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Marek's disease virus (MDV) is an extremely widespread avian immunosuppressive virus. In recent years, many reports have shown that there are still cases of MDV infection and immunosuppression after immunization with the vaccine. Consequently, there is a need to develop alternative complementary approaches for strengthening the efficacy of MDV prevention and control measures. Lentinan (LNT) is a macromolecular compound with immune-enhancing activity extracted from shiitake mushrooms. To explore the value and effectiveness of administering LNT through drinking water in the prevention and control of MDV, this study first observed the effects of high and low doses of LNT on weight gain, organ development, viral replication, and antibody titer of an avian influenza virus subtype H9 (AIV-H9) inactivated vaccine in specific pathogen-free (SPF) chicks infected with the wild strain of MDV. The results showed that both high and low doses of LNT significantly alleviated the weight gain retardation and liver and spleen enlargement caused by MDV infection, and significantly inhibited the replication of MDV in SPF chicks (P < 0.05), compared with the MDV-positive control group, both high and low doses of LNT significantly increased the antibody titer of AIV-H9 after immunization with inactivated AIV-H9 vaccine (P < 0.0001). On this basis, we also observed the effects of a chicken Marek's disease meq gene deletion live vaccine (SC9-1 strain), administered alone or in combination with LNT, on MDV infections of varying virulence in Hy-Line Brown chicks. The results showed that combined administration of LNT and the SC9-1 vaccine resulted in a significant alleviation of weight gain retardation and liver and spleen enlargement due to MDV infection (P < 0.05), as well as a significant inhibition of MDV replication and release in Hy-Line Brown chicks compared to the vaccine alone (P < 0.0001). These findings suggest that LNT not only alleviates the adverse effects of MDV infection in chickens but also enhances the efficacy of MDV vaccination, offering a potential auxiliary measure for controlling MDV infection.
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BACKGROUND: We compared overall survival (OS) and disease-free survival (DFS) for hepatocellular carcinoma (HCC) following radiofrequency ablation (RFA), microwave ablation (MWA), cryoablation, and liver resection (LR), with the aim of evaluating treatment plans for early-stage HCC. METHODS: Studies in PubMed, Web of Science, and Cochrane databases from April 1, 2004, to April 1, 2024, were searched. Articles were evaluated for quality using the randomized controlled trials tool. Two tool and the Newcastle-Ottawa Scale. Data obtained from the literature were netted using Stata 15.0 and r 4.2.3. The assessed primary outcomes were OS and DFS at 1 and 3 y. RESULTS: A total of 25 publications with 4548 patients were included, including 13 studies in mainland China and 12 in other regions. For 1-y DFS, the hazard ratio (HR) was 0.54 (95% credible interval (CrI): 0.38-0.76) for LR compared with RFA and 0.57 (95% CrI: 0.3--0.82) for LR compared with MWA. For 3-y DFS, the HR was 0.52 (95% CrI: 0.38-0.72) for LR compared with RFA and 0.53 (95% CrI: 0.37-0.76). In the Chinese mainland, LR may have a better 1- and 3-y DFS than MWA, but similar survival to RFA. In the other regions, LR had a better DFS than MWA and RFA patients. The rest of the comparisons were not statistically significant. CONCLUSIONS: For early-stage HCC, LR may be more effective in reducing tumor recurrence than ablative treatments. Cryoablation may be a potential treatment for HCC. The differences in treatment effectiveness in different regions are worth further study.
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Terrestrial animal intestines are hotspots for the enrichment of micro/nano plastics (M/NPs) and antibiotic-resistant genes (ARGs). However, little is known about the further impact of M/NPs on the spread of ARGs in animal guts. This study investigates the role of M/NPs (polystyrene) with varying particle sizes (0.082, 42, and 182 µm), concentrations (10 and 100 mg/L), and exposure durations (4 and 16 days) in the ARGs dissemination via conjugation in the edible snail (Achatina fulica) gut. Combination of qPCR with 16S rRNA-based sequencing, we found that PS exposure caused intestinal cell impairment and shifts in the gut microbial community of snails. Conjugation rate increased with PS particle sizes in the snail gut. After 4 days of exposure, significantly higher conjugation rates were observed in the gut exposed to 100 mg/L PS compared to 10 mg/L, however, this trend reversed after 16 days. Consistently, the abundances of conjugation relevant genes trfA and trbB shared similar trends to the conjugation ratios in the snail gut after PS exposure. Transconjugant diversity was much lower in 10 mg/L PS groups than in 100 mg/L PS treatments. Therefore, this study suggests that the presence of M/NPs would complicate management of ARG spread. The selection pressure exerted by M/NPs may sustain or even amplify the spread of ARGs in the gut of terrestrial animals even in the absence of antibiotics. It highlights the necessity of avoiding M/NPs intake as a part of comprehensive strategy for cubing ARG dissemination in the gut of animals.
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Furin cleavage site (FCS) of the SARS-CoV-2 S protein, which connects the S1/S2 junction, is essential for facilitating fusion with the host cells. Wild-type (Wt) SARS-CoV-2 S protein, PDB ID: 6yvb, lacks a sequence of amino acid residues, including the FCS that links the S1/S2 junction. For the first time, we demonstrated that a stretch of 14 amino acid residues (677QTNSPRRARSVASQ689) forms an antiparallel ß-sheet comprising of PRRAR sequence in the FCS within a short loop. Upon comparing the loop content of the S1/S2 junction with that of Wt SARS-CoV-2 containing PRRAR in the FCS, we observed a decrease in antiparallel ß-sheet content and an increase in loop content in the B.1.1.7 variant with HRRAR in the FCS. This short loop within antiparallel ß-sheet can serve as a docking site for various proteases, including TMPRSS2 and α1AT. We performed a 300-ns simulation of the SARS-CoV-2 receptor binding domain (RBD) using several antibacterial and antiviral ligands commonly used to treat various infections. Our findings indicate that the receptor binding domain (RBD) comprising the receptor binding motif (RBM) utilizes ß6 and a significant portion of the loop to bind with ligands, suggesting its potential for treating SARS-CoV-2 infections.
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Characterizing radioactive aerosol particles released from actinide metals on fires represents a pivotal process in nuclear emergency response. However, the precise characterization of these particles and the deep understanding of their formation mechanism remain a daunting challenge due to the lack of in-situ measurement techniques. We presented the first real-time investigation of respirable particles with the size ranging from 2 nm to 10 µm, emitted from the combustion of cerium metal (CM) as surrogate for actinide counterparts. The evolution of such particles was revealed by the methodology combining scanning mobility particle sizer and optical particle sizer, showing the consistent generation of multimodal ultrafine particles with diameters of 2-100 nm during the combustion reaction. Numerous polydisperse 0.2-0.5 µm accumulated particles and a few 2-10 µm coarse particles were also produced via droplet dispersion and explosion during molten CM self-enhanced combustion. These particles were predominantly composed of CeO2 and exhibited lognormal distributions. The spherical, aggregated, chain-like and fractured particles implied the evolution of particles including nucleation, coagulation, agglomeration and oxide layer cracking. Comparative analyses of particle size distributions reveal that bulk CM combustion predominantly generated ultrafine particles in the absence of CM droplet dispersion. Our finding will guide a critical evaluation of respirable actinide aerosols in the case of fire accidents involving actinide metals.
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The polarized bidirectional reflectance distribution function (pBRDF) can describe the changes between the Stokes vectors of incident and reflected light. The existing model can only describe the spatial distribution of the target's polarization characteristics at a single wavelength, so further research is needed for the description of the target's polarized spectral characteristics. In this paper, a modified three-component polarized spectral bidirectional reflectance distribution function (pSBRDF) is proposed, which combines Fresnel equation in the specular reflection component with Cauchy's empirical dispersion equation, by introducing the wavelength variable and dispersion constants that do not change with wavelength. The degree of the linear polarization (DoLP) of two types of coated fabric samples was measured at three incident angles and 400 to 760 nm wavelength. The error of the model in describing the spectral and the spatial distribution of DoLP are controlled within 0.00743 and 0.0757 respectively, which proves the accuracy of the model. This research provides the model basis for analysis of the target's polarization characteristics and the theoretical basis for the application of polarization detection.
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OBJECTIVE: The rabbit knee osteoarthritis(KOA) model was established by simple anterior cruciate ligament disruption. METHODS: The selected 40 adult white rabbits were randomly divided into two groups, blank group with 6 rabbits and model group with 34 rabbits. The rabbits in model group were given the disruption of anterior cruciate ligament of right knee joint. In the fourth, eighth and the twelfth weeks of modeling, different degrees of degenerative changes have been observed on the rabbits articular cartilages from both macroscopic and microscopic aspects. RESULTS: At 4, 8 and 12 weeks after modeling, the articular cartilage of the rabbits in the model group showed degenerative changes in different degrees. At 8 and 12 weeks, the typical pathological manifestations of KOA in the middle and late stages were found in the infrapatellar fat pad and synovium, respectively. There were no changes in articular cartilage, infrapatellar fat pad and synovial membrane in the blank group at the same time. There were significant differences in the gross score between the model group and the blank group at 4 weeks [(1.300±0.674) vs 0.000], 8 weeks [(2.400±0.516) vs 0.000] and 12 weeks [(3.583±0.668) vs 0.000] (P<0.05), the histopathological scores were significantly different, at 4 weeks [(2.900±0.567) vs 0.000], 8 weeks [(7.500±1.178) vs (0.500±0.707)], 12 weeks[(11.833±1.337) vs (1.500±0.707)], (P<0.05). CONCLUSION: The establishment of rabbit knee arthritis model by simply cutting the anterior cruciate ligament is simple and feasible, with good stability, high success rate, small trauma, short modeling cycle and less changes in animal physiological structure. The rabbit knee arthritis model established by simply cutting the anterior cruciate ligament has good modeling effect on different stages and grades of knee osteoarthritis, and the postoperative infection and trauma can be controlled, which can meet the test requirements.
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Lesiones del Ligamento Cruzado Anterior , Modelos Animales de Enfermedad , Osteoartritis de la Rodilla , Animales , Conejos , Masculino , Ligamento Cruzado Anterior/cirugía , Femenino , Cartílago Articular/patologíaRESUMEN
Obesity and related diseases pose a major health risk, yet current anti-obesity drugs inadequately addressing clinical needs. Here we show AA005, an annonaceous acetogenin mimic, resists obesity induced by high-fat diets and leptin mutations at non-toxic doses, with the alpha subunit of the mitochondrial trifunctional protein (HADHA) as a target identified through proteomics and in vitro validation. Pharmacokinetic analysis shows AA005 enriches in adipose tissue, prompting the creation of adipose-specific Hadha-deficient mice. These mice significantly mitigate diet-induced obesity, echoing AA005's anti-obesity effects. AA005 treatment and Hadha deletion in adipose tissues increase body temperature and energy expenditure in high-fat diet-fed mice. The beneficial impact of AA005 on obesity mitigation is ineffective without uncoupling protein 1 (UCP1), essential for thermogenesis regulation. Our investigation shows the interaction between AA005 and HADHA in mitochondria, activating the UCP1-mediated thermogenic pathway. This substantiates AA005 as a promising compound for obesity treatment, targeting HADHA specifically.
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Acetogeninas , Fármacos Antiobesidad , Obesidad , Animales , Humanos , Masculino , Ratones , Acetogeninas/farmacología , Acetogeninas/química , Tejido Adiposo/metabolismo , Tejido Adiposo/efectos de los fármacos , Fármacos Antiobesidad/farmacología , Fármacos Antiobesidad/uso terapéutico , Fármacos Antiobesidad/química , Dieta Alta en Grasa , Metabolismo Energético/efectos de los fármacos , Leptina/metabolismo , Ratones Endogámicos C57BL , Ratones Noqueados , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Subunidad alfa de la Proteína Trifuncional Mitocondrial/metabolismo , Subunidad alfa de la Proteína Trifuncional Mitocondrial/genética , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Obesidad/genética , Termogénesis/efectos de los fármacos , Termogénesis/genética , Proteína Desacopladora 1/metabolismo , Proteína Desacopladora 1/genéticaRESUMEN
Building on the concept of a thermoelectrocatalyst (TECatal), we propose a simple yet efficient TECatal material, vacancy defect engineered SrTiO3, for stable H2O2 production under temperature gradients. A solid-phase reaction was applied to introduce oxygen vacancies, generating free electrons and inducing a thermoelectric response in SrTiO3. This approach achieved an impressive H2O2 production rate of approximately 764 µmol L-1 g-1 h-1 at a temperature gradient of 130 °C conceiving the feasibility of the thermoelectrocatalyst for harvesting low-grade waste heat.
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Purpose: To investigate risk factors associated with the formation of parastomal hernia after Miles operation, and to provide scientific evidence for the prevention and treatment of parastomal hernia. Methods: Clinical data from 205 patients with rectal cancer undergoing Miles operation in the Department of General Surgery, Affiliated Hospital of Xuzhou Medical University between May 2016 and May 2021 were analyzed retrospectively. Fourteen potential factors were selected and analyzed by single factor analysis and two element logistic regression analysis for their potential relationship to incidence of parastomal hernia. Results: 49 cases of parastomal hernia occurred among 194 patients during follow-up (incidence 25.26%). Univariate analysis showed that age, thickness of subcutaneous abdominal fat, BMI, and stoma pathway were related to the formation of post-surgical parastomal hernia (P < 0.05). Two element logistic regression analysis showed that advanced age, thickness of subcutaneous abdominal fat, BMI > 25 kg/m2, and transperitoneal surgical approach were independent risk factors for the formation of parastomal hernia after Miles operation (P < 0.05). Conclusion: Advanced age, thickness of subcutaneous abdominal fat, BMI > 25 kg/m2, and transperitoneal surgical approach are independent risk factors for the formation of parastomal hernia after Miles.
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Most of the traditional fluorescent molecules have the advantages of high fluorescence quantum yield, good stability, and excellent structural adjustability, but they exhibit the characteristics of fluorescence quenching caused by aggregation, which restricts their application in aqueous solutions or solids. The excellent luminescence properties and photosensitive potential of aggregation-induced emission (AIE) materials in a condensed state have made them widely concerned in the scientific research field, so it is very challenging to regulate the transformation of traditional aggregation-caused quenching (ACQ) fluorophores into AIE fluorophores. In this study, the traditional coumarin fluorophore was used as a matrix. After conjugating the triphenylamine AIE group, the triphenylphosphine cation was linked through the alkyl chain to obtain a molecular probe NCTPP with excellent AIE characteristic, water solubility, mitochondrial green light imaging, chemotherapy and photodynamic therapy capabilities. As far as we know, it was the first time that the photosensitivity of coumarin fluorescent molecules was imparted by the ACQ-AIE conversion method.
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Cumarinas , Colorantes Fluorescentes , Mitocondrias , Fotoquimioterapia , Fármacos Fotosensibilizantes , Cumarinas/química , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Humanos , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Colorantes Fluorescentes/química , Imagen Óptica , Antineoplásicos/química , Antineoplásicos/farmacología , Células HeLa , Neoplasias/tratamiento farmacológico , Neoplasias/diagnóstico por imagenRESUMEN
Objective: To assess the clinical impact of unilateral laminotomy for bilateral decompression (ULBD) in managing patients with adjacent vertebrae following lumbar fusion. Methods: A retrospective analysis was conducted on 21 patients, with a mean age of 67.4 years, who underwent ULBD for adjacent vertebra disease at our department from January 2021 to November 2023. We reviewed demographic data, surgical techniques, imaging studies, and patient-reported outcomes. The study compared Visual Analog Scale (VAS) scores, Numeric Rating Scale (NRS) scores, Japanese Orthopaedic Association (JOA) scores, Short Form-36 (SF-36) scores, and imaging outcomes before surgery, immediately post-surgery, and at 1 month, 6 months, and 12 months post-surgery. Results: Evaluation of 21 patients with adjacent segment disease (ASD) (13 males, 8 females; mean age 67.42 years) was performed with follow-ups at various intervals post-surgery. Postoperative VAS, NRS, JOA, and SF-36 scores showed significant improvements compared to preoperative scores. Immediately after surgery, there were significant improvements in NRS score (2.76 ± 0.70 vs. 3.71 ± 0.85, P < 0.05) and JOA score (15.38 ± 1.02 vs. 9.29 ± 1.01, P < 0.05) compared to preoperative scores. Similarly, at 12 months post-surgery, significant improvements were observed in NRS score (1.52 ± 0.51 vs. 3.71 ± 0.85, P < 0.05) and JOA score (25.0 ± 1.10 vs. 9.29 ± 1.01, P < 0.05) compared to preoperative scores. The clinical satisfaction rate was 95.0% among all patients, with postoperative imaging examinations revealing a significant decompression effect. No complications were reported among the surgical patients. Conclusions: This study suggests that endoscopic ULBD can be a safe and effective technique for managing symptomatic ASD, providing satisfactory clinical outcomes for patients with ASD. Endoscopic ULBD may serve as an alternative treatment option for ASD with lumbar stenosis.
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The design of efficient heterogeneous redox mediators with favorable affinity to substrate and electrolyte are much desired yet still challenging for the development of indirect electrolysis system. Herein, for the first time, we have developed a solid-liquid-gas three-phase indirect electrolysis system based on a covalent organic framework (Dha-COF-Cu) as heterogeneous redox mediator for S-S coupling reaction. Dha-COF-Cu with the integration of high porosity, nanorod morphology, abundant hydroxyl groups and active Cu sites is much beneficial for the adsorption/activation of thiols, uniform dispersion and high wettability in electrolyte, and efficient interfacial electron transfer. Notably, Dha-COF-Cu as solid-phase redox mediator exhibits excellent electrocatalytic efficiency for the formation of value-added liquid-phase S-S bond product (yields up to 99 %) coupling with the generation of gas-phase product of H2 (~1.40â mmol g-1 h-1), resulting in a powerful three-phase indirect electrolysis system. This is the first work about COFs that can be applied in three-phase indirect electrolysis system, which might promote the development of porous crystalline materials in this field.
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Tumorigenesis and metastasis are highly dependent on the interactions between the tumor and the surrounding microenvironment. In 3D matrix, the fibrous structure of the extracellular matrix (ECM) undergoes dynamic remodeling during tumor progression. In particular, during the late stage of tumor development, the fibers become more aggregated and oriented. However, it remains unclear how cancer cells respond to the organizational change of ECM fibers and exhibit distinct morphology and behavior. Here, we used electrospinning technology to fabricate biomimetic ECM with distinct fiber arrangements, which mimic the structural characteristics of normal or tumor tissues and found that aligned and oriented nanofibers induce cytoskeletal rearrangement to promote directed migration of cancer cells. Mechanistically, caveolin-1(Cav-1)-expressing cancer cells grown on aligned fibers exhibit increased integrin ß1 internalization and actin polymerization, which promoted stress fiber formation, focal adhesion dynamics and YAP activity, thereby accelerating the directional cell migration. In general, the linear fibrous structure of the ECM provides convenient tracks on which tumor cells can invade and migrate. Moreover, histological data from both mice and patients with tumors indicates that tumor tissue exhibits a greater abundance of isotropic ECM fibers compared to normal tissue. And Cav-1 downregulation can suppress cancer cells muscle invasion through the inhibition of YAP-dependent mechanotransduction. Taken together, our findings revealed the Cav-1 is indispensable for the cellular response to topological change of ECM, and that the Cav-1/YAP axis is an attractive target for inhibiting cancer cell directional migration which induced by linearization of ECM fibers.
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A visible-light-mediated radical cascade cyclization of N-(o-cyanobiaryl)acrylamides with oxime esters for the assembly of acyl-containing pyrido[4,3,2-gh]phenanthridines has been developed. The present protocol tolerates a wide range of oxime esters through a single reaction via fragmentation, radical addition, nitrile insertion, and cyclization under mild conditions.
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The connectivity (valency) of building blocks for constructing 3D covalent organic frameworks (COFs) has long been limited to 4, 6, 8, and 12. Developing a higher connectivity remains a great challenge in the field of COF structural design. Herein, this work reports a hierarchical expansion strategy for making 16-connected building blocks to construct 3D COFs with sqc topology. The [16 + 2] construction achieved by condensation between a 16-connected carbazolyl dicyanobenzene-based building block (CzTPN) and linear diamino linkers (BD or Bpy) affords two 3D COFs (named CzBD COF and CzBpy COF). Furthermore, attributed to the well-organized donor-acceptor (D-A) heterojunction, the Ni chelated CzBpy COF (Ni@CzBpy COF) exhibits excellent performance for photoredox/Ni dual catalytic C(sp3)-C(sp2) cross-coupling of alkyltrifluoroborates with aryl halides, achieving a maximum 98% conversion and 94% yield for various substrates. This work developed the first case of high-connectivity COFs bearing 16-connected units, which is the highest connectivity reported until now, and achieved efficient photocatalysis applications, thus greatly enriching the possibilities of COFs.
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The Narasaka-Heck reaction is one of the most straightforward methods for constructing pyrroline derivatives. Herein, we report a novel nickel-catalyzed three-component carbonylation reaction, which cleverly realizes the continuous construction of C(sp3)-N bonds and C(sp3)-C(sp2) bonds and effectively promotes the synthesis of acyl-substituted pyrroline derivatives. Furthermore, this strategy not only expands the conversion pathway of γ,δ-unsaturated oxime esters but also provides a new method for the synthesis of nitrogen-containing heterocyclic compounds.
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Low temperature is a common abiotic stress that causes significant damage to crop production. Polyamines (PAs) are a class of aliphatic amine compounds that serve as regulatory molecules involved in plant growth, development, and response to abiotic and biotic stresses. In this study, we found that the exogenous application of two concentrations of spermidine (Spd) significantly enhanced the freezing tolerance of three differently matured rapeseed (Brassica napus L.) varieties, as manifested by higher survival rates, lower freezing injury indexes, and reduced H2O2 content. RNA-seq and qRT-PCR analyses showed that Spd enhanced the freezing tolerance of rapeseed by regulating genes related to the PA metabolic pathway and antioxidant mechanism, and generally inhibited the expression of genes related to the JA signaling pathway. This study provides a reference basis for understanding the functionality and molecular mechanisms of polyamines in the response of rapeseed to freezing stress.
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Pathological observations show that cancer cells frequently invade the surrounding normal tissue in collective rather than individual cell migration. However, general principles governing collective cell migration remain to be discovered. Different from individual cell migration, we demonstrated that the Notch-1-activation reduced collective cells speed and distances. In particular, Notch-1-activation induced cellular cytoskeletal remodelling, strengthened the intercellular junctions and cell-matrix adhesions. Mechanistically, Notch-1 activation prevented the phosphorylation of GSK-3ß and the translocation of cytoplasmic free ß-catenin to the nucleus, which increased E-cadherin expression and tight intercellular junctions. Moreover, Notch-1 signalling also activated the RhoA/ROCK pathway, promoting reorganization of F-actin and contractile forces produced by myosin. Further, Notch-1 activation increased cell adhesion to the extracellular substrate, which inhibited collective cell migration. These findings highlight that cell adhesions and cell-cell junctions contribute to collective cell migration and provide new insights into mechanisms of the modulation of Notch-1 signalling pathway on cancer cell malignancy.