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1.
Br J Haematol ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38960381

RESUMO

This prospective clinical study aimed to evaluate the efficacy and safety of the pre-emptive treatment modality of azacitidine in combination with interferon-α (IFN-α) in AML/MDS patients post-transplantation. Forty-seven patients aged 17-62 were enrolled with 14 patients having completed the planned 12 cycles. Following initiation, 72.3% responded positively after the first cycle, peaking at 77.2% by the fifth cycle. Notably, 24 patients maintained sustained responses throughout a median follow-up of 1050 days (range, 866-1234). Overall survival, leukaemia-free survival and event-free survival probabilities at 3 years were 69.5%, 60.4% and 35.7% respectively. Cumulative incidences of relapse and non-relapse mortality were 36.5% and 4.3% respectively. Multivariate analysis identified that receiving pre-emptive treatment for fewer than six cycles and the absence of chronic graft-versus-host disease after intervention was significantly associated with poorer clinical outcomes. The combination of azacitidine with IFN-α was well-tolerated with no observed severe myelotoxicity, and the majority of adverse events were reversible and manageable. In conclusion, the use of azacitidine in conjunction with IFN-α as pre-emptive therapy is a safe and effective treatment to prevent disease progression in AML/MDS patients with MRD positivity post-allo-HSCT.

2.
Ann Hematol ; 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38981923

RESUMO

The low-dose anti-thymocyte globulin (ATG) plus low-dose post transplantation cyclophosphamide (PTCy) -based (low-dose ATG/PTCy-based) regimen had a promising activity in preventing of graft-versus-host disease (GVHD) in adult patients. However, its efficacy in pediatric patients remain to be defined. Here, we presented the findings from 35 pediatric patients undergoing haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) with the new regimen for GVHD prophylaxis. The cumulative incidences (CIs) of grades II-III and III-IV acute GVHD (aGVHD) were 34% (95% CI, 17-48%) and 11% (95% CI, 0-21%) within 180 days post-transplantation, respectively. The CIs of chronic GVHD (cGVHD) and moderate-to-severe cGVHD within 2 years were 26% (95% CI, 7-41%) and 12% (95% CI, 0-25%), respectively. The 2-year probabilities of overall survival, relapse-free survival, and graft-versus-host disease and relapse-free survival were 89% (95% CI, 78-100%), 82% (95% CI, 68-98%) and 59% (95% CI, 43-80%), respectively. The CIs of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) reactivation by day 180 were 37% (95% CI, 19-51%) and 20% (95% CI, 6-32%) respectively. These results strongly advocate for the efficacy of the low-dose ATG/PTCy-based regimen as a robust strategy for GVHD prevention in haplo-PBSCT for pediatric patients.

3.
Cell Commun Signal ; 22(1): 359, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38992691

RESUMO

PURPOSE: Bietti crystalline dystrophy (BCD) is an inherited retinal degeneration disease caused by mutations in the CYP4V2 gene. Currently, there is no clinical therapy approach available for BCD patients. Previous research has suggested that polyunsaturated fatty acids (PUFAs) may play a significant role in the development of BCD, implicating the involvement of ferroptosis in disease pathogenesis. In this work, we aimed to investigate the interplay between ferroptosis and BCD and to detect potential therapeutic strategies for the disease. METHODS: Genetic-edited RPE cell line was first established in this study by CRISPR-Cas9 technology. Cyp4v3 (the homologous gene of human CYP4V2) knock out (KO) mice have also been used. Lipid profiling and transcriptome analysis of retinal pigment epithelium (RPE) cells from Cyp4v3 KO mice have been conducted. Ferroptosis phenotypes have been first investigated in BCD models in vitro and in vivo, including lipid peroxidation, mitochondrial changes, elevated levels of reactive oxygen species (ROS), and altered gene expression. Additionally, an iron chelator, deferiprone (DFP), has been tested in vitro and in vivo to determine its efficacy in suppressing ferroptosis and restoring the BCD phenotype. RESULTS: Cyp4v3 KO mice exhibited progressive retinal degeneration and lipid accumulation, similar to the BCD phenotype, which was exacerbated by a high-fat diet (HFD). Increased levels of PUFAs, such as EPA (C22:5) and AA (C20:4), were observed in the RPE of Cyp4v3 KO mice. Transcriptome analysis of RPE in Cyp4v3 KO mice revealed changes in genes involved in iron homeostasis, particularly an upregulation of NCOA4, which was confirmed by immunofluorescence. Ferroptosis-related characteristics, including mitochondrial defects, lipid peroxidation, ROS accumulation, and upregulation of related genes, were detected in the RPE both in vitro and in vivo. Abnormal accumulation of ferrous iron was also detected. DFP, an iron chelator administration suppressed ferroptosis phenotype in CYP4V2 mutated RPE. Oral administration of DFP also restored the retinal function and morphology in Cyp4v3 KO mice. CONCLUSION: This study represented the first evidence of the substantial role of ferroptosis in the development of BCD. PUFAs resulting from CYP4V2 mutation may serve as substrates for ferroptosis, potentially working in conjunction with NCOA4-regulated iron accumulation, ultimately leading to RPE degeneration. DFP administration, which chelates iron, has demonstrated its ability to reverse BCD phenotype both in vitro and in vivo, suggesting a promising therapeutic approach in the future.


Assuntos
Distrofias Hereditárias da Córnea , Ferroptose , Camundongos Knockout , Epitélio Pigmentado da Retina , Animais , Ferroptose/genética , Ferroptose/efeitos dos fármacos , Distrofias Hereditárias da Córnea/genética , Distrofias Hereditárias da Córnea/patologia , Distrofias Hereditárias da Córnea/metabolismo , Distrofias Hereditárias da Córnea/tratamento farmacológico , Humanos , Epitélio Pigmentado da Retina/metabolismo , Epitélio Pigmentado da Retina/patologia , Epitélio Pigmentado da Retina/efeitos dos fármacos , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Doenças Retinianas/genética , Doenças Retinianas/patologia , Doenças Retinianas/metabolismo , Doenças Retinianas/tratamento farmacológico , Família 4 do Citocromo P450/genética , Camundongos Endogâmicos C57BL , Linhagem Celular , Peroxidação de Lipídeos/efeitos dos fármacos
4.
Anim Sci J ; 95(1): e13964, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38831612

RESUMO

This study evaluated the effects of supplementation with Antrodia cinnamomea mycelium by-product (ACBP) on growth performance and immune response in weaning piglets. Total available content and antioxidant capacity of ACBP were determined. Ninety-six black pigs were randomly distributed to 24 pens. Study compared four groups which were supplemented with ACBP at 0%, 2.5%, 5%, or 10% for 6 weeks after weaning at 4 weeks. Results showed that ACBP on total phenolic, total flavonoid, and total triterpenoids contents were 13.68 mg GAE/g DW, 1.67 µg QE/g DW, and 15.6 mg/g, respectively. Weaning piglets fed 2.5% ACBP showed a significant decreased body weight gain compared with those supplemented with 5% ACBP, 10% ACBP, and control groups. Results showed that all ACBP groups increased the villi height of jejunum significantly. Incidence of diarrhea in 11 weeks with supplementation with 5% and 10% ACBP diets were lower than in control group. The 10% ACBP group showed significantly lower expression of immune response genes (IL-1ß, IL-6, IL-8, TNF-α, and IFN-γ) than the 2.5% and 5% ACBP groups. Based on results, dietary supplementation with 10% ACBP did not significantly affect body weight but could decrease piglet diarrhea condition and expression of IL-1ß and IL-6 genes.


Assuntos
Ração Animal , Antioxidantes , Dieta , Suplementos Nutricionais , Micélio , Desmame , Aumento de Peso , Animais , Suínos/crescimento & desenvolvimento , Suínos/imunologia , Aumento de Peso/efeitos dos fármacos , Dieta/veterinária , Antioxidantes/metabolismo , Diarreia/veterinária , Triterpenos/farmacologia , Triterpenos/administração & dosagem , Expressão Gênica/efeitos dos fármacos , Citocinas/metabolismo , Jejuno/metabolismo , Fenóis/análise , Fenômenos Fisiológicos da Nutrição Animal , Doenças dos Suínos/microbiologia , Doenças dos Suínos/prevenção & controle , Doenças dos Suínos/imunologia , Polyporales/química
5.
Biochim Biophys Acta Mol Basis Dis ; 1870(6): 167259, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38796918

RESUMO

BACKGROUND: Alcohol-associated liver disease (ALD) is a leading cause of liver disease-related deaths worldwide. Unfortunately, approved medications for the treatment of this condition are quite limited. One promising candidate is the anthocyanin, Cyanidin-3-O-glucoside (C3G), which has been reported to protect mice against hepatic lipid accumulation, as well as fibrosis in different animal models. However, the specific effects and mechanisms of C3G on ALD remain to be investigated. EXPERIMENTAL APPROACH: In this report, a Gao-binge mouse model of ALD was used to investigate the effects of C3G on ethanol-induced liver injury. The mechanisms of these C3G effects were assessed using AML12 hepatocytes. RESULTS: C3G administration ameliorated ethanol-induced liver injury by suppressing hepatic oxidative stress, as well as through reducing hepatic lipid accumulation and inflammation. Mechanistically, C3G activated the AMPK pathway and enhanced mitophagy to eliminate damaged mitochondria, thus reducing mitochondria-derived reactive oxidative species in ethanol-challenged hepatocytes. CONCLUSIONS: The results of this study indicate that mitophagy plays a potentially important role underlying the hepatoprotective action of C3G, as demonstrated in a Gao-binge mouse model of ALD. Accordingly, C3G may serve as a promising, new therapeutic drug candidate for use in ALD.


Assuntos
Antocianinas , Modelos Animais de Doenças , Etanol , Glucosídeos , Hepatopatias Alcoólicas , Mitofagia , Estresse Oxidativo , Animais , Antocianinas/farmacologia , Mitofagia/efeitos dos fármacos , Camundongos , Glucosídeos/farmacologia , Hepatopatias Alcoólicas/metabolismo , Hepatopatias Alcoólicas/patologia , Hepatopatias Alcoólicas/tratamento farmacológico , Hepatopatias Alcoólicas/prevenção & controle , Etanol/toxicidade , Etanol/efeitos adversos , Estresse Oxidativo/efeitos dos fármacos , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Hepatócitos/patologia , Masculino , Camundongos Endogâmicos C57BL , Fígado/metabolismo , Fígado/efeitos dos fármacos , Fígado/patologia , Espécies Reativas de Oxigênio/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos
6.
Nat Immunol ; 25(3): 525-536, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38356061

RESUMO

Regulatory T (Treg) cells are critical for immune tolerance but also form a barrier to antitumor immunity. As therapeutic strategies involving Treg cell depletion are limited by concurrent autoimmune disorders, identification of intratumoral Treg cell-specific regulatory mechanisms is needed for selective targeting. Epigenetic modulators can be targeted with small compounds, but intratumoral Treg cell-specific epigenetic regulators have been unexplored. Here, we show that JMJD1C, a histone demethylase upregulated by cytokines in the tumor microenvironment, is essential for tumor Treg cell fitness but dispensable for systemic immune homeostasis. JMJD1C deletion enhanced AKT signals in a manner dependent on histone H3 lysine 9 dimethylation (H3K9me2) demethylase and STAT3 signals independently of H3K9me2 demethylase, leading to robust interferon-γ production and tumor Treg cell fragility. We have also developed an oral JMJD1C inhibitor that suppresses tumor growth by targeting intratumoral Treg cells. Overall, this study identifies JMJD1C as an epigenetic hub that can integrate signals to establish tumor Treg cell fitness, and we present a specific JMJD1C inhibitor that can target tumor Treg cells without affecting systemic immune homeostasis.


Assuntos
Doenças Autoimunes , Humanos , Citocinas , Epigenômica , Histona Desmetilases , Homeostase , Oxirredutases N-Desmetilantes , Histona Desmetilases com o Domínio Jumonji/genética
7.
Small ; 20(17): e2307728, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38263806

RESUMO

Herein, the structure of integrated M3D inverters are successfully demonstrated where a chemical vapor deposition (CVD) synthesized monolayer WSe2 p-type nanosheet FET is vertically integrated on top of CVD synthesized monolayer MoS2 n-type film FET arrays (2.5 × 2.5 cm) by semiconductor industry techniques, such as transfer, e-beam evaporation (EBV), and plasma etching processes. A low temperature (below 250 °C) is employed to protect the WSe2 and MoS2 channel materials from thermal decomposition during the whole fabrication process. The MoS2 NMOS and WSe2 PMOS device fabricated show an on/off current ratio exceeding 106 and the integrated M3D inverters indicate an average voltage gain of ≈9 at VDD = 2 V. In addition, the integrated M3D inverter demonstrates an ultra-low power consumption of 0.112 nW at a VDD of 1 V. Statistical analysis of the fabricated inverters devices shows their high reliability, rendering them suitable for large-area applications. The successful demonstration of M3D inverters based on large-scale 2D monolayer TMDs indicate their high potential for advancing the application of 2D TMDs in future integrated circuits.

8.
J Anim Sci ; 1022024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38071666

RESUMO

This paper presents a non-contact method for the detection of changes in sow vulva size in a group pen. The traditional approach to estrus detection is manually pressing down on the back of the sow to elicit standing responses; however, this method causes undue distress for sows not in estrus. When a sow is in estrus, the vulva is red and swollen due to the presence of endocrine. Monitoring changes in vulva size to detect estrus with as little impact on the sow as possible is the focus of this study. This is achieved using a single camera combined with a deep learning framework. Our approach comprises two steps: vulva detection and vulva size conversion. Images of sows of Yorkshire, Landrace, and Duroc breeds were collected in group housing, and the vulva was detected through artificial markers and the network architecture of YOLO v4. Based on the internal and external parameters of the camera, the detected size was converted into millimeters and the results of manual measurement (MM) and automatic calculation combined to calculate the size of the vulva. Analysis of the calculated size compared with MM indicates that the object recognition rate of the system exceeds 97.06%, with a size error of only + 1.70 to -4.47 mm and high-calculation efficiency (>2.8 frames/s). Directions for future research include the automatic detection of pig width.


The size of a sow's vulva is an important indicator of sow estrus. Non-contact means of monitoring size changes for estrus timing would represent a significant contribution to the field of pig farming. This paper thus focuses on development of a system for the automatic detection of sow vulva size using a single camera combined with a deep learning framework. Experiments showed that the object recognition rate of the system exceeds 97.06%, the vulva size error is +1.70 to −4.47 mm, and the calculation efficiency is high (>2.8 frames/s).


Assuntos
Aprendizado Profundo , Suínos , Animais , Feminino , Abrigo para Animais , Desmame , Estro/fisiologia , Vulva/fisiologia
9.
Int J Biol Macromol ; 254(Pt 3): 127879, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37944722

RESUMO

The water solubility and brittleness of unplasticized sodium alginate (SA) films hinder their widely application. Glycerol (GLY), the most commonly used plasticizer, is compatible with alginate due to the formation of hydrogen bonding owing to the hydroxyl functional groups. However, GLY is a small water-soluble molecule, and the resulting leaching problem may lead to decline in mechanical properties of SA films. Aimed at better plasticizers for alginate (ALG) films, this work focuses on the effects of polymerization degree of polyglycerol on physical properties of ALG films. The cross-sectional morphology, crystallinity, mechanical and thermal properties, water solubility, water content and barrier property of ALG films plasticized with GLY, triglycerol (TG) and decaglycerol (DG) were characterized and discussed. Results illustrated that owing to the long molecular chains of TG and DG and their strong interactions with ALG matrix, the plasticized films possessed better mechanical properties, higher water content and lower water solubility. Moreover, it was worth mentioning that even after water treatment, the mechanical properties of ALG-TG and ALG-DG films were superior than that plasticized with GLY. The results of this study were believed to provide particular insights into the plasticization mechanism and the improvement in performance of SA films in packaging applications.


Assuntos
Alginatos , Glicerol , Estudos Transversais , Polímeros , Plastificantes , Permeabilidade
10.
Front Immunol ; 14: 1252879, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37954615

RESUMO

Introduction: The novel low-dose anti-thymocyte (ATG, 5 mg/kg) plus low-dose post-transplant cyclophosphamide (PTCy, 50 mg/kg) (low-dose ATG/PTCy)-based regimen had promising activity for prevention of graft-versus-host disease (GVHD) in haploidentical-peripheral blood stem cell transplantation (haplo-PBSCT), but its impacts on long-term outcomes remain to be defined. Methods: We performed a large sample, long-term follow-up retrospective study to evaluate its efficacy for GVHD prophylaxis. Results: The study enrolled 260 patients, including 162 with myeloid malignancies and 98 with lymphoid malignancies. The median follow-up time was 27.0 months. For the entire cohort, the cumulative incidences (CIs) of grade II-IV and III-IV acute GVHD (aGVHD) by 180 days were 13.46% (95% CI, 9.64%-17.92%) and 5.77% (95% CI, 3.37%-9.07%); while total and moderate/severe chronic GVHD (cGVHD) by 2 years were 30.97% (95% CI, 25.43%-36.66%) and 18.08% (95% CI, 13.68%-22.98%), respectively. The 2-year overall survival (OS), relapse-free survival (RFS), GVHD-free, relapse-free survival (GRFS), non-relapse mortality (NRM), and CIs of relapse were 60.7% (95% CI, 54.8%-67.10%), 58.1% (95% CI, 52.2%-64.5%), 50.6% (95% CI, 44.8-57.1%), 23.04% (95% CI, 18.06%-28.40%), and 18.09% (95% CI, 14.33%-23.97%, respectively. The 1-year CIs of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) reactivation were 43.46% (95% CI, 37.39%-49.37%) and 18.08% (95% CI, 13.68%-22.98%), respectively. In multivariate analysis, the disease status at transplantation was associated with inferior survivor outcomes for all patients and myeloid and lymphoid malignancies, while cGVHD had superior outcomes for all patients and myeloid malignancies, but not for lymphoid malignancies. Discussion: The results demonstrated that the novel regimen could effectively prevent the occurrence of aGVHD in haplo-PBSCT.


Assuntos
Infecções por Vírus Epstein-Barr , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Neoplasias , Transplante de Células-Tronco de Sangue Periférico , Células-Tronco de Sangue Periférico , Humanos , Soro Antilinfocitário/uso terapêutico , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Seguimentos , Estudos Retrospectivos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Infecções por Vírus Epstein-Barr/complicações , Células-Tronco de Sangue Periférico/patologia , Herpesvirus Humano 4 , Ciclofosfamida/uso terapêutico , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Doença Enxerto-Hospedeiro/patologia , Neoplasias/tratamento farmacológico
12.
Animals (Basel) ; 13(19)2023 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-37835712

RESUMO

Formosan sambar deer (Rusa unicolor swinhoei) are of great economic significance in Taiwan, resulting in a substantial increase in deer farming to meet the high demand for velvet antlers. Inbreeding depression and reduced genetic variability can lead to the deterioration of captive populations. In this study, 239 Formosan sambar deer were genotyped using 13 microsatellites to analyze their genetic diversity and population genetic structure. Our results indicate a high-resolution power of these microsatellites in individual discrimination and parentage analysis. However, captive populations exhibit a low level of genetic diversity, likely because of inbreeding and bottleneck effects. Both principal coordinate analysis (PCoA) and STRUCTURE analyses revealed two distinct and segregated genetic groups within the captive populations and indicated no clear population genetic structure among the captive populations. Introducing new genetic material from the wild through translocation offers a potential solution for mitigating the impact of inbreeding and enhancing genetic diversity. The comprehensive information obtained from these genetic analyses is crucial for the development of effective breeding strategies aimed at preserving and enhancing Formosan sambar deer populations.

13.
Bioresour Technol ; 388: 129763, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37704091

RESUMO

Low composting temperature and long maturation periods are two major problems during food waste composting. In this study, a novel array-based electric field-assisted aerobic composting (Pin-EAC) process was tested on food waste compost. Pin-EAC increase the composting temperature to 69.3 °C, and improved the germination index by 15%. The Pin-EAC took at least 40% less time to reach the standard compost maturity. The fluorescent spectroscopy results showed that Pin-EAC could increase humic acid and fulvic acid by 33% and 37%, respectively. Pin-EAC could increase the diversity of thermophilic bacteria during composting. The co-occurrence network shown that Pin-EAC are more closely related to oxygen and temperature. This work has initially shown that the use of an electric field could improve food waste composting quality, suggesting that the Pin-EAC process is an effective strategy for high-water and high-oil organic solid waste aerobic composting.

14.
ACS Med Chem Lett ; 14(8): 1079-1087, 2023 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-37583816

RESUMO

The use of small agonists to target stimulators of interferon genes (STING) has been demonstrated to be a promising strategy for the treatment of various cancers and infectious diseases. Herein, we discovered a series of 1H-pyrrole-3-carbonitrile derivatives as potential STING agonists. On this basis, the structure-activity relationship of this scaffold was studied by introducing various substituents on the aniline ring system. Representative compounds 7F, 7P, and 7R all displayed comparable activities to the reported STING agonist SR-717 in binding various hSTING alleles and induced reporter signal in human THP1 cell lines. Model compound 7F induced phosphorylation of TBK1, IRF3, p65, and STAT3 in a STING-dependent fashion and stimulated the expression of target genes IFNB1, CXCL10, and IL6 in a time-dependent manner in human THP1 cells. Our findings afforded a series of novel STING agonists with promising potential.

15.
Infect Dis Ther ; 12(8): 2103-2115, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37541984

RESUMO

INTRODUCTION: Unbiased metagenomic next-generation sequencing (mNGS) has been used for infection diagnosis. In this study, we explored the clinical diagnosis value of mNGS for pulmonary complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: From August 2019 to June 2021, a prospective study was performed to comparatively analyze the pathogenic results of mNGS and conventional tests for bronchoalveolar lavage fluid (BALF) from 134 cases involving 101 patients with pulmonary complications after allo-HSCT. RESULTS: More pathogens were identified by mNGS than with conventional tests (226 vs 120). For bacteria, the diagnostic sensitivity (P = 0.144) and specificity (P = 0.687) were similar between the two methods. For fungus except Pneumocystis jirovecii (PJ), conventional tests had a significantly higher sensitivity (P = 0.013) with a similarly high specificity (P = 0.109). The sensitivities for bacteria and fungi could be increased with the combination of the two methods. As for PJ, both the sensitivity (100%) and specificity (99.12%) of mNGS were very high. For viruses, the sensitivity of mNGS was significantly higher (P = 0.021) and the negative predictive value (NPV) was 95.74% (84.27-99.26%). Pulmonary infection complications accounted for 90.30% and bacterium was the most common pathogen whether in single infection (63.43%) or mixed infection (81.08%). The 6-month overall survival (OS) of 88.89% in the early group (mNGS ≤ 7 days) was significantly higher than that of 65.52% (HR 0.287, 95% CI 0.101-0.819, P = 0.006) in the late group (mNGS > 7 days). CONCLUSIONS: mNGS for BALF could facilitate accurate and fast diagnosis for pulmonary complications. Early mNGS could improve the prognosis of patients with pulmonary complications after allo-HSCT. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT04051372.

16.
Front Pharmacol ; 14: 1128699, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37124197

RESUMO

Hesperetin is a natural flavonoid with many biological activities. In view of hyperuricemia treatment, the effects of hesperetin in vivo and in vitro, and the underlying mechanisms, were explored. Hyperuricemia models induced by yeast extract (YE) or potassium oxonate (PO) in mice were created, as were models based on hypoxanthine and xanthine oxidase (XOD) in L-O2 cells and sodium urate in HEK293T cells. Serum level of uric acid (UA), creatinine (CRE), and urea nitrogen (BUN) were reduced significantly after hesperetin treatment in vivo. Hesperetin provided hepatoprotective effects and inhibited xanthine oxidase activity markedly, altered the level of malondialdehyde (MDA), glutathione peroxidase (GSH-PX) and catalase (CAT), downregulated the XOD protein expression, toll-like receptor (TLR)4, nucleotide binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, interleukin-18 (IL-18), upregulated forkhead box O3a (FOXO3a), manganese superoxide dismutase (MnSOD) in a uric acid-synthesis model in mice. Protein expression of organic anion transporter 1 (OAT1), OAT3, organic cationic transporter 1 (OCT1), and OCT2 was upregulated by hesperetin intervention in a uric acid excretion model in mice. Our results proposal that hesperetin exerts a uric acid-lowering effect through inhibiting xanthine oxidase activity and protein expression, intervening in the TLR4-NLRP3 inflammasome signaling pathway, and up-regulating expression of FOXO3a, MnSOD, OAT1, OAT3, OCT1, and OCT2 proteins. Thus, hesperetin could be a promising therapeutic agent against hyperuricemia.

17.
Micromachines (Basel) ; 14(3)2023 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-36984983

RESUMO

In this study, we report a low ohmic contact resistance process on a 650 V E-mode p-GaN gate HEMT structure. An amorphous silicon (a-Si) assisted layer was inserted in between the ohmic contact and GaN. The fabricated device exhibits a lower contact resistance of about 0.6 Ω-mm after annealing at 550 °C. In addition, the threshold voltage shifting of the device was reduced from -0.85 V to -0.74 V after applying a high gate bias stress at 150 °C for 10-2 s. The measured time to failure (TTF) of the device shows that a low thermal budget process can improve the device's reliability. A 100-fold improvement in HTGB TTF was clearly demonstrated. The study shows a viable method for CMOS-compatible GaN power device fabrication.

18.
Cell Transplant ; 32: 9636897231157054, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36905323

RESUMO

The contribution of lymphocyte subset composition of the graft on the outcomes following haploidentical peripheral blood stem cell transplantation (haploPBSCT) is not fully elucidated. We retrospectively analyzed 314 patients with hematological malignancies who underwent haploPBSCT from 2016 to 2020 in our center. We obtained a cutoff value of CD3+ T cell dose (2.96 × 108/kg) that separated the risk of II-IV acute graft-versus-host disease (aGvHD) and divided patients into the low CD3+ T cell dose group (CD3+ low) and the high CD3+ T cell dose (CD3+ high) group. Significantly higher incidences of I-IV aGvHD, II-IV aGvHD, and III-IV aGvHD were identified in the CD3+ high group (50.8%, 19.8%, and 8.1% in the high group, 23.1%, 6.0%, and 0.9% in the low group, P < 0.0001, P = 0.002, and P = 0.02, respectively). We found that CD4+ T cell and its naïve and memory subpopulations of grafts had a significant impact on aGvHD (P = 0.005, P = 0.018, and P = 0.044). Besides, we found an inferior reconstitution of natural killer (NK) cells in the CD3+ high group than in the low group within the first-year posttransplant (239 cells/µL vs 338 cells/µL, P = 0.0003). No differences in engraftment, chronic GvHD (cGvHD), relapse rate, transplant-related mortality (TRM), and overall survival (OS) were identified between the two groups. In conclusion, our study found that a high CD3+ T cell dose led to a high risk of aGvHD and inferior reconstitution of NK cells in the haploPBSCT setting. In the future, carefully manipulating the composition of lymphocyte subsets of grafts might reduce the risk of aGvHD and improve the transplant outcome.


Assuntos
Doença Enxerto-Hospedeiro , Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Transplante de Células-Tronco de Sangue Periférico , Humanos , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Estudos Retrospectivos , Recidiva Local de Neoplasia , Doença Enxerto-Hospedeiro/etiologia , Subpopulações de Linfócitos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Condicionamento Pré-Transplante
19.
Int J Biol Macromol ; 238: 124123, 2023 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-36963550

RESUMO

Recurrent infection of chronic wounds remains a major clinical challenge. Recently, the hydrogel antibacterial materials have attracted extensive attention for preventing infection in wound healing. In this study, a hybrid hydrogel made of polyvinyl alcohol - iodine (PAI), sodium carboxymethyl cellulose (CMC), and carbamino quantum dot (CQDs) was prepared by the cross-linking of hydrogen bonds, named as polyvinyl alcohol­iodine/sodium carboxymethyl cellulose/carbon quantum dots (PAI/CMC/CQDs). The composite hydrogels exhibited the outstanding photothermal conversion efficiency with near infrared (NIR) light irradiation, and the high antibacterial activity against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). Meanwhile, the elevated temperature of the composite hydrogels up to ∼45 °C was able to stimulate the migration of epidermal cell to accelerate skin repair. Given that PAI and CQDs could respond to different pH values (5-8), the real-time would pH information was provided by the visible light and fluorescent light dual monitoring system by naked eye. Moreover, the visible-fluorescent images could be collected and transformed into RGB signals to quantify the would pH levels, avoiding secondary injuries caused by frequent dressing changes. PAI/CMC/CQDs was demonstrated the significant therapeutic effect on chronic wounds by eliminating bacterial infections and promoting skin repair under the smart RGB monitoring system.


Assuntos
Carboximetilcelulose Sódica , Iodo , Carboximetilcelulose Sódica/farmacologia , Escherichia coli , Álcool de Polivinil , Staphylococcus aureus , Antibacterianos/farmacologia , Bandagens , Corantes , Hidrogéis/farmacologia , Iodo/farmacologia , Sódio , Concentração de Íons de Hidrogênio
20.
Poult Sci ; 102(5): 102389, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36913753

RESUMO

This study aims to determine the effects of normal and angel wing on morphological and histological characteristics of white Roman geese. Angel wing is a torsion of a wing at the carpometacarpus all the way down to the end, stretching outward away from the body lateral. In this study, 30 geese were raised for observing the whole appearance, including stretched wings and morphologies of defeathered wings at 14 wk old. A group of 30 goslings was raised to observe the feature of conformation development of wing bones from 4 to 8 wk old by X-ray photography. The results show that normal wing on angles of the metacarpals and radioulnar bones has a trend greater than the angel wing group (P = 0.927) at the age of 10 wk. According to 64-slice images of computerized tomography scanner on a group of 10-wk-old geese, the interstice at the carpus joint of the angel wing was larger than that of the normal wing. The slight to moderate dilated space of the carpometacarpal joint was found in the angel wing group. In conclusion, the angel wing is torqued outward away from the body laterals at the carpometacarpus and has a slight to moderate dilated space in the carpometacarpal joint. The normal wing geese exhibited an angel that is 9.24% greater than those of angel wing geese at the age of 14 wk (130 vs. 118.5°).


Assuntos
Galinhas , Gansos , Animais , Gansos/anatomia & histologia , Asas de Animais
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