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The substantial increase of infections, caused by novel, sudden, and drug-resistant pathogens, poses a significant threat to human health. While numerous studies have demonstrated the antibacterial and antiviral effects of Traditional Chinese Medicine, the potential of a complex mixture of traditional Chinese Medicine with a broad-spectrum antimicrobial property remains underexplored. This study aimed to develop a complex mixture of Traditional Chinese Medicine (TCM), JY-1, and investigate its antimicrobial properties, along with its potential mechanism of action against pathogenic microorganisms. Antimicrobial activity was assessed using a zone of inhibition assay and the drop plate method. Hyphal induction of Candida albicans was conducted using RPMI1640 medium containing 10% FBS, followed by microscopic visualization. Quantitative real-time PCR (RT-qPCR) was employed to quantify the transcript levels of hyphal-specific genes such as HWP1 and ALS3. The impact of JY-1 on biofilm formation was evaluated using both the XTT reduction assay and scanning electron microscopy (SEM). Furthermore, the cell membrane integrity was assessed by protein and nucleic acid leakage assays. Our results clearly showed that JY-1 significantly inhibits the vegetative growth of Candida spp. and Cryptococcus spp. In addition, this complex mixture is effectively against a wide range of pathogenic bacteria, including Staphylococcus aureus, Vancomycin-resistant enterococci, Escherichia coli, Klebsiella pneumoniae and Enterobacter cloacae. More interestingly, JY-1 plays a direct anti-viral role against the mammalian viral pathogen vesicular stomatitis virus (VSV). Further mechanistic studies indicate that JY-1 acts to reduce the expression of hyphal specific genes HWP1 and ALS3, resulting in the suppression of the hyphal formation of C. albicans. The antimicrobial property of JY-1 could be attributed to its ability to reduce biofilm formation and disrupt the cell membrane permeability, a process resulting in microbial cell death and the release of cellular contents. Taken together, our work identified a potent broad-spectrum antimicrobial agent, a complex mixture of TCM which might be developed as a potential antimicrobial drug.
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Anti-Infecciosos , Medicina Tradicional Chinesa , Animais , Humanos , Permeabilidade da Membrana Celular , Biofilmes , Candida albicans , Anti-Infecciosos/farmacologia , Misturas Complexas/farmacologia , Permeabilidade , Testes de Sensibilidade Microbiana , MamíferosRESUMO
KEY MESSAGE: Sucrose invertase activity is positively related to osmotic and salt stress resistance in peanut. Sucrose invertases (INVs) have important functions in plant growth and response to environmental stresses. However, their biological roles in peanut are still not fully revealed. In this research, we identified 42 AhINV genes in the peanut genome. They were highly conserved and clustered into three groups with 24 segmental duplication events occurred under purifying selection. Transcriptional expression analysis exhibited that they were all ubiquitously expressed, and most of them were up-regulated by osmotic and salt stresses, with AhINV09, AhINV23 and AhINV19 showed the most significant up-regulation. Further physiochemical analysis showed that the resistance of peanut to osmotic and salt stress was positively related to the high sugar content and sucrose invertase activity. Our results provided fundamental information on the structure and evolutionary relationship of INV gene family in peanut and gave theoretical guideline for further functional study of AhINV genes in response to abiotic stress.
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Arachis , Açúcares , Arachis/genética , beta-Frutofuranosidase/genética , Estresse Salino , SacaroseRESUMO
PURPOSE: To evaluate whether depth of focus after the implantation of extended depth of focus (EDoF) intraocular lenses (IOLs) correlates with pupillary size. METHODS: This retrospective case series study evaluated eyes undergoing cataract surgery with implantation of EDoF IOLs. At least one month postoperatively, the depth of focus (DoF) was measured to determine the correlation with pupillary size, age, anterior chamber depth (ACD), axial length (AXL), and corneal spherical aberrations (SA). RESULTS: The study evaluated 64 eyes of 49 patients. The mean depth of focus was 2.67 diopters (D). The mean preoperative photopic pupil size was 3.36 mm. A significant negative association was found between preoperative photopic pupil size and depth of focus (r = 0.30, Pearson's correlation coefficient) and between preoperative mesopic pupil size and depth of focus (r = 0.274, Pearson's correlation coefficient).
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Inspired by nature, it has been considered an effective approach to design artificial photosynthetic system by fabricating Z-scheme photocatalysts to eliminate environmental issues and alleviate the global energy crisis. However, the development of low cost, environment-friendly, and high-efficient photocatalysts by utilizing solar energy still confronts huge challenge. Herein, we constructed a Bi2 O3 /(BiO)2 CO3 /Bi2 MoO6 ternary heterojunction via a facile solvothermal method and calcination approach and used it as a photocatalyst for the degradation of phenol. The optimized Bi2 O3 /(BiO)2 CO3 /Bi2 MoO6 heterojunction delivers a considerable activity for phenol photodegradation with an impressive removal efficiency of 98.8 % and about total organic carbon (TOC) of 68 % within 180â min under visible-light irradiation. The excellent photocatalytic activity was ascribed to the formation of a Z-scheme heterojunction, more importantly, the presence of (BiO)2 CO3 as an electron bridge greatly shortens the migration distance of photogenerated electron from ECB of Bi2 O3 to EVB of Bi2 MoO6 , thus prolonging the lifetime of photogenerated electrons, which is verified by trapping experiments, electron spin-resonance spectroscopy (ESR) results, and density functional theory (DFT) calculations. This work provides a potential strategy to fabricate highly efficient Bi-based Z-scheme photocatalysts with wide application prospects in solar-to-fuel conversion and environmental protection.
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Bismuto , Fenol , Elétrons , Fenóis , Espectroscopia de Ressonância de Spin EletrônicaRESUMO
BACKGROUND: Helicobacter pylori (HP) infection is associated with various diseases. Early detection can prevent the onset of illness. We constructed a nomogram to predict groups at high risk of HP infection. METHODS: Patients who underwent regular medical check-ups at hospital in Chaoshan, China from March to September 2022 were randomly allocated to the training and validation cohorts. Risk factors including basic characteristics and lifestyle habits associated with HP infection were analyzed by logistic regression analyses. The independent varieties were calculated and plotted into a nomogram. The nomogram was internally validated by receiver operating characteristic curve, calibration, and decision curve analyses (DCAs). RESULTS: Of the 945 patients, 680 were included in the training cohort and 265 in the validation cohort. 356 patients in training cohort with positive 13 C-UBT results served as the infected group, and 324 without infection were the control group. The multivariate regression analyses showed that the risk factors for HP infection included alcohol consumption (OR = 1.29, 95%CI = 0.78-2.13, P = 0.03), family history of gastric disease (OR = 4.35, 95%CI = 1.47-12.84, P = 0.01), living with an HP-positive individual (OR = 18.09, 95%CI = 10.29-31.82, P < 0.0001), drinking hot tea (OR = 1.58, 95%CI = 1.05-2.48, P = 0.04), and infection status of co-drinkers unknown (OR = 2.29, 95%CI = 1.04-5.06, P = 0.04). However, drinking tea > 3 times per day (OR = 0.56, 95%CI = 0.33-0.95, P = 0.03), using serving chopsticks (OR = 0.30, 95%CI = 0.12-0.49, P < 0.0001) were protective factors for HP infection. The nomogram had an area under the curve (AUC) of 0.85 in the training cohort. The DCA was above the reference line within a large threshold range, indicating that the model was better. The calibration analyses showed the actual occurrence rate was basically consistent with the predicted occurrence rate. The model was validated in the validation cohort, and had a good AUC (0.80), DCA and calibration curve results. CONCLUSIONS: This nomogram, which incorporates basic characteristics and lifestyle habits, is an efficient model for predicting those at high risk of HP infection in the Chaoshan region.
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Infecções por Helicobacter , Helicobacter pylori , Humanos , China/epidemiologia , Infecções por Helicobacter/epidemiologia , Estilo de Vida , Nomogramas , CháRESUMO
PURPOSE: To evaluate the association between microvascular changes in the iris and refractive errors. METHODS: A cross-sectional case study. Seventy eyes from 70 patients with refractive errors were enrolled. Iris microvasculature was analyzed using optical coherence tomography angiography (OCTA). We divided the iris images into three regions and calculated the vessel area density (VAD) and vessel skeleton density (VSD) of the inner one-third, inner two-thirds, and the entirety of the iris. RESULTS: The VADs and VSDs of the different regions were significantly different. The VAD and VSD of the inner one-third of the iris were higher than those of the other regions. The iris blood vessels were denser near the pupil margin, and blood vessels from the iris root to the pupil edge were radially distributed. The VAD and VSD of patients with mild hyperopia and emmetropia were higher than those of patients with moderate and high myopia. As the spherical equivalent increased, the VAD and VSD of the iris increased. Neither age nor sex contributed to significant differences in VAD and VSD. CONCLUSION: Quantitative changes in iris microvasculature may indicate the development of myopia.
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Miopia , Erros de Refração , Estudos Transversais , Angiofluoresceinografia , Humanos , Iris , Vasos Retinianos , Tomografia de Coerência ÓpticaRESUMO
PURPOSE: The aim of this study was to evaluate the short-term efficacy and safety of ultrasound cycloplasty (UCP) procedure in Chinese glaucoma patients. METHODS: As a single-center, prospective, noncomparative study, 23 eyes of 23 patients suffering from glaucoma with uncontrolled intraocular pressure (IOP) ≥21 mm Hg underwent a multidose UCP treatment with the activations of 6, 8, or10 sectors. Types of glaucoma include primary open-angle glaucoma (7/23), primary angle closure glaucoma (PACG) (9/23), and secondary glaucoma (SG) (7/23). A complete ophthalmic examination including intraocular pressure (IOP) measurements was performed before UCP procedure and at 1 day, 1 month, 3 months, and 6 months after the procedure. An IOP reduction of ≥20% and IOP >5 mm Hg without increasing hypotensive medication at the follow-up visit was defined as therapeutic success. The postoperative complications were also recorded and compared to baseline for safety evaluation. RESULTS: The mean baseline IOP of 23 treated eyes was 37.2 ± 12.1 mm Hg. The IOP reduction after UCP procedure was 23, 49, 33, and 34% at 1 day, 1 month, 3 months, and 6 months, respectively. Thus, the corresponding overall therapeutic success rates reached 61% (14/23), 83% (19/23), 65% (15/23), and 61% (14/23), respectively. Baseline IOPs of 8- and 10-sector groups (37.0 ± 9.9 mm Hg and 50.1 ± 12.2 mm Hg) were significantly higher than that of 6 sector groups (30.1 ± 8.2 mm Hg). Therapeutic success rates of 6-, 8-, and 10-sector groups reached 44% (4/9), 56% (5/9), and 100% (5/5), respectively. There were the highest percentage of IOP reduction (50 and 41%) and therapeutic success rate (6/7; 86% and 7/9; 78%) in the SG group and PACG group, respectively. In addition, preoperative ocular pain symptoms of 4 patients were all disappeared within 1 week after UCP. No serious intraoperative or postoperative complications occurred. CONCLUSION: UCP procedure is an effective and well-tolerated treatment to reduce IOP in Chinese glaucoma patients, which offered a novel alternative for glaucoma treatment.
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Glaucoma de Ângulo Aberto , Glaucoma , Hipotensão Ocular , China/epidemiologia , Seguimentos , Glaucoma/cirurgia , Glaucoma de Ângulo Aberto/diagnóstico , Glaucoma de Ângulo Aberto/cirurgia , Humanos , Pressão Intraocular , Complicações Pós-Operatórias , Estudos Prospectivos , Tonometria Ocular , Resultado do TratamentoRESUMO
BACKGROUND: To evaluate quantitative changes in iris blood circulation in patients with ischemic risk. METHODS: This observational case-control study included 79 patients with diabetic retinopathy (DR) and retinal vein occlusion (RVO). The RVO group included 21 patients; the monocular proliferative diabetic retinopathy (PDR) group included 19 patients; the nondiabetic retinopathy (NDR) group included 18 patients; and the healthy control group included 21 healthy controls. In the RVO group, we analyzed RVO affected eyes, RVO contralateral eyes, and healthy control eyes. We also compared eyes with PDR and contralateral eyes without PDR, patients with diabetes mellitus (DM) without DR, and healthy control eyes. The microvascular networks of the iris and retina were analyzed using optical coherence tomography angiography. The analysis included vessel area density (VAD) and vessel skeleton density (VSD) of iris and retina. RESULTS: In the RVO group, the VAD and VSD of iris in the affected eye were higher than those in contralateral and healthy control eyes, and the VAD and VSD of contralateral eyes were higher than those of healthy control eyes. The retinal blood flow of the RVO eyes was less than that of the contralateral and healthy control eyes, but there were no difference between the contralateral eyes and healthy control eyes. The VAD and VSD of iris in PDR were larger than nonproliferative diabetic retinopathy (NPDR) and the NPDR were larger than NDR. There were no differences between NDR and healthy control eyes. Also, there were no differences among the four groups with respect to retinal blood flow. CONCLUSIONS: Compared with the retina, iris blood circulation quantitative analysis data seem to be more sensitive to ischemia and may be used as a new predictor of ischemic disease, even if further research is needed to better understand the clinical value and importance of this analysis. TRIAL REGISTRATION: The trial is registered with the clinical trial registration number nct03631108 .
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Retinopatia Diabética , Vasos Retinianos , Estudos de Casos e Controles , Angiofluoresceinografia , Humanos , Iris/diagnóstico por imagem , Isquemia , Vasos Retinianos/diagnóstico por imagemRESUMO
OBJECTIVE: To quantify the iris vessels and its circadian rhythm in normal eyes. METHODS: Fifteen healthy subjects were enrolled in this retrospective, cross-sectional study. All subjects underwent optical coherence tomography angiography (OCTA) and indocyanine green angiography (ICGA) examinations, in which 3/15 completed ICGA and OCTA at the same visit. Upon visit, consecutive OCTA scans were then obtained at the time points of the hour 3:00, 6:00, 8:00, 10:00, 12:00, 14:00, 16:00, 18:00, 20:00, 22:00, and 24:00, respectively. Vessel area density (VAD) and vessel skeleton density (VSD) were used to quantitatively describe the OCTA images of the iris vessels. RESULTS: The VAD and VSD of the iris vessels had circadian rhythm with the highest values observed at about 18:00 h and lowest at 0:00 h; the overall values were relatively stable within the 24 h. The contour analysis suggested that the iris VAD and VSD were correlated with the changes in blood pressure and inversely correlated with the changes in the intraocular pressure. CONCLUSIONS: OCTA can be used accurately for quantitative analysis of the iris vessels.
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Iris , Vasos Retinianos , Tomografia de Coerência Óptica , Estudos Transversais , Angiofluoresceinografia , Humanos , Iris/diagnóstico por imagem , Estudos RetrospectivosRESUMO
Photocatalysis with potentially low cost and sustainable utilization is a typically environmentally benign method for the degradation of organic pollutants, but the rational design and fabrication of photocatalysts with high catalytic performance is still an enormous challenge. The efficient segregation of photogenerated electron-hole pairs in photocatalysts is a key and essential factor to decide photocatalytic activity. Herein, a novel Step-scheme (S-scheme) heterojunction photocatalyst, a g-C3N4/Bi2MoO6 (g-CN/BMO) composite, was successfully fabricated using g-C3N4 nanosheet-wrapped Bi2MoO6 microspheres. By adjusting the amount of g-C3N4 in BMO, a series of g-CN/BMO composites was prepared while optimizing posttreatment temperature. The resulting g-CN/BMO indicated well the photocatalytic performance for the degradation of phenol and hydrogen evolution reactions, especially, 100 g of g-CN was integrated into 100 g of the pre-calcined BMO at 200 °C to produce 100% g-CN/BMO-200, showing the highest photocatalytic performance compared to single composite BMO, BMO-200, g-CN, and g-CN/BMO-200 with other mass ratios. Combining the results from the density functional theory calculations and the results of X-ray photoelectron spectroscopy, for S-scheme heterojunction-structured g-CN/BMO-200, the internal electric field-, band edge bending- and coulomb interaction-driven efficient segregation of photogenerated electrons and holes at the interface is elucidated to explain the photocatalytic mechanism, and the resulting holes on the VB of BMO and electrons on the CB of g-CN are responsible for the improvement of the photocatalytic performance. This study revealed that for the S-scheme g-CN/BMO composite the internal electric field, band edge bending and coulomb interaction at the interface between g-CN and BMO can not only promote the effective segregation of electrons and holes, but also retain stronger redox ability. Such an investigation provides a facile and simple strategy to fabricate novel S-scheme heterojunction-structured photocatalysts for solar energy conversion.
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BACKGROUND: To investigate the distribution of peripheral anterior chamber depth (ACD) and the relationship between peripheral ACD and gonioscopy compared to other ocular parameters for primary angle closure disease (PACD) screening. We performed a population-based survey in Pudong New District of Shanghai, China, in 2011. METHODS: Cross-sectional study. Adults 50 and older were enrolled from a population-based study using cluster random sampling in Pudong New District, Shanghai. Remote ocular screening was performed with digital anterior eye structure photography. Van Herrick measurements were used to evaluate the peripheral ACD, the depth of the peripheral anterior chamber, and corneal thickness (CT), and the ACD to CT ratio was calculated. Subjects with peripheral ACD less than 0.5 CT were made follow-up appointments for clinical examination with gonioscopy. Receiver operating characteristic curves (ROC) were generated to show the performance of different tests in screening for primary angle closure disease (PACD). RESULTS: Two thousand five hundred twenty-eight adults participated in the study with 91 patients diagnosed with PACD. Two thousand four hundred sixty-three subjects had valid data in the right eye available for analysis. The mean peripheral ACD values for men and women were significantly different: 1.04 ± 0.46 (range 0.11-2.93) CT and 0.87 ± 0.41 (range 0.12-2.96) CT respectively (t = - 4.18; P<0.0001). Multivariate logistic regression analysis reveals that peripheral ACD declined by 0.31 CT (P < 0.0001) per diopter of SE and was 0.19 CT (P < 0.0001) shallower in women than in men (r2 = 0.1304, P < 0.0001). Peripheral ACD performed best in screening for PACD. CONCLUSIONS: Peripheral ACD measurement is recommended for PACD screening in community elderly Chinese.
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Glaucoma de Ângulo Fechado , Adulto , Idoso , Câmara Anterior/diagnóstico por imagem , China/epidemiologia , Estudos Transversais , Feminino , Glaucoma de Ângulo Fechado/diagnóstico , Glaucoma de Ângulo Fechado/epidemiologia , Gonioscopia , Humanos , Pressão Intraocular , MasculinoRESUMO
PURPOSE: To determine which utility value assessment method is more suitable to evaluate changes in the quality of life due to dry eye symptoms. METHODS: Dry eye outpatients with a presenting visual acuity of 20/25 or better in the worse-seeing eye were recruited. Presenting distance visual acuity, tear film break-up time, Schirmer I test and fluorescein were assessed. The severity of dry eye symptoms was assessed using the Ocular Surface Disease Index (OSDI), and utility values were measured using the time trade-off (TTO), standard gamble (SG1 and SG2) and rating scale (RS) methods. Different utility values were compared with each other. The most appropriate utility value method to evaluate quality-of-life changes solely due to dry eye symptoms is determined by calculating the correlation between the OSDI score and different utility values. RESULTS: A total of 104 patients were enrolled. The three sections of OSDI in the order of high to low scores were as follows: "environmental trigger," "eye discomfort" and "visual function." The utility scores measured with TTO, SG1, SG2 and RS were 0.95 ± 0.11, 0.96 ± 0.10, 0.99 ± 0.07 and 0.89 ± 0.10, respectively. The utility scores evaluated by the TTO, SG1, SG2 and RS methods were significantly different from each other (p < 0.05). Only the utility scores measured with RS were significantly correlated with the composite OSDI score, "environmental trigger" and "eye discomfort" section scores (p < 0.05). CONCLUSIONS: RS is more sensitive than TTO and SG for the evaluation of altered quality of life due to dry eye symptoms.
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Síndromes do Olho Seco/psicologia , Qualidade de Vida , Inquéritos e Questionários , Acuidade Visual/fisiologia , Adulto , Idoso , Estudos Transversais , Síndromes do Olho Seco/diagnóstico , Síndromes do Olho Seco/fisiopatologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
PURPOSE: To observe the long-term changes in dry eye symptoms and vision-related quality of life in age-related cataract patients after phacoemulsification. METHODS: A total of 101 cataract patients after phacoemulsification combined with IOL implantation (Ph-IOL) in one eye were enrolled. Visual acuity, tear film breakup time (BUT), and Schirmer test 1 (ST1) were measured before and 1, 3, and 6 months after surgery. Ocular Surface Disease Index (OSDI) scores were used to evaluate the severity of dry eye symptoms. Utility values were assessed by the time trade-off (TTO), standard gamble for death (SGD), standard gamble for blindness (SGB) and rating scale (RS). RESULTS: The average LogMAR visual acuity in the operated eye was 1.35 ± 0.50 and increased rapidly after Ph-IOL, approaching a peak at 3 months (0.26 ± 0.15). The BUT and ST1 results decreased abruptly 1 month after surgery and gradually recovered until 6 months. OSDI scores increased significantly after surgery and gradually decreased until 6 months. Utility values evaluated by TTO, SGD, SGB and RS before surgery were 0.67 ± 0.19, 0.75 ± 0.15, 0.67 ± 0.20 and 0.2 ± 0.18, respectively, and increased to 0.91 ± 0.06, 0.98 ± 0.04, 0.92 ± 0.52 and 0.91 ± 0.06, 6 months after. Utility values measured with TTO, SGB or RS correlated significantly (P < 0.05) with visual acuity and OSDI scores pre- and postoperatively. CONCLUSIONS: Dry eye symptoms persist more than 3 months after Ph-IOL. Utility values were negatively influenced by dry eye symptoms.
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Síndromes do Olho Seco/etiologia , Facoemulsificação/efeitos adversos , Complicações Pós-Operatórias/etiologia , Qualidade de Vida , Acuidade Visual , Adulto , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Síndromes do Olho Seco/epidemiologia , Síndromes do Olho Seco/fisiopatologia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/fisiopatologia , Estudos Prospectivos , Inquéritos e Questionários , Fatores de TempoRESUMO
Background: Cytomegalovirus (CMV) establishes a lifelong latent infection after primary infection and may reactivate periodically, with the shedding of infectious virus in body fluids. To better understand the prevalence and shedding model of CMV in immunocompetent seropositive women of childbearing age, a 6-month longitudinal study was conducted in healthy female college students. Methods: A total of 102 nonpregnant female college students aged 18-30 years were enrolled and followed up every 2 weeks for 6 months. Saliva and urine samples were collected at each visit. Serum samples were collected at the first and last visits. Results: All participants were positive for anti-CMV immunoglobulin G (IgG) at entry. During the 6-month period, 29.4% of participants (30 of 102) shed CMV intermittently in saliva or urine. At each visit, the CMV shedding prevalence varied from 2.0% to 10.4% and presented only in 1 bodily fluid. The viral load was low and did not induce marked antibody increases. The baseline anti-CMV IgG level was not found to be associated with viral shedding. Conclusions: CMV shedding in saliva and urine is common and intermittent and does not stimulate an anamnestic antibody response in seropositive immunocompetent women of childbearing age with a low risk of exposure to exogenous infectious sources.
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Anticorpos Antivirais/sangue , Citomegalovirus/fisiologia , Imunoglobulina G/sangue , Eliminação de Partículas Virais/fisiologia , Adolescente , Adulto , Feminino , Humanos , Imunocompetência , Estudos Longitudinais , Saliva/virologia , Estudos Soroepidemiológicos , Estudantes , Universidades , Urina/virologia , Adulto JovemRESUMO
BCR-ABL kinase mutations, accounting for clinical resistance to tyrosine kinase inhibitor (TKI) such as imatinib, frequently occur in acquired resistance or in advanced phases of chronic myeloid leukemia (CML). Emerging evidence implicates a critical role for non-mutational drug resistance mechanisms underlying the survival of residual cancer 'persister' cells. Here, we utilized non-mutational imatinib-resistant K562/G cells to reveal SHP-2 as a resistance modulator of imatinib treatment response during the early phase. SHP-2 phosphorylation was significantly higher in K562/G cells than in sensitive K562 cells. In K562 cells, both short-term and long-term exposure to imatinib induced SHP-2 phosphorylation. Consistently, gain- and loss-of-function mutants in SHP-2 proved its regulation of imatinib resistance. SHP-2 inhibitor and imatinib exhibited a strong antitumor synergy in in vitro and in vivo K562/G models. Mechanistically, dual SHP-2 and BCR-ABL inhibition blocked RAF/MEK/ERK and PI3K/AKT/mTOR pathways, respectively, leading to dramatic apoptotic death of K562/G cells. In conclusion, our results highlight that SHP-2 could be exploited as a biomarker and therapeutic target during the early phase of imatinib resistance development in CML.
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Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Mesilato de Imatinib/farmacologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Proteína Tirosina Fosfatase não Receptora Tipo 11/metabolismo , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proteínas de Fusão bcr-abl/metabolismo , Humanos , Células K562 , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismoRESUMO
In this work, the surface plasmon resonance effect of metallic Ag, surface oxygen vacancies (SOVs), and Bi2 MoO6 (BMO) material were rationally combined to construct new oxygen-vacancy-rich Ag/Bi2 MoO6 (A/BMO-SOVs) photocatalysts. Their synergistic effect on the photocatalytic degradation of phenol and 4-nitrophenol under visible-light irradiation (λ≥420â nm) was also investigated. TEM, EPR, and Raman spectra demonstrate the co-existence of metallic Ag nanoparticles, surface oxygen vacancies, and Bi2 MoO6 due to a controlled calcination process. The experimental results disclose that the 2 %A/BMO-SOVs-375 sample exhibited the highest photocatalytic activity for the degradation of both phenol and 4-nitrophenol under visible-light irradiation, achieving nearly 100 and 80 % removal efficiency, respectively, and demonstrated the apparent reaction rate constants (kapp ) 183 and 26.5â times, respectively, higher than that of pure Bi2 MoO6 . The remarkable photodegradation performance of A/BMO-SOVs for organic substances is attributed to the synergistic effect between the surface oxygen vacancies, metallic Ag nanoparticles, and Bi2 MoO6 , which not only improves the visible-light response ability, but also facilitates charge separation. Thus, this work provides an effective strategy for the design and fabrication of highly efficient photocatalysts through integrating surface oxygen vacancies and the surface plasmon resonance effect of nanoparticles, which has the potential for both water treatment and air purification.
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Pyocyanin, an important virulence factor, is synthesized and secreted by Pseudomonas aeruginosa PAO1and plays a critical role in pathogen-host interaction during infection. Sigma38 (σ38, σS) is a central regulator for many virulence production in pathogens. Objective: Our aim is to identify expression and regulation of two phenazine-producing operons mediated by the sigma38 factor in Pseudomonas aeruginosa PAO1. Methods: We first cloned the flanking fragments of rpoS from the chromosomal DNA of P. aeruginosa PAO1 and constructed the deletion mutant ΔrpoS with the insertion of gentamycin resistance cassette (aacC1). Complementation of rpoS was then carried out after construction and introduction of pME10S (containing the whole rpoS region). Finally, we created the mutant ΔrpoSphz1 and ΔrpoSphz2, and measured pyocyanin production by these mutants in GA medium, using the parental strain Δphz1 and Δphz2 as controls. Results: In GA medium, pyocyanin production by mutant ΔrpoS increased dramatically in comparison with the wild-type strain PAO1. Production of pyocyanin, however, was decreased to the level of the wild-type strain with complementation of the derivative ΔrpoS harboring pME10S. Mutant ΔrpoSphz2 produced much more pyocyanin than mutant Δphz2. Mutant ΔrpoSphz1, however, produced much less pyocyanin than mutant Δphz1. Conclusion: By positively regulating the expression of phz2 and negatively regulating the phz1, sigma38 factor exerts negative modulation on pyocyanin biosynthesis in P. aeruginosa PAO1.
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Proteínas de Bactérias/metabolismo , Regulação Bacteriana da Expressão Gênica , Pseudomonas aeruginosa/metabolismo , Piocianina/biossíntese , Fator sigma/metabolismo , Fatores de Virulência/biossíntese , Proteínas de Bactérias/genética , Óperon , Fenazinas/metabolismo , Pseudomonas aeruginosa/genética , Fator sigma/genéticaRESUMO
Composite coagulants have drawn a widespread attention recently for its superior coagulation-flocculation performance. Fe and Ti based coagulants, as a kind of inorganic metal water treatment agent, h have received huge attention, but there is little study about the preparation and characterization of composite coagulate composite with Ti4+. In this paper we prepared a composite coagulant, in which the Ti (SO4)2 was introduced as coordination complexes, PO3-4 as stabilizer and complexant. Then, the FT-Infra Red spectrum (FT-IR) and ultraviolet/visible absorption spectrum (UV-Vis) were adopted to characterizse the changes of chemical group, species distribution of coagulants in case of varies Ti/Fe, P/Fe and OH/Fe molar ratio. The results shows other than simple mixture of the raw materials, the introduction of Ti4+ and PO4 group synthesized the chemical group bond as TiO, FePFe and TiPTi, which were beneficial to the degree of polymerization and increased the stability of the product. Furthermore, when the Ti/Fe molar ratio of 1â¶8, P/Fe was in the range of 0.2~0.3, the optimal material is suitable for the generation of FePTi chemistry bond and medium polymer as Fe6(OH)6+12ï¼[Fex(OH)y]2H2PO(6x-2y-1)+4. Whereas, too much addition of Ti4+, PO3-4 and HCO-3 deteriorated the polymer structure, leading to the presentation of precipitate as TiO2, Ti3(PO4)4 and FePO4, which will decrease the coagulation performance.
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Cationic Polyacrylamide P(AM-DAC-BA) was synthesized by UV initiation, with acrylamide (AM), acryloyloxyethyl trimethyl ammonium chloride (DAC), butyl acrylate (BA) as the monomers. P(AM-DAC-BA). UV spectroscopy and infrared spectroscopy were employed to study the structural characteristics. Attributions of typical infrared vibrational frequencies in AM/DAC/BA/P(AM-DAC-BA) were analysed. By comparing with infrared spectroscopy of the monomers, symmetrical characteristic of P(AM-DAC-BA) increasesd, and the infrared spectroscopy of polymerization product was simpler. The intrinsic viscosity increased with the increase in light intensity, BA content, photoinitiator concentration and illumination time. The groups of -CONH2, -COOCH2(C=O), -COOCH2--(C-O-C), -CH2--N(CH3 )3 group in AM, DAC, BA were selected as characteristic absorption peaks for studying. With the increase in light intensity and BA content, the characteristic peak areas increased. With the increase in photoinitiator concentration, the characteristic peak areas decreased. The characteristic peak areas decreased firstly and then increased with increasing the illumination time. But the corresponding characteristic IR absorption peaks of P(AM-DAC-BA) were similar, and the positions of characteristic peaks were basically the same.
RESUMO
BACKGROUND: Painful neuropathy is a pathological condition caused by numerous factors including diabetes, chemotherapy or cancer. ART26.12 is a novel fatty acid-binding protein 5 inhibitor, which our group showed could prevent and treat persistent pain in a preclinical model of oxaliplatin-induced peripheral neuropathy. METHODS: In the current study, the efficacy of orally dosed ART26.12 was tested in multiple neuropathy models of different aetiology. Paw withdrawal threshold to von Frey monofilaments and latency to escape a cold plate were used as measurements of mechanical and cold sensitivity. RESULTS: ART26.12 (25 and 50 mg/kg BID), dosed prior to the induction of paclitaxel-induced peripheral neuropathy (PIPN), reversed mechanical allodynia induced by paclitaxel in both male and female rats, and ART26.12 (50 mg/kg BID) prevented the induction of PIPN in female rats. ART26.12 (50 mg/kg BID) also had a protective effect on body weight in the PIPN model. ART26.12 (25 and 100 mg/kg BID) reversed mechanical allodynia when treating established streptozotocin-induced diabetic neuropathy in male rats. In a model of breast cancer-induced bone pain in female rats, ART26.12 (100 mg/kg BID) reversed mechanical allodynia within 1 h of dosing. In the same model, ART26.12 (25 mg/kg BID) reversed mechanical allodynia from day 4 of treatment. CONCLUSION: Overall, these preclinical data suggest that ART26.12 is a safe and efficacious therapeutic drug for continued development towards the prevention and treatment of peripheral neuropathy. SIGNIFICANCE STATEMENT: This work now shows that ART26.12, a novel and selective inhibitor of FABP5, can prevent and treat multiple preclinical models of peripheral neuropathy. Given its excellent safety profile, further work is warranted to develop ART26.12 as a potential therapeutic tool for pain management.