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1.
BMC Infect Dis ; 21(1): 85, 2021 Jan 19.
Article in English | MEDLINE | ID: mdl-33468073

ABSTRACT

BACKGROUND: To determine the phenotype, molecular characterisation and risk factors of postoperative meningitis induced by Extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae (EPE) in China. METHODS: We performed a multi-centre comparative cohort study of postoperative meningitis patients infected with Enterobacteriaceae in 4 neurosurgical centres in China from January 2014 to December 2019. Phenotype and molecular characteristics of the isolates were reviewed and tested, and independent risk factors of the EPE meningitis were evaluated by binary logistic regression. RESULTS: In total, 220 Enterobacteriaceae include 78 EPE were available in this study. 85.6% (67/78) ESBL-related genes were tested, and blaSHV (14.9%) and blaSHV + blaTEM + blaCTX-M-9 (20.9%) were found to be the most frequent mono and combined ESBL-related genes harboured by Enterobacteriaceae. On binary logistic analysis, craniotomy (OR. 2.583, 95% C.I. 1.274-5.235, P = 0.008) and malignancy (OR. 2.406, 95% C.I. 1.299-4.456, P = 0.005) were the associated independent risk factors to meningitis induced by EPE. CONCLUSIONS: To the best of our knowledge, this is the largest series focusing on risk factors of EPE meningitis which has been conducted in China. Craniotomy and malignancy were independent risk factors for EPE meningitis. The risk factors identified may be further utilized in clinical practice and research to avoid and reduce the mortality in future.


Subject(s)
Enterobacteriaceae Infections/epidemiology , Enterobacteriaceae/isolation & purification , Meningitis, Bacterial/epidemiology , beta-Lactamases/metabolism , Adult , China/epidemiology , Cohort Studies , Enterobacteriaceae/genetics , Enterobacteriaceae/metabolism , Enterobacteriaceae Infections/cerebrospinal fluid , Enterobacteriaceae Infections/microbiology , Female , Humans , Male , Meningitis, Bacterial/cerebrospinal fluid , Meningitis, Bacterial/microbiology , Phenotype , Polymerase Chain Reaction , Postoperative Complications/cerebrospinal fluid , Postoperative Complications/epidemiology , Postoperative Complications/microbiology , Retrospective Studies , Risk Factors
2.
Sensors (Basel) ; 21(13)2021 Jun 23.
Article in English | MEDLINE | ID: mdl-34201559

ABSTRACT

Power electronic devices are essential components of high-capacity industrial converters. Accurate assessment of their power loss, including switching loss and conduction loss, is essential to improving electrothermal stability. To accurately calculate the conduction loss, a drain-source voltage clamp circuit is required to measure the on-state voltage. In this paper, the conventional drain-source voltage clamp circuit based on a transistor is comprehensively investigated by theoretical analysis, simulations, and experiments. It is demonstrated that the anti-parallel diodes and the gate-shunt capacitance of the conventional drain-source voltage clamp circuit have adverse impacts on the accuracy and security of the conduction loss measurement. Based on the above analysis, an improved drain-source voltage clamp circuit, derived from the conventional drain-source voltage clamp circuit, is proposed to solve the above problems. The operational advantages, physical structure, and design guidelines of the improved circuit are fully presented. In addition, to evaluate the influence of component parameters on circuit performance, this article comprehensively extracts three electrical quantities as judgment indicators. Based on the working mechanism of the improved circuit and the indicators mentioned above, general mathematical analysis and derivation are carried out to give guidelines for component selection. Finally, extensive experiments and detailed analyses are presented to validate the effectiveness of the proposed drain-source voltage clamp circuit. Compared with the conventional drain-source voltage clamp circuit, the improved drain-source voltage clamp circuit has higher measurement accuracy and working security when measuring conduction loss, and the proposed component selection method is verified to be reasonable and effective for better utilizing the clamp circuit.

3.
Int J Mol Sci ; 22(21)2021 Nov 08.
Article in English | MEDLINE | ID: mdl-34769493

ABSTRACT

The sugar distribution mechanism in fruits has been the focus of research worldwide; however, it remains unclear. In order to elucidate the relevant mechanisms in grape berries, the expression, localization, function, and regulation of three sucrose transporters were studied in three representative Vitis varieties. Both SUC11 and SUC12 expression levels were positively correlated with sugar accumulation in grape berries, whereas SUC27 showed a negative relationship. The alignment analysis and sucrose transport ability of isolated SUCs were determined to reflect coding region variations among V. vinifera, V. amurensis Ruper, and V. riparia, indicating that functional variation existed in one SUT from different varieties. Furthermore, potentially oligomerized abilities of VvSUCs colocalized in the sieve elements of the phloem as plasma membrane proteins were verified. The effects of oligomerization on transport properties were characterized in yeast. VvSUC11 and VvSUC12 are high-affinity/low-capacity types of SUTs that stimulate each other by upregulating Vmax and Km, inhibiting sucrose transport, and downregulating the Km of VvSUC27. Thus, changes in the distribution of different SUTs in the same cell govern functional regulation. The activation and inhibition of sucrose transport could be achieved in different stages and tissues of grape development to achieve an effective distribution of sugar.


Subject(s)
Fruit/metabolism , Membrane Transport Proteins/metabolism , Plant Proteins/metabolism , Sucrose/metabolism , Vitis/metabolism , Biological Transport , Fruit/growth & development , Membrane Transport Proteins/chemistry , Membrane Transport Proteins/genetics , Plant Proteins/chemistry , Plant Proteins/genetics , Protein Multimerization , Structure-Activity Relationship , Vitis/growth & development
4.
Cancer Control ; 27(1): 1073274820969447, 2020.
Article in English | MEDLINE | ID: mdl-33121259

ABSTRACT

BACKGROUNDS: Acinar cell carcinoma of the pancreas is a rare malignancy, and its features remain unclear. We aimed to analyze the clinical characteristics, treatment and prognosis of acinar cell carcinoma with our institutional case series. METHODS: Patients diagnosed with acinar cell carcinoma in our hospital between 2005 and 2019 were reviewed. Investigations on clinicopathological features, treatment details and long-term survival were performed. RESULTS: A total of 45 pathologically confirmed acinar cell carcinomas were identified. The median age at diagnosis was 58 years with a male-to-female ratio of 3.1:1. There were 24 (53.3%) localized, 5 (11.1%) locally advanced and 16 (35.6%) metastatic cases, with a pancreatic head-to-body/tail ratio of 1:1.4 for all the primary lesions. In the localized group, there were 10 pancreatoduodenectomy, 12 distal pancreatectomy, 1 total pancreatectomy, and 1 distal pancreatectomy combined with proximal gastrectomy. Among the locally advanced and metastatic cases, 13 patients received chemotherapy, 1 received concurrent radiochemotherapy, 1 underwent synchronous resection of primary tumor and liver metastasis, 1 underwent palliative operation, 1 underwent exploratory laparotomy, and 4 required no treatment. The median overall survival of this series was 18.9 months with a 5-year survival rate of 19.6%. Moreover, the resected acinar cell carcinoma patients were associated with prolonged survival compared with the unresected cases (36.6 vs. 8.5 months, P < 0.001). CONCLUSIONS: Surgical resection could improve the long-term survival of acinar cell carcinoma patients, which might also improve the prognosis of selected metastatic cases. Large-scale studies are needed to further clarify the biological behavior and clinical features, and to seek the optimal treatments.


Subject(s)
Carcinoma, Acinar Cell/therapy , Liver Neoplasms/therapy , Pancreatectomy/statistics & numerical data , Pancreatic Neoplasms/therapy , Pancreaticoduodenectomy/statistics & numerical data , Aged , Carcinoma, Acinar Cell/mortality , Carcinoma, Acinar Cell/secondary , Chemotherapy, Adjuvant/statistics & numerical data , Female , Follow-Up Studies , Gastrectomy/statistics & numerical data , Hepatectomy/statistics & numerical data , Humans , Kaplan-Meier Estimate , Liver Neoplasms/mortality , Liver Neoplasms/secondary , Male , Middle Aged , Palliative Care/statistics & numerical data , Pancreas/pathology , Pancreas/surgery , Pancreatic Neoplasms/mortality , Pancreatic Neoplasms/pathology , Retrospective Studies , Survival Rate , Treatment Outcome
5.
Int J Mol Sci ; 21(7)2020 Apr 09.
Article in English | MEDLINE | ID: mdl-32283825

ABSTRACT

Sucrose is the predominant form of sugar transported from photosynthetic (source) to non-photosynthetic (sink) organs in higher plants relying on the transporting function of sucrose transporters (SUTs or SUCs). Many SUTs have been identified and characterized in both monocots and dicots. However, the function of sucrose transporters (SUTs or SUCs) from Vitis is not clear. As the world's most planted grape species, Vitis vinifera owns three sucrose transport activity verified SUTs. In this study, we constructed three kinds of VvSUC (Vitis vinifera SUC)-overexpressing transgenic Arabidopsis. VvSUC-overexpressing transgenic Arabidopsis was cultured on sucrose-supplemented medium. VvSUC11- and VvSUC12-overexpressing lines had similar thrived growth phenotypes, whereas the size and number of leaves and roots from VvSUC27-overexpressing lines were reduced compared with that of WT. When plants were cultured in soil, all SUT transgenic seedlings produced more number of leaves and siliques, resulting in higher yield (38.6% for VvSUC12-transformants) than that of WT. Besides, VvSUC27-transformants and VvSUC11-transformants enhanced drought resistance in Arabidopsis, providing a promising target for crop improvement.


Subject(s)
Adaptation, Biological/genetics , Arabidopsis/genetics , Arabidopsis/metabolism , Droughts , Genes, Plant , Sucrose/economics , Vitis/genetics , Amino Acid Sequence , Arabidopsis/growth & development , Biological Transport , Gene Expression Regulation, Plant , Phenotype , Plant Development/genetics , Sucrose/metabolism
6.
Plant Mol Biol ; 100(1-2): 111-132, 2019 May.
Article in English | MEDLINE | ID: mdl-30806883

ABSTRACT

KEY MESSAGE: The whole promoter regions of SUTs in Vitis were firstly isolated. SUTs are involved in the adaptation to biotic and abiotic stresses. The vulnerability of Vitis vinifera to abiotic and biotic stresses limits its yields. In contrast, Vitis amurensis displays resistance to environmental stresses, such as microbial pathogens, low temperatures, and drought. Sucrose transporters (SUTs) are important regulators for plant growth and stress tolerance; however, the role that SUTs play in stress resistance in V. amurensis is not known. Using V. amurensis Ruper. 'Zuoshan-1' and V. vinifera 'Chardonnay', we found that SUC27 was highly expressed in several vegetative organs of Zuoshan-1, SUC12 was weakly expressed or absent in most organs in both the species, and the distribution of SUC11 in source and sink organs was highest in Zuoshan-1. A search for cis-regulatory elements in the promoter sequences of SUTs revealed that they were regulated by light, environmental stresses, physiological correlation, and hormones. The SUTs in Zuoshan-1 mostly show a higher and rapid response than in Chardonnay under the induction by Plasmopara viticola infection, cold, water deficit, and dark conditions. The induction of SUTs was associated with the upregulation of key genes involved in sucrose metabolism and the biosynthesis of plant hormones. These results indicate that stress resistance in Zuoshan-1 is governed by the differential distribution and induction of SUTs by various stimuli, and the subsequent promotion of sucrose metabolism and hormone synthesis.


Subject(s)
Disease Resistance , Membrane Transport Proteins/metabolism , Plant Proteins/metabolism , Stress, Physiological , Vitis/physiology , Base Sequence , Biological Transport , Cold Temperature , Darkness , Gene Expression Regulation, Plant , Membrane Transport Proteins/genetics , Oomycetes/physiology , Organ Specificity , Osmosis , Plant Diseases/genetics , Plant Diseases/microbiology , Plant Growth Regulators/metabolism , Plant Leaves/metabolism , Plant Proteins/genetics , Promoter Regions, Genetic/genetics , Sucrose/metabolism , Sugars/metabolism , Vitis/genetics , Vitis/microbiology
7.
Bioorg Med Chem ; 27(5): 760-768, 2019 03 01.
Article in English | MEDLINE | ID: mdl-30665675

ABSTRACT

Considering the vital role of mitochondria in the anti-cancer mechanism of organic arsenical, the mitochondria-targeted precursor PDT-PAO-TPP was designed and synthesized. PDT-PAO-TPP, as a delocalization lipophilic cation (DLCs) which mainly accumulated in mitochondria, contributed to improve anti-cancer efficacy and selectivity towards NB4 cells. In detail, PDT-PAO-TPP inhibited the activity of PDHC resulting in the suppression of ATP synthesis and thermogenesis disorder. Additionally, the inhibition of respiratory chain complex I and IV by short-time incubation of PDT-PAO-TPP also accelerated the respiration dysfunction and continuous generation of ROS. These results led to the release of cytochrome c and activation of caspase family-dependent apoptosis. Different from the mechanism of PDT-PAO in HL-60 cells, it mainly induced the mitochondrial metabolic disturbance resulting in the intrinsic apoptosis via inhibiting the activity of PDHC in NB4 cells, which also implied that the efficacy exertion of organic arsenical was a complex process involved in many aspects of cellular function. This study systematically clarifies the anti-cancer mechanism of mitochondria-targeted organic arsenical PDT-PAO-TPP and confirms the new target PDHC of organic arsenicals, which further supports the organic arsenical as a promising anticancer drug.


Subject(s)
Antineoplastic Agents/pharmacology , Arsenicals/pharmacology , Mitochondria/drug effects , Antineoplastic Agents/chemical synthesis , Apoptosis/drug effects , Arsenicals/chemical synthesis , Cell Line, Tumor , Cell Respiration/drug effects , Cytochromes c/metabolism , Humans , Mitochondrial Membranes/metabolism , Permeability/drug effects , Pyruvate Dehydrogenase Complex/metabolism , Reactive Oxygen Species/metabolism , Thermogenesis/drug effects
8.
Appl Environ Microbiol ; 80(23): 7134-41, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25217009

ABSTRACT

Bacillus coagulans 2-6 is an excellent producer of optically pure l-lactic acid. However, little is known about the mechanism of synthesis of the highly optically pure l-lactic acid produced by this strain. Three enzymes responsible for lactic acid production-NAD-dependent l-lactate dehydrogenase (l-nLDH; encoded by ldhL), NAD-dependent d-lactate dehydrogenase (d-nLDH; encoded by ldhD), and glycolate oxidase (GOX)-were systematically investigated in order to study the relationship between these enzymes and the optical purity of lactic acid. Lactobacillus delbrueckii subsp. bulgaricus DSM 20081 (a d-lactic acid producer) and Lactobacillus plantarum subsp. plantarum DSM 20174 (a dl-lactic acid producer) were also examined in this study as comparative strains, in addition to B. coagulans. The specific activities of key enzymes for lactic acid production in the three strains were characterized in vivo and in vitro, and the levels of transcription of the ldhL, ldhD, and GOX genes during fermentation were also analyzed. The catalytic activities of l-nLDH and d-nLDH were different in l-, d-, and dl-lactic acid producers. Only l-nLDH activity was detected in B. coagulans 2-6 under native conditions, and the level of transcription of ldhL in B. coagulans 2-6 was much higher than that of ldhD or the GOX gene at all growth phases. However, for the two Lactobacillus strains used in this study, ldhD transcription levels were higher than those of ldhL. The high catalytic efficiency of l-nLDH toward pyruvate and the high transcription ratios of ldhL to ldhD and ldhL to the GOX gene provide the key explanations for the high optical purity of l-lactic acid produced by B. coagulans 2-6.


Subject(s)
Bacillus/enzymology , Bacillus/metabolism , Lactate Dehydrogenases/metabolism , Lactic Acid/metabolism , Bacillus/genetics , Fermentation , Gene Expression Profiling , Kinetics , Lactate Dehydrogenases/genetics , Lactobacillus delbrueckii/enzymology , Lactobacillus delbrueckii/genetics , Lactobacillus delbrueckii/metabolism , Lactobacillus plantarum/enzymology , Lactobacillus plantarum/genetics , Lactobacillus plantarum/metabolism
9.
Am J Surg Pathol ; 48(4): 417-425, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-37997470

ABSTRACT

OBJECTIVE: Immunohistochemistry is routinely performed to detect mismatch repair deficiency in solid tumors. Heterogeneous MMR expression (MMR-het) has been reported occasionally but not systemically studied. METHODS: In this study, we depicted MMR-het patterns of 40 tumors of different anatomical sites and analyzed MMR genetic alterations and tumor mutational burdens (TMB) through comprehensive genomic profiling. RESULTS: The MMR-het patterns were classified into 4 subgroups: "single-loss" (3 cases), "MLH1/PMS2 double-loss" (16 cases), "MSH2/MSH6 double-loss" (8 cases), and "triple/tetra-loss" (13 cases). Seventeen MMR-het cases exhibited histological heterogeneity, in which MMR protein loss was generally confined to either poorly differentiated or well-differentiated tumor areas. All "single-loss" tumors had MMR somatic mutations and coexisting POLE exonuclease domain mutations. "MLH1/PMS2 double-loss" tumors unexceptionally harbored MLH1 hypermethylation without MMR germline mutations. In the "MSH2/MSH6 double-loss" subgroup, 4 cases had MSH2/MSH6 germline mutations, while another 4 cases had multiple MSH2/MSH6 somatic mutations. Additional POLE exonuclease domain mutations were identified in 2 cases. Tumors in the "triple/tetra-loss" subgroup generally had MLH1 abnormalities (8 MLH1 hypermethylation, 4 MLH1 germline mutation, 1 MLH1 double somatic mutations), and coexistent somatic mutations on MSH2/MSH6 . Thirty-one cases (83.8%) were TMB-H, and all POLE -mutated cases exhibited ultra-high TMB (111.4 to 524.2 mut/Mb). CONCLUSION: Our findings highlighted the importance of accurately interpreting heterogeneous MMR protein staining patterns for developing a more efficient personalized genetic investigation strategy.


Subject(s)
Colorectal Neoplasms , DNA Mismatch Repair , Humans , Mismatch Repair Endonuclease PMS2/genetics , Mismatch Repair Endonuclease PMS2/metabolism , MutS Homolog 2 Protein/genetics , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Colorectal Neoplasms/pathology , Exonucleases/genetics , Exonucleases/metabolism , MutL Protein Homolog 1/genetics , MutL Protein Homolog 1/metabolism
10.
Virol Sin ; 39(4): 632-644, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38945214

ABSTRACT

Hand, foot and mouth disease (HFMD), mainly caused by enterovirus 71 (EV71), has frequently occurred in the Asia-Pacific region, posing a significant threat to the health of infants and young children. Therefore, research on the infection mechanism and pathogenicity of enteroviruses is increasingly becoming important. The 3D polymerase, as the most critical RNA-dependent RNA polymerase (RdRp) for EV71 replication, is widely targeted to inhibit EV71 infection. In this study, we identified a novel host protein, AIMP2, capable of binding to 3D polymerase and inhibiting EV71 infection. Subsequent investigations revealed that AIMP2 recruits the E3 ligase SMURF2, which mediates the polyubiquitination and degradation of 3D polymerase. Furthermore, the antiviral effect of AIMP2 extended to the CVA16 and CVB1 serotypes. Our research has uncovered the dynamic regulatory function of AIMP2 during EV71 infection, revealing a novel antiviral mechanism and providing new insights for the development of antienteroviral therapeutic strategies.


Subject(s)
Enterovirus A, Human , Ubiquitin-Protein Ligases , Virus Replication , Humans , Cell Line , Enterovirus A, Human/genetics , Enterovirus A, Human/physiology , Enterovirus Infections/virology , Enterovirus Infections/metabolism , Enterovirus Infections/genetics , HEK293 Cells , Host-Pathogen Interactions , Proteolysis , RNA-Dependent RNA Polymerase/metabolism , RNA-Dependent RNA Polymerase/genetics , Ubiquitin-Protein Ligases/metabolism , Ubiquitin-Protein Ligases/genetics , Ubiquitination
11.
Int J Womens Health ; 16: 1401-1411, 2024.
Article in English | MEDLINE | ID: mdl-39161646

ABSTRACT

Introduction: This study used single-center data to analyze the clinicopathological features of site-specific endometrial cancer. Methods: Patients with endometrial carcinoma who had undergone surgery at Peking Union Medical College Hospital, China, between March 2016 and January 2022 were enrolled. Clinical information and pathological characteristics were summarized, and microsatellite status was analyzed using the immunohistochemical method. Patient prognoses were measured in terms of the rates of overall survival and progression-free survival. Results: The mean patient age was 49 years (ranging: from 25 to 76 years old), and there was no difference in clinicopathological features between endometrioid and type II endometrial carcinoma in LUSC. The ER and PR expression ratios were 80.4% and 64.3%, respectively, in this LUSC cohort, and the MMR deficiency ratio was 33.9%, including 39.6% in endometrioid carcinoma and 15.4% in type II endometrial carcinoma. Combined MSH2&MSH6 loss was more common than combined MLH1&PMS2 being unexpressed (16.1% vs 12.5%), and dMMR patients differed significantly from the pMMR group in terms of vascular invasion (P=0.003). The combination of chemotherapy and radiotherapy did not provide a statistically significant improvement in prognosis compared to chemotherapy alone. Conclusion: The results of this study showed that LUSC patients tended to be younger and their tumors had less expression of hormone markers. The biological behavior of both endometrioid cancer and type II EC may be similar when EC occurs in this area. Furthermore, this type of tumor also showed a higher incidence of vascular invasion, and the combination of chemotherapy and radiotherapy did not provide significant improvement. Thus, successful treatment of LUSC tumors requires aggressive surgical intervention and a more effective postoperative treatment approach.

12.
World J Clin Cases ; 10(3): 856-869, 2022 Jan 21.
Article in English | MEDLINE | ID: mdl-35127901

ABSTRACT

BACKGROUND: Tumor-infiltrating lymphocytes (TILs) constitute a prognostic factor in hepatocellular carcinoma (HCC). However, different methods of assessing TILs have various pre-analytical, analytical, and post-analytical challenges. The evaluation of TILs in hematoxylin and eosin (H&E)-stained tumor sections proposed by the International Immuno-Oncology Biomarker Working Group was demonstrated to be a reproducible, affordable and easily applied method in many tumors. AIM: To evaluate the prognostic significance of TILs in H&E-stained slides of HCCs. METHODS: This was a retrospective study performed in the hospital. HCC patients who underwent liver resection between 2015 and 2017 in Zhongshan Hospital were enrolled in this study. Patients who experienced recurrence or received therapy in addition to antiviral therapy before surgery at this time were excluded. A total of 204 patients were enrolled in the study. The ILs were counted manually in tumor sections stained with H&E under an optical microscope at 400 ×. The ILs were assessed separately in the center of the tumor (TILsCT), the invasive front (TILsIF), and peritumor (PILs) areas. Univariate and multivariate survival analyses were performed using a Cox regression model. P < 0.05 was considered statistically significant and all P-values were two-sided. RESULTS: Among the 204 patients, univariate analysis indicated that macrovascular invasion (MaVI) (P = 0.001), microvascular invasion (MVI) (P = 0.012), multiple tumors (P = 0.008), large tumors (> 10 cm) (P = 0.001), absence of a tumor capsule (P = 0.026), macrotrabecular histological subtype (P = 0.001), low density of TILsCT (P = 0.039), TILsIF (P = 0.014), and PILs (P = 0.010) were predictors of progression-free survival (PFS). Cox multivariate analysis indicated that MaVI (P = 0.009), absence of a tumor capsule (P = 0.031), low-density of TILsIF (P = 0.047) and PILs (P = 0.0495) were independent predictors of PFS. A three-category analysis was carried out by combining TILsCT, TILsIF, and PILs, after which HCCs were classified into immunehigh [(TILsCT)high, (TILsIF)high, and PILshigh, 83 cases], immunemod (tumors other than immunehigh and immunelow subtypes, 94 cases), and immunelow [(TILsCT)low, (TILsIF)low, and PILslow, 27 cases)] subtypes. The immunehigh subtype had a lower rate of MVI (40.96%) than the immunemod (61.70%, P = 0.017) and immunelow (66.67%, P = 0.020) subtypes. The recurrence rates of the immunehigh, immunemod and immunelow subtypes were 10.8%, 25.5% and 33.3%, respectively. CONCLUSION: HCC patients with high infiltrating lymphocytes tend to have a lower recurrence rate and less MVI. The evaluation of TILs in H&E-stained specimens could be a prognostic parameter for HCC.

13.
Food Res Int ; 158: 111462, 2022 08.
Article in English | MEDLINE | ID: mdl-35840194

ABSTRACT

Plant-based meat alternatives (PMAs) is a new type of food that meets people's health needs, but the lack of awareness of its nutritional properties limits product development and promotion. Here, we compared the similarities and differences of the nutritional properties of PMAs and meat before and after in vitro simulation of gastrointestinal digestion by chemical composition analysis, peptidomics and bioactivity tests. The molecular weights of Plant-based meat alternatives derived peptides (PDPs) as well as meat-derived peptides (MDPs) in the beef and pork groups were mainly concentrated in the low mass range from 800 Da to 1500 Da. The principal component analysis indicated that the composition of MDPs in the beef and pork groups significantly differed from PDPs but overlapped slightly with the chicken group. Also, there were very few common peptides among them. The proportion of high-biological-scoring peptides (33.3%-40%) in PDPs was more than that in MDPs (4.8%-20.8%). PDPs were predicted to have higher antibacterial activity than others. PDPs and MDPs showed a certain antioxidant capacity and angiotensin converting enzyme inhibitory activity (62.2%-92.5%) in vitro. Some peptides weakly inhibited the growth of Escherichia coli (ATCC 25922) and Staphylococcus aureus (ATCC 25923) while promoting the growth of probiotics. This research provides a theoretical basis for in-depth exploration of the nutritional characteristics of PMAs.


Subject(s)
Digestion , Pork Meat , Animals , Cattle , Chickens , Humans , Meat/analysis , Peptides/chemistry
14.
J Hematol Oncol ; 15(1): 168, 2022 11 25.
Article in English | MEDLINE | ID: mdl-36434634

ABSTRACT

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with poor prognosis. Proteogenomic characterization and integrative proteomic analysis provide a functional context to annotate genomic abnormalities with prognostic value. METHODS: We performed an integrated multi-omics analysis, including whole-exome sequencing, RNA-seq, proteomic, and phosphoproteomic analysis of 217 PDAC tumors with paired non-tumor adjacent tissues. In vivo functional experiments were performed to further illustrate the biological events related to PDAC tumorigenesis and progression. RESULTS: A comprehensive proteogenomic landscape revealed that TP53 mutations upregulated the CDK4-mediated cell proliferation process and led to poor prognosis in younger patients. Integrative multi-omics analysis illustrated the proteomic and phosphoproteomic alteration led by genomic alterations such as KRAS mutations and ADAM9 amplification of PDAC tumorigenesis. Proteogenomic analysis combined with in vivo experiments revealed that the higher amplification frequency of ADAM9 (8p11.22) could drive PDAC metastasis, though downregulating adhesion junction and upregulating WNT signaling pathway. Proteome-based stratification of PDAC revealed three subtypes (S-I, S-II, and S-III) related to different clinical and molecular features. Immune clustering defined a metabolic tumor subset that harbored FH amplicons led to better prognosis. Functional experiments revealed the role of FH in altering tumor glycolysis and in impacting PDAC tumor microenvironments. Experiments utilizing both in vivo and in vitro assay proved that loss of HOGA1 promoted the tumor growth via activating LARP7-CDK1 pathway. CONCLUSIONS: This proteogenomic dataset provided a valuable resource for researchers and clinicians seeking for better understanding and treatment of PDAC.


Subject(s)
Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Proteogenomics , Humans , Proteomics , Carcinoma, Pancreatic Ductal/genetics , Carcinoma, Pancreatic Ductal/pathology , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/pathology , Carcinogenesis/genetics , Cell Transformation, Neoplastic , Tumor Microenvironment , Membrane Proteins , ADAM Proteins , Ribonucleoproteins , Pancreatic Neoplasms
15.
Front Plant Sci ; 12: 759047, 2021.
Article in English | MEDLINE | ID: mdl-34868153

ABSTRACT

Seedless fruits are favorable in the market because of their ease of manipulation. Sucrose transporters (SUTs or SUCs) are essential for carbohydrate metabolism in plants. Whether SUTs participate directly in causing stenospermocarpy, thereby increasing fruit quality, remains unclear. Three SUTs, namely, VvSUC11, VvSUC12, and VvSUC27 from Vitis vinifera, were characterized and ectopic expression in tomatoes. VvSUC11- and VvSUC12-overexpressing lines had similar flower and fruit phenotypes compared with those of the wild type. VvSUC27-overexpressing lines produced longer petals and pistils, an abnormal stigma, much less and shrunken pollen, and firmer seedless fruits. Moreover, produced fruits from all VvSUC-overexpressing lines had a higher soluble solid content and sugar concentration. Transcriptomic analysis revealed more genes associated with carbohydrate metabolism and sugar transport and showed downregulation of auxin- and ethylene-related signaling pathways during early fruit development in VvSUC27-overexpressing lines relative to that of the wild type. Our findings demonstrated that stenospermocarpy can be induced by overexpression of VvSUC27 through a consequential reduction in nutrient delivery to pollen at anthesis, with a subsequent downregulation of the genes involved in carbohydrate metabolism and hormone signaling. These commercially desirable results provide a new strategy for bioengineering stenospermocarpy in tomatoes and in other fruit plants.

16.
Sci Rep ; 10(1): 1568, 2020 01 31.
Article in English | MEDLINE | ID: mdl-32005939

ABSTRACT

Central nervous system infection (CNSI) is a significant type of infection that plagues the fields of neurology and neurosurgical science. Prompt and accurate diagnosis of CNSI is a major challenge in clinical and laboratory assessments; however, developing new methods may help improve diagnostic protocols. This study evaluated the second-generation micro/nanofluidic chip platform (MNCP-II), which overcomes the difficulties of diagnosing bacterial and fungal infections in the CNS. The MNCP-II is simple to operate, and can identify 44 genus or species targets and 35 genetic resistance determinants in 50 minutes. To evaluate the diagnostic accuracy of the second-generation micro/nanofluidic chip platform for CNSI in a multicenter study. The limit of detection (LOD) using the second-generation micro/nanofluidic chip platform was first determined using six different microbial standards. A total of 180 bacterium/fungi-containing cerebrospinal fluid (CSF) cultures and 26 CSF samples collected from CNSI patients with negative microbial cultures were evaluated using the MNCP-II platform for the identification of microorganism and determinants of genetic resistance. The results were compared to those obtained with conventional identification and antimicrobial susceptibility testing methods. The LOD of the various microbes tested with the MNCP-II was found to be in the range of 250-500 copies of DNA. For the 180 CSF microbe-positive cultures, the concordance rate between the platform and the conventional identification method was 90.00%; eight species attained 100% consistency. In the detection of 9 kinds of antibiotic resistance genes, including carbapenemases, ESBLs, aminoglycoside, vancomycin-related genes, and mecA, concordance rates with the conventional antimicrobial susceptibility testing methods exceeded 80.00%. For carbapenemases and ESBLs-related genes, both the sensitivity and positive predictive values of the platform tests were high (>90.0%) and could fully meet the requirements of clinical diagnosis. MNCP-II is a very effective molecular detection platform that can assist in the diagnosis of CNSI and can significantly improve diagnostic efficiency.


Subject(s)
Central Nervous System Infections/diagnosis , Lab-On-A-Chip Devices , Anti-Bacterial Agents/therapeutic use , Antifungal Agents/therapeutic use , Central Nervous System Bacterial Infections/cerebrospinal fluid , Central Nervous System Bacterial Infections/diagnosis , Central Nervous System Bacterial Infections/drug therapy , Central Nervous System Fungal Infections/cerebrospinal fluid , Central Nervous System Fungal Infections/diagnosis , Central Nervous System Fungal Infections/drug therapy , Central Nervous System Infections/cerebrospinal fluid , Central Nervous System Infections/drug therapy , China , Drug Resistance, Bacterial/genetics , Drug Resistance, Fungal/genetics , Humans , Limit of Detection , Microbial Sensitivity Tests , Prospective Studies , Reproducibility of Results , Sensitivity and Specificity
17.
18.
Front Plant Sci ; 9: 970, 2018.
Article in English | MEDLINE | ID: mdl-30123225

ABSTRACT

9-cis-epoxycarotenoid dioxygenase (NCED) is a key enzyme involved in the biosynthesis of abscisic acid (ABA), which is associated with drought tolerance in plants. An osmotic-inducible VaNCED1 gene was isolated from a drought-resistant cultivar of Vitis amurensis and constitutively overexpressed in a drought-sensitive cultivar of Vitis vinifera. Transgenic plants showed significantly improved drought tolerance, including a higher growth rate and better drought resistant under drought conditions, compared to those of wild-type (WT) plants. After water was withheld for 50 days, the upper leaves of transgenic plants remained green, whereas most leaves of WT plants turned yellow and fell. Besides the increase in ABA content, overexpression of VaNCED1 induced the production of jasmonic acid (JA) and accumulation of JA biosynthesis-related genes, including allene oxide cyclase (AOC) and 12-oxophytodienoate reductase (OPR3). Moreover, transgenic plants possessed advantageous physiological indices, including lower leaf stomatal density, lower photosynthesis rate, and lower accumulation of proline and superoxide dismutase (SOD), compared to those of WT plants, indicating increased resistance to drought stress. Quantitative real time polymerase chain reaction (RT-qPCR) analysis revealed that overexpression of VaNCED1 enhanced the expression of drought-responsive genes, such as ABA-responsive element1 (ABRE1), ABRE binding factors 2 (ABF2), plasma membrane intrinsic proteins 2 (PIP2), C-repeat/DRE-Binding Factor 4 (VvCBF4) and ABA-insensitive 5 (ABI5). Although the development of transgenic plants was delayed by 4 months than WT plants, because of seed dormancy and abnormal seedlings, the surviving transgenic plants provided a solid method for protection of woody plants from drought stress.

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Front Plant Sci ; 8: 1069, 2017.
Article in English | MEDLINE | ID: mdl-28676814

ABSTRACT

The import of sugar from source leaves and it further accumulation in grape berries are considerably high during ripening, and this process is mediated via sucrose transporters. In this study, a grape sucrose transporter (SUT) gene, VvSUC27, located at the plasma membrane, was transferred to tobacco (Nicotiana tabacum). The transformants were more sensitive to sucrose and showed more rapid development, especially roots, when cultured on MS agar medium containing sucrose, considering that the shoot/root dry weight ratio was only half that of the control. Moreover, all transformed plants exhibited light-colored leaves throughout their development, which indicated chlorosis and an associated reduction in photosynthesis. The total sugar content in the roots and stems of transformants was higher than that in control plants. No significant difference was observed in the leaves between the transformants and control plants. The levels of growth-promoting hormones were increased, and those of stress-mediating hormones were reduced in transgenic tobacco plants. The qRT-PCR analysis revealed that the expression of VvSUC27 was 1,000 times higher than that of the autologous tobacco sucrose transporter, which suggested that the markedly increased growth rate of transformants was because of the heterogeneously expressed gene. The transgenic tobacco plants showed resistance to abiotic stresses. Strikingly, the overexpression of VvSUC27 leaded to the up regulation of most reactive oxygen species scavengers and abscisic acid-related genes that might enable transgenic plants to overcome abiotic stress. Taken together, these results revealed an important role of VvSUC27 in plant growth and response to abiotic stresses, especially in the presence of sucrose in vitro.

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