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1.
J Am Chem Soc ; 146(26): 17728-17737, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38899504

RESUMO

Targeted protein degradation technology holds great potential in biomedicine, particularly in treating tumors and other protein-related diseases. Research on intracellular protein degradation using molecular glues and PROTAC technology is leading, while research on the degradation of membrane proteins and extracellular proteins through the lysosomal pathway is still in the preclinical stage. The scarcity of useful targets is an immense limitation to technological advancement, making it essential to explore novel, potentially effective approaches for targeted lysosomal degradation. Here, we employed the glucose transporter Glut1 as an innovative lysosome-targeting receptor and devised the Glut1-Facilitated Lysosomal Degradation (GFLD) strategy. We synthesized potential Glut1 ligands via reversible addition-fragmentation chain transfer (RAFT) polymerization and acquired antibody-glycooligomer conjugates through bioorthogonal reactions as lysosome-targeting protein degradation molecules, utilized in the management of PD-L1 high-expressing triple-negative breast cancer. The glucose transporter Glut1 as a lysosome-targeting receptor exhibits potential for the advancement of a broader array of medications in the future.


Assuntos
Transportador de Glucose Tipo 1 , Lisossomos , Proteólise , Lisossomos/metabolismo , Transportador de Glucose Tipo 1/metabolismo , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Linhagem Celular Tumoral , Ligantes
2.
Biomacromolecules ; 25(3): 1671-1681, 2024 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-38354397

RESUMO

Nanoparticles (NPs) containing light-responsive polymers and imaging agents show great promise for controlled drug delivery. However, most light-responsive NPs rely on short-wavelength excitation, resulting in poor tissue penetration and potential cytotoxicity. Moreover, excessively sensitive NPs may prematurely release drugs during storage and circulation, diminishing their efficacy and causing off-target toxicity. Herein, we report visible-light-responsive NPs composed of an amphiphilic block copolymer containing responsive 4-acrylamide benzenesulfonyl azide (ABSA) and hydrophilic N,N'-dimethylacrylamide (DMA) units. The polymer pDMA-ABSA was loaded with the chemotherapy drug dasatinib and zinc tetraphenylporphyrin (ZnTPP). ZnTPP acted as an imaging reagent and a photosensitizer to reduce ABSA upon visible light irradiation, converting hydrophobic units to hydrophilic units and disrupting NPs to trigger drug release. These NPs enabled real-time fluorescence imaging in cells and exhibited synergistic chemophotodynamic therapy against multiple cancer cell lines. Our light-responsive NP platform holds great promise for controlled drug delivery and cancer theranostics, circumventing the limitations of traditional photosensitive nanosystems.


Assuntos
Portadores de Fármacos , Metaloporfirinas , Nanopartículas , Portadores de Fármacos/química , Azidas , Polímeros/química , Luz , Nanopartículas/química , Liberação Controlada de Fármacos
3.
BMC Infect Dis ; 24(1): 257, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38395803

RESUMO

PURPOSE: To identify the key infection processes and risk factors in Computed Tomography (CT) examination process within the standard prevention and control measures for the COVID-19 epidemic, aiming to mitigate cross-infection occurrences in the hospital. METHOD: The case hospital has assembled a team of 30 experts specialized in CT examination. Based on the CT examination process, the potential failure modes were assessed from the perspective of severity (S), occurrence probability (O), and detectability (D); they were then combined with corresponding risk prevention measures. Finally, key infection processes and risk factors were identified according to the risk priority number (RPN) and expert analysis. RESULTS: Through the application of RPN and further analysis, four key potential infection processes were identified, including "CT request form (A1)," "during the scan of CT patient (B2)," "CT room and objects disposal (C2)," and "medical waste (garbage) disposal (C3)". In addition, eight key risk factors were also identified, including "cleaning personnel does not wear masks normatively (C32)," "nurse does not select the vein well, resulting in extravasation of the peripheral vein for enhanced CT (B25)," "patient cannot find the CT room (A13)," "patient has obtained a CT request form but does not know the procedure (A12)," "patient is too unwell to continue with the CT scan (B24)," "auxiliary staff (or technician) does not have a good grasp of the sterilization and disinfection standards (C21)," "auxiliary staff (or technician) does not sterilize the CT machine thoroughly (C22)," and "cleaning personnel lacks of knowledge of COVID-19 prevention and control (C33)". CONCLUSION: Hospitals can publicize the precautions regarding CT examination through various channels, reducing the incidence of CT examination failure. Hospitals' cleaning services are usually outsourced, and the educational background of the staff employed in these services is generally not high. Therefore, during training and communication, it is more necessary to provide a series of scope and training programs that are aligned with their understanding level. The model developed in this study effectively identifies the key infection prevention process and critical risk factors, enhancing the safety of medical staff and patients. This has significant research implications for the potential epidemic of major infectious diseases.


Assuntos
COVID-19 , Infecção Hospitalar , Humanos , Infecção Hospitalar/prevenção & controle , Fatores de Risco , Tomografia Computadorizada por Raios X , Tomografia
4.
Plant Cell ; 32(7): 2178-2195, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32358072

RESUMO

Chromatin remodeling and histone modifications are important for development and floral transition in plants. However, it is largely unknown whether and how these two epigenetic regulators coordinately regulate the important biological processes. Here, we identified three types of Imitation Switch (ISWI) chromatin-remodeling complexes in Arabidopsis (Arabidopsis thaliana). We found that AT-RICH INTERACTING DOMAIN5 (ARID5), a subunit of a plant-specific ISWI complex, can regulate development and floral transition. The ARID-PHD dual domain cassette of ARID5 recognizes both the H3K4me3 histone mark and AT-rich DNA. We determined the ternary complex structure of the ARID5 ARID-PHD cassette with an H3K4me3 peptide and an AT-containing DNA. The H3K4me3 peptide is combinatorially recognized by the PHD and ARID domains, while the DNA is specifically recognized by the ARID domain. Both PHD and ARID domains are necessary for the association of ARID5 with chromatin. The results suggest that the dual recognition of AT-rich DNA and H3K4me3 by the ARID5 ARID-PHD cassette may facilitate the association of the ISWI complex with specific chromatin regions to regulate development and floral transition.


Assuntos
Proteínas de Arabidopsis/genética , Arabidopsis/fisiologia , Proteínas de Ligação a DNA/genética , Flores/fisiologia , Histonas/metabolismo , Proteínas de Arabidopsis/metabolismo , Montagem e Desmontagem da Cromatina , Cristalografia por Raios X , DNA de Plantas/genética , DNA de Plantas/metabolismo , Proteínas de Ligação a DNA/metabolismo , Regulação da Expressão Gênica de Plantas , Histonas/genética , Complexos Multiproteicos/genética , Complexos Multiproteicos/metabolismo , Plantas Geneticamente Modificadas , Domínios Proteicos
5.
J Integr Plant Biol ; 64(12): 2385-2395, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36149781

RESUMO

DNA methylation, a conserved epigenetic mark, is critical for tuning temporal and spatial gene expression. The Arabidopsis thaliana DNA glycosylase/lyase REPRESSOR OF SILENCING 1 (ROS1) initiates active DNA demethylation and is required to prevent DNA hypermethylation at thousands of genomic loci. However, how ROS1 is recruited to specific loci is not well understood. Here, we report the discovery of Arabidopsis AGENET Domain Containing Protein 3 (AGDP3) as a cellular factor that is required to prevent gene silencing and DNA hypermethylation. AGDP3 binds to H3K9me2 marks in its target DNA via its AGD12 cassette. Analysis of the crystal structure of the AGD12 cassette of AGDP3 in complex with an H3K9me2 peptide revealed that dimethylated H3K9 and unmodified H3K4 are specifically anchored into two different surface pockets. A histidine residue located in the methyllysine binding aromatic cage provides AGDP3 with pH-dependent H3K9me2 binding capacity. Our results uncover a molecular mechanism for the regulation of DNA demethylation by the gene silencing mark H3K9me2.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/genética , Arabidopsis/metabolismo , Metilação de DNA/genética , Proteínas de Transporte/metabolismo , Proteínas Tirosina Quinases/genética , Proteínas Tirosina Quinases/metabolismo , Proteínas Nucleares/metabolismo , Proteínas Proto-Oncogênicas/genética , Proteínas de Arabidopsis/metabolismo , Inativação Gênica , DNA/metabolismo
6.
J Integr Plant Biol ; 63(6): 1091-1096, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33913587

RESUMO

RNA-directed DNA methylation (RdDM) is a plant-specific de novo DNA methylation pathway, which has extensive cross-talk with histone modifications. Here, we report that the maize RdDM regulator SAWADEE HOMEODOMAIN HOMOLOG 2 (SHH2) is an H3K9me1 reader. Our structural studies reveal that H3K9me1 recognition is achieved by recognition of the methyl group via a classic aromatic cage and hydrogen-bonding and salt-bridge interactions with the free protons of the mono-methyllysine. The di- and tri-methylation states disrupt the polar interactions, decreasing the binding affinity. Our study reveals a mono-methyllysine recognition mechanism which potentially links RdDM to H3K9me1 in maize.


Assuntos
Proteínas de Plantas/metabolismo , Zea mays/metabolismo , Metilação de DNA/genética , Metilação de DNA/fisiologia , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Epigênese Genética/genética , Proteínas de Plantas/genética , RNA de Plantas/genética , RNA de Plantas/metabolismo , Zea mays/genética
7.
Microb Pathog ; 126: 343-350, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30468852

RESUMO

Type IV secretion system (T4SS) is a specialized nanomachine that is utilized for the pathogenicity of gram-negative bacteria. However, the role of T4SS genes in virulence of rice bacterial brown stripe pathogen Acidovorax oryzae (Ao) strain RS-2 is not clear, which contains T4SS gene cluster based on genome-wide analysis. Here we compared the virulence-related phenotypes between the wild-type strain RS-2 and nine T4SS mutants, which were constructed in this study. Results indicated that mutation of pilT, pilM, pilQ, or pilZ3 genes not only significantly reduced bacterial virulence, but also caused a reduction of 20.4-62.0% in biofilm formation and 37.7-47.7% reduction in motility, but had no effect on exopolysaccharide (EPS) production or extracellular enzymatic activities when compared to the wild type. The four T4SS genes had a differential effect on bacterial growth after 24 h post-incubation. The complemented strains of the four T4SS mutants restored similar virulence symptom as the wild type. In addition, no change was observed in bacterial virulence by mutation of the other five T4SS genes. Totally, these results demonstrated that T4SS played vital roles in bacterial virulence, motility and biofilm formation in plant pathogen Ao strain RS-2.


Assuntos
Comamonadaceae/genética , Comamonadaceae/patogenicidade , Genes Bacterianos/genética , Oryza/microbiologia , Doenças das Plantas/microbiologia , Sistemas de Secreção Tipo IV/genética , Fatores de Virulência/genética , Proteínas de Bactérias/genética , Biofilmes/crescimento & desenvolvimento , Comamonadaceae/efeitos dos fármacos , Comamonadaceae/crescimento & desenvolvimento , DNA Bacteriano/genética , Tolerância a Medicamentos , Regulação Bacteriana da Expressão Gênica , Genoma Bacteriano , Peróxido de Hidrogênio/farmacologia , Família Multigênica , Mutação , Sistemas de Secreção Tipo IV/metabolismo , Virulência/genética
8.
Mol Cell Probes ; 43: 84-85, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30582957

RESUMO

Reverse transcription recombinase polymerase amplification (RT-RPA) for detection of Cucumber green mottle mosaic virus (CGMMV) was developed in this study. It was found to be specific, with a limit of detection of 0.5 pg of total CGMMV RNA. CGMMV on inoculated leaves was tested using RT-RPA assay, suggesting that this method is suitable for CGMMV detection from leaves.


Assuntos
Reação em Cadeia da Polimerase/métodos , Recombinases/metabolismo , Transcrição Reversa/genética , Tobamovirus/genética , Tobamovirus/isolamento & purificação , Sensibilidade e Especificidade
10.
Int J Mol Sci ; 16(12): 28050-62, 2015 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-26602922

RESUMO

Biofilm formation is important for virulence of a large number of plant pathogenic bacteria. Indeed, some virulence genes have been found to be involved in the formation of biofilm in bacterial fruit blotch pathogen Acidovorax citrulli. However, some virulent strains of A. citrulli were unable to format biofilm, indicating the complexity between biofilm formation and virulence. In this study, virulence-related genes were identified in the biofilm-defective strain A1 of A. citrulli by using Tn5 insertion, pathogenicity test, and high-efficiency thermal asymmetric interlaced PCR (hiTAIL-PCR). Results from this study indicated that 22 out of the obtained 301 mutants significantly decreased the virulence of strain A1 compared to the wild-type. Furthermore, sequence analysis indicated that the obtained 22 mutants were due to the insertion of Tn5 into eight genes, including Aave 4244 (cation diffusion facilitator family transporter), Aave 4286 (hypothetical protein), Aave 4189 (alpha/beta hydrolase fold), Aave 1911 (IMP dehydrogenase/GMP reductase domain), Aave 4383 (bacterial export proteins, family 1), Aave 4256 (Hsp70 protein), Aave 0003 (histidine kinase, DNA gyrase B, and HSP90-like ATPase), and Aave 2428 (pyridoxal-phosphate dependent enzyme). Furthermore, the growth of mutant Aave 2428 was unaffected and even increased by the change in incubation temperature, NaCl concentration and the pH of the LB broth, indicating that this gene may be directly involved in the bacterial virulence. Overall, the determination of the eight pathogenicity-related genes in strain A1 will be helpful to elucidate the pathogenesis of biofilm-defective A. citrulli.


Assuntos
Biofilmes , Comamonadaceae/genética , Comamonadaceae/patogenicidade , Elementos de DNA Transponíveis , Mutagênese , Virulência/genética , Sequência de Aminoácidos , Biologia Computacional/métodos , Genes Bacterianos , Dados de Sequência Molecular , Mutagênese Insercional , Mutação , Alinhamento de Sequência , Estresse Fisiológico
11.
Molecules ; 20(1): 1161-75, 2015 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-25587790

RESUMO

Glyphosate formulations that are used as a broad-spectrum systemic herbicide have been widely applied in agriculture, causing increasing concerns about residues in soils. In this study, the degradation dynamics of glyphosate in different types of citrus orchard soils in China were evaluated under field conditions. Glyphosate soluble powder and aqueous solution were applied at 3000 and 5040 g active ingredient/hm2, respectively, in citrus orchard soils, and periodically drawn soil samples were analyzed by high performance liquid chromatography. The results showed that the amount of glyphosate and its degradation product aminomethylphosphonic acid (AMPA) in soils was reduced with the increase of time after application of glyphosate formulations. Indeed, the amount of glyphosate in red soil from Hunan and Zhejiang Province, and clay soil from Guangxi Province varied from 0.13 to 0.91 µg/g at 42 days after application of aqueous solution. Furthermore, the amount of glyphosate in medium loam from Zhejiang and Guangdong Province, and brown loam from Guizhou Province varied from less than 0.10 to 0.14 µg/g, while the amount of AMPA varied from less than 0.10 to 0.99 µg/g at 42 days after application of soluble powder. Overall, these findings demonstrated that the degradation dynamics of glyphosate aqueous solution and soluble powder as well as AMPA depend on the physicochemical properties of the applied soils, in particular soil pH, which should be carefully considered in the application of glyphosate herbicide.


Assuntos
Citrus , Produtos Agrícolas , Glicina/análogos & derivados , Poluentes do Solo/química , China , Cromatografia Líquida de Alta Pressão , Glicina/química , Cinética , Espectrometria de Fluorescência , Glifosato
12.
Zhonghua Yu Fang Yi Xue Za Zhi ; 49(1): 21-5, 2015 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-25876490

RESUMO

OBJECTIVE: To characterize the O3: K6 serovariant of Vibrio parahaemolyticus on virulence gene and molecular typing, and analyze the genetic relationship between O3: K6 and O3: K6 serovariants. METHODS: PFGE was performed on 115 strains of V.parahaemolyticus which were collected from the anal swab of cases of foodbrone diseases in Shenzhen during 2006-2012. According to isolation times and locations, 7 strains of O3: K6 were selected as control strains. Tdh gene, trh gene, orf8 gene were detected, GS-PCR, multi-locus sequence typing (MLST) were used to chracterize 7 strains of O3: K6 and O3: K6 serovariants. RESULTS: PFGE indicated that 58.3% (67/115) of V. parahaemolyticus strains shared a high similarity of band pattern (similarity > 80%) , which comprised of O3: K6 (44/67), O1: KUT(4/67), and O3: K6 serovariants(19/67). Among the O3: K6 serovariants, O1: K25 accounted for 7% (5/67), O4: K68 accounted for 10% (7 /67), O11: K36 accounted for 10% (7 /67). They all carried both tdh and trh gene, and 53% (10/19) was GS-PCR positive and carried orf8 gene, 26% (5/19) was both GS-PCR and orf8 gene negative, 21% (4/19) was GS-PCR negative, orf8 gene positive, 89% (17/19) was assigned to ST-3, 11% (2/19) was assigned to ST-305. Seven strains of O3: K6 was GS-PCR positive, carried orf8 gene, assigned to ST-3. ST-305 and ST-3 had differences in 2 housekeeping genes, which was dtdS gene and pntA gene. In the 305th base of dtdS gene, ST-305(147 allele profile) was T, while ST-3(4 allele profile) was C. In the 33th base of pntA gene, ST-305(93 allele profile) was T, while ST-3(29 allele profile ) was C. CONCLUSION: O4: K68,O1: K25 and O11: K36 were highly similar in virulencec gene carriage, MLST type of O3: K6, and aslo shared a close genetic relationship with O3: K6, thus were considered as O3: K6 serovirants.


Assuntos
Genótipo , Vibrio parahaemolyticus , Virulência , Alelos , Humanos , Tipagem de Sequências Multilocus , Reação em Cadeia da Polimerase
13.
Zhonghua Gan Zang Bing Za Zhi ; 23(8): 622-7, 2015 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-26447628

RESUMO

OBJECTIVE: To describe the incidence and related risk factors of fatty liver disease in the general population of Northwest China. METHODS: The study was a cross-sectional survey with multiplestage stratified cluster and random sampling. All participants were 18 years or older and resided in northwest provinces of China.Demographic and behavioral data was gathered by questionnaire.Clinical data such as height, body weight, waist circumference, biochemical function (standard tests) and liver status (ultrasonographic examination) were also collected. RESULTS: Among the 2 300 total study participants, 1 523 were habitual drinkers (total drinking rate: 66.2%). This population of drinkers was composed almost exclusively of males. There were 201 cases of alcoholic liver disease (total prevalence:8.7%), represented by mild alcoholic injury (prevalence: 4.2%), alcoholic fatty liver (3.8%), alcoholic hepatitis (0.5%), and alcoholic cirrhosis (0.3%).When examined according to provinces of residence, the prevalence of alcoholic liver disease followed this pattern: Shaanxi (14.0%), Gansu (8.6%), and Xinjiang autonomous region (5.0%). Of the total 337 cases of nonalcoholic fatty liver disease (total prevalence: 14.7%), the prevalence by province was: Shaanxi (18.5%), Gansu (10.3%), and Xinjiang autonomous region (16.6%). Individuals with alcoholic liver disease had significantly higher mean age (years), body weight, body mass index (BMI), waist circumference, average daily alcohol intake, and level of aspartate aminotransferase (AST), and alanine aminotraasferase (ALT) (vs. Those with no liver disease, P less than 0.05). Individuals with nonalcoholic fatty liver disease had significantly higher mean age (years), height, body weight, BMI, waist circumference, level of AST and ALT, and presence of obesity, abdominal obesity, hyperlipidemia, diabetes mellitus and hypertension (vs. Those with no liver disease, P less than 0.05). Multiple logistic regression demonstrated that alcoholic liver disease was closely related to age, sex, and average daily alcohol intake. The prevalence of nonalcoholic fatty liver disease was positively correlated to age, female sex, hyperlipidemia, diabetes mellitus, and BMI. CONCLUSION: The drinking-rate and prevalence of fatty liver disease is high in Northwest China, but the most prevalent type is nonalcoholic fatty liver disease.Fatty liver disease is closely related to age, sex, average daily alcohol intake, hyperlipidemia, diabetes mellitus, and BMI.


Assuntos
Fígado Gorduroso , Aspartato Aminotransferases , Índice de Massa Corporal , Peso Corporal , China , Estudos Transversais , Diabetes Mellitus , Feminino , Humanos , Hiperlipidemias , Hipertensão , Modelos Logísticos , Masculino , Obesidade , Prevalência , Fatores de Risco , Inquéritos e Questionários , Circunferência da Cintura
14.
Colloids Surf B Biointerfaces ; 238: 113877, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38615390

RESUMO

An ideal bone metastasis animal model is critical and fundamental for mechanistic research and following development of new drug and treatment. Caudal artery (CA) injection allows bone metastasis in the hindlimb, while in-depth targeted and quantitative studies of bone metastasis require a new model to overcome its limitations. Here, we developed a targeted, quantitative, and highly consistent method for the modeling of bone metastasis with cell-based magnetic micro-living-motor (MLM) system created by effectively combining Fe3O4-PDA-Au with biosafety. The MLM system can achieve efficient migration, target site colonization and control tumorigenesis in bone precisely with the application of a magnetic field. In vivo, day 3 post cell injection, tumor bone metastasis signals were observed locally in the injected femur among 82.76% mice of the MLM group as compared to the 56.82% in the CA group, and the signal intensity was 45.1 and 95.9 times stronger than that in the left and right lower limbs of the CA group, respectively. Post-injection day 28, metastasis in vital organs was reduced by approximately 90% in the MLM group compared to the CA group. Our innovative use of the MLM system in the field of tumor modeling opens a new avenue for exploring the mechanisms of tumor bone metastasis, recurrence and drug resistance.


Assuntos
Neoplasias Ósseas , Animais , Neoplasias Ósseas/secundário , Neoplasias Ósseas/patologia , Camundongos , Modelos Animais de Doenças , Linhagem Celular Tumoral , Humanos , Feminino , Campos Magnéticos , Camundongos Endogâmicos BALB C
15.
Int J Ophthalmol ; 17(6): 1110-1119, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38895674

RESUMO

AIM: To compare high or low concentration of hyaluronic acid eye drops (HY) for dry eye syndromes (DES). METHODS: Randomized controlled trials (RCTs) comparing various concentrations of HY were searched in PubMed, Embase, Web of Science, Cochrane, SinoMed, CNKI, Wanfang Database, CQVIP, and Chinese journals databases between inception and July 2023. Pooled standardized mean differences (SMD) or weighted mean difference (WMD) with 95% confidence intervals (CI) from RCTs evaluating Schirmer's I test (SIT), corneal fluorescein staining score (CFS), tear breakup time (TBUT), DES score (DESS), and Ocular Surface Disease Index (OSDI) were calculated. Sensitivity analysis, Egger's test and Meta-regression analysis were performed for all indicators. RESULTS: We conducted a Meta-analysis of 10 RCTs that met the inclusion criteria, involving 1796 cases. High-concentrations group significantly improved the outcome of CFS according to random effects modelling (SMD, -3.37; 95%CI, -5.25 to -1.48; P=0.0005). The rest of the results were not statistically significant, including indicators such as SIT, TBUT, DESS and OSDI. CONCLUSION: For dry eyes with positive corneal staining, a high concentration of HY is recommended, whereas in other cases, a high concentration of HY does not offer a more pronounced advantage over a low concentration of HY in the treatment of dry eyes.

16.
Oral Oncol ; 158: 106980, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39151333

RESUMO

OBJECTIVE: The early response to concurrent chemoradiotherapy in patients with locally advanced nasopharyngeal carcinoma (LA-NPC) is closely correlated with prognosis. In this study, we aimed to predict early response using a combined model that combines sub-regional radiomics features from multi-sequence MRI with clinically relevant factors. METHODS: A total of 104 patients with LA-NPC were randomly divided into training and test cohorts at a ratio of 3:1. Radiomic features were extracted from subregions within the tumor area using the K-means clustering method, and feature selection was performed using LASSO regression. Four models were established: a radiomics model, a clinical model, an Intratumor Heterogeneity (ITH) score-based model and a combined model that integrates the ITH score with clinical factors. The predictive performance of these models was evaluated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). RESULTS: Among the models, the combined model incorporating the ITH score and clinical factors exhibited the highest predictive performance in the test cohort (AUC=0.838). Additionally, the models based on ITH score showed superior prognostic value in both the training cohort (AUC=0.888) and the test cohort (AUC=0.833). CONCLUSION: The combined model that integrates the ITH score with clinical factors exhibited superior performance in predicting early response following concurrent chemoradiotherapy in patients with LA-NPC.


Assuntos
Imageamento por Ressonância Magnética , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Masculino , Feminino , Imageamento por Ressonância Magnética/métodos , Carcinoma Nasofaríngeo/diagnóstico por imagem , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/patologia , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/patologia , Adulto , Quimiorradioterapia/métodos , Idoso , Prognóstico , Resultado do Tratamento , Curva ROC
17.
Pest Manag Sci ; 80(3): 1279-1288, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37897195

RESUMO

BACKGROUND: To address the challenges of food security for the ever-increasing population, the emergence of nanotechnology provides an alternate technology of choice for the production of safer pesticides which serves as a substitute for conventional fertilizer. The antidrug resistance of Xanthomonas oryzae pv. oryzae (Xoo) and build-up of chemicals in the environment has made it necessary to find alternative safe techniques for effective disease management. Hence, in this study, copper oxide nanoparticles (CuONPs) were produced by green synthesis using a Hibiscus rosa-sinensis L. flower extract. RESULTS: The characterization of CuONPs using ultraviolet-visible spectrophotometry, scanning electron microscopy with an energy-dispersive spectrum profile, Fourier transform infrared spectroscopy, and X-ray diffraction ascertained the presence of CuONPs, which were nanorods of 28.1 nm. CuONPs significantly obstructed the growth and biofilm development of Xoo by 79.65% and 79.17% respectively. The antibacterial mechanism of CuONPs was found to result from wounding the cell membrane, giving rise to an exodus of intracellular content and generation of oxidative reactive oxygen species that invariably inhibited Xoo respiration and growth. A toxicity study under greenhouse conditions revealed that CuONPs significantly increased growth variables and the biomass of rice, and reduced bacterial leaf blight. Application of CuONPs on Arabidopsis improved the chlorophyll fluorescence parameters; the ΦPSII was significantly increased by 152.05% in comparison to the control. CONCLUSION: Altogether, these results suggest that CuONPs in low concentration (200.0 µg mL-1 ) are not toxic to plants and can serve as nano-fertilizers and nano-pesticides. © 2023 Society of Chemical Industry.


Assuntos
Nanopartículas , Oryza , Xanthomonas , Cobre/farmacologia , Nanopartículas/química , Bactérias , Antibacterianos/farmacologia , Óxidos/farmacologia
18.
Oral Oncol ; 154: 106865, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38823173

RESUMO

OBJECTIVE: The aim of this study is to evaluate the efficacy and cost-effectiveness of various induction chemotherapy (IC) regimens as first-line treatment for Locoregionally advanced nasopharyngeal carcinoma (LA-NPC), aiming to provide clinicians and patients with informed insights to aid in treatment decision-making. PATIENTS AND METHODS: We conducted a network meta-analysis (NMA) and cost-effectiveness analysis (CEA) based on data from 10 clinical trials investigating IC regimens for the treatment of LA-NPC. A Bayesian NMA was performed, with the primary outcomes being hazard ratios (HRs) for disease-free survival (DFS) and overall survival (OS). To model the disease progression of LA-NPC, we developed a dynamic partitioned survival model consisting of three disease states: progression-free survival (PFS), progression disease (PD), and death. The model was run on a 3-week cycle for a research period of 10 years, with quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs) serving as outcome measures. RESULTS: According to the surface under the cumulative ranking curve (SUCRA) estimates derived from the NMA, TPC and TP, as IC regimens, appear to exhibit superior efficacy compared to other treatment modalities. In terms of CEA, concurrent chemoradiotherapy (CCRT), TPF + CCRT, and GP + CCRT were found to be dominated (more costs and less QALYs). Comparatively, TPC + CCRT emerged as a cost-effective option with an ICER of $1260.57/QALY when compared to PF + CCRT. However, TP + CCRT demonstrated even greater cost-effectiveness than TPC + CCRT, with an associated increase in costs of $3300.83 and an increment of 0.1578 QALYs per patient compared to TPC + CCRT, resulting in an ICER of $20917.62/QALY. CONCLUSION: Based on considerations of efficacy and cost-effectiveness, the TP + CCRT treatment regimen may emerge as the most favorable first-line therapeutic approach for patients with LA-NPC.


Assuntos
Análise Custo-Benefício , Quimioterapia de Indução , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Metanálise em Rede , Humanos , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/economia , Carcinoma Nasofaríngeo/mortalidade , Quimioterapia de Indução/economia , Quimioterapia de Indução/métodos , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/economia , Anos de Vida Ajustados por Qualidade de Vida , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/economia , Análise de Custo-Efetividade
19.
Viruses ; 16(10)2024 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-39459951

RESUMO

Erwinia amylovora, the causative agent of fire blight, causes significant economic losses for farmers worldwide by inflicting severe damage to the production and quality of plants in the Rosaceae family. Historically, fire blight control has primarily relied on the application of copper compounds and antibiotics, such as streptomycin. However, the emergence of antibiotic-resistant strains and growing environmental concerns have highlighted the need for alternative control methods. Recently, there has been a growing interest in adopting bacteriophages (phages) as a biological control strategy. Phages have demonstrated efficacy against the bacterial plant pathogen E. amylovora, including strains that have developed antibiotic resistance. The advantages of phage therapy includes its minimal impact on microbial community equilibrium, the lack of a detrimental impact on plants and beneficial microorganisms, and its capacity to eradicate drug-resistant bacteria. This review addresses recent advances in the isolation and characterization of E. amylovora phages, including their morphology, host range, lysis exertion, genomic characterization, and lysis mechanisms. Furthermore, this review evaluates the environmental tolerance of E. amylovora phages. Despite their potential, E. amylovora phages face certain challenges in practical applications, including stability issues and the risk of lysogenic conversion. This comprehensive review examines the latest developments in the application of phages for controlling fire blight and highlights the potential of E. amylovora phages in plant protection strategies.


Assuntos
Bacteriófagos , Erwinia amylovora , Especificidade de Hospedeiro , Doenças das Plantas , Erwinia amylovora/virologia , Bacteriófagos/fisiologia , Bacteriófagos/genética , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , Genoma Viral , Rosaceae/microbiologia , Rosaceae/virologia , Terapia por Fagos/métodos
20.
Viruses ; 16(9)2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39339926

RESUMO

Xanthomonas oryzae pv. oryzae (Xoo) is a significant bacterial pathogen responsible for outbreaks of bacterial leaf blight in rice, posing a major threat to rice cultivation worldwide. Effective management of this pathogen is crucial for ensuring rice yield and food security. In this study, we identified and characterized a novel Xoo phage, ZP3, isolated from diseased rice leaves in Zhejiang, China, which may offer new insights into biocontrol strategies against Xoo and contribute to the development of innovative approaches to combat bacterial leaf blight. Transmission electron microscopy indicated that ZP3 had a short, non-contractile tail. Genome sequencing and bioinformatic analysis showed that ZP3 had a double-stranded DNA genome with a length of 44,713 bp, a G + C content of 52.2%, and 59 predicted genes, which was similar to other OP1-type Xoo phages belonging to the genus Xipdecavirus. ZP3's endolysin LysZP was further studied for its bacteriolytic action, and the N-terminal transmembrane domain of LysZP is suggested to be a signal-arrest-release sequence that mediates the translocation of LysZP to the periplasm. Our study contributes to the understanding of phage-Xoo interactions and suggests that phage ZP3 and its endolysin LysZP could be developed into biocontrol agents against this phytopathogen.


Assuntos
Bacteriófagos , Genoma Viral , Oryza , Doenças das Plantas , Xanthomonas , Xanthomonas/virologia , Xanthomonas/efeitos dos fármacos , Bacteriófagos/genética , Bacteriófagos/fisiologia , Bacteriófagos/isolamento & purificação , Oryza/microbiologia , Oryza/virologia , Doenças das Plantas/microbiologia , Doenças das Plantas/virologia , Endopeptidases/farmacologia , Endopeptidases/genética , Endopeptidases/química , Endopeptidases/metabolismo , Filogenia , Folhas de Planta/virologia , Folhas de Planta/microbiologia , China , Genômica/métodos
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