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Monitoring variations in the virus genome to understand the SARS-CoV-2 evolution and spread of the virus is extremely important. Seven early SARS-CoV-2 isolates in China were cultured in vitro and were analyzed for their viral infectivity through viral growth assay, tissue culture infectious dose (TCID50 ) assay, spike protein quantification, and next generation sequencing analysis, and the resultant mutations in spike protein were used to generate the corresponding pseudoviruses for analysis of immune escape from vaccination and postinfection immunity. The results revealed that in vitro cultured SARS-CoV-2 virus had much higher mutation frequency (up to ~20 times) than that in infected patients, suggesting that SARS-CoV-2 diversify under favorable conditions. Monitoring viral mutations is not only helpful for better understanding of virus evolution and virulence change, but also the key to prevent virus transmission and disease progression. Compared with the D614G reference strain, a pseudovirus strain of SARS-CoV-2 was constructed with a high mutation rate site on the spike protein. We found some novel spike mutations during in vitro culture, such as E868Q, conferred further immune escape ability.
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COVID-19 , Humanos , SARS-CoV-2/genética , Glicoproteína de la Espiga del Coronavirus/genética , Bioensayo , Mutación , InmunidadRESUMEN
Wounds can lead to skin and soft tissue damage and their improper management may lead to the growth of pathogenic bacteria at the site of injury. Identifying better ways to promote wound healing is a major unmet need and biomedical materials with the ability to promote wound healing are urgently needed. Here, we report a thermosensitive black phosphorus hydrogel composed of black phosphorus nano-loaded drug silver sulfadiazine (SSD) and chitosan thermosensitive hydrogel for wound healing. The hydrogel has temperature-sensitive properties and enables the continuous release of SSD under near-infrared irradiation to achieve synergistic photothermal and antibacterial treatment. Additionally, it exerts antibacterial effects on Staphylococcus aureus. In a rat skin injury model, it promotes collagen deposition, boosts neovascularization, and suppresses inflammatory markers. In summary, the excellent thermosensitivity, biocompatibility, and wound-healing-promoting qualities of the reported thermosensitive hydrogel make it suitable as an ideal wound dressing in the clinic.
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Hidrogeles , Sulfadiazina de Plata , Animales , Ratas , Sulfadiazina de Plata/farmacología , Antibacterianos/farmacología , Cicatrización de Heridas , FósforoRESUMEN
The spike trimer of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an effective target for inducing neutralizing antibodies by coronavirus disease 2019 (COVID-19) vaccines. However, the diversity of spike protein from emerging SASR-CoV-2 variants has become the major challenge for development of a universal vaccine. To investigate the immunogenicity of spike proteins from various circulating strains including wild type, Delta, and Omicron variants, we produced various natural spike trimers and designed three vaccination strategies, that is, individual, sequential, and bivalent regimens to assess autologous and heterogenous antibody responses in a mouse model. The results indicated that monovalent vaccine strategy with individual spike trimer could only induce binding and neutralizing antibodies against homologous viruses. However, sequential and bivalent immunization with Delta and Omicron spike trimers could induce significantly broader neutralizing antibody responses against heterogenous SARS-CoV-2. Interestingly, the spike trimer from Omicron variant showed superior immunogenicity in inducing antibody response against recently emerging XE variant. Taken together, our data supported the development of novel vaccination strategies or multivalent vaccine against emerging variants.
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COVID-19 , SARS-CoV-2 , Animales , Anticuerpos Neutralizantes , Anticuerpos Antivirales , COVID-19/prevención & control , Vacunas contra la COVID-19 , Inmunidad Humoral , Ratones , SARS-CoV-2/genética , Glicoproteína de la Espiga del Coronavirus/genética , Vacunas CombinadasRESUMEN
An improved aqueous extraction method has been established for extraction of oil from corn germs. This method primarily included steam explosion pretreatment and aqueous ethanol extraction. Process variables such as steam pressure, resident time, particle size and ethanol concentration were investigated. The highest yield of 93.74 % was obtained when ground steam-exploded corn germ (1.3 MPa, 30 s, 30-35 µm particle size) was treated with 30 % (v/v) aqueous ethanol for 2 h, at 60 °C and pH 9.0. The residual oil content in water and sediment phase decreased dramatically to 4 % and 3 %, respectively. The enhancement mechanism of the process induced by steam explosion was analyzed by confocal laser scanning microscope (CLSM). The quality of extracted crude oil was also investigated. The results showed that the quality of extracted oil was superior to commercial oils.
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BACKGROUND: The detection rate of peptic ulcer in children is improving, with development of diagnostic procedures. Gastroscopy is the gold standard for the diagnosis of peptic ulcer, but it is an invasive procedure. Gastrointestinal contrast-enhanced ultrasonography (CEUS) has the advantages of being painless, noninvasive, nonradioactive, easy to use, and safe. AIM: To investigate the clinical value of CEUS for diagnosis and treatment of peptic ulcer in children. METHODS: We investigated 43 children with digestive tract symptoms in our hospital from January 2021 to June 2022. All children were examined by routine ultrasound, gastrointestinal CEUS, and gastroscopy. The pathological results of gastroscopy were taken as the gold standard. Routine ultrasonography was performed before gastrointestinal CEUS. Conventional ultrasound showed the thickness of the gastroduodenal wall, gastric peristalsis, and the adjacent organs and tissues around the abdominal cavity. Gastrointestinal CEUS recorded the thickness of the gastroduodenal wall; the size, location and shape of the ulcer; gastric peristalsis; and adjacent organs and tissues around the abdominal cavity. The results of routine ultrasound and gastrointestinal ultrasound were compared with those of gastroscopy to evaluate the diagnostic results and coincidence rate of routine ultrasound and gastrointestinal CEUS. All children received informed consent from their guardians for CEUS. This study was reviewed and approved by the hospital medical ethics committee. RESULTS: Among the 43 children, 17 (15 male, 2 female) were diagnosed with peptic ulcer by gastroscopy. There were 26 children with nonpeptic ulcer. There were eight cases of peptic ulcer and 35 of nonpeptic ulcer diagnosed by conventional ultrasound. The diagnostic coincidence rate of peptic ulcer in children diagnosed by conventional ultrasound was 79.1% (34/43), which was significantly different from that of gastroscopy (P = 0.033). It indicates that the coincidence rate of gastrointestinal contrast-enhanced ultrasound and gastroscope is low. Fifteen cases of peptic ulcer and 28 of nonpeptic ulcer were diagnosed by CEUS. The diagnostic coincidence rate of peptic ulcer in children was 95.3% (41/43). There was no significant difference between CEUS and gastroscopy (P = 0.655). It indicates that the coincidence rate of gastrointestinal contrast-enhanced ultrasound and gastroscope is high. CONCLUSION: Gastrointestinal CEUS has a high coincidence rate in the diagnosis of peptic ulcer in children, and can be used as a preliminary examination method.
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Medios de Contraste , Úlcera Péptica , Niño , Humanos , Masculino , Femenino , Úlcera , Úlcera Péptica/diagnóstico por imagen , Úlcera Péptica/terapia , Ultrasonografía/métodosRESUMEN
The purpose of this study was to assess ADAM17 expression and to explore its contribution to the non-small cell lung cancer (NSCLC). Real-time quantitative reverse transcriptase-polymerase chain reaction was conducted to detect ADAM17 mRNA expression. In addition, ADAM17 expression was analyzed by immunohistochemistry in 124 clinicopathologically characterized NSCLC cases. The correlation of ADAM17 expression with patients' survival rate was assessed by Kaplan-Meier and Cox regression. The expression levels of ADAM17 mRNA and protein in NSCLC tissues were both significantly higher than those in non-cancerous tissues. In addition, high expression of ADAM17 was significantly correlated with tumor grade (P=0.026), tumor size (P=0.001), clinical stage (P=0.016), and lymph node metastases (P<0.001). Furthermore, multivariate analysis suggested that tumor grade, tumor size, clinical stage, lymph node metastases, and ADAM17 expression were independent prognostic indicators for NSCLC. Our data suggest for the first time that the increased expression of ADAM17 in NSCLC is associated significantly with aggressive progression and poor prognosis. ADAM17 may be an important molecular marker for predicting the carcinogenesis, progression, and prognosis of NSCLC.
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Proteínas ADAM/metabolismo , Adenocarcinoma/metabolismo , Biomarcadores de Tumor/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Células Escamosas/metabolismo , Neoplasias Pulmonares/metabolismo , Proteínas ADAM/genética , Proteína ADAM17 , Adenocarcinoma/mortalidad , Adenocarcinoma/secundario , Biomarcadores de Tumor/genética , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/secundario , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/secundario , Femenino , Estudios de Seguimiento , Humanos , Técnicas para Inmunoenzimas , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Metástasis Linfática , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Pronóstico , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Estudios Retrospectivos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Tasa de SupervivenciaRESUMEN
The upregulated expression of JMJD6 was observed in various human cancers. However, little was known about JMJD6 expression and its clinicopathological significance in lung adenocarcinoma. The aim of this study was to investigate the expression and significance of JMJD6 in lung adenocarcinoma progression and prognosis. The levels of JMJD6 mRNA and protein in lung adenocarcinoma specimens and corresponding non-tumorous lung tissues were evaluated by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and Western blot. In order to investigate the correlations between JMJD6 and the clinicopathological features of lung adenocarcinoma, the expression of JMJD6 in 154 patients with lung adenocarcinoma was detected by immunohistochemistry. By qRT-PCR and Western blot, the relative expression levels of JMJD6 mRNA and protein were significantly higher in lung adenocarcinoma tissues than in corresponding non-tumorous lung tissues (P < 0.001). Immunohistochemical staining revealed that high JMJD6 expression was closely correlated with tumor size (P = 0.005), pathological grade (P = 0.003), pT status (P = 0.012), pN status (P = 0.003), and pleural invasion (P < 0.001). Moreover, the results of Kaplan-Meier analysis indicated that a high expression level of JMJD6 resulted in a significantly poor prognosis of lung adenocarcinoma patients. Multivariate analysis showed that the status of JMJD6 expression was an independent prognostic factor for lung adenocarcinoma patients. Our results showed that JMJD6 plays a key role in lung adenocarcinoma and therefore may provide an opportunity for developing a novel therapeutic target as well as a prognostic marker in lung adenocarcinoma.
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Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidad , Histona Demetilasas con Dominio de Jumonji/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidad , Adenocarcinoma/genética , Adenocarcinoma del Pulmón , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Progresión de la Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Estudios de Asociación Genética , Humanos , Histona Demetilasas con Dominio de Jumonji/genética , Neoplasias Pulmonares/genética , Masculino , Persona de Mediana Edad , Pronóstico , ARN Mensajero/metabolismoRESUMEN
Background: Testicular torsion is the reduction of blood flow to the testis after spermatic cord torsion. For patients, the diagnosis of testicular torsion is controversial and complicated by the fact that ultrasound blood flow signals are not significantly reduced in comparison to the unaffected, healthy, testis, despite persistent symptoms on the affected side. Our study aims to investigate the diagnostic characteristics of high-resolution ultrasonography (US) in pediatric testicular torsion with the preserved flow to increase diagnostic accuracy. Methods: Seven pediatric patients aged 49 days to 15 years old, with the preserved blood flow, but surgically diagnosed as testicular torsion, from October 2017 to August 2019, were retrospectively included in the study. The imaging manifestations of high-frequency ultrasonography were evaluated. Results: All cases had preserved testicular blood flow, but the surgical findings showed various degrees of twist, from 90 to 540 degrees. Preoperative ultrasound showed spermatic cord distortion in all cases, and testicular long axis tilting in four cases (4/7 = 57.1%). Conclusion: In some testicular torsion cases, Color Doppler may show normal or increased blood flow signals in the testis. We should further observe the morphology and position of the testes and epididymides, the echo of the testicular parenchyma, and, especially evaluate the "whirlpool sign" in the spermatic cord, to avoid missing testicular torsion with blood flow signals.
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ETHNOPHARMACOLOGICAL RELEVANCE: Loki zupa (LKZP) decoction, a traditional Uyghur medicine prescription, has been commonly used to treat numerous respiratory ailments in the Xinjiang region of western China, especially chronic airway inflammatory diseases such as allergic asthma. Due to its complex chemical composition, however, the mechanism of action of LKZP has yet to be fully elucidated. AIM OF THE STUDY: Based on the balanced regulation theory of pro-inflammation and anti-inflammation, we tried to investigate the effectiveness of LKZP on asthma and its related protective mechanisms. MATERIALS AND METHODS: In this study, an experimental model of asthma was established using ovalbumin (OVA) in BALB/c mice to assess the effects of LKZP. The potential mechanism of LKZP anti allergic asthma were researched by the combination of in silico systems pharmacology and in vivo transcriptomics. RESULTS: Our data revealed that LKZP exerted a therapeutic effect against OVA-induced asthma by reducing airway hyperresponsiveness (AHR), peribronchial inflammation, and mucus hypersecretion. Meanwhile, LKZP downregulated the expression of OVA-induced IgE, interleukin (IL)-4, IL-5, IL-13, and tumor necrosis factor (TNF)-α and concurrently promoted the expression of interferon (IFN)-γ in serum and bronchoalveolar lavage fluid (BALF). Systems pharmacology analysis identified 10 core bioactive ingredients and 26 hub targets of LKZP against asthma. Transcriptomic analysis confirmed 246 differentially expressed genes (DEGs) after LKZP treatment. These were mainly expressed in cytokine-cytokine receptor interactions and immune and inflammatory response-related signaling pathways. Additionally, the real-time quantitative PCR (qPCR) results for the nine selected DEGs matched those of the RNA-seq analysis. Nuclear factor (NF)-κB and hypoxia-inducible factor (HIF)-1 signaling pathways were identified as candidate targets involved in the action of LKZP on allergic asthma, which was highly consistent with the findings in silico. By qPCR, Western blot, and immunohistochemical analysis, it was verified that LKZP treatment dramatically inhibited the activation of NF-κB p65 and HIF-1α stimulated by OVA in asthmatic mice. CONCLUSIONS: Taken together, our experimental data revealed that LKZP could be a candidate for the treatment of allergic asthma via NF-κB and HIF-1 signaling pathways.
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Asma , Transcriptoma , Animales , Asma/inducido químicamente , Asma/tratamiento farmacológico , Asma/genética , Líquido del Lavado Bronquioalveolar , Citocinas/metabolismo , Modelos Animales de Enfermedad , Inflamación/tratamiento farmacológico , Pulmón , Ratones , Ratones Endogámicos BALB C , FN-kappa B/metabolismo , Farmacología en Red , Ovalbúmina , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
The mutants resulted from the ongoing SARS-CoV-2 epidemic have showed resistance to antibody neutralization and vaccine-induced immune response. The present study isolated and identified two novel SARS-CoV-2 neutralizing antibodies (nAbs) from convalescent COVID-19 patients. These two nAbs (XG81 and XG83) were then systemically compared with nine nAbs that were reconstructed by using published data, and revealed that, even though these two nAbs shared targeting epitopes on spike protein, they were different from any of the nine nAbs. Compared with XG81, XG83 exhibited a higher RBD binding affinity and neutralization potency against wild-typed pseudovirus, variant pseudoviruses with mutated spike proteins, such as D614G, E484Q, and A475V, as well as the authentic SARS-CoV-2 virus. To explore potential broadly neutralizing antibodies, heavy and light chains from all 18 nAbs (16 published nAbs, XG81 and XG83) were cross-recombined, and some of the functional antibodies were screened and studied for RBD binding affinity, and neutralizing activity against pseudovirus and the authentic SARS-CoV-2 virus. The results demonstrated that several recombined antibodies had a more potent neutralization activity against variant pseudoviruses compared with the originally paired Abs. Taken together, the novel neutralizing antibodies identified in this study are a likely valuable addition to candidate antibody drugs for the development of clinical therapeutic agents against SARS-CoV-2 to minimize mutational escape.
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Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Anticuerpos ampliamente neutralizantes/inmunología , Anticuerpos ampliamente neutralizantes/uso terapéutico , SARS-CoV-2/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Anticuerpos Neutralizantes/genética , Anticuerpos Neutralizantes/uso terapéutico , Anticuerpos Antivirales/genética , Anticuerpos Antivirales/uso terapéutico , Afinidad de Anticuerpos/inmunología , Linfocitos B/inmunología , Anticuerpos ampliamente neutralizantes/genética , COVID-19/inmunología , COVID-19/terapia , Línea Celular , Epítopos/inmunología , Humanos , Inmunoterapia/métodos , Pruebas de Neutralización , SARS-CoV-2/efectos de los fármacosRESUMEN
BACKGROUND/AIMS: Current epidemiological data suggest that the incidence of gastric polyps (GP) is rare, and its etiology and pathogenesis are still not clear. This study analyzed and compared the occurrence and pathological types of GPs in southeast Chinese patients according to gender and age. MATERIALS AND METHODS: This was a retrospective study of patients diagnosed with GP (n=2125) in Wenzhou People's Hospital (China) between January 2004 and December 2013. The relationships between the detection rate, the characteristics of GP, and the patients' demographic data were analyzed. RESULTS: The detection rate of GP was 2.3% and 3.9% in males and females, respectively (p<0.01). The detection rate increased with increasing age in both genders. Polyps in the gastric antrum and gastric body were the most prevalent in both genders. Similarly, inflammatory polyps and hyperplastic polyps were the most prevalent in both genders. Hyperplastic polyps were more common in females than in males (28.6% vs. 24.2%, p<0.05), while there was no difference for inflammatory polyps, fundic GP, and adenoma (p>0.05). Age had no impact on the pathology of GP (p>0.05). CONCLUSIONS: The incidence of GPs was associated with gender and age.