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1.
Neural Regen Res ; 18(3): 568-576, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36018179

RESUMO

Recent studies have shown that chlorogenic acid (CGA), which is present in coffee, has protective effects on the nervous system. However, its role in neonatal hypoxic-ischemic brain injury remains unclear. In this study, we established a newborn mouse model of hypoxic-ischemic brain injury using a modified Rice-Vannucci method and performed intraperitoneal injection of CGA. We found that CGA intervention effectively reduced the volume of cerebral infarct, alleviated cerebral edema, restored brain tissue structure after injury, and promoted axon growth in injured brain tissue. Moreover, CGA pretreatment alleviated oxygen-glucose deprivation damage of primary neurons and promoted neuron survival. In addition, changes in ferroptosis-related proteins caused by hypoxic-ischemic brain injury were partially reversed by CGA. Furthermore, CGA intervention upregulated the expression of the key ferroptosis factor glutathione peroxidase 4 and its upstream glutamate/cystine antiporter related factors SLC7A11 and SLC3A2. In summary, our findings reveal that CGA alleviates hypoxic-ischemic brain injury in neonatal mice by reducing ferroptosis, providing new ideas for the treatment of neonatal hypoxic-ischemic brain injury.

2.
Transl Lung Cancer Res ; 11(8): 1713-1721, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36090644

RESUMO

Background: Despite significant recent advances in characterizing the molecular pathogenesis of undifferentiated small round cell sarcoma (USRCS), rare cases without reported gene alterations remain unclassified. To date, the efficacy and prognostic biomarker of immunotherapy in the treatment of unresectable USRCS has not been demonstrated, especially when these cases occurring in uncommon thoracic visceral organs with a novel gene fusion. Case Description: We report a case of locally advanced and unresectable USRCS of the lung (cT4N1M0) with SDCCAG8-AKT3 fusion identified by RNA-based next-generation sequencing (NGS). He initially admitted to our hospital chiefly complained of cough and dyspnea without any intervention. Imaging examinations, positron emission tomography/computed tomography (PET/CT), tumor biopsy, and a series of molecular tests based on tumor specimens were conducted for diagnosis. The molecular tests supplied more information delineating the case's molecular characteristics including PMS2 mutation, CD274 amplification, high tumor mutational burden (TMB-H), and high microsatellite instability (MSI-H). Multiple immunofluorescence (mIF) staining further revealed a specific immune-microenvironment phenotype with a 100% programmed death ligand 1 (PD-L1) expression and type II tumor immunity in the microenvironment (type II TIME) of this case. This 31-year-old non-smoking male received vincristine sulfate, dactinomycin, and cyclophosphamide (VAC) regimen chemotherapy combined with pembrolizumab and sequential radiotherapy. He had maintained a partial response (PR) according to response evaluation criteria in solid tumors (RECIST) 1.1 and a good quality of life for almost 14 months except for mild loss of appetite and hair loss after chemotherapy to the latest follow-up date. Conclusions: Our study showed a rare case of lung USRCS harboring a novel SDCCAG8-AKT3 fusion. And we indicated that a comprehensive treatment including the combination of systemic VAC chemotherapy and anti-programmed cell death protein 1 (PD-1) immunotherapy, and sequential radiotherapy could be considered for similar cases, prophylactic managements of chemotherapy-related myelosuppression and urotoxicity should be administrated along with chemotherapy as well. Tumor immune microenvironment analysis and gene sequencing are recommended to obtain more prognostic biomarkers in addition to routine pathologic examinations in diagnosis and treatment of USRCS.

3.
Abdom Radiol (NY) ; 2022 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-36121457

RESUMO

PURPOSE: Ultrasound (US)-guided thermal ablation (TA) may cause major biliary complications, particularly in patients with malignant liver tumors (MLTs) adjacent to the bile ducts. Fusion imaging (FI), is postulated to reduce complication rate; however, there is a lack of clinical data to support this theory. Thus, the aim of our study was to evaluate the safety and efficacy of FI for TA of MLTs proximal to the bile ducts. METHODS: A retrospective single-center review was conducted on a total of 289 patients with 316 MLTs adjacent to the bile ducts. The patients were divided into two groups based on whether FI was used in the ablation procedures. The choice of the FI-assisted procedure always depends on different operation periods and whether registrations will succeed. The baseline demographics and outcomes of these patients were compared. The efficacy was determined at the 1-month follow-up using contrast-enhanced computed tomography/magnetic resonance. Biliary complications and local tumor progression were subsequently followed-up every 3-6 months. The last follow-up visit was before August 30, 2019. RESULTS: Among the included tumors, the incidence rate of major biliary complications after ablation in the FI group was 1.6%, which was significantly lower than that in the non-FI group (7.9%, p = 0.005). There was no significant difference in the efficacy rates of the techniques [99.5% (185/186) versus 98.4% (123/125), p = 0.56] or local progression rates [3.8% (7/185) versus 5.7% (7/123), p = 0.61] between the FI and non-FI groups. CONCLUSION: FI for US-guided TA could be a noninvasive means to decrease major biliary complications. Trial registration number and date of registration: retrospectively registered.

4.
Water Res ; 225: 119117, 2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36126427

RESUMO

The microplastics in nature water are important for the environmental fate of nitrous oxide (N2O). This study investigated the influence and microbial mechanism of microplastic abundance to the N2O flux in typical inflow rivers of Taihu lake. The microplastic abundance were in a range of 160-700 particles/m3 surface water, and 514-3018 particles/kg dry sediment. The highest percentage of microplastic color was transparent, significantly higher than other color (p<0.0001) in both surface water and sediment. The dominant microplastic size was 500-5000 µm in surface water, while size lower than 1000 µm was dominant in sediment. The microplastic abundance in sediment was negatively correlated with the concentration of suspended sediments (SPS) (p<0.05), Chl-a (p<0.05), NH4+-N (p<0.05) and TP (p<0.01) in inflow river surface water. The dissolved N2O concentration were 45.71-132.42 nmol/L, and the N2O fluxes were 29.85-276.60 µmol/m2/d. The dissolved N2O concentration was significantly correlated with the nirK abundance and nirK/nosZI ratio negatively (p<0.05), revealed that sediment nirK-type denitrification was the main driver of dissolved N2O. Meanwhile, the N2O flux (water-air interface) was significantly correlated with nosZI, napA, narG and nirS negatively, implied that nitrification and denitrification interaction in sediment is the main influence factor. The denitrification process in sediment was the main driven factor of N2O releasing. Mantel-test shows that microplastic abundance in surface water was significantly correlated with nitrification (p = 0.001∼0.01) and denitrification (p = 0.01∼0.05) genera in water. The dominant denitrification microorganism was Dechloromonas in sediment and Flavobacterium in surface water. These results provided new insight into the fact that plastisphere which comprises microbial community on microplastic could affect the N2O emission in aquatic system.

5.
J Agric Food Chem ; 2022 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-36129378

RESUMO

Usually, the recognition of sex pheromone signals is restricted to adult moths. Here, our behavioral assay showed that fourth-instar Spodoptera litura larvae are attracted to cabbage laced with minor sex pheromones Z9,E12-tetradecadienyl acetate (Z9,E12-14:Ac) or Z9-tetradecenyl acetate (Z9-14:Ac). Seven odorant-binding proteins (OBPs) were upregulated after exposure to Z9,E12-14:Ac, and one OBP was upregulated after exposure to Z9-14:Ac. Fluorescence competitive binding assays showed that GOBP2 and OBP7 bound to sex pheromones. RNAi treatment significantly downregulated GOBP2 and OBP7 mRNA expression by 70.37 and 63.27%, respectively. The siOBP-treated larvae were not attracted to Z9,E12-14:Ac or Z9-14:Ac, and the corresponding preference indices were significantly lower than those in siGFP-treated larvae. Therefore, we concluded that GOBP2 and OBP7 are involved in the attraction of S. litura larvae to food containing Z9,E12-14:Ac and Z9-14:Ac. These results provide an important basis for exploring the olfactory mechanisms underlying sex pheromone attraction in moth larvae.

6.
Anal Chem ; 2022 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-36122350

RESUMO

Isolating and obtaining sufficient numbers of cancer stem-like cells from bulk cancer cells for cancer stem cells (CSCs)-specific drug evaluation remain challenging due to the rarity and their relative instability in culture. Here, we report a label-free microfluidic method to isolate low-adhesion cells (LACs) with stem properties based on a cell adhesion microfluidic chip (CA-chip) using cell adhesion differences. In this chip, suspended cells are driven by hydrodynamic force to flow through microchannels coated with basement membrane extract (BME). By manipulating the hydrodynamic force, heterogeneous tumor cells can be separated into different adhesive cell subpopulations. LACs flow out first and are collected from the outlet, while high-adhesion cells (HACs) are captured into the chip and can be recovered by washing with a cell dissociation buffer. We found that the isolated LACs showed cancer stem-like properties, which were further utilized as rare CSC candidates to evaluate CSC-specific drugs. The results showed that only CSC-specific drugs had complete inhibition of sphere formation, demonstrating the feasibility of evaluating the specificity of CSC drugs. The label-free method is highly versatile as it employs cell adhesion as a unique phenotypic marker to effectively isolate cancer stem-like cells and offers an opportunity to evaluate on the large scale CSC-specific drugs, making it applicable to the analysis of certain cancer types, especially CSC-specific biomarkers that have not been identified.

7.
Front Microbiol ; 13: 990091, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36118193

RESUMO

Antimicrobial resistance (AMR) is a global concern threatening public health. Developing novel antibiotics is one of the effective strategies to tackle AMR. Serine/threonine kinases (STKs) have been recently shown to play critical roles in the physiology and pathogenesis of several important bacterial pathogens which are regarded as a promising antimicrobial drug target. We previously reported the roles of STK in the regulation of bacterial cell division, metabolism, and pathogenesis in Streptococcus suis, an important zoonotic bacterial pathogen. In this study, we firstly identified the Thr167 and Ser175 residues in the activation loop of S. suis STK (ssSTK) as the kinase autophosphorylation sites. Phenotyping results demonstrated that the autophosphorylation deficient strain resembled the stk deletion strain showing essentiality for bacterial growth in minimal medium, abnormal morphology, and decreased virulence when compared with the wild-type S. suis SC19 strain. Based on these findings, we established an ssSTK inhibitor screening approach by measuring the growth of S. suis in a minimal medium and testing the autophosphorylation inhibition by measuring the consumption of ATP in an enzymatic reaction by ssSTK. A series of inhibitors against ssSTK are identified from a commercial kinase inhibitors library, including Staurosporine, K252a, AT9283, and APY29. These inhibitors showed antimicrobial activity in vitro. Moreover, by using Galleria mellonella larvae infection assay, compound APY29 displayed in vivo efficacy against S. suis infection. Additionally, it was predicted by molecular docking that these inhibitors could interact with ssSTK. Collectively, our data illustrated the essential roles of ssSTK autophosphorylation in the physiology and pathogenicity of S. suis and consider these inhibitors as promising antimicrobial lead compounds.

8.
Front Pharmacol ; 13: 806728, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36105225

RESUMO

Objectives: The purpose of this study was to quantify the efficacies and safety profiles of the three first-line non-platinum chemotherapy regimens recommended in the National Comprehensive Cancer Network guidelines. Materials and Methods: The PubMed and Cochrane Library databases were searched comprehensively, and clinical trials involving patients with advanced non-small cell lung cancer treated with one of three first-line non-platinum regimens (gemcitabine combined with vinorelbine, gemcitabine combined with docetaxel, or gemcitabine alone) were included in the analysis. A parametric proportional hazard survival model was established to analyze the time course of overall survival (OS). The objective response rate (ORR) and incidence rates of grade 3-4 adverse events (AEs) were summarized using a single-arm meta-analysis with a random-effects model. Results: Seventeen studies met the inclusion criteria. Age and performance status (PS) scores were significant predictors of OS. For each 10-years increase in age, mortality risk increased by 18.5%, and the mortality risk increased by 4% for every 10% increase in the proportion of patients with a PS score of 2. After correcting for the above factors, we found that the three first-line non-platinum chemotherapy regimens did not differ based on OS or toxicity. Conclusion: There was no significant difference in OS or toxicity among the three first-line non-platinum chemotherapy regimens. Age and PS scores were significant predictors of OS, and their heterogeneity across different studies should be considered in cross-study comparisons and sample size estimations when designing clinical trials.

9.
Front Bioeng Biotechnol ; 10: 977215, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36110310

RESUMO

Alkaline protease has been widely applied in food, medicine, environmental protection and other industrial fields. However, the current activity and yield of alkaline protease cannot meet the demand. Therefore, it is important to identify new alkaline proteases with high activity. In this study, we cloned a potential alkaline protease gene bsp-1 from a Bacillus subtilis strain isolated in our laboratory. BSP-1 shows the highest sequence similarity to subtilisin NAT (S51909) from B. subtilis natto. Then, we expressed BSP-1 in Bacillus amyloliquefaciens BAX-9 and analyzed the protein expression level under a collection of promoters. The results show that the P43 promoter resulted in the highest transcription level, protein level and enzyme activity. Finally, we obtained a maximum activity of 524.12 U/mL using the P43 promoter after fermentation medium optimization. In conclusion, this study identified an alkaline protease gene bsp-1 from B. subtilis and provided a new method for high-efficiency alkaline protease expression in B. amyloliquefaciens.

10.
Ann Transl Med ; 10(16): 908, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36111011

RESUMO

Background and Objective: The coronavirus disease of 2019 (COVID-19) is highly infectious and mainly involves the respiratory system, with some patients rapidly progress to acute respiratory distress syndrome (ARDS), which is the leading cause of death in COVID-19 patients. Hence, fully understanding the features of COVID-19-related ARDS (CARDS) and early management of this disease would improve the prognosis and reduce the mortality of severe COVID-19. With the development of recent studies which have focused on CARDS, whether CARDS is "typical" or "atypical" ARDS has become a hotly debated topic. Methods: We searched for relevant literature from 1999 to 2021 published in PubMed by using the following keywords and their combinations: "COVID-19", "CARDS", "ARDS", "pathophysiological mechanism", "clinical manifestations", "prognosis", and "clinical trials". Then, we analyzed, compared and highlighted the differences between classic ARDS and CARDS from all of the aspects above. Key Content and Findings: Classical ARDS commonly occurs within 1 week after a predisposing cause, yet the median time from symptoms onset to CARDS is longer than that of classical ARDS, manifesting within a period of 9.0-12.0 days. Although the lung mechanics exhibited in CARDS grossly match those of classical ARDS, there are some atypical manifestations of CARDS: the severity of hypoxemia seemed not to be proportional to injury of lung mechanics and an increase of thrombogenic processes. Meanwhile, some patients' symptoms do not correspond with the extent of the organic injury: a chest computed tomography (CT) will reveal the severe and diffuse lung injuries, yet the clinical presentations of patients can be mild. Conclusions: Despite the differences between the CARDS and ARDS, in addition to the treatment of antivirals, clinicians should continue to follow the accepted evidence-based framework for managing all ARDS cases, including CARDS.

11.
Artigo em Inglês | MEDLINE | ID: mdl-36112792

RESUMO

Objective: We aimed to explore the relationship between the withdrawal of antiviral therapy after delivery and the risk for abnormal liver function (ALF) after delivery in pregnant women with high hepatitis B virus (HBV) DNA load by meta-analysis, in order to provide the corresponding theoretical basis for further guiding the clinical use of antiviral drugs in such pregnant women. Methods: We searched multiple databases for controlled studies that enrolled pregnant women with chronic HBV infection treated with antiviral therapy from January 1, 2010 to November 1, 2020. Study selection and data extraction were performed by pairs of independent reviewers. The main index was the percentage of ALF higher than the upper limit of normal at 0 to 12 and 12 to 24 weeks after delivery. Meta-analysis was used to compare the risk for ALF after stopping antiviral drugs at different time points following delivery, and subgroup analysis was conducted according to the types of drugs used. Results: We included 10 studies that enrolled 1080 pregnant women. There were 749 pregnant women in the treatment group and 331 pregnant women in the control group (who were not treated with antiviral therapy). The risk ratio (RR) for ALF in the 2 groups at 0 to 12 weeks after delivery: RR = 0.88; 95% CI, 0.71-1.09; at 12-24 weeks: RR = 0.46; 95% CI, 0.29-0.73, were compared. According to the different types of medication, subgroup analysis showed that the lamivudine treatment group compared with the control group at 0-12 weeks: RR = 0.67; 95% CI, 0.26-1.75; at 12-24 weeks, RR = 0.27; 95% CI, 0.11-0.67. The telbivudine treatment group was compared with the control group: at 0-12 weeks: RR = 0.77; 95% CI, 0.43-1.39; at 12-24 weeks: RR = 0.62, 95% CI, 0.23-1.64. The tenofovir treatment group was compared with the control group: at 0-12 weeks RR = 1.02; 95% CI, 0.67-1.55; at 12-24 weeks RR = 0.5; 95% CI, 0.25, 0.99. The lamivudine antiviral treatment group was further analyzed according to different treatment withdrawal time points. Compared with the control group, the immediate withdrawal of lamivudine in labor group at 0-12 weeks RR = 0.29; 95% CI, 0.11-0.77; at 12-24 weeks RR = 0.22; 95% CI, 0.05-0.88; the results were significantly different. There was no significant difference between the 4-week group and the 4-12 week group and the control group. Conclusion: In pregnant women with a high HBV DNA load, immediate withdrawal after antiviral treatment in the second or third trimester of pregnancy did not increase the risk for ALF after delivery.

12.
J Healthc Eng ; 2022: 2206454, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36072419

RESUMO

Magnetic resonance image has important application value in disease diagnosis. Due to the particularity of its imaging mechanism, the resolution of hardware imaging needs to be improved by increasing radiation intensity and radiation time. Excess radiation can cause the body to overheat and, in severe cases, inactivate the protein. This problem is expected to be solved by the image superresolution method based on joint dictionary learning, which has good superresolution performance. In the process of dictionary learning, the loss function will directly affect the dictionary performance. The general method only uses the cascade error as the optimization function in dictionary training, and the method does not consider the individual reconstruction error of high- and low-resolution image dictionary. In order to solve the above problem, In this paper, the loss function of dictionary learning is optimized. While ensuring that the coefficients are sufficiently sparse, the high- and low-resolution dictionaries are trained separately to reduce the error generated by the joint high- and low-resolution dictionary block pair and increase the high-resolution reconstruction error. Experiments on neck and ankle MR images show that the proposed algorithm has better superresolution reconstruction performance on ×2 and ×4 compared with bicubic interpolation, nearest neighbor, and original dictionary learning algorithms.


Assuntos
Algoritmos , Imageamento por Ressonância Magnética , Humanos , Imageamento por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética
13.
Foods ; 11(17)2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36076902

RESUMO

Durian fruit puree (DFP) is a nutrient-dense food, but it has a short shelf life. Presently, little research has been undertaken on extending the shelf life of DFP. Hence, it is necessary to develop treatment methods that can prolong the shelf life of DFP. In the present study, thermal processing (TP), high-pressure processing (HPP), and CO2-assisted HPP (CO2 + HPP) treatments are used for DFP, and their influences on quality properties of DFP during storage (35 days, 4 °C) are investigated. Compared to other treatments, the CO2 + HPP treatment had a lower pressure and a shorter time to achieve the same effect of inactivating the microorganisms of DFP. During storage, CO2 + HPP treated DFP showed higher retention rates of sugars, total soluble solids, color, bioactive components, and antioxidant capacity in comparison with other treated DFPs. Moreover, after 35 days of storage, the microbial count of (CO2 + HPP)-treated DFP (3.80 × 103 CFU/g) was much lower than those of TP (4.77 × 105 CFU/g) and HPP (8.53 × 103 CFU/g)-treated DFPs. The results of this study reveal that CO2 + HPP treatment could not only better preserve the quality of DFP, but also effectively extend the shelf life of DFP, providing an effective method for the processing of DFP.

14.
Cell Discov ; 8(1): 85, 2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36068205

RESUMO

Determination of malignancy in thyroid nodules remains a major diagnostic challenge. Here we report the feasibility and clinical utility of developing an AI-defined protein-based biomarker panel for diagnostic classification of thyroid nodules: based initially on formalin-fixed paraffin-embedded (FFPE), and further refined for fine-needle aspiration (FNA) tissue specimens of minute amounts which pose technical challenges for other methods. We first developed a neural network model of 19 protein biomarkers based on the proteomes of 1724 FFPE thyroid tissue samples from a retrospective cohort. This classifier achieved over 91% accuracy in the discovery set for classifying malignant thyroid nodules. The classifier was externally validated by blinded analyses in a retrospective cohort of 288 nodules (89% accuracy; FFPE) and a prospective cohort of 294 FNA biopsies (85% accuracy) from twelve independent clinical centers. This study shows that integrating high-throughput proteomics and AI technology in multi-center retrospective and prospective clinical cohorts facilitates precise disease diagnosis which is otherwise difficult to achieve by other methods.

16.
Oncogene ; 2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36068334

RESUMO

Deciphering the crosstalk between RNA-binding proteins and corresponding RNAs will provide a better understanding of gastric cancer (GC) progression. The comprehensive bioinformatics study identified cytoplasmic polyadenylation element-binding protein 3 (CPEB3) might play a vital role in GC progression. Then we found CPEB3 was downregulated in GC and correlated with prognosis. In addition, CPEB3 suppressed GC cell proliferation, invasion and migration in vitro, as well as tumor growth and metastasis in vivo. Mechanistic study demonstrated CPEB3 interacted with 3'-UTR of ADAR1 mRNA through binding to CPEC nucleotide element, and then inhibited its translation by localizing it to processing bodies (P bodies), eventually leading to the suppression of ADAR1-mediated RNA editing. Microscale thermophoresis assay further revealed that the direct interaction between CPEB3 and GW182, the P-body's major component, was through the 440-698AA region of CPEB3 binding to the 403-860AA region of GW182. Finally, AAV9-CPEB3 was developed and administrated in mouse models to assess its potential value in gene therapy. We found AAV9-CPEB3 inhibited GC growth and metastasis. Besides, AAV9-CPEB3 induced hydropic degeneration in mouse liver, but did not cause kidney damage. These findings concluded that CPEB3 suppresses GC progression by inhibiting ADAR1-mediated RNA editing via localizing ADAR1 mRNA to P bodies.

17.
Zhongguo Zhong Yao Za Zhi ; 47(15): 3977-3985, 2022 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-36046886

RESUMO

As one of the most advanced technologies, single-cell omics technology develops rapidly in recent years. Based on different technical strategies, it enables unbiased and high-throughput access to multiple omics information at single-cell resolution. So far, single-cell omics technology, by virtue of its great powder in resolving tissue heterogeneity, has become a revolutionary tool to deeply understand the functional structure of tissues, reveal complex disease processes, and elucidate drug mechanisms of action. In view of the technical challenges in deconstructing the complexity of Chinese medicine and clarifying the modern scientific connotation of traditional Chinese medicine(TCM) theory, single-cell omics technology has huge application potential in the discovery of pharmacodynamic substances, construction of action networks, and elucidation of integrated regulatory mechanisms, which brings new opportunities for modern research in TCM. The present study briefly introduced three representative single-cell omics technologies, i.e., single-cell transcriptome sequencing, spatial transcriptomics, and single-cell multimodal omics, and their main application patterns. On this basis, an outlook was proposed on the strategies and applications for modern research in TCM using single-cell omics technology.


Assuntos
Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Medicamentos de Ervas Chinesas/farmacologia , Tecnologia
18.
Math Biosci Eng ; 19(11): 11756-11767, 2022 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-36124612

RESUMO

We deal with a single-machine scheduling problem with an optional maintenance activity (denoted by $ ma $), where the actual processing time of a job is a function of its starting time and position. The optional $ ma $ means that the machine will perform a $ ma $, after $ ma $ is completed, the machine will return to the initial state. The objective is to determine an optimal job sequence and the location of the maintenance activity such that makespan is to be minimized. Based on some properties of an optimal sequence, we introduce a polynomial time algorithm to solve the problem, and the time complexity is $ O({n}^4) $, where $ {n} $ is the number of jobs.


Assuntos
Algoritmos
19.
Pestic Biochem Physiol ; 187: 105212, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36127056

RESUMO

Lymantria dispar is one of the most devastating forest pests worldwide. Fungal biopesticides have great potential as alternatives owing to their high lethality to pests and eco-friendly feature, which is, however, often severely compromised by the pests' innate immunity. A better understanding of the antifungal immune system in L. dispar would significantly facilitate the development of the biopesticide. Here, we investigated phylogenetic characteristics of immunity-related genes as well as the tissue expression patterns in L. dispar after the infection of an entomopathogen Beauveria bassiana using RNA-sequencing data. Results showed most immune genes remain at a low level of response after 24 h post-infection (HPI). Almost all genes in the Toll pathway were significantly up-regulated at 48 HPI, and SPH1, SPN6, Toll6, Toll12, Myd88, pelle, and Drosal were significantly down-regulated at 72 HPI. Immunoblotting analysis revealed that the protein levels of ßGRP3 and PPO1 were significantly upregulated at 24 and 48 HPI, while Myd88 was downregulated at 24 HPI, which was further confirmed by Quantitative real-time PCR experiments. Moreover, the relative content of H2O2, a potent reactive oxygen species (ROS), was significantly increased with the decrease of the total antioxidant capacity, indicating that oxidative stress system positively participates in the clearance of the pathogenic fungus. Together, our study provides detailed genetic characteristics of antifungal immunity as well as profiling of the host defense against entomopathogenic infection, and comprehensive insight into molecular interaction between L. dispar and the entomopathogen.


Assuntos
Beauveria , Antifúngicos , Antioxidantes , Beauveria/fisiologia , Agentes de Controle Biológico , Peróxido de Hidrogênio , Sistema Imunitário , Fator 88 de Diferenciação Mieloide , Filogenia , RNA , Espécies Reativas de Oxigênio
20.
Oncol Rep ; 48(5)2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36129153

RESUMO

Circular RNA (circRNA/circ) profiles have been suggested to be involved in the prognosis of several types of solid tumors and hematological malignancies, including multiple myeloma (MM). Therefore, the aim of the present study was to comprehensively explore the involvement of circRNA profiles in MM prognosis. A total of 60 patients with MM that underwent bortezomib­based induction therapy were enrolled. Next, eight patients with complete response (CR) and eight with no response (NR) were randomly selected to detect their circRNA profiles in bone marrow plasma cells (BMPCs) by microarray. Next, 10 candidate circRNAs were verified via reverse transcription­quantitative PCR (RT­qPCR) in the BMPCs of 60 patients with MM. Finally, the molecular mechanism of circ_0026652 knockdown underlying the regulation of chemosensitivity to bortezomib was assessed. Microarray showed that 79 circRNAs were upregulated and 167 were downregulated in CR compared with NR cases, which were found to be enriched in carcinogenic and chemoresistance­related pathways (Wnt, mTOR and MAPK pathways). RT­qPCR showed that 8/10 circRNAs (circ_0026652, circ_0068708, circ_0088128, circ_0001566, circ_0031113, circ_0083587, circ_0005552 and circ_0007171) were associated with treatment response [CR or objective response rate (ORR)] and 5/10 circRNAs (circ_0026652, circ_0068708, circ_0001566, circ_0031113 and circ_0005552) were associated with progression­free survival (PFS) or overall survival (OS). Of note, circ_0026652 was a key prognostic marker simultaneously associated with CR, ORR, PFS and OS. Cellular experiments showed that circ_0026652 knockdown enhanced chemosensitivity to bortezomib through the microRNA (miR)­608­mediated Wnt/ß­catenin pathway in U266 and RPIM­8226 cells. In conclusion, dysregulated circRNA profiles were closely associated with MM prognosis, with circ_0026652 being linked to bortezomib­based treatment response and survival through the miR­608­mediated Wnt/ß­catenin pathway.


Assuntos
MicroRNAs , Mieloma Múltiplo , Bortezomib/farmacologia , Bortezomib/uso terapêutico , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/genética , Prognóstico , RNA Circular/genética , Serina-Treonina Quinases TOR , beta Catenina/genética
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