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1.
Cell ; 166(1): 102-14, 2016 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-27293192

RESUMEN

Co-option of RAG1 and RAG2 for antigen receptor gene assembly by V(D)J recombination was a crucial event in the evolution of jawed vertebrate adaptive immunity. RAG1/2 are proposed to have arisen from a transposable element, but definitive evidence for this is lacking. Here, we report the discovery of ProtoRAG, a DNA transposon family from lancelets, the most basal extant chordates. A typical ProtoRAG is flanked by 5-bp target site duplications and a pair of terminal inverted repeats (TIRs) resembling V(D)J recombination signal sequences. Between the TIRs reside tail-to-tail-oriented, intron-containing RAG1-like and RAG2-like genes. We demonstrate that ProtoRAG was recently active in the lancelet germline and that the lancelet RAG1/2-like proteins can mediate TIR-dependent transposon excision, host DNA recombination, transposition, and low-efficiency TIR rejoining using reaction mechanisms similar to those used by vertebrate RAGs. We propose that ProtoRAG represents a molecular "living fossil" of the long-sought RAG transposon.


Asunto(s)
Elementos Transponibles de ADN , Evolución Molecular , Anfioxos/genética , Recombinación V(D)J , Animales , Proteínas de Unión al ADN , Proteínas de Homeodominio , Secuencias Repetidas Terminales
2.
J Virol ; 98(3): e0168623, 2024 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-38376196

RESUMEN

The porcine reproductive and respiratory syndrome virus (PRRSV) can lead to severe reproductive problems in sows, pneumonia in weaned piglets, and increased mortality, significantly negatively impacting the economy. Post-translational changes are essential for the host-dependent replication and long-term infection of PRRSV. Uncertainty surrounds the function of the ubiquitin network in PRRSV infection. Here, we screened 10 deubiquitinating enzyme inhibitors and found that the ubiquitin-specific proteinase 1 (USP1) inhibitor ML323 significantly inhibited PRRSV replication in vitro. Importantly, we found that USP1 interacts with nonstructural protein 1ß (Nsp1ß) and deubiquitinates its K48 to increase protein stability, thereby improving PRRSV replication and viral titer. Among them, lysine at position 45 is essential for Nsp1ß protein stability. In addition, deficiency of USP1 significantly reduced viral replication. Moreover, ML323 loses antagonism to PRRSV rSD16-K45R. This study reveals the mechanism by which PRRSV recruits the host factor USP1 to promote viral replication, providing a new target for PRRSV defense.IMPORTANCEDeubiquitinating enzymes are critical factors in regulating host innate immunity. The porcine reproductive and respiratory syndrome virus (PRRSV) nonstructural protein 1ß (Nsp1ß) is essential for producing viral subgenomic mRNA and controlling the host immune system. The host inhibits PRRSV proliferation by ubiquitinating Nsp1ß, and conversely, PRRSV recruits the host protein ubiquitin-specific proteinase 1 (USP1) to remove this restriction. Our results demonstrate the binding of USP1 to Nsp1ß, revealing a balance of antagonism between PRRSV and the host. Our research identifies a brand-new PRRSV escape mechanism from the immune response.


Asunto(s)
Síndrome Respiratorio y de la Reproducción Porcina , Virus del Síndrome Respiratorio y Reproductivo Porcino , Animales , Femenino , Endopeptidasas/genética , Péptido Hidrolasas/metabolismo , Síndrome Respiratorio y de la Reproducción Porcina/metabolismo , Síndrome Respiratorio y de la Reproducción Porcina/virología , Virus del Síndrome Respiratorio y Reproductivo Porcino/metabolismo , Porcinos , Proteínas no Estructurales Virales/genética , Proteínas no Estructurales Virales/metabolismo , Replicación Viral
3.
Nature ; 569(7754): 79-84, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30971819

RESUMEN

Domestication of a transposon (a DNA sequence that can change its position in a genome) to give rise to the RAG1-RAG2 recombinase (RAG) and V(D)J recombination, which produces the diverse repertoire of antibodies and T cell receptors, was a pivotal event in the evolution of the adaptive immune system of jawed vertebrates. The evolutionary adaptations that transformed the ancestral RAG transposase into a RAG recombinase with appropriately regulated DNA cleavage and transposition activities are not understood. Here, beginning with cryo-electron microscopy structures of the amphioxus ProtoRAG transposase (an evolutionary relative of RAG), we identify amino acid residues and domains the acquisition or loss of which underpins the propensity of RAG for coupled cleavage, its preference for asymmetric DNA substrates and its inability to perform transposition in cells. In particular, we identify two adaptations specific to jawed-vertebrates-arginine 848 in RAG1 and an acidic region in RAG2-that together suppress RAG-mediated transposition more than 1,000-fold. Our findings reveal a two-tiered mechanism for the suppression of RAG-mediated transposition, illuminate the evolution of V(D)J recombination and provide insight into the principles that govern the molecular domestication of transposons.


Asunto(s)
Elementos Transponibles de ADN/genética , Evolución Molecular , Genes RAG-1 , Proteínas de Homeodominio/química , Proteínas de Homeodominio/ultraestructura , Anfioxos/enzimología , Recombinación V(D)J , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Microscopía por Crioelectrón , División del ADN , Proteínas de Homeodominio/metabolismo , Modelos Moleculares , Dominios Proteicos , Relación Estructura-Actividad
4.
EMBO J ; 39(21): e105857, 2020 11 02.
Artículo en Inglés | MEDLINE | ID: mdl-32945578

RESUMEN

Jawed vertebrate adaptive immunity relies on the RAG1/RAG2 (RAG) recombinase, a domesticated transposase, for assembly of antigen receptor genes. Using an integration-activated form of RAG1 with methionine at residue 848 and cryo-electron microscopy, we determined structures that capture RAG engaged with transposon ends and U-shaped target DNA prior to integration (the target capture complex) and two forms of the RAG strand transfer complex that differ based on whether target site DNA is annealed or dynamic. Target site DNA base unstacking, flipping, and melting by RAG1 methionine 848 explain how this residue activates transposition, how RAG can stabilize sharp bends in target DNA, and why replacement of residue 848 by arginine during RAG domestication led to suppression of transposition activity. RAG2 extends a jawed vertebrate-specific loop to interact with target site DNA, and functional assays demonstrate that this loop represents another evolutionary adaptation acquired during RAG domestication to inhibit transposition. Our findings identify mechanistic principles of the final step in cut-and-paste transposition and the molecular and structural logic underlying the transformation of RAG from transposase to recombinase.


Asunto(s)
Proteínas de Unión al ADN/química , Evolución Molecular , Proteínas de Homeodominio/química , Recombinasas/química , Animales , Microscopía por Crioelectrón , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Proteína HMGB1/química , Proteína HMGB1/genética , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Humanos , Modelos Moleculares , Proteínas Nucleares , Conformación Proteica , Recombinasas/genética , Recombinación Genética , Transposasas/química , Transposasas/genética , Transposasas/metabolismo , Vertebrados
5.
Ann Surg ; 2024 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-38482684

RESUMEN

OBJECTIVE: To evaluate whether a machine learning algorithm (i.e. the "NightSignal" algorithm) can be used for the detection of postoperative complications prior to symptom onset after cardiothoracic surgery. SUMMARY BACKGROUND DATA: Methods that enable the early detection of postoperative complications after cardiothoracic surgery are needed. METHODS: This was a prospective observational cohort study conducted from July 2021 to February 2023 at a single academic tertiary care hospital. Patients aged 18 years or older scheduled to undergo cardiothoracic surgery were recruited. Study participants wore a Fitbit watch continuously for at least 1 week preoperatively and up to 90-days postoperatively. The ability of the NightSignal algorithm-which was previously developed for the early detection of Covid-19-to detect postoperative complications was evaluated. The primary outcomes were algorithm sensitivity and specificity for postoperative event detection. RESULTS: A total of 56 patients undergoing cardiothoracic surgery met inclusion criteria, of which 24 (42.9%) underwent thoracic operations and 32 (57.1%) underwent cardiac operations. The median age was 62 (IQR: 51-68) years and 30 (53.6%) patients were female. The NightSignal algorithm detected 17 of the 21 postoperative events a median of 2 (IQR: 1-3) days prior to symptom onset, representing a sensitivity of 81%. The specificity, negative predictive value, and positive predictive value of the algorithm for the detection of postoperative events were 75%, 97%, and 28%, respectively. CONCLUSIONS: Machine learning analysis of biometric data collected from wearable devices has the potential to detect postoperative complications-prior to symptom onset-after cardiothoracic surgery.

6.
Anal Chem ; 96(17): 6674-6682, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38642044

RESUMEN

Photodynamic therapy (PDT) is a significant noninvasive therapeutic modality, but it is often limited in its application due to the restricted tissue penetration depth caused by the wavelength limitations of the light source. Two-photon (TP) fluorescence techniques are capable of having an excitation wavelength in the NIR region by absorbing two NIR photons simultaneously, which offers the potential to achieve higher spatial resolution for deep tissue imaging. Thus, the adoption of TP fluorescence techniques affords several discernible benefits for photodynamic therapy. Organic TP dyes possess a high fluorescence quantum yield. However, the biocompatibility of organic TP dyes is poor, and the method of coating organic TP dyes with silica can effectively overcome the limitations. Herein, based on the TP silica nanoparticles, a functionalized intelligent biogenic missile TP-SiNPs-G4(TMPyP4)-dsDNA(DOX)-Aptamer (TGTDDA) was developed for effective TP bioimaging and synergistic targeted photodynamic therapy and chemotherapy in tumors. First, the Sgc8 aptamer was used to target the PTK7 receptor on the surface of tumor cells. Under two-photon light irradiation, the intelligent biogenic missile can be activated for TP fluorescence imaging to identify tumor cells and the photosensitizer assembled on the nanoparticle surface can be activated for photodynamic therapy. Additionally, this intelligent biogenic missile enables the controlled release of doxorubicin (DOX). The innovative strategy substantially enhances the targeted therapeutic effectiveness of cancer cells. The intelligent biogenic missile provides an effective method for the early detection and treatment of tumors, which has a good application prospect in the real-time high-sensitivity diagnosis and treatment of tumors.


Asunto(s)
Imagen Óptica , Fotoquimioterapia , Fotones , Fármacos Fotosensibilizantes , Humanos , Animales , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Ratones , Nanopartículas/química , Doxorrubicina/química , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Dióxido de Silicio/química , Aptámeros de Nucleótidos/química , Colorantes Fluorescentes/química , Neoplasias/tratamiento farmacológico , Neoplasias/diagnóstico por imagen , Antineoplásicos/química , Antineoplásicos/farmacología , Ratones Desnudos , Línea Celular Tumoral , Ratones Endogámicos BALB C
7.
Small ; : e2401789, 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38855992

RESUMEN

Rechargeable aqueous Zn-ion batteries (ZIBs) are considered as a new energy storage device for wearable electronic equipment. Nowadays, dendrite growth and uneven deposition of zinc have been the principal problems to suppress the development of high-performance wearable zinc-ion batteries. Herein, a perovskite material of LaAlO3 nanoparticle has been applied for interface engineering and zinc anode protection. By adjusting transport channels and accelerating the Zn2+ diffusion, the hydrogen evolution reaction potential is improved, and electric field distribution on the Zn electrode surface is regulated to navigate the fast and uniform deposition of Zn2+. As a proof of demonstration, the assembled LAO@Zn||MnO2 batteries can display the highest capacity of up to 140 mAh g-1 without noticeable decay even after 1000 cycles. Moreover, a motor-driven fan and electronic wristwatch powered by wearable ZIBs can demonstrate the practical feasibility of LAO@Zn||MnO2 in wearable electronic equipment.

8.
J Virol ; 97(9): e0056923, 2023 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-37607059

RESUMEN

Proinflammatory factors play important roles in the pathogenesis of African swine fever virus (ASFV), which is the causative agent of African swine fever (ASF), a highly contagious and severe hemorrhagic disease. Efforts in the prevention and treatment of ASF have been severely hindered by knowledge gaps in viral proteins responsible for modulating host antiviral responses. In this study, we identified the I10L protein (pI10L) of ASFV as a potential inhibitor of the TNF-α- and IL-1ß-triggered NF-κB signaling pathway, the most canonical and important part of host inflammatory responses. The ectopically expressed pI10L remarkably suppressed the activation of NF-κB signaling in HEK293T and PK-15 cells. The ASFV mutant lacking the I10L gene (ASFVΔI10L) induced higher levels of proinflammatory cytokines production in primary porcine alveolar macrophages (PAMs) compared with its parental ASFV HLJ/2018 strain (ASFVWT). Mechanistic studies suggest that pI10L inhibits IKKß phosphorylation by reducing the K63-linked ubiquitination of NEMO, which is necessary for the activation of IKKß. Morever, pI10L interacts with the kinase domain of IKKß through its N-terminus, and consequently blocks the association of IKKß with its substrates IκBα and p65, leading to reduced phosphorylation. In addition, the nuclear translocation efficiency of p65 was also altered by pI10L. Further biochemical evidence supported that the amino acids 1-102 on pI10L were essential for the pI10L-mediated suppression of the NF-κB signaling pathway. The present study clarifies the immunosuppressive activity of pI10L, and provides novel insights into the understanding of ASFV pathobiology and the development of vaccines against ASF. IMPORTANCE African swine fever (ASF), caused by the African swine fever virus (ASFV), is now widespread in many countries and severely affects the commercial rearing of swine. To date, few safe and effective vaccines or antiviral strategies have been marketed due to large gaps in knowledge regarding ASFV pathobiology and immune evasion mechanisms. In this study, we deciphered the important role of the ASFV-encoded I10L protein in the TNF-α-/IL-1ß-triggered NF-κB signaling pathway. This study provides novel insights into the pathogenesis of ASFV and thus contributes to the development of vaccines against ASF.

9.
J Med Virol ; 96(2): e29470, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38362933

RESUMEN

The 2022 multi-country mpox outbreak raised public concern globally. Self-isolation and informing close contacts after developing mpox-related symptoms are critical measures in controlling the outbreak. This study investigated behavioral intentions of self-isolation and informing close contacts after developing mpox-related symptoms and associated factors among young men who have sex with men (YMSM) aged 18-29 years in China. The cross-sectional study was conducted among 2493 YMSM in six provincial regions in China from September 10th to 30th, 2022. Descriptive and logistic analyses were applied, using the intentions of self-isolation and informing close contacts after developing mpox-related symptoms as binary outcomes. The mean age of the participants was 24.6 (SD = 2.9) years. The prevalence of having intentions of self-isolation and informing close contacts after developing mpox-related symptoms was 88.6% (95% CI: 87.3%-89.9%) and 84.9% (95% CI: 83.5%-86.3%). Participants who were employed (adjusted odds ratio (AOR) = 1.474, 95% CI: 1.035-2.097; AOR = 1.371, 95% CI:1.002, 1.876), had higher mpox knowledge scores (AOR = 1.474, 95% CI: 1.035-2.097; AOR = 1.371, 95% CI: 1.002-1.876), and had higher perceived threats of mpox (AOR = 1.079, 95% CI: 1.030-1.130; AOR = 1.045, 95% CI: 1.002-1.090) were more likely to intend to self-isolate and inform close contacts. Participants who had MSM in-person gatherings in the past 6 months were more likely to intend to self-isolate (AOR = 1.392, 95% CI: 1.066-1.208). Participants with higher depression scores (AOR = 0.968, 95% CI: 0.948-0.989) and self-stigma (AOR = 0.975, 95% CI: 0.954-0.997) were less likely to intend to self-isolate and inform close contacts, respectively. Self-isolation and informing close contacts when developing disease-related symptoms are acceptable measures in response to mpox in China. Strengthening targeted risk communication and self-efficacy, raising disease knowledge, providing mental support, and reducing stigma toward the affected community are warranted.


Asunto(s)
Infecciones por VIH , Mpox , Minorías Sexuales y de Género , Masculino , Humanos , Adulto Joven , Adulto , Homosexualidad Masculina , Estudios Transversales , Intención , China/epidemiología , Infecciones por VIH/epidemiología
10.
Theor Appl Genet ; 137(3): 58, 2024 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-38407646

RESUMEN

KEY MESSAGE: SNP-based and InDel-based GWAS on multi-environment data identified genomic regions associated with barley grain size. Barley yield and quality are greatly influenced by grain size. Improving barley grain size in breeding programs requires knowledge of genetic loci and alleles in germplasm resources. In this study, a collection of 334 worldwide two-rowed barley accessions with extensive genetic diversity was evaluated for grain size including grain length (GL), grain width (GW), and thousand-grain weight (TGW) across six independent field trials. Significant differences were observed in genotype and environments for all measured traits. SNP- and InDel-based GWAS were applied to dissect the genetic architecture of grain size with an SLAF-seq strategy. Two approaches using the FarmCPU model revealed 38 significant marker-trait associations (MTAs) with PVE ranging from 0.01% to 20.68%. Among these MTAs, five were on genomic regions where no previously reported QTL for grain size. Superior alleles of TGW-associated SNP233060 and GL-associated InDel11006 exhibited significantly higher levels of phenotype. The significant MTAs could be used in marker-assisted selection breeding.


Asunto(s)
Hordeum , Hordeum/genética , Estudio de Asociación del Genoma Completo , Fitomejoramiento , Alelos , Grano Comestible/genética
11.
Eur Radiol ; 34(1): 695-704, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37566268

RESUMEN

OBJECTIVES: The current study aimed to explore the moderating role of psychological resilience in the association between workload and depressive symptoms among radiology residents during standardized residency training (SRT) in China. METHODS: A nationwide cross-sectional online survey was conducted among radiology residents in China. Workload was measured by working hours per week and the frequency of frontline nightwork in the last month. Resilience was assessed by the 2-item Connor-Davidson Resilience Scale. Depressive symptoms were measured by the Depression Anxiety Stress Scales. The hierarchical regression and simple slope analyses were performed to examine the moderating effect of resilience. RESULTS: Among 3666 radiology residents, the mean age was 27.3 years (SD = 2.6) and 58% were female. About 24.4% of the participants reported medium to severe depressive symptoms. The hierarchical regression showed that working hours (ba = 0.11, 95%CI: 0.08, 0.14) and having frontline nightwork more than once (ba = 1.22, 95%CI: 0.67, 1.78) were positively associated with depressive symptoms; the moderating effect of resilience was significant in the association of depressive symptoms with working hours (ba = - 0.02, 95%CI: - 0.03, - 0.01) and having frontline nightwork more than once (ba = - 0.28, 95%CI: - 0.49, - 0.07). The simple slope test showed the association between workload-related variables and depressive symptoms was only significant in those with a relatively lower level of resilience. CONCLUSIONS: The study found that resilience was an important modifier buffering the positive association between workload and depressive symptoms among radiology residents in China. Future medical training programs are suggested to include effective intervention components to increase personal resilience. CLINICAL RELEVANCE STATEMENT: Heavy workload in clinical setting may pose adverse effect on mental health and job performance of radiology residents. The study investigated whether psychological resilience would mitigate the association between workload and depressive symptoms among Chinese radiology residents. KEY POINTS: • Radiology residents with a heavier workload presented a higher level of depressive symptoms in China. • Psychological resilience mitigated the positive association between workload and depressive symptoms. • The association between workload and depressive symptoms was only statistically significant in radiology residents with a relatively lower level of resilience.


Asunto(s)
Pruebas Psicológicas , Radiología , Resiliencia Psicológica , Humanos , Femenino , Adulto , Masculino , Carga de Trabajo , Depresión/epidemiología , Estudios Transversales , China/epidemiología
12.
Inorg Chem ; 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-38995295

RESUMEN

The influence of cooling history for the Zn3Ga2Ge2O10/Cr3+ phosphors prepared by solid state reaction on the spectral properties was discovered, and an anticounterfeiting scheme based on the identification with smartphone was proposed and experimentally demonstrated using the studied phosphors. A combination of color-tunable visible fluorescence emission and near-infrared (NIR) afterglow emission in Zn3Ga2Ge2O10/x mol % Cr3+(x = 0, 0.05, 1, 2, 3, and 4) phosphors to achieve multimode anticounterfeiting was reported. It is found that with the increasing Cr3+ concentrations, the visible emission can be tuned from green, light pink, and light red to deep red under 254 nm ultraviolet (UV) excitation. This phenomenon is related to the formation of oxygen vacancies in the host during the process of natural cooling and the characteristic emission of Cr3+. In addition, the persistent time of the Cr3+ emission centered at 700 nm can be also tuned by various Cr3+ concentrations. A possible mechanism was deduced to explain the afterglow phenomenon. Lastly, a flower pattern applied in anticounterfeiting was fabricated using the Zn3Ga2Ge2O10/x mol % Cr3+ (x = 0, 0.05, 1, 2, 3, and 4) phosphors to present tunable color and NIR afterglow signals at different excitation modes, and the camera of smartphone was chosen as a detection tool to take the NIR images. The results obtained above suggest that the prepared phosphors at natural cooling condition have great potential in affording advanced optical anticounterfeiting.

13.
Mol Breed ; 44(2): 16, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38371442

RESUMEN

WNK kinases are a unique class of serine/threonine protein kinases that lack a conserved catalytic lysine residue in the kinase domain, hence the name WNK (with no K, i.e., lysine). WNK kinases are involved in various physiological processes in plants, such as circadian rhythm, flowering time, and stress responses. In this study, we identified 26 WNK genes in soybean and analyzed their phylogenetic relationships, gene structures, chromosomal distribution, cis-regulatory elements, expression patterns, and conserved protein motifs. The soybean WNK genes were unevenly distributed on 15 chromosomes and underwent 21 segmental duplication events during evolution. We detected 14 types of cis-regulatory elements in the promoters of the WNK genes, indicating their potential involvement in different signaling pathways. The transcriptome database revealed tissue-specific and salt stress-responsive expression of WNK genes in soybean, the second of which was confirmed by salt treatments and qRT-PCR analysis. We found that most WNK genes were significantly up-regulated by salt stress within 3 h in both roots and leaves, except for WNK5, which showed a distinct expression pattern. Our findings provide valuable insights into the molecular characteristics and evolutionary history of the soybean WNK gene family and lay a foundation for further analysis of WNK gene functions in soybean. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01440-5.

14.
BMC Vet Res ; 20(1): 187, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38730463

RESUMEN

BACKGROUND: Porcine epidemic diarrhea virus (PEDV), a type of coronavirus, is one of the main pathogens that can infect pigs of all ages. It causes diarrhea and acute death of newborn piglets, resulting in massive economic losses to the worldwide swine industry. While vaccination remains the primary approach in combating PEDV, it often fails to address all the challenges posed by the infection, particularly in light of the emergence of evolving mutant strains. Therefore, there is a critical need to identify potent antiviral drugs that can effectively safeguard pigs against PEDV infection. RESULTS: In this study, the antiviral efficacy of SP2509, a specific antagonist of Lysine-specific demethylase 1(LSD1), was evaluated in vitro. The RT-qPCR, Western blot, TCID50, and IFA showed that at a concentration of 1µmol/L, SP2509 significantly inhibited PEDV infection. Additionally, viral life cycle assays showed that SP2509 operates by impeding PEDV internalization and replication rather than attachment and release. Regarding mechanism, in Huh-7 cells, knockdowns LSD1 can suppress PEDV replication. This indicated that the inhibition effect of SP2509 on PEDV largely depends on the activity of its target protein, LSD1. CONCLUSION: Our results in vitro show that SP2509 can inhibit PEDV infection during the internalization and replication stage and revealed a role of LSD1 as a restriction factor for PEDV. These imply that LSD1 might be a target for interfering with the viral infection, and SP2509 could be developed as an effective anti-PEDV agent.


Asunto(s)
Antivirales , Histona Demetilasas , Virus de la Diarrea Epidémica Porcina , Replicación Viral , Virus de la Diarrea Epidémica Porcina/efectos de los fármacos , Animales , Antivirales/farmacología , Replicación Viral/efectos de los fármacos , Histona Demetilasas/antagonistas & inhibidores , Porcinos , Chlorocebus aethiops , Enfermedades de los Porcinos/virología , Enfermedades de los Porcinos/tratamiento farmacológico , Infecciones por Coronavirus/veterinaria , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/virología , Células Vero
15.
Ecotoxicol Environ Saf ; 269: 115747, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-38070415

RESUMEN

Microplastics (MPs) are global environmental pollutants with potential toxicity concerns, and their effects on the reproductive system have attracted increasing attention. This study investigated the interaction between MPs and mammalian biomolecules, focusing on the relationship between the testosterone adsorption behavior of MPs and male reproductive health. The adsorption capacity of different types of MPs for testosterone was evaluated in vitro experiments. Polyamide (PA)-MPs exhibited stronger adsorption, while polymethyl methacrylate (PMMA)-MPs displayed the weakest adsorption. Sorption equilibrium between PA-MPs and testosterone was achieved within 6 h, fitting the Pseudo-2nd-order model and Langmuir isotherm. The effects of MPs on male reproduction in mice was determined in vivo experiments. Male mice were treated with 0.1 and 0.5 mg/d PA-MPs/PMMA-MPs by gavage once per day for 28 days. The results showed that only 0.5 mg/d PA-MP exposure induced decreased serum testosterone levels, increased testicular testosterone levels compared to the control, and more severe damage to seminiferous tubule structure, sperm motility and sperm morphology compared to the PMMA-MPs group. Meanwhile, PA-MPs could reduce intracellular nuclear translocation of androgen receptor (AR) mediated by testosterone, while PMMA-MPs had no impact. The study revealed that PA-MP adsorption reduced testosterone bioavailability and caused sperm quality to decline, offering new insights into the combined toxicity mechanism of MPs in male mammals.


Asunto(s)
Microplásticos , Contaminantes Químicos del Agua , Masculino , Animales , Ratones , Microplásticos/toxicidad , Plásticos/toxicidad , Plásticos/química , Nylons , Testosterona , Adsorción , Disponibilidad Biológica , Polimetil Metacrilato , Salud Reproductiva , Semen/química , Motilidad Espermática , Contaminantes Químicos del Agua/análisis , Mamíferos
16.
Chem Biodivers ; 21(6): e202400524, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38634793

RESUMEN

Baihe is a commonly used Chinese medicine for the treatment of neurological disorders. Clinically, the bulbs of Lilium brownii are used to act as Baihe. In the study, two new phenylpropanoid compounds including 3-O-acetyl-1-O-caffeoylglycerol (1) and 3-O-acetyl-1-O-p-coumaroylglycerol (2) were isolated from the bulbs of L. brownii. Their structures were identified by spectroscopic method and the effect on monoamine oxidase activity was determined using an enzyme labeling method. The results show 1 and 2 have anti-monoamine oxidase activity with 20.96 % and 22.31 % inhibition rates at 50 µg/ml, respectively.


Asunto(s)
Lilium , Inhibidores de la Monoaminooxidasa , Monoaminooxidasa , Lilium/química , Monoaminooxidasa/metabolismo , Inhibidores de la Monoaminooxidasa/farmacología , Inhibidores de la Monoaminooxidasa/química , Inhibidores de la Monoaminooxidasa/aislamiento & purificación , Estructura Molecular , Raíces de Plantas/química , Relación Estructura-Actividad , Relación Dosis-Respuesta a Droga
17.
Chem Biodivers ; : e202400568, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38771291

RESUMEN

Four new monoterpene rhamnosides, graphiumisides A-D (1-4), along with four known steroid compounds (5-8) were isolated from the fermentation extract of animal-derived endophytic fungus, Graphium sp. GD-11. The chemical structures of all compounds were elucidated using 1D and 2D NMR, HRESIMS spectroscopic analyses, and other spectroscopic methods. Compounds 1-4 exhibit a distinctive structure connected by one p-menthane type monoterpene and one L-rhamnose. This is the first report of monoterpene glycosides from Graphium sp. All compounds (1-8) were tested for cytotoxic activities against four cancer cell lines (HepG2, SMMC7721, SW480, and A549), and only compound 1 showed weak anti-tumor activity against SMMC7721 cells.

18.
Mikrochim Acta ; 191(6): 350, 2024 05 28.
Artículo en Inglés | MEDLINE | ID: mdl-38806865

RESUMEN

Gold nanomaterials have been widely explored in electrochemical sensors due to their high catalytic property and good stability in multi-medium. In this paper, the reproducibility of the signal among batches of gold nanorods (AuNRs)-modified electrodes was investigated to improve the data stabilization and repeatability. Ordered and random self-assembled AuNRs-modified electrodes were used as electrochemical sensors for the simultaneous determination of dopamine (DA) and topotecan (TPC), with the aim of obtaining an improved signal stability in batches of electrodes and realizing the simultaneous determination of both substances. The morphology and structure of the assemblies were analyzed and characterized by UV-Vis spectra, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and X-ray powder diffraction (XRD). Electrochemical studies showed that the ordered AuNRs/ITO electrodes have excellent signal reproducibility among several individuals due to the homogeneous mass transfer in the ordered arrangement of the AuNRs. Under the optimized conditions, the simultaneous detection results of DA and TPC showed good linearity in the ranges 1.75-45 µM and 1.5-40 µM, and the detection limits of DA and TPC were 0.06 µM and 0.17 µM, respectively. The results showed that the prepared ordered AuNR/ITO electrode had high sensitivity, long-term stability, and reproducibility for the simultaneous determination of DA and TPC, and it was expected to be applicable for real sample testing.


Asunto(s)
Dopamina , Técnicas Electroquímicas , Electrodos , Oro , Límite de Detección , Nanotubos , Topotecan , Dopamina/análisis , Oro/química , Topotecan/análisis , Topotecan/química , Reproducibilidad de los Resultados , Técnicas Electroquímicas/métodos , Técnicas Electroquímicas/instrumentación , Nanotubos/química , Humanos
19.
Sensors (Basel) ; 24(5)2024 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-38474999

RESUMEN

In this study, a cationic amphiphilic self-assembling peptide (SAP) Z23 was designed, and a simple bisphenol a (BPA) sensor, based on SAP Z23/multiwalled carbon nanotubes (Z23/MWCNTs) composite, was successfully fabricated on the surface of a glassy carbon electrode (GCE). The composite material was formed by π-π stacking interaction between the aromatic group on the hydrophobic side of Z23 and the side-wall of MWCNTs, with the charged hydrophilic group of Z23 exposed. During the electrocatalytic process of BPA, a synergistic effect was observed between Z23 and MWCNTs. The current response of the sensor based on composite material was 3.24 times that of the MWCNTs-modified electrode, which was much higher than that of the peptide-based electrode. Differential pulse voltammetry (DPV) was used to optimize the experimental conditions affecting the analytical performance of the modified electrode. Under optimal conditions, the linear range of the sensor was from 10 nM to 100 µM by amperometric measurement with sensitivity and limit of detection (LOD) at 6.569 µAµM-1cm-2 and 1.28 nM (S/N = 3), respectively. Consequently, the sensor has excellent electrochemical performance and is easy to fabricate, making it a good prospect in the field of electrochemical detection in the future.


Asunto(s)
Compuestos de Bencidrilo , Nanocompuestos , Nanotubos de Carbono , Fenoles , Técnicas Electroquímicas/métodos , Nanotubos de Carbono/química , Límite de Detección , Nanocompuestos/química , Electrodos
20.
Sensors (Basel) ; 24(2)2024 Jan 07.
Artículo en Inglés | MEDLINE | ID: mdl-38257448

RESUMEN

In this work, silver nanoparticles (AgNPs)/reduced graphene oxide (rGO) nanocomposites were electrodeposited on glassy carbon electrodes (GCE) to construct electrochemical sensors for the detection of hydrogen peroxide (H2O2) and dopamine (DA). The AgNPs were synthesized on graphene oxide (GO) by the hydrothermal method, followed by the reduction of the GO during the electrodeposition process, resulting in the formation of the nanocomposites on the surface of the electrodes. The generation of AgNPs on the graphene sheets was verified by scanning electron microscopy (SEM) and electrochemical impedance spectroscopy (EIS). The AgNPs/rGO/GCE showed a linear response to H2O2 in the range of 5 µM to 620 µM, with a sensitivity of 49 µA mM-1cm-2 and a limit of detection (LOD) of 3.19 µA. The linear response of the AgNPs/rGO/GCE to DA ranged from 1 µM to 276 µM, the sensitivity was 7.86 µA mM-1cm-2, and the LOD was 0.18 µM. Furthermore, DA and H2O2 were detected simultaneously in the same solution without interferences, and the sensors displayed good stability over time. The preparation method for the sensors is relatively eco-friendly, convenient, and efficient, exhibiting great potential for sensitive detection of DA and H2O2.

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