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1.
RSC Adv ; 14(29): 20604-20608, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38946766

ABSTRACT

Precise control of the size and morphology of metal-organic framework (MOF) crystals is challenging yet critical for the expansion of the application potential of MOF materials. This work presents a detailed investigation of the impact of various synthetic conditions such as reactant ratio, acidity, capping agent, reaction solution (H2O, ethanol and DMF) etc. on the size and morphology of Mg-MOF-74, a classical MOF with record high CO2 uptake capacity. By varying these fabrication parameters and modulators, the morphology and size of crystals can be precisely tuned in the nanometer to micrometer range. Particularly, the nanosized flaky Mg-MOF-74 crystals with an aspect ratio of ∼0.5 were synthesized for the first time by varying the amount of water. The MOF-74 crystals with different size and morphologies are good candidates for more advanced applications favored by crystal size and morphology control.

2.
Asian J Androl ; 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38978290

ABSTRACT

ABSTRACT: Compounds isolated from Epimedium include the total flavonoids of Epimedium, icariin, and its metabolites (icaritin, icariside I, and icariside II), which have similar molecular structures. Modern pharmacological research and clinical practice have proved that Epimedium and its active components have a wide range of pharmacological effects, especially in improving sexual function, hormone regulation, anti-osteoporosis, immune function regulation, anti-oxidation, and anti-tumor activity. To date, we still need a comprehensive source of knowledge about the pharmacological effects of Epimedium and its bioactive compounds on the male reproductive system. However, their actions in other tissues have been reviewed in recent years. This review critically focuses on the Epimedium, its bioactive compounds, and the biochemical and molecular mechanisms that modulate vital pathways associated with the male reproductive system. Such intrinsic knowledge will significantly further studies on the Epimedium and its bioactive compounds that protect the male reproductive system and provide some guidances for clinical treatment of related male reproductive disorders.

3.
Int J Chron Obstruct Pulmon Dis ; 19: 1491-1513, 2024.
Article in English | MEDLINE | ID: mdl-38957709

ABSTRACT

Background: Chronic obstructive pulmonary disease (COPD) stands as a predominant cause of global morbidity and mortality. This study aims to elucidate the relationship between pyroptosis-related genes (PRGs) and COPD diagnosis in the context of immune infiltration, ultimately proposing a PRG-based diagnostic model for predicting COPD outcomes. Methods: Clinical data and PRGs of COPD patients were sourced from the GEO database. The "ConsensusClusterPlus" package was employed to generate molecular subtypes derived from PRGs that were identified through differential expression analysis and LASSO Cox analysis. A diagnostic signature including eight genes (CASP4, CASP5, ELANE, GPX4, NLRP1, GSDME, NOD1and IL18) was also constructed. Immune cell infiltration calculated by the ESTIMATE score, Stroma scores and Immune scores were also compared on the basis of pyroptosis-related molecular subtypes and the risk signature. We finally used qRT - PCR to detect the expression levels of eight genes in COPD patient and normal. Results: The diagnostic model, anchored on eight PRGs, underwent validation with an independent experimental cohort. The area under the receiver operating characteristic (ROC) curves (AUC) for the diagnostic model showcased values of 0.809, 0.765, and 0.956 for the GSE76925, GSE8545, and GSE5058 datasets, respectively. Distinct expression patterns and clinical attributes of PRGs were observed between the comparative groups, with functional analysis underscoring a disparity in immune-related functions between them. Conclusion: In this study, we developed a potential as diagnostic biomarkers for COPD and have a significant role in modulating the immune response. Such insights pave the way for novel diagnostic and therapeutic strategies for COPD.


Subject(s)
Databases, Genetic , Predictive Value of Tests , Pulmonary Disease, Chronic Obstructive , Pyroptosis , Humans , Pulmonary Disease, Chronic Obstructive/genetics , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/immunology , Pyroptosis/genetics , Gene Expression Profiling , Lung/immunology , Male , Female , Middle Aged , Genetic Markers , Case-Control Studies , Transcriptome , Aged , Reproducibility of Results , Genetic Predisposition to Disease , Prognosis
4.
Ecotoxicol Environ Saf ; 280: 116538, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38833980

ABSTRACT

Methamphetamine (Meth) is a potent psychostimulant with well-established hepatotoxicity. Gut microbiota-derived short-chain fatty acids (SCFAs) have been reported to yield beneficial effects on the liver. In this study, we aim to further reveal the mechanisms of Meth-induced hepatic injuries and investigate the potential protective effects of SCFAs. Herein, mice were intraperitoneally injected with 15 mg/kg Meth to induce hepatic injuries. The composition of fecal microbiota and SCFAs was profiled using 16 S rRNA sequencing and Gas Chromatography/Mass Spectrometry (GC/MS) analysis, respectively. Subsequently, SCFAs supplementation was performed to evaluate the protective effects against hepatic injuries. Additionally, Sigma-1 receptor knockout (S1R-/-) mice and fluvoxamine (Flu), an agonist of S1R, were introduced to investigate the mechanisms underlying the protective effects of SCFAs. Our results showed that Meth activated S1R and induced hepatic autophagy, inflammation, and oxidative stress by stimulating the MAPK/ERK pathway. Meanwhile, Meth disrupted SCFAs product-related microbiota, leading to a reduction in fecal SCFAs (especially Acetic acid and Propanoic acid). Accompanied by the optimization of gut microbiota, SCFAs supplementation normalized S1R expression and ameliorated Meth-induced hepatic injuries by repressing the MAPK/ERK pathway. Effectively, S1R knockout repressed Meth-induced activation of the MAPK/ERK pathway and further ameliorated hepatic injuries. Finally, the overexpression of S1R stimulated the MAPK/ERK pathway and yielded comparable adverse phenotypes to Meth administration. These findings suggest that Meth-induced hepatic injuries relied on the activation of S1R, which could be alleviated by SCFAs supplementation. Our study confirms the crucial role of S1R in Meth-induced hepatic injuries for the first time and provides a potential preemptive therapy.


Subject(s)
Chemical and Drug Induced Liver Injury , Fatty Acids, Volatile , Gastrointestinal Microbiome , Methamphetamine , Mice, Knockout , Receptors, sigma , Sigma-1 Receptor , Methamphetamine/toxicity , Animals , Receptors, sigma/metabolism , Fatty Acids, Volatile/metabolism , Mice , Gastrointestinal Microbiome/drug effects , Male , Chemical and Drug Induced Liver Injury/prevention & control , Liver/drug effects , Liver/metabolism , Mice, Inbred C57BL , Oxidative Stress/drug effects , Feces/chemistry , Feces/microbiology
5.
Front Microbiol ; 15: 1403478, 2024.
Article in English | MEDLINE | ID: mdl-38939192

ABSTRACT

Introduction: Sodium pheophorbide a (SPA) is a natural plant-derived photosensitizer, with high photoactivated antifungal activity against some phytopathogenic fungi. However, its fungicidal effect on Diaporthe mahothocarpus, a novel pathogen that causes Camellia oleifera leaf spot blight, is unclear. Methods: In the present study, we explored its inhibitory effects on spore germination and mycelial growth of D. mahothocarpus. Then we determined its effects on the cell membrane, mycelial morphology, redox homeostasis, and cell death through bioassay. Finally, RNA-seq was used further to elucidate its mode of action at the transcriptional level. Results: We found that SPA effectively inhibited the growth of D. mahothocarpus, with half-maximal effective concentrations to inhibit mycelial growth and spore germination of 1.059 and 2.287 mg/mL, respectively. After 1.0 mg/mL SPA treatment, the conductivity and malondialdehyde content of D. mahothocarpus were significantly increased. Scanning electron microscopy and transmission electron microscopy indicated that SPA significantly affected the morphology and ultrastructure of D. mahothocarpus hyphae, revealing that SPA can destroy the mycelial morphology and cell structure, especially the cell membrane of D. mahothocarpus. Furthermore, transcriptome analysis revealed that SPA significantly suppressed the expression of genes involved in morphology, cell membrane permeability, and oxidative stress. Then, we also found that SPA significantly promoted the accumulation of reactive oxygen species (ROS) in of D. mahothocarpus, while it decreased the content of reduced glutathione, inhibited the enzyme activities of superoxide dismutase and catalase, and exacerbated DNA damage. Annexin V-FITC/PI staining also confirmed that 1.0 mg/mL SPA could significantly induce apoptosis and necrosis. Discussion: Generally, SPA can induce ROS-mediated oxidative stress and cell death, thus destroying the cell membrane and hyphal morphology, and ultimately inhibiting mycelial growth, which indicates that SPA has multiple modes of action, providing a scientific basis for the use of SPA as an alternative plant-derived photoactivated fungicide against C. oleifera leaf spot blight.

6.
Plant Commun ; : 101002, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38872306

ABSTRACT

Despite considerable advancements in extracting crucial insights from bio-omics data to unravel the intricate mechanisms underlying complex traits, the absence of a universal multimodal computational tool with robust interpretability for accurate phenotype prediction and identification of trait-associated genes remains a challenge. This study introduces the Dual-Extraction Modeling (DEM) approach, a multimodal deep learning architecture designed to extract representative features from heterogeneous omics datasets, enabling the prediction of complex trait phenotypes. Through comprehensive benchmarking experiments, we demonstrate DEM's efficacy in classification and regression prediction of complex traits. DEM consistently exhibits superior accuracy, robustness, generalizability, and flexibility. Notably, we establish its effectiveness in predicting pleiotropic genes influencing both flowering time and rosette leaf number, underscoring its commendable interpretability. Additionally, user-friendly software has been developed to facilitate the seamless utilization of DEM's functions. In summary, this study presents a state-of-the-art approach with the capability to effectively predict qualitative and quantitative traits, as well as identify functional genes, affirming its potential as a valuable tool in exploring the genetic basis of complex traits. Source code and software of DEM are available at https://github.com/cma2015/DEM/.

7.
Sci Total Environ ; 935: 173285, 2024 Jul 20.
Article in English | MEDLINE | ID: mdl-38772488

ABSTRACT

Dietary pollution of Aflatoxin B1 (AFB1) poses a great threat to global food safety, which can result in serious hepatic injuries. Following the widespread use of plastic tableware, co-exposure to microplastics and AFB1 has dramatically increased. However, whether microplastics could exert synergistic effects with AFB1 and amplify its hepatotoxicity, and the underlying mechanisms are still unelucidated. Here, mice were orally exposed to 100 nm polystyrene nanoplastics (NPs) and AFB1 to investigate the influences of NPs on AFB1-induced hepatic injuries. We found that exposure to only NPs or AFB1 resulted in colonic inflammation and the impairment of the intestinal barrier, which was exacerbated by combined exposure to NPs and AFB1. Meanwhile, co-exposure to NPs exacerbated AFB1-induced dysbiosis of gut microbiota and remodeling of the fecal metabolome. Moreover, NPs and AFB1 co-exposure exhibited higher levels of systemic inflammatory factors compared to AFB1 exposure. Additionally, NPs co-exposure further exacerbated AFB1-induced hepatic fibrosis and inflammation, which could be associated with the overactivation of the TLR4/MyD88/NF-κB pathway. Notably, Spearman's correlation analysis revealed that the exacerbation of NPs co-exposure was closely associated with microbial dysbiosis. Furthermore, microbiota from NPs-exposed mice (NPsFMT) partly reproduced the exacerbation of NPs on AFB1-induced systemic and hepatic inflammation, but not fibrosis. In summary, our findings indicate that gut microbiota could be involved in the exacerbation of NPs on AFB1-induced hepatic injuries, highlighting the health risks of NPs.


Subject(s)
Aflatoxin B1 , Gastrointestinal Microbiome , Liver , Microplastics , Polystyrenes , Aflatoxin B1/toxicity , Animals , Mice , Gastrointestinal Microbiome/drug effects , Polystyrenes/toxicity , Microplastics/toxicity , Liver/drug effects , Chemical and Drug Induced Liver Injury , Dysbiosis/chemically induced , Nanoparticles/toxicity
8.
Front Genet ; 15: 1385293, 2024.
Article in English | MEDLINE | ID: mdl-38818040

ABSTRACT

Background: Varicose veins (VV) are a common chronic venous disease that is influenced by multiple factors. It affects the quality of life of patients and imposes a huge economic burden on the healthcare system. This study aimed to use integrated analysis methods, including Mendelian randomization analysis, to identify potential pathogenic genes and drug targets for VV treatment. Methods: This study conducted Summary-data-based Mendelian Randomization (SMR) analysis and colocalization analysis on data collected from genome-wide association studies and cis-expression quantitative trait loci databases. Only genes with PP.H4 > 0.7 in colocalization were chosen from the significant SMR results. After the above analysis, we screened 12 genes and performed Mendelian Randomization (MR) analysis on them. After sensitivity analysis, we identified four genes with potential causal relationships with VV. Finally, we used transcriptome-wide association studies and The Drug-Gene Interaction Database data to identify and screen the remaining genes and identified four drug targets for the treatment of VV. Results: We identified four genes significantly associated with VV, namely, KRTAP5-AS1 [Odds ratio (OR) = 1.08, 95% Confidence interval (CI): 1.05-1.11, p = 1.42e-10] and PLEKHA5 (OR = 1.13, 95% CI: 1.06-1.20, p = 6.90e-5), CBWD1 (OR = 1.05, 95% CI: 1.01-1.11, p = 1.42e-2) and CRIM1 (OR = 0.87, 95% CI: 0.81-0.95, p = 3.67e-3). Increased expression of three genes, namely, KRTAP5-AS1, PLEKHA5, and CBWD1, was associated with increased risk of the disease, and increased expression of CRIM1 was associated with decreased risk of the disease. These four genes could be targeted for VV therapy. Conclusion: We identified four potential causal proteins for varicose veins with MR. A comprehensive analysis indicated that KRTAP5-AS1, PLEKHA5, CBWD1, and CRIM1 might be potential drug targets for varicose veins.

9.
J Dig Dis ; 25(2): 100-108, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38599672

ABSTRACT

OBJECTIVES: The perceptions and attitudes of inflammatory bowel disease (IBD) patients towards pregnancy may affect their fertility plan and disease progression. We performed a nationwide multicenter survey of pregnancy-related knowledge among gastroenterologists and IBD patients in China to investigate whether specific educational interventions could improve their understanding and broadly influence fertility plan. METHODS: A cross-sectional questionnaire regarding pregnancy-specific knowledge was carried out among 63 IBD centers in China. Questionnaires were collected from 185 physicians and 609 patients. The patients then received education regarding pregnancy during IBD and filled in the same questionnaire again. Their knowledge regarding pregnancy during IBD was compared before and after education. RESULTS: Compared to physicians, patients' knowledge regarding fertility (39.1% vs 70.8%), imaging examinations (22.8% vs 72.4%), endoscopy performed during pregnancy (19.9% vs 71.4%), and vaccination for infants (16.6% vs 46.5%) was significantly more limited (all P < 0.001). There was a lack of knowledge among gastroenterologists regarding the delivery mode (36.8%), medications (36.8%), and emergency surgery (26.5%) during pregnancy in patients with IBD. After education, the patients showed significant improvement in knowledge regarding medications (26.7% vs 51.7%), fertility (45.0% vs 63.3%), heritability (40.0% vs 58.3%), indications for emergency surgery (15.0% vs 53.3%), imaging examinations during pregnancy (20.0% vs 40.0%), and vaccinations for infants (26.7% vs 45.0%) (all P < 0.05). CONCLUSIONS: Pregnancy-specific IBD knowledge needs to be improved among certain gastroenterologists and patients in China. Educational interventions can partially improve the knowledge levels of the patients.


Subject(s)
Health Knowledge, Attitudes, Practice , Inflammatory Bowel Diseases , Pregnancy , Female , Humans , Cross-Sectional Studies , Surveys and Questionnaires , Inflammatory Bowel Diseases/drug therapy , China
10.
Cancer Cell Int ; 24(1): 134, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38622617

ABSTRACT

Some noncoding RNAs (ncRNAs) carry open reading frames (ORFs) that can be translated into micropeptides, although noncoding RNAs (ncRNAs) have been previously assumed to constitute a class of RNA transcripts without coding capacity. Furthermore, recent studies have revealed that ncRNA-derived micropeptides exhibit regulatory functions in the development of many tumours. Although some of these micropeptides inhibit tumour growth, others promote it. Understanding the role of ncRNA-encoded micropeptides in cancer poses new challenges for cancer research, but also offers promising prospects for cancer therapy. In this review, we summarize the types of ncRNAs that can encode micropeptides, highlighting recent technical developments that have made it easier to research micropeptides, such as ribosome analysis, mass spectrometry, bioinformatics methods, and CRISPR/Cas9. Furthermore, based on the distribution of micropeptides in different subcellular locations, we explain the biological functions of micropeptides in different human cancers and discuss their underestimated potential as diagnostic biomarkers and anticancer therapeutic targets in clinical applications, information that may contribute to the discovery and development of new micropeptide-based tools for early diagnosis and anticancer drug development.

11.
ChemSusChem ; : e202400424, 2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38682649

ABSTRACT

High-performance rechargeable aluminum-sulfur batteries (RASB) have great potential for various applications owing to their high theoretical capacity, abundant sulfur resources, and good safety. Nevertheless, the practical application of RASB still faces several challenges, including the polysulfide shuttle phenomenon and low sulfur utilization efficiency. Here, we first developed a synergistic copper heterogeneous metal oxide MoO2 derived from polymolybdate-based metal-organic framework as an efficient catalyst for mitigating polysulfide diffusion. This composite enhances sulfur utilization and electrical conductivity of the cathode. DFT calculations and experimental results reveal the catalyst Cu/MoO2@C not only effectively anchors aluminum polysulfides (AlPSs) to mitigate the shuttle effect, but also significantly promotes the catalytic conversion of AlPSs on the sulfur cathode side during charging and discharging. The unique nanostructure contains abundant electrocatalytic active sites of oxide nanoparticles and Cu clusters, resulting in excellent electrochemical performance. Consequently, the established RASB exhibits an initial capacity of 875 mAh g-1 at 500 mA g-1 and maintains a capacity of 967 mAh g-1 even at a high temperature of 50 °C.

12.
Medicine (Baltimore) ; 103(9): e37357, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38428890

ABSTRACT

OBJECTIVE: This study aimed to examine the changes in serum Low Density Lipoprotein Cholesterol (LDL-C) and Soluble Growth Stimulating Expressed Gene 2 Protein (sST2) among Heart Failure (HF) patients with varying ejection fractions and their clinical significance, providing a reference for the clinical assessment of HF severity. METHODS: A total of 238 HF patients treated in our hospital's cardiology department from September 2019 to December 2021 were selected; 68 patients hospitalized in the same period were selected as the control group. General information, LDL-C and echocardiographic results of admitted patients were collected. According to LVEF results and the latest European Society of Cardiology standards in 2021, HF patients were categorized into those with HFpEF (n = 95), HFmrEF (n = 60), and HFrEF (n = 83). Meanwhile, venous blood was collected to determine sST2 and NT-proBNP to compare and analyze the changes and clinical significance of sST2 and LDL-C across the groups. RESULTS: Compared to the control group, the HF group showed significant differences in age, gender, heart rate, smoking history, history of atrial fibrillation, history of diabetes, LVEDD, LVEF, sST2, and NT-proBNP levels (P < .05), but not in LDL-C levels. Significant differences (P < .05) were also found among the 3 HF groups in terms of age, gender, history of atrial fibrillation, LVEDD, LVEF, LDL-C, sST2, and NT-proBNP levels, with an increase in LVEDD, LDL-C, sST2, and NT-proBNP values as the ejection fraction decreased. ROC curve analysis indicated that the area under the curve (AUC) for sST2 in diagnosing HF was 0.915 (P < .05), with an optimal cutoff value of 23.71 ng/mL, a sensitivity of 76.5%, and a specificity of 95.6%; LDL-C was not a significant diagnostic marker for HF (P > .05). Coronary artery disease, NT-proBNP, and sST2 were identified as risk factors for HF. With each unit increase in coronary artery disease, the risk of HF increased by 36.3%; for NT-proBNP, the risk increased by 1.3% per unit; and for sST2, it increased by 18.3% per unit. CONCLUSION: As the ejection fraction decreases in HF patients, serum sST2 and LDL-C values progressively increase, which is clinically significant for predicting the severity of HF. sST2 is an independent risk factor for HF and can enhance the diagnostic accuracy for HF.


Subject(s)
Atrial Fibrillation , Coronary Artery Disease , Heart Failure , Humans , Biomarkers , Prognosis , Stroke Volume , Clinical Relevance , Cholesterol, LDL , Natriuretic Peptide, Brain , Peptide Fragments
13.
Exp Cell Res ; 436(1): 113956, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38341081

ABSTRACT

Patients with hepatocellular carcinoma (HCC) are vulnerable to drug resistance. Although drug resistance has been taken much attention to HCC therapy, little is known of regorafenib and regorafenib resistance (RR). This study aimed to determine the drug resistance pattern and the role of RhoA in RR. Two regorafenib-resistant cell lines were constructed based on Huh7 and Hep3B cell lines. In vitro and in vivo assays were conducted to study RhoA expression, the activity of Hippo signaling pathway and cancer stem cell (CSC) traits. The data showed that RhoA was highly expressed, Hippo signaling was hypoactivated and CSC traits were more prominent in RR cells. Inhibiting RhoA could reverse RR, and the alliance of RhoA inhibition and regorafenib synergistically attenuated CSC phenotype. Furthermore, inhibiting LARG/RhoA increased Kibra/NF2 complex formation, prevented YAP from shuttling into the nucleus and repressed CD44 mRNA expression. Clinically, the high expression of RhoA correlated with poor prognosis. LARG, RhoA, YAP1 and CD44 show positive correlation with each other. Thus, inhibition of RhoGEF/RhoA has the potential to reverse RR and repress CSC phenotype in HCC.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Pyridines , Humans , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/genetics , Hippo Signaling Pathway , Liver Neoplasms/drug therapy , Liver Neoplasms/genetics , Phenylurea Compounds/pharmacology
14.
EClinicalMedicine ; 68: 102431, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38318126

ABSTRACT

Background: Frail elderly patients with newly diagnosed multiple myeloma (NDMM) have inferior survival and less benefit from high-dose therapies. This prospective study aimed to investigate the efficacy, safety, and quality of life (QoL) of induction treatment of ixazomib/lenalidomide/dexamethasone (IRd) and ixazomib/pegylated liposomal doxorubicin/dexamethasone (IDd) followed by ixazomib/dexamethasone (Id) maintenance therapy in frail, elderly patients with NDMM. Methods: From July 2019 to December 2021, this non-randomized concurrent controlled clinical study enrolled 120 NDMM patients aged ≥65 years with frailty defined by the International Myeloma Working Group (IMWG) frailty score or Mayo geriatric scoring system. The enrolled patients received 6-8 cycles of IRd or IDd followed by Id maintenance therapy for a minimum of 2 years at the discretion of physicians based on patient's clinical characteristics (chiCTR1900024917). Findings: The median age was 71 years and 55% of the patients were males. The overall response rate (ORR) was 82% and 77%, complete response (CR) rate was 25% and 12% for IRd and IDd groups, respectively. The difference in ORR of the Idd group minus the IRd group was -5.36% (95% CI: -18.9% to 8.19%), indicating that the ORR of the IDd group was neither inferior nor non-inferior to the IRd group. After a median follow-up of 34.3 months, the median progression-free survival (PFS) was 21.6 and 13.9 months, OS was not reached and 29.2 months in IRd and IDd groups, respectively. 28 and 33 patients discontinued induction therapy, 20 and 19 discontinued maintenance therapy in IRd and IDd groups, respectively. Cumulative Grade 3 or higher hematological adverse events (AEs) occurred in 10 of the 60 patients (17%) and non-hematological AEs occurred in 15 of the 60 patients (25%) in the IRd group, while 13 of the 60 patients (22%) and 21 of the 60 patients (35%) in the IDd group. Patients were observed with clinically significant improvement in QoL when compared with that at baseline in both IRd and IDd groups by evaluation per cycle (P < 0.0001). Interpretation: The results demonstrated that compared with IRd regimen, IDd regimen showed no significant advantage, but the survival of the IDd group was shorter than that of the IRd group, indicating an all-oral outpatient triplet regimen with IRd, which has low toxicity and has improved QoL, could be the viable first-line treatment option for frail NDMM patients. Funding: The Young Elite Scientist sponsorship program by bast of Beijing Association for Science and Technology (No. BYESS2023116) and Beijing Medical Award Foundation (No. YXJL-2018-0539-0073).

15.
Nat Commun ; 15(1): 1425, 2024 Feb 16.
Article in English | MEDLINE | ID: mdl-38365888

ABSTRACT

Developing a facile and feasible strategy to fabricate thermally activated delayed fluorescence materials exhibiting full-color tunability remains an appealing yet challenging task. In this work, a general supramolecular strategy for fabricating thermally activated delayed fluorescence materials is proposed. Consequently, a series of host-guest cocrystals are prepared by electron-donating calix[3]acridan and various electron-withdrawing guests. Owing to the through-space charge transfer mediated by multiple noncovalent interactions, these cocrystals all display efficient thermally activated delayed fluorescence. Especially, by delicately modulating the electron-withdrawing ability of the guest molecules, the emission colors of these cocrystals can be continuously tuned from blue (440 nm) to red (610 nm). Meanwhile, high photoluminescence quantum yields of up to 87% is achieved. This research not only provides an alternative and general strategy for the fabrication of thermally activated delayed fluorescence materials, but also establishes a reliable supramolecular protocol toward the design of advanced luminescent materials.

16.
BMC Urol ; 24(1): 40, 2024 Feb 16.
Article in English | MEDLINE | ID: mdl-38365673

ABSTRACT

BACKGROUND: To investigate the value of semi-quantitative and quantitative parameters (PI-RADS score, T2WI score, ADC, Ktrans, and Kep) based on multiparametric MRI (mpMRI) or biparametric MRI (bpMRI) combined with prostate specific antigen density (PSAD) in detecting clinically significant prostate cancer (csPCa). METHODS: A total of 561 patients (276 with csPCa; 285 with non-csPCa) with biopsy-confirmed prostate diseases who underwent preoperative mpMRI were included. Prostate volume was measured for calculation of PSAD. Prostate index lesions were scored on a five-point scale on T2WI images (T2WI score) and mpMRI images (PI-RADS score) according to the PI-RADS v2.1 scoring standard. DWI and DCE-MRI images were processed to measure the quantitative parameters of the index lesion, including ADC, Kep, and Ktrans values. The predictors of csPCa were screened by logistics regression analysis. Predictive models of bpMRI and mpMRI were established. ROC curves were used to evaluate the efficacy of parameters and the model in diagnosing csPCa. RESULTS: The independent diagnostic accuracy of PSA density, PI-RADS score, T2WI score, ADCrec, Ktrans, and Kep for csPCa were 80.2%, 89.5%, 88.3%, 84.6%, 58.5% and 61.6%, respectively. The diagnostic accuracy of bpMRI T2WI score and ADC value combined with PSAD was higher than that of PI-RADS score. The combination of mpMRI PI­RADS score, ADC value with PSAD had the highest diagnostic accuracy. CONCLUSIONS: PI-RADS score according to the PI-RADS v2.1 scoring standard was the most accurate independent diagnostic index. The predictive value of bpMRI model for csPCa was slightly lower than that of mpMRI model, but higher than that of PI-RADS score.


Subject(s)
Multiparametric Magnetic Resonance Imaging , Prostatic Neoplasms , Male , Humans , Prostatic Neoplasms/pathology , Magnetic Resonance Imaging/methods , Retrospective Studies , Multiparametric Magnetic Resonance Imaging/methods , Prostate-Specific Antigen , Multivariate Analysis
17.
Angew Chem Int Ed Engl ; 63(3): e202315032, 2024 Jan 15.
Article in English | MEDLINE | ID: mdl-38057563

ABSTRACT

The oxygen evolution reaction (OER), characterized by a four-electron transfer kinetic process, represents a significant bottleneck in improving the efficiency of hydrogen production from water electrolysis. Consequently, extensive research efforts have been directed towards identifying single-atom electrocatalysts with exceptional OER performance. Despite the comprehensive understanding of the OER mechanism, its application to other valuable synthetic reactions has been limited. Herein, we leverage the MOOH intermediate, a key species in the Mn-N-C single-atom catalyst (Mn-SA@NC), which can be cyclically delivered in the OER. We exploit this intermediate' s capability to facilitate electrophilic transfer with silane, enabling efficient silane oxidation under electrochemical conditions. The SAC electrocatalytic system exhibits remarkable performance with catalyst loadings as low as 600 ppm and an exceptional turnover number of 9132. Furthermore, the catalytic method demonstrates stability under a 10 mmol flow chemistry setup. By serving as an OER electrocatalyst, the Mn-SA@NC drives the entire reaction, establishing a practical Mn SAC-catalyzed organic electrosynthesis system. This synthesis approach not only presents a promising avenue for the utilization of electrocatalytic OER but also highlights the potential of SACs as an attractive platform for organic electrosynthesis investigations.

18.
Chem Biol Interact ; 387: 110818, 2024 Jan 05.
Article in English | MEDLINE | ID: mdl-38000455

ABSTRACT

Hyperglycaemia causes impairment of osteogenic differentiation and accelerates stem cell senescence, resulting in weakened osteogenesis and disordered bone metabolism. Phytic acid (PA) is an antioxidant that is reportedly beneficial to bone homeostasis. The present study aims to clarify how PA affects the osteogenic capacity and cellular senescence of bone marrow mesenchymal stem cells (BMSCs) exposed to high-glucose environments, as well as the potential molecular mechanisms. Our results indicate that osteogenic differentiation in BMSCs cultivated in high-glucose conditions is enhanced by PA, as evidenced by increased alkaline phosphatase activity and staining, Alizarin Red S staining, osteogenic marker in in vitro studies, and increased osteogenesis in animal experiments. PA also prevented high-glucose-induced senescence of BMSCs, as evidenced by the repression of reactive oxygen species production, senescence-associated ß-galactosidase staining, and P21 and P53 expression. Furthermore, it was found that PA rescued the high-glucose-inhibited expression of phosphorylated extracellular regulated protein kinases (p-ERK). The inhibition of ERK pathway by the specific inhibitor PD98059 blocked the PA-enhanced osteogenesis of BMSCs and promoted cell senescence. Our results revealed that PA enhances osteogenic differentiation and inhibits BMSC senescence in a high-glucose environment. In addition, the activation of the ERK pathway seems to mediate the beneficial effects of PA. The findings provide novel insights that could facilitate bone regeneration in patients with diabetes.


Subject(s)
Mesenchymal Stem Cells , Osteogenesis , Animals , Humans , Phytic Acid/pharmacology , Phytic Acid/metabolism , MAP Kinase Signaling System , Cell Differentiation , Glucose/metabolism , Cells, Cultured , Bone Marrow Cells
19.
Nano Lett ; 23(23): 11368-11375, 2023 Dec 13.
Article in English | MEDLINE | ID: mdl-38047597

ABSTRACT

The design of catalysts has attracted a great deal of attention in the field of electrocatalysis. The accurate design of the catalysts can avoid an unnecessary process that occurs during the blind trial. Based on the interaction between different metal species, a metallic compound supported by the carbon nanotube was designed. Among these compounds, RhFeP2CX (R-RhFeP2CX-CNT) was found to be in a rich-electron environment at the Fermi level (denoted as a flat Fermi surface), beneficial to the hydrogen evolution reaction (HER). R-RhFeP2CX-CNT exhibits a small overpotential of 15 mV at the current density of 10 mA·cm-2 in acidic media. Moreover, the mass activity of R-RhFeP2CX-CNT is 21597 A·g-1, which also demonstrates the advance of the active sites on R-RhFeP2CX-CNT. Therefore, R-RhFeP2CX-CNT can be an alternative catalyst applied in practical production, and the strategies of a flat Fermi surface will be a reliable strategy for catalyst designing.

20.
Animals (Basel) ; 13(23)2023 Nov 27.
Article in English | MEDLINE | ID: mdl-38067011

ABSTRACT

Varroa destructor injects a salivary secretion into honeybees during their feeding process. The salivary secretion plays a vital role in mite-bee interactions and is the main cause of honeybee illness. To determine the biological function of cystatin-L2-like, one of the components of V. destructor salivary secretion, its gene expression in mites during the reproductive phase and dispersal phase was quantified using RT-qPCR, respectively. Moreover, the E. coli-expressed and -purified cystatin was injected into the white-eyed honeybee pupae, and its effects on the survival, the weight of the newly emerged bee, and the transcriptome were determined. The results showed that cystatin was significantly upregulated in mites during the reproductive phase. Cystatin significantly shortened the lifespan of pupae and decreased the weight of the newly emerged bees. Transcriptome sequencing showed that cystatin upregulated 1496 genes and downregulated 1483 genes in pupae. These genes were mainly enriched in ATP synthesis, the mitochondrial respiratory chain, and cuticle structure and function. Cystatin comprehensively downregulated the metabolism of carbohydrates, fatty acids, and amino acids, and energy production in the pupae. The downregulation of metabolic activity could save more nutrients and energy for V. destructor, helping it to maximize its reproduction potential, implying that the mite could manipulate the metabolism of host bees through the injected salivary secretion. The results provide new insights into mite-bee interactions, providing a basis for related studies and applications.

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