RESUMO
Lithium-sulfur (Li-S) batteries are one of the most promising energy storage devices due to their environmental friendliness, low cost, and high specific capacity. However, the slow electrochemical kinetics and the "shuttle effect" have seriously hindered their commercialization. Herein, the nanoflower Bi2S3âMoS2 (BMS) heterostructure is synthesized by a two-step hydrothermal method, and then the Bi2S3âMoS2-Polypropylene (BMS-PP) interlayer is constructed. The heterostructure is rich in active sites, in which BMS has strong adsorption to lithium polysulfides (LiPSs) and can effectively anchor LiPSs while catalyzing LiPSs and promote the redox of Li2S at the same time, which can improve the utilization of active substances. More importantly, the d-band center can be tuned by the formation of Bi2S3âMoS2 heterostructure. Thus, Li-S batteries containing the BMS-PP interlayer show excellent rate performance (841.6 mAh g-1 at 5 C) and cycling performance (70.3% capacity retention after 500 cycles at 3 C). This work provides a new route for high-performance lithium-sulfur batteries.
RESUMO
MOTIVATION: Gene expression is characterized by stochastic bursts of transcription that occur at brief and random periods of promoter activity. The kinetics of gene expression burstiness differs across the genome and is dependent on the promoter sequence, among other factors. Single-cell RNA sequencing (scRNA-seq) has made it possible to quantify the cell-to-cell variability in transcription at a global genome-wide level. However, scRNA-seq data are prone to technical variability, including low and variable capture efficiency of transcripts from individual cells. RESULTS: Here, we propose a novel mathematical theory for the observed variability in scRNA-seq data. Our method captures burst kinetics and variability in both the cell size and capture efficiency, which allows us to propose several likelihood-based and simulation-based methods for the inference of burst kinetics from scRNA-seq data. Using both synthetic and real data, we show that the simulation-based methods provide an accurate, robust and flexible tool for inferring burst kinetics from scRNA-seq data. In particular, in a supervised manner, a simulation-based inference method based on neural networks proves to be accurate and useful when applied to both allele and nonallele-specific scRNA-seq data. AVAILABILITY AND IMPLEMENTATION: The code for Neural Network and Approximate Bayesian Computation inference is available at https://github.com/WT215/nnRNA and https://github.com/WT215/Julia_ABC, respectively.
Assuntos
Perfilação da Expressão Gênica , Transcriptoma , Perfilação da Expressão Gênica/métodos , Análise de Sequência de RNA/métodos , Software , Teorema de Bayes , Cinética , Funções Verossimilhança , Análise de Célula Única/métodos , RNARESUMO
Optical multiplexing technologies, by utilizing various dimensions of light, can effectively expand the information capacity and density for holography but may also lead to multiplexing cross talk. Here, we propose and demonstrate a novel, to our knowledge, multiplicative-noise-multiplexing holography by utilizing the orthogonality between multiplicative noises as a multiplexing dimension. The results prove that this holography can provide a new multiplexing dimension, significantly enhancing information capacity and effectively lowering cross talk. This promising scheme for ultrahigh-capacity holography has the potential to address the limitations of traditional holographic multiplexing technologies.
RESUMO
RATIONALE: Rapid, accurate, and easy-to-perform diagnostic assays are required to address the current need for the diagnosis of resistant pathogens. That is particularly the case for mycobacteria, such as the human pathogen Mycobacterium tuberculosis, which requires up to 2 weeks for the determination of the drug susceptibility profile using the conventional broth microdilution method. To address this challenge, we investigated the incorporation of deuterium, the stable isotope of hydrogen, into lipids as a read out of the drug susceptibility profile. METHODS: Deuterium is incorporated into newly synthesized proteins or lipids in place of hydrogen as bacterial cells grow, increasing the mass of the macromolecules, which can then be observed via matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS). As proof-of-concept, we used the non-pathogenic Mycobacterium smegmatis mc2155 strain, which is susceptible to the aminoglycoside antibiotic kanamycin, and M. smegmatis mc2155 containing the empty vector pVV16, which is kanamycin-resistant. Bacteria were incubated in a culture medium containing 50% of deuterium oxide (D2O) and either 1 or 2 times the minimal inhibitory concentration (MIC50) of kanamycin. Lipids were then analyzed using the MBT lipid Xtract matrix combined with routine MALDI mass spectrometry in the positive ion mode to evaluate the changes in the lipid profile. RESULTS: Using this approach, we were able to distinguish susceptible from resistant bacteria in less than 5 h, a process that would take 72 h using the conventional broth microdilution method. CONCLUSIONS: We therefore propose a solution for the rapid determination of drug susceptibility profiles using a phenotypic assay combining D2O stable isotope labelling and lipid analysis by routine MALDI mass spectrometry.
Assuntos
Lipidômica , Testes de Sensibilidade Microbiana , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Lipidômica/métodos , Mycobacterium smegmatis/efeitos dos fármacos , Mycobacterium smegmatis/química , Deutério/química , Deutério/análise , Lipídeos/análise , Lipídeos/química , Antibacterianos/farmacologia , Humanos , Canamicina/farmacologia , Canamicina/análise , Canamicina/químicaRESUMO
OBJECTIVE: To investigate the impact of age, various hormonal levels, and biochemical markers on penile cavernous body vascular function in patients with erectile dysfunction (ED). Me-thods: A retrospective analysis of clinical data from male patients with ED who underwent color duplex Doppler ultrasonography (CDDU) and intracavernosal injection test (ICI) at the Reproductive Medicine Center of Peking University Third Hospital from January 2020 to August 2023. Data were managed and processed using SPSS 29.0, and a multivariable Logistic regression analysis was conducted. RESULTS: A total of 700 ED patients were included, with 380 showing negative ICI results and 320 positive. In the study, 84 patients had a peak systolic velocity (PSV) < 25 cm/s, while 616 had PSV≥25 cm/s; 202 patients had end-diastolic velocity (EDV)>5 cm/s, and 498 had EDV≤5 cm/s. 264 patients had abnormal PSV and/or EDV results, and 436 had normal results for both. Patients with vascular ED had significantly lower estrogen levels (t=-3.546, P < 0.001), lower testosterone levels (t=-2.089, P=0.037), and a higher rate of hyperglycemia (χ2=12.772, P=0.002) compared with those with non-vascular ED. The patients with arterial ED were older (t=3.953, P < 0.001), had a higher rate of hyperglycemia (χ2=9.518, P=0.009), and a higher estrogen/testosterone ratio (t=2.330, P=0.020) compared with those with non-arterial ED. The patients with mixed arteriovenous ED had higher age (t=3.567, P < 0.001), lower testosterone levels (t=-2.288, P=0.022), a higher rate of hyperglycemia (χ2=12.877, P=0.002), and a larger estrogen/testosterone ratio (t=2.096, P=0.037) compared with those with normal findings. Multifactorial Logistic regression analysis indicated that higher levels of estrogen were a protective factor for vascular ED (OR=1.009, 95%CI: 1.004-1.014), and glucose≥7.0 mmol/L was a risk factor (OR=0.381, 95%CI: 0.219-0.661). Older age was a risk factor for arterial ED (OR=0.960, 95%CI: 0.938-0.982). Additionally, older age (OR=0.976, 95%CI: 0.958-0.993) and glucose levels of 5.6-6.9 mmol/L (OR=0.591, 95%CI: 0.399-0.876) were also risk factors for mixed arterio-venous ED. CONCLUSION: Hyperglycemia and aging may impair penile cavernous body vascular function, while higher levels of estrogen may have a protective effect on it.
Assuntos
Disfunção Erétil , Pênis , Testosterona , Humanos , Masculino , Estudos Retrospectivos , Pênis/irrigação sanguínea , Testosterona/sangue , Disfunção Erétil/fisiopatologia , Ultrassonografia Doppler em Cores , Estrogênios/sangue , Pessoa de Meia-Idade , Fatores Etários , AdultoRESUMO
A major issue with Li-O2 batteries is their slow oxygen reduction and evolution kinetics, necessitating catalysts with high catalytic activity to improve reaction kinetics and cycle stability. Herein, a nano-heterostructured catalyst composed of Co3 O4 and Fe2 O3 (Co3 O4 /Fe2 O3 ) with a porous rod morphology is achieved through an interfacial engineering strategy by constructing Fe2 O3 on the Co3 O4 surface, which can function as a high-performance cathode in order to efficiently encourage the oxygen reduction and evolution while also reduce the battery polarization during charging and discharging. The density functional theory (DFT) calculations show the differences in charge density at the interface of nano-heterostructures, demonstrating the occurrence of an electron transfer process in the interface region of Co3 O4 and Fe2 O3 , implying a strong electronic coupling transfer, and in turn changing the electronic structure of the Co3 O4 . This significantly reduces the adsorption energy of LiO2 intermediates, thereby effectively lowering the overpotential. The resultant Li-O2 battery has larger discharge specific capacity, lower overpotential for the efficient oxygen evolution/reduction, as well as good cycling stability of 280 cycles. This work demonstrates an effective method to fabricate the nano-heterostrucutred materials with enhanced catalytic efficiency for advanced energy applications.
RESUMO
Commercial polymer separators usually have limited porosity, poor electrolyte wettability, and poor thermal and mechanical stability, which can deteriorate the performance of battery, especially at high current densities. In this work, a functional polyethylene (PE) separator is prepared by surface engineering a layer of Ti-doped SiO2 @Al2 O3 particles (denoted as ST@Al2 O3 -PE) with strong Lewis acid property and uniform porous structure on one side of the PE separator. On the other hand, ST@Al2 O3 particles with abundant pore structures and large cavities can store a large amount of electrolyte, providing a shortened pathway for lithium-ion transport, and the Lewis acid sites and porous structure of the ST@Al2 O3 can tune Li plating/stripping behavior and stabilize the lithium metal anode. The ST@Al2 O3 -PE separators exhibit better ionic conductivity (5.55 mS cm-1 ) and larger lithium-ion transference number (0.62). At a current density of 1 mA cm-2 , Li/Li symmetric cells with ST@Al2 O3 -PE separator can be stably cycled for more than 400 h, and both lithium iron phosphate /Li cells and lithium cobaltate/Li cells with ST@Al2 O3 -PE separator have good cycling and rate performance. This work provides a new strategy for developing functional separators and promoting the application of lithium metal batteries.
RESUMO
The precursors that appear when geological disasters occur are geotechnical deformations. This paper studies the TDR (Time Domain Reflection) measurement technology for the distributed measurement of geotechnical deformation using parallel spiral wire as a sensor, which is used for monitoring and early warning detection of geological disasters. Based on the mechanism of the electromagnetic field distribution parameters of the parallel spiral sensing wire, the relationship between the stretching amount of the parallel spiral wire and the change in its characteristic impedance is analyzed. When the parallel spiral wire is buried in the soil, the geotechnical deformation causes the parallel spiral wire to be stretched, and according to its characteristic impedance change, the stretching position and the stretching degree can be obtained, thus realizing the distributed measurement of geotechnical deformation. Based on this principle, the TDR measurement system is developed, and a local single-point stretching amount and stretching positioning experiment are designed for the parallel spiral sensing line to verify the effectiveness of the sensing technology and the usability of the measurement system.
RESUMO
The ability to craft high-efficiency and non-precious bifunctional oxygen catalysts opens an enticing avenue for the real-world implementation of metal-air batteries (MABs). Herein, Co3 O4 encapsulated within nitrogen defect-rich g-C3 N4 (denoted Co3 O4 @ND-CN) as a bifunctional oxygen catalyst for MABs is prepared by graphitizing the zeolitic imidazolate framework (ZIF)-67@ND-CN. Co3 O4 @ND-CN possesses superb bifunctional catalytic performance, which facilitates the construction of high-performance MABs. Concretely, the rechargeable zinc-air battery based on Co3 O4 @ND-CN shows a superior round-trip efficiency of ≈60% with long-term durability (over 340 cycles), exceeding the battery with the state-of-the-art noble metals. The corresponding lithium-oxygen battery using Co3 O4 @ND-CN exhibits an excellent maximum discharge/charge capacity (9838.8/9657.6 mAh g-1 ), an impressive discharge/charge overpotential (1.14 V/0.18 V), and outstanding cycling stability. Such compelling electrocatalytic processes and device performances of Co3 O4 @ND-CN originate from concurrent compositional (i.e., defect-engineering) and structural (i.e., wrinkled morphology with abundant porosity) elaboration as well as the well-defined synergy between Co3 O4 and ND-CN, which produce an advantageous surface electronic environment corroborated by theoretical modeling. By extension, a rich diversity of other metal oxides@ND-CN with adjustable defects, architecture, and enhanced activities may be rationally designed and crafted for both scientific research on catalytic properties and technological development in renewable energy conversion and storage systems.
RESUMO
Gastric cancer (GC) is one of the major causes of cancer-related mortality. The use of oncolytic virus for cancer gene-virotherapy is a new approach for the treatment of human cancers. In this study, a novel Survivin promoter-driven recombinant oncolytic adenovirus carrying mK5 or MnSOD gene was constructed, which was modified after deletion of the E1B gene. Human plasminogen Kringle 5 mutant (mK5) and manganese superoxide dismutase (MnSOD) are both potential tumor suppressor genes. By constructing Ad-Surp-mK5 and Ad-Surp-MnSOD oncolytic adenoviruses, we hypothesized that the combination of the two viruses would enhance the therapeutic efficacy of GC as compared to the one virus alone. The results of the in vitro experiments revealed that the combination of adenovirus carrying mK5 and MnSOD gene exhibited stronger cytotoxicity to GC cell lines as compared to the virus alone. Additionally, the virus could selectively kill cancer cells and human somatic cells. Cell staining, flow cytometry, and western blot analysis showed that the combination of two adenoviruses containing therapeutic genes could promote the apoptosis of cancer cells. In vivo experiments further verified that Ad-Surp-mK5 in combination with Ad-Surp-MnSOD exhibited a significant inhibitory effect on the growth of GC tumor xenograft as compared to the virus alone, and no significant difference was observed in the bodyweight of treatment and the normal mice. In conclusion, the combination of our two newly constructed recombinant oncolytic adenoviruses containing mK5 or MnSOD therapeutic genes could significantly inhibit gastric cancer growth by inducing apoptosis, suggestive of its potential for GC therapy.
Assuntos
Adenoviridae , Neoplasias Gástricas , Adenoviridae/genética , Animais , Linhagem Celular Tumoral , Humanos , Camundongos , Camundongos Nus , Neoplasias Gástricas/genética , Neoplasias Gástricas/terapia , Superóxido Dismutase/genética , Survivina/genética , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Circular RNAs are widely existing in eukaryotes. However, there is as yet no tissue-specific Arabidopsis circular RNA database, which hinders the study of circular RNA in plants. Here, we used 622 Arabidopsis RNA sequencing data sets from 87 independent studies hosted at NCBI SRA and developed AtCircDB to systematically identify, store and retrieve circular RNAs. By analyzing back-splicing sites, we characterized 84 685 circular RNAs, 30 648 tissue-specific circular RNAs and 3486 microRNA-circular RNA interactions. In addition, we used a metric (detection score) to measure the detection ability of the circular RNAs using a big-data approach. By experimental validation, we demonstrate that this metric improves the accuracy of the detection algorithm. We also defined the regions hosting enriched circular RNAs as super circular RNA regions. The results suggest that these regions are highly related to alternative splicing and chloroplast. Finally, we developed a comprehensive tissue-specific database (AtCircDB) to help the community store, retrieve, visualize and download Arabidopsis circular RNAs. This database will greatly expand our understanding of circular RNAs and their related regulatory networks. AtCircDB is freely available at http://genome.sdau.edu.cn/circRNA.
Assuntos
Arabidopsis/genética , Bases de Dados de Ácidos Nucleicos/estatística & dados numéricos , RNA de Plantas/genética , RNA/genética , Algoritmos , Big Data , Biologia Computacional , Internet , MicroRNAs/genética , RNA Circular , Análise de Sequência de RNA/estatística & dados numéricos , Distribuição Tecidual/genética , Interface Usuário-ComputadorRESUMO
MOTIVATION: Normalization of single-cell RNA-sequencing (scRNA-seq) data is a prerequisite to their interpretation. The marked technical variability, high amounts of missing observations and batch effect typical of scRNA-seq datasets make this task particularly challenging. There is a need for an efficient and unified approach for normalization, imputation and batch effect correction. RESULTS: Here, we introduce bayNorm, a novel Bayesian approach for scaling and inference of scRNA-seq counts. The method's likelihood function follows a binomial model of mRNA capture, while priors are estimated from expression values across cells using an empirical Bayes approach. We first validate our assumptions by showing this model can reproduce different statistics observed in real scRNA-seq data. We demonstrate using publicly available scRNA-seq datasets and simulated expression data that bayNorm allows robust imputation of missing values generating realistic transcript distributions that match single molecule fluorescence in situ hybridization measurements. Moreover, by using priors informed by dataset structures, bayNorm improves accuracy and sensitivity of differential expression analysis and reduces batch effect compared with other existing methods. Altogether, bayNorm provides an efficient, integrated solution for global scaling normalization, imputation and true count recovery of gene expression measurements from scRNA-seq data. AVAILABILITY AND IMPLEMENTATION: The R package 'bayNorm' is publishd on bioconductor at https://bioconductor.org/packages/release/bioc/html/bayNorm.html. The code for analyzing data in this article is available at https://github.com/WT215/bayNorm_papercode. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
Assuntos
RNA , Software , Teorema de Bayes , Perfilação da Expressão Gênica , Hibridização in Situ Fluorescente , Análise de Sequência de RNA , Análise de Célula ÚnicaRESUMO
GGNBP1 is known as gametogenetin protein 1 (GGN1)-interacting protein. It is specifically expressed in the mitochondria of the testis, while its functional role during spermatogenesis is still unknown. Here, we showed that the disruption of Ggnbp1 resulted in abnormal spermiogenesis in around 40% mice, while the others show no defects in the genital system. Moreover, upon treatment with low dose of bisphenol A (BPA), Ggnbp1 knockout mice were more sensitive to environmental pollutant than control mice. The treatment led to decrease in sperm motility and production of abnormal spermatozoa. These results suggest that GGNBP1 mainly ensures proper spermiogenesis in response to various stresses in male mice.
Assuntos
Proteínas de Transporte/metabolismo , Espermatogênese , Estresse Fisiológico , Animais , Sequência de Bases , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Espermatozoides/metabolismo , Espermatozoides/ultraestruturaRESUMO
RATIONALE: Glycosyl-inositol-phospho-ceramides (GIPCs) or glycosylphosphatidylinositol-anchored fungal polysaccharides are known to be major lipids in plant and fungal plasma membranes and to play an important role in stress adaption. However, their analysis remains challenging due to the several steps involved for their extractions and purifications prior to mass spectrometric analysis. To address this challenge, we developed a rapid and sensitive method to identify GIPCs from the four common fungal plant pathogens Botrytis cinerea, Fusarium graminearium, Neurospora crassa and Ustilago maydis. METHODS: Fungal plant pathogens were cultured, harvested, heat-inactivated and washed three times with double-distilled water. Intact fungi were deposited on a matrix-assisted laser desorption ionization (MALDI) target plate, mixed with the matrix consisting of a 9:1 mixture of 2,5-dihydroxybenzoic acid and 2-hydroxy-5-methoxybenzoic acid solubilized at 10 mg/mL in chloroform-methanol (9:1 v/v) and analyzed using a Bruker MALDI Biotyper Sirius system in the linear negative ion mode. Mass spectra were acquired from m/z 700 to 2000. RESULTS: MALDI time-of-flight (TOF) mass spectrometric analysis of cultured fungi showed clear signature of GIPCs in B. cinerea, F. graminearium, N. crassa and U. maydis. CONCLUSIONS: We have demonstrated that routine MALDI-TOF in the linear negative ion mode combined with an apolar solvent system to solubilize the matrix is applicable to the detection of filamentous fungal GIPCs.
Assuntos
Ceramidas/análise , Fungos/química , Glicosilfosfatidilinositóis/análise , Plantas/microbiologia , Técnicas de Tipagem Micológica , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
Ran-binding protein 3 (RanBP3) is a Ran-interacting protein, which participates in the Ran GTPase system in cancer cell biology. However, the expression pattern and physiological role of RanBP3 remain largely unknown. In this study, we found that RanBP3 was expressed in human testes and localised to spermatogonium and spermatocyte of germ cells. In subcellular structure, its localisation is in the nucleus and cytoplasm. Interestingly, compared with normal groups, RanBP3 expression was lower in groups of patients with Maturation Arrest (MA) and Sertoli cell-only syndrome (SCO) when considered by the Johnson Score. RanBP3 expression in the MA group and SCO groups was dramatically lower than that in the normal control group. Studies have shown that RanBP3, which is one of the helper factors of Ran, is mainly participate in the nucleocytoplasmic transport of cells. RanBP3 helps Ran to achieve some functions such as nucleocytoplasmic transport, spindle assembly during mitosis and nuclear assembly after mitosis. Consequent changes in the expression of RanBP3 may associate with human spermatogenesis disorders and male infertility. The identification and characterisation of RanBP3 enhances our understanding of the molecular mechanisms underpinning its function in human spermatogenesis and male infertility.
Assuntos
Azoospermia/metabolismo , Proteínas Nucleares/metabolismo , Proteínas de Transporte Nucleocitoplasmático/metabolismo , Síndrome de Células de Sertoli/metabolismo , Espermatogênese , Testículo/metabolismo , Azoospermia/patologia , Estudos de Casos e Controles , Humanos , Masculino , Síndrome de Células de Sertoli/patologia , Testículo/patologiaRESUMO
Acephalic spermatozoa syndrome has been reported for many decades; it is characterized by very few intact spermatozoa and tailless sperm heads in the semen and causes severe male infertility. The only gene in which mutations have been found to be associated with this syndrome encodes Sad1 and UNC84 domain-containing 5 (SUN5), a testis-specific nuclear envelope protein. The functional role of SUN5 has been well-studied in mouse models, but the molecular basis for the pathogenic effects of mutations in the human SUN5 gene remains elusive. Here, we report a new SUN5 mutation (c.475CâT; p.Arg159*), and explore the pathogenic effects of all known SUN5 mutations on acephalic spermatozoa syndrome. Using an artificial splicing system, we found that the intronic mutation affects the splicing of SUN5 mRNA, yielding a premature stop codon that results in a truncated SUN5 protein. We also found that SUN5 interacts with the coupling apparatus protein DnaJ heat shock protein family (Hsp40) member B13 (DNAJB13) during spermatogenesis, and the substitutions in the SUN5 SUN domain impair its interaction with DNAJB13. Furthermore, we observed that many SUN5 mutations affect the secondary structure of the protein and influence its folding and cellular localization. In summary, our findings indicate an interaction of SUN5 with DNAJB13 during spermatogenesis, provide mechanistic insights into the functional role of this interaction in sperm head-tail integration, and elucidate the molecular etiology of acephalic spermatozoa syndrome-associated SUN5 mutations.
Assuntos
Proteínas de Membrana/genética , Proteínas/genética , Teratozoospermia/genética , Adulto , Animais , Proteínas Reguladoras de Apoptose , Proteínas de Choque Térmico HSP40/genética , Proteínas de Choque Térmico HSP40/metabolismo , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Humanos , Íntrons , Masculino , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Knockout , Chaperonas Moleculares , Mutação Puntual , Ligação Proteica , Proteínas/metabolismo , Splicing de RNA , Espermatogênese , Espermatozoides/citologia , Espermatozoides/metabolismo , Teratozoospermia/metabolismoRESUMO
SET domain containing protein 2 (SETD2, also known as HYPB) is a 230-kD protein which is located at cytogenetic band p21.31 of chromosome 3. SETD2 is usually transformed or eradicated in multiple forms of tumours in humans. However, its primary function in gastric cancer (GC) remains unclear. In the current study, we investigated the mRNA and protein expression levels of SETD2 using immunohistochemistry, qPCR, RT-PCR, and immunoblotting. The function of SETD2 in GC cells was investigated by MTT and transwell assays. Our results revealed remarkably lower levels of SETD2 mRNA and protein in the tumour samples than in tumour-adjacent tissues. Decreased expression of SETD2 mRNA was observed in 122 (79.7%) of 153 primary tumour tissue samples. On the basis of the overall survival analysis, we could interpret that a low expression of SETD2 was correlated with a poor prognosis (Pâ¯<â¯0.001, log-rank test). Multivariate survival analysis indicated that SETD2 was an obvious prognostic factor in patients with GC. SETD2 overexpression in GC cell lines significantly inhibited cell proliferation, migration, and invasion. Altogether, the investigation demonstrated the clinical significance of SETD2 expression, supporting the fundamental principle that a decrease in its level is an unfavourable event in the progression and prognosis of GC. Therefore, down-regulated SETD2 can presumably be a potential negative prognostic and progression marker for GC.
Assuntos
Regulação Neoplásica da Expressão Gênica , Histona-Lisina N-Metiltransferase/genética , Invasividade Neoplásica/genética , Neoplasias Gástricas/genética , Idoso , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação para Baixo , Feminino , Mucosa Gástrica/metabolismo , Histona-Lisina N-Metiltransferase/análise , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/diagnóstico , Invasividade Neoplásica/patologia , Prognóstico , Estômago/patologia , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patologiaRESUMO
PURPOSE: Sperm-specific sodium-hydrogen exchanger (sNHE) is essential to maintain sperm normal function in mice; however, its role in human sperm has not been clarified to date. The aim of this study is to investigate the expression pattern of sNHE in human spermatozoa and its relationship with sperm functional parameters. METHOD: Semen samples from 68 asthenozoospermic and 61 normozoospermic men were analyzed for sperm concentration, motility, and acrosome reaction, and high motile spermatozoa were collected by swim-up method. The expression of sNHE in spermatozoa was detected by Western blot and immunofluorescence staining. The relationship between sNHE expression and sperm parameters was assessed. RESULTS: We identified sNHE is mainly localized to the principal piece of the human sperm tail. The expression of sNHE was positively correlated with sperm concentration, total number, and progressive motility. Moreover, sNHE expression was upregulated in swim-up sperm and associated with most of sperm motility parameters including straight line velocity and curvilinear velocity. Our results also showed that sNHE expression is decreased in sperm from patients with asthenozoospermia compared with that from normal controls. However, no correlation was found between sNHE expression and acrosome reaction in spermatozoa. CONCLUSIONS: The expression pattern of sNHE suggested that this protein may be involved in the regulation of sperm motility, and aberration of its expression in sperm may contribute to the pathogenesis of asthenozoospermia.
Assuntos
Reação Acrossômica/genética , Sêmen/metabolismo , Trocadores de Sódio-Hidrogênio/genética , Espermatozoides/metabolismo , Astenozoospermia/genética , Astenozoospermia/patologia , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Masculino , Sêmen/fisiologia , Contagem de Espermatozoides , Motilidade dos Espermatozoides/genética , Cauda do Espermatozoide/metabolismo , Cauda do Espermatozoide/fisiologia , Espermatozoides/crescimento & desenvolvimentoRESUMO
OBJECTIVE: To study the effect of transcutaneous electrical acupoint stimulation (TEAS) in the treatment of asthenozoospermia. METHODS: We randomly divided 72 asthenozoospermia patients into a 2 Hz TEAS (n = 29), a 100 Hz TEAS (n = 20), and a blank control group (n = 23), those in the former two groups treated by 30 minutes of TEAS at 2 Hz and 100 Hz respectively, applied to the acupoints of bilateral Shenshu, left Zusanli, and Guanyuan, once a day for 60 days, while those in the blank control group left untreated. Using computer-assisted sperm analysis (CASA), we examined sperm concentration and motility as well as the percentages of grade a and grade a+b sperm in different groups of the patients. RESULTS: Compared with the baseline, 2 Hz TEAS significantly increased sperm motility (ï¼»12.76 ± 1.39ï¼½ vs ï¼»18.89 ± 2.46ï¼½%, P<0.05) and the percentage of grade a+b sperm ( ï¼»10.68 ± 1.22ï¼½ vs ï¼»16.32 ± 2.10ï¼½%, P<0.05) in the asthenozoospermic patients, while 100 Hz TEAS improved not only sperm motility (ï¼»12.32 ± 2.21ï¼½ vs ï¼»23.81 ± 3.42ï¼½%, P<0.01) and the percentage of grade a+b sperm (ï¼»10.45 ± 1.98ï¼½ vs ï¼»20.25 ± 2.82 ï¼½%, P<0.01), but also the percentage of grade a sperm (ï¼»6.44 ± 1.16ï¼½ vs ï¼»13.31 ± 2.30ï¼½%, P<0.05). Moreover, in comparison with the blank control group, 2 Hz TEAS also remarkably increased sperm motility (ï¼»9.57 ± 1.60ï¼½ vs ï¼»18.89 ± 2.46ï¼½%, P<0.05) and the percentage of grade a+b sperm (ï¼»7.81 ± 1.31ï¼½ vs ï¼»16.32 ± 2.10ï¼½%, P<0.05) in the asthenozoosperma patients, while 100 Hz TEAS improved not only sperm motility (ï¼»9.57 ± 1.60ï¼½ vs ï¼»23.81 ± 3.42ï¼½%, P<0.01) and the percentage of grade a+b sperm (ï¼»7.81 ± 1.31ï¼½ vs ï¼»20.25 ± 2.82ï¼½%, P<0.01) but also the percentage of grade a sperm (ï¼»4.87 ± 1.01ï¼½ vs ï¼»13.31 ± 2.30ï¼½%, P<0.01). Meanwhile, the rate of clinical effectiveness was significantly higher in the 100 Hz TEASthan in the blank control group either in intention-to-treat (ITT) analysis (100% vs 18.18%) orper-protocol (PP) analysis (90% vs 0%), and so was it than in the 2 Hz TEAS group based on the data of ITT (100% vs 33.33%). CONCLUSIONS: Both 2 Hz and 100 Hz TEAS are effective for the treatment of asthenozoospermia by improving sperm motility and vitality.
Assuntos
Pontos de Acupuntura , Astenozoospermia/terapia , Eletroacupuntura/métodos , Motilidade dos Espermatozoides , Humanos , Masculino , Contagem de Espermatozoides/métodos , Espermatozoides , Resultado do TratamentoRESUMO
OBJECTIVE: To investigate the influence of high fat diet-induced obesity (HFDIO) on the differentially methylated region (DMR) of the imprinted gene and global genome methylation of sperm DNA. METHODS: We performed bisulfite sequencing on the DMR of the imprinted gene and global genome methylation of sperm DNA in the mouse model of HFDIO. RESULTS: No statistically significant differences were found between the HFDIO model and normal control mice in MEG3-IG (93.73 vs 97.26%, P = 0.252), H19 (98.00 vs 97.83%, P = 0.920), IGF2 (97.34 vs 96.25%, P =0.166), IGF2R (1.43 vs 1.11%, P = 0.695), PEG3 (0.19 vs 0.38%, P = 0.537), MEST (0.23 vs 0.68%, P = 0.315), NNAT (0.31 vs 0.00%, P = 0.134), or SNRPN (1.88 vs 3.13%, P = 0.628). A total of 8 942 DMRs were detected across the sperm genome (P <0.05). Gene functional enrichment analysis indicated that the enriched terms with the largest numbers of genes were the metabolic process (n = 1 482), RNA synthesis (n = 779), and transcription (n = 767). CONCLUSIONS: The methylation level underwent no significant change in the DMRs of the imprinted genes from the mice with HFDIO, but the CG methylation of the genes involved in the metabolic process, RNA synthesis and transcription were significantly altered.