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1.
Chem Rev ; 124(10): 6643-6689, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38723152

RESUMEN

1,1'-Bi-2-naphthol (BINOL) has been extensively used as the chirality source in the fields of molecular recognition, asymmetric synthesis, and materials science. The direct electrophilic substitution at the aromatic rings of the optically active BINOL has been developed as one of the most convenient strategies to structurally modify BINOL for diverse applications. High regioselectivity has been achieved for the reaction of BINOL with electrophiles. Depending upon the reaction conditions and substitution patterns, various functional groups can be introduced to the specific positions, such as the 6-, 5-, 4-, and 3-positions, of BINOL. Ortho-lithiation at the 3-position directed by the functional groups at the 2-position of BINOL have been extensively used to prepare the 3- and 3,3'-substituted BINOLs. The use of transition metal-catalyzed C-H activation has also been explored to functionalize BINOL at the 3-, 4-, 5-, 6-, and 7-positions. These regioselective substitutions of BINOL have allowed the construction of tremendous amount of BINOL derivatives with fascinating structures and properties as reviewed in this article. Examples for the applications of the optically active BINOLs with varying substitutions in asymmetric catalysis, molecular recognition, chiral sensing and materials are also provided.

2.
J Virol ; 97(2): e0160022, 2023 02 28.
Artículo en Inglés | MEDLINE | ID: mdl-36757205

RESUMEN

Infection by Kaposi sarcoma-associated herpesvirus (KSHV) can cause severe consequences, such as cancers and lymphoproliferative diseases. Whole inactivated viruses (WIV) with chemically destroyed genetic materials have been used as antigens in several licensed vaccines. During KSHV productive replication, virus-like vesicles (VLVs) that lack capsids and viral genomes are generated along with virions. Here, we investigated the immunogenicity of KSHV VLVs produced from a viral mutant that was defective in capsid formation and DNA packaging. Mice immunized with adjuvanted VLVs generated KSHV-specific T cell and antibody responses. Neutralization of KSHV infection by the VLV immune serum was low but was markedly enhanced in the presence of the complement system. Complement-enhanced neutralization and complement deposition on KSHV-infected cells was dependent on antibodies targeting viral open reading frame 4 (ORF4). However, limited complement-mediated enhancement was detected in the sera of a small cohort of KSHV-infected humans which contained few neutralizing antibodies. Therefore, vaccination that induces antibody effector functions can potentially improve infection-induced humoral immunity. Overall, our study highlights a potential benefit of engaging complement-mediated antibody functions in future KSHV vaccine development. IMPORTANCE KSHV is a virus that can lead to cancer after infection. A vaccine that prevents KSHV infection or transmission would be helpful in preventing the development of these cancers. We investigated KSHV VLV as an immunogen for vaccination. We determined that antibodies targeting the viral protein ORF4 induced by VLV immunization could engage the complement system and neutralize viral infection. However, ORF4-specific antibodies were seldom detected in the sera of KSHV-infected humans. Moreover, these human sera did not potently trigger complement-mediated neutralization, indicating an improvement that immunization can confer. Our study suggests a new antibody-mediated mechanism to control KSHV infection and underscores the benefit of activating the complement system in a future KSHV vaccine.


Asunto(s)
Anticuerpos Neutralizantes , Herpesvirus Humano 8 , Animales , Humanos , Ratones , Anticuerpos Neutralizantes/inmunología , Infecciones por Herpesviridae , Herpesvirus Humano 8/inmunología , Sistemas de Lectura Abierta/inmunología , Vacunación , Proteínas Virales/inmunología
3.
Pestic Biochem Physiol ; 199: 105797, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38458690

RESUMEN

Antennae and legs (primarily the tarsal segments) of insects are the foremost sensory organs that contact a diverse range of toxic chemicals including insecticides. Binding proteins expressed in the two tissues are potential molecular candidates serving as the binding and sequestering of insecticides, like chemosensory proteins (CSPs). Insect CSPs endowed with multiple roles have been suggested to participate in insecticide resistance, focusing mainly on moths, aphids and mosquitos. Yet, the molecular underpinnings underlying the interactions of cerambycid CSPs and insecticides remain unexplored. Here, we present binding properties of three antenna- and tarsus-enriched RhorCSPs (RhorCSP1, CSP2 and CSP3) in Rhaphuma horsfieldi to eight insecticide classes totaling 15 chemicals. From the transcriptome of this beetle, totally 16 CSP-coding genes were found, with seven full-length sequences. In phylogeny, these RhorCSPs were distributed dispersedly in different clades. Expression profiles revealed the abundant expression of RhorCSP1, CSP2 and CSP3 in antennae and tarsi, thus as representatives for studying the protein-insecticide interactions. Binding assays showed that the three RhorCSPs were tuned differentially to insecticides but exhibited the highest affinities with hexaflumuron, chlorpyrifos and rotenone (dissociation constants <13 µM). In particular, RhorCSP3 could interact strongly with 10 of tested insecticides, of which four residues (Tyr25, Phe42, Val65 and Phe68) contributed significantly to the binding of six, four, three and four ligands, respectively. Of these, the binding of four mutated RhorCSP3s to a botanical insecticide rotenone was significantly weakened compared to the wildtype protein. Furthermore, we also evidenced that RhorCSP3 was a broadly-tuned carrier protein in response to a wide variety of plant odorants outside insecticides. Altogether, our findings shed light on different binding mechanisms and odorant-tuning profiles of three RhorCSPs in R. horsfieldi and identify key residues of the RhorCSP3-insecticide interactions.


Asunto(s)
Escarabajos , Insecticidas , Animales , Insecticidas/farmacología , Insecticidas/metabolismo , Tobillo , Rotenona , Escarabajos/genética , Escarabajos/metabolismo , Insectos/genética , Transcriptoma , Filogenia , Proteínas de Insectos/metabolismo , Antenas de Artrópodos/metabolismo , Perfilación de la Expresión Génica
4.
Mol Pharm ; 20(2): 1404-1414, 2023 02 06.
Artículo en Inglés | MEDLINE | ID: mdl-36594589

RESUMEN

The combination cancer therapy of nitric oxide (NO) with gene therapy is a promising method for tumor treatment. However, efficient co-delivery of gas and therapeutic genes to tumor cells remains a challenge. Herein, we designed a nano-sized ultraviolet (UV) light-responsive cationic lipid vector DPNO(Zn). Fluorescence spectroscopy and confocal imaging experiments revealed that DPNO(Zn) lipid nanoparticles (LNPs) could rapidly release NO under low-power UV light irradiation. Moreover, the fluorescence turn-on might take place along with the release of NO, indicating the self-reporting ability. Gene delivery experiments showed that DPNO(Zn) LNPs had good gene transfection ability, making such materials a good candidate for gas/gene combination therapy. In vitro antitumor assay demonstrated that the co-delivery system was more effective in inhibiting tumor cell proliferation than individual NO or pTrail treatment. Studies on the mechanism of tumor cell apoptosis induced by NO/pTrail co-delivery showed that NO could not only effectively increase the accumulation of p53 protein in tumor cells, thereby promoting the activation of caspase-3, but also induce mitochondrial damage. On the other hand, the Trail protein expressed by pTrail gene could enhance the degree of NO-induced caspase-3 activation, indicating the synergistic effect. These results proved that DPNO(Zn) LNP may serve as a multifunctional nanocarrier for potential tumor therapy.


Asunto(s)
Nanopartículas , Neoplasias , Humanos , Caspasa 3/genética , Óxido Nítrico/uso terapéutico , Plásmidos , Terapia Genética , Nanopartículas/química , Neoplasias/tratamiento farmacológico , Colorantes
5.
J Org Chem ; 88(1): 211-217, 2023 01 06.
Artículo en Inglés | MEDLINE | ID: mdl-36525553

RESUMEN

A highly chemoselective and enantioselective fluorescent probe has been discovered for the recognition of prolinol among various primary and secondary amine-based amino alcohols. The mechanistic studies including 1D and 2D 1H/13C NMR and mass spectroscopic analyses and DFT calculations have shown that the aldehyde group of the probe can react with prolinol to generate a bicyclic oxazolidine unit which, through a possible intramolecular hydrogen bond interaction, will lead to highly selective fluorescence enhancement.


Asunto(s)
Aminas , Colorantes Fluorescentes , Estereoisomerismo , Colorantes Fluorescentes/química , Pirrolidinas
6.
Epidemiol Infect ; 151: e63, 2023 02 27.
Artículo en Inglés | MEDLINE | ID: mdl-37114752

RESUMEN

The resurgence and outbreaks of mumps occur frequently in many countries worldwide in recent years, even in countries with high vaccination coverage. In this study, a descriptive and spatiotemporal clustering analysis at the township level was conducted to explore the dynamic spatiotemporal aggregation and epidemiological characteristics of mumps in Wuhan. During 2005 and 2019, there were 40 685 cases reported in Wuhan, with an average annual morbidity of 28.11 per 100 000 populations. The morbidity showed a fluctuating tendency, and peaked in 2010 and 2018. Bimodal seasonality was found, with a large peak between May and July, and a mild peak from November to January in the following year. Male students aged 5-9-year-old were the main risk group of mumps infection. Significant global spatial auto-correlation was detected except in 2007, 2009 and 2015. The spatial and temporal scan statistics indicated that the hot-spots mainly located at the western and southern areas of Wuhan with variations almost every year. Our findings could assist the public health authorities to develop and improve targeted health strategies, and allocate health resources rationally.


Asunto(s)
Paperas , Humanos , Masculino , Preescolar , Niño , Paperas/epidemiología , Incidencia , Análisis Espacio-Temporal , Brotes de Enfermedades , China/epidemiología
7.
Phytother Res ; 37(12): 5700-5723, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37748788

RESUMEN

Galangin is an important flavonoid with natural activity, that is abundant in galangal and propolis. Currently, various biological activities of galangin have been disclosed, including anti-inflammation, antibacterial effect, anti-oxidative stress and aging, anti-fibrosis, and antihypertensive effect. Based on the above bioactivities, more and more attention has been paid to the role of galangin in neurodegenerative diseases, rheumatoid arthritis, osteoarthritis, osteoporosis, skin diseases, and cancer. In this paper, the natural sources, pharmacokinetics, bioactivities, and therapeutic potential of galangin against various diseases were systematically reviewed by collecting and summarizing relevant literature. In addition, the molecular mechanism and new preparation of galangin in the treatment of related diseases are also discussed, to broaden the application prospect and provide reference for its clinical application. Furthermore, it should be noted that current toxicity and clinical studies of galangin are insufficient, and more evidence is needed to support its possibility as a functional food.


Asunto(s)
Flavonoides , Estrés Oxidativo , Flavonoides/farmacología , Flavonoides/uso terapéutico
8.
Plant Dis ; 2023 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-37386704

RESUMEN

Eucalyptus urophylla × E. camaldulensis, named Chiwei eucalypt, is a hybrid species widely used in China. Many of its clones are cultivated for afforestation due to cold tolerance, high yield, high strength and disease resistance. Clone LH1 is planted extensively for its high stability and machinability in South China. In December 2021, severe powdery mildew signs were observed on clone LH1 in Zhanjiang, Guangdong (N28°8'29"; E110°17'5"). Whitish powder principally appeared on both abaxial and adaxial leaf surfaces. All plants were infected within about a week and above 90% leaves were diseased, which resulted in abnormal growth and shrinkage of leaves. Hyphae with single, lobed appressoria were hyaline, septate, branched, 3.3-6.8 µm (ave. 4.9 µm, n>50) wide. Conidiophores with a straight to flexuous foot-cell (14.7-46.1×5.4-9.7 µm, ave. 25.8×7.9 µm, n>30) were erect, hyaline, 2-septate, unbranched, 35.4-81.8 × 5.7-10.7 (ave. 56.7×8.7 µm, n>50). Conidia were solitary, hyaline, cylindrical to elliptical, 27.7-46.6 ×11.2-19.0 (ave. 35.7×16.6 µm, n>50). Chamothecia were not found on infected trees. The further identification was confirmed by partial sequences of internal transcribed spacer (ITS), large submit rRNA gene (LSU), Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), glutamine synthetase (GS), and RNA polymerase II second largest subunit (RPB2) gene. A very small amount of mycelia and spores from voucher specimens CCAS-ASBF-1 and CCAS-ASBF-2 were deposited in the herbarium of Guangdong Ocean University. Specimens were PCR amplified and sequenced with primer pairs ITS1/ITS4 (White et al 1990), LROR/LR7 (Moncalvo et al 1995), PMGAPDH1/PMGAPDH3R, GSPM2/GSPM3R and PmRpb2_4/ PMRpb2_6R (Bradshaw, et al. 2022), respectively. BLASTn results showed that ITS (OP270019 and OQ380937), LSU (OP270018 and OQ380938), GAPDH, GS and RPB2 (OQ414445- OQ414450) were above 99% identical with those of E. elevata on Catalpa bignonioides (ITS: AY587013) (Cook et al 2004), Plumeria rubra (ITS: MH985631) (Yeh et al 2019), Cerbera manghas (ITS: MZ379159; LSU: MZ379160) (Mukhtar et al 2022), and Eucalyptus camaldulensis (LSU: LC177375-6) (Meebon et al. 2017), and above 99% identical with those of Erysiphe vaccinii FH00941201 on Vaccinium corymbosum (ITS: ON073869; RPB2: ON119159; GS: ON075687) and FH00112205 on V. vacillans (ITS: ON073870; GAPDH: ON075646) (Bradshaw et al 2022). This is the first sequence data for non rDNA of E. elevata. In an ITS tree phylogenetic analysis with Maximum likelihood (ML) method showed the fungus clustered in a highly supported clade with E. elevata and E. vaccinii. In a multi-locus tree, E. elevata grouped in a sister position to E. vaccinii FH00941201. Thus, the pathogen was identified as E. elevata based on morphology, DNA BLASTn and phylogenetic analysis (Braun and Cook 2012). Pathogenicity tests were conducted on healthy leaves of 1-year-old potted plants. Ten leaves were cleaned with sterile water, inoculated by gently dusting conidia from single lesion on the naturally infected leaves, and then covered with plastic bags containing wet absorbent cotton. Non-inoculated leaves served as controls. Symptoms developed on all inoculated leaves 3 to 5 days after inoculation, and the fungus was identical to the original fungus on the infected leaves, whereas control plants remained symptomless. This is the first report of powdery mildew caused by E. elevata on Eucalyptus sp. from China. This finding is helpful for land managers to diagnose and control the disease.

9.
BMC Plant Biol ; 21(1): 333, 2021 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-34256694

RESUMEN

BACKGROUND: Canavalia rosea (Sw.) DC. (bay bean) is an extremophile halophyte that is widely distributed in coastal areas of the tropics and subtropics. Seawater and drought tolerance in this species may be facilitated by aquaporins (AQPs), channel proteins that transport water and small molecules across cell membranes and thereby maintain cellular water homeostasis in the face of abiotic stress. In C. rosea, AQP diversity, protein features, and their biological functions are still largely unknown. RESULTS: We describe the action of AQPs in C. rosea using evolutionary analyses coupled with promoter and expression analyses. A total of 37 AQPs were identified in the C. rosea genome and classified into five subgroups: 11 plasma membrane intrinsic proteins, 10 tonoplast intrinsic proteins, 11 Nod26-like intrinsic proteins, 4 small and basic intrinsic proteins, and 1 X-intrinsic protein. Analysis of RNA-Seq data and targeted qPCR revealed organ-specific expression of aquaporin genes and the involvement of some AQP members in adaptation of C. rosea to extreme coral reef environments. We also analyzed C. rosea sequences for phylogeny reconstruction, protein modeling, cellular localizations, and promoter analysis. Furthermore, one of PIP1 gene, CrPIP1;5, was identified as functional using a yeast expression system and transgenic overexpression in Arabidopsis. CONCLUSIONS: Our results indicate that AQPs play an important role in C. rosea responses to saline-alkaline soils and drought stress. These findings not only increase our understanding of the role AQPs play in mediating C. rosea adaptation to extreme environments, but also improve our knowledge of plant aquaporin evolution more generally.


Asunto(s)
Acuaporinas/genética , Canavalia/genética , Sequías , Suelo/química , Adaptación Fisiológica , Secuencias de Aminoácidos , Acuaporinas/fisiología , Evolución Biológica , Canavalia/fisiología , Mapeo Cromosómico , Cromosomas de las Plantas , Ecosistema , Genoma de Planta , Familia de Multigenes , Proteínas de Plantas/genética , Regiones Promotoras Genéticas , RNA-Seq , Estrés Fisiológico , Transcriptoma
10.
J Virol ; 94(4)2020 01 31.
Artículo en Inglés | MEDLINE | ID: mdl-31776277

RESUMEN

The strongest evidence of the oncogenicity of Epstein-Barr virus (EBV) in vitro is its ability to immortalize human primary B lymphocytes into lymphoblastoid cell lines (LCLs). Yet the underlying mechanisms explaining how the virus tempers the growth program of the host cells have not been fully elucidated. The mitogen-activated protein kinases (MAPKs) are implicated in many cellular processes and are constitutively activated in LCLs. We questioned the expression and regulation of the dual-specificity phosphatases (DUSPs), the main negative regulator of MAPKs, during EBV infection and immortalization. Thirteen DUSPs, including 10 typical and 3 atypical types of DUSPs, were tested. Most of them were downregulated after EBV infection. Here, a role of viral oncogene latent membrane protein 1 (LMP1) in limiting DUSP6 and DUSP8 expression was identified. Using MAPK inhibitors, we found that LMP1 activates extracellular signal-regulated kinase (ERK) or p38 to repress the expression of DUSP6 and DUSP8, with corresponding substrate specificity. Morphologically, overexpression of DUSP6 and DUSP8 attenuates the ability of EBV-immortalized LCL cells to clump together. Mechanistically, apoptosis induced by restoring DUSP6 and DUSP8 in LCLs indicated a novel mechanism for LMP1 to provide a survival signal during EBV immortalization. Collectively, this report provides the first description of the interplay between EBV genes and DUSPs and contributes considerably to the interpretation of MAPK regulation in EBV immortalization.IMPORTANCE Infections by the ubiquitous Epstein-Barr virus (EBV) are associated with a wide spectrum of lymphomas and carcinomas. It has been well documented that activation levels of MAPKs are found in cancer cells to translate various external or intrinsic stimuli into cellular responses. Physiologically, the dual-specificity phosphates (DUSPs) exhibit great ability in regulating MAPK activities with respect to their capability of dephosphorylating MAPKs. In this study, we found that DUSPs were generally downregulated after EBV infection. EBV oncogenic latent membrane protein 1 (LMP1) suppressed DUSP6 and DUSP8 expression via MAPK pathway. In this way, LMP1-mediated MAPK activation was a continuous process. Furthermore, DUSP downregulation was found to contribute greatly to prevent apoptosis of EBV-infected cells. To sum up, this report sheds light on a novel molecular mechanism explaining how EBV maintains the unlimited proliferation status of the immortalized cells and provides a new link to understand EBV-induced B cell survival.


Asunto(s)
Fosfatasas de Especificidad Dual/genética , Herpesvirus Humano 4/metabolismo , Proteínas de la Matriz Viral/metabolismo , Apoptosis/genética , Linfocitos B/virología , Línea Celular Tumoral , Fosfatasas de Especificidad Dual/metabolismo , Infecciones por Virus de Epstein-Barr/virología , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Genes Virales/genética , Humanos , Proteínas Quinasas Activadas por Mitógenos/metabolismo , FN-kappa B/metabolismo , Cultivo Primario de Células , Proteínas de la Matriz Viral/fisiología , Proteínas Virales/metabolismo , Latencia del Virus/genética , Latencia del Virus/fisiología , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
11.
J Org Chem ; 86(6): 4607-4615, 2021 03 19.
Artículo en Inglés | MEDLINE | ID: mdl-33667096

RESUMEN

A perfluoroalkyl ketone-based molecular probe was found to show highly enantioselective fluorescent enhancement in the fluorous phase when treated with an amino alcohol generated from the asymmetric reaction of a meso-epoxide with an alkyl amine. The two enantiomeric probes (R)- and (S)-2 were used to screen catalysts for this asymmetric reaction. The use of the probe in the fluorous phase allowed the fluorescent sensing of the products to be conducted away from the other reaction components with minimized interference. It was further found that when (R)- or (S)-2 was used to determine the enantiomeric composition of the amino alcohol product, there was a large nonlinear effect. That is, only when one enantiomer of the substrate was in excess was there a large fluorescence enhancement for the chirality-matched probe-substrate interaction. This allowed the racemic probe rac-2 to be used to evaluate the asymmetric induction in the catalyst screening. The catalyst screening using the fluorescent probes led to the discovery of a more enantioselective and efficient method for the desymmetrization of 1,2-epoxycyclohexane with iPrNH2 to form the corresponding chiral amino alcohol. This work presents a novel method to conduct catalyst screening for asymmetric synthesis and has potential to become a high-throughput process.


Asunto(s)
Amino Alcoholes , Colorantes Fluorescentes , Aminas , Catálisis , Estereoisomerismo
12.
J Org Chem ; 86(9): 6780-6786, 2021 05 07.
Artículo en Inglés | MEDLINE | ID: mdl-33900764

RESUMEN

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.


Asunto(s)
Aminas , Aminoácidos , Estructura Molecular , Espectrometría de Fluorescencia , Estereoisomerismo
13.
J Org Chem ; 86(14): 9603-9609, 2021 07 16.
Artículo en Inglés | MEDLINE | ID: mdl-34165295

RESUMEN

A new red-light-emitting fluorescent probe (R)-5 was synthesized. In the presence of Zn2+, this compound was found to exhibit good enantioselective fluorescence enhancement at λ = 655 nm when treated with a variety of amino acids in aqueous solution. This probe in combination with a green-light-emitting probe (S)-4 that has enantioselective fluorescence enhancement at λ = 505 nm has formed a pseudoenantiomeric sensor pair because of their opposite enantioselectivities. This sensor pair can simultaneously detect both enantiomers of a chiral amino acid at two very different wavelengths (Δ = 150 nm). It was used to visually and semiquantitatively determine the enantiomeric compositions of amino acids. For example, when a 1:1 mixture of (R)-5 and (S)-4 was treated with Zn(OAc)2 and histidine samples of 0-100% [d-His], the color of the mixtures changed from green to yellow, orange, and red under a UV lamp (365 nm), which allowed a quick quantification of [d-His]%. This is the first example of using fluorescence to visually quantify the enantiomeric composition of chiral compounds.


Asunto(s)
Aminoácidos , Colorantes Fluorescentes , Aminas , Espectrometría de Fluorescencia , Estereoisomerismo
14.
BMC Infect Dis ; 21(1): 885, 2021 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-34461841

RESUMEN

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) posed an enormous threat to public health. The use of antiviral drugs in patients with this disease have triggered people's attentions. Whether interferon alfa-2b or lopinavir/ritonavir (LPV/r) plus interferon alfa-2b treatment can against SARS-CoV-2 was unknown. The objectives of this study was to evaluate the efficacy and safety of interferon alfa-2b and LPV/r plus interferon alfa-2b for SARS-CoV-2 infection in adult patients hospitalized with COVID-19. METHODS: This is a retrospective cohort study of 123 patients confirmed SARS-CoV-2 infection by PCR on nasopharyngeal swab and symptoms between Jan. 13 and Apr. 23, 2020. All patients received standard supportive care and regular clinical monitoring. Patients were assigned to standard care group (n = 12), interferon alfa-2b group (n = 44), and combination LPV/r plus interferon alfa-2b group (n = 67). The primary endpoints were duration of required oxygen support and virus clearance time. Associations between therapies and these outcomes were assessed by Cox proportional hazards regression. RESULTS: Baseline clinical characteristics were not significantly different among the three groups (P > 0.05). No significant associations were observed between LPV/r/interferon alfa-2b and faster SARS-CoV-2 RNA clearance (HR, 0.85 [95% confidence interval (CI) 0.45-1.61]; P = 0.61 in interferon alfa-2b group vs HR, 0.59 [95% CI 0.32-1.11]; P = 0.10 in LPV/r plus interferon alfa-2b group). Individual therapy groups also showed no significant association with duration of required oxygen support. There were no significant differences among the three groups in the incidence of adverse events (P > 0.05). CONCLUSIONS: In patients with confirmed SARS-CoV-2 infection, no benefit was observed from interferon alfa-2b or LPV/r plus interferon alfa-2b treatment. The findings may provide references for treatment guidelines of patients with SARS-CoV-2 infection.


Asunto(s)
Tratamiento Farmacológico de COVID-19 , Ritonavir , Adulto , Antivirales/uso terapéutico , Combinación de Medicamentos , Humanos , Interferón alfa-2 , Lopinavir/uso terapéutico , ARN Viral , Estudios Retrospectivos , Ritonavir/uso terapéutico , SARS-CoV-2
15.
Neurol Sci ; 42(5): 1827-1833, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-32895776

RESUMEN

Spinal muscular atrophy (SMA) is a type of autosomal recessive genetic disease, which seriously threatens the health and lives of children and adolescents. We attempted to find some genes and mutations related to the onset of SMA. Eighty-three whole-blood samples were collected from 28 core families, including 28 probands with clinically suspected SMA (20 SMA patients, 5 non-SMA children, and 3 patients with unknown etiology) and their parents. The multiplex ligation probe amplification (MLPA) was performed for preliminary diagnosis. The high-throughput sequencing technology was used to conduct the whole-exome sequencing analysis. We analyzed the mutations in adjacent genes of SMN1 gene and the unique mutations that only occurred in SMA patients. According to the MLPA results, 20 probands were regarded as experimental group and 5 non-SMA children as control group. A total of 10 mutations were identified in the adjacent genes of SMN1 gene. GUSBP1 g.[69515863G>A], GUSBP1 g.[69515870C>T], and SMA4 g.[69515738C>A] were the top three most frequent sites. SMA4 g.[69515726A>G] and OCLN c.[818G>T] have not been reported in the existing relevant researches. Seventeen point mutations in the DYNC1H1 gene were only recognized in SMA children, and the top two most common mutations were c.[2869-34A>T] and c.[345-89A>G]; c.[7473+105C>T] was the splicing mutation that might change the mRNA splicing site. The mutations of SMA4 g.[69515726A>G], OCLN c.[818G>T], DYNC1H1 c.[2869-34A>T], DYNC1H1 c.[345-89A>G], and DYNC1H1 c.[7473+105C>T] in the adjacent genes of SMN1 gene and other genes might be related to the onset of SMA.


Asunto(s)
Atrofia Muscular Espinal , Adolescente , Niño , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Atrofia Muscular Espinal/genética , Mutación/genética , Padres , Mutación Puntual , Proteína 1 para la Supervivencia de la Neurona Motora/genética
16.
Int J Mol Sci ; 22(2)2021 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-33429984

RESUMEN

Aquaporins are channel proteins that facilitate the transmembrane transport of water and other small neutral molecules, thereby playing vital roles in maintaining water and nutrition homeostasis in the life activities of all organisms. Canavalia rosea, a seashore and mangrove-accompanied halophyte with strong adaptability to adversity in tropical and subtropical regions, is a good model for studying the molecular mechanisms underlying extreme saline-alkaline and drought stress tolerance in leguminous plants. In this study, a PIP2 gene (CrPIP2;3) was cloned from C. rosea, and its expression patterns and physiological roles in yeast and Arabidopsis thaliana heterologous expression systems under high salt-alkali and high osmotic stress conditions were examined. The expression of CrPIP2;3 at the transcriptional level in C. rosea was affected by high salinity and alkali, high osmotic stress, and abscisic acid treatment. In yeast, the expression of CrPIP2;3 enhanced salt/osmotic and oxidative sensitivity under high salt/osmotic and H2O2 stress. The overexpression of CrPIP2;3 in A. thaliana could enhance the survival and recovery of transgenic plants under drought stress, and the seed germination and seedling growth of the CrPIP2;3 OX (over-expression) lines showed slightly stronger tolerance to high salt/alkali than the wild-type. The transgenic plants also showed a higher response level to high-salinity and dehydration than the wild-type, mostly based on the up-regulated expression of salt/dehydration marker genes in A. thaliana plants. The reactive oxygen species (ROS) staining results indicated that the transgenic lines did not possess stronger ROS scavenging ability and stress tolerance than the wild-type under multiple stresses. The results confirmed that CrPIP2;3 is involved in the response of C. rosea to salt and drought, and primarily acts by mediating water homeostasis rather than by acting as an ROS transporter, thereby influencing physiological processes under various abiotic stresses in plants.


Asunto(s)
Arabidopsis/genética , Canavalia/genética , Plantas Tolerantes a la Sal/genética , Estrés Fisiológico/genética , Álcalis/toxicidad , Arabidopsis/crecimiento & desarrollo , Canavalia/crecimiento & desarrollo , Sequías , Regulación de la Expresión Génica de las Plantas , Germinación/efectos de los fármacos , Peróxido de Hidrógeno/química , Presión Osmótica/efectos de los fármacos , Plantas Modificadas Genéticamente/efectos de los fármacos , Plantas Modificadas Genéticamente/genética , Salinidad , Tolerancia a la Sal/genética , Plantones/efectos de los fármacos , Cloruro de Sodio/toxicidad
17.
J Transl Med ; 18(1): 206, 2020 05 20.
Artículo en Inglés | MEDLINE | ID: mdl-32434518

RESUMEN

BACKGROUND: Patients with critical illness due to infection with the 2019 coronavirus disease (COVID-19) show rapid disease progression to acute respiratory failure. The study aimed to screen the most useful predictive factor for critical illness caused by COVID-19. METHODS: The study prospectively involved 61 patients with COVID-19 infection as a derivation cohort, and 54 patients as a validation cohort. The predictive factor for critical illness was selected using LASSO regression analysis. A nomogram based on non-specific laboratory indicators was built to predict the probability of critical illness. RESULTS: The neutrophil-to-lymphocyte ratio (NLR) was identified as an independent risk factor for critical illness in patients with COVID-19 infection. The NLR had an area under receiver operating characteristic of 0.849 (95% confidence interval [CI], 0.707 to 0.991) in the derivation cohort and 0.867 (95% CI 0.747 to 0.944) in the validation cohort, the calibration curves fitted well, and the decision and clinical impact curves showed that the NLR had high standardized net benefit. In addition, the incidence of critical illness was 9.1% (1/11) for patients aged ≥ 50 and having an NLR < 3.13, and 50% (7/14) patients with age ≥ 50 and NLR ≥ 3.13 were predicted to develop critical illness. Based on the risk stratification of NLR according to age, this study has developed a COVID-19 pneumonia management process. CONCLUSIONS: We found that NLR is a predictive factor for early-stage prediction of patients infected with COVID-19 who are likely to develop critical illness. Patients aged ≥ 50 and having an NLR ≥ 3.13 are predicted to develop critical illness, and they should thus have rapid access to an intensive care unit if necessary.


Asunto(s)
Infecciones por Coronavirus/diagnóstico , Enfermedad Crítica , Linfocitos/patología , Neutrófilos/patología , Neumonía Viral/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Betacoronavirus/patogenicidad , COVID-19 , Niño , Preescolar , Estudios de Cohortes , Infecciones por Coronavirus/sangre , Infecciones por Coronavirus/patología , Progresión de la Enfermedad , Femenino , Historia del Siglo XXI , Humanos , Lactante , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/sangre , Neumonía Viral/patología , Pronóstico , Estudios Prospectivos , SARS-CoV-2 , Índice de Severidad de la Enfermedad , Adulto Joven
18.
Chemistry ; 26(32): 7258-7262, 2020 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-32128894

RESUMEN

Reaction of (R)-3,3'-diformyl-1,1'-bi-2-naphthol with concentrated sulfuric acid gives the corresponding 6,6'-disulfonated compound (R)-2 selectively. This provides a simple and efficient method to convert a water-insoluble compound to a water-soluble fluorescent probe. It is found that (R)-2 in combination with Zn2+ shows a highly enantioselective fluorescent response toward various amino acids in the aqueous HEPES buffer solution at pH 7.4. For example, an enantioselective fluorescence enhancement ratio [ef=ΔID /ΔIL ] up to 35.8 is observed for the recognition of asparagine. NMR and mass spectroscopic investigations are conducted to explore the reaction of (R)-2 with asparagine.


Asunto(s)
Aminoácidos/química , Colorantes Fluorescentes/química , Naftoles/química , Sulfonas/química , Espectroscopía de Resonancia Magnética , Estructura Molecular , Espectrometría de Fluorescencia , Estereoisomerismo , Agua , Zinc/química
19.
J Org Chem ; 85(10): 6352-6358, 2020 05 15.
Artículo en Inglés | MEDLINE | ID: mdl-32297514

RESUMEN

A detailed investigation was conducted on the reaction of a 1,1'-bi-2-naphthol-coumarin-based fluorescent probe with amino acids. On the basis of the studies, including fluorescence spectroscopy, 1H NMR, UV-vis, mass spectroscopy, single-crystal X-ray analysis, and molecular modeling, it was found that the distinctively different fluorescent responses of the probe toward the amino acid at the two excitation wavelengths are due to two different reaction pathways that generate different intermediates and products.

20.
J Org Chem ; 85(11): 7342-7348, 2020 06 05.
Artículo en Inglés | MEDLINE | ID: mdl-32397707

RESUMEN

A novel BINOL-based near-IR fluorescent probe was designed and synthesized by incorporating a rhodamine-like dye. In the presence of Zn(II), this compound was found to exhibit highly enantioselective fluorescence enhancement at λemi > 730 nm and λexc = 690 nm when treated with 14 common amino acids in aqueous solution. An enantioselective fluorescence enhancement ratio up to 163 was observed. The mechanism of the fluorescence response of this probe was investigated by various spectroscopic methods.

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