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Drought stress is a major constraint on crop development, potentially causing huge yield losses and threatening global food security. Improving Crop's stress tolerance is usually associated with a yield penalty. One way to balance yield and stress tolerance is modification specific gene by emerging precision genome editing technology. However, our knowledge of yield-related drought-tolerant genes is still limited. Foxtail millet (Setaria italica) has a remarkable tolerance to drought and is considered to be a model C4 crop that is easy to engineer. Here, we have identified 46 drought-responsive candidate genes by performing a machine learning-based transcriptome study on two drought-tolerant and two drought-sensitive foxtail millet cultivars. A total of 12 important drought-responsive genes were screened out by principal component analysis and confirmed experimentally by qPCR. Significantly, by investigating the haplotype of these genes based on 1844 germplasm resources, we found two genes (Seita.5G251300 and Seita.8G036300) exhibiting drought-tolerant haplotypes that possess an apparent advantage in 1000 grain weight and main panicle grain weight without penalty in grain weight per plant. These results demonstrate the potential of Seita.5G251300 and Seita.8G036300 for breeding drought-tolerant high-yielding foxtail millet. It provides important insights for the breeding of drought-tolerant high-yielding crop cultivars through genetic manipulation technology.
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Biología Computacional , Sequías , Regulación de la Expresión Génica de las Plantas , Aprendizaje Automático , Setaria (Planta) , Estrés Fisiológico , Setaria (Planta)/genética , Setaria (Planta)/crecimiento & desarrollo , Biología Computacional/métodos , Estrés Fisiológico/genética , Perfilación de la Expresión Génica/métodos , Genes de Plantas , Haplotipos/genética , Transcriptoma/genética , Proteínas de Plantas/genéticaRESUMEN
BACKGROUND: The treatment of the displaced proximal humerus fractures (PHF) still facing a lot of unsolved problems. The aim of this study was to evaluate the clinical effect of MultiLoc nails for the treatment of PHF and present outcomes of patients with different Neer's classification and reduction quality. METHODS: Adult patients with PHFs were recruited and treated with MultiLoc nail. Intraoperative data, radiographic and functional outcomes, as well as occurrence of postoperative complications were assessed. RESULTS: 48 patients met inclusion and exclusion criteria and were included in this study. The DASH Score were 32.2 ± 3.1 points at 12 months, and 37.3 ± 2.5 points at the final follow-up. The mean ASES score at 12 months and final follow-up were 74.4 ± 6.2 and 78.8 ± 5.1, respectively. The mean CM Score in all 48 patients reached 68 ± 6.4 points at the final follow-up, relative side related CM Score 75.2 ± 7.7% of contralateral extremity. The incidence rate of complications was 20.8%. Patients with fracture mal-union, adhesive capsulitis were observed but no secondary surgeries were performed. There was no significantly difference of DASH Score 12 months after surgery and at the last follow-up among patients with different Neer's classification or reduction quality. However, functional outcomes such as ASES score and CM score were significantly influenced by severity of fracture and the quality of fracture reduction. CONCLUSIONS: Our study demonstrated that MultiLoc nails is well suited for proximal humeral fractures, with satisfactory health status recovery, good radiographic results, positive clinical outcomes and low rates of complications. The treatment for four part PHF still faces great challenges. Accurate fracture reduction was an important factor for good functional result.
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Clavos Ortopédicos , Fijación Intramedular de Fracturas , Complicaciones Posoperatorias , Fracturas del Hombro , Humanos , Fracturas del Hombro/cirugía , Fracturas del Hombro/diagnóstico por imagen , Masculino , Femenino , Persona de Mediana Edad , Fijación Intramedular de Fracturas/métodos , Fijación Intramedular de Fracturas/instrumentación , Fijación Intramedular de Fracturas/efectos adversos , Anciano , Resultado del Tratamiento , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Adulto , Estado de Salud , Estudios de Seguimiento , Radiografía , Estudios RetrospectivosRESUMEN
BACKGROUND: Previous research has identified a significant role of Thioredoxin-interacting protein (TXNIP) in bone loss. The purpose of this investigation was to assess the role and the underlying molecular mechanisms of TXNIP in the osteogenic differentiation of human bone marrow stromal cells (hBMSCs) and pre-osteoblast MC3T3-E1 cells. METHODS: Human bone marrow stem cells (hBMSCs) and MC3T3-E1 cells were used to induce osteogenic differentiation. The expression of genes and proteins was assessed using RT-qPCR and western blot, respectively. ChIP assay was used to validate the interaction between genes. The osteogenic differentiation ability of cells was reflected using ALP staining and detection of ALP activity. The mineralization ability of cells was assessed using ARS staining. DCFCA staining was employed to evaluate the intracellular ROS level. RESULTS: Initially, downregulation of TXNIP and upregulation of EZH2 were observed during osteogenesis in hBMSCs and MC3T3-E1 cells. Additionally, it was discovered that EZH2 negatively regulates TXNIP expression in these cells. Furthermore, experiments indicated that the knockdown of TXNIP stimulated the activation of the PI3K/AKT/Nrf2 signaling pathway in hBMSCs and MC3T3- E1 cells, thus inhibiting the production of reactive oxygen species (ROS). Further functional experiments revealed that overexpression of TXNIP inhibited the osteogenic differentiation in hBMSCs and MC3T3-E1 cells by enhancing ROS produc-tion. On the other hand, knockdown of TXNIP promoted the osteogenic differentiation capacity of hBMSCs and MC3T3-E1 cells through the activation of the PI3K/AKT/Nrf2 pathway. CONCLUSION: In conclusion, this study demonstrated that TXNIP expression, under the regulation of EZH2, plays a crucial role in the osteogenic differentiation of hBMSCs and MC3T3-E1 cells by regulating ROS production and the PI3K/AKT/Nrf2 pathway.
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Proteínas Portadoras , Diferenciación Celular , Proteína Potenciadora del Homólogo Zeste 2 , Células Madre Mesenquimatosas , Factor 2 Relacionado con NF-E2 , Osteogénesis , Estrés Oxidativo , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Factor 2 Relacionado con NF-E2/metabolismo , Humanos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteína Potenciadora del Homólogo Zeste 2/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Portadoras/metabolismo , Animales , Ratones , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/citología , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Especies Reactivas de Oxígeno/metabolismo , TiorredoxinasRESUMEN
Photodynamic Therapy (PDT) is recognized for its exceptional effectiveness as a promising cancer treatment method. However, it is noted that overexposure to the dosage and sunlight in traditional PDT can result in damage to healthy tissues, due to the low tumor selectivity of currently available photosensitizers (PSs). To address this challenge, we introduce herein a new strategy where the small molecule-targeted agent, erlotinib, is integrated into a boron dipyrromethene (BODIPY)-based PS to form conjugate 6 to enhance the precision of PDT. This conjugate demonstrates optical absorption, fluorescence emission, and singlet oxygen generation efficiency comparable to the reference compound 7, which lacks erlotinib. In vitro studies reveal that, after internalization, conjugate 6 predominantly accumulates in the lysosomes of HepG2 cells, exhibiting significant photocytotoxicity with an IC50 value of 3.01 µM. A distinct preference for HepG2 cells over HELF cells is observed with conjugate 6 but not with compound 7. In vivo experiments further confirm that conjugate 6 has a specific affinity for tumor tissues, and the combination treatment of conjugate 6 with laser illumination can effectively eradicate H22 tumors in mice with outstanding biosafety. This study presents a novel and potential PS for achieving precise PDT against cancer.
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Clorhidrato de Erlotinib , Neoplasias Hepáticas , Fotoquimioterapia , Fármacos Fotosensibilizantes , Porfobilinógeno , Humanos , Fotoquimioterapia/métodos , Animales , Ratones , Porfobilinógeno/análogos & derivados , Porfobilinógeno/química , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/química , Células Hep G2 , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Clorhidrato de Erlotinib/farmacología , Clorhidrato de Erlotinib/química , Compuestos de Boro/química , Compuestos de Boro/farmacologíaRESUMEN
This study aimed to provide data for the clinical features of invasive pneumococcal disease (IPD) and the molecular characteristics of Streptococcus pneumoniae isolates from paediatric patients in China. We conducted a multi-centre prospective study for IPD in 19 hospitals across China from January 2019 to December 2021. Data of demographic characteristics, risk factors for IPD, death, and disability was collected and analysed. Serotypes, antibiotic susceptibility, and multi-locus sequence typing (MLST) of pneumococcal isolates were also detected. A total of 478 IPD cases and 355 pneumococcal isolates were enrolled. Among the patients, 260 were male, and the median age was 35 months (interquartile range, 12-46 months). Septicaemia (37.7%), meningitis (32.4%), and pneumonia (27.8%) were common disease types, and 46 (9.6%) patients died from IPD. Thirty-four serotypes were detected, 19F (24.2%), 14 (17.7%), 23F (14.9%), 6B (10.4%) and 19A (9.6%) were common serotypes. Pneumococcal isolates were highly resistant to macrolides (98.3%), tetracycline (94.1%), and trimethoprim/sulfamethoxazole (70.7%). Non-sensitive rates of penicillin were 6.2% and 83.3% in non-meningitis and meningitis isolates. 19F-ST271, 19A-ST320 and 14-ST876 showed high resistance to antibiotics. This multi-centre study reports the clinical features of IPD and demonstrates serotype distribution and antibiotic resistance of pneumococcal isolates in Chinese children. There exists the potential to reduce IPD by improved uptake of pneumococcal vaccination, and continued surveillance is warranted.
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Antibacterianos , Tipificación de Secuencias Multilocus , Infecciones Neumocócicas , Serogrupo , Streptococcus pneumoniae , Preescolar , Femenino , Humanos , Lactante , Masculino , Antibacterianos/farmacología , China/epidemiología , Pueblos del Este de Asia , Hospitales/estadística & datos numéricos , Pruebas de Sensibilidad Microbiana , Infecciones Neumocócicas/microbiología , Infecciones Neumocócicas/epidemiología , Infecciones Neumocócicas/mortalidad , Estudios Prospectivos , Factores de Riesgo , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/efectos de los fármacos , Streptococcus pneumoniae/clasificación , Streptococcus pneumoniae/aislamiento & purificaciónRESUMEN
The exploration of two-dimensional (2D) wide-band-gap semiconductors (WBGSs) holds significant scientific and technological importance in the field of condensed matter physics and is actively being pursued in optoelectronic research. In this study, we present the discovery of a novel WBGS, namely monolayer BiSnO3, using first-principles calculations in conjunction with the quasi-particle G0W0approximation. Our calculations confirm that monolayer BiSnO3exhibits moderate cleavage energy, positive phonon modes, mechanical resilience, and high temperature resistance (up to 1000 K), which demonstrate its structural stability, flexibility, and potential for experimental realization. Furthermore, band-structure calculations reveal that monolayer BiSnO3is a typical WBGS material with a band-gap energy (Eg) of 3.61 eV and possesses a unique quasi-direct electronic feature due to its quasi-flat valence band. The highest occupied valence flat-band originates from the electronic hybridization between Bi-6pand O-2pstates, which are in close proximity to the Fermi level. Remarkably, monolayer BiSnO3exhibits a high absorption capacity for ultraviolet light spanning the UVA to UVC regions, displaying optical isotropy absorption and an unusual excitonic effect. These intriguing structural and electronic properties establish monolayer BiSnO3as a promising candidate for the development of new multi-function-integrated electronic and optoelectronic devices in the emerging field of 2D WBGSs.
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OBJECTIVES: To investigate the clinical characteristics and prognosis of pneumococcal meningitis (PM), and drug sensitivity of Streptococcus pneumoniae (SP) isolates in Chinese children. METHODS: A retrospective analysis was conducted on clinical information, laboratory data, and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country. RESULTS: Among the 160 children with PM, there were 103 males and 57 females. The age ranged from 15 days to 15 years, with 109 cases (68.1%) aged 3 months to under 3 years. SP strains were isolated from 95 cases (59.4%) in cerebrospinal fluid cultures and from 57 cases (35.6%) in blood cultures. The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87) and 27% (21/78), respectively. Fifty-five cases (34.4%) had one or more risk factors for purulent meningitis, 113 cases (70.6%) had one or more extra-cranial infectious foci, and 18 cases (11.3%) had underlying diseases. The most common clinical symptoms were fever (147 cases, 91.9%), followed by lethargy (98 cases, 61.3%) and vomiting (61 cases, 38.1%). Sixty-nine cases (43.1%) experienced intracranial complications during hospitalization, with subdural effusion and/or empyema being the most common complication [43 cases (26.9%)], followed by hydrocephalus in 24 cases (15.0%), brain abscess in 23 cases (14.4%), and cerebral hemorrhage in 8 cases (5.0%). Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old, with rates of 91% (39/43) and 83% (20/24), respectively. SP strains exhibited complete sensitivity to vancomycin (100%, 75/75), linezolid (100%, 56/56), and meropenem (100%, 6/6). High sensitivity rates were also observed for levofloxacin (81%, 22/27), moxifloxacin (82%, 14/17), rifampicin (96%, 25/26), and chloramphenicol (91%, 21/23). However, low sensitivity rates were found for penicillin (16%, 11/68) and clindamycin (6%, 1/17), and SP strains were completely resistant to erythromycin (100%, 31/31). The rates of discharge with cure and improvement were 22.5% (36/160) and 66.2% (106/160), respectively, while 18 cases (11.3%) had adverse outcomes. CONCLUSIONS: Pediatric PM is more common in children aged 3 months to under 3 years. Intracranial complications are more frequently observed in children under 1 year old. Fever is the most common clinical manifestation of PM, and subdural effusion/emphysema and hydrocephalus are the most frequent complications. Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates. Adverse outcomes can be noted in more than 10% of PM cases. SP strains are high sensitivity to vancomycin, linezolid, meropenem, levofloxacin, moxifloxacin, rifampicin, and chloramphenicol.
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Empiema , Hidrocefalia , Meningitis Neumocócica , Efusión Subdural , Lactante , Femenino , Masculino , Humanos , Niño , Recién Nacido , Adolescente , Meningitis Neumocócica/tratamiento farmacológico , Meningitis Neumocócica/epidemiología , Meropenem , Vancomicina , Levofloxacino , Linezolid , Moxifloxacino , Estudios Retrospectivos , Rifampin , Streptococcus pneumoniae , CloranfenicolRESUMEN
Periodontitis is a prevalent oral inflammatory disease that can result in tooth loss and is closely linked to type 2 diabetes (T2D). In this study, we analyzed the salivary proteome and intact N-glycopeptides (IGPs) of individuals with mild-moderate, severe, aggressive periodontitis, and periodontitis with T2D, including those treated with antidiabetic drugs, to identify specific signatures associated with the disease. Our results revealed that salivary proteins and glycoproteins were altered in all periodontitis groups (PRIDE ID: 1-20230612-72345), with fucose- and sialic acid-containing N-glycans showing the greatest increase. Additionally, differentially expressed proteins were classified into 9 clusters, including those that were increased in all periodontitis groups and those that were only altered in certain types of periodontitis. Interestingly, treatment with antidiabetic drugs reversed many of the changes observed in the salivary proteome and IGPs in T2D-related periodontitis, suggesting a potential therapeutic approach for managing periodontitis in patients with T2D. Consistent with MS/MS results, the expression of salivary IGHA2 and Fucα1-3/6GlcNAc (AAL) was significantly increased in MP. These findings provide new insights into the pathogenesis of periodontitis and highlight the potential of salivary biomarkers for diagnosis, prognosis, and monitoring of disease progression and treatment response.
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Diabetes Mellitus Tipo 2 , Periodontitis , Humanos , Proteoma/genética , Proteoma/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Glicopéptidos/metabolismo , Espectrometría de Masas en Tándem , Biomarcadores/metabolismo , Hipoglucemiantes , Saliva/metabolismoRESUMEN
Organic semiconductor materials featuring lightweight, and flexibility may play a significant role in various future applications, such as foldable displays, wearable devices, and artificial skin. For developing high-performance organic devices, organic crystals are highly desired, while a remaining fundamental issue is their contact problem. Here, we have grown a high-quality rubrene single crystal by utilizing a simple in-air sublimation technique. The contact characteristics (barrier height and contact resistance) are detail-studied by resist-free transfer electrodes (Au metal or graphene/Au). The Schottky barrier of the rubrene/graphene interface is lower and can be also modulated by gate bias, which is confirmed by spatial photocurrent mapping. Finally, we demonstrated the zero-bias photocurrent imaging application by constructing the asymmetrical device employing different electrode contacts. Our work would be of significance for studying the contact issue of organic crystals and wireless imaging.
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BACKGROUND: Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) represent an effective and promising strategy for periodontitis, although studies remain pre-clinical. Herein, a meta-analysis was conducted to assess the efficacy of MSC-EVs in animal models of periodontitis. METHODS: The PubMed, Web of Science, and Embase electronic databases were searched up to Dec 2022 to retrieve preclinical studies examining the use of MSC-EVs for periodontitis treatment. Meta-analyses and sub-group analyses were performed to assess the effect of MSC-EVs on Bone Volume/Total Volume (BV/TV) or the distance between the cementoenamel junction and alveolar bone crest (CEJ-ABC) in pre-clinical animal models of periodontitis. RESULTS: 11 studies published from Mar 2019 to Oct 2022 met the inclusion criteria. Overall, MSC-EVs contributed to periodontal bone regeneration in the inflammatory bone loss area due to periodontitis, as represented by a weighted mean difference (WMD) of 14.07% (95% CI = 6.73, 21.41%, p < 0.001) for BV/TV and a WMD of -0.12 mm (95% CI= -0.14, -0.11 mm, p < 0.001) for CEJ-ABC. However, sub-analysis suggested that there was no significant difference in CEJ-ABC between studies with bioactive scaffolds and studies without bioactive scaffolds (p = 0.60). CONCLUSIONS: The present study suggests that MSC-EVs may represent an attractive therapy for the treatment of inflammatory bone loss within periodontitis.
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Vesículas Extracelulares , Células Madre Mesenquimatosas , Periodontitis , Animales , Regeneración Ósea , Modelos Animales de Enfermedad , Periodontitis/terapiaRESUMEN
Chondrocyte degeneration and classically activated macrophage (AM)-related inflammation play critical roles in osteoarthritis (OA). Here, we explored the effects of astaxanthin and Rspo2 on OA in vitro and in vivo. We observed that the Rspo2 gene was markedly elevated in synovial tissues of OA patients compared with healthy controls. In 2D cultures, Rspo2 and inflammatory factors were enhanced in AMs compared with nonactivated macrophages (NMs), and the protein expression levels of Rspo2, ß-catenin, and inflammatory factors were increased, and anabolic markers were reduced in osteoarthritic chondrocytes (OACs) compared to normal chondrocytes (NCs). Astaxanthin reversed these changes in AMs and OACs. Furthermore, Rspo2 shRNA significantly abolished inflammatory factors and elevated anabolic markers in OACs. In NCs cocultured with AM, and in OACs cocultured with AMs or NMs, astaxanthin reversed these changes in these coculture systems and promoted secretion of Rspo2, ß-catenin and inflammatory factors and suppressed anabolic markers compared to NCs or OACs cultured alone. In AMs, coculture with NCs resulted in a slight elevation of Rspo2 and AM-related genes, but not protein expression, compared to culture alone, but when cocultured with OACs, these inflammatory mediators were significantly enhanced at both the gene and protein levels. Astaxanthin reversed these changes in all the groups. In vivo, we observed a deterioration in cartilage quality after intra-articular injection of Rspo2 associated with medial meniscus (DMM)-induced instability in the OA group, and astaxanthin was protective in these groups. Our results collectively revealed that astaxanthin attenuated the process of OA by abolishing Rspo2 both in vitro and in vivo.
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Condrocitos , Osteoartritis , Humanos , Condrocitos/metabolismo , beta Catenina/genética , beta Catenina/metabolismo , Osteoartritis/genética , Osteoartritis/prevención & control , Osteoartritis/metabolismo , Vía de Señalización Wnt , Macrófagos/metabolismo , Células CultivadasRESUMEN
The idea that energy taxes and innovation may contribute to lowering greenhouse gas emissions and fostering the development of a more sustainable energy future is gaining popularity. Therefore, the study's main goal is to explore the asymmetric impact of energy taxes and innovation on CO2 emissions in China by employing linear and nonlinear ARDL econometric methods. The outcomes of the linear model demonstrate that long-term increases in energy taxes, energy technological innovation, and financial development cause CO2 emissions to reduce, while increases in economic development cause CO2 emissions to climb. Similarly, energy taxes and energy technological innovation cause CO2 emissions to fall in the short run, while financial development promotes CO2 emissions. On the other hand, in the nonlinear model, the positive energy changes, positive energy innovation changes, financial development, and human capital help reduce the long-run CO2 emissions, and economic development increase the CO2 emissions. In the short run, the positive energy and innovation changes are negatively and significantly connected to CO2 emissions, while financial development is positively linked to CO2 emissions. The negative energy innovation changes are insignificant in both the short and long run. Therefore, Chinese policymakers should try to promote energy taxes and innovations as tools to achieve green sustainability.
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Dióxido de Carbono , Desarrollo Económico , Energía Renovable , Desarrollo Sostenible , Impuestos , Dióxido de Carbono/análisis , China , Energía Renovable/economía , Impuestos/economía , Desarrollo Sostenible/economíaRESUMEN
OBJECTIVES: To develop a risk prediction model for severe adenovirus pneumonia (AVP) in children, and to explore the appropriate timing for intravenous immunoglobulin (IVIG) therapy for severe AVP. METHODS: Medical data of 1 046 children with AVP were retrospectively analyzed, and a risk prediction model for severe AVP was established using multivariate logistic regression. The model was validated with 102 children with AVP. Then, 75 children aged ≤14 years who were considered at risk of developing severe AVP by the model were prospectively enrolled and divided into three groups (A, B and C) in order of visit, with 25 children in each group. Group A received symptomatic supportive therapy only. With the exception of symptomatic supportive therapy, group B received IVIG treatment at a dose of 1g/(kg·d) for 2 consecutive days, before progressing to severe AVP. With the exception of symptomatic supportive therapy, group C received IVIG treatment at a dose of 1 g/(kg·d) for 2 consecutive days after progressing to severe AVP. Efficacy and related laboratory indicators were compared among the three groups after treatment. RESULTS: Age<18.5 months, underlying diseases, fever duration >6.5 days, hemoglobin level <84.5 g/L, alanine transaminase level >113.5 U/L, and co-infection with bacteria were the six variables that entered into the risk prediction model for severe AVP. The model had an area under the receiver operating characteristic curve of 0.862, sensitivity of 0.878, and specificity of 0.848. The Hosmer-Lemeshow test showed good consistency between the predicted values and the actual observations (P>0.05). After treatment, group B had the shortest fever duration and hospital stay, the lowest hospitalization costs, the highest effective rate of treatment, the lowest incidence of complications, the lowest white blood cell count and interleukin (IL)-1, IL-2, IL-6, IL-8, IL-10 levels, and the highest level of tumor necrosis factor alpha (P<0.05). CONCLUSIONS: The risk model for severe AVP established in this study has good value in predicting the development of severe AVP. IVIG therapy before progression to severe AVP is more effective in treating AVP in children.
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Infecciones por Adenoviridae , Neumonía Viral , Niño , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Estudios Prospectivos , Estudios Retrospectivos , Infecciones por Adenoviridae/tratamiento farmacológico , Neumonía Viral/tratamiento farmacológico , AdenoviridaeRESUMEN
BACKGROUND: Spermatozoa have the task of delivering an intact paternal genome to the oocyte and supporting successful embryo development. The detection of sperm DNA fragmentation (SDF) has been emerging as a complementary test to conventional semen analysis for male infertility evaluation, but the mechanism leading to SDF and its impact on assisted reproduction remain unclear. Therefore, the study identified and analyzed the differentially expressed proteins of sperm with high and low SDF. METHODS: Semen samples from men attended the infertility clinic during June 2020 and August 2020 were analyzed, and sperm DNA fragmentation index (DFI) was detected by the sperm chromatin structure assay. Semen samples with low DFI (< 30%, control group) and high DFI (≥ 30%, experimental group) were optimized by density gradient centrifugation (DGC), and the differentially expressed proteins of obtained sperm were identified by the Sequential Window Acquisition of All Theoretical Mass Spectra Mass Spectrometry (SWATH-MS) and performed GO and KEGG analysis. RESULTS: A total of 2186 proteins were identified and 1591 proteins were quantified, of which 252 proteins were identified as differentially expressed proteins, including 124 upregulated and 128 downregulated. These differentially expressed proteins were involved in metabolic pathways, replication/recombination/repair, acrosomal vesicles, kinase regulators, fertilization, tyrosine metabolism, etc. Western blotting results showed that the expression levels of RAD23B and DFFA proteins and the levels of posttranslational ubiquitination and acetylation modifications in the experimental group were significantly higher than those in the control group, which was consistent with the results of proteomics analysis. CONCLUSIONS: Proteomic markers of sperm with high DNA fragmentation can be identified by the SWATH-MS and bioinformatic analysis, and new protein markers and posttranslational modifications related to sperm DNA damage are expected to be intensively explored. Our findings may improve our understanding of the basic molecular mechanism of sperm DNA damage.
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RESEARCH QUESTION: What are the molecular mechanisms leading to human sperm DNA damage? DESIGN: Semen samples were collected and the sperm DNA fragmentation index (DFI) was assessed. Differentially expressed RNA in spermatozoa with a high (DFI ≥30%, experimental group) or normal (DFI <30%, control group) DFI were identified by RNA-sequencing (RNA-seq) technology, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was performed. Three differentially expressed RNA related to sperm DNA damage and repair, namely PMS1, TP53BP1 and TLK2, were validated using real-time quantitative (RT-qPCR). RESULTS: A total of 19,970 expressed RNA were detected in the two groups. Compared with the control group, the expression levels of 189 RNA in the experimental group were significantly increased and those of 163 genes decreased. Gene Ontology enrichment analysis showed that these RNA were mainly concentrated in the ATPase-dependent transmembrane transport complex, extracellular exosome, somatic cell DNA recombination, protein binding, cytoplasm and regulation of localization. KEGG pathway analysis showed that these RNA were mainly related to the PI3K-Akt signalling pathway, endocytosis, p53 signalling pathway and cGMP-PKG signalling pathway. The RT-qPCR results showed that the expression levels of PMS1, TP53BP1 and TLK2 in the experimental group were significantly lower than in the control group (Pâ¯=â¯0.01, 0.015 and 0.004, respectively), which was identical to the results of RNA sequencing. CONCLUSIONS: Differentially expressed RNA related to sperm DNA damage and repair may be identified by RNA-seq technology, which provides new insights into the understanding of sperm DNA damage and repair, and will help to discover new biomarkers related to sperm DNA damage.
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Fosfatidilinositol 3-Quinasas , Semen , Humanos , Masculino , RNA-Seq , Fosfatidilinositol 3-Quinasas/metabolismo , Espermatozoides/metabolismo , Daño del ADN , Perfilación de la Expresión Génica , Análisis de Secuencia de ARN , ARN/genética , Fragmentación del ADNRESUMEN
Increasing Investigations show that photosensitizers (PSs) which target mitochondria are useful for enhancing photodynamic therapy (PDT) efficacy. Herein, we carefully designed and synthesized four triphenylphosphonium (TPP)-modified boron dipyrromethene (BDP)-based PSs through Cu(I)-assisted "3+2" cycloaddition reaction. All of them exhibit intense red light absorption with maxima between 659 and 663â nm, considerable fluorescence emission with quantum yields of 0.16-0.23, high singlet oxygen generation efficiency ranging from 0.22 to 0.34, excellent mitochondria-targeting ability, and good biocompatibility. Upon illumination, they induce significant cancer cell death through a mitochondria-related apoptosis pathway. The IC50 values of these BDP dyes against MCF-7 cells were determined to be as low as 0.046-0.113â µM under rather low dosage of light irradiation (1.5â J â cm-2 ).
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Fotoquimioterapia , Fármacos Fotosensibilizantes , Boro/metabolismo , Colorantes/metabolismo , Mitocondrias/metabolismo , Fármacos Fotosensibilizantes/farmacología , Porfobilinógeno/análogos & derivados , Oxígeno Singlete/metabolismoRESUMEN
Objective: This study aimed to explore the impact of the sperm DNA fragmentation index (DFI) on the clinical outcomes in women undergoing artificial insemination by husband intrauterine insemination (AIH-IUI). Methods: In this retrospective study, the value of sperm DFI was detected by sperm chromatin structure assay (SCSA) in a semen analysis collected before fertility treatment (basal DFI) in 1,500 IUI cycles at the infertility clinic of Northern Jiangsu People's Hospital Reproductive Medicine Center from Jan 2016 to April 2021. Receiver operating characteristic (ROC) curves were used to calculate the cut-off value for the clinical outcomes of IUI, including the biochemical pregnancy rate, clinical pregnancy rate, delivery rate, and live birth rate, and multivariate logistic regression was conducted to analyse the risk factors for clinical outcomes after IUI. Result: In 1,500 IUI cycles, the results showed that there were no statistically significant differences between the normal DFI group and the abnormal DFI group in biochemical pregnancy rate (14.41% vs. 11.3%, P = 0.386), clinical pregnancy rate (12.9% vs. 10.5%, P = 0.433), delivery rate (11.0% vs. 8.9%, P = 0.456), live birth rate (10.9% vs. 8.9%, P = 0.484) or pregnancy loss rate (14.6% vs. 15.4%, P = 1.000). Conclusion: Sperm DFI alone may have limited predictive power for IUI clinical outcomes.
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Cromatina , Semen , Fragmentación del ADN , Femenino , Humanos , Inseminación Artificial/métodos , Masculino , Embarazo , Estudios Retrospectivos , EspermatozoidesRESUMEN
Purpose: To evaluate the effect of elevated sperm DNA fragmentation index (DFI) on fresh and frozen embryo transfer cycles. Methods: A retrospective study was performed with 549 fresh embryo transfer cycles and 1340 frozen embryo transfer cycles after in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) from 2016 to 2021. Results: The statistical results of 549 fresh embryo transfer cycles showed that the delivery rate in the normal sperm DFI group (43.9% vs. 27.1%, P = 0.014) was significantly higher than that in the abnormal sperm DFI group, and there were no significant differences in the biochemical pregnancy rate (59.0% vs. 50.8%, P = 0.232), clinical pregnancy rate (53.1% vs. 40.7%, P = 0.072), or miscarriage rate (17.3% vs. 33.3%, P = 0.098) between the two groups. The results of 1340 frozen embryo transfer cycles showed that the biochemical pregnancy rate (57.9% vs. 45.6%, P = 0.006) and clinical pregnancy rate (50.3% vs. 40.7%, P = 0.027) in the normal sperm DFI group were significantly higher than those in the abnormal sperm DFI group. The delivery rate (40.9% vs. 33.3%, P = 0.074) and miscarriage rate (18.6% vs. 18.0%, P = 0.919) were not significantly different between the two groups. Conclusion: The increase of sperm DFI significantly reduced the delivery rate of fresh embryo transfer cycles and the biochemical pregnancy rate and clinical pregnancy rate of frozen embryo transfer cycles.
Asunto(s)
Aborto Espontáneo , Aborto Espontáneo/epidemiología , Fragmentación del ADN , Transferencia de Embrión , Femenino , Fertilización In Vitro , Humanos , Masculino , Embarazo , Estudios Retrospectivos , Semen , EspermatozoidesRESUMEN
Invasive Salmonella infections result in a significant burden of disease including morbidity, mortality, and financial cost in many countries. Besides typhoid fever, the clinical impact of non-typhoid Salmonella infections is increasingly recognized with the improvement of laboratory detection capacity and techniques. A retrospective multicenter study was conducted to analyze the clinical profiles and antimicrobial resistance patterns of invasive Salmonella infections in hospitalized children in China during 2016-2018. A total of 130 children with invasive Salmonella infections were included with the median age of 12 months (range: 1-144 months). Seventy-nine percent of cases occurred between May and October. Pneumonia was the most common comorbidity in 33 (25.4%) patients. Meningitis and septic arthritis caused by nontyphoidal Salmonella (NTS) infections occurred in 12 (9.2%) patients and 5 (3.8%) patients. Patients < 12 months (OR: 16.04) and with septic shock (OR: 23.4), vomit (OR: 13.33), convulsion (OR: 15.86), C-reactive protein (CRP) ≥ 40 g/L (OR: 5.56), and a higher level of procalcitonin (PCT) (OR: 1.05) on admission were statistically associated to an increased risk of developing meningitis. Compared to 114 patients with NTS infections, 16 patients with typhoid fever presented with higher levels of CRP and PCT (P < 0.05). The rates of resistance to ampicillin, sulfamethoxazole/trimethoprim, ciprofloxacin, and ceftriaxone among Salmonella Typhi and NTS isolates were 50% vs 57.3%, 9.1% vs 24.8%, 0% vs 11.2%, and 0% vs 9.9%, respectively. NTS has been the major cause of invasive Salmonella infections in Chinese children and can result in severe diseases. Antimicrobial resistance among NTS was more common.
Asunto(s)
Infecciones por Salmonella , Fiebre Tifoidea , Ampicilina , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Proteína C-Reactiva , Ceftriaxona , Niño , Preescolar , China/epidemiología , Ciprofloxacina , Farmacorresistencia Bacteriana , Humanos , Lactante , Pruebas de Sensibilidad Microbiana , Polipéptido alfa Relacionado con Calcitonina , Salmonella , Infecciones por Salmonella/epidemiología , Infecciones por Salmonella/microbiología , Combinación Trimetoprim y Sulfametoxazol , Fiebre Tifoidea/tratamiento farmacológicoRESUMEN
Plasmon-enhanced light-matter interactions have been widely investigated in the past decades. Here, we report surface plasmon-enhanced structural dynamics in multi-walled carbon nanotubes. The optical polarization dependent dynamic properties of multi-walled carbon nanotubes are investigated using ultrafast transmission electron microscopy. Lattice contractions in the femtosecond time regime are observed upon excitation of the azimuthal plasmon by light polarized perpendicular to the tubular axis. The polarization dependence of the plasmon near field was examined using photon-induced near-field electron microscopy. The lattice changes resulting from the azimuthal plasmon enhance ultrafast alterations in both localized evanescent fields and the collective charge excitation, which play critical roles governing the light-matter interaction. These results suggest that the ultrafast responses of lattice degrees of freedom in nanomaterials could be essential for understanding the mechanism of surface plasmon enhanced effects.