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1.
Nat Immunol ; 25(4): 622-632, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38454157

RESUMO

The development of a vaccine specific to severe acute respiratory syndrome coronavirus 2 Omicron has been hampered due to its low immunogenicity. Here, using reverse mutagenesis, we found that a phenylalanine-to-serine mutation at position 375 (F375S) in the spike protein of Omicron to revert it to the sequence found in Delta and other ancestral strains significantly enhanced the immunogenicity of Omicron vaccines. Sequence FAPFFAF at position 371-377 in Omicron spike had a potent inhibitory effect on macrophage uptake of receptor-binding domain (RBD) nanoparticles or spike-pseudovirus particles containing this sequence. Omicron RBD enhanced binding to Siglec-9 on macrophages to impair phagocytosis and antigen presentation and promote immune evasion, which could be abrogated by the F375S mutation. A bivalent F375S Omicron RBD and Delta-RBD nanoparticle vaccine elicited potent and broad nAbs in mice, rabbits and rhesus macaques. Our research suggested that manipulation of the Siglec-9 pathway could be a promising approach to enhance vaccine response.


Assuntos
COVID-19 , SARS-CoV-2 , Animais , Camundongos , Coelhos , Anticorpos Neutralizantes , Anticorpos Antivirais , Macaca mulatta , Macrófagos , Nanovacinas , Fagocitose , Lectinas Semelhantes a Imunoglobulina de Ligação ao Ácido Siálico
2.
Hum Brain Mapp ; 45(9): e26693, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38924235

RESUMO

The corpus callosum (CC) is a large white matter fiber bundle in the brain and is involved in various cognitive, sensory, and motor processes. While implicated in various developmental and psychiatric disorders, much is yet to be uncovered about the normal development of this structure, especially in young children. Additionally, while sexual dimorphism has been reported in prior literature, observations have not necessarily been consistent. In this study, we use morphometric measures including surface tensor-based morphometry (TBM) to investigate local changes in the shape of the CC in children between the ages of 12 and 60 months, in intervals of 12 months. We also analyze sex differences in each of these age groups. We observed larger significant clusters in the earlier ages between 12 v 24 m and between 48 v 60 m and localized differences in the anterior region of the body of the CC. Sex differences were most pronounced in the 12 m group. This study adds to the growing literature of work aiming to understand the developing brain and emphasizes the utility of surface TBM as a useful tool for analyzing regional differences in neuroanatomical morphometry.


Assuntos
Corpo Caloso , Caracteres Sexuais , Humanos , Corpo Caloso/diagnóstico por imagem , Corpo Caloso/crescimento & desenvolvimento , Corpo Caloso/anatomia & histologia , Masculino , Feminino , Lactente , Pré-Escolar , Imagem de Tensor de Difusão , Imageamento por Ressonância Magnética , Processamento de Imagem Assistida por Computador/métodos
3.
BMC Microbiol ; 24(1): 62, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38373936

RESUMO

BACKGROUND: In this study, we investigated the effects of alpine meadow in different phenological periods on ruminal fermentation, serum biochemical indices, and gastrointestinal tract microbes in grazing yak on the Qinghai-Tibetan Plateau. A total of eighteen female freely grazing yaks with an average age of 3 years old and a body weight of 130 ± 19 kg were selected. According to the plant phenological periods, yaks were randomly allocated to one of three treatments: (1) regreen periods group (RP, n = 6); (2) grassy periods group (GP, n = 6); and (3) hay periods group (HP, n = 6). At the end of the experiment, the blood, rumen fluids, and rectal contents were collected to perform further analysis. RESULTS: The concentrations of total volatile fatty acid (TVFA), acetate, glucose (GLU), triglyceride (TG), cholesterol (CHO), high density lipoprotein (HDL), and low density lipoprotein (LDL) were higher in the GP group than in the HP group (P < 0.05). However, compared with the RP and GP groups, the HP group had higher concentrations of isobutyrate, isovalerate, valerate, and creatinine (CREA) (P < 0.05). The abundance of Prevotella in the rumen, and the abundances of Rikenellaceae_RC9_gut_group, Eubacterium_coprostanoligenes_group, and Prevotellaceae_UCG-004 in the gut were higher in the GP group compared with the HP group (P < 0.05). The HP had higher abundance of Eubacterium_coprostanoligenes_group in the rumen as well as the abundances of Romboutsia and Arthrobacter in the gut compared with the RP and GP groups (P < 0.05). CONCLUSIONS: Based on the results of rumen fermentation, serum biochemical, differential biomarkers, and function prediction, the carbohydrate digestion of grazing yak would be higher with the alpine meadow regreen and grassy due to the gastrointestinal tract microbes. However, the risk of microbe disorders and host inflammation in grazing yak were higher with the alpine meadow wither.


Assuntos
Pradaria , Rúmen , Animais , Bovinos , Bactérias/genética , Bacteroidetes , Fermentação , Trato Gastrointestinal , Rúmen/microbiologia , Tibet
4.
BMC Med Imaging ; 24(1): 78, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38570748

RESUMO

BACKGROUND: To investigate the feasibility of Diffusion Kurtosis Imaging (DKI) in assessing renal interstitial fibrosis induced by hyperuricemia. METHODS: A hyperuricemia rat model was established, and the rats were randomly split into the hyperuricemia (HUA), allopurinol (AP), and AP + empagliflozin (AP + EM) groups (n = 19 per group). Also, the normal rats were selected as controls (CON, n = 19). DKI was performed before treatment (baseline) and on days 1, 3, 5, 7, and 9 days after treatment. The DKI indicators, including mean kurtosis (MK), fractional anisotropy (FA), and mean diffusivity (MD) of the cortex (CO), outer stripe of the outer medulla (OS), and inner stripe of the outer medulla (IS) were acquired. Additionally, hematoxylin and eosin (H&E) staining, Masson trichrome staining, and nuclear factor kappa B (NF-κB) immunostaining were used to reveal renal histopathological changes at baseline, 1, 5, and 9 days after treatment. RESULTS: The HUA, AP, and AP + EM group MKOS and MKIS values gradually increased during this study. The HUA group exhibited the highest MK value in outer medulla. Except for the CON group, all the groups showed a decreasing trend in the FA and MD values of outer medulla. The HUA group exhibited the lowest FA and MD values. The MKOS and MKIS values were positively correlated with Masson's trichrome staining results (r = 0.687, P < 0.001 and r = 0.604, P = 0.001, respectively). The MDOS and FAIS were negatively correlated with Masson's trichrome staining (r = -626, P < 0.0014 and r = -0.468, P = 0.01, respectively). CONCLUSION: DKI may be a non-invasive method for monitoring renal interstitial fibrosis induced by hyperuricemia.


Assuntos
Hiperuricemia , Ratos , Animais , Hiperuricemia/diagnóstico por imagem , Rim/diagnóstico por imagem , Imagem de Tensor de Difusão/métodos , Imagem de Difusão por Ressonância Magnética/métodos , Fibrose
5.
Drug Resist Updat ; 69: 100974, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37230023

RESUMO

AIMS: Neoadjuvant chemotherapy (NAC) is the primary preoperative therapy for breast cancer. The luminal subtype of breast cancer shows less NAC response than the basal subtype, with an inefficient NAC treatment effect. Understanding of the molecular and cellular mechanisms responsible for this chemoresistance is an important issue when determining optimal treatment. METHODS: Doxorubicin-induced apoptosis and ferroptosis was investigated using cytotoxicity, western blotting, and flow cytometry assays. The role of GATA3 in modulating doxorubicin-induced cell death was investigated both in vitro and in vivo. RNA-seq, qPCR, ChIP, and luciferase assay and association analyses were performed to investigate the regulation of CYB5R2 by GATA3. The function of GATA3 and CYB5R2 in regulating doxorubicin-induced ferroptosis was evaluated with iron, ROS, and lipid peroxidation detection assays. Immunohistochemistry was performed for results validation. RESULTS: Doxorubicin-induced basal breast cancer cell death is dependent on iron-mediated ferroptosis. Overexpression of the luminal signature transcriptional factor GATA3 mediates doxorubicin resistance. GATA3 promotes cell viability by decreasing ferroptosis-related gene CYB5R2 expression and by maintaining iron homeostasis. Analyzing data from the public and our cohorts demonstrates that GATA3 and CYB5R2 are associated with NAC response. CONCLUSIONS: GATA3 promotes doxorubicin resistance by inhibiting CYB5R2-mediated iron metabolism and ferroptosis. Therefore, patients with breast cancer who display high GATA3 expression do not benefit from doxorubicin-based NAC regimens.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Apoptose , Ferro/metabolismo , Ferro/uso terapêutico , Catálise , Fator de Transcrição GATA3/genética , Fator de Transcrição GATA3/metabolismo , Fator de Transcrição GATA3/uso terapêutico
6.
Mar Drugs ; 22(2)2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38393028

RESUMO

Oxidative stress, which damages cellular components and causes mitochondrial dysfunction, occurs in a variety of human diseases, including neurological disorders. The clearance of damaged mitochondria via mitophagy maintains the normal function of mitochondria and facilitates cell survival. Astaxanthin is an antioxidant known to have neuroprotective effects, but the underlying mechanisms remain unclear. This study demonstrated that astaxanthin inhibited H2O2-induced apoptosis in SH-SY5Y cells by ameliorating mitochondrial damage and enhancing cell survival. H2O2 treatment significantly reduced the levels of activated Akt and mTOR and induced mitophagy, while pretreatment with astaxanthin prevented H2O2-induced inhibition of Akt and mTOR and attenuated H2O2-induced mitophagy. Moreover, the inhibition of Akt attenuated the protective effect of astaxanthin against H2O2-induced cytotoxicity. Taken together, astaxanthin might inhibit H2O2-induced apoptosis by protecting mitochondrial function and reducing mitophagy. The results also indicate that the Akt/mTOR signaling pathway was critical for the protection of astaxanthin against H2O2-induced cytotoxicity. The results from the present study suggest that astaxanthin can reduce neuronal oxidative injury and may have the potential to be used for preventing neurotoxicity associated with neurodegenerative diseases.


Assuntos
Neuroblastoma , Proteínas Proto-Oncogênicas c-akt , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Peróxido de Hidrogênio/toxicidade , Mitofagia , Neuroblastoma/tratamento farmacológico , Apoptose , Estresse Oxidativo , Serina-Treonina Quinases TOR/metabolismo , Linhagem Celular Tumoral , Espécies Reativas de Oxigênio/metabolismo , Xantofilas
7.
Nano Lett ; 23(5): 1810-1819, 2023 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-36648158

RESUMO

The low piezoelectricity of piezoelectric polymers significantly restricts their applications. Introducing inorganic fillers can slightly improve the piezoelectricity of polymers, whereas it is usually at the cost of flexibility and durability. In this work, using a modulus-modulated core-shell structure strategy, all-organic nanofibers with remarkable piezoelectricity were designed and prepared by a coaxial electrospinning method. It was surprisingly found that the introduction of a nonpiezoelectric polymeric core (e.g., polycarbonate, PC) can result in 110% piezoelectric coefficient (d33) enhancement in a poly(vinylidenefluoride-co-trifluoroethylene) (PVDF-TrFE) nanofiber. Accordingly, the all-organic PVDF-TrFE@PC core-shell nanofiber exhibits record-high energy-harvesting performance (i.e., 126 V output voltage, 710 mW m-2 power density) among the reported organic piezoelectric materials. In addition, the excellent sensing capability of the core-shell nanofiber enabled us to develop a wireless vibration monitoring and analyzing system, which realizes the real-time vibration detection of a power transformer.

8.
J Integr Plant Biol ; 66(7): 1334-1350, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38804844

RESUMO

Drought stress has negative effects on crop growth and production. Characterization of transcription factors that regulate the expression of drought-responsive genes is critical for understanding the transcriptional regulatory networks in response to drought, which facilitates the improvement of crop drought tolerance. Here, we identified an Alfin-like (AL) family gene ZmAL14 that negatively regulates drought resistance. Overexpression of ZmAL14 exhibits susceptibility to drought while mutation of ZmAL14 enhances drought resistance. An abscisic acid (ABA)-activated protein kinase ZmSnRK2.2 interacts and phosphorylates ZmAL14 at T38 residue. Knockout of ZmSnRK2.2 gene decreases drought resistance of maize. A dehydration-induced Rho-like small guanosine triphosphatase gene ZmROP8 is directly targeted and repressed by ZmAL14. Phosphorylation of ZmAL14 by ZmSnRK2.2 prevents its binding to the ZmROP8 promoter, thereby releasing the repression of ZmROP8 transcription. Overexpression of ZmROP8 stimulates peroxidase activity and reduces hydrogen peroxide accumulation after drought treatment. Collectively, our study indicates that ZmAL14 is a negative regulator of drought resistance, which can be phosphorylated by ZmSnRK2.2 through the ABA signaling pathway, thus preventing its suppression on ZmROP8 transcription during drought stress response.


Assuntos
Secas , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas , Zea mays , Fosforilação , Zea mays/genética , Zea mays/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Ácido Abscísico/metabolismo , Estresse Fisiológico/genética , Regiões Promotoras Genéticas/genética , Resistência à Seca
9.
J Appl Biomed ; 22(1): 23-32, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38505967

RESUMO

Dictyophora indusiata, commonly known as bamboo fungus, is a type of edible mushroom that is highly popular worldwide for its rich flavor and nutritional value. It is also recognized for its pharmaceutical efficacy, with medicinal benefits attributed to its consumption. One of the most important components of Dictyophora indusiata is polysaccharide, which has been acknowledged as a promising regulator of biological response due to its immunostimulatory and anti-inflammatory properties. However, the specific roles of polysaccharide in modulating the NOD-like receptor protein 3 (NLRP3) inflammasome activation within macrophages remain relatively under-researched. To investigate this further, the mechanism by which Dictyophora indusiata polysaccharide (DIP) exerts its immunostimulatory activity in RAW 264.7 macrophages was analyzed. Results indicated that DIP has the potential to facilitate the priming of NLRP3 inflammasome activation by enhancing TLR4 expression, phosphorylation of IκB-α, and nuclear translocation of NF-κB p65 subunit. It was noted that DIP was unable to mediate the second step of NLRP3 inflammasome activation. The findings of this study provide compelling evidence that DIP has immunomodulatory effects by modulating the NLRP3 inflammasome in RAW264.7 macrophages.


Assuntos
Basidiomycota , Inflamassomos , NF-kappa B , NF-kappa B/metabolismo , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Receptor 4 Toll-Like/metabolismo , Proteínas NLR , Transdução de Sinais , Polissacarídeos/farmacologia
10.
New Phytol ; 237(5): 1728-1744, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36444538

RESUMO

Drought is a major environmental stress that threatens crop production. Therefore, identification of genes involved in drought stress response is of vital importance to decipher the molecular mechanism of stress signal transduction and breed drought tolerance crops, especially for maize. Clade A PP2C phosphatases are core abscisic acid (ABA) signaling components, regulating ABA signal transduction and drought response. However, the roles of other clade PP2Cs in drought resistance remain largely unknown. Here, we discovered a clade F PP2C, ZmPP84, that negatively regulates drought tolerance by screening a transgenic overexpression maize library. Quantitative RT-PCR indicates that the transcription of ZmPP84 is suppressed by drought stress. We identified that ZmMEK1, a member of the MAPKK family, interacts with ZmPP84 by immunoprecipitation and mass spectrometry analysis. Additionally, we found that ZmPP84 can dephosphorylate ZmMEK1 and repress its kinase activity on the downstream substrate kinase ZmSIMK1, while ZmSIMK1 is able to phosphorylate S-type anion channel ZmSLAC1 at S146 and T520 in vitro. Mutations of S146 and T520 to phosphomimetic aspartate could activate ZmSLAC1 currents in Xenopus oocytes. Taken together, our study suggests that ZmPP84 is a negative regulator of drought stress response that inhibits stomatal closure through dephosphorylating ZmMEK1, thereby repressing ZmMEK1-ZmSIMK1 signaling pathway.


Assuntos
Ácido Abscísico , Zea mays , Ácido Abscísico/farmacologia , Ácido Abscísico/metabolismo , Zea mays/genética , Zea mays/metabolismo , Resistência à Seca , Melhoramento Vegetal , Fosfoproteínas Fosfatases/genética , Fosfoproteínas Fosfatases/metabolismo , Secas , Regulação da Expressão Gênica de Plantas , Estresse Fisiológico/genética
11.
Org Biomol Chem ; 21(22): 4540-4552, 2023 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-37212028

RESUMO

Aggregation of amyloid-ß (Aß) peptides is characteristic of Alzheimer's disease (AD), which is the most common neurodegenerative disorder. Increasing evidence shows that Aß oligomers, the intermediates during aggregation, rather than the fully mature fibrils are the most toxic species of Aß and the key contributors to neurodegeneration. Aß oligomers have been considered as both biomarkers and drug targets for the diagnosis and treatment of AD. However, the high heterogeneity and metastability of oligomers make it difficult to determine their exact pathogenic mechanisms. Recent developments in Aß oligomer-targeting agents and techniques have provided great opportunities for overcoming the existing limitations. This review introduces the formation, structure, and toxicity of Aß oligomers and categorizes the Aß oligomer-targeting agents based on their chemical biological applications, including recognition and detection of Aß oligomers for diagnosis, intervention of Aß oligomerization for treatment, and stabilization of Aß oligomers for pathogenic studies. The design strategies and working mechanisms of the representative examples published in the past five years are highlighted. Finally, future development directions and challenges of Aß oligomer targeting are tentatively proposed.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Humanos , Peptídeos beta-Amiloides/química , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/tratamento farmacológico , Biologia , Fragmentos de Peptídeos/uso terapêutico
12.
Int J Med Sci ; 20(6): 737-748, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37213672

RESUMO

Purpose: The effectiveness of inactivated vaccines against acute respiratory syndrome coronavirus 2 (SARS­CoV­2), the causative agent of coronavirus disease 2019 (COVID-19), has become a global concern. Hence, the aim of this study was to evaluate vaccine safety and to assess immune responses in individuals with chronic respiratory disease (CRD) following a two-dose vaccination. Methods: The study cohort included 191 participants (112 adult CRD patients and 79 healthy controls [HCs]) at least 21 (range, 21-159) days after a second vaccination. Frequencies of memory B cells (MBCs) subsets and titers of SARS-CoV-2 neutralizing antibodies (NAbs) and anti-receptor binding domain (RBD) IgG antibodies (Abs) were analyzed. Results: As compared to the HCs, CRD patients had lower seropositivity rates and titers of both anti-RBD IgG Abs and NAbs, in addition to lower frequencies of RBD-specific MBCs (all, p < 0.05). At 3 months, CRD patients had lower seropositivity rates and titers of anti-RBD IgG Abs than the HCs (p < 0.05). For CoronaVac, the seropositivity rates of both Abs were lower in patients with old pulmonary tuberculosis than HCs. For BBIBP-CorV, the seropositivity rates of CoV-2 NAbs were lower in patients with chronic obstructive pulmonary disease than HCs (all, p < 0.05). Meanwhile, there was no significant difference in overall adverse events between the CRD patients and HCs. Univariate and multivariate analyses identified the time interval following a second vaccination as a risk factor for the production of anti-RBD IgG Abs and CoV-2 NAbs, while the CoronaVac had a positive effect on the titers of both Abs. Female was identified as a protective factor for CoV-2 NAb levels. Conclusion: Inactivated COVID-19 vaccines were safe and well tolerated by CRD patients but resulted in lower Ab responses and the frequencies of RBD-specific MBCs. Therefore, CRD patients should be prioritized for booster vaccinations.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Adulto , Feminino , Humanos , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/prevenção & controle , População do Leste Asiático , Imunidade , Imunoglobulina G , SARS-CoV-2 , Eficácia de Vacinas , Imunogenicidade da Vacina , Doenças Respiratórias/imunologia , Doença Crônica
13.
Neoplasma ; 70(1): 71-81, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36620876

RESUMO

Breast cancer is one of the leading cancer deaths around the world. Targeted drugs have greatly increased the survival rate of breast cancer patients in recent years. But in some patients, the current regimen is still ineffective. Therefore, more therapeutic targets for treating breast cancer are demanding. The core heterochromatin-related genes of breast cancer were identified by utilizing prognostic survival analysis and multivariate Cox hazard proportional regression analysis. Both breast cancer and adjacent normal tissue were collected and analyzed with western blot and immunohistochemistry. Colony formation assay, CCK-8 assay, and EdU assay were used to measure the effect of CBX3 on breast cancer cell growth, wound-healing assay and Transwell assay were used to analyze the effect of CBX3 on breast cancer cell migration and invasion. Flow cytometry assay and western blot were used to study the molecular mechanism of CBX3 in breast cancer. High expression of heterochromatin-related proteins CBX3, H2AFY, and SULF1 showed a poor prognosis in patients in both TCGA dataset and GEO datasets. Western blot demonstrated that the expression level of CBX3 was significantly higher in breast cancer than that in adjacent normal tissues. Colony formation assay, CCK-8 assay, and EdU assay showed that the knockdown of CBX3 could significantly inhibit breast cancer cell growth, and the overexpression of CBX3 could promote the growth of breast cancer cells. Transwell assay and wound healing assay showed that knockdown of CBX3 inhibited breast cancer cell migration and invasion, and the overexpression of CBX3 promoted breast cancer cell migration and invasion. Western blot showed that CBX3 might promote breast cancer cell proliferation, invasion, and migration in breast cancer by modulating the ERK1/2 signaling pathway and epithelial-mesenchymal transition (EMT)-related genes. CBX3 was a biomarker of poor prognosis in breast cancer patients. CBX3 promoted the proliferation of breast cancer cells through the ERK signaling pathway, and migration and invasion of breast cancer cells through EMT-related genes. The CBX3/p-ERK1/2 signaling axis might provide a new therapeutic method against breast cancer.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/metabolismo , Heterocromatina , Linhagem Celular Tumoral , Movimento Celular/genética , Prognóstico , Transformação Celular Neoplásica/genética , Proliferação de Células/genética , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Proteínas Cromossômicas não Histona/genética
14.
Acta Cardiol Sin ; 39(1): 144-150, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36685156

RESUMO

Background: Angiotensin receptor neprilysin inhibition (ARNI) is superior to enalapril in reducing the risk of cardiovascular death and heart failure hospitalization (HFH). However, whether prescription pattern is associated with heart failure outcome is unknown. Methods: This is a retrospective study of 153 patients who received ARNI in a tertiary medical center in Taiwan. We analyzed the impact of dose up-titration and prescription timing including during initial admission, within 3 months after initial HFH discharge, and at outpatient clinics without prior HFH. The primary endpoint was the composite of cardiovascular death and HFH. Results: After a mean follow-up period of 287 ± 197 days, the primary endpoint occurred in 43 (28.1%) subjects. Patients without and with a primary endpoint significantly differed in terms of history of valvular heart disease (VHD, p = 0.006), ventricular tachyarrhythmia (VT, p = 0.043), percutaneous coronary intervention (p = 0.007), coronary artery bypass grafting (p = 0.002), chronic kidney disease (p = 0.002), age (p = 0.002), diastolic blood pressure (p = 0.025), and prescription timing (p = 0.002). Kaplan-Meier analysis showed ARNI up-titration and prescription timing had a significant association with primary endpoint-free survival (Breslow test; p = 0.032, and log-rank test; p = 0.001, respectively). Cox regression analysis showed that independent predictors for the primary endpoint were ARNI up-titration [hazard ratio (HR): 0.41, p = 0.024], non-hospital ARNI versus hospital ARNI (HR: 0.41, p = 0.009), VHD (HR: 2.71, p = 0.013), VT (HR: 3.09, p = 0.02), and age (HR: 1.03, p = 0.033). Conclusions: The prescription pattern of ARNI could be associated with heart failure events.

15.
PLoS Comput Biol ; 17(8): e1009216, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34339414

RESUMO

Retinotopic mapping, i.e., the mapping between visual inputs on the retina and neuronal activations in cortical visual areas, is one of the central topics in visual neuroscience. For human observers, the mapping is obtained by analyzing functional magnetic resonance imaging (fMRI) signals of cortical responses to slowly moving visual stimuli on the retina. Although it is well known from neurophysiology that the mapping is topological (i.e., the topology of neighborhood connectivity is preserved) within each visual area, retinotopic maps derived from the state-of-the-art methods are often not topological because of the low signal-to-noise ratio and spatial resolution of fMRI. The violation of topological condition is most severe in cortical regions corresponding to the neighborhood of the fovea (e.g., < 1 degree eccentricity in the Human Connectome Project (HCP) dataset), significantly impeding accurate analysis of retinotopic maps. This study aims to directly model the topological condition and generate topology-preserving and smooth retinotopic maps. Specifically, we adopted the Beltrami coefficient, a metric of quasiconformal mapping, to define the topological condition, developed a mathematical model to quantify topological smoothing as a constrained optimization problem, and elaborated an efficient numerical method to solve the problem. The method was then applied to V1, V2, and V3 simultaneously in the HCP dataset. Experiments with both simulated and real retinotopy data demonstrated that the proposed method could generate topological and smooth retinotopic maps.


Assuntos
Mapeamento Encefálico/métodos , Retina/fisiologia , Córtex Visual/fisiologia , Adulto , Algoritmos , Mapeamento Encefálico/estatística & dados numéricos , Biologia Computacional , Simulação por Computador , Conectoma/métodos , Conectoma/estatística & dados numéricos , Bases de Dados Factuais , Feminino , Neuroimagem Funcional/estatística & dados numéricos , Humanos , Imageamento por Ressonância Magnética/estatística & dados numéricos , Masculino , Modelos Neurológicos , Estimulação Luminosa , Retina/diagnóstico por imagem , Razão Sinal-Ruído , Córtex Visual/diagnóstico por imagem , Vias Visuais/diagnóstico por imagem , Vias Visuais/fisiologia , Adulto Jovem
16.
Acta Pharmacol Sin ; 43(1): 10-14, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33731774

RESUMO

Metabolic-associated fatty liver disease (MAFLD) is the most common metabolic disease with a global prevalence of 25%. While MAFLD is serious and incurable at the later stage, it can be controlled or reversed at the early stage of hepatosteatosis originating from unhealthy diets. Recent laboratory evidence implicates a critical role of the mammalian target of rapamycin (mTOR)-autophagy signaling pathway in the pathogenesis of MAFLD induced by a high-fructose diet mimicking the overconsumption of sugar in humans. This review discusses the possible molecular mechanisms of mTOR-autophagy-endoplasmic reticulum (ER) stress in MAFLD. Based on careful analysis of recent studies, we suggest possible new therapeutic concepts or targets that can be explored for the discovery of new anti-MAFLD drugs.


Assuntos
Autofagia , Frutose/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Estresse do Retículo Endoplasmático , Frutose/efeitos adversos , Humanos , Transdução de Sinais
17.
J Environ Manage ; 311: 114820, 2022 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-35276560

RESUMO

Establishing a practicable ecological compensation scheme is crucial to raise sufficient funds for habitat conservation. This study proposes a cross-region ecological compensation scheme by integrating habitat maintenance services production and consumption. In addition, the suitability evaluation method and InVEST model of habitat quality were employed to estimate the habitat maintenance services production and consumption, respectively. We used 1980 as the benchmark year and applied the scheme to a three-level hierarchy of the Jing-Jin-Ji region for 2000, 2008 and 2013. At the provincial level, Beijing paid the most habitat maintenance services ecological compensation, with an increasing trend from 1.64 × 109 RMB to 2.22 × 109 RMB, and Hebei received the most, from 2.06 × 109 RMB to 2.72 × 109 RMB. At the municipal level, Chengde, which is the most underdeveloped region in Hebei, was the largest beneficiary, receiving 1.31 × 109 RMB, 1.42 × 109 RMB and 1.46 × 109 RMB, respectively, and the ratio of ecological compensation to fiscal revenue was 7.59%. At the county level, Fengning and Weichang, the top two underdeveloped counties in Chengde, received the highest compensation. The results are consistent with each region's ecological function positioning and economic development status of the Jing-Jin-Ji region. This study can clarify the ecological responsibilities and rights, and provides the suggestions for establishing the cross administrative region ecological compensation scheme and long-term funding mechanism for habitat conservation.

18.
J Org Chem ; 86(9): 6780-6786, 2021 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-33900764

RESUMO

Condensation of the methoxymethyl-protected (R)-3,3'-diformyl-1,1'-bi-2-naphthol (BINOL) with (pyridine-2,6-diylbis(methylene))bis(triphenyl phosphonium)dibromide in the presence of a base followed by deprotection gave a new bisBINOL-based fluorescent probe (R,R)-4. This compound showed expanded substrate scope in the recognition of amino acids with good enantioselective fluorescence responses toward 17 common amino acids. Two diastereomeric imines were synthesized from the condensation of (R,R)-4 with l- and d-valine, and the reactions of these imines with Zn(OAc)2 were investigated by various spectroscopic methods for a better understanding of the enantioselective fluorescent recognition process.


Assuntos
Aminas , Aminoácidos , Estrutura Molecular , Espectrometria de Fluorescência , Estereoisomerismo
19.
Environ Sci Technol ; 55(23): 15694-15704, 2021 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-34784716

RESUMO

A prominent source of hydroxyl radicals (•OH), nitrous acid (HONO) plays a key role in tropospheric chemistry. Apart from direct emission, HONO (or its conjugate base nitrite, NO2-) can be formed secondarily in the atmosphere. Yet, how secondary HONO forms requires elucidation, especially for heterogeneous processes involving numerous organic compounds in atmospheric aerosols. We investigated nitrite production from aqueous photolysis of nitrate for a range of conditions (pH, organic compound, nitrate concentration, and cation). Upon adding small oxygenates such as ethanol, n-butanol, or formate as •OH scavengers, the average intrinsic quantum yield of nitrite [Φ(NO2-)] was 0.75 ± 0.15%. With near-UV-light-absorbing vanillic acid (VA), however, the effective Φ(NO2-) was strongly pH-dependent, reaching 8.0 ± 2.1% at a pH of 8 and 1.5 ± 0.39% at a more atmospherically relevant pH of 5. Our results suggest that brown carbon (BrC) may greatly enhance the nitrite production from the aqueous nitrate photolysis through photosensitizing reactions, where the triplet excited state of BrC may generate solvated electrons, which reduce nitrate to NO2 for further conversion to nitrite. This photosensitization process by BrC chromophores during nitrate photolysis under mildly acidic conditions may partly explain the missing HONO in urban environments.


Assuntos
Nitratos , Nitritos , Ácido Nitroso , Fotólise , Ácido Vanílico
20.
Biomed Eng Online ; 20(1): 122, 2021 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-34863194

RESUMO

BACKGROUND: Heart rate (HR) is an important vital sign for evaluating the physiological condition of a newborn infant. Recently, for measuring HR, novel RGB camera-based non-contact techniques have demonstrated their specific superiority compared with other techniques, such as dopplers and thermal cameras. However, they still suffered poor robustness in infants' HR measurements due to frequent body movement. METHODS: This paper introduces a framework to improve the robustness of infants' HR measurements by solving motion artifact problems. Our solution is based on the following steps: morphology-based filtering, region-of-interest (ROI) dividing, Eulerian video magnification and majority voting. In particular, ROI dividing improves ROI information utilization. The majority voting scheme improves the statistical robustness by choosing the HR with the highest probability. Additionally, we determined the dividing parameter that leads to the most accurate HR measurements. In order to examine the performance of the proposed method, we collected 4 hours of videos and recorded the corresponding electrocardiogram (ECG) of 9 hospitalized neonates under two different conditions-rest still and visible movements. RESULTS: Experimental results indicate a promising performance: the mean absolute error during rest still and visible movements are 3.39 beats per minute (BPM) and 4.34 BPM, respectively, which improves at least 2.00 and 1.88 BPM compared with previous works. The Bland-Altman plots also show the remarkable consistency of our results and the HR derived from the ground-truth ECG. CONCLUSIONS: To the best of our knowledge, this is the first study aimed at improving the robustness of neonatal HR measurement under motion artifacts using an RGB camera. The preliminary results have shown the promising prospects of the proposed method, which hopefully reduce neonatal mortality in hospitals.


Assuntos
Artefatos , Fotopletismografia , Eletrocardiografia , Frequência Cardíaca , Humanos , Lactente , Recém-Nascido , Movimento (Física)
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