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1.
Mitochondrial DNA B Resour ; 9(6): 841-844, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38919809

RESUMEN

Cyprinus acutidorsalis (Wang, 1979) is an endemic fish in China that is sparsely distributed in the Hainan provinces and Guangxi Zhuang Autonomous Region (GZAR). In this study, the complete mitochondrial genome of C. acutidorsalis from the Hainan population from the Wanquan River was sequenced, and its phylogenetic relationship was analyzed. The circular mtDNA was 16,581 bp in length, and the overall base composition was A (32.0%), C (27.5%), T (24.8%), and G (15.70%), with a slight bias toward A + T. The complete mitogenome encoded 13 protein-coding genes (PCGs), 22 tRNA genes, two rRNA genes, and a control region. Phylogenetic analysis indicated that the most closely related fish to C. acutidorsalis from the Hainan population was C. acutidorsalis from the Guangxi population. These findings offer basic molecular data and a better understanding of the phylogenetic relationships among the Cyprinus species.

2.
FASEB J ; 38(13): e23745, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38923065

RESUMEN

Idiopathic granulomatous mastitis (IGM), a recurrent inflammation disease of the non-lactating breast, has had an increasing clinical morbidity rate in recent years, and its complicated symptoms and unclear etiology make it challenging to treat. This rare benign inflammatory breast disease, centered on the lobules, represents the most challenging type of non-puerperal mastitis (NPM), also known as non-lactating mastitis. In this study, patients diagnosed with IGM (M, n = 23) were recruited as cases, and patients with benign control breast disease (C, n = 17) were enrolled as controls. Cytokine microarray detection measured and analyzed the differentially expressed cytokine factors between IGM and control patients. Then, we verified the mRNA and protein expression levels of the significantly changed cytokine factors using Q-RT-PCR, ELISA, western blot, and IHC experiments. The cytokine factor expression levels significantly changed compared to the control group. We observed a significant increase between IGM and control patients in cytokine factors expression, such as interleukin-1ß (IL-1ß), monokine induced by gamma interferon (MIG), macrophage inflammatory protein (MIP)-1α, MIP-1ß, tumor necrosis factor receptor 2 (TNF RII). Then, we verified the expression of these top five dysregulated factors in both mRNA and protein levels. Our results demonstrated the cytokine map in IGM and indicated that several cytokines, especially chemokines, were associated with and significantly dysregulated in IGM tissues compared to the control group. The chemokine factors involved might be essential in developing and treating IGM. These findings would be helpful for a better understanding of IGM and offer valuable insights for devising novel diagnostic and therapeutic strategies.


Asunto(s)
Quimiocinas , Mastitis Granulomatosa , Humanos , Femenino , Mastitis Granulomatosa/metabolismo , Mastitis Granulomatosa/genética , Adulto , Quimiocinas/metabolismo , Quimiocinas/genética , Persona de Mediana Edad , Citocinas/metabolismo , Citocinas/genética , Interleucina-1beta/metabolismo , Interleucina-1beta/genética , Estudios de Casos y Controles , Quimiocina CXCL9/metabolismo , Quimiocina CXCL9/genética
3.
Wei Sheng Yan Jiu ; 53(3): 410-418, 2024 May.
Artículo en Chino | MEDLINE | ID: mdl-38839582

RESUMEN

OBJECTIVE: To explore the dairy consumption among children and adolescents aged 7-17 in China. METHODS: 10 rounds of follow-up data from the "China Health and Nutrition Survey" from 1991 to 2018 were collected, and individuals aged 7-17 were selected as the study subjects. Dietary data was collected by using 3-day 24-hour dietary review method and household weighing accounting method(edible oils and seasonings). Dairy consumption was calculated by converting various dairy products into liquid milk intake using the China Food Composition. After excluding those with missing demographic information, missing data from the "3 days and 24 hours" dietary survey, and abnormal daily energy intake, 18 529 participants were included in the final analysis. Joinpoint regression model was used to analyze the trend of changes in dairy intake. RESULTS: The dairy consumption rate increased from 2.8% in 1991 to 42.3% in 2018, while it increased from 8.4% to 58.8% in urban and from 0.9% to 32.1% in rural areas. Meanwhile, the proportion of people whose dairy intake reaches the recommended intake(300 g/d) increased from 0.2% to 3.0%, and the proportion in rural area was 2.0%, which was lower than that in urban areas(4.9%). From 1991 to 2018, dairy intake increased at a rate of 12.97%(P=0.02), and the growth rate of urban and rural areas were 9.79%(P=0.03) and 15.67%(P<0.01), respectively. There was a faster growth trend from 1991-2004 compared to 2004-2018. The growth rate in urban and rural areas also showed different growth trends. CONCLUSION: The dairy intake of children and adolescents aged 7-17 in China improved significantly from 1991 to 2018, with higher consumption rate in urban areas than in rural areas, but it still need to be improved for health.


Asunto(s)
Productos Lácteos , Dieta , Encuestas Nutricionales , Población Rural , Humanos , China , Adolescente , Niño , Femenino , Masculino , Dieta/tendencias , Dieta/estadística & datos numéricos , Población Rural/estadística & datos numéricos , Encuestas sobre Dietas , Población Urbana , Ingestión de Energía , Conducta Alimentaria
4.
Wei Sheng Yan Jiu ; 53(3): 419-434, 2024 May.
Artículo en Chino | MEDLINE | ID: mdl-38839583

RESUMEN

OBJECTIVE: To analyze the dietary patterns changes of young people aged 18-35 in 15 provinces(autonomous regions, municipalities) from 1989 to 2018. METHODS: Using the data of China Health and Nutrition Survey, a total of 25 400 young people aged 18-35 with complete dietary and sociodemographic information from 1989 to 2018 in 15 provinces(autonomous regions, municipalities) were selected as the research objects. Nutrition survey was carried out by using 3 consecutive days of 24-hour review method combined with weighing accounting method. Energy and nutrient intake was calculated based on food composition list. The principal component cluster analysis was used to select food groups and K-mean cluster was uesd to extract dietary patterns. Dwass-Steel-Critchlow-Fligner was used to test the difference of food intake in different dietary patterns. Cochran-Armitage trend test was to analyze the change of dietary patterns with the years. Chi-square test was to analyze the difference of people with different dietary patterns in 2018. RESULTS: The dietary patterns of young people aged 18-35 in 15 provinces(autonomous regions, municipalities) were mainly divided into three categories: "traditional rice", "traditional pasta" and "high-quality protein". In 2018, the proportion of "traditional rice" dietary patterns was higher for men than for women, and the proportion of "high-quality protein" dietary patterns was lower than for women. The proportion of "traditional pasta" dietary pattern in people aged 25-35 was higher than that aged 18-24, and the proportion of "high-quality protein" dietary pattern was lower than that aged 18-24. The proportion of people in urban with "traditional rice" dietary pattern was lower than that in rural areas, and the proportion of "high-quality protein" dietary pattern was higher than that in rural areas. The northern region was dominated by "traditional pasta" dietary pattern, while the southern region was dominated by "traditional rice" dietary pattern, and the proportion of people with "high-quality protein" dietary pattern was higher in the northern region than in the southern region. With the increase of education level and income level, the proportion of people with "high-quality protein" dietary pattern showed an increasing trend. From 1989 to 2018, the "traditional rice" dietary pattern had always maintained a high proportion among young people aged 18-35 in 15 provinces(autonomous regions, municipalities) in China, and the "traditional pasta" dietary pattern had been decreasing since 2009, and the "high-quality protein" dietary pattern had significantly increased since 2011. CONCLUSION: From 1989 to 2018, the proportion of young people aged 18-35 with reasonable dietary pattern has increased in 15 provinces(autonomous regions, municipalities), but the traditional dietary pattern still needs to be improved.


Asunto(s)
Dieta , Conducta Alimentaria , Encuestas Nutricionales , Humanos , China , Masculino , Adolescente , Femenino , Adulto Joven , Adulto , Dieta/estadística & datos numéricos , Dieta/tendencias , Ingestión de Energía , Patrones Dietéticos
5.
ACS Nano ; 18(23): 15249-15260, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38818704

RESUMEN

Bimetallic iron-noble metal alloy nanoparticles have emerged as promising contrast agents for magnetic resonance imaging (MRI) due to their biocompatibility and facile control over the element distribution. However, the inherent surface energy discrepancy between iron and noble metal often leads to Fe atom segregation within the nanoparticle, resulting in limited iron-water molecule interactions and, consequently, diminished relaxometric performance. In this study, we present the development of a class of ligand-induced atomically segregation-tunable alloy nanoprobes (STAN) composed of bimetallic iron-gold nanoparticles. By manipulating the oxidation state of Fe on the particle surface through varying molar ratios of oleic acid and oleylamine ligands, we successfully achieve surface Fe enrichment. Under the application of a 9 T MRI system, the optimized STAN formulation, characterized by a surface Fe content of 60.1 at %, exhibits an impressive r1 value of 2.28 mM-1·s-1, along with a low r2/r1 ratio of 6.2. This exceptional performance allows for the clear visualization of hepatic tumors as small as 0.7 mm in diameter in vivo, highlighting the immense potential of STAN as a next-generation contrast agent for highly sensitive MR imaging.


Asunto(s)
Aleaciones , Medios de Contraste , Oro , Imagen por Resonancia Magnética , Nanopartículas del Metal , Aleaciones/química , Ligandos , Oro/química , Animales , Medios de Contraste/química , Nanopartículas del Metal/química , Humanos , Ratones , Hierro/química , Propiedades de Superficie , Tamaño de la Partícula , Neoplasias Hepáticas/diagnóstico por imagen , Ácido Oléico/química
6.
Nano Lett ; 24(22): 6696-6705, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38796774

RESUMEN

Ultra-high-field (UHF) magnetic resonance imaging (MRI) stands as a pivotal cornerstone in biomedical imaging, yet the challenge of false imaging persists, constraining its full potential. Despite the development of dual-mode contrast agents improving conventional MRI, their effectiveness in UHF remains suboptimal due to the high magnetic moment, resulting in diminished T1 relaxivity and excessively enhanced T2 relaxivity. Herein, we report a DNA-mediated magnetic-dimer assembly (DMA) of iron oxide nanoparticles that harnesses UHF-tailored nanomagnetism for fault-free UHF-MRI. DMA exhibits a dually enhanced longitudinal relaxivity of 4.42 mM-1·s-1 and transverse relaxivity of 26.23 mM-1·s-1 at 9 T, demonstrating a typical T1-T2 dual-mode UHF-MRI contrast agent. Importantly, DMA leverages T1-T2 dual-modality image fusion to achieve artifact-free breast cancer visualization, effectively filtering interference from hundred-micrometer-level false-positive signals with unprecedented precision. The UHF-tailored T1-T2 dual-mode DMA contrast agents hold promise for elevating the accuracy of MR imaging in disease diagnosis.


Asunto(s)
Medios de Contraste , ADN , Imagen por Resonancia Magnética , Imagen por Resonancia Magnética/métodos , Medios de Contraste/química , Humanos , ADN/química , Ratones , Nanopartículas Magnéticas de Óxido de Hierro/química , Femenino , Animales , Neoplasias de la Mama/diagnóstico por imagen , Nanopartículas de Magnetita/química , Línea Celular Tumoral
7.
Sensors (Basel) ; 24(10)2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38794054

RESUMEN

Based on the decorrelation calculation of diffusion ultrasound in time-frequency domain, this paper discusses the repeatability and potential significance of Disturbance Sensitive Zone (DSZ) in time-frequency domain. The experimental study of Barely Visible Impact Damage (BVID) on Carbon Fiber Reinforced Polymer (CFRP) is carried out. The decorrelation coefficients of time, frequency, and time-frequency domains and DSZ are calculated and compared. It has been observed that the sensitivity of the scattered wave disturbance caused by impact damage is non-uniformly distributed in both the time and frequency domains. This is evident from the non-uniform distribution of the decorrelation coefficient in time-domain and frequency-domain decorrelation calculations. Further, the decorrelation calculation in the time-frequency domain can show the distribution of the sensitivity of the scattered wave disturbance in the time domain and frequency domain. The decorrelation coefficients in time, frequency, and time-frequency domains increase monotonically with the number of impacts. In addition, in the time-frequency domain decorrelation calculation results, stable and repetitive DSZ are observed, which means that the specific frequency component of the scattered wave is extremely sensitive to the damage evolution of the impact region at a specific time. Finally, the DSZ obtained from the first 15 impacts is used to improve the decorrelation calculation in the 16-th to 20-th impact. The results show that the increment rate of the improved decorrelation coefficient is 10.22%. This study reveals that the diffusion ultrasonic decorrelation calculation improved by DSZ makes it feasible to evaluate early-stage damage caused by BVID.

8.
PLoS One ; 19(5): e0302216, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38781198

RESUMEN

The real-time monitoring on the risk status of the vehicle and its driver can provide the assistance for the early detection and blocking control of single-vehicle accidents. However, complex risk coupling relationship is one of the main features of single-vehicle accidents with high mortality rate. On the basis of investigating the coupling effect among multi-risk factors and establishing a safety management database throughout the life cycle of vehicles, single-vehicle driving risk network (SVDRN) with a three-level threshold was developed, and its topology features were analyzed to assessment the importance of nodes. To avoid the one-sidedness of single indicator, the multi-attribute comprehensive evaluation model was applied to measure the comprehensive effect of characteristic indicators for nodes importance. A algorithm for real-time monitoring of vehicle driving risk status was proposed to identify key risk chains. The result revealed that improper operation, speeding, loss of vehicle control and inefficient driver management were the sequence of top four risk factors in the comprehensive evaluation result of nodes importance (mean value = 0.185, SD = 0.119). There were minor differences of 0.017 in the node importance among environmental factors, among which non-standard road alignment had the larger value. The improper operation and non-standard road alignment were the highest combination correlation of factors affecting road safety, with the support of 51.81% and the confidence of 69.35%. This identification algorithm of key risk chains that combines node importance and its risk state threshold can effectively determine the high-frequency risk transmission paths and risk factors through multi-vehicle test, providing a basis for centralization management of transport enterprises.


Asunto(s)
Accidentes de Tránsito , Algoritmos , Accidentes de Tránsito/prevención & control , Accidentes de Tránsito/estadística & datos numéricos , Factores de Riesgo , Humanos , Conducción de Automóvil , Medición de Riesgo/métodos
9.
Pathogens ; 13(5)2024 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-38787219

RESUMEN

With shared routes of transmission, HBV and HCV co-infection are estimated to occur more in subjects with HIV. This study aimed to characterize and describe the prevalence of HBV and HCV co-infections in a cohort of newly diagnosed HIV+ subjects living in China. We conducted a cross-sectional study among newly diagnosed HIV+ subjects aged 18-100 who participated in surveys on the national HIV molecular epidemiology in 2015 and 2023. (The epidemiological table survey is located in the national database alongside serologic testing). The chi-square test was used to identify changes in infections between the studying populations in 2015 and 2023, and conditional logistic regression models were fit to identify risk factors for each co-infection. Among the 11,024 newly diagnosed HIV+ subjects who were surveyed (n = 4501 in 2015; n = 6523 in 2023), the prevalence of HBV, HCV, and HBV/HCV in 2023 was lower than that in 2015, respectively. No decrease was observed in HCV co-infection in men who had sex with men (MSM) in North China, Northeast China, and East China. Increasing recognition among those at high risk of heterosexual transmission and those with low educational backgrounds is paramount to the prevention and control of HIV/HBV/HCV infections.

10.
Adv Mater ; : e2401538, 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38738793

RESUMEN

The identification of metastasis "seeds," isolated tumor cells (ITCs), is of paramount importance for the prognosis and tailored treatment of metastatic diseases. The conventional approach to clinical ITCs diagnosis through invasive biopsies is encumbered by the inherent risks of overdiagnosis and overtreatment. This underscores the pressing need for noninvasive ITCs detection methods that provide histopathological-level insights. Recent advancements in ultra-high-field (UHF) magnetic resonance imaging (MRI) have ignited hope for the revelation of minute lesions, including the elusive ITCs. Nevertheless, currently available MRI contrast agents are susceptible to magnetization-induced strong T2-decaying effects under UHF conditions, which compromises T1 MRI capability and further impedes the precise imaging of small lesions. Herein, this study reports a structural defect-enabled magnetic neutrality nanoprobe (MNN) distinguished by its paramagnetic properties featuring an exceptionally low magnetic susceptibility through atomic modulation, rendering it almost nonmagnetic. This unique characteristic effectively mitigates T2-decaying effect while concurrently enhancing UHF T1 contrast. Under 9 T MRI, the MNN demonstrates an unprecedentedly low r2/r1 value (≈1.06), enabling noninvasive visualization of ITCs with an exceptional detection threshold of ≈0.16 mm. These high-performance MNNs unveil the domain of hitherto undetectable minute lesions, representing a significant advancement in UHF-MRI for diagnostic purposes and fostering comprehensive metastasis research.

11.
Adv Sci (Weinh) ; : e2403116, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38816935

RESUMEN

To overcome current limitations in photoimmunotherapy, such as insufficient tumor antigen generation and a subdued immune response, a novel photo-/metallo dual-mode immunotherapeutic agent (PMIA) is introduced for potent near-infrared (NIR) light-triggered cancer therapy. PMIA features a dumbbell-like AuPt heterostructure decorated with starry Pt nanoclusters, meticulously engineered for enhancing plasmonic catalysis through multi-dimensional regulation of Pt growth on Au nanorods. Under NIR laser exposure, end-tipped Pt nanoclusters induce efficient electron-hole spatial separation along the longitudinal axis, resulting in radial and axial electron distribution polarization, conferring unique anisotropic properties to PMIA. Additionally, starry Pt nanoclusters on the sides of Au nanorods augment the local electron enrichment field. Validated through finite-difference time-domain analysis and Raman scattering, this configuration fosters local electron enrichment, facilitating robust reactive oxygen species generation for potent photoimmunotherapy. Moreover, Pt nanoclusters facilitate Pt2+ ion release, instigating intranuclear DNA damage and inducing synergistic immunogenic cell death (ICD) for metalloimmunotherapy. Consequently, PMIA elicits abundant danger-associated molecular patterns, promotes T cell infiltration, and triggers systemic immune responses, effectively treating primary and distant tumors, inhibiting metastasis in vivo. This study unveils a pioneering dual-mode ICD amplification strategy driven by NIR light, synergistically integrating photoimmunotherapy and metalloimmunotherapy, culminating in potent cancer photometalloimmunotherapy.

12.
STAR Protoc ; 5(2): 102958, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38568818

RESUMEN

Sepsis trains stressed granulocytes to boost nonspecific response and trigger a new wave of inflammation when facing secondary infection. Here, we present a protocol for a murine model of sepsis with secondary infection. We describe steps for cecal ligation and puncture operation and rechallenging with lipopolysaccharide or Pseudomonas aeruginosa during the recovery phase. We also detail steps to characterize the stressed granulocytes by assessing their functional phenotypes and effect on the mortality of rechallenged mice. For complete details on the use and execution of this protocol, please refer to Wang et al.1.


Asunto(s)
Modelos Animales de Enfermedad , Granulocitos , Sepsis , Animales , Ratones , Sepsis/microbiología , Pseudomonas aeruginosa , Lipopolisacáridos , Infecciones por Pseudomonas/inmunología , Infecciones por Pseudomonas/microbiología , Ratones Endogámicos C57BL , Masculino
13.
J Control Release ; 369: 517-530, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38569942

RESUMEN

Cancer cells rely on aerobic glycolysis and DNA repair signals to drive tumor growth and develop drug resistance. Yet, fine-tuning aerobic glycolysis with the assist of nanotechnology, for example, dampening lactate dehydrogenase (LDH) for cancer cell metabolic reprograming remains to be investigated. Here we focus on anaplastic thyroid cancer (ATC) as an extremely malignant cancer with the high expression of LDH, and develop a pH-responsive and nucleus-targeting platinum nanocluster (Pt@TAT/sPEG) to simultaneously targets LDH and exacerbates DNA damage. Pt@TAT/sPEG effectively disrupts LDH activity, reducing lactate production and ATP levels, and meanwhile induces ROS production, DNA damage, and apoptosis in ATC tumor cells. We found Pt@TAT/sPEG also blocks nucleotide excision repair pathway and achieves effective tumor cell killing. In an orthotopic ATC xenograft model, Pt@TAT/sPEG demonstrates superior tumor growth suppression compared to Pt@sPEG and cisplatin. This nanostrategy offers a feasible approach to simultaneously inhibit glycolysis and DNA repair for metabolic reprogramming and enhanced tumor chemotherapy.


Asunto(s)
Antineoplásicos , Reparación del ADN , Glucólisis , Ratones Desnudos , Platino (Metal) , Carcinoma Anaplásico de Tiroides , Neoplasias de la Tiroides , Humanos , Glucólisis/efectos de los fármacos , Animales , Carcinoma Anaplásico de Tiroides/tratamiento farmacológico , Carcinoma Anaplásico de Tiroides/patología , Carcinoma Anaplásico de Tiroides/metabolismo , Reparación del ADN/efectos de los fármacos , Línea Celular Tumoral , Neoplasias de la Tiroides/tratamiento farmacológico , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/metabolismo , Platino (Metal)/química , Platino (Metal)/farmacología , Antineoplásicos/farmacología , Antineoplásicos/administración & dosificación , Antineoplásicos/uso terapéutico , Núcleo Celular/metabolismo , Núcleo Celular/efectos de los fármacos , L-Lactato Deshidrogenasa/metabolismo , Ratones Endogámicos BALB C , Apoptosis/efectos de los fármacos , Daño del ADN/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo
15.
Acta Pharm Sin B ; 14(3): 1132-1149, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38486992

RESUMEN

Cancer, a complex and heterogeneous disease, arises from genomic instability. Currently, DNA damage-based cancer treatments, including radiotherapy and chemotherapy, are employed in clinical practice. However, the efficacy and safety of these therapies are constrained by various factors, limiting their ability to meet current clinical demands. Metal nanoparticles present promising avenues for enhancing each critical aspect of DNA damage-based cancer therapy. Their customizable physicochemical properties enable the development of targeted and personalized treatment platforms. In this review, we delve into the design principles and optimization strategies of metal nanoparticles. We shed light on the limitations of DNA damage-based therapy while highlighting the diverse strategies made possible by metal nanoparticles. These encompass targeted drug delivery, inhibition of DNA repair mechanisms, induction of cell death, and the cascading immune response. Moreover, we explore the pivotal role of physicochemical factors such as nanoparticle size, stimuli-responsiveness, and surface modification in shaping metal nanoparticle platforms. Finally, we present insights into the challenges and future directions of metal nanoparticles in advancing DNA damage-based cancer therapy, paving the way for novel treatment paradigms.

16.
Nat Commun ; 15(1): 2039, 2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38448420

RESUMEN

Reversible protein phosphorylation, regulated by protein phosphatases, fine-tunes target protein function and plays a vital role in biological processes. Dysregulation of this process leads to aberrant post-translational modifications (PTMs) and contributes to disease development. Despite the widespread use of artificial catalysts as enzyme mimetics, their direct modulation of proteins remains largely unexplored. To address this gap and enable the reversal of aberrant PTMs for disease therapy, we present the development of artificial protein modulators (APROMs). Through atomic-level engineering of heterogeneous catalysts with asymmetric catalytic centers, these modulators bear structural similarities to protein phosphatases and exhibit remarkable ability to destabilize the bridging µ3-hydroxide. This activation of catalytic centers enables spontaneous hydrolysis of phospho-substrates, providing precise control over PTMs. Notably, APROMs, with protein phosphatase-like characteristics, catalytically reprogram the biological function of α-synuclein by directly hydrolyzing hyperphosphorylated α-synuclein. Consequently, synaptic function is reinforced in Parkinson's disease. Our findings offer a promising avenue for reprogramming protein function through de novo PTMs strategy.


Asunto(s)
Ursidae , alfa-Sinucleína , Animales , alfa-Sinucleína/genética , Catálisis , Ingeniería , Hidrólisis , Fosfoproteínas Fosfatasas/genética
17.
Aging Dis ; 2024 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-38421826

RESUMEN

Diminished ovarian reserve (DOR) refers to a decrease in the number and/or quality of oocytes, leading to infertility, poor ovarian response and adverse pregnancy outcomes. Currently, the pathogenesis of DOR is largely unknown, and the efficacy of existing therapeutic methods is limited. Therefore, in-depth exploration of the mechanism underlying DOR is highly important for identifying molecular therapeutic targets for DOR. Our study showed that estrogen receptor beta (ERß) mRNA and protein expression was upregulated in granulosa cells (GCs) from patients with DOR and in the ovaries of DOR model mice. Mechanistically, elevated ERß promotes forkhead transcription factor family 3a (FOXO3a) expression, which contributes to autophagic activation in GCs. Activation of FOXO3a/autophagy signalling leads to decreased cell proliferation and increased cell apoptosis and ultimately leads to DOR. In a cyclophosphamide (Cy)-induced DOR mouse model, treatment with PHTPP, a selective ERß antagonist, rescued fertility by restoring normal sex hormone secretion, estrus cycle duration, follicle development, oocyte quality and litter size. Taken together, these findings reveal a pathological mechanism of DOR based on ERß overexpression and identify PHTPP as a potential therapeutic agent for DOR.

18.
J Insect Sci ; 24(1)2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-38297809

RESUMEN

Chemosensory proteins (CSPs) are highly efficient carry tools to bind and deliver hydrophobic compounds, which play an important role in the chemosensory process in insects. The diamondback moth, Plutella xylostella L. (Lepidoptera: Plutellidae), is a cosmopolitan pest that attacks cruciferous crops. However, the detailed physiological functions of CSPs in P. xylostella remain limited to date. Here, we identified a typical CSP, named PxylCSP18, in P. xylostella and investigated its expression patterns and binding properties of volatiles. PxylCSP18 was highly expressed in antennae and head (without antennae), and the expression level in the male antennae of P. xylostella was obviously higher than that in the female antennae. Moreover, PxylCSP18 has a relatively broad binding spectrum. Fluorescence competitive binding assays showed that PxylCSP18 had strong binding abilities with 14 plant volatiles (Ki < 10 µM) that were repellent or attractive to P. xylostella. Notably, PxylCSP18 had no significant binding affinity to (Z)-11-hexadecenal, (Z)-11-hexadecenyl acetate, and (Z)-11-hexadecenyl alcolol, which are the pheromone components of P. xylostella. The attractive effects of trans-2-hexen-1-ol and isopropyl isothiocyanate to male adults and the attractive effects of isopropyl isothiocyanate and the repellent effects of linalool to female adults were significantly decreased after knocked down the expression of PxylCSP18. Our results revealed that PxylCSP18 might play an important role in host plant detection, avoidance of unsuitable hosts, and selection of oviposition sites; however, it does not participate in mating behavior. Overall, these results extended our knowledge on the CSP-related functions, which provided insightful information about CSP-targeted insecticides.


Asunto(s)
Insecticidas , Lepidópteros , Mariposas Nocturnas , Femenino , Animales , Mariposas Nocturnas/fisiología , Isotiocianatos/farmacología , Insecticidas/farmacología , Productos Agrícolas
20.
Antimicrob Agents Chemother ; 68(2): e0093723, 2024 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-38169282

RESUMEN

Entering a dormant state is a prevailing mechanism used by bacterial cells to transiently evade antibiotic attacks and become persisters. The dynamic progression of bacterial dormancy depths driven by protein aggregation has been found to be critical for antibiotic persistence in recent years. However, our current understanding of the endogenous genes that affects dormancy depth remains limited. Here, we discovered a novel role of phage shock protein A (pspA) gene in modulating bacterial dormancy depth. Deletion of pspA of Escherichia coli resulted in increased bacterial dormancy depths and prolonged lag times for resuscitation during the stationary phase. ∆pspA exhibited a higher persister ratio compared to the wild type when challenged with various antibiotics. Microscopic images revealed that ∆pspA showed accelerated formation of protein aggresomes, which were collections of endogenous protein aggregates. Time-lapse imaging established the positive correlation between protein aggregation and antibiotic persistence of ∆pspA at the single-cell level. To investigate the molecular mechanism underlying accelerated protein aggregation, we performed transcriptome profiling and found the increased abundance of chaperons and a general metabolic slowdown in the absence of pspA. Consistent with the transcriptomic results, the ∆pspA strain showed a decreased cellular ATP level, which could be rescued by glucose supplementation. Then, we verified that replenishment of cellular ATP levels by adding glucose could inhibit protein aggregation and reduce persister formation in ∆pspA. This study highlights the novel role of pspA in maintaining proteostasis, regulating dormancy depth, and affecting antibiotic persistence during stationary phase.


Asunto(s)
Antibacterianos , Agregado de Proteínas , Antibacterianos/farmacología , Escherichia coli/genética , Adenosina Trifosfato/metabolismo , Glucosa/metabolismo
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