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1.
PLoS Pathog ; 19(2): e1011166, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36753521

RESUMEN

Congenital human cytomegalovirus (HCMV) infection causes severe damage to the fetal brain, and the underlying mechanisms remain elusive. Cytokine signaling is delicately controlled in the fetal central nervous system to ensure proper development. Here we show that suppressor of cytokine signaling 3 (SOCS3), a negative feedback regulator of the IL-6 cytokine family signaling, was upregulated during HCMV infection in primary neural progenitor cells (NPCs) with a biphasic expression pattern. From viral protein screening, pUL97 emerged as the viral factor responsible for prolonged SOCS3 upregulation. Further, by proteomic analysis of the pUL97-interacting host proteins, regulatory factor X 7 (RFX7) was identified as the transcription factor responsible for the regulation. Depletion of either pUL97 or RFX7 prevented the HCMV-induced SOCS3 upregulation in NPCs. With a promoter-luciferase activity assay, we demonstrated that the pUL97 kinase activity and RFX7 were required for SOCS3 upregulation. Moreover, the RFX7 phosphorylation level was increased by either UL97-expressing or HCMV-infection in NPCs, suggesting that pUL97 induces RFX7 phosphorylation to drive SOCS3 transcription. We further revealed that elevated SOCS3 expression impaired NPC proliferation and migration in vitro and caused NPCs migration defects in vivo. Taken together, these findings uncover a novel regulatory mechanism of sustained SOCS3 expression in HCMV-infected NPCs, which perturbs IL-6 cytokine family signaling, leads to NPCs proliferation and migration defects, and consequently affects fetal brain development.


Asunto(s)
Infecciones por Citomegalovirus , Citomegalovirus , Humanos , Citomegalovirus/fisiología , Interleucina-6/metabolismo , Proteómica , Factores de Transcripción/metabolismo , Células Madre , Proteína 3 Supresora de la Señalización de Citocinas/metabolismo
2.
PLoS Pathog ; 19(4): e1011316, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-37058447

RESUMEN

The presence of human cytomegalovirus (HCMV) in glioblastoma (GBM) and improved outcomes of GBM patients receiving therapies targeting the virus have implicated HCMV in GBM progression. However, a unifying mechanism that accounts for the contribution of HCMV to the malignant phenotype of GBM remains incompletely defined. Here we have identified SOX2, a marker of glioma stem cells (GSCs), as a key determinant of HCMV gene expression in gliomas. Our studies demonstrated that SOX2 downregulated promyelocytic leukemia (PML) and Sp100 and consequently facilitated viral gene expression by decreasing the amount of PML nuclear bodies in HCMV-infected glioma cells. Conversely, the expression of PML antagonized the effects of SOX2 on HCMV gene expression. Furthermore, this regulation of SOX2 on HCMV infection was demonstrated in a neurosphere assay of GSCs and in a murine xenograft model utilizing xenografts from patient-derived glioma tissue. In both cases, SOX2 overexpression facilitated the growth of neurospheres and xenografts implanted in immunodeficient mice. Lastly, the expression of SOX2 and HCMV immediate early 1 (IE1) protein could be correlated in tissues from glioma patients, and interestingly, elevated levels of SOX2 and IE1 were predictive of a worse clinical outcome. These studies argue that HCMV gene expression in gliomas is regulated by SOX2 through its regulation of PML expression and that targeting molecules in this SOX2-PML pathway could identify therapies for glioma treatment.


Asunto(s)
Glioma , Proteínas Inmediatas-Precoces , Animales , Humanos , Ratones , Citomegalovirus/fisiología , Regulación hacia Abajo , Expresión Génica , Glioma/genética , Glioma/patología , Proteínas Inmediatas-Precoces/metabolismo , Factores de Transcripción SOXB1/genética , Factores de Transcripción SOXB1/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo
3.
J Virol ; 97(5): e0031323, 2023 05 31.
Artículo en Inglés | MEDLINE | ID: mdl-37097169

RESUMEN

Human cytomegalovirus (HCMV) is a leading cause of congenital birth defects. Though the underlying mechanisms remain poorly characterized, mouse models of congenital CMV infection have demonstrated that the neuronal migration process is damaged. In this study, we evaluated the effects of HCMV infection on connexin 43 (Cx43), a crucial adhesion molecule mediating neuronal migration. We show in multiple cellular models that HCMV infection downregulated Cx43 posttranslationally. Further analysis identified the immediate early protein IE1 as the viral protein responsible for the reduction of Cx43. IE1 was found to bind the Cx43 C terminus and promote Cx43 degradation through the ubiquitin-proteasome pathway. Deletion of the Cx43-binding site in IE1 rendered it incapable of inducing Cx43 degradation. We validated the IE1-induced loss of Cx43 in vivo by introducing IE1 into the fetal mouse brain. Noteworthily, ectopic IE1 expression induced cortical atrophy and neuronal migration defects. Several lines of evidence suggest that these damages result from decreased Cx43, and restoration of Cx43 levels partially rescued IE1-induced interruption of neuronal migration. Taken together, the results of our investigation reveal a novel mechanism of HCMV-induced neural maldevelopment and identify a potential intervention target. IMPORTANCE Congenital CMV (cCMV) infection causes neurological sequelae in newborns. Recent studies of cCMV pathogenesis in animal models reveal ventriculomegaly and cortical atrophy associated with impaired neural progenitor cell (NPC) proliferation and migration. In this study, we investigated the mechanisms underlying these NPC abnormalities. We show that Cx43, a critical adhesion molecule mediating NPC migration, is downregulated by HCMV infection in vitro and HCMV-IE1 in vivo. We provide evidence that IE1 interacts with the C terminus of Cx43 to promote its ubiquitination and consequent degradation through the proteasome. Moreover, we demonstrate that introducing IE1 into mouse fetal brains led to neuronal migration defects, which was associated with Cx43 reduction. Deletion of the Cx43-binding region in IE1 or ectopic expression of Cx43 rescued the IE1-induced migration defects in vivo. Our study provides insight into how cCMV infection impairs neuronal migration and reveals a target for therapeutic interventions.


Asunto(s)
Conexina 43 , Infecciones por Citomegalovirus , Citomegalovirus , Proteínas Inmediatas-Precoces , Animales , Humanos , Recién Nacido , Ratones , Conexina 43/genética , Conexina 43/metabolismo , Citomegalovirus/fisiología , Infecciones por Citomegalovirus/metabolismo , Proteínas Inmediatas-Precoces/genética , Proteínas Inmediatas-Precoces/metabolismo , Complejo de la Endopetidasa Proteasomal/metabolismo
4.
Analyst ; 149(7): 2045-2050, 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38407274

RESUMEN

Copper ions (Cu2+) play an essential role in various cellular functions, including respiration, nerve conduction, tissue maturation, oxidative stress defense, and iron metabolism. Covalent organic frameworks (COFs) are a class of porous crystalline materials with directed structural designability and high stability due to the combination of different monomers through covalent bonds. In this study, we synthesized a porphyrin-tetrathiazole COF (TT-COF(Zn)) with Zn-porphyrin and tetrathiafulvalene (TTF) as monomers and used it as a photoactive material. The strong light absorption of metalloporphyrin and the electron-rich properties of supplied TTF contribute to its photoelectrochemical performance. Additionally, the sulfur (S) in the TTF can coordinate with Cu2+. Based on these properties, we constructed a highly sensitive photoelectrochemical sensor for detecting Cu2+. The sensor exhibited a linear range from 0.5 nM to 500 nM (R2 = 0.9983) and a detection limit of 0.15 nM for Cu2+. Notably, the sensor performed well when detecting Cu2+ in water samples.

5.
Ecotoxicol Environ Saf ; 281: 116663, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38964059

RESUMEN

Biological characteristics of pregnant women during early pregnancy make them susceptible to both poor sleep quality and metal/metalloid exposure. However, the effects of metal(loid) exposure on sleep quality in pregnant women remain unknown and unexplored. We aimed to examine the relationship between exposure to a mixture of metal(loid)s and pregnant women's sleep quality during early pregnancy. We recruited 493 pregnant women in the first trimester from prenatal clinics in Jinan, Shandong Province, China, and collected their spot urine samples. All urine specimens were assessed for eight metal(loid)s: arsenic (As), cadmium (Cd), iron (Fe), zinc (Zn), molybdenum (Mo), lead (Pb), selenium (Se), and mercury (Hg). We used the Pittsburgh Sleep Quality Index (PSQI) to assess sleep quality. Linear regression, logistic regression, generalized additive models (GAMs), quantile g-computation, and Bayesian kernel machine regression (BKMR) were applied to investigate the relationships between metal(loid) exposure and sleep quality. The results from single metal(loid) models, quantile g-computation models, and BKMR models consistently suggested that Fe was positively related to women's sleep quality. Moreover, in the quantile g-computation models, As was the most critical contributor to the negative effects of the metal(loid) mixture on sleep quality. In addition, we found significant As by Fe interaction for scores of PSQI and habitual sleep efficiency, Pb by Fe interaction for PSQI and sleep latency, and Hg by Fe interaction for PSQI, suggesting the interactive effects of As and Fe, Pb and Fe, Hg and Fe on sleep quality and specific sleep components. Our study provided the first-hand evidence of the effects of metal(loid) exposure on pregnant women's sleep quality. The underlying mechanisms need to be explored in the future.


Asunto(s)
Calidad del Sueño , Humanos , Femenino , Embarazo , Estudios Transversales , Adulto , China , Contaminantes Ambientales/orina , Contaminantes Ambientales/toxicidad , Selenio/orina , Arsénico/orina , Arsénico/toxicidad , Metales/orina , Metales/toxicidad , Metales Pesados/orina , Metales Pesados/toxicidad , Mercurio/orina , Mercurio/toxicidad , Adulto Joven , Plomo/orina , Plomo/toxicidad , Exposición Materna , Cadmio/orina , Cadmio/toxicidad , Primer Trimestre del Embarazo
6.
BMC Biol ; 21(1): 165, 2023 07 31.
Artículo en Inglés | MEDLINE | ID: mdl-37525156

RESUMEN

BACKGROUND: The development of cotton fiber is regulated by the orchestrated binding of regulatory proteins to cis-regulatory elements associated with developmental genes. The cis-trans regulatory dynamics occurred throughout the course of cotton fiber development are elusive. Here we generated genome-wide high-resolution DNase I hypersensitive sites (DHSs) maps to understand the regulatory mechanisms of cotton ovule and fiber development. RESULTS: We generated DNase I hypersensitive site (DHS) profiles from cotton ovules at 0 and 3 days post anthesis (DPA) and fibers at 8, 12, 15, and 18 DPA. We obtained a total of 1185 million reads and identified a total of 199,351 DHSs through ~ 30% unique mapping reads. It should be noted that more than half of DNase-seq reads mapped multiple genome locations and were not analyzed in order to achieve a high specificity of peak profile and to avoid bias from repetitive genomic regions. Distinct chromatin accessibilities were observed in the ovules (0 and 3 DPA) compared to the fiber elongation stages (8, 12, 15, and 18 DPA). Besides, the chromatin accessibility during ovules was particularly elevated in genomic regions enriched with transposable elements (TEs) and genes in TE-enriched regions were involved in ovule cell division. We analyzed cis-regulatory modules and revealed the influence of hormones on fiber development from the regulatory divergence of transcription factor (TF) motifs. Finally, we constructed a reliable regulatory network of TFs related to ovule and fiber development based on chromatin accessibility and gene co-expression network. From this network, we discovered a novel TF, WRKY46, which may shape fiber development by regulating the lignin content. CONCLUSIONS: Our results not only reveal the contribution of TEs in fiber development, but also predict and validate the TFs related to fiber development, which will benefit the research of cotton fiber molecular breeding.


Asunto(s)
Cromatina , Factores de Transcripción , Cromatina/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Óvulo Vegetal/genética , Óvulo Vegetal/metabolismo , Redes Reguladoras de Genes , Desoxirribonucleasa I/genética
7.
Anal Chem ; 95(8): 4243-4250, 2023 02 28.
Artículo en Inglés | MEDLINE | ID: mdl-36799075

RESUMEN

Conjugated acetylenic polymers (CAPs) have emerged as a unique class of metal-free semiconductors with tunable electrical and optical properties yet their full potential remains largely unexplored. Organic bioelectronics is envisioned to create more opportunities for innovative biomedical applications. Herein, we report a poly(1,4-diethynylbenzene) (pDEB)/NiO gated enhancement-mode poly(ethylene dioxythiophene)-poly(styrene sulfonate) organic photoelectrochemical transistor (OPECT) and its structural evolution toward bioelectronic detection. pDEB was synthesized via copper-mediated Glaser polycondensation of DEB monomers on the NiO/FTO substrate, and the as-synthesized pDEB/NiO/FTO can efficiently modulate the enhancement-mode device with a high current gain. Linking with a sandwich immunoassay, the labeled alkaline phosphatase can catalyze sodium thiophosphate to generate H2S, which will react with the diacetylene group in pDEB through the Michael addition reaction, resulting in an altered molecular structure and thus the transistor response. Exemplified by HIgG as the model target, the developed biosensor achieves highly sensitive detection with a linear range of 70 fg mL-1-10 ng mL-1 and a low detection limit of 28.5 fg mL-1. This work features the dual functional CAP-gated OPECT, providing not only a novel gating module but also a structurally new rationale for bioelectronic detection.


Asunto(s)
Acetileno , Técnicas Biosensibles , Alquinos , Polímeros/química , Técnicas Biosensibles/métodos , Semiconductores
8.
Small ; 19(6): e2205970, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36453593

RESUMEN

Herein, an efficient method to prepare sulfonated polyether ether ketone (SPEEK) based cation exchange membranes (CEMs) is developed, where polyethersulfone (PES) is used as an additive. The optimized membrane of 30 wt.%PES/SPEEK-M exhibits a rather low anion permeability and a high ionic conductivity of 9.52 mS cm-1 together with low volume swelling in water. Meanwhile, tensile strength of the membrane is as high as 31.4 MPa with a tensile strain of 162%. As separators for aqueous K-ion batteries (AKIBs) with decoupled gel electrolytes (Zn anode in alkaline and Prussian blue (FeHCF) cathode in neutral). Discharge voltage of the AKIB can reach 2.3 V. Meanwhile, Zn dendrites can be effectively suppressed in the gel anolyte. Specific capacities of the FeHCF cathode are 116.7 mAh g-1 at 0.3 A g-1 (close to its theoretical value), and 95.0 mAh g-1 at 1.0 A g-1 , indicating good rate performance. Capacity retention of the cathode is as high as 91.2% after 1000 cycles' cycling owing to the well remained neutral environment of the catholyte. There is almost no pH change for the catholyte after cycling, indicating good anion-blocking or cation-selecting ability of the 30 wt.%PES/SPEEK-M, much better than other membranes.

9.
J Virol ; 96(2): e0147621, 2022 01 26.
Artículo en Inglés | MEDLINE | ID: mdl-34730396

RESUMEN

Human cytomegalovirus (HCMV) establishes a persistent/latent infection after primary infection, and the host factor(s) plays a key role in regulating HCMV infection status. The spread of reactivated HCMV via the hematogenous or neural route usually results in severe diseases in newborns and immunocompromised individuals. As the primary reservoirs in vivo, cells of myeloid lineage have been utilized extensively to study HCMV infection. However, the molecular mechanism of HCMV latency/reactivation in neural cells is still poorly understood. We previously showed that HCMV-infected T98G cells maintain a large number of viral genomes and support HCMV reactivation from latency upon cAMP/IBMX treatment. Here, we employed an isobaric tag for relative and absolute quantitation (iTRAQ)-based proteomics to characterize cellular protein changes during HCMV latency and reactivation in T98G cells. A total of 168 differentially expressed proteins (DEPs) were identified, including 89 proteins in latency and 85 proteins in reactivation. Bioinformatics analysis showed that a few biological pathways were associated with HCMV latency or reactivation. Moreover, we validated 16 DEPs by both mRNA and protein expression profiles and further evaluated the effects of ApoE and the phosphatidylinositol 3-kinase (PI3K) pathway on HCMV infection. ApoE knockdown reduced HCMV loads and virus release, whereas overexpressing ApoE hampered HCMV latent infection, indicating a role in HCMV latency establishment/maintenance. Blocking the PI3K pathway by LY294002, a PI3K inhibitor, induced HCMV reactivation from latency in T98G cells. Overall, this comparative proteomics analysis delineates the cellular protein changes during HCMV latency and reactivation and provides a road map to advance our understanding of the mechanism(s) in the context of neural cells. IMPORTANCE Human cytomegalovirus (HCMV) is a highly transmissible betaherpesvirus that has a prevalence of 60% to 90% worldwide. This opportunist pathogen poses a significant threat to newborns and immunosuppressed individuals. One major obstacle for developing effective therapeutics is a poor understanding of HCMV latency/reactivation mechanisms. This study presents, for the first time, a systemic analysis of host cell protein expression changes during HCMV latency establishment and reactivation processes in neural cells. We showed that ApoE was downregulated by HCMV to facilitate latent infection. Also, the proteomics analysis has associated a few PI3K pathway-related proteins with HCMV reactivation. Altogether, this study highlights multiple host proteins and signaling pathways that can be further investigated as potential druggable targets for HCMV-related diseases, especially brain disorders.


Asunto(s)
Citomegalovirus/fisiología , Proteómica , Activación Viral , Latencia del Virus , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , Línea Celular Tumoral , Ontología de Genes , Humanos , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Mapas de Interacción de Proteínas , Proteoma/genética , Proteoma/metabolismo , Transducción de Señal
10.
J Virol ; 96(5): e0182721, 2022 03 09.
Artículo en Inglés | MEDLINE | ID: mdl-35020472

RESUMEN

Human cytomegalovirus (HCMV) has a large (∼235 kb) genome with more than 200 predicted open reading frames that exploits numerous cellular factors to facilitate its replication. A key feature of HCMV-infected cells is the emergence of a distinctive membranous cytoplasmic compartment termed the virion assembly compartment (vAC). Here, we report that host protein WD repeat domain 11 (WDR11) plays a key role in vAC formation and virion morphogenesis. We found that WDR11 was upregulated at both mRNA and protein levels during HCMV infection. At the late stage of HCMV replication, WDR11 relocated to the vAC and colocalized with markers of the trans-Golgi network (TGN) and vAC. Depletion of WDR11 hindered HCMV-induced membrane reorganization of the Golgi and TGN, altered vAC formation, and impaired HCMV secondary envelopment and virion morphogenesis. Further, motifs critical for the localization of WDR11 in TGN were identified by alanine-scanning mutagenesis. Mutation of these motifs led to WDR11 mislocation outside the TGN and loss of vAC formation. Taken together, these data indicate that host protein WDR11 is required for efficient viral replication at the stage of virion assembly, possibly by facilitating the remodeling of the endomembrane system for vAC formation and virion morphogenesis. IMPORTANCE During the late phase of human cytomegalovirus (HCMV) infection, the endomembrane system is dramatically reorganized, resulting in the formation of a unique structure termed the virion assembly compartment (vAC), which is critical for the assembly of infectious virions. The mechanism of HCMV-induced vAC formation is still not fully understood. In this report, we identified a host factor, WDR11, that plays an important role in vAC formation. Our findings argue that WDR11 contributes to the relocation of the Golgi and trans-Golgi network to the vAC, a membrane reorganization process that appears to be required for efficient virion maturation. The present work provides new insights into the vAC formation and HCMV virion morphogenesis and a potential novel target for antiviral treatment.


Asunto(s)
Infecciones por Citomegalovirus , Citomegalovirus , Interacciones Microbiota-Huesped , Repeticiones WD40 , Citomegalovirus/genética , Citomegalovirus/metabolismo , Infecciones por Citomegalovirus/fisiopatología , Infecciones por Citomegalovirus/virología , Humanos , Morfogénesis , Virión/metabolismo , Ensamble de Virus/genética , Replicación Viral/genética , Repeticiones WD40/genética , Red trans-Golgi/metabolismo
11.
Nano Lett ; 22(19): 8008-8017, 2022 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-36018258

RESUMEN

Lithium metal anode possesses overwhelming capacity and low potential but suffers from dendrite growth and pulverization, causing short lifespan and low utilization. Here, a fundamental novel insight of using single-atomic catalyst (SAC) activators to boost lithium atom diffusion is proposed to realize delocalized deposition. By combining electronic microscopies, time-of-flight secondary ion mass spectrometry, theoretical simulations, and electrochemical analyses, we have unambiguously depicted that the SACs serve as kinetic activators in propelling the surface spreading and lateral redistribution of the lithium atoms for achieving dendrite-free plating morphology. Under the impressive capacity of 20 mA h cm-2, the Li modified with SAC-activator exhibits a low overpotential of ∼50 mV at 5 mA cm-2, a long lifespan of 900 h, and high Coulombic efficiencies during 150 cycles, much better than most literature reports. The so-coupled lithium-sulfur full battery delivers high cycling and rate performances, showing great promise toward the next-generation lithium metal batteries.

12.
Anal Chem ; 94(45): 15856-15863, 2022 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-36315837

RESUMEN

Semiconductor metal-organic frameworks (MOFs) and heterojunctions have gained increasing attention in many fields, yet their full potential remains largely unexplored. Advanced optobioelectronics are envisioned to create more opportunities for innovative biomedical applications. This study reports a UiO-66-NH2 (U6N)/CdS quantum dots (QDs)-gated organic photoelectrochemical transistor (OPECT) and its application toward energy-transfer-based sensitive microRNA-166a (miRNA-166a) detection assisted by duplex-specific nuclease (DSN)-enabled target recycling. Specifically, a U6N/CdS QDs photoanode was fabricated and shown to be efficiently gating a poly(3,4-ethylenedioxythiophene) doped with poly(styrene sulfonate) (PEDOT/PSS) channel, while the DSN-enabled release of Au-reporters and hybridization upon the U6N/CdS QDs photoanode could significantly inhibit the photoanode response via an energy transfer process and thus modulate the device response, permitting novel dual-amplified optobioelectronic miRNA-166a detection with a low detection limit of 1.0 fM. This work not only features the DSN-amplified miRNA detection via an OPECT route but also unveils the potential of semiconductor MOF heterojunctions for futuristic optobioelectronics.


Asunto(s)
Técnicas Biosensibles , Nanopartículas del Metal , Estructuras Metalorgánicas , MicroARNs , Puntos Cuánticos , MicroARNs/genética , Transferencia de Energía , Endonucleasas , Límite de Detección , Técnicas Electroquímicas
13.
J Virol ; 95(8)2021 03 25.
Artículo en Inglés | MEDLINE | ID: mdl-33504601

RESUMEN

We previously reported that human cytomegalovirus (HCMV) utilizes the cellular protein WD repeat-containing protein 5 (WDR5) to facilitate capsid nuclear egress. Here, we further show that HCMV infection results in WDR5 localization in a juxtanuclear region, and that its localization to this cellular site is associated with viral replication and late viral gene expression. Furthermore, WDR5 accumulated in the virion assembly compartment (vAC) and co-localized with vAC markers of gamma-tubulin (γ-tubulin), early endosomes, and viral vAC marker proteins pp65, pp28, and glycoprotein B (gB). WDR5 co-immunoprecipitated with multiple virion proteins, including MCP, pp150, pp65, pIRS1, and pTRS1, which may explain WDR5 accumulation in the vAC during infection. WDR5 fractionated with virions either in the presence or absence of Triton X-100 and was present in purified viral particles, suggesting that WDR5 was incorporated into HCMV virions. Thus, WDR5 localized to the vAC and was incorporated into virions, raising the possibility that in addition to capsid nuclear egress, WDR5 could also participate in cytoplasmic HCMV virion morphogenesis.Importance Human cytomegalovirus (HCMV) has a large (∼235-kb) genome that contains over 170 ORFs and exploits numerous cellular factors to facilitate its replication. In the late phase of HCMV infection cytoplasmic membranes are reorganized to establish the virion assembly compartment (vAC), which has been shown to necessary for efficient assembly of progeny virions. We previously reported that WDR5 facilitates HCMV nuclear egress. Here, we show that WDR5 is localized to the vAC and incorporated into virions, perhaps contributing to efficient virion maturation. Thus, findings in this study identified a potential role for WDR5 in HCMV assembly in the cytoplasmic phase of virion morphogenesis.

14.
J Med Virol ; 94(11): 5492-5506, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35879101

RESUMEN

During the long coevolution of human cytomegalovirus (HCMV) and humans, the host has formed a defense system of multiple layers to eradicate the invader, and the virus has developed various strategies to evade host surveillance programs. The intrinsic immunity primarily orchestrated by promyelocytic leukemia (PML) nuclear bodies (PML-NBs) represents the first line of defense against HCMV infection. Here, we demonstrate that microrchidia family CW-type zinc finger 3 (MORC3), a PML-NBs component, is a restriction factor targeting HCMV infection. We show that depletion of MORC3 through knockdown by RNA interference or knockout by CRISPR-Cas9 augmented immediate-early protein 1 (IE1) gene expression and subsequent viral replication, and overexpressing MORC3 inhibited HCMV replication by suppressing IE1 gene expression. To relief the restriction, HCMV induces transient reduction of MORC3 protein level via the ubiquitin-proteasome pathway during the immediate-early to early stage. However, MORC3 transcription is upregulated, and the protein level recovers in the late stages. Further analyses with temporal-controlled MORC3 expression and the major immediate-early promoter (MIEP)-based reporters show that MORC3 suppresses MIEP activity and consequent IE1 expression with the assistance of PML. Taken together, our data reveal that HCMV enforces temporary loss of MORC3 to evade its repression against the initiation of immediate-early gene expression.


Asunto(s)
Infecciones por Citomegalovirus , Proteínas Inmediatas-Precoces , Adenosina Trifosfatasas/metabolismo , Citomegalovirus/genética , Proteínas de Unión al ADN/metabolismo , Humanos , Proteínas Inmediatas-Precoces/genética , Proteínas Inmediatas-Precoces/metabolismo , Proteína de la Leucemia Promielocítica/genética , Proteína de la Leucemia Promielocítica/metabolismo , Replicación Viral
15.
Arch Microbiol ; 204(3): 176, 2022 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-35166931

RESUMEN

Two extremely halophilic strains, designated SYSU A558-1T and SYSU A121-1, were isolated from a saline sediment sample collected from Aiding salt-lake, China. Cells of strains SYSU A558-1T and SYSU A121-1 were Gram-stain-negative, coccoid, and non-motile. The strains were aerobic and grew at NaCl concentration of 10-30% (optimum, 20-22%), at 20-55 °C (optimum, 37-42 °C) and at pH 6.5-8.5 (optimum, 7.0-8.0). Cells lysed in distilled water. The polar lipids were phosphatidyl choline, phosphatidylglycerol phosphate methyl ester, disulfated diglycosyl diether-1 and unidentified glycolipid. Phylogenetic analysis based on the 16S rRNA gene sequence revealed that the two strains SYSU A558-1T and SYSU A121-1 were closely related to the membranes of the genus Haloterrigena. Phylogenetic and phylogenomic trees of strains SYSU A558-1T and SYSU A121-1 demonstrated a robust clade with Haloterrigena turkmenica, Haloterrigena salifodinae and Haloterrigena salina. The genomic DNA G + C content of strains SYSU A558-1T and SYSU A121-1 were 65.8 and 65.0%, respectively. Phenotypic, phylogenetic, chemotaxonomic and genome analysis suggested that the two strains SYSU A558-1T and SYSU A121-1 represent a novel species of the genus Haloterrigena, for which the name Haloterrigena gelatinilytica sp. nov. is proposed. The type strain is SYSU A558-1T (= KCTC 4259T = CGMCC 1.15953T).


Asunto(s)
Halobacteriaceae , Lagos , China , ADN de Archaea/genética , Halobacteriaceae/genética , Fosfolípidos , Filogenia , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Cloruro de Sodio
16.
Chem Rec ; 22(10): e202200114, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35785428

RESUMEN

Aqueous zinc-ion batteries (ZIBs) have attracted widespread attention due to the intrinsic features of Zn-based anodes, mainly including high capacity, low cost, and low working potential together with high over-potential for hydrogen evolution reaction. Aqueous ZIBs are considered to be strong competitors and substitutes for lead-acid, nickel-metal hydrogen, nickel-cadmium, and even lithium-ion batteries. Great efforts have been made in the past few years towards the issues existed in aqueous ZIBs, mainly including alkaline and mild acidic systems. In this perspective, we illustrate the advantages, the main challenges, and the corresponding solution strategies of Zn-based anodes in various aqueous rechargeable ZIBs with alkaline and mild acidic electrolytes. Furthermore, feasible aqueous ZIBs for practical use are prospected.

17.
Nutr Cancer ; 74(3): 1058-1070, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34121543

RESUMEN

Puffballs are a class of fungi widely distributed worldwide and associated with various bioactivities. This research mainly showed the antitumor bioactivity of extracts from Calvatia lilacina (CL), which is a common variety of puffballs. NMR and high-performance liquid chromatography methods are used to characterize the extracts. Results showed that CL extracts obtained with petroleum ether, ethyl acetate, ethanol, and water elicited obvious inhibitory effects on the proliferation of A549, Caco-2, and MDA-MB-231. Among these extracts, petroleum ether extract demonstrated the highest performance. This extract was then separated into seven sub-fractions (SFs). Three of these SFs (3#, 6#, and 7#) induces a decrease in the viability of MDA-MB-231 cells in which 7# SF exhibited the highest cytotoxicity, where the major component was found to be ergosta-7,22-dien-3-one. Further tests revealed that 7# SF from petroleum ether extract could trigger severe cell death in human breast cancer cells (MDA-MB-231) by activating the apoptotic pathway dependent on mitochondrial reactive oxygen species and caspase activation. All these results in combination indicate that the mechanism of extract-potentiated apoptosis associates closely with ROS-dependent mitochondrial dysfunction events which further induces mitochondria-mediated intrinsic cytochrome C-caspase-related pathway of apoptosis.Supplemental data for this article is available online at https://doi.org/10.1080/01635581.2021.1936576.


Asunto(s)
Agaricales , Neoplasias de la Mama , Apoptosis , Neoplasias de la Mama/patología , Células CACO-2 , Caspasas/metabolismo , Muerte Celular , Línea Celular Tumoral , Proliferación Celular , Femenino , Humanos , Potencial de la Membrana Mitocondrial , Mitocondrias , Extractos Vegetales/química , Especies Reactivas de Oxígeno/metabolismo
18.
Nano Lett ; 21(7): 3245-3253, 2021 Apr 14.
Artículo en Inglés | MEDLINE | ID: mdl-33725455

RESUMEN

Lithium metal electrodes have shown great promise for high capacity and the lowest potential. However, wide application is restricted by uncontrollable plating/stripping lithium behaviors, an uneven solid electrolyte interphase, and a lithium dendrite. Herein, the highly active single metal atom anchored in vacant catalyst is synthesized on the hierarchical porous nanocarbon (SACo/ADFS@HPSC). Acting as an artificial protective modulation layer on the lithium surface, the numerous atomic sites show the superiority in modulating lithium ion behaviors and smoothing the lithium surface without dendrite growth. As a consequence, the SACo/ADFS@HPSC-modified Li electrode lowers nucleation barrier (15 mV), extends the smooth plating lifespan (1600 h), and improves Coulombic efficiency, significantly accelerating the horizonal deposition of plated lithium. Coupled with a sulfur cathode, the fabricated pouch cell with 5.4 mg cm-2 delivers a high capacity of 3.78 mA h cm-2 corresponding to 1505 Wh kg-1, showing the promising practical application.

19.
Int J Mol Sci ; 23(5)2022 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-35269989

RESUMEN

As one of the pioneer crops widely planted in saline-alkaline areas, Gossypium provides daily necessities, including natural fiber, vegetable proteins, and edible oils. However, cotton fiber yield and quality are highly influenced by salt stress. Therefore, elucidating the molecular mechanisms of cotton in response to salinity stress is importance to breed new cultivars with high tolerance. In this study, we first developed a method for single-cell RNA-seq based on isolating protoplast from cotton root tips; then, we studied the impact of salinity stress on gene expression profiling and their dynamic changes using the developed high-efficiency method for protoplast dissociation suitable for single-cell RNA-seq. A total of 3391 and 2826 differentially expressed genes (DEGs) were identified in salt-treated samples before and after protoplast dissociation, respectively, which were enriched into several molecular components, including response to stimulus, response to stress, and cellular macromolecule metabolic process by gene ontology (GO) analysis. Plant hormone signal transduction, phenylpropanoid biosynthesis, and MAPK signaling pathway were found to be enriched via Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Twenty-two and nine salinity-responsive DEGs participated in plant hormone signaling and MAPK signaling in roots, before and after protoplast dissociation, respectively; six upregulated DEGs were involved in ABA signaling transduction, namely, Ga04G2111, Ga07G0142, Ga09G2061, Ga10G0262, Ga01G0063, and Ga08G1915 which indicates their potential functions on plants adapting to salt stress. Additionally, 384 and 257 transcription factors (TFs) were differentially expressed in salt-stress roots before and after protoplast dissociation, respectively, of which significantly up-regulated TFs mainly belonged to the AP2/ERF-ERF family, which implied their potential roles responding to salt stress. These results not only provide novel insights to reveal the regulatory networks in plant's root response to salt stress, but also lay the solid foundation for further exploration on cellular heterogeneity by single-cell transcriptome sequencing.


Asunto(s)
Gossypium , Reguladores del Crecimiento de las Plantas , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Gossypium/genética , Gossypium/metabolismo , Fitomejoramiento , Reguladores del Crecimiento de las Plantas/metabolismo , Protoplastos , Estrés Salino/genética , Estrés Fisiológico/genética , Transcriptoma
20.
Int J Mol Sci ; 23(19)2022 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-36232609

RESUMEN

Glutathione S-transferases (GSTs) play an essential role in plant cell detoxification and secondary metabolism. However, their accurate functions in the growth and response to abiotic stress in woody plants are still largely unknown. In this work, a Phi class Glutathione S-transferase encoding gene PtGSTF1 was isolated from poplar (P. trichocarpa), and its biological functions in the regulation of biomass production and salt tolerance were investigated in transgenic poplar. PtGSTF1 was ubiquitously expressed in various tissues and organs, with a predominant expression in leaves and inducible expression by salt stress. Transgenic poplar overexpressing PtGSTF1 showed improved shoot growth, wood formation and improved salt tolerance, consistent with the increased xylem cell number and size under normal condition, and the optimized Na+ and K+ homeostasis and strengthened reactive oxygen species scavenging during salt stress. Further transcriptome analyses demonstrated that the expressions of genes related to hydrolase, cell wall modification, ion homeostasis and ROS scavenging were up- or down-regulated in transgenic plants. Our findings imply that PtGSTF1 improves both biomass production and salt tolerance through regulating hydrolase activity, cell wall modification, ion homeostasis and ROS scavenging in transgenic poplar, and that it can be considered as a useful gene candidate for the genetic breeding of new tree varieties with improved growth under salt stress conditions.


Asunto(s)
Populus , Tolerancia a la Sal , Biomasa , Proliferación Celular , Regulación de la Expresión Génica de las Plantas , Glutatión/metabolismo , Glutatión Transferasa/genética , Glutatión Transferasa/metabolismo , Homeostasis , Hidrolasas/metabolismo , Fitomejoramiento , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente/genética , Populus/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Tolerancia a la Sal/genética , Xilema/metabolismo
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