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1.
Small ; 20(13): e2308877, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37948431

RESUMEN

Tin halide perovskite solar cells (PSCs) are regarded as the most promising lead-free alternatives for photovoltaic applications. However, they still suffer from uncompetitive photovoltaic performance because of the facile Sn2+ oxidation and Sn-related defects. Herein, a defect and carrier management strategy by using diaminopyridine (DP) and 4-bromo-2,6-diaminopyridine (4BrDP) as multifunctional additives for tin halide perovskites is reported. Both DP and 4BrDP induced strong interaction with tin perovskites by coordinate bonding and N─H···I hydrogen bonding, which greatly suppresses the micro-strain and Urbach energy of tin halide perovskite films. The strong hydrogen bonding inhibits the formation of I3 - and related defect density. Meanwhile, the electron-donor species of halogen bond in 4BrDP provides higher reactivity of 2 and 6 sites, which indicates stronger passivation ability with tin halide perovskites. These advances enable a champion power conversion efficiency (PCE) of 13.40% in 4BrDP-processed devices with remarkable improvement in both open-circuit voltage (Voc) of 881 mV and fill factor (FF) of 71.26%. The 4BrDP devices retain 91% and 82% of the pristine PCE after 2000 h storage in N2 atmosphere and 1000 h under 85 °C, respectively. Therefore, this work provides new insight into molecular design for high-performance and stable lead-free optoelectronics.

2.
J Virol ; 97(9): e0079023, 2023 09 28.
Artículo en Inglés | MEDLINE | ID: mdl-37607058

RESUMEN

Bats carry genetically diverse severe acute respiratory syndrome-related coronaviruses (SARSr-CoVs). Some of them utilize human angiotensin-converting enzyme 2 (hACE2) as a receptor and cannot efficiently replicate in wild-type mice. Our previous study demonstrated that the bat SARSr-CoV rRsSHC014S induces respiratory infection and lung damage in hACE2 transgenic mice but not wild-type mice. In this study, we generated a mouse-adapted strain of rRsSHC014S, which we named SMA1901, by serial passaging of wild-type virus in BALB/c mice. SMA1901 showed increased infectivity in mouse lungs and induced interstitial lung pneumonia in both young and aged mice after intranasal inoculation. Genome sequencing revealed mutations in not only the spike protein but the whole genome, which may be responsible for the enhanced pathogenicity of SMA1901 in wild-type BALB/c mice. SMA1901 induced age-related mortality similar to that observed in SARS and COVID-19. Drug testing using antibodies and antiviral molecules indicated that this mouse-adapted virus strain can be used to test prophylactic and therapeutic drug candidates against SARSr-CoVs. IMPORTANCE The genetic diversity of SARSr-CoVs in wildlife and their potential risk of cross-species infection highlights the importance of developing a powerful animal model to evaluate the antibodies and antiviral drugs. We acquired the mouse-adapted strain of a bat-origin coronavirus named SMA1901 by natural serial passaging of rRsSHC014S in BALB/c mice. The SMA1901 infection caused interstitial pneumonia and inflammatory immune responses in both young and aged BALB/c mice after intranasal inoculation. Our model exhibited age-related mortality similar to SARS and COVID-19. Therefore, our model will be of high value for investigating the pathogenesis of bat SARSr-CoVs and could serve as a prospective test platform for prophylactic and therapeutic candidates.


Asunto(s)
Quirópteros , Ratones , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo , Animales , Ratones/virología , Quirópteros/virología , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/clasificación , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/efectos de los fármacos , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/genética , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/patogenicidad , Ratones Endogámicos BALB C , COVID-19/mortalidad , Síndrome Respiratorio Agudo Grave/tratamiento farmacológico , Síndrome Respiratorio Agudo Grave/mortalidad , Pase Seriado , Antivirales/farmacología , Antivirales/uso terapéutico , Anticuerpos Antivirales/farmacología , Anticuerpos Antivirales/uso terapéutico , Zoonosis Virales/tratamiento farmacológico , Zoonosis Virales/transmisión , Zoonosis Virales/virología , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Enfermedades Pulmonares Intersticiales/virología , Envejecimiento , Evaluación Preclínica de Medicamentos
3.
J Virol ; 97(2): e0171922, 2023 02 28.
Artículo en Inglés | MEDLINE | ID: mdl-36688655

RESUMEN

Coronavirus disease 2019 (COVID-19), which is caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the most severe emerging infectious disease in the current century. The discovery of SARS-CoV-2-related coronaviruses (SARSr-CoV-2) in bats and pangolins in South Asian countries indicates that SARS-CoV-2 likely originated from wildlife. To date, two SARSr-CoV-2 strains have been isolated from pangolins seized in Guangxi and Guangdong by the customs agency of China, respectively. However, it remains unclear whether these viruses cause disease in animal models and whether they pose a transmission risk to humans. In this study, we investigated the biological features of a SARSr-CoV-2 strain isolated from a smuggled Malayan pangolin (Manis javanica) captured by the Guangxi customs agency, termed MpCoV-GX, in terms of receptor usage, cell tropism, and pathogenicity in wild-type BALB/c mice, human angiotensin-converting enzyme 2 (ACE2)-transgenic mice, and human ACE2 knock-in mice. We found that MpCoV-GX can utilize ACE2 from humans, pangolins, civets, bats, pigs, and mice for cell entry and infect cell lines derived from humans, monkeys, bats, minks, and pigs. The virus could infect three mouse models but showed limited pathogenicity, with mild peribronchial and perivascular inflammatory cell infiltration observed in lungs. Our results suggest that this SARSr-CoV-2 virus from pangolins has the potential for interspecies infection, but its pathogenicity is mild in mice. Future surveillance among these wildlife hosts of SARSr-CoV-2 is needed to monitor variants that may have higher pathogenicity and higher spillover risk. IMPORTANCE SARS-CoV-2, which likely spilled over from wildlife, is the third highly pathogenic human coronavirus. Being highly transmissible, it is perpetuating a pandemic and continuously posing a severe threat to global public health. Several SARS-CoV-2-related coronaviruses (SARSr-CoV-2) in bats and pangolins have been identified since the SARS-CoV-2 outbreak. It is therefore important to assess their potential of crossing species barriers for better understanding of their risk of future emergence. In this work, we investigated the biological features and pathogenicity of a SARSr-CoV-2 strain isolated from a smuggled Malayan pangolin, named MpCoV-GX. We found that MpCoV-GX can utilize ACE2 from 7 species for cell entry and infect cell lines derived from a variety of mammalian species. MpCoV-GX can infect mice expressing human ACE2 without causing severe disease. These findings suggest the potential of cross-species transmission of MpCoV-GX, and highlight the need of further surveillance of SARSr-CoV-2 in pangolins and other potential animal hosts.


Asunto(s)
COVID-19 , Especificidad del Huésped , Pangolines , Animales , Humanos , Ratones , Enzima Convertidora de Angiotensina 2/genética , Línea Celular , China , COVID-19/transmisión , COVID-19/virología , Pulmón/patología , Pulmón/virología , Ratones Transgénicos , Pangolines/virología , SARS-CoV-2/clasificación , SARS-CoV-2/genética , SARS-CoV-2/patogenicidad , Porcinos , Quirópteros
4.
J Virol ; 97(10): e0091623, 2023 10 31.
Artículo en Inglés | MEDLINE | ID: mdl-37772826

RESUMEN

IMPORTANCE: Gaining insight into the cell-entry mechanisms of swine acute diarrhea syndrome coronavirus (SADS-CoV) is critical for investigating potential cross-species infections. Here, we demonstrated that pretreatment of host cells with tunicamycin decreased SADS-CoV attachment efficiency, indicating that N-linked glycosylation of host cells was involved in SADS-CoV entry. Common N-linked sugars Neu5Gc and Neu5Ac did not interact with the SADS-CoV S1 protein, suggesting that these molecules were not involved in SADS-CoV entry. Additionally, various host proteases participated in SADS-CoV entry into diverse cells with different efficiencies. Our findings suggested that SADS-CoV may exploit multiple pathways to enter cells, providing insights into intervention strategies targeting the cell entry of this virus.


Asunto(s)
Alphacoronavirus , Infecciones por Coronavirus , Endopeptidasas , Glicoproteínas , Enfermedades de los Porcinos , Porcinos , Internalización del Virus , Animales , Alphacoronavirus/fisiología , Infecciones por Coronavirus/enzimología , Infecciones por Coronavirus/metabolismo , Infecciones por Coronavirus/veterinaria , Infecciones por Coronavirus/virología , Endopeptidasas/metabolismo , Glicoproteínas/química , Glicoproteínas/metabolismo , Porcinos/virología , Enfermedades de los Porcinos/enzimología , Enfermedades de los Porcinos/metabolismo , Enfermedades de los Porcinos/virología , Internalización del Virus/efectos de los fármacos , Tunicamicina/farmacología , Glicosilación
5.
Plant Cell Environ ; 47(5): 1668-1684, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38282271

RESUMEN

Drought stress is one of the main environmental factors limiting plant growth and development. Plants adapt to changing soil moisture by modifying root architecture, inducing stomatal closure, and inhibiting shoot growth. The AP2/ERF transcription factor DREB2A plays a key role in maintaining plant growth in response to drought stress, but the molecular mechanism underlying this process remains to be elucidated. Here, it was found that overexpression of MdDREB2A positively regulated nitrogen utilisation by interacting with DRE cis-elements of the MdNIR1 promoter. Meanwhile, MdDREB2A could also directly bind to the promoter of MdSWEET12, which may enhance root development and nitrogen assimilation, ultimately promoting plant growth. Overall, this regulatory mechanism provides an idea for plants in coordinating with drought tolerance and nitrogen assimilation to maintain optimal plant growth and development under drought stress.


Asunto(s)
Sequías , Proteínas de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente/metabolismo , Regiones Promotoras Genéticas , Sacarosa/metabolismo , Regulación de la Expresión Génica de las Plantas , Estrés Fisiológico/genética
6.
Acta Pharmacol Sin ; 45(2): 327-338, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37845344

RESUMEN

Tricyclic antidepressants (TCAs) are widely used to treat depression and anxiety-related mood disorders. But evidence shows that TCAs elevate blood glucose levels and inhibit insulin secretion, suggesting that TCAs are a risk factor, particularly for individuals with diabetes. Curcumin is a bioactive molecule from the rhizome of the Curcuma longa plant, which has shown both antidepressant and anti-diabetic activities. In the present study, we investigated the protective effect of curcumin against desipramine-induced apoptosis in ß cells and the underlying molecular mechanisms. In the mouse forced swimming test (FST), we found that lower doses of desipramine (5 and 10 mg/kg) or curcumin (2.5 mg/kg) alone did not affect the immobility time, whereas combined treatment with curcumin (2.5 mg/kg) and desipramine (5, 10 mg/kg) significantly decreased the immobility time. Furthermore, desipramine dose-dependently inhibited insulin secretion and elevated blood glucose levels, whereas the combined treatment normalized insulin secretion and blood glucose levels. In RIN-m5F pancreatic ß-cells, desipramine (10 µM) significantly reduced the cell viability, whereas desipramine combined with curcumin dose-dependently prevented the desipramine-induced impairment in glucose-induced insulin release, most effectively with curcumin (1 and 10 µM). We demonstrated that desipramine treatment promoted the cleavage and activation of Caspase 3 in RIN-m5F cells. Curcumin treatment inhibited desipramine-induced apoptosis, increased mitochondrial membrane potential and Bcl-2/Bax ratio. Desipramine increased the generation of reactive oxygen species, which was reversed by curcumin treatment. Curcumin also inhibited the translocation of forkhead box protein O1 (FOXO1) from the cytoplasm to the nucleus and suppressed the binding of A-kinase anchor protein 150 (AKAP150) to protein phosphatase 2B (PP2B, known as calcineurin) that was induced by desipramine. These results suggest that curcumin protects RIN-m5F pancreatic ß-cells against desipramine-induced apoptosis by inhibiting the phosphoinositide 3-kinase/AKT/FOXO1 pathway and the AKAP150/PKA/PP2B interaction. This study suggests that curcumin may have therapeutic potential as an adjunct to antidepressant treatment.


Asunto(s)
Curcumina , Ratones , Animales , Curcumina/farmacología , Desipramina/farmacología , Glucemia , Fosfatidilinositol 3-Quinasas/metabolismo , Apoptosis , Antidepresivos/farmacología
7.
Molecules ; 29(5)2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38474548

RESUMEN

Transient receptor potential vanilloid 4 (TRPV4) is a widely expressed cation channel that plays an important role in many physiological and pathological processes. However, most TRPV4 drugs carry a risk of side effects. Moreover, existing screening methods are not suitable for the high-throughput screening (HTS) of drugs. In this study, a cell model and HTS method for targeting TRPV4 channel drugs were established based on a calcium-activated chloride channel protein 1 Anoctamin 1 (ANO1) and a double mutant (YFP-H148Q/I152L) of the yellow fluorescent protein (YFP). Patch-clamp experiments and fluorescence quenching kinetic experiments were used to verify that the model could sensitively detect changes in intracellular Ca2+ concentration. The functionality of the TRPV4 cell model was examined through temperature variations and different concentrations of TRPV4 modulators, and the performance of the model in HTS was also evaluated. The model was able to sensitively detect changes in the intracellular Ca2+ concentration and also excelled at screening TRPV4 drugs, and the model was more suitable for HTS. We successfully constructed a drug cell screening model targeting the TRPV4 channel, which provides a tool to study the pathophysiological functions of TRPV4 in vitro.


Asunto(s)
Ensayos Analíticos de Alto Rendimiento , Canales Catiónicos TRPV , Canales Catiónicos TRPV/metabolismo , Anoctamina-1 , Calcio/metabolismo
8.
BMC Oral Health ; 24(1): 673, 2024 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-38851679

RESUMEN

BACKGROUND: Early childhood caries (ECC) remain a serious oral health problem on a global scale. Risk-based caries management (RBCM) implemented in some parts of the world has been effective in preventing ECC. However, there is a lack of prospective research on the application of RBCM among Chinese children, and little is known about its effectiveness. The purpose of this study was to evaluate the effectiveness of RBCM in preventing caries among children aged 3-5 years in Wanzhou District, Chongqing Municipality, China. METHODS: Three- to five-year-old children from four kindergartens in Wanzhou were randomly selected for baseline dental examination and caries risk assessment (CRA) and randomly assigned to the experimental group (EG) or the control group (CG) according to the kindergarten. The EG received caries prevention measures of different intensities based on the child's caries risk level. The CG received full-mouth fluoride twice a year according to standard prevention, regardless of their caries risk. One year later, another dental examination and CRA were conducted, to observe changes in the decayed, missing, and filled teeth (dmft) index and caries risk, and to analyze potential factors that may affect the incidence of new caries. RESULTS: Complete data were collected from 291 children (EG, N = 140, 84.8%; CG, N = 181, 83.4%). A total of 25.7% of the EG and 50.3% of the CG children developed new caries, with newly added dmft scores of 0.54 ± 1.12 and 1.32 ± 1.72, respectively (P < 0.05). Multivariate logistic regression indicated that children living in rural areas, assigned to the CG, and rated as high-risk at baseline were more likely to develop new caries (P < 0.05). The proportion of children with an increased caries risk in the EG was significantly lower than that in the CG (P < 0.05). CONCLUSIONS: RBCM effectively prevented new caries in 3- to 5-year-old Wanzhou children and reduced the proportion of children at increased risk of caries. It is an effective approach for preventing ECC. CLINICAL TRIAL REGISTRATION: This trial was registered in the Chinese Clinical Trials Register. The registration number was ChiCTR230067551 (11/01/2023).


Asunto(s)
Cariostáticos , Índice CPO , Caries Dental , Humanos , Caries Dental/prevención & control , Caries Dental/epidemiología , Preescolar , China/epidemiología , Método Simple Ciego , Masculino , Femenino , Cariostáticos/uso terapéutico , Medición de Riesgo , Estudios Prospectivos , Susceptibilidad a Caries Dentarias , Estudios de Seguimiento , Resultado del Tratamiento , Fluoruros/uso terapéutico , Pueblos del Este de Asia
9.
J Virol ; 96(15): e0095822, 2022 08 10.
Artículo en Inglés | MEDLINE | ID: mdl-35852351

RESUMEN

The spike protein on sarbecovirus virions contains two external, protruding domains: an N-terminal domain (NTD) with unclear function and a C-terminal domain (CTD) that binds the host receptor, allowing for viral entry and infection. While the CTD is well studied for therapeutic interventions, the role of the NTD is far less well understood for many coronaviruses. Here, we demonstrate that the spike NTD from SARS-CoV-2 and other sarbecoviruses binds to unidentified glycans in vitro similarly to other members of the Coronaviridae family. We also show that these spike NTD (S-NTD) proteins adhere to Calu3 cells, a human lung cell line, although the biological relevance of this is unclear. In contrast to what has been shown for Middle East respiratory syndrome coronavirus (MERS-CoV), which attaches sialic acids during cell entry, sialic acids present on Calu3 cells inhibited sarbecovirus infection. Therefore, while sarbecoviruses can interact with cell surface glycans similarly to other coronaviruses, their reliance on glycans for entry is different from that of other respiratory coronaviruses, suggesting sarbecoviruses and MERS-CoV have adapted to different cell types, tissues, or hosts during their divergent evolution. Our findings provide important clues for further exploring the biological functions of sarbecovirus glycan binding and adds to our growing understanding of the complex forces that shape coronavirus spike evolution. IMPORTANCE Spike N-terminal domains (S-NTD) of sarbecoviruses are highly diverse; however, their function remains largely understudied compared with the receptor-binding domains (RBD). Here, we show that sarbecovirus S-NTD can be phylogenetically clustered into five clades and exhibit various levels of glycan binding in vitro. We also show that, unlike some coronaviruses, including MERS-CoV, sialic acids present on the surface of Calu3, a human lung cell culture, inhibit SARS-CoV-2 and other sarbecoviruses. These results suggest that while glycan binding might be an ancestral trait conserved across different coronavirus families, the functional outcome during infection can vary, reflecting divergent viral evolution. Our results expand our knowledge on the biological functions of the S-NTD across diverse sarbecoviruses and provide insight on the evolutionary history of coronavirus spike.


Asunto(s)
Evolución Molecular , Coronavirus del Síndrome Respiratorio de Oriente Medio , Polisacáridos , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , COVID-19/virología , Línea Celular , Humanos , Coronavirus del Síndrome Respiratorio de Oriente Medio/química , Coronavirus del Síndrome Respiratorio de Oriente Medio/clasificación , Coronavirus del Síndrome Respiratorio de Oriente Medio/metabolismo , Polisacáridos/metabolismo , Dominios Proteicos , Receptores Virales/metabolismo , SARS-CoV-2/química , SARS-CoV-2/clasificación , SARS-CoV-2/metabolismo , Ácidos Siálicos/metabolismo , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/metabolismo
10.
J Virol ; 96(8): e0016922, 2022 04 27.
Artículo en Inglés | MEDLINE | ID: mdl-35343762

RESUMEN

Severe acute respiratory syndrome coronavirus (SARS-CoV-1) and SARS-CoV-2 are highly pathogenic to humans and have caused pandemics in 2003 and 2019, respectively. Genetically diverse SARS-related coronaviruses (SARSr-CoVs) have been detected or isolated from bats, and some of these viruses have been demonstrated to utilize human angiotensin-converting enzyme 2 (ACE2) as a receptor and to have the potential to spill over to humans. A pan-sarbecovirus vaccine that provides protection against SARSr-CoV infection is urgently needed. In this study, we evaluated the protective efficacy of an inactivated SARS-CoV-2 vaccine against recombinant SARSr-CoVs carrying two different spike proteins (named rWIV1 and rRsSHC014S, respectively). Although serum neutralizing assays showed limited cross-reactivity between the three viruses, the inactivated SARS-CoV-2 vaccine provided full protection against SARS-CoV-2 and rWIV1 and partial protection against rRsSHC014S infection in human ACE2 transgenic mice. Passive transfer of SARS-CoV-2-vaccinated mouse sera provided low protection for rWIV1 but not for rRsSHC014S infection in human ACE2 mice. A specific cellular immune response induced by WIV1 membrane protein peptides was detected in the vaccinated animals, which may explain the cross-protection of the inactivated vaccine. This study shows the possibility of developing a pan-sarbecovirus vaccine against SARSr-CoVs for future preparedness. IMPORTANCE The genetic diversity of SARSr-CoVs in wildlife and their potential risk of cross-species infection highlight the necessity of developing wide-spectrum vaccines against infection of various SARSr-CoVs. In this study, we tested the protective efficacy of the SARS-CoV-2 inactivated vaccine (IAV) against two SARSr-CoVs with different spike proteins in human ACE2 transgenic mice. We demonstrate that the SARS-CoV-2 IAV provides full protection against rWIV1 and partial protection against rRsSHC014S. The T-cell response stimulated by the M protein may account for the cross protection against heterogeneous SARSr-CoVs. Our findings suggest the feasibility of the development of pan-sarbecovirus vaccines, which can be a strategy of preparedness for future outbreaks caused by novel SARSr-CoVs from wildlife.


Asunto(s)
Vacunas contra la COVID-19 , Infecciones por Coronavirus , Protección Cruzada , Glicoproteína de la Espiga del Coronavirus , Vacunas de Productos Inactivados , Enzima Convertidora de Angiotensina 2/genética , Animales , COVID-19/prevención & control , Vacunas contra la COVID-19/inmunología , Quirópteros , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/prevención & control , Protección Cruzada/inmunología , Humanos , Ratones , Ratones Transgénicos , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/genética , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/metabolismo , SARS-CoV-2/genética , Glicoproteína de la Espiga del Coronavirus/genética , Glicoproteína de la Espiga del Coronavirus/inmunología , Vacunas de Productos Inactivados/inmunología , Zoonosis Virales/prevención & control
11.
Physiol Plant ; 175(1): e13853, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36628625

RESUMEN

The AP2/ERF family is an important class of transcription factors involved in plant growth and various biological processes. One of the AP2/ERF transcription factors, RAP2.6L, participates in various stresses responses. However, the function of RAP2.6L is largely unknown in apples (Malus domestica). In this study, an apple gene homologous to Arabidopsis AtRAP2.6L, MdERF113, was analyzed by bioinformatic characterization, gene expression analysis and subcellular localization assessment. MdERF113 was highly expressed in the sarcocarp and was responsive to hormonal signals and abiotic stresses. MdERF113-overexpression apple calli were less sensitive to low temperature, drought, salinity, and abscisic acid than wild-type. Subcellular localization revealed that MdERF113 was a nuclear-localized transcription factor, and yeast experiments confirmed that MdERF113 has no autonomous activation activity. Overall, this study indicated that MdERF113 plays a role in regulating plant growth under abiotic conditions.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Malus , Malus/metabolismo , Plantas Modificadas Genéticamente/metabolismo , Factores de Transcripción/metabolismo , Arabidopsis/metabolismo , Ácido Abscísico/metabolismo , Estrés Fisiológico/genética , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas/metabolismo , Filogenia , Sequías , Proteínas de Arabidopsis/metabolismo
12.
Zhongguo Zhong Yao Za Zhi ; 48(15): 4015-4026, 2023 Aug.
Artículo en Zh | MEDLINE | ID: mdl-37802769

RESUMEN

The purpose of this study was to investigate the effect of aqueous extract of Corni Fructus on ß-amyloid protein 25-35(Aß_(25-35))-induced brain injury and neuroinflammation in Alzheimer's disease(AD) mice to provide an experimental basis for the treatment of AD by aqueous extract of Corni Fructus. Sixty C57BL/6J male mice were randomly divided into a sham group, a model group, a positive control group(huperizine A, 0.2 mg·kg~(-1)), a low-dose aqueous extract of Corni Fructus group(1.3 g·kg~(-1)), a medium-dose aqueous extract of Corni Fructus group(2.6 g·kg~(-1)), and a high-dose aqueous extract of Corni Fructus group(5.2 g·kg~(-1)). The AD model was induced by lateral ventricular injection of Aß_(25-35) in mice except for those in the sham group, and AD model mice were treated with corresponding drugs by gavage for 24 days. The behavioral test was performed one week before animal dissection. Hematoxylin-eosin(HE) staining was performed to observe the morphology of neurons in the hippocampal region. Flow cytometry was used to detect the apoptosis level of primary hippocampal cells in mice. ELISA kits were used to detect the levels of ß-amyloid protein 1-42(Aß_(1-42)) and phosphorylated microtubule-associated protein Tau(p-Tau) in mouse brain tissues. Immunofluorescence and Western blot were used to detect the expression of related proteins in mouse brain tissues. MTT assay was used to detect the effect of compounds in aqueous extract of Corni Fructus on Aß_(25-35)-induced N9 cell injury. Molecular docking was employed to analyze the interactions of caffeic acid, trans-p-hydroxy cinnamic acid, isolariciresinol-9'-O-ß-D-glucopyranoside, esculetin, and(+)-lyoniresinol with ß-amyloid precursor protein(APP), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α). Aqueous extract of Corni Fructus could improve the learning and memory abilities of Aß_(25-35)-induced mice by increasing the duration of the autonomous activity, the rate of autonomous alternation, the preference coefficient, and the discrimination coefficient, and reduce Aß_(25-35)-induced brain injury and neuroinflammation in mice by increasing the expression levels of interleukin-10(IL-10) and B-cell lymphoma-2(Bcl-2) in brain tissues, decreasing the expression levels of Aß_(1-42), p-Tau, IL-6, TNF-α, cysteine aspartate-specific protease 3(caspase-3), cysteine aspartate-specific protease 9(caspase-9), and Bcl-2-associated X protein(Bax), and decreasing the number of activated glial cells in brain tissues. The results of cell experiments showed that esculetin and(+)-lyoniresinol could improve Aß_(25-35)-induced N9 cell injury. Molecular docking results showed that caffeic acid, trans-p-hydroxy cinnamic acid, isolariciresinol-9'-O-ß-D-glucopyranoside, esculetin, and(+)-lyoniresinol had good binding affinity with APP and weak binding affinity with IL-6 and TNF-α. Aqueous extract of Corni Fructus could ameliorate cognitive dysfunction and brain damage in Aß_(25-35)-induced mice by reducing the number of apoptotic cells and activated glial cells in the brain and decreasing the expression level of inflammatory factors. Caffeic acid, trans-p-hydroxy cinnamic acid, isolariciresinol-9'-O-ß-D-glucopyranoside, esculetin, and(+)-lyoniresinol may be the material basis for the anti-AD effect of aqueous extract of Corni Fructus.


Asunto(s)
Enfermedad de Alzheimer , Lesiones Encefálicas , Cornus , Ratones , Masculino , Animales , Enfermedad de Alzheimer/inducido químicamente , Enfermedad de Alzheimer/tratamiento farmacológico , Péptidos beta-Amiloides/toxicidad , Péptidos beta-Amiloides/metabolismo , Cornus/metabolismo , Enfermedades Neuroinflamatorias , Factor de Necrosis Tumoral alfa/metabolismo , Interleucina-6 , Ácido Aspártico , Cisteína/uso terapéutico , Simulación del Acoplamiento Molecular , Ratones Endogámicos C57BL , Péptido Hidrolasas , Modelos Animales de Enfermedad , Ratones Transgénicos
13.
J Biol Chem ; 297(4): 101152, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34478715

RESUMEN

Tissue factor (TF) is the principal initiator of blood coagulation and is necessary for thrombosis. We previously reported that lysophosphatidic acid (LPA), a potent bioactive lipid, highly induces TF expression at the transcriptional level in vascular smooth muscle cells. To date, however, the specific role of the LPA receptor is unknown, and the intracellular signaling pathways that lead to LPA induction of TF have been largely undetermined. In the current study, we found that LPA markedly induced protein kinase D (PKD) activation in mouse aortic smooth muscle cells (MASMCs). Small-interfering RNA-mediated knockdown of PKD2 blocked LPA-induced TF expression and activity, indicating that PKD2 is the key intracellular mediator of LPA signaling leading to the expression and cell surface activity of TF. Furthermore, our data reveal a novel finding that PKD2 mediates LPA-induced TF expression via the p38α and JNK2 MAPK signaling pathways, which are accompanied by the PKD-independent MEK1/2-ERK-JNK pathway. To identify the LPA receptor(s) responsible for LPA-induced TF expression, we isolated MASMCs from LPA receptor-knockout mice. Our results demonstrated that SMCs isolated from LPA receptor 1 (LPA1)-deficient mice completely lost responsiveness to LPA stimulation, which mediates induction of TF expression and activation of PKD and p38/JNK MAPK, indicating that LPA1 is responsible for PKD2-mediated activation of JNK2 and p38α. Taken together, our data reveal a new signaling mechanism in which the LPA1-PKD2 axis mediates LPA-induced TF expression via the p38α and JNK2 pathways. This finding provides new insights into LPA signaling, the PKD2 pathway, and the mechanisms of coagulation/atherothrombosis.


Asunto(s)
Aorta/metabolismo , Sistema de Señalización de MAP Quinasas , Proteína Quinasa 14 Activada por Mitógenos/metabolismo , Proteína Quinasa 9 Activada por Mitógenos/metabolismo , Músculo Liso Vascular/metabolismo , Miocitos del Músculo Liso/metabolismo , Receptores del Ácido Lisofosfatídico/metabolismo , Canales Catiónicos TRPP/metabolismo , Animales , Activación Enzimática , Lisofosfolípidos/metabolismo , Ratones
14.
Small ; 18(15): e2105783, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35038213

RESUMEN

Organic-inorganic hybrid perovskite (OIHPs) solar cells are the most promising alternatives to traditional silicon solar cells, with a certified power conversion efficiency beyond 25%. However, the poor stability of OHIPs is one of the thorniest obstacles that hinder its commercial development. Among all the factors affecting stability, ion migration is prominent because it is unavoidable and intrinsic in OHIPs. Therefore, it is important to understand the mechanism for ion migration and regulation strategies. Herein, the types of ions that may migrate in OHIPs are first discussed; afterward, the migrating channels are demonstrated. The effects of ion migration are further elaborated. While ion migration can facilitate the p-i-n structure in some cases, the current hysteresis and other adverse effects such as phase segregation in OHIPs attract widespread attention. Based on these, several recent strategies to suppress the ion migration are enumerated, including the introduction of alkali cations, organic additives, grain boundaries passivation, and employment of low-dimensional perovskites. Finally, the prospect for further modulating the ion migration and more stable perovskite solar cells is proposed.

15.
Langmuir ; 38(18): 5472-5480, 2022 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-35465678

RESUMEN

The solid electrolyte interphase (SEI) plays a pivotal role in enabling fast ionic transport and preserving the battery electrodes from parasitic reactions with solvents. However, due to large volume changes of lithium (Li) electrodes, the SEI layer can potentially undergo mechanical failure, resulting in electrolyte degradation. The mechanical stability of the SEI is a critical aspect that needs to be modulated for designing rechargeable metal batteries with optimal performance. In this work, we perform density functional theory calculations to investigate the mechanical properties of lithium fluoride (LiF) and lithium oxide (Li2O) nanofilms and quantify the Li surface diffusion kinetics over these two SEI materials. Based on our analysis, it is identified that Young's modulus and the ideal strength of the SEI are strong functions of the nanofilm thickness and crystallographic direction. Interestingly, we find that mechanical strain substantially alters the Li surface diffusion behavior on the SEI. For a strain of 4%, while the Li surface diffusion rate decreases by two orders of magnitude on the stretched Li2O film, it increases two times on the stretched LiF film, indicating critical implications on the morphological stability of the metal anode. A fundamental correlation between inherent SEI properties and Li plating behavior is revealed, suggesting a potential pathway to achieve dendrite-free electrodeposition via SEI modulation.

16.
Crit Rev Food Sci Nutr ; 62(13): 3437-3452, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-33393366

RESUMEN

Cancer is one of the most devastating diseases, and recently, a variety of natural compounds with preventive effects on cancer developments have been reported. Sulforaphane (SFN) is a potent anti-cancer isothiocyanate originating from Brassica oleracea (broccoli). SFN, mainly metabolized via mercapturic acid pathway, has high bioavailability and absorption. The present reviews mainly discussed the metabolism and absorption of SFN and newly discovered mechanistic understanding recent years for SFN's anti-cancer effects including promoting autophagy, inducing epigenetic modifications, suppressing glycolysis and fat metabolism. Moreover, its inhibitory effects on cancer stem cells and synergetic effects with other anti-cancer agents are also reviewed along with the clinical trials in this realm.


Asunto(s)
Brassica , Neoplasias , Humanos , Isotiocianatos/farmacología , Neoplasias/tratamiento farmacológico , Sulfóxidos
17.
Prev Med ; 164: 107269, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36162486

RESUMEN

The pandemic has disrupted public health and social well-being for more than two years. With the vaccine efficacy waning over time and the spread of new variants, a booster becomes increasingly imperative. This study investigates predictors of the American public's COVID-19 booster intention. A national survey was conducted from September 23rd to October 31st, 2021, on a representative sample. The survey data is merged with state-level indicators of vaccination rate, case rate, political context, and economic recovery. Multilevel regression modeling is adopted for statistical estimation. Results show that a higher proportion of vaccinated people in the network is positively related to one's chance of getting the booster (ß = 0.593, p = 0.000). In comparison, a higher proportion of infected people in the network is negatively related to one's intention to become boosted (ß = -0.240, p = 0.039). Additionally, the higher educated (ß = 0.080, p = 0.001) and older (ß = 0.004, p = 0.013) were more likely to say they would get the booster than their counterparts. Meanwhile, the odds of people taking the COVID-19 booster decrease by 3.541 points (p = 0.002) for each unit increase in the case rate at the state level. This study articulates that individual intention to take the booster is a function of their personal characteristics and is also rooted in social networks. These findings contribute to the literature and have policy implications. Knowledge of the profiles among people who intend to take/refuse the booster provides essential information to leverage certain factors and maximize booster uptake to mitigate the pandemic's devastating impact.


Asunto(s)
COVID-19 , Estados Unidos/epidemiología , Humanos , COVID-19/prevención & control , Intención , Pandemias/prevención & control , Vacunación , Encuestas y Cuestionarios
18.
Bioorg Chem ; 123: 105749, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35364556

RESUMEN

Two pairs of unprecedented enantiomeric phthalide dimers, spiroligustolides A (1a/1b) and B (2a/2b), featuring a unique spiroorthoster linkage between two monomeric units to form a 5/6/5/6/6-fused ring system, were isolated from the roots of Ligusticum chuanxiong. The structures and relative configurations of 1 and 2 were determined by HR-ESI-MS, IR, and NMR spectroscopic data, coupled with single-crystal X-ray diffraction analysis, and the absolute configurations of 1a, 1b, 2a, and 2b were established by comparing the experimental and calculated electronic circular dichroism (ECD) data. Plausible biosynthetic pathway for 1 and 2 was proposed. Moreover, compounds 1, 1b, and 2b showed remarkable inhibitory activities on Cav3.1 calcium channel with IC50 values of 8.34, 7.08, and 8.60 µM, respectively.


Asunto(s)
Benzofuranos , Ligusticum , Benzofuranos/química , Benzofuranos/farmacología , Canales de Calcio , Ligusticum/química , Estructura Molecular , Estereoisomerismo
19.
Health Promot Int ; 37(6)2022 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-36367427

RESUMEN

As new coronavirus variants continue to emerge, in order to better address vaccine-related concerns and promote vaccine uptake in the next few years, the role played by online communities in shaping individuals' vaccine attitudes has become an important lesson for public health practitioners and policymakers to learn. Examining the mechanism that underpins the impact of participating in online communities on the attitude toward COVID-19 vaccines, this study adopted a two-stage hybrid structural equation modeling (SEM)-artificial neural networks (ANN) approach to analyze the survey responses from 1037 Reddit community members. Findings from SEM demonstrated that in leading up to positive COVID-19 vaccine attitudes, sense of online community mediates the positive effects of perceived emotional support and social media usage, and perceived social norm mediates the positive effect of sense of online community as well as the negative effect of political conservatism. Health self-efficacy plays a moderating role between perceived emotional support and perceived social norm of COVID-19 vaccination. Results from the ANN model showed that online community members' perceived social norm of COVID-19 vaccination acts as the most important predictor of positive COVID-19 vaccine attitudes. This study highlights the importance of harnessing online communities in designing COVID-related public health interventions and accelerating normative change in relation to vaccination.


Asunto(s)
COVID-19 , Vacunas , Humanos , Vacunas contra la COVID-19 , Análisis de Clases Latentes , COVID-19/prevención & control , Vacunación , Actitud , Redes Neurales de la Computación
20.
Chem Biodivers ; 19(1): e202100868, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34837325

RESUMEN

Two new seco-prezizaane-type sesquiterpenes, 2ß-hydroxy-6-deoxyneoanisatin (1) and 3,4-anhydro-2-oxo-1α-hydroxy-6-deoxyneoanisatin (2), and two new prenylated C6 -C3 compounds, illilanceofunones A (3) and B (4), were obtained from the fruits of Illicium lanceolatum, along with four known prenylated C6 -C3 compounds (5-8). Their structures were proposed through HR-ESI-MS, 1 H, 13 C, and 2D NMR data interpretation. Moreover, the absolute configuration of 1 and 2 were further assigned by single-crystal X-ray diffraction analysis and electronic circular dichroism (ECD) calculations, respectively. Illihenryipyranol A (6) exhibited neuroprotective activity against MPP+ -induced PC12 cell damage in a dose-dependent manner.


Asunto(s)
Illicium/química , Fármacos Neuroprotectores/química , Sesquiterpenos/química , Animales , Supervivencia Celular/efectos de los fármacos , Dicroismo Circular , Frutas/química , Frutas/metabolismo , Illicium/metabolismo , Espectroscopía de Resonancia Magnética , Conformación Molecular , Fármacos Neuroprotectores/aislamiento & purificación , Fármacos Neuroprotectores/farmacología , Células PC12 , Extractos Vegetales/química , Prenilación , Ratas , Sesquiterpenos/aislamiento & purificación , Sesquiterpenos/farmacología , Espectrometría de Masa por Ionización de Electrospray
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