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1.
Nucleic Acids Res ; 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-39351872

ABSTRACT

Manipulating gene expression is crucial for understanding gene function, with high-throughput sequencing techniques such as RNA-seq elucidating the downstream mechanisms involved. However, the lack of a standardized metadata format for small-scale perturbation expression datasets in public repositories hinders their reuse. To address this issue, we developed PerturbAtlas, an add-value resource that re-analyzes publicly archived RNA-seq libraries to provide quantitative data on gene expression, transcript profiles, and alternative splicing events following genetic perturbation. PerturbAtlas assists users in identifying trends at the gene and isoform levels in perturbation assays by re-analyzing a curated set of 122 801 RNA-seq libraries across 13 species. This resource is freely available at https://perturbatlas.kratoss.site as both raw data tables and an interactive browser, allowing searches by species, tissue or genomic features. The results provide detailed information on alterations following perturbations, accessible through both forward and reverse approaches, thereby enabling the exploration of perturbation consequences and the identification of potential causal perturbations.

2.
BMC Med Inform Decis Mak ; 24(1): 256, 2024 Sep 16.
Article in English | MEDLINE | ID: mdl-39285363

ABSTRACT

BACKGROUND: Coronary artery disease (CAD) is a major global cardiovascular health threat and the leading cause of death in many countries. The disease has a significant impact in China, where it has become the leading cause of death. There is an urgent need to develop non-invasive, rapid, cost-effective, and reliable techniques for the early detection of CAD using machine learning (ML). METHODS: Six hundred eight participants were divided into three groups: healthy, hypertensive, and CAD. The raw data of pulse wave from those participants was collected. The data were de-noised, normalized, and analyzed using several applications. Seven ML classifiers were used to model the processed data, including Decision Tree (DT), Random Forest (RF), Gradient Boosting Decision Tree (GBDT), Extra Trees (ET), Extreme Gradient Boosting (XGBoost), Light Gradient Boosting (LightGBM), and Unbiased Boosting with Categorical Features (CatBoost). RESULTS: The Extra Trees classifier demonstrated the best classification performance. After tunning, the results performance evaluation on test set are: 0.8579 accuracy, 0.9361 AUC, 0.8561 recall, 0.8581 precision, 0.8571 F1 score, 0.7859 kappa coefficient, and 0.7867 MCC. The top 10 feature importances of ET model are w/t1, t3/tmax, tmax, t3/t1, As, hf/3, tf/3/tmax, tf/5, w and tf/3/t1. CONCLUSION: Radial artery pulse wave can be used to identify healthy, hypertensive and CAD participants by using Extra Trees Classifier. This method provides a potential pathway to recognize CAD patients by using a simple, non-invasive, and cost-effective technique.


Subject(s)
Coronary Artery Disease , Machine Learning , Pulse Wave Analysis , Radial Artery , Humans , Coronary Artery Disease/classification , Middle Aged , Male , Female , Aged , Adult , Hypertension/classification , China
3.
J Med Food ; 2024 Sep 24.
Article in English | MEDLINE | ID: mdl-39315928

ABSTRACT

Schisandra chinensis (Turcz) Baill (S. chinensis) is the key traditional Chinese medicine for the treatment of asthma used by ancient and modern medical practitioners. However, the material basis and the main mechanism of its antiasthmatic effect remain unclear. Our preliminary results showed that schisandrol A (SCA), a representative monomer of Schisandra lignans, had the best relaxation effect on tracheal rings in isolated rats. In this research, a mouse asthma model was prepared by combining ovalbumin (OVA) with Al (OH)3 for exploring the antiasthmatic action and the underlying mechanism of SCA. The study results demonstrated that SCA improved the behavior of mice with asthma and pathological changes in their lung tissues and airways, decreased serum immunoglobulin E (IgE) and OVA-IgE levels, interleukin-4 (IL-4), IL-5, IL-13, and eotaxin contents, and leukocytes number in bronchoalveolar lavage fluid. SCA downregulated the gene expressions of keratinocyte-derived protein chemokines and ILs and reduced the expressions of phosphorylated IκB kinase α (p-IKKα) and p-nuclear factor kappa-B (NF-κB) proteins in lung tissues. In addition, it was found that SCA could significantly increase T-superoxide dismutase and catalase activities, decrease malondialdehyde content, and elevate p-IκBα, NF-E2-related-factor 2 (Nrf2), and heme oxygenase-1 (HO-1) protein expressions. In summary, SCA treatment resulted in a significant improvement in the allergic bronchial asthma in mice, and its mechanisms may involve the regulation of the NF-κB/IκBα pathway to reduce inflammatory response and the Nrf2/HO-1 pathway to improve the body's antioxidant capacity. These results suggest that SCA is a key component of S. chinensis in exerting antiasthmatic effects.

4.
Zhongguo Zhong Yao Za Zhi ; 49(16): 4298-4312, 2024 Aug.
Article in Chinese | MEDLINE | ID: mdl-39307767

ABSTRACT

Chronic obstructive pulmonary disease(COPD) is a progressive lung dysfunction(disease) caused by long-term inhalation of toxic particles, especially smoking. The continued exposure to harmful substances triggers an abnormal inflammatory response, which causes permanent damage to the respiratory system, ultimately leading to irreversible pathological changes. Lung macrophages(LMs) are key innate immune effectors involved in the recognition, phagocytosis, and clearance of pathogens, as well as in the processing of inhaled hazardous particulate matter(e. g., cigarette smoke and particulate matter). LMs are polarized toward the M1 or M2 phenotype in response to the activation of inflammatory mediators to exert pro-/anti-inflammatory effects, respectively, thus being involved in the pulmonary parenchymal damage(emphysema) and repair(airway remodeling) throughout the process of COPD.In addition, they are responsible for phagocytosis and clearance of apoptotic or necrotic tissue cells, which helps to maintain the stability of the microenvironment in the lungs of COPD patients. Modern studies have revealed that macrophage polarization plays a pivotal role in the pathogenesis and development of COPD and is considered a potential target for treating COPD because of its ability to reduce airway inflammation, inhibit tissue remodeling, and combat oxidative stress. In recent years, traditional Chinese medicine(TCM) and its active ingredients have become a hot area in the treatment of COPD by targeting the balance of M1/M2 macrophage polarization. TCM and its active ingredients can intervene in the inflammatory response to promote the repair of the lung tissue in the patients with COPD. This paper reviews the research achievements of TCM and its active ingredients in this field in recent years,aiming to provide a scientific basis and strong support for the precise diagnosis and treatment of COPD.


Subject(s)
Drugs, Chinese Herbal , Macrophages , Pulmonary Disease, Chronic Obstructive , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/immunology , Humans , Animals , Macrophages/drug effects , Macrophages/immunology , Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/pharmacology , Medicine, Chinese Traditional
5.
Ying Yong Sheng Tai Xue Bao ; 35(6): 1653-1660, 2024 Jun.
Article in Chinese | MEDLINE | ID: mdl-39235024

ABSTRACT

The construction of road infrastructure has resulted in the degradation of wildlife habitat and the decrease of ecological network connectivity and stability. Studying the impacts of road infrastructure on wildlife life and migration is significant for regional wildlife conservation and ecological network optimization. We assessed the impacts of road infrastructure on habitat suitability using the MaxEnt model based on wildlife occurrence point data in the Guangdong-Hong Kong-Macao Greater Bay Area. We constructed the ecological networks and identified ecological breakpoints using the minimum cumulative resistance model, and compared the ecological network connectivity of different scenarios with the landscape connectivity index and graph theory index. The results showed that railway and motorway significantly affected habitat suitability, causing a decrease in wildlife habitat suitability. Affected by road infrastructure, the fragmentation of ecological sources intensified, the resistance of ecological corridors increased, and the ecological network connectivity and stability significantly decreased. A total of 536 ecological breakpoints were identified, which were concentrated in the area adjacent to ecological sources. The results would provide important scientific references for wildlife habitat conservation and ecological restoration in the Guangdong-Hong Kong-Macao Greater Bay Area.


Subject(s)
Conservation of Natural Resources , Ecosystem , China , Animals , Animals, Wild/growth & development , Bays , Ecology , Hong Kong , Models, Theoretical , Transportation , Railroads
6.
Diabetes Obes Metab ; 2024 Sep 16.
Article in English | MEDLINE | ID: mdl-39285685

ABSTRACT

AIMS: To explore the associations between cuprotosis-related genes (CRGs) across different stages of liver disease in metabolic dysfunction-associated fatty liver disease (MAFLD), including hepatocellular carcinoma (HCC). MATERIALS AND METHODS: We analysed several bulk RNA sequencing datasets from patients with MAFLD (n = 331) and MAFLD-related HCC (n = 271) and two MAFLD single-cell RNA sequencing datasets. To investigate the associations between CRGs and MAFLD, we performed differential correlation, logistic regression and functional enrichment analyses. We also validated the findings in an independent Wenzhou PERSONS cohort of MAFLD patients (n = 656) used for a genome-wide association study (GWAS). RESULTS: GLS, GCSH and ATP7B genes showed significant differences across the MAFLD spectrum and were significantly associated with liver fibrosis stages. GLS was closely associated with fibrosis stages in patients with MAFLD and those with MAFLD-related HCC. GLS is predominantly expressed in monocytes and T cells in MAFLD. During the progression of metabolic dysfunction-associated fatty liver to metabolic-associated steatohepatitis, GLS expression in T cells decreased. GWAS revealed that multiple single nucleotide polymorphisms in GLS were associated with clinical indicators of MAFLD. CONCLUSIONS: GLS may contribute to liver inflammation and fibrosis in MAFLD mainly through cuprotosis and T-cell activation, promoting the progression of MAFLD to HCC. These findings suggest that cuprotosis may play a role in MAFLD progression, potentially providing new insights into MAFLD pathogenesis.

7.
Nat Commun ; 15(1): 7713, 2024 Sep 04.
Article in English | MEDLINE | ID: mdl-39231979

ABSTRACT

Tertiary lymphoid structures are immune cell aggregates linked with cancer outcomes, but their interactions with tumour cell aggregates are unclear. Using nasopharyngeal carcinoma as a model, here we analyse single-cell transcriptomes of 343,829 cells from 77 biopsy and blood samples and spatially-resolved transcriptomes of 31,316 spots from 15 tumours to decipher their components and interactions with tumour cell aggregates. We identify essential cell populations in tertiary lymphoid structure, including CXCL13+ cancer-associated fibroblasts, stem-like CXCL13+CD8+ T cells, and B and T follicular helper cells. Our study shows that germinal centre reaction matures plasma cells. These plasma cells intersperse with tumour cell aggregates, promoting apoptosis of EBV-related malignant cells and enhancing immunotherapy response. CXCL13+ cancer-associated fibroblasts promote B cell adhesion and antibody production, activating CXCL13+CD8+ T cells that become exhausted in tumour cell aggregates. Tertiary lymphoid structure-related cell signatures correlate with prognosis and PD-1 blockade response, offering insights for therapeutic strategies in cancers.


Subject(s)
CD8-Positive T-Lymphocytes , Chemokine CXCL13 , Immunotherapy , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Single-Cell Analysis , Tertiary Lymphoid Structures , Humans , Nasopharyngeal Carcinoma/genetics , Nasopharyngeal Carcinoma/immunology , Nasopharyngeal Carcinoma/pathology , Nasopharyngeal Carcinoma/therapy , Nasopharyngeal Carcinoma/metabolism , Tertiary Lymphoid Structures/immunology , Tertiary Lymphoid Structures/genetics , Chemokine CXCL13/metabolism , Chemokine CXCL13/genetics , Immunotherapy/methods , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , Nasopharyngeal Neoplasms/genetics , Nasopharyngeal Neoplasms/immunology , Nasopharyngeal Neoplasms/pathology , Nasopharyngeal Neoplasms/therapy , Gene Expression Profiling , Disease Progression , Transcriptome , B-Lymphocytes/immunology , B-Lymphocytes/metabolism , Tumor Microenvironment/immunology , Tumor Microenvironment/genetics , Prognosis , Fibroblasts/metabolism , Fibroblasts/immunology
8.
Front Public Health ; 12: 1421211, 2024.
Article in English | MEDLINE | ID: mdl-39257951

ABSTRACT

Objective: We investigated the risk factors associated with severe or critical Coronavirus disease 2019 (COVID-19) infection due to the Omicron variant in patients with myasthenia gravis (MG) and determined the potential effect of COVID-19 on myasthenic exacerbation during the Omicron pandemic. Methods: This retrospective study included 287 patients with MG in Tianjin, China. Clinical data of the patients were collected using electronic questionnaires, databases, and clinical records. Results: The overall infection rate was 84.7%. Advanced age, comorbidities, generalized phenotype, and MG instability were drivers of COVID-19 severity, and post-COVID-19 myasthenic exacerbation. The concurrent use of a steroid-sparing agent did not affect COVID-19 susceptibility or severity. It did lower the risk of myasthenic exacerbation after COVID-19 infection. Patients with severe COVID-19 experienced myasthenic exacerbation earlier than patients with non-severe infection (p < 0.001). The severity of COVID-19 (Hazards Ratio = 3.04, 95% CI: 1.41-6.54, p = 0.004) and the clinical phenotype (Hazards Ratio = 3.29, 95% CI: 1.63-6.63, p < 0.001) emerged as independent risk factors for early MG exacerbation. Conclusion: Generally, patients with MG appear to be susceptible to the Omicron strains. Immunotherapy for MG did not increase COVID-19 susceptibility or severity. We do not advocate an immediate cessation of ongoing immunosuppressive treatments once a COVID-19 infection is diagnosed. Instead, a judicious evaluation of the risks and benefits, tailored to each individual, is recommended.


Subject(s)
COVID-19 , Myasthenia Gravis , SARS-CoV-2 , Humans , COVID-19/epidemiology , COVID-19/complications , Retrospective Studies , Male , Female , Middle Aged , China/epidemiology , Adult , Risk Factors , Aged , Severity of Illness Index , Comorbidity
9.
Zhongguo Zhong Yao Za Zhi ; 49(14): 3758-3768, 2024 Jul.
Article in Chinese | MEDLINE | ID: mdl-39099350

ABSTRACT

The function of the Trihelix transcription factor is that it plays an important role in many abiotic stresses, especially in the signaling pathway of low temperature, drought, flood, saline, abscisic acid, methyl jasmonate, and other abiotic stresses. However, there are few studies on the Trihelix gene family of ginseng. In this study, 41 Trihelix gene family members were identified and screened from the ginseng genome database, and their physicochemical properties, cis-acting elements, subcellular localization, chromosomal assignment, and abiotic stress-induced expression patterns were analyzed by bioinformatics methods. The results showed that 85% of Trihelix family members of ginseng were located in the nucleus, and the main secondary structure of Trihelix protein was random coil and α helix. In the promoter region of Trihelix, cis-acting regulatory elements related to various abiotic stresses such as low temperature, hormone response, and growth and development were identified. Through the collinearity analysis of interspecific Trihelix transcription factors of model plants Arabidopsis thaliana and ginseng, 19 collinear gene pairs were found between A. thaliana and ginseng, and no collinear gene pairs existed on chromosomes 3, 6, and 12 only. qRT-PCR analysis showed that the expression of GWHGBEIJ010320.1 was significantly up-regulated under low temperature stress, a significant response to low temperature stress. This study lays a foundation for further research on the role of the Trihelix transcription factor of ginseng in abiotic stress, as well as the growth and development of ginseng.


Subject(s)
Gene Expression Regulation, Plant , Multigene Family , Panax , Phylogeny , Plant Proteins , Stress, Physiological , Transcription Factors , Panax/genetics , Panax/chemistry , Plant Proteins/genetics , Plant Proteins/metabolism , Gene Expression Regulation, Plant/drug effects , Transcription Factors/genetics , Transcription Factors/metabolism , Stress, Physiological/genetics , Promoter Regions, Genetic , Gene Expression Profiling
10.
Nano Lett ; 24(32): 9990-9997, 2024 Aug 14.
Article in English | MEDLINE | ID: mdl-39101516

ABSTRACT

Liquid crystal elastomers (LCEs), consisting of polymer networks and liquid crystal mesogens, show a reversible phase change under thermal stimuli. However, the kinetic performance is limited by the inherently low thermal conductivity of the polymers. Transforming amorphous bulk into a fiber enhances thermal conductivity through the alignment of polymer chains. Challenges are present due to their rigid networks, while cross-links are crucial for deformation. Here, we employ hydrodynamic alignment to orient the LCE domains assisted by controlled in situ cross-linking and to remarkably reduce the diameter to submicrons. We report that the intrinsic thermal conductivity of LCE fibers at room temperature reaches 1.44 ± 0.32 W/m-K with the sub-100 nm diameter close to the upper limit determined in the quasi-1D regime. Combining the outstanding thermal conductivity and thin diameters, we anticipate these fibers to exhibit a rapid response and high force output in thermomechanical systems. The fabrication method is expected to apply to other cross-linked polymers.

11.
BMC Ophthalmol ; 24(1): 352, 2024 Aug 19.
Article in English | MEDLINE | ID: mdl-39160465

ABSTRACT

BACKGROUND: This study aimed to identify the differentially expressed proteins in the vitreous humor (VH) of eyes with and without pathologic myopia (PM), providing insights into the molecular pathogenesis. METHODS: A cross-sectional, observational study was conducted. VH samples were collected from patients undergoing vitrectomy for idiopathic epiretinal membrane (ERM), macular hole (MH), or myopic retinoschisis (MRS). Label-free quantitative proteomic analysis identified differential protein expression, with validation using ELISA. RESULTS: The proteomic profiling revealed significantly higher expressions of tubulin alpha 1a (TUBA1A) and eukaryotic translation elongation factor 1 alpha 1 (EEF1A1) in PM groups (MH-PM, MRS-PM) compared to controls (MH, ERM). Conversely, xylosyltransferase 1 (XYLT1), versican core protein (VCAN), and testican-2 (SPOCK2) expressions were lower in PM. ELISA validation confirmed these findings. CONCLUSIONS: Our study provides novel insights into the molecular mechanisms of PM. The differentially expressed proteins EEF1A1, TUBA1A, XYLT1, VCAN, and SPOCK2 may play crucial roles in chorioretinal cell apoptosis, scleral extracellular matrix (ECM) synthesis, and scleral remodeling in PM. These proteins represent potential new targets for therapeutic intervention in PM, highlighting the importance of further investigations to elucidate their functions and underlying mechanisms in disease pathogenesis.


Subject(s)
Myopia, Degenerative , Proteomics , Vitreous Body , Humans , Vitreous Body/metabolism , Proteomics/methods , Male , Female , Cross-Sectional Studies , Aged , Middle Aged , Myopia, Degenerative/metabolism , Enzyme-Linked Immunosorbent Assay , Eye Proteins/metabolism , Vitrectomy
12.
Gut ; 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-39089860

ABSTRACT

BACKGROUND: Statins have multiple benefits in patients with metabolic-associated steatotic liver disease (MASLD). AIM: To explore the effects of statins on the long-term risk of all-cause mortality, liver-related clinical events (LREs) and liver stiffness progression in patients with MASLD. METHODS: This cohort study collected data on patients with MASLD undergoing at least two vibration-controlled transient elastography examinations at 16 tertiary referral centres. Cox regression analysis was performed to examine the association between statin usage and long-term risk of all-cause mortality and LREs stratified by compensated advanced chronic liver disease (cACLD): baseline liver stiffness measurement (LSM) of ≥10 kPa. Liver stiffness progression was defined as an LSM increase of ≥20% for cACLD and from <10 kPa to ≥10 or LSM for non-cACLD. Liver stiffness regression was defined as LSM reduction from ≥10 kPa to <10 or LSM decrease of ≥20% for cACLD. RESULTS: We followed up 7988 patients with baseline LSM 5.9 kPa (IQR 4.6-8.2) for a median of 4.6 years. At baseline, 40.5% of patients used statins, and cACLD was present in 17%. Statin usage was significantly associated with a lower risk of all-cause mortality (adjusted HR=0.233; 95% CI 0.127 to 0.426) and LREs (adjusted HR=0.380; 95% CI 0.268 to 0.539). Statin usage was also associated with lower liver stiffness progression rates in cACLD (HR=0.542; 95% CI 0.389 to 0.755) and non-cACLD (adjusted HR=0.450; 95% CI 0.342 to 0.592), but not with liver stiffness regression (adjusted HR=0.914; 95% CI 0.778 to 1.074). CONCLUSIONS: Statin usage was associated with a relatively lower long-term risk of all-cause mortality, LREs and liver stiffness progression in patients with MASLD.

13.
China CDC Wkly ; 6(34): 857-861, 2024 Aug 23.
Article in English | MEDLINE | ID: mdl-39211412

ABSTRACT

What is already known about this topic?: Fine particulate matter (PM2.5) and ozone (O3) are prevalent pollutants in the atmosphere, which threaten human health, especially the respiratory system. Typically, people are exposed to a mixture of various pollutants in the environment. Thus, the single and combined effects of both pollutants need to be investigated. What is added by this report?: PM2.5 and O3 increase the risk of death from lung cancer, chronic obstructive pulmonary disease (COPD), and respiratory diseases, with their lagged and cumulative effects analyzed, indicating an acute effect. In addition, combined exposure to both pollutants can significantly affect disease deaths. What are the implications for public health practice?: This study provides further evidence of the single and combined effects of PM2.5 and O3 on respiratory diseases, emphasizing the need for sustained efforts in air pollution control, with greater attention to the synergistic management of air pollutants.

14.
Nano Lett ; 24(28): 8770-8777, 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-38968171

ABSTRACT

Oxygen-mediated triplet-triplet annihilation upconversion (TTA-UC) quenching limits the application of such organic upconversion materials. Here, we report that the photooxidation of organic amines is an effective and versatile strategy to suppress oxygen-mediated upconversion quenching in both organic solvents and aqueous solutions. The strategy is based on the dual role of organic amines in photooxidation, i.e., as singlet oxygen scavengers and electron donors. Under photoexcitation, the photosensitizer sensitizes oxygen to produce singlet oxygen for the oxidation of alkylamine, reducing the oxygen concentration. However, photoinduced electron transfer among photosensitizers, organic amines, and oxygen leads to the production of superoxide anions that suppress TTA-UC. To observe oxygen-tolerating TTA-UC, we find that alkyl secondary amines can balance the production of singlet oxygen and superoxide anions. We then utilize polyethyleneimine (PEI) to synthesize amphiphilic polymers to encapsulate TTA-UC pairs for the formation of water-dispersible, ultrasmall, and multicolor-emitting TTA-UC nanoparticles.

15.
Pharmaceutics ; 16(7)2024 Jul 10.
Article in English | MEDLINE | ID: mdl-39065618

ABSTRACT

The gut microbiota is closely associated with human health, and alterations in gut microbiota can influence various physiological and pathological activities in the human body. Therefore, microbiota regulation has become an important strategy in current disease treatment, albeit facing numerous challenges. Nanomaterials, owing to their excellent protective properties, drug release capabilities, targeting abilities, and good biocompatibility, have been widely developed and utilized in pharmaceuticals and dietary fields. In recent years, significant progress has been made in research on utilizing nanomaterials to assist in regulating gut microbiota for disease intervention. This review explores the latest advancements in the application of nanomaterials for microbiota regulation and offers insights into the future development of nanomaterials in modulating gut microbiota.

16.
Clin Pharmacol Ther ; 2024 Jul 28.
Article in English | MEDLINE | ID: mdl-39072721

ABSTRACT

Targeted covalent inhibitors (TCIs) are an emerging class of anticancer therapeutics. TCIs are designed to selectively engage their targeted proteins via covalent warheads. From the drug development standpoint, the covalent inhibition mechanism is anticipated to elicit the following theoretical benefits: (i) an extended duration of therapeutic action that is determined by the target protein turnover rate and not necessarily by drug half-life, (ii) a lower therapeutic dose owing to greater pharmacological potency, (iii) lower risk of off-target binding and associated adverse events, and (iv) reduced drug-drug interaction (DDI) liability due to high selectivity and low dose. Elucidating the clinical relevance of these expected benefits requires an integrated assessment of pharmacokinetics (PK), efficacy, safety, and DDI data. In this review, we compared the clinical pharmacology attributes of FDA-approved oncology TCIs within the last 10 years against their reversible inhibitor (RI) counterparts. Our findings indicated that (i) PK half-lives of TCIs were typically shorter and (ii) at their respective recommended clinical doses per drug label, the molar unbound steady state areas under the concentration-time curve (AUCss) of TCIs were lower than those of RIs, but with longer clinically observed durations of response. However, (iii) there was no conclusive evidence supporting improved clinical safety profiles for TCIs, and (iv) DDI perpetrator profiles appeared to be similar between TCIs and RIs. The overall clinical pharmacology comparison of TCI vs. RI surveyed in this paper suggested that at least two of the four forecasted clinical benefits were achieved by TCIs.

17.
J Am Chem Soc ; 146(31): 21791-21805, 2024 Aug 07.
Article in English | MEDLINE | ID: mdl-39069661

ABSTRACT

The diagnosis of disease biomarkers is crucial for the identification, monitoring, and prognostic assessment of malignant disease. However, biological samples with autofluorescence, complex components, and heterogeneity pose major challenges to reliable biosensing. Here, we report the self-assembly of natural proteins and the triplet-triplet annihilation upconversion (TTA-UC) pair to form upconverted protein clusters (∼8.2 ± 1.1 nm), which were further assembled into photon upconversion supramolecular assemblies (PUSA). This PUSA exhibited unique features, including a small size (∼44.1 ± 4.1 nm), oxygen tolerance, superior biocompatibility, and easy storage via lyophilization, all of which are long sought after for photon upconversion materials. Further, we have revealed that the steric hindrance of the annihilator suppresses the stacking of the annihilator in PUSA, which is vital for maintaining the water dispersibility and enhancing the upconversion performance of PUSA. In conjunction with sarcosine oxidase, this near infrared (NIR)-excitable PUSA nanoprobe could perform background-free biosensing of urinary sarcosine, which is a common biomarker for prostatic carcinoma (PCa). More importantly, this nanoprobe not only allows for qualitative identification of urinary samples from PCa patients by the unaided eye under NIR-light-emitting diode (LED) illumination but also quantifies the concentration of urinary sarcosine. These remarkable findings have propelled photon upconversion materials to a new evolutionary stage and expedited the progress of upconversion biosensing in clinical diagnostics.


Subject(s)
Biosensing Techniques , Photons , Humans , Sarcosine/urine , Sarcosine/chemistry , Sarcosine Oxidase/chemistry , Proteins/analysis , Proteins/chemistry
18.
Oral Oncol ; 157: 106963, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39032343

ABSTRACT

OBJECTIVE: There is a lack of effective biomarkers for predicting the distant metastasis in nasopharyngeal carcinoma (NPC). We aimed to explore the expression of FAP+Cancer-associated fibroblasts (CAFs) derived CXCL1 in NPC and its predictive values for distant metastasis and correlation with PD-L1 expression. MATERIALS AND METHODS: A total of 345 patients with locoregionally advanced NPC were retrospectively enrolled (the training cohort: the validation cohort = 160:185). Co-expression of CXCL1 and FAP and the expression of PD-L1 were detected by multi-immunofluorescence staining and immunohistochemistry, respectively. The primary end-point was distant metastasis-free survival (DMFS). The Kaplan-Meier method was used to calculate the survival. The Cox proportional hazards model was used to assess prognostic risk factors. RESULTS: A novel CXCL1+_FAP+ phenotype in CAFs was identified in NPC and then used to divide patients into low and high risk groups. Both in the training cohort and validation cohort, patients in the high risk group had poorer DMFS, overall survival (OS), progression-free survival (PFS) and locoregional relapse-free survival (LRFS) than patients in the low risk group. Multivariate analysis revealed CXCL1+_FAP+ phenotype was an independent prognostic factor for DMFS, OS, PFS and LRFS. Further results showed patients in the high risk group had higher PD-L1 expression than those in the low risk group. CONCLUSION: Our study showed CXCL1+_FAP+ phenotype in CAFs could effectively classified locoregionally advanced NPC patients into different risk groups for distant metastasis and might be a potential biomarker for anti-PD-1/PD-L1 immunotherapy.


Subject(s)
B7-H1 Antigen , Cancer-Associated Fibroblasts , Chemokine CXCL1 , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Humans , B7-H1 Antigen/metabolism , Male , Female , Nasopharyngeal Carcinoma/metabolism , Nasopharyngeal Carcinoma/pathology , Nasopharyngeal Carcinoma/mortality , Middle Aged , Nasopharyngeal Neoplasms/metabolism , Nasopharyngeal Neoplasms/pathology , Nasopharyngeal Neoplasms/mortality , Chemokine CXCL1/metabolism , Cancer-Associated Fibroblasts/metabolism , Adult , Retrospective Studies , Neoplasm Metastasis , Prognosis , Phenotype , Biomarkers, Tumor/metabolism , Aged , Serine Endopeptidases/metabolism , Endopeptidases/metabolism , Membrane Proteins/metabolism
20.
Front Med (Lausanne) ; 11: 1366362, 2024.
Article in English | MEDLINE | ID: mdl-39055692

ABSTRACT

Aims: The health management of end-stage renal disease patients is a complicated process, and mobile health management technology provides a new choice for the health management of end-stage renal disease patients. The scope of clinical studies on mobile health management for patients with end-stage renal disease was reviewed, and found that about mobile health management problems existing in the literature were identified to provide ideas for subsequent mobile health management research. Methods: The databases Web of Science, PubMed, The Cochrane Library, Embase, CNKI, Wan Fang Data, BMJ, and VIP were systematically searched for studies on Mobile health management among end-stage renal disease in adult and adolescent patients or children undergoing kidney replacement therapy. The search covered the period from the inception of the databases to June 20, 2023. Two independent reviewers conducted the literature screening process. Following eligibility screening, a total of 38 papers were included for data extraction and descriptive analysis. Results: A total of 38 studies from 14 countries were finally included. The majority of which were interventional trials. The platforms used in these studies included remote monitoring systems, apps, websites, mobile phones or tablets, and social platforms. These platforms provided patients with a wide range of services, including disease management, behavioral intervention, social support, and follow-up care. Most studies focused on patient clinical indicators, patient experience, quality of life, and healthcare costs. Conclusion: Our findings that mobile health management has been widely used in disease management of end-stage renal disease patients, with rich management content and many evaluation indicators. Future studies should strengthen the evaluation of patients' mental health, quality of life, and healthcare costs. Additionally, developing a clinical decision support system would enable mobile health management to play a more effective role in end-stage renal disease patients.

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