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Nickel and palladium complexes bearing "sandwich" diimine ligands with perfluorinated aryl caps have been synthesized, characterized, and explored in ethylene polymerization reactions. The X-ray crystallographic analysis of the precatalysts 16 and 6b shows differences from their nonfluorinated analogues 17 and 19, with the perfluorinated aryl caps centered precisely over the nickel and palladium centers, which results in higher buried volumes of the metal centers relative to the nonfluorinated analogues. The sandwich diimine-palladium complexes 5a and 5b containing perfluorinated aryl caps polymerize ethylene in a controlled fashion with activities that are substantially increased compared with their nonfluorinated analogues. Migratory insertion rates in relevant methyl ethylene complexes agree with the activities exhibited in bulk polymerization experiments. DFT studies suggest that facility of ethylene rotation from its preferred orientation perpendicular to the Pd-alkyl bond into a parallel in-plane conformation contributes to the higher polymerization activity for 5b relative to 18a. For these palladium systems, polymer molecular weights can be controlled via hydrogen addition (hydrogenolysis), which is unusual for late-transition-metal-catalyzed olefin polymerizations with no catalyst deactivation occurring. Sandwich diimine-nickel complexes 6a and 6b with perfluorinated aryl caps show ethylene polymerization activities that are about half of those of classical tetraisopropyl-substituted catalyst 2 but again are more active than the analogous nonfluorinated sandwich complexes. Ethylene polymerizations exhibit living behavior, and branched ultrahigh-molecular-weight polyethylenes (UHMWPEs) with very low-molecular-weight distributions (less than 1.1) are obtained. The activated nickel catalysts are stable in the absence of monomer and show good long-term stability at 25 °C.
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Curcumin, an extensively utilized natural pigment in the food industry, has attracted considerable attention due to its potential therapeutic effects, such as anti-tumorigenic and anti-inflammatory activities. The enzyme 17ß-Hydroxysteroid dehydrogenase 1 (17ß-HSD1) holds a crucial position in oestradiol production and exhibits significant involvement in oestrogen-responsive breast cancers and endometriosis. This study investigated the inhibitory effects of curcuminoids, metabolites, and analogues on 17ß-HSD1, a key enzyme in oestradiol synthesis. Screening 10 compounds, including demethoxycurcumin (IC50, 3.97 µM) and dihydrocurcumin (IC50, 5.84 µM), against human and rat 17ß-HSD1 revealed varying inhibitory potencies. These compounds suppressed oestradiol secretion in human BeWo cells at ≥ 5-10 µM. 3D-Quantitative structure-activity relationship (3D-QSAR) and molecular docking analyses elucidated the interaction mechanisms. Docking studies and Gromacs simulations suggested competitive or mixed binding to the steroid or NADPH/steroid binding sites of 17ß-HSD1. Predictive 3D-QSAR models highlighted the importance of hydrophobic regions and hydrogen bonding in inhibiting 17ß-HSD1 activity. In conclusion, this study provides valuable insights into the inhibitory effects and mode of action of curcuminoids, metabolites, and analogues on 17ß-HSD1, which may have implications in the field of hormone-related disorders.
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17-Hidroxiesteroide Desidrogenases , Curcumina , Simulação de Acoplamento Molecular , Relação Quantitativa Estrutura-Atividade , Humanos , Ratos , Animais , Curcumina/análogos & derivados , Curcumina/farmacologia , Curcumina/química , 17-Hidroxiesteroide Desidrogenases/antagonistas & inibidores , 17-Hidroxiesteroide Desidrogenases/metabolismo , Estradiol/análogos & derivados , Estradiol/química , Estradiol/farmacologia , Estradiol/metabolismo , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/químicaRESUMO
Cross-species studies are important for a comprehensive understanding of brain functions. However, direct quantitative comparison of behaviors across species presents a significant challenge. To enable such comparisons in perceptual decision-making, we developed a synchronized evidence accumulation task for rodents and humans, by aligning mechanics, stimuli, and training. Rats, mice and humans readily learned the task and exhibited qualitatively similar performance. Quantitative model comparison revealed that all three species employed an evidence accumulation strategy, but differed in speed, accuracy, and key decision parameters. Human performance prioritized accuracy, whereas rodent performance was limited by internal time-pressure. Rats optimized reward rate, while mice appeared to switch between evidence accumulation and other strategies trial-to-trial. Together, these results reveal striking similarities and species-specific priorities in decision-making. Furthermore, the synchronized behavioral framework we present may facilitate future studies involving cross-species comparisons, such as evaluating the face validity of animal models of neuropsychiatric disorders. Highlights: Development of a free response evidence accumulation task for rats and miceSynchronized video game allows direct comparisons with humansRat, mouse and human behavior are well fit by the same decision modelsModel parameters reveal species-specific priorities in accumulation strategy.
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Next-generation humanised mouse models and single-cell RNA sequencing (scRNAseq) approaches enable in-depth studies into human immune cell biology. Here we used NSG-SGM3 mice engrafted with human umbilical cord haematopoietic stem cells to investigate how human immune cells respond to and/or are changed by traumatic spinal cord injury (SCI). We hypothesised that the use of such mice could help advance our understanding of spinal cord injury-induced immune depression syndrome (SCI-IDS), and also how human leukocytes change as they migrate from the circulation into the lesion site. Our scRNAseq experiments, supplemented by flow cytometry, demonstrate the existence of up to 11 human immune cell (sub-) types and/or states across the blood and injured spinal cord (7 days post-SCI) of humanised NSG-SGM3 mice. Further comparisons of human immune cell transcriptomes between naïve, sham-operated and SCI mice identified a total of 579 differentially expressed genes, 190 of which were 'SCI-specific' (that is, genes regulated only in response to SCI but not sham surgery). Gene ontology analysis showed a prominent downregulation of immune cell function under SCI conditions, including for T cell receptor signalling and antigen presentation, confirming the presence of SCI-IDS and the transcriptional signature of human leukocytes in association with this phenomenon. We also highlight the activating influence of the local spinal cord lesion microenvironment by comparing the transcriptomes of circulating versus infiltrated human immune cells; those isolated from the lesion site were enriched for genes relating to both immune cell activity and function (e.g., oxidative phosphorylation, T cell proliferation and antigen presentation). We lastly applied an integrated bioinformatics approach to determine where immune responses in humanised NSG-SGM3 mice appear congruent to the native responses of human SCI patients, and where they diverge. Collectively, our study provides a valuable resource and methodological framework for the use of these mice in translational research.
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Doenças da Medula Espinal , Traumatismos da Medula Espinal , Camundongos , Humanos , Animais , Traumatismos da Medula Espinal/metabolismo , Leucócitos/patologia , Expressão Gênica , Análise de Sequência de RNARESUMO
BACKGROUND: Thyroid microcarcinoma (TMC) incidence has significantly increased in recent decades. The rates of lymph node metastasis extrathyroidal extension have been significantly different in patients with TMC ≤5 mm versus those with size >5 mm. The current analysis aimed to examine the clinicopathologic features of TMC measuring <5 mm and to compare them with those of TMC ≥5 mm. METHODS: A total of 273 patients with TMC confirmed by histological examination from December 2020 to May 2021 were enrolled in Bach Mai Hospital, Hanoi, Vietnam. Unconditional logistic regression models were used to determine the association between clinicopathological factors and tumor size, central lymph node metastasis and extrathyroidal extension. RESULTS: We found 212/273 patients (77.7%) were diagnosed incidentally. The majority of patients were female (87.5%) and had a mean age of 44.2 years. The mean tumor size (±standard deviation (SD)) was 5.72 ± 2.33 mm. Most of the patients were also diagnosed with papillary TMC. Multifocal and bilateral lesions accounted for 13.2% and 12.1%, respectively. The extrathyroidal invasion was observed in 14.7% (40 patients), while 24.5% (67 patients) were those with central lymph node metastases. The rate of extrathyroidal extension in patients with tumor size ≥5 mm was significantly higher than in patients with tumor size <5 mm (odds ratio (OR) = 4.98; 95% confidence interval (CI): 1.48-16.70; p = 0.004). Patients with body mass index (BMI) <23 kg/m2 were found to be protected against the odds of extrathyroidal extension (OR = 0.38, 95% CI: 0.19-0.75; p = 0.004) compared to those with BMI ≥23 kg/m2. In univariable mode, central lymph node metastasis was positively associated with the odds of the presence of extrathyroidal extension (OR = 2.70, 95% CI: 1.34-5.45; p = 0.004). In the multivariable model, central lymph node metastasis was also associated with the presence of extrathyroidal extension (OR = 2.507, 95% CI: 1.194-5.264; p = 0.017). Univariate analysis demonstrated that tumor size ≥5 mm (OR = 2.04; 95% CI: 1.01-4.17; p = 0.047) and extrathyroidal extension (OR = 2.71; 95% CI: 1.34-5.45; p = 0.004) were risk factors of central cervical lymph node metastasis. In multivariable models, the extrathyroidal extension was associated with central lymph metastasis. CONCLUSIONS: TMC <5 mm tumor size is less likely to have aggressive characteristics, including extrathyroidal extension, than a TMC ≥5 mm. Long-term follow-up studies are thus warranted to investigate the factors in the prognosis of TMC.
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Neoplasias da Glândula Tireoide , Humanos , Masculino , Feminino , Adulto , Metástase Linfática/patologia , Vietnã/epidemiologia , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/patologia , Linfonodos/patologia , Fatores de RiscoRESUMO
BACKGROUND: After-hour calls can be resource intensive and remain a significant challenge to medical practices, though they have historically been poorly or non-reimbursable services. This study reviews after-hour calls from hematology/oncology patients at a cancer center to characterize after-hour care needs, identify care gaps, and look for opportunities to improve outpatient healthcare delivery. METHODS: This descriptive, retrospective Institutional Review Board-approved study analyzed patient calls between June 2015 to February 2021 in an academic hematology/oncology practice. Data from 500 calls were reviewed and cataloged into a database including patient demographics, clinical history, and information surrounding the call (e.g., primary reason for the call, outcome of the call). Calls were also categorized as being urgent or not from a patient or provider's perspective. RESULTS: Among 500 calls, representing 398 unique patients, the average patient was 62 years old and 52% of calls were from females. Most calls were made to report symptoms (65%), followed by calls to follow-up on labs, tests, or imaging (13%), and clarifying treatment plans (10%). Oncology patients represented 67% of calls and hematology (malignant and benign) patients represented 33%. More specifically, patients with gastrointestinal cancer (25%), hematologic malignancies (24%), and thoracic cancer (13%) represented the diagnoses with the highest call volume. CONCLUSIONS: This study explores the complexity and variety of after-hour cancer patient calls. By systematically exploring patient calls, this data can provide insight into patients' needs outside of regular clinic times and help practices develop strategies to anticipate these needs, reduce after-hour call burden, and improve overall quality of care.
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Hematologia , Neoplasias , Feminino , Humanos , Pessoa de Meia-Idade , Oncologia , Estudos Retrospectivos , Telefone , MasculinoRESUMO
How and where patients with advanced cancer facing limited survival spend their time is critical. Healthcare contact days (days with healthcare contact outside the home) offer a patient-centered and practical measure of how much of a person's life is consumed by healthcare. We retrospectively analyzed contact days among decedent veterans with stage IV gastrointestinal cancer at the Minneapolis Veterans Affairs Healthcare System from 2010 to 2021. Among 468 decedents, the median overall survival was 4 months. Patients spent 1 in 3 days with healthcare contact. Over the course of illness, the percentage of contact days followed a "U-shaped" pattern, with an initial post-diagnosis peak, a lower middle trough, and an eventual rise as patients neared the end-of-life. Contact days varied by clinical factors and by sociodemographics. These data have important implications for improving care delivery, such as through care coordination and communicating expected burdens to and supporting patients and care partners.
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Neoplasias Gastrointestinais , Veteranos , Humanos , Estados Unidos/epidemiologia , Estudos Retrospectivos , Atenção à Saúde , Neoplasias Gastrointestinais/terapiaRESUMO
AIM: To establish an artificial neural network (ANN) model to predict subsolid nodules (SSNs) before percutaneous core-needle biopsy (PCNB). The results of the two methods were compared to provide guidance on the treatment of SSNs. MATERIALS AND METHODS: This was a single-centre retrospective study using data from 1,459 SSNs between 2013 and 2021. The ANN was developed using data from patients who underwent surgery following computed tomography (CT) (SFC) and validated using data from patients who underwent surgery following biopsy (SFB). The prediction results of the ANN for the PCNB group and the histopathological results obtained after biopsy were compared with the histopathological results of lung nodules in the same group after surgery. Additionally, the choice of predictors for PCNB was analysed using multivariate analysis. RESULTS: There was no significant difference between the accuracies of the ANN and PCNB in the SFB group (p=0.086). The sensitivity of PCNB was lower than that of the ANN (p=0.000), but the specificity was higher (p=0.001). PCNB had better diagnostic ability than the ANN. The incidence of precursor lesions and non-neoplastic lesions in the SFB group was lower than that in the SFC group (p=0.000). A history of malignant tumours, size (2-3 cm), volume (>400 cm3) and mean CT value (≥-450 HU) are important factors for selecting PCNB. CONCLUSIONS: Both ANN and PCNB have comparable accuracy in diagnosing SSNs; however, PCNB has a slightly higher diagnostic ability than ANN. Selecting appropriate patients for PCNB is important for maximising the benefit to SSN patients.
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Neoplasias Pulmonares , Nitrobenzenos , Tomografia Computadorizada por Raios X , Humanos , Estudos Retrospectivos , Biópsia , Biópsia com Agulha de Grande Calibre , Tomografia Computadorizada por Raios X/métodos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologiaRESUMO
In quantum thermodynamics, the two-projective-measurement (TPM) scheme provides a successful description of stochastic work only in the absence of initial quantum coherence. Extending the quantum work distribution to quasiprobability is a general way to characterize work fluctuation in the presence of initial coherence. However, among a large number of different definitions, there is no consensus on the most appropriate work quasiprobability. In this article, we list several physically reasonable requirements including the first law of thermodynamics, time-reversal symmetry, positivity of second-order moment, and a support condition for the work distribution. We prove that the only definition that satisfies all these requirements is the Margenau-Hill (MH) quasiprobability of work. In this sense, the MH quasiprobability of work shows its advantages over other definitions. As an illustration, we calculate the MH work distribution of a breathing harmonic oscillator with initial squeezed states and show the convergence to classical work distribution in the classical limit.
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Spatial transcriptomics (ST) technologies generate multiple data types from biological samples, namely gene expression, physical distance between data points, and/or tissue morphology. Here we developed three computational-statistical algorithms that integrate all three data types to advance understanding of cellular processes. First, we present a spatial graph-based method, pseudo-time-space (PSTS), to model and uncover relationships between transcriptional states of cells across tissues undergoing dynamic change (e.g. neurodevelopment, brain injury and/or microglia activation, and cancer progression). We further developed a spatially-constrained two-level permutation (SCTP) test to study cell-cell interaction, finding highly interactive tissue regions across thousands of ligand-receptor pairs with markedly reduced false discovery rates. Finally, we present a spatial graph-based imputation method with neural network (stSME), to correct for technical noise/dropout and increase ST data coverage. Together, the algorithms that we developed, implemented in the comprehensive and fast stLearn software, allow for robust interrogation of biological processes within healthy and diseased tissues.
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Algoritmos , Software , Comunicação Celular , Perfilação da Expressão Gênica/métodos , Redes Neurais de Computação , TranscriptomaRESUMO
We analytically calculate the cumulant generating function of energy and particle transport in an open one-dimensional Kitaev chain at finite temperature by utilizing the Keldysh technique. The joint distribution of particle and energy currents satisfies different fluctuation relations in different regions of the parameter space as a result of U(1) symmetry breaking and energy conservation. Furthermore, we investigate the linear response behavior of the Kitaev chain within the framework of three-terminal systems, deriving the expressions for the Seebeck coefficient and thermal conductance. Notably, we observe a pronounced peak in the thermal conductance near the phase transition point, in agreement with previous predictions. Additionally, we prove that the peak value saturates at half of the thermal conductance quantum for finite-length chains at the zero temperature limit.
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The stochastic thermodynamics of systems with a few degrees of freedom has been studied extensively so far. We would like to extend the study to systems with more degrees of freedom and even further-continuous fields with infinite degrees of freedom. The simplest case for a continuous stochastic field is the Edwards-Wilkinson elastic manifold. It is an exactly solvable model of which the heat statistics in the relaxation process can be calculated analytically. The cumulants require a cutoff spacing to avoid ultraviolet divergence. The scaling behavior of the heat cumulants with time and the system size as well as the large deviation rate function of the heat statistics in the large size limit is obtained.
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For driven open systems in contact with multiple heat reservoirs, we find the marginal distributions of work or heat do not satisfy any fluctuation theorem, but only the joint distribution of work and heat satisfies a family of fluctuation theorems. A hierarchical structure of these fluctuation theorems is discovered from microreversibility of the dynamics by adopting a step-by-step coarse-graining procedure in both classical and quantum regimes. Thus, we put all fluctuation theorems concerning work and heat into a unified framework. We also propose a general method to calculate the joint statistics of work and heat in the situation of multiple heat reservoirs via the Feynman-Kac equation. For a classical Brownian particle in contact with multiple heat reservoirs, we verify the validity of the fluctuation theorems for the joint distribution of work and heat.
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BACKGROUND: Gastric cancer (GC) is the fifth most common type of cancer and the fourth most common cause of cancer-related mortality. Although the risk of GC and peptic ulcer disease (PUD) is known to be increased by H. pylori infection, evidence regarding the direct relationship between PUD and GC across ethnicities is inconclusive. Therefore, we investigated the association between PUD and GC in the Stomach cancer Pooling (StoP) consortium. METHODS: History of peptic ulcer disease was collected using a structured questionnaire in 11 studies in the StoP consortium, including 4106 GC cases and 6922 controls. The two-stage individual-participant data meta-analysis approach was adopted to generate a priori. Unconditional logistic regression and Firth's penalized maximum likelihood estimator were used to calculate study-specific odds ratios (ORs) and 95% confidence intervals (CIs) for the association between gastric ulcer (GU)/duodenal ulcer (DU) and risk of GC. RESULTS: History of GU and DU was thoroughly reported and used in association analysis, respectively, by 487 cases (12.5%) and 276 controls (4.1%), and 253 cases (7.8%) and 318 controls (6.0%). We found that GU was associated with an increased risk of GC (OR = 3.04, 95% CI: 2.07-4.49). No association between DU and GC risk was observed (OR = 1.03, 95% CI: 0.77-1.39). CONCLUSIONS: In the pooled analysis of 11 case-control studies in a large consortium (i.e., the Stomach cancer Pooling (StoP) consortium), we found a positive association between GU and risk of GC and no association between DU and GC risk.
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The Curzon-Ahlborn (CA) efficiency, as the efficiency at the maximum power (EMP) of the endoreversible Carnot engine, has significant impact on finite-time thermodynamics. However, the CA engine is based on many assumptions. In the past few decades, although a lot of efforts have been made, a microscopic theory of the CA engine is still lacking. By adopting the method of the stochastic differential equation of energy, we formulate a microscopic theory of the CA engine realized with a highly underdamped Brownian particle in a class of nonharmonic potentials. This theory gives microscopic interpretation of all assumptions made by Curzon and Ahlborn. In other words, we find a microscopic counterpart of the CA engine in stochastic thermodynamics. Also, based on this theory, we derive the explicit expression of the protocol associated with the maximum power for any given efficiency, and we obtain analytical results of the power and the efficiency statistics for the Brownian CA engine. Our research brings new perspectives to experimental studies of finite-time microscopic heat engines featured with fluctuations.
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We provide a detailed investigation of the fluctuations of the currents in the discrete model of Feynman's ratchet proposed by Jarzynski and Mazonka in 1999. Two macroscopic currents are identified, with the corresponding affinities determined using Schnakenberg's graph analysis. We also investigate full counting statistics of the two currents and show that fluctuation theorem holds for their joint probability distribution. Moreover, fluctuation-dissipation relation, Onsager reciprocal relation and their nonlinear generalizations are numerically shown to be satisfied in this model.
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OBJECTIVE: To explore whether the using of mimetic peptide Gap27, a selective inhibitor of connexin 43 (Cx43), could block the death of dopamine neurons and influence the expression of Cx43 in 6-hydroxydopamine (6-OHDA)-induced Parkinson's disease mouse models. METHODS: Eighteen C57BL/6 mice were randomly divided into control group, 6-OHDA group and 6-OHDA+Gap27 group, with 6 mice in each group. Bilateral substantia nigra stereotactic injection was performed. The control group was injected with ascorbate solution, 6-OHDA group was injected with 6-OHDA solution, and 6-OHDA+Gap27 group was injected with 6-OHDA and Gap27 mixed solution. Immuno-histochemical staining was used to detect the number of dopamine neurons, quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of Cx43 messenger ribonucleic acid (mRNA), immuno-fluorescence staining was used to detect the distribution of Cx43 protein, the contents of Cx43 protein and Cx43 phosphorylation at serine 368 (Cx43-ps368) in mouse midbrain were detected by Western blot. RESULTS: After injection of 6-OHDA, numerous dopamine neurons in substantia nigra died as Cx43 content increased, Cx43-ps368 content decreased. Mixing Gap27 while injecting 6-OHDA could reduce the number of death dopamine neurons and weaken the changes of Cx43 and Cx43-ps368 content caused by 6-OHDA. The number of tyrosine hydroxylase (TH) immunoreactive positive neurons in 6-OHDA group decreased to 27.7% ± 0.02% of the control group (P < 0.01); The number of TH immunoreactive positive neurons in 6-OHDA+Gap27 group was (1.64±0.16) times higher than that in 6-OHDA group (P < 0.05); The content of total Cx43 protein in 6-OHDA group was (1.44±0.07) times higher than that in 6-OHDA+Gap27 group (P < 0.05) while (1.68±0.07) times higher than that in control group (P < 0.01). In 6-OHDA group, the content of Cx43-ps368 protein and its proportion in total Cx43 protein were significantly lower than that in 6-OHDA+Gap27 group (P < 0.05). CONCLUSION: In 6-OHDA mouse models, mimetic peptide Gap27 played a protective role in reducing the damage to substantia nigra dopamine neurons, which was induced by 6-OHDA. The overexpression of Cx43 protein might have neurotoxicity to dopamine neuron. Meanwhile, decreasing Cx43 protein level and keeping Cx43-ps368 protein level may be the protective mechanisms of Gap27.
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Doença de Parkinson , Animais , Conexina 43/genética , Conexina 43/metabolismo , Conexina 43/farmacologia , Modelos Animais de Doenças , Neurônios Dopaminérgicos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Oxidopamina/efeitos adversos , Oxidopamina/metabolismo , Doença de Parkinson/metabolismo , Peptídeos/metabolismo , Peptídeos/farmacologia , Tirosina 3-Mono-Oxigenase/metabolismo , Tirosina 3-Mono-Oxigenase/farmacologiaAssuntos
Hipopotassemia , Erros Inatos do Metabolismo , Humanos , Hipopotassemia/genética , LinhagemRESUMO
Background: Nanocovax is a recombinant severe acute respiratory syndrome coronavirus 2 subunit vaccine composed of full-length prefusion stabilized recombinant SARS-CoV-2 spike glycoproteins (S-2P) and aluminium hydroxide adjuvant. Methods: We conducted a dose-escalation, open label trial (phase 1) and a randomized, double-blind, placebo-controlled trial (phase 2) to evaluate the safety and immunogenicity of the Nanocovax vaccine (in 25 mcg, 50 mcg, and 75 mcg doses, aluminium hydroxide adjuvanted (0·5 mg/dose) in 2-dose regime, 28 days apart (ClinicalTrials.gov number, NCT04683484). In phase 1, 60 participants received two intramuscular injection of the vaccine following dose-escalation procedure. The primary outcomes were reactogenicity and laboratory tests to evaluate the vaccine safety. In phase 2, 560 healthy adults received either vaccine doses similar in phase 1 (25 or 50 or 75 mcg S antigen in 0·5 mg aluminium per dose) or adjuvant (0·5 mg aluminium) in a ratio of 2:2:2:1. One primary outcome was the vaccine safety, including solicited adverse events for 7 day and unsolicited adverse events for 28 days after each injection as well as serious adverse event or adverse events of special interest throughout the study period. Another primary outcome was anti-S IgG antibody response (Index unit/ml). Secondary outcomes were surrogate virus neutralisation (inhibition percentage), wild-type SARS-CoV-2 neutralisation (dilution fold), and T-cell responses by intracellular staining for interferon gamma (IFNg). Anti-S IgG and neutralising antibody levels were compared with convalescent serum samples from symptomatic Covid-19 patients. Findings: For phase 1 study, no serious adverse events were observed for all 60 participants. Most adverse events were grade 1 and disappeared shortly after injection. For phase 2 study, after randomisation, 480 participants were assigned to receive the vaccine with adjuvant, and 80 participants were assigned to receive the placebo (adjuvant only). Reactogenicity was absent or mild in the majority of participants and of short duration (mean ≤3 days). Unsolicited adverse events were mild in most participants. There were no serious adverse events related to Nanocovax. Regarding the immunogenicity, Nanocovax induced robust anti-S antibody responses. In general, there humoral responses were similar among vaccine groups which reached their peaks at day 42 and declined afterward. At day 42, IgG levels of vaccine groups were 60·48 [CI95%: 51·12-71·55], 49·11 [41·26-58·46], 57·18 [48·4-67·5] compared to 7·10 [6·32-13·92] of convalescent samples. IgG levels reported here can be converted to WHO international standard binding antibody unit (BAU/ml) by multiplying them to a conversion factor of 21·8. Neutralising antibody titre of vaccine groups at day 42 were 89·2 [52·2-152·3], 80·0 [50·8-125.9] and 95·1 [63·1-143·6], compared to 55·1 [33·4-91·0] of the convalescent group. Interpretation: Up to day 90, Nanocovax was found to be safe, well tolerated, and induced robust immune responses. Funding: This work was funded by the Coalition for Epidemic Preparedness Innovations (CEPI), the Ministry of Science and Technology of Vietnam, and Nanogen Pharmaceutical Biotechnology JSC.