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DExD/H-box helicases are crucial regulators of RNA metabolism and antiviral innate immune responses; however, their role in bacteria-induced inflammation remains unclear. Here, we report that DDX5 interacts with METTL3 and METTL14 to form an m6A writing complex, which adds N6-methyladenosine to transcripts of toll-like receptor (TLR) 2 and TLR4, promoting their decay via YTHDF2-mediated RNA degradation, resulting in reduced expression of TLR2/4. Upon bacterial infection, DDX5 is recruited to Hrd1 at the endoplasmic reticulum in an MyD88-dependent manner and is degraded by the ubiquitin-proteasome pathway. This process disrupts the DDX5 m6A writing complex and halts m6A modification as well as degradation of TLR2/4 mRNAs, thereby promoting the expression of TLR2 and TLR4 and downstream NF-κB activation. The role of DDX5 in regulating inflammation is also validated in vivo, as DDX5- and METTL3-KO mice exhibit enhanced expression of inflammatory cytokines. Our findings show that DDX5 acts as a molecular switch to regulate inflammation during bacterial infection and shed light on mechanisms of quiescent inflammation during homeostasis.
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Adenina , Infecciones Bacterianas , Receptor Toll-Like 2 , Animales , Ratones , Adenina/análogos & derivados , Inflamación/genética , Metiltransferasas/genética , Receptor Toll-Like 2/genética , Receptor Toll-Like 4/genéticaRESUMEN
By utilizing biorthogonal bases, we develop a comprehensive framework for studying biorthogonal dynamical quantum phase transitions in non-Hermitian systems. With the help of the previously overlooked associated state, we define the automatically normalized biorthogonal Loschmidt echo. This approach is capable of handling arbitrary non-Hermitian systems with complex eigenvalues and naturally eliminates the negative value of Loschmidt rate obtained without the biorthogonal bases. Taking the non-Hermitian Su-Schrieffer-Heeger model as a concrete example, a 1/2 change of dynamical topological order parameter in biorthogonal bases is observed which is not shown in self-normal bases. Furthermore, we discover that the periodicity of biorthogonal dynamical quantum phase transitions depends on whether the two-level subsystem at the critical momentum oscillates or reaches a steady state.
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Realizing the promise of chiral inorganic nanomaterials hinges on improving their structural stability under various chemical and environmental conditions. Here, we examine the stability of 1-D gold nanoparticle (Au NP) single helices prepared using the amphiphilic peptide conjugate Cx-(PEPAuM-ox)2 (PEPAuM-ox = AYSSGAPPMoxPPF; x = 16-22). We present a general template-independent strategy of tuning helix stability that relies on controlling the dimensions of constituent NPs. As NP dimensions increase, Au NP single helices become both more thermally stable and more stable in the presence of chemical denaturants and protein digestion agents (e.g., urea and proteinase K, respectively). We use this strategy for imparting helix stability to create colloidal suspensions of thermally robust Au NP single helices which maintain their plasmonic chiroptical activity up to â¼80 °C.
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Ovotransferrin(OVT)is a protein found in many types of egg white and has a wide range of functional properties. It has 50% homology with human/bovine lactoferrin, and is expected to be one of the most important alternative proteins for use in food and nutritional applications. This paper mainly reviews the structural characteristics and chemical properties of OVT, as well as its extraction and purification methods. It also systematically describes the various biological activities of OVT and its applications in food and medical industries. The challenges and limitations in the research of OVT were suggested. This review recommends some possible methods such as nanoparticle carriers and microencapsulation to improve the bioavailability and stability of OVT. In addition, this review highlights several strategies to overcome the limitations of OVT in terms of preparation and purification. This review systematically summarizes the recent advances in OVT and will provide guidance for the its development for food and nutritional applications.
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ABSTRACT: This study aimed to compare the cost-effectiveness of the new quadruple therapy regimen of adding sodium-glucose-linked transporter 2 (SGLT2) inhibitors, with standard treatment for patients with heart failure (HF) in China. From the payer's perspective, the dates of cardiovascular event recurrences were extracted from a meta-analysis including 6 trials, combined with the treatment cost for patients with HF in China to construct a Markov model. The outcomes included per capita medical costs and incremental cost-effectiveness ratio, using quality-adjusted life years (QALYs) data. Single-factor, probability sensitivity analysis, and scenario analysis were used to explore the potential uncertainties of the model. The per capita costs of the new quadruple therapy regimen and standard treatment were $87441.26 and $87087.54, respectively. The new regimen was associated with a mean of 21.44 QALYs gained, compared with 18.60 QALYs gained with the standard treatment. The incremental cost-effectiveness ratio was $124.03 per QALY gained. The sensitivity analysis revealed that changes in the parameters within the set range did not affect the model results. In China, compared with standard treatment, the new quadruple therapy regimen with SGLT2 inhibitors reduce the frequency of cardiovascular events among patients with HF, and it has economic advantages.
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Análisis Costo-Beneficio , Insuficiencia Cardíaca , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , China , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/tratamiento farmacológico , Inhibidores del Cotransportador de Sodio-Glucosa 2/economíaRESUMEN
INTRODUCTION: This study evaluated the phenotypic and pathology characteristics of patients undergoing kidney biopsy at a single center, while also determining the frequency and factors associated with clinical outcomes. METHODS: The incidence and distribution of biopsy-proven kidney diseases in 2000-2019 were surveyed. Consecutive individuals diagnosed with membranous nephropathy (MN), immunoglobulin A nephropathy (IgAN), and minimal change disease (MCD) between August 2015 and December 2019 were enrolled in the prospective 2-year follow-up study. Outcomes included remission of proteinuria and kidney disease progression events. Multivariable-adjusted Cox proportional hazards model was applied. RESULTS: 4,550 kidney biopsies were performed in 2000-2019, showing a noticeable increase in the proportion of MN. 426 patients were enrolled in the follow-up cohort. 346 (81.2%) achieved remission of proteinuria, 39 (9.2%) suffered kidney disease progression and 51.3% of them were diagnosed with IgAN. Kidney pathological diagnosis (MN vs. MCD: hazard ratio [HR], 0.42; 95% confidence interval [95% CI], 0.31-0.57; IgAN vs. MCD: 0.58; 0.39-0.85), levels of 24-h urine protein at biopsy (1.04; 1.00-1.08) and presence of nodular mesangial sclerosis (0.70; 0.49-0.99) were significantly correlated with remission of proteinuria after adjusting for baseline variables. 24-h urine protein levels at biopsy (1.14; 1.04-1.25) and the presence of crescents (2.30; 1.06-4.95) were the independent risk factors for kidney disease progression events after adjusting for baseline variables. CONCLUSION: The increasing frequency of MN has been affirmed over the past 2 decades. The therapeutic status, clinical outcomes, and factors influencing these outcomes were presented in this single-center study for the three primary glomerular diseases.
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Progresión de la Enfermedad , Glomerulonefritis por IGA , Glomerulonefritis Membranosa , Riñón , Nefrosis Lipoidea , Humanos , Glomerulonefritis Membranosa/patología , Glomerulonefritis Membranosa/diagnóstico , Glomerulonefritis por IGA/patología , Glomerulonefritis por IGA/diagnóstico , Nefrosis Lipoidea/patología , Masculino , Femenino , Persona de Mediana Edad , Adulto , Biopsia , Riñón/patología , Estudios Prospectivos , Estudios de Seguimiento , Proteinuria/etiologíaRESUMEN
VEGFR, a receptor tyrosine kinase inhibitor (TKI), is an important regulatory factor that promotes angiogenesis and vascular permeability. It plays a significant role in processes such as tumor angiogenesis, tumor cell invasion, and metastasis. VEGFR is mainly composed of three subtypes: VEGFR-1, VEGFR-2, and VEGFR-3. Among them, VEGFR-2 is the crucial signaling receptor for VEGF, which is involved in various pathological and physiological functions. At present, VEGFR-2 is closely related to a variety of cancers, such as non-small cell lung cancer (NSCLC), Hepatocellular carcinoma, Renal cell carcinoma, breast cancer, gastric cancer, glioma, etc. Consequently, VEGFR-2 serves as a crucial target for various cancer treatments. An increasing number of VEGFR inhibitors have been discovered to treat cancer, and they have achieved tremendous success in the clinic. Nevertheless, VEGFR inhibitors often exhibit severe cytotoxicity, resistance, and limitations in indications, which weaken the clinical therapeutic effect. In recent years, many small molecule inhibitors targeting VEGFR have been identified with anti-drug resistance, lower cytotoxicity, and better affinity. Here, we provide an overview of the structure and physiological functions of VEGFR, as well as some VEGFR inhibitors currently in clinical use. Also, we summarize the in vivo and in vitro activities, selectivity, structure-activity relationship, and therapeutic or preventive use of VEGFR small molecule inhibitors reported in patents in the past three years (2021-2023), thereby presenting the prospects and insights for the future development of targeted VEGFR inhibitors.
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Antineoplásicos , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Renales , Neoplasias Pulmonares , Humanos , Receptor 1 de Factores de Crecimiento Endotelial Vascular , Receptor 2 de Factores de Crecimiento Endotelial Vascular , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Inhibidores de la Angiogénesis/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Neoplasias Renales/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/químicaRESUMEN
BACKGROUND: Animal and human health are seriously threatened by bacterial infections, which can lead to bacteremia and extremely high rates of morbidity and mortality. Recently, there have been reports indicating the involvement of exosomal circular RNAs (circRNAs) in a range of human disorders and tumor types. However, the role of exosomal circRNAs in bacterial infection remains elusive. METHODS: We extracted and identified exosomes from the culture medium of PIEC cells infected with or without Glaesserella parasuis. RNA sequencing analysis was performed on the exosomes to screen and identify circRNAs (circHIF1α) associated with Glaesserella parasuis infection. PIEC cells were infected with Staphylococcus aureus or Streptococcus suis 2 to further determine whether exosome-derived circHIF1α was the crucial circHIF1α associated with bacterial infections. The transmission process of exosomes and their circHIF1α between cells was clarified via exosome tracing and co-culture assay. Moreover, the mechanism of circHIF1α being packaged into exosomes was explored, and the effects of exosomes and their circHIF1α on cell proliferation, DNA damage and cell cycle were analyzed. In addition, the binding mode and site of interacting proteins with circHIF1α were further determined. In vivo and in vitro, the role of exosomes and their circHIF1α in host resistance to bacterial infection was confirmed. RESULTS: We first discovered a new circHIF1α that was very stable and detectable, encapsulated into exosomes by hnRNPA2B1, and whose expression in exosomes of bacterially infected PIEC cells significantly decreased. Additionally, exosomal circHIF1α reduced bacterial infection both in vitro and in vivo and suppressed the growth of reception cells. Mechanistically, the circHIF1α interacted with the KH domain of IGF2BP3 in an m6A-modified manner, which mediated DNA damage to arrest the cells at the G1/S phase through the interaction between the regulator of Chromosome Condensation 2 (RCC2) and γ-H2AX protein. Exosomal circHIF1α is a unique therapeutic target for bacterial infection since this work highlights its critical function in fighting bacterial infection.
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Bacteriemia , Daño del ADN , Exosomas , ARN Circular , Proteínas de Unión al ARN , Exosomas/metabolismo , Animales , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Bacteriemia/microbiología , Bacteriemia/metabolismo , Ratones , Humanos , ARN Circular/genética , ARN Circular/metabolismo , Proliferación Celular , Staphylococcus aureus/genética , Línea Celular , Adenosina/análogos & derivadosRESUMEN
BACKGROUND: Facial fold and groove formation is influenced by the ptosis of the superficial fat compartments in the mid-face region. OBJECTIVE: This study aimed to design a facial rejuvenation technique that targets sagging of the mid-face fat compartments and achieves a youthful facial configuration. MATERIALS AND METHODS: A total of 102 patients underwent suture net restoration. Each specific ptosis fat compartment was carefully lifted and held at the regional facial ligaments to effectively restore volume distribution. Patient outcomes were evaluated through preoperative and postoperative photography comparison, 3-D photographic analysis, and postoperative evaluations. RESULTS: Significant mid-cheek rejuvenation was observed. The procedure resulted in a remarkable, 10.89% increase in malar projection. The nasolabial fold improved by at least 1 grade in 61.43% of the patients and by at least 2 grades in 37.14%. A total of 87.65% of the patients expressed high satisfaction or satisfaction with the outcomes of the procedure. CONCLUSION: By specifically targeting the mid-face ptosis fat compartments, the technique demonstrated significant enhancements of both the nasolabial fold and the malar projection. The results indicate that this novel technique holds promise as an efficient approach for satisfactorily addressing facial aging concerns.
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Satisfacción del Paciente , Rejuvenecimiento , Ritidoplastia , Técnicas de Sutura , Humanos , Femenino , Persona de Mediana Edad , Ritidoplastia/métodos , Adulto , Masculino , Grasa Subcutánea/cirugía , Anciano , Cara , Surco Nasolabial/cirugía , Envejecimiento de la Piel , Resultado del Tratamiento , FotograbarRESUMEN
BACKGROUND: The causal relationships between testosterone, estradiol, estrogen sulfotransferase, and idiopathic pulmonary fibrosis (IPF) are not well understood. This study employs a bidirectional two-sample Mendelian Randomization (MR) approach to explore these associations. METHODS: All genetic data utilized in our study were obtained from the IEU Open GWAS project. For the MR analysis, we employed the inverse variance weighted (IVW), MR-Egger, and weighted median methods to assess the causal relationships. We also conducted a multivariate MR (MVMR) analysis, with adjustments made for smoking. To ensure the robustness of our findings, sensitivity analyses were conducted using Cochran's Q test, MR-Egger regression, the MR-PRESSO global test, and the leave-one-out method. RESULTS: Genetically predicted increases in serum testosterone levels by one standard deviation were associated with a 58.7% decrease in the risk of developing IPF (OR = 0.413, PIVW=0.029, 95% CI = 0.187 â¼ 0.912), while an increase in serum estrogen sulfotransferase by one standard deviation was associated with a 32.4% increase in risk (OR = 1.324, PIVW=0.006, 95% CI = 1.083 â¼ 1.618). No causal relationship was found between estradiol (OR = 1.094, PIVW=0.735, 95% CI = 0.650 â¼ 1.841) and the risk of IPF. Reverse MR analysis did not reveal any causal relationship between IPF and testosterone (OR = 1.001, PIVW=0.51, 95% CI = 0.998 â¼ 1.004), estradiol (OR = 1.001, PIVW=0.958, 95% CI = 0.982 â¼ 1.019), or estrogen sulfotransferase (OR = 0.975, PIVW=0.251, 95% CI = 0.933 â¼ 1.018). The MVMR analysis demonstrated that the association between testosterone (OR = 0.442, P = 0.037, 95% CI = 0.205 â¼ 0.953) and estrogen sulfotransferase (OR = 1.314, P = 0.001, 95% CI = 1.118 â¼ 1.545) and the risk of IPF persisted even after adjusting for smoking. CONCLUSIONS: Increased serum levels of testosterone are associated with a reduced risk of IPF, while increased levels of serum estrogen sulfotransferase are associated with an increased risk. No causal relationship was found between estradiol and the development of IPF. No causal relationship was identified between IPF and testosterone, estradiol, or estrogen sulfotransferase.
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Estradiol , Fibrosis Pulmonar Idiopática , Análisis de la Aleatorización Mendeliana , Sulfotransferasas , Testosterona , Humanos , Estradiol/sangre , Sulfotransferasas/genética , Testosterona/sangre , Fibrosis Pulmonar Idiopática/genética , Fibrosis Pulmonar Idiopática/sangre , Estudio de Asociación del Genoma Completo , Polimorfismo de Nucleótido Simple , Femenino , Masculino , Factores de RiesgoRESUMEN
BACKGROUND: Pseudomonas aeruginosa (PA) isolation in patients with chronic obstructive pulmonary disease (COPD) has been associated with a poor prognosis. This meta-analysis aimed to determine significant risk factors for PA isolation among patients with COPD. METHODS: A systematic literature retrieval from PubMed, Embase, Web of Science and China National Knowledge Infrastructure (CNKI) was conducted, including studies from January 2003 to September 2024. Case-control and cohort studies exploring the risk factors for PA isolation in patients with COPD were included in this analysis. A random-effects model was applied to estimate the pooled adjusted odds ratio (paOR) or hazard ratio (paHR) with the corresponding 95% confidence intervals (CI). RESULTS: Thirteen eligible studies with a total of 25,802 participants were included in this meta-analysis. Prior systemic steroid therapy (paOR: 2.67; 95% CI: 1.29-5.53; P = 0.008), previous antibiotic treatment (paOR: 2.83; 95% CI: 1.14-6.97; P = 0.02), high "Body mass index, airflow Obstruction, Dyspnea, Exercise capacity" (BODE) index (paOR: 4.13; 95% CI: 1.67-10.23; P = 0.002), 6-min walking distance (6MWD) < 250 m (paOR: 4.27; 95% CI: 2.59-7.01; P < 0.001), COPD assessment test (CAT) score > 20 points (paOR: 2.49; 95% CI: 1.46-4.23; P = 0.001), hypoproteinemia (paOR: 2.62; 95%CI: 1.32-5.19; P = 0.006), hospitalizations in the previous year (paOR: 3.74; 95%CI: 1.22-11.49; P = 0.021), Bronchiectasis (paOR = 4.81; 95% CI: 3.66-6.33; P < 0.001) and prior PA isolation (paOR: 16.39; 95% CI: 7.65-35.10; P < 0.001) were associated with PA isolation in patients with COPD. CONCLUSIONS: Our study identified nine risk factors associated with an increased risk of PA isolation in COPD patients. These findings are significant for the early identification of patients at risk for PA isolation, which might contribute to reducing mortality and improving clinical outcomes.
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Infecciones por Pseudomonas , Pseudomonas aeruginosa , Enfermedad Pulmonar Obstructiva Crónica , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Humanos , Pseudomonas aeruginosa/aislamiento & purificación , Factores de Riesgo , Infecciones por Pseudomonas/epidemiología , Infecciones por Pseudomonas/complicaciones , Antibacterianos/uso terapéuticoRESUMEN
BACKGROUND: Both interpregnancy intervals (IPI) and environmental factors might contribute to low birth weight (LBW). However, the extent to which air pollution influences the effect of IPIs on LBW remains unclear. We aimed to investigate whether IPI and air pollution jointly affect LBW. METHODS: A retrospective cohort study was designed in this study. The data of birth records was collected from the Jiangsu Maternal Child Information System, covering January 2020 to June 2021 in Nantong city, China. IPI was defined as the duration between the delivery date for last live birth and date of LMP for the subsequent birth. The maternal exposure to ambient air pollutants during pregnancy-including particulate matter (PM) with an aerodynamic diameter of ≤ 2.5 µm (PM2.5), PM10, ozone (O3), nitrogen dioxide (NO2), sulfur dioxide (SO2) and carbon monoxide (CO)-was estimated using a hybrid kriging-LUR-RF model. A novel air pollution score was proposed, assessing combined exposure to five pollutants (excluding CO) by summing their concentrations, weighted by LBW regression coefficients. Multivariate logistic regression models were used to estimate the effects of IPI, air pollution and their interactions on LBW. Relative excess risk due to interaction (RERI), attributable proportion of interaction (AP) and synergy index (S) were utilized to assess the additive interaction. RESULTS: Among 10, 512 singleton live births, the LBW rate was 3.7%. The IPI-LBW risk curve exhibited an L-shaped pattern. The odds ratios (ORs) for LBW for each interquartile range increase in PM2.5, PM10, O3 and the air pollution score were 1.16 (95% CI: 1.01-1.32), 1.30 (1.06-1.59), 1.22 (1.06-1.41), and 1.32 (1.10-1.60) during the entire pregnancy, respectively. An additive interaction between IPI and PM2.5 was noted during the first trimester. Compared to records with normal IPI and low PM2.5 exposure, those with short IPI and high PM2.5 exposure had the highest risk of LBW (relative risk = 3.53, 95% CI: 1.85-6.49, first trimester). CONCLUSION: The study demonstrates a synergistic effect of interpregnancy interval and air pollution on LBW, indicating that rational birth spacing and air pollution control can jointly improve LBW outcomes.
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Contaminantes Atmosféricos , Contaminación del Aire , Intervalo entre Nacimientos , Recién Nacido de Bajo Peso , Exposición Materna , Humanos , Estudios Retrospectivos , China/epidemiología , Femenino , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , Embarazo , Adulto , Recién Nacido , Intervalo entre Nacimientos/estadística & datos numéricos , Exposición Materna/efectos adversos , Exposición Materna/estadística & datos numéricos , Contaminantes Atmosféricos/análisis , Contaminantes Atmosféricos/efectos adversos , Factores de Riesgo , Material Particulado/análisis , Material Particulado/efectos adversos , Masculino , Adulto JovenRESUMEN
Diabetic wound healing is a significant clinical challenge because abnormal immune cells in the wound cause chronic inflammation and impair tissue regeneration. Therefore, regulating the behavior and function of macrophages may be conducive to improving treatment outcomes in diabetic wounds. Herein, sulfated chitosan (26SCS)-containing composite sponges (26SCS-SilMA/Col-330) with well-arranged layers and high porosity were constructed based on collagen and silk fibroin, aiming to induce an appropriate inflammatory response and promote angiogenesis. The results indicated that the ordered topological structure of composite sponges could trigger the pro-inflammatory response of Mφs in the early stage, and rapid release of 26SCS in the early and middle stages (within the concentration range of 1-3 mg/mL) induced a positive inflammatory response; initiated the pro-inflammatory reaction of Mφs within 3 days; shifted M1 Mφs to the M2 phenotype within 3-7 days; and significantly up-regulated the expression of two typical angiogenic growth factors, namely VEGF and PDGF-BB, on day 7, leading to rapid HUVEC migration and angiogenesis. In vivo data also demonstrated that on the 14th day after surgery, the 26SCS-SilMA/Col-330-implanted areas exhibited less inflammation, faster re-epithelialization, more abundant collagen deposition and a greater number of blood vessels in the skin tissue. The composite sponges with higher 26SCS contents (the (5.0) 26SCS-SilMA/Col-330 and the (7.5) 26SCS-SilMA/Col-330) could better orchestrate the phenotype and function of Mφs and facilitate wound healing. These findings highlight that the 26SCS-SilMA/Col-330 sponges developed in this work might have great potential as a novel dressing for the treatment of diabetic wounds.
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Quitosano , Inflamación , Macrófagos , Neovascularización Fisiológica , Cicatrización de Heridas , Animales , Humanos , Masculino , Ratones , Ratas , Angiogénesis , Quitosano/química , Colágeno/química , Diabetes Mellitus Experimental , Fibroínas/química , Células Endoteliales de la Vena Umbilical Humana , Inflamación/patología , Macrófagos/metabolismoRESUMEN
Yeast cell wall (YCW) polysaccharides, including ß-glucans, mannans, chitins, and glycogens, can be extracted from the waste of beer industry. They are environmentally friendly, abundant, inexpensive raw materials, and have shown broad biological activities and application potentials. The exploitation of yeast polysaccharides is of great importance for environmental protection and resource utilization. This paper reviews the structural features and preparation of YCW polysaccharides. The solubility and emulsification of yeast polysaccharides and the properties of binding metal ions are presented. In addition, biological activities such as blood glucose and lipid lowering, immune regulation, antioxidant, promotion of intestinal health, and promotion of wound healing are proposed, highlighting the beneficial effects of yeast polysaccharides on human health. Through modification, the physical and chemical properties of yeast polysaccharides are changed, which emphasizes the promotion of their biological activities and properties. In addition, the food applications of yeast polysaccharides, including the food packaging film, emulsifier, thickening agent, and fat alternatives, are focused and discussed.
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Polisacáridos , Polisacáridos/química , Polisacáridos/farmacología , Saccharomyces cerevisiae/química , Levaduras/química , Humanos , Embalaje de Alimentos/métodos , Polisacáridos Fúngicos/química , Polisacáridos Fúngicos/farmacología , Emulsionantes/química , Pared Celular/químicaRESUMEN
Bacillus subtilis is a widespread Gram-positive facultative aerobic bacterium that is recognized as generally safe. It has shown significant application value and great development potential in the animal farming industry. As a probiotic, it is frequently used as a feed growth supplement to effectively replace antibiotics due to its favourable effects on regulating the intestinal flora, improving intestinal immunity, inhibiting harmful microorganisms, and secreting bioactive substances. Consequently, the gut health and disease resistance of farmed animals can be improved. Both vegetative and spore forms of B. subtilis have also been utilized as vaccine carriers for delivering the antigens of infectious pathogens for over a decade. Notably, its spore form is regarded as one of the most prospective for displaying heterologous antigens with high activity and stability. Previously published reviews have predominantly focused on the development and applications of B. subtilis spore surface display techniques. However, this review aims to summarize recent studies highlighting the important role of B. subtilis as a probiotic and vaccine carrier in maintaining animal health. Specifically, we focus on the beneficial effects and underlying mechanisms of B. subtilis in enhancing disease resistance among farmed animals as well as its potential application as mucosal vaccine carriers. It is anticipated that B. subtilis will assume an even more prominent role in promoting animal health with in-depth research on its characteristics and genetic manipulation tools.
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Bacillus subtilis , Probióticos , Probióticos/administración & dosificación , Bacillus subtilis/genética , Animales , Esporas Bacterianas/inmunología , Microbioma Gastrointestinal , Resistencia a la Enfermedad , Vacunas/inmunologíaRESUMEN
Assembling nanoparticles (NPs) into well-defined superstructures can lead to emergent collective properties that depend on their 3-D structural arrangement. Peptide conjugate molecules designed to both bind to NP surfaces and direct NP assembly have proven useful for constructing NP superstructures, and atomic- and molecular-level alterations to these conjugates have been shown to manifest in observable changes to nanoscale structure and properties. The divalent peptide conjugate, C16-(PEPAu)2 (PEPAu = AYSSGAPPMPPF), directs the formation of one-dimensional helical Au NP superstructures. This study examines how variation of the ninth amino acid residue (M), which is known to be a key Au anchoring residue, affects the structure of the helical assemblies. A series of conjugates of differential Au binding affinities based on variation of the ninth residue were designed, and Replica Exchange with Solute Tempering (REST) Molecular Dynamics simulations of the peptides on an Au(111) surface were performed to determine the approximate surface contact and to assign a binding score for each new peptide. A helical structure transition from double helices to single helices is observed as the peptide binding affinity to the Au(111) surface decreases. Accompanying this distinct structural transition is the emergence of a plasmonic chiroptical signal. REST-MD simulations were also used to predict new peptide conjugate molecules that would preferentially direct the formation of single-helical AuNP superstructures. Significantly, these findings demonstrate how small modifications to peptide precursors can be leveraged to precisely direct inorganic NP structure and assembly at the nano- and microscale, further expanding and enriching the peptide-based molecular toolkit for controlling NP superstructure assembly and properties.
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Oro , Nanopartículas del Metal , Oro/química , Nanopartículas del Metal/química , Péptidos/química , Simulación de Dinámica MolecularRESUMEN
OBJECTIVE: Investigation of a Jr(a-) family samples, identification of the mutant and assessment of the differences of Jr antigen density of the Jr(a-) family members, random adult and newborn individuals' RBCs. BACKGROUND: The anti-Jra antibody is generated when a Jr(a-) individual pregnant or transfused with Jr(a+) blood unit, which can lead to mild-to-moderate hemolytic disease of the foetus and newborn (HDFN) or hemolytic transfusion reaction (HTR). Several mutations had been identified. The anti-Jra caused HDFN is not rare in East Asia, but due to the lack of antibody and molecular background, it is likely to lead missed detection. METHODS AND MATERIALS: One G4P1 woman had been detected as IAT positive during prenatal examination. Suspected as anti-Jra after the laboratory serological testing, the maternal sample was further assessed by molecular analysis. The antigen density was detected by flow cytometry after reacting with anti-Jra serum in family members and the normal individuals. RESULTS: One novel frameshift mutation c.717delC and one previously identified mutation c.706C > T in ABCG2 was identified on proband. The infant haemoglobin(Hb) and bilirubin increased significantly after exchange transfusion and the severe HDFN was relieved. Flow cytometry results showed that the Jra antigens on adult RBCs were significantly less than those on the infant. CONCLUSION: The c.717delC mutation can lead to the shortening of protein ABCG2 in the site of p.Leu307Stop, result in the loss of Jra antigen. The difference in antigen density between adult and infant RBCs may be a possible reason that leads to severe HDFN but not transfusion reaction. Breastfeeding may lead to slower recovery from HDFN.
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Antígenos de Grupos Sanguíneos , Eritroblastosis Fetal , Adulto , Femenino , Embarazo , Recién Nacido , Humanos , Madres , Pueblos del Este de Asia , Antígenos de Grupos Sanguíneos/genética , Hemólisis , Mutación , Hemoglobinas , IsoanticuerposRESUMEN
The posttranscriptional modification of messenger RNA (mRNA) and transfer RNA (tRNA) provides an additional layer of regulatory complexity during gene expression. Here, we show that a tRNA methyltransferase, TRMT10A, interacts with an mRNA demethylase FTO (ALKBH9), both in vitro and inside cells. TRMT10A installs N1-methylguanosine (m1G) in tRNA, and FTO performs demethylation on N6-methyladenosine (m6A) and N6,2'-O-dimethyladenosine (m6Am) in mRNA. We show that TRMT10A ablation not only leads to decreased m1G in tRNA but also significantly increases m6A levels in mRNA. Cross-linking and immunoprecipitation, followed by high-throughput sequencing results show that TRMT10A shares a significant overlap of associated mRNAs with FTO, and these mRNAs have accelerated decay rates potentially through the regulation by a specific m6A reader, YTHDF2. Furthermore, transcripts with increased m6A upon TRMT10A ablation contain an overrepresentation of m1G9-containing tRNAs codons read by tRNAGln(TTG), tRNAArg(CCG), and tRNAThr(CGT) These findings collectively reveal the presence of coordinated mRNA and tRNA methylations and demonstrate a mechanism for regulating gene expression through the interactions between mRNA and tRNA modifying enzymes.
Asunto(s)
Adenosina/genética , Metiltransferasas/genética , ARN Mensajero/genética , ARN de Transferencia/genética , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/genética , Regulación de la Expresión Génica/genética , Células HEK293 , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Metilación , Proteínas de Unión al ARN/genética , ARNt Metiltransferasas/genéticaRESUMEN
The gut microbiota has been confirmed as an important part in human health, and is even take as an 'organ'. The interaction between the gut microbiota and host intestinal environment plays a key role in digestion, metabolism, immunity, inflammation, and diseases. The dietary component is a major factor that affects the composition and function of gut microbiota. Food additives have been widely used to improve the color, taste, aroma, texture, and nutritional quality of processed food. The increasing variety and quantity of processed food in diets lead to increased frequency and dose of food additives exposure, especially artificial food additives, which has become a concern of consumers. There are studies focusing on the impact of food additives on the gut microbiota, as long-term exposure to food additives could induce changes in the microbes, and the gut microbiota is related to human health and disease. Therefore, the aim of this review is to summarize the interaction between the gut microbiota and food additives.
Asunto(s)
Aditivos Alimentarios , Microbioma Gastrointestinal , Humanos , Aditivos Alimentarios/farmacología , Dieta , Intestinos , InflamaciónRESUMEN
We map a quantum Rabi ring, consisting of N cavities arranged in a ring geometry, into an effective magnetic model containing the XY exchange and the Dzyaloshinskii-Moriya (DM) interactions. The analog of the latter is induced by an artificial magnetic field, which modulates photon hopping between nearest-neighbor cavities with a phase. This mapping facilitates the description and understanding of the different phases in the quantum optical model through simple arguments of competing magnetic interactions. For the square geometry (N=4) the rich phase diagram exhibits three superradiant phases denoted as ferro-superradiant, antiferro-superradiant, and chiral superradiant. In particular, the DM interaction is responsible for the chiral phase in which the energetically degenerate configurations of the order parameters are similar to the in-plane magnetizations of skyrmions with different helicities. The antiferro-superradiant phase is suppressed in the triangle geometry (N=3) as geometric frustration contributes to stabilize the chiral phase even for small values of the DM interaction. The chiral phases for odd and even N show a different scaling behavior close to the phase transition. The equivalent behavior on both systems opens the possibility of simulating chiral magnetism in a few-body quantum optical platform, as well as understanding one system using the insights gained from the other.