of SYKFT can be combined with various target proteins. In vivo experiments confirmed that SYKFT may alleviate renal pathological injury by regulating core genes, thereby reducing urinary protein. CONCLUSION: This study demonstrated for the first time the multicomponent, multitarget, and multipathway characteristics of SYKFT for GN treatment.
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Antineoplásicos Fitogênicos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Glomerulonefrite/tratamento farmacológico , Aprendizado de Máquina , Simulação de Acoplamento Molecular , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Glomerulonefrite/metabolismo , Glomerulonefrite/patologia , Humanos , Medicina Tradicional Chinesa , Estresse Oxidativo/efeitos dos fármacos , ComprimidosRESUMO
Receptor Interacting Serine/Threonine Kinase 2 (RIPK2) is located on chromosome 8q21 and encodes a protein containing a C-terminal caspase activation and recruitment domain (CARD), which is a component of signaling complexes in both the innate and adaptive immune pathways. To estimate the value of RIPK2 in evaluating the prognosis and guiding the targeted therapy for patients with kidney renal clear cell carcinoma (KIRC), we analyzed total 526 KIRC samples from The Cancer Genome Atlas (TCGA) database. Our result showed that RIPK2 was upregulated in KIRC tumor samples compared with normal samples. Cox regression was performed to calculate the hazard ratio of RIPK2 expression as an unfavorable prognosis feature for overall survival. Moreover, RIPK2 expression was positively correlated to the high-risk clinical stage, and metastasis features. The upregulation of RIPK2 was strongly correlated with various immune signaling pathway dysregulations as well as immune phenotypes changes in KIRC patient's cohort. In addition, inhibition of RIPK2 activity by either shRNA-mediated knockdown or inhibitor significantly reduced kidney cancer cell viability, trans-migration in vitro, and impaired tumor growth in vivo. In conclusion, elevated RIPK2 expression indicates a worse prognosis for KIRC patients and could serve as a potential prognostic biomarker and therapeutic target in kidney cancer.
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Carcinoma de Células Renais/metabolismo , Neoplasias Renais/metabolismo , Rim/patologia , Proteína Serina-Treonina Quinase 2 de Interação com Receptor/metabolismo , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Bases de Dados Genéticas , Regulação Neoplásica da Expressão Gênica , Humanos , Rim/metabolismo , Neoplasias Renais/genética , Neoplasias Renais/patologia , Prognóstico , Transdução de Sinais/fisiologiaRESUMO
Many studies have shown that the space environment plays a pivotal role in changing the characteristics of conditional pathogens, especially their pathogenicity and virulence. However, Stenotrophomonas maltophilia, a type of conditional pathogen that has shown to a gradual increase in clinical morbidity in recent years, has rarely been reported for its impact in space. In this study, S. maltophilia was exposed to a simulated microgravity (SMG) environment in high-aspect ratio rotating-wall vessel bioreactors for 14days, while the control group was exposed to the same bioreactors in a normal gravity (NG) environment. Then, combined phenotypic, genomic, transcriptomic, and proteomic analyses were conducted to compare the influence of the SMG and NG on S. maltophilia. The results showed that S. maltophilia in simulated microgravity displayed an increased growth rate, enhanced biofilm formation ability, increased swimming motility, and metabolic alterations compared with those of S. maltophilia in normal gravity and the original strain of S. maltophilia. Clusters of Orthologous Groups (COG) annotation analysis indicated that the increased growth rate might be related to the upregulation of differentially expressed genes (DEGs) involved in energy metabolism and conversion, secondary metabolite biosynthesis, transport and catabolism, intracellular trafficking, secretion, and vesicular transport. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed that the increased motility might be associated the upregulation of differentially expressed proteins (DEPs) involved in locomotion, localization, biological adhesion, and binding, in accordance with the upregulated DEGs in cell motility according to COG classification, including pilP, pilM, flgE, flgG, and ronN. Additionally, the increased biofilm formation ability might be associated with the upregulation of DEPs involved in biofilm formation, the bacterial secretion system, biological adhesion, and cell adhesion, which were shown to be regulated by the differentially expressed genes (chpB, chpC, rpoN, pilA, pilG, pilH, and pilJ) through the integration of transcriptomic and proteomic analyses. These results suggested that simulated microgravity might increase the level of corresponding functional proteins by upregulating related genes to alter physiological characteristics and modulate growth rate, motility, biofilm formation, and metabolism. In conclusion, this study is the first general analysis of the phenotypic, genomic, transcriptomic, and proteomic changes in S. maltophilia under simulated microgravity and provides some suggestions for future studies of space microbiology.
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BACKGROUND: GPRIN1 may be a novel tumor regulator, but its role and mechanism in tumors are still unclear. METHODS: First, a pan-cancer correlation analysis was conducted on the expression and prognosis of GPRIN1 based on the data downloaded from The Cancer Genome Atlas (TCGA) database. Second, the Starbase database was used to predict the upstream miRNAs and lncRNAs of GPRIN1, and the expression analysis, survival analysis, and correlation analysis were performed to screen the microRNA (miRNAs)/long non-coding RNAs (lncRNAs) that had a correlation with kidney renal papillary cell carcinoma (KIRP) or lung adenocarcinoma (LUAD). Third, the CIBERSORT algorithm was employed to calculate the proportion of various types of immune cells, and then the R packages were used for evaluating the relation between GPRIN1 expression and tumor immune cell infiltration as well as between GPRIN1 and the immune cell biomarker. Finally, the correlation analysis was made on GPRIN1 and immune checkpoints (CD274, CTLA4, and PDCD1). RESULTS: The pan-cancer analysis suggested that GPRIN1 was up-expressed in KIRP and LUAD, and it correlated with poor prognosis. LINC00894/MMP25-AS1/SNHG1/LINC02298/MIR193BHG-miR-140-3p was likely to be the most promising upstream regulation pathway of GPRIN1. Upexpression of LINC00894/MMP25-AS1/SNHG1/LINC02298/MIR193BHG and downexpression of miR-140-3p were found relevant with poor outcomes of KIRP and LUAD. GPRIN1 expression was significantly correlated with tumor immune cell infiltration, immune cell biomarkers, and immune checkpoints. CONCLUSIONS: The competitive endogenous (ceRNA) of miR-140-3p-GPRIN1 axis and its upstream lncRNAs are closely related to KIRP and LUAD, and might affect the prognosis and therapeutic effect of KIRP and LUAD.
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Adenocarcinoma de Pulmão/genética , Carcinoma de Células Renais/genética , Neoplasias Renais/genética , Neoplasias Pulmonares/genética , MicroRNAs/genética , Proteínas do Tecido Nervoso/genética , Receptores de N-Metil-D-Aspartato/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , RNA Longo não Codificante/genéticaRESUMO
BACKGROUND: The rapid outbreak of coronavirus disease 2019 (COVID-19) is a major health concern, in response to which widespread risk factor research is being carried out. OBJECTIVE: To discover how physical activity and lifestyle affect the epidemic as well as the disease severity and prognosis of COVID-19 patients. METHODS: This multicenter, retrospective cohort study included 203 adults infected with COVID-19 and 228 uninfected adults in three Chinese provinces, with 164 (80.7%) of the infected participants and 188 (82.5%) of the uninfected participants answering a doctor-administered telephone questionnaire on lifestyle. The binary logistic regression model and the ordinal logit model were used to observe relevance. RESULTS: Comparing sick and non-sick patients, we found that irregular exercise (P=0.004), sedentary lifestyle (P=0.010), and overexertion (P<0.001) may be associated with the susceptibility to COVID-19. In symptomatic patients, using the recommended status as a reference, risk of severe infection increased with decreased sleep status, being 6.729 (95% CI=2.138-21.181) times higher for potentially appropriate sleep (P=0.001) and peaking at 8.612 (95% CI=1.913-38.760) times higher for lack of sleep (P=0.005). Reduction in average daily sleep time significantly increased the likely severity (P=0.002). DISCUSSION: Through further examination of damage of external lung organs, we found that lack of sleep affected not only disease severity but also prognosis. Based on these findings, the public should prioritize a healthy lifestyle and get adequate sleep in response to the outbreak. The study of life habits may bring new ideas for the prevention and treatment of COVID-19.
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China launched the Tiangong-2 space laboratory in 2016 and will eventually build a basic space station by the early 2020s. These spaceflight missions require astronauts to stay on the space station for more than 6 months, and they inevitably carry microbes into the space environment. It is known that the space environment affects microbial behavior, including growth rate, biofilm formation, virulence, drug resistance, and metabolism. However, the mechanisms of these alternations have not been fully elucidated. Therefore, it is beneficial to monitor microorganisms for preventing infections among astronauts in a space environment. Salmonella enteritidis is a Gram-negative bacterial pathogen that commonly causes acute gastroenteritis in humans. In this study, to better understand the effects of the space environment on S. enteritidis, a S. enteritidis strain was taken into space by the Shenzhou-11 spacecraft from 17 October 2016 to 18 November 2016, and a ground simulation with similar temperature conditions was simultaneously performed as a control. It was found that the flight strain displayed an increased growth rate, enhanced amikacin resistance, and some metabolism alterations compared with the ground strain. Enrichment analysis of proteome revealed that the increased growth rate might be associated with differentially expressed proteins involved in transmembrane transport and energy production and conversion assembly. A combined transcriptome and proteome analysis showed that the amikacin resistance was due to the downregulation of the oppA gene and oligopeptide transporter protein OppA. In conclusion, this study is the first systematic analysis of the phenotypic, genomic, transcriptomic, and proteomic variations in S. enteritidis during spaceflight and will provide beneficial insights for future studies on space microbiology.
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Amicacina/farmacologia , Antibacterianos/farmacologia , Farmacorresistência Bacteriana , Salmonella enteritidis/efeitos dos fármacos , Salmonella enteritidis/crescimento & desenvolvimento , Astronave , Ausência de Peso , Proteínas de Bactérias/biossíntese , China , Regulação para Baixo , Microbiologia Ambiental , Regulação Bacteriana da Expressão Gênica , Humanos , Lipoproteínas/biossíntese , Proteoma , Salmonella enteritidis/química , Salmonella enteritidis/genética , TranscriptomaRESUMO
Many studies have shown that the space environment can affect bacteria by causing a range of mutations. However, to date, few studies have explored the effects of long-term spaceflight (>1 month) on bacteria. In this study, a Staphylococcus warneri strain that was isolated from the Shenzhou-10 spacecraft and had experienced a spaceflight (15 days) was carried into space again. After a 64-day flight, combined phenotypic, genomic, transcriptomic, and proteomic analyses were performed to compare the influence of the two spaceflights on this bacterium. Compared with short-term spaceflight, long-term spaceflight increased the biofilm formation ability of S. warneri and the cell wall resistance to external environmental stress but reduced the sensitivity to chemical stimulation. Further analysis showed that these changes might be associated with the significantly upregulated gene expression of the phosphotransferase system, which regulates the metabolism of sugars, including glucose, mannose, fructose, and cellobiose. The mutation of S. warneri caused by the 15-day spaceflight was limited at the phenotype and gene level after cultivation on the ground. After 79 days of spaceflight, significant changes in S. warneri were observed. The phosphotransferase system of S. warneri was upregulated by long-term space stimulation, which resulted in a series of changes in the cell wall, biofilm, and chemical sensitivity, thus enhancing the resistance and adaptability of the bacterium to the external environment.
Assuntos
Metabolismo Energético , Ambientes Extremos , Voo Espacial , Staphylococcus/fisiologia , Antibacterianos/farmacologia , Biofilmes , Biologia Computacional/métodos , Farmacorresistência Bacteriana , Regulação Bacteriana da Expressão Gênica , Genoma Bacteriano , Genômica/métodos , Anotação de Sequência Molecular , Fenótipo , Proteômica/métodos , Staphylococcus/efeitos dos fármacos , Staphylococcus/ultraestrutura , Transcriptoma , Ausência de PesoRESUMO
China has prepared for construction of a space station by the early 2020s. The mission will require astronauts to stay on the space station for at least 180 days. Microbes isolated from the International Space Station (ISS) have shown profound resistance to clinical antibiotics and environmental stresses. Previous studies have demonstrated that the space environment could affect microbial survival, growth, virulence, biofilms, metabolism, as well as their antibiotic-resistant phenotypes. Furthermore, several studies have reported that astronauts experience a decline in their immunity during long-duration spaceflights. Monitoring microbiomes in the ISS or the spacecraft will be beneficial for the prevention of infection among the astronauts during spaceflight. The development of a manned space program worldwide not only provides an opportunity to investigate the impact of this extreme environment on opportunistic pathogenic microbes, but also offers a unique platform to detect mutations in pathogenic bacteria. Various microorganisms have been carried on a spacecraft for academic purposes. Acinetobacter baumannii is a common multidrug-resistant bacterium often prevalent in hospitals. Variations in the ability to cope with environmental hazards increase the chances of microbial survival. Our study aimed to compare phenotypic variations and analyze genomic and transcriptomic variations in A. baumannii among three different groups: SS1 (33 days on the Shenzhou 11 spacecraft), GS1 (ground control), and Aba (reference strain). Consequently, the biofilm formation ability of the SS1 strain decreased after 33 days of spaceflight. Furthermore, high-throughput sequencing revealed that some differentially expressed genes were downregulated in the SS1 strain compared with those in the GS1 strain. In conclusion, this present study provides insights into the environmental adaptation of A. baumannii and might be useful for understanding changes in the opportunistic pathogenic microbes on our spacecraft and on China's future ISS.