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Efficient methane photooxidation to formic acid (HCOOH) has emerged as a sustainable approach to simultaneously generate value-added chemicals and harness renewable energy. However, the persistent challenge lies in achieving a high yield and selectivity for HCOOH formation, primarily due to the complexities associated with modulating intermediate conversion and desorption after methane activation. In this study, we employ first-principles calculations as a comprehensive guiding tool and discover that by precisely controlling the O2 activation process on noble metal cocatalysts and the adsorption strength of carbon-containing intermediates on metal oxide supports, one can finely tune the selectivity of methane photooxidation products. Specifically, a bifunctional catalyst comprising Pd nanoparticles and monoclinic WO3 (Pd/WO3) would possess optimal O2 activation kinetics and an intermediate oxidation/desorption barrier, thereby promoting HCOOH formation. As evidenced by experiments, the Pd/WO3 catalyst achieves an exceptional HCOOH yield of 4.67 mmol gcat-1 h-1 with a high selectivity of 62% under full-spectrum light irradiation at room temperature using molecular O2. Notably, these results significantly outperform the state-of-the-art photocatalytic systems operated under identical condition.
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As fuel and an important chemical feedstock, n-propanol is highly desired in electrochemical CO2/CO reduction on Cu catalysts. However, the precise regulation of the Cu localized structure is still challenging and poorly understood, thus hindering the selective n-propanol electrosynthesis. Herein, by decorating Au nanoparticles (NPs) on CuO nanosheets (NSs), we present a counterintuitive transformation of CuO into undercoordinated Cu sites locally around Au NPs during CO reduction. In situ spectroscopic techniques reveal the Au-steered formation of abundant undercoordinated Cu sites during the removal of oxygen on CuO. First-principles accuracy molecular dynamic simulation demonstrates that the localized Cu atoms around Au tend to rearrange into disordered layer rather than a Cu (111) close-packed plane observed on bare CuO NSs. These Au-steered undercoordinated Cu sites facilitate CO binding, enabling selective electroreduction of CO into n-propanol with a high Faradaic efficiency of 48% in a flow cell. This work provides new insight into the regulation of the oxide-derived catalysts reconstruction with a secondary metal component.
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Electrocatalytic ethylene (C2H4) evolution from CO2 reduction is an intriguing route to mitigate both the energy and environmental crises; however, to acquire industrially relevant high productivity and selectivity at low energy cost remains to be challenging. Membrane assembly electrode has shown great prospect and tailoring its architecture for maximizing C2H4 yield at minimum voltage with long-term stability becomes critical. Here a freestanding Cu membrane cathode is designed and constructed by electrochemically depositing mesoporous Cu film on Cu foam to simultaneously manage CO2, electron, water, and product transport, which shows an extraordinary C2H4 Faradaic efficiency of 85.6% with a full cell power conversion efficiency of 33% at a current density of 368 mA cm-2, heading the techno-economic viability for electrocatalytic C2H4 production.
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Intracardiac thrombosis is a severe complication in patients with non-ischemic dilated cardiomyopathy. This study aims to develop and validate an individualized nomogram to evaluate the risk of intracardiac thrombosis in patients with non-ischemic dilated cardiomyopathy. This retrospective study included patients diagnosed with dilated cardiomyopathy at first admission. Clinical baseline characteristics were acquired from electronic medical record systems. Multiple methods were applied to screen the key variables and generate multiple different variable combinations. Multivariable logistic regression was used to build the models, and the optimal model was chosen by comparing the discrimination. Then we checked the performance of the model in different thrombus subgroups. Finally, the model was presented using a nomogram and evaluated from the perspectives of discrimination, calibration, and clinical usefulness. Internal validation was performed by extracting different proportions of data for Bootstrapping. Ultimately, 564 eligible patients were enrolled, 67 of whom developed an intracardiac thrombosis. Risk factors included d-dimer, white blood cell count, high-sensitivity C-reactive protein, pulse pressure, history of stroke, hematocrit, and NT-proBNP in the optimal model. The model had good discrimination and calibration, and the area under the curve (AUC) was 0.833 (0.782-0.884), and the model's performance in each subgroup was stable. Clinical decision curve analysis showed that the model had clinical application value when the high-risk threshold was between 2% and 78%. The AUC of interval validation (30% and 70% data resampling) was 0.844 (0.765-0.924) and 0.833 (0.775-0.891), respectively. This novel intracardiac thrombosis nomogram could be conveniently applied to facilitate the individual intracardiac thrombosis risk assessment in patients with non-ischemic dilated cardiomyopathy.
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Cardiomiopatía Dilatada , Trombosis , Humanos , Estudios Retrospectivos , Cardiomiopatía Dilatada/complicaciones , Nomogramas , Trombosis/etiología , Factores de RiesgoRESUMEN
Objective:To compare the effectiveness of cylindrical-shaped and conical-shaped cuff catheters for airway closure using different pressure measurement methods at the lowest safe pressure and to guide the clinical application.Methods:Twenty-four patients with endotracheal intubation admitted to the intensive care unit (ICU) of Guangxi Medical University Cancer Hospital from December 2021 to January 2022 were enrolled. Leakage test in vitro was performed on the secretion on the patients' cuff. The needle and plunger from 20 mL syringe was separated, the syringe was sealed with adhesive, and the syringe nozzle was filled thoroughly to create a tracheal model. Consecutively, both cylindrical-shaped and conical-shaped cuff catheters were inserted into the simulated trachea, and the cuff pressure was calibrated to 20 cmH 2O (1 cmH 2O≈0.098 kPa) before commencing the experiment. The viscosity of the secretion on the patients' cuff was classified (grade Ⅰ was watery subglottic secretion, grade Ⅱ was thick subglottic secretion, grade Ⅲ was gel-like subglottic secretion), and the same viscosity secretion was injected into the catheter cuff. Utilizing a self-control approach, intermittent pressure measurement was initially conducted on both the cylindrical-shaped and conical-shaped cuff by improved pressure measurement method (intermittent pressure measurement group), followed by continuous pressure measurement experiment (continuous pressure measurement group). The leakage volume of the three viscosity subglottic secretions and the values of cuff pressure measurement of different shaped cuff catheters at 4, 6, 8 hours of inflation were recorded. Results:A total of 180 retention samples were extracted from 24 patients with tracheal intubation during ventilation, with 90 samples in each of the two groups using different pressure measurement methods, and 30 samples of retention materials with different viscosities in each group. In the intermittent pressure measurement group, at 4 hours of inflation, all samples of secretion with grade Ⅰ and grade Ⅱ on cylindrical-shaped cuff leaked, while 3 samples of secretion with grade Ⅲ also leaked. For conical-shaped cuff, 28 samples of secretion with grade Ⅰ leaked, only 2 samples of secretion with grade Ⅱ leaked, and there was no leak for secretion with grade Ⅲ. At 6 hours of inflation, all samples of the three viscosity secretions on different shaped cuffs leaked. The leakage was gradually increased with the prolongation of inflation time. In the continuous pressure measurement group, at 4 hours of inflation, all samples of secretion with grade Ⅰ on cylindrical-shaped cuff leaked, while 29 samples of secretion with grade Ⅱ leaked, and there was no leak for secretion with grade Ⅲ. For the conical-shaped cuff, 26 samples of secretion with grade Ⅰ leaked, and there was no leak for secretion with grade Ⅱ and grade Ⅲ. At 6 hours of inflation, the conical-shaped cuff still had no leak for secretion with grade Ⅲ. As the inflation time prolonged, the leakage of subglottic secretion on different shaped cuffs in both groups was gradually increased. At 8 hours of inflation, all samples experienced leakage, but the leakage of subglottic secretion on different shaped cuffs in the continuous pressure measurement group was significantly reduced as compared with the intermittent pressure measurement group [leakage for secretion with grade Ⅲ (mL): 1.00 (0.00, 1.25) vs. 2.00 (1.00, 2.00) on the cylindrical-shaped cuff, 1.00 (0.00, 1.00) vs. 2.00 (2.00, 2.00) on the conical-shaped cuff, both P < 0.01]. The values of pressure measurement of cuffs with different shapes at different time points of inflation in the continuous pressure measurement group were within the set range (20-21 cmH 2O). The cuff pressure at 4 hours of inflation in the intermittent pressure measurement group was significantly lower than the initial value (cmH 2O: 18.3±0.6 vs. 20.0±0.0 in the cylindrical-shaped cuff, 18.4±0.6 vs. 20.0±0.0 in the conical-shaped cuff, both P < 0.01), and the cuff pressure in both shaped cuffs showed a significant decrease tendency as inflation time prolonged. However, there was no statistically significant difference in values of pressure measurement between the different shaped cuff catheters. Conclusions:Continuous pressure monitoring devices can maintain the effective sealing of conical-shaped cuff catheters at the lowest safe pressure. When using an improved pressure measurement method for intermittent pressure measurement and/or using a cylindrical cuff catheter, the target pressure should be set at 25-30 cmH 2O, and the cuff pressure should be adjusted regularly.
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Highly enantioretentive alcoholysis of epoxides is an important way to synthesize enantiopure ß-alkoxy alcohols, which are irreplaceable intermediates demanded by biomedicines, fine chemicals and other industries. In this report, we exploit a series of Zr-based metal-organic frameworks (Zr-MOFs) as the catalysts to achieve high activity and enantioretentivity in the alcoholysis of styrene oxide via modulating their assembly fashions. It is explored that hcp-UiO-66 not only exhibits a â¼10 fold improved catalytic activity than both hxl-CAU-26 and fcc-UiO-66 of varied assemblies but also maintains superior product enantioretentivity. Theoretic calculations together with experimental proof discloses the origin of distinct catalytic activity caused by different assembly fashions. This assembly modulation strategy offers a potential protocol for seeking high-performance catalysts among MOFs by virtue of their rich polymorphisms.
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Oxide-derived copper (OD-Cu) is the most efficient and likely practical electrocatalyst for CO2 reduction toward multicarbon products. However, the inevitable but poorly understood reconstruction from the pristine state to the working state of OD-Cu under strong reduction conditions largely hinders the rational construction of catalysts toward multicarbon products, especially C3 products like n-propanol. Here, we simulate the reconstruction of CuO and Cu2O into their derived Cu by molecular dynamics, revealing that CuO-derived Cu (CuOD-Cu) intrinsically has a richer population of undercoordinated Cu sites and higher surficial Cu atom density than the counterpart Cu2O-derived Cu (Cu2OD-Cu) because of the vigorous oxygen removal. In situ spectroscopes disclose that the coordination number of CuOD-Cu is considerably lower than that of Cu2OD-Cu, enabling the fast kinetics of CO2 reaction and strengthened binding of *C2 intermediate(s). Benefiting from the rich undercoordinated Cu sites, CuOD-Cu achieves remarkable n-propanol faradaic efficiency up to ~17.9%, whereas the Cu2OD-Cu dominantly generates formate.
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Oxidizing species or radicals generated in water are of vital importance in catalysis, the environment, and biology. In addition to several related reactive oxygen species, using electron paramagnetic resonance (EPR), we present a nontrapping chemical transformation pathway to track water radical cation (H2O+â¢) species, whose formation is very sensitive to the conditioning environments, such as light irradiation, mechanical action, and gas/chemical introduction. We reveal that H2O+⢠can oxidize the 5,5-dimethyl-1-pyrroline N-oxide (DMPO) to the crucial epoxy hydroxylamine (HDMP=O) intermediate, which further reacts with the hydroxyl radical (â¢OH) for the formation of the EPR-active sextet radical (DMPO=Oâ¢). Interestingly, we uncover that H2O+⢠can react with dimethyl methylphosphonate (DMMP), 2-methyl-2-nitrosopropane (MNP), 5-tert-butoxycarbonyl-5-methyl-1-pyrroline N-oxide (BMPO), and α-phenyl-N-tert-butylnitrone (PBN) which contain a double-bond structure to produce corresponding derivatives as well. It is thus expected that both H2O+⢠and â¢OH are ubiquitous in nature and in various water-containing experimental systems. These findings provide a novel perspective on radicals for water redox chemistry.
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The invasiveness and dissemination of exotic species are strongly influenced by its sexual reproduction characteristics, including blooming characteristics and breeding system. Exploring the association of these sexual reproductive traits with invasiveness would be helpful for revealing the mechanism of its successful invasion. We examined the blooming characteristics and breeding system of Gaura parviflora based on field observations, out-crossing index (OCI) estimation, and hand-pollination experiments. The results showed flowering duration of the G. parviflora population (flowering period) was short (more than 3 months). The life span of single flower (floral longevity) was 40.46 h. Its flower diameter was 3.99 mm. Over seven flowers in bloom per inflorescence and most individuals often bloomed synchronously, which showed a 'mass-flowering pattern'. The changing trend of pollen and stigma vitality was relatively similar, but the duration of stigma vitality was 2 h longer than that of pollen. The stigma and the anthers were close to each other at the initial flowering stage, but the stigma removed from the anthers at the full-blooming stage with the style curving downwards. Many pollinators visited flowers in late full-blooming stage, which were mainly Apis mellifera and Syrphidae spp. Their average visiting frequency was 9.8 times·m-2·h-1. The fruit set in natural pollination after emasculation treatment (insect or wind pollination) was signi-ficantly higher than that in bagged and emasculation treatment, and the treatment of emasculated and bagged with nylon net (excluding insect pollination) could also bear fruits, indicating possible existence of ambophily in G. parviflora. The results of pollen ovule ratio (P/O) mensuration, OCI estimation and hand-pollination experiments showed that its mating system type belonged to additive mixed mating system. So, its characteristics, such as smaller flower size, shorter floral longevity and flowering period, were conducive to allocating more resources to plant growth and seed development, which would help improve its total fitness. The changes of spatial position of male and female organs not only avoided interference between male and female functions, but also created opportunities for stigmas to receive outcross pollen. In addition, the 'mass-flowering pattern' was conducive to attracting pollinators. The pollination mechanism of ambophily was helpful to ensure cross-pollination. The additive mixed mating system could provide double reproductive assurance for this species. These reproductive characteristics were significant for the successful invasion and expansion of G. parviflora.
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Fitomejoramiento , Reproducción , Humanos , Animales , Abejas , Polen , Polinización , FloresRESUMEN
Electrochemical CO2 conversion to value-added multicarbon (C2+ ) chemicals holds promise for reducing CO2 emissions and advancing carbon neutrality. However, achieving both high conversion rate and selectivity remains challenging due to the limited active sites on catalysts for carbon-carbon (CâC) coupling. Herein, porous CuO is coated with amorphous CuSiO3 (p-CuSiO3 /CuO) to maximize the active interface sites, enabling efficient CO2 reduction to C2+ products. Significantly, the p-CuSiO3 /CuO catalyst exhibits impressive C2+ Faradaic efficiency (FE) of 77.8% in an H-cell at -1.2 V versus reversible hydrogen electrode in 0.1 M KHCO3 and remarkable C2 H4 and C2+ FEs of 82% and 91.7% in a flow cell at a current density of 400 mA cm-2 in 1 M KOH. In situ characterizations and theoretical calculations reveal that the active interfaces facilitate CO2 activation and lower the formation energy of the key intermediate *OCCOH, thus promoting CO2 conversion to C2+ . This work provides a rational design for steering the active sites toward C2+ products.
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Electrochemical chlorine evolution reaction is of central importance in the chlor-alkali industry, but the chlorine evolution anode is largely limited by water oxidation side reaction and corrosion-induced performance decay in strong acids. Here we present an amorphous CoOxCly catalyst that has been deposited in situ in an acidic saline electrolyte containing Co2+ and Cl- ions to adapt to the given electrochemical condition and exhibits ~100% chlorine evolution selectivity with an overpotential of ~0.1 V at 10 mA cm-2 and high stability over 500 h. In situ spectroscopic studies and theoretical calculations reveal that the electrochemical introduction of Cl- prevents the Co sites from charging to a higher oxidation state thus suppressing the O-O bond formation for oxygen evolution. Consequently, the chlorine evolution selectivity has been enhanced on the Cl-constrained Co-O* sites via the Volmer-Heyrovsky pathway. This study provides fundamental insights into how the reactant Cl- itself can work as a promoter toward enhancing chlorine evolution in acidic brine.
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Selective electrochemical upgrading of CO2 to multicarbon (C2+) products requires a C-C coupling process, yet the underlying promoting mechanism of widely involved Cu oxidation states remains largely unclear, hindering the subtle design of efficient catalysts. Herein, we unveil the critical role of Cu+ in promoting C-C coupling via coordination with a CO intermediate during electrochemical CO2 reduction. We find that, relative to other halogen anions, iodide (I-) in HCO3- electrolytes accelerates the generation of strongly oxidative hydroxyl radicals that accounts for the formation of Cu+, which can be dynamically stabilized by I- via the formation of CuI. The in situ generated CO intermediate strongly binds to CuI sites, forming nonclassical Cu(CO)n+ complexes, leading to an approximately 3.0-fold increase of C2+ Faradaic efficiency at -0.9 VRHE relative to that of I--free Cu surfaces. Accordingly, a deliberate introduction of CuI into I--containing HCO3- electrolytes for direct CO electroreduction brings about a 4.3-fold higher C2+ selectivity. This work provides insights into the role of Cu+ in C-C coupling and the enhanced C2+ selectivity for CO2 and CO electrochemical reduction.
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Strategies to generate high-valence metal species capable of oxidizing water often employ composition and coordination tuning of oxide-based catalysts, where strong covalent interactions with metal sites are crucial. However, it remains unexplored whether a relatively weak "non-bonding" interaction between ligands and oxides can mediate the electronic states of metal sites in oxides. Here we present an unusual non-covalent phenanthroline-CoO2 interaction that substantially elevates the population of Co4+ sites for improved water oxidation. We find that phenanthroline only coordinates with Co2+ forming soluble Co(phenanthroline)2(OH)2 complex in alkaline electrolytes, which can be deposited as amorphous CoOxHy film containing non-bonding phenanthroline upon oxidation of Co2+ to Co3+/4+. This in situ deposited catalyst demonstrates a low overpotential of 216 mV at 10 mA cm-2 and sustainable activity over 1600 h with Faradaic efficiency above 97%. Density functional theory calculations reveal that the presence of phenanthroline can stabilize CoO2 through the non-covalent interaction and generate polaron-like electronic states at the Co-Co center.
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Selective CH4 oxidation to CH3OH or HCHO with O2 in H2O under mild conditions provides a desired sustainable pathway for synthesis of commodity chemicals. However, manipulating reaction selectivity while maintaining high productivity remains a huge challenge due to the difficulty in the kinetic control of the formation of a desired oxygenate against its overoxidation. Here, we propose a highly efficient strategy, based on the precise control of the type of as-formed radicals by rational design on photocatalysts, to achieve both high selectivity and high productivity of CH3OH and HCHO in CH4 photooxidation for the first time. Through tuning the band structure and the size of active sites (i.e., single atoms or nanoparticles) in our Au/In2O3 catalyst, we show alternative formation of two important radicals, â¢OOH and â¢OH, which leads to distinctly different reaction paths to the formation of CH3OH and HCHO, respectively. This approach gives rise to a remarkable HCHO selectivity and yield of 97.62% and 6.09 mmol g-1 on In2O3-supported Au single atoms (Au1/In2O3) and an exceptional CH3OH selectivity and yield of 89.42% and 5.95 mmol g-1 on In2O3-supported Au nanoparticles (AuNPs/In2O3), respectively, upon photocatalytic CH4 oxidation for 3 h at room temperature. This work opens a new avenue toward efficient and selective CH4 oxidation by delicate design of composite photocatalysts.
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The intestinal mechanical barrier is the first line of defense against intestinal bacteria,and its damage can lead to a variety of diseases.Lactobacillus,as a probiotic with clinical application prospect,can stimulate the proliferation and differentiation of intestinal epithelial cells,reduce the death of intestinal epithelial cells,enhance the connectivity between intestinal epithelial cells,and promote mucin secretion and improve and maintain the mechanical barrier of intestinal tract.This article reviews the role and mechanism of Lactobacillus in protecting the intestinal mechanical barrier,aiming to deepen the understanding of Lactobacillus,explore its prevention and treatment of intestinal diseases in future clinical practice,and inspire new microbial strategies for the clinical application of Lactobacillus and its products.
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Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
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Masculino , Femenino , Humanos , Anciano , Péptido Natriurético Encefálico , Simendán/uso terapéutico , Infarto del Miocardio sin Elevación del ST , Insuficiencia Cardíaca/tratamiento farmacológico , Fragmentos de Péptidos , Arritmias Cardíacas , Biomarcadores , PronósticoRESUMEN
Objective@#The real-world INFORM study analyzed sociodemographics, treatment patterns and clinical outcomes for patients with newly diagnosed advanced epithelial ovarian cancer (EOC) in Australia, South Korea (S.Korea) and Taiwan preceding incorporation of poly(ADP-ribose) polymerase inhibitors into clinical practice. @*Methods@#Retrospective data from patients diagnosed with EOC (high-grade serous EOC for Taiwan) between January 2014 and December 2018 with ≥12 months follow-up from diagnosis were analyzed descriptively. Survival was evaluated by Kaplan-Meier with two-sided 95% confidence interval (CI). @*Results@#Of the 987 patients (Australia, 223; S.Korea, 513; Taiwan, 251), 98% received platinum-based chemotherapy (CT). In S.Korea and Taiwan 76.0% and 78.9% respectively underwent primary cytoreductive surgery; in Australia, 56.5% had interval debulking surgery. Bevacizumab was included in primary/maintenance therapy for 22.4%, 14.6% and 6.8% of patients in Australia, S.Korea and Taiwan, respectively. Patients receiving bevacizumab were high-risk (reimbursement policy) and achieved similar real-world progression-free survival (PFS) compared with CT only. Overall, the median real-world PFS (months; 95% CI) was similar across Australia (16.0 [14.63–18.08]), S.Korea (17.7 [16.18–19.27]) and Taiwan (19.1 [17.56–22.29]). @*Conclusion@#This study reveals poor prognosis despite differences in demographics and treatment patterns for patients with EOC across Asia-Pacific suggesting the need for biomarker-driven novel therapies to improve outcomes.
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Objectives:To establish a model of Mycobacterium tuberculosis infection of osteoclasts(OC)and explore the mechanism of Mycobacterium tuberculosis infection on OC.Methods:Peripheral blood mononuclear cells(peripheral blood mononuclear cells,PBMCs)were isolated from healthy volunteers.Receptor activator of nuclear factor-KB ligand(RANKL)and macrophage-colony stimulating factor(M-CSF)were used to make PBMCS into OC,and tartrate resistant acid phosphatase(TRAP)staining was performed on the cells.The constructed kanamycin resistant H37Rv pMV261-GFP green fluorescent strain was resuscitated and cultured with 10%oleic albumin dextrose catalase(OADC),7H9 and kanamycin containing Mycobacterium tuberculosis special liquid medium in an incubator at 37℃ until the optical density(OD)value was about 0.5 at 600nm.The OC cells cultured alone were set as the blank control group.And OC cells were also infected with Mycobacterium tuberculosis at different multiplicity of infection(MOI)for 24h,and MTT colorimetric method was used to detect cell survival rate.The MOI with the highest cell survival rate was selected as experimental MOI,and OC cells infected with H37Rv at experimental MOI were set as the experimental group.Fluorescence microscopy and Mycobacterium tuberculosis acid-fast staining were used to observe the transfection of Mycobacterium tuberculosis at the experimental MOI.Quantitative real-time PCR(qRT-PCR)was used to detect the expressions of non-receptor tyrosine kinase C-src,cathepsin K(CK),carbonic anhydrase 2(CA2),Integrin-β3 and matrix metalloproteinase-9(MMP-9).Immunohistochemistry was used to detect the expressions of P-src,CK,CA2,Integrin-β3 and MMP-9 on the cell surface.Western blot(WB)was used to detect the protein expression levels of P-src,CK,CA2,Integrin-β3,and MMP-9.Results:TRAP staining showed that more than 90%of the cells were OC after 15d of culture,which could be used for experiments.The results of MTT colorimetric assay showed that the cell survival rate was the highest when the MOI was 20:1(P<0.05).This transfection multiplicity can be used as the concentration of experimental group.Fluorescence microscopy showed that when the transfection multiplicity ratio was 20:1,the green fluorescent Mycobacterium tuberculosis entered the OC and was successfully transfected into the OC.The results of acid-fast staining after infection of OC with Mycobacterium tuberculosis showed that when the MOI was 20:1,the acid-fast Mycobacterium tuberculosis stained red entered OC and was also successfully transfected into OC.The results of qRT-PCR,cell immunohistochemistry,and WB showed that the expressions of MMP-9,CK,C-src,CA2,and Integrin-β3 in the experimental group were higher than those in the blank control group(P<0.05).Conclusions:Mycobacterium tuberculosis can transfect OC;Compared with the blank control group,the levels of five bone destruction factors in the experimental group transfected with OC by Mycobacterium tuberculosis were increased,suggesting that bone destruction of spinal tuberculosis may be related to this,which may provide a new exploration direction for the diagnosis and treatment of bone tuberculosis diseases.
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Background: The peripheral blood gene expression profile of patients with coronary artery disease (CAD) has not been fully resolved. The aim of this study was to further analyze the peripheral blood transcriptome information of CAD patients and to uncover key genes and regulatory mechanisms in the pathogenesis and disease progression of CAD. Methods: The Gene Expression Omnibus (GEO) database was applied to screen out differentially expressed genes (DEGs) in the peripheral blood of CAD patients, and the DEGs were subjected to Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA). The core genes were screened by GO, KEGG, and GSEA, and the gene-gene interaction (GGI) and protein-protein interaction (PPI) networks of DEGs were constructed. The GeneCards database was used to obtain CAD-related genes, and the GEO dataset was used to obtain intersecting genes. The intersecting genes were analyzed for bioenrichment and prediction of potential therapeutic agents, and predictive models were constructed for the intersecting genes. Finally, immune infiltrating cells from the GEO dataset were analyzed. Results: A total of 79 DEGs were screened in the peripheral blood of CAD patients, of which three were autophagy-related genes. Biological enrichment analysis showed that the DEGs were associated with metabolic pathways, and vascular smooth muscle contraction and were mainly involved the MAPK signaling pathway, metabolic pathways, and the PI3K-Akt signaling pathway. The S100A8, ENTPD1, and MMP9 further screened were screened. A total of 11 CAD crossover genes and 75 potential therapeutic agents were obtained, and the column line graph prediction models constructed for S100A8, HSPB1, F5, MMP9, and PDE9A had good predictive power. There were significant differences in immune cells in CAD patients compared to healthy individuals, especially in T cells regulatory (Tregs) and B cells naïve. Conclusions: The peripheral blood of CAD patients screened by the GEO dataset was significantly different from that of the healthy population, and the DEGs and intersecting genes were involved in numerous key biological processes that may be involved in the development and progression of CAD and could serve as its regulatory sites and therapeutic drug targets.