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1.
Acta Biochim Biophys Sin (Shanghai) ; 56(8): 1208-1220, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-39225075

ABSTRACT

Aging, a complex biological process, involves the progressive decline of physiological functions across various systems, leading to increased susceptibility to neurodegenerative diseases. In society, demographic aging imposes significant economic and social burdens due to these conditions. This review specifically examines the association of protein glycosylation with aging and neurodegenerative diseases. Glycosylation, a critical post-translational modification, influences numerous aspects of protein function that are pivotal in aging and the pathophysiology of diseases such as Alzheimer's disease, Parkinson's disease, and other neurodegenerative conditions. We highlight the alterations in glycosylation patterns observed during aging, their implications in the onset and progression of neurodegenerative diseases, and the potential of glycosylation profiles as biomarkers for early detection, prognosis, and monitoring of these age-associated conditions, and delve into the mechanisms of glycosylation. Furthermore, this review explores their role in regulating protein function and mediating critical biological interactions in these diseases. By examining the changes in glycosylation profiles associated with each part, this review underscores the potential of glycosylation research as a tool to enhance our understanding of aging and its related diseases.


Subject(s)
Aging , Neurodegenerative Diseases , Protein Processing, Post-Translational , Humans , Glycosylation , Aging/metabolism , Neurodegenerative Diseases/metabolism , Alzheimer Disease/metabolism , Animals , Biomarkers/metabolism , Parkinson Disease/metabolism
2.
Sci Signal ; 17(853): eadf9388, 2024 Sep 10.
Article in English | MEDLINE | ID: mdl-39255338

ABSTRACT

Extranodal natural killer/T cell lymphoma (ENKTL) shows a high rate of recurrence after chemoradiotherapy. Drug resistance can be mediated by the cargo of small extracellular vesicles (sEVs). Here, we show that high abundance of the transmembrane glycoprotein CD98hc in tumor cells and serum sEVs was associated with ENKTL progression and drug resistance. Mechanistically, PEGylated-asparaginase (PEG-asp) treatment, a common therapy against ENKTL, promoted the translocation of the transcription factor ATF4 to the nucleus, where it was stabilized by USP1 and subsequently increased CD98hc expression. CD98hc delivered in tumor cell-derived sEVs increased tumor cell proliferation and drug resistance in a cultured human NK lymphoma cell line, animal models, and samples from patients with refractory/relapse ENKTL. Moreover, inhibiting both USP1 and EV secretion synergistically enhanced the cytotoxicity of PEG-asp. These data suggest that targeting CD98hc in the treatment of ENKTL may be beneficial in overcoming drug resistance.


Subject(s)
Drug Resistance, Neoplasm , Extracellular Vesicles , Fusion Regulatory Protein 1, Heavy Chain , Lymphoma, Extranodal NK-T-Cell , Humans , Extracellular Vesicles/metabolism , Drug Resistance, Neoplasm/drug effects , Lymphoma, Extranodal NK-T-Cell/metabolism , Lymphoma, Extranodal NK-T-Cell/drug therapy , Lymphoma, Extranodal NK-T-Cell/genetics , Lymphoma, Extranodal NK-T-Cell/pathology , Animals , Cell Line, Tumor , Fusion Regulatory Protein 1, Heavy Chain/metabolism , Fusion Regulatory Protein 1, Heavy Chain/genetics , Mice , Female , Asparaginase/pharmacology , Cell Proliferation/drug effects , Male
3.
Sci Data ; 11(1): 739, 2024 Jul 07.
Article in English | MEDLINE | ID: mdl-38972884

ABSTRACT

Cellular senescence (CS) is closely related to tumor progression. However, the studies about CS genes across human cancers have not explored the relationship between cancer senescence signature and telomere length. Additionally, single-cell analyses have not revealed the evolutionary trends of malignant cells and immune cells at the CS level. We defined a CS-associated signature, called "senescence signature", and found that patients with higher senescence signature had worse prognosis. Higher senescence signature was related to older age, higher genomic instability, longer telomeres, increased lymphocytic infiltration, higher pro-tumor immune infiltrates (Treg cells and MDSCs), and could predict responses to immune checkpoint inhibitor therapy. Single-cell analysis further reveals malignant cells and immune cells share a consistent evolutionary trend at the CS level. MAPK signaling pathway and apoptotic processes may play a key role in CS, and senescence signature may effectively predict sensitivity of MEK1/2 inhibitors, ERK1/2 inhibitors and BCL-2 family inhibitors. We also developed a new CS prediction model of cancer survival and established a portal website to apply this model ( https://bio-pub.shinyapps.io/cs_nomo/ ).


Subject(s)
Cellular Senescence , Neoplasms , Single-Cell Analysis , Humans , Neoplasms/immunology , Immunosenescence , Genomic Instability , Prognosis , Multiomics
4.
Int J Mol Sci ; 25(14)2024 Jul 21.
Article in English | MEDLINE | ID: mdl-39063209

ABSTRACT

'Duli' (Pyrus betulifolia Bunge) is one of the main rootstocks of pear trees in China. Gibberellin (GA) is a key plant hormone and the roles of GA in nitrate (NO3-) uptake and metabolism in plants remain unclear. In this study, we investigated the effects of exogenous GA3 on the N metabolism of 'Duli' seedlings under NO3- deficiency. The results showed that exogenous GA3 significantly improves 'Duli' growth under NO3- deficiency. On the one hand, GA3 altered the root architecture, increased the content of endogenous hormones (GA3, IAA, and ZR), and enhanced photosynthesis; on the other hand, it enhanced the activities of N-metabolizing enzymes and the accumulation of N, and increased the expression levels of N absorption (PbNRT2) and the metabolism genes (PbNR, PbGILE, PbGS, and PbGOGAT). However, GA3 did not delay the degradation of chlorophyll. Paclobutrazol had the opposite effect on growth. Overall, GA3 can increase NO3- uptake and metabolism and relieve the growth inhibition of 'Duli' seedlings under NO3- deficiency.


Subject(s)
Gibberellins , Nitrates , Nitrogen , Pyrus , Seedlings , Seedlings/metabolism , Seedlings/growth & development , Seedlings/drug effects , Nitrates/metabolism , Gibberellins/metabolism , Nitrogen/metabolism , Pyrus/metabolism , Pyrus/genetics , Pyrus/growth & development , Pyrus/drug effects , Gene Expression Regulation, Plant/drug effects , Photosynthesis/drug effects , Plant Roots/metabolism , Plant Roots/growth & development , Plant Roots/drug effects , Plant Growth Regulators/metabolism , Chlorophyll/metabolism
5.
Materials (Basel) ; 17(14)2024 Jul 09.
Article in English | MEDLINE | ID: mdl-39063673

ABSTRACT

Rare earth resource recycling is an important endeavor for environmental protection and resource utilization. This study explores the method of preparing regenerated magnets using waste magnets as raw materials based on existing processes. By utilizing existing Nd-Fe-B production equipment, various waste magnets are transformed into recycled powder. Next, nascent Nd-Fe-B powders with slightly higher rare earth content are selected as the repairing agent. The regenerated magnets are prepared by incorporating the nascent powder into the recycled powder. The focus lies in investigating the repairing effect of the nascent powder repairing agent on the microstructure of regenerated magnets and exploring the influence of sintering temperature and powder addition on the magnetic properties and microstructure of the regenerated magnets. The results showed that the nascent powder increased the proportion of grain boundary phases and effectively repaired the grain boundary structure of the regenerated magnets. In addition, the Pr element in the nascent powder replaces the Ce element in the recycled powder, which ultimately improves the magnetic properties of the regenerated magnet in a comprehensive manner. This study provides valuable insights and guidance for rare earth resource recycling and the preparation of regenerated magnets.

6.
Sci China Life Sci ; 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-39034351

ABSTRACT

Measurable residual disease (MRD) is a powerful prognostic factor of relapse in acute myeloid leukemia (AML). We applied the single-cell RNA sequencing to bone marrow (BM) samples from patients with (n=20) and without (n=12) MRD after allogeneic hematopoietic stem cell transplantation. A comprehensive immune landscape with 184,231 cells was created. Compared with CD8+ T cells enriched in the MRD-negative group (MRD-_CD8), those enriched in the MRD-positive group (MRD+_CD8) showed lower expression levels of cytotoxicity-related genes. Three monocyte clusters (i.e., MRD+_M) and three B-cell clusters (i.e., MRD+_B) were enriched in the MRD-positive group. Conversion from an MRD-positive state to an MRD-negative state was accompanied by an increase in MRD-_CD8 clusters and vice versa. MRD-enriched cell clusters employed the macrophage migration inhibitory factor pathway to regulate MRD-_CD8 clusters. These findings revealed the characteristics of the immune cell landscape in MRD positivity, which will allow for a better understanding of the immune mechanisms for MRD conversion.

7.
Adv Ther ; 41(7): 2953-2965, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38833140

ABSTRACT

INTRODUCTION: Stapokibart, a novel humanized anti-interleukin (IL)-4 receptor alpha monoclonal antibody, inhibits the signaling of IL-4 and IL-13, which are key drivers of type 2 inflammation in atopic dermatitis (AD). This study aimed to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of stapokibart in a randomized, double-blind, placebo-controlled single ascending dose (SAD) study and a multiple ascending dose (MAD) study. METHODS: The SAD study enrolled 33 healthy male adults aged 18-65 years at a single center. The MAD study enrolled 39 patients with moderate-to-severe AD aged 18-70 years at seven centers. Enrolled subjects were randomized to subcutaneous (SC) doses of stapokibart (75-600 mg) or placebo. Serum thymus and activation-regulated chemokine (TARC) and total immunoglobulin E (IgE) were measured as PD biomarkers for stapokibart. RESULTS: Similar PK characteristics were observed in healthy volunteers and subjects with AD after the initial administration. Stapokibart exhibited non-linear pharmacokinetics in both types of subjects. Following single doses, the mean maximum serum concentration (Cmax) ranged from 5.3 to 63.0 µg/mL, median Tmax ranged from 3.0 to 7.0 days, mean terminal half-life (t1/2z) ranged from 2.39 to 7.43 days, and mean apparent volume (Vz/F) ranged from 3.64 to 6.73 L in healthy subjects. The mean AUC accumulation ratio was 2.29 in subjects with AD after three doses of stapokibart 300 mg administered every 2 weeks. The median serum total IgE and TARC levels on day 43 decreased from baseline by 14.9-25.2% and 48.6-77.0%, respectively, among subjects with AD receiving three doses of stapokibart. No subjects developed grade ≥ 3 adverse events (AEs) or serious AEs or discontinued the study because of AEs. The incidence of AEs was similar between stapokibart and placebo groups. CONCLUSION: Stapokibart showed favorable pharmacokinetics, pharmacodynamics, safety, and tolerability in the SAD and MAD studies. Based on these results, phase II and phase III trials of stapokibart have been performed in subjects with moderate-to-severe AD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT06161090 (29 November, 2023), NCT04893941 (15 May, 2021).


Subject(s)
Antibodies, Monoclonal, Humanized , Dermatitis, Atopic , Healthy Volunteers , Humans , Dermatitis, Atopic/drug therapy , Adult , Male , Middle Aged , Double-Blind Method , Young Adult , Antibodies, Monoclonal, Humanized/pharmacokinetics , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Monoclonal, Humanized/administration & dosage , Aged , Chemokine CCL17/blood , Adolescent , Dose-Response Relationship, Drug , Immunoglobulin E/blood , Injections, Subcutaneous , Interleukin-4 Receptor alpha Subunit/antagonists & inhibitors
8.
Front Public Health ; 12: 1391906, 2024.
Article in English | MEDLINE | ID: mdl-38873307

ABSTRACT

Currently, there are still many patients who require outpatient triage assistance. ChatGPT, a natural language processing tool powered by artificial intelligence technology, is increasingly utilized in medicine. To facilitate and expedite patients' navigation to the appropriate department, we conducted an outpatient triage evaluation of ChatGPT. For this evaluation, we posed 30 highly representative and common outpatient questions to ChatGPT and scored its responses using a panel of five experienced doctors. The consistency of manual triage and ChatGPT triage was assessed by five experienced doctors, and statistical analysis was performed using the Chi-square test. The expert ratings of ChatGPT's answers to these 30 frequently asked questions revealed 17 responses earning very high scores (10 and 9.5 points), 7 earning high scores (9 points), and 6 receiving low scores (8 and 7 points). Additionally, we conducted a prospective cohort study in which 45 patients completed forms detailing gender, age, and symptoms. Triage was then performed by outpatient triage staff and ChatGPT. Among the 45 patients, we found a high level of agreement between manual triage and ChatGPT triage (consistency: 93.3-100%, p<0.0001). We were pleasantly surprised to observe that ChatGPT's responses were highly professional, comprehensive, and humanized. This innovation can help patients win more treatment time, improve patient diagnosis and cure rates, and alleviate the pressure of medical staff shortage.


Subject(s)
Artificial Intelligence , Outpatients , Triage , Humans , Prospective Studies , Female , Male , Outpatients/statistics & numerical data , Middle Aged , Adult , Natural Language Processing , Aged
9.
ERJ Open Res ; 10(3)2024 May.
Article in English | MEDLINE | ID: mdl-38779041

ABSTRACT

Background: Data on viral kinetics and variants affecting the duration of viral shedding were limited. Our objective was to determine viral shedding in distinct severe acute respiratory syndrome coronavirus 2 variants, including Omicron BA.4/5 and BF.7, and to identify the relevant influencing factors. Methods: We carried out a longitudinal cohort study at Beijing Xiaotangshan Fangcang shelter hospital from May to June 2022 (Omicron BA.4/5) and from November to December 2022 (Omicron BF.7). Nucleocapsid protein (N) and open reading frame (ORF) genes were considered as the target genes of the reverse transcription PCR. The daily results of cycle threshold (CT), including lowest ORF1ab-CT values for days 1-3 post-hospitalisation and lowest N-CT values for days 1-3 post-hospitalisation (CT3minN) and demographic and clinical characteristics were collected. Results: 1433 patients with coronavirus disease 2019 (COVID-19) were recruited from the Fangcang shelter hospital, in which 278 patients were diagnosed with Omicron BA.4/5 and 1155 patients with Omicron BF.7. Patients with BF.7 infection showed a longer duration of viral shedding. The duration of viral shedding was associated with the variants age, alcohol use, the severity of COVID-19 and CT3minN. Moreover, the nomogram had excellent accuracy in predicting viral shedding. Conclusions: Our results indicated that patients with Omicron BF.7 had a longer period of contagiousness than those with BA.4/5. The duration of viral shedding was affected by a variety of factors and the nomogram may become an applicable clinical instrument to predict viral shedding. Furthermore, we developed a new COVID-19 viral shedding predicting model that can accurately predict the duration of viral shedding for COVID-19, and created a user-friendly website to apply this prediction model (https://puh3.shinyapps.io/CVSP_Model/).

10.
J Transl Med ; 22(1): 414, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38693538

ABSTRACT

Primary testicular lymphoma (PTL) is a rare lymphoma predominantly occurring in the elderly male population. It is characterized by a limited response to treatment and a heightened tendency towards relapse. Histologically, approximately 90% of PTL cases are classified as diffuse large B-cell lymphomas (DLBCL). Genetic features of PTL were delineated in a limited scope within several independent studies. Some of the articles which analyzed the genetic characterization of DLBCL have incorporated PTL samples, but these have been constrained by small sample sizes. In addition, there have been an absence of independent molecular typing studies of PTL. This report summarizes the common mutational features, copy number variations (CNVs) and molecular typing of PTL patients, based on whole-exome sequencing (WES) conducted on a cohort of 25 PTL patients. Among them, HLA, CDKN2A and MYD88 had a high mutation frequency. In addition, we found two core mutational characteristics in PTL including mutation in genes linked to genomic instability (TP53 and CDKN2A) and mutation in immune-related genes (HLA, MYD88, CD79B). We performed molecular typing of 25 PTL patients into C1 subtype with predominantly TP53 mutations and C2 subtype with predominantly HLA mutations. Notably, mutations in the TP53 gene predicted a poor outcome in most types of lymphomas. However, the C1 subtype, dominated by TP53 mutations, had a better prognosis compared to the C2 subtype in PTL. C2 subtype exhibited a worse prognosis, aligning with our finding that the mechanism of immune escape in PTL was primarily the deletions of HLA rather than PD-L1/PD-L2 alterations, a contrast to other DLBCLs. Moreover, we calculated the tumor mutation burden (TMB) and identified that TMB can predict prognosis and recurrence rate in PTL. Our study underscores the significance of molecular typing in PTL based on mutational characteristics, which plays a crucial role in prognostication and guiding therapeutic strategies for patients.


Subject(s)
DNA Copy Number Variations , Genomics , Mutation , Testicular Neoplasms , Humans , Male , Testicular Neoplasms/genetics , Testicular Neoplasms/pathology , Testicular Neoplasms/classification , Mutation/genetics , DNA Copy Number Variations/genetics , Aged , Middle Aged , Lymphoma/genetics , Lymphoma/pathology , Lymphoma/classification , Exome Sequencing , Aged, 80 and over , Adult , Lymphoma, Large B-Cell, Diffuse/genetics , Lymphoma, Large B-Cell, Diffuse/pathology , Lymphoma, Large B-Cell, Diffuse/classification
11.
Front Med (Lausanne) ; 11: 1357299, 2024.
Article in English | MEDLINE | ID: mdl-38596791

ABSTRACT

Background: Lianhuaqingwen (LHQW), a traditional Chinese medicine comprised of 13 herbal extracts renowned for their robust heat-clearing and detoxifying properties, has gained widespread utilization in China but has yet to garner similar recognition abroad. It is believed to exhibit efficacy in ameliorating symptoms in individuals afflicted with coronavirus disease 2019 (COVID-19). However, the precise impact of LHQW on viral shedding (VS), particularly in the context of mild or asymptomatic infections caused by the Omicron BF.4/5 or BF.7 variants of COVID-19, remained inadequately elucidated. Consequently, a real-world study was conducted, involving patients diagnosed with COVID-19, with the primary objective of ascertaining the effectiveness of LHQW in this specific clinical context. Methods: We conducted an investigation on Omicron-infected patients through a single-center, propensity score-matched real-world study conducted at Xiaotangshan Fangcang Hospital from May to November 2022. A total of 3,368 COVID-19 patients were enrolled in the study, all of whom presented mild or asymptomatic infections caused by either BF.4/5 or BF.7 strains of the virus. Demographic and clinical data were systematically collected from medical records. Patients were allocated to receive treatment with LHQW (designated as the treatment group) or received no LHQW treatment (designated as the not-treated/no-treatment group). Viral load was quantified utilizing quantitative real-time PCR (qPCR), and the duration of VS was defined as the time interval between the initial negative test result and the date of COVID-19 diagnosis or symptom onset. Results: The study encompassed a cohort of 3,368 patients, and following propensity score matching, a subset of 296 patients was meticulously chosen for subsequent analysis. Notably, baseline characteristics exhibited disparities between the treatment and not-treated/no-treatment groups. However, post-matching, these characteristics achieved a commendable level of comparability. Our findings unequivocally demonstrated that there existed no statistically significant disparity in VS. This holds true when comparing patients subjected to LHQW treatment against those not administered LHQW, as well as when contrasting individuals presenting asymptomatic and mild COVID-19 manifestations. Conclusion: No statistically significant difference in VS was observed between patients who underwent LHQW treatment and those who did not. Additional investigations are imperative to provide a comprehensive assessment of LHQW's efficacy, particularly in patients afflicted with severe COVID-19 or those infected with viral strains distinct from BF.4/5 or BF.7.

12.
J Oral Biosci ; 66(2): 403-411, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38663496

ABSTRACT

OBJECTIVES: Osteoporosis is the most common metabolic bone disease worldwide. The decrease in bone mass is primarily accompanied by a decrease in the number and activity of osteoblasts. Peroxiredoxins (PRDXs) are proteins that detect extremely low peroxide levels and act as sensors that regulate oxidation signals, thereby regulating various cellular functions. This study aimed to evaluate the effects of PRDX1 and estrogen on the biological behavior of osteoblasts, including their proliferation and differentiation. METHODS: Ovariectomized (OVX) mice were used to establish a model of osteoporosis and perform morphological and immunohistochemical analyses. Prdx1 gene knockout and overexpression were performed in mouse MC3T3-E1 pre-osteoblasts to assess proliferation and osteogenic differentiation using the cell counting kit-8, quantitative reverse transcription polymerase chain reaction, western blotting (WB), Alizarin Red S staining, etc. RESULTS: The OVX mice exhibited osteoporosis and PRDX1 expression increased. In vitro experiments showed that during the osteogenic differentiation of osteoblasts, PRDX1 expression decreased, while the expression of COL1 and RUNX2 increased. After Prdx1 knockout, the proliferation of osteoblasts decreased; expression of Runx2, ALP, and COL1 increased; and mineralization increased. However, after Prdx1 overexpression, osteoblast proliferation was enhanced, whereas osteogenic differentiation and mineralization were inhibited. Estrogen inhibits the H2O2-induced decrease in osteoblastic differentiation and increase in PRDX1 expression. WB revealed that when LY294002 inhibited the AKT signaling pathway, the levels of p-AKT1, p-P65, and PRDX1 protein in MC3T3-E1 cells decreased. However, when pyrrolidine dithiocarbamate (PDTC) inhibited the NF-κB signaling pathway, the expression of p-AKT1 and PRDX1 did not change except for a significant reduction of p-P65 expression. Furthermore, PDTC reversed the decreased expression of RUNX2, ALP, and COL1 caused by PRDX1 overexpression. CONCLUSIONS: PRDX1 promotes the proliferation of osteoblasts and inhibits osteogenic differentiation. Estrogen regulated osteoblastic differentiation by affecting the expression of PRDX1 in osteoblasts, and the effect is related to the AKT1/NF-κB signaling pathway.


Subject(s)
Cell Differentiation , Cell Proliferation , NF-kappa B , Osteoblasts , Osteogenesis , Peroxiredoxins , Proto-Oncogene Proteins c-akt , Signal Transduction , Animals , Peroxiredoxins/genetics , Peroxiredoxins/metabolism , Mice , Cell Differentiation/drug effects , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction/drug effects , NF-kappa B/metabolism , Cell Proliferation/drug effects , Osteoblasts/drug effects , Osteoblasts/metabolism , Osteogenesis/drug effects , Female , Osteoporosis/metabolism , Osteoporosis/pathology , Osteoporosis/genetics , Ovariectomy , Blotting, Western , Mice, Knockout , Disease Models, Animal
13.
Inorg Chem ; 63(6): 2954-2966, 2024 Feb 12.
Article in English | MEDLINE | ID: mdl-38288974

ABSTRACT

Carbon dioxide (CO2) cycloaddition not only produces highly valued cyclic carbonate but also utilizes CO2 as C1 resources with 100% atomic efficiency. However, traditional catalytic routes still suffer from inferior catalytic efficiency and harsh reaction conditions. Developing multienergy-field catalytic technology with expected efficiency offers great opportunity for satisfied yield under mild conditions. Herein, Zn3In2S6 with sulfur vacancies (Sv) was fabricated with the assistance of cetyltrimethylammonium bromide (CTAB), which is further employed for photothermally driven CO2 cycloaddition first. Photoluminescence spectroscopy and photoelectrochemical characterization demonstrated its superior separation kinetics of photoinduced carriers induced by defect engineering. The temperature-programmed desorption (TPD) technique indicated its excellent Lewis acidity-basicity characters. Due to the combination of above merits from photocatalysis and thermal catalysis, defective Zn3In2S6-Sv achieved a yield as high as 73.2% for cyclic carbonate at 80 °C under blue LED illumination within 2 h (apparent quantum yield of 0.468% under illumination of 380 nm monochromatic light at 36 mW·cm-2), which is 2.9, 2.0, and 6.9 times higher than that in dark conditions and those of pristine Zn3In2S6 and industrial representative tetrabutylammonium bromide (TBAB) thermal-catalysis process under the same conditions, respectively. The synergistic reaction path of photocatalysis and thermal catalysis was discriminated by theoretical calculation. This work provides new insights into the photothermal synergistic catalysis CO2 cycloaddition with defective ternary metal sulfides.

14.
Ann Hematol ; 103(7): 2381-2391, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38165416

ABSTRACT

Blastoid or pleomorphic mantle cell lymphoma (B/P-MCL) is characterized by high invasiveness and unfavorable outcomes, which is still a challenge for treating MCL. This retrospective study was performed to comprehensively analyze the clinical, genomic characteristics and treatment options of patients with B/PMCL from multicenter in China. Data were obtained from 693 patients with B/PMCL from three centers in China between April 1999 and December 2019. Seventy-four patients with BMCL (n = 43) or PMCL (n = 31) were included in the analysis. The median age of the cohort was 60.0 years with a male-to-female ratio of 2.89:1. The 3-year progression-free survival (PFS) and overall survival (OS) rates were 44.1% and 46.0%, respectively. Mutations of TP53, ATM, NOTCH1, NOTCH2, NSD2, SMARCA4, CREBBP, KMT2D, FAT1, and TRAF2 genes were the most common genetic changes in B/P-MCL. Progression of disease within 12 months (POD12) could independently predict the poor prognosis of patients with blastoid and pleomorphic variants. Patients with POD12 carried a distinct mutation profile (TP53, SMARCA4, NSD2, NOTCH2, KMT2D, PTPRD, CREBBP, and CDKN2A mutations) compared to patients with non-POD12. First-line high-dose cytosine arabinoside exposure obtained survival benefits in these populations, and BTKi combination therapy as the front-line treatment had somewhat improvement in survival with no significant difference in the statistic. In conclusion, B/P-MCL had inferior outcomes and a distinct genomic profile. Patients with POD12 displayed a distinct mutation profile and a poor prognosis. New therapeutic drugs and clinical trials for B/P-MCL need to be further explored.


Subject(s)
Lymphoma, Mantle-Cell , Mutation , Humans , Lymphoma, Mantle-Cell/genetics , Lymphoma, Mantle-Cell/mortality , Lymphoma, Mantle-Cell/drug therapy , Male , Female , Middle Aged , China/epidemiology , Retrospective Studies , Aged , Adult , Prognosis , Survival Rate , Aged, 80 and over
15.
J Ethnopharmacol ; 322: 117278, 2024 Mar 25.
Article in English | MEDLINE | ID: mdl-37972908

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Lonicerae japonicae flos (LJF) and Lonicerae flos (LF) belong to different genera of Caprifoliaceae with analogous appearances and functions. Historically, they have been used as herbal medicines to treat various diseases with confirmed wind-heat evacuation, heat-clearing, and detoxification effects. However, the Chinese Pharmacopoeia (2005 Edition) lists LJF and LF under different categories. AIM OF THE STUDY: Few studies have systematically compared the similarities and dissimilarities of LJF and LF concerning their research achievements. This systematic review and comparison of the traditional use, identification, and phytochemical and pharmacological properties of LJF and LF provides valuable insights for their further application and clinical safety. MATERIALS AND METHODS: Related document information was collected from databases that included Web of Science, X-MOL, Science Direct, PubMed, and the China National Knowledge Infrastructure. RESULTS: The chemical constituents and pharmacological effects of LJF and LF were similar. A total of 337 and 242 chemical constituents were isolated and identified in LJF and LF, respectively. These included volatile oils, cyclic ether terpenes, flavonoids, phenolic acids, triterpenoids, and their saponins. Additionally, LJF plants contain more iridoids and flavonoids than LF plants. The latter have a variety of triterpenoid saponins and significantly higher chlorogenic acid content than LJF plants. Pharmacological studies have shown that LJF and LF have various anti-inflammatory, antiviral, antibacterial, anti-endotoxic, antioxidant, anti-tumor, anti-platelet, myocardial protective, and hepatoprotective effects. CONCLUSIONS: This review was undertaken to explore whether LJF and LF should be listed separately in the Chinese Pharmacopoeia in terms of their disease prevention and treatment strategies. Although LJF and LF showed promising effects, their action mechanisms remains unclear. Specifically, their impact on gut microbiota, gastrointestinal tract, and blood parameters requires further investigation. These studies will provide the foundation for scientific utilization and clinical/non-clinical applications of LJF and LF, and the maximum benefits from their mutual use.


Subject(s)
Botany , Drugs, Chinese Herbal , Lonicera , Plant Extracts , Saponins , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Drugs, Chinese Herbal/chemistry , Flavonoids , Lonicera/chemistry
16.
Infect Drug Resist ; 16: 7165-7174, 2023.
Article in English | MEDLINE | ID: mdl-38023407

ABSTRACT

Purpose: This retrospective cohort study aimed to evaluate the clinical efficacy of ulinastatin (UTI) and azithromycin (AZM) combination therapy in treating severe pneumonia in children and its impact on inflammatory cytokines and oxidative stress. Patients and Methods: This retrospective cohort study was conducted from January 1, 2019, to January 1, 2021, involving pediatric patients diagnosed with severe mycoplasma pneumonia (SMPP). The pediatric patients were divided into two groups: those receiving UTI and AZM combination therapy (treatment group) and those receiving azithromycin alone (control group). We compared the two groups regarding clinical data, disease outcomes, inflammatory cytokines, and oxidative stress levels. Results: Baseline characteristics did not significantly differ between the two groups. UTI, in combination with AZM, significantly improved blood oxygen levels, inflammatory infection markers, and relevant clinical symptoms in patients with SMPP on the 3rd day of treatment. Additionally, it significantly reduced the levels of inflammatory cytokines TNF-a, IL-6, IL-1ß, and IL-10, as well as oxidative stress markers GSH and SOD. Conclusion: Combining UTI and AZM can rapidly alleviate clinical symptoms and effectively control the progression of patients with SMPP. Therefore, this treatment approach deserves consideration for clinical promotion and utilization.

17.
Chem Commun (Camb) ; 59(79): 11859-11862, 2023 Oct 04.
Article in English | MEDLINE | ID: mdl-37721313

ABSTRACT

Atomic-level structure engineering has proven indispensable for fast ion transport kinetics. Herein, a unique framework of NiSe/Ni heterostructure with abundant heterointerface encapsulated hollow carbon spheres, namely NiSe/Ni@C, is synthesized as an anode for SIBs. The NiSe/Ni@C electrode delivers enhanced Na+ storage performance in terms of high specific capacity (490 mA h g-1) and excellent rate capability (546 mA h g-1) at a current of 5.0 A g-1 over 2000 cycles. This study can provide in-depth insights into the interface effect in hybrid structures and shed light on designing energy storage materials.

18.
Hematology ; 28(1): 2251199, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37650932

ABSTRACT

Objective: Diffuse Large B-Cell Lymphoma (DLBCL) is a common and frequently occurring subtype of Non-Hodgkin Lymphoma (NHL). The effective treatment and prognosis of DLBCL are still urgently needed to be explored. This article aims to shed light on the connection between DLBCL survival and NR3C1 expression levels. Methods: First, we divided the 952 DLBCL patients into an NR3C1 high-expression group and an NR3C1 low-expression group and compared the baseline characteristics of the two groups. Second, we used multivariate analysis to predict the dependent variable for age, pathology, ECOG score, lactate dehydrogenase (LDH) ratio, and NR3C1 expression level. Finally, we analyzed the progression-free survival (PFS) and overall survival rate (OS) of DLBCL patients with high or low NR3C1 expression. Results: DLBCL patients with high NR3C1 expression had a better prognosis than those with low NR3C1 expression (OS, P < 0.0001). In DLBCL patients of CHOP therapy, high NR3C1 expression was associated with a good survival prognosis in OS (OS, P = 0.028). Conclusion: In multivariate analysis, NR3C1 high expression was an independent prognostic factor that predicted a longer OS of DLBCL (OS, P = 0.0003). NR3C1 is considered an independent predictor of DLBCL patients and can be used as a biomarker for the prognosis of DLBCL.


Subject(s)
Lymphoma, Large B-Cell, Diffuse , Lymphoma, Non-Hodgkin , Humans , Prognosis , Lymphoma, Large B-Cell, Diffuse/genetics , L-Lactate Dehydrogenase , Gene Expression , Receptors, Glucocorticoid
19.
Sci Rep ; 13(1): 12110, 2023 Jul 26.
Article in English | MEDLINE | ID: mdl-37495638

ABSTRACT

To study the basic mechanical behavior and the reloading reinforcement characteristics of fractured coal, conventional triaxial loading tests with different fissure angle were first carried out. On this basis, conventional triaxial loading and unloading tests were conducted to investigate the reloading reinforcement characteristics of fractured coal. The results reveal that when the fissure angle was small, the stress-strain curve exhibited the multi-peak phenomena. As the fissure angle increased, the stress drop phenomenon in the peak region was weakened. With the increase of the fissure angle, the peak stress of the specimens increased and then decreased, while the elastic modulus showed an overall increasing trend, demonstrating the controlling effect of the crack angle. Meanwhile, the cyclic loading exhibited a certain enhancement effect on the strength of the fractured coals when the specimens was unloaded near the crack closure stress. The findings can provide a better understanding of the failure mechanism and reloading reinforcement characteristics of fractured coal.

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