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1.
Nature ; 586(7829): 390-394, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-33057223

RESUMEN

Owing to its high thermal and electrical conductivities, its ductility and its overall non-toxicity1-3, copper is widely used in daily applications and in industry, particularly in anti-oxidation technologies. However, many widespread anti-oxidation techniques, such as alloying and electroplating1,2, often degrade some physical properties (for example, thermal and electrical conductivities and colour) and introduce harmful elements such as chromium and nickel. Although efforts have been made to develop surface passivation technologies using organic molecules, inorganic materials or carbon-based materials as oxidation inhibitors4-12, their large-scale application has had limited success. We have previously reported the solvothermal synthesis of highly air-stable copper nanosheets using formate as a reducing agent13. Here we report that a solvothermal treatment of copper in the presence of sodium formate leads to crystallographic reconstruction of the copper surface and formation of an ultrathin surface coordination layer. We reveal that the surface modification does not affect the electrical or thermal conductivities of the bulk copper, but introduces high oxidation resistance in air, salt spray and alkaline conditions. We also develop a rapid room-temperature electrochemical synthesis protocol, with the resulting materials demonstrating similarly strong passivation performance. We further improve the oxidation resistance of the copper surfaces by introducing alkanethiol ligands to coordinate with steps or defect sites that are not protected by the passivation layer. We demonstrate that the mild treatment conditions make this technology applicable to the preparation of air-stable copper materials in different forms, including foils, nanowires, nanoparticles and bulk pastes. We expect that the technology developed in this work will help to expand the industrial applications of copper.

2.
J Virol ; 98(2): e0154623, 2024 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-38299865

RESUMEN

Vaccine-induced mucosal immunity and broad protective capacity against various severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants remain inadequate. Formyl peptide receptor-like 1 inhibitory protein (FLIPr), produced by Staphylococcus aureus, can bind to various Fcγ receptor subclasses. Recombinant lipidated FLIPr (rLF) was previously found to be an effective adjuvant. In this study, we developed a vaccine candidate, the recombinant Delta SARS-CoV-2 spike (rDS)-FLIPr fusion protein (rDS-F), which employs the property of FLIPr binding to various Fcγ receptors. Our study shows that rDS-F plus rLF promotes rDS capture by dendritic cells. Intranasal vaccination of mice with rDS-F plus rLF increases persistent systemic and mucosal antibody responses and CD4/CD8 T-cell responses. Importantly, antibodies induced by rDS-F plus rLF vaccination neutralize Delta, Wuhan, Alpha, Beta, and Omicron strains. Additionally, rDS-F plus rLF provides protective effects against various SARS-CoV-2 variants in hamsters by reducing inflammation and viral loads in the lung. Therefore, rDS-F plus rLF is a potential vaccine candidate to induce broad protective responses against various SARS-CoV-2 variants.IMPORTANCEMucosal immunity is vital for combating pathogens, especially in the context of respiratory diseases like COVID-19. Despite this, most approved vaccines are administered via injection, providing systemic but limited mucosal protection. Developing vaccines that stimulate both mucosal and systemic immunity to address future coronavirus mutations is a growing trend. However, eliciting strong mucosal immune responses without adjuvants remains a challenge. In our study, we have demonstrated that using a recombinant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike-formyl peptide receptor-like 1 inhibitory protein (FLIPr) fusion protein as an antigen, in combination with recombinant lipidated FLIPr as an effective adjuvant, induced simultaneous systemic and mucosal immune responses through intranasal immunization in mice and hamster models. This approach offered protection against various SARS-CoV-2 strains, making it a promising vaccine candidate for broad protection. This finding is pivotal for future broad-spectrum vaccine development.


Asunto(s)
Proteínas Bacterianas , Vacunas contra la COVID-19 , COVID-19 , Inmunidad Mucosa , Lípidos , Proteínas Recombinantes de Fusión , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Animales , Cricetinae , Ratones , Adyuvantes Inmunológicos , Anticuerpos Antivirales/inmunología , Proteínas Bacterianas/química , Proteínas Bacterianas/genética , Proteínas Bacterianas/inmunología , Proteínas Bacterianas/metabolismo , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , COVID-19/inmunología , COVID-19/prevención & control , COVID-19/virología , Vacunas contra la COVID-19/administración & dosificación , Vacunas contra la COVID-19/química , Vacunas contra la COVID-19/genética , Vacunas contra la COVID-19/inmunología , Células Dendríticas/inmunología , Modelos Animales de Enfermedad , Receptores de IgG/clasificación , Receptores de IgG/inmunología , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/inmunología , Proteínas Recombinantes de Fusión/metabolismo , SARS-CoV-2/clasificación , SARS-CoV-2/inmunología , Glicoproteína de la Espiga del Coronavirus/genética , Glicoproteína de la Espiga del Coronavirus/inmunología , Glicoproteína de la Espiga del Coronavirus/metabolismo , Staphylococcus aureus , Desarrollo de Vacunas , Carga Viral
3.
Apoptosis ; 29(5-6): 620-634, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38281282

RESUMEN

Maleic acid (MA) induces renal tubular cell dysfunction directed to acute kidney injury (AKI). AKI is an increasing global health burden due to its association with mortality and morbidity. However, targeted therapy for AKI is lacking. Previously, we determined mitochondrial-associated proteins are MA-induced AKI affinity proteins. We hypothesized that mitochondrial dysfunction in tubular epithelial cells plays a critical role in AKI. In vivo and in vitro systems have been used to test this hypothesis. For the in vivo model, C57BL/6 mice were intraperitoneally injected with 400 mg/kg body weight MA. For the in vitro model, HK-2 human proximal tubular epithelial cells were treated with 2 mM or 5 mM MA for 24 h. AKI can be induced by administration of MA. In the mice injected with MA, the levels of blood urea nitrogen (BUN) and creatinine in the sera were significantly increased (p < 0.005). From the pathological analysis, MA-induced AKI aggravated renal tubular injuries, increased kidney injury molecule-1 (KIM-1) expression and caused renal tubular cell apoptosis. At the cellular level, mitochondrial dysfunction was found with increasing mitochondrial reactive oxygen species (ROS) (p < 0.001), uncoupled mitochondrial respiration with decreasing electron transfer system activity (p < 0.001), and decreasing ATP production (p < 0.05). Under transmission electron microscope (TEM) examination, the cristae formation of mitochondria was defective in MA-induced AKI. To unveil the potential target in mitochondria, gene expression analysis revealed a significantly lower level of ATPase6 (p < 0.001). Renal mitochondrial protein levels of ATP subunits 5A1 and 5C1 (p < 0.05) were significantly decreased, as confirmed by protein analysis. Our study demonstrated that dysfunction of mitochondria resulting from altered expression of ATP synthase in renal tubular cells is associated with MA-induced AKI. This finding provides a potential novel target to develop new strategies for better prevention and treatment of MA-induced AKI.


Asunto(s)
Lesión Renal Aguda , Apoptosis , Maleatos , Ratones Endogámicos C57BL , Mitocondrias , ATPasas de Translocación de Protón Mitocondriales , Animales , Humanos , Masculino , Ratones , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/genética , Lesión Renal Aguda/patología , Apoptosis/efectos de los fármacos , Línea Celular , Células Epiteliales/metabolismo , Células Epiteliales/efectos de los fármacos , Células Epiteliales/patología , Túbulos Renales Proximales/patología , Túbulos Renales Proximales/efectos de los fármacos , Túbulos Renales Proximales/metabolismo , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Mitocondrias/patología , ATPasas de Translocación de Protón Mitocondriales/metabolismo , ATPasas de Translocación de Protón Mitocondriales/genética , Especies Reactivas de Oxígeno/metabolismo
4.
Chemistry ; 30(9): e202303092, 2024 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-38057492

RESUMEN

While great achievements have been made in the development of mechanically robust nanocomposite hydrogels, incorporating multiple interactions on the bases of two demensional inorganic cross-linkers to construct self-strengthening hydrogels has rarely been investigated. To this end, we propose here a new method for the coupling the dynamic covalent bonds and non-covalent interactions within a pseudo double-network system. The pseudo first network, formed through the Schiff Base reation between Tris-modified layered double hydroxides (Tris-LDHs) and oxidized dextran (ODex), is linked to the second network built upon non-covalent interactions between Tris-LDHs and poly(acrylamide-co-2-acrylamido-2-methyl-propanesulfonate) (p-(AM-co-AMPS). The swelling and mechanical properties of the resulting hydrogels have been investigated as a function of the ODex and AMPS contents. The as-prepared hydrogel can swell to 420 times of its original size and retain more than 99.9 wt.% of water. Mechanical tests show that the hydrogel can bear 90 % of compression and is able to be stretched to near 30 times of its original length. Cyclic tensile tests reveal that the hydrogels are capable of self-strengthening after mechanical training. The unique energy dissipation mechanism based on the dynamic covalent and non-covalent interactions is considered to be responsible for the outstanding swelling and mechanical performances.

5.
J Biomed Sci ; 31(1): 62, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38862973

RESUMEN

BACKGROUND: Ovarian carcinoma (OC) is a fatal malignancy, with most patients experiencing recurrence and resistance to chemotherapy. In contrast to hematogenous metastasizing tumors, ovarian cancer cells disseminate within the peritoneal cavity, especially the omentum. Previously, we reported omental crown-like structure (CLS) number is associated with poor prognosis of advanced-stage OC. CLS that have pathologic features of a dead or dying adipocyte was surrounded by several macrophages is well known a histologic hallmark for inflammatory adipose tissue. In this study, we attempted to clarify the interaction between metastatic ovarian cancer cells and omental CLS, and to formulate a therapeutic strategy for advanced-stage ovarian cancer. METHODS: A three-cell (including OC cells, adipocytes and macrophages) coculture model was established to mimic the omental tumor microenvironment (TME) of ovarian cancer. Caspase-1 activity, ATP and free fatty acids (FFA) levels were detected by commercial kits. An adipocyte organoid model was established to assess macrophages migration and infiltration. In vitro and in vivo experiments were performed for functional assays and therapeutic effect evaluations. Clinical OC tissue samples were collected for immunochemistry stain and statistics analysis. RESULTS: In three-cell coculture model, OC cells-derived IL-6 and IL-8 could induce the occurrence of pyroptosis in omental adipocytes. The pyroptotic adipocytes release ATP to increase macrophage infiltration, release FFA into TME, uptake by OC cells to increase chemoresistance. From OC tumor samples study, we demonstrated patients with high gasdermin D (GSDMD) expression in omental adipocytes is highly correlated with chemoresistance and poor outcome in advanced-stage OC. In animal model, by pyroptosis inhibitor, DSF, effectively retarded tumor growth and prolonged mice survival. CONCLUSIONS: Omental adipocyte pyroptosis may contribute the chemoresistance in advanced stage OC. Omental adipocytes could release FFA and ATP through the GSDMD-mediate pyroptosis to induce chemoresistance and macrophages infiltration resulting the poor prognosis in advanced-stage OC. Inhibition of adipocyte pyroptosis may be a potential therapeutic modality in advanced-stage OC with omentum metastasis.


Asunto(s)
Adipocitos , Resistencia a Antineoplásicos , Epiplón , Neoplasias Ováricas , Piroptosis , Microambiente Tumoral , Femenino , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/patología , Epiplón/metabolismo , Humanos , Adipocitos/metabolismo , Ratones , Animales , Línea Celular Tumoral , Técnicas de Cocultivo
6.
Lupus ; 33(6): 608-614, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38518059

RESUMEN

OBJECTIVE: The objective of this study is to provide a description of a group of retrospective cohort outcomes in patients with systemic lupus erythematosus (SLE) complicated with immune thrombocytopenia (ITP) receiving belimumab. METHODS: This study reports on the treatment of 10 female patients (mean age 34.3 ± 14.0 years, mean weight 58.7 ± 18.2 kg) with both SLE and ITP who received belimumab in addition to basic drug therapy. The belimumab treatment regimen consisted of a dosage of 10 mg/kg, with an initial infusion every 2 weeks for the first 3 doses, followed by an infusion every 4 weeks. RESULTS: Ten patients were included in the study. The overall response rate of thrombocytopenia was 90% after treatment. The parameters such as platelet count, lymphocyte count, erythrocyte count, hemoglobin, dsDNA, C3, and C4 were significantly improved (p < .05). The SLE Disease Activity Index (SLEDAI), British Islet lupus Assessment Group 2004 (BILAG-2004), and Physician Global assessment (PGA) scores were significantly decreased (p < .05). There were no significant differences in glutamic pyruvic transaminase (ALT), glutamic oxaloacetic transaminase (AST), and serum creatinine (Scr) before and after treatment (p > .05). CONCLUSION: Belimumab shows promising clinical outcomes in the treatment on patients with both SLE and ITP. Further studies are needed to validate these findings in larger patient populations and compare the efficacy of belimumab with other treatments for SLE complicated with ITP. Long-term response rates and adverse events associated with belimumab treatment also warrant further investigation.


Asunto(s)
Anticuerpos Monoclonales Humanizados , Lupus Eritematoso Sistémico , Púrpura Trombocitopénica Idiopática , Trombocitopenia , Humanos , Femenino , Adulto Joven , Adulto , Persona de Mediana Edad , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/tratamiento farmacológico , Estudios Retrospectivos , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Resultado del Tratamiento , Trombocitopenia/tratamiento farmacológico , Inmunosupresores/efectos adversos , Índice de Severidad de la Enfermedad
7.
Inorg Chem ; 63(19): 8764-8774, 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38686432

RESUMEN

In-based halide perovskites have attracted a lot of attention because of their unique broadband emission properties. Herein, a series of In-based hybrid perovskites of (H2MP)2InCl7·H2O (1), (H2EP)2InCl7·H2O (2), (H2MP)2InBr7·H2O (3), and (H2EP)2InBr7·H2O (4) were synthesized under the control of halogen ions and organic cations. 1, 2, and 4 exhibit obvious photoluminescence properties with peaks at 392, 442, and 652 nm, respectively. The effects of the different components on the crystal structure and photoluminescence properties are discussed by calculating the structural distortion of the [InX6]3- octahedron. The photoluminescence properties of 1 and 4 were significantly improved after Sb3+ doping with PLQY values of 57.12 and 41.53%. Finally, a white LED was successfully fabricated with the two doped compounds coated onto the 365 nm blue LED chip.

8.
Clin Exp Ophthalmol ; 2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38757252

RESUMEN

BACKGROUND: To identify genotypes associated with neovascular age-related macular degeneration (nAMD) and investigate the associations between genotype variations and anti-vascular endothelial growth factor (VEGF) treatment response. METHODS: This observational, retrospective, case series study enrolled patients diagnosed with nAMD who received anti-VEGF treatment in National Taiwan University Hospital with at least one-year follow-up between 2012 and 2020. A genome-wide association study (GWAS) was conducted on enrolled patients and controls. Correlations between the genotypes identified from GWAS and the treatment response of functional/anatomical biomarkers, including visual acuity (VA), presence of intraretinal or subretinal fluid (SRF), serous or fibrovascular pigmented epithelium detachment (PED), and disruption of the ellipsoid zone (EZ), were analysed. RESULTS: In total, 182 patients with nAMD and 1748 controls were enrolled. GWAS revealed 16 single nucleotide polymorphisms (SNPs) as risk loci for nAMD, including seven loci in CFH and ARMS2/HTRA1 and nine novel loci, including rs117517872 and rs79835234(COPB2-DT), rs7525578(RAP1A), rs2123738(LOC105376755), rs1374879(CNTN3), rs3812692(SAR1A), rs117501587(PRKCA), rs9965945(CNDP1), and rs189769231(MATK). Our study revealed rs800292(CFH), rs11200638(HTRA1), and rs2123738(LOC105376755) correlated with poor treatment response in VA (P = 0.005), SRF (P = 0.044), and fibrovascular PED (P = 0.007), respectively. Rs9965945(CNDP1) was correlated with poor response in disruption of EZ (P = 0.046) and serous PED (P = 0.049). CONCLUSIONS: Among the 16 SNPs found in the GWAS, four loci-CFH, ARMS2/HTRA1, and two novel loci-were correlated with the susceptibility of nAMD and anatomical/functional responses after anti-VEGF treatment.

9.
Environ Toxicol ; 39(5): 3198-3210, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38351887

RESUMEN

In this presentation, we explored the molecular mechanisms of N. nucifera leaf water extracts (NLWEs) and polyphenol extract (NLPE) on scopolamine-induced cell apoptosis and cognition defects. The administration of NLWE and NLPE did not alter the body weight and serum biomarker rs and significantly ameliorated scopolamine-induced cognition impairment according to Y-maze test analysis. In mice, treatment with scopolamine disrupted normal histoarchitecture in the hippocampus, whereas the administration of NLWE and NLPE reversed the phenomenon. Western blot analysis revealed that scopolamine mitigated the expression of doublecortin (DCX), nestin, and NeuN, and cotreatment with NLWE or NLPE significantly recovered the expression of these proteins. NLWE and NLPE upregulated DCX and NeuN expression in the hippocampus region, as evidenced by immunohistochemical staining analysis of scopolamine-treated mice. NLWE and NLPE obviously elevated brain-derived neurotrophic factor (BDNF) and enhanced its downstream proteins activity. NLWE and NLPE attenuated scopolamine-induced apoptosis by reducing Bax and increased Bcl-2 expression. In addition, scopolamine also triggered apoptosis in human neuroblastoma SH-SY5Y cells whereas co-treatment with NLWE or quercetin-3-glucuronide (Q3G) reversed the phenomenon. NLWE or Q3G enhanced Bcl-2 and reduced Bax expression in the presence of scopolamine in SH-SY5Y cells. NLWE or Q3G recovered the inhibitory effects of scopolamine on neurogenesis and BDNF signals in SH-SY5Y cells. Overall, our results revealed that N. nucifera leaf extracts and Q3G promoted adult hippocampus neurogenesis and prevented apoptosis to mitigate scopolamine-induced cognition dysfunction through the regulation of BDNF signaling pathway.


Asunto(s)
Nelumbo , Neuroblastoma , Ratones , Humanos , Animales , Escopolamina/farmacología , Escopolamina/metabolismo , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Nelumbo/química , Nelumbo/metabolismo , Proteína X Asociada a bcl-2/metabolismo , Neuroblastoma/metabolismo , Hipocampo/metabolismo , Neurogénesis , Aprendizaje por Laberinto , Extractos Vegetales/química , Cognición
10.
J Formos Med Assoc ; 2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38423923

RESUMEN

We presented the development of a consensus guideline for managing juvenile idiopathic arthritis-associated uveitis (JIAU) in Taiwan, considering regional differences in manifestation and epidemiology. The Taiwan Ocular Inflammation Society (TOIS) committee formulated this guideline using a modified Delphi approach with two panel meetings. Recommendations were based on a comprehensive evidence-based literature review and expert clinical experiences, and were graded according to the Oxford Centre for Evidence-Based Medicine's "Levels of Evidence" guideline (March 2009). The TOIS consensus guideline consists of 10 recommendations in four categories: screening and diagnosis, treatment, complications, and monitoring, covering a total of 27 items. These recommendations received over 75% agreement from the panelists. Early diagnosis and a coordinated referral system between ophthalmologists and pediatric rheumatologists are crucial to prevent irreversible visual impairment in children with JIAU. However, achieving a balance between disease activity and medication use remains a key challenge in JIAU management, necessitating further clinical studies.

11.
Chembiochem ; 24(11): e202300205, 2023 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-37069132

RESUMEN

The O-acetylation of the muramic acid residues in peptidoglycan (PG) is a modification that protects the bacteria from lysis due to the action of lysozyme. In Gram-negative bacteria, deacetylation is required to allow lytic transglycosylases to promote PG cleavage during cell growth and division. This deacetylation is catalyzed by O-acetylpeptidoglycan esterase (Ape) which is a serine esterase and employs covalent catalysis via a serine-linked acyl enzyme intermediate. Loss of Ape activity affects the size and shape of bacteria and dramatically reduces virulence. In this work, we report the first rationally designed aldehyde-based inhibitors of Ape from Campylobacter jejuni. The most potent of these acts as a competitive inhibitor with a Ki value of 13 µM. We suspect that the inhibitors are forming adducts with the active site serine that closely mimic the tetrahedral intermediate of the normal catalytic cycle. Support for this notion is found in the observation that reduction of the aldehyde to an alcohol effectively abolishes the inhibition.


Asunto(s)
Acetilesterasa , Hominidae , Animales , Peptidoglicano/química , Aldehídos/farmacología , Esterasas/química , Bacterias/metabolismo , Serina , Hominidae/metabolismo
12.
Opt Express ; 31(26): 43667-43685, 2023 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-38178457

RESUMEN

Structured light systems often suffer interference of the fringes by blooming when scanning metal objects. Unfortunately, this problem cannot be reliably solved using conventional methods such as the high dynamic range (HDR) method or adaptive projection technique. Therefore, this study proposes a method to adaptively suppress the oversaturated areas that cause blooming as the exposure time increases and then fuse the multi-exposure time decoding results using a decoding inheritance method. The experimental results demonstrate that the proposed method provides a more effective suppression of blooming interference than existing methods.

13.
BMC Cancer ; 23(1): 871, 2023 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-37715113

RESUMEN

BACKGROUND: While the treatment guidelines have been established for pure urothelial carcinoma (pUC), patients with variant type urothelial carcinoma (vUC) face limited effective treatment options. The effectiveness of immune checkpoint inhibitors (ICI) in patients with vUC remains uncertain and necessitates additional research. METHOD: We conducted a retrospective, multicenter study to explore the effectiveness of ICI in patients with pUC or vUC in Taiwan. We evaluated the overall response rate (ORR) through univariate logistic regression analysis and examined the overall survival (OS) and progression-free survival (PFS) using Kaplan-Meier analysis. Additionally, we employed univariate and multivariate Cox proportional hazards models to analyze the data. RESULT: A total of 142 patients (116 pUC, 26 vUC) were included in our final analysis. The ORR was marginally higher in patients with pUC compared to those with vUC (34.5% vs. 23.1%, p = 0.26). Among all patients, 12.9% with pUC achieved a complete response (CR) after ICI treatment, while no vUC cases achieved CR (p = 0.05). There were no significant differences in PFS (median 3.6 months vs. 4.1 months, p = 0.34) or OS (median 16.3 months vs. 11.0 months, p = 0.24) when comparing patients with pUC or vUC. In the subgroup analysis, patients with pUC who underwent first-line ICI treatment exhibited significantly improved OS compared to those with vUC (24.6 months vs. 9.1 months, p = 0.004). CONCLUSION: The use of ICI as monotherapy is a feasible and effective treatment approach for patients with metastatic vUC.


Asunto(s)
Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Humanos , Carcinoma de Células Transicionales/tratamiento farmacológico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Pronóstico , Estudios Retrospectivos
14.
J Biomed Sci ; 30(1): 41, 2023 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-37316861

RESUMEN

BACKGROUND: Flavivirus causes many serious public health problems worldwide. However, licensed DENV vaccine has restrictions on its use, and there is currently no approved ZIKV vaccine. Development of a potent and safe flavivirus vaccine is urgently needed. As a previous study revealed the epitope, RCPTQGE, located on the bc loop in the E protein domain II of DENV, in this study, we rationally designed and synthesized a series of peptides based on the sequence of JEV epitope RCPTTGE and DENV/ZIKV epitope RCPTQGE. METHODS: Immune sera were generated by immunization with the peptides which were synthesized by using five copies of RCPTTGE or RCPTQGE and named as JEV-NTE and DV/ZV-NTE. Immunogenicity and neutralizing abilities of JEV-NTE or DV/ZV-NTE-immune sera against flavivirus were evaluated by ELISA and neutralization tests, respectively. Protective efficacy in vivo were determined by passive transfer the immune sera into JEV-infected ICR or DENV- and ZIKV-challenged AG129 mice. In vitro and in vivo ADE assays were used to examine whether JEV-NTE or DV/ZV-NTE-immune sera would induce ADE. RESULTS: Passive immunization with JEV-NTE-immunized sera or DV/ZV-NTE-immunized sera could increase the survival rate or prolong the survival time in JEV-challenged ICR mice and reduce the viremia levels significantly in DENV- or ZIKV-infected AG129 mice. Furthermore, neither JEV -NTE- nor DV/ZV-NTE-immune sera induced antibody-dependent enhancement (ADE) as compared with the control mAb 4G2 both in vitro and in vivo. CONCLUSIONS: We showed for the first time that novel bc loop epitope RCPTQGE located on the amino acids 73 to 79 of DENV/ZIKV E protein could elicit cross-neutralizing antibodies and reduced the viremia level in DENV- and ZIKV-challenged AG129 mice. Our results highlighted that the bc loop epitope could be a promising target for flavivirus vaccine development.


Asunto(s)
Infección por el Virus Zika , Virus Zika , Animales , Ratones , Ratones Endogámicos ICR , Anticuerpos Neutralizantes , Viremia , Sueros Inmunes , Epítopos , Factores de Transcripción
15.
Environ Res ; 216(Pt 2): 114423, 2023 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-36228691

RESUMEN

Polycarboxylate (PCE) is a high performance superplasticizer for modern concrete. With the high quality sand becoming precious, more and more low quality sands are used in concrete. However, low quality sands generally contain a relatively high content of montmorillonite (MMT), which could seriously reduce the efficiency of PCE. In order to develop PCE suitable for concrete with low quality sands, the absorption behavior on MMT of PCE with different side chains and acid/ether ratio was investigated. In order to explore the effect of MMT on PCE, two macromonomers were selected, isoprene glycol ether 400(TPEG400) and isoprene glycol ether 2400 (TPEG2400), to synthesize six long and short side chain comb-type PCEs with acid-ether ratios of 1.5:1, 2.5:1 and 3.5:1, respectively. The MMT tolerance mechanism of comb-type PCE in MMT-containing cement slurry was examined by FT-IR, DLS, TOC and other analysis. The PCE with long side chain is much easier to be inserted into the layered structure of MMT, resulting in intercalation absorption. The absorption amount of two kinds of side chain PCE on the MMT particles decreased as the acid ether ratio increases. PCE with long side chains showed shear-thickening properties in MMT-containing cement slurry, on the contrary, short side chains showed shear-thinning properties.

16.
Appl Microbiol Biotechnol ; 107(1): 219-232, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36434113

RESUMEN

The spread of chikungunya virus (CHIKV) is reaching pandemic levels, and vaccines and antivirals to control CHIKV infection have yet to be approved. Virus-like particles (VLPs), a self-assembled native multi-subunit protein structure, could potentially be used as an antigen for serological detection and vaccine development. In the current study, we describe the production of novel CHIKV VLPs from mosquitoes using a Baculovirus/Mosquito (BacMos) system in a simple Biosafety Level-2 laboratory. Substantial envelope and capsid protein secretions were detected in culture medium. Co-fractionation of CHIKV E2, E1, and capsid proteins via sucrose gradient ultracentrifugation provided evidence of VLP formation. Transmission electron microscopy and dynamic light scattering analysis revealed the formation of VLPs in the form of spherical particles with a diameter of roughly 40 nm in transduced cells and culture medium. VLP-based IgM capture ELISA in CHIKV patient sera revealed native epitopes on the VLPs. These non-purified VLPs were shown to act as an antigen in CHIKV-specific IgM capture ELISA. The immunization of CHIKV-VLPs alone in mice induced a balance CHIKV-specific IgG2a/IgG1 antibodies and neutralized antibody responses. The study provides support for the hypothesis that mosquito cell-derived CHIKV VLPs could serve as a novel antigen for serological detection and the development of vaccines against CHIKV infection. KEY POINTS: • CHIKV VLPs secreted from BacMos-CHIKV 26S-transduced mosquito cell. • This CHIKV VLPs potentially serve as an alternative capture antigen for MAC-ELISA. • Unadjuvanted CHIK VLPs induce CHIKV-specific IgG and NT responses in mice.


Asunto(s)
Fiebre Chikungunya , Virus Chikungunya , Culicidae , Ratones , Animales , Fiebre Chikungunya/prevención & control , Anticuerpos Antivirales , Inmunoglobulina M , Inmunoglobulina G , Proteínas de la Cápside
17.
Retina ; 43(1): 57-63, 2023 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-36161999

RESUMEN

PURPOSE: To explore the clinical features and outcomes of cytomegalovirus retinitis (CMVR) in patients with HIV and non-HIV. METHODS: This retrospective cohort study included all patients with CMVR in National Taiwan University Hospital from 2013 to 2018. Demographic data, clinical characteristics, CMVR recurrence, and overall survival were compared between the HIV and non-HIV groups. Generalized estimating equation models were implemented to analyze the risk factors of poor visual prognosis. The Kaplan-Meier survival analysis was performed to investigate recurrence and survival. RESULTS: A total of 66 patients (95 eyes) with CMVR were enrolled, with no significant differences between the HIV (41 patients; 61 eyes) and non-HIV (25 patients; 34 eyes) groups in initial/final visual acuity, lesion area, or viral loads. Poor visual outcome was associated with poor initial visual acuity, retinal detachment, and a higher plasma cytomegalovirus titer. The HIV group had significantly longer survival rate ( P = 0.033) and lower recurrence rate ( P = 0.01) than the non-HIV group, and it also presented with better prognosis in recurrence-free survival analysis ( P = 0.01). CONCLUSION: Patients with CMVR without HIV had higher mortality and recurrence rates than the HIV group. Risk factors of poor visual outcome included poor initial visual acuity, retinal detachment, and a high plasma cytomegalovirus titer.


Asunto(s)
Retinitis por Citomegalovirus , Infecciones por VIH , Desprendimiento de Retina , Humanos , Retinitis por Citomegalovirus/diagnóstico , Retinitis por Citomegalovirus/tratamiento farmacológico , Retinitis por Citomegalovirus/patología , Infecciones por VIH/complicaciones , Pronóstico , Estudios Retrospectivos , Trastornos de la Visión
18.
J Appl Clin Med Phys ; 24(9): e14010, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37170691

RESUMEN

BACKGROUND: Extended field-of-view (eFOV) methods have been proposed to generate larger demonstration FOVs for computed tomography (CT) simulators with a limited scanning FOV (sFOV) size in order to ensure accurate dose calculation and patient collision avoidance. Although the efficacy of these strategies has been evaluated for photon applications, the effect of stopping power ratio (SPR) estimation on proton therapy has not been studied. This study investigated the effect of an eFOV approach on the accuracy of SPR to water estimation in homogeneous and heterogeneous phantoms. MATERIALS AND METHODS: To simulate patient geometries, tissue-equivalent material (TEM) and customized extension phantoms were used. The TEM phantom supported various rod arrangements through predefined holes. Images were reconstructed to three FOV sizes using a commercial eFOV technique. A single-energy CT stoichiometric method was used to generate Hounsfield unit (HU) to SPR (HU-to-SPR) conversion curves for each FOV. To investigate the effect of rod location in the sFOV and eFOV regions, eight TEM rods were placed at off-center distances in the homogeneous phantom and scanned individually. Similarly, 16 TEM rods were placed in the heterogeneous TEM phantom and scanned simultaneously. RESULTS: The conversion curves derived from the sFOV and eFOV data were identical. The average SPR differences of soft-tissue, bone, and lung materials for rods placed at various off-center locations were 3.3%, 4.8%, and 39.6%, respectively. In the heterogeneous phantom, the difference was within 1.0% in the absence of extension. However, in the presence of extension, the difference increased to 2.8% for all rods, except for lung materials, whose difference was 4.8%. CONCLUSIONS: When an eFOV method is used, the SPR variation in phantoms considerably increases for all TEM rods, especially for lung TEM rods. This phenomenon may substantially increase the uncertainty of HU-to-SPR conversion. Therefore, image reconstruction with a standard FOV size is recommended.


Asunto(s)
Terapia de Protones , Tomografía Computarizada por Rayos X , Humanos , Tomografía Computarizada por Rayos X/métodos , Fantasmas de Imagen , Huesos , Procesamiento de Imagen Asistido por Computador/métodos
19.
J Formos Med Assoc ; 122(11): 1117-1124, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37258323

RESUMEN

PURPOSE: To investigate the treatment outcome, visual outcome, and adverse effects of five-fraction stereotactic radiosurgery (SRS) to medium- and large-sized uveal melanoma with a non-invasive eye immobilization device. METHODS: Medical records of 14 patients with uveal melanoma receiving SRS with a total dose of 50 Gy in five fractions from 2008 to 2017 were retrospectively reviewed. A non-invasive eye fixation device was used to achieve and monitor eye immobilization. RESULTS: Local tumor control rates were 85.7% and 75.0% at 2 and 5 years, respectively. The average tumor diameter decreased significantly from 10.0 ± 3.21 mm to 8.36 ± 3.71 mm (p = 0.038) 15 months after SRS, while the average tumor thickness decreased significantly from 5.45 ± 2.21 mm to 4.34 ± 2.29 (p = 0.036) 21 months after SRS. The 5-year metastasis-free survival was 87.5%. The mean best-corrected visual acuity (BCVA) deteriorated from logMAR 0.296 at baseline to logMAR 1.112 at the last individual follow-up visits (p < 0.001). Adverse effects of SRS were comparable to those reported with proton-beam radiotherapy or Gamma knife therapy. CONCLUSION: SRS combined with a non-invasive eye immobilization device is an effective and safe alternative eye-preserving treatment for medium- to large-sized uveal melanoma. BCVA at 3 months may be a predictor for BCVA at 1 year.


Asunto(s)
Melanoma , Radiocirugia , Neoplasias de la Úvea , Humanos , Radiocirugia/efectos adversos , Estudios Retrospectivos , Neoplasias de la Úvea/radioterapia , Neoplasias de la Úvea/cirugía , Neoplasias de la Úvea/patología , Melanoma/radioterapia , Melanoma/cirugía , Resultado del Tratamiento
20.
J Formos Med Assoc ; 122(8): 668-674, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37003913

RESUMEN

Cytomegalovirus (CMV) uveitis, a type of herpetic uveitis, is a major cause of infectious uveitis. Anterior and posterior CMV uveitis have diverse clinical presentations and treatment modalities. Based on expert consensus in Taiwan, this article provides suggestions regarding clinical manifestations, diagnosis, and treatment strategies for CMV uveitis based on clinical practice experience in Taiwan. CMV uveitis may have a distinct clinical presentation. Polymerase chain reaction (PCR) is an essential diagnostic tool to confirm a diagnosis. Antiviral therapy is the mainstay of treatment. Different agents, routes, and other supplemental treatments have been summarized and discussed in this article. Early diagnosis and appropriate treatment of CMV uveitis are crucial to avoid irreversible complications and vision loss. This consensus provides practical guidelines for ophthalmologists in Taiwan.


Asunto(s)
Infecciones por Citomegalovirus , Infecciones Virales del Ojo , Uveítis Anterior , Uveítis , Humanos , Citomegalovirus/genética , Infecciones por Citomegalovirus/diagnóstico , Infecciones por Citomegalovirus/tratamiento farmacológico , Taiwán , Consenso , Uveítis Anterior/diagnóstico , Uveítis Anterior/tratamiento farmacológico , Infecciones Virales del Ojo/diagnóstico , Infecciones Virales del Ojo/tratamiento farmacológico , ADN Viral , Uveítis/diagnóstico , Uveítis/tratamiento farmacológico , Uveítis/etiología
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