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BACKGROUND: Microbes in the cold polar and alpine environments play a critical role in feedbacks that amplify the effects of climate change. Defining the cold adapted ecotype is one of the prerequisites for understanding the response of polar and alpine microbes to climate change. RESULTS: Here, we analysed 85 high-quality, de-duplicated genomes of Deinococcus, which can survive in a variety of harsh environments. By leveraging genomic and phenotypic traits with reverse ecology, we defined a cold adapted clade from eight Deinococcus strains isolated from Arctic, Antarctic and high alpine environments. Genome-wide optimization in amino acid composition and regulation and signalling enable the cold adapted clade to produce CO2 from organic matter and boost the bioavailability of mineral nitrogen. CONCLUSIONS: Based primarily on in silico genomic analysis, we defined a potential cold adapted clade in Deinococcus and provided an updated view of the genomic traits and metabolic potential of Deinococcus. Our study would facilitate the understanding of microbial processes in the cold polar and alpine environments.
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Frío , Deinococcus , Genoma Bacteriano , Genómica , Deinococcus/genética , Adaptación Fisiológica/genética , FilogeniaRESUMEN
BACKGROUND: Endosonographers are highly dependent on the diagnosis of pancreatic ductal adenocarcinoma (PDAC). The objectives of this study were to develop a deep-learning radiomics (DLR) model based on endoscopic ultrasonography (EUS) images for identifying PDAC and to explore its true clinical benefit. METHODS: A retrospective data set of EUS images that included PDAC and benign lesions was used as a training cohort (N = 368 patients) to develop the DLR model, and a prospective data set was used as a test cohort (N = 123 patients) to validate the effectiveness of the DLR model. In addition, seven endosonographers performed two rounds of reader studies on the test cohort with or without DLR assistance to further assess the clinical applicability and true benefits of the DLR model. RESULTS: In the prospective test cohort, DLR exhibited an area under the receiver operating characteristic curves of 0.936 (95% confidence interval [CI], 0.889-0.976) with a sensitivity of 0.831 (95% CI, 0.746-0.913) and 0.904 (95% CI, 0.820-0.980), respectively. With DLR assistance, the overall diagnostic performance of the seven endosonographers improved: one endosonographer achieved a significant expansion of specificity (p = .035,) and another achieved a significant increase in sensitivity (p = .038). In the junior endosonographer group, the diagnostic performance with the help of the DLR was higher than or comparable to that of the senior endosonographer group without DLR assistance. CONCLUSIONS: A prospective test cohort validated that the DLR model based on EUS images effectively identified PDAC. With the assistance of this model, the gap between endosonographers at different levels of experience narrowed, and the accuracy of endosonographers expanded.
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Carcinoma Ductal Pancreático , Aprendizaje Profundo , Neoplasias Pancreáticas , Humanos , Endosonografía/métodos , Estudios Retrospectivos , Estudios Prospectivos , Neoplasias Pancreáticas/patología , Carcinoma Ductal Pancreático/diagnóstico por imagen , Carcinoma Ductal Pancreático/patología , Neoplasias PancreáticasRESUMEN
BACKGROUND: Gastric cancer is one of the most common malignancies of the digestive system with a high lethal rate. Studies have shown that inherited and acquired mutations in pyruvate metabolism and citric acid cycle (P-CA) enzymes are involved in tumorigenesis and tumor development. However, it is unclear how different P-CA patterns affect the tumor microenvironment (TME), which is critical for cancer progression. METHODS: This study mainly concentrated on investigating the role of the P-CA patterns in multicellular immune cell infiltration of GC TME. First, the expression levels of P-CA regulators were profiled in GC samples from The Cancer Genome Atlas and Gene Expression Omnibus cohorts to construct a consensus clustering analysis and identify three distinct P-CA clusters. GSVA was conducted to reveal the different biological processes in three P-CA clusters. Subsequently, 1127 cluster-related differentially expressed genes were identified, and prognostic-related genes were screened using univariate Cox regression analysis. A scoring system was then set up to quantify the P-CA gene signature and further evaluate the response of the patients to the immunotherapy. RESULTS: We found that GC patients in the high P-CA score group had a higher tumor mutational burden, higher microsatellite instability, and better prognosis. The opposite was observed in the low P-CA score group. Interestingly, we demonstrated P-CA gene cluster could predict the sensitivity to immunotherapy and ferroptosis-induced therapy. CONCLUSION: Collectively, the P-CA gene signature in this study exhibits potential roles in the tumor microenvironment and predicts the response to immunotherapeutic. The identification of these P-CA patterns may significantly accelerate the strategic development of immunotherapy for GC.
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Herein, we reported a practical and efficient strategy combining photoredox and enzyme catalysis for the construction of 3-aminoalkyl chromones from o-hydroxyaryl enaminones and N-arylglycine esters. A variety of 3-aminoalkyl chromones were synthesized with good yields under mild conditions in one pot. This synthetic protocol consists of sequential enzymatic hydrolysis and photoredox decarboxylation of N-arylglycine esters, oxidation of aminoalkyl radicals, Mannich reaction, and intramolecular nucleophilic cyclization, which affords a convenient pathway for the preparation of various 3-substituted chromones.
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Cromonas , Ésteres , Catálisis , Ciclización , Oxidación-ReducciónRESUMEN
BACKGROUND: Ferroptosis is a newly identified type of programmed cell death, which preferentially targets iron-rich cancer cells such as hepatocellular carcinoma (HCC). Ferritin heavy chain (FTH) is a major iron storing nanocage to store redox-inactive iron, and harbors ferroxidase activity to prevent the iron-mediated production of ROS. Our previous studies have demonstrated that FTH acts as a protective role to increase the cellular resistance to ferroptosis. However, the specific role of FTH in the development of HCC and ferroptosis resistance remains unclear. METHODS: The indicated databases were used for bioinformatics analysis. The abilities of cell proliferation, migration were measured by cell proliferation assay, transwell assay and wound healing assay. The levels of reactive oxygen species (ROS), lipid peroxide, free iron, mitochondrial superoxide, mitochondrial morphology and mitochondrial membrane potential (MMP) were determined by DCF-DA, C11-BODIPY, mitoSOX, mitoTracker, JC-10 and TMRM staining, respectively. The mitochondrial oxygen consumption rate was monitored by the Seahorse XF24 Analyzer. RESULTS: The pan-cancer analysis was performed and showed that FTH expression is upregulated in multiple cancers, such as LIHC, CHOL, HNSC, compared to corresponding normal tissues. In addition, the level of serum ferritin is positively associated with the progression of hepatitis, cirrhosis liver and hepatocellular carcinoma. Further investigation shed light on the strong correlation between FTH expression and tumor grades, cancer stages and prognosis of HCC. Importantly, the proteins interaction network elucidated that FTH is involved in iron homeostasis maintenance and lysosomal-dependent degradation. Enforced expression of FTH accelerates proliferation, migration and endows HCC cells specifically resistant to ferroptosis, but does not protect against cell death caused by cytotoxic compounds like oxaliplatin, irinotecan, and adriamycin. Mechanically, FTH reconstituted cells exhibit diminished peroxides accumulation, reduce mitochondrial ROS level, attenuate the impaired mitochondrial respiratory and rescue the mitochondrial homeostasis. Notably, FTH expression boosts tumorigenic potential in vivo with increased PCNA staining and lesser lipid peroxides generation. CONCLUSION: These results provide new insights that FTH acts as an oncogene in the carcinogenesis and progression of HCC, and is hopeful to be a potential target for therapeutic intervention through ferroptosis.
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The polygrammoids (Polypodiaceae) are the most species-rich and diversified epiphytic fern lineages, and hold an important role to understand the deep diverging events and rapid adaptation to changing environments in the plant tree of life. Despite progress in the phylogeny of this group of ferns in previous multilocus phylogenetic studies, uncertainty remains especially in backbone relationships among closely related clades, and the phylogenetic placement of recalcitrant species or lineages. Here, we investigated the deep phylogenetic relationships within Polypodiaceae by sampling all major lineages and using 81 plastid genomes (plastomes), of which 70 plastomes were newly sequenced with high-throughput sequencing technology. Based on parsimony, maximum-likelihood, Bayesian and multispecies coalescent analyses of genome skimming data, we achieved a better resolution of the backbone phylogeny of Polypodiaceae. Using simulated data matrices, we detected that potential phylogenetic artefacts, such as long-branch attraction and insufficient taxonomic sampling, may have a confounding impact on the incongruence of phylogenetic inferences. Furthermore, our phylogenetic analyses offer greater resolution than previous multilocus studies, providing a robust framework for future phylogenetic implications on the subfamilial taxonomy of Polypodiaceae. Our phylogenomic study not only demonstrates the advantage of a character-rich plastome dataset for resolving the recalcitrant lineages that have undergone rapid radiation, but also sheds new light on integrative explorations understanding the evolutionary history of large fern groups in the genomic era.
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Plastidios/genética , Polypodiaceae/genética , Genoma de Plastidios , Genómica , Secuenciación de Nucleótidos de Alto Rendimiento , Filogenia , Plastidios/clasificación , Polypodiaceae/clasificaciónRESUMEN
BACKGROUND: Pruritus, or itch, is a prevalent symptom causing profound health burden in many dermatological and non-dermatological disorders. Several itch questionnaires have been created to assess itch. Particularly, Eppendorf Itch Questionnaire (EIQ) is widely accepted since it encompasses various aspects of itch, including intensity, affects, coping behavior, and motivation to scratch. METHODS: In a cross-sectional survey, we examined the validity, reliability and clinical utility of Traditional Chinese EIQ. RESULTS: We administered the consensus version to 128 adults (median: 48.5 years, interquartile range [IQR]: 39-63) with active itch for more than 6 weeks at the Outpatient Clinics of three medical centers in Taiwan. Clinical diagnoses included psoriasis (N = 82), xerosis (N = 34), or other dermatitis (N = 12). Cronbach's alpha for each EIQ scale ranged 0.82-0.98, suggesting good to excellent internal consistency and reliability. Three EIQ scales significantly correlated with visual analogue scale (VAS) for itch intensity (P ≤ 0.001 for median test), supporting for its concurrent validity. None of EIQ scale was statistically correlated with Psoriasis Area Severity Index (PASI) scores in psoriasis patients, confirming its discriminant validity. Moreover, patients of different diagnoses had distinct responses to the multi-scale EIQ index, affording it a better clinical test (area-under-the-ROC curve [AUC]: 0.76, 95% CI: 0.63-0.90) than VAS alone (AUC: 0.42, 95%CI: 0.24-0.59) in distinguishing dermatitis/eczema-related itch from psoriasis or xerosis-related itch. CONCLUSION: We demonstrated the reliability and validity of Chinese EIQ in adult patients with chronic itch at the outpatient setting. The study also revealed the diversified aspects of itch across patients with various dermatoses.
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Prurito , Calidad de Vida , Adulto , China , Estudios Transversales , Humanos , Prurito/diagnóstico , Reproducibilidad de los Resultados , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios , TaiwánRESUMEN
BACKGROUND: The first identified cases of avian influenza A(H7N9) virus infection in humans occurred in China during February and March 2013. We analyzed data obtained from field investigations to describe the epidemiologic characteristics of H7N9 cases in China identified as of December 1, 2013. METHODS: Field investigations were conducted for each confirmed case of H7N9 virus infection. A patient was considered to have a confirmed case if the presence of the H7N9 virus was verified by means of real-time reverse-transcriptase-polymerase-chain-reaction assay (RT-PCR), viral isolation, or serologic testing. Information on demographic characteristics, exposure history, and illness timelines was obtained from patients with confirmed cases. Close contacts were monitored for 7 days for symptoms of illness. Throat swabs were obtained from contacts in whom symptoms developed and were tested for the presence of the H7N9 virus by means of real-time RT-PCR. RESULTS: Among 139 persons with confirmed H7N9 virus infection, the median age was 61 years (range, 2 to 91), 71% were male, and 73% were urban residents. Confirmed cases occurred in 12 areas of China. Nine persons were poultry workers, and of 131 persons with available data, 82% had a history of exposure to live animals, including chickens (82%). A total of 137 persons (99%) were hospitalized, 125 (90%) had pneumonia or respiratory failure, and 65 of 103 with available data (63%) were admitted to an intensive care unit. A total of 47 persons (34%) died in the hospital after a median duration of illness of 21 days, 88 were discharged from the hospital, and 2 remain hospitalized in critical condition; 2 patients were not admitted to a hospital. In four family clusters, human-to-human transmission of H7N9 virus could not be ruled out. Excluding secondary cases in clusters, 2675 close contacts of case patients completed the monitoring period; respiratory symptoms developed in 28 of them (1%); all tested negative for H7N9 virus. CONCLUSIONS: Most persons with confirmed H7N9 virus infection had severe lower respiratory tract illness, were epidemiologically unrelated, and had a history of recent exposure to poultry. However, limited, nonsustained human-to-human H7N9 virus transmission could not be ruled out in four families.
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Subtipo H7N9 del Virus de la Influenza A , Gripe Humana/epidemiología , Neumonía Viral/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Animales , Niño , Preescolar , China/epidemiología , Familia , Femenino , Estudios de Seguimiento , Humanos , Gripe Aviar/transmisión , Gripe Humana/transmisión , Gripe Humana/virología , Masculino , Persona de Mediana Edad , Neumonía Viral/virología , Aves de CorralRESUMEN
BACKGROUND: The bacteria Streptococcus pneumoniae (pneumococcus) and Haemophilus influenzae type b (Hib) are leading causes of childhood pneumonia and meningitis and are major contributors to worldwide mortality in children younger than 5 years of age. Asymptomatic nasopharyngeal carriage of pneumococcus and Hib was determined for healthy children in Shanghai in 2009. METHODS: Children from 5 immunization clinics were enrolled in this study. Specimens from the nasopharynx were collected and cultured in Columbia and chocolate agar to identify pneumococcal and Hib carriage. Pneumococcal specimens were serotyped with the Neufeld test, and antibiotic resistance for pneumococcal and Hib specimens used the E-test method. Significance of risk factors for carriage was assessed through chi-square tests. RESULTS: Among 614 children, 16.6% had pneumococcal carriage and 8.0% Hib carriage. The predominant serotype of pneumococcus that was isolated was 19 F (52.9%); serotype coverage was 68.6% for both 7-valent pneumococcal conjugate vaccine (PCV) and PCV-10, and 82.3% for PCV-13. Household residency and father's education were both significantly related to pneumococcal and Hib carriage. The majority of S. pneumoniae isolates were sensitive to most antimicrobials but there were high levels of resistance to azithromycin (51.0 %) and erythromycin (51.0%). Haemophilus influenzae isolates were sensitive to almost all antimicrobials tested although 12.2% of isolates were resistant to ampicillin. CONCLUSIONS: The pneumococcal and Hib vaccines require payment, and the children with the highest burden of disease may not be receiving these vaccines. Moreover, the presence of high antibiotic susceptibility towards pneumococcus, and to a lesser extent towards Hib, underscores the need for preventive protection against these diseases. Public funding of pneumococcal and Hib vaccines would be one mechanism to increase uptake of these vaccines.
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Infecciones por Haemophilus/diagnóstico , Haemophilus influenzae tipo b/aislamiento & purificación , Infecciones Neumocócicas/diagnóstico , Streptococcus pneumoniae/aislamiento & purificación , Antiinfecciosos/farmacología , Azitromicina/farmacología , China/epidemiología , Estudios Transversales , Farmacorresistencia Bacteriana Múltiple , Femenino , Infecciones por Haemophilus/epidemiología , Infecciones por Haemophilus/microbiología , Haemophilus influenzae tipo b/efectos de los fármacos , Humanos , Lactante , Masculino , Pruebas de Sensibilidad Microbiana , Nasofaringe/microbiología , Oportunidad Relativa , Infecciones Neumocócicas/epidemiología , Infecciones Neumocócicas/microbiología , Streptococcus pneumoniae/efectos de los fármacosRESUMEN
BACKGROUND: Norovirus is an important cause of gastroenteritis both in children and adults. In China, few studies have been conducted on adult populations. This study aimed to determine the contribution of norovirus to gastroenteritis, characterize the features of norovirus infections, compare them with other pathogens, and test the effectiveness of the surveillance system. METHODS: A citywide surveillance network on diarrhea patients was established. Samples were collected with intervals from both children and adults among diarrhea outpatients in hospitals and tested for viruses using rRT-PCR and for bacteria in CDCs. Patient information was acquired through interviews and recorded into a dedicated online system. The Pearson χ2 test, multivariate logistic regression models and discriminant models were fitted into its comparisons with the non-norovirus group and other pathogens. RESULTS: Norovirus was detected in 22.91% of sampled diarrhea patients. The seasonal distribution of norovirus infections was different from non-norovirus patients (p<0.001), with a half-year peak. Higher proportions of males (p=0.001, OR=1.303, 95% CI=1.110-1.529), local citizens (p<0.001) and officials/clerks (p=0.001, OR=1.348, 95% CI=1.124-1.618) were affected with norovirus when compared with non-norovirus patients. Diarrhea patients affected with norovirus featured nausea (p<0.001, OR=1.418, 95% CI=1.176-1.709) and vomiting (p<0.001, OR=1.969, 95% CI=1.618-2.398), while fewer manifested fever (p=0.046, OR=0.758, 95% CI=0.577-0.996) and abdominal pain (p=0.018, OR=0.815, 95% CI=0.689-0.965). Children were more vulnerable to rotavirus (p=0.008, OR=1.637, 95% CI=1.136-2.358) and bacteria (p=0.027, OR=1.511, 95% CI=1.053-2.169) than norovirus. There was a seasonal difference between the GI and GII genotypes (p<0.001). Officials or clerks were more easily affected with GI than GII (p=0.006, OR=1.888, 95% CI=1.205-2.958). CONCLUSIONS: This study was based on a citywide hospital-sentinel surveillance system with multiple enteric pathogens included. Norovirus was recognized as the most prevalent enteric pathogen in Shanghai. The seasonal peak was from October to April. Males had a higher prevalence than females. Local citizens and officials/clerks were more vulnerable to norovirus than other pathogens. Compared with rotavirus and bacteria, children were less frequently affected by norovirus. Nausea and vomiting were typical of norovirus, whereas fever and abdominal pain were uncommon symptoms of this pathogen. GI and GII infections were centered in different seasons. Officials and clerks were more easily affected by GI than GII.
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Infecciones por Caliciviridae/epidemiología , Diarrea/epidemiología , Gastroenteritis/epidemiología , Infecciones por Rotavirus/epidemiología , Dolor Abdominal , Adolescente , Adulto , Anciano , Atención Ambulatoria , Infecciones por Caliciviridae/fisiopatología , Niño , Preescolar , China/epidemiología , Estudios Transversales , Diarrea/virología , Femenino , Fiebre , Gastroenteritis/virología , Genotipo , Humanos , Lactante , Masculino , Persona de Mediana Edad , Epidemiología Molecular , Náusea , Norovirus/genética , Norovirus/aislamiento & purificación , Prevalencia , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Rotavirus/genética , Rotavirus/aislamiento & purificación , Infecciones por Rotavirus/fisiopatología , Estaciones del Año , Vigilancia de Guardia , Virus/genética , Adulto JovenRESUMEN
BACKGROUND: The novel avian influenza H7N9 virus has caused severe diseases in humans in eastern China since the spring of 2013. On January 18(th) 2014, a doctor working in the emergency department of a hospital in Shanghai died of H7N9 virus infection. To understand possible reasons to explain this world's first fatal H7N9 case of a health care worker (HCW), we summarize the clinical presentation, epidemiological investigations, laboratory results, and prevention and control policies and make important recommendations to hospital-related workers. CASE PRESENTATION: The patient was a 31-year-old male Chinese surgeon who was obese and had a five-year history of hypertension and suspected diabetes. On January 11(th) 2014, he showed symptoms of an influenza-like illness. Four days later, his illness rapidly progressed with bilateral pulmonary infiltration, hypoxia and lymphopenia. On January 17th, the case had a high fever, productive cough, chest tightness and shortness of breath, so that he was administered with oseltamivir, glucocorticoid, immunoglobulin, and broad-spectrum antibiotic therapy. The case died in the early morning of next day after invasive ventilation. He had no contact with poultry nor had he visited live-poultry markets (LPMs), where positive rates of H7N9 were 14.6 % and 18.5 %. Before his illness, he cared for three febrile patients and had indirect contact with one severe pneumonia patient. Follow-up with 35 close contacts identified two HCWs who had worked also in emergency department but had not worn masks were anti-H7N9-positive. Viral sequence identity percentages between the patient and two LPM-H7N9 isolates were fewer than between the patient and another human case in shanghai in January of 2014. CONCLUSIONS: Important reasons for the patient's death might include late treatment with oseltamivir, and the infected H7N9 virus carrying both mammalian-adapted signature (HA-Q226L) and aerosol transmissibility (PB2-D701N). The LPM he passed every day was an unlikely source of his infection, but a contaminated environment, or an unidentified mild/asymptomatic H7N9 carrier were more probable. We advocate rigorous standard operating procedures for infection control practices in hospital settings and evaluations thereafter.
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Subtipo H7N9 del Virus de la Influenza A/aislamiento & purificación , Gripe Humana/diagnóstico , Adulto , Antibacterianos/uso terapéutico , China , Glucocorticoides/uso terapéutico , Humanos , Inmunoglobulinas/uso terapéutico , Subtipo H7N9 del Virus de la Influenza A/clasificación , Subtipo H7N9 del Virus de la Influenza A/genética , Gripe Humana/tratamiento farmacológico , Gripe Humana/virología , Pulmón/diagnóstico por imagen , Masculino , Oseltamivir/uso terapéutico , Filogenia , Médicos , Neumonía , ARN Viral/análisis , Radiografía , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Understanding host antibody response is crucial for predicting disease severity and for vaccine development. We investigated antibody responses against influenza A(H7N9) virus in 48 serum samples from 21 patients, including paired samples from 15 patients. IgG against subtype H7 and neutralizing antibodies (NAbs) were not detected in acute-phase samples, but ELISA geometric mean titers increased in convalescent-phase samples; NAb titers were 20-80 (geometric mean titer 40). Avidity to IgG against subtype H7 was significantly lower than that against H1 and H3. IgG against H3 was boosted after infection with influenza A(H7N9) virus, and its level in acute-phase samples correlated with that against H7 in convalescent-phase samples. A correlation was also found between hemagglutinin inhibition and NAb titers and between hemagglutinin inhibition and IgG titers against H7. Because of the relatively weak protective antibody response to influenza A(H7N9), multiple vaccinations might be needed to achieve protective immunity.
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Reacción de Fase Aguda/inmunología , Anticuerpos Antivirales/biosíntesis , Inmunoglobulina G/biosíntesis , Subtipo H7N9 del Virus de la Influenza A/inmunología , Gripe Humana/inmunología , Reacción de Fase Aguda/sangre , Reacción de Fase Aguda/virología , Anciano , Anciano de 80 o más Años , Anticuerpos Antivirales/sangre , Afinidad de Anticuerpos , Niño , Preescolar , Convalecencia , Protección Cruzada , Femenino , Pruebas de Inhibición de Hemaglutinación , Hemaglutinación por Virus/inmunología , Humanos , Inmunoglobulina G/sangre , Subtipo H1N1 del Virus de la Influenza A/inmunología , Subtipo H3N2 del Virus de la Influenza A/inmunología , Gripe Humana/sangre , Gripe Humana/virología , MasculinoRESUMEN
BACKGROUND: In China, caregivers of chronic viral hepatitis patients experience considerable burdens, stress and disruption of their own well-being and social activities. Measurement of the effect on caregivers is an under-researched area. The Family Burden Interview Schedule (FBIS) was primarily devised for the caregivers of schizophrenia patients, and the adverse effect of the disease was similar to the effect of chronic viral hepatitis on family caregivers. In this study, we prospectively evaluated the psychometric properties of FBIS in the field of chronic viral hepatitis and used it to determine the factors affecting the caregiver burden on the family members of chronic viral hepatitis patients in Shanghai, China. METHODS: A representative sample of patients (n = 1478) and caregivers (n = 1478) was randomly obtained through a multi-stage cluster sampling in Shanghai, China. Reliability and validity tests were used to verify the psychometric properties of the instrument. The two-level random intercept model was applied to determine the factors of the caregiver burden between the household and the community level. RESULTS: Cronbach's alpha coefficient was 0.90 for the overall instrument with statistical significance. Factor analysis suggested a three-factor model for the FBIS and confirmed that the adjusted unidimensional model and the second-order multidimensional model had better fit statistics. The average score of the caregiver burden in Shanghai was 12.62 ± 10.74, and financial burden constituted the major effect. The two-level random intercept model demonstrated that the risk factors were hospitalisation (ß 1.69, 95%CI 0.48 to 2.90), elevated serum alanine aminotransferase levels (ß 1.05, 95%CI 0.15 to 1.95), HCV infection (ß 4.49, 95%CI 1.22 to 7.77), and acceptance of the hepatitis B vaccine (ß 2.20, 95%CI 0.56 to 3.85), whereas the protective factors were no consumption of alcohol (ß -2.69, 95%CI -5.19 to -0.19), average monthly costs for patients less than or equal to 100 US dollars (ß -2.96, 95%CI -5.83 to -0.09), and good health status of family caregivers (ß -9.91, 95%CI -12.76 to -7.05). CONCLUSIONS: FBIS can accurately measure the caregiver burden for chronic hepatitis. Targeting interventions toward the conditions associated with the caregiver burden is of great importance.
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Cuidadores/psicología , Costo de Enfermedad , Hepatitis B Crónica/terapia , Hepatitis C Crónica/terapia , Adolescente , Adulto , Anciano , China , Análisis Factorial , Familia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Psicometría , Reproducibilidad de los Resultados , Factores de Riesgo , Encuestas y Cuestionarios , Adulto JovenRESUMEN
It is important to quantitatively assess the level of high-quality development of the Silk Road Economic Belt and the global economy. In the past, many scholars have conducted relevant studies on high-quality economic development, but little attention has been given to China's Silk Road Economic Belt, and there is a lack of dynamic quantitative research on long time series. Based on these findings, we constructed an evaluation index system for the high-quality economic development of China's Silk Road Economic Belt based on statistical data using geographic information technology such as the Moran index and econometric methods such as the entropy weight method and the Mann-Kendall test. Then, we quantitatively depicted the spatial and temporal evolution of the high-quality economic development of China's Silk Road Economic Belt from 2007 to 2021. The results of the study showed that over time, the overall level of high-quality economic development in China's Silk Road Economic Belt and the scores of all dimensions showed a significant upwards trend from 2007 to 2021. Spatially, the level of high-quality economic development in China's Silk Road Economic Belt shows a spatial distribution pattern of being lowest in the North, followed by that in the South, and that in the Centre. Furthermore, there is a clustering distribution of high-quality economic development in China's Silk Road Economic Belt, and there is a spatial spillover effect; science and technology expenditures and the total amount of imports and exports are also crucial in promoting high-quality development of the region's economy and accelerating spatial spillovers from the Silk Road Economic Belt. The results of this study can provide an important scientific basis for the high-quality and sustainable development of the Silk Road Economic Belt in China, as well as be an important reference for related studies in other similar regions in the world.
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BACKGROUND: Sodium-glucose cotransporter-2 (SGLT2) inhibitors are known to be cardioprotective independent of glucose control, but the mechanisms of these benefits are unclear. We previously demonstrated improved cardiac function and decreased fibrosis in a swine model of chronic myocardial ischemia. The goal of this study is to use high-sensitivity proteomic analyses to characterize specific molecular pathways affected by SGLT-2 inhibitor canagliflozin (CAN) therapy in a swine model of chronic myocardial ischemia. METHODS: Chronic myocardial ischemia was induced in sixteen Yorkshire swine via the placement of an ameroid constrictor to the left circumflex coronary artery. After two weeks of recovery, swine received either 300 mg of CAN daily (n = 8) or a control (n = 8). After five weeks of therapy, the group of swine were euthanized, and left ventricular tissue was harvested and sent for proteomic analysis. RESULTS: Total proteomic analysis identified a total of 3256 proteins between the CAN and control groups. Three hundred and five proteins were statistically different. This included 55 proteins that were downregulated (p < 0.05, fold change <0.5) and 250 that were upregulated (p < 0.05, fold change >2) with CAN treatment. Pathway analysis demonstrated the upregulation of several proteins involved in metabolism and redox activity in the CAN-treated group. The CAN group also exhibited a downregulation of proteins involved in motor activity and cytoskeletal structure. CONCLUSIONS: In our swine model of chronic myocardial ischemia, CAN therapy alters several proteins involved in critical molecular pathways, including redox regulation and metabolism. These findings provide additional mechanistic insights into the cardioprotective effects of canagliflozin.
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BACKGROUND: In recent years, notified pertussis cases have been increasingly documented in China. It raised a new public health concern of potential optimization in immunization strategy. This study was aimed to determine the cost-effectiveness of different immunization strategies against pertussis-containing vaccines for 6-year-old pre-school children in Shanghai. METHODS: A Markov-decision tree model was applied to evaluate two pertussis immunization strategies for 6-year-old pre-school children as following: (1) 1 dose of acellular pertussis (aP) contained vaccine (DTaP or Tdap) booster vaccinated at 6 years of age, and (2) no booster at 6 years of age regimen. Primary outcomes included quality-adjusted life years (QALYs), costs, and incremental cost-utility ratios (ICUR). Sensitivity analyses were performed. The analysis was conducted over a study period of 14 years from a societal perspective. RESULTS: Compared to no booster immunization strategy, administering 1 dose of acellular pertussis (aP) contained vaccine (DTaP or Tdap) booster at 6 years of age, resulted in an average cost reduction of CNY 814.16 (USD 116) per individual, an increase in QALYs by 0.00066, and a rise in per capita net monetary benefit (NMB) by CNY 933.51 (USD 132). The total costs over the study period were reduced by CNY 160.59 million (USD 23 million), utility increased by 130.49 QALYs, and NMB increased by CNY 184.14 million (USD 26 million). CONCLUSIONS: Implementing acellular pertussis booster immunization for 6-year-old pre-school children in Shanghai emerges as a cost-saving immunization strategy, with both cost savings and utility gains.
Asunto(s)
Análisis de Costo-Efectividad , Inmunización Secundaria , Años de Vida Ajustados por Calidad de Vida , Tos Ferina , Niño , Femenino , Humanos , Masculino , China/epidemiología , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/economía , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/administración & dosificación , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/inmunología , Inmunización Secundaria/economía , Cadenas de Markov , Vacuna contra la Tos Ferina/economía , Vacuna contra la Tos Ferina/administración & dosificación , Vacuna contra la Tos Ferina/inmunología , Vacunación/economía , Vacunación/métodos , Tos Ferina/prevención & control , Tos Ferina/economíaRESUMEN
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide and presents a significant threat to human health. Despite its prevalence, the underlying regulatory mechanisms of HCC remain unclear. In this study, we integrated RNA-seq datasets, proteome dataset and survival analysis and unveiled Stratifin (SFN) as a potential prognostic biomarker for HCC. SFN knockdown inhibited HCC progression in cell cultures and mouse models. Conversely, ectopic expression of Sfn in primary mouse HCC model accelerated HCC progression. Mechanistically, SFN acted as an adaptor protein, activating AKT1 signaling by fostering the interaction between PDK1 and AKT1, with the R56 and R129 sites on SFN proving to be crucial for this binding. In the syngeneic implantation model, the R56A/R129A mutant of SFN inhibited Akt signaling activation and impeded HCC growth. Additionally, peptide inhibitors designed based on the binding motif of AKT1 to SFN significantly inhibited HCC progression. In summary, our findings establish that SFN promotes HCC progression by activating AKT signaling through the R56 and R129 binding sites. This discovery opens new avenues for a promising therapeutic strategy for the treatment of HCC.
RESUMEN
The biosynthetic route for flavonol in Camptotheca acuminata has been recently elucidated from a chemical point of view. However, the genes involved in flavonol methylation remain unclear. It is a critical step for fully uncovering the flavonol metabolism in this ancient plant. In this study, the multi-omics resource of this plant was utilized to perform flavonol O-methyltransferase-oriented mining and screening. Two genes, CaFOMT1 and CaFOMT2 are identified, and their recombinant CaFOMT proteins are purified to homogeneity. CaFOMT1 exhibits strict substrate and catalytic position specificity for quercetin, and selectively methylates only the 4'-OH group. CaFOMT2 possesses sequential O-methyltransferase activity for the 4'-OH and 7-OH of quercetin. These CaFOMT genes are enriched in the leaf and root tissues. The catalytic dyad and critical substrate-binding sites of the CaFOMTs are determined by molecular docking and further verified through site-mutation experiments. PHE181 and MET185 are designated as the critical sites for flavonol substrate selectivity. Genomic environment analysis indicates that CaFOMTs evolved independently and that their ancestral genes are different from that of the known Ca10OMT. This study provides molecular insights into the substrate-binding pockets of two new CaFOMTs responsible for flavonol metabolism in C. acuminata.
Asunto(s)
Camptotheca , Metiltransferasas , Simulación del Acoplamiento Molecular , Especificidad por Sustrato , Camptotheca/enzimología , Camptotheca/genética , Metiltransferasas/genética , Metiltransferasas/metabolismo , Metiltransferasas/química , Flavonoles/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Filogenia , Metilación , Secuencia de AminoácidosRESUMEN
Endowing flexible and adaptable fiber devices with light-emitting capabilities has the potential to revolutionize the current design philosophy of intelligent, wearable interactive devices. However, significant challenges remain in developing fiber devices when it comes to achieving uniform and customizable light effects while utilizing lightweight hardware. Here, we introduce a mass-produced, wearable, and interactive photochromic fiber that provides uniform multicolored light control. We designed independent waveguides inside the fiber to maintain total internal reflection of light as it traverses the fiber. The impact of excessive light leakage on the overall illuminance can be reduced by utilizing the saturable absorption effect of fluorescent materials to ensure light emission uniformity along the transmission direction. In addition, we coupled various fluorescent composite materials inside the fiber to achieve artificially controllable spectral radiation of multiple color systems in a single fiber. We prepared fibers on mass-produced kilometer-long using the thermal drawing method. The fibers can be directly integrated into daily wearable devices or clothing in various patterns and combined with other signal input components to control and display patterns as needed. This work provides a new perspective and inspiration to the existing field of fiber display interaction, paving the way for future human-machine integration.