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Atherosclerosis (AS) is the common pathophysiological basis of various cardiovascular diseases and the leading cause of death from cardiovascular disease worldwide. When the body is in a hypoxic environment, enhanced oxidative stress and significant accumulation of reactive oxygen species (ROS) in tissue cells exacerbate the inflammatory response, resulting in increased release of myeloperoxidase (MPO), catalyzing the formation of large quantities of hypochlorous acid (HOCl), further oxidative modification of low-density lipoprotein (LDL), and exacerbating the formation and progression of atherosclerotic plaques. The MAPK signaling pathway is important in oxidative stress-mediated promotion of atherogenesis. MPO -/- mice were used in this study to establish a hypoxia model simulating 5000 m altitude and a Western high-fat diet-induced atherosclerosis model for 12 weeks. Exploring the role of MPO in the atherosclerotic process in hypoxic mice by observing the MAPK signaling pathway to provide a therapeutic target for the prevention and treatment of hypoxic atherosclerotic disease in the plateau. We found that hypoxia promotes the formation of atherosclerosis in mice, and the mechanism may be that increased MPO in vivo promotes an inflammatory response, which plays a crucial role in the formation of atherosclerosis. In addition, hypoxia further exacerbates plaque instability by activating the MAPK signaling pathway to upregulate vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP9), which in turn promotes angiogenesis within the plaque. Therefore, a potential target for preventing and treating hypoxic atherosclerotic disease is the inhibition of MPO.
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Aterosclerose , Hipóxia , Sistema de Sinalização das MAP Quinases , Peroxidase , Animais , Masculino , Camundongos , Aterosclerose/metabolismo , Aterosclerose/patologia , Dieta Hiperlipídica/efeitos adversos , Hipóxia/metabolismo , Sistema de Sinalização das MAP Quinases/fisiologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Peroxidase/metabolismo , Peroxidase/genéticaRESUMO
Mastitis in dairy cows is mainly caused by bacteria, in which Staphylococcus aureus appears frequently. Epithelial cells, as a major physical barrier of mammary gland, play an important role in preventing mastitis in dairy cows. Our previous study reported that Rab11fip4 (an effector of Rab11) was significantly changed in response to stimulation by S. aureus. So, in this study, the role of Rab11A in phagocytosis of bovine mammary epithelial cells (MAC-T) against S. aureus was evaluated. First, changes of Rab11A and Rab11fip4 were analyzed in response to S. aureus by immunofluorescence and western blotting. Subsequently, the effects of Rab11A and Rab11fip4 on proliferation of S. aureus, as well as formation and function of late endosomes (LEs) and lysosomes (LYSs) were investigated. The results showed that, after infection, Rab11A and Rab11fip4 were recruited to phagosomes containing S. aureus. Rab11A promoted bacterial clearance and rescues the destruction of LEs and LYSs by S. aureus, whereas Rab11fip4 did the opposite. These findings provide new insights into phagocytosis and control of S. aureus in host cells, thus lay the foundation to elucidate the pathogenesis of S. aureus in bovine mastitis.
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Células Epiteliais , Mastite Bovina , Fagocitose , Infecções Estafilocócicas , Staphylococcus aureus , Proteínas rab de Ligação ao GTP , Animais , Bovinos , Proteínas rab de Ligação ao GTP/metabolismo , Proteínas rab de Ligação ao GTP/genética , Staphylococcus aureus/fisiologia , Feminino , Células Epiteliais/microbiologia , Infecções Estafilocócicas/veterinária , Infecções Estafilocócicas/microbiologia , Mastite Bovina/microbiologia , Glândulas Mamárias Animais/microbiologia , Endossomos/metabolismo , Endossomos/microbiologia , Lisossomos/metabolismo , Lisossomos/microbiologia , Linhagem Celular , Fagossomos/microbiologiaRESUMO
Hexavalent chromium [Cr(VI)] is an environmental pollutant known for its strong oxidizing and carcinogenic effects. However, its potential to induce ferroptosis in poultry remains poorly understood. This study aims to investigate the induction of ferroptosis by Cr(VI) in DF-1 cells and elucidate the underlying mechanisms. DF-1 cells exposed to Cr(VI) showed increased lipid reactive oxygen species and changes in ferroptosis marker genes (decreased expression of GPX4 and increased expression of COX2). Notably, the addition of the ferroptosis-specific inhibitor ferrostatin-1 (Fer-1) can reverse this effect. During the cell death process, Cr(VI) induced ferritinophagy, disrupting iron homeostasis and releasing labile iron ions. We predicted by docking that these iron ions would bind to mitochondrial membrane proteins through virtual docking. This binding was validated through colocalization analysis. In addition, Cr(VI) caused mitophagy, which releases additional ferrous ions. Therefore, Cr(VI) can induce the simultaneous release of ferrous ions through these pathways, thereby exacerbating lipid peroxidation and ultimately triggering ferroptosis in DF-1 cells. This study demonstrates that Cr(VI) can induce ferroptosis in DF-1 cells by disrupting intracellular iron homeostasis and providing valuable insights into the toxic effects of Cr(VI) in poultry and potentially other organisms.
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Cromo , Ferroptose , Mitofagia , Ferro/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Homeostase , ÍonsRESUMO
Antimicrobials are extensively utilized in dairy farms to prevent and control diseases in cattle. However, their use contributes to the emergence of antimicrobial-resistant bacteria (ARB) and antimicrobial-resistant genes (ARG), and these can be transmitted to the environment. Regular monitoring of antimicrobial resistance (AMR) is crucial for implementing effective mitigation strategies. This research aimed to assess the environmental microbial species present on dairy farms in Shandong Province and characterize the antimicrobial resistance profiles of the isolates. Five dairy farms located in Shandong Province were selected, representing the prevalent large-scale farming patterns in the area. Sampling took place from April to June 2022, with a total of 223 isolates collected from various environmental locations within each farm (bedding, sports field, and milking parlor). Matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS) was employed to identify the species of the clinical isolates. The main pathogens isolated were Aerococcus viridans (5.38%, n = 12), Corynebacterium xerosis (4.93%, n = 11), and Acinetobacter lwoffii (4.03%, n = 9). Among the bacterial isolates, resistance to lincomycin was highest at 91%, and 88% were resistant to sulfadiazine. Antimicrobial resistance genes were detected in only a small proportion of the isolates, the most common of which was sul1. These findings highlight the necessity for careful evaluation of antimicrobial usage in maintaining their effectiveness in human medicine. Understanding the microbial species present and their antimicrobial resistance profiles aids in focusing efforts toward sustainable antimicrobial use and safeguarding human health.
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AIMS: HNF1B syndrome is caused by defects in the hepatocyte nuclear factor 1B (HNF1B) gene, which leads to maturity-onset diabetes of the young type 5 and congenital organ malformations. This study aimed to identify a gene defect in a patient presenting with diabetes and severe diarrhea, while also analyzing the prevalence of hypomagnesemia and its correlation with the HNF1B genotype. MATERIALS AND METHODS: Whole exome sequencing was used to identify responsible point mutations and small indels in the proband and their family members. Multiplex ligation-dependent probe amplification was carried out to identify HNF1B deletions. Furthermore, an analysis of published data on 539 cumulative HNF1B cases, from 29 literature sources, was carried out to determine the correlation between the HNF1B genotype and the phenotype of serum magnesium status. RESULTS: Using multiplex ligation-dependent probe amplification, we identified a de novo heterozygous HNF1B deletion in the patient, who showed dorsal pancreas agenesis and multiple kidney cysts, as detected by magnetic resonance imaging. Magnesium supplementation effectively alleviated the symptoms of diarrhea. Hypomagnesemia was highly prevalent in 192 out of 354 (54.2%) patients with HNF1B syndrome. Compared with patients with intragenic mutations, those with HNF1B deletions were more likely to suffer from hypomagnesemia, with an odds ratio of 3.1 (95% confidence interval 1.8-5.4). CONCLUSIONS: Hypomagnesemia is highly prevalent in individuals with HNF1B syndrome, and those with HNF1B deletion are more susceptible to developing hypomagnesemia compared with those with intragenic mutations. The genotype-phenotype associations in HNF1B syndrome have significant implications for endocrinologists in terms of genotype detection, treatment decisions and prognosis assessment.
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Diabetes Mellitus Tipo 2 , Magnésio , Humanos , Diabetes Mellitus Tipo 2/complicações , Diarreia/complicações , Fator 1-beta Nuclear de Hepatócito/genética , Mutação , SíndromeRESUMO
BACKGROUND: High-altitude exposure can cause oxidative stress damage in the intestine, which leads to increased intestinal permeability and bacterial translocation, resulting in local and systemic inflammation. Control of infection is critically dependent on the host's ability to kill pathogens with reactive oxygen species (ROS). Myeloperoxidase (MPO) targets ROS in pathogens. This study aimed to investigate the effects of hypoxia on the colonic mucosal barrier and myeloperoxidase (MPO)-mediated innate immune response in the colon. METHODS AND RESULTS: Genetically engineered mice were exposed to a hypobaric oxygen chamber for 3 days and an inflammation model was established using Salmonella Typhimurium infection. We found that hypoxic exposure caused the development of exacerbated bacterial colitis and enhanced bacterial dissemination in MPO-deficient mice. Infection and disease severity were associated with significantly increased Ly6G+ neutrophil and F4/80+ macrophage counts in infected tissues, which is consistent with elevated proinflammatory cytokines and chemoattractant molecules. Hypoxia restrained antioxidant ability and MPO deficiency aggravated the respiratory burst in the colon. CONCLUSION: Hypoxia can damage the colonic mucosa. MPO mediates the innate immune response and regulates the mucosal and systemic inflammatory responses to Salmonella infection during hypoxia.
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In this work, a p-n junction-coupled metal-insulator-semiconductor (MIS) normally-off high-electron-mobility transistor (HEMT) UVPD is proposed. A two-dimensional electron gas (2DEG) at the AlN/U-GaN interface is entirely depleted with a dark current of 1.97 × 10-11 A because of the design of the sandwiched p-GaN layers. Under 365â nm illumination, the 2DEG is light triggered at Vds = 1â V with a high light on/off ratio of over 107 at a light power density of 286.39â mW·cm-2. Meanwhile, it exhibits fast rise and decay times of 248.39 and 584.79 µs, respectively. Moreover, a maximum responsivity (R) of 2.33 A/W, a maximum EQE of 793%, and a D* of 1.08 × 1013 Jones are obtained at Vds = 1â V. This can be attributed to the built-in electric fields in the configuration, which accelerate the flow of photogenerated carriers into the AlN/U-GaN channel. Additionally, the device showcases stable durability, repeatability, and a low driving voltage, making it highly suitable for applications in UV communication and space exploration.
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Extracellular vesicles (EVs) are nano-sized bilayer EVs with various components. EV secretion in pathogenic Gram-positive bacteria is a universal feature that can cause disease and damage the targeted host. In this study, we isolated and purified Staphylococcus aureus (S. aureus) EVs, and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analyzed Ev's protein composition. After that, the pathway of EVs internalized into MAC-T cells was evaluated. Moreover, the activation of mitogen-activated protein kinase (MAPK) and the nuclear factor κB (NF-κB) pathway was measured by Western blot. Meanwhile, Western blot and confocal microscopy detected mitochondrial damage, apoptosis, and Parkin-mediated mitophagy. Results showed that purified S. aureus EVs exhibited a typical cup-shaped structure and internalized into MAC-T cells by lipid raft-mediated endocytic pathway. S. aureus EVs caused mitochondrial damage and apoptosis in MAC-T cells. However, degradation of the damaged mitochondria was impeded due to the Parkin-mediated mitophagy pathway being restrained by the disruption of the acidic environment of lysosomes by S. aureus EVs. Hence, our study reveals the role of S. aureus EVs in immune stimulation, disruption of mitochondria, and lysosomal acidic environment in bovine mammary epithelial cells. These findings help us understand the role of EVs in the pathogenic mechanism of S. aureus.
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Vesículas Extracelulares , Infecções Estafilocócicas , Animais , Bovinos , Staphylococcus aureus , Mitofagia , Cromatografia Líquida , Espectrometria de Massas em Tandem , Apoptose , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/patologia , Ubiquitina-Proteína Ligases/metabolismo , Mitocôndrias/patologiaRESUMO
High altitude hypoxia can lead to a spectrum of gastrointestinal problems. As the first line of host immune defense, innate immune response in the intestinal mucosa plays a pivotal role in maintaining intestinal homeostasis and protecting against intestinal injury at high altitude. This study aimed to investigate the effect of hypoxia on the colonic mucosal barrier and toll-like receptor 4 (TLR4)-mediated innate immune responses in the colon. The mice were exposed to a hypobaric chamber to simulate a 5,000 m plateau environment for 7 days, and the colonic mucosa changes were recorded. At the same time, the inflammation model was established by lipopolysaccharide (LPS) to explore the effects of hypoxia on the TLR4/nuclear factor kappa B (NF-κB) signaling pathway and its downstream inflammatory factors [tumor necrosis factor-α, interleukin (IL)-1ß, IL-6, and interferon (IFN)-γ] in the colon. We found that hypoxic exposure caused weight loss and structural disturbance of the colonic mucosa in mice. Compared with the control group, the protein levels of TLR4 [fold change (FC) = 0.75 versus FC = 0.23], MyD88 (FC = 0.80 versus FC = 0.30), TIR-domain-containing adaptor protein inducing interferon-ß (TRIF: FC = 0.89 versus FC = 0.38), and NF-κB p65 (FC = 0.75 versus FC = 0.24) in the colon of mice in the hypobaric hypoxia group were significantly decreased. LPS-induced upregulation of the TLR4/NF-κB signaling and its downstream inflammatory factors was inhibited by hypoxia. Specifically, compared with the LPS group, the protein levels of TLR4 (FC = 1.18, FC = 0.86), MyD88 (FC = 1.20, FC = 0.80), TRIF (FC = 1.20, FC = 0.86), and NF-κB p65 (FC = 1.29, FC = 0.62) and the mRNA levels of IL-1ß (FC = 7.38, FC = 5.06), IL-6 (FC = 16.06, FC = 9.22), and IFN-γ (FC = 2.01, FC = 1.16) were reduced in the hypobaric hypoxia plus LPS group. Our findings imply that hypoxia could lead to marked damage of the colonic mucosa and a reduction of TLR4-mediated colonic innate immune responses, potentially reducing host defense responses to colonic pathogens.
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Hipóxia , Imunidade Inata , NF-kappa B , Receptor 4 Toll-Like , Animais , Camundongos , Proteínas Adaptadoras de Transporte Vesicular/genética , Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Proteínas Adaptadoras de Transporte Vesicular/farmacologia , Colo/imunologia , Colo/patologia , Hipóxia/imunologia , Hipóxia/metabolismo , Interleucina-6/metabolismo , Lipopolissacarídeos/farmacologia , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais , Receptor 4 Toll-Like/genéticaRESUMO
Background: To explore the feasibility and effectiveness of the metal artifact reduction software (MARs) reconstruction algorithm in reducing metal artifacts of knee prostheses and to explore the optimal monochromatic level of virtual monochromatic spectral (VMS) images for artifact reduction to provide high-quality images and reliable diagnosis in patients after total knee arthroplasty (TKA). Methods: A total of 31 patients underwent gemstone spectral computed tomography. VMS images with MARs and without MARs were obtained at different energy levels (80, 100, 120, and 140 keV). Two observers scored each group of images, and interobserver agreement was evaluated. Artificial indices (AIs), percentage500HU and structural similarity index measure (SSIM) values were calculated in the objective analysis to evaluate the image quality and impact of metal artifacts. Results: The consistency of the scores of the 2 observers was good (kappa value =0.78), and the score of the VMS images with MARs was higher than that of VMS images without MARs. AI values and percentage500HU of the MARs group were significantly lower than those of the without MARs group, while SSIM values were significantly higher. In the comparison of different keV images, the AI value decreased with the increase in keV in the range of 80-120 keV, but there was no significant difference between the 120 keV images and 140 keV images. In the group with MARs, the percentage500HU of 100-140 keV images was significantly lower than that of the 80 keV images, but there was no significant difference between 100, 120, and 140 keV images. In the group without MARs, the percentage500HU was significantly different among all keV groups. Conclusions: VMS images combined with the MARs algorithm can significantly reduce the metal artifacts of knee prostheses and improve image quality. At an energy level of 100-120 keV, a good metal artifact removal effect and soft tissue contrast can be achieved, and the best metal artifact removal effect can be achieved at 140 keV.
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In response to vascular injury or alterations in the local environment, such as hypoxia and hypertension, contractile vascular smooth muscle cells (VSMCs) are able to switch to a synthetic phenotype characterized by increased extracellular matrix synthesis with decreased expression of contractile markers. miR-182-5p has recently been reported to play a regulatory role in VSMCs proliferation. However, little is known about its target genes and related pathways in VSMCs phenotypic switch. Here, we investigated the function of miR-182-5p in VSMCs phenotypic switch. The results showed that upregulation of miR-182-5p promoted the switching of VSMCs from a contractile to a synthetic phenotype under hypoxic conditions. Mechanistically, hypoxia elevated miR-182-5p, leading to a reduction in expression of contractile markers and weakened RhoA signaling. Using bioinformatics analysis, dual-luciferase reporter assays and rescue assays, we demonstrated that miR-182-5p suppressed RhoA signaling by targeting RGS5. Collectively, the results from the present study indicated that miR-182-5p/RGS5/RhoA axis regulated hypoxia-induced VSMCs phenotypic switch.
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MicroRNAs , Proteínas RGS , Movimento Celular , Proliferação de Células , Células Cultivadas , Humanos , Hipóxia/metabolismo , MicroRNAs/metabolismo , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Fenótipo , Proteínas RGS/genética , Proteínas RGS/metabolismoRESUMO
Bovine mastitis is an important disease affecting dairy farming, and it causes large economic losses to the dairy industry. Escherichia coli (E. coli) is considered to be a causative environmental pathogen and frequently enters into mammary glands, causing inflammation. Artemisinin is a highly effective malaria remedy and is not easy to develop drug resistance to. In recent years, other effects of artemisinin (including antitumor, anti-inflammatory, antifungal, etc.) have been increasingly discovered and applied. The current study aimed to investigate whether artemisinin could attenuate E. coli-induced inflammation. Through the E. coli mastitis model in MAC-T cells and mice, the protective effects of artemisinin were analyzed by CCK-8 (Cell Counting Kit-8), Western blot, and RT-qPCR. The results showed that artemisinin reversed the decrease of cell viability and upregulated TLR4 (toll-like receptor 4)/NF-κB (nuclear factor κB) and MAPK (mitogen activated protein kinase)/p38 signaling pathways, as well as restrained the expression of TNF-α, IL-6, and IL-1ß mRNA caused by E. coli. Meanwhile, artemisinin also alleviated mammary tissue damage, reduced inflammatory cells' infiltration, and decreased the levels of inflammatory factors in a mice mastitis model. This study demonstrated that artemisinin alleviated the inflammatory response of mouse mastitis and MAC-T cells induced by E. coli, thus providing a practical approach for the clinical control of mastitis.
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Polarization-sensitive photodetectors based on van der Waals heterojunctions (vdWH) have excellent polarization-resolved optoelectronic properties that can enable the applications in polarized light identification and imaging. With the development of optical microcomputer control systems (OMCS), it is crucial and energy efficient to adopt the self-powered and polarization-resolved signal-generators to optimize the circuit design of OMCS. In this work, the selenium (Se) flakes with in-plane anisotropy and p-type character are grown and incorporated with n-type tungsten disulfide (WS2 ) to construct the type-II vdWH for polarization-sensitive and self-powered photodetectors. Under 405 nm monochrome laser with 1.33 mW cm-2 power density, the photovoltaic device exhibits superior photodetection performance with the photoelectric conversion efficiency (PCE) of 3.6%, the responsivity (R) of 196 mA W-1 and the external quantum efficiency (EQE) of about 60%. The strong in-plane anisotropy of Se crystal structure gives rise to the capability of polarized light detection with anisotropic photocurrent ratio of ≈2.2 under the 405 nm laser (13.71 mW cm-2 ). Benefiting from the well polarization-sensitive and photovoltaic properties, the p-Se/n-WS2 vdWH is successfully applied in the OMCS as multivalued signal trigger. This work develops the new anisotropic vdWH and demonstrates its feasibility for applications in logic circuits and control systems.
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Many studies have shown that hydrogen has anti-inflammatory and anti-oxidant effects. Because of its ability to quickly pass through cell membranes, hydrogen has become a hot spot in the research of inflammatory diseases. Vitamin E glycerin (VEG) and hydrogen-rich Vitamin E glycerin (HR-VEG) were prepared, aiming to explore their anti-inflammatory activities in mice mastitis induced by Staphylococcus aureus (S. aureus). In the early part of this study, the prepared vitamin E medium (VEM) and hydrogen-rich vitamin E medium (HR-VEM) were added to mammary epithelial cells infected with S. aureus. HR-VEM was found to be more effective in reducing the phosphorylation of p65 and p38 and in reducing the production of interleukin-1 beta (IL-1ß) than VEM. Whereafter, the mice model of mastitis was established by injecting S. aureus from the mammary duct. Then VEG and HR-VEG were applied to the mammary gland for seven consecutive days. After that, the clinical symptoms, histopathology, bacterial load, inflammatory factors, as well as the related pathway were analyzed. The results showed that HR-VEG can more significantly alleviate the damage of mammary tissue than VEG, and reduce the production of tumor necrosis factor-alpha (TNF-α), IL-1ß and interleukin 6 (IL-6). In addition, HR-VEG inhibited the TLR2 and Nod2 signaling pathways and reduced the phosphorylation level of MAPK and NF-κB signaling pathways in S. aureus-induced murine mastitis. This study indicates that hydrogen helps to ameliorate S. aureus-induced mastitis in mice through attenuating TLR2 and Nod2 mediated NF-κB and MAPK activation.
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Mastite , Infecções Estafilocócicas , Animais , Anti-Inflamatórios/uso terapêutico , Feminino , Glicerol/metabolismo , Glicerol/farmacologia , Glicerol/uso terapêutico , Humanos , Hidrogênio/farmacologia , Hidrogênio/uso terapêutico , Interleucina-6/metabolismo , Glândulas Mamárias Animais/patologia , Mastite/patologia , Camundongos , NF-kappa B/metabolismo , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/fisiologia , Receptor 2 Toll-Like/metabolismo , Vitamina E/uso terapêuticoRESUMO
Plasmonic sensors are promising for ultrasensitive chemical and biological analysis. Gold nanoplates (Au NPLs) show unique geometrical structures with high ratios of surface to bulk atoms, which display fascinating plasmonic properties but require optimization. This study presented a systematic investigation of the influence of different parameters (shape, aspect ratio, and resonance mode) on localized surface plasmon resonance properties, refractive index (RI, n) sensitivities, and surface-enhanced Raman scattering (SERS) enhancement ability of different types of Au NPLs through finite-difference time-domain (FDTD) simulations. As a proof of concept, triangular, circular, and hexagonal Au NPLs with varying aspect ratios were fabricated via a three-step seed-mediated growth method by the experiment. Both FDTD-simulated and measured experimental results confirm that the RI sensitivities increase with the aspect ratio. Furthermore, choosing a lower order resonance mode of Au NPLs benefits higher RI sensitivities. The SERS enhancement abilities of Au NPLs also predicted to be highly dependent on the shape and aspect ratio. The triangular Au NPLs showed the highest SERS enhancement ability, while it drastically decreased for circular Au NPLs after the rounding process. The SERS enhancement ability gradually became more intense as the hexagonal Au NPLs overgrown on circular Au NPLs with increasing volumes of HAuCl4 solution. The results are expected to help develop effective biosensors.
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Ouro , Nanopartículas Metálicas , Refratometria , Ouro/química , Nanopartículas Metálicas/química , Refratometria/instrumentação , Análise Espectral Raman/métodos , Ressonância de Plasmônio de Superfície/métodosRESUMO
Novel polymers containing a refractory metal in the main chain are highly desired as ultra-high temperature ceramic precursors. Herein, a low oxidation state active species Cp2Zr(ii) with two semi-filled outer orbits was firstly obtained using Cp2ZrCl2 with Mg. This active species of Cp2Zr(ii) was subsequently copolymerized with (CH3)2Si(CH2Cl)2 to form a PZCS precursor with a Zr-C-Si main chain. The pathways of constructing the Zr-C-Si main chain were proposed based on the active species Cp2Zr(ii) polymerization combined with the auxiliary function of ·MgCl, quite different from the conventional understanding of using the Grignard reaction mechanism to explain the synthesis of metal-containing polymer precursors. The ceramic yield of the PZCS precursor at 900 °C is 43.9 wt%, and the ZrC/SiC/C composite preceramic powder was prepared by the pyrolysis of the PZCS precursor, which has important application prospects in ultra-high sonic aircraft and aero rocket engines. It is expected that this stepwise method of using refractory metal-containing active species to synthesize main-chain metallopolymers would provide significant guidance for preparing novel UHTCs precursors.
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BACKGROUND: Spinal muscular atrophy (SMA) is a neuromuscular disease mainly caused by the absence of both copies of the survival motor neuron 1 (SMN1) gene. Multiple regions recommended population-wide SMA screening to quantify the copy number of SMN1. SMN1 diagnostic assays for the simplified procedure, high sensitivity, and throughput continue to be needed. METHODS: Real-time PCR with high-resolution melting for the quantifying of the SMN1 gene exon 7 copies and exon 8 copies were established and confirmed by multiplex ligation-dependent probe amplification (MLPA). The diagnosis of 2563 individuals, including SMA patients, suspected cases, and the general population, was tested by real-time PCR. The results were compared with the gold standard test MLPA. RESULTS: In this study, the homozygous and heterozygous deletions were detected by real-time PCR with a high-resolution melting method with an incidence of 10.18% and 2.26%, respectively. In addition, the R-value distribution (P > 0.05) among 8 replicates and the coefficient of variation (CV < 0.003) suggested that the real-time PCR screening test had high reproducibility. High concordance was obtained between real-time PCR with high-resolution melting and MLPA. CONCLUSIONS: The real-time PCR based on high-resolution melting provides a sensitive and high-throughput approach to large-scale SMA carrier screening with low cost and labor.
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Variações do Número de Cópias de DNA , Atrofia Muscular Espinal , Variações do Número de Cópias de DNA/genética , Humanos , Neurônios Motores , Atrofia Muscular Espinal/diagnóstico , Atrofia Muscular Espinal/genética , Reação em Cadeia da Polimerase em Tempo Real/métodos , Reprodutibilidade dos Testes , Proteína 1 de Sobrevivência do Neurônio Motor/genéticaRESUMO
Cell death and inflammation are intimately linked during mastitis due to Staphylococcus aureus (S. aureus). Pyroptosis, a programmed necrosis triggered by gasdermin protein family, often occurs after inflammatory caspase activation. Many pathogens invade host cells and activate cell-intrinsic death mechanisms, including pyroptosis, apoptosis, and necroptosis. We reported that bovine mammary epithelial cells (MAC-T) respond to S. aureus by NOD-like receptor protein 3 (NLRP3) inflammasome activation through K+ efflux, leading to the recruitment of apoptosis-associated speck-like protein (ASC) and the activation of caspase-1. The activated caspase-1 cleaves gasdermin D (GSDMD) and forms a N-terminal pore forming domain that drives swelling and membrane rupture. Membrane rupture results in the release of the pro-inflammatory cytokines IL-18 and IL-1ß, which are activated by caspase-1. Can modulate GSDMD activation by NLRP3-dependent caspase-1 activation and then cause pyroptosis of bovine mammary epithelial cells.
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Inflamassomos , Piroptose , Animais , Bovinos , Células Epiteliais/metabolismo , Feminino , Inflamassomos/metabolismo , Interleucina-1beta/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteínas NLR , Staphylococcus aureus/metabolismoRESUMO
As a highly toxic heavy metal, chromium has caused a certain threat to public health and livestock breeding in recent years. In poultry, as one of our most commonly consumed meat product, its health issues will seriously threaten the safety of human life. As previous studies have confirmed, when cells are stimulated by the external environment, mitochondria, as an organelle that provides energy to the cells, can cause damage and autophagy. The purpose of this study is to confirm whether Cr(VI) can cause mitophagy in cock heart. We first randomly divided 32 cocks into four groups to explore the mechanism of this effect. The cocks were then separately exposed to four different dose levels, namely, the control level and 10, 30, and 50 mg/kg levels, via daily oral intake into the body through mixed feeding for 45 days. After 45 days, we sampled and detected pathological changes and the levels of inflammatory factors (IL-6, TNF-α, and IFN-γ), mitochondrial membrane potential (MMP), adenosine triphosphatases (ATPases), and mitophagy-related proteins (LC3, p62/SQTM1, TOMM20, and Parkin). We found that IL-6, TNF-α, IFN-γ, and LC3II contents increased with the increase in Cr(VI) concentration. However, MMP, ATPases, p62/SQTM1, and TOMM20 levels decreased with the increase in Cr(VI) concentration. At the same time, Cr(VI) exposure caused heart tissue damages and Parkin translocation. In conclusion, our results proved that inflammatory damage, mitochondrial function damage, and mitophagy in cock heart tissues were dependent on Cr(VI) concentration.
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Cromo , Mitofagia , Animais , Administração Oral , Cromo/toxicidade , Mitocôndrias , Aves DomésticasRESUMO
Introduction: Hexavalent chromium or Cr(VI) is essential to various industries, such as leather manufacturing and stainless steel production. Given that inevitable leakage from industries pollutes the soil and thereby affects the soil environment. Microbial communities could improve the quality of the soil. Abundant bacterial communities would significantly enhance the soil richness and resist external pressure, benefiting agriculture. But the pollution of heavy metal broke the balance and decrease the abundance of bacterial communities, which weak the self-adjust ability of soil. This study aimed to explore changes in the diversity of soil bacterial communities and to identify the influences of soil bacterial communities on enzymes in soil polluted by Cr(VI). Methods: The target soils were sampled quickly and aseptically. Their chromium content was detected through inductively coupled plasma-mass spectrometry, and bacterial microbiome communities were explored through MiSeq high-throughput sequencing. Then, the content of nitrite reductase and catalases were investigated through enzyme-linked immunosorbent assay (ELISA). Results: Chromium content in polluted soils was higher than that in the control soils at all depths. Sobs, Chao1, Ace, and Shannon diversity estimators in the control were higher, whereas Simpson's diversity estimators in the control soils were lower than those of contaminated samples at all depths. Contaminants affected the composition of the bacterial community. The soil microbial species were relatively single and inhomogeneous in the polluted soils. The bacterial phyla in polluted and controlled soils include Proteobacteria, Actinobacteria, Chloroflexi, and Acidobacteria, which differ markedly in abundance. Discussion: The results of these observations provide insights into the ecotoxicological effects of Cr(VI) exposure to soil microorganisms. To sum up these results are critical for evaluating the stabilized state of microbial community structures, contributing to the assessment of the potential risk of metal accumulation in soils.