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1.
Pharmacol Res ; : 107271, 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38906202

RESUMEN

Colorectal cancer is the second most prevalent and deadly cancer worldwide. The emergence of immune checkpoint therapy has provided a revolutionary strategy for the treatment of solid tumors. However, less than 5% of colorectal cancer patients respond to immune checkpoint therapy. Thus, it is of great scientific significance to develop "potentiators" for immune checkpoint therapy. In this study, we found that knocking down different DNMT and HDAC isoforms could increase the expression of IFNs in colorectal cancer cells, which can enhance the effectiveness of immune checkpoint therapy. Therefore, the combined inhibition of DNMT and HDAC cloud synergistically enhance the effect of immunotherapy. We found that dual DNMT and HDAC inhibitors C02S could inhibit tumor growth in immunocompetent mice but not in immunocompromised nude mice, which indicates that C02S exerts its antitumor effects through the immune system. Mechanistically, C02S could increase the expression of ERVs, which generated the intracellular levels of dsRNA in tumor cells, and then promotes the expression of IFNs through the RIG-I/MDA5-MAVS signaling pathway. Moreover, C02S increased the immune infiltration of DCs and T cells in microenvironment, and enhanced the efficacy of anti-PD-L1 therapy in MC38 and CT26 mice model. These results confirmed that C02S can activate IFNs through the RIG-I/MDA5-MAVS signaling pathway, remodel the tumor immune microenvironment and enhance the efficacy of immune checkpoint therapy, which provides new evidence and solutions for the development of "potentiator" for colorectal cancer immunotherapy.

2.
Environ Sci Technol ; 58(24): 10717-10728, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38847549

RESUMEN

Ruthenium single-atom catalysts have great potential in ammonia-selective catalytic oxidation (NH3-SCO); however, the stable sp3 hybrid orbital of NH3 molecules makes N(sp3)-H dissociation a challenge for conventional symmetrical metallic oxide catalysts. Herein, we propose a heterogeneous interface reverse atom capture strategy to construct Ru with unique asymmetric Ru1N2O1 coordination. Ru1N2O1/CeO2 exhibits intrinsic low-temperature conversion (T100 at 160 °C) compared to symmetric coordinated Ru-based (280 °C), Ir-based (220 °C), and Pt-based (200 °C) catalysts, and the TOF is 65.4 times that of Ag-based catalysts. The experimental and theoretical studies show that there is a strong d-p orbital interaction between Ru and N atoms, which not only enhances the adsorption of ammonia at the Ru1N2O1 position but also optimizes the electronic configuration of Ru. Furthermore, the affinity of Ru1N2O1/CeO2 to water is significantly weaker than that of conventional catalysts (the binding energy of the Pd3Au1 catalyst is -1.19 eV, but it is -0.39 eV for our material), so it has excellent water resistance. Finally, the N(sp3)-H activation of NH3 requires the assistance of surface reactive oxygen species, but we found that asymmetric Ru1N2O1 can directly activate the N(sp3)-H bond without the involvement of surface reactive oxygen species. This study provides a novel principle for the rational design of the proximal coordination of active sites to achieve its optimal catalytic activity in single-atom catalysis.


Asunto(s)
Amoníaco , Oxidación-Reducción , Rutenio , Amoníaco/química , Catálisis , Rutenio/química
3.
Biologics ; 18: 115-127, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38746773

RESUMEN

Background and Objectives: Gene expression, morphology, and electrophysiological combination are essential for assessing the dynamic development of human induced pluripotent stem cell-derived atrial- and ventricular-like cardiomyocytes (iPS-AM and iPS-VM, respectively). Methods: For iPS-AM/VM differentiation, we performed the small molecule-based temporal modulation of the retinoic acid and bone morphogenetic protein signaling pathways. We investigated the gene expression and morphology using immunofluorescence, quantitative real-time polymerase chain reaction, flow cytometry, and transmission electron microscopy as well as registered electrophysiological functions using a whole-cell patch clamp on days 20, 30, and 60 post-differentiations. Results: Pan-cardiomyocyte marker, including troponin T2 (TNNT2) and alpha-actinin-2 (ACTN2), expressions increased both in iPS-AMs and iPS-VMs. Similarly, the mRNA expression of both iPS-AM-specific markers, ie, natriuretic peptide A (NPPA), myosin light chain 7 (MYL7), and K+ channel Kir3.4 (KCNJ5), and iPS-VM-specific markers, ie, gap junction α-1 (GJA1), myosin light chain 2 (MYL2), and alpha-1-subunit of a voltage-dependent L-type calcium channel (CACNA1C), increased from 0 to 20 days, and then decreased from 30 to 60 days. Concerning morphology, cardiac troponin-T (cTnT) arrangement was progressively organized and developed from a disorderly myofibrillar distribution to an organized sarcomere pattern both in iPS-AMs and iPS-VMs. Mitochondrial numbers gradually increased and those of lipid droplets decreased during dynamic development. Regarding physiological function, the resting and action potential amplitudes remained statistically indifferent in both cell types, and the action potential duration was prolonged during the development. Conclusion: IPS-AMs/VMs displayed dynamic development concerning their gene expression, morphology, and electrophysiological function. The discoveries of this study could provide novel insights into heart development and encourage further research.

4.
PLoS One ; 19(5): e0304471, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38820389

RESUMEN

As a response to the damage caused by the spread of COVID-19, the Chinese government has implemented severe quarantine measures that have greatly affected the operational patterns of small and medium-sized enterprises (SMEs). This paper explores the critical role of dynamic capabilities (DCs) in helping Chinese SMEs manage crises, adjust their business strategies, and mitigate the uncertainty caused by the epidemic. Although the importance of DCs in promoting organizational resilience is well recognized, academic research on their specific contributions to business model innovation (BMI) and SME performance improvement during crises remains scarce. Our study fills this gap by pioneering the development and empirical testing of a microintegrated mediation model linking DCs, BMI and organizational performance. By surveying 257 Chinese SMEs severely affected by a pandemic, we verify our hypotheses using partial least squares structural equation modeling (PLS-SEM). Our results strongly show a positive relationship between DCs and BMI and SME performance. In addition, we found that BMI plays a partial mediating role in the interrelationship between DCs and SME performance. Our findings clarify the critical role of BMI as a channel through which SMEs' DCs can be transformed into higher performance in the face of sudden crises. Thus, our results not only contribute to the broader discussion of strategic management and organizational theory but also provide theoretical and practical insights into the mechanisms by which SMEs can increase their flexibility and resilience in a crisis. Thus, our results not only contribute to the broader discussion of strategic management and organizational theory but also provide theoretical and practical insights into the mechanisms by which SMEs can increase their flexibility and resilience in a crisis. Importantly, this study suggests policy and market strategies that can support SMEs in leveraging DCs and BMI for sustained performance, thereby contributing valuable insights for policymakers and business leaders aiming to fortify economic stability and growth in the face of global health emergencies.


Asunto(s)
COVID-19 , COVID-19/epidemiología , Humanos , China/epidemiología , SARS-CoV-2 , Comercio , Pandemias , Cuarentena
5.
Environ Sci Technol ; 58(15): 6704-6715, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38574268

RESUMEN

The transformation of toxic arsine (AsH3) gas into valuable elemental arsenic (As0) from industrial exhaust gases is important for achieving sustainable development goals. Although advanced arsenic removal catalysts can improve the removal efficiency of AsH3, toxic arsenic oxides generated during this process have not received adequate attention. In light of this, a novel approach for obtaining stable As0 products was proposed by performing controlled moderate oxidation. We designed a tailored Ni-based catalyst through an acid etching approach to alter interactions between Ni and NaY. As a result, the 1Ni/NaY-H catalyst yielded an unprecedented proportion of As0 as the major product (65%), which is superior to those of other reported catalysts that only produced arsenic oxides. Density functional theory calculations clarified that Ni species changed the electronic structure of oxygen atoms, and the formed [NiIII-OH (µ-O)] active centers facilitated the adsorption of AsH2*, AsH*, and As* reaction intermediates for As-H bond cleavage, thereby decreasing the direct reactivity of oxygen with the arsenic intermediates. This work presents pioneering insights into inhibiting excessive oxidation during AsH3 removal, demonstrating potential environmental applications for recovery of As0 from toxic AsH3.


Asunto(s)
Arsénico , Zeolitas , Níquel/química , Electrones , Oxígeno , Gases
6.
Surg Innov ; : 15533506241249260, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38654530

RESUMEN

BACKGROUND: Minimally invasive treatment has become the most popular and effective treatment for pelvic fractures. This study aimed to evaluate the safety and efficacy of a new technique, titanium elastic nailing (TEN), for the minimally invasive treatment of pelvic fractures. METHOD: Twenty-four patients with pelvic fractures were referred to us between January 2020 to January 2022, including sixteen males and 8 females. Pelvic fractures were temporarily fixed by pelvic fixation belt accompanied by traction from the lower limb bone. Anterior pelvic ring injuries (superior ramus of pubis) and ilium fractures were treated with closed reduction and intramedullary fixation with minimally invasive TEN. Intraoperative C-arm, including pelvic anteroposterior, pelvic outlet, inlet and ilium oblique views, and O-arm fluoroscopy (intraoperative CT) were employed to assess fractures reduction and determine the location of the elastic titanium nail within the bone channel. RESULTS: By adopting closed reduction and minimally invasive incision techniques, pelvic fractures could be safely fixed by placing an elastic titanium nail in the osseous medullary cavity channels of the pelvis. Postoperative investigation indicated that the wounds of all patients were healed in the first stage without any occurrence of complications, such as injuries to the nerves, blood vessels, and important tissue structures. Patients are essential quickly after the operation and could perform the functional exercise in the early stages of the recovery. CONCLUSION: TEN can be used for minimally invasive treatment of pelvic fractures. This novel technique has no obvious complications and is worthwhile in clinical practice.

7.
Nat Commun ; 15(1): 3362, 2024 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-38637534

RESUMEN

Capturing gaseous mercury (Hg0) from sulfur dioxide (SO2)-containing flue gases remains a common yet persistently challenge. Here we introduce a low-temperature sulfur chemical vapor deposition (S-CVD) technique that effectively converts SO2, with intermittently introduced H2S, into deposited sulfur (Sd0) on metal sulfides (MS), facilitating self-sustained adsorption of Hg0. ZnS, as a representative MS model, undergoes a decrease in the coordination number of Zn-S from 3.9 to 3.5 after Sd0 deposition, accompanied by the generation of unsaturated-coordinated polysulfide species (Sn2-, named Sd*) with significantly enhanced Hg0 adsorption performance. Surprisingly, the adsorption product, HgS (ZnS@HgS), can serve as a fresh interface for the activation of Sd0 to Sd* through the S-CVD method, thereby achieving a self-sustained Hg0 adsorption capacity exceeding 300 mg g-1 without saturation limitations. Theoretical calculations substantiate the self-sustained adsorption mechanism that S8 ring on both ZnS and ZnS@HgS can be activated to chemical bond S4 chain, exhibiting a stronger Hg0 adsorption energy than pristine ones. Importantly, this S-CVD strategy is applicable to the in-situ activation of synthetic or natural MS containing chalcophile metal elements for Hg0 removal and also holds potential applications for various purposes requiring MS adsorbents.

8.
Polymers (Basel) ; 16(5)2024 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-38475306

RESUMEN

A military helicopter is easily attacked by bullets in a battlefield environment. The composite blade is the main lifting surface and control surface of the helicopter. Its ballistic performance directly determines the vulnerability and survivability of the helicopter in the battlefield environment. To study the ballistic performance of the composite helicopter blade, the damage characteristics of the impacted composite rotor blade are obtained by experiments. A numerical simulation model is established by applying Abaqus software to predict the blade ballistic damage. The three-dimensional progressive damage failure model is used to analyze the ballistic damage under the experimental conditions. The effectiveness and accuracy of the numerical simulation model are verified through a comparison with the experimental results. The ballistic damage of composite blades under three experimental conditions was investigated. The results show that the ballistic damage type of composite blade mainly includes delamination, fiber breakage, and foam collapse. The damage to the composite material at the position of bullet incidence is mainly local shear fracture, while the damage to the composite material at the exit position is mainly fiber tensile fracture. The ballistic damage size of the composite blade is closely related to the ballistic position, incident angle, and structure characteristics along the ballistic path. The larger the incident angle, the smaller the ballistic damage size of the blade. The greater the structural stiffness of the structure near the exit, the greater the damage size of the exit. The numerical simulation model presented in this paper can provide a reference for research on the ballistic performance of composite helicopter blades.

9.
Cell Death Discov ; 10(1): 143, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38490978

RESUMEN

The existing conventional treatments for breast cancer, including immune checkpoint blockade, exhibit limited effects in some cancers, particularly triple-negative breast cancer. Epigenetic alterations, specifically DNMT and HDAC alterations, are implicated in breast cancer pathogenesis. We demonstrated that DNMTs and HDACs are overexpressed and positively correlated in breast cancer. The combination of DNMT and HDAC inhibitors has shown synergistic antitumour effects, and our previously designed dual DNMT and HDAC inhibitor (termed DNMT/HDACi) 15a potently inhibits breast cancer cell proliferation, migration, and invasion and induces apoptosis in vitro and in vivo. Mechanistically, 15a induces a viral mimicry response by promoting the expression of endogenous retroviral elements in breast cancer cells, thus increasing the intracellular level of double-stranded RNA to activate the RIG-I-MAVS pathway. This in turn promotes the production of interferons and chemokines and augments the expression of interferon-stimulated genes and PD-L1. The combination of 15a and an anti-PD-L1 antibody had an additive effect in vivo. These findings indicate that this DNMT/HDACi has immunomodulatory functions and enhances the effectiveness of immune checkpoint blockade therapy. A novel dual DNMT and HDAC inhibitor induces viral mimicry, which induces the accumulation of dsRNA to activate tumoral IFN signalling and cytokine production to enhance the immune response in breast cancer.

10.
Materials (Basel) ; 17(5)2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38473678

RESUMEN

In the field of aerospace and advanced equipment manufacturing, accurate response analysis has been paid more attention, requiring a more comprehensive study of the variation of mechanical parameters with the service environment. The damping variation characteristics of 304 aluminum alloy, Sa564 high-strength alloy, GW63K magnesium alloy, and Q235 steel were investigated in this paper, which plays a significant role in the dynamic responses of structures. Variable damping ratios were revealed by the damping tests based on a dynamic mechanical analysis (DMA). The numerical method of temperature/frequency-dependent damping parameters in stochastic dynamics was focused on. With a large variation in the damping ratio, a numerical constitutive relation for temperature-dependent damping was proposed, and an efficient stochastic dynamics method was derived to analyze the responses of structures based on the pseudo excitation method (PEM) and variable damping theory. The computational accuracy and validity of the proposed method are confirmed during the vibration tests and numerical analysis. Based on the comparison results of the two damping models and the experiments on GW63K alloy, we proved that the proposed method is more accurate to the real response of the actual engineering structure. The differences in dynamic responses between the constant damping and experiments are significant, and more attention should be paid to the numerical method of stochastic dynamic response of variable damping materials in the aviation and aerospace fields and high-temperature environments.

11.
Mater Horiz ; 11(8): 1889-1898, 2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38372122

RESUMEN

Developing reliable solid sorbents for efficient capture and removal of trace sulfur dioxide (SO2) under ambient conditions is critical for industrial desulfurization operations, but poses a great challenge. Herein, we focus on SNFSIX-Cu-TPA, a highly stable fluorinated MOF that utilizes SnF62- as pillars, for effectively capturing SO2 at extremely low pressures. The exceptional affinity of SNFSIX-Cu-TPA towards SO2 over CO2 and N2 was demonstrated through single-component isotherms and corroborated by computational simulations. At 298 K and 0.002 bar, this material displays a remarkable gas uptake of 2.22 mmol g-1. Among various anion fluorinated MOFs, SNFSIX-Cu-TPA shows the highest SO2/MF62- of 1.39 mmol mmol-1 and exhibits a low Qst of 58.81 kJ mol-1. Additionally, SNFSIX-Cu-TPA displays excellent potential for SO2/CO2 separation, as evidenced by its ideal adsorbed solution theory (IAST) selectivity of 148 at a molar fraction of SO2 of 0.01. Dynamic breakthrough curves were obtained to reveal the effective removal of trace SO2 from simulated flue gas (SO2/CO2/N2; v/v/v 0.2/10/89.8) with a high dynamic capacity of up to 1.52 mmol g-1. Furthermore, in situ TGA demonstrated the efficient and reversible capture of 500 ppm SO2 over 20 adsorption-desorption tests. This durable material presents a rare combination of exceptional SO2 capturing performance, good adsorption selectivity, and mild regeneration, thus making it a good candidate for a realistic desulfurization process.

12.
Conserv Physiol ; 12(1): coad083, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38369984

RESUMEN

Physiological indexes like blood parameters have been widely used to monitor the health of free-roaming animals. Attempts to reintroduce one of China's most endangered species, the giant panda (Ailuropoda melanoleuca), have been hampered by a lack of data on its ecology and physiology. We examined three giant pandas' hematological and blood chemistry parameters in a soft release program and 30 captive giant pandas as controls and determined the reference intervals (RIs) for those blood parameters in the captive animals. Elevation, captivity status and the interaction of those factors were statistically significant for hematologic measures. Release pandas had significantly higher hemoglobin and hematocrit values after they moved to high elevation locations. We also found significant difference in the enzyme parameters between high and low elevation pandas such as higher aspartate aminotransferase, alanine aminotransferase, creatinine kinase, amylase and lower lactate dehydrogenase and alkaline phosphatase. Release pandas also had higher nutrition parameter values such as higher albumin, globulin and creatinine. The RI for blood parameters in our study provides a baseline to monitor the health of captive animals and forms the basis for assessing the health of free-roaming giant pandas in future reintroduction efforts.

13.
Mil Med Res ; 11(1): 14, 2024 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-38374260

RESUMEN

BACKGROUND: Computed tomography (CT) plays a great role in characterizing and quantifying changes in lung structure and function of chronic obstructive pulmonary disease (COPD). This study aimed to explore the performance of CT-based whole lung radiomic in discriminating COPD patients and non-COPD patients. METHODS: This retrospective study was performed on 2785 patients who underwent pulmonary function examination in 5 hospitals and were divided into non-COPD group and COPD group. The radiomic features of the whole lung volume were extracted. Least absolute shrinkage and selection operator (LASSO) logistic regression was applied for feature selection and radiomic signature construction. A radiomic nomogram was established by combining the radiomic score and clinical factors. Receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA) were used to evaluate the predictive performance of the radiomic nomogram in the training, internal validation, and independent external validation cohorts. RESULTS: Eighteen radiomic features were collected from the whole lung volume to construct a radiomic model. The area under the curve (AUC) of the radiomic model in the training, internal, and independent external validation cohorts were 0.888 [95% confidence interval (CI) 0.869-0.906], 0.874 (95%CI 0.844-0.904) and 0.846 (95%CI 0.822-0.870), respectively. All were higher than the clinical model (AUC were 0.732, 0.714, and 0.777, respectively, P < 0.001). DCA demonstrated that the nomogram constructed by combining radiomic score, age, sex, height, and smoking status was superior to the clinical factor model. CONCLUSIONS: The intuitive nomogram constructed by CT-based whole-lung radiomic has shown good performance and high accuracy in identifying COPD in this multicenter study.


Asunto(s)
Nomogramas , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Radiómica , Estudios Retrospectivos , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico por imagen , Biomarcadores , Tomografía Computarizada por Rayos X , Pulmón/diagnóstico por imagen
14.
Cell Death Dis ; 15(1): 10, 2024 01 05.
Artículo en Inglés | MEDLINE | ID: mdl-38182579

RESUMEN

PARP inhibitors and HDAC inhibitors have been approved for the clinical treatment of malignancies, but acquired resistance of or limited effects on solid tumors with a single agent remain as challenges. Bioinformatics analyses and a combination of experiments had demonstrated the synergistic effects of PARP and HDAC inhibitors in triple-negative breast cancer. A series of novel dual PARP and HDAC inhibitors were rationally designed and synthesized, and these molecules exhibited high enzyme inhibition activity with excellent antitumor effects in vitro and in vivo. Mechanistically, dual PARP and HDAC inhibitors induced BRCAness to restore synthetic lethality and promoted cytosolic DNA accumulation, which further activates the cGAS-STING pathway and produces proinflammatory chemokines through type I IFN-mediated JAK-STAT pathway. Moreover, these inhibitors promoted neoantigen generation, upregulated antigen presentation genes and PD-L1, and enhanced antitumor immunity when combined with immune checkpoint blockade therapy. These results indicated that novel dual PARP and HDAC inhibitors have antitumor immunomodulatory functions in triple-negative breast cancer. Novel dual PARP and HDAC inhibitors induce BRCAness to restore synthetic lethality, activating tumoral IFN signaling via the cGAS-STING pathway and inducing cytokine production, promoting neoantigen generation and presentation to enhance the immune response.


Asunto(s)
Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/genética , Inhibidores de Histona Desacetilasas/farmacología , Quinasas Janus , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Factores de Transcripción STAT , Transducción de Señal , Nucleotidiltransferasas/genética
15.
CNS Neurosci Ther ; 30(3): e14178, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-36949617

RESUMEN

AIMS: Idiopathic Normal pressure hydrocephalus (iNPH) is a neurodegenerative disease characterized by gait disturbance, dementia, and urinary dysfunction. The neural network mechanisms underlying this phenomenon is currently unknown. METHODS: To investigate the resting-state functional connectivity (rs-FC) abnormalities of iNPH-related brain connectivity from static and dynamic perspectives and the correlation of these abnormalities with clinical symptoms before and 3-month after shunt. We investigated both static and dynamic functional network connectivity (sFNC and dFNC, respectively) in 33 iNPH patients and 23 healthy controls (HCs). RESULTS: The sFNC and dFNC of networks were generally decreased in iNPH patients. The reduction in sFNC within the default mode network (DMN) and between the somatomotor network (SMN) and visual network (VN) were related to symptoms. The temporal properties of dFNC and its temporal variability in state-4 were sensitive to the identification of iNPH and were correlated with symptoms. The temporal variability in the dorsal attention network (DAN) increased, and the average instantaneous FC was altered among networks in iNPH. These features were partially associated with clinical symptoms. CONCLUSION: The dFNC may be a more sensitive biomarker for altered network function in iNPH, providing us with extra information on the mechanisms of iNPH.


Asunto(s)
Hidrocéfalo Normotenso , Trastornos del Movimiento , Enfermedades Neurodegenerativas , Humanos , Hidrocéfalo Normotenso/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Cabeza , Imagen por Resonancia Magnética , Mapeo Encefálico
16.
Cell Prolif ; 57(4): e13573, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37916452

RESUMEN

Pompe disease (PD) is a rare autosomal recessive disorder that presents with progressive hypertrophic cardiomyopathy. However, the detailed mechanism remains clarified. Herein, PD patient-specific induced pluripotent stem cells were differentiated into cardiomyocytes (PD-iCMs) that exhibited cardiomyopathic features of PD, including decreased acid alpha-glucosidase activity, lysosomal glycogen accumulation and hypertrophy. The defective mitochondria were involved in the cardiac pathology as shown by the significantly decreased number of mitochondria and impaired respiratory function and ATP production in PD-iCMs, which was partially due to elevated levels of intracellular reactive oxygen species produced from depolarized mitochondria. Further analysis showed that impaired fusion and autophagy of mitochondria and declined expression of mitochondrial complexes underlies the mechanism of dysfunctional mitochondria. This was alleviated by supplementation with recombinant human acid alpha-glucosidase that improved the mitochondrial function and concomitantly mitigated the cardiac pathology. Therefore, this study suggests that defective mitochondria underlie the pathogenesis of cardiomyopathy in patients with PD.


Asunto(s)
Cardiomiopatía Hipertrófica , Enfermedad del Almacenamiento de Glucógeno Tipo II , Células Madre Pluripotentes Inducidas , Enfermedades Mitocondriales , Humanos , Enfermedad del Almacenamiento de Glucógeno Tipo II/metabolismo , Enfermedad del Almacenamiento de Glucógeno Tipo II/patología , Miocitos Cardíacos/metabolismo , Células Madre Pluripotentes Inducidas/metabolismo , Cardiomiopatía Hipertrófica/metabolismo , Cardiomiopatía Hipertrófica/patología , Enfermedades Mitocondriales/metabolismo , Enfermedades Mitocondriales/patología
17.
J Org Chem ; 89(1): 710-718, 2024 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-38101332

RESUMEN

The proton of alcohols as the sole hydrogen source in diboron-mediated nickel-catalyzed asymmetric transfer hydrogenation of cyclic N-sulfonyl imines has been developed, providing the chiral cyclic sulfamidates in excellent enantioselectivities. The mechanistic investigations suggested that the proton of alcohols could be activated by tetrahydroxydiboron to form active nickel hydride species.

18.
Environ Sci Technol ; 58(1): 960-969, 2024 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-38150269

RESUMEN

SO2 reduction with CH4 to produce elemental sulfur (S8) or other sulfides is typically challenging due to high energy barriers and catalyst poisoning by SO2. Herein, we report that a comproportionation reaction (CR) induced by H2S recirculating significantly accelerates the reactions, altering reaction pathways and enabling flexible adjustment of the products from S8 to sulfides. Results show that SO2 can be fully reduced to H2S at a lower temperature of 650 °C, compared to the 800 °C required for the direct reduction (DR), effectively eliminating catalyst poisoning. The kinetic rate constant is significantly improved, with CR at 650 °C exhibiting about 3-fold higher value than DR at 750 °C. Additionally, the apparent activation energy decreases from 128 to 37 kJ/mol with H2S, altering the reaction route. This CR resolves the challenges related to robust sulfur-oxygen bond activation and enhances CH4 dissociation. During the process, the well-dispersed lamellar MoS2 crystallites with Co promoters (CoMoS) act as active species. H2S facilitates the comproportionation reaction, reducing SO2 to a nascent sulfur (Sx*). Subsequently, CH4 efficiently activates CoMoS in the absence of SO2, forming H2S. This shifts the mechanism from Mars-van Krevelen (MvK) in DR to sequential Langmuir-Hinshelwood (L-H) and MvK in CR. Additionally, it mitigates sulfation poisoning through this rapid activation reaction pathway. This unique comproportionation reaction provides a novel strategy for efficient sulfur resource utilization.


Asunto(s)
Metano , Dióxido de Azufre , Metano/química , Sulfuros/química , Temperatura , Azufre/química , Oxidación-Reducción
19.
Environ Sci Technol ; 57(50): 21272-21283, 2023 Dec 19.
Artículo en Inglés | MEDLINE | ID: mdl-38051813

RESUMEN

Cobalt-based catalysts have been identified for effective CO oxidation, but their activity is limited by molecular O2 and interfacial oxygen passivation at low temperatures. Optimization of the d-band structure of the cobalt center is an effective method to enhance the dissociation of oxygen species. Here, we developed a novel Co/FeOx catalyst based on selective cationic deposition to anchor Co cations at the defect site of FeOx, which exhibited superior intrinsic low-temperature activity (100%, 115 °C) compared to that of Pt/Co3O4 (100%, 140 °C) and La/Co2O3 (100%, 150 °C). In contrast to catalysts with oxygen defects, the cationic Fe defect in Co/FeOx showed an exceptional ability to accept electrons from the Co 3d orbital, resulting in significant electron delocalization at the Co sites. The Co/FeOx catalyst exhibited a remarkable turnover frequency of 178.6 per Co site per second, which is 2.3 times higher than that of most previously reported Co-based catalysts. The d-band center is shifted upward by electron redistribution effects, which promotes the breaking of the antibonding orbital *π of the O═O bond. In addition, the controllable regulation of the Fe-Ov-Co oxygen defect sites enlarges the Fe-O bond from 1.97 to 2.02 Å to activate the lattice oxygen. Moreover, compared to CoxFe3-xO4, Co/FeOx has a lower energy barrier for CO oxidation, which significantly accelerates the rate-determining step, *COO formation. This study demonstrates the feasibility of modulating the d-band structure to enhance O2 molecular and interfacial lattice oxygen activation.


Asunto(s)
Nanoestructuras , Cationes , Cobalto , Electrónica , Oxígeno
20.
Quant Imaging Med Surg ; 13(12): 8121-8131, 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-38106275

RESUMEN

Background: Extracellular volume (ECV) fraction has been used in cardiovascular diseases, pancreatic fibrosis, and hepatic fibrosis. The diagnostic value of ECV for focal lung lesions remains to be explored. The aim of this study was to evaluate the feasibility of ECV derived from a dual-layer detector computed tomography (DLCT) to differentiate lung cancer (LC) from benign lung lesions (BLLs). Methods: Retrospectively, 128 consecutive patients with pathologically confirmed LC (n=86) or BLLs (n=42) were included. Conventional computed tomography (CT) characteristics and spectral CT parameters were assessed. All patients' hematocrits were measured to correct contrast volume distributions in blood while calculating ECV. After performing logistic regression analysis, a conventional CT-based model (Model A), DLCT-based model (Model B), combined diagnostic models (Model C), and an ECV-based model (Model D) were developed. The diagnostic effectiveness of each model was examined using the receiver operating characteristic (ROC) curve and their corresponding 95% confidence intervals (CIs). The area under the curve (AUC) of each model was compared using the DeLong test. Results: Certain conventional CT features (such as lesion size, lobulation, spiculation, pleural indentation, and enlarged lymph nodes) differed significantly between the LC and BLL groups (all P<0.05). Statistical differences were found in the following DLCT parameters (all P<0.05): effective atomic number (Zeff) (non-enhancement), electron density (ED) (non-enhancement), ECV, iodine concentration (IC), and normalized iodine concentration (NIC). Models A, B, C, and D had AUCs of 0.801 [95% confidence interval (CI): 0.721-0.866], 0.805 (95% CI: 0.726-0.870), 0.925 (95% CI: 0.865-0.964), and 0.754 (95% CI: 0.671-0.826), respectively. The AUC of Model D (ECV) showed no significant difference from that of Models A and B (DeLong test, P>0.05). Conclusions: The ECV derived from DLCT may be a potential new method to differentiate LC from BLLs, broadening the scope of ECV in clinical research.

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