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1.
Front Oncol ; 13: 1116205, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36874138

RESUMO

Background: AMKL without DS is a rare but aggressive hematological malignant disease in children, and it is associated with inferior outcomes. Several researchers have regarded pediatric AMKL without DS as high-risk or at least intermediate-risk AML and proposed that upfront allogenic hematopoietic stem cell transplantation (HSCT) in first complete remission might improve long-term survival. Patients and method: We conducted a retrospective study with twenty-five pediatric (< 14 years old) AMKL patients without DS who underwent haploidentical HSCT in the Peking University Institute of Hematology, Peking University People's Hospital from July 2016 to July 2021. The diagnostic criteria of AMKL without DS were adapted from the FAB and WHO: ≥ 20% blasts in the bone marrow, and those blasts expressed at least one or more of the platelet glycoproteins: CD41, CD61, or CD42. AMKL with DS and therapy related AML was excluded. Children without a suitable closely HLA-matched related or unrelated donor (donors with more than nine out of 10 matching HLA-A, HLA-B, HLA-C, HLA-DR, and HLA-DQ loci), were eligible to receive haploidentical HSCT. Definition was adapted from international cooperation group. All statistical tests were conducted with SPSS v.24 and R v.3.6.3. Results: The 2-year OS was 54.5 ± 10.3%, and the EFS was 50.9 ± 10.2% in pediatric AMKL without DS undergoing haplo-HSCT. Statistically significantly better EFS was observed in patients with trisomy 19 than in patients without trisomy 19 (80 ± 12.6% and 33.3 ± 12.2%, respectively, P = 0.045), and OS was better in patients with trisomy 19 but with no statistical significance (P = 0.114). MRD negative pre-HSCT patients showed a better OS and EFS than those who were positive (P < 0.001 and P = 0.003, respectively). Eleven patients relapsed post HSCT. The median time to relapse post HSCT was 2.1 months (range: 1.0-14.4 months). The 2-year cumulative incidence of relapse (CIR) was 46.1 ± 11.6%. One patient developed bronchiolitis obliterans and respiratory failure and died at d + 98 post HSCT. Conclusion: AMKL without DS is a rare but aggressive hematological malignant disease in children, and it is associated with inferior outcomes. Trisomy 19 and MRD negative pre-HSCT might contribute to a better EFS and OS. Our TRM was low, haplo-HSCT might be an option for high-risk AMKL without DS.

2.
Water Res ; 235: 119829, 2023 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-36958219

RESUMO

Advanced oxidation/reduction of PFAS is challenged and concerned by the formation of toxic, short-chain intermediates during water treatments. In this study, we investigated the complete defluorination of PFOA by ultrasound/persulfate (US/PS) with harmless end-products of CO2, H2O, and F‒ ions. We observed 100% defluorination after 4 h of US treatment alone with a power input of 900 W. PS addition, however, suppressed defluorination. We demonstrated by kinetics-fitted Langmuir-type adsorption modeling, the added PS increased competition with PFOA for adsorption sites on the bubble-water interface where radical oxidation and pyrolysis may occur. Providing sulfate (SO4•-) and hydroxyl (•OH) radicals by means other than US did not defluorinate PFOA, indicating that pyrolysis likely contributes to the high defluorination performance. Bond dissociation energies for CC and CF were independent of pressure but decreased at elevated temperatures within cavitation bubbles (i.e., 5000 K) favoring the pyrolysis reactions. Furthermore, bond length calculations indicated that PFOA cleavage only begins to occur at temperatures in excess of those generated at the bubble interface (i.e., >1500 K) at the femtosecond level. This suggests that PFOA vaporizes or injects by nanodrops upon attachment to the cavitation bubble, enters the bubble, and is then cleaved within the bubble by pyrolysis. Our research in low-frequency ultrasonic horn system challenges the previous founding that defluorination of PFOA initiates and occurs at the bubble-water interface. We describe here that supplementing US-based processes with complementary treatments may have undesired effects on the efficacy of US. The mechanistic insights will further promote the implementation of US technology for PFAS treatment in achieving the zero fluoro-pollution goal.

3.
J Pain Res ; 16: 725-747, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36923648

RESUMO

Background: Migraine is a serious global health concern that imposed a huge economic burden on social health care. Over the past few decades, the analgesic effects of acupuncture have been widely recognized, and there is a growing body of research on acupuncture for migraine. Citation analysis is a branch of bibliometrics that helps researchers analyze and identify historical or landmark studies within the scientific literature. Currently, there is no analysis of the 100 most highly cited publications on acupuncture for migraine. Methods: The 100 most highly cited publications on acupuncture for migraine were screened using the Science Citation Index Expanded of the Web of Science Core Collection database. CiteSpace and VOSviewer programs were used for bibliometric analysis. Results: A total of 493 publications on acupuncture for migraine were identified. 100 of the most highly cited publications on acupuncture for migraine were published from 1984-2020. These publications were cited 6142 times with an h-index of 44 and 84% were original articles. The highest frequency of citations was 416. A total of 335 authors were involved in the study with 37 lead authors. 212 institutions from 20 countries contributed to the 100 most highly cited publications. The most published studies came from the United States (n=36), followed by China (n=27) and Germany (n=26). The Technical University of Munich published the largest number of papers (n = 15). Top-cited publications mainly came from the Headache (n=13, citations=582). Neuroimaging is gradually emerging as a hot topic of research. Conclusion: This is the first bibliometric analysis to offer a thorough list of the 100 most highly cited papers on acupuncture for migraine, demonstrating significant progress and emerging trends in this field to assist researchers in determining the direction for further research.

4.
Artigo em Inglês | MEDLINE | ID: mdl-36943347

RESUMO

A lactic acid bacterium isolated from pig faeces was characterized using a polyphasic approach. The strain was Gram-stain-positive, rod-shaped, and facultative anaerobic. Phylogenetic analysis of the 16S rRNA gene sequence indicated that the isolate belonged to the genus Lacticaseibacillus. The multi-locus sequence tree revealed that the strain formed a sub-cluster adjacent to Lacticaseibacillus kribbianus. The main fatty acids were C16 : 0 and C18 : 1ω9c. The average nucleotide identity value, average amino acid identity, and genome-to-genome distance for YH-lacS6T and its most closely related strain, L. kribbianus, were 85.4, 85.2 and 29.2 %, respectively. The G+C content of the genomic DNA was 61.6 mol%. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, aminophospholipids and phospholipids. The cell-wall peptidoglycan did not contain meso-diaminopimelic acid. Thus, YH-lacS6T (=KCTC 21186T=JCM 34954T) represents a novel species. The name Lacticaseibacillus parakribbianus sp. nov. is proposed.


Assuntos
Ácidos Graxos , Lacticaseibacillus , Suínos , Animais , Ácidos Graxos/química , Filogenia , RNA Ribossômico 16S/genética , Fazendas , DNA Bacteriano/genética , Composição de Bases , Técnicas de Tipagem Bacteriana , Análise de Sequência de DNA , Fosfolipídeos/química , Fezes/microbiologia , Peptidoglicano/química
6.
Environ Sci Technol ; 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36920429

RESUMO

Identifying phosphorus (P) sources is critical for solving eutrophication and controlling P in aquatic environments. Phosphate oxygen isotopes (δ18Op) have been used to trace P sources. However, the application of this method has been greatly restricted due to δ18OP values from the potential source having wide and overlapping ranges. In this research, P sources were traced by combining δ18Op with multiple stable isotopes of nitrogen (δ15N), hydrogen (δD), and dissolved inorganic carbon (δ13C). Then, a Bayesian-based Stable Isotope Analysis in R (SIAR) model and IsoSource model were used to estimate the proportional contributions of the potential sources in the Tuojiang River. δ18Op was not in equilibrium with ambient water, and statistically significant differences in the δ18Op values were found between the potential sources, indicating that δ18Op can be used to trace the P sources. δ15N, δD, and δ13C could assist δ18Op in identifying the main sources of P. The SIAR and IsoSource models suggested that industrial and domestic sewage was the largest contributor, followed by phosphate rock and phosphogypsum and agricultural sewage. The uncertainty of the calculation results of the SIAR model was lower than that of the IsoSource model. These findings provide new insights into tracing P sources using multiple stable isotopes in watersheds.

7.
Bioorg Med Chem Lett ; 85: 129217, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36889652

RESUMO

6-O-[18F]Fluoroethylerlotinib (6-O-[18F]FEE), with a suitable half-life for commercial distribution, may be a good replacement for [11C]erlotinib to identify epidermal growth factor receptor (EGFR) positive tumors with activating mutations to tyrosine kinase inhibitors therapy. In this study, we explored the fully automated synthesis of 6-O-[18F]FEE and investigated its pharmacokinetics in tumor-bearing mice. 6-O-[18F]FEE with high specific activity (28-100 GBq/µmol) and radiochemistry purity (over 99 %) was obtained by two-step reaction and Radio-HPLC separation in PET-MF-2 V-IT-1 automated synthesizer. PET imaging of 6-O-[18F]FEE in HCC827, A431, and U87 tumor-bearing mice with different EGFR expression and mutation was performed. Uptake and blocking of PET imaging indicated that the probe specifically targeted exon 19 deleted EGFR (the quantitative analysis of tumor-to-mouse ratio for HCC827, HCC827 blocking, U87, A431 was 2.58 ± 0.24, 1.20 ± 0.15, 1.18 ± 0.19, and 1.05 ± 0.13 respectively). Dynamic imaging was used to study the pharmacokinetics of the probe in tumor-bearing mice. Logan plot graphical analysis demonstrated late linearity and a high fitting correlation coefficient (0.998), supporting reversible kinetics. According to the Akaike Information Criterion (AIC) rule, the 2-compartment reversible model was more consistent with the metabolic properties of 6-O-[18F]FEE. The automated radiosynthesis and pharmacokinetic analysis will promote clinically transformation of 6-O-[18F]FEE.


Assuntos
Neoplasias Pulmonares , Tomografia por Emissão de Pósitrons , Animais , Camundongos , Cloridrato de Erlotinib , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/genética , Receptores ErbB , Mutação , Linhagem Celular Tumoral
8.
ACS Biomater Sci Eng ; 9(3): 1307-1319, 2023 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-36744996

RESUMO

Biomass carbon dots (CDs) derived from natural plants possess the advantages of low cost, photostability, and excellent biocompatibility, with potential applications in chemical sensing, bioimaging, and nanomedicine. However, the development of biomass CDs with excellent antioxidant activity and good biocompatibility is still a challenge. Herein, we propose a hypothesis for enhancing the antioxidant capacity of biomass CDs based on precursor optimization, extraction solvent, and other conditions with broccoli as the biomass. Compared to broccoli water extracts, broccoli powders, and broccoli organic solvent extracts, CDs derived from broccoli water extracts (BWE-CDs) have outstanding antioxidant properties due to the abundant C═C, carbonyl, and amino groups on their surface. After optimization of the preparation condition, the obtained BWE-CDs exhibit excellent free-radical scavenging activity with an EC50 of 68.2 µg/mL for DPPH• and 22.4 µg/mL for ABTS•+. Cytotoxicity and zebrafish embryotoxicity results indicated that BWE-CDs have lower cytotoxicity and better biocompatibility than that of CDs derived from organic solvents. In addition, BWE-CDs effectively scavenged reactive oxygen species (ROS) in A549 cells, 293T cells, and zebrafish, as well as eliminating inflammation in LPS-stimulated zebrafish. Mechanistic studies showed that the anti-inflammatory effect of BWE-CDs was dependent on the direct reaction of CDs with free radicals, the regulation of NO levels, and the upregulation of the expression of SOD and GPX-4. This work indicates that the antioxidant activity of CDs could be enhanced by using solvent extracts of biomass as precursors, and the obtained BWE-CDs exhibit characteristics of greenness, low toxicity, and excellent antioxidant and anti-inflammatory activities, which suggests the potential promising application of BWE-CDs as an antioxidant nanomedicine for inflammatory therapy.


Assuntos
Antioxidantes , Brassica , Animais , Peixe-Zebra , Carbono/química , Água , Anti-Inflamatórios/química , Solventes
9.
Biophys J ; 122(3S1): 18a-19a, 2023 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-36782905
10.
Opt Express ; 31(3): 4507-4520, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36785417

RESUMO

The scintillation of the orbital angular momentum (OAM) of a Bessel Gaussian beam was derived based on the Rytov method to characterize the performance of the OAM communication. Moreover, a multi-parameter demultiplexing method was also proposed which could decode the OAM state, the amplitude and two additional beam width information dimensions. The advantages of the OAM states as the communication carrier over the beam intensity were that the minimum scintillation of the fundamental mode was smaller, and its corresponding radius also diverged slower. The coefficient of variation of the decoding amplitude was approximated to the square root of the radial minimum scintillation, and it provided an estimated decoding precision for the input sample selection. This study not only provided theoretical basis for communication link design, but also had a promising application on the large capacity beam multiplexing in free-space laser communication.

11.
Sci Rep ; 13(1): 2691, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36792764

RESUMO

Accurate forecasting of hospital outpatient visits is beneficial to the rational planning and allocation of medical resources to meet medical needs. Several studies have suggested that outpatient visits are related to meteorological environmental factors. We aimed to use the autoregressive integrated moving average (ARIMA) model to analyze the relationship between meteorological environmental factors and outpatient visits. Also, outpatient visits can be forecast for the future period. Monthly outpatient visits and meteorological environmental factors were collected from January 2015 to July 2021. An ARIMAX model was constructed by incorporating meteorological environmental factors as covariates to the ARIMA model, by evaluating the stationary [Formula: see text], coefficient of determination [Formula: see text], mean absolute percentage error (MAPE), and normalized Bayesian information criterion (BIC). The ARIMA [Formula: see text] model with the covariates of [Formula: see text], [Formula: see text], and [Formula: see text] was the optimal model. Monthly outpatient visits in 2019 can be predicted using average data from past years. The relative error between the predicted and actual values for 2019 was 2.77%. Our study suggests that [Formula: see text], [Formula: see text], and [Formula: see text] concentration have a significant impact on outpatient visits. The model built has excellent predictive performance and can provide some references for the scientific management of hospitals to allocate staff and resources.


Assuntos
Modelos Estatísticos , Pacientes Ambulatoriais , Humanos , Teorema de Bayes , Previsões , Hospitais , Incidência , China
12.
Int J Mol Sci ; 24(4)2023 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-36835485

RESUMO

Rice leaf width (RLW) is a crucial determinant of photosynthetic area. Despite the discovery of several genes controlling RLW, the underlying genetic architecture remains unclear. In order to better understand RLW, this study conducted a genome-wide association study (GWAS) on 351 accessions from the rice diversity population II (RDP-II). The results revealed 12 loci associated with leaf width (LALW). In LALW4, we identified one gene, Narrow Leaf 22 (NAL22), whose polymorphisms and expression levels were associated with RLW variation. Knocking out this gene in Zhonghua11, using CRISPR/Cas9 gene editing technology, resulted in a short and narrow leaf phenotype. However, seed width remained unchanged. Additionally, we discovered that the vein width and expression levels of genes associated with cell division were suppressed in nal22 mutants. Gibberellin (GA) was also found to negatively regulate NAL22 expression and impact RLW. In summary, we dissected the genetic architecture of RLW and identified a gene, NAL22, which provides new loci for further RLW studies and a target gene for leaf shape design in modern rice breeding.


Assuntos
Estudo de Associação Genômica Ampla , Oryza , Estudo de Associação Genômica Ampla/métodos , Genótipo , Oryza/genética , Edição de Genes , Melhoramento Vegetal/métodos , Folhas de Planta/genética
13.
Front Immunol ; 14: 1104881, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36845150

RESUMO

Background: Smad7 is protective in a mouse model of rheumatoid arthritis. Here we investigated whether Smad7-expressing CD4+ T cells and the methylation of Smad7 gene in CD4+ T cells contribute to the disease activity of RA in patients. Methods: Peripheral CD4+ T cells were collected from 35 healthy controls and 57 RA patients. Smad7 expression by CD4+ T cells were determined and correlated with the clinical parameters of RA including RA score and serum levels of IL-6, CRP, ESR, DAS28-CRP, DAS28-ESR, Swollen joints and Tender joints. Bisulfite sequencing (BSP-seq) was used to determine the DNA methylation in Smad7 promoter (-1000 to +2000) region in CD4+ T cells. In addition, a DNA methylation inhibitor, 5-Azacytidine (5-AzaC), was added to CD4+ T cells to examine the possible role of Smad7 methylation in CD4+ T cell differentiation and functional activity. Results: Compared to the heath controls, Smad7 expression was significantly decreased in CD4+ T cells from RA patients and inversely correlated with the RA activity score and serum levels of IL-6 and CRP. Importantly, loss of Smad7 in CD4+ T cell was associated with the alteration of Th17/Treg balance by increasing Th17 over the Treg population. BSP-seq detected that DNA hypermethylation occurred in the Smad7 promoter region of CD4+ T cells obtained from RA patients. Mechanistically, we found that the DNA hypermethylation in the Smad7 promoter of CD4+ T cells was associated with decreased Smad7 expression in RA patients. This was associated with overreactive DNA methyltransferase (DMNT1) and downregulation of the methyl-CpG binding domain proteins (MBD4). Inhibition of DNA methylation by treating CD4+ T cells from RA patients with 5-AzaC significantly increased Smad7 mRNA expression along with the increased MBD4 but reduced DNMT1 expression, which was associated with the rebalance in the Th17/Treg response. Conclusion: DNA hypermethylation at the Smad7 promoter regions may cause a loss of Smad7 in CD4+ T cells of RA patients, which may contribute to the RA activity by disrupting the Th17/Treg balance.


Assuntos
Artrite Reumatoide , Interleucina-6 , Animais , Camundongos , Artrite Reumatoide/tratamento farmacológico , DNA/uso terapêutico , Metilação de DNA , Interleucina-6/genética , Linfócitos T Reguladores , Linfócitos T CD4-Positivos/imunologia
14.
Front Oncol ; 13: 1055122, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36756152

RESUMO

Background: High expression of matrix metalloproteinase-11 (MMP11) is associated with various tumors and immune microenvironments. Conversely, poor response to immunotherapy in epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma (LUAD) patients is closely related to the characteristics of immune microenvironment. Methods: The Cancer Genome Atlas (TCGA)-LUAD database and our gathered clinical LUAD samples were used to examine the relationship between MMP11 expression and EGFR mutation. Then the correlation between MMP11 and immune response and the difference of immune cell infiltration in different groups were analyzed. Compared the differences in the immune microenvironment between the MMP11-positive and MMP11-negative expression groups using immunohistochemistry (IHC) and multiplex immunohistochemistry. Results: The expression of MMP11 in samples with exon 19 deletions, exon 21 L858R or de novo exon 20 T790M mutations was higher than wild type, but there was no difference between the samples with uncommon mutation and the wild-type. The high MMP11 expression group had a higher Tumor Immune Dysfunction and Exclusion (TIDE) score. Pathways associated with enrichment in the extracellular matrix (ECM) were the main biological functions of differential genes between the high and low MMP11 groups. The IHC score of MMP11 in the EGFR-mutant group was higher than in the EGFR-wild group. In TCGA-LUAD, the high MMP11 group had a lower proportion of T cell CD8+ and NK cells activated. In the clinical samples, the infiltration levels of T cell CD8+ and NK cells in the tumor parenchyma of EGFR-mutant LUAD was lower in the MMP11-positive than in the MMP11-negative group. The expression levels of tumor cell PD-L1 were higher in the MMP11-positive expression group than in the MMP11-negative expression group, and the proportion of PD1+CD8+ T cells infiltrated was reduced in the MMP11-positive group compared to the MMP11-negative group. Conclusions: High expression of MMP11 was associated with EGFR mutations. Patients with EGFR-mutant LUAD with high expression of MMP11 responded poorly to immunotherapy, and the percentage of T cell CD8+ and NK cells in immune cell infiltration was lower in MMP11. Consequently, MMP11 is related to the immunological microenvironment of EGFR-mutant lung adenocarcinoma, which may be a predictor of possible immunotherapeutic response.

15.
Foods ; 12(4)2023 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-36832951

RESUMO

As a "rare bird on the plateau", the Tibetan chicken is rich in nutrition and has high medicinal value. In order to quickly and effectively identify the source of food safety problems and to label fraud regarding this animal, it is necessary to identify the geographical traceability of the Tibetan chicken. In this study, Tibetan chicken samples from four different cities in Tibet, China were analyzed. The amino acid profiles of Tibetan chicken samples were characterized and further subjected to chemometric analyses, including orthogonal least squares discriminant analysis, hierarchical cluster analysis, and linear discriminant analysis. The original discrimination rate was 94.4%, and the cross-validation rate was 93.3%. Moreover, the correlation between amino acid concentrations and altitudes in Tibetan chicken was studied. With the increase in altitude, all amino acid contents showed a normal distribution. For the first time, amino acid profiling has been comprehensively applied to trace the origin of plateau animal food with satisfactory accuracy.

16.
Hepatology ; 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36683360

RESUMO

BACKGROUND AND AIMS: Deregulation of adenosine-to-inosine (A-to-I) editing by adenosine deaminase acting on RNA 1 (ADAR1) leads to tumor-specific transcriptome diversity with prognostic values for hepatocellular carcinoma (HCC). However, ADAR1 editase-dependent mechanisms governing liver cancer stem cell (LCSC) generation and maintenance have remained elusive. APPROACH AND RESULTS: RNA-seq profiling identified ADAR1-responsive recoding editing events in HCC and showed editing frequency of GLI1 rather than transcript abundance, was clinically relevant. Functional differences in LCSC self-renewal and tumor aggressiveness between wild-type (GLI1 wt ) and edited GLI1 (GLI1 R701G ) were elucidated. We showed that overediting of GLI1 induced an arginine-to-glycine (R701G) substitution, augmenting tumor-initiating potential and exhibiting a more aggressive phenotype. GLI1 R701G harbored weak affinity to SUFU; which in turn, promoted its cytoplasmic-to-nuclear translocation to support LCSC self-renewal by increased pluripotency gene expression. Moreover, editing predisposes to stabilized GLI1 by abrogating ß-TrCP-GLI1 interaction. Integrative analysis of single-cell transcriptome further revealed hyperactivated mitophagy in ADAR1-enriched LCSCs. GLI1 editing promoted a metabolic switch to oxidative phosphorylation (OXPHOS) to control stress and stem-like state via PINK1-Parkin-mediated mitophagy in HCC, thereby conferring exclusive metastatic and sorafenib-resistant capacities. CONCLUSIONS: Our findings demonstrate a novel role of ADAR1 as an active regulator for LCSCs properties via editing GLI1 in the highly heterogeneous HCC.

17.
Diagnostics (Basel) ; 13(2)2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36673091

RESUMO

Legionella pneumonia is a relatively rare but extremely progressive pulmonary infection with high mortality. Traditional cultural isolation remains the gold standard for the diagnosis of Legionella pneumonia. However, its harsh culture conditions, long turnaround time, and suboptimal sensitivity do not meet the clinical need for rapid and accurate diagnosis, especially for critically ill patients. So far, pathogenic detection techniques including serological assays, urinary antigen tests, and mass spectrometry, as well as nucleic acid amplification technique, have been developed, and each has its own advantages and limitations. This review summarizes the clinical characteristics and imaging findings of Legionella pneumonia, then discusses the advances, advantages, and limitations of the various pathogenetic detection techniques used for Legionella pneumonia diagnosis. The aim is to provide rapid and accurate guiding options for early identification and diagnosis of Legionella pneumonia in clinical practice, further easing healthcare burden.

18.
ACS Chem Biol ; 18(1): 102-111, 2023 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-36623177

RESUMO

Guvermectin is a novel plant growth regulator that has been registered as a new agrochemical in China. It is an adenosine analogue with an unusual psicofuranose instead of ribose. Herein, the gene cluster responsible for guvermectin biosynthesis in Streptomyces caniferus NEAU6 is identified using gene interruption and heterologous expression experiments. A key intermediate psicofuranine 6'-phosphate (PMP) is chemically synthesized, and the functions of GvmB, C, D, and E are verified by individual stepwise enzyme reactions in vitro. The results also show that the biosynthesis of guvermectin is coupled with adenosine production by a single cluster. The higher catalytic efficiency of GvmB on PMP than AMP ensures the effective biosynthesis of guvermectin. Moreover, a phosphoribohydrolase GvmA is employed in the pathway that can hydrolyze AMP but not PMP and shows higher catalytic efficiency for the AMP hydrolysis than that of the AMP dephosphorylation by GvmB, leading to shunting of adenosine biosynthesis toward the production of guvermectin. Finally, the crystal structure of GvmE in complex with the product PMP has been solved. Glu160 at the C-terminal is identified as the acid/base for protonation/deprotonation of N7 of the adenine ring, demonstrating that GvmE is a noncanonical adenine phosphoribosyltransferase.


Assuntos
Adenina Fosforribosiltransferase , Ácido Glutâmico , Adenina Fosforribosiltransferase/química , Monofosfato de Adenosina/química , Modelos Moleculares , Adenosina
19.
Gastrointest Endosc ; 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36657608

RESUMO

BACKGROUND AND AIMS: Treatment strategies for early cancers or precancerous lesions of the upper gastrointestinal tract in cirrhotic patients with esophagogastric varices (EGV) are complicated and risky. We aimed to assess the efficacy and safety of endoscopic submucosal dissection (ESD) in the treatment of such patients and explore optimal treatment strategies. METHODS: We retrospectively enrolled 15 cirrhotic patients with EGV who underwent ESD for early cancers or precancerous lesions of the upper gastrointestinal tract from January 2012 to December 2021 at our center. Clinical features, endoscopic findings, treatment methods, adverse events and follow-up data were analyzed. RESULTS: Of the 15 patients, 1 had a platelet count <30×1000/mm3. Five were untreated for EGV, 1 was treated after ESD, 6 were treated before ESD, 1 was treated before and during ESD, and 2 were treated during ESD. The R0 resection rate was 100%. Of the 16 mucosal lesions, 15 were ERB-0 or ERB-c1, and 1 was ERB-c2. No patient experienced deterioration in liver function. The only adverse events were fever in 2 patients and postoperative bleeding (PB) in 2 patients. During a median follow-up of 27 months, 1 patient's esophageal HGD recurred at 19 months. No death resulted from the ESD procedure, liver function injury or gastrointestinal tumor itself. CONCLUSION: ESD is an effective and safe treatment for early cancers or precancerous lesions of the upper gastrointestinal tract in cirrhotic patients with EGV. The incidence of severe adverse events is very low due to the development of individualized clinical treatment strategies.

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