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1.
Blood ; 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38958479

ABSTRACT

This study aimed to compare the efficacy and safety of eltrombopag plus diacerein vs. eltrombopag alone in patients with primary immune thrombocytopenia (ITP) who were previously unresponsive to 14 days of eltrombopag treatment at the full dose. Recruited patients were randomly assigned 1:1 to receive either eltrombopag plus diacerein (n=50) or eltrombopag monotherapy (n=52). Overall response rate, defined as a platelet count at or above 30×109/L, at least doubling of the baseline platelet count, and no bleeding, was reached in 44% of patients in the eltrombopag plus diacerein group compared with 13% in the eltrombopag group at day 15 (P = .0009), and reached in 42% of patients in the combination group compared with 12% in the monotherapy group at day 28 (P = .0006). The addition of diacerein to eltrombopag also led to a longer duration of response (P = .0004). The two most common treatment-emergent adverse events were respiratory infection and gastrointestinal reactions in the combination group, and fatigue and respiratory infection in the eltrombopag group. In conclusion, eltrombopag plus diacerein was well tolerated, and induced higher overall response rates and longer duration of response than eltrombopag alone, offering a rejuvenating salvage therapy for ITP patients unresponsive to 14 days of full dosage eltrombopag. Our work has the potential to enhance the care of patients treated with thrombopoietin receptor agonists, reducing the need for rapid transitions to less-preferable therapies. This study is registered at ClinicalTrials.gov as NCT04917679.

2.
Foods ; 13(11)2024 May 22.
Article in English | MEDLINE | ID: mdl-38890836

ABSTRACT

Nisin is used as a natural food preservative because of its broad-spectrum antimicrobial activity against Gram-positive bacteria. However, free nisin is susceptible to various factors that reduce its antimicrobial activity. Milk protein, a protein derived from milk, has self-assembly properties and is a good carrier of bioactive substances. In this study, lactoferrin-nisin nanoparticles (L-N), bovine serum albumin-nisin nanoparticles (B-N), and casein-nisin nanoparticles (C-N) were successfully prepared by a self-assembly technique, and then their properties were investigated. The studies revealed that lactoferrin (LF) and nisin formed L-N mainly through hydrophobic interactions and hydrogen bonding, and L-N had the best performance. The small particle size (29.83 ± 2.42 nm), dense reticular structure, and good thermal stability, storage stability, and emulsification of L-N laid a certain foundation for its application in food. Further bacteriostatic studies showed that L-N enhanced the bacteriostatic activity of nisin, with prominent inhibitory properties against Listeria monocytogenes, Staphylococcus aureus, and Bacillus cereus, which mainly disrupted the cell membrane of the bacteria. The above results broaden our understanding of milk protein-nisin nanoparticles, while the excellent antibacterial activity of L-N makes it promising for application as a novel food preservative, which will help to improve the bioavailability of nisin in food systems.

3.
Int J Psychophysiol ; 200: 112358, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38710371

ABSTRACT

Recent studies have shown that the processing of neutral facial expressions could be modulated by the valence and self-relevance of preceding verbal evaluations. However, these studies have not distinguished the dimension (i.e., morality and competence) from verbal evaluations. In fact, there is a hot controversy about whether morality or competence receives more weight. Therefore, using the ERP technique, the current study aimed to address this issue by comparing the influence of morality and competence evaluations on behavioral and neural responses to neutral facial expressions when these evaluations varied with contextual valence and self-relevance. Our ERP results revealed that the early EPN amplitudes were larger for neutral faces after receiving evaluations about self relative to evaluations about senders. Moreover, the EPN was more negative after a competence evaluation relative to a morality evaluation when these evaluations were positive, while this effect was absent when these evaluations were negative. The late LPP was larger after a morality evaluation compared to a competence evaluation when these evaluations were negative and directed to self. However, no significant LPP effect between morality and competence evaluations was observed when these evaluations were positive. The present study extended previous studies by showing that early and late processing stages of faces are affected by the evaluation dimension in a top-down manner and further modulated by contextual valence and self-relevance.


Subject(s)
Electroencephalography , Evoked Potentials , Morals , Humans , Female , Male , Young Adult , Adult , Evoked Potentials/physiology , Facial Expression , Facial Recognition/physiology , Photic Stimulation/methods , Adolescent , Self Concept
4.
Brain Cogn ; 177: 106167, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38704903

ABSTRACT

Although previous research has shown that social power modulates individuals' sensitivity to rewards, it is currently unclear whether social power increases or decreases individuals' sensitivity to rewards. This study employed event-related potentials (ERPs) to investigate the effects of social power on individuals' neural responses to monetary and social rewards. Specifically, participants underwent an episodic priming task to manipulate social power (high-power vs. low-power) and then completed monetary and social delayed incentive tasks while their behavioral responses and electroencephalograms (EEG) were recorded. According to ERP analysis, during the anticipatory stage, low-power individuals exhibited a greater cue-P3 amplitude than high-power individuals in both monetary and social tasks. In the consummatory stage, though no impact of social power on the reward positivity (RewP) was found, low-power individuals showed a higher feedback-P3 (FB-P3) amplitude than high-power individuals, regardless of task types (the MID and SID tasks). In conclusion, these results provide evidence that social power might decrease one's sensitivity to monetary and social rewards in both the anticipatory and consummatory stages.


Subject(s)
Electroencephalography , Evoked Potentials , Reward , Humans , Male , Female , Electroencephalography/methods , Young Adult , Evoked Potentials/physiology , Adult , Power, Psychological , Brain/physiology , Motivation/physiology , Anticipation, Psychological/physiology , Social Behavior , Cues , Adolescent
5.
Nano Lett ; 24(15): 4602-4609, 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38567988

ABSTRACT

Oxygen vacancy (OV) engineering has been widely applied in different types of metal oxide-based photocatalytic reactions. Our study has shown that the redistributed OVs resulting from voids in CeO2 rods lead to significant differences in the band structure in space. The flat energy band within the highly crystallized bulk region hinders the recombination of photogenerated carrier pairs during the transfer process. The downward curved energy band in the surface region enhances the activation of the absorbents. Therefore, the localization of the band structure through crystal structure regionalization renders V-CeO2 capable of achieving efficient utilization of photogenerated carriers. Practically, the V-CeO2 rod shows a remarkable turnover number of 190.58 µmol g-1 h-1 in CO2 photoreduction, which is ∼9.4 times higher than that of D-CeO2 (20.46 µmol g-1 h-1). The designed modularization structure in our work is expected to provide important inspiration and guidance in coordinating the kinetic behavior of carriers in OV defect-rich photocatalysts.

7.
J Cancer ; 15(3): 737-746, 2024.
Article in English | MEDLINE | ID: mdl-38213734

ABSTRACT

This study was designed to develop a model of serum thymidine kinase 1 protein (STK1p) concentration in combination with low-dose computed tomography (LDCT) to predict the risk of benign pulmonary nodules progressing into lung cancer within three years in a large screening population. The study included a retrospective cohort of 6,841 individuals aged > 30 years who had LDCT-detected pulmonary nodules, but no cancer history or baseline cancer. The outcome was a lung cancer diagnosis recorded within three years after the first detection of pulmonary nodules. The adaptive least absolute shrinkage and selection operator was used to select candidate predictors and fit a logistic model. The model was validated internally by examining discrimination (area under the receiver operating characteristic curve (AUC), calibration (calibration plot)) and net benefit. A web application was developed based on the model. The results showed that the proportion of incident lung cancer cases was 0.79% (n=52). Predictors selected for the model were STK1p and three LDCT parameters (nodule size, type, and count). The AUC of the model was 0.91 (95% confidence interval (CI): 0.86, 0.96). The model had satisfactory discrimination at internal validation (AUC: 0.90 (0.84, 0.96)) and in subgroups (AUC=0.69-0.93). The high-risk group identified by the model exhibited a significantly higher three-year lung cancer risk than the low-risk group (odds ratio (OR): 66.03 (95% CI: 30.49, 162.98)). We concluded that the novel model of STK1p and LDCT parameters together can be used to accurately predict the three-year risk of lung cancer in people with pulmonary nodules.

8.
Int J Biol Macromol ; 259(Pt 1): 129152, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38176500

ABSTRACT

Probiotics such as Bifidobacterium spp. generally possess important physiological functions. However, maintaining probiotic viability is a challenge during processing, storage, and digestive transit period. Microencapsulation is widely considered to be an attractive approach. In this study, B. animalis F1-7 microcapsules and B. animalis F1-7-HMO microcapsules were successfully prepared by emulsification/internal gelation with high encapsulation efficiency (90.67 % and 92.16 %, respectively). The current study revealed that HMO-supplemented microcapsules exhibited more stable lyophilized forms and thermal stability. Additionally, a significant improvement in probiotic cell viability was observed in such microcapsules during simulated gastrointestinal (GI) fluids or storage. We also showed that the individual HMO mixtures 6'-SL remarkably promoted the growth and acetate yield of B. animalis F1-7 for 48 h (p < 0.05). The synbiotic combination of 6'-SL with B. animalis F1-7 enhanced SCFAs production in vitro fecal fermentation, decreasing several harmful intestinal bacteria such as Dorea, Escherichia-Shigella, and Streptococcus while enriching the probiotic A. muciniphila. This study provides strong support for HMO or 6'-SL combined with B. animalis F1-7 as an innovative dietary ingredient to bring health benefits. The potential of the synbiotic microcapsules with this combination merits further exploration for future use in the food industry.


Subject(s)
Bifidobacterium animalis , Probiotics , Synbiotics , Humans , Milk, Human , Capsules , Health Maintenance Organizations , Oligosaccharides
9.
ACS Sens ; 9(1): 139-148, 2024 Jan 26.
Article in English | MEDLINE | ID: mdl-38096168

ABSTRACT

The high density of surface active sites, high efficiency of interfacial carrier transport, and molecular diffusion path determine the efficiency of the electrochemical sensors. The ultrathin structures have atomic-level thickness, carrier migration and heat diffusion are limited in the two-dimensional plane, resulting in excellent conductivity and high carrier concentration. A one-step chemical method is applied to synthesize defect-rich Au-SnO2 in an ultrathin nanosheet form (thickness of 2-3 nm). The strong interaction between Au and SnO2 via the Au-O-Sn bonding and the catalytic effect of Au can prolong the service life via decreasing the optimal operating temperature (55 °C) and promote the Au-SnO2 sensor to exclusively detect formaldehyde at the ppb level (300 ppb). The experimental findings along with theoretical study reveal that Au nanoparticles have a different effect on the competitive adsorption and chemical reaction over the surface of the Au-SnO2 with formaldehyde and other interfering VOC gases, such as methanol, ethanol, and acetone. This study provides mechanistic insights into the correlation between operating temperature and the performance of the Au-SnO2 chemiresistive sensor. This work allows the development of highly efficient and stable electrochemical sensors to detect VOC gases at room temperature in the future.


Subject(s)
Metal Nanoparticles , Volatile Organic Compounds , Gold , Formaldehyde , Gases
10.
Phys Rev Lett ; 131(14): 141601, 2023 Oct 06.
Article in English | MEDLINE | ID: mdl-37862633

ABSTRACT

Using holographic duality, we present an analytically controlled theory of quantum critical points without quasiparticles, at finite disorder and finite charge density. These fixed points are obtained by perturbing a disorder-free quantum critical point with relevant disorder whose operator dimension is perturbatively close to Harris marginal. We analyze these fixed points both using field theoretic arguments, and by solving the bulk equations of motion in holography. We calculate the critical exponents of the IR theory, together with thermoelectric transport coefficients. Our predictions for the critical exponents of the disordered fixed point are consistent with previous work, both in holographic and nonholograpic models.

11.
Clin Exp Hypertens ; 45(1): 2272062, 2023 Dec 31.
Article in English | MEDLINE | ID: mdl-37899350

ABSTRACT

BACKGROUND AND PURPOSE: Substitution of Cys674 (C674) in the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2 (SERCA2) causes SERCA2 dysfunction which leads to activated inositol requiring enzyme 1 alpha (IRE1α) and spliced X-box binding protein 1 (XBP1s) pathway accelerating cell proliferation of pulmonary artery smooth muscle cells (PASMCs) followed by significant pulmonary vascular remodeling resembling human pulmonary hypertension. Based on this knowledge, we intend to investigate other potential mechanisms involved in SERCA2 dysfunction-induced pulmonary vascular remodeling. EXPERIMENTAL APPROACH: Heterozygous SERCA2 C674S knock-in (SKI) mice of which half of cysteine in 674 was substituted by serine to mimic the partial irreversible oxidation of C674 were used. The lungs of SKI mice and their littermate wild-type mice were collected for PASMC culture, protein expression, and pulmonary vascular remodeling analysis. RESULTS: SERCA2 dysfunction increased intracellular Ca2+ levels, which activated Ca2+-dependent calcineurin (CaN) and promoted the nuclear translocation and protein expression of the nuclear factor of activated T-lymphocytes 4 (NFAT4) in an IRE1α/XBP1s pathway-independent manner. In SKI PASMCs, the scavenge of intracellular Ca2+ by BAPTA-AM or inhibition of CaN by cyclosporin A can prevent PASMC phenotypic transition. CDN1163, a SERCA2 agonist, suppressed the activation of CaN/NFAT4 and IRE1α/XBP1s pathways, reversed the protein expression of PASMC phenotypic transition markers and cell cycle-related proteins, and inhibited cell proliferation and migration when given to SKI PASMCs. Furthermore, CDN1163 ameliorated pulmonary vascular remodeling in SKI mice. CONCLUSIONS AND IMPLICATIONS: SERCA2 dysfunction promotes PASMC phenotypic transition and pulmonary vascular remodeling by multiple mechanisms, which could be improved by SERCA2 agonist CDN1163.


'What is already known' l The dysfunction of SERCA2 promotes PASMC hyperproliferation and pulmonary vascular remodeling through activation of the IRE1α/XBP1s pathway.'What this study adds' l The dysfunction of SERCA2 activates the Ca2+-dependent CaN-mediated NFAT4 pathway to promote the PASMC phenotypic transition.l Revitalization of SERCA2 suppresses PASMC phenotypic transition and pulmonary vascular remodeling caused by SERCA2 dysfunction.'Clinical significance' l SERCA2 dysfunction-induced pulmonary vascular remodeling involves more than one mechanism, implicating that more drugable targets are to be discovered.l SERCA2 is a potential therapeutic target for preventing pulmonary vascular remodeling.


Subject(s)
Hypertension, Pulmonary , Pulmonary Arterial Hypertension , Mice , Humans , Animals , Pulmonary Artery , Endoribonucleases/metabolism , Vascular Remodeling , Protein Serine-Threonine Kinases/metabolism , Pulmonary Arterial Hypertension/metabolism , Cell Proliferation , Myocytes, Smooth Muscle/metabolism , Cells, Cultured
12.
Anal Chim Acta ; 1279: 341789, 2023 Oct 23.
Article in English | MEDLINE | ID: mdl-37827683

ABSTRACT

There has been significant interest in the preparation and versatile applications of carbon dots (CDs) due to their immense potential value in sensors and imaging. In this work, silicon-doped green carbon dots (Si-CDs) with high quantum yield and rich epoxypropyl were effectively synthesized. Given the clinical diagnostic importance of abnormal levels of tyrosinase (TYR), sensitive detection of TYR is significant for clinical research. A fluorescence signal-off strategy with Si-CDs as probe was constructed to determine TYR based on the oxidation of dopamine by TYR. The detection ranges of this method were 0.01-1.5 and 10-30 U/mL with the detection limit of 0.0046 U/mL, the lower limit of quantification (LLOQ) was 0.01 U/mL, and TYR was successfully and accurately monitored in human serum. Additionally, due to the role of lysosomes in cellular regulatory processes, including TYR levels and fluorescence stability characteristics of Si-CDs in acidic conditions, it was envisaged to use Si-CDs as probe to establish real-time monitoring of lysosomes. According to fluorescence colocation analysis, Si-CDs had intrinsic lysosomal targeting ability to HepG2 and L-02 (with Pearson correlation coefficients were 0.90 and 0.91, respectively). The targeting of Si-CDs to lysosomes was due to the acidophilic effect of the epoxypropyl on its surface.


Subject(s)
Monophenol Monooxygenase , Quantum Dots , Humans , Carbon , Dopamine , Oxidation-Reduction , Fluorescent Dyes , Nitrogen
13.
Nat Commun ; 14(1): 6590, 2023 Oct 18.
Article in English | MEDLINE | ID: mdl-37852952

ABSTRACT

Electrocatalytic oxidation offers opportunities for sustainable environmental remediation, but it is often hampered by the slow mass transfer and short lives of electro-generated radicals. Here, we achieve a four times higher kinetic constant (18.9 min-1) for the oxidation of 4-chlorophenol on the reactive electrochemical membrane by reducing the pore size from 105 to 7 µm, with the predominate mechanism shifting from hydroxyl radical oxidation to direct electron transfer. More interestingly, such an enhancement effect is largely dependent on the molecular structure and its sensitivity to the direct electron transfer process. The spatial distributions of reactant and hydroxyl radicals are visualized via multiphysics simulation, revealing the compressed diffusion layer and restricted hydroxyl radical generation in the microchannels. This study demonstrates that both the reaction kinetics and the electron transfer pathway can be effectively regulated by the spatial confinement effect, which sheds light on the design of cost-effective electrochemical platforms for water purification and chemical synthesis.

14.
RMD Open ; 9(3)2023 08.
Article in English | MEDLINE | ID: mdl-37648396

ABSTRACT

OBJECTIVES: To compare the annual and period prevalence of modifiable cardiovascular risk factors (MCVRFs) between populations with and without osteoarthritis (OA) in the UK over 25 years. METHODS: 215 190 patients aged 35 years and over from the UK Clinical Practice Research Datalink GOLD database who were newly diagnosed OA between 1992 and 2017, as well as 1:1 age-matched, sex-matched, practice-matched and index year-matched non-OA individuals, were incorporated. MCVRFs including smoking, hypertension, type 2 diabetes, obesity and dyslipidaemia were defined by Read codes and clinical measurements. The annual and period prevalence and prevalence rate ratios (PRRs) of individual and clustering (≥1, ≥2 and ≥3) MCVRFs were estimated by Poisson regression with multiple imputations for missing values. RESULTS: The annual prevalence of MCVRFs increased in the population with OA between 1992 and 2017 and was consistently higher in the population with OA compared with the population without OA between 2004 and 2017. Trends towards increased or stable annual PRRs for individuals and clustering of MCVRFs were observed. A 26-year period prevalence of single and clustering MCVRFs was significantly higher in individuals with OA compared with non-OA individuals. Period PRRs were higher in Southern England, women and increased with age for most MCVRFs except for obesity, which has the higher PRR in the youngest age group. CONCLUSIONS: A consistently higher long-term prevalence of MCVRFs was observed in individuals with OA compared to those without OA. The higher prevalence of obesity in the youngest age group with OA highlights the need for public health strategies. Further research to understand MCVRF management in OA populations is necessary.


Subject(s)
Cardiovascular Diseases , Diabetes Mellitus, Type 2 , Osteoarthritis , Humans , Female , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Prevalence , Risk Factors , Heart Disease Risk Factors , Obesity/complications , Obesity/epidemiology , Osteoarthritis/epidemiology , United Kingdom/epidemiology
15.
J Am Chem Soc ; 145(31): 17220-17231, 2023 Aug 09.
Article in English | MEDLINE | ID: mdl-37492900

ABSTRACT

In electrochemical ethanol oxidation reactions (EOR) catalyzed by Pt metal nanoparticles through a C2 route, the dissociation of the C-C bond in the ethanol molecule can be a limiting factor. Complete EOR processes producing CO2 were always exemplified by the oxidative dehydrogenation of C1 intermediates, a reaction route with less energy utilization efficiency. Here, we report a Pt3Ga/C electrocatalyst with a uniform distribution of Ga over the nanoparticle surface for EOR that produces CO2 at medium potentials (>0.3 V vs SCE) efficiently through direct and sustainable oxidation of C2 intermediate species, i.e., acetaldehyde. We demonstrate the excellent performance of the Pt3Ga-200/C catalyst by using electrochemical in situ Fourier transform infrared reflection spectroscopy (FTIR) and an isotopic labeling method. The atomic interval structure between Pt and Ga makes the surface of nanoparticles nonensembled, avoiding the formation of poisonous *CHx and *CO species via bridge-type adsorption of ethanol molecules. Meanwhile, the electron redistribution from Ga to Pt diminishes the *O/*OH adsorption and CO poisoning on Pt atoms, exposing more available sites for interaction with the C2 intermediates. Furthermore, the dissociation of H2O into *OH is facilitated by the high hydrophilicity of Ga, which is supported by DFT calculations, promoting the deep oxidation of C2 intermediates. Our work represents an extremely rare EOR process that produces CO2 without observing kinetic limitations under medium potential conditions.

16.
ACS Catal ; 13(5): 2892-2903, 2023 Mar 03.
Article in English | MEDLINE | ID: mdl-36910870

ABSTRACT

The aerobic oxidation of alcohols and aldehydes over supported heterogeneous catalysts can be considered as comprising two complementary and linked processes: dehydrogenation and oxygen reduction. Significant rate enhancements can be observed when these processes are catalyzed by independent active sites, coupled by electron transport between the two catalysts. This effect, termed cooperative redox enhancement (CORE), could significantly influence how researchers approach catalyst design, but a greater understanding of the factors which influence it is required. Herein, we demonstrate that the Au/Pd ratio used in physical mixtures of monometallic catalysts and phase-separated Au and Pd bimetallic catalysts dramatically influences the degree to which CORE effects can promote alcohol oxidation. Perhaps more interestingly, the roles of Au and Pd in this coupled system are determined to be interchangeable. Preliminarily, we hypothesize that this is attributed to the relative rates of the coupled reactions and demonstrate how physical properties can influence this. This deeper understanding of the factors which influence CORE is an important development in bimetallic catalysis.

17.
Biol Psychol ; 177: 108506, 2023 02.
Article in English | MEDLINE | ID: mdl-36736571

ABSTRACT

Previous work has demonstrated the interpersonal implications of advisees' decisions (acceptance or rejection) on advisors' advice-giving behavior in subsequent exchanges. Here, using an ERP technique, we investigated how advisees' facial feedback (smiling, neutral, or frowning) accompanying their decisions (acceptance or rejection) influenced advisors' feedback evaluation from advisees and their advice-giving in subsequent exchanges. Behaviorally, regardless of whether the advice was accepted or rejected, advisors who received smiling-expression feedback would show higher willingness rates in subsequent advice-giving decisions, while advisors who received frowning-expression feedback would show lower willingness rates. On the neural level, in the feedback evaluation stage, the FRN and P3 responses were not sensitive to facial feedback. In contrast, frowning-expression feedback elicited a larger LPC amplitude than neutral- and smiling-expression feedback, regardless of whether the advice was accepted or rejected. In the advice decision stage, advisors who received neutral-expression feedback showed a larger N2 in making decisions than advisors who received frowning-expression feedback only after the advice was rejected. Additionally, Advisors who received smiling- and neutral-expression feedback showed a larger P3 in making decisions than advisors who received frowning-expression feedback only after the advice was accepted. In sum, the current findings extended previous research findings by showing that the effect of advisees' facial expressions on the advisors' advice-giving existed in multiple stages, including both the feedback evaluation stage and the advice decision stage.


Subject(s)
Decision Making , Smiling , Humans , Feedback , Facial Expression
18.
Eur J Pharmacol ; 940: 175473, 2023 Feb 05.
Article in English | MEDLINE | ID: mdl-36566916

ABSTRACT

The aberrant proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs) are critical contributors to the pulmonary vascular remodeling that occurs during the development of Pulmonary arterial hypertension (PAH). Krüppel-like Factor 7 (KLF7) has been reported to be involved in the development of certain cardiovascular diseases. However, the role of KLF7 in PAH remains unknown. Here, we aimed to explore whether KLF7 mediates the proliferation and migration of PASMCs and its underlying mechanism. In this study, Sprague Dawley rats were exposed to 60 mg/kg monocrotaline (MCT) for 3 weeks to induce PAH and human PASMCs were stimulated with 20 ng/ml platelet-derived growth factor-BB (PDGF-BB) for 24 h to induce proliferation and migration. The mRNA and protein expression of KLF7 were significantly down-regulated in MCT-induced PAH rats and PDGF-BB-treated PASMCs. Under normal conditions, KLF7 knockdown obviously promoted PASMCs proliferation and migration, whereas KLF7 overexpression exhibited the opposite effects. Furthermore, PDGF-BB promoted the PASMCs proliferation and migration, increased the cell proportion in S phase, which was significantly attenuated by overexpression of KLF7. Mechanistic investigation indicated that KLF7 through activation its target protein, the cell cycle inhibitor p21, which finally leading to the inhibition of PASMCs growth. Consistently, UC2288, a specific inhibitor of p21, partially reversed the PASMCs proliferation inhibited by KLF7 overexpression. Taken collectively, the data suggested that KLF7 inhibits PASMCs proliferation and migration via p21 pathway and it may be used as a new therapeutic target for the PAH.


Subject(s)
Hypertension, Pulmonary , Pulmonary Arterial Hypertension , Animals , Humans , Rats , Becaplermin/pharmacology , Cell Proliferation , Cells, Cultured , Familial Primary Pulmonary Hypertension , Hypertension, Pulmonary/metabolism , Kruppel-Like Transcription Factors/genetics , Kruppel-Like Transcription Factors/metabolism , Myocytes, Smooth Muscle , Pulmonary Arterial Hypertension/metabolism , Pulmonary Artery , Rats, Sprague-Dawley , ras Proteins
19.
ACS Nano ; 17(1): 636-647, 2023 Jan 10.
Article in English | MEDLINE | ID: mdl-36524746

ABSTRACT

Developing highly efficient and stable noble-metal-free electrocatalysts for water splitting is critical for producing clean and sustainable energy. Here, we design a hierarchical transition metal hydroxide/sulfide (NiFe(OH)x-Ni3S2/NF) electrode with dual heterointerface coexistence using a cation exchange-induced surface reconfiguration strategy. The electrode exhibits superior electrocatalytic activities, achieving low overpotentials of 55 mV for hydrogen evolution and 182 mV for oxygen evolution at 10 mA cm-2. Furthermore, the assembled two-electrode system requires voltages as low as 1.55 and 1.62 V to deliver industrially relevant current densities of 500 and 1000 mA cm-2, respectively, with excellent durability for over 200 h, which is comparable to commercial electrolysis. Theoretical calculations reveal that the hierarchical heterostructure increases the electronic delocalization of the Fe and Ni catalytic centers, lowering the energy barrier of the rate-limiting step and promoting O2 desorption. Finally, by implementing the catalysts in a solar-driven water electrolysis system, we demonstrate a record and durable solar-to-hydrogen (STH) conversion efficiency of up to 20.05%. This work provides a promising strategy for developing low-cost and high-efficiency bifunctional catalysts for a large-scale solar-to-hydrogen generation.

20.
China Tropical Medicine ; (12): 994-2023.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1016567

ABSTRACT

@#Abstract: Objective To explore the prevalence and bacterial strains of Francisella tularensis (F. tularensis) in wild rodents in Changbai Mountain area of China, and to further understand the epidemiological characteristics of F. tularensis infections in this area. Methods Wild rodents were captured from forest and forest-edge farmland from Kuandian County and Jianshi Forest District in the Changbai Mountain area, 2012-2014. DNA was extracted from the spleen tissues of the rodents, and the fopA gene of F. tularensis in wild rodents was detected using nested PCR. The infection rates were calculated for different areas and rat species. The bacterial subspecies of positive samples were identified using type-specific primers (C1/C4), and sequencing and comparative analysis were performed. Results A total of 133 wild rodents belonging to 6 rat species were captured. Among them, eight samples from three rat species (Apodemus agrarius, Apodemus peninsulae, Tscherskia triton ) were detected positive, with the overall positive rate of 6.01%. The positive rates of F. tularensis of Ji'an and Kuandian were 7.46% and 4.54%, respectively, and there was no difference in positive rates for different regions (χ2=0.117, P=0.732) and different rat species (χ2=0.641, P=0.986). The subspecies analysis showed that the detected 8 trains of F.tularensisall belonged to F.tularensis type B (F.subspecies subsp. holarctica). Genetic evolution analysis was performed on the fopA gene sequences of three positive samples (JA56, JA33, and JA38), which clustered together with Russia strains(CP009694.1, CP044004.1) and China strains (HM371344.1, HM371343.1) F.tularensis type B, with sequence similarities ranging from 99.21% to 99.47%. Conclusions Infection of F.tularensis subsp. holarctica existed in wild rodents in Changbai Mountain area of China, which suggests the existence of F.tularensis infection risks in this area.

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