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1.
Chem Soc Rev ; 53(10): 5014-5053, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38600823

ABSTRACT

Alumina materials, as one of the cornerstones of the modern chemical industry, possess physical and chemical properties that include excellent mechanical strength and structure stability, which also make them highly suitable as catalyst supports. Alumina-supported Pd-based catalysts with the advantages of exceptional catalytic performance, flexible regulated surface metal/acid sites, and good regeneration ability have been widely used in many traditional chemical industry fields and have also shown great application prospects in emerging fields. This review aims to provide an overview of the recent advances in alumina and its supported Pd-based catalysts. Specifically, the synthesis strategies, morphology transformation mechanisms, and structural properties of alumina with various morphologies are comprehensively summarized and discussed in-depth. Then, the preparation approaches of Pd/Al2O3 catalysts (impregnation, precipitation, and other emerging methods), as well as the metal-support interactions (MSIs), are revisited. Moreover, Some promising applications have been chosen as representative reactions in fine chemicals, environmental purification, and sustainable development fields to highlight the universal functionality of the alumina-supported Pd-based catalysts. The role of the Pd species, alumina support, promoters, and metal-support interactions in the enhancement of catalytic performance are also discussed. Finally, some challenges and upcoming opportunities in the academic and industrial application of the alumina and its supported Pd-based are presented and put forward.

2.
Sci Total Environ ; 927: 172039, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38552977

ABSTRACT

Alpine grassland is the main vegetation on the Qinghai-Tibetan Plateau (QTP) and exhibits high sensitivity to extreme weather events. With global warming, extreme weather events are projected to become more frequent on the QTP. However, the impact of these extreme weather events on the carbon cycle of alpine grassland remains unclear. The long-term in-situ carbon fluxes data was collected from 2013 to 2022 at an alpine grassland site to examine the impact of extreme low air temperature (ELT) and reduced moisture (including air and soil) on carbon fluxes during the growing season. Our findings indicated that a significant increase in net ecosystem production (NEP) after 2019, with the average NEP increasing from 278.91 ± 43.27 g C m-2 year-1 during 2013-2018 to 415.45 ± 45.29 g C m-2 year-1 during 2019-2022. The ecosystem carbon use efficiency (CUE) increased from 0.38 ± 0.06 during 2013-2018 to 0.62 ± 0.11 during 2019-2022. By combining concurrently measured environmental factors and remote sensing data, we identified the factors responsible for the abrupt change in the NEP after 2019. This phenomenon was caused by an abrupt decrease in ecosystem respiration (Reco) after 2019, which resulted from the inhibition imposed by ELT and reduced moisture. In contrast, gross primary production (GPP) remained stable from 2013 to 2022, which was confirmed by the remotely sensed vegetation index. This study highlights that combined extreme weather events associated with climate change can significantly impact the NEP of alpine grassland, potentially affecting different carbon fluxes at different rates. These findings provide new insights into the mechanisms governing the carbon cycle of alpine grassland.


Subject(s)
Carbon Cycle , Environmental Monitoring , Grassland , Tibet , Climate Change , Cold Temperature , Ecosystem
3.
World J Gastroenterol ; 30(6): 565-578, 2024 Feb 14.
Article in English | MEDLINE | ID: mdl-38463028

ABSTRACT

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a deadly malignancy with limited treatment options. Deubiquitinases (DUBs) have been confirmed to play a crucial role in the development of malignant tumors. JOSD2 is a DUB involved in controlling protein deubiquitination and influencing critical cellular processes in cancer. AIM: To investigate the impact of JOSD2 on the progression of ESCC. METHODS: Bioinformatic analyses were employed to explore the expression, prognosis, and enriched pathways associated with JOSD2 in ESCC. Lentiviral transduction was utilized to manipulate JOSD2 expression in ESCC cell lines (KYSE30 and KYSE150). Functional assays, including cell proliferation, colony formation, drug sensitivity, migration, and invasion, were performed, revealing the impact of JOSD2 on ESCC cell lines. JOSD2's role in xenograft tumor growth and drug sensitivity in vivo was also assessed. The proteins that interacted with JOSD2 were identified using mass spectrometry. RESULTS: Preliminary research indicated that JOSD2 was highly expressed in ESCC tissues, which was associated with poor prognosis. Further analysis demonstrated that JOSD2 was upregulated in ESCC cell lines compared to normal esophageal cells. JOSD2 knockdown inhibited ESCC cell activity, including proliferation and colony-forming ability. Moreover, JOSD2 knockdown decreased the drug resistance and migration of ESCC cells, while JOSD2 overexpression enhanced these phenotypes. In vivo xenograft assays further confirmed that JOSD2 promoted tumor proliferation and drug resistance in ESCC. Mechanistically, JOSD2 appears to activate the MAPK/ERK and PI3K/AKT signaling pathways. Mass spectrometry was used to identify crucial substrate proteins that interact with JOSD2, which identified the four primary proteins that bind to JOSD2, namely USP47, IGKV2D-29, HSP90AB1, and PRMT5. CONCLUSION: JOSD2 plays a crucial role in enhancing the proliferation, migration, and drug resistance of ESCC, suggesting that JOSD2 is a potential therapeutic target in ESCC.


Subject(s)
Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Humans , Esophageal Squamous Cell Carcinoma/pathology , Esophageal Neoplasms/pathology , Phosphatidylinositol 3-Kinases/metabolism , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation , Deubiquitinating Enzymes/genetics , Gene Expression Regulation, Neoplastic , Protein-Arginine N-Methyltransferases
4.
Cell Biochem Biophys ; 2024 Feb 06.
Article in English | MEDLINE | ID: mdl-38319584

ABSTRACT

The ubiquitin proteasome system is a highly specific and selective protein regulatory system that plays an essential role in the regulation of the cell cycle. Despite its significance, the role of ubiquitination in cardiomyocyte proliferation remains largely unclear. This study aimed to investigate the potential impact of E3 ubiquitin ligase ASB14 (Ankyrin Repeat And SOCS Box Containing 14) on cardiac regeneration. We conducted a microarray analysis of apical resection ventricle tissues, and our findings revealed that ASB14 was down-regulated during the cardiac regenerative response. Subsequently, we examined the effect of ASB14 silencing on cardiomyocyte nuclear proliferation both in vitro and in vivo. Our results indicated that ASB14 silencing promoted cardiomyocyte nuclear proliferation, suggesting that ASB14 may play a role in regulating cardiac regeneration. To further investigate the potential therapeutic implications of ASB14 deficiency, we examined the cardiac function of mice with ASB14 deficiency in response to ischemic injury. Our findings showed that mice with ASB14 deficiency exhibited preserved cardiac function and a therapeutic effect in response to ischemic injury, which was attributed to the enhancement of cardiomyocyte nuclear proliferation. To elucidate the underlying mechanisms, we investigated the effect of ASB14 on microtubule-associated protein RP/EB family member 2 (MAPRE2) protein degradation. Our results indicated that the loss of ASB14 decreased the degradation of MAPRE2 protein, subsequently promoting cardiomyocyte nuclear proliferation and enhancing cardiac repair after myocardial infarction (MI). In conclusion, our study provides evidence that inhibition of ASB14-mediated MAPRE2 ubiquitination promotes cardiomyocyte nuclear proliferation, which may serve as a potential target for treating heart failure induced by MI injury.

5.
Immunol Rev ; 321(1): 246-262, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37823450

ABSTRACT

Cell death can be executed through distinct subroutines. PANoptosis is a unique inflammatory cell death modality involving the interactions between pyroptosis, apoptosis, and necroptosis, which can be mediated by multifaceted PANoptosome complexes assembled via integrating components from other cell death modalities. There is growing interest in the process and function of PANoptosis. Accumulating evidence suggests that PANoptosis occurs under diverse stimuli, for example, viral or bacterial infection, cytokine storm, and cancer. Given the impact of PANoptosis across the disease spectrum, this review briefly describes the relationships between pyroptosis, apoptosis, and necroptosis, highlights the key molecules in PANoptosome formation and PANoptosis activation, and outlines the multifaceted roles of PANoptosis in diseases together with a potential for therapeutic targeting. We also discuss important concepts and pressing issues for future PANoptosis research. Improved understanding of PANoptosis and its mechanisms is crucial for identifying novel therapeutic targets and strategies.


Subject(s)
Apoptosis , Pyroptosis , Humans , Cell Death , Cytokine Release Syndrome , Biology
6.
Comput Struct Biotechnol J ; 21: 5039-5048, 2023.
Article in English | MEDLINE | ID: mdl-37867973

ABSTRACT

The CRISPR/Cas9 system has significantly advanced the field of gene editing, yet its clinical application is constrained by the considerable challenge of off-target effects. Although numerous deep learning models for off-target prediction have been proposed, most struggle to effectively extract the nuanced features of guide RNA (gRNA) and DNA sequence pairs and to mitigate information loss during data transmission within the model. To address these limitations, we introduce a novel Hybrid Neural Network (HNN) model that employs a parallelized network structure to fully extract pertinent features from different positions and types of bases in the sequence to minimize information loss. Notably, this study marks the first application of word embedding techniques to extract information from sequence pairs that contain insertions and deletions (Indels). Comprehensive evaluation across diverse datasets indicates that our proposed model outperforms existing state-of-the-art prediction methods in off-target prediction. The datasets and source codes supporting this study can be found at https://github.com/Yang-k955/CRISPR-HW.

7.
Foodborne Pathog Dis ; 20(10): 442-452, 2023 10.
Article in English | MEDLINE | ID: mdl-37669036

ABSTRACT

In this study, we investigated the inhibitory effects of coenzyme Q0 (CoQ0) on biofilm formation and the expression of virulence genes by Cronobacter sakazakii. We found that the minimum inhibitory concentration of CoQ0 against C. sakazakii strains ATCC29544 and ATCC29004 was 100 µg/mL, while growth curve assays showed that subinhibitory concentrations (SICs) of CoQ0 for both strains were 6.4, 3.2, 1.6 and 0.8 µg/mL. Assays exploring the inhibition of specific biofilm formation showed that SICs of CoQ0 inhibited biofilm formation by C. sakazakii in a dose-dependent manner, which was confirmed by scanning electron microscopy and confocal laser scanning microscopy analyses. CoQ0 inhibited the swimming and swarming motility of C. sakazakii and reduced its ability to adhere to and invade HT-29 cells. In addition, CoQ0 impeded the ability of C. sakazakii to survive and replicate within RAW 264.7 cells. Finally, real-time polymerase chain reaction analysis confirmed that nine C. sakazakii genes associated with biofilm formation and virulence were downregulated in response to CoQ0 treatment. Overall, our findings suggest that CoQ0 is a promising antibiofilm agent and provide new insights for the prevention and control of infections caused by C. sakazakii.


Subject(s)
Cronobacter sakazakii , Ubiquinone/pharmacology , Virulence Factors/genetics , Microbial Sensitivity Tests , Biofilms
8.
Sci Total Environ ; 880: 163255, 2023 Jul 01.
Article in English | MEDLINE | ID: mdl-37031934

ABSTRACT

Glacial sediments as an important end member of the global dust system, could indicate changes in global climate, aerosols sources, ocean elements, and productivity. With global warming, ice caps shrinking and glaciers retreat at high latitudes have attracted concern. To understand the response of glacier to environment and climate in modern high latitude ice-marginal environments, this paper investigated glacial sediments in the Ny-Ålesund region of the Arctic and clarified the response of polar environmental to global changes through geochemical characteristics of glacial sediments. The results showed that: 1) main factors affecting the elements distribution of the Ny-Ålesund glacial sediments were thought as soil formation, bedrock and weathering, and biological activity; 2) variations of SiO2/Al2O3 and SiO2/Al2O3 + Fe2O3, indicating low weathering of the soil. The ratio of Na2O/K2O indicating a weak chemical weathering, was negatively correlated to the CIA. With the average CIA of Ny-Ålesund glacial sediments for main minerals of quartz, feldspar, and muscovite as well as dolomite and calcite 50.13, which implied glacial sediments at the early stage of chemical weathering and depletion of Ca and Na; 3) the separating effect of stones and soils by stone circle formation due to thermal conductivity and frost heave makes sediments in stone circle have lower chemical weathering with only two main minerals, albite and quartz; 4) changes of carbonate content in sediments with glacier front retreating in different period implied that weathering rate of calcite averagely reached an estimate of 0.0792%wt/year in glacier A. The succession of vegetation made biological weathering become an important driving force for carbonate leaching from glacial sediments. These results and data provide scientifically significant archive for future global change studies.

9.
Gerontology ; 69(5): 603-614, 2023.
Article in English | MEDLINE | ID: mdl-36882028

ABSTRACT

BACKGROUND: Hypertension is the most common cardiovascular disease, and its main harmful effect is chronic damage to target organs. In some patients with well-controlled blood pressure, target organ damage still occurs. GLP-1 agonists have significant cardiovascular benefits, but their antihypertensive effect is limited. The cardiovascular protective effect of GLP-1 is worth studying. METHODS: The ambulatory blood pressure of spontaneously hypertensive rats (SHRs) was detected by ambulatory blood pressure monitoring, and the characteristics of blood pressure and the effect of subcutaneous intervention with a GLP-1R agonist on blood pressure were observed. To explore the mechanism of the cardiovascular benefit of GLP-1R agonists in SHRs, we evaluated the effects of GLP-1R agonists on vasomotor function and calcium homeostasis in vascular smooth muscle cells (VSMCs) in vitro. RESULTS: Although the blood pressure of SHRs was significantly higher than that of WKY rats, the blood pressure variability of SHRs was also significantly higher than that of the control group. The GLP-1R agonist significantly reduced blood pressure variability in SHRs, but the antihypertensive effect was not obvious. GLP-1R agonists can significantly improve the cytoplasmic calcium overload of VSMCs in SHRs by upregulating the expression of NCX1, improving the systolic and diastolic functions of arterioles, and reducing blood pressure variability. CONCLUSIONS: Taken together, these results provide evidence that GLP-1R agonists improved VSMC cytoplasmic Ca2+ homeostasis through upregulated NCX1 expression in SHRs, which plays a key role in blood pressure stability and broad cardiovascular benefits.


Subject(s)
Hypertension , Hypotension , Rats , Animals , Blood Pressure , Muscle, Smooth, Vascular/metabolism , Calcium/metabolism , Calcium/pharmacology , Antihypertensive Agents/metabolism , Antihypertensive Agents/pharmacology , Glucagon-Like Peptide 1/metabolism , Glucagon-Like Peptide 1/pharmacology , Rats, Inbred WKY , Blood Pressure Monitoring, Ambulatory , Hypertension/drug therapy , Rats, Inbred SHR , Homeostasis
10.
Am J Cancer Res ; 12(11): 5095-5104, 2022.
Article in English | MEDLINE | ID: mdl-36504890

ABSTRACT

Despite advances in rectal cancer treatments, its local recurrence rate is still 4-10 percent. And an evidence-based definition of early recurrence is lacking. Our study hopes to establish a clear threshold to distinguish early and late recurrence, and analyze risk and prognostic factors for them. Rectal cancer patients who underwent proctectomy from 2009 to 2019 were included. Patients who received neoadjuvant treatment and with incomplete records were excluded. The optimal interval was obtained using the minimum P value approach. Risk factors for early recurrence were analyzed by logistic regression models, and prognostic factors associated with additional surgery were assessed by Cox proportional hazards models. The optimal interval for the definition of early recurrence was 26 months based on the subsequent prognosis (P < 0.001). The 5-year survival rate of early and late recurrence cohort was 32.5% and 57.1%, respectively (P < 0.001). Adjuvant radiotherapy was the independent protective factor for early recurrence. And the presence of lymphovascular invasion, positive surgical margin, and no re-neoadjuvant radiotherapy were independent prognostic factors for the survival of LRRC patients under additional surgery.

11.
Foods ; 11(17)2022 Sep 02.
Article in English | MEDLINE | ID: mdl-36076869

ABSTRACT

Cronobacter sakazakii, an emerging foodborne pathogen that was isolated primarily from powdered infant formula, poses an important issue in food safety due to its high stress tolerance and pathogenicity. The Hpr (encoded by ptsH gene) has been shown to regulate carbon metabolism as well as stress response and virulence. However, the functional properties of ptsH in C. sakzakii have not been investigated. In this study, we clarified the role of ptsH in the C. sakzakii stress response and virulence, and explored its possible regulatory mechanism by RNA-seq. Compared with wild-type, the ΔptsH mutant showed a slower growth rate in the log phase but no difference in the stationary phase. Moreover, the resistance to heat stress (65 °C, 55 °C), simulated gastric fluid (pH = 2.5), biofilm formation and adhesion to HT-29 cells of ΔptsH mutant were significantly decreased, whereas the oxidative resistance (1, 5, 10 mM H2O2), osmotic resistance (10%, 15%, 20% NaCl), and superoxide dismutase activity were enhanced. Finally, RNA-seq analysis revealed the sulfur metabolism pathway is significantly upregulated in the ΔptsH mutant, but the bacterial secretion system pathway is dramatically downregulated. The qRT-PCR assay further demonstrated that the ΔptsH mutant has elevated levels of genes that are related to oxidative and osmotic stress (sodA, rpoS, cpxA/R, osmY). This study provides a great understanding of the role of ptsH in diverse stress responses and virulence in C. sakazakii, and it contributes to our understanding of the genetic determinant of stress resistance and pathogenicity of this important foodborne pathogen.

12.
Syst Rev ; 11(1): 136, 2022 07 04.
Article in English | MEDLINE | ID: mdl-35788246

ABSTRACT

BACKGROUND: Surgery is the main treatment option for patients with local gastric cancer. However, surgery alone is usually not sufficient for stomach cancer patients, and combined therapies are recommended for these patients. In recent studies, some preoperative treatments have shown benefits. However, the treatment selection is still uncertain because previous studies failed to obtain a statistically significant difference between preoperative chemotherapy and preoperative chemoradiotherapy. Therefore, we plan to perform a systematic review and meta-analysis to compare the benefits among these preoperative treatments. METHODS/DESIGN: This review includes randomized controlled trials with or without blinding as well as published studies, high-quality unpublished studies, full articles and meeting abstracts with an English context if sufficient results were provided for analysis. Data sources include the Cochrane Central Register of Controlled Trials, Embase, MEDLINE, major relevant international conferences and manual screening of references. Patients with a diagnosis of resectable primary gastric or EGJ adenocarcinoma (stage II or higher) who underwent surgery alone or preoperative treatment followed by surgery and who were pathologically confirmed as proposed by the AJCC 2017 guidelines without age, sex, race, subtypes of adenocarcinoma and molecular pathology limitations will be included. The following three interventions will be included: surgery alone, neoadjuvant chemistry followed by surgery and neoadjuvant chemoradiotherapy followed by surgery. All-cause mortality, overall survival (OS, the time interval from diagnosis to death) and/or progression-free survival (PFS, the time interval from diagnosis to disease progression or death from any cause) will be defined as major results of concern. The clinical and pathological response rate (according to RECIST and tumour regression score), R0 resection rate, quality of life and grade 3 or above adverse events (according to the National Cancer Institute Common Terminology Criteria for Adverse Events, NCI-CTCAE) will be defined as the secondary outcomes. DISCUSSION: The aim of this systematic review is to compare the benefits of different preoperative treatments for patients with locoregional stomach cancer. This systematic review will improve the understanding of the relative efficacy of these treatment options by providing the latest evidence on the efficacy of various treatment options in the management of gastric cancer patients and may guide clinical practice. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD4202123718.


Subject(s)
Adenocarcinoma , Esophageal Neoplasms , Stomach Neoplasms , Adenocarcinoma/etiology , Humans , Neoadjuvant Therapy/methods , Quality of Life , Stomach Neoplasms/therapy
13.
Food Res Int ; 154: 111027, 2022 04.
Article in English | MEDLINE | ID: mdl-35337579

ABSTRACT

Cronobacter sakazakii, a foodborne opportunistic pathogen, mainly affects neonates and infants, with mortality rates of 26.9%. Most outbreaks arise from powdered infant formula (PIF). The aim of this study was to investigate the efficacy and mechanism of 405-nm light-emitting diode (LED) and citral treatment used in combination against C. sakazakii in reconstituted PIF. LED-illumination combined with citral showed better antimicrobial effects than either treatment alone. In reconstituted PIF, the abundance of C. sakazakii cells was reduced by 6.5 log 10 CFU/mL following combined LED and 9 µL/mL citral treatment for 90 min compared with untreated controls, respectively. Combined LED and 6 µL/mL citral treatment destroyed C. sakazakii cellular morphology and membrane integrity, prolonged the recovery time of sublethally-injured cells, and induced lipid peroxidation. Besides, LED treatment decreased the amount of lipid peroxidation caused by citral treatment alone. Neither LED illumination nor citral treatment resulted in breakdown of C. sakazakii genomic DNA. Because of its safe, environmentally-friendly, economical, and high-performance characteristics, the combination of LED-illumination and citral treatment has the potential to be developed into a strategy to control C. sakazakii contamination in stored and reconstituted PIF.


Subject(s)
Cronobacter sakazakii , Acyclic Monoterpenes , Food Microbiology , Humans , Infant , Infant Formula , Infant, Newborn , Lighting , Powders
14.
J Colloid Interface Sci ; 617: 372-382, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35279572

ABSTRACT

With continuous development of artificial intelligence technology, strain sensors have attracted widespread attention. In this work, a novel high-performance wearable strain sensor is prepared by using a kind of ultra-stretchable, super-hydrophobic and high-conductive composite. The preparation process is as follows, i.e., using common elastic band (EB) as the polymer matrix, nano carbon black (CB) and carbon nanotubes (CNTs) as mixed conductive filler, and then modified by polydimethylsiloxane (PDMS) to obtain the PDMS/(CB + CNTs)/EB composite for assembling assemble flexible wearable strain sensors. Experimental results reveal the following excellent properties: 1) The composite exhibits excellent mechanical properties and super-hydrophobicity, i.e., the tensile strength is up to 996.5%, and the elastic modulus and tensile strength increase 49.2% and 59.2%, compared with pristine EB; 2) The composite strain sensor exhibits high sensitivity (the gauge factor reaches up to 648.83 under strain range of 979.9-996.5%), and it still shows stable performance after 3000 cycles tests (100% strain); 3) It is a well candidate to be used for monitoring human body motions including large and subtle body movements; 4) The composite sensor also has advantages of easy access of raw materials, simple preparation, easy mass production and relatively low production cost, showing a broad application prospect in wearable electronic products.


Subject(s)
Nanotubes, Carbon , Wearable Electronic Devices , Artificial Intelligence , Electric Conductivity , Humans , Hydrophobic and Hydrophilic Interactions , Nanotubes, Carbon/chemistry
15.
Foods ; 11(2)2022 Jan 06.
Article in English | MEDLINE | ID: mdl-35053867

ABSTRACT

Salmonella Typhimurium is a widely distributed foodborne pathogen and is tolerant of various environmental conditions. It can cause intestinal fever, gastroenteritis and bacteremia. The aim of this research was to explore the effect of illumination with 405 nm light-emitting diodes (LEDs) on the resistance of S. Typhimurium to environmental stress. Beef slices contaminated with S. Typhimurium were illuminated by 405 nm LEDs (18.9 ± 1.4 mW/cm2) for 8 h at 4 °C; controls were incubated in darkness at 7 °C. Then, the illuminated or non-illuminated (control) cells were exposed to thermal stress (50, 55, 60 or 65 °C); oxidative stress (0.01% H2O2 [v/v]); acid stress (simulated gastric fluid [SGF] at pH 2 or 3); or bile salts (1%, 2%, or 3% [w/v]). S. Typhimurium treated by 405 nm LED irradiation showed decreased resistance to thermal stress, osmotic pressure, oxidation, SGF and bile salts. The transcription of eight environmental tolerance-related genes were downregulated by the illumination. Our findings suggest the potential of applying 405 nm LED-illumination technology in the control of pathogens in food processing, production and storage, and in decreasing infection and disease related to S. Typhimurium.

16.
Gastric Cancer ; 25(3): 503-514, 2022 05.
Article in English | MEDLINE | ID: mdl-34826008

ABSTRACT

BACKGROUND: Fibroblasts are the predominant cell type in the stroma of tumor, and cancer-associated fibroblasts (CAFs) promote cancer chemoresistance by secreting various bioactive molecules. However, the differential expression between CAFs and normal fibroblasts (NFs) and how can CAFs uniquely impact cancer cells are still unexplored. METHODS: Primary CAFs and NFs were cultured from gastric cancer specimens, and their variant expression was analyzed by RNA-sequencing. Chemoresistance was evaluated by measuring cell viability, apoptosis, and 3D-coculture techniques. RESULTS: CAFs were isolated from gastric cancers and defined by specific cell-surface markers. CAFs decreased the sensitivity of gastric cancer cells to 5-FU. RNA-sequencing showed that CAFs expressed a higher level of NRP2 than NFs. And the high expression of NRP2 was correlated with worse oncological outcomes in gastric cancer patients. Further study showed that the knockdown of NRP2 eradicated the resistance to 5-FU. And the secretion of stromal cell-derived factor-1 (SDF-1) was reduced following NRP2 knockdown. Furthermore, we found that the increased sensitivity to 5-FU was induced by DNA damage. And this process was mediated by predominant effectors of the Hippo pathway, YAP/TAZ. CONCLUSIONS: The present study indicated that CAFs within gastric cancers promote chemoresistance through the expression of NRP2. The secretion of SDF-1 that mediated by VEGF/NRP2 signaling in CAFs and the activation of Hippo pathway in cancer cells in large part participated in this project.


Subject(s)
Cancer-Associated Fibroblasts , Stomach Neoplasms , Cancer-Associated Fibroblasts/pathology , Cell Line, Tumor , Cell Proliferation/physiology , Drug Resistance, Neoplasm , Fibroblasts/pathology , Fluorouracil/pharmacology , Humans , RNA/metabolism , Stomach Neoplasms/pathology
17.
Front Cell Dev Biol ; 9: 770994, 2021.
Article in English | MEDLINE | ID: mdl-34926458

ABSTRACT

Gastric cancer is one of the most heterogeneous tumors with multi-level molecular disturbances. Sustaining proliferative signaling and evading growth suppressors are two important hallmarks that enable the cancer cells to become tumorigenic and ultimately malignant, which enable tumor growth. Discovering and understanding the difference in tumor proliferation cycle phenotypes can be used to better classify tumors, and provide classification schemes for disease diagnosis and treatment options, which are more in line with the requirements of today's precision medicine. We collected 691 eligible samples from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database, combined with transcriptome data, to explore different heterogeneous proliferation cycle phenotypes, and further study the potential genomic changes that may lead to these different phenotypes in this study. Interestingly, two subtypes with different clinical and biological characteristics were identified through cluster analysis of gastric cancer transcriptome data. The repeatability of the classification was confirmed in an independent Gene Expression Omnibus validation cohort, and consistent phenotypes were observed. These two phenotypes showed different clinical outcomes, and tumor mutation burden. This classification helped us to better classify gastric cancer patients and provide targeted treatment based on specific transcriptome data.

18.
Front Oncol ; 11: 690037, 2021.
Article in English | MEDLINE | ID: mdl-34458140

ABSTRACT

A good prediction model is useful to accurately predict patient prognosis. Tumor-node-metastasis (TNM) staging often cannot accurately predict prognosis when used alone. Some researchers have shown that the infiltration of M2 macrophages in many tumors indicates poor prognosis. This approach has the potential to predict prognosis more accurately when used in combination with TNM staging, but there is less research in gastric cancer. A multivariate analysis demonstrated that CD163 expression, TNM staging, age, and gender were independent risk factors for overall survival. Thus, these parameters were assessed to develop the nomogram in the training data set, which was tested in the validation and whole data sets. The model showed a high degree of discrimination, calibration, and good clinical benefit in the training, validation, and whole data sets. In conclusion, we combined CD163 expression in macrophages, TNM staging, age, and gender to develop a nomogram to predict 3- and 5-year overall survivals after curative resection for gastric cancer. This model has the potential to provide further diagnostic and prognostic value for patients with gastric cancer.

19.
Foodborne Pathog Dis ; 18(6): 398-404, 2021 06.
Article in English | MEDLINE | ID: mdl-33709804

ABSTRACT

Coenzyme Q0 (CoQ0) is a natural compound found in Antrodia cinnamomea, which has a variety of biological activities. Here, the antibacterial activity and possible antibacterial mechanism of CoQ0 against Escherichia coli were investigated. The antibacterial effect was evaluated by determining minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values, and by assessing bacterial survival and the effect on the growth of E. coli after CoQ0 treatment in Luria-Bertani (LB) broth. To reveal the antibacterial mechanism of CoQ0, changes in intracellular adenosine triphosphate (ATP) concentration, membrane potential, and bacterial protein content, as well as effects on cell morphology and membrane integrity, were investigated. Both the MICs and MBCs of CoQ0 against E. coli were 0.1 mg/mL. After treatment of E. coli (6.5 log colony-forming units/mL) with 0.1 mg/mL of CoQ0 in LB broth for 3 h, the number of viable cells dropped below the detection limit. In addition, CoQ0 treatment resulted in the reduction in intracellular ATP concentration, cell membrane hyperpolarization, decreased bacterial protein concentrations, and damage to cell membrane integrity and cellular morphology. These results indicated that CoQ0 has effective antibacterial activity against E. coli, suggesting potential applications in food industry safety.


Subject(s)
Anti-Bacterial Agents/pharmacology , Benzoquinones/pharmacology , Escherichia coli/drug effects , Adenosine Triphosphate/metabolism , Cell Membrane/drug effects , Microbial Sensitivity Tests , Polyporales/chemistry
20.
Front Oncol ; 11: 795137, 2021.
Article in English | MEDLINE | ID: mdl-34976836

ABSTRACT

AIM: Accumulated studies have verified that tumor regression is associated with the prognosis of rectal cancer. However, stratified analysis within a certain stage is still unknown. The purpose of our study was to assess the impact of pathologic response on the survival of stageII and III rectal cancer patients after neoadjuvant chemoradiotherapy (nCRT). METHODS: Clinicopathologic characteristics and tumor regression scores (TRS) were assessed in 236 rectal cancer patients who treated with nCRT followed by surgery. Survival analysis was performed using Cox proportional hazards models. RESULTS: Among these patients, the stage of 88 patients was ypII, and 91 patients were with the stage of ypIII. The median follow-up time was 59.8 months. TRS was not an independent prognostic factor in ypII patients while it was significantly associated with the prognosis of ypIII patients (5-year survival rate 67.2% vs. 42.5%, P < 0.001). Furthermore, ypIII patients with the response to nCRT had similar survival to that of ypII patients (5-year survival rate 67.2% vs. 70.5%, P = 0.56). For ypIII patients, multivariable analysis showed that well differentiation, negative surgical margin, and the administration of adjuvant chemotherapy were associated with better survival. The surgical margin and differentiation were prognostic factors for ypII patients. CONCLUSIONS: ypIII rectal cancer patients with poor response to preoperative treatment are at high risk of worse oncological outcomes.

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