Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Resultados 1 - 20 de 793
Filtrar
1.
Circ Res ; 134(3): 290-306, 2024 02 02.
Artículo en Inglés | MEDLINE | ID: mdl-38197258

RESUMEN

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most prevalent monogenic heart disorder. However, the pathogenesis of HCM, especially its nongenetic mechanisms, remains largely unclear. Transcription factors are known to be involved in various biological processes including cell growth. We hypothesized that SP1 (specificity protein 1), the first purified TF in mammals, plays a role in the cardiomyocyte growth and cardiac hypertrophy of HCM. METHODS: Cardiac-specific conditional knockout of Sp1 mice were constructed to investigate the role of SP1 in the heart. The echocardiography, histochemical experiment, and transmission electron microscope were performed to analyze the cardiac phenotypes of cardiac-specific conditional knockout of Sp1 mice. RNA sequencing, chromatin immunoprecipitation sequencing, and adeno-associated virus experiments in vivo were performed to explore the downstream molecules of SP1. To examine the therapeutic effect of SP1 on HCM, an SP1 overexpression vector was constructed and injected into the mutant allele of Myh6 R404Q/+ (Myh6 c. 1211C>T) HCM mice. The human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from a patient with HCM were used to detect the potential therapeutic effects of SP1 in human HCM. RESULTS: The cardiac-specific conditional knockout of Sp1 mice developed a typical HCM phenotype, displaying overt myocardial hypertrophy, interstitial fibrosis, and disordered myofilament. In addition, Sp1 knockdown dramatically increased the cell area of hiPSC-CMs and caused intracellular myofibrillar disorganization, which was similar to the hypertrophic cardiomyocytes of HCM. Mechanistically, Tuft1 was identified as the key target gene of SP1. The hypertrophic phenotypes induced by Sp1 knockdown in both hiPSC-CMs and mice could be rescued by TUFT1 (tuftelin 1) overexpression. Furthermore, SP1 overexpression suppressed the development of HCM in the mutant allele of Myh6 R404Q/+ mice and also reversed the hypertrophic phenotype of HCM hiPSC-CMs. CONCLUSIONS: Our study demonstrates that SP1 deficiency leads to HCM. SP1 overexpression exhibits significant therapeutic effects on both HCM mice and HCM hiPSC-CMs, suggesting that SP1 could be a potential intervention target for HCM.


Asunto(s)
Cardiomiopatía Hipertrófica , Células Madre Pluripotentes Inducidas , Humanos , Ratones , Animales , Células Madre Pluripotentes Inducidas/metabolismo , Cardiomiopatía Hipertrófica/metabolismo , Miofibrillas/metabolismo , Miocitos Cardíacos/metabolismo , Cardiomegalia/metabolismo , Factores de Transcripción/metabolismo , Mamíferos
2.
Proc Natl Acad Sci U S A ; 120(12): e2221526120, 2023 03 21.
Artículo en Inglés | MEDLINE | ID: mdl-36913592

RESUMEN

Ruminants have a semi-invasive placenta, which possess highly vascularized placentomes formed by maternal endometrial caruncles and fetal placental cotyledons and required for fetal development to term. The synepitheliochorial placenta of cattle contains at least two trophoblast cell populations, including uninucleate (UNC) and binucleate (BNC) cells that are most abundant in the cotyledonary chorion of the placentomes. The interplacentomal placenta is more epitheliochorial in nature with the chorion developing specialized areolae over the openings of uterine glands. Of note, the cell types in the placenta and cellular and molecular mechanisms governing trophoblast differentiation and function are little understood in ruminants. To fill this knowledge gap, the cotyledonary and intercotyledonary areas of the mature day 195 bovine placenta were analyzed by single nuclei analysis. Single-nuclei RNA-seq analysis found substantial differences in cell type composition and transcriptional profiles between the two distinct regions of the placenta. Based on clustering and cell marker gene expression, five different trophoblast cell types were identified in the chorion, including proliferating and differentiating UNC and two different types of BNC in the cotyledon. Cell trajectory analyses provided a framework for understanding the differentiation of trophoblast UNC into BNC. The upstream transcription factor binding analysis of differentially expressed genes identified a candidate set of regulator factors and genes regulating trophoblast differentiation. This foundational information is useful to discover essential biological pathways underpinning the development and function of the bovine placenta.


Asunto(s)
Placenta , Trofoblastos , Embarazo , Bovinos , Animales , Femenino , Trofoblastos/metabolismo , Placenta/metabolismo , ARN Nuclear Pequeño/metabolismo , Rumiantes , Análisis de Secuencia de ARN
3.
Eur J Immunol ; : e2451178, 2024 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-39444061

RESUMEN

Liver injury releases danger-associated molecular patterns, which trigger the immune response. CD24 negatively regulates the immune response by binding with danger-associated molecular patterns, but the specific role of CD24 in modulating macrophage-related inflammation during liver injury remains largely unexplored. Here, we aimed to investigate the mechanisms of macrophage CD24 in the development of liver injury. Our results show that CD24 expression is upregulated primarily in hepatic macrophages (HMs) during acute liver injury. CD24-deficient mice exhibited more severe liver injury and showed a significantly higher frequency and number of HMs, particularly Ly6Chi monocyte-derived macrophages. Mechanistically, the CD24-Siglec-G interaction plays a vital role in mitigating acute liver injury. CD24-mediated inhibitory signaling in HMs primarily limits downstream NF-κB and p38 MAPK activation through the recruitment of SHP1. Our work unveils the critical role of macrophage CD24 in negatively regulating innate immune responses and protecting against acute liver injury, thus providing potential therapeutic targets for liver-associated diseases.

4.
Cereb Cortex ; 34(5)2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38700440

RESUMEN

While the auditory and visual systems each provide distinct information to our brain, they also work together to process and prioritize input to address ever-changing conditions. Previous studies highlighted the trade-off between auditory change detection and visual selective attention; however, the relationship between them is still unclear. Here, we recorded electroencephalography signals from 106 healthy adults in three experiments. Our findings revealed a positive correlation at the population level between the amplitudes of event-related potential indices associated with auditory change detection (mismatch negativity) and visual selective attention (posterior contralateral N2) when elicited in separate tasks. This correlation persisted even when participants performed a visual task while disregarding simultaneous auditory stimuli. Interestingly, as visual attention demand increased, participants whose posterior contralateral N2 amplitude increased the most exhibited the largest reduction in mismatch negativity, suggesting a within-subject trade-off between the two processes. Taken together, our results suggest an intimate relationship and potential shared mechanism between auditory change detection and visual selective attention. We liken this to a total capacity limit that varies between individuals, which could drive correlated individual differences in auditory change detection and visual selective attention, and also within-subject competition between the two, with task-based modulation of visual attention causing within-participant decrease in auditory change detection sensitivity.


Asunto(s)
Atención , Percepción Auditiva , Electroencefalografía , Percepción Visual , Humanos , Atención/fisiología , Masculino , Femenino , Adulto Joven , Adulto , Percepción Auditiva/fisiología , Percepción Visual/fisiología , Estimulación Acústica/métodos , Estimulación Luminosa/métodos , Potenciales Evocados/fisiología , Encéfalo/fisiología , Adolescente
5.
Small ; 20(16): e2306325, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38032161

RESUMEN

Due to the manufacturability of highly well-defined structures and wide-range versatility in its microstructure, SiO2 is an attractive template for synthesizing graphene frameworks with the desired pore structure. However, its intrinsic inertness constrains the graphene formation via methane chemical vapor deposition. This work overcomes this challenge by successfully achieving uniform graphene coating on a trimethylsilyl-modified SiO2 (denote TMS-MPS). Remarkably, the onset temperature for graphene growth dropped to 720 °C for the TMS-MPS, as compared to the 885 °C of the pristine SiO2. This is found to be mainly from the Si radicals formed from the decomposition of the surface TMS groups. Both experimental and computational results suggest a strong catalytic effect of the Si radicals on the CH4 dissociation. The surface engineering of SiO2 templates facilitates the synthesis of high-quality graphene sheets. As a result, the graphene-coated SiO2 composite exhibits a high electrical conductivity of 0.25 S cm-1. Moreover, the removal of the TMP-MPS template has released a graphene framework that replicates the parental TMS-MPS template on both micro- and nano- scales. This study provides tremendous insights into graphene growth chemistries as well as establishes a promising methodology for synthesizing graphene-based materials with pre-designed microstructures and porosity.

6.
Nat Methods ; 18(1): 92-99, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33408405

RESUMEN

Many experimental and bioinformatics approaches have been developed to characterize the human T cell receptor (TCR) repertoire. However, the unknown functional relevance of TCR profiling hinders unbiased interpretation of the biology of T cells. To address this inadequacy, we developed tessa, a tool to integrate TCRs with gene expression of T cells to estimate the effect that TCRs confer on the phenotypes of T cells. Tessa leveraged techniques combining single-cell RNA-sequencing with TCR sequencing. We validated tessa and showed its superiority over existing approaches that investigate only the TCR sequences. With tessa, we demonstrated that TCR similarity constrains the phenotypes of T cells to be similar and dictates a gradient in antigen targeting efficiency of T cell clonotypes with convergent TCRs. We showed this constraint could predict a functional dichotomization of T cells postimmunotherapy treatment and is weakened in tumor contexts.


Asunto(s)
Linfocitos Infiltrantes de Tumor/inmunología , Neoplasias/inmunología , Receptores de Antígenos de Linfocitos T/genética , Receptores de Antígenos de Linfocitos T/inmunología , Análisis de la Célula Individual/métodos , Linfocitos T/inmunología , Transcriptoma , Biología Computacional/métodos , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Neoplasias/genética , Neoplasias/patología
7.
Opt Express ; 32(6): 8937-8949, 2024 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-38571139

RESUMEN

In this study, PbS/Er co-doped fibers (PEDFs) were fabricated by atomic layer deposition (ALD) combined with modified chemical vapor deposition (MCVD). A pumping scheme based on two-photon absorption at 1310 nm of PEDF is proposed for L + band amplification. Through the theoretical analysis, the local environment of Er3+ is changed due to the co-doping of PbS, which improves the two-photon absorption efficiency near 1300 nm. Compared with the 980 nm pump, the PEDFs excited by the 1310 nm pump show better amplification performance in the L + band. And in a bi-directional pumping system, PEDF achieves over 22 dB of gain in the whole L band. In particular, the bandwidth of over 20 dB gain was extended to 1627 nm with a noise figure as low as 4.9 dB. To the best of our knowledge, this is the first time that a high-gain bandwidth of L band amplification has been extended to 1627 nm. The results of unsaturated loss also show that PbS co-doping improves the two-photon absorption efficiency of PEDF to broaden the amplification bandwidth of L + band. These results demonstrate that an effective L + band amplification method is practically provided for future ultra-wideband optical communications.

8.
Cardiovasc Diabetol ; 23(1): 381, 2024 Oct 26.
Artículo en Inglés | MEDLINE | ID: mdl-39462409

RESUMEN

BACKGROUND: Atherosclerotic cardiovascular diseases remain the leading cause of mortality in diabetic patients, with endothelial cell (EC) dysfunction serving as the initiating step of atherosclerosis, which is exacerbated in diabetes. Krüppel-like factor 11 (KLF11), known for its missense mutations leading to the development of diabetes in humans, has also been identified as a novel protector of vascular homeostasis. However, its role in diabetic atherosclerosis remains unexplored. METHODS: Diabetic atherosclerosis was induced in both EC-specific KLF11 transgenic and knockout mice in the Ldlr-/- background by feeding a diabetogenic diet with cholesterol (DDC). Single-cell RNA sequencing (scRNA-seq) was utilized to profile EC dysfunction in diabetic atherosclerosis. Additionally, gain- and loss-of-function experiments were conducted to investigate the role of KLF11 in hyperglycemia-induced endothelial cell dysfunction. RESULTS: We found that endothelial KLF11 deficiency significantly accelerates atherogenesis under diabetic conditions, whereas KLF11 overexpression remarkably inhibits it. scRNA-seq profiling demonstrates that loss of KLF11 increases endothelial-to-mesenchymal transition (EndMT) during atherogenesis under diabetic conditions. Utilizing gain- and loss-of-function approaches, our in vitro study reveals that KLF11 significantly inhibits EC inflammatory activation and TXNIP-induced EC oxidative stress, as well as Notch1/Snail-mediated EndMT under high glucose exposure. CONCLUSION: Our study demonstrates that endothelial KLF11 is an endogenous protective factor against diabetic atherosclerosis. These findings indicate that manipulating KLF11 could be a promising approach for developing novel therapies for diabetes-related cardiovascular complications.


Asunto(s)
Aterosclerosis , Células Endoteliales , Ratones Endogámicos C57BL , Ratones Noqueados , Proteínas Represoras , Animales , Aterosclerosis/genética , Aterosclerosis/metabolismo , Aterosclerosis/prevención & control , Aterosclerosis/patología , Células Endoteliales/metabolismo , Células Endoteliales/patología , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , Placa Aterosclerótica , Transducción de Señal , Células Cultivadas , Masculino , Estrés Oxidativo , Modelos Animales de Enfermedad , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Transición Epitelial-Mesenquimal , Humanos , Angiopatías Diabéticas/metabolismo , Angiopatías Diabéticas/prevención & control , Angiopatías Diabéticas/genética , Angiopatías Diabéticas/fisiopatología , Angiopatías Diabéticas/etiología , Receptores de LDL/genética , Receptores de LDL/deficiencia , Receptores de LDL/metabolismo , Diabetes Mellitus Experimental/metabolismo , Ratones , Enfermedades de la Aorta/genética , Enfermedades de la Aorta/metabolismo , Enfermedades de la Aorta/prevención & control , Enfermedades de la Aorta/patología , Glucemia/metabolismo , Proteínas Reguladoras de la Apoptosis
9.
Opt Lett ; 49(20): 5747-5750, 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-39404528

RESUMEN

Mode-locked oscillators with high-order transverse modes are excellent platforms for generating femtosecond optical vortices with high average power and good propagation stability. These have important applications in diverse fields such as optical communication, strong-field physics, and laser processing. So far, generating vortex pulses with ultrashort pulse duration remains a challenge. In this Letter, we report a Kerr-lens mode-locked Yb:CALGO laser oscillator delivering Hermite-Gaussian (HG) pulses with a pulse duration of 86 fs using a non-collinear pumping technique. 91 fs optical vortex pulses were generated by using a cylindrical-lens mode converter. To the best of our knowledge, this is the shortest pulse duration ever obtained from a diode pumped solid-state mode-locked oscillator with a pure high-order Hermite-Gaussian mode. The phase structures of the generated femtosecond vortices are characterized.

10.
BMC Cancer ; 24(1): 715, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38862908

RESUMEN

BACKGROUND: Resistance to immune checkpoint inhibitors (ICIs) represents a major unmet medical need in non-small cell lung cancer (NSCLC) patients. Vascular endothelial growth factor (VEGF) inhibition may reverse a suppressive microenvironment and recover sensitivity to subsequent ICIs. METHODS: This phase Ib/IIa, single-arm study, comprised dose-finding (Part A) and expansion (Part B) cohorts. Patients with ICIs-refractory NSCLC were enrolled to receive anlotinib (a multi-target tyrosine kinase inhibitor) orally (from days 1 to 14 in a 21-day cycle) and nivolumab (360 mg every 3 weeks, intravenously) on a 21-day treatment cycle. The first 21-day treatment cycle was a safety observation period (phase Ib) followed by a phase II expansion cohort. The primary objectives were recommended phase 2 dose (RP2D, part A), safety (part B), and objective response rate (ORR, part B), respectively. RESULTS: Between November 2020 and March 2022, 34 patients were screened, and 21 eligible patients were enrolled (6 patients in Part A). The RP2D of anlotinib is 12 mg/day orally (14 days on and 7 days off) and nivolumab (360 mg every 3 weeks). Adverse events (AEs) of any cause and treatment-related AEs (TRAEs) were reported in all treated patients. Two patients (9.5%) experienced grade 3 TRAE. No grade 4 or higher AEs were observed. Serious AEs were reported in 4 patients. Six patients experienced anlotinib interruption and 4 patients experienced nivolumab interruption due to TRAEs. ORR and disease control rate (DCR) was 19.0% and 76.2%, respectively. Median PFS and OS were 7.4 months (95% CI, 4.3-NE) and 15.2 months (95% CI, 12.1-NE), respectively. CONCLUSION: Our study suggests that anlotinib combined with nivolumab shows manageable safety and promising efficacy signals. Further studies are warranted. TRIAL REGISTRATION: NCT04507906 August 11, 2020.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma de Pulmón de Células no Pequeñas , Inhibidores de Puntos de Control Inmunológico , Neoplasias Pulmonares , Nivolumab , Inhibidores de Proteínas Quinasas , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Resistencia a Antineoplásicos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inhibidores de Puntos de Control Inmunológico/administración & dosificación , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Indoles/administración & dosificación , Indoles/efectos adversos , Indoles/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Nivolumab/administración & dosificación , Nivolumab/efectos adversos , Nivolumab/uso terapéutico , Estudios Prospectivos , Inhibidores de Proteínas Quinasas/administración & dosificación , Inhibidores de Proteínas Quinasas/efectos adversos , Inhibidores de Proteínas Quinasas/uso terapéutico , Quinolinas/administración & dosificación , Quinolinas/efectos adversos , Quinolinas/uso terapéutico , Adolescente
11.
Biomacromolecules ; 25(2): 838-852, 2024 02 12.
Artículo en Inglés | MEDLINE | ID: mdl-38164823

RESUMEN

Nowadays, wearable devices derived from flexible conductive hydrogels have attracted enormous attention. Nevertheless, the utilization of conductive hydrogels in practical applications under extreme conditions remains a significant challenge. Herein, a series of inorganic salt-ion-enhanced conductive hydrogels (HPE-LiCl) consisting of hydroxyethyl cellulose, hydroxyethyl acrylate, lithium chloride, and ethylene glycol/water binary solvent were fabricated via a facile one-pot method. Apart from outstanding self-adhesion, high stretchability, and remarkable fatigue resistance, the HPE-LiCl hydrogels possessed especially excellent antifreezing and long-lasting moisture performances, which could maintain satisfactory flexibility and electric conductivity over extended periods of time, even in challenging conditions such as extremely low temperatures (as low as -40 °C) and high temperatures (as high as 80 °C). Consequently, the HPE-LiCl-based sensor could timely and accurately monitor various human motion signals even in adverse environments and after long-term storage. Hence, this work presents a facile strategy for the design of long-term reliable hydrogels as smart strain sensors, especially used in extreme environments.


Asunto(s)
Celulosa , Frío , Humanos , Conductividad Eléctrica , Hidrogeles , Iones
12.
Br J Nutr ; 131(1): 27-40, 2024 01 14.
Artículo en Inglés | MEDLINE | ID: mdl-37492950

RESUMEN

An 8-week experiment was performed to investigate the influence on growth performance, plasma biochemistry, glucose metabolism and the insulin pathway of supplementation of dietary taurine to a high-carbohydrate diet for grass carp. In this study, fish were fed diets at one of two carbohydrate levels, 31·49 % (positive control) or 38·61 % (T00). The high-carbohydrate basal diet (T00), without taurine, was supplemented with 0·05 % (T05), 0·10 % (T10), 0·15 % (T15) or 0·20 % (T20) taurine, resulting in six isonitrogenous (30·37 %) and isolipidic (2·37 %) experimental diets. The experimental results showed that optimal taurine level improved significantly weight gain, specific growth rate (SGR), feed utilisation, reduced plasma total cholesterol levels, TAG and promoted insulin-like growth factor level. Glucokinase, pyruvate kinase and phosphoenolpyruvate carboxykinase activities showed a quadratic function model with increasing dietary taurine level, while hexokinase, fatty acid synthetase activities exhibited a positive linear trend. Optimal taurine supplementation in high-carbohydrate diet upregulated insulin receptor (Ir), insulin receptor substrate (Irs1), phosphatidylinositol 3-kinase (pi3k), protein kinase B (akt1), glycogen synthase kinase 3 ß (gs3kß) mRNA level and downregulated insulin-like growth factor (igf-1), insulin-like growth factor 1 receptor (igf-1R) and Fork head transcription factor 1 (foxo1) mRNA level. The above results suggested that optimal taurine level could improve growth performance, hepatic capacity for glycolipid metabolism and insulin sensitivity, thus enhancing the utilisation of carbohydrates in grass carp. Based on SGR, dietary optimal tributyrin taurine supplementation in grass carp was estimated to be 0·08 %.


Asunto(s)
Carpas , Microbioma Gastrointestinal , Animales , Proteínas Proto-Oncogénicas c-akt , Receptor de Insulina , Carpas/metabolismo , Fosfatidilinositol 3-Quinasas , Proteínas de Peces/genética , Dieta/veterinaria , Suplementos Dietéticos/análisis , ARN Mensajero/metabolismo , Carbohidratos , Glucosa , Alimentación Animal/análisis , Inmunidad Innata
13.
Arch Virol ; 169(3): 42, 2024 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-38332318

RESUMEN

Beauveria bassiana Vuillemin is an entomopathogenic fungus that has been developed as a biological insecticide. B. bassiana can be infected by single or multiple mycoviruses, most of which are double-stranded RNA (dsRNA) viruses, while infections with single-stranded RNA (ssRNA) viruses, especially negative single-stranded RNA (-ssRNA) viruses, have been observed less frequently. In the present study, we sequenced and analyzed the complete genomes of two new different mycoviruses coinfecting a single B. bassiana strain: a -ssRNA virus which we have named "Beauveria bassiana negative-strand RNA virus 1" (BbNSRV1), and a dsRNA virus, which we have named "Beauveria bassiana orthocurvulavirus 1" (BbOCuV1). The genome of BbNSRV1 consists of a single segment of negative-sense, single-stranded RNA with a length of 6169 nt, containing a single open reading frame (ORF) encoding a putative RNA-dependent RNA polymerase (RdRp) with 1949 aa (220.1 kDa). BLASTx analysis showed that the RdRp had the highest sequence similarity (59.79%) to that of Plasmopara viticola lesion associated mononegaambi virus 2, a member of the family Mymonaviridae. This is the first report of a -ssRNA mycovirus infecting B. bassiana. The genome of BbOCuV1 consists of two dsRNA segments, 2164 bp and 1765 bp in length, respectively, with dsRNA1 encoding a protein with conserved RdRp motifs and 70.75% sequence identity to the putative RdRp of the taxonomically unassigned mycovirus Fusarium graminearum virus 5 (FgV5), and the dsRNA2 encoding a putative coat protein with sequence identity 64.26% to the corresponding protein of the FgV5. Phylogenetic analysis indicated that BbOCuV1 belongs to a taxonomically unassigned group of dsRNA mycoviruses related to members of the families Curvulaviridae and Partitiviridae. Hence, it might be the member of a new family that remains to be named and formally recognized.


Asunto(s)
Beauveria , Virus Fúngicos , Virus ARN , Virus , Humanos , Beauveria/genética , ARN Bicatenario/genética , Filogenia , Genoma Viral , Virus ARN/genética , Virus/genética , Virus ARN Bicatenario/genética , Virus Fúngicos/genética , ARN Polimerasa Dependiente del ARN/genética , ARN Viral/genética , Sistemas de Lectura Abierta
14.
Cryobiology ; 115: 104892, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38593909

RESUMEN

Refreezing the remaining genetic resources after in vitro fertilization (IVF) can conserve genetic materials. However, the precise damage inflicted by repeated freezing and thawing on bovine sperm and its underlying mechanism remain largely unexplored. Thus, this study investigates the impact of repeated freeze-thaw cycles on sperm. Our findings indicate that such cycles significantly reduce sperm viability and motility. Furthermore, the integrity of the sperm plasma membrane and acrosome is compromised during this process, exacerbating the advanced apoptosis triggered by oxidative stress. Additionally, transmission electron microscopy exposed severe damage to the plasma membranes of both the sperm head and tail. Notably, the "9 + 2" structure of the tail was disrupted, along with a significant decrease in the level of the axonemal protein DNAH10, leading to reduced sperm motility. IVF outcomes revealed that repeated freeze-thaw cycles considerably impair sperm fertilization capability, ultimately reducing the blastocyst rate. In summary, our research demonstrates that repeated freeze-thaw cycles lead to a decline in sperm viability and motility, attributed to oxidative stress-induced apoptosis and DNAH10-related dynamic deficiency. As a result, the utility of semen is compromised after repeated freezing.


Asunto(s)
Apoptosis , Criopreservación , Fertilización In Vitro , Congelación , Estrés Oxidativo , Preservación de Semen , Motilidad Espermática , Espermatozoides , Animales , Masculino , Bovinos , Criopreservación/veterinaria , Criopreservación/métodos , Preservación de Semen/veterinaria , Preservación de Semen/métodos , Espermatozoides/fisiología , Fertilización In Vitro/veterinaria , Congelación/efectos adversos , Membrana Celular , Supervivencia Celular , Acrosoma
15.
Bull Entomol Res ; 114(4): 482-490, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38708572

RESUMEN

Carboxylesterases (CarEs) is an important detoxification enzyme system in phase Ⅰ participating in insecticides resistance. In our previous study, SlCarE054, a CarEs gene from lepidoptera class, was screened out to be upregulated in a pyrethroids and organophosphates resistant population. Its overexpression was verified in two field-collected populations of Spodoptera litura (Lepidoptera: Noctuidae) resistant to pyrethroids and organophosphates by qRT-PCR. Spatiotemporal expression results showed that SlCarE054 was highly expressed in the pupae stage and the digestive tissue midgut. To further explore its role in pyrethroids and organophosphates resistance, its metabolism activity to insecticides was determined by UPLC. Its recombinant protein showed significant metabolism activity to cyhalothrin and fenvalerate, but not to phoxim or chlorpyrifos. The metabolic activity of SlCarE054 to ß-cypermethrin showed stereoselectivity, with higher metabolic activity to θ-cypermethrin than the enantiomer α-cypermethrin. The metabolite of ß-cypermethrin was identified as 3-phenoxybenzaldehyde. Further modelling and docking analysis indicated that ß-cypermethrin, cyhalothrin and fenvalerate could bind with the catalytic triad of the 3D structure of SlCarE054. The interaction of ß-cypermethrin with SlCarE054 also showed the lowest binding energy. Our work provides evidence that SlCarE054 play roles in ß-cypermethrin resistance in S. litura.


Asunto(s)
Insecticidas , Piretrinas , Spodoptera , Animales , Piretrinas/farmacología , Insecticidas/farmacología , Spodoptera/genética , Spodoptera/metabolismo , Spodoptera/efectos de los fármacos , Proteínas de Insectos/metabolismo , Proteínas de Insectos/genética , Resistencia a los Insecticidas/genética , Estereoisomerismo , Carboxilesterasa/metabolismo , Carboxilesterasa/genética
16.
Acta Biochim Biophys Sin (Shanghai) ; 56(7): 1034-1043, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38655618

RESUMEN

The linear ubiquitin chain assembly complex (LUBAC) is the only known E3 ligase complex in which the ubiquitin-like (UBL) domains of SHARPIN and HOIL-1L interact with HOIP to determine the structural stability of LUBAC. The interactions between subunits within LUBAC have been a topic of extensive research. However, the impact of the LTM motif on the interaction between the UBL domains of SHARPIN and HOIL-1L with HOIP remains unclear. Here, we discover that the absence of the LTM motif in the AlphaFold2-predicted LUBAC structure alters the HOIP-UBA structure. We employ GeoPPI to calculate the changes in binding free energy (ΔG) caused by single-point mutations between subunits, simulating their protein-protein interactions. The results reveal that the presence of the LTM motif decreases the interaction between the UBL domains of SHARPIN and HOIL-1L with HOIP, leading to a decrease in the structural stability of LUBAC. Furthermore, using the AlphaFold2-predicted results, we find that HOIP (629‒695) and HOIP-UBA bind to both sides of HOIL-1L-UBL, respectively. The experiments of Gromacs molecular dynamics simulations, SPR and ITC demonstrate that the elongated domain formed by HOIP (629‒695) and HOIP-UBA, hereafter referred to as the HOIP (466‒695) structure, interacts with HOIL-1L-UBL to form a structurally stable complex. These findings illustrate the collaborative interaction between HOIP-UBA and HOIP (629‒695) with HOIL-1L-UBL, which influences the structural stability of LUBAC.


Asunto(s)
Unión Proteica , Ubiquitina-Proteína Ligasas , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/química , Ubiquitina-Proteína Ligasas/genética , Humanos , Ubiquitina/metabolismo , Ubiquitina/química , Ubiquitina/genética , Simulación de Dinámica Molecular , Secuencias de Aminoácidos , Ubiquitinas
17.
Int J Mol Sci ; 25(19)2024 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-39409024

RESUMEN

Milk production is an essential economic trait in cattle, and understanding the genetic regulation of this trait can enhance breeding strategies. The discoidin domain receptor 1 (DDR1) gene has been identified as a key candidate gene that influences milk production, and ETS homologous factor (EHF) is recognized as a critical transcription factor that regulates DDR1 expression. Codon usage bias, which affects gene expression and protein function, has not been fully explored in cattle. This study aims to examine the codon usage bias of DDR1 and EHF transcription factors to understand their roles in dairy production traits. Data from 24 species revealed that both DDR1 and EHF predominantly used G/C-ending codons, with the GC3 content averaging 75.49% for DDR1 and 61.72% for EHF. Synonymous codon usage analysis identified high-frequency codons for both DDR1 and EHF, with 17 codons common to both genes. Correlation analysis indicated a negative relationship between the effective number of codons and codon adaptation index for both DDR1 and EHF. Phylogenetic and clustering analyses revealed similar codon usage patterns among closely related species. These findings suggest that EHF plays a crucial role in regulating DDR1 expression, offering new insights into genetically regulating milk production in cattle.


Asunto(s)
Uso de Codones , Receptor con Dominio Discoidina 1 , Filogenia , Animales , Bovinos , Codón/genética , Receptor con Dominio Discoidina 1/genética , Receptor con Dominio Discoidina 1/metabolismo , Regulación de la Expresión Génica , Factores de Transcripción/genética , Factores de Transcripción/metabolismo
18.
Molecules ; 29(3)2024 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-38338364

RESUMEN

To develop a cost-effective method for the effective removal of reactive brilliant blue KN-R (RBB KN-R) from wastewater, we investigated the interactions between RBB KN-R and three cationic surfactants with different alkyl chain lengths, namely dodecyltrimethylammonium bromide (DTAB), tetradecyltrimethylammonium bromide (TTAB), and cetyltrimethylammonium bromide (CTAB). Employing a conductivity analysis, surface tension analysis, ultraviolet-visible spectrophotometry, and molecular dynamics simulation, we ascertained that RBB KN-R formed a 1:1 molar ratio dye-surfactant complex with each surfactant through electrostatic attraction. Notably, an augmentation in alkyl chain length correlated with increased binding strength between RBB KN-R and the surfactant. The resulting dye-surfactant complex exhibited heightened surface activity, enabling interactions through hydrophobic forces to generate dye-surfactant aggregates when the molar ratio was below 1:1. Within these mixed aggregates, self-assembly of RBB KN-R molecules occurred, leading to the formation of dye aggregates. Due to the improved hydrophobicity with increased alkyl chain length, TTAB and CTAB could encapsulate dye aggregates within the mixed aggregates, but DTAB could not. The RBB KN-R aggregates tended to distribute on the surface of the RBB KN-R-DTAB mixed aggregates, resulting in low stability. Thus, at a DTAB concentration lower than CMC, insoluble particles readily formed and separated from surfactant aggregates at an RBB KN-R and DTAB molar ratio of 1:4. Analyzing the RBB KN-R precipitate through scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR) and measuring the DTAB concentration in the supernate revealed that, at this molar ratio, all RBB KN-R precipitated from the dye-surfactant mixed solution, with only 7.5 ± 0.5% of DTAB present in the precipitate. Furthermore, the removal ratio of RBB KN-R reached nearly 100% within a pH range of 1.0 to 9.0 and standing time of 6 h. The salt type and concentration did not significantly affect the precipitation process. Therefore, this simultaneous achievement of successful RBB KN-R removal and effective separation from DTAB underscores the efficacy of the proposed approach.

19.
Zhongguo Zhong Yao Za Zhi ; 49(16): 4477-4487, 2024 Aug.
Artículo en Zh | MEDLINE | ID: mdl-39307784

RESUMEN

Aurantii Fructus Immaturus(AFI) is a traditional Chinese herbal medicine with multiple origins from Citrus aurantium and its legally cultivated variants. With advancements in agricultural biotechnology, many new cultivated varieties have sprung up,leading to an abundance of AFI adulterants and chaos in the herbal medicine markets. This study developed a specific identification method for AFI and its closely related adulterants by examining the appearance trait, content of extract, and multiple ingredients,involving indicators such as the ratio of pulp capsule to cross section diameter(Pc/Cs ratio), the content of extract, and the profile of 11 ingredients. The research finds that:(1) Pc/Cs ratio can conveniently identify adulterants such as Poncirus trifoliata, Ju, and Babagan from the genuine AFI.(2) The extract content can be used to identify adulterants originated from C. wilsonii with C. aurantium.(3) The contents of synephrine in all the samples were in accordance with the Chinese Pharmacopoeia except for the adulterants from P. trifoliata, C. wilsonii, C. aurantium 'Changshanhuyou' and orah mandarins. The synephrine content was high as 1. 40% in some C. sinensis varieties. The mass fraction of hesperidin was over 10. 00% in C. sinensis, while it was below 2. 50% in C. aurantium. C. aurantium contained high levels of naringin(3. 96%-15. 21%) and neo-hesperidin(9. 38%-21. 93%).(4) The compositions of adulterants from P. trifoliata and C. wilsonii were more similar to that of C. aurantium 'Daidai', but with significantly lower neo-hesperidin content(0. 03%-0. 14%) than that in C. aurantium, and they lacked hesperetin and tangeretin. C. maxima(originating from C. maxima) showed closer composition to Choucheng and hybrid originated from Citrus aurantium × Poncirus trifoliata, but had higher hesperidin content(3. 13%) than that in C. aurantium. Ju was closely related to C. sinensis and neither contained naringin nor neo-hesperidin. Hesperidins in Babagan and orah mandarins were similar to that in C. sinensis, with none containing rhoifolin. These quality indicators in combination can accurately distinguish between C. sinensis, C. aurantium, and their closely related adulterants(P. trifoliata, C. wilsonii, C. maxima, orah mandarins and C. reticulata), which are expected to provide a systematic method for quality control of AFI.


Asunto(s)
Citrus , Contaminación de Medicamentos , Medicamentos Herbarios Chinos , Control de Calidad , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/análisis , Citrus/clasificación , Citrus/química , Cromatografía Líquida de Alta Presión , Hesperidina/análisis , Hesperidina/química , Hesperidina/análogos & derivados , China , Sinefrina/análisis
20.
Anal Chem ; 95(5): 3037-3044, 2023 02 07.
Artículo en Inglés | MEDLINE | ID: mdl-36693785

RESUMEN

Effective identification of multiple pathogenic bacteria in unknown samples is important for disease prevention and control but remains a challenge yet. A single-mode array-based sensing approach is simple and sensitive, but it usually relies on the use of multiple cross-reactive receptors to construct sensor arrays, which is cumbersome and insufficiently accurate. Here, we developed a sensor array with colorimetric and photothermal dual mode of differentiating multiple pathogenic bacteria. The sensor array was based on boronic acid-functionalized Au-Fe3O4 nanoparticles (BA-GMNPs), which not only possess localized surface plasmon resonance properties, showing a burgundy color similar to that of AuNPs, but also exhibit mild superparamagnetism, allowing for the differentiation of bacteria before and after binding to the nanoparticles. Immobilization of BA-GMNPs on the bacterial cell surface by covalent bonding would diminish NaCl-induced assembly of BA-GMNPs. Different BA-GMNPs@bacterial complexes differed in their ability to resist assembly and produced different colorimetric and photothermal response signals. A unique molecular fingerprint of each bacterium was obtained by linear discriminant analysis of the response patterns, demonstrating an effective differentiation among the six species studied. Compared with single-mode sensing arrays based on multiple receptors, this method only requires the preparation of a single nanomaterial, which produces two signal outputs for the identification of multiple bacteria with better differentiation. It can distinguish not only multiple pathogenic bacteria but also Gram-negative and Gram-positive bacteria, and, more importantly, it can perform preliminary discrimination of unknown samples.


Asunto(s)
Nanopartículas del Metal , Nanoestructuras , Colorimetría/métodos , Nanopartículas del Metal/química , Oro/química , Bacterias
SELECCIÓN DE REFERENCIAS
Detalles de la búsqueda