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Coronavirus disease 2019 (COVID-19) has been reported to decrease semen quality in reproductive-age men. Semen quality in vaccinated men after SARS-CoV-2 infection remains unclear. We recruited reproductive-age Chinese men scheduled for COVID-19 vaccination from December 2022 to March 2023. Among 1,639 vaccinated participants, an upward trend was found in sperm concentration (p < .001), progressive motility (p < .001), total motility (p < .001), total motile sperm count (TMSC) (p < .001), and normal morphology (p = .01) over time following COVID-19 recovery. Among men with an SARS-CoV-2 infection that lasted less than 30 days, men who received an inactivated vaccine booster had higher sperm progressive (p = .006) and total motility (p = .005) as well as TMSC (p = .008) than those without a booster vaccine, whereas no difference was found in semen parameters among men who received a recombinant protein vaccine. Similarly, an upward trend in semen quality was found among 122 men who provided semen samples before and after COVID-19. Higher risks of asthenozoospermia (odds ratio [OR] = 2.23, p < .001) and teratozoospermia (OR = 2.09, p = .03) were found among men who had an SARS-CoV-2 infection that lasted less than 30 days than among those without COVID-19. Collectively, after receiving SARS-CoV-2 vaccination, adverse but reversible semen parameters were observed in men recovering from COVID-19 over time. Recombinant protein vaccines and inactivated vaccine boosters should be recommended to all reproductive-age men.
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Vacunas contra la COVID-19 , COVID-19 , Análisis de Semen , Humanos , Masculino , COVID-19/prevención & control , Estudios Retrospectivos , Adulto , Vacunas contra la COVID-19/administración & dosificación , SARS-CoV-2 , China , Recuento de Espermatozoides , Motilidad Espermática , Persona de Mediana EdadRESUMEN
A new idea to alleviate environmental pollution is the development of low-cost adsorbents using natural minerals and fishery wastes to treat high concentrations of heavy metal pollutants in acid mine drainage (AMD). Adsorbent morphology, adsorptive and regenerative capacity, and application potential are limiting factors for their large-scale use. Oyster shells capable of releasing alkalinity were loaded on the surface of lignite to develop two composite adsorbents with different morphologies (powdery and globular) for the treatment of AMD containing Pb(II) and Cd(II). The results show that the ability of the adsorbent to treat AMD is closely related to its morphologies. The pseudo-second-order kinetic model and the Langmuir model are suitable to describe the adsorption process of OS-M(P), and the maximum adsorption saturation capacities of Pb(II) and Cd(II) are 332.6219 mg/g and 318.9854 mg/g, respectively. The pseudo-second-order kinetic model and the Freundlich model are suitable to describe the adsorption process of OS-M(G). A synergistic result of electrostatic adsorption, neutralization precipitation, ion exchange and complex reaction is achieved in the removal of Pb(II) and Cd(II) by two morphologies of adsorbents. The regeneration times (5 times) and recovery rate (75.75%) of OS-M(G) are higher than those of OS-M(P) (3 times) and recovery rate (20%). The ability of OS-M(G) to treat actual AMD wastewater is still better than that of OS-M(P). OS-M(G) can be used as a promising environmentally friendly adsorbent for the long-term remediation of AMD. This study provides a comprehensive picture of resource management and reuse opportunities for natural mineral and fishery wastes.
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Exoesqueleto , Cadmio , Plomo , Minería , Ostreidae , Contaminantes Químicos del Agua , Plomo/química , Cadmio/química , Adsorción , Animales , Ostreidae/química , Exoesqueleto/química , Contaminantes Químicos del Agua/química , CinéticaRESUMEN
Reversible solid-state hydrogen storage of magnesium hydride, traditionally driven by external heating, is constrained by massive energy input and low systematic energy density. Herein, a single phase of Mg2Ni(Cu) alloy is designed via atomic reconstruction to achieve the ideal integration of photothermal and catalytic effects for stable solar-driven hydrogen storage of MgH2. With the intra/inter-band transitions of Mg2Ni(Cu) and its hydrogenated state, over 85% absorption in the entire spectrum is achieved, resulting in the temperature up to 261.8 °C under 2.6 W cm-2. Moreover, the hydrogen storage reaction of Mg2Ni(Cu) is thermodynamically and kinetically favored, and the imbalanced distribution of the light-induced hot electrons within CuNi and Mg2Ni(Cu) facilitates the weakening of Mg-H bonds of MgH2, enhancing the "hydrogen pump" effect of Mg2Ni(Cu)/Mg2Ni(Cu)H4. The reversible generation of Mg2Ni(Cu) upon repeated dehydrogenation process enables the continuous integration of photothermal and catalytic roles stably, ensuring the direct action of localized heat on the catalytic sites without any heat loss, thereby achieving a 6.1 wt.% H2 reversible capacity with 95% retention under 3.5 W cm-2.
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Selective phosphorus removal from aquatic media has become an ideal strategy to mitigate eutrophication and meet increasingly stringent discharge requirements. To achieve phosphorus control and resource utilization of low-calorific-value lignite, iron and magnesium salts were used to functionalize lignite, and iron-magnesium functionalized lignite (called IM@BC) was prepared for phosphate recovery from water media. The adsorption properties of IM@BC were systematically evaluated, especially the influence of ambient pH and co-existing ions. The kinetic, isothermal, and thermodynamic adsorption behaviors of IM@BC were analyzed. The adsorption mechanism was revealed by microscopic characterization. The potential application of phosphate-containing IM@BC (P-IM@BC) was explored. The results show that IM@BC has a strong phosphate adsorption capacity, and the maximum adsorption capacity is 226.22 mgP/g at pH = 3. Co-existing CO32- inhibits phosphate adsorption, while coexisting Ca2+ and Mg2+ enhance the effect. At the initial adsorption stage, the amount of phosphate adsorbed by IM@BC continues to increase, and the adsorption equilibrium state is gradually reached after 24 h. The adsorption process conforms to the pseudo-second-order kinetic model (PSO) and Langmuir isothermal adsorption model, and the adsorption process is mainly chemical adsorption. The phosphate absorption capacity is positively correlated with temperature (283.15 K~313.15 K), and the adsorption process is spontaneous, endothermic, and entropy-increasing. Its adsorption mechanism includes electrostatic attraction, ion exchange, surface precipitation, and coordination exchange. IM@BC can efficiently recover phosphate from actual phosphorus-containing wastewater with a recovery efficiency of up to 90%. P-IM@BC slowly releases phosphate from pH 3 to 11. Plant growth experiments showed that P-IM@BC could be used as a slow-release fertilizer to promote the root growth of cowpeas. The novelty of this work lies in the development of a highly efficient phosphate recovery adsorbent, which provides a feasible method of phosphorus control in water media and resource utilization of lignite.
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Hydrogen storage in MgH2 is an ideal solution for realizing the safe storage of hydrogen. High operating temperature, however, is required for hydrogen storage of MgH2 induced by high thermodynamic stability and kinetic barrier. Herein, flower-like microspheres uniformly constructed by N-doped TiO2 nanosheets coated with TiN nanoparticles are fabricated to integrate the light absorber and thermo-chemical catalysts at a nanometer scale for driving hydrogen storage of MgH2 using solar energy. N-doped TiO2 is in situ transformed into TiNxOy and Ti/TiH2 uniformly distributed inside of TiN matrix during cycling, in which TiN and Ti/TiHx pairs serve as light absorbers that exhibit strong localized surface plasmon resonance effect with full-spectrum light absorbance capability. On the other hand, it is theoretically and experimentally demonstrated that the intimate interface between TiH2 and MgH2 can not only thermodynamically and kinetically promote H2 desorption from MgH2 but also simultaneously weaken TiâH bonds and hence in turn improve H2 desorption from the combination of weakened TiâH and TiâH bonds. The uniform integration of photothermal and catalytic effect leads to the direct action of localized heat generated from TiN on initiating the catalytic effect in realizing hydrogen storage of MgH2 with a capacity of 6.1 wt.% under 27 sun.
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Background: Locally advanced prostate cancer (PCa) carries a high risk of recurrence and metastasis after surgery, and the prognosis is poor. We explored the risk factors for locally advanced PCa among clinical factors (neutrophil: lymphocyte ratio, lymphocyte: monocyte ratio) and indicators of systemic inflammation [prostate-specific antigen (PSA) level, Gleason score, body mass index (BMI)] through retrospective evaluation of patients with PCa diagnosed at our center. The pathologic T stage was a key indicator of locally advanced PCa. Methods: Data from patients with pathologically confirmed PCa at our center from 1 January 2015 to 1 May 2020 were collected in strict accordance with inclusion and exclusion criteria. Clinical data were collected and the relationship between the indicators and the pathologic T stage was explored. First, Spearman rank correlation analysis was used to find the correlates of the pathologic T stage. Then, logistic ordered multiple regression analysis was used to identify independent risk factors. Finally, receiver operating characteristic (ROC) curves were used to assess the diagnostic accuracy for the T stage of PCa. Results: After rigorous screening, the data of 177 patients were obtained. Spearman correlation analysis showed that BMI, the PSA level, Gleason score, hypertension, N stage, and M stage were significantly correlated with the T stage (P<0.05), suggesting that these factors may be involved in locally advanced PCa. Analyses of ROC curves showed that the PSA level [area under the ROC curve (AUC) =0.802] had greater value than BMI (0.675) for the diagnosis of the pathologic T stage PCa, and that a combination of BMI and PSA (combined AUC =0.822) could improve locally advanced PCa diagnosis. Conclusions: BMI and PSA are independent risk factors for locally advanced PCa. They may play a key part in locally advanced PCa.
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Despite advancements, prostate cancers (PCa) pose a significant global health challenge due to delayed diagnosis and therapeutic resistance. This review delves into the complex landscape of prostate cancer, with a focus on long-noncoding RNAs (lncRNAs). Also explores the influence of aberrant lncRNAs expression in progressive PCa stages, impacting traits like proliferation, invasion, metastasis and therapeutic resistance. The study elucidates how lncRNAs modulate crucial molecular effectors, including transcription factors and microRNAs, affecting signaling pathways such as androgen receptor signaling. Besides, this manuscript sheds light on novel concepts and mechanisms driving PCa progression through lncRNAs, providing a critical analysis of their impact on the disease's diverse characteristics. Besides, it discusses the potential of lncRNAs as diagnostics and therapeutic targets in PCa. Collectively, this work highlights state of art mechanistic comprehension and rigorous scientific approaches to advance our understanding of PCa and depict innovations in this evolving field of research.
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MicroARNs , Neoplasias de la Próstata , ARN Largo no Codificante , Masculino , Humanos , ARN Largo no Codificante/genética , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/terapia , Transducción de Señal , Regulación Neoplásica de la Expresión GénicaRESUMEN
A new adsorbent called iron-magnesium oxide coupled lignite (CIMBC) was developed to address the challenges of recovering high concentrations of ammonia nitrogen and phosphate in livestock farm wastewater and improving the inefficient use of lignite (BC) with low calorific value. CIMBC was synthesized using the modified ferromagnesium salt double-coating method. The experiments demonstrated that Fe2O3 and MgO could be effectively loaded onto the surface of BC at a Fe/Mg molar ratio of 1:2 and pyrolysis temperature of 500 °C. The optimal conditions for adsorption were determined to be an N/P concentration ratio of 2:1, adsorbent dosage of 1 g/L, and pH of 7. The presence of coexisting cations (Ca2+ and Mg2+) inhibited the removal of ammonia nitrogen but enhanced the removal of phosphate. Likewise, the presence of coexisting anions (CO32- and SO42-) hindered the removal of both ammonia nitrogen and phosphate. The adsorption behavior followed the pseudo-second-order model and the Langmuir model, with a maximum adsorption capacity of 95.69 mg N/g for ammonia nitrogen and 101.32 mg P/g for phosphate. The adsorption process was a spontaneous endothermic process controlled by multiple levels. The main mechanisms of adsorption involved electrostatic attraction, intra-particle diffusion, ion exchange, chemical precipitation, and coordination exchange. After 5 times of adsorption-desorption, the recovery rate of CIMBC is less than 50%, and the removal rate of phosphate is less than 40%. Although the RCIMBC exhibited low reusability, but also it showed potential in removing heavy metals (Pb) from wastewater and for use as a slow-release fertilizer. CIMBC is a promising new adsorbent, which can realize resource utilization of lignite with low calorific value while removing nitrogen and phosphorus.
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Compuestos Férricos , Óxido de Magnesio , Contaminantes Químicos del Agua , Animales , Fosfatos , Magnesio , Aguas Residuales , Hierro , Amoníaco , Ganado , Carbón Mineral , Granjas , Adsorción , Nitrógeno , CinéticaRESUMEN
The inhibition and toxicity of high acidity and heavy metals on sulfate-reducing bacteria in acid mine drainage (AMD) were targeted. Highly active SRB immobilized particles were prepared using SRB, warm sticker wastes (iron powders), corncobs, and Maifan stones as the main matrix materials, employing microbial immobilization technology. The repair ability and reusability of highly active immobilized particles for AMD were explored. The results indicate that the adaptability of immobilized particles to AMD varied under different initial conditions, such as pH, Mn2+, and SO42-. The adsorption process of immobilized particles on Mn2+ follows the quasi-second-order kinetic model, suggesting that it involves both physical and chemical adsorption. The maximum adsorption capacity of immobilized particles for Mn2+ is 3.878 mg/g at a concentration of 2.0 mg/L and pH 6. On the other hand, the reduction process of immobilized particles on SO42- adheres to the first-order reaction kinetics, indicating that the reduction of SO42- is primarily driven by the dissimilation reduction of SRB. The maximum reduction rate of SO42- by immobilized particles is 94.23% at a concentration of 800 mg/L and pH 6. A layered structure with a flocculent appearance formed on the surface of the immobilized particles. The structure's characteristics were found to be consistent with sulfate green rust (FeII4FeIII2(OH)12SO4·8H2O). The chemisorption, ion exchange, dissimilation reduction, and surface complexation occurring between the matrices in the immobilized particles can enhance the alkalinity of AMD and decrease the concentration of heavy metals and sulfates. These results are expected to offer novel insights and materials for the treatment of AMD using biological immobilization technology, as well as improve our understanding of the mechanisms behind biological and abiotic enhanced synergistic decontamination.
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Metales Pesados , Contaminantes Químicos del Agua , Hierro , Metales Pesados/química , Sulfatos/químicaRESUMEN
ABSTRACT: Genetic risk factors have been shown to contribute to the development of sexual dysfunction. However, the role of methylenetetrahydrofolate reductase (MTHFR) gene variants in the risk of erectile dysfunction (ED) remains unclear. In this study, we recruited 1254 participants who underwent ED assessed by the International Index of Erectile Function-5. The MTHFR c.677C>T variant was also measured by fluorescence polymerase chain reaction (PCR). No significant difference in the genotypic frequency of the MTHFR C677T polymorphism (CC, CT, and TT) was observed between men from the ED and non-ED groups. In addition, on binary logistic regression analysis, both crude and adjusted models showed that the risk of ED was not significantly associated with the C677T polymorphism. Interestingly, a significantly higher frequency of the 677TT polymorphism was found in severe and moderate ED (P = 0.02). The positive correlation between the MTHFR 677TT polymorphism and severe ED was confirmed by logistic regression analysis, even after adjusting for potential confounders (odds ratio [OR] = 2.46, 95% confidence interval [CI]: 1.15-5.50, P = 0.02). These findings suggest a positive correlation between the MTHFR 677TT polymorphism and the risk of severe ED. Identification of MTHFR gene polymorphisms may provide complementary information for ED patients during routine clinical diagnosis.
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Background: It is suggested that body mass index (BMI) can affect male semen quality; however, the results remain controversial. In addition, most studies have focused on the effect of obesity on semen quality. Evidence on the relationship of underweight or waist-hip ratio (WHR) with semen quality is rare. This study aimed to assess the association of BMI and WHR with semen quality. Methods: Data, including BMI and WHR, was collected from 715.00 men who underwent a fertility evaluation. BMI (kg/m2) was categorized as <18.50 (underweight), 18.50-24.90 (normal), 25.00-27.90 (overweight), and ≥28.00 (obese) kg/m2 for analysis. WHR was categorized as <0.81 (normal) and ≥0.81 (high). Semen volume, sperm concentration, progressive motility, and total motile sperm count were detected by experienced clinical technicians. Results: Spearman's correlation showed that BMI was weakly associated with sperm progressive motility (r = 0.076, P < 0.05), while WHR showed no relationship with semen parameters. The azoospermia rate was significantly higher (33.33% vs. 2.10%, P < 0.001) and the sperm concentration was lower (P < 0.05) in the underweight group. The nonlinear correlation analysis showed that BMI was negatively associated with sperm concentration while BMI was more than 22.40 kg/m2 (P < 0.05), while WHR was negatively related to sperm progressive motility within 0.82 to 0.89 (P < 0.05). Furthermore, the multivariate logistic analysis showed that follicular stimulating hormone (FSH) was an independent risk factor for normal sperm concentration (odds ratio [OR]: 0.791, P = 0.001) and morphology (OR: 0.821, P = 0.002), BMI was an independent risk factor for normal sperm progressive motility, and testosterone was an independent risk factor for sperm morphology (OR: 0.908, P = 0.023). Conclusion: BMI and WHR were significantly associated with semen parameters, while BMI was an independent risk factor for normal sperm progressive motility. Reproductive hormones, including FSH and testosterone, had a significant influence on sperm concentration and sperm morphology.
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Infertilidad Masculina , Semen , Humanos , Masculino , Análisis de Semen , Índice de Masa Corporal , Estudios Retrospectivos , Relación Cintura-Cadera , Infertilidad Masculina/etiología , Delgadez , Obesidad/complicaciones , Hormona Folículo Estimulante , TestosteronaRESUMEN
Abnormal body mass index (BMI) is associated with an increased risk of erectile dysfunction (ED). However, the relationship between different BMI categories and the levels of ED severity remains unclear. In the current study, 878 men from the andrology clinic in Central China were recruited. Erectile function was assessed by the International Index of Erectile Function (IIEF) scores. Questionnaires included questions about demographic characteristics (age, height, weight, educational status), lifestyle habits (drinking, smoking, sleep time), and medical history. Logistic regression was used to examine the association between ED risk and BMI. The incidence of ED was 53.1%. BMI was significantly higher in men from the ED group than in those from the non-ED group (P = 0.01). Compared with the normal weight group, obese men had a higher risk of ED (OR = 1.97, 95% CI = 1.25-3.14, P = 0.004), even after adjustment for potential confounders (OR = 1.78, 95% CI = 1.10-2.90, P = 0.02). Moreover, the positive correlation between obesity and moderate/severe ED severity was confirmed by logistic regression analysis (moderate/severe ED, OR = 2.71, 95% CI = 1.44-5.04, P = 0.002), even after adjusting for potential confounders (OR = 2.51 95% CI = 1.24-5.09, P = 0.01). Collectively, our findings indicate a positive correlation between obesity and the risk of moderate/severe ED. Clinicians could pay more attention to moderate/severe ED patients to maintain a healthy body weight to improve erectile function.
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Andrología , Disfunción Eréctil , Masculino , Humanos , Disfunción Eréctil/epidemiología , Disfunción Eréctil/etiología , Estudios Transversales , Índice de Masa Corporal , Obesidad/complicaciones , Obesidad/epidemiologíaRESUMEN
Erectile dysfunction is a common disease of the male reproductive system, which seriously affects the life quality of patients and their partners. At present, erectile dysfunction is considered as a social-psychological-physiological disease with complex etiology and various treatment methods. Oral PDE5I is the first-line treatment for erectile dysfunction with the advantages of high safety, good effect and non-invasiveness. But intracavernosal injection, hormonal replacement therapy, vacuum erection device, penile prosthesis implantation can also be alternative treatments for patients have organic erectile dysfunction or tolerance to PDE5I. With the rapid development of technologies, some new methods, such as low-intensity extracorporeal shock wave and stem cell injection therapy can even repair the organic damage of the corpora cavernosa. These are important directions for the treatment of male erectile dysfunction in the future. In this mini-review, we will introduce these therapies in detail.
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Disfunción Eréctil , Masculino , Humanos , Disfunción Eréctil/terapia , Disfunción Eréctil/etiología , Inhibidores de Fosfodiesterasa 5/efectos adversos , Resultado del TratamientoRESUMEN
The process of semen collection plays a key role in the quality of semen specimens. However, the association between semen collection time and semen quality is still unclear. In this study, ejaculates by masturbation from 746 subfertile men or healthy men who underwent semen analysis were examined. The median (interquartile range) semen collection time for all participants was 7.0 (5.0-11.0) min, and the median time taken for semen collection was lower in healthy men than that in subfertile men (6.0 min vs 7.0 min). An increase in the time required to produce semen samples was associated with poorer semen quality. Among those undergoing assisted reproductive technology (ART), the miscarriage rate was positively correlated with the semen collection time. After adjusting for confounders, the highest quartile (Q4) of collection time was negatively associated with semen volume and sperm concentration. A longer time to produce semen samples (Q3 and Q4) was negatively correlated with progressive and total sperm motility. In addition, there was a significant negative linear association between the semen collection time and the sperm morphology. Higher risks of asthenozoospermia (adjusted odds ratio [OR] = 2.06, 95% confidence interval [CI]: 1.31-3.25, P = 0.002) and teratozoospermia (adjusted OR = 1.98, 95% CI: 1.10-3.55, P = 0.02) were observed in Q3 than those in Q1. Our results indicate that a higher risk of abnormal semen parameter values was associated with an increase in time for semen collection, which may be related to male fertility through its association with semen quality.
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Astenozoospermia , Análisis de Semen , Masculino , Humanos , Semen , Motilidad Espermática , Recuento de Espermatozoides , EspermatozoidesRESUMEN
The lack of safe and efficient hydrogen storage is a major bottleneck for large-scale application of hydrogen energy. Reversible hydrogen storage of light-weight metal hydrides with high theoretical gravimetric and volumetric hydrogen density is one ideal solution but requires extremely high operating temperature with large energy input. Herein, taking MgH2 as an example, a concept is demonstrated to achieve solar-driven reversible hydrogen storage of metal hydrides via coupling the photothermal effect and catalytic role of Cu nanoparticles uniformly distributed on the surface of MXene nanosheets (Cu@MXene). The photothermal effect of Cu@MXene, coupled with the "heat isolator" role of MgH2 indued by its poor thermal conductivity, effectively elevates the temperature of MgH2 upon solar irradiation. The "hydrogen pump" effect of Ti and TiHx species that are in situ formed on the surface of MXene from the reduction of MgH2 , on the other hand, plays a catalytic role in effectively alleviating the kinetic barrier and hence decreasing the operating temperature required for reversible hydrogen adsorption and desorption of MgH2 . Based on the combination of photothermal and catalytic effect of Cu@MXene, a reversible hydrogen storage capacity of 5.9 wt% is achieved for MgH2 after 30 cycles using solar irradiation as the only energy source.
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Myocardium is an excitable tissue with electrical conductivity and mechanical strength. In this work, carbon fibers (CFs) and co-axial fibrous mesh were integrated which combined the high modulus and excellent electrical conductivity of CFs and the fibrous and porous structures of the electrospun fibers. The scaffold was fabricated by simply integrating coaxial electrospun fibers and carbon fibers through a freeze-drying procedure. It was shown that the integration of carbon fibers have the conductivity and Young's modulus of the fibrous mesh increased significantly, meanwhile, upregulated the expression of CX43, α-actinin, RhoA of the neonatal rat primary cardiomyocytes and primary human umbilical vein endothelial cells (HUVECs), and promoted the secretion of VEGF of HUVECs. Moreover, the cardiomyocytes grown on the scaffolds increased the ability of HUVECs migration. When implanted to the injury area post myocardial infraction, the scaffolds were able to effectively enhance the tissue regeneration and new vessel formation, which rescued the heart dysfunction induced by the myocardial infraction, evidenced by the results of echocardiography and histochemical analysis. In conclusion, the composite scaffolds could promote the myocardium regeneration and function's recovery by enhancing cardiomyocytes maturation and angiogenesis and establishing the crosstalk between the cardiomyocytes and the vascular endothelial cells.
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Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults. Due to the development of drug resistance to traditional chemotherapies and high relapse rate, AML still has a low survival rate and there is in an urgent need for better treatment strategies. CD123 is widely expressed by AML cells, also associated with the poor prognosis of AML. In this study, we fabricated nanomicelles loaded with a lab-designed CD123 antagonistic peptide, which were referred to as mPO-6. The antagonistic and therapeutic effects were investigated with CD123+ AML cell lines and a refractory AML mouse (AE and CKITD816V) model. Results show that mPO-6 can specifically bind to the CD123+ AML cells and inhibit the cell viability effectively. Intravenous administration of mPO-6 significantly reduces the percentage of AML cells' infiltration and prolongs the median survival of AML mice. Further, the efficiency of mPO-6 is demonstrated to interfere with the axis of CD123/IL-3 via regulating the activation of STAT5, PI3K/AKT, and NF-κB signaling pathways related to cell proliferation or apoptosis at the level of mRNA and protein in vivo and in vitro. In conclusion, the novel CD123 antagonistic peptide micelle formulation mPO-6 can significantly enhance apoptosis and prolong the survival of AML mice by effectively interfering with the axis of CD123/IL-3 and therefore is a promising therapeutic candidate for the treatment of refractory AML.
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Subunidad alfa del Receptor de Interleucina-3 , Leucemia Mieloide Aguda , Animales , Proliferación Celular , Interleucina-3/farmacología , Interleucina-3/uso terapéutico , Subunidad alfa del Receptor de Interleucina-3/metabolismo , Subunidad alfa del Receptor de Interleucina-3/uso terapéutico , Leucemia Mieloide Aguda/tratamiento farmacológico , Ratones , Fosfatidilinositol 3-QuinasasRESUMEN
Background: Homeodomain (HD) proteins contain an evolutionarily conserved helix-turn-helix (HTH) DNA-binding motif and act as transcription factors to control gene expression. A previous study showed that the HD gene Homez is highly enriched in adult testes. However, the role of HOMEZ in spermatogenesis and male fertility remains unknown. Methods: Using CRISPR/Cas9 technology, Homez mutant mice were generated and performed histological, immunofluorescence, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blot and mating assays to analyze the phenotype of Homez mutants. Results: Molecular phylogenetic analyses indicated that the HOMEZ is evolutionarily conserved among mammalian species. qRT-PCR and Western blot analyses showed that Homez is highly expressed in the testis, with a relatively increased expression trend during spermatogenesis. Homez mutant males were viable and showed no differences in body and testis weight compared to their wild-type. In addition, mating between Homez mutant males and wild-type females produced normal litter sizes. Moreover, histopathology detected complete spermatogenesis in the seminiferous tubules and mature spermatozoa in the epididymides from Homez knockout males. Furthermore, significantly increased transcription of three Zhx genes were found in Homez mutatnt testes compared with wild-type testes. Conclusions: Homez knockout mice are fertile and are not essential for germ cell development. These findings could prevent unnecessary duplicative work by other groups.
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Currently, the cryopreservation of human spermatozoa must overcome the adverse effects of excessive oxidation. In this study, we aimed to evaluate the effect of supplementation of cryopreservation medium with cyanidin-3-Ο-glucoside (C3G) on sperm quality. Semen samples were obtained from men with normozoospermia according to WHO criteria (n = 39). The sperm parameter values were compared after cryopreservation in medium supplemented with and without C3G.Compared with the control group (without additive), low doses (50 µM and 100 µM) of C3G improved sperm viability and motility and decreased the reactive oxygen species (ROS) of spermatozoa, while high doses (200 µM) of C3G did not obviously enhance sperm quality. The amount of DNA fragmentation index (DFI) and high DNA stainability (HDS) after freezing were higher in the control group than in the C3G supplementation groups. Low-concentration C3G supplementation (50 µM) was negatively correlated with sperm ROS levels (r = -0.2, p = 0.03). Collectively, our findings suggest that C3G could be an efficient semen cryoprotectant that ameliorates oxidative stress in human sperm during cryopreservation.