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We report on the development of a microwave frequency standard based on a laser-cooled 171 Y b + ion trap system. The electronics , lasers, and magnetic shields are integrated into a single physical package. With over 105 ions are stably trapped, the system offers a high signal-to-noise ratio Ramsey line-shape. In comparison with previous work, the frequency instability of a 171 Y b + microwave clock was further improved to 8.5×10-13/τ for averaging times between 10 and 1000 s. Essential systematic shifts and uncertainties are also estimated.
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During infectious disease outbreaks, inference of summary statistics characterizing transmission is essential for planning interventions. An important metric is the time-dependent reproduction number (Rt), which represents the expected number of secondary cases generated by each infected individual over the course of their infectious period. The value of Rt varies during an outbreak due to factors such as varying population immunity and changes to interventions, including those that affect individuals' contact networks. While it is possible to estimate a single population-wide Rt, this may belie differences in transmission between subgroups within the population. Here, we explore the effects of this heterogeneity on Rt estimates. Specifically, we consider two groups of infected hosts: those infected outside the local population (imported cases), and those infected locally (local cases). We use a Bayesian approach to estimate Rt, made available for others to use via an online tool, that accounts for differences in the onwards transmission risk from individuals in these groups. Using COVID-19 data from different regions worldwide, we show that different assumptions about the relative transmission risk between imported and local cases affect Rt estimates significantly, with implications for interventions. This highlights the need to collect data during outbreaks describing heterogeneities in transmission between different infected hosts, and to account for these heterogeneities in methods used to estimate Rt. This article is part of the theme issue 'Technical challenges of modelling real-life epidemics and examples of overcoming these'.
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COVID-19 , Teorema de Bayes , COVID-19/epidemiologia , Surtos de Doenças , Humanos , Reprodução , TempoRESUMO
AIM: To investigate the associations of skeletal muscle area and density with coronary atherosclerotic plaques and significant stenosis in asymptomatic adults. MATERIALS AND METHODS: A total of 243 consecutive subjects who had voluntarily undergone abdominal unenhanced computed tomography (CT) and coronary CT angiography (CCTA) as part of a general health examination were investigated retrospectively. Skeletal muscle area index (SMI) and skeletal muscle density (SMD) was assessed using CT. Coronary atherosclerotic plaques and stenosis on CCTA were evaluated. The associations of low SMI and low SMD with coronary atherosclerotic plaques and significant stenosis were determined by logistic regression analysis. RESULTS: After adjustment for cardiovascular risk factors, there were significant associations of low SMI or low SMD with atherosclerotic plaque, total significant stenosis, and significant stenosis caused by calcified or mixed plaques (for all p<0.05). In addition, multivariate regression analysis also showed that low SMI was independently associated with calcified plaque (p=0.038) and non-calcified plaque (p=0.006), and individuals with low SMD were more likely to have mixed plaque (p=0.001). CONCLUSION: Assessment of the skeletal muscle on CT help to identify asymptomatic adults at risk for coronary atherosclerosis.
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Composição Corporal , Músculo Esquelético/anatomia & histologia , Placa Aterosclerótica/epidemiologia , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/diagnóstico por imagem , Estudos RetrospectivosRESUMO
Objective: Systematically summarize the research progress of clinical trials of gastric cancer oncology drugs and the overview of marketed drugs in China from 2012 to 2021, providing data and decision-making evidence for relevant departments. Methods: Based on the registration database of the drug clinical trial registration and information disclosure platform of Food and Drug Administration of China and the data query system of domestic and imported drugs, the information on gastric cancer drug clinical trials, investigational drugs and marketed drugs from January 1, 2012 to December 31, 2021 was analyzed, and the differences between Chinese and foreign enterprises in terms of trial scope, trial phase, treatment lines and drug type, effect and mechanism studies were compared. Results: A total of 114 drug clinical trials related to gastric tumor were registered in China from 2012 to 2021, accounting for 3.7% (114/3 041) of all anticancer drug clinical trials in the same period, the registration number showed a significant growth rate after 2016 and reached its peak with 32 trials in 2020. Among them, 85 (74.6%, 85/114) trials were initiated by Chinese pharmaceutical enterprise. Compared with foreign pharmaceutical enterprise, Chinese pharmaceutical enterprise had higher rates of phase I trials (35.3% vs 6.9%, P=0.001), but the rate of international multicenter trials (11.9% vs 67.9%, P<0.001) was relatively low. There were 76 different drugs involved in relevant clinical trials, of which 65 (85.5%) were targeted drugs. For targeted drugs, HER2 is the most common one (14 types), followed by PD-1 and multi-target VEGER. In the past ten years, 3 of 4 marketed drugs for gastric cancer treatment were domestic and included in the national medical insurance directory. Conclusions: From 2012 to 2021, China has made some progress in drug research and development for gastric carcinoma. However, compared with the serious disease burden, it is still insufficient. Targeted strengthening of research and development of investment in many aspects of gastric cancer drugs, such as new target discovery, matured target excavating, combination drug development and early line therapy promotion, is the key work in the future, especially for domestic companies.
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Fármacos Gastrointestinais , Neoplasias Gastrointestinais , China , Fármacos Gastrointestinais/uso terapêutico , Humanos , Preparações Farmacêuticas , Estados Unidos , United States Food and Drug AdministrationRESUMO
Objective: To develop a nomogram model for the differential diagnosis of benign and malignant breast BI-RADS (Breast Imaging Reporting and Data System) category 4 nodules based on serum tumor specific protein 70 (SP70) and conventional laboratory indicators and validate its predictive efficacy. Methods: A case-control study design was used to retrospectively analyze the data of 429 female patients diagnosed with BI-RADS category 4 breast nodules by breast color doppler flow imaging at the First Affiliated Hospital of Nanjing Medical University from January 2021 to April 2022 with an age range of 16 to 91 years and a median age of 50 years, and the patients were divided into a training cohort (314 patients) and a validation cohort (115 patients) according to the inclusion time successively. Using postoperative pathological findings as the"gold standard", univariate and multivariate logistic regression analyses were used to identify the predictor variables used for the model. The nomogram, receiver operating characteristic (ROC) curves and calibration curves were drawn for the prediction model, and the discrimination and calibration of the model were evaluated using the consistency index (C-index) and calibration plots. Results: The postoperative pathological results showed that 286 (66.7%) were malignant nodules and 143 (33.3%) were benign nodules of 429 breast BI-RADS category 4 nodules. The serum SP70 (OR=1.227,95%CI: 1.033-1.458,P=0.020), NLR (OR=1.545,95%CI: 1.047-2.280,P=0.028), LDL-C (OR=2.215, 95%CI: 1.354-3.622, P=0.002), GLU (OR=2.050,95%CI:1.222-3.438,P=0.007), PT (OR=1.383,95%CI: 1.046-1.828,P=0.023), nodule diameter (OR=1.042, 95%CI: 1.008-1.076, P=0.015) and age (OR=1.062,95%CI: 1.011-1.116,P=0.016) were independent risk factors which could be used to distinguish benign and malignant breast BI-RADS category 4 nodules (P<0.05). The nomogram was plotted by the above seven independent variables, and the concordance index (C-index) for the training cohort and validation cohort were 0.842 (95%CI:0.786-0.898) and 0.787 (95%CI:0.687-0.886), respectively. The sensitivity and specificity of using this model to identify benign and malignant breast BI-RADS category 4 nodules in the training and validation cohort were 83.5%, 72.5% and 79.2%, 73.6%, respectively. The calibration curves showed good agreement between the predicted and actual values in the nomogram. Conclusions: This study combined serum SP70, conventional laboratory indicators and breast color doppler flow imaging to develop a nomogram model for the differential diagnosis of benign and malignant breast BI-RADS category 4 nodules. The model may have good predictive efficacy and may provide a basis for clinical treatment options, which is beneficial for guiding breast cancer screening and prevention.
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Neoplasias da Mama , Mama , Feminino , Humanos , Pessoa de Meia-Idade , Adolescente , Adulto Jovem , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Estudos Retrospectivos , Estudos de Casos e Controles , Mama/patologia , Neoplasias da Mama/patologiaRESUMO
Objective: To investigate the corneal graft survival and related risk factors of primary penetrating keratoplasty in congenital corneal opacity infants. Methods: It was a retrospective cohort study. Data were collected from forty-two infants (51 eyes) who were aged ≤12 months and diagnosed with congenital corneal opacity in Beijing Tongren Hospital and Beijing Anzhen Hospital from January 1, 2017 to January 31, 2018. The mean age at surgery was (5.7±2.2) months (3-12 months). The mean follow-up duration was (28.6±2.6) months (24-33 months). All the patients underwent penetrating keratoplasty. The status of the corneal grafts and complications were observed and recorded during the regular follow-up. The survival probabilities were estimated by using the Kaplan-Meier and Log-rank test. The graft survival between different influence factors was analyzed by using the χ2 test. Results: The Kaplan-Meier survival rates for penetrating keratoplasty were 84.3% (43/51) at 6 months, 78.4% (40/51) at 12 months and 60.8% (31/51) at the last follow-up. The presence of corneal neovascularization was significantly correlated with graft failure (χ²=5.264, P=0.022). The graft survival differed between eyes receiving combined surgery and mere penetrating keratoplasty and in eyes with varied surgical indications (P=0.039, <0.01). Increased intraocular pressure (7 eyes, 13.7%) and persistent epithelial defects (7 eyes, 13.7%) were the most common postoperative complications, followed by complicated cataract (4 eyes, 7.8%) and posterior capsule opacification (2 eyes, 3.9%). Conclusions: The graft survival rate was satisfactory following pediatric keratoplasty although it had a tendency to decrease with the follow-up time. Corneal neovascularization was a major risk factor of graft failure. Surgical indications and procedures also had a certain effect on the graft survival.
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Doenças da Córnea , Neovascularização da Córnea , Opacidade da Córnea , Anormalidades do Olho , Criança , Doenças da Córnea/complicações , Doenças da Córnea/cirurgia , Neovascularização da Córnea/complicações , Neovascularização da Córnea/cirurgia , Opacidade da Córnea/cirurgia , Anormalidades do Olho/cirurgia , Seguimentos , Sobrevivência de Enxerto , Humanos , Lactente , Ceratoplastia Penetrante/efeitos adversos , Ceratoplastia Penetrante/métodos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
We measured the ground-state hyperfine splitting of trapped 113Cd+ ions to be 15199862855.02799(27) Hz with a fractional uncertainty of 1.8×10-14. The ions were trapped and laser-cooled in a linear quadrupole Paul trap. The fractional frequency stability was measured to be 4.2×10-13/τ, obtained from Ramsey fringes of high signal-to-noise ratios and taken over a measurement time of nearly 5 h, which is close to the short-term stability limit estimated from the Dick effect. Our result is consistent with previously reported values, but the measurement precision is four times better than the best result obtained to date.
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Objiective: To evaluate the prognosis of visual function and the impact of surgery in pediatric patients with sellar mass lesions, as evidenced by diffusion tensor imaging (DTI) and visual evoked potentials. Methods: Twenty patients with sellar mass lesions were included in the study. DTI and visual evoked potentials were obtained before and after surgery. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were calculated for both optic nerves. DTI parameters and visual evoked potential amplitudes were compared for all patients to assess the correlation between DTI parameters and visual function. Results: The 20 patients were divided into two groups according the relationship between the lesions and the optic chiasm. The FA values increased significantly after operation, while the ADC values decreased (P<0.05). And the average amplitude of visual evoked potentials after operation was significantly higher than before operation (P<0.05). Conclusions: DTI assessments of the affected sides, with the resulting FA and ADC values, may help to estimate the visual improvement produced by surgical therapy in the early postoperative period. Surgical removal can improve visual function dramatically.
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Imagem de Tensor de Difusão , Oftalmopatias , Anisotropia , Criança , Imagem de Difusão por Ressonância Magnética , Potenciais Evocados Visuais , HumanosRESUMO
This study aimed to investigate the effects of Wuzhi capsule on blood concentration of tacrolimus after renal transplantation. Sixty patients after allogenic renal transplantation were enrolled in this study and randomly divided into an experimental group and a control group. One oral Wuzhi capsule was taken in the morning and evening for patients in the experimental group, while none was given to the control group, maintaining the trough blood concentration of tacrolimus in the normal range. After 3 weeks, the changes of tacrolimus dosage and hepatorenal function in the two groups were compared. Comparisons of drug dosage and blood concentration C0 value of tacrolimus before initiating the experiment showed that there was no statistically ignificant difference (P>0.05) between the two groups. The differences of blood concentration of tacrolimus and hepatorenal function for patients in both two groups after 3 weeks treatment also showed no statistical significance (P>0.05), whereas a statistically significant decrease was demonstrated in the tacrolimus dosage of the Wuzhi capsule group compared with that of the control group (P=0.0083). After renal transplantation, Wuzhi capsules were added so as to enable tacrolimus to reach a suitable blood concentration, which can prevent the occurrence of renal transplantation rejection, thus alleviating the economic burden of patients and producing larger social benefits.
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Medicamentos de Ervas Chinesas/uso terapêutico , Transplante de Rim , Tacrolimo/sangue , Adulto , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/farmacologia , Feminino , Humanos , Rim/efeitos dos fármacos , Rim/fisiopatologia , Fígado/efeitos dos fármacos , Fígado/fisiopatologia , Masculino , Pessoa de Meia-Idade , Tacrolimo/efeitos adversos , Adulto JovemRESUMO
We investigated the effect of pregnane X receptor (PXR) polymorphisms on tacrolimus (FK506) blood trough concentrations and the associated adverse reactions in kidney transplantation recipients (KTRs). Polymerase chain reaction (PCR)-restriction fragment length polymorphism was used to detect the genotypes of single nucleotide polymorphism loci in 336 KTRs. The PXR six-base deletion mutation was classified using specific allele PCR, and the FK506 blood trough concentration in the KTRs was measured by chemiluminescent microparticle immunoassay. There were significant differences in adverse reactions resulting from FK506 in age, weight, body mass index (BMI) and treatment course (P < 0.05). Logistical regression revealed that the FK506 treatment course and BMI were risk factors for hyperlipidemia, and the risk of hyperlipidemia increased 27.534 times when the BMI was less than 18.5. Moreover, age was also a risk factor leading to hyperglycemia. FK506 blood trough concentration and C0/D value had an impact on adverse reactions induced by hyperglycemia. The KTRs' PXR rs3842689, rs6785049, and rs1523127 mutation frequencies were 26.07, 11.79, and 16.07%, respectively. There was no statistically significant difference in the mutation frequency of each locus between the control group and the adverse reaction groups. Therefore, rs3842689, 7635G>A (rs6785049), and 24381C>A (rs1523127) PXR polymorphisms have no obvious impact on FK506; furthermore, the PXR rs3842689 wild-type homozygous WW genotype is a risk factor of FK506 and results in gastrointestinal reactions.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/genética , Transplante de Rim/efeitos adversos , Receptores de Esteroides/genética , Tacrolimo/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/sangue , Genótipo , Humanos , Imunossupressores/sangue , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Receptor de Pregnano X , Fatores de Risco , Deleção de Sequência , Tacrolimo/uso terapêuticoRESUMO
Hepatocellular carcinoma (HCC) is the fifth most common cancer. An important approach to control HCC is chemoprevention. This study aims at investigating the antitumor effect of Tetramethylpyrazine (TMP). Rats were injected with N-Nitrosodiethylamine (DEN) to establish HCC. Tumor development was observed. Liver function was evaluated. Apoptosis and cell cycle arrest-related makers and signaling cascades were determined by Western blot, RT-PCR and flow cytometric analysis. The administration of TMP could significantly inhibit tumor development in DEN-induced HCC rats, shown by reduced incidence of tumor, decreased number of tumor nodules and reduced maximal size of tumor. DEN-induced increase of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase and alkaline phosphatase activities were significantly inhibited by TMP. TMP exhibited inhibitory effect on HCC through induction of apoptosis and cell cycle arrest in rats. TMP induced apoptosis through increasing Bax, decreasing Bcl-2, increasing the release of cytochrome c, and activating caspase, which consisted of the mitochondrial apoptotic pathway. TMP induced G2/M cell cycle arrest through down-regulation of cyclin B1/cdc2. In addition, inhibition of Akt and ERK signaling and the antioxidant activities of TMP may also contribute to its antitumor effect. These data provide new insight into the mechanisms underlying the antitumor effect of TMP.
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Antineoplásicos Fitogênicos/uso terapêutico , Hepatócitos/efeitos dos fármacos , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Pirazinas/uso terapêutico , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Animais , Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/biossíntese , Proteínas Reguladoras de Apoptose/genética , Aspartato Aminotransferases/sangue , Ciclo Celular/efeitos dos fármacos , Dietilnitrosamina , Ensaios de Seleção de Medicamentos Antitumorais , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Hepatócitos/patologia , L-Lactato Desidrogenase/sangue , Neoplasias Hepáticas Experimentais/sangue , Neoplasias Hepáticas Experimentais/genética , Neoplasias Hepáticas Experimentais/patologia , Mitocôndrias Hepáticas/efeitos dos fármacos , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/sangue , Proteínas de Neoplasias/genética , Oxirredução , Pirazinas/farmacologia , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Carga TumoralRESUMO
We conducted this case-control study to assess the role of the VEGF -2578C/A, +1612G/A, +936C/T and -634G/C gene polymorphisms in the development of renal cell carcinoma (RCC). A hospital-based case-control study was conducted in a 360 consecutive primary RCC patients and 360 age and gender-matched controls during January 2010 and January 2014. The polymerase chain reaction-restriction fragment length polymorphism was used for VEGF -2578C/A, +1612G/A, +936C/T and -634G/C genotyping. Multivariate conditional logistic regression analyses showed that subjects carrying the AA and the CA+AA genotypes of VEGF -2578C/A had significant association with increased risk of RCC compared to those having the CC genotype, and the ORs (95%CI) were 1.77 (1.10-2.85) and 1.37 (1.01-1.86), respectively. Using the conditional logistic regression model, CA+AA genotype of VEGF -2578C/A had a significantly increased risk of RCC in ever cigarette smokers, and individuals with hypertension, and the ORs (95%CI) were 1.93 (1.08-3.45) and 2.57 (1.06-6.57), respectively. In conclusion, our results showed that AA genotype of VEGF -2578C/A genetic variants is associated with increased risk of RCC.
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Carcinoma de Células Renais/genética , Neoplasias Renais/genética , Fator A de Crescimento do Endotélio Vascular/genética , Adulto , Estudos de Casos e Controles , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , RiscoRESUMO
The Bit-1 protein appears to be aâ¯part of the integrin-specific signaling pathway involved into anoikis. When Bit1 is released from the mitochondria into the cytoplasm it can elicit caspase-independent apoptosis. The expression of Bit1 in 78 serous papillary adenocarcinomas and 78 normal epithelial ovarian tissue specimens was analyzed by immunohistochemistry. We also investigate Bit1 function by transfection. Bit1 was expressed in 100% and 33.3% of ovarian cancers and normal epithelial tissues, respectively, and its expression was significantly correlated with histologic grade and overall survival. However, Bit1 expression was not associated with age. We also confirmed that Bit1 overexpression in cytosol of Caov-3 cells induced apoptosis. Bit1 may be a useful pathological marker and a prognostic marker for serous papillary adenocarcinomas outcome. Its pro-apoptotic property also makes it a potential gene medicine for ovarian cancers therapy.
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Adenocarcinoma Papilar/patologia , Hidrolases de Éster Carboxílico/fisiologia , Cistadenocarcinoma Seroso/patologia , Proteínas Mitocondriais/fisiologia , Neoplasias Ovarianas/patologia , Transcrição Gênica , Adenocarcinoma Papilar/mortalidade , Apoptose , Hidrolases de Éster Carboxílico/análise , Ciclo Celular , Linhagem Celular Tumoral , Cistadenocarcinoma Seroso/mortalidade , Feminino , Humanos , Proteínas Mitocondriais/análise , Neoplasias Ovarianas/mortalidadeRESUMO
An in vitro fermentation was conducted to determine the effects of hainanmycin on protein degradation and populations of ammonia-producing bacteria. The substrates (DM basis) for in vitro fermentation consisted of alfalfa hay (31.7%), Chinese wild rye grass hay (28.3%), ground corn grain (24.5%), soybean meal (15.5%) with a forage: concentrate of 60:40. Treatments were the control (no additive) and hainanmycin supplemented at 0.1 (H0.1), 1 (H1), 10 (H10), and 100 mg/kg (H100) of the substrates. After 24 h of fermentation, the highest addition level of hainanmycin decreased total VFA concentration and increased the final pH. The high addition level of hainanmycin (H1, H10, and H100) reduced (p<0.05) branched-chain VFA concentration, the molar proportion of acetate and butyrate, and ratio of acetate to propionate; and increased the molar proportion of propionate, except that for H1 the in molar proportion of acetate and isobutyrate was not changed (p>0.05). After 24 h of fermentation, H10 and H100 increased (p<0.05) concentrations of peptide nitrogen and AA nitrogen and proteinase activity, and decreased (p<0.05) NH3-N concentration and deaminase activity compared with control. Peptidase activitives were not affected by hainanmycin. Hainanmycin supplementation only inhibited the growth of Butyrivibrio fibrisolvens, which is one of the species of low deaminative activity. Hainanmycin supplementation also decreased (p<0.05) relative population sizes of hyper-ammonia-producing species, except for H0.1 on Clostridium aminophilum. It was concluded that dietary supplementation with hainanmycin could improve ruminal fermentation and modify protein degradation by changing population size of ammonia-producing bacteria in vitro; and the addition level of 10 mg/kg appeared to achieve the best results.
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Presented here is a magnetic hydrogel particle enabled workflow for capturing and concentrating SARS-CoV-2 from diagnostic remnant swab samples that significantly improves sequencing results using the Oxford Nanopore Technologies MinION sequencing platform. Our approach utilizes a novel affinity-based magnetic hydrogel particle, circumventing low input sample volumes and allowing for both rapid manual and automated high throughput workflows that are compatible with Nanopore sequencing. This approach enhances standard RNA extraction protocols, providing up to 40 × improvements in viral mapped reads, and improves sequencing coverage by 20-80% from lower titer diagnostic remnant samples. Furthermore, we demonstrate that this approach works for contrived influenza virus and respiratory syncytial virus samples, suggesting that it can be used to identify and improve sequencing results of multiple viruses in VTM samples. These methods can be performed manually or on a KingFisher automation platform.
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COVID-19 , Sequenciamento por Nanoporos , Humanos , SARS-CoV-2 , Sequenciamento por Nanoporos/métodos , Hidrogéis , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Fenômenos MagnéticosRESUMO
OBJECTIVE: To investigate the effect of suppressing high-mobility group box 1 (HMGB1) on neuronal autophagy and apoptosis in rats after intracerebral hemorrhage (ICH) in rats. METHODS: Rat models of ICH induced by intracerebral striatum injection of 0.2 U/mL collagenase â £ were treated with 1 mg/kg anti-HMGB1 mAb or a control anti-IgG mAb injected via the tail immediately and at 6 h after the operation (n=5). The rats in the sham-operated group (with intracranial injection of 2 µL normal saline) and ICH model group (n=5) were treated with PBS in the same manner after the operation. The neurological deficits of the rats were evaluated using modified neurological severity score (mNSS). TUNEL staining was used to detect apoptosis of the striatal neurons, and the expressions of HMGB1, autophagy-related proteins (Beclin-1, LC3-â ¡ and LC3-â ) and apoptosis-related proteins (Bcl-2, Bax and cleaved caspase-3) in the brain tissues surrounding the hematoma were detected using Western blotting. The expression of HMGB1 in the striatum was detected by immunohistochemistry, and serum level of HMGB1 was detected with ELISA. RESULTS: The rat models of ICH showed significantly increased mNSS (P < 0.05), which was markedly lowered after treatment with anti- HMGB1 mAb (P < 0.05). ICH caused a significant increase of apoptosis of the striatal neurons (P < 0.05), enhanced the expressions of beclin-1, LC3-â ¡, Bax and cleaved caspase-3 (P < 0.05), lowered the expressions of LC3-â and Bcl-2 (P < 0.05), and increased the content of HMGB1 (P < 0.05). Treatment with anti-HMGB1 mAb obviously lowered the apoptosis rate of the striatal neurons (P < 0.05), decreased the expressions of Beclin-1, LC3-â ¡, Bax and cleaved caspase-3 (P < 0.05), increased the expressions of LC3-â and Bcl-2 (P < 0.05), and reduced the content of HMGB1 in ICH rats (P < 0.05). CONCLUSION: Down- regulation of HMGB1 by anti-HMGB1 improves neurological functions of rats after ICH possibly by inhibiting autophagy and apoptosis of the neurons.
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Autofagia , Hemorragia Cerebral , Animais , Apoptose , Proteínas Reguladoras de Apoptose/metabolismo , Proteína Beclina-1 , Caspase 3/metabolismo , Hemorragia Cerebral/terapia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Sprague-Dawley , Proteína X Associada a bcl-2/metabolismoRESUMO
The currently used vaccine against tuberculosis, Bacille Calmette-Guérin (BCG), has variable efficacy, so new vaccine development is crucial. In this study, we evaluated a recombinant vaccine prepared from non-pathogenic Mycobacterium smegmatis (rMS) that expresses a fusion of early secreted antigenic target 6-kDa antigen (ESAT6) and culture filtrate protein 10 (CFP10). C57BL/6 mice were immunized with the rMS expressing the ESAT6-CFP10 fusion protein (rM.S-e6c10) or with BCG. The mice in the rM.S-e6c10 group had a significantly higher titre of anti-ESAT6-CFP10 antibodies than did animals in the BCG or saline groups. Spleen cells from rM.S-e6c10-immunized mice exhibited a cytotoxic response to ESAT6 and CFP10-expressed target cells, but spleen cells from animals in the other groups did not. Levels of IFN-γ and IL-2 production by purified T cells from spleens were significantly higher in rM.S-e6c10 group than in BCG group. Finally, after M. tuberculosis (MTB)-challenged mice, dramatic reduction in the numbers of MTB colony-forming units (CFUs) in the lungs was observed for the mice immunized with the rMS. The protective efficacy of rM.S-e6c10 and BCG vaccination was similar based on measures of MTB burden and lung pathology. Our data indicate that the recombinant M. smegmatis vaccine expressing the ESAT6-CFP10 fusion protein has potential in clinic application.
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Antígenos de Bactérias/imunologia , Proteínas de Bactérias/imunologia , Mycobacterium smegmatis/imunologia , Mycobacterium tuberculosis/imunologia , Proteínas Recombinantes de Fusão/imunologia , Animais , Anticorpos Antibacterianos/sangue , Antígenos de Bactérias/genética , Antígenos de Bactérias/metabolismo , Vacina BCG/administração & dosagem , Vacina BCG/imunologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Citotoxicidade Imunológica/imunologia , Ensaio de Imunoadsorção Enzimática , Imunofluorescência , Imunização/métodos , Interferon gama/metabolismo , Interleucina-2/metabolismo , Linfócitos/imunologia , Linfócitos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Mycobacterium smegmatis/genética , Mycobacterium smegmatis/metabolismo , Proteínas Recombinantes de Fusão/metabolismo , Baço/imunologia , Baço/metabolismo , Transfecção , Tuberculose/imunologia , Tuberculose/prevenção & controle , Vacinas contra a Tuberculose/administração & dosagem , Vacinas contra a Tuberculose/imunologiaRESUMO
Dead plant tissues and ash from a prescribed fire play an important role in nutrient balance and cycling in the Florida Everglades ecosystem. The objective of this study was to assess the dynamic changes in total phosphorus release (TPr) from ash or tissues of either cattail (Typha domingensis Pers.) or sawgrass (Cladium jamaicense Crantz) to water. Natural-dead (senesced-dead) and burning-dead (standing-dead due to a prescribed fire) cattail and sawgrass were collected from highly (H) and moderately (M) impacted zones in the Florida Everglades. This experiment was conducted by incubation and water-extraction of the materials in plastic bottles for 65 d at room temperature (24 +/- 1 degrees C). Results showed that 63 to 88%, 17 to 48%, 9 to 20%, and 13 to 28% of total P (TPp) were released as TPr from cattail and sawgrass ash, cattail tissues from the H zone, cattail tissues, and sawgrass tissues from the M zone, respectively. TPp means total P of plant tissues, whereas TPr is total P release from the tissues or ash. Most of the TPr was released within 24 h after burning. The quick release of TPr observed in this experiment may help explain the P surge in the surface water immediately following a fire in the marsh. These findings suggest that prescribed burning accelerates P release from cattail and sawgrass. They also imply that it is very important to keep the water stagnant in the first 24 h to maximize the benefits of a prescribed fire in the Everglades.
Assuntos
Fósforo/metabolismo , Poaceae/metabolismo , Áreas Alagadas , Poaceae/classificação , Solubilidade , Especificidade da EspécieRESUMO
Here we present a rapid and versatile method for capturing and concentrating SARS-CoV-2 from contrived transport medium and saliva samples using affinity-capture magnetic hydrogel particles. We demonstrate that the method concentrates virus from 1 mL samples prior to RNA extraction, substantially improving detection of virus using real-time RT-PCR across a range of viral titers (100-1,000,000 viral copies/mL) and enabling detection of virus using the 2019 nCoV CDC EUA Kit down to 100 viral copies/mL. This method is compatible with commercially available nucleic acid extraction kits (i.e., from Qiagen) and a simple heat and detergent method that extracts viral RNA directly off the particle, allowing a sample processing time of 10 min. We furthermore tested our method in transport medium diagnostic remnant samples that previously had been tested for SARS-CoV-2, showing that our method not only correctly identified all positive samples but also substantially improved detection of the virus in low viral load samples. The average improvement in cycle threshold value across all viral titers tested was 3.1. Finally, we illustrate that our method could potentially be used to enable pooled testing, as we observed considerable improvement in the detection of SARS-CoV-2 RNA from sample volumes of up to 10 mL.