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1.
J Imaging Inform Med ; 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38844718

ABSTRACT

This study aims to investigate the feasibility of preoperatively predicting histological subtypes of pituitary neuroendocrine tumors (PitNETs) using machine learning and radiomics based on multiparameter MRI. Patients with PitNETs from January 2016 to May 2022 were retrospectively enrolled from four medical centers. A cfVB-Net network was used to automatically segment PitNET multiparameter MRI. Radiomics features were extracted from the MRI, and the radiomics score (Radscore) of each patient was calculated. To predict histological subtypes, the Gaussian process (GP) machine learning classifier based on radiomics features was performed. Multi-classification (six-class histological subtype) and binary classification (PRL vs. non-PRL) GP model was constructed. Then, a clinical-radiomics nomogram combining clinical factors and Radscores was constructed using the multivariate logistic regression analysis. The performance of the models was evaluated using receiver operating characteristic (ROC) curves. The PitNET auto-segmentation model eventually achieved the mean Dice similarity coefficient of 0.888 in 1206 patients (mean age 49.3 ± SD years, 52% female). In the multi-classification model, the GP of T2WI got the best area under the ROC curve (AUC), with 0.791, 0.801, and 0.711 in the training, validation, and external testing set, respectively. In the binary classification model, the GP of T2WI combined with CE T1WI demonstrated good performance, with AUC of 0.936, 0.882, and 0.791 in training, validation, and external testing sets, respectively. In the clinical-radiomics nomogram, Radscores and Hardy' grade were identified as predictors for PRL expression. Machine learning and radiomics analysis based on multiparameter MRI exhibited high efficiency and clinical application value in predicting the PitNET histological subtypes.

2.
J Transl Med ; 22(1): 537, 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38844969

ABSTRACT

Accumulating evidence indicated that HHEX participated in the initiation and development of several cancers, but the potential roles and mechanisms of HHEX in hepatocellular carcinoma (HCC) were largely unclear. Cancer stem cells (CSCs) are responsible for cancer progression owing to their stemness characteristics. We reported that HHEX was a novel CSCs target for HCC. We found that HHEX was overexpressed in HCC tissues and high expression of HHEX was associated with poor survival. Subsequently, we found that HHEX promoted HCC cell proliferation, migration, and invasion. Moreover, bioinformatics analysis and experiments verified that HHEX promoted stem cell-like properties in HCC. Mechanistically, ABI2 serving as a co-activator of transcriptional factor HHEX upregulated SLC17A9 to promote HCC cancer stem cell-like properties and tumorigenesis. Collectively, the HHEX-mediated ABI2/SLC17A9 axis contributes to HCC growth and metastasis by maintaining the CSC population, suggesting that HHEX serves as a promising therapeutic target for HCC treatment.


Subject(s)
Carcinogenesis , Carcinoma, Hepatocellular , Cell Proliferation , Liver Neoplasms , Neoplastic Stem Cells , Humans , Neoplastic Stem Cells/pathology , Neoplastic Stem Cells/metabolism , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/metabolism , Liver Neoplasms/pathology , Liver Neoplasms/genetics , Liver Neoplasms/metabolism , Carcinogenesis/pathology , Animals , Cell Line, Tumor , Transcription Factors/metabolism , Transcription Factors/genetics , Gene Expression Regulation, Neoplastic , Cell Movement , Male , Neoplasm Invasiveness , Signal Transduction , Adaptor Proteins, Signal Transducing/metabolism , Adaptor Proteins, Signal Transducing/genetics , Mice, Nude , Female , Neoplasm Metastasis
3.
Front Public Health ; 12: 1308867, 2024.
Article in English | MEDLINE | ID: mdl-38832225

ABSTRACT

Background: Perinatal depression affects the physical and mental health of pregnant women. It also has a negative effect on children, families, and society, and the incidence is high. We constructed a cost-utility analysis model for perinatal depression screening in China and evaluated the model from the perspective of health economics. Methods: We constructed a Markov model that was consistent with the screening strategy for perinatal depression in China, and two screening strategies (screening and non-screening) were constructed. Each strategy was set as a cycle of 3 months, corresponding to the first trimester, second trimester, third trimester, and postpartum. The state outcome parameters required for the model were obtained based on data from the National Prospective Cohort Study on the Mental Health of Chinese Pregnant Women from August 2015 to October 2016. The cost parameters were obtained from a field investigation on costs and screening effects conducted in maternal and child health care institutions in 2020. The cost-utility ratio and incremental cost-utility ratio of different screening strategies were obtained by multiplicative analysis to evaluate the health economic value of the two screening strategies. Finally, deterministic and probabilistic sensitivity analyses were conducted on the uncertain parameters in the model to explore the sensitivity factors that affected the selection of screening strategies. Results: The cost-utility analysis showed that the per capita cost of the screening strategy was 129.54 yuan, 0.85 quality-adjusted life years (QALYs) could be obtained, and the average cost per QALY gained was 152.17 yuan. In the non-screening (routine health care) group, the average cost was 171.80 CNY per person, 0.84 QALYs could be obtained, and the average cost per QALY gained was 205.05 CNY. Using one gross domestic product per capita in 2021 as the willingness to pay threshold, the incremental cost-utility ratio of screening versus no screening (routine health care) was about -3,126.77 yuan, which was lower than one gross domestic product per capita. Therefore, the screening strategy was more cost-effective than no screening (routine health care). Sensitivity analysis was performed by adjusting the parameters in the model, and the results were stable and consistent, which did not affect the choice of the optimal strategy. Conclusion: Compared with no screening (routine health care), the recommended perinatal depression screening strategy in China is cost-effective. In the future, it is necessary to continue to standardize screening and explore different screening modalities and tools suitable for specific regions.


Subject(s)
Cost-Benefit Analysis , Decision Trees , Depression , Markov Chains , Mass Screening , Humans , Female , Pregnancy , China , Mass Screening/economics , Depression/diagnosis , Depression/economics , Prospective Studies , Pregnancy Complications/diagnosis , Pregnancy Complications/economics , Adult , Quality-Adjusted Life Years
4.
Cancer Immunol Immunother ; 73(8): 150, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38832948

ABSTRACT

Hotspot driver mutations presented by human leukocyte antigens might be recognized by anti-tumor T cells. Based on their advantages of tumor-specificity and immunogenicity, neoantigens derived from hotspot mutations, such as PIK3CAH1047L, may serve as emerging targets for cancer immunotherapies. NetMHCpan V4.1 was utilized for predicting neoepitopes of PIK3CA hotspot mutation. Using in vitro stimulation, antigen-specific T cells targeting the HLA-A*11:01-restricted PIK3CA mutation were isolated from healthy donor-derived peripheral blood mononuclear cells. T cell receptors (TCRs) were cloned using single-cell PCR and sequencing. Their functionality was assessed through T cell activation markers, cytokine production and cytotoxic response to cancer cell lines pulsed with peptides or transduced genes of mutant PIK3CA. Immunogenic mutant antigens from PIK3CA and their corresponding CD8+ T cells were identified. These PIK3CA mutation-specific CD8+ T cells were subsequently enriched, and their TCRs were isolated. The TCR clones exhibited mutation-specific and HLA-restricted reactivity, demonstrating varying degrees of functional avidity. Identified TCR genes were transferred into CD8+ Jurkat cells and primary T cells deficient of endogenous TCRs. TCR-expressing cells demonstrated specific recognition and reactivity against the PIK3CAH1047L peptide presented by HLA-A*11:01-expressing K562 cells. Furthermore, mutation-specific TCR-T cells demonstrated an elevation in cytokine production and profound cytotoxic effects against HLA-A*11:01+ malignant cell lines harboring PIK3CAH1047L. Our data demonstrate the immunogenicity of an HLA-A*11:01-restricted PIK3CA hotspot mutation and its targeting therapeutic potential, together with promising candidates of TCR-T cell therapy.


Subject(s)
Class I Phosphatidylinositol 3-Kinases , Mutation , Neoplasms , Receptors, Antigen, T-Cell , Humans , Class I Phosphatidylinositol 3-Kinases/genetics , Class I Phosphatidylinositol 3-Kinases/immunology , Receptors, Antigen, T-Cell/immunology , Receptors, Antigen, T-Cell/genetics , Neoplasms/immunology , Neoplasms/therapy , Neoplasms/genetics , Immunotherapy/methods , HLA-A11 Antigen/genetics , HLA-A11 Antigen/immunology , CD8-Positive T-Lymphocytes/immunology , Epitopes, T-Lymphocyte/immunology , Epitopes, T-Lymphocyte/genetics , Antigens, Neoplasm/immunology , Antigens, Neoplasm/genetics , Cell Line, Tumor
5.
Front Microbiol ; 15: 1376144, 2024.
Article in English | MEDLINE | ID: mdl-38841056

ABSTRACT

Low-level viremia (LLV) ranging from 50 to 1,000 copies/ml is common in most HIV-1-infected patients receiving antiretroviral therapy (ART). However, the source of LLV and the impact of LLV on the HIV-1 reservoir during ART remain uncertain. We hypothesized that LLV may arise from the HIV reservoir and its occurrence affect the composition of the reservoir after LLV episodes. Accordingly, we investigated the genetic linkage of sequences obtained from plasma at LLV and pre-ART time points and from peripheral blood mononuclear cells (PBMCs) at pre-ART, pre-LLV, LLV, and post-LLV time points. We found that LLV sequences were populated with a predominant viral quasispecies that accounted for 67.29%∼100% of all sequences. Two episodes of LLV in subject 1, spaced 6 months apart, appeared to have originated from the stochastic reactivation of latently HIV-1-infected cells. Moreover, 3.77% of pre-ART plasma sequences were identical to 67.29% of LLV-3 plasma sequences in subject 1, suggesting that LLV may have arisen from a subset of cells that were infected before ART was initiated. No direct evidence of sequence linkage was found between LLV viruses and circulating cellular reservoirs in all subjects. The reservoir size, diversity, and divergence of the PBMC DNA did not differ significantly between the pre- and post-LLV sampling points (P > 0.05), but the composition of viral reservoir quasispecies shifted markedly before and after LLV episodes. Indeed, subjects with LLV had a higher total PBMC DNA level, greater viral diversity, a lower proportion of variants with identical sequences detected at two or more time points, and a shorter variant duration during ART compared with subjects without LLV. Overall, our findings suggested that LLV viruses may stem from an unidentified source other than circulating cellular reservoirs. LLV episodes may introduce great complexity into the HIV reservoir, which brings challenges to the development of treatment strategies.

6.
J Drug Target ; : 1-58, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38832845

ABSTRACT

The use of reactive oxygen species (ROS) to target cancer cells has become a hot topic in tumor therapy. Although ROS has strong cytotoxicity against tumor cells, the key issue currently is how to generate a large amount of ROS within tumor cells. Organic/inorganic hybrid nanoreactor materials combine the advantages of organic and inorganic components and can amplify cancer treatment by increasing targeting and material self-action. The multifunctional organic/inorganic hybrid nanoreactor is helpful to overcome the shortcomings of current reactive oxygen species in cancer treatment. It can realize the combination of in situ dynamic therapy and immunotherapy strategies, and has a synergistic anti-tumor effect. This paper reviews the research progress of organic/inorganic hybrid nanoreactor materials using tumor components to amplify reactive oxygen species for cancer treatment.The article reviews the tumor treatment strategies of nanohybrids from the perspectives of cancer cells, immune cells, tumor microenvironment, as well as 3D printing and electrospinning techniques, which are different from traditional nanomaterial technologies, and will arouse interest among scientists in tumor therapy and nanomedicine.

7.
Drug Deliv ; 31(1): 2354687, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38823413

ABSTRACT

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-associated death worldwide. Beside early detection, early diagnosis, and early surgery, it is urgent to try new strategies for the treatment of HCC. Triptolide (TPL) has been employed to treat HCC. However, its clinical applications were restricted by the narrow therapeutic window, severe toxicity, and poor water-solubility. In this study, we developed cancer cell membrane-camouflaged biomimetic PLGA nanoparticles loading TPL (TPL@mPLGA) with the homologous targeting property for the treatment of HCC. The TPL@mPLGA was successfully prepared with particle size of 195.5 ± 7.5 nm and zeta potential at -21.5 ± 0.2 mV with good stability. The drug loading (DL) of TPL@mPLGA was 2.94%. After Huh-7 cell membrane coating, the natural Huh-7 cell membrane proteins were found to be retained on TPL@mPLGA, thus endowing the TPL@mPLGA with enhanced accumulation at tumor site, and better anti-tumor activity in vitro and in vivo when compared with TPL or TPL@PLGA. The TPL@mPLGA showed enhanced anti-tumor effects and reduced toxicity of TPL, which could be adopted for the treatment of HCC.


Subject(s)
Carcinoma, Hepatocellular , Diterpenes , Epoxy Compounds , Liver Neoplasms , Nanoparticles , Phenanthrenes , Polylactic Acid-Polyglycolic Acid Copolymer , Diterpenes/administration & dosage , Diterpenes/pharmacology , Diterpenes/chemistry , Diterpenes/pharmacokinetics , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/pathology , Epoxy Compounds/chemistry , Epoxy Compounds/administration & dosage , Epoxy Compounds/pharmacology , Phenanthrenes/administration & dosage , Phenanthrenes/pharmacology , Phenanthrenes/chemistry , Phenanthrenes/pharmacokinetics , Liver Neoplasms/drug therapy , Liver Neoplasms/pathology , Humans , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Nanoparticles/chemistry , Animals , Cell Line, Tumor , Mice , Cell Membrane/drug effects , Particle Size , Drug Carriers/chemistry , Mice, Nude , Biomimetic Materials/chemistry , Biomimetic Materials/pharmacology , Mice, Inbred BALB C
8.
Sci Rep ; 14(1): 12659, 2024 06 03.
Article in English | MEDLINE | ID: mdl-38830942

ABSTRACT

Bladder carcinoma (BC) accounts for > 90% of all urothelial cancers. Pathological diagnosis through cytoscopic biopsy is the gold standard, whereas non-invasive diagnostic tools remain lacking. The "Atyp.C" parameter of the Sysmex UF-5000 urine particle analyzer represents the ratio of nucleus to cytoplasm and can be employed to detect urinary atypical cells. The present study examined the association between urinary Atyp.C values and BC risk. This two-center, retrospective case-control study identified clinical primary or newly recurrent BC (study period, 2022-2023; n = 473) cases together with controls with urinary tract infection randomly matched by age and sex (1:1). Urinary sediment differences were compared using non-parametric tests. The correlations between urinary Atyp.C levels and BC grade or infiltration were analyzed using Spearman's rank correlation. The BC risk factor odds ratio of Atyp.C was calculated using conditional logistic regression, and potential confounder effects were adjusted using stepwise logistic regression (LR). Primary risk factors were identified by stratified analysis according to pathological histological diagnosis. The mean value of urinary Atyp.C in BC cases (1.30 ± 3.12) was 8.7 times higher than that in the controls (0.15 ± 0.68; P < 0.001). Urinary Atyp.C values were positively correlated with BC pathological grade and invasion (r = 0.360, P < 0.001; r = 0.367, P < 0.001). Urinary Atyp.C was an independent risk factor for BC and closely related with BC pathological grade and invasion. Elevated urinary Atyp.C values was an independent risk factor for BC. Our findings support the use of Atyp.C as a marker that will potentially aid in the early diagnosis and long-term surveillance of new and recurrent BC cases.


Subject(s)
Urinary Bladder Neoplasms , Humans , Urinary Bladder Neoplasms/urine , Urinary Bladder Neoplasms/diagnosis , Urinary Bladder Neoplasms/pathology , Male , Female , Risk Factors , Aged , Middle Aged , Retrospective Studies , Case-Control Studies , Cell Nucleus
9.
Appl Opt ; 63(16): 4251, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38856600

ABSTRACT

This publisher's note serves to correct errors in Appl. Opt.63, 2528 (2024)APOPAI0003-693510.1364/AO.517400.

10.
Heliyon ; 10(11): e32133, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38868052

ABSTRACT

Carbon dots (CDs), as a new kind of fluorescent nanomaterials, show great potential for application in several fields due to their unique nano-size effect, easy surface functionalization, controllable photoluminescence, and excellent biocompatibility. Conventional preparation methods for CDs typically involve top-down and bottom-up approaches. Doping is a major step forward in CDs design methodology. Chemical doping includes both non-metal and metal doping, in which non-metal doping is an effective strategy for modulating the fluorescence properties of CDs and improving photocatalytic performance in several areas. In recent years, Metal-doped CDs have aroused the interest of academics as a promising nano-doping technique. This approach has led to improvements in the physicochemical and optical properties of CDs by altering their electron density distribution and bandgap capacity. Additionally, the issues of metal toxicity and utilization have been addressed to a large extent. In this review, we categorize metals into two major groups: transition group metals and rare-earth group metals, and an overview of recent advances in biomedical applications of these two categories, respectively. Meanwhile, the prospects and the challenges of metal-doped CDs for biomedical applications are reviewed and concluded. The aim of this paper is to break through the existing deficiencies of metal-doped CDs and fully exploit their potential. I believe that this review will broaden the insight into the synthesis and biomedical applications of metal-doped CDs.

11.
Opt Express ; 32(8): 13552-13561, 2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38859322

ABSTRACT

The effect of crystal-water contents on the optical properties and dielectric characteristics of calcium sulfate in the THz band is investigated. The complex dielectric constant and conductivity are analyzed using the Drude-Smith model. The refractive index and absorption coefficient are linearly increased with the content of crystal-water, and the corresponding linear fitting lines of R2 over 0.97 are obtained. The dielectric properties of calcium sulfate are significantly affected by the crystal-water content. These results indicate that a new method to quantitative measurement of the crystal-water content in hydrous minerals is provided.

12.
Opt Express ; 32(8): 14674-14684, 2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38859405

ABSTRACT

Miniature acoustic sensors with high sensitivity are highly desired for applications in medical photoacoustic imaging, acoustic communications and industrial nondestructive testing. However, conventional acoustic sensors based on piezoelectric, piezoresistive and capacitive detectors usually require a large element size on a millimeter to centimeter scale to achieve a high sensitivity, greatly limiting their spatial resolution and the application in space-confined sensing scenarios. Herein, by using single-crystal two-dimensional gold flakes (2DGFs) as the sensing diaphragm of an extrinsic Fabry-Perot interferometer on a fiber tip, we demonstrate a miniature optical acoustic sensor with high sensitivity. Benefiting from the ultrathin thickness (∼8 nm) and high reflectivity of the 2DGF, the fiber-tip acoustic sensor gives an acoustic pressure sensitivity of ∼300 mV/Pa in the frequency range from 100 Hz to 20 kHz. The noise-equivalent pressure of the fiber-tip acoustic sensor at the frequency of 13 kHz is as low as 62.8 µPa/Hz1/2, which is one or two orders of magnitude lower than that of reported optical acoustic sensors with the same size.

13.
Article in English | MEDLINE | ID: mdl-38837929

ABSTRACT

Mining discriminative graph topological information plays an important role in promoting graph representation ability. However, it suffers from two main issues: (1) the difficulty/complexity of computing global inter-class/intra-class scatters, commonly related to mean and covariance of graph samples, for discriminant learning; (2) the huge complexity and variety of graph topological structure that is rather challenging to robustly characterize. In this paper, we propose the Wasserstein Discriminant Dictionary Learning (WDDL) framework to achieve discriminant learning on graphs with robust graph topology modeling, and hence facilitate graph-based pattern analysis tasks. Considering the difficulty of calculating global inter-class/intra-class scatters, a reference set of graphs (aka graph dictionary) is first constructed by generating representative graph samples (aka graph keys) with expressive topological structure. Then, a Wasserstein Graph Representation (WGR) process is proposed to project input graphs into a succinct dictionary space through the graph dictionary lookup. To further achieve discriminant graph learning, a Wasserstein discriminant loss (WD-loss) is defined on the graph dictionary, in which the graph keys are optimizable, to make the intra-class keys more compact and inter-class keys more dispersed. Hence, the calculation of global Wasserstein metric (W-metric) centers can be bypassed. For sophisticated topology mining in the WGR process, a joint-Wasserstein graph embedding module is constructed to model both between-node and between-edge relationships across inputs and graph keys by encapsulating both the Wasserstein metric (between cross-graph nodes) and proposed novel Kron-Gromov-Wasserstein (KGW) metric (between cross-graph adjacencies). Specifically, the KGW-metric comprehensively characterizes the cross-graph connection patterns with the Kronecker operation, then adaptively captures those salient patterns through connection pooling. To evaluate the proposed framework, we study two graph-based pattern analysis problems, i.e. graph classification and cross-modal retrieval, with the graph dictionary flexibly adjusted to cater to these two tasks. Extensive experiments are conducted to comprehensively compare with existing advanced methods, as well as dissect the critical component of our proposed architecture. The experimental results validate the effectiveness of the WDDL framework.

14.
Article in English | MEDLINE | ID: mdl-38862032

ABSTRACT

OBJECTIVE: To explore the effect sizes of different HIIT protocols on cardiorespiratory parameters when compared with the MICT in different HF subtypes. DATA SOURCES: Electronic databases were searched from their inception date until January 23rd, 2023. STUDY SELECTION: Randomized controlled trials (RCTs) were included if they compared HIIT to MICT in HF patients. The primary outcomes was peak oxygen consumption (VO2peak). Two reviewers independently evaluated 99 initially identified studies, resulting in the selection of 15 RCTs that met the eligibility criteria. DATA EXTRACTION: Data was extracted independently by two observers using data extraction form drafted based on the CONSORT statement and the TIDieR; and the The methodological quality of the studies was analyzed individually based on the TESTEX scale. DATA SYNTHESIS: Fifteen RCTs with 553 HF patients were included in the systematic review. The studies included had moderate to good overall methodological quality. The results showed that HIIT was generally more effective than MICT at improving VO2peak in HF patients (n=541, 15 RCT; MD: 1.49 mL/kg/min, I2=66%, p<0.001). However, the effect size varied depending on the HF subtype and HIIT protocol used. For HFrEF patients, the long-interval (high-intensity interval lasting≥ 4 min) and high-volume HIIT (high-intensity efforts in total ≥ 15 min) showed the largest benefits over the MICT (n=261, 6 RCT; MD: 2.11 mL/kg/min, p<0.001); followed by the short-interval (≤ 1 min) and high-volume HIIT (≥ 15 min; n=71, 3 RCT; MD: 0.91 mL/kg/min, p=0.12); and the short-interval and low-volume HIIT showed the least superiority over MICT (n=68, 3 RCT; MD: 0.54 mL/kg/min; p=0.05). For HFpEF patients, there was a modest beneficial effect from HIIT over MICT (n=141, 3 RCT; MD: 0.55 mL/kg/min; p=0.32). CONCLUSIONS: The long-interval and high-volume HIIT protocol may produce greater benefits than MICT for improving cardiopulmonary fitness in HFrEF patients. Further research is needed to determine the optimal HIIT protocol for different HF subtypes and to provide definitive recommendations for clinical practice.

15.
Phytochemistry ; 225: 114170, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38830388

ABSTRACT

Eleven alkaloids including four previously undescribed oxoisoaporphine alkaloids, menisoxoisoaporphines A-D (1-4), four known analogues (5-8), and three aporphine alkaloids (9-11), were isolated and identified from the rhizomes of Menispermum dauricum. Their structures were elucidated by extensive spectroscopic data and single-crystal X-ray diffraction analyses. Among them, compounds 1 and 4 were the first samples of oxoisoaporphine with C-6 isopentylamino moiety, and 2 was a rare C-4 methylation product of oxoisoaporphine alkaloid. The in vitro anti-inflammatory activity of compounds 1-11 was performed by evaluating the inhibition of NO level in LPS-induced RAW264.7 macrophages. Among them, compound 4 exhibited the most potent NO inhibition activity with an IC50 value of 1.95 ± 0.33 µM. The key structure-activity relationships of those oxoisoaporphine alkaloids for anti-inflammatory effects have been summarized.

16.
Sci Rep ; 14(1): 12704, 2024 06 03.
Article in English | MEDLINE | ID: mdl-38830996

ABSTRACT

To explore the role of YAP, a key effector of the Hippo pathway, in temporomandibular joint (TMJ) ankylosis. The temporal and spatial expression of YAP was detected via immunohistochemistry and multiplex immunohistochemistry on postoperative Days 1, 4, 7, 9, 11, 14 and 28 in a sheep model. Isolated mesenchymal stem cells (MSCs) from samples of the Day 14. The relative mRNA expression of YAP was examined before and after the osteogenic induction of MSCs. A YAP-silenced MSC model was constructed, and the effect of YAP knockdown on MSC function was examined. YAP is expressed in the nucleus of the key sites that determine the ankylosis formation, indicating that YAP is activated in a physiological state. The expression of YAP increased gradually over time. Moreover, the number of cells coexpressing of RUNX2 and YAP-with the osteogenic active zone labelled by RUNX2-tended to increase after Day 9. After the osteogenic induction of MSCs, the expression of YAP increased. After silencing YAP, the osteogenic, proliferative and migratory abilities of the MSCs were inhibited. YAP is involved in the early development of TMJ bony ankylosis. Inhibition of YAP using shRNA might be a promising way to prevent or treat TMJ ankylosis.


Subject(s)
Ankylosis , Mesenchymal Stem Cells , Osteogenesis , Temporomandibular Joint Disorders , Animals , Mesenchymal Stem Cells/metabolism , Temporomandibular Joint Disorders/metabolism , Temporomandibular Joint Disorders/pathology , Temporomandibular Joint Disorders/genetics , Ankylosis/metabolism , Ankylosis/pathology , Ankylosis/genetics , YAP-Signaling Proteins/metabolism , Temporomandibular Joint/metabolism , Temporomandibular Joint/pathology , Sheep , Cell Proliferation , Disease Models, Animal , Cell Differentiation , Adaptor Proteins, Signal Transducing/metabolism , Adaptor Proteins, Signal Transducing/genetics , Core Binding Factor Alpha 1 Subunit/metabolism , Core Binding Factor Alpha 1 Subunit/genetics , Cell Movement , Transcription Factors/metabolism , Transcription Factors/genetics
17.
Front Pharmacol ; 15: 1389922, 2024.
Article in English | MEDLINE | ID: mdl-38831883

ABSTRACT

Combination therapies can enhance the sensitivity of cancer to drugs, lower drug doses, and reduce side effects in cancer treatment. However, differences in the physicochemical properties and pharmacokinetics of different therapeutic agents limit their application. To avoid the above dilemma and achieve accurate control of the synergetic ratio, a nanoscale co-delivery system (NCDS) has emerged as a prospective tool for combined therapy in cancer treatment, which is increasingly being used to co-load different therapeutic agents. In this study, we have summarized the mechanisms of therapeutic agents in combination for cancer therapy, nanoscale carriers for co-delivery, drug-loading strategies, and controlled/targeted co-delivery systems, aiming to give a general picture of these powerful approaches for future NCDS research studies.

18.
BMC Infect Dis ; 24(1): 587, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38879487

ABSTRACT

BACKGROUND: Early diagnosis of HIV infection decreases the time from HIV diagnosis to viral suppression and reduces further HIV transmission. The Chinese Guidelines for the Diagnosis and Treatment of HIV/AIDS (2021 edition) state that an HIV RNA level > 5,000 copies/mL is the threshold for diagnosing HIV infection. The impact of low viral load values on HIV diagnosis needs to be investigated. METHODS: There were 3455 human immunodeficiency virus (HIV1 + 2) antibody results (immunoblotting method) and 65,129 HIV viral load values at Beijing Youan Hospital from 2019 to 2022. A total of 2434 patients had both antibody confirmatory results and viral load results. The confirmatory antibody results and HIV viral load results of 2434 patients were analyzed to investigate the impact of low viral load values on HIV diagnosis. RESULTS: Of the 2434 patients who had both confirmatory antibody results and viral load results, the viral load values of 140 patients (5.8%) had viral loads ranging from 40 copies/mL to 5,000 copies/mL before positive confirmatory antibody result, and of these 140 patients, the sample receipt time for the viral load tests of 96 (66.7%) individuals was 1 to 6 days earlier than the corresponding sample receipt time for the confirmatory antibody test. In addition, 34 patients (1.4%) had low viral loads ranging from 40 copies/mL to 1,000 copies/mL before positive confirmatory antibody result. CONCLUSION: This study revealed that there is a risk of missed diagnosis if a threshold of 5000 copies/mL is used for the diagnosis of HIV infection. These data provide valuable information for the early diagnosis of HIV infection, and our findings have potential benefits for decreasing HIV transmission.


Subject(s)
HIV Infections , Tertiary Care Centers , Viral Load , Humans , HIV Infections/diagnosis , HIV Infections/virology , Male , Female , Adult , Beijing , Middle Aged , HIV-1/genetics , HIV-1/isolation & purification , RNA, Viral/blood , HIV Antibodies/blood , Young Adult , China/epidemiology , Early Diagnosis , Adolescent
19.
Article in English | MEDLINE | ID: mdl-38877995

ABSTRACT

Metal-semiconductor junctions play an important role in the development of electronic and optoelectronic devices. A Schottky junction photodetector based on two-dimensional (2D) materials is promising for self-powered photodetection with fast response speed and large signal-to-noise ratio. However, it usually suffers from an uncontrolled Schottky barrier due to the Fermi level pinning effect arising from the interface states. In this work, all-2D Schottky junctions with near-ideal Fermi level depinning are realized, attributed to the high-quality interface between 2D semimetals and semiconductors. We further demonstrate asymmetric diodes based on multilayer graphene/MoS2/PtSe2 with a current rectification ratio exceeding 105 and an ideality factor of 1.2. Scanning photocurrent mapping shows that the photocurrent generation mechanism in the heterostructure switches from photovoltaic effect to photogating effect at varying drain biases, indicating both energy conversion and optical sensing are realized in a single device. In the photovoltaic mode, the photodetector is self-powered with a response time smaller than 100 µs under the illumination of a 405 nm laser. In the photogating mode, the photodetector exhibits a high responsivity up to 460 A/W originating from a high photogain. Finally, the photodetector is employed for single-pixel imaging, demonstrating its high-contrast photodetection ability. This work provides insight into the development of high-performance self-powered photodetectors based on 2D Schottky junctions.

20.
Cureus ; 16(5): e60372, 2024 May.
Article in English | MEDLINE | ID: mdl-38883073

ABSTRACT

Erythroderma, also known as exfoliative dermatitis, is a rarely reported atypical cutaneous manifestation of adult-onset Still's disease (AOSD). We present the case of erythroderma in association with AOSD that was steroid dependent and responded to tocilizumab therapy. Skin rash, pruritis, and related laboratory findings were significantly improved upon the addition of tocilizumab, while prednisolone was successfully tapered to an ever-lowest maintenance level. To our knowledge, this is the first to report the sole therapeutic effect of tocilizumab in erythroderma related to AOSD.

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