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1.
Cancer Res ; 84(9): 1410-1425, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38335304

RESUMO

Cancer immunotherapy has revolutionized the treatment of lung adenocarcinoma (LUAD); however, a significant proportion of patients do not respond. Recent transcriptomic studies to understand determinants of immunotherapy response have pinpointed stromal-mediated resistance mechanisms. To gain a better understanding of stromal biology at the cellular and molecular level in LUAD, we performed single-cell RNA sequencing of 256,379 cells, including 13,857 mesenchymal cells, from 9 treatment-naïve patients. Among the mesenchymal cell subsets, FAP+PDPN+ cancer-associated fibroblasts (CAF) and ACTA2+MCAM+ pericytes were enriched in tumors and differentiated from lung-resident fibroblasts. Imaging mass cytometry revealed that both subsets were topographically adjacent to the perivascular niche and had close spatial interactions with endothelial cells (EC). Modeling of ligand and receptor interactomes between mesenchymal and ECs identified that NOTCH signaling drives these cell-to-cell interactions in tumors, with pericytes and CAFs as the signal receivers and arterial and PLVAPhigh immature neovascular ECs as the signal senders. Either pharmacologically blocking NOTCH signaling or genetically depleting NOTCH3 levels in mesenchymal cells significantly reduced collagen production and suppressed cell invasion. Bulk RNA sequencing data demonstrated that NOTCH3 expression correlated with poor survival in stroma-rich patients and that a T cell-inflamed gene signature only predicted survival in patients with low NOTCH3. Collectively, this study provides valuable insights into the role of NOTCH3 in regulating tumor stroma biology, warranting further studies to elucidate the clinical implications of targeting NOTCH3 signaling. SIGNIFICANCE: NOTCH3 signaling activates tumor-associated mesenchymal cells, increases collagen production, and augments cell invasion in lung adenocarcinoma, suggesting its critical role in remodeling tumor stroma.


Assuntos
Adenocarcinoma de Pulmão , Fibroblastos Associados a Câncer , Neoplasias Pulmonares , Invasividade Neoplásica , Receptor Notch3 , Análise de Célula Única , Células Estromais , Microambiente Tumoral , Humanos , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/genética , Fibroblastos Associados a Câncer/metabolismo , Fibroblastos Associados a Câncer/patologia , Comunicação Celular , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/genética , Receptor Notch3/metabolismo , Receptor Notch3/genética , Transdução de Sinais , Células Estromais/metabolismo , Células Estromais/patologia
2.
Heliyon ; 10(4): e25609, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38375273

RESUMO

Climate change alters the climate condition and ocean environment, leading to accelerated coastal erosion and a shift in the coastline shape. From previous studies, Southeast Asia's coastal region is suffering from severe coastal erosion. It is most sensitive and vulnerable to climate change, has broad and densely populated coastlines, and is under ecological pressure. Efforts to systematically review these studies are still insufficient despite many studies on the climate change linked to coastal erosion, the correlation between coastal erosion and coastal communities, and the adaptative measures to address these issues and their effectiveness in Southeast Asia. Therefore, by analyzing the existing literature, the purpose of this review was to bridge the knowledge gap and identify the link between climate change and coastal erosion in Southeast Asia in terms of sea-level rise, storm surge, and monsoon patterns. The RepOrting standards for Systematic Evidence Syntheses (ROSES) guided the study protocol, including articles from the Scopus and Dimension databases. There were five main themes considered: 1) climate change impact, 2) contributing factors to coastal erosion, 3) coastal erosion impact on coastal communities, 4) adaptation measure and 5) effectiveness of adaptation measure using thematical analysis. Subsequently, nine sub-themes were produced from the themes. Generally, in Southeast Asia, coastal erosion was reflected by the rising sea level. Throughout reviewing past literature, an interesting result was explored. Storm surges also had the potential to affect coastal erosion due to alterations of the atmospheric system and seasonal monsoon as the result of climate change. Meanwhile, an assessment of current erosion control strategies in relation to the relative hydrodynamic trend was required to avoid the failure of defence structures and the resulting danger to coastal communities. Systematically reviewing the existing literature was critical, hence it could significantly contribute to the body of knowledge. It provides valuable information for interested parties, such as authorities, the public, researchers, and environmentalists, while comprehending existing adaptation practices. This kind of review could strategize adaptation and natural resource management in line with coastal communities' needs, abilities, and capabilities in response to environmental and other change forms.

3.
Life (Basel) ; 14(1)2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38276279

RESUMO

Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women that is characterized by fluid-filled sacs in the ovaries and various symptoms, including high androgen levels, endometrial irregularities, and cysts. Although the main cause of PCOS remains unknown, it has been linked to genetic, endocrine, and metabolic factors, and there are several treatment options, including lifestyle modifications, medications, and surgery. Natural products such as medicinal plants and fruits are being explored as potential treatments for PCOS because of their bioactive compounds with pharmacological effects related to antioxidant, antimicrobial, anticancer, and antidiabetic properties. Some of these compounds improve insulin sensitivity, reduce inflammation, and enhance glucose metabolism, thereby benefiting patients with PCOS. This mini-review examined the effects of natural products on PCOS, including their effects on ovarian histological changes, blood glucose, sex hormones, and lipid profiles, based on animal and human studies. This study suggests that the use of natural products as complementary medicines can be a promising resource for the development of effective therapeutics for PCOS; however, further research is needed to fully understand their benefits.

4.
Sci Total Environ ; 912: 169187, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38097068

RESUMO

The most recent set of General Circulation Models (GCMs) derived from the Coupled Model Intercomparison Project Phase 6 (CMIP6) was used in this work to analyse the spatiotemporal patterns of future rainfall distribution across the Johor River Basin (JRB) in Malaysia. A group of 23 GCMs were chosen for comparative assessment in simulating basin-scale rainfall based on daily rainfall from the historical period of the Climate Hazards Group InfraRed Precipitation with Station Data (CHIRPS). The methodological novelty of this study lies in the application of relative importance metrics (RIM) to rank and select historical GCM simulations for reproducing rainfall at 109 CHIRPS grid points within the JRB. In order to choose the top GCMs, the rankings given by RIM were aggregated using the compromise programming index (CPI) and Jenks optimised classification (JOC). It was found that ACCESS-ESM1-5 and CMCC-ESM2 were ranked the highest in most of the grid. The final GCM was then bias-corrected using the linear scaling method before being ensemble based on the Bayesian model averaging (BMA) technique. The spatiotemporal assessment of the ensemble model for the different months over the near-future period 2021-2060 and far-future period 2061-2100 was compared with those under Shared Socioeconomic Pathways (SSPs), namely, SSP1-2.6, SSP2-4.5, SSP3-7.0, and SSP5-8.5. Heterogeneous changes in rainfall were projected across the JRB, with both increasing and decreasing trends. In the near-future and far-future scenarios, higher rainfall was projected for December, indicating an elevated risk of flooding during the end of the North East monsoon (NEM). Conversely, August showed a decreasing trend in rainfall, implying an increasing risk of severe drought. The findings of this study provide valuable insights for effective water resource management and climate change adaptation in the region.

5.
Comput Biol Med ; 167: 107636, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37925910

RESUMO

BACKGROUND: Artificial intelligence (AI) has potential uses in healthcare including the detection of health conditions and prediction of health outcomes. Past systematic reviews had reviewed the accuracy of artificial neural networks (ANN) on Electrocardiogram (ECG) readings but that of other AI models on other Acute Coronary Syndrome (ACS) detection tools remains unclear. METHODS: Nine electronic databases were searched from 2012 to 31 August 2022 including grey literature search and hand searching of references of included articles. Risk of bias was assessed by two independent reviewers using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). Test characteristics namely true positives, false positives, true negatives, and false negatives were extracted from all included articles into a 2x2 table. Study-specific estimates of sensitivity and specificity were pooled using hierarchical summary receiver operating characteristic (HSROC) model and displayed using a forest plot and HSROC curve. RESULTS: 66 studies were included in the review. A total of 518,931 patients were included whose mean ages varied from 32.62 to 70 years old. In 66 studies, the sensitivity and specificity of AI-based detection for ACS screening ranged from 64 % to 100 % and 65 %-100 %, respectively. The overall quality of evidence was low due to the inclusion of case-control studies. CONCLUSION: Results of the study inform the potential of using AI-assisted ACS detection for accurate diagnosis and prompt treatment for ACS. Adherence to the Standards for Reporting of Diagnostic Accuracy (STARD) guideline and having more cohort studies for future Diagnostic Test Accuracy (DTA) studies are necessary to improve the quality of evidence of AI-based detection of ACS.


Assuntos
Síndrome Coronariana Aguda , Inteligência Artificial , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Síndrome Coronariana Aguda/diagnóstico , Sensibilidade e Especificidade , Curva ROC , Testes Diagnósticos de Rotina
6.
RSC Adv ; 13(47): 32918-32926, 2023 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-38025850

RESUMO

The increasing levels of carbon dioxide (CO2) in the atmosphere may dissolve into the ocean and affect the marine ecosystem. It is crucial to determine the level of dissolved CO2 in the ocean to enable suitable mitigation actions to be carried out. The conventional electrode materials are expensive and susceptible to chloride ion attack. Therefore, there is a need to find suitable alternative materials. This novel study investigates the electrochemical behaviour of dissolved CO2 on roughened molybdenum (Mo) microdisk electrodes, which were mechanically polished using silicon carbide paper. Pits and dents can be seen on the electrode surface as observed using scanning electron microscopy. X-ray diffraction spectra confirm the absence of abrasive materials and the presence of defects on the electrode surface. The electrochemical surface for the roughened electrodes is higher than that for the smoothened electrodes. Our findings show that the roughened electrodes exhibit a significantly higher electrocatalytic activity than the smoothened electrodes for the reduction of dissolved CO2. Our results reveal a linear relationship between the current and square root of scan rate. Furthermore, we demonstrate that saturating the electrolyte solution with CO2 using a bubbling time of just 20 minutes at a flow rate of 5 L min-1 for a 50 mL solution is sufficient. This study provides new insights into the electrochemical behaviour of dissolved CO2 on roughened Mo microdisk electrodes and highlights their potential as a promising material for CO2 reduction and other electrochemical applications. Ultimately, our work contributes to the ongoing efforts to mitigate the effects of climate change and move towards a sustainable future.

7.
Biomed Eng Online ; 22(1): 50, 2023 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-37217941

RESUMO

BACKGROUND: Over the decades, many publications have established respiratory muscle training (RMT) as an effective way in improving respiratory dysfunction in multiple populations. The aim of the paper is to determine the trend of research and multidisciplinary collaboration in publications related to RMT over the last 6 decades. The authors also sought to chart the advancement of RMT among people with spinal cord injury (SCI) over the last 60 years. METHODS: Bibliometric analysis was made, including the publications' profiles, citation analysis and research trends of the relevant literature over the last 60 years. Publications from all time frames were retrieved from Scopus database. A subgroup analysis of publications pertinent to people with SCI was also made. RESULTS: Research on RMT has been steadily increasing over the last 6 decades and across geographical locations. While medicine continues to dominate the research on RMT, this topic also continues to attract researchers and publications from other areas such as engineering, computer science and social science over the last 10 years. Research collaboration between authors in different backgrounds was observed since 2006. Source titles from non-medical backgrounds have also published articles pertinent to RMT. Among people with SCI, researchers utilised a wide range of technology from simple spirometers to electromyography in both intervention and outcome measures. With various types of interventions implemented, RMT generally improves pulmonary function and respiratory muscle strength among people with SCI. CONCLUSIONS: While research on RMT has been steadily increasing over the last 6 decades, more collaborations are encouraged in the future to produce more impactful and beneficial research on people who suffer from respiratory disorders.


Assuntos
Exercícios Respiratórios , Traumatismos da Medula Espinal , Humanos , Pulmão , Traumatismos da Medula Espinal/terapia , Bibliometria , Músculos Respiratórios/fisiologia
8.
Sci Total Environ ; 892: 164471, 2023 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-37257620

RESUMO

This paper aims to select the most appropriate rain-based meteorological drought index for detecting drought characteristics and identifying tropical drought events in the Johor River Basin (JRB). Based on a multi-step approach, the study evaluated seven drought indices, including the Rainfall Anomaly Index (RAI), Standardized Precipitation Index (SPI), China-Z Index (CZI), Modified China-Z Index (MCZI), Percent of Normal (PN), Deciles Index (DI), and Z-Score Index (ZSI), based on the CHIRPS rainfall gridded-based datasets from 1981 to 2020. Results showed that CZI, MCZI, SPI, and ZSI outperformed the other indices based on their correlation and linearity (R2 = 0.96-0.99) along with their ranking based on the Compromise Programming Index (CPI). The historical drought evaluation revealed that MCZI, SPI, and ZSI performed similarly in detecting drought events, but SPI was more effective in detecting spatial coverage and the occurrence of 'very dry' and 'extremely dry' drought events. Based on SPI, the study found that the downstream area, north-easternmost area, and eastern boundary of the basin were more prone to higher frequency and longer duration droughts. Furthermore, the study found that prolonged droughts are characterized by episodic drought events, which occur with one to three months of 'relief period' before another drought event occurs. The study revealed that most drought events that coincide with El Niño, positive Indian Ocean Dipole (IOD), and negative Madden-Julian Oscillation (MJO) events, or a combination of these events, may worsen drought conditions. The application of CHIRPS datasets enables better spatiotemporal mapping and prediction of drought for JRB, and the output is pertinent for improving water management strategies and adaptation measures. Understanding spatiotemporal drought conditions is crucial to ensuring sustainable development and policies through better regulation of human activities. The framework of this research can be applied to other river basins in Malaysia and other parts of Southeast Asia.


Assuntos
Secas , Monitoramento Ambiental , Humanos , Malásia , Monitoramento Ambiental/métodos , Rios , Chuva
9.
Food Technol Biotechnol ; 61(1): 39-50, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37200792

RESUMO

Research background: Various approaches have been used to present functional lipids including lycopene in a palatable food form to consumers. However, being highly hydrophobic, lycopene is insoluble in aqueous systems and has a limited bioavailability in the body. Lycopene nanodispersion is expected to improve the properties of lycopene, but its stability and bioaccessibility are also affected by emulsifier type and environmental conditions such as pH, ionic strength and temperature. Experimental approach: The influence of soy lecithin, sodium caseinate and soy lecithin/sodium caseinate at 1:1 ratio on the physicochemical properties and stability of lycopene nanodispersion prepared using the emulsification-evaporation methods before and after treatment at different pH, ionic strength and temperature were investigated. The in vitro bioaccessibility of the nanodispersions was also studied. Results and conclusion: Under neutral pH conditions, nanodispersion stabilized with soy lecithin had the highest physical stability and the smallest particle size (78 nm), the lowest polydispersity index (PDI) value (0.180) and highest zeta potential (-64 mV) but the lowest lycopene concentration (1.826 mg/100 mL). Conversely, nanodispersion stabilized with sodium caseinate had the lowest physical stability. Combining the soy lecithin with sodium caseinate at 1:1 ratio resulted in a physically stable lycopene nanodispersion with the highest lycopene concentration (2.656 mg/100 mL). The lycopene nanodispersion produced by soy lecithin also had high physical stability under different pH range (pH=2-8) where the particle size, PDI and zeta potential remained fairly consistent. The nanodispersion containing sodium caseinate was unstable and droplet aggregation occurred when the pH was reduced close to the isoelectric point of sodium caseinate (pH=4-5). The particle size and PDI value of nanodispersion stabilized with soy lecithin and sodium caseinate mixture increased sharply when the NaCl concentration increased above 100 mM, while the soy lecithin and sodium caseinate counterparts were more stable. All of the nanodispersions showed good stability with respect to temperature changes (30-100 °C) except for the one stabilized by sodium caseinate, which exhibited an increased particle size when heated to above 60 °C. The combination of soy lecithin and sodium caseinate was found to increase the bioaccessibility of the lycopene nanodispersion. The physicochemical properties, stability and extent of the lycopene nanodispersion digestion highly depend on the emulsifier type. Novelty and scientific contribution: Producing a nanodispersion is considered one of the best ways to overcome the poor water solubility, stability and bioavailability issues of lycopene. Currently, studies related to lycopene-fortified delivery systems, particularly in the form of nanodispersion, are still limited. The information obtained on the physicochemical properties, stability and bioaccessibility of lycopene nanodispersion is useful for the development of an effective delivery system for various functional lipids.

10.
Materials (Basel) ; 16(5)2023 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-36902968

RESUMO

This paper presents an assessment of the effect of isothermal annealing of Sn whisker growth behavior on the surface of Sn0.7Cu0.05Ni solder joints using the hot-dip soldering technique. Sn0.7Cu and Sn0.7Cu0.05Ni solder joints with a similar solder coating thickness was aged up to 600 h in room temperature and annealed under 50 °C and 105 °C conditions. Through the observations, the significant outcome was the suppressing effect of Sn0.7Cu0.05Ni on Sn whisker growth in terms of density and length reduction. The fast atomic diffusion of isothermal annealing consequently reduced the stress gradient of Sn whisker growth on the Sn0.7Cu0.05Ni solder joint. It was also established that the smaller (Cu,Ni)6Sn5 grain size and stability characteristic of hexagonal η-Cu6Sn5 considerably contribute to the residual stress diminished in the (Cu,Ni)6Sn5 IMC interfacial layer and are able to suppress the growth of Sn whiskers on the Sn0.7Cu0.05Ni solder joint. The findings of this study provide environmental acceptance with the aim of suppressing Sn whisker growth and upsurging the reliability of the Sn0.7Cu0.05Ni solder joint at the electronic-device-operation temperature.

11.
J Environ Manage ; 333: 117391, 2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-36774836

RESUMO

The complexity of the coastal environment and the advent of climate change cause coastal erosion, which is incontrovertibly a significant concern worldwide, including Peninsular Malaysia, where, the coast is threatened by severe erosion linked to anthropogenic factors and monsoonal wind-driven waves. Consequently, the Malaysian government implemented a mitigation plan using several coastal defence systems to overcome the coastal erosion problem. This study assesses coastal erosion management strategies along a monsoon-dominated coasts by evaluating the efficacy of coastal protection structures against the coast. To this end, we analysed 244 km of the coastline of Terengganu, a federal state located on the east coast of Peninsular Malaysia. Due to a higher frequency of storms and the ensuing inception of high wave energy environments during the northeast monsoon (relative to southwest monsoon), the study area is the most impacted region in Malaysia with regard to coastal erosion. Fifty-five (55) coastal defence structures were detected along the Terengganu coastline. The Digital Shoreline Analysis System (DSAS) was utilised to compute changes in the rate statistics for various historical shoreline positions along the Terengganu coast to assess the efficacy of the defence structures. Additionally, this study acquired the perception of the existing coastal management strategies through an interview session with the concerned stakeholders. The rate statistics revealed the effectiveness and impact of the coastal defence structure on the coastline. Assessing the functionality of the coastal defence structures shed light on the present scenario of coastal erosion management. Greater efficacy and lower impact of coastal defence structures are prescribed for coastal erosion management strategies across the monsoon-dominated coast.


Assuntos
Aclimatação , Tempestades Ciclônicas , Malásia , Mudança Climática , Vento
12.
Heliyon ; 9(1): e13035, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36699271

RESUMO

This study explored the effect of humor on teacher-student relationship quality (TSRQ) and student engagement by uncovering the mediating role of TSRQ and the moderating role of individual differences (personal sense of humor). Data were collected using a cross-sectional time-lag approach with 2 phases; 367 students participated. The hypotheses were tested with a moderated mediation model. Perceived humor was positively related to TSRQ and student engagement. The results also confirmed the mediating role of TSRQ; a sense of humor positively moderated the relationship between perceived related humor and TSRQ, as well as perceived related humor and student engagement. The present study uncovers the relationship between humor and relationship quality in learning settings. Moreover, our study provides the first empirical data on the mediating effects of TSRQ on perceived related humor and student engagement. It also reveals the role of individual differences (sense of humor) in the proposed model.

13.
Front Aging Neurosci ; 15: 1274452, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38259635

RESUMO

Currently, there exists a limited comprehension regarding the correlation between COVID-19 and Alzheimer's disease (AD). To elucidate the interrelationship and its impact on outcomes, a comprehensive investigation was carried out utilising time-unrestricted searches of reputable databases such as Scopus, PubMed, Web of Science, and Google Scholar. Our objective was to evaluate the impact of various medical conditions on severe COVID-19-related events. We focused on identifying and analysing articles that discussed the clinical characteristics of COVID-19 patients, particularly those pertaining to severe events such as ICU admission, mechanical ventilation, pneumonia, mortality and acute respiratory distress syndrome (ARDS) a serious lung condition that causes low blood oxygen. Through careful data analysis and information gathering, we tried to figure out how likely it was that people with conditions, like AD, would have serious events. Our research investigated potential mechanisms that link AD and COVID-19. The ability of the virus to directly invade the central nervous system and the role of ACE-2 receptors were investigated. Furthermore, the OAS1 gene served as the genetic link between AD and COVID-19. In the context of COVID-19, our findings suggest that individuals with AD may be more susceptible to experiencing severe outcomes. Consequently, it is crucial to provide personalised care and management for this demographic. Further investigation is required to attain a comprehensive comprehension of the intricate correlation between Alzheimer's disease and COVID-19, as well as its ramifications for patient outcomes.

14.
Artigo em Inglês | MEDLINE | ID: mdl-36443559

RESUMO

Alzheimer's disease (AD) is characterized by aggregation of amyloid beta (Aß) plaque. RhoA may serve as a potential target for prevention against AD given its role in the amyloidogenic pathway. The recent emergence of the gut-brain axis has linked lactic acid bacteria (LAB) to neuroprotection against AD. This study assessed the importance of RhoA inhibition in mediating the neuroprotective potential of LAB. To this end, de Man, Rogosa and Sharpe (MRS) broth fermented by lactobacilli or pediococci were tested against SK-N-SH (a human neuroblastoma cell line) in the presence of RhoA activator II for 24 h after which the RhoA activity was measured using the G-LISA Kit. Fluorescence staining of f-actin stress fibres was performed to validate RhoA inhibition. SK-N-SH was transfected with plasmid expressing amyloid precursor protein (APP) gene. The Aß concentration in transfected cells exposed to LAB-derived cell free supernatant (CFS) in the presence of RhoA activator II was measured using the ELISA kit. Furthermore, this study measured organic acids in LAB-derived CFS using the gas chromatography. It was found that LAB-derived CFS yielded strain-dependent inhibition of RhoA, with LAB6- and LAB12-derived CFS being the most potent Pediococcal- and Lactiplantibacillus-based RhoA inhibitor, respectively. Lesser stress fibres were formed under treatment with LAB-derived CFS. The LAB-derived CFS also significantly inhibited Aß in SK-N-SH transfected with APP gene in the presence of RhoA activator II. The LAB-derived CFS was presented with increased lactic acid, acetic acid, butyric acid and propionic acid. The present findings warrant in-depth study using animal models.

15.
Molecules ; 27(20)2022 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-36296662

RESUMO

Our study used the full-potential linearized augmented plane waves (FP-LAPW) method to conduct a first-principles evaluation of the structural, electronic, and magnetic properties of ThMn2X2 (X = Si and Ge) compounds. To establish theoretical dependability with the currently available experimental results, computations for the structural findings of ternary intermetallic thorium (Th)-based compounds were achieved using the generalized gradient approximation in the scheme of Perdew-Burke-Ernzerhof (PBE-GGA) potential, while the generalized gradient approximation plus the Hubbard U (GGA + U) approach was employed to improve the electrical and magnetic properties. In contrast with both the paramagnetic (PM) and antiferromagnetic (AFM) phases, the ThMn2X2 compounds were optimized in a stable ferromagnetic (FM) phase, which was more suited for studying and analyzing magnetic properties. The electronic band structures (BS) and the density of state (DOS) were computed using the two PBE-GGA and GGA + U approximations. The thorium (Th)-based ThMn2X2 compound has full metallic character, due to the crossing and overlapping of bands across the Fermi level of energy, as well as the absence of a gap through both spin (up and down) channels. There was a significant hybridization between (Mn-d and (X = Si and Ge)-p states of conduction band with Th-f states in the valence band. The total magnetic moment of ThMn2Si2 in the ferromagnetic phase was 7.94534 µB, while for ThMn2Ge2 it was 8.73824 µB with a major contribution from the Mn atom. In addition, the ThMn2Ge2 compound's total magnetic moment confirmed that it exhibits higher ferromagnetism than does the ThMn2Si2 compound.

16.
Molecules ; 27(17)2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36080478

RESUMO

Rare-earth zirconate pyrochlores (RE2Zr2O7) are of much fundamental and technological interest as optoelectronic, scintillator and thermal barrier coating materials. For the first time, we report the detailed optoelectronic properties of rare-earth zirconates Nd2Zr2O7 in both, i.e., for spin up and spin down states, via the use of first-principles density functional theory (DFT) procedure. To obtain the desired optoelectronic properties, we used a highly accurate method called full-potential linearized augmented plane wave (FPLAPW) within the generalized gradient approximation (GGA), parametrized with Hubbard potential U as an exchange-correlation function. The band gaps predicted for Nd2Zr2O7 were of the order 2.4 eV and 2.5 eV in Fd-3m and Pmma symmetrical phases, respectively. For both the phases, our research involved a complete examination of the optical properties of Nd2Zr2O7, including extinction coefficient, absorption coefficient, energy loss, function, reflectivity, refractive index, and real optical conductivity, analyzed in the spectral range from 0.0 eV to 14 eV. The calculated optical properties in both phases showed a considerable spin-dependent effect. The electronic bonding characteristics of different species in Nd2Zr2O7 within the two crystal symmetries were explored via the density distribution mapping of charge.

17.
Cell Rep ; 40(8): 111240, 2022 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-36001968

RESUMO

Endogenous retroviruses (ERVs) have been reported to participate in pre-implantation development of mammalian embryos. In early human embryogenesis, different ERV sub-families are activated in a highly stage-specific manner. How the specificity of ERV activation is achieved remains largely unknown. Here, we demonstrate the mechanism of how LTR7Ys, the human morula-blastocyst-specific HERVH long terminal repeats, are activated by the naive pluripotency transcription network. We find that KLF5 interacts with and rewires NANOG to bind and regulate LTR7Ys; in contrast, the primed-specific LTR7s are preferentially bound by NANOG in the absence of KLF5. The specific activation of LTR7Ys by KLF5 and NANOG in pluripotent stem cells contributes to human-specific naive pluripotency regulation. KLF5-LTR7Y axis also promotes the expression of trophectoderm genes and contributes to the expanded cell potential toward extra-embryonic lineage. Our study suggests that HERVs are activated by cell-state-specific transcription machinery and promote stage-specific transcription network and cell potency.


Assuntos
Células-Tronco Embrionárias , Fatores de Transcrição Kruppel-Like/metabolismo , Células-Tronco Pluripotentes , Blastocisto/metabolismo , Diferenciação Celular , Células-Tronco Embrionárias/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Fatores de Transcrição Kruppel-Like/genética , Proteína Homeobox Nanog/genética , Proteína Homeobox Nanog/metabolismo , Células-Tronco Pluripotentes/metabolismo , Fatores de Transcrição/metabolismo
18.
Int J Mol Sci ; 23(6)2022 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-35328506

RESUMO

Cerebrovascular events, notably acute ischemic strokes (AIS), have been reported in the setting of novel coronavirus disease (COVID-19) infection. Commonly regarded as cryptogenic, to date, the etiology is thought to be multifactorial and remains obscure; it is linked either to a direct viral invasion or to an indirect virus-induced prothrombotic state, with or without the presence of conventional cerebrovascular risk factors. In addition, patients are at a greater risk of developing long-term negative sequelae, i.e., long-COVID-related neurological problems, when compared to non-COVID-19 stroke patients. Central to the underlying neurobiology of stroke recovery in the context of COVID-19 infection is reduced angiotensin-converting enzyme 2 (ACE2) expression, which is known to lead to thrombo-inflammation and ACE2/angiotensin-(1-7)/mitochondrial assembly receptor (MasR) (ACE2/Ang-(1-7)/MasR) axis inhibition. Moreover, after AIS, the activated nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) inflammasome may heighten the production of numerous proinflammatory cytokines, mediating neuro-glial cell dysfunction, ultimately leading to nerve-cell death. Therefore, potential neuroprotective therapies targeting the molecular mechanisms of the aforementioned mediators may help to inform rehabilitation strategies to improve brain reorganization (i.e., neuro-gliogenesis and synaptogenesis) and secondary prevention among AIS patients with or without COVID-19. Therefore, this narrative review aims to evaluate the mediating role of the ACE2/Ang- (1-7)/MasR axis and NLRP3 inflammasome in COVID-19-mediated AIS, as well as the prospects of these neuroinflammation mediators for brain repair and in secondary prevention strategies against AIS in stroke rehabilitation.


Assuntos
Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19/metabolismo , Inflamassomos/metabolismo , AVC Isquêmico/metabolismo , Doenças Neuroinflamatórias/metabolismo , Proteínas/metabolismo , Angiotensina I/metabolismo , COVID-19/complicações , COVID-19/virologia , Humanos , AVC Isquêmico/complicações , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Doenças Neuroinflamatórias/complicações , Fragmentos de Peptídeos/metabolismo , Proto-Oncogene Mas/metabolismo , SARS-CoV-2/metabolismo , SARS-CoV-2/fisiologia , Transdução de Sinais
19.
Membranes (Basel) ; 12(3)2022 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-35323758

RESUMO

An investigation of the effect of the molecular weight of polyethylene glycol (PEG) on thin-film composite (TFC) flat sheet polysulfone membrane performance was conducted systematically, for application in forward osmosis (FO) and pressure retarded osmosis (PRO). The TFC flat sheet PSf-modified membranes were prepared via a non-solvent phase-separation technique by introducing PEGs of different molecular weights into the dope solution. The TFC flat sheet PSf-PEG membranes were characterized by SEM, FTIR and AFM. The PSf membrane modified with PEG 600 was found to have the optimum composition. Under FO mode, this modified membrane had a water permeability of 12.30 Lm-2h-1 and a power density of 2.22 Wm-2, under a pressure of 8 bar in PRO mode, using 1 M NaCl and deionized water as the draw and feed solutions, respectively. The high water permeability and good mechanical stability of the modified TFC flat sheet PSF-PEG membrane in this study suggests that this membrane has great potential in future osmotically powered generation systems.

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