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1.
bioRxiv ; 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38979166

ABSTRACT

Monocyte-derived macrophages (mo-macs) drive immunosuppression in the tumor microenvironment (TME) and tumor-enhanced myelopoiesis in the bone marrow (BM) fuels these populations. Here, we performed paired transcriptome and chromatin analysis over the continuum of BM myeloid progenitors, circulating monocytes, and tumor-infiltrating mo-macs in mice and in patients with lung cancer to identify myeloid progenitor programs that fuel pro-tumorigenic mo-macs. Analyzing chromatin accessibility and histone mark changes, we show that lung tumors prime accessibility for Nfe2l2 (NRF2) in BM myeloid progenitors as a cytoprotective response to oxidative stress. NRF2 activity is sustained and increased during monocyte differentiation into mo-macs in the lung TME to regulate oxidative stress, in turn promoting metabolic adaptation, resistance to cell death, and contributing to immunosuppressive phenotype. NRF2 genetic deletion and pharmacological inhibition significantly reduced mo-macs' survival and immunosuppression in the TME, enabling NK and T cell therapeutic antitumor immunity and synergizing with checkpoint blockade strategies. Altogether, our study identifies a targetable epigenetic node of myeloid progenitor dysregulation that sustains immunoregulatory mo-macs in the TME.

2.
Nat Immunol ; 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39009838

ABSTRACT

Interleukin-17 (IL-17)-producing helper T (TH17) cells are heterogenous and consist of nonpathogenic TH17 (npTH17) cells that contribute to tissue homeostasis and pathogenic TH17 (pTH17) cells that mediate tissue inflammation. Here, we characterize regulatory pathways underlying TH17 heterogeneity and discover substantial differences in the chromatin landscape of npTH17 and pTH17 cells both in vitro and in vivo. Compared to other CD4+ T cell subsets, npTH17 cells share accessible chromatin configurations with regulatory T cells, whereas pTH17 cells exhibit features of both npTH17 cells and type 1 helper T (TH1) cells. Integrating single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) and single-cell RNA sequencing (scRNA-seq), we infer self-reinforcing and mutually exclusive regulatory networks controlling different cell states and predicted transcription factors regulating TH17 cell pathogenicity. We validate that BACH2 promotes immunomodulatory npTH17 programs and restrains proinflammatory TH1-like programs in TH17 cells in vitro and in vivo. Furthermore, human genetics implicate BACH2 in multiple sclerosis. Overall, our work identifies regulators of TH17 heterogeneity as potential targets to mitigate autoimmunity.

3.
Mol Cancer Res ; 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38847604

ABSTRACT

The blast crisis (BC) of chronic myeloid leukemia (CML) has poor efficacy against existing treatments and extremely short survival. However, the molecular mechanism of CML-chronic phase (CP) transformation to CML-BC is not yet fully understood. Here, we show that Lin28B, a RNA binding protein, acted as an activator enhancing the transformation to CML-BC by mediating excessive cell proliferation. The level of Lin28B expression was apparently elevated in CML-BC patients compared with newly diagnosed CML-CP patients. The overexpression of Lin28B promoted the proliferation of leukemia cells. Mechanistically, we identified Lin28B as a DNA binding protein by binding to the promoter region of miR-181d and upregulating its expression, which inhibited the expression of Programmed cell death 4 (PDCD4) by binding to the PDCD4 3'UTR region, thereby enhancing the proliferation of CML cells. Overall, the "Lin28B-miR-181d-PDCD4" regulatory axis promoted CML blast crisis. Implications: Our findings highlight the oncogenic role of Lin28B in CML blast crisis, acting as a DNA binding protein which transcriptionally upregulates miR-181d expression.

4.
Medicine (Baltimore) ; 103(24): e38458, 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38875399

ABSTRACT

Increasing evidence has underscored the role of long noncoding RNAs (lncRNAs) make up the major proportion of the competing endogenous RNAs (ceRNAs) network and can regulate gene expression by competitively binding to miRNAs in the development and progression of tumors. Nevertheless, the role of lncRNA-mediated ceRNAs in gastric cancer (GC) and their regulatory mechanisms have not been elucidated to some extent. This study is aimed at constructing a prognostic risk model for GC based on lncRNAs. A TCGA (The Cancer Genome Atlas) dataset was analyzed using edgeR to identify differentially expressed lncRNAs (DElncRNAs) in GC tissues vs normal tissues. Subsequently, DElncRNAs that could predict GC prognosis were determined using a training set. A prognostic risk model based on the DElncRNAs was then constructed. The performance of the model was tested using a test set. The functions of these lncRNAs in GC were investigated using a lncRNA-miRNA-mRNA network. Analysis of lncRNA expression in 407 TCGA GC cases identified 3 lncRNAs that significantly correlated with prognosis. GC cases with high-risk scores showed markedly poor prognosis relative to those with low-risk scores in both the training and test sets. Univariate and multivariate Cox regression analysis of the relationship between various clinical features and prognosis found that these lncRNAs and stage significantly correlated with GC prognosis. A lncRNA-miRNA-mRNA network based on 3 lncRNAs and functional enrichment analysis of interacting mRNA indicated that these genes are enriched in various intracellular receptor signaling pathways, including regulation of muscle system process, and protein deubiquitylation. The current study provides novel insights into the lncRNA-related ceRNA network in GC and sheds lights on underlying 3 lncRNA biomarkers may be independent prognostic signatures in predicting the survival of GC patients.


Subject(s)
RNA, Long Noncoding , Stomach Neoplasms , Humans , Stomach Neoplasms/genetics , Stomach Neoplasms/mortality , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Prognosis , Male , Female , Middle Aged , MicroRNAs/genetics , MicroRNAs/metabolism , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Gene Expression Regulation, Neoplastic , RNA, Messenger/metabolism , RNA, Messenger/genetics , Gene Regulatory Networks , Aged , RNA, Competitive Endogenous
5.
Ren Fail ; 46(2): 2365396, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38874150

ABSTRACT

OBJECTIVE: The aim of this study was to investigate the potential importance of complement system activation, with particular emphasis on the complement alternative pathway (AP), in the pathogenesis of hypertensive renal damage. METHODS: Serum complement C3, complement Factor H (CFH) and AP activation were assessed in 66 participants with established essential hypertension with renal damage (RD). Fifty-nine patients with age- and sex-matched essential hypertension without renal damage (NRD) and 58 healthy participants (normal) were selected. RESULTS: Our study revealed that C3 and AP50 continuously increased from normal to NRD to RD (p < 0.05, respectively), while CFH was significantly lower than that in NRD and healthy participants (p < 0.05, respectively). After multifactorial logistic regression analysis corrected for confounders, elevated serum C3 (p = 0.001) and decreased CFH (p < 0.001) were found to be independent risk factors for hypertension in healthy participants; elevated serum C3 (p = 0.034), elevated AP50 (p < 0.001), decreased CFH (p < 0.001), increased age (p = 0.011) and increased BMI (p = 0.013) were found to be independent risk factors for the progression of hypertension to hypertensive renal damage; elevated serum C3 (p = 0.017), elevated AP50 (p = 0.023), decreased CFH (p = 0.005) and increased age (p = 0.041) were found to be independent risk factors for the development of hypertensive renal damage in healthy participants. CONCLUSION: Abnormal activation of complement, particularly complement AP, may be a risk factor for the development and progression of hypertensive renal damage.


Subject(s)
Complement C3 , Complement Factor H , Humans , Male , Female , Middle Aged , Case-Control Studies , Complement C3/metabolism , Complement C3/analysis , Risk Factors , Aged , Adult , Hypertension/complications , Hypertension/blood , Complement Activation , Essential Hypertension/blood , Essential Hypertension/complications , Essential Hypertension/physiopathology , Logistic Models , Complement Pathway, Alternative , Disease Progression
6.
J Agric Food Chem ; 72(21): 12003-12013, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38748811

ABSTRACT

Insect gustatory receptors (GRs) aid in the precise identification of deterrent or stimulant compounds associated with food, mating, and egg-laying. Thus, they are promising targets for developing efficient insecticides. Here, 61 GRs in the chemosensory organs of Spodoptera litura larvae and adults were identified. Among them, SlitGR206 exhibited larval labium (LL)-specific expression characteristics. To explore the role of SlitGR206, a bacterial expression system was established to produce high-quality double-stranded RNA (dsRNA) and suppress SlitGR206 expression in LL. Subsequent behavioral assessments revealed that SlitGR206 silencing influenced larval feeding preferences and absorption. Moreover, it was found to reduce the ability of larvae to forage the five crucial host odorants. These findings demonstrate that SlitGR206 likely plays an indirect regulatory role in host recognition, consequently affecting foraging behavior. This provides a crucial foundation for the analysis of functional diversity among insect GRs and the precise development of nucleic acid pesticides in the future.


Subject(s)
Feeding Behavior , Insect Proteins , Larva , Spodoptera , Animals , Spodoptera/metabolism , Spodoptera/physiology , Spodoptera/genetics , Spodoptera/growth & development , Larva/metabolism , Larva/growth & development , Larva/physiology , Insect Proteins/metabolism , Insect Proteins/genetics , Receptors, Cell Surface/metabolism , Receptors, Cell Surface/genetics
7.
Front Oncol ; 14: 1374278, 2024.
Article in English | MEDLINE | ID: mdl-38756651

ABSTRACT

Objective: In physical health examinations, breast sonography is a commonly used imaging method, but it can lead to repeated exams and unnecessary biopsy due to discrepancies among radiologists and health centers. This study explores the role of off-the-shelf artificial intelligence (AI) software in assisting radiologists to classify incidentally found breast masses in two health centers. Methods: Female patients undergoing breast ultrasound examinations with incidentally discovered breast masses were categorized according to the 5th edition of the Breast Imaging Reporting and Data System (BI-RADS), with categories 3 to 5 included in this study. The examinations were conducted at two municipal health centers from May 2021 to May 2023.The final pathological results from surgical resection or biopsy served as the gold standard for comparison. Ultrasonographic images were obtained in longitudinal and transverse sections, and two junior radiologists and one senior radiologist independently assessed the images without knowing the pathological findings. The BI-RADS classification was adjusted following AI assistance, and diagnostic performance was compared using receiver operating characteristic curves. Results: A total of 196 patients with 202 breast masses were included in the study, with pathological results confirming 107 benign and 95 malignant masses. The receiver operating characteristic curve showed that experienced breast radiologists had higher diagnostic performance in BI-RADS classification than junior radiologists, similar to AI classification (AUC = 0.936, 0.806, 0.896, and 0.950, p < 0.05). The AI software improved the accuracy, sensitivity, and negative predictive value of the adjusted BI-RADS classification for the junior radiologists' group (p< 0.05), while no difference was observed in the senior radiologist group. Furthermore, AI increased the negative predictive value for BI-RADS 4a masses and the positive predictive value for 4b masses among radiologists (p < 0.05). AI enhances the sensitivity of invasive breast cancer detection more effectively than ductal carcinoma in situ and rare subtypes of breast cancer. Conclusions: The AI software enhances diagnostic efficiency for breast masses, reducing the performance gap between junior and senior radiologists, particularly for BI-RADS 4a and 4b masses. This improvement reduces unnecessary repeat examinations and biopsies, optimizing medical resource utilization and enhancing overall diagnostic effectiveness.

8.
BMC Cancer ; 24(1): 559, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38702644

ABSTRACT

In contrast to the decreasing trends in developed countries, the incidence and mortality rates of cervical squamous cell carcinoma in China have increased significantly. The screening and identification of reliable biomarkers and candidate drug targets for cervical squamous cell carcinoma are urgently needed to improve the survival rate and quality of life of patients. In this study, we demonstrated that the expression of MUC1 was greater in neoplastic tissues than in non-neoplastic tissues of the cervix, and cervical squamous cell carcinoma patients with high MUC1 expression had significantly worse overall survival than did those with low MUC1 expression, indicating its potential for early diagnosis of cervical squamous cell carcinoma. Next, we explored the regulatory mechanism of MUC1 in cervical squamous cell carcinoma. MUC1 could upregulate ITGA2 and ITGA3 expression via ERK phosphorylation, promoting the proliferation and metastasis of cervical cancer cells. Further knockdown of ITGA2 and ITGA3 significantly inhibited the tumorigenesis of cervical cancer cells. Moreover, we designed a combination drug regimen comprising MUC1-siRNA and a novel ERK inhibitor in vivo and found that the combination of these drugs achieved better results in animals with xenografts than did MUC1 alone. Overall, we discovered a novel regulatory pathway, MUC1/ERK/ITGA2/3, in cervical squamous cell carcinoma that may serve as a potential biomarker and therapeutic target in the future.


MUC1 is overexpressed in cervical squamous cell carcinoma. MUC1 regulates ERK phosphorylation, and subsequently upregulates ITGA2 and ITGA3 expression to promote tumorigenesis in cervical squamous cell carcinoma. A combination drug regimen targeting MUC1 and ERK achieved better results compared than MUC1 alone.


Subject(s)
Carcinoma, Squamous Cell , Cell Proliferation , Integrin alpha2 , Integrin alpha3 , Mucin-1 , Uterine Cervical Neoplasms , Humans , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/metabolism , Uterine Cervical Neoplasms/drug therapy , Female , Integrin alpha2/metabolism , Integrin alpha2/genetics , Animals , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/drug therapy , Mucin-1/metabolism , Mucin-1/genetics , Mice , Phosphorylation , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Xenograft Model Antitumor Assays , MAP Kinase Signaling System , Mice, Nude , Extracellular Signal-Regulated MAP Kinases/metabolism
9.
Crit Rev Food Sci Nutr ; : 1-23, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38821105

ABSTRACT

Edible mushroom polysaccharides (EMPs) as a natural macromolecular carbohydrate have a very complex structure and composition. EMPs are considered ideal candidates for developing healthy products and functional foods and have received significant research attention due to their unique physiological activities such as immunomodulatory, anti-inflammatory, anti-tumor/cancer, gut microbiota regulation, metabolism improvement, and nervous system protection. The structure and monosaccharide composition of edible mushroom polysaccharides have an unknown relationship with their functional activity, which has not been widely studied. Therefore, we summarized the preparation techniques of EMPs and discussed the association between functional activity, preparation methods, structure and composition of EMPs, laying a theoretical foundation for the personalized nutritional achievements of EMP. We also establish the foundation for the further investigation and application of EMPs as novel functional foods and healthy products.

11.
Eur J Med Chem ; 274: 116532, 2024 Aug 05.
Article in English | MEDLINE | ID: mdl-38805937

ABSTRACT

Histone H3 lysine 36 (H3K36) methylation is a typical epigenetic histone modification that is involved in various biological processes such as DNA transcription, repair and recombination in vivo. Mutations, translocations, and aberrant gene expression associated with H3K36 methyltransferases have been implicated in different malignancies such as acute myeloid leukemia, lung cancer, multiple myeloma, and others. Herein, we provided a comprehensive overview of the latest advances in small molecule inhibitors targeting H3K36 methyltransferases. We analyzed the structures and biological functions of the H3K36 methyltransferases family members. Additionally, we discussed the potential directions for future development of inhibitors targeting H3K36 methyltransferases.


Subject(s)
Antineoplastic Agents , Enzyme Inhibitors , Histone-Lysine N-Methyltransferase , Neoplasms , Humans , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Histone-Lysine N-Methyltransferase/antagonists & inhibitors , Histone-Lysine N-Methyltransferase/metabolism , Neoplasms/drug therapy , Neoplasms/pathology , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/chemical synthesis , Histones/metabolism , Molecular Structure , Animals
12.
Leuk Res ; 142: 107507, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38692191

ABSTRACT

PURPOSE: To assess the real-world efficacy and safety of flumatinib as first-line and post-line treatments for chronic myeloid leukemia in the chronic phase (CML-CP). RESULTS: Among 141 patients receiving flumatinib as first-line and post-line treatment, the 12-month major molecular response (MMR) rates were 69.4% and 67.6%, respectively. The median time to response was 6 and 10.5 months, respectively. In post-line treatment, the early molecular response (EMR) of flumatinib as second-line is significantly superior to that of third-line treatment (3-month EMR rate: 79.2% vs. 39.3%, P<0.001; 3-month MMR rate: 45.8% vs. 21.4%, P=0.033). Contrastively, patients who switched to flumatinib due to intolerance had significantly higher MMR rates at 3, 6, and 12 months compared to patients who switched due to inadequate response (60.6% vs. 24.2%, P=0.003; 66.7% vs. 36.0%, P=0.027; 84.2% vs. 50.0%, P=0.038). Premature drug discontinuation was observed in 28.4% of the patients. Grades 3-4 hematologic adverse events (AEs) were identified as independent risk factors for premature drug discontinuation. Patients who discontinued treatment and those who previously received only imatinib therapy had a poorer molecular response and failure-free survival. CONCLUSIONS: Flumatinib demonstrates favorable efficacy and safety. Treatment discontinuation can result in a poorer molecular response and long-term prognosis.


Subject(s)
Aminopyridines , Humans , Female , Male , Middle Aged , Retrospective Studies , Aged , Adult , Aminopyridines/adverse effects , Aminopyridines/administration & dosage , Aminopyridines/therapeutic use , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Benzamides/adverse effects , Benzamides/therapeutic use , Young Adult , Aged, 80 and over , Treatment Outcome , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Protein Kinase Inhibitors/adverse effects , Protein Kinase Inhibitors/therapeutic use , Protein Kinase Inhibitors/administration & dosage , Survival Rate
13.
Nano Lett ; 24(15): 4571-4579, 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38565076

ABSTRACT

Efficient pure-red emission light-emitting diodes (LEDs) are essential for high-definition displays, yet achieving pure-red emission is hindered by challenges like phase segregation and spectral instability when using halide mixing. Additionally, strongly confined quantum dots (QDs) produced through traditional hot-injection methods face byproduct contamination due to poor solubility of metal halide salts in the solvent octadecene (ODE) at low temperatures. Herein, we introduced a novel method using a benzene-series strongly electrostatic potential solvent instead of ODE to prevent PbI2 intermediates and promote their dissolution into [PbI3]-. Increasing methyl groups on benzene yields precisely sized (4.4 ± 0.1 nm) CsPbI3 QDs with exceptional properties: a narrow 630 nm PL peak with photoluminescence quantum yield (PLQY) of 97%. Sequential ligand post-treatment optimizes optical and electrical performance of QDs. PeLEDs based on optimized QDs achieve pure-red EL (CIE: 0.700, 0.290) approaching Rec. 2020 standards, with an EQE of 25.2% and T50 of 120 min at initial luminance of 107 cd/m2.

14.
Pestic Biochem Physiol ; 201: 105874, 2024 May.
Article in English | MEDLINE | ID: mdl-38685243

ABSTRACT

In insects, chemosensory proteins (CSPs) play an important role in the perception of the external environment and have been widely used for protein-binding characterization. Riptortus pedestris has received increased attention as a potential cause of soybean staygreen syndrome in recent years. In this study, we found that RpedCSP4 expression in the antennae of adult R. pedestris increased with age, with no significant difference in expression level observed between males and females, as determined through quantitative real-time polymerase chain reaction (qRT-PCR). Subsequently, we investigated the ability of RpedCSP4 to bind various ligands (five aggregated pheromone components and 13 soybean volatiles) using a prokaryotic expression system and fluorescence competitive binding assays. We found that RpedCSP4 binds to three aggregated pheromone components of R. pedestris, namely, ((E)-2-hexenyl (Z)-3-hexenoate (E2Z3), (E)-2-hexenyl (E)-2-hexenoate (E2E2), and (E)-2-hexenyl hexenoate (E2HH)), and that its binding capacities are most stable under acidic condition. Finally, the structure and protein-ligand interactions of RpedCSP4 were further analyzed via homology modeling, molecular docking, and targeted mutagenesis experiments. The L29A mutant exhibited a loss of binding ability to these three aggregated pheromone components. Our results show that the olfactory function of RpedCSP4 provides new insights into the binding mechanism of RpedCSPs to aggregation pheromones and contributes to discover new target candidates that will provide a theoretical basis for future population control of R. pedestris.


Subject(s)
Insect Proteins , Pheromones , Animals , Pheromones/metabolism , Insect Proteins/metabolism , Insect Proteins/genetics , Insect Proteins/chemistry , Male , Female , Protein Binding , Heteroptera/metabolism , Heteroptera/genetics
15.
Mikrochim Acta ; 191(5): 231, 2024 04 03.
Article in English | MEDLINE | ID: mdl-38565795

ABSTRACT

Blood stasis syndrome (BSS) has persistent health risks; however, its pathogenesis remains elusive. This obscurity may result in missed opportunities for early intervention, increased susceptibility to chronic diseases, and reduced accuracy and efficacy of treatments. Metabolomics, employing the matrix-assisted laser desorption/ionization (MALDI) strategy, presents distinct advantages in biomarker discovery and unraveling molecular mechanisms. Nonetheless, the challenge is to develop efficient matrices for high-sensitivity and high-throughput analysis of diverse potential biomarkers in complex biosamples. This work utilized nitrogen-doped porous transition metal carbides and nitrides (NP-MXene) as a MALDI matrix to delve into the molecular mechanisms underlying BSS pathogenesis. Structural optimization yielded heightened peak sensitivity (by 1.49-fold) and increased peak numbers (by 1.16-fold) in clinical biosamples. Validation with animal models and clinical serum biosamples revealed significant differences in metabolic fingerprints between BSS and control groups, achieving an overall diagnostic efficacy of 0.905 (95% CI, 0.76-0.979). Prostaglandin F2α was identified as a potential biomarker (diagnostics efficiency of 0.711, specificity = 0.7, sensitivity = 0.6), and pathway enrichment analysis disclosed disruptions in arachidonic acid metabolism in BSS. This innovative approach not only advances comprehension of BSS pathogenesis, but also provides valuable insights for personalized treatment and diagnostic precision.


Subject(s)
Drugs, Chinese Herbal , Animals , Dinoprost , Feedback , Nitrogen , Porosity , Organic Chemicals , Biomarkers
16.
Infect Agent Cancer ; 19(1): 12, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38622727

ABSTRACT

Little is known about the outcome for HIV-associated Hodgkin lymphoma (HIV-HL) as this is less common than HIV-negative lymphoma. Therefore, we performed a multi-center study to analyze the clinical characteristics and outcomes of HIV-HL patients in China. Nineteen cases of HIV-HL were diagnosed and treated at three center and including the sixth people's hospital of Zhengzhou, Peking union medical college hospital, and Chongqing university cancer hospital, between December 2013 and June 2022. Data on the clinical features, laboratory results, response, and prognosis were collected and analyzed. The median age at diagnosis was 43(22-74) years. All patients were infected with HIV through sexual transmission, with ten cases transmitted through man having sex with man (MSM) and nine cases transmitted through heterosexual transmission. Seven patients were diagnosed with lymphoma and found to be infected with HIV. Four cases were in stage III, and fifteen cases were in stage IV. After a median follow up of 46.8(4.0-112.9) months, 17 cases were alive after ABVD regimen chemotherapy combined with combination antiretroviral therapy (cART). The 5-year progression-free survival (PFS) and overall survival (OS) rate were 83.9% and 89.5%,respectively. HIV-HL exhibits an invasive process in clinical practice, and cART combined with ABVD regimen chemotherapy can achieve long-term survival for patients.

17.
Phys Chem Chem Phys ; 26(11): 8945-8951, 2024 Mar 13.
Article in English | MEDLINE | ID: mdl-38436414

ABSTRACT

Two-dimensional (2D) valley materials are promising materials for writing and storing information. The search for 2D materials with large valley splitting is essential for the development of spintronics and valley electronics. In this study, we theoretically design 2D W2NSCl MXenes with large valley splitting based on first-principle calculations. Due to the strong spin-orbit coupling (SOC) and the broken inversion symmetry, the W2NSCl monolayer exhibits valley splitting values of 491 meV and 83 meV at K/K' of the valence and conduction bands, respectively. The valley splitting of W2NSCl is robust to biaxial strain. Because of the broken mirror symmetry of W2NSCl, there is a Rashba effect at Γ with a Rashba parameter of 1.019 V Å. Based on the maximum localization of the Wannier function, we found the non-zero Berry curvature at K/K'. Furthermore, the non-zero Berry curvature at the K/K' valley increases monotonically with an external strain from -4% to 4%. Our finding shows that W2NSCl is a candidate material for valley electronics and spintronics applications.

18.
Biomed Pharmacother ; 173: 116344, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38412716

ABSTRACT

BACKGROUND: Depression is closely linked to an imbalance in the autonomic nervous system (ANS). However, the role of this imbalance in mediating the effects of sleep deprivation (SD) and vagus nerve stimulation (VNS) on emotional well-being is not fully understood. METHODS: A population-based analysis was conducted to explore the relationship between sleep duration, depression scores, and heart rate variability (HRV). Additionally, the chronic SD mouse model was established to assess the impact of preventive transcutaneous auricular VNS (taVNS) on pathological and behavioral changes. RESULTS: Our study found a significant link between sleep duration, depression severity, and HRV. Shorter sleep duration was associated with higher depression scores and lower RMSSD (a measure of HRV). In our rat model, insufficient sleep consistently impaired HRV. This effect was mitigated by taVNS, accompanied by corresponding changes in levels of IL-1ß and IL-6, astrocyte and microglia activation, and tail suspension times. CONCLUSIONS: Using VNS as a preventive treatment for depression-risk individuals with insufficient sleep shows promise. It not only broadens the potential applications of VNS but also sheds light on its mechanism-particularly its role in enhancing vagal nerve function and balancing the ANS, as evidenced by HRV measurements.


Subject(s)
Sleep Deprivation , Vagus Nerve Stimulation , Mice , Rats , Animals , Depression/prevention & control , Autonomic Nervous System , Time Factors
19.
Front Mol Biosci ; 11: 1297437, 2024.
Article in English | MEDLINE | ID: mdl-38384498

ABSTRACT

Atherosclerosis is a complex vascular disorder characterized by the deposition of lipids, inflammatory cascades, and plaque formation in arterial walls. A thorough understanding of its causes and progression is necessary to develop effective diagnostic and therapeutic strategies. Recent breakthroughs in metabolomics have provided valuable insights into the molecular mechanisms and genetic factors involved in atherosclerosis, leading to innovative approaches for preventing and treating the disease. In our study, we analyzed clinical serum samples from both atherosclerosis patients and animal models using laser desorption ionization mass spectrometry. By employing methods such as orthogonal partial least-squares discrimination analysis (OPLS-DA), heatmaps, and volcano plots, we can accurately classify atherosclerosis (AUC = 0.892) and identify key molecules associated with the disease. Specifically, we observed elevated levels of arachidonic acid and its metabolite, leukotriene B4, in atherosclerosis. By inhibiting arachidonic acid and monitoring its downstream metabolites, we discovered the crucial role of this metabolic pathway in regulating atherosclerosis. Metabolomic research provides detailed insights into the metabolic networks involved in atherosclerosis development and reveals the close connection between abnormal metabolism and the disease. These studies offer new possibilities for precise diagnosis, treatment, and monitoring of disease progression, as well as evaluating the effectiveness of therapeutic interventions.

20.
Food Sci Nutr ; 12(2): 1318-1329, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38370047

ABSTRACT

Pleurotus eryngii polysaccharides (PEPs) have been proven to display multiple activities through digestive system action, from which the digestion products should first interact with intestinal mucus (MUC), followed by the function of intestinal cells. Hence, possible interacting characterizations between MUC and in vitro simulated digestion products of P. eryngii polysaccharides (DPEPs) and PEP were carried out in the present study. Results showed that both PEP and DPEP could significantly interact with MUC. Moreover, digestion can modify the interaction between polysaccharides and MUC; the degree of interaction also changes with time incrementing. Viscosity could be decreased after digesting. According to the zeta potential and stability analysis result, the digestive behavior could be regular and stable between polysaccharides and MUC interactions. Following fluorescence and infrared spectra, the structure of polysaccharides and mucin might be changed by digestion between polysaccharides and MUC. The study indicates that the interaction formed between DPEP and MUC might indirectly impact the exercise and immune activities of polysaccharides and influence the transportation of other nutrients. Overall, our results, the absorption and transport pathways of PEP, can be initially revealed and may provide a novel research viewpoint on the active mechanism of PEP in the intestinal tract.

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