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1.
Theranostics ; 14(8): 3193-3212, 2024.
Article En | MEDLINE | ID: mdl-38855185

As a developing radiation treatment for tumors, neutron capture therapy (NCT) has less side effects and a higher efficacy than conventional radiation therapy. Drugs with specific isotopes are indispensable counterparts of NCT, as they are the indespensable part of the neutron capture reaction. Since the creation of the first and second generations of boron-containing reagents, NCT has significantly advanced. Notwithstanding, the extant NCT medications, predominantly comprised of small molecule boron medicines, have encountered challenges such monofunctionality, inadequate targeting of tumors, and hypermetabolism. There is an urgent need to promote the research and development of new types of NCT drugs. Bio-nanomaterials can be introduced into the realm of NCT, and nanotechnology can give conventional medications richer functionality and significant adaptability. This can complement the advantages of each other and is expected to develop more new drugs with less toxicity, low side effects, better tumor targeting, and high biocompatibility. In this review, we summarized the research progress of nano-drugs in NCT based on the different types and sources of isotopes used, and introduced the attempts and efforts made by relevant researchers in combining nanomaterials with NCT, hoping to provide pivotal references for promoting the development of the field of tumor radiotherapy.


Neoplasms , Humans , Neoplasms/radiotherapy , Neoplasms/drug therapy , Animals , Neutron Capture Therapy/methods , Nanoparticles/chemistry , Nanostructures/therapeutic use , Nanostructures/chemistry , Nanotechnology/methods , Boron Neutron Capture Therapy/methods , Boron Compounds/therapeutic use , Boron Compounds/chemistry , Boron Compounds/pharmacology
2.
Opt Express ; 32(12): 20571-20588, 2024 Jun 03.
Article En | MEDLINE | ID: mdl-38859436

Frequency-scanning interferometry (FSI) utilizing external cavity diode lasers (ECDL) stands out as a potent technique for absolute distance measurement. Nevertheless, the inherent scanning nonlinearity of ECDL and phase noise pose a challenge, as it can compromise the accuracy of phase extraction from interference signals, thereby reducing the measurement accuracy of FSI. In this study, we propose a composite algorithm aimed at mitigating non-orthogonal errors by integrating the least-squares and Heydemann correction technique. Furthermore, we employ Kalman filtering for precise phase tracking. We introduce a parameter selection strategy based on the statistical distribution of instantaneous frequency to achieve the fusion estimation of phase observation values and theoretical models, which starts a new perspective for the application of multi-dimensional data fusion in FSI measurement. Through simulation and experimental validation, the efficacy of this approach is confirmed. The experimental results show promising outcomes: with an average phase error of 0.12%, a standard deviation of less than 1.7 µm in absolute distance measurement, and an average positioning accuracy error of 0.29 µm.

3.
Int J Biol Macromol ; 272(Pt 1): 132779, 2024 Jun.
Article En | MEDLINE | ID: mdl-38825268

The effects of high-resistant starch (RS) content rice flour, psyllium husk powder (PHP), and psyllium powder (PP) on the edible quality and starch digestibility of rice noodles were investigated in this study. High-RS rice noodles showed lower digestibility but poor edible quality. With the addition of PHP and PP, high-RS rice noodles' cooking and texture quality were improved significantly, especially the breakage rates, cooking losses, and chewiness (P < 0.05). Compared to traditional white rice noodle's estimated glycemic index (eGI) of 86.69, the eGI values for 5PHP-RN and 5PHP-2PP-RN were significantly decreased to 66.74 and 65.77, achieving a medium GI status (P < 0.05). This resulted from the high amylose and lipid content in the modified rice flour and psyllium, leading to increase of starch crystallinity. Besides, based on the analysis of Pearson's correlation, it can be found that PHP rich in insoluble dietary fiber (IDF) could improve high-RS noodle cooking and texture quality better, while PP rich in soluble dietary fiber (SDF) can further reduce the RDS content and its starch digestibility. Therefore, utilizing modified rice flour with an appropriate addition of PHP and PP can be considered an effective strategy for producing superior-quality lower glycemic index rice noodles.


Dietary Fiber , Flour , Oryza , Psyllium , Starch , Oryza/chemistry , Psyllium/chemistry , Flour/analysis , Starch/chemistry , Dietary Fiber/analysis , Glycemic Index , Cooking/methods , Amylose/analysis , Amylose/chemistry , Resistant Starch/analysis
4.
Gut Microbes ; 16(1): 2367342, 2024.
Article En | MEDLINE | ID: mdl-38889450

Alcohol-related liver disease (ALD) is recognized as a global health crisis, contributing to approximately 20% of liver cancer-associated fatalities. Dysbiosis of the gut microbiome is associated with the development of ALD, with the gut microbial metabolite urolithin A (UA) exhibiting a potential for alleviating liver symptoms. However, the protective efficacy of UA against ALD and its underlying mechanism mediated by microbiota remain elusive. In this study, we provide evidence demonstrating that UA effectively ameliorates alcohol-induced metabolic disorders and hepatic endoplasmic reticulum (ER) stress through a specific gut-microbiota-liver axis mediated by major urinary protein 1 (MUP1). Moreover, UA exhibited the potential to restore alcohol-induced dysbiosis of the intestinal microbiota by enriching the abundance of Bacteroides sartorii (B. sartorii), Parabacteroides distasonis (P. distasonis), and Akkermansia muciniphila (A. muciniphila), along with their derived metabolite propionic acid. Partial attenuation of the hepatoprotective effects exerted by UA was observed upon depletion of gut microbiota using antibiotics. Subsequently, a fecal microbiota transplantation (FMT) experiment was conducted to evaluate the microbiota-dependent effects of UA in ALD. FMT derived from mice treated with UA exhibited comparable efficacy to direct UA treatment, as it effectively attenuated ER stress through modulation of MUP1. It was noteworthy that strong associations were observed among the hepatic MUP1, gut microbiome, and metabolome profiles affected by UA. Intriguingly, oral administration of UA-enriched B. sartorii, P. distasonis, and A. muciniphila can enhance propionic acid production to effectively suppress ER stress via MUP1, mimicking UA treatment. Collectively, these findings elucidate the causal mechanism that UA alleviated ALD through the gut-microbiota-liver axis. This unique mechanism sheds light on developing novel microbiome-targeted therapeutic strategies against ALD.


Coumarins , Endoplasmic Reticulum Stress , Gastrointestinal Microbiome , Liver Diseases, Alcoholic , Liver , Mice, Inbred C57BL , Gastrointestinal Microbiome/drug effects , Animals , Mice , Liver/metabolism , Liver/drug effects , Liver Diseases, Alcoholic/microbiology , Liver Diseases, Alcoholic/metabolism , Liver Diseases, Alcoholic/prevention & control , Male , Endoplasmic Reticulum Stress/drug effects , Coumarins/pharmacology , Coumarins/metabolism , Dysbiosis/microbiology , Humans , Bacteria/metabolism , Bacteria/classification , Bacteria/genetics , Bacteria/isolation & purification
5.
Br J Cancer ; 2024 Jun 04.
Article En | MEDLINE | ID: mdl-38834745

BACKGROUND: Diffuse invasion remains a primary cause of treatment failure in pediatric high-grade glioma (pHGG). Identifying cellular driver(s) of pHGG invasion is needed for anti-invasion therapies. METHODS: Ten highly invasive patient-derived orthotopic xenograft (PDOX) models of pHGG were subjected to isolation of matching pairs of invasive (HGGINV) and tumor core (HGGTC) cells. RESULTS: pHGGINV cells were intrinsically more invasive than their matching pHGGTC cells. CSC profiling revealed co-positivity of CD133 and CD57 and identified CD57+CD133- cells as the most abundant CSCs in the invasive front. In addition to discovering a new order of self-renewal capacities, i.e., CD57+CD133- > CD57+CD133+ > CD57-CD133+ > CD57-CD133- cells, we showed that CSC hierarchy was impacted by their spatial locations, and the highest self-renewal capacities were found in CD57+CD133- cells in the HGGINV front (HGGINV/CD57+CD133- cells) mediated by NANOG and SHH over-expression. Direct implantation of CD57+ (CD57+/CD133- and CD57+/CD133+) cells into mouse brains reconstituted diffusely invasion, while depleting CD57+ cells (i.e., CD57-CD133+) abrogated pHGG invasion. CONCLUSION: We revealed significantly increased invasive capacities in HGGINV cells, confirmed CD57 as a novel glioma stem cell marker, identified CD57+CD133- and CD57+CD133+ cells as a new cellular driver of pHGG invasion and suggested a new dual-mode hierarchy of HGG stem cells.

6.
Front Nutr ; 11: 1371691, 2024.
Article En | MEDLINE | ID: mdl-38835960

Chondroitin sulfate (CS) is a sulfated linear polysaccharide with different functional activities, including antioxidant, anti-inflammatory, lipid-lowering, and immune regulation. As natural sulfated polysaccharides have high molecular weight, high apparent viscosity, low water solubility, complex structure, and high negative charge, they have difficulty binding to receptors within cells across tissue barriers, resulting in low bioavailability and unclear structure-activity relationships. In this study, an H2O2-Vc oxidative degradation system was employed to perform environmentally friendly and controllable degradation of CS extracted from the nasal cartilage of Shaanxi Yellow cattle. Two low-molecular-weight chondroitin sulfates (LMWCSs), CS-1 (14.8 kDa) and CS-2 (50.9 kDa), that exhibit strong in vitro free radical scavenging ability were obtained, and their structures were characterized. Mice intraperitoneally administered lipopolysaccharide (LPS) were used to explore the cognitive intervention effects of LMWCS. Supplementing CS-1 and CS-2 significantly downregulated the levels of the serum inflammatory factors, TNF-α and IL-1ß, promoted the expression of GSH in the brain, and inhibited the production of the lipid peroxidation product, malondialdehyde (MDA), ultimately inhibiting LPS-induced cognitive impairment in mice. Surprisingly, compared to the LPS model group, the abundances of Streptococcus, Eisenbergiella, Vampirovibrio, Coprococcus, Enterococcus and Lachnoanaerobaculum were significantly increased in the intestines of mice in the CS-1 and CS-2 group, whereas those of Parabacteroides and Mycoplasma were significantly decreased. Altogether, this study provides a theoretical basis for the comprehensive utilization of agricultural and animal resources and the application of brain nutrition, anti-inflammatory, and LMWCS health products.

7.
J Control Release ; 371: 470-483, 2024 Jun 10.
Article En | MEDLINE | ID: mdl-38849094

Hypoimmunogenicity and the immunosuppressive microenvironment of ovarian cancer severely restrict the capability of immune-mediated tumor killing. Immunogenic cell death (ICD) introduces a theoretical principle for antitumor immunity by increasing antigen exposure and presentation. Despite recent research progress, the currently available ICD inducers are still very limited, and many of them can hardly induce sufficient ICD based on traditional endoplasmic reticulum (ER) stress. Accumulating evidence indicates that inducing mitochondrial stress usually shows a higher efficiency in evoking large-scale ICD than that via ER stress. Inspired by this, herein, a mitochondria-targeted polyprodrug nanoparticle (named Mito-CMPN) serves as a much superior ICD inducer, effectively inducing chemo-photodynamic therapy-caused mitochondrial stress in tumor cells. The rationally designed stimuli-responsive polyprodrugs, which can self-assemble into nanoparticles, were functionalized with rhodamine B for mitochondrial targeting, cisplatin and mitoxantrone (MTO) for synergistic chemo-immunotherapy, and MTO also serves as a photosensitizer for photodynamic immunotherapy. The effectiveness and robustness of Mito-CMPNs in reversing the immunosuppressive microenvironment is verified in both an ovarian cancer subcutaneous model and a high-grade serous ovarian cancer model. Our results support that the induction of abundant ICD by focused mitochondrial stress is a highly effective strategy to improve the therapeutic efficacy of immunosuppressive ovarian cancer.

8.
Biomed Pharmacother ; 176: 116888, 2024 Jul.
Article En | MEDLINE | ID: mdl-38861859

OBJECTIVES: Co-agonists at the glucagon-like peptide-1 and glucagon receptors (GLP1R/GCGR) show promise as treatments for metabolic dysfunction-associated steatotic liver disease (MASLD). Although most co-agonists to date have been heavily GLP1R-biased, glucagon directly acts on the liver to reduce fat content. The aims of this study were to investigate a GCGR-biased co-agonist as treatment for hepatic steatosis in mice. METHODS: Mice with diet-induced obesity (DIO) were treated with Dicretin, a GLP1/GCGR co-agonist with high potency at the GCGR, Semaglutide (GLP1R monoagonist) or food restriction over 24 days, such that their weight loss was matched. Hepatic steatosis, glucose tolerance, hepatic transcriptomics, metabolomics and lipidomics at the end of the study were compared with Vehicle-treated mice. RESULTS: Dicretin lead to superior reduction of hepatic lipid content when compared to Semaglutide or equivalent weight loss by calorie restriction. Markers of glucose tolerance and insulin resistance improved in all treatment groups. Hepatic transcriptomic and metabolomic profiling demonstrated many changes that were unique to Dicretin-treated mice. These include some known targets of glucagon signaling and others with as yet unclear physiological significance. CONCLUSIONS: Our study supports the development of GCGR-biased GLP1/GCGR co-agonists for treatment of MASLD and related conditions.


Fatty Liver , Glucagon-Like Peptide 1 , Mice, Inbred C57BL , Obesity , Receptors, Glucagon , Weight Loss , Animals , Obesity/drug therapy , Obesity/metabolism , Weight Loss/drug effects , Receptors, Glucagon/agonists , Receptors, Glucagon/metabolism , Male , Fatty Liver/drug therapy , Fatty Liver/metabolism , Mice , Glucagon-Like Peptide 1/metabolism , Diet, High-Fat/adverse effects , Liver/metabolism , Liver/drug effects , Glucagon-Like Peptide-1 Receptor/agonists , Glucagon-Like Peptide-1 Receptor/metabolism , Insulin Resistance , Glucagon-Like Peptides/pharmacology
9.
J Hazard Mater ; 472: 134487, 2024 Jul 05.
Article En | MEDLINE | ID: mdl-38704906

Atmospheric pressure dielectric barrier discharge (DBD) plasma is an emerging and promising technique for air disinfection in public environments. Power supply is a crucial factor but it remains unclear about its impacts on the air disinfection performance of plasmas. In this work, a nanosecond (ns) pulsed power supply was applied to drive an in-duct grating-like DBD array to achieve fast single-pass air disinfection. The influence of pulse parameters and environmental factors on both the discharge characteristics and the single-pass bacterial inactivation efficiency were uncovered. At a close relative humidity (RH) level, the efficiency was dominated by the discharge power, namely, specific input energy could serve as the disinfection dose. A higher frequency, shorter pulse rising time, and suitable pulse width are preferred to obtain a higher Z value. The pulsed source was not notably superior to an alternating current source, or even worse at a low voltage frequency at the same discharge power. Airflow humidity was a predominant factor to improve the efficiency and a single-pass efficiency of ∼ 99% and a Z value of 2.2 L/J were achieved under an optimal RH of 50%-60%. This work provides fundamental knowledge of ns-pulsed DBD on discharge characteristics and air disinfection behaviors.

11.
Small Methods ; : e2301755, 2024 May 08.
Article En | MEDLINE | ID: mdl-38716608

Nanocomposites combining inorganic nanoparticles with high dielectric constant and polymers with high breakdown strength are promising for the high energy density storage of electricity, and carrier traps can significantly affect the dielectric breakdown process. Nevertheless, there still lacks direct experimental evidence on how nanoparticles affect the trap characteristics of nanocomposites, especially in a spatially resolved manner. Here, a technique is developed to image the trap distribution based on sequential Kelvin probe force microscopy (KPFM) in combination with the isothermal surface potential decay (ISPD) technique, wherein both shallow and deep trap densities and the corresponding energy levels can be mapped with nanoscale resolution. The technique is first validated using the widely-used commercial biaxially oriented polypropylene, yielding consistent results with macroscopic ISPD. The technique is then applied to investigate polyvinylidene fluoride-based nanocomposites filled with barium titanate nanoparticles, revealing higher deep trap density around surface-modified nanoparticles, which correlates well with its increased breakdown strength. This technique thus provides a powerful spatially resolved tool for understanding the microscopic mechanism of dielectric breakdown of nanocomposites.

12.
Sci Rep ; 14(1): 10595, 2024 05 08.
Article En | MEDLINE | ID: mdl-38719908

Delayed diagnosis in patients with pulmonary tuberculosis (PTB) often leads to serious public health problems. High throughput sequencing was used to determine the expression levels of lncRNAs, mRNAs, and miRNAs in the lesions and adjacent health lung tissues of patients with PTB. Their differential expression profiles between the two groups were compared, and 146 DElncRs, 447 DEmRs, and 29 DEmiRs were obtained between lesions and adjacent health tissues in patients with PTB. Enrichment analysis for mRNAs showed that they were mainly involved in Th1, Th2, and Th17 cell differentiation. The lncRNAs, mRNAs with target relationship with miRNAs were predicted respectively, and correlation analysis was performed. The ceRNA regulatory network was obtained by comparing with the differentially expressed transcripts (DElncRs, DEmRs, DEmiRs), then 2 lncRNAs mediated ceRNA networks were established. The expression of genes within the network was verified by quantitative real-time PCR (qRT-PCR). Flow cytometric analysis revealed that the proportion of Th1 cells and Th17 cells was lower in PTB than in controls, while the proportion of Th2 cells increased. Our results provide rich transcriptome data for a deeper investigation of PTB. The ceRNA regulatory network we obtained may be instructive for the diagnosis and treatment of PTB.


Gene Regulatory Networks , MicroRNAs , RNA, Long Noncoding , RNA, Messenger , Tuberculosis, Pulmonary , Humans , Tuberculosis, Pulmonary/genetics , RNA, Long Noncoding/genetics , MicroRNAs/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , Gene Expression Profiling , Transcriptome , Th17 Cells/immunology , Th17 Cells/metabolism , Female , Male , Adult , Middle Aged , Gene Expression Regulation , Lung/pathology , Lung/metabolism , RNA, Competitive Endogenous
13.
Transl Oncol ; 45: 101988, 2024 Jul.
Article En | MEDLINE | ID: mdl-38733642

Radiation is one of the standard therapies for pediatric high-grade glioma (pHGG), of which the prognosis remains poor. To gain an in-depth understanding of biological consequences beyond the classic DNA damage, we treated 9 patient-derived orthotopic xenograft (PDOX) models, including one with DNA mismatch repair (MMR) deficiency, with fractionated radiations (2 Gy/day x 5 days). Extension of survival time was noted in 5 PDOX models (P < 0.05) accompanied by γH2AX positivity in >95 % tumor cells in tumor core and >85 % in the invasive foci as well as ∼30 % apoptotic and mitotic catastrophic cell death. The model with DNA MMR (IC-1406HGG) was the most responsive to radiation with a reduction of Ki-67(+) cells. Altered metabolism, including mitochondria number elevation, COX IV activation and reactive oxygen species accumulation, were detected together with the enrichment of CD133+ tumor cells. The latter was caused by the entry of quiescent G0 cells into cell cycle and the activation of self-renewal (SOX2 and BMI1) and epithelial mesenchymal transition (fibronectin) genes. These novel insights about the cellular and molecular mechanisms of fractionated radiation in vivo should support the development of new radio-sensitizing therapies.

14.
Cancers (Basel) ; 16(9)2024 Apr 28.
Article En | MEDLINE | ID: mdl-38730671

Background: Despite multimodality therapies, the prognosis of patients with malignant brain tumors remains extremely poor. One of the major obstacles that hinders development of effective therapies is the limited availability of clinically relevant and biologically accurate (CRBA) mouse models. Methods: We have developed a freehand surgical technique that allows for rapid and safe injection of fresh human brain tumor specimens directly into the matching locations (cerebrum, cerebellum, or brainstem) in the brains of SCID mice. Results: Using this technique, we successfully developed 188 PDOX models from 408 brain tumor patient samples (both high-and low-grade) with a success rate of 72.3% in high-grade glioma, 64.2% in medulloblastoma, 50% in ATRT, 33.8% in ependymoma, and 11.6% in low-grade gliomas. Detailed characterization confirmed their replication of the histopathological and genetic abnormalities of the original patient tumors. Conclusions: The protocol is easy to follow, without a sterotactic frame, in order to generate large cohorts of tumor-bearing mice to meet the needs of biological studies and preclinical drug testing.

15.
Genes (Basel) ; 15(5)2024 04 25.
Article En | MEDLINE | ID: mdl-38790174

Black spot, caused by Alternaria brassicicola (Ab), poses a serious threat to crucifer production, and knowledge of how plants respond to Ab infection is essential for black spot management. In the current study, combined transcriptomic and metabolic analysis was employed to investigate the response to Ab infection in two cabbage (Brassica oleracea var. capitata) genotypes, Bo257 (resistant to Ab) and Bo190 (susceptible to Ab). A total of 1100 and 7490 differentially expressed genes were identified in Bo257 (R_mock vs. R_Ab) and Bo190 (S_mock vs. S_Ab), respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that "metabolic pathways", "biosynthesis of secondary metabolites", and "glucosinolate biosynthesis" were the top three enriched KEGG pathways in Bo257, while "metabolic pathways", "biosynthesis of secondary metabolites", and "carbon metabolism" were the top three enriched KEGG pathways in Bo190. Further analysis showed that genes involved in extracellular reactive oxygen species (ROS) production, jasmonic acid signaling pathway, and indolic glucosinolate biosynthesis pathway were differentially expressed in response to Ab infection. Notably, when infected with Ab, genes involved in extracellular ROS production were largely unchanged in Bo257, whereas most of these genes were upregulated in Bo190. Metabolic profiling revealed 24 and 56 differentially accumulated metabolites in Bo257 and Bo190, respectively, with the majority being primary metabolites. Further analysis revealed that dramatic accumulation of succinate was observed in Bo257 and Bo190, which may provide energy for resistance responses against Ab infection via the tricarboxylic acid cycle pathway. Collectively, this study provides comprehensive insights into the Ab-cabbage interactions and helps uncover targets for breeding Ab-resistant varieties in cabbage.


Alternaria , Brassica , Gene Expression Regulation, Plant , Metabolome , Plant Diseases , Transcriptome , Alternaria/pathogenicity , Alternaria/genetics , Brassica/microbiology , Brassica/genetics , Brassica/metabolism , Plant Diseases/microbiology , Plant Diseases/genetics , Transcriptome/genetics , Metabolome/genetics , Disease Resistance/genetics , Metabolic Networks and Pathways/genetics , Gene Expression Profiling/methods , Plant Proteins/genetics , Plant Proteins/metabolism
16.
Comput Biol Med ; 177: 108660, 2024 Jul.
Article En | MEDLINE | ID: mdl-38820774

Omics-based technologies have revolutionized our comprehension of microproteins encoded by ncRNAs, revealing their abundant presence and pivotal roles within complex functional landscapes. Here, we developed MicroProteinDB (http://bio-bigdata.hrbmu.edu.cn/MicroProteinDB), which offers and visualizes the extensive knowledge to aid retrieval and analysis of computationally predicted and experimentally validated microproteins originating from various ncRNA types. Employing prediction algorithms grounded in diverse deep learning approaches, MicroProteinDB comprehensively documents the fundamental physicochemical properties, secondary and tertiary structures, interactions with functional proteins, family domains, and inter-species conservation of microproteins. With five major analytical modules, it will serve as a valuable knowledge for investigating ncRNA-derived microproteins.


Databases, Protein , RNA, Untranslated , RNA, Untranslated/chemistry , RNA, Untranslated/genetics , Humans , Proteins/chemistry , Animals , Micropeptides
17.
Stem Cell Res Ther ; 15(1): 153, 2024 May 31.
Article En | MEDLINE | ID: mdl-38816870

BACKGROUND: The therapeutic status of allogeneic stem cell transplantation (allo-SCT) as a post-remission treatment for patients with high-risk acute myeloid leukemia (AML) was well-accepted. However, the optimal treatment for patients with low/favorable- or intermediate-risk AML who achieve complete remission has remained controversial. Therefore, we conducted a network meta-analysis to discuss this disputed problem. METHODS: We compared the effects of treatment strategies including allo-SCT, autologous stem cell transplantation (auto-SCT) and consolidation chemotherapy (CT) for patients with low/favorable- or intermediate-risk AML. The pooled HRs and 95% CIs for overall survival and disease-free survival were estimated with Stata12 and R software. Thirty clinical studies with 6682 patients were included in the meta-analysis. RESULTS: The results indicated that the treatment outcome of allo-SCT was the best, followed by auto-SCT, and CT was likely the worst in the total AML patients. In patients with low/favorable-risk AML, the treatment outcome of auto-SCT was likely ranked first, followed by allo-SCT, and CT was the worst. In patients with intermediate-risk AML, the treatment outcome of haploidentical stem cell transplantation (haplo-SCT) was the best, followed by allo-SCT (excluding haplo-SCT), and auto-SCT and CT were the worst. However, the median age of the haplo-SCT group was much younger than that of the control group, which may be one of the reasons for the better prognosis of the haplo-SCT group. CONCLUSIONS: Patients with low/favorable- and intermediate-risk (non-high-risk) AML should prioritize allo-SCT if they are eligible for transplantation, and auto-SCT is optional. However, in the subgroup analysis, auto-SCT was the optimal treatment choice for patients with low/favorable-risk AML, and allo-SCT was the priority selection for patients with intermediate-risk AML, especially young patients. These findings could provide references for clinical practice.


Leukemia, Myeloid, Acute , Humans , Leukemia, Myeloid, Acute/therapy , Leukemia, Myeloid, Acute/mortality , Hematopoietic Stem Cell Transplantation/methods , Transplantation, Homologous , Transplantation, Autologous , Stem Cell Transplantation , Disease-Free Survival , Network Meta-Analysis , Treatment Outcome , Male
18.
Biochem Pharmacol ; 225: 116282, 2024 Jul.
Article En | MEDLINE | ID: mdl-38762147

IPF is a chronic, progressive, interstitial lung disease with high mortality. Current drugs have limited efficacy in curbing disease progression and improving quality of life. Selpercatinib, a highly selective inhibitor of receptor tyrosine kinase RET (rearranged during transfection), was approved in 2020 for the treatment of a variety of solid tumors with RET mutations. In this study, the action and mechanism of Selpercatinib in pulmonary fibrosis were evaluated in vivo and in vitro. In vivo experiments demonstrated that Selpercatinib significantly ameliorated bleomycin (BLM)-induced pulmonary fibrosis in mice. In vitro, Selpercatinib inhibited the proliferation, migration, activation and extracellular matrix deposition of fibroblasts by inhibiting TGF-ß1/Smad and TGF-ß1/non-Smad pathway, and suppressed epithelial-mesenchymal transition (EMT) like process of lung epithelial cells via inhibiting TGF-ß1/Smad pathway. The results of in vivo pharmacological tests corroborated the results obtained from the in vitro experiments. Further studies revealed that Selpercatinib inhibited abnormal phenotypes of lung fibroblasts and epithelial cells in part by regulating its target RET. In short, Selpercatinib inhibited the activation of fibroblasts and EMT-like process of lung epithelial cells by inhibiting TGF-ß1/Smad and TGF-ß1/non-Smad pathways, thus alleviating BLM-induced pulmonary fibrosis in mice.


Bleomycin , Mice, Inbred C57BL , Pulmonary Fibrosis , Signal Transduction , Transforming Growth Factor beta1 , Animals , Bleomycin/toxicity , Transforming Growth Factor beta1/metabolism , Mice , Signal Transduction/drug effects , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/drug therapy , Pulmonary Fibrosis/metabolism , Pulmonary Fibrosis/pathology , Pulmonary Fibrosis/prevention & control , Male , Pyrazoles/pharmacology , Pyrazoles/therapeutic use , Pyridines/pharmacology , Epithelial-Mesenchymal Transition/drug effects , Humans , Fibroblasts/drug effects , Fibroblasts/metabolism
19.
J Acoust Soc Am ; 155(4): 2517-2537, 2024 Apr 01.
Article En | MEDLINE | ID: mdl-38591940

The shear stress transport turbulence model is employed to conduct a detailed study of flow characteristics at the highest efficiency point and near-stall point in a full-channel 1.5-stage compressor in this paper. The simulation results for the compressor's total pressure ratio and efficiency exhibit good agreement with experimental data. Emphasis is placed on examining the internal flow structure in the tip area of the compressor rotor under near-stall conditions. The results reveal that significant differences in flow structure primarily occur in the tip area as the compressor approaches stall. Specifically, a reduction in turbulent kinetic energy is observed in a region spanning approximately 20%-60% of the chord length on the rotor suction face near-stall conditions. Two additional peak frequencies, at 0.8 and 1.6 times the blade passage frequency, are observed, and the intricate flow phenomena are elaborated at the near-stall point. The near-stall point exhibits greater noise levels than the highest efficiency point, where the intensity of the surface source increases by more than 10 dB, peaking at 20 dB. This additional peak serves as a significant supplementary noise source near the stall point, leading to a maximum increase of 33.3 dB in the free radiated sound power. The acoustic response within the duct indicates that the compressor operating at the near-stall point continues to produce substantial noise on the actual test bench, showing an average increase of 6 dB in noise levels, and the distribution of the additional peak single-tone noise at the entrance significantly differs from that observed at the highest efficiency point.

20.
J Fluoresc ; 2024 Apr 22.
Article En | MEDLINE | ID: mdl-38647962

We have prepared a simple, universal and efficient coumarin-derived fluorescent probe (XDS1) to detecting HOCl. The experimental findings revealed that the introduction of HOCl produced an obvious quenching effect on the probe with high selectivity and sensitivity. The calculated limit of detection (LOD) was as low as 0.02 µM. Furthermore, an impressive response time of less than 10 s was observed when XDS1 detecting HOCl. Importantly, the probe XDS1 exhibited negligible cytotoxicity, thereby facilitating its application for imaging HOCl within biological environment. The probe XDS1 had been successfully used for specific detection in cells.

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