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The rechargeable aqueous ammonium ion battery shows great potential in low-cost energy storage system because of its long life and environmental friendliness. However, most inorganic host materials used in ammonium ion batteries are still limited by slow diffusion kinetics. Herein, it is identified that a 2D heteroligand-based copper-organic framework featuring numerous ammonium ion adsorption site in the π-conjugated periodic skeleton supplies multiple accessible redox-active sites for high-performance ammonium storage. Benefitting from the effective regulation of electron delocalization by heteroligand and the inherent hydrogen bond cage mechanism between ammonium ions, the resultant full battery delivers a large specific energy density of 211.84 Wh kg-1, and it can be stably operated for 12000 cycles at 5 A g-1 for over 80 days. This explanatory understanding provides a new idea for the rational design of high-performance MOF-based ammonium ion battery cathode materials for efficient energy storage and conversion in the future.
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DENV infection outcomes depend on the host's variable expression of immune receptors and mediators, leading to either resolution or exacerbation. While the NS3 protein is known to induce robust immune responses, the specific impact of its protease region epitopes remains unclear. This study investigated the effect of recombinant NS3 protease region proteins from all four DENV serotypes on splenocyte activation in BALB/c mice (n = 5/group). Mice were immunized with each protein, and their splenocytes were subsequently stimulated with homologous antigens. We measured the expression of costimulatory molecules (CD28, CD80, CD86, CD152) by flow cytometry, along with IL-2 production, CD25 expression, and examined the antigen-specific activation of CD4 + and CD8 + T cells. Additionally, the expression of IL-1, IL-10, and TGF-ß1 in splenocytes from immunized animals was assessed. Apoptosis was evaluated using Annexin V/PI staining and DNA fragmentation analysis. Stimulation of splenocytes from immunized mice triggered apoptosis (phosphatidylserine exposure and caspase 3/7 activation) and increased costimulatory molecule expression, particularly CD152. Low IL-2 production and low CD25 expression, as well as sustained expression of the IL-10 gene. These results suggest that these molecules might be involved in mechanisms by which the NS3 protein contributes to viral persistence and disease pathogenesis.
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The half-life of the extinct radiolanthanide 146 Sm , important for both geochronological and astrophysical applications, was re-determined by a combination of mass spectrometry and α -decay counting. Earlier studies provided only limited information on all potential factors that could influence the quantification of the half-life of 146 Sm . Thus, special attention was given here to a complete documentation of all experimental steps to provide information about any possible artifacts in the data analysis. The half-life of 146 Sm was derived to be 92.0 Ma ± 2.6 Ma, with an uncertainty coverage factor of k = 1 .
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Japanese encephalitis virus (JEV) is a mosquito-borne, zoonotic orthoflavivirus causing human encephalitis and reproductive disorders in pigs. Cell-intrinsic antiviral restriction factors are the first line of defense that prevent a virus from establishing a productive infection, while the molecular mechanism of the virus-host interaction is still not fully understood. Our in vitro experiments demonstrated that the Solute Carrier Family 25 Member 12 (SLC25A12) interacted with the JEV nonstructural protein 1 (NS1) and inhibited JEV replication. Furthermore, we showed that knockdown or knockout of SLC25A12 promoted JEV replication, while overexpression of SLC25A12 repressed viral replication. Finally, we demonstrated that SLC25A12 increased IRF7 mRNA levels, which promoted IFN-ß expression and subsequently induced antiviral effects. Collectively, our study revealed that SLC25A12 interacted with NS1, inhibiting viral RNA synthesis and transcription and enhancing type I interferon induction for antiviral effects.
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Developing self-powered and flexible optoelectronic sensors with high responsivity and speed is crucial for modern applications, motivating continuous efforts to enhance their performance. Flexo-phototronics is a less-explored but promising technique to elevate the performance of optoelectronics. Therefore, this work addresses the potential of utilizing the flexo-phototronic effect to enhance the performance of a flexible and self-powered ultraviolet photodetector (UV PD) based on ZnAl:LDH (layered double hydroxides) nanosheets (Ns)/NiO heterostructure. The vertically oriented ZnAl:LDH Ns are synthesized via a simple method involving the immersion of a sputtered 10% Al-doped ZnO thin film in deionized water at room ambient conditions. The fabricated PD exhibits an impressive response to 365 nm UV light, with high sensitivity in the order of 103. The device's photocurrent and responsivity are significantly enhanced by the flexo-phototronic effect, attributed to the flexoelectric properties of ZnAl:LDH Ns. Specifically, applying an inhomogeneous tensile strain of 2% boosted the device responsivity by 57.1% and improved its operational speed. Furthermore, a working model revealing the altered energy-band structure is demonstrated to elucidate the flexo-phototronic-induced boost in the photoresponse. The PD also demonstrated a sustainable performance under severe bending cycles, underlining the good flexibility of the device. The results presented in this study demonstrate a self-powered and flexible UV PD and provide a viable approach to augment the performance of optoelectronics through the flexo-phototronic effect.
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The filter design of H ∞ for an interconnecting system (IS) with uncertain discrete time switching is examined. Discrete-time N -linear subsystems with coupling states that have time delays, external disturbances and uncertainty are taken into account. Utilising Lyapunov-Krasovskii functional (LKF) and the Linear-Matrix-Inequality (LMI) approach, an appropriate filter is designed for the considered interconnected system. To remove an outside disruption, H ∞ performances (HP) are implemented. Sufficient criteria are developed to assure the Exponentially Mean-Square Stability (EMSS). Then, using MATLAB-LMI toolbox filter parameters were established. Finally, the efficiency of the designed filter is illustrated with mathematical instances.
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PURPOSE: This study aims to map the transmit magnetic field ( B 1 + $$ {B}_1^{+} $$ ) in the human body at 7T using MR fingerprinting (MRF), with a focus on achieving high accuracy and precision across a large dynamic range, particularly at low flip angles (FAs). METHODS: A FLASH-based MRF sequence (B1-MRF) with high B 1 + $$ {B}_1^{+} $$ sensitivity was developed. Phantom and in vivo abdominal imaging were performed at 7T, and the results were compared with established reference methods, including a slow but precise preparation-based method (PEX), saturated TurboFLASH (satTFL), actual flip angle imaging (AFI) and Bloch-Siegert shift (BSS). RESULTS: The MRF signal curve was highly sensitive to B 1 + $$ {B}_1^{+} $$ , while T1 sensitivity was comparatively low. The phantom experiment showed good agreement of B 1 + $$ {B}_1^{+} $$ to PEX for a T1 range of 204-1691 ms evaluated at FAs from 0° to 70°. Compared to the references, a dynamic range increase larger than a factor of two was determined experimentally. In vivo liver scans showed a strong correlation between B1-MRF, satTFL, and RPE-AFI in a low body mass index (BMI) subject (18.1 kg/m2). However, in larger BMI subjects (≥25.5 kg/m2), inconsistencies were observed in low B 1 + $$ {B}_1^{+} $$ regions for satTFL and RPE-AFI, while B1-MRF still provided consistent results in these regions. CONCLUSION: B1-MRF provides accurate and precise B 1 + $$ {B}_1^{+} $$ maps over a wide range of FAs, surpassing the capabilities of existing methods in the FA range < 60°. Its enhanced sensitivity at low FAs is advantageous for various applications requiring precise B 1 + $$ {B}_1^{+} $$ estimates, potentially advancing the frontiers of ultra-high field (UHF) body imaging at 7T and beyond.
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Background: Dengue is a mosquito-borne tropical disease, caused by the Dengue virus (DENV). It has become a severe problem and is a rising threat to public health. In this study, we have evaluated commercial Merilisa i Dengue NS1 Antigen kit (Meril LifeSciences India Pvt. Ltd.) to detect recombinant dengue virus 2 NS1 antigen (rDNS1Ag) and secreted forms of NS1 antigen (sDNS1Ag). Methods: To determine the detection limit of the kit, 100 nanogram (ng) to 0.001 ng rDNS1Ag was tested. The sensitivity and specificity of the kit was determined using recombinant NS1 antigens of all serotypes of DENV and other flaviviruses. For testing sDNS1Ag, the culture supernatant of the Vero cell lines infected with DENV-2 was tested. Further, a spiking experiment was carried out to check the sensitivity of the kit to detect rDNS1Ag in the pools of Aedes aegypti mosquitoes. Results: It was observed that the kit can detect the rDNS1Ag at 1 ng concentration. The kit was sensitive to detect NS1 antigen of DENV-1, DENV-2 and DENV-3 serotypes and specific for detection of only DNS1Ag as it did not cross-react with NS1 antigen of flaviviruses. The kit was sensitive to detect rDNS1Ag in the mosquito pools as well. In addition, the kit was able to detect the sDNS1Ag in Vero cell culture supernatant. Conclusions: Overall, we observed that the Merilisa i Dengue NS1 Ag kit is sensitive and specific for the detection of DNS1Ag both in recombinant and secretory forms.
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For m , n ∈ N , let X = ( X ij ) i ≤ m , j ≤ n be a random matrix, A = ( a ij ) i ≤ m , j ≤ n a real deterministic matrix, and X A = ( a ij X ij ) i ≤ m , j ≤ n the corresponding structured random matrix. We study the expected operator norm of X A considered as a random operator between â p n and â q m for 1 ≤ p , q ≤ ∞ . We prove optimal bounds up to logarithmic terms when the underlying random matrix X has i.i.d. Gaussian entries, independent mean-zero bounded entries, or independent mean-zero ψ r ( r ∈ ( 0 , 2 ] ) entries. In certain cases, we determine the precise order of the expected norm up to constants. Our results are expressed through a sum of operator norms of Hadamard products A ∘ A and ( A ∘ A ) T .
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Dengue fever is a rapidly emerging tropical disease and an important cause of morbidity in its severe form worldwide. A wide spectrum of the pathophysiology is associated with the transition of dengue fever to severe dengue, which is driven by the host immune response and might reflect in patients' proteome profile. This study aims to analyze the plasma from different phases of dengue-infected patients at two time points. A mass-spectrometry-based proteomic approach was utilized to understand the involvement of probable candidate proteins toward developing a more severe, hemorrhagic form of dengue fever. Dengue-infected hospital-admitted patients with <5 days of fever were included in this study. Patient samples from the acute phase were screened for the presence of NS1 antigen using ELISA and subjected to molecular serotyping. Dengue molecular serotype-confirmed patient samples, pairwise from acute and critical phases with healthy control were subjected to qualitative and quantitative proteomic analysis, and then pathway analysis was performed. The protein-protein interaction network between the dengue virus and host proteins was depicted in the search for proteins associated with severe dengue pathophysiology. An array of apolipoprotein, cytokines, and endothelial proteins in association with virus replication and endothelial dysfunction were validated as biomolecules involved in severe dengue pathophysiology.
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Leveraging the simplicity of nucleotide mismatch distributions, we provide an intuitive window into the evolution of the human influenza A 'nonstructural' (NS) gene segment. In an analysis suggested by the eminent Danish biologist Freddy B. Christiansen, we illustrate the existence of a continuous genetic "backbone" of influenza A NS sequences, steadily increasing in nucleotide distance to the 1918 root over more than a century. The 2009 influenza A/H1N1 pandemic represents a clear departure from this enduring genetic backbone. Utilizing nucleotide distance maps and phylogenetic analyses, we illustrate remaining uncertainties regarding the origin of the 2009 pandemic, highlighting the complexity of influenza evolution. The NS segment is interesting precisely because it experiences less pervasive positive selection, and departs less strongly from neutral evolution than e.g. the HA antigen. Consequently, sudden deviations from neutral diversification can indicate changes in other genes via the hitchhiking effect. Our approach employs two measures based on nucleotide mismatch counts to analyze the evolutionary dynamics of the NS gene segment. The rooted Hamming map of distances between a reference sequence and all other sequences over time, and the unrooted temporal Hamming distribution which captures the distribution of genotypic distances between simultaneously circulating viruses, thereby revealing patterns of nucleotide diversity and epi-evolutionary dynamics.
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Both copper and zinc are known to be important for maintaining health, but most research has focused on deficiencies of these elements. Recent studies have shown that high levels of Cu can be toxic, especially to the cardiovascular (CV) system. However, little research has been done on the effects of higher levels of Zn on the CV system. In this study, male Wistar rats aged 12 months were given a diet with twice the recommended daily allowance of zinc (31.8 mg/kg of diet) and compared to a control group (15.9 mg/kg of diet) after 8 weeks. Blood plasma and internal organs of both groups were examined for levels of copper, zinc, selenium and iron, as well as several key enzymes. Aortic rings from both groups were also examined to determine vascular functioning. There were very few changes in the vascular system functioning after chronic exposure to zinc, and only one enzyme, heme oxygenase-1 (HO-1) was elevated, whereas vascular contraction to noradrenaline decreased with no changes in vasodilation to acetylcholine. Of the micronutrients, zinc and selenium were elevated in the blood plasma, while copper decreased. Meanwhile, the total antioxidant status increased. These were not observed in the liver. Therefore, it is proposed that there is a mechanism in place within the vascular system to protect against the overproduction of heme, caused by chronic zinc exposure.
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Gold is generally considered a noble metal since it is inherently inert in its bulk state. However, gold demonstrates reactivity when it is in its ionic state. The inherent inertness of bulk gold has resulted in its widespread recognition as a vital raw material in various biomedical processes. The applications of these technologies include drug delivery microchips, dental prostheses, reconstructive surgery, culinary additives, and cardiovascular stents. Gold can also exist in molecules or ions, particularly gold ions, which facilitates the production of gold nanomaterials. In this paper, we have computed differential and integral operators by using the M -Polynomial of gold crystals and by utilizing this polynomial, we have also computed eleven topological indices like 1 s t Zagreb, 2 n d Zagreb, Hyper, Sigma, Second Modified, General Randic, General Reciprocal Randic, 3 r d Redefined Zagreb, Symmetric Division Degree, Harmonic, Inverse Sum indices for the structure of Gold crystal.
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The benzofuran core inhibitors HCV-796, BMS-929075, MK-8876, compound 2, and compound 9B exhibit good pan-genotypic activity against various genotypes of NS5B polymerase. To elucidate their mechanism of action, multiple molecular simulation methods were used to investigate the complex systems of these inhibitors binding to GT1a, 1b, 2a, and 2b NS5B polymerases. The calculation results indicated that these five inhibitors can not only interact with the residues in the palm II subdomain of NS5B polymerase, but also with the residues in the palm I subdomain or the palm I/III overlap region. Interestingly, the binding of inhibitors with longer substituents at the C5 position (BMS-929075, MK-8876, compound 2, and compound 9B) to the GT1a and 2b NS5B polymerases exhibits different binding patterns compared to the binding to the GT1b and 2a NS5B polymerases. The interactions between the para-fluorophenyl groups at the C2 positions of the inhibitors and the residues at the binding pockets, together with the interactions between the substituents at the C5 positions and the residues at the reverse ß-fold (residues 441-456), play a key role in recognition and the induction of the binding. The relevant studies could provide valuable information for further research and development of novel anti-HCV benzofuran core pan-genotypic inhibitors.
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Antivirais , Benzofuranos , Genótipo , Hepacivirus , Proteínas não Estruturais Virais , Proteínas não Estruturais Virais/antagonistas & inibidores , Proteínas não Estruturais Virais/metabolismo , Proteínas não Estruturais Virais/química , Benzofuranos/química , Benzofuranos/farmacologia , Hepacivirus/efeitos dos fármacos , Hepacivirus/enzimologia , Hepacivirus/genética , Antivirais/farmacologia , Antivirais/química , Simulação de Dinâmica Molecular , Simulação de Acoplamento Molecular , Sítios de Ligação , Ligação Proteica , Humanos , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , RNA Polimerase Dependente de RNARESUMO
Background: Noonan syndrome (NS) and Noonan-like syndrome with loose anagen hair (NS/LAH) are neurodevelopmental syndromes resulting from germline mutations in genes that participate in the rat sarcoma/mitogen-activated protein kinases (RAS/MAPK) pathway. The aim of this retrospective study was to describe common and rare manifestations of NS and NS/LAH. Methods: We collected and analyzed clinical and genetic data from 25 patients with NS and NS/LAH. Results: The patients' median age was 6.3 years (range, 1-13 years), and the male-to-female ratio was 18:7. In total, 19 patients had NS caused by a mutation in PTPN11. Another causative gene was found in six patients, including two patients with a SHOC2 mutation, one patient with a KRAS mutation, one patient with an LZTR1 mutation, one patient with a BRAF mutation, and one patient with a PPP1CB mutation. Short stature was detected in 100% of the patients. This study provides an overview of the clinical features of NS, including unique facial features, short stature, congenital heart defects, and other manifestations. Notably, systemic lupus erythematosus (SLE) was found in two SHOC2-positive patients. One patient had a posterior urethral valve, which is very rare in NS patients. Conclusions: Our study identified several clinical features that were previously poorly related to NS, including SLE. We concluded that SHOC2-related NS is associated with a particularly high risk of SLE, which may have a significant impact on quality of life, and a posterior urethral valve is a novel phenotype. These findings could be helpful in enhancing the understanding of the clinical spectrum of NS.
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The ZIKA virus (ZIKV) evades the host immune response by degrading STAT2 through its NS5 protein, thereby inhibiting type I interferon (IFN)-mediated antiviral immunity. However, the molecular mechanism underlying this process has remained elusive. In this study, we performed a genome-wide CRISPR/Cas9 screen, revealing that ZSWIM8 as the substrate receptor of Cullin3-RING E3 ligase is required for NS5-mediated STAT2 degradation. Genetic depletion of ZSWIM8 and CUL3 substantially impeded NS5-mediated STAT2 degradation. Biochemical analysis illuminated that NS5 enhances the interaction between STAT2 and the ZSWIM8-CUL3 E3 ligase complex, thereby facilitating STAT2 ubiquitination. Moreover, ZSWIM8 knockout endowed A549 and Huh7 cells with partial resistance to ZIKV infection and protected cells from the cytopathic effects induced by ZIKV, which was attributed to the restoration of STAT2 levels and the activation of IFN signaling. Subsequent studies in a physiologically relevant model, utilizing human neural progenitor cells, demonstrated that ZSWIM8 depletion reduced ZIKV infection, resulting from enhanced IFN signaling attributed to the sustained levels of STAT2. Our findings shed light on the role of ZIKV NS5, serving as the scaffold protein, reprograms the ZSWIM8-CUL3 E3 ligase complex to orchestrate STAT2 proteasome-dependent degradation, thereby facilitating evasion of IFN antiviral signaling. Our study provides unique insights into ZIKV-host interactions and holds promise for the development of antivirals and prophylactic vaccines.
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Proteínas Culina , Interferon Tipo I , Proteólise , Fator de Transcrição STAT2 , Transdução de Sinais , Ubiquitina-Proteína Ligases , Ubiquitinação , Proteínas não Estruturais Virais , Infecção por Zika virus , Zika virus , Humanos , Fator de Transcrição STAT2/metabolismo , Zika virus/imunologia , Zika virus/fisiologia , Zika virus/metabolismo , Proteínas não Estruturais Virais/metabolismo , Proteínas não Estruturais Virais/genética , Interferon Tipo I/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Infecção por Zika virus/metabolismo , Infecção por Zika virus/imunologia , Infecção por Zika virus/virologia , Proteínas Culina/metabolismo , Células A549 , Células HEK293 , Sistemas CRISPR-CasRESUMO
OBJECTIVE: In Guangdong Province, hepatitis C virus (HCV) had been found to confer resistance to direct-acting antivirals (DAAs). There were few studies of HCV subtypes and resistance-associated substitutions (RASs) of HCV in different high-risk populations. In this study, we aimed to determine the subtype distribution and the RASs in high-risk population groups, including drug users (DU), men who have sex with men (MSM), female sex workers (FSW), and male patients with sexually transmitted diseases (STD) in Guangdong Province (a highly developed province with a large population). METHODS: Using a city-based sampling strategy,1356 samples were obtained from different population groups. Phylogenetic analyses determined subtypes based on Core, NS5B, or NS5A sequences. HCV subtype distribution and RASs in various risk groups and regions were analyzed. RESULTS: Ten subtypes, of which 6 h and 6 k were novel in Guangdong, were identified. The primary subtype among all risk groups was 6a. RASs in 1b and 3a were different from those observed in other studies. Subtype 3b in western Guangdong was higher than the other three regions. No RASs were found in 6a or any other genotype 6. CONCLUSIONS: The HCV subtypes are expanding in high-risk populations in Guangdong. Drug use by other risk groups and commercial sex by DU may bridge the dissemination of 6a from DU to other populations. The RAS profiles of 1b and 3a differed from those reported in studies conducted in southwestern China. Further research is required to determine the reason for this discrepancy. Moreover, the combination of RASs was high in subtype 3b. To guide HCV treatment of subtype 3b, pretreatment subtyping of HCV genotype 3 should be considered in western cities in the near future.
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A well-known person fit statistic in the item response theory (IRT) literature is the l z statistic (Drasgow et al. in Br J Math Stat Psychol 38(1):67-86, 1985). Snijders (Psychometrika 66(3):331-342, 2001) derived l z ∗ , which is the asymptotically correct version of l z when the ability parameter is estimated. However, both statistics and other extensions later developed concern either only the unidimensional IRT models or multidimensional models that require a joint estimate of latent traits across all the dimensions. Considering a marginalized maximum likelihood ability estimator, this paper proposes l zt and l zt ∗ , which are extensions of l z and l z ∗ , respectively, for the Rasch testlet model. The computation of l zt ∗ relies on several extensions of the Lord-Wingersky algorithm (1984) that are additional contributions of this paper. Simulation results show that l zt ∗ has close-to-nominal Type I error rates and satisfactory power for detecting aberrant responses. For unidimensional models, l zt and l zt ∗ reduce to l z and l z ∗ , respectively, and therefore allows for the evaluation of person fit with a wider range of IRT models. A real data application is presented to show the utility of the proposed statistics for a test with an underlying structure that consists of both the traditional unidimensional component and the Rasch testlet component.
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We discuss the existence of a fixed point for a self mapping and its uniqueness satisfying ( Ï Ë , η Ë ) -generalized contractive condition including altering distance functions of rational terms in an ordered b-metric space. It is also discussed whether the two self-maps under the same contraction condition can be coincident and coupled coincident. The results are backed up by a dearth of numerical examples and application to nonlinear quadratic integral equation.
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INTRODUCTION: From 2008 and following the withdrawal of rosiglitazone, obligatory cardiovascular outcomes trials are performed for glucose lowering drugs introduced to the market to ensure their cardiovascular (CV) safety. Paradoxically, these studies have demonstrated CV safety but also shown additional cardio-reno-vascular protection of some therapeutic agents. Additionally, nonsteroidal mineralocorticoid receptor antagonists (ns-MRA) have emerged as novel drugs for cardio - and renoprotection in type 2 diabetes (T2D) and chronic kidney disease (CKD). In addition to atherosclerotic cardiovascular disease, heart failure (HF) and CKD are important clinical problems in T2D leading to poor quality of life and premature death as such cardio-reno-vascular protection is an important clinical issue. AREAS COVERED: We provide new insights into pharmacotherapeutic cardio-reno-vascular protection in T2D based on the new glucose lowering drugs and ns-MRA. PUB MED/CINAHL/Web of Science/Scopus were searched (May 2024). EXPERT OPINION: The conventional glucose lowering approach alone which was implemented for decades is now replaced by the use of disease modifying drugs which lower the rates of CV events, HF decompensation, hospitalization due to HF, slow progression of CKD and all-cause mortality. Indeed, the choice of medications in T2D should be focused on underlying co-morbidities with cardio-reno-vascular protection rather than a gluco-centric approach.