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1.
Reprod Biol Endocrinol ; 22(1): 65, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38849798

ABSTRACT

BACKGROUND: The cumulative live birth rate (CLBR) has been regarded as a key measure of in vitro fertilization (IVF) success after a complete treatment cycle. Women undergoing IVF face great psychological pressure and financial burden. A predictive model to estimate CLBR is needed in clinical practice for patient counselling and shaping expectations. METHODS: This retrospective study included 32,306 complete cycles derived from 29,023 couples undergoing IVF treatment from 2014 to 2020 at a university-affiliated fertility center in China. Three predictive models of CLBR were developed based on three phases of a complete cycle: pre-treatment, post-stimulation, and post-treatment. The non-linear relationship was treated with restricted cubic splines. Subjects from 2014 to 2018 were randomly divided into a training set and a test set at a ratio of 7:3 for model derivation and internal validation, while subjects from 2019 to 2020 were used for temporal validation. RESULTS: Predictors of pre-treatment model included female age (non-linear relationship), antral follicle count (non-linear relationship), body mass index, number of previous IVF attempts, number of previous embryo transfer failure, type of infertility, tubal factor, male factor, and scarred uterus. Predictors of post-stimulation model included female age (non-linear relationship), number of oocytes retrieved (non-linear relationship), number of previous IVF attempts, number of previous embryo transfer failure, type of infertility, scarred uterus, stimulation protocol, as well as endometrial thickness, progesterone and luteinizing hormone on trigger day. Predictors of post-treatment model included female age (non-linear relationship), number of oocytes retrieved (non-linear relationship), cumulative Day-3 embryos live-birth capacity (non-linear relationship), number of previous IVF attempts, scarred uterus, stimulation protocol, as well as endometrial thickness, progesterone and luteinizing hormone on trigger day. The C index of the three models were 0.7559, 0.7744, and 0.8270, respectively. All models were well calibrated (p = 0.687, p = 0.468, p = 0.549). In internal validation, the C index of the three models were 0.7422, 0.7722, 0.8234, respectively; and the calibration P values were all greater than 0.05. In temporal validation, the C index were 0.7430, 0.7722, 0.8234 respectively; however, the calibration P values were less than 0.05. CONCLUSIONS: This study provides three IVF models to predict CLBR according to information from different treatment stage, and these models have been converted into an online calculator ( https://h5.eheren.com/hcyc/pc/index.html#/home ). Internal validation and temporal validation verified the good discrimination of the predictive models. However, temporal validation suggested low accuracy of the predictive models, which might be attributed to time-associated amelioration of IVF practice.


Subject(s)
Birth Rate , Fertilization in Vitro , Live Birth , Humans , Female , Fertilization in Vitro/methods , Adult , China/epidemiology , Retrospective Studies , Pregnancy , Live Birth/epidemiology , Male , Pregnancy Rate , Ovulation Induction/methods , Embryo Transfer/methods
2.
Thorac Cancer ; 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38837623

ABSTRACT

BACKGROUND: To evaluate a novel intraoperative localization technique utilizing temporary pulmonary arteriovenous occlusion for enhancing the precision of sublobar resections in early-stage NSCLC. METHODS: Conducted from January to November 2023, this study involved 140 patients. During the surgery, key pulmonary vessels were identified using preoperative three-dimensional (3D) imaging and temporarily occluded with noninvasive clamps to isolate the target lung segment. Following vascular occlusion, indocyanine green (ICG) was administered intravenously to precisely delineate the resection margins. After visually confirming the marked areas, the clamps were released, and a targeted partial resection was performed on the delineated segment. Surgical data, including operation times, surgical margins, and hospitalization costs, were collected and compared with those from a historical control group of 110 patients who underwent traditional pulmonary wedge resections. RESULTS: In the study group, the median surgical margin achieved was 16 mm, which was statistically significant compared to 15 mm in the control group (p < 0.05). Operation times were reduced to an average of 58.43 ± 12.962 min, showing a decrease from the control group's average of 69.50 ± 17.544 min (p < 0.05). Hospitalization costs were also lower, averaging $4772.98 ± 624.339 for the study group versus $5161.34 ± 856.336 for the control group (p < 0.05). Patient safety was maintained with no increase in surgical complications. CONCLUSION: The technique, leveraging temporary pulmonary arteriovenous occlusion, offered a significant advancement in the surgical treatment of peripheral early-stage NSCLC. It reduced operation time and lowered overall surgical costs. This method represented a promising alternative to traditional surgical approaches.

3.
Adv Funct Mater ; 34(8)2024 Feb 19.
Article in English | MEDLINE | ID: mdl-38828467

ABSTRACT

Most nanomedicines require efficient in vivo delivery to elicit diagnostic and therapeutic effects. However, en route to their intended tissues, systemically administered nanoparticles often encounter delivery barriers. To describe these barriers, we propose the term "nanoparticle blood removal pathways" (NBRP), which summarizes the interactions between nanoparticles and the body's various cell-dependent and cell-independent blood clearance mechanisms. We reviewed nanoparticle design and biological modulation strategies to mitigate nanoparticle-NBRP interactions. As these interactions affect nanoparticle delivery, we studied the preclinical literature from 2011-2021 and analyzed nanoparticle blood circulation and organ biodistribution data. Our findings revealed that nanoparticle surface chemistry affected the in vivo behavior more than other nanoparticle design parameters. Combinatory biological-PEG surface modification improved the blood area under the curve by ~418%, with a decrease in liver accumulation of up to 47%. A greater understanding of nanoparticle-NBRP interactions and associated delivery trends will provide new nanoparticle design and biological modulation strategies for safer, more effective, and more efficient nanomedicines.

4.
Appl Microbiol Biotechnol ; 108(1): 359, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38836885

ABSTRACT

Vacuum foam drying (VFD) has been shown to improve the thermostability and long-term shelf life of Newcastle Disease Virus (NDV). This study optimized the VFD process to improve the shelf life of NDV at laboratory-scale and then tested the optimized conditions at pilot-scale. The optimal NDV to T5 formulation ratio was determined to be 1:1 or 3:2. Using the 1:1 virus to formulation ratio, the optimal filling volumes were determined to be 13-17% of the vial capacity. The optimized VFD process conditions were determined to be at a shelf temperature of 25℃ with a minimum overall drying time of 44 h. The vaccine samples prepared using these optimized conditions at laboratory-scale exhibited virus titer losses of ≤ 1.0 log10 with residual moisture content (RMC) below 3%. Furthermore, these samples were transported for 97 days around China at ambient temperature without significant titer loss, thus demonstrating the thermostability of the NDV-VFD vaccine. Pilot-scale testing of the NDV-VFD vaccine at optimized conditions showed promising results for up-scaling the process as the RMC was below 3%. However, the virus titer loss was slightly above 1.0 log10 (approximately 1.1 log10). Therefore, the NDV-VFD process requires further optimization at pilot scale to obtain a titer loss of ≤ 1.0 log10. Results from this study provide important guidance for possible industrialization of NDV-VFD vaccine in the future. KEY POINTS: • The process optimization and scale-up test of thermostable NDV vaccine prepared through VFD is reported for the first time in this study. • The live attenuated NDV-VFD vaccine maintained thermostability for 97 days during long distance transportation in summer without cold chain conditions. • The optimized NDV-VFD vaccine preparations evaluated at pilot-scale maintained acceptable levels of infectivity after preservation at 37℃ for 90 days, which demonstrated the feasibility of the vaccine for industrialization.


Subject(s)
Newcastle Disease , Newcastle disease virus , Temperature , Viral Vaccines , Newcastle disease virus/immunology , Newcastle disease virus/chemistry , Pilot Projects , Newcastle Disease/prevention & control , Newcastle Disease/virology , Viral Vaccines/chemistry , Viral Vaccines/immunology , Vacuum , Animals , Chickens , Desiccation , China , Drug Stability , Viral Load
5.
J Transl Med ; 22(1): 533, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38831470

ABSTRACT

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is a common disease in the urinary system, with a high incidence and poor prognosis in advanced stages. Although γ-interferon-inducible protein 16 (IFI16) has been reported to play a role in various tumors, its involvement in ccRCC remains poorly documented, and the molecular mechanisms are not yet clear. METHODS: We conducted bioinformatics analysis to study the expression of IFI16 in ccRCC using public databases. Additionally, we analyzed and validated clinical specimens that we collected. Subsequently, we explored the impact of IFI16 on ccRCC cell proliferation, migration, and invasion through in vitro and in vivo experiments. Furthermore, we predicted downstream molecules and pathways using transcriptome analysis and confirmed them through follow-up experimental validation. RESULTS: IFI16 was significantly upregulated in ccRCC tissue and correlated with poor patient prognosis. In vitro, IFI16 promoted ccRCC cell proliferation, migration, and invasion, while in vivo, it facilitated subcutaneous tumor growth and the formation of lung metastatic foci. Knocking down IFI16 suppressed its oncogenic function. At the molecular level, IFI16 promoted the transcription and translation of IL6, subsequently activating the PI3K/AKT signaling pathway and inducing epithelial-mesenchymal transition (EMT). CONCLUSION: IFI16 induced EMT through the IL6/PI3K/AKT axis, promoting the progression of ccRCC.


Subject(s)
Carcinoma, Renal Cell , Cell Movement , Cell Proliferation , Disease Progression , Epithelial-Mesenchymal Transition , Interleukin-6 , Kidney Neoplasms , Nuclear Proteins , Phosphatidylinositol 3-Kinases , Phosphoproteins , Proto-Oncogene Proteins c-akt , Signal Transduction , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/pathology , Carcinoma, Renal Cell/metabolism , Humans , Proto-Oncogene Proteins c-akt/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Kidney Neoplasms/pathology , Kidney Neoplasms/genetics , Kidney Neoplasms/metabolism , Cell Line, Tumor , Interleukin-6/metabolism , Phosphoproteins/metabolism , Phosphoproteins/genetics , Nuclear Proteins/metabolism , Nuclear Proteins/genetics , Animals , Cell Movement/genetics , Epithelial-Mesenchymal Transition/genetics , Gene Expression Regulation, Neoplastic , Mice, Nude , Neoplasm Invasiveness , Male , Female , Prognosis
6.
Plant Cell Environ ; 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38847345

ABSTRACT

Shoot branching from axillary bud (AB) directly determines plant architecture. However, the mechanism through which AB remains dormant or emerges to form branches as plants grow remains largely unknown. Here, the auxin-strigolactone (IAA-SL) pathway was first shown to regulate shoot branching in poplar, and we found that PagKNAT2/6b could modulate this pathway. PagKNAT2/6b was expressed mainly in the shoot apical meristem and AB and was induced by shoot apex damage. PagKNAT2/6b overexpressing poplar plants (PagKNAT2/6b OE) exhibited multiple branches that mimicked the branching phenotype of nontransgenic plants after decapitation treatment, while compared with nontransgenic controls, PagKNAT2/6b antisense transgenic poplar and Pagknat2/6b mutant lines exhibited a significantly decreased number of branches after shoot apex damage treatment. In addition, we found that PagKNAT2/6b directly inhibits the expression of the key IAA synthesis gene PagYUC6a, which is specifically expressed in the shoot apex. Moreover, overexpression of PagYUC6a in the PagKNAT2/6b OE background reduced the number of branches after shoot apex damage treatment. Overall, we conclude that PagKNAT2/6b responds to shoot apical injury and regulates shoot branching through the IAA-SL pathway. These findings may provide a theoretical basis and candidate genes for genetic engineering to create new forest tree species with different crown types.

7.
BMJ Health Care Inform ; 31(1)2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38830766

ABSTRACT

BACKGROUND: Current approaches for initial coronary artery disease (CAD) assessment rely on pretest probability (PTP) based on risk factors and presentations, with limited performance. Infrared thermography (IRT), a non-contact technology that detects surface temperature, has shown potential in assessing atherosclerosis-related conditions, particularly when measured from body regions such as faces. We aim to assess the feasibility of using facial IRT temperature information with machine learning for the prediction of CAD. METHODS: Individuals referred for invasive coronary angiography or coronary CT angiography (CCTA) were enrolled. Facial IRT images captured before confirmatory CAD examinations were used to develop and validate a deep-learning IRT image model for detecting CAD. We compared the performance of the IRT image model with the guideline-recommended PTP model on the area under the curve (AUC). In addition, interpretable IRT tabular features were extracted from IRT images to further validate the predictive value of IRT information. RESULTS: A total of 460 eligible participants (mean (SD) age, 58.4 (10.4) years; 126 (27.4%) female) were included. The IRT image model demonstrated outstanding performance (AUC 0.804, 95% CI 0.785 to 0.823) compared with the PTP models (AUC 0.713, 95% CI 0.691 to 0.734). A consistent level of superior performance (AUC 0.796, 95% CI 0.782 to 0.811), achieved with comprehensive interpretable IRT features, further validated the predictive value of IRT information. Notably, even with only traditional temperature features, a satisfactory performance (AUC 0.786, 95% CI 0.769 to 0.803) was still upheld. CONCLUSION: In this prospective study, we demonstrated the feasibility of using non-contact facial IRT information for CAD prediction.


Subject(s)
Coronary Artery Disease , Face , Thermography , Humans , Thermography/methods , Coronary Artery Disease/diagnostic imaging , Male , Female , Middle Aged , Face/diagnostic imaging , Aged , Predictive Value of Tests , Feasibility Studies , Body Temperature , Machine Learning , Coronary Angiography , Computed Tomography Angiography , Prospective Studies , Infrared Rays
8.
Digit Health ; 10: 20552076241259047, 2024.
Article in English | MEDLINE | ID: mdl-38840661

ABSTRACT

Background: Falls pose a serious health risk for the elderly, particular for those who are living alone. The utilization of WiFi-based fall detection, employing Channel State Information (CSI), emerges as a promising solution due to its non-intrusive nature and privacy preservation. Despite these advantages, the challenge lies in optimizing cross-individual performance for CSI-based methods. Objective: This study aimed to develop a resilient real-time fall detection system across individuals utilizing CSI, named TCS-Fall. This method was designed to offer continuous monitoring of activities over an extended timeframe, ensuring accurate and prompt detection of falls. Methods: Extensive CSI data on 1800 falls and 2400 daily activities was collected from 20 volunteers. The grouped coefficient of variation of CSI amplitudes were utilized as input features. These features capture signal fluctuations and are input to a convolutional neural network classifier. Cross-individual performance was extensively evaluated using various train/test participant splits. Additionally, a user-friendly CSI data collection and detection tool was developed using PyQT. To achieve real-time performance, data parsing and pre-processing computations were optimized using Numba's just-in-time compilation. Results: The proposed TCS-Fall method achieved excellent performance in cross-individual fall detection. On the test set, AUC reached 0.999, no error warning ratio score reached 0. 955 and correct warning ratio score reached of 0.975 when trained with data from only two volunteers. Performance can be further improved to 1.00 when 10 volunteers were included in training data. The optimized data parsing/pre-processing achieved over 20× speedup compared to previous method. The PyQT tool parsed and detected the fall within 100 ms. Conclusions: TCS-Fall method enables excellent real-time cross-individual fall detection utilizing WiFi CSI, promising swift alerts and timely assistance to elderly. Additionally, the optimized data processing led to a significant speedup. These results highlight the potential of our approach in enhancing real-time fall detection systems.

11.
Bioorg Med Chem ; 108: 117776, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38852257

ABSTRACT

Myocardial ischemia/reperfusion (MI/R) is a common cardiovascular disease that seriously affects the quality of life and prognosis of patients. In recent years, matrine has attracted widespread attention in the treatment of cardiovascular diseases. This study designed, synthesized, and characterized 20 new matrine derivatives and studied their protective effects on ischemia-reperfusion injury through in vivo and in vitro experiments. Based on cellular assays, most newly synthesized derivatives have a certain protective effect on Hypoxia/Reoxygenation (H/R) induced H9C2 cell damage, with compound 22 having the best activity and effectively reducing cell apoptosis and necrosis. In vitro experimental data shows that compound 22 can significantly reduce the infarct size of rat myocardium and improve cardiac function after MI/R injury. In summary, compound 22 is a new potential cardioprotective agent that can promote angiogenesis and enhance antioxidant activity by activating ADCY5, CREB3l4, and VEGFA, thereby protecting myocardial cell apoptosis and necrosis induced by MI/R.

12.
Langmuir ; 2024 Jun 09.
Article in English | MEDLINE | ID: mdl-38853520

ABSTRACT

The design of single-atom nanozymes with dual active sites to increase their activity and for the detection and degradation of contaminants is rare and challenging. In this work, a single-atom nanozyme (FeCu-NC) based on a three-dimensional porous Fe/Cu dual active site was developed as a colorimetric sensor for both the quantitative analysis of isoniazid (INH) and the efficient degradation of levofloxacin (LEV). FeCu-NC was synthesized using a salt template and freeze-drying method with a three-dimensional hollow porous structure and dual active sites (Fe-Nx and Cu-Nx). In terms of morphology and structure, FeCu-NC exhibits excellent peroxidase-like activity and catalytic properties. Therefore, a colorimetric sensor was constructed around FeCu-NC for sensitive and rapid quantitative analysis of INH with a linear range of 0.9-10 µM and a detection limit as low as 0.3 µM, and the sensor was successfully applied to the analysis of INH in human urine. In addition, FeCu-NC promoted the efficient degradation of LEV by peroxymonosulfate activation, with a degradation rate of 90.4% for LEV at 30 min. This work sheds new light on the application of single-atom nanozymes to antibiotics for colorimetric sensing and degradation.

13.
OTO Open ; 8(2): e147, 2024.
Article in English | MEDLINE | ID: mdl-38846015

ABSTRACT

Objective: To evaluate for correlation between intraoperative ultrasound (IOUS)-measured tumor thickness (TT) (uTT) and histopathological TT (hTT), and to compare IOUS-assisted resection with conventional resection in patients with oral tongue cancers. Data Sources: Ovid MEDLINE (1946-2023), Embase.com (1947-2023), and Web of Science (All Databases 1900-2023). Review Methods: Inclusion criteria were the use of IOUS for the management of oral tongue cancer. Studies that did not report quantitative data were excluded. Additionally, studies that were not contributory to meta-analysis, or a narrative analysis of pooled results were excluded. Selection was carried out by 2 reviewers. A total of 2417 studies were initially identified, with 12 ultimately being included in this review, and 7 included in the meta-analysis. Data were extracted by 2 investigators and were pooled using a random-effects model. Results: Our meta-analysis reveals a pooled correlation coefficient of 0.92 (95% confidence interval: 0.80-0.96) for studies comparing uTT to hTT. Studies comparing IOUS-assisted resection to conventional resection found IOUS-assisted resection yielded wider nearest margins in all studies reporting this outcome. Conclusion: IOUS reliably measures TT, similarly to that of histopathology measurement. IOUS-assisted resection, which allows the surgeon to view the deep extent of tumor invasion, may increase closest radial margin distance compared to conventional resection. IOUS-assisted resection may represent a more reliable approach to achieving clear margins than conventional resection.

14.
Front Neurol ; 15: 1389950, 2024.
Article in English | MEDLINE | ID: mdl-38846042

ABSTRACT

Background and objective: Current data on the optimal treatment modality for ruptured anterior communicating artery (AComA) aneurysms are limited. We conducted this multicenter retrospective study to evaluate the safety and clinical outcomes of endovascular treatment (EVT) and microsurgical clipping (MC) for the treatment of ruptured AComA patients. Methods: Patients with ruptured AComA aneurysms were screened from the Chinese Multicenter Cerebral Aneurysm Database. Propensity score matching (PSM) was used to adjust for baseline characteristic imbalances between the EVT and MC groups. The safety outcomes included total procedural complications, procedure-related morbidity/death and remedial procedure for complication. The primary clinical outcome was 2-year functional independence measured by the modified Rankin scale (mRS) score. Results: The analysis included 893 patients with ruptured AComA aneurysms (EVT: 549; MC: 346). PSM yielded 275 pairs of patients in the EVT and MC cohorts for comparison. Decompressive craniectomy being more prevalent in the MC group (19.3% vs. 1.5%, p < 0.001). Safety data revealed a lower rate of total procedural complications (odds ratio [OR] = 0.62, 95% CI 0.39-0.99; p = 0.044) in the EVT group and similar rates of procedure-related morbidity/death (OR = 0.91, 95% CI 0.48-1.73; p = 0.880) and remedial procedure for complication (OR = 1.35, 95% CI 0.51-3.69, p = 0.657) between the groups. Compared with that of MC patients, EVT patients had a greater likelihood of functional independence (mRS score 0-2) at discharge (OR = 1.68, 95% CI 1.14-2.50; p = 0.008) and at 2 years (OR = 1.89, 95% CI 1.20-3.00; p = 0.005), a lower incidence of 2-year all-cause mortality (OR = 0.54, 95% CI 0.31-0.93; p = 0.023) and a similar rate of retreatment (OR = 1.00, 95% CI 0.23-4.40; p = 1.000). Conclusion: Clinical outcomes after treatment for ruptured AComA aneurysms appear to be superior to those after treatment with MC, with fewer overall procedure-related complications and no increase in the retreatment rate. Additional studies in other countries are needed to verify these findings.

15.
Front Immunol ; 15: 1361606, 2024.
Article in English | MEDLINE | ID: mdl-38846937

ABSTRACT

Introduction: Pathological changes in the articular cartilage (AC) and synovium are major manifestations of osteoarthritis (OA) and are strongly associated with pain and functional limitations. Exosome-derived microRNAs (miRNAs) are crucial regulatory factors in intercellular communication and can influence the progression of OA by participating in the degradation of chondrocytes and the phenotypic transformation in the polarization of synovial macrophages. However, the specific relationships and pathways of action of exosomal miRNAs in the pathological progression of OA in both cartilage and synovium remain unclear. Methods: This study evaluates the effects of fibroblast-like synoviocyte (FLS)-derived exosomes (FLS-Exos), influenced by miR-146a, on AC degradation and synovial macrophage polarization. We investigated the targeted relationship between miR-146a and TRAF6, both in vivo and in vitro, along with the involvement of the NF-κB signaling pathway. Results: The expression of miR-146a in the synovial exosomes of OA rats was significantly higher than in healthy rats. In vitro, the upregulation of miR-146a reduced chondrocyte apoptosis, whereas its downregulation had the opposite effect. In vivo, exosomes derived from miR-146a-overexpressing FLSs (miR-146a-FLS-Exos) reduced AC injury and chondrocyte apoptosis in OA. Furthermore, synovial proliferation was reduced, and the polarization of synovial macrophages shifted from M1 to M2. Mechanistically, the expression of TRAF6 was inhibited by targeting miR-146a, thereby modulating the Toll-like receptor 4/TRAF6/NF-κB pathway in the innate immune response. Discussion: These findings suggest that miR-146a, mediated through FLS-Exos, may alleviate OA progression by modulating cartilage degradation and macrophage polarization, implicating the NF-κB pathway in the innate immune response. These insights highlight the therapeutic potential of miR-146a as a protective agent in OA, underscoring the importance of exosomal miRNAs in the pathogenesis and potential treatment of the disease.


Subject(s)
Exosomes , Macrophages , MicroRNAs , Osteoarthritis , Synoviocytes , TNF Receptor-Associated Factor 6 , MicroRNAs/genetics , Animals , Exosomes/metabolism , Osteoarthritis/metabolism , Osteoarthritis/pathology , Osteoarthritis/immunology , Rats , Macrophages/immunology , Macrophages/metabolism , Synoviocytes/metabolism , Synoviocytes/pathology , Male , TNF Receptor-Associated Factor 6/metabolism , TNF Receptor-Associated Factor 6/genetics , Cartilage, Articular/metabolism , Cartilage, Articular/pathology , Chondrocytes/metabolism , NF-kappa B/metabolism , Signal Transduction , Rats, Sprague-Dawley , Fibroblasts/metabolism , Synovial Membrane/metabolism , Synovial Membrane/pathology , Synovial Membrane/immunology , Cells, Cultured , Apoptosis , Toll-Like Receptor 4/metabolism , Toll-Like Receptor 4/genetics , Macrophage Activation
16.
Nucleic Acids Res ; 2024 Jun 08.
Article in English | MEDLINE | ID: mdl-38850160

ABSTRACT

A fundamental analysis task for single-cell transcriptomics data is clustering with subsequent visualization of cell clusters. The genes responsible for the clustering are only inferred in a subsequent step. Clustering cells and genes together would be the remit of biclustering algorithms, which are often bogged down by the size of single-cell data. Here we present 'Correspondence Analysis based Biclustering on Networks' (CAbiNet) for joint clustering and visualization of single-cell RNA-sequencing data. CAbiNet performs efficient co-clustering of cells and their respective marker genes and jointly visualizes the biclusters in a non-linear embedding for easy and interactive visual exploration of the data.

17.
J Colloid Interface Sci ; 672: 350-362, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38850862

ABSTRACT

To overcome the biological barriers in the journey of systemic gene delivery, a multifaceted genomic synthetic nanomedicine was elaborated and strategically equipped with a multiple of intriguing responsiveness. Particularly, core-shell plasmid DNA condensates were created based on polyionic complexation with block copolymer of polyethylene glycol (PEG)-polylysine (PLys), namely, the nanoscaled PLys&pDNA nanoparticle tethered with the biocompatible PEG surroundings. Furthermore, redox-reversible disulfide crosslinking was introduced into PLys&pDNA nanoparticle to accomplish adequate structural stabilities, and thermal-responsive polypropylacrylamide (PNIPAM) was introduced as the secondary intermediate surroundings onto the pre-formulated PLys&pDNA nanoparticle with the aim of preventing the potential enzymatic degradation from the environmental nucleases. Hence, hundreds of times prolonged survival and retention was determined in pertinent to the blood circulation properties. Additionally, the installation of a guide ligand at the distal end of PEG segments was proposed to encourage selective tumor uptake. A linear peptide of GPLGVRG, which is selectively susceptible to digestion by the tumor-enriched matrix metalloproteinase 2 (MMP-2), was used as the linkage between the shell and core. This peptide has been shown to detach the bio-inert PEGylation, resulting in further facilitated cell endocytosis and intracellular trafficking activities. Hence, the precisely defined synthetic nanomedicine, which exhibits desirable characteristics, efficient expression of the therapeutic gene in the affected cells, and contributed to potent therapeutic efficacy in systemic treatment of intractable tumors by encapsulating the anti-angiogenic gene.

18.
J Control Release ; 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38851536

ABSTRACT

Glioma is an aggressive malignant brain tumor with a very poor prognosis for survival. The poor tumor targeting efficiency and tumor microenvironment penetration barrier also as troubles inhibited the effective glioma chemotherapy. Here, we design a core-shell structure cascade amplified hybrid catalytic nanopotentiators CFpAD with DM1 encapsulated to overcome the glioma therapeutic obstacles. NIR laser-based BBB penetrating enhances the tumor accumulation of CFpAD. When CFpAD, as the cascade amplified drug, is treated on the cancer cells, the bomb-like CFpAD releases gold nanoparticles as glucose oxidase (GOx) and ferric oxide nanoparticles (FNPs) as peroxides (POx) after blasting, producing ROS via a cascade amplification for tumor cell apoptosis. Gold nanoparticles can rest CAFs and reduce ECM secretion, achieving deep penetration of CFpAD. Moreover, CFpAD also cuts off the nutritional supply of the tumor, reduces the pH value, and releases free radicals to destroy the cancer. The glioma cell viability was significantly decreased through DNA damage and ROS aggregation due to the DM1-based chemotherapy synergistically combined with interventional photothermal therapy (IPTT) and radiotherapy (RT). This domino cascade amplified loop, combined with starvation therapy with IPTT and RT, has good tumor penetration and outstanding antitumor efficacy, and is a promising glioma treatment system.

19.
Article in English | MEDLINE | ID: mdl-38846323

ABSTRACT

Background: Currently, endovascular treatment of intracranial aneurysms (ICAs) is limited by low complete occlusion rates. The advent of novel endovascular technology has expanded the applicability of endovascular therapy; however, the superiority of novel embolic devices over the traditional Guglielmi detachable coils (GDCs) is still debated. We performed a systematic review of literature that reported Raymond-Roy occlusion classification (RROC) rates of modern endovascular devices to determine their immediate and follow-up occlusion effectiveness for the treatment of unruptured saccular ICAs. Methods: A search was conducted using electronic databases (PUBMED, Cochrane, ClinicalTrials.gov, Web of Science). We retrieved studies published between 2000-2022 reporting immediate and follow-up RROC rates of subjects treated with different endovascular ICA therapies. We extracted demographic information of the treated patients and their reported angiographic RROC rates. Results: A total of 80 studies from 15 countries were included for data extraction. RROC rates determined from angiogram were obtained for 21,331 patients (72.5% females, pooled mean age: 58.2 (95% CI: 56.8-59.6), harboring 22,791 aneurysms. The most frequent aneurysm locations were the internal carotid artery (46.4%, 95% CI: 41.9%-50.9%), the anterior communicating artery (26.4%, 95% CI: 22.5%-30.8%), the middle cerebral artery (24.5%, 95% CI:19.2%-30.8%) and the basilar tip (14.4%, 95% CI:11.3%-18.3%). The complete occlusion probability (RROC-I) was analyzed for GDCs, the Woven EndoBridge (WEB), and flow diverters. The RROC-I rate was the highest in balloon-assisted coiling (73.9%, 95% CI: 65.0%-81.2%) and the lowest in the WEB (27.8%, 95% CI:13.2%-49.2%). The follow-up RROC-I probability was homogenous in all analyzed devices. Conclusions: We observed that the coil-based endovascular therapy provides acceptable rates of complete occlusion, and these rates are improved in balloon-assisted coils. Out of the analyzed devices, the WEB exhibited the shortest time to achieve >90% probability of follow-up complete occlusion (~18 months). Overall, the GDCs remain the gold standard for endovascular treatment of unruptured saccular aneurysms.

20.
BMC Public Health ; 24(1): 1224, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38702746

ABSTRACT

BACKGROUND: Accumulating evidence suggests a pivotal role of vitamin B2 in the pathogenesis and progression of prostate cancer (PCa). Vitamin B2 intake has been postulated to modulate the screening rate for PCa by altering the concentration of prostate-specific antigen(PSA). However, the relationship between vitamin B2 and PSA remains indeterminate. Hence, we conducted a comprehensive evaluation of the association between vitamin B2 intake and PSA levels, utilizing data from the National Health and Nutrition Examination Survey (NHANES) database. METHODS: From a pool of 20,371 participants in the NHANES survey conducted between 2003 and 2010, a cohort of 2,323 participants was selected for the present study. The male participants were classified into four distinct groups based on their levels of vitamin B2 intake. We employed a multiple linear regression model and a non-parametric regression method to investigate the relationship between vitamin B2 and PSA levels. RESULTS: The study cohort comprised of 2,323 participants with a mean age of 54.95 years (± 11.73). Our findings revealed a statistically significant inverse correlation between vitamin B2 intake (mg) and PSA levels, with a reduction of 0.13 ng/ml PSA concentration for every unit increase in vitamin B2 intake. Furthermore, we employed a fully adjusted model to construct a smooth curve to explore the possible linear relationship between vitamin B2 intake and PSA concentration. CONCLUSIONS: Our study in American men has unveiled a notable inverse association between vitamin B2 intake and PSA levels, potentially posing a challenge for the identification of asymptomatic prostate cancer. Specifically, our findings suggest that individuals with higher vitamin B2 intake may be at a greater risk of being diagnosed with advanced prostate cancer in the future, possibly indicating a detection bias. These results may offer a novel explanation for the observed positive correlation between vitamin B2 intake and prostate cancer.


Subject(s)
Nutrition Surveys , Prostate-Specific Antigen , Prostatic Neoplasms , Riboflavin , Humans , Male , Prostate-Specific Antigen/blood , Middle Aged , United States/epidemiology , Aged , Prostatic Neoplasms/blood , Prostatic Neoplasms/epidemiology , Riboflavin/administration & dosage , Adult
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