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Hypothetical chloroplast open reading frames (ycfs) are putative genes in the plastid genomes of photosynthetic eukaryotes. Many ycfs are also conserved in the genomes of cyanobacteria, the presumptive ancestors of present-day chloroplasts. The functions of many ycfs are still unknown. Here, we generated knock-out mutants for ycf51 (sll1702) in the cyanobacterium Synechocystis sp. PCC 6803. The mutants showed reduced photoautotrophic growth due to impaired electron transport between photosystem II (PSII) and PSI. This phenotype results from greatly reduced PSI content in the ycf51 mutant. The ycf51 disruption had little effect on the transcription of genes encoding photosynthetic complex components and the stabilization of the PSI complex. In vitro and in vivo analyses demonstrated that Ycf51 cooperates with PSI assembly factor Ycf3 to mediate PSI assembly. Furthermore, Ycf51 interacts with the PSI subunit PsaC. Together with its specific localization in the thylakoid membrane and the stromal exposure of its hydrophilic region, our data suggest that Ycf51 is involved in PSI complex assembly. Ycf51 is conserved in all sequenced cyanobacteria, including the earliest branching cyanobacteria of the Gloeobacter genus, and is also present in the plastid genomes of glaucophytes. However, Ycf51 has been lost from other photosynthetic eukaryotic lineages. Thus, Ycf51 is a PSI assembly factor that has been functionally replaced during the evolution of oxygenic photosynthetic eukaryotes.
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Proteínas Bacterianas , Sistemas de Lectura Abierta , Complejo de Proteína del Fotosistema I , Synechocystis , Complejo de Proteína del Fotosistema I/metabolismo , Complejo de Proteína del Fotosistema I/genética , Synechocystis/genética , Synechocystis/metabolismo , Sistemas de Lectura Abierta/genética , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Cloroplastos/metabolismo , Fotosíntesis/genética , Tilacoides/metabolismo , Complejo de Proteína del Fotosistema II/metabolismo , Complejo de Proteína del Fotosistema II/genética , MutaciónRESUMEN
The modern pattern of the Asian monsoon is thought to have formed around the Oligocene/Miocene transition and is generally attributed to Himalaya-Tibetan Plateau (H-TP) uplift. However, the timing of the ancient Asian monsoon over the TP and its response to astronomical forcing and TP uplift remains poorly known because of the paucity of well-dated high-resolution geological records from the TP interior. Here, we present a precession-scale cyclostratigraphic sedimentary section of 27.32 to 23.24 million years ago (Ma) during the late Oligocene epoch from the Nima Basin to show that the South Asian monsoon (SAM) had already advanced to the central TP (32°N) at least by 27.3 Ma, which is indicated by cyclic arid-humid fluctuations based on environmental magnetism proxies. A shift of lithology and astronomically orbital periods and amplified amplitude of proxy measurements as well as a hydroclimate transition around 25.8 Ma suggest that the SAM intensified at ~25.8 Ma and that the TP reached a paleoelevation threshold for enhancing the coupling between the uplifted plateau and the SAM. Orbital short eccentricity-paced precipitation variability is argued to be mainly driven by orbital eccentricity-modulated low-latitude summer insolation rather than glacial-interglacial Antarctic ice sheet fluctuations. The monsoon data from the TP interior provide key evidence to link the greatly enhanced tropical SAM at 25.8 Ma with TP uplift rather than global climate change and suggest that SAM's northward expansion to the boreal subtropics was dominated by a combination of tectonic and astronomical forcing at multiple timescales in the late Oligocene epoch.
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IFN-γ is a pleiotropic cytokine that plays a controversial role in regulatory T cell (Treg) activity. In this study, we sought to understand how IFN-γ receptor (IFN-γR) signaling affects donor Tregs following allogeneic hematopoietic cell transplant (allo-HCT), a potentially curative therapy for leukemia. We show that IFN-γR signaling inhibits Treg expansion and conversion of conventional T cells (Tcons) to peripheral Tregs in both mice and humans. Mice receiving IFN-γR-deficient allo-HCT showed markedly reduced graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effects, a trend associated with increased frequencies of Tregs, compared with recipients of wild-type allo-HCT. In mice receiving Treg-depleted allo-HCT, IFN-γR deficiency-induced peripheral Treg conversion was effective in preventing persistent GVHD while minimally affecting GVL effects. Thus, impairing IFN-γR signaling in Tcons may offer a promising strategy for achieving GVL effects without refractory GVHD. Similarly, in a human PBMC-induced xenogeneic GVHD model, significant inhibition of GVHD and an increase in donor Tregs were observed in mice cotransferred with human CD4 T cells that were deleted of IFN-γR1 by CRISPR/Cas9 technology, providing proof-of-concept support for using IFN-γR-deficient T cells in clinical allo-HCT.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia , Ratones , Humanos , Animales , Linfocitos T Reguladores , Trasplante Homólogo , Leucocitos Mononucleares , Ratones NoqueadosRESUMEN
BACKGROUND: PREDICT is a web-based tool for forecasting breast cancer outcomes. PREDICT version 3.0 was recently released. This study aimed to validate this tool for a large population in mainland China and compare v3.0 with v2.2. METHODS: Women who underwent surgery for nonmetastatic primary invasive breast cancer between 2010 and 2020 from the First Affiliated Hospital of Wenzhou Medical University were selected. Predicted and observed 5-year overall survival (OS) for both v3.0 and v2.2 were compared. Discrimination was compared using receiver-operator curves and DeLong test. Calibration was evaluated using calibration plots and chi-squared test. A difference greater than 5% was deemed clinically relevant. RESULTS: A total of 5424 patients were included, with median follow-up time of 58 months (IQR 38-89 months). Compared to v2.2, v3.0 did not show improved discriminatory accuracy for 5-year OS (AUC: 0.756 vs 0.771), same as ER-positive and ER-negative patients. However, calibration was significantly improved in v3.0, with predicted 5-year OS deviated from observed by -2.0% for the entire cohort, -2.9% for ER-positive and -0.0% for ER-negative patients, compared to -7.3%, -4.7% and -13.7% in v2.2. In v3.0, 5-year OS was underestimated by 9.0% for patients older than 75 years, and 5.8% for patients with micrometastases. Patients with distant metastases postdiagnosis was overestimated by 10.6%. CONCLUSIONS: PREDICT v3.0 reliably predicts 5-year OS for the majority of Chinese patients with breast cancer. PREDICT v3.0 significantly improved the predictive accuracy for ER-negative groups. Furthermore, caution is advised when interpreting 5-year OS for patients aged over 70, those with micrometastases or metastases postdiagnosis.
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Neoplasias de la Mama , Humanos , Neoplasias de la Mama/patología , Neoplasias de la Mama/mortalidad , Femenino , Persona de Mediana Edad , China/epidemiología , Adulto , Pronóstico , Anciano , Estudios de Cohortes , Pueblos del Este de AsiaRESUMEN
OBJECTIVE: To investigate the levels of 12 kinds of cytokines in seminal plasma and their correlations with routine semen parameters. METHODS: The remaining seminal plasma samples of 134 patients undergoing routine semen examination were collected for detecting cytokines. The parameters for sperm concentration, percentage of progressively motile sperm (PR), and motility were analyzed by a computer-assisted sperm analysis (CASA) system. According to the results of sperm concentration, PR and motility, 134 patients were divided into the normal routine semen parameters group, oligoasthenospermia group and azoospermia group. The levels of 12 kinds of cytokines in seminal plasma, including interleukin (IL)-1ß, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12P70, IL-17, interferin (IFN)-α, IFN-γ, and tumor necrosis factor (TNF)-α, were detected by flow cytometry. Two seminal plasma samples were detected for 10 times, respectively, to calculate the coefficients of variation (CV) of each cytokine. The linear range of each cytokine was measured using the standard, and the correlation coefficient (r) was calculated. RESULTS: The r2 of 12 kinds of cytokines detected by flow cytometry were all greater than 0.99. The reproducibility of 2 seminal plasma samples showed that the CVs of all cytokines were lower than 15 % except for TNF-α in sample 1 (15.15 %). Seminal plasma IL-6 levels were negatively correlated with semen volume (P < 0.01). Seminal plasma IL-5 levels were positively correlated with sperm concentration (P < 0.01). Seminal plasma IL-8 levels were negatively correlated with sperm motility (P < 0.01). Seminal plasma IL-8, IL-17 and IL-12P70 levels were negatively correlated with sperm PR (P < 0.05). In addition to the significant negative correlation between IL-5 and IL-17 (P < 0.05), there was a significant positive correlation between the majority of other cytokines. The levels of seminal plasma IL-17 and IL-12P70 in the oligoasthenospermia group and IL-1ß and IL-12P70 in the azoospermia group were significantly higher than those in the normal routine semen parameters group (P ≤ 0.05), while the levels of IL-10 in the azoospermia group were significantly lower than that in the normal routine semen parameters group (P < 0.05). CONCLUSION: There are certain correlations between seminal plasma cytokines and routine semen parameters and strong correlations between different seminal plasma cytokines, suggesting that the imbalance between seminal plasma cytokines may affect sperm quality. However, it still needs to be further confirmed by large samples and multi-center clinical studies and related basic researches.
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Neuroinflammation is being increasingly recognized as a vital factor in the development of various neurological and neuropsychiatric diseases. Lipopolysaccharides (LPS), an outer membrane component of gram-negative bacteria, can trigger innate immune responses, resulting in neuroinflammation and subsequent cognitive deficits. The expression of glutamate receptors (GluRs) on glial cells can induce glial activation. Therefore, we hypothesized that repeated LPS exposure can increase GluR levels, promoting microglial activation and ultimately affecting synaptic plasticity and cognitive function. In this study, C57/BL6 mice were repeatedly exposed to LPS to construct a neuroinflammation animal model. The levels of GluRs, inflammatory cytokines, ionized calcium-binding adaptor molecule 1, postsynaptic density protein 95, synaptophysin 38, NMDA receptor 2 A, and NMDA receptor 2B (GluN2B) were measured in the hippocampi. Furthermore, dendritic spine density in the CA1 hippocampal region was determined. Repeated LPS exposure induced cognitive impairments and microglial activation and increased GluR1 and GluR2 levels. This was accompanied by a significant decrease in GluN2B expression and dendritic spine density in the hippocampi. However, CFM-2, an α-amino-3- hydroxy-5-methyl-4-isoxazolepropionate receptor antagonist, reversed these anomalies. Furthermore, minocycline, a microglial inhibitor, reversed these anomalies and downregulated GluR2 but not GluR1 expression. In summary, we demonstrated that GluR2 plays an essential role in microglia-induced neuroinflammation, resulting in synaptic plasticity and cognitive impairment induced by repeated exposure to LPS.
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Disfunción Cognitiva , Lipopolisacáridos , Ratones Endogámicos C57BL , Enfermedades Neuroinflamatorias , Receptores AMPA , Animales , Lipopolisacáridos/toxicidad , Disfunción Cognitiva/metabolismo , Disfunción Cognitiva/inducido químicamente , Receptores AMPA/metabolismo , Masculino , Enfermedades Neuroinflamatorias/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Ratones , Hipocampo/metabolismo , Hipocampo/efectos de los fármacos , Microglía/metabolismo , Microglía/efectos de los fármacos , Plasticidad Neuronal/efectos de los fármacosRESUMEN
Hard limestone substrates, which are extensively distributed, are believed to exacerbate drought and increase the difficulty of restoration in vulnerable karst regions. Fissures in such substrates may alleviate the negative effect of drought on plants, but the underlying mechanisms remain poorly understood. In a two-way factorial block design, the growth and photosynthesis of 2-year-old Phoebe zhennan seedlings were investigated in two water availabilities (high versus low) and three stimulated fissure habitat groups (soil, soil-filled fissure and non-soil-filled fissure). Moreover, the fissure treatments included both small and big fissures. Compared to the soil group, the non-soil-filled fissure group had decreased the total biomass, root biomass, total root length, and the root length of fine roots in the soil layer at both water availabilities, but increased net photosynthetic rate (Pn) and retained stable water use efficiency (WUE) at low water availability. However, there were no significant differences between the soil-filled fissure group and soil group in the biomass accumulation and allocation as well as Pn. Nevertheless, the SF group decreased the root distribution in total and in the soil layer, and also increased WUE at low water availability. Across all treatments, fissure size had no effect on plant growth or photosynthesis. Karst fissures filled with soil can alleviate drought impacts on plant root growth, which involves adjusting root distribution strategies and increasing water use efficiency. These results suggest that rock fissures can be involved in long-term plant responses to drought stress and vegetation restoration in rocky mountain environments under global climate change.
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Sequías , Fotosíntesis , Suelo , Biomasa , Agua , Raíces de Plantas/crecimiento & desarrollo , EcosistemaRESUMEN
PURPOSE: This study aimed to investigate the efficacy and safety of ultrasound-guided percutaneous radiofrequency ablation (RFA) for the treatment of synovial hyperplasia in the knee joints of antigen-induced arthritis (AIA) model rabbits. METHODS: Forty Japanese large-eared white rabbits were divided into AIA and control groups. After successful induction of the AIA model, the knee joints were randomly assigned to RFA and non-RFA groups. The RFA group underwent ultrasound-guided RFA to treat synovial hyperplasia in the knee joint. Dynamic observation of various detection indices was conducted to evaluate the safety and effectiveness of the RFA procedure. RESULTS: Successful synovial ablation was achieved in the RFA group, with no intraoperative or perioperative mortality. Postoperative the circumference of the knee joint reached a peak before decreasing in the third week after surgery. The incidence and diameter of postoperative skin ulcers were not significantly different compared to the non-RFA group (p > .05). Anatomical examination revealed an intact intermuscular fascia around the ablated area in the RFA group. The ablated synovial tissue initially presented as a white mass, which subsequently liquefied into a milky white viscous fluid. Gross articular cartilage was observed, along with liquefied necrosis of the synovium on pathological histology and infiltration of inflammatory cells in the surrounding soft tissue. CONCLUSION: The experimental results demonstrated that ultrasound-guided RFA of the knee in the treatment of synovial hyperplasia in AIA model animals was both effective and safe.
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Hiperplasia , Ablación por Radiofrecuencia , Animales , Conejos , Ablación por Radiofrecuencia/métodos , Hiperplasia/cirugía , Hiperplasia/patología , Membrana Sinovial/patología , Membrana Sinovial/diagnóstico por imagen , Ultrasonografía/métodos , Masculino , Ultrasonografía Intervencional/métodosRESUMEN
BACKGROUND: Postoperative cognitive dysfunction (POCD) is a common complication after anesthesia/surgery, especially among elderly patients, and poses a significant threat to their postoperative quality of life and overall well-being. While it is widely accepted that elderly patients may experience POCD following anesthesia/surgery, the exact mechanism behind this phenomenon remains unclear. Several studies have indicated that the interaction between silent mating type information regulation 2 homologue 1 (SIRT1) and brain-derived neurotrophic factor (BDNF) is crucial in controlling cognitive function and is strongly linked to neurodegenerative disorders. Hence, this research aims to explore how SIRT1/BDNF impacts cognitive decline caused by anesthesia/surgery in aged mice. METHODS: Open field test (OFT) was used to determine whether anesthesia/surgery affected the motor ability of mice, while the postoperative cognitive function of 18 months old mice was evaluated with Novel object recognition test (NORT), Object location test (OLT) and Fear condition test (FC). The expressions of SIRT1 and other molecules were analyzed by western blot and immunofluorescence staining. The hippocampal synaptic plasticity was detected by Golgi staining and Long-term potentiation (LTP). The effects of SIRT1 and BDNF overexpression as well as chemogenetic activation of glutamatergic neurons in hippocampal CA1 region of 18 months old vesicular glutamate transporter 1 (VGLUT1) mice on POCD were further investigated. RESULTS: The research results revealed that older mice exhibited cognitive impairment following intramedullary fixation of tibial fracture. Additionally, a notable decrease in the expression of SIRT1/BDNF and neuronal excitability in hippocampal CA1 glutamatergic neurons was observed. By increasing levels of SIRT1/BDNF or enhancing glutamatergic neuron excitability in the CA1 region, it was possible to effectively mitigate synaptic plasticity impairment and ameliorate postoperative cognitive dysfunction. CONCLUSIONS: The decline in SIRT1/BDNF levels leading to changes in synaptic plasticity and neuronal excitability in older mice could be a significant factor contributing to cognitive impairment after anesthesia/surgery.
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Factor Neurotrófico Derivado del Encéfalo , Región CA1 Hipocampal , Regulación hacia Abajo , Plasticidad Neuronal , Neuronas , Complicaciones Cognitivas Postoperatorias , Sirtuina 1 , Animales , Sirtuina 1/metabolismo , Sirtuina 1/genética , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Factor Neurotrófico Derivado del Encéfalo/genética , Ratones , Neuronas/metabolismo , Complicaciones Cognitivas Postoperatorias/metabolismo , Complicaciones Cognitivas Postoperatorias/etiología , Región CA1 Hipocampal/metabolismo , Masculino , Ratones Endogámicos C57BL , Potenciación a Largo Plazo , Ácido Glutámico/metabolismo , Disfunción Cognitiva/etiología , Disfunción Cognitiva/metabolismo , Disfunción Cognitiva/fisiopatologíaRESUMEN
X-ray images typically contain complex background information and abundant small objects, posing significant challenges for object detection in security tasks. Most existing object detection methods rely on complex networks and high computational costs, which poses a challenge to implement lightweight models. This article proposes Fine-YOLO to achieve rapid and accurate detection in the security domain. First, a low-parameter feature aggregation (LPFA) structure is designed for the backbone feature network of YOLOv7 to enhance its ability to learn more information with a lighter structure. Second, a high-density feature aggregation (HDFA) structure is proposed to solve the problem of loss of local details and deep location information caused by the necked feature fusion network in YOLOv7-Tiny-SiLU, connecting cross-level features through max-pooling. Third, the Normalized Wasserstein Distance (NWD) method is employed to alleviate the convergence complexity resulting from the extreme sensitivity of bounding box regression to small objects. The proposed Fine-YOLO model is evaluated on the EDS dataset, achieving a detection accuracy of 58.3% with only 16.1 M parameters. In addition, an auxiliary validation is performed on the NEU-DET dataset, the detection accuracy reaches 73.1%. Experimental results show that Fine-YOLO is not only suitable for security, but can also be extended to other inspection areas.
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For chemical measurements, calibration is typically conducted by regression analysis. In many cases, generalized approaches are required to account for a complex-structured variance-covariance matrix of (in)dependent variables. However, in the particular case of highly correlated independent variables, the ordinary least squares (OLS) method can play a rational role with an approximated propagation of uncertainties of the correlated independent variables into that of a calibrated value for a particular case in which standard deviation of fit residuals are close to the uncertainties along the ordinate of calibration data. This proposed method aids in bypassing an iterative solver for the minimization of the implicit form of the squared residuals. This further allows us to derive the explicit expression of budgeted uncertainties corresponding to a regression uncertainty, the measurement uncertainty of the calibration target, and correlated independent variables. Explicit analytical expressions for the calibrated value and associated uncertainties are given for straight-line and second-order polynomial fit models for the highly correlated independent variables.
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BACKGROUND: SHR7390 is a novel, selective MEK1/2 inhibitor. Here, we report results from two phase I trials conducted to evaluate the tolerability, safety and antitumor activity of SHR7390 monotherapy for advanced solid tumors and SHR7390 plus camrelizumab for treatment-refractory advanced or metastatic colorectal cancer (CRC). PATIENTS AND METHODS: Patients received SHR7390 alone or combined with fixed-dose camrelizumab (200 mg every 2 weeks) in an accelerated titration scheme to determine the maximum tolerated dose (MTD). A recommended dose for expansion was determined based on the safety and tolerability of the dose-escalation stage. The primary endpoints were dose limiting toxicity (DLT) and MTD. RESULTS: In the SHR7390 monotherapy trial, 16 patients were enrolled. DLTs were reported in the 1.0 mg cohort, and the MTD was 0.75 mg. Grade ≥3 treatment-related adverse events (TRAEs) were recorded in 4 patients (25.0%). No patients achieved objective response. In the SHR7390 combination trial, 22 patients with CRC were enrolled. One DLT was reported in the 0.5 mg cohort and the MTD was not reached. Grade ≥3 TRAEs were observed in 8 patients (36.4%), with the most common being rash (n=4). One grade 5 TRAE (increased intracranial pressure) occurred. Five patients (22.7%) achieved partial response, including one of 3 patients with MSS/MSI-L and BRAF mutant tumors, one of 15 patients with MSS/MSI-L and BRAF wild type tumors, and all 3 patients with MSI-H tumors. CONCLUSIONS: SHR7390 0.5 mg plus camrelizumab showed a manageable safety profile. Preliminary clinical activity was reported regardless of MSI and BRAF status.
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Neoplasias , Proteínas Proto-Oncogénicas B-raf , Humanos , Neoplasias/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversosRESUMEN
BACKGROUND: Microglial activation-mediated neuroinflammation is one of the essential pathogenic mechanisms of sepsis-associated encephalopathy (SAE). Mounting evidence suggests that high mobility group box-1 protein (HMGB1) plays a pivotal role in neuroinflammation and SAE, yet the mechanism by which HMGB1 induces cognitive impairment in SAE remains unclear. Therefore, this study aimed to investigate the mechanism of HMGB1 underlying cognitive impairment in SAE. METHODS: An SAE model was established by cecal ligation and puncture (CLP); animals in the sham group underwent cecum exposure alone without ligation and perforation. Mice in the inflachromene (ICM) group were continuously injected with ICM intraperitoneally at a daily dose of 10 mg/kg for 9 days starting 1 h before the CLP operation. The open field, novel object recognition, and Y maze tests were performed on days 14-18 after surgery to assess locomotor activity and cognitive function. HMGB1 secretion, the state of microglia, and neuronal activity were measured by immunofluorescence. Golgi staining was performed to detect changes in neuronal morphology and dendritic spine density. In vitro electrophysiology was performed to detect changes in long-term potentiation (LTP) in the CA1 of the hippocampus. In vivo electrophysiology was performed to detect the changes in neural oscillation of the hippocampus. RESULTS: CLP-induced cognitive impairment was accompanied by increased HMGB1 secretion and microglial activation. The phagocytic capacity of microglia was enhanced, resulting in aberrant pruning of excitatory synapses in the hippocampus. The loss of excitatory synapses reduced neuronal activity, impaired LTP, and decreased theta oscillation in the hippocampus. Inhibiting HMGB1 secretion by ICM treatment reversed these changes. CONCLUSIONS: HMGB1 induces microglial activation, aberrant synaptic pruning, and neuron dysfunction in an animal model of SAE, leading to cognitive impairment. These results suggest that HMGB1 might be a target for SAE treatment.
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Disfunción Cognitiva , Proteína HMGB1 , Encefalopatía Asociada a la Sepsis , Sepsis , Animales , Ratones , Disfunción Cognitiva/metabolismo , Modelos Animales de Enfermedad , Hipocampo/metabolismo , Proteína HMGB1/metabolismo , Enfermedades Neuroinflamatorias , Sepsis/complicaciones , Encefalopatía Asociada a la Sepsis/metabolismoRESUMEN
Refractory metals (W, Nb, or Mo) microalloying Pt-based alloys with unprecedented performance may serve as advanced electrocatalysts for proton exchange membrane fuel cells (PEMFCs). These alloys are endowed with unique stabilizing substructures or lattice defects through the microalloying effect. Herein, trace W microalloying PtCuCo medium entropy alloys (W-PtCuCo) are reported via a stepwise synthesis strategy, starting with home-made Cu nanowires as sacrificial templates by anhydrous solid-phase milling route, and then followed by galvanic replacement-assisted solvothermal in ethylene glycol (EG). In PEMFC tests, the obtained W-PtCuCo exhibits an ultrahigh peak power density and mass power density (relative to cathode) reaching 2.09 W cm-2 and 20.9 W mgPt -1 , respectively. During the accelerated degradation test (ADT), the mass activity just lost only 3% after 30 k cycles, much better than the above benchmark catalyst. The microalloying-dependent performances shall be attributed to the presence of abundant stepped surfaces, twisted edges, and other lattice defects terminated by W via substructure reconstruction that indeed alters the electronic structure and strain level of the alloys. This work first provides an atomic-level insight into the microalloying-dependent electrocatalytic performance of Pt-based alloys, which is of great significance for developing next-generation efficient catalysts for PEMFC.
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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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OBJECTIVE: To investigate the association between serum unconjugated bilirubin (UCB) within normal limits and chronic kidney disease (CKD) in T2DM patients. METHOD: This cross-sectional, real-world study was performed in 8661 hospitalised T2DM patients. The subjects were stratified into quintiles based on serum UCB levels. The clinical characteristics and CKD prevalence were compared among the UCB quantile groups. The associations of serum UCB levels and quintiles with CKD were also analysed by binary logistic regression. RESULTS: After controlling for age, sex, and diabetes duration (DD), the CKD prevalence (20.4%, 12.2%, 10.6%, 8.3%, and 6.4% for the first, second, third, fourth, and fifth quintiles, respectively, p < 0.001 for trend) was significantly decreased across the serum UCB quintiles. The fully adjusted regression model showed negative associations of serum UCB levels (OR: 0.660, 95% CI: 0.585-0.744; p < 0.001 for trend) and quintiles (p < 0.001) with the presence of CKD. Compared with the subjects in the lowest UCB quintile, the risk of CKD decreased by 36.2%, 54.3%, 53.8%, and 62.1%, respectively, in those from the second to the highest UCB quintile. Additionally, C-reactive protein (CRP) levels were significantly higher in the subjects with CKD than in those without CKD (p < 0.001), and significantly decreased across the UCB quintiles (p < 0.001 for trend). CONCLUSIONS: Serum UCB levels within the normal range were significantly and negatively linked to CKD in T2DM patients. High-normal UCB may be an independent protective factor for CKD by its antioxidant and the following anti-inflammatory activities through its signalling activity, which was indicated by clearly decreased CRP levels across the UCB quintiles.
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Diabetes Mellitus Tipo 2 , Insuficiencia Renal Crónica , Humanos , Diabetes Mellitus Tipo 2/epidemiología , Estudios Transversales , Bilirrubina , Antioxidantes , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/etiologíaRESUMEN
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
Two Gram-stain-negative bacterial strains, S13-6-6 and S13-6-22T, were isolated from sediment sample collected at a water depth of 4 m from Lake Hongze, Jiangsu Province, PR China. The cells of strains S13-6-6 and S13-6-22T were non-spore-forming, aerobic, non-motile and formed orange colonies on R2A agar. Comparative 16S rRNA gene sequence studies revealed a clear affiliation of the two strains with he phylum Bacteroidota, and revealed the highest pairwise sequence similarities with Lacibacter daechungensis H32-4T (97.8â%), Lacibacter cauensis NJ-8T (97.8â%), Lacibacter luteus TTM-7T (97.4â%) and Lacibacter nakdongensis SS2-56T (97.4â%). The results of phylogenetic analysis based on 16S rRNA gene sequences indicated that the strains formed a clear phylogenetic lineage with the genus Lacibacter. The major fatty acids were identified as iso-C15â:â1G, iso-C15â:â0, iso-C17â:â0 3-OH and summed feature 3 (C16â:â1ω7c and/or C16â:â1ω6c) (>10â%), and the respiratory quinone was identified as menaquinone MK-7. The polar lipids consisted of phosphatidylethanolamine, two unidentified aminolipids, an unidentified phospholipid and six unidentified lipids. The genomic DNA G+C content was determined to be 40.2 mol% (HPLC) for strain S13-6-6 and 40.3â% (genome) for strain S13-6-22T. The combined genotypic and phenotypic data indicated that strains S13-6-6 and S13-6-22T represent a novel species of the genus Lacibacter, for which the name Lacibacter sediminis sp. nov. is proposed. The type strain is S13-6-22T (=CGMCC 1.17450T =JCM 35802T).
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Ácidos Grasos , Fosfolípidos , Ácidos Grasos/química , Filogenia , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , ADN Bacteriano/genética , Composición de Base , Técnicas de Tipificación Bacteriana , Fosfolípidos/análisis , Lagos/microbiología , Vitamina K 2RESUMEN
BACKGROUND: The aim of this study was to explore the mechanism whereby LACC1 regulates the intestinal flora in a mouse model of inflammatory bowel disease (IBD). METHODS: C57BL/6 and Lacc1-/- mice were used to establish a mouse model of IBD induced by dextran sodium sulfate (DSS). The effects of Lacc1 deletion in mice were evaluated. Changes in the body weight and stool blood were recorded daily. After 7 days of successful modeling, the mice were sacrificed, blood was collected from the eyeballs, the entire colon was dissected and separated, and the length of the colon was measured. RESULTS: Compared with the wild-type (WT) DSS model group, the Lacc1-/- DSS model group showed a significantly higher disease activity index score (P < 0.05), significantly faster weight loss (P < 0.05), and a significantly shorter colon (P < 0.05), indicating that the colonic mucosal tissue was seriously damaged in the Lacc1-/- DSS model group (P < 0.05). Serum IL-1ß, IL-6, TNF-α, and IFN-γ levels were significantly higher in the Lacc1-/- DSS model group than the WT DSS model group. Principal coordinate analysis showed that there were significant microbiome differences between the WT, Lacc1-/-, WT DSS model, and Lacc1-/- DSS model groups (P < 0.05). Linear discriminant analysis effect size analysis showed that under natural conditions, Lacc1-/- mice had significant changes in their intestinal flora compared with control mice (LDA value > 3 or < 3, P < 0.05). CONCLUSIONS: Lacc1 deletion aggravates DSS-induced IBD in mice.
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Colitis , Microbioma Gastrointestinal , Enfermedades Inflamatorias del Intestino , Animales , Ratones , Colitis/inducido químicamente , Colon , Sulfato de Dextran/efectos adversos , Modelos Animales de Enfermedad , Enfermedades Inflamatorias del Intestino/inducido químicamente , Ratones Endogámicos C57BL , Factor de Necrosis Tumoral alfaRESUMEN
A polyphasic taxonomic study was conducted on two Gram-negative, non-sporulating, non-motile bacterial strains, S2-20-2T and S2-21-1, isolated from a contaminated freshwater sediment in China. Comparative 16S rRNA gene sequence studies revealed a clear affiliation of two strains with Bacteroidetes, which showed the highest pairwise sequence similarities with Hymenobacter duratus BT646T (99.3%), Hymenobacter psychrotolerans Tibet-IIU11T (99.3%), Hymenobacter kanuolensis T-3T (97.6%), Hymenobacter swuensis DY53T (96.9%), Hymenobacter tenuis POB6T (96.8%), Hymenobacter seoulensis 16F7GT (96.7%), and Hymenobacter rigui KCTC 12533T (96.5%). The phylogenetic analysis based on 16S rRNA gene sequences showed that two strains formed a clear phylogenetic lineage with the genus Hymenobacter. Major fatty acids were identified as iso-C15:0, anteiso-C15:0, and summed feature 3 (C16:1 ω6c and/or C16:1 ω7c/t) and summed feature 4 (iso-C17:1 I and/or anteiso-C17:1 B). Major cellular polar lipids were identified as phosphatidylethanolamine, three unidentified aminolipids, an unidentified aminophosopholipid and an unidentified lipid. The respiratory quinone was detected as MK-7 and the genomic DNA G + C content was determined to be 57.9% (genome) for type strain S2-20-2T and 57.7 mol% (HPLC) for strain S2-21-1. The observed ANI and dDDH values between strain S2-20-2T and its closely related strains were 75.7-91.4% and 21.2-43.9%, respectively. Based on physiological, biochemical, genetic and genomic characteristics, we propose that strains S2-20-2T and S2-21-1 represent a novel species of the genus Hymenobacter, for which the name Hymenobacter sediminicola sp. nov. is proposed. The type strain is S2-20-2T (= CGMCC 1.18734T = JCM 35801T).