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1.
Langmuir ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38719232

RESUMO

The practical utilization of the hydrogen evolution reaction (HER) necessitates the creation of electrocatalysts that are both efficient and abundant in earth elements, capable of operating effectively within a wide pH range. However, this objective continues to present itself as an arduous obstacle. In this research, we propose the incorporation of sulfur vacancies in a novel heterojunction formed by MoS2@CoS2, designed to exhibit remarkable catalytic performances. This efficacy is attributed to the advantageous combination of the low work function and space charge zone at the interface between MoS2 and CoS2 in the heterojunction. The MoS2@CoS2 heterojunction manifests outstanding hydrogen evolution activity over an extensive pH range. Remarkably, achieving a current density of 10 mA cm-2 in aqueous solutions 1.0 M KOH, 0.5 M H2SO4, and 1.0 M phosphate-buffered saline (PBS), respectively, requires only an overpotential of 48, 62, and 164 mV. The Tafel slopes for each case are 43, 32, and 62 mV dec-1, respectively. In this study, the synergistic effect of MoS2 and CoS2 is conducive to electron transfer, making the MoS2@CoS2 heterojunction show excellent electrocatalytic performance. The synergistic effects arising from the heterojunction and sulfur vacancy not only contribute to the observed catalytic prowess but also provide a valuable model and reference for the exploration of other efficient electrocatalysts. This research marks a significant stride toward overcoming the challenges associated with developing electrocatalysts for practical hydrogen evolution applications.

2.
Int J Gen Med ; 17: 1451-1466, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38645401

RESUMO

Purpose: B-cell lymphoma 9 (BCL9), a key transcription co-activator of the Wnt pathway, contributed to tumor progression and metastasis in various tumors, whereas, the role of BCL9 in papillary thyroid cancer (PTC) has not been investigated. Methods: We acquired PTC gene expression data from The Cancer Genome Atlas (TCGA) database. Fifty-nine PTC tissues were applied to validate the clinical significance of BCL9. Cell experiments were applied to investigate the role of BCL9. Bioinformatics analysis was employed to investigate the biological functions of BCL9. Results: We found that BCL9 was higher expressed (P < 0.05) and an independent risk factor for lymph node metastasis (OR = 3.770, P = 0.025), as well as associated with poorer progression-free survival (PFS) (P = 0.049) in PTC. BCL9 knockdown inhibited proliferation and invasion of PTC cells. BCL9 was positively associated with the key genes of Wnt/ß-catenin and MAPK pathway by co-expression analysis. GO, KEGG and GSEA analysis showed BCL9 might participated in PPAR, cAMP, and focal adhesion pathway. CIBERSORT analysis found BCL9 was negatively associated with CD8+ T cells and NK cell infiltration and positively with PD-L1 expression. Conclusion: Therefore, BCL9 was associated with lymph node metastasis and shorter PFS of PTC, due to promotion of PTC cell proliferation and invasion, activation of Wnt/ß-catenin and MAPK pathway, inhibition of CD8+ T and NK cell infiltration, and promotion of PD-L1 expression.

3.
Sci Rep ; 14(1): 7703, 2024 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-38565937

RESUMO

Bioactive molecules in tick saliva are considered to be key to successful feeding and further the transmission of tick-borne pathogens. Problems such as pathogen transmission and animal weight loss result in tick infestation can cause tremendous economic losses to the livestock industry. Therefore, the development of a universal tick vaccine is urgently needed. In this paper, three serine protease inhibitor (serpin) proteins RMS-3, L7LRK7 and L7LTU1 were analyzed with bioinformatics methods. Subsequently the proteins were expressed and purified, and inoculated into Kunming mice for immune protection analysis. The amino acid sequence similarities between RMS-3, L7LRK7 and L7LTU1 were up to 90% in Rhipicephalus sanguineus. The recombinant RMS-3 + L7LRK7 + L7LTU1 showed anticoagulant reaction function and could inhibit the activity of CD4+ lymphocytes, when inoculated into Kunming mice. Additionally, After the immunized mice were challenged with Rhipicephalus sanguineus, the percentage of larvae and nymphs that were fully engorged dropped to 40.87% (P < 0.05) and 87.68% (P > 0.05) in the RmS-3 + L7LRK7 immune group, 49.57% (P < 0.01) and 52.06% (P < 0.05) in the RmS-3 + L7LTU1 group, and 45.22% (P < 0.05) and 60.28% (P < 0.05) in the RmS-3 + L7LRK7 + L7LTU1 immune group, in comparison with the control group. These data indicate that RmS-3 + L7LRK7 + L7LTU1 has good immune protection and has the potential to be developed into a vaccine against the larvae and nymphs of R. sanguineus.


Assuntos
Animais não Endogâmicos , Rhipicephalus sanguineus , Rhipicephalus , Vacinas , Camundongos , Animais , Inibidores de Serina Proteinase/metabolismo , Rhipicephalus/metabolismo , Ninfa , Larva
4.
iScience ; 27(4): 109050, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38571763

RESUMO

The African swine fever virus (ASFV) and its variants have induced substantial economic losses in China, prompting a critical need for efficient detection methods. Several PCR-based methods have been developed to discriminate between wild-type ASFV and gene-deleted variants. However, the requirement for sophisticated equipment and skilled operators limits their use in field settings. Here, we developed a CRISPR-Cas12b/Cas13a-based detection assay that can identify ASFV variants with minimal equipment requirements and a short turnaround time. The assay utilizes the distinct DNA/RNA collateral cleavage preferences of Cas12b/Cas13a to detect two amplified targets from multiplex recombinase polymerase amplification (RPA) in a single tube, and the results can be visualized through fluorescent or lateral-flow readouts. When tested with clinical samples in field settings, our assay successfully detected all ASFV-positive samples in less than 60 min. This assay provides a rapid on-site surveillance tool for detecting ASFV and its emerging variants.

5.
Microorganisms ; 12(4)2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38674758

RESUMO

The past decades have witnessed intensive research on the biological effects of graphene-based nanomaterials (GBNs) and the application of GBNs in different fields. The published literature shows that GBNs exhibit inhibitory effects on almost all microorganisms under pure culture conditions, and that this inhibitory effect is influenced by the microbial species, the GBN's physicochemical properties, the GBN's concentration, treatment time, and experimental surroundings. In addition, microorganisms exist in the soil in the form of microbial communities. Considering the complex interactions between different soil components, different microbial communities, and GBNs in the soil environment, the effects of GBNs on soil microbial communities are undoubtedly intertwined. Since bacteria and fungi are major players in terrestrial biogeochemistry, this review focuses on the antibacterial and antifungal performance of GBNs, their antimicrobial mechanisms and influencing factors, as well as the impact of this effect on soil microbial communities. This review will provide a better understanding of the effects of GBNs on microorganisms at both the individual and population scales, thus providing an ecologically safe reference for the release of GBNs to different soil environments.

6.
Viruses ; 16(4)2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38675989

RESUMO

BACKGROUND: After the adjustment of COVID-19 epidemic policy, mainland China experienced two consecutive waves of Omicron variants within a seven-month period. In Guangzhou city, as one of the most populous regions, the viral infection characteristics, molecular epidemiology, and the dynamic of population immunity are still elusive. METHODS: We launched a prospective cohort study in the Guangdong Provincial CDC from December 2022 to July 2023. Fifty participants who received the same vaccination regimen and had no previous infection were recruited. RESULTS: 90% of individuals were infected with Omicron BA.5* variants within three weeks in the first wave. Thirteen cases (28.26%) experienced infection with XBB.1* variants, occurring from 14 weeks to 21 weeks after the first wave. BA.5* infections exhibited higher viral loads in nasopharyngeal sites compared to oropharyngeal sites. Compared to BA.5* infections, the XBB.1* infections had significantly milder clinical symptoms, lower viral loads, and shorter durations of virus positivity. The infection with the BA.5* variant elicited varying levels of neutralizing antibodies against XBB.1* among different individuals, even with similar levels of BA.5* antibodies. The level of neutralizing antibodies specific to XBB.1* determined the risk of reinfection. CONCLUSIONS: The rapid large-scale infections of the Omicron variants have quickly established herd immunity among the population in mainland China. In the future of the COVID-19 epidemic, a lower infection rate but a longer duration can be expected. Given the large population size and ongoing diversified herd immunity, it remains crucial to closely monitor the molecular epidemiology of SARS-CoV-2 for the emergence of new variants of concern in this region. Additionally, the timely evaluation of the immune status across different age groups is essential for informing future vaccination strategies and intervention policies.


Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19 , SARS-CoV-2 , Carga Viral , Humanos , COVID-19/epidemiologia , COVID-19/virologia , COVID-19/imunologia , China/epidemiologia , SARS-CoV-2/genética , SARS-CoV-2/imunologia , SARS-CoV-2/classificação , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Estudos Prospectivos , Anticorpos Antivirais/sangue , Estudos de Coortes , Adulto Jovem , Idoso
7.
Artigo em Inglês | MEDLINE | ID: mdl-38602968

RESUMO

A high-performance planar structure metal-semiconductor-metal-type solar-blind photodetector (SBPD) was fabricated on the basis of (010)-plane ß-Ga2O3 thermally oxidized from nonpolar (110)-plane GaN. A full width at half maximum of 0.486° was achieved for the X-ray rocking curve associated with (020)-plane ß-Ga2O3, which is better than most reported results for the heteroepitaxially grown (-201)-plane ß-Ga2O3. As a result of the relatively high crystalline quality, a dark current as low as 6.30 × 10-12 A was achieved at 5 V, while the photocurrent reached 1.86 × 10-5 A under 254 nm illumination at 600 µW/cm2. As a result, the photo-to-dark current ratio, specific detectivity, responsivity, and external quantum efficiency were calculated to be 2.95 × 106, 2.39 × 1012 Jones, 3.72 A/W, and 1815%, respectively. Moreover, the SBPD showed excellent repeatability and stability in the time-dependent photoresponse characteristics with fast relaxation time constants for the rise and decay processes of only 0.238 and 0.062 s, respectively. This study provides a promising approach to fabricate the device-level (010)-plane ß-Ga2O3 film and a new way for the epitaxial growth of (010)-plane ß-Ga2O3 and (110)-plane GaN as mutual substrates.

8.
Zool Res ; 45(2): 284-291, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38485498

RESUMO

Hereditary hearing loss (HHL), a genetic disorder that impairs auditory function, significantly affects quality of life and incurs substantial economic losses for society. To investigate the underlying causes of HHL and evaluate therapeutic outcomes, appropriate animal models are necessary. Pigs have been extensively used as valuable large animal models in biomedical research. In this review, we highlight the advantages of pig models in terms of ear anatomy, inner ear morphology, and electrophysiological characteristics, as well as recent advancements in the development of distinct genetically modified porcine models of hearing loss. Additionally, we discuss the prospects, challenges, and recommendations regarding the use pig models in HHL research. Overall, this review provides insights and perspectives for future studies on HHL using porcine models.


Assuntos
Orelha Interna , Perda Auditiva Neurossensorial , Perda Auditiva , Doenças dos Suínos , Animais , Suínos/genética , Qualidade de Vida , Perda Auditiva Neurossensorial/genética , Perda Auditiva Neurossensorial/veterinária , Perda Auditiva/genética , Perda Auditiva/terapia , Perda Auditiva/veterinária , Modelos Animais
9.
Quant Imaging Med Surg ; 14(3): 2225-2239, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38545061

RESUMO

Background: An accurate assessment of isocitrate dehydrogenase (IDH) status in patients with glioma is crucial for treatment planning and is a key factor in predicting patient outcomes. In this study, we investigated the potential value of whole-tumor histogram metrics derived from synthetic magnetic resonance imaging (MRI) in distinguishing IDH mutation status between astrocytoma and glioblastoma. Methods: In this prospective study, 80 glioma patients were enrolled from September 2019 to June 2022. All patients underwent pre- and post-contrast synthetic MRI scan protocol. Immunohistochemistry (IHC) staining or gene sequencing were used to assess IDH mutation status in tumor tissue samples. Whole-tumor histogram metrics, including T1, T2, proton density (PD), etc., were extracted from the quantitative maps, while radiological features were assessed by synthetic contrast-weighted maps. Basic clinical features of the patients were also evaluated. Differences in clinical, radiological, and histogram metrics between IDH-mutant astrocytoma and IDH-wildtype glioblastoma were analyzed using univariate analyses. Variables with statistical significance in univariate analysis were included in multivariate logistic regression analysis to develop the combined model. Receiver operating characteristic (ROC) and area under the curve (AUC) were used to assess the diagnostic performance of metrics and models. Results: The histopathologic analysis revealed that of the 80 cases, 41 were classified as IDH-mutant astrocytoma and 39 as IDH-wildtype glioblastoma. Compared to IDH-wildtype glioblastoma, IDH-mutant astrocytoma showed significantly lower T1 [10th percentile (10th), mean, and median] and post-contrast PD (10th, 90th percentile, mean, median, and maximum) values as well as higher post-contrast T1 (cT1) (10th, mean, median, and minimum) values (all P<0.05). The combined model (T1-10th + cT1-10th + age) was developed by integrating the independent influencing factors of IDH-mutant astrocytoma using the multivariate logistic regression. The diagnostic performance of this model [AUC =0.872 (0.778-0.936), sensitivity =75.61%, and specificity =89.74%] was superior to the clinicoradiological model, which was constructed using age and enhancement degree (AUC =0.822 (0.870-0.898), P=0.035). Conclusions: The combined model constructed using histogram metrics derived from synthetic MRI could be a valuable preoperative tool to distinguish IDH mutation status between astrocytoma and glioblastoma, and subsequently, could assist in the decision-making process of pretreatment.

10.
Am J Cancer Res ; 14(2): 526-544, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38455411

RESUMO

Cancer-associated fibroblasts (CAFs) are prevalent in the tumor microenvironment of breast cancer, comprising a group of cell subpopulations with spatial, phenotypic, and functional heterogeneity. Due to the lack of specific markers for CAF subpopulations, their specific mechanisms in breast cancer remain unclear. We identified eight distinct CAF phenotypes in breast cancer using multiple single-cell RNA sequencing datasets and determined distinct transcription factors (TFs) of CAFs through SCENIC analysis. Our study highlights one CAF subtype in breast cancer, FN1+CAF2, associated with metastasis and macrophage polarization. We observed elevated FN1 expression in the stromal tissue of breast cancer patients. Furthermore, FN1 knockdown in CAFs reduced the migration ability of breast cancer cells. We identified a regulatory gene, MXRA5, in CAF2, which may play crucial roles in breast cancer. Our results indicated upregulated MXRA5 expression in breast cancer tissues and CAFs from patients with lymph node metastasis in the following experiment. Overall, our study reveals that the FN1+CAF2 subtype is associated with metastasis and suggests that MXRA5 may be a novel marker mediating the effects of CAF2 on breast cancer metastasis. This study enriches our understanding of CAF heterogeneity and offers new insights for treating breast cancer metastasis.

11.
PLoS One ; 19(3): e0297892, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38451974

RESUMO

Graphene has promising applications in agriculture and forestry. In the current study, six different concentrations of graphene (0mg/L, 0.01mg/L, 0.10mg/L, 1.00mg/L, 10.00mg/L, and 100.00mg/L) were used to investigate its effect on the growth and development of V. angularis plants in soil culture. The results showed that the group treated with 1.00mg/L graphene (G-1) had significantly increased plant height (19.86%), stem diameter (24.33%), and leaf area (13.69%), compared to the control group (CK). Moreover, all concentrations of graphene had positive effects on the total root length, total root surface area, and the number of root tips of V. angularis. Compared to the CK group, the G-1 group had significantly increased leaf water potential (37.89%), leaf conductivity (2.25%), and SOD, POD, and CAT activities (47.67%, 35.22%, and 199.3%, respectively). The G-1 group also showed improved leaf net photosynthetic rate, chlorophyll content, and soluble sugar content (51.28%, 24.25%, and 38.35%, respectively), compared to the CK group. Additionally, 1.00mg/L graphene led to a 23.88% increase in the podding rate and a 17.04% increase in the yield of V. angularis plants. The rhizosphere soil of V. angularis treated with 1.00mg/L graphene had a 25.14% increase in hydrolyzable nitrogen content and a 66.67% increase in available phosphorus content. RNA-seq data indicated that 1.00mg/L graphene induced the expression of photosynthesis and nitrogen transmembrane transport genes, including ATP synthase subunit b, photosystem I reaction center subunit XI, photosystem I reaction center subunit IV A, ferredoxin, and psbP-like protein 1, as well as genes for photosynthesis antenna proteins, glutamine synthetase, glutamate dehydrogenase 1, cyanate hydratase, protein fluG-like, and NRT1/PTR family, suggesting that graphene promoted the growth and development of V. angularis by enhancing the photosynthesis and nitrogen metabolism processes in V. angularis plants. Our results indicated that a suitable concentration of graphene could significantly promote the growth of V. angularis plants in soil.


Assuntos
Grafite , Vigna , Vigna/metabolismo , Grafite/farmacologia , Grafite/metabolismo , Fotossíntese/fisiologia , Folhas de Planta/metabolismo , Nitrogênio/metabolismo , Solo
12.
Zool Res ; 45(2): 242-252, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38287905

RESUMO

PTEN-induced putative kinase 1 (PINK1), a mitochondrial kinase that phosphorylates Parkin and other proteins, plays a crucial role in mitophagy and protection against neurodegeneration. Mutations in PINK1 and Parkin can lead to loss of function and early onset Parkinson's disease. However, there is a lack of strong in vivo evidence in rodent models to support the theory that loss of PINK1 affects mitophagy and induces neurodegeneration. Additionally, PINK1 knockout pigs ( Sus scrofa) do not appear to exhibit neurodegeneration. In our recent work involving non-human primates, we found that PINK1 is selectively expressed in primate brains, while absent in rodent brains. To extend this to other species, we used multiple antibodies to examine the expression of PINK1 in pig tissues. In contrast to tissues from cynomolgus monkeys ( Macaca fascicularis), our data did not convincingly demonstrate detectable PINK1 expression in pig tissues. Knockdown of PINK1 in cultured pig cells did not result in altered Parkin and BAD phosphorylation, as observed in cultured monkey cells. A comparison of monkey and pig striatum revealed more PINK1-phosphorylated substrates in the monkey brain. Consistently, PINK1 knockout in pigs did not lead to obvious changes in the phosphorylation of Parkin and BAD. These findings provide new evidence that PINK1 expression is specific to primates, underscoring the importance of non-human primates in investigating PINK1 function and pathology related to PINK1 deficiency.


Assuntos
Primatas , Proteínas Quinases , Animais , Fosforilação , Proteínas Quinases/genética , Proteínas Quinases/metabolismo , Primatas/genética , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Haplorrinos
13.
Children (Basel) ; 11(1)2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38255416

RESUMO

Low human papillomavirus (HPV) vaccine uptake is a key barrier to cervical cancer elimination. We aimed to evaluate the health impact and cost-effectiveness of introducing different HPV vaccines into immunization programs and scaling up the screening program in Guangdong. We used a dynamic compartmental model to estimate the impact of intervention strategies during 2023-2100. We implemented the incremental cost-effectiveness ratio (ICER) in costs per averted disability-adjusted life year (DALY) as an indicator to assess the effectiveness of the intervention. We used an age-standardized incidence of 4 cases per 100,000 women as the threshold for the elimination of cervical cancer. Compared with the status quo, scaling up cervical cancer screening coverage alone would prevent 215,000 (95% CI: 205,000 to 227,000) cervical cancer cases and 49,000 (95% CI: 48,000 to 52,000) deaths during 2023-2100. If the coverage of vaccination reached 90%, domestic two-dose 2vHPV vaccination would be more cost-effective than single-dose and two-dose 9vHPV vaccination. If Guangdong introduced domestic two-dose 2vHPV vaccination at 90% coverage for schoolgirls from 2023 and increased the screening coverage, cervical cancer would be eliminated by 2049 (95% CI 2047 to 2051). Introducing two doses of domestic 2vHPV vaccination for schoolgirls and expanding cervical cancer screening is estimated to be highly cost-effective to accelerate the elimination of cervical cancer in Guangdong.

15.
Plant Commun ; 5(3): 100742, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-37919898

RESUMO

We investigated the effects of graphene on the model herb Artemisia annua, which is renowned for producing artemisinin, a widely used pharmacological compound. Seedling growth and biomass were promoted when A. annua was cultivated with low concentrations of graphene, an effect which was attributed to a 1.4-fold increase in nitrogen uptake, a 15%-22% increase in chlorophyll fluorescence, and greater abundance of carbon cycling-related bacteria. Exposure to 10 or 20 mg/L graphene resulted in a âˆ¼60% increase in H2O2, and graphene could act as a catalyst accelerator, leading to a 9-fold increase in catalase (CAT) activity in vitro and thereby maintaining reactive oxygen species (ROS) homeostasis. Importantly, graphene exposure led to an 80% increase in the density of glandular secreting trichomes (GSTs), in which artemisinin is biosynthesized and stored. This contributed to a 5% increase in artemisinin content in mature leaves. Interestingly, expression of miR828 was reduced by both graphene and H2O2 treatments, resulting in induction of its target gene AaMYB17, a positive regulator of GST initiation. Subsequent molecular and genetic assays showed that graphene-induced H2O2 inhibits micro-RNA (miRNA) biogenesis through Dicers and regulates the miR828-AaMYB17 module, thus affecting GST density. Our results suggest that graphene may contribute to yield improvement in A. annua via dynamic physiological processes together with miRNA regulation, and it may thus represent a new cultivation strategy for increasing yield capacity through nanobiotechnology.


Assuntos
Artemisia annua , Artemisininas , Grafite , MicroRNAs , Fenômenos Fisiológicos , Plantas Medicinais , Artemisia annua/genética , Artemisia annua/metabolismo , Grafite/metabolismo , Grafite/farmacologia , Peróxido de Hidrogênio/metabolismo , Plantas Medicinais/genética , Artemisininas/metabolismo , Artemisininas/farmacologia
16.
J Virol Methods ; 324: 114874, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38154579

RESUMO

BACKGROUND: Varicella zoster virus (VZV) is the pathogen of varicella and herpes zoster, it is necessary to develop a rapid, sensitive and specific detection method for the prevention and control of related diseases. METHODS: We inserted the gB protein extracellular region gene (gB-ex, 1-2208 bp) of VZV into lentivirus vector, and then obtained the recombinant gB protein through mammalian expression system. BALB/c mice were immunized multiple times with purified gB protein as immunogen. Then four strains of high affinity monoclonal antibodies targeting gB protein were prepared by cell fusion technique. Monoclonal antibodies 5G4 and HRP-4E9 were selected as capture and detection antibodies respectively, and a double-antibody sandwich ELISA method was established for detection. RESULTS: The detection limit of the DAS-ELISA was 156 PFU/mL, and there was no cross-reaction with Herpes simplex virus-1/Herpes simplex virus-2/Pseudorabies virus. The coefficients of variation of intra-assay and inter-assay repeatability were less than 5%. CONCLUSIONS: In this study, a double-antibody sandwich enzyme-linked immunosorbent assay (DAS-ELISA) was established for the detection of VZV. The assay has good sensitivity, specificity and repeatability, which provides strong technical support and product guarantee for the rapid clinical detection of VZV.


Assuntos
Herpes Zoster , Herpesvirus Humano 3 , Animais , Camundongos , Anticorpos Antivirais , Ensaio de Imunoadsorção Enzimática/métodos , Anticorpos Monoclonais , Simplexvirus , Proteínas Recombinantes , Mamíferos
17.
Cell Mol Life Sci ; 81(1): 1, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38038747

RESUMO

Multiple morphological abnormalities of the flagella (MMAF) is a severe disease of male infertility, while the pathogenetic mechanisms of MMAF are still incompletely understood. Previously, we found that the deficiency of Ccdc38 might be associated with MMAF. To understand the underlying mechanism of this disease, we identified the potential partner of this protein and found that the coiled-coil domain containing 146 (CCDC146) can interact with CCDC38. It is predominantly expressed in the testes, and the knockout of this gene resulted in complete infertility in male mice but not in females. The knockout of Ccdc146 impaired spermiogenesis, mainly due to flagellum and manchette organization defects, finally led to MMAF-like phenotype. Furthermore, we demonstrated that CCDC146 could interact with both CCDC38 and CCDC42. It also interacts with intraflagellar transport (IFT) complexes IFT88 and IFT20. The knockout of this gene led to the decrease of ODF2, IFT88, and IFT20 protein levels, but did not affect CCDC38, CCDC42, or ODF1 expression. Additionally, we predicted and validated the detailed interactions between CCDC146 and CCDC38 or CCDC42, and built the interaction models at the atomic level. Our results suggest that the testis predominantly expressed gene Ccdc146 is essential for sperm flagellum biogenesis and male fertility, and its mutations might be associated with MMAF in some patients.


Assuntos
Infertilidade Masculina , Proteínas Associadas aos Microtúbulos , Cauda do Espermatozoide , Animais , Masculino , Camundongos , Fertilidade/genética , Proteínas de Choque Térmico/metabolismo , Infertilidade Masculina/metabolismo , Camundongos Knockout , Sêmen , Cauda do Espermatozoide/metabolismo , Cauda do Espermatozoide/patologia , Espermatozoides/metabolismo , Testículo/metabolismo , Proteínas Associadas aos Microtúbulos/genética
18.
Curr Treat Options Oncol ; 24(12): 1935-1947, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38153687

RESUMO

OPINION STATEMENT: With the development of molecular biology and histology techniques, targeted therapy for non-small cell lung cancer (NSCLC) has emerged, which is highly effective and has marginal side effects. Epidermal growth factor receptor (EGFR) was the first driver gene discovered, whose three generations of therapeutic use have its characteristics and benefits in clinical practice. However, cardiovascular complications by EGFR-tyrosine kinase inhibitors (EGFR-TKIs) in preclinical studies have been increasingly reported, including heart failure, cardiomyopathy, and QT prolongation, among others. Cardiotoxicity of targeted drugs significantly affects the therapeutic effect of NSCLC and has become the second leading cause of death in NSCLC. The aim of the present review was to recognize the potential cardiotoxicity of third-generation targeted drugs in the treatment of NSCLC and their associated mechanisms to help clinicians identify and prevent it early in the treatment, minimize the cardiotoxicity of targeted drugs, and improve the therapeutic effect of patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Cardiotoxicidade/etiologia , Cardiotoxicidade/prevenção & controle , Inibidores de Proteínas Quinases/efeitos adversos , Mutação , Receptores ErbB/genética
19.
ACS Omega ; 8(45): 42678-42688, 2023 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-38024676

RESUMO

The poly(methacrylic acid) (PMAA) polymer stabilized silver nanoclusters Agn (n = 2-9), synthesized in aqueous solution by the selected light wavelength irradiation photolysis approach, have been functionalized with thiol and amine ligands and successfully transferred from aqueous to organic media. Low- or high-resolution positive mass spectra showed constant species composites with the molecular formula AgnLn-1 [n = 2 to ∼9, L = butylmercaptan (C4H9S), thiolphenol (C6H5S), or dodecanethiol (C12H25S)] and proved that the molecules consist of deprotonated sulfur ligands in each species with one positive charge. Fourier transform infrared and X-ray photoelectron spectroscopy are consistent, indicating deprotonated sulfur, while silver has a zero valence value. The composition of the functionalized silver clusters is in agreement with that observed from polymer-wrapped "naked" silver clusters, which strongly indicates their real existence. For the silver cluster amine systems (heptylamine, dodecylamine, and oleylamine), only "naked" silver cluster species were detected from mass spectroscopy, similar to the polymer-wrapped case, indicating they are not stable enough in the gas phase. The development of a new antibacterial mask material is very important. The dodecylamine-capping silver nanoclusters were selected by coating the coffee filter surface to conduct antibacterial tests with Staphylococcus aureus and Escherichia coli, demonstrating very efficient antimicrobial properties even with organic capping ligands. Experiments also show that they work on mask material. One nanowire assembly with polystyrene and dodecylamine-capping silver nanoclusters was prepared, showing uniform nanofibers generated via the electrospray technique.

20.
Front Microbiol ; 14: 1250891, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37789859

RESUMO

Introduction: The accelerated aging of the global population has emerged as a critical public health concern, with increasing recognition of the influential role played by the microbiome in shaping host well-being. Nonetheless, there remains a dearth of understanding regarding the functional alterations occurring within the microbiota and their intricate interactions with metabolic pathways across various stages of aging. Methods: This study employed a comprehensive metagenomic analysis encompassing saliva and stool samples obtained from 45 pigs representing three distinct age groups, alongside serum metabolomics and lipidomics profiling. Results: Our findings unveiled discernible modifications in the gut and oral microbiomes, serum metabolome, and lipidome at each age stage. Specifically, we identified 87 microbial species in stool samples and 68 in saliva samples that demonstrated significant age-related changes. Notably, 13 species in stool, including Clostridiales bacterium, Lactobacillus johnsonii, and Oscillibacter spp., exhibited age-dependent alterations, while 15 salivary species, such as Corynebacterium xerosis, Staphylococcus sciuri, and Prevotella intermedia, displayed an increase with senescence, accompanied by a notable enrichment of pathogenic organisms. Concomitant with these gut-oral microbiota changes were functional modifications observed in pathways such as cell growth and death (necroptosis), bacterial infection disease, and aging (longevity regulating pathway) throughout the aging process. Moreover, our metabolomics and lipidomics analyses unveiled the accumulation of inflammatory metabolites or the depletion of beneficial metabolites and lipids as aging progressed. Furthermore, we unraveled a complex interplay linking the oral-gut microbiota with serum metabolites and lipids. Discussion: Collectively, our findings illuminate novel insights into the potential contributions of the oral-gut microbiome and systemic circulating metabolites and lipids to host lifespan and healthy aging.

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