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The purification and removal of organic sulfur from natural gas is conducive to increasing the added value of natural gas and reducing environmental pollution. In this study, the adsorption properties of methyl mercaptan (CH3SH), dimethyl sulfide (C2H6S) and H2O on the surface of hydroxyl-modified ZrO2 were investigated using density functional theory (DFT) calculations. Additionally, a reaction mechanism was proposed for hydroxyl-modified ZrO2 catalyzing the hydrolysis of CH3SH and C2H6S. The chemisorption of H2O molecules on the catalyst surface is attributed to H-O and H-Zr bonds. The chemisorption of CH3SH and C2H6S on the catalyst surface is attributed to Zr-S bonds. Competitive adsorption between the three gases exists only between CH3SH and C2H6S. It reveals the water-resistant properties of hydroxyl-modified ZrO2 in desulfurization. The adsorption energies of the three gas molecules on the hydroxyl-modified ZrO2 surface are in the order of CH3SH - (Zr) > C2H6S - (Zr) > H2O - (OH). The natural hydrolysis of CH3SH and C2H6S is a heat-absorbing process that cannot occur spontaneously. The rate-determining step for CH3SH catalytic hydrolysis is the formation of CH3O. The fracture of CH3SHO is the rate-determining step for C2H6S catalytic hydrolysis. The depletion of the surface hydroxyl groups can be replenished by the dissociation of H2O molecules. Hydroxyl-modified ZrO2 facilitated the hydrolysis process of CH3SH to a greater extent than that of C2H6S. This study provides theoretical guidance for industrial applications and the design of hydroxyl-containing hydrolysis catalysts.
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AIMS: Limited literature shows the existence of sex differences in the long-term prognosis of heart failure (HF) patients with frailty. In this study, whether sex differences exist in the impact of frailty on death from cardiovascular causes in patients with HF was investigated by conducting a retrospective cohort study. METHODS AND RESULTS: Data from the National Health and Nutrition Examination Survey (NHANES) study (2009-2018) were used to conduct a retrospective cohort study of 958 participants with HF. Patients were grouped based on sex and frailty index (FI). The relationship between death from cardiovascular causes and baseline frailty was assessed by Cox proportional hazard analysis and the Kaplan-Meier (K-M) plot. The study population had an age of 67.3 ± 12.3. Among them, around 54.5% were male. A median follow-up of 3.6 years was performed. After that, females who died from cardiovascular causes exhibited higher baseline FI values, while males did not show this trend (P < 0.05; P = 0.1253). Cox regression analysis demonstrated a significant association between FI and cardiovascular mortality in females (most frail: hazard ratio (HR) = 3.65, 95% confidence interval (CI): 1.07 ~ 12.39, P < 0.05; per 1-unit increase in FI: HR = 1.78, 95% CI: 1.33 ~ 2.39, P < 0.001). A dose-response association between FI and cardiovascular mortality was presented by restricted cubic splines. CONCLUSIONS: Frailty is related to an increased risk of cardiovascular mortality in HF patients, particularly female patients.
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OBJECTIVE: Dedifferentiated endometrial carcinoma (DDEC) characterized by SWItch/Sucrose Non-Fermentable (SWI/SNF) complex inactivation is a highly aggressive type of endometrial cancer without effective systemic therapy options. Its uncommon nature and aggressive disease trajectory pose significant challenges for therapeutic progress. To address this obstacle, we focused on developing preclinical models tailored to this tumor type and established patient tumor-derived three-dimensional (3D) spheroid models of DDEC. METHODS: High-throughput drug repurposing screens were performed on in vitro 3D spheroid models of DDEC cell lines (SMARCA4-inactivated DDEC-1 and ARID1A/ARID1B co-inactivated DDEC-2). The dose-response relationships of the identified candidate drugs were evaluated in vitro, followed by in vivo evaluation using xenograft models of DDEC-1 and DDEC-2. RESULTS: Drug screen in 3D models identified multiple cardiac glycosides including digoxin and digitoxin as candidate drugs in both DDEC-1 and DDEC-2. Subsequent in vitro dose-response analyses confirmed the inhibitory activity of digoxin and digitoxin with both drugs showing lower IC50 in DDEC cells compared to non-DDEC endometrial cancer cells. In in vivo xenograft models, digoxin significantly suppressed the growth of DDEC tumors at clinically relevant serum concentrations. CONCLUSION: Using biologically precise preclinical models of DDEC derived from patient tumor samples, our study identified digoxin as an effective drug in suppressing DDEC tumor growth. These findings provide compelling preclinical evidence for the use of digoxin as systemic therapy for SWI/SNF-inactivated DDEC, which may also be applicable to other SWI/SNF-inactivated tumor types.
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OBJECTIVE: To investigate the macular morphological and visual outcomes of combined idiopathic epiretinal membrane (iERM) removal with triamcinolone acetonide (TA) injection based on consideration of the ectopic inner foveal layer (EIFL) staging scheme. METHODS: Retrospective case-control study. The clinical data of 84 eyes of 84 patients who underwent vitrectomy for iERM between 2018 and 2022 were reviewed. The enrolled subjects were divided into the TA and non-TA groups. Fifty-one eyes received intravitreal TA injection following vitrectomy and ERM peeling (TA group), and 33 were only treated by standard vitrectomy and ERM peeling (non-TA group). Preoperative and postoperative EIFL stages, central foveal thickness (CFT), and best-corrected visual acuity (BCVA) were compared between both groups. RESULTS: After a mean follow-up of 7.69 ± 3.68 months, both groups exhibited significant improvement in EIFL stages (P < 0.01), with no discernible advantage observed in the TA group. The TA and non-TA groups demonstrated improvement in the EIFL stages in 56.86 and 63.64% of eyes, respectively (P = 0.43). The CFT and BCVA significantly improved in both groups at the final visit (P < 0.01). However, CFT in the non-TA group displayed a more significant reduction during the follow-up (P < 0.03). Subgroup analysis revealed no significant differences in postoperative CFT and BCVA between the two groups in cases with or without continuous EIFL (P > 0.10). CONCLUSION: Our findings indicate that combined intravitreal TA injection following ERM removal conferred no significant benefits in alleviating macular thickening or improving visual acuity in iERM.
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Membrana Epirretinal , Fóvea Central , Glucocorticoides , Inyecciones Intravítreas , Tomografía de Coherencia Óptica , Triamcinolona Acetonida , Agudeza Visual , Vitrectomía , Humanos , Membrana Epirretinal/diagnóstico , Membrana Epirretinal/cirugía , Estudios Retrospectivos , Masculino , Femenino , Tomografía de Coherencia Óptica/métodos , Glucocorticoides/administración & dosificación , Fóvea Central/patología , Vitrectomía/métodos , Triamcinolona Acetonida/administración & dosificación , Estudios de Casos y Controles , Anciano , Persona de Mediana Edad , Estudios de Seguimiento , Resultado del TratamientoRESUMEN
OBJECTIVE: To identify the risk factors for the development of diabetic retinopathy (DR), diabetic macular edema (DME), and sight-threatening DR (STDR) based on a city-wide diabetes screening program. RESEARCH DESIGN AND METHODS: Diabetic patients were prospectively recruited between June 2016 and December 2022. All patients underwent dilated fundus photography centered on the disc and macula or macular spectral domain optical coherence tomography (SD-OCT) scan. Complete medical history was documented. Systematic examination, blood analysis, and urinalysis were performed. Multivariate logistic regression analysis adjusting for age and sex was conducted. RESULTS: Out of 7274 diabetic patients, 6840 had gradable images, among which 3054 (42.0%) were graded as DR, 1153 (15.9%) as DME, and 1500 (20.6%) as STDR. The factors associated with DR, DME, and STDR included younger age (odds ratio [OR]: 0.96, 0.97, and 0.96 respectively), lower BMI (OR: 0.97, 0.95, and 0.95 respectively), longer duration of diabetes (OR: 1.07, 1.03, and 1.05 respectively) and positive of urinary albumin (OR: 2.22, 2.56, and 2.88 respectively). Other associated factors included elevated blood urea nitrogen (OR: 1.22, 1.28, and 1.27 respectively), higher LDL-cholesterol, lower blood hemoglobin (OR: 0.98, 0.98, and 0.98), insulin intake, presence of diabetic foot pathologies and diabetic peripheral neuropathy. We also identified novel risk factors, including high serum potassium (OR: 1.37, 1.46, and 1.55 respectively), high-serum sodium (OR: 1.02, 1.02, and 1.04 respectively). Better family income was a protective factor for DR, DME, and STDR. Alcohol consumption once a week was also identified as a protective factor for DR. CONCLUSIONS: Similar risk factors for DR, DME, and STDR were found in this study. Our data also indicates high serum sodium, high serum potassium, low blood hemoglobin, and level of family income as novel associated factors for DR, DME, and STDR, which can help with DR monitoring and management.
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Retinopatía Diabética , Edema Macular , Tomografía de Coherencia Óptica , Humanos , Retinopatía Diabética/epidemiología , Retinopatía Diabética/diagnóstico , Masculino , Factores de Riesgo , Edema Macular/etiología , Edema Macular/epidemiología , Edema Macular/diagnóstico , Femenino , Persona de Mediana Edad , Estudios Prospectivos , Tomografía de Coherencia Óptica/métodos , Anciano , Agudeza Visual , Adulto , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiologíaRESUMEN
Li-ion batteries suffer from two key safety issues: thermal overload and compression recovery, which may lead to flammability and mechanical failure. Silica aerogels are promising solutions to both these issues owing to their excellent thermal stability and tailored mechanical properties. However, finding the optimum sol composition in sol-gel-based aerogel synthesis is needed to address these issues at industry-relevant scales. Here, we propose an innovative approach to determine the optimum sol composition for methylsilsesquioxane (MSQ) aerogel sheets, which is based on the mechanisms of the effects of molar ratios of hydrolysis water and isopropyl alcohol (IPA) to methyltrimethoxysilane (MTMS) on the physical properties of MSQ aerogel sheets and according to the ternary contour distribution of their properties. The synthesized MSQ aerogels exhibited a soft, light, and powderless texture and featured superhydrophobic properties (150.2°), low thermal conductivity of 33.6 mW/(m·K), high thermal stability temperature in nitrogen atmosphere at 479.3 °C and moderate short-term (<6 h) service temperature of 120.0 °C. Significantly, the structural stability and elasticity of the aerogels surpassed the current state-of-the-art, showing recovery to 81.3 % of the original thickness and 85.2 % of the original stress after being subjected to 400 cycles of high-speed and high-strain consecutive compression, respectively. These excellent properties make the MSQ aerogel sheets promising for applications in thermal load and compression recovery management of diverse energy storage devices, including batteries for next-generation electric vehicles.
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Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy in North America. Current therapeutic regimens are ineffective against advanced EOC. A better understanding of the molecular mechanisms that regulate the biology of EOC will be a critical step toward developing more efficacious therapies against EOC. Herein, we demonstrate that elevated expression of transcription factor ZIC2 was associated with lower survival of EOC patients. Knockout of endogenous ZIC2 in EOC cells attenuated the tumorigenic phenotypes associated with both bulk and cancer stem cells in vitro and in vivo, indicating a pro-tumorigenic role of ZIC2 in EOC. On the other hand, however, overexpression of ZIC2 in EOC cells that do not express endogenous ZIC2 promoted cell migration and sphere formation, but inhibited cell growth and colony formation in vitro and tumor growth in vivo, indicating that the role for ZIC2 in EOC is context dependent. Our transcriptomic analysis showed that ZIC2-regulated genes were involved in multiple biological processes and signaling pathways associated with tumor progression. In conclusion, our findings reveal a context-dependent role for ZIC2 in regulating tumorigenic phenotypes in EOC, providing evidence that ZIC2 can be a potential therapeutic target for EOCs that express a high level of ZIC2.
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Carcinoma Epitelial de Ovario , Células Madre Neoplásicas , Neoplasias Ováricas , Factores de Transcripción , Humanos , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Femenino , Neoplasias Ováricas/patología , Neoplasias Ováricas/genética , Neoplasias Ováricas/metabolismo , Células Madre Neoplásicas/patología , Células Madre Neoplásicas/metabolismo , Carcinoma Epitelial de Ovario/patología , Carcinoma Epitelial de Ovario/genética , Carcinoma Epitelial de Ovario/metabolismo , Animales , Línea Celular Tumoral , Ratones , Fenotipo , Regulación Neoplásica de la Expresión Génica , Carcinogénesis/genética , Carcinogénesis/patología , Proliferación Celular/genética , Movimiento Celular/genética , Neoplasias Glandulares y Epiteliales/patología , Neoplasias Glandulares y Epiteliales/genética , Neoplasias Glandulares y Epiteliales/metabolismo , Proteínas NuclearesRESUMEN
A series of organic-inorganic composite geopolymer paste samples were prepared with slag-based geopolymer and three types of hydrophilic organic polymers, i.e., PVA, PAA, and CPAM, by ordinary molding and pressure-mixing processes. The reaction mechanism between slag-based geopolymer and organic polymers was studied by FT-IR, NMR, and SEM techniques. The experimental results showed that the slag-based geopolymer with the addition of 3% PVA presented the highest 28-day flexural strength of 19.0 MPa by means of a pressure-mixing process and drying curing conditions (80 °C, 24 h) compared with the geopolymers incorporating PAA and CPAM. A more homogeneous dispersion morphology was also observed by BSE and SEM for the 3% PVA-incorporated slag-based geopolymer. The FT-IR testing results confirmed the formation of a C-O-Si (Al) bond between PVA and the slag-based geopolymer. The deconvolution of the Q3 and Q2(1Al) species obtained by 29Si NMR testing manifested the addition of PVA and increased the length of the silicon backbone chain in the geopolymer. These findings confirmed that a composite geopolymer with high toughness can be produced based on the interpenetrating network structure formed between organic polymers and inorganic geopolymer.
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When precious nano-metals are used as environmental catalysts, it is important to tune the particle sizes and the reusability of the nano-metals for achieving their highly efficient catalytic performance at a low cost. In the present work, magnetic iron oxides (FeOx-Y) nanoparticles were pre-prepared as supports of nano-metals, where Y represented the mole percentage of Fe(III) in the total iron (Y ≥ 50 %). FeOx-Y (support), PdCl42- (Pd source) and NaBH4 (reducing agent) were added into the organic pollutant solution containing 2,2',4,4'-tetrabromodiphenyl ether (BDE47). After the NaBH4 was added, the followed reaction realized not only the rapid in-situ preparation of a Pd-loaded FeOx-Y composite catalyst (Pd-FeOx-Y), but also the ultra-fast and complete debromination of BDE47 within 30 s. Comparing the case without adding FeOx-Y, the debromination efficiency of BDE47 was much promoted in the presence of FeOx-Y. The support-induced enhancing effect on the catalytic ability of Pd nanoparticles was improved by increasing the Fe(III) content in the support, being attributed to the much more hydroxyl groups on the support surface. Considering both the catalytic and recovery abilities of Pd-FeOx-Y, Pd-FeOx-75 was the optimal choice because it could be magnetically recovered and re-used for multiple cycles with high catalytic activities. The presently developed "catalyst preparation-pollutant degradation" one-pot system could be applied to conduct complete debromination of all the PBDEs.
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In the context of the resource allocation hypothesis regarding the trade-off between growth and defence, compared with native species, invasive species generally allocate more energy to growth and less energy to defence. However, it remains unclear how global change and nutrient enrichment will influence the competition between invasive species and co-occurring native species. Here, we tested whether nitrogen (N) and phosphorus (P) addition under elevated CO2 causes invasive species (Mikania micrantha and Chromolaena odorata) to produce greater biomass, higher growth-related compounds and lower defence-related compounds than native plants (Paederia scandens and Eupatorium chinense). We grew these native and invasive species with similar morphology with the addition of N and P under elevated CO2 in open-top chambers. The addition of N alone increased the relative growth rate (RGR) by 5.4% in invasive species, and its combination with P addition or elevated CO2 significantly increased the RGR of invasive species by 7.5 or 8.1%, respectively, and to a level higher than that of native species (by 14.4%, P < 0.01). Combined N + P addition under elevated CO2 decreased the amount of defence-related compounds in the leaf, including lipids (by 17.7%) and total structural carbohydrates (by 29.0%), whereas it increased the growth-related compounds in the leaf, including proteins (by 75.7%), minerals (by 9.6%) and total non-structural carbohydrates (by 8.5%). The increased concentrations of growth-related compounds were possibly associated with the increase in ribulose 1,5-bisphosphate carboxylase oxygenase content and mineral nutrition (magnesium, iron and calcium), all of which were higher in the invasive species than in the native species. These results suggest that rising atmospheric CO2 concentration and N deposition combined with nutrient enrichment will increase the growth of invasive species more than that of native species. Our result also suggests that invasive species respond more readily to produce growth-related compounds under an increased soil nutrient availability and elevated CO2.
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Dióxido de Carbono , Especies Introducidas , Dióxido de Carbono/metabolismo , Fósforo/metabolismo , Nitrógeno/metabolismo , Nutrientes , CarbohidratosRESUMEN
Edema disease (ED) is a severe and lethal infectious ailment in swine, stemming from Shiga-toxin-producing Escherichia coli (STEC). An efficient, user-friendly, and safe vaccine against ED is urgently required to improve animal welfare and decrease antibiotic consumption. Recombinant attenuated Salmonella vaccines (RASV) administered orally induce both humoral and mucosal immune responses to the immunizing antigen. Their potential for inducing protective immunity against ED is significant through the delivery of STEC antigens. rSC0016 represents an enhanced recombinant attenuated vaccine vector designed for Salmonella enterica serotype Choleraesuis. It combines sopB mutations with a regulated delay system to strike a well-balanced equilibrium between host safety and immunogenicity. We generated recombinant vaccine strains, namely rSC0016 (pS-FedF) and rSC0016 (pS-rStx2eA), and assessed their safety and immunogenicity in vivo. The findings demonstrated that the mouse models immunized with rSC0016 (pS-FedF) and rSC0016 (pS-rStx2eA) generated substantial IgG antibody responses to FedF and rStx2eA, while also provoking robust mucosal and cellular immune responses against both FedF and rStx2eA. The protective impact of rSC0016 (pS-FedF) against Shiga-toxin-producing Escherichia coli surpassed that of rSC0016 (pS-rStx2eA), with percentages of 83.3%. These findings underscore that FedF has greater suitability for vaccine delivery via recombinant attenuated Salmonella vaccines (RASVs). Overall, this study provides a promising candidate vaccine for infection with STEC.
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Infecciones por Escherichia coli , Vacunas contra la Salmonella , Salmonella enterica , Escherichia coli Shiga-Toxigénica , Animales , Ratones , Porcinos , Escherichia coli Shiga-Toxigénica/genética , Salmonella , Vacunas Sintéticas/genética , InmunizaciónRESUMEN
The protein phenotypes of extracellular vesicles (EVs) have emerged as promising biomarkers for cancer diagnosis and treatment monitoring. However, the technical challenges in rapid isolation and multiplexed molecular detection of EVs have limited their clinical practice. Herein, we developed a magnetically driven tandem chip to achieve streamlined rapid isolation and multiplexed profiling of surface protein biomarkers of EVs. Driven by magnetic force, the magnetic nanomixers not only act as tiny stir bars to promote mass transfer and enhance reaction efficiency of EVs, but also transport on communicating vessels of the tandem chip continuously and expedite the assay workflow. We designed cyclic surface enhancement of Raman scattering (SERS) tags to bind with target EVs and then release them by exonuclease I, eliminating steric hindrance and amplifying the SERS signal of multiple protein biomarkers on EVs. Due to the excellent assay performance, six breast cancer biomarkers were detected simultaneously on EVs using only 10â µL plasma within 1.5â h. The unweighted SUM signature offers great accuracy in discriminating breast cancer patients from healthy donors. Overall, the dynamic magnetic driving tandem chip offers a new avenue to advance the clinical application of EV-based liquid biopsy.
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Neoplasias de la Mama , Vesículas Extracelulares , Humanos , Femenino , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/metabolismo , Biomarcadores de Tumor/metabolismo , Vesículas Extracelulares/metabolismo , FenotipoRESUMEN
The clinical potential of miRNA-based liquid biopsy has been largely limited by the heterogeneous sources in plasma and tedious assay processes. Here, we develop a precise and robust one-pot assay called dual-surface-protein-guided orthogonal recognition of tumor-derived exosomes and in situ profiling of microRNAs (SORTER) to detect tumor-derived exosomal miRNAs and enhance the diagnostic accuracy of prostate cancer (PCa). The SORTER uses two allosteric aptamers against exosomal marker CD63 and tumor marker EpCAM to create an orthogonal labeling barcode and achieve selective sorting of tumor-specific exosome subtypes. Furthermore, the labeled barcode on tumor-derived exosomes initiated targeted membrane fusion with liposome probes to import miRNA detection reagents, enabling in situ sensitive profiling of tumor-derived exosomal miRNAs. With a signature of six miRNAs, SORTER differentiated PCa and benign prostatic hyperplasia with an accuracy of 100%. Notably, the diagnostic accuracy reached 90.6% in the classification of metastatic and nonmetastatic PCa. We envision that the SORTER will promote the clinical adaptability of miRNA-based liquid biopsy.
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Exosomas , MicroARNs , Neoplasias de la Próstata , Masculino , Humanos , Exosomas/genética , Proteínas de la Membrana , MicroARNs/genética , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Biomarcadores de Tumor/genéticaRESUMEN
Synthesis of methylsilsesquioxane aerogels by ambient pressure drying instead of supercritical drying has recently emerged as a major trend, but the issues of low mechanical strength and unstable performance still need to be resolved. This work reveals the microscopic formation mechanisms of gel skeleton based on the kinetic characteristics of methyltrimethoxysilane (MTMS) precursor hydrolysis and the associated sol-gel reactions. The effects of oxalic acid concentration (cOA) and hydrolysis time of MTMS solution (th) on the gelation time, morphologies, microstructures, chemical structure, and compression properties of the as-synthesized methylsilsesquioxane aerogels are investigated. The optimal cOA and th are 38.4 mmol/L and 120 min, respectively, endowing the methylsilsesquioxane aerogels with a compression strength of 0.170 MPa and a maximum compression strain of 61.2%. Precise control of the hydrolysis conditions ensures the formation of branched particle-to-particle networks, which is crucial for maximizing the compression properties of methylsilsesquioxane aerogels synthesized under industry-relevant conditions.
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Mycoplasma synoviae is an extremely significant avian pathogen, causing substantial financial harm to poultry farmers worldwide, and impacting both chicken and turkey production. Multi-epitope vaccines offer higher immunity and lower allergenicity compared to conventional vaccines. In this study, our objective is to develop a multi-epitope vaccine for M. synoviae (MSMV) and to evaluate the immune responses and protective efficacy of MSMV in chickens. We successfully identified a total of 14 B-cell, 5 MHC-I, and 16 MHC-II binding epitopes from the immunodominant proteins RS01790, BMP, GrpE, RS00900, and RS00275. Subsequently, we synthesized the multi-epitope vaccine by connecting all conserved epitopes using appropriate linkers. The resulting MSMV demonstrated notable antigenicity, non-allergenic properties, and stability. Notably, the MSMV effectively stimulated high levels of antibody production in chickens. Furthermore, MSMV the vaccine elicited a robust cellular immune response in chickens, characterized by a well-balanced Th1/Th2-type cytokine profile and enhanced lymphocyte proliferation. In immune protection experiments, the vaccinated chickens exhibited reduced air sac lesion scores and tracheal mucosal thickness compared to their non-vaccinated chickens. Additionally, vaccinated chickens displayed lower M. synoviae loads in throat swabs. These findings collectively suggested that the MSMV holds significant potential as a promising vaccine candidate for managing M. synoviae infections.
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Infecciones por Mycoplasma , Mycoplasma synoviae , Enfermedades de las Aves de Corral , Animales , Pollos , Epítopos , Vacunas Bacterianas , Infecciones por Mycoplasma/prevención & control , Infecciones por Mycoplasma/veterinaria , Vacunas de Subunidad , Enfermedades de las Aves de Corral/prevención & controlRESUMEN
Mycoplasma synoviae (M. synoviae) is a serious avian pathogen that causes significant economic losses to chicken and turkey producers worldwide. The currently available live attenuated and inactivated vaccines provide limited protection. The objective of this study was to identify potential subunit vaccine candidates using immunoproteomics and reverse vaccinology analyses and to evaluate their preliminary protection. Twenty-four candidate antigens were identified, and five of them, namely RS01790 (a putative sugar ABC transporter lipoprotein), BMP (a substrate-binding protein of the BMP family ABC transporter), GrpE (a nucleotide exchange factor), RS00900 (a putative nuclease), and RS00275 (an uncharacterized protein), were selected to evaluate their immunogenicity and preliminary protection. The results showed that all five antigens had good immunogenicity, and they were localized on the M. synoviae cell membrane. The antigens induced specific humoral and cellular immune responses, and the vaccinated chickens exhibited significantly greater body weight gain and lower air sac lesion scores and tracheal mucosal thicknesses. Additionally, the vaccinated chickens had lower M. synoviae loads in throat swabs than non-vaccinated chickens. The protective effect of the RS01790, BMP, GrpE, and RS00900 vaccines was better than that of the RS00275 vaccine. In conclusion, our study demonstrates the potential of subunit vaccines as a new approach to developing M. synoviae vaccines, providing new ideas for controlling the spread of M. synoviae worldwide.
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OBJECTIVE: Dedifferentiated endometrial cancer (DDEC) is an uncommon and clinically highly aggressive subtype of endometrial cancer characterized by genomic inactivation of SWItch/Sucrose Non-Fermentable (SWI/SNF) complex protein. It responds poorly to conventional systemic treatment and its rapidly progressive clinical course limits the therapeutic windows to trial additional lines of therapies. This underscores a pressing need for biologically accurate preclinical tumor models to accelerate therapeutic development. METHODS: DDEC tumor from surgical samples were implanted into immunocompromised mice for patient-derived xenograft (PDX) and cell line development. The histologic, immunophenotypic, genetic and epigenetic features of the patient tumors and the established PDX models were characterized. The SMARCA4-deficienct DDEC model was evaluated for its sensitivity toward a KDM6A/B inhibitor (GSK-J4) that was previously reported to be effective therapy for other SMARCA4-deficient cancer types. RESULTS: All three DDEC models exhibited rapid growth in vitro and in vivo, with two PDX models showing spontaneous development of metastases in vivo. The PDX tumors maintained the same undifferentiated histology and immunophenotype, and exhibited identical genomic and methylation profiles as seen in the respective parental tumors, including a mismatch repair (MMR)-deficient DDEC with genomic inactivation of SMARCA4, and two MMR-deficient DDECs with genomic inactivation of both ARID1A and ARID1B. Although the SMARCA4-deficient cell line showed low micromolecular sensitivity to GSK-J4, no significant tumor growth inhibition was observed in the corresponding PDX model. CONCLUSIONS: These established patient tumor-derived models accurately depict DDEC and represent valuable preclinical tools to gain therapeutic insights into this aggressive tumor type.
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Neoplasias Encefálicas , Neoplasias Colorrectales , Neoplasias Endometriales , Femenino , Humanos , Animales , Ratones , Neoplasias Endometriales/tratamiento farmacológico , Neoplasias Endometriales/genética , Neoplasias Endometriales/metabolismo , Diferenciación Celular , Biomarcadores de Tumor/genética , ADN Helicasas , Proteínas Nucleares/genética , Factores de Transcripción/genética , Proteínas de Unión al ADN/genéticaRESUMEN
In recent years, the number of live streaming platforms and the number of viewers have exploded. For example, in China, there are already more than 100 live streaming platforms as well as more than 300 million consumers. In live commerce, streamers use 'information overload' to affect purchase decisions, by making it difficult for consumers to think systematically; however, the mechanism of impact in this way has not been confirmed. In order to clarify how information overload affects users' purchasing decisions in live commerce, this study introduces information overload from the perspective of "Heuristic-systematic model" to develop a research model. And 400 respondents were randomly recruited through various SNS platforms in Guangdong Province, China from July 1 to July 20, 2022 using a random survey method, and finally 297 valid sample data were obtained. To verify the validity of the model and to illustrate the impact of information overload marketing on consumer purchase decisions in live commerce this study conducted an empirical analysis using Smart PLS 3.0. The findings show that perceived product quality and fit, and streamer influence and expertise, positively affect consumers' purchase intentions. The information overload strategy can significantly reduce consumers' perceptions of merchandise fit and enhance their perceptions of streamer influence and expertise. The results of this study provide a theoretical basis for marketing strategies in live commerce, and enrich literature in the field of marketing.
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Comercio , Heurística , China , Intención , MercadotecníaRESUMEN
Background: Diabetic retinopathy (DR) is the microvascular ocular complication of diabetes mellitus (DM), which can lead to irreversible blindness and visual impairment if not properly treated. Tears can be collected non-invasively, and the compositions of tears could be the potential biomarkers for ocular diseases. Here we aimed to delineate the metabolomics signature in tears collected from Chinese type-2 DM patients with DR. Methods: The metabolomics profiles of tear samples from 41 Chinese type-2 DM patients with DR and 21 non-diabetic subjects were determined by the untargeted liquid chromatography-mass spectrometry. The associated pathways of the differentially abundant metabolites were delineated, and the receiver operating characteristic curve analysis was conducted to identify the metabolites differentiating non-proliferative DR (NPDR) from proliferative DR (PDR). Results: Total 14 differentially abundant metabolites were identified between total DR and non-diabetic subjects, and 17 differentially abundant metabolites were found between the NPDR and PDR subjects. Moreover, total 18 differentially abundant metabolites were identified between the NPDR and PDR subjects with stratification in DR duration and blood glucose level. d-Glutamine and d-glutamate metabolism was significantly highlighted in the PDR group as compared to the non-diabetic group. For the predictive performance, azelaic acid combined with guanosine achieved the area under receiver operating characteristic curve of 0.855 in the comparison between NPDR and PDR groups. Conclusion: This study revealed the metabolomics changes in tear samples of DR patients. The metabolites in tears could be the potential biomarkers in the DR analysis.