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1.
J Immunol ; 211(1): 23-33, 2023 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-37171180

RESUMEN

Intracellular binding of small-molecule phospho-Ags to the HMBPP receptor complex in infected cells leads to extracellular detection by T cells expressing the Vγ9Vδ2 TCR, a noncanonical method of Ag detection. The butyrophilin proteins BTN2A1 and BTN3A1 are part of the complex; however, their precise roles are unclear. We suspected that BTN2A1 and BTN3A1 form a tetrameric (dimer of dimers) structure, and we wanted to probe the importance of the BTN2A1 homodimer. We analyzed mutations to human BTN2A1, using internal domain or full-length BTN2A1 constructs, expressed in Escherichia coli or human K562 cells, that might disrupt its structure and/or function. Although BTN2A1 is a disulfide-linked homodimer, mutation of cysteine residues C247 and C265 did not affect the ability to stimulate T cell IFN-γ production by ELISA. Two mutations of the juxtamembrane region (at EKE282) failed to impact BTN2A1 function. In contrast, single point mutations (L318G and L325G) near the BTN2A1 B30.2 domain blocked phospho-Ag response. Size exclusion chromatography and nuclear magnetic resonance (NMR) experiments showed that the isolated BTN2A1 B30.2 domain is a homodimer, even in the absence of its extracellular and transmembrane region. [31P]-NMR experiments confirmed that HMBPP binds to BTN3A1 but not BTN2A1, and binding abrogates signals from both phosphorus atoms. Furthermore, the BTN2A1 L325G mutation but not the L318G mutation prevents both homodimerization of BTN2A1 internal domain constructs in size exclusion chromatography (and NMR) experiments and their binding to HMBPP-bound BTN3A1 in isothermal titration calorimetry experiments. Together, these findings support the importance of homodimerization within the BTN2A1 internal domain for phospho-Ag detection.


Asunto(s)
Activación de Linfocitos , Receptores de Antígenos de Linfocitos T gamma-delta , Humanos , Antígenos/metabolismo , Antígenos CD/metabolismo , Butirofilinas/genética , Mutación , Receptores de Antígenos de Linfocitos T gamma-delta/genética , Linfocitos T
2.
Pharmacol Rev ; 74(3): 680-711, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35710136

RESUMEN

Drug conjugates, including antibody-drug conjugates, are a step toward realizing Paul Ehrlich's idea from over 100 years ago of a "magic bullet" for cancer treatment. Through balancing selective targeting molecules with highly potent payloads, drug conjugates can target specific tumor microenvironments and kill tumor cells. A drug conjugate consists of three parts: a targeting agent, a linker, and a payload. In some conjugates, monoclonal antibodies act as the targeting agent, but new strategies for targeting include antibody derivatives, peptides, and even small molecules. Linkers are responsible for connecting the payload to the targeting agent. Payloads impact vital cellular processes to kill tumor cells. At present, there are 12 antibody-drug conjugates on the market for different types of cancers. Research on drug conjugates is increasing year by year to solve problems encountered in conjugate design, such as tumor heterogeneity, poor circulation, low drug loading, low tumor uptake, and heterogenous expression of target antigens. This review highlights some important preclinical research on drug conjugates in recent years. We focus on three significant areas: improvement of antibody-drug conjugates, identification of new conjugate targets, and development of new types of drug conjugates, including nanotechnology. We close by highlighting the critical barriers to clinical translation and the open questions going forward. SIGNIFICANCE STATEMENT: The development of anticancer drug conjugates is now focused in three broad areas: improvements to existing antibody drug conjugates, identification of new targets, and development of new conjugate forms. This article focuses on the exciting preclinical studies in these three areas and advances in the technology that improves preclinical development.


Asunto(s)
Antineoplásicos , Inmunoconjugados , Neoplasias , Anticuerpos Monoclonales/química , Anticuerpos Monoclonales/uso terapéutico , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Humanos , Inmunoconjugados/química , Inmunoconjugados/farmacología , Inmunoconjugados/uso terapéutico , Neoplasias/tratamiento farmacológico , Microambiente Tumoral
3.
Transfus Med Hemother ; 51(1): 32-40, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38314240

RESUMEN

Background: CD36 deficiency is closely associated with fetal/neonatal alloimmune thrombocytopenia, platelet transfusion refractoriness, and other hemorrhage disorders, particularly in Asian and African populations. There is a clinical need for rapid and high-throughput methods of platelet CD36 (pCD36) phenotyping to improve the availability of CD36 typing of donors and assist clinical blood transfusions for patients with anti-CD36 antibodies. Such methods can also support the establishment of databases of pCD36-negative phenotypes. Study Design and Methods: A sandwich enzyme-linked immunosorbent assay (ELISA) for CD36 phenotyping of human platelets was developed using anti-CD36 monoclonal antibodies. The reliability of the assay was evaluated by calculating the intra-assay and inter-assay coefficients of variation (CV). A total of 1,691 anticoagulant whole blood samples from healthy blood donors were randomly selected. PCD36 expression was measured using a sandwich ELISA. PCD36 deficiency was confirmed by flow cytometry (FC). Mutations underlying pCD36 deficiency were identified using polymerase chain reaction sequence-based typing (PCR-SBT). Results: The sandwich ELISA for pCD36 phenotyping had high reliability (intra-assay CV, 2.1-4.8%; inter-assay CV, 2.3-5.2%). The sandwich ELISA was used to screen for CD36 expression on platelets isolated from 1,691 healthy blood donors. Of these, 36 samples were pCD36-negative. FC demonstrated absence of CD36 expression on monocytes in three of the 36 cases. In the present study population, the frequency of CD36 deficiency was 2.13% (36/1,691), of which 0.18% (3/1,691) was type I deficiency and 1.95% (33/1,691) was type II deficiency. In addition, we used PCR-SBT to characterize the gene mutations in exons 3-14 of the CD36 gene in 27 cases of CD36 deficiency and discovered 10 types of mutations in 13 pCD36-negative samples. Conclusion: The present study describes the development and characterization of a highly reliable sandwich ELISA for high-throughput screening for pCD36 expression. This novel method is feasible for clinical applications and provides a useful tool for the establishment of databases of pCD36-negative phenotype donors.

4.
J Am Chem Soc ; 145(22): 12051-12058, 2023 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-37218973

RESUMEN

The mechanism of the kinetic pH effect in hydrogen electrocatalysis, that is, the order-of-magnitude kinetic gap between the hydrogen oxidation and evolution reactions (HOR/HER) in acidic and alkaline electrolytes, has been drastically explored but still intractable to reach a consensus, which severely limits the catalyst advance for alkaline-based hydrogen energy technologies. Herein, the HOR/HER kinetics on a number of precious metal-based electrocatalysts are evaluated in electrolytes with pHs spanning a wide range from 1 to 13. Instead of a monotonous decrease with pH as generally believed, we surprisingly find a universal inflection-point behavior in the pH dependence of HOR/HER kinetics on these catalysts, with both the inflection-point pH and the acid-alkaline activity gap depending on the hydroxide binding energy of the catalyst. Based on a triple-path microkinetic model, in which hydronium (H3O+) and water (H2O) with and without formation of adsorbed hydroxide (OHad), respectively, act as hydrogen donors participating in HOR/HER in various pHs, we reveal that the formation of OHad should promote the HOR/HER kinetics mainly by improving the hydrogen-bond network in the electric double layer (EDL), rather than merely through modulating the energetics of surface reaction steps such as disassociation/formation of water. The present results and conclusions indicate that it is the interfacial EDL that dominates the substantial kinetic pH effects of hydrogen electrocatalysis.

5.
Small ; 19(11): e2207603, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36642789

RESUMEN

Developing highly efficient catalysts toward alkaline hydrogen oxidation reaction (HOR) and narrowing the kinetic gap between acidic and alkaline electrolytes are of great importance for the practical application of alkaline exchange membrane fuel cell . Herein, ordered Ru3 Sn7 /C intermetallic compound has been developed for the HOR under alkaline and acidic conditions. The authors demonstrate that the ordered intermetallic Ru3 Sn7 /C shows much enhanced HOR activity, stability, and CO-tolerance compared with its disordered RuSn solid solution alloy counterpart. More importantly, the authors find that the kinetic gap of HOR between acidic and alkaline media is significantly narrowed in the as-synthesized intermetallic Ru3 Sn7 /C catalysts. Combined experiment results and theoretical calculations, the authors understand that promoted hydroxyl-binding energy on Ru3 Sn7 /C derived from the intermetallic-induced strong electron interaction is responsible for the accelerated alkaline HOR performance and narrowed kinetic gap.

6.
Angew Chem Int Ed Engl ; 62(2): e202215585, 2023 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-36354203

RESUMEN

Developing highly efficient electrocatalysts for hydrogen oxidation reaction (HOR) under alkaline media is essential for the commercialization of alkaline exchange membrane fuel cell (AEMFC). However, the kinetics of HOR in alkaline media is complicated, resulting in orders of magnitude slower than that in acid, even for the state-of-the-art Pt/C. Here, we find that Ru-Ru2 P/C heterostructure shows HOR performance with a non-monotonous variation in a whole pH region. Unexpectedly, an inflection point located at pH≈7 is observed, showing an anomalous behavior that HOR activity under alkaline media surpasses acidic media. Combining experimental results and theoretical calculations, we propose the roles of discrepant reactive intermediates for pH-universal HOR, while H* and H2 O* adsorption strengths are responsible for acidic HOR, and OH* adsorption strength is essential for alkaline HOR. This work not only sheds light on fundamentally understanding the mechanism of HOR but also provides new designing principles for pH-targeted electrocatalysts.

7.
Proteins ; 2021 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-33629765

RESUMEN

Molecular dynamics (MD) simulations are a popular method of studying protein structure and function, but are unable to reliably sample all relevant conformational space in reasonable computational timescales. A range of enhanced sampling methods are available that can improve conformational sampling, but these do not offer a complete solution. We present here a proof-of-principle method of combining MD simulation with machine learning to explore protein conformational space. An autoencoder is used to map snapshots from MD simulations onto a user-defined conformational landscape defined by principal components analysis or specific structural features, and we show that we can predict, with useful accuracy, conformations that are not present in the training data. This method offers a new approach to the prediction of new low energy/physically realistic structures of conformationally dynamic proteins and allows an alternative approach to enhanced sampling of MD simulations.

8.
Small ; 13(8)2017 02.
Artículo en Inglés | MEDLINE | ID: mdl-27925434

RESUMEN

MWCNTs self-assemble into various homocentric rings in a thermo-driven self-assembly system. Closely packed and scatteredly packed MWCNT rings self-assemble on a Si-SiO2 substrate, whereas on a Au substrate smoothly packed MWCNT rings, rings with waviness, and rings with shuttle-like holes are seen to self-assemble. The dynamic self-assembly process includes convection flow and swirling flow.

9.
Nano Lett ; 16(10): 6042-6051, 2016 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-27607151

RESUMEN

Operation time of implantable electronic devices is largely constrained by the lifetime of batteries, which have to be replaced periodically by surgical procedures once exhausted, causing physical and mental suffering to patients and increasing healthcare costs. Besides the efficient scavenging of the mechanical energy of internal organs, this study proposes a self-powered, flexible, and one-stop implantable triboelectric active sensor (iTEAS) that can provide continuous monitoring of multiple physiological and pathological signs. As demonstrated in human-scale animals, the device can monitor heart rates, reaching an accuracy of ∼99%. Cardiac arrhythmias such as atrial fibrillation and ventricular premature contraction can be detected in real-time. Furthermore, a novel method of monitoring respiratory rates and phases is established by analyzing variations of the output peaks of the iTEAS. Blood pressure can be independently estimated and the velocity of blood flow calculated with the aid of a separate arterial pressure catheter. With the core-shell packaging strategy, monitoring functionality remains excellent during 72 h after closure of the chest. The in vivo biocompatibility of the device is examined after 2 weeks of implantation, proving suitability for practical use. As a multifunctional biomedical monitor that is exempt from needing an external power supply, the proposed iTEAS holds great potential in the future of the healthcare industry.


Asunto(s)
Monitoreo Fisiológico/instrumentación , Prótesis e Implantes , Animales , Arritmias Cardíacas/diagnóstico , Presión Sanguínea , Suministros de Energía Eléctrica , Frecuencia Cardíaca , Humanos
10.
Bioorg Med Chem ; 23(19): 6258-70, 2015 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-26349626

RESUMEN

Histone deacetylases inhibitors (HDACIs) have captured more and more attention in many diseases therapies, of which cancer is the most intractable. A novel series of N-hydroxybenzamide derivatives containing indole cap group was designed and synthesized. Most compounds exhibited excellent HDACs inhibitory activity, especially 8q-8v with low nanomolar IC50 values (1.5-13.0 nM), which were much more potent than the positive control SAHA. The most potent compound 8r showed slightly higher growth inhibitory activity than SAHA in multiple tumor cell lines, even though, antiproliferative activity of 8r seemed inferior to its HDAC inhibition activity. Poor transcellular permeability obtained from the result of HDAC class I cellular assay could explain the inferior antiproliferative activity. In addition, 8r displayed similar HDAC IIa cellular activity to class I, which indicated 8r might be a potent pan-HDAC inhibitor.


Asunto(s)
Benzamidas/química , Inhibidores de Histona Desacetilasas/química , Histona Desacetilasas/química , Indoles/química , Benzamidas/síntesis química , Benzamidas/toxicidad , Sitios de Unión , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Células HeLa , Inhibidores de Histona Desacetilasas/metabolismo , Inhibidores de Histona Desacetilasas/toxicidad , Histona Desacetilasas/metabolismo , Humanos , Simulación del Acoplamiento Molecular , Unión Proteica , Estructura Terciaria de Proteína , Relación Estructura-Actividad
11.
Arch Virol ; 159(5): 1143-7, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24162825

RESUMEN

In this study, we have evaluated four different 21-nt duplexes of small interfering RNA (siRNA-469, siRNA-852, siRNA-1802 and siRNA-1806) that specifically target the ORF2 gene of human astrovirus (HAstV) in inhibiting HAstV capsid protein expression in transfected BHK-21 cells. Furthermore, fluorescence analysis, real-time quantitative PCR (RT-qPCR) and western blot assays showed that pGPU6/GFP/Neo-shRNA inhibits ORF2 gene expression in Caco2 cells. The results indicate that siRNA/shRNA-469 and siRNA/shRNA-1802 can interfere with capsid protein expression in cell culture, and this provides a powerful tool for the study of HAstV gene functions and the biological properties of the capsid protein.


Asunto(s)
Regulación Viral de la Expresión Génica/fisiología , Mamastrovirus/metabolismo , ARN Interferente Pequeño/genética , Proteínas Virales/metabolismo , Animales , Línea Celular , Cricetinae , Humanos , Mamastrovirus/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Proteínas Virales/genética
12.
Zhonghua Yi Xue Za Zhi ; 94(26): 2045-9, 2014 Jul 08.
Artículo en Zh | MEDLINE | ID: mdl-25312667

RESUMEN

OBJECTIVE: To explore the clinical characteristics and outcomes of lung cancer patients with venous thromboembolism (VTE). METHODS: The clinical data of 80 lung cancer patients with VTE hospitalized from January 2003 to April 2013 at our hospital were reviewed. The clinical factors of age, gender, clinical manifestations, pathological type, clinical stage, performance status and therapeutic regimen were recorded and analyzed. And the pulmonary thromboembolism (PTE) patients with deep venous thrombosis (DVT) were enrolled into PTE group. The occurrences, clinical manifestations and prognosis of VTE were evaluated. RESULTS: A total of 80 patients were enrolled. There were 40 males and 40 females with a mean age of (65.8 ± 11.3) years. Adenocarcimoma was identified in 58 (72.5%) patients and advanced lung cancer in 71 (88.8%) patients. Among 37 (46.3%) patients with histodifferentiation results, 89.2% (33/37) of them were moderately and/or poorly differentiated. In 32 (40.0%) patients on chemotherapy, 71.9% (23/32) of them received a platinum-based regimen. There were 35 (43.8%) pulmonary thromboembolism embolism (PTE) and 45 (56.2%) DVT patients. Among PTE patents, 14 (40.0%) were identified incidentally. Dyspnea and swollen of limb were the most common symptoms. Only 20.0% (16/80) patients received VTE prophylaxis. After a definite diagnosis of cancer, 73.8%, 77.5%, 82.5% and 85.0% of patients experienced an event within 3, 6, 9 and 12 months respectively. Up to April 2014, among 53 deceased patients, 77.4% (41/53) died from lung cancer, 9.3% (5/53) PTE while 13.2% (7/53) due to other causes. The cumulative mortality rates within 3, 6, 9 and 12 months after VTE event were 49.1%, 67.9%, 77.4% and 79.2% respectively. CONCLUSIONS: Adenocarcimoma, advanced lung cancer, poor histodifferentiation and platinum-based chemotherapy regimen are the risk factors of VTE in lung cancer patients. Most events of VTE occur within 3-6 months after a diagnosis of lung cancer while most mortality cases within 1 year after VTE events.


Asunto(s)
Neoplasias Pulmonares/complicaciones , Tromboembolia Venosa/terapia , Anciano , Femenino , Hospitales , Humanos , Masculino , Pronóstico , Embolia Pulmonar , Factores de Riesgo
13.
Microsyst Nanoeng ; 10: 11, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38261871

RESUMEN

This paper presents a high-performance MEMS accelerometer with a DC/AC electrostatic stiffness tuning capability based on double-sided parallel plates (DSPPs). DC and AC electrostatic tuning enable the adjustment of the effective stiffness and the calibration of the geometric offset of the proof mass, respectively. A dynamical model of the proposed accelerometer was developed considering both DC/AC electrostatic tuning and the temperature effect. Based on the dynamical model, a self-centering closed loop is proposed for pulling the reference position of the force-to-rebalance (FTR) to the geometric center of DSPP. The self-centering accelerometer operates at the optimal reference position by eliminating the temperature drift of the readout circuit and nulling the net electrostatic tuning forces. The stiffness closed-loop is also incorporated to prevent the pull-in instability of the tuned low-stiffness accelerometer under a dramatic temperature variation. Real-time adjustments of the reference position and the DC tuning voltage are utilized to compensate for the residue temperature drift of the proposed accelerometer. As a result, a novel controlling approach composed of a self-centering closed loop, stiffness-closed loop, and temperature drift compensation is achieved for the accelerometer, realizing a temperature drift coefficient (TDC) of approximately 7 µg/°C and an Allan bias instability of less than 1 µg.

14.
Nat Commun ; 15(1): 5419, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38926414

RESUMEN

Suppressing the kinetically favorable lattice oxygen oxidation mechanism pathway and triggering the adsorbate evolution mechanism pathway at the expense of activity are the state-of-the-art strategies for Ru-based electrocatalysts toward acidic water oxidation. Herein, atomically dispersed Ru species are anchored into an acidic stable vinyl-linked 2D covalent organic framework with unique crossed π-conjugation, termed as COF-205-Ru. The crossed π-conjugated structure of COF-205-Ru not only suppresses the dissolution of Ru through strong Ru-N motifs, but also reduces the oxidation state of Ru by multiple π-conjugations, thereby activating the oxygen coordinated to Ru and stabilizing the oxygen vacancies during oxygen evolution process. Experimental results including X-ray absorption spectroscopy, in situ Raman spectroscopy, in situ powder X-ray diffraction patterns, and theoretical calculations unveil the activated oxygen with elevated energy level of O 2p band, decreased oxygen vacancy formation energy, promoted electrochemical stability, and significantly reduced energy barrier of potential determining step for acidic water oxidation. Consequently, the obtained COF-205-Ru displays a high mass activity with 2659.3 A g-1, which is 32-fold higher than the commercial RuO2, and retains long-term durability of over 280 h. This work provides a strategy to simultaneously promote the stability and activity of Ru-based catalysts for acidic water oxidation.

15.
Neural Regen Res ; 19(12): 2760-2772, 2024 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-38595293

RESUMEN

JOURNAL/nrgr/04.03/01300535-202412000-00031/figure1/v/2024-04-08T165401Z/r/image-tiff Neonatal hypoxic-ischemic brain injury is the main cause of hypoxic-ischemic encephalopathy and cerebral palsy. Currently, there are few effective clinical treatments for neonatal hypoxic-ischemic brain injury. Here, we investigated the neuroprotective and molecular mechanisms of exogenous nicotinamide adenine dinucleotide, which can protect against hypoxic injury in adulthood, in a mouse model of neonatal hypoxic-ischemic brain injury. In this study, nicotinamide adenine dinucleotide (5 mg/kg) was intraperitoneally administered 30 minutes before surgery and every 24 hours thereafter. The results showed that nicotinamide adenine dinucleotide treatment improved body weight, brain structure, adenosine triphosphate levels, oxidative damage, neurobehavioral test outcomes, and seizure threshold in experimental mice. Tandem mass tag proteomics revealed that numerous proteins were altered after nicotinamide adenine dinucleotide treatment in hypoxic-ischemic brain injury mice. Parallel reaction monitoring and western blotting confirmed changes in the expression levels of proteins including serine (or cysteine) peptidase inhibitor, clade A, member 3N, fibronectin 1, 5'-nucleotidase, cytosolic IA, microtubule associated protein 2, and complexin 2. Proteomics analyses showed that nicotinamide adenine dinucleotide ameliorated hypoxic-ischemic injury through inflammation-related signaling pathways (e.g., nuclear factor-kappa B, mitogen-activated protein kinase, and phosphatidylinositol 3 kinase/protein kinase B). These findings suggest that nicotinamide adenine dinucleotide treatment can improve neurobehavioral phenotypes in hypoxic-ischemic brain injury mice through inflammation-related pathways.

16.
Heliyon ; 10(8): e29268, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38638976

RESUMEN

The establishment of a platelet-apheresis donor database may provide a feasible solution to improve the efficacy of platelet transfusion in patients with immune platelet transfusion refractoriness (PTR). This study aimed to establish HLA genotype database in Suzhou, to provide HLA-I compatible platelets for PTR patients to ensure the safety and effectiveness of platelet transfusions. We used a polymerase chain reaction sequence-based typing (PCR-SBT) method to establish the database by performing high-resolution HLA-A, -B, and -C genotyping on 900 platelet-apheresis donors. HLA-I antibody was detected in patients using a Luminex device, and HLA-I gene matching was performed by an HLA-Matchmaker. We found that the highest frequency of the HLA-A allele was A*11:01 (17.06 %), followed by A*24:02 (14.67 %) and A*02:01 (13.61 %). The highest frequency of the HLA-B allele was B*46:01 (9.78 %), followed by B*40:01 (8.39 %) and B*13:02 (33 %). After the detection of platelet antibodies in 74 patients with immune PTR, we found 30 HLA-A antibodies and 48 HLA-B antibodies, and there were a variety of high frequency antibodies whose alleles were low in the donor database, such as HLA-A*68:02, and B*57:01. After avoiding donor-specific antibodies (DSA) matching, 102 of 209 platelet-compatible transfusions were effective, resulting in an effective rate of 48.8 %, which significantly improved the efficacy of platelet transfusion. The establishment of a platelet donor database is of great significance to improve the therapeutic effect of platelet transfusion in patients with hematologic disorder, and save blood resources, and it is also the premise and guarantee of precise platelet transfusion.

17.
Front Immunol ; 15: 1372771, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38887300

RESUMEN

Introduction: Myeloid-derived suppressor cell (MDSC) exhibits immunosuppressive functions and affects cancer progression, but its relationship with prostate cancer remains unclear. We elucidated the association of polymorphonuclear MDSC (PMN-MDSC) and monocytic MDSC (M-MDSC) levels of the total peripheral blood mononuclear cells (PBMCs) with prostate cancer progression and evaluated their roles as prognostic indicators. Methods: We enrolled 115 patients with non-metastatic hormone-sensitive prostate cancer (nmHSPC, n = 62), metastatic hormone-sensitive prostate cancer (mHSPC, n = 23), and metastatic castration-resistant prostate cancer (mCRPC, n = 30). Subsequently, the proportions of MDSCs in each disease progression were compared. Log-rank tests and multivariate Cox regression analyses were performed to ascertain the associations of overall survival. Results: The patients with mCRPC had significantly higher PMN-MDSC percentage than those with nmHSPC and mHSPC (P = 7.73 × 10-5 and 0.0014). Significantly elevated M-MDSC levels were observed in mCRPC patients aged <70 years (P = 0.016) and with a body mass index (BMI) <25 kg/m2 (P = 0.043). The high PMN-MDSC group had notably shorter median survival duration (159 days) than the low PMN-MDSC group (768 days, log-rank P = 0.018). In the multivariate analysis including age, BMI, and MDSC subset, PMN-MDSC was significantly associated with prognosis (hazard ratios, 3.48; 95% confidence interval: 1.05-11.56, P = 0.042). Discussion: PMN-MDSC levels are significantly associated with mCRPC prognosis. Additionally, we highlight the remarkable associations of age and BMI with M-MDSC levels in mCRPC, offering novel insights into MDSC dynamics in prostate cancer progression.


Asunto(s)
Células Supresoras de Origen Mieloide , Neoplasias de la Próstata Resistentes a la Castración , Humanos , Masculino , Células Supresoras de Origen Mieloide/inmunología , Células Supresoras de Origen Mieloide/metabolismo , Neoplasias de la Próstata Resistentes a la Castración/inmunología , Neoplasias de la Próstata Resistentes a la Castración/patología , Neoplasias de la Próstata Resistentes a la Castración/mortalidad , Neoplasias de la Próstata Resistentes a la Castración/sangre , Anciano , Pronóstico , Persona de Mediana Edad , Neutrófilos/inmunología , Progresión de la Enfermedad , Anciano de 80 o más Años , Metástasis de la Neoplasia
18.
Zhonghua Jie He He Hu Xi Za Zhi ; 36(5): 357-9, 2013 May.
Artículo en Zh | MEDLINE | ID: mdl-24047810

RESUMEN

OBJECTIVE: To improve recognition of saddle pulmonary embolism (SPE). METHODS: A retrospectively review was performed for patients diagnosed with SPE determined by CTPA from Jan 2004 to Jan 2012. RESULTS: Fifteen SPE patients(4.44%) were found in 338 documented PE patients confirmed by CTPA. There were 7 males and 8 females, with an average age of (57 ± 13) years. The bifurcation of the main pulmonary artery was completely blocked in one case, while partial obstruction was found in the others. Hemodynamic stability was observed in 11 cases, shock in 1 case, and hypotension in 3 cases. Thromboembolectomy was performed in 1 case accompanied by patent foramen ovale straddling thrombus, and thrombolytic therapy was administered in 5 cases while anticoagulant therapy alone in 9 cases. All the cases survived. Minor bleeding was observed in 2 patients and no major bleeding occurred. CONCLUSION: The prevalence of SPE in this series was similar to that reported in the literature. But the incidence might be underestimated. Mortality rate was low. No more aggressive therapeutic interventions (thrombolytics or catheter thrombectomy) were needed in those patients with hemodynamic stability and without patent foramen ovale straddling thrombus.


Asunto(s)
Fibrinolíticos/uso terapéutico , Arteria Pulmonar/diagnóstico por imagen , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/terapia , Terapia Trombolítica/métodos , Adulto , Anciano , Angiografía , Disnea/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Arteria Pulmonar/patología , Embolia Pulmonar/etiología , Estudios Retrospectivos , Síncope/etiología , Trombectomía , Tomografía Computarizada por Rayos X/métodos
19.
ACS Omega ; 8(37): 33321-33331, 2023 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-37744809

RESUMEN

Ammonia thermochemical energy storage is based on a reversible reaction and realizes energy storage and utilization by absorbing and releasing heat. Under different energy flow densities, the efficiency of an ammonia reactor composed of multiple ammonia reaction tubes is different. Based on the coupling model of light, heat, and chemical energy of an ammonia decomposition reaction system, taking a 20 MW solar thermal power plant as the research object, this paper proposes a new model of ammonia energy storage system, which places the ammonia decomposition side in a low-pressure environment and the ammonia synthesis side in a high-pressure environment. The effects of different inlet temperatures, inlet flow rates, flow distribution, and energy flow density distribution on the ammonia energy storage system were studied. The results show that the increase of inlet temperature and the decrease of inlet flow rate are beneficial to the improvement of thermal efficiency and exergy efficiency of the system to a certain extent, but when the inlet temperature increases or the inlet flow rate decreases to a certain extent, the efficiency of the system will decline. Under the condition of nonuniform energy flow density and nonuniform inlet flow distribution, more ideal system thermal efficiency and exergy efficiency can be obtained.

20.
J Cancer ; 14(10): 1935-1945, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37476192

RESUMEN

Objective: We retrospectively studied cancer mortality and incidence in China from 1990 to 2019, investigated the cancer trends and risk factors, and analyzed the effects of Gross Domestic Product (GDP) on cancer mortality and incidence. Methods: Data was obtained in "Our world in data" in October 2022 to explore mortality rates of different cancers and their trends and the roles of cancer risk factors, including GDP, air pollution, etc. Results: Over the past 30 years, cancer had been China's second leading cause of death. Tracheal, bronchial, and lung cancers, with an annual growth rate of 6.5%, were the most frequently diagnosed cancers. The burden of different cancers changed as the mortality rate of cancer changed. The age-standardized cancer mortality rate had decreased by 19.0%; cancer deaths in all age groups had increased. While the number of cancer deaths in the elderly aged ≥70 did not increase distinctively, its percentage increased by 52.1% and 1.7% annually. The percentage of patients with new-onset cancer increased by 240% and 8.6% annually. For every USD 1,000 increase in GDP, cancer deaths decreased by 2.3/100,000. Tobacco, meat, and alcohol consumption and BMI had increased and were not conducive to the future control of cancer. Conclusions: We summarized the incidence and mortality of major cancers and their trends in China over the past 30 years and analyzed the effects of GDP and the roles of cancer risk factors. Overall GDP growth and effective control of air pollution reduced cancer mortality, while population aging, smoking, alcohol consumption, BMI increasing, and meat consumption brought challenges for cancer control.

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