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1.
ACS Synth Biol ; 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38847341

ABSTRACT

Aromatic d-amino acids (d-AAs) play a pivotal role as important chiral building blocks and key intermediates in fine chemical and drug synthesis. Meso-diaminopimelate dehydrogenase (DAPDH) serves as an excellent biocatalyst in the synthesis of d-AAs and their derivatives. However, its strict substrate specificity and the lack of efficient engineering methods have hindered its widespread application. Therefore, this study aims to elucidate the catalytic mechanism underlying DAPDH from Proteus vulgaris (PvDAPDH) through the examination of its crystallographic structure, computational simulations of potential energies and molecular dynamics simulations, and site-directed mutagenesis. Mechanism-guided computational design showed that the optimal mutant PvDAPDH-M3 increased specific activity and catalytic efficiency (kcat/Km) for aromatic keto acids up to 124-fold and 92.4-fold, respectively, compared to that of the wild type. Additionally, it expanded the substrate scope to 10 aromatic keto acid substrates. Finally, six high-value-added aromatic d-AAs and their derivatives were synthesized using a one-pot three-enzyme cascade reaction, exhibiting a good conversion rate ranging from 32 to 84% and excellent stereoselectivity (enantiomeric excess >99%). These findings provide a potential synthetic pathway for the green industrial production of aromatic d-AAs.

2.
BMC Med Educ ; 24(1): 531, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38741079

ABSTRACT

BACKGROUND: An urgent need exists for innovative surgical video recording techniques in head and neck reconstructive surgeries, particularly in low- and middle-income countries where a surge in surgical procedures necessitates more skilled surgeons. This demand, significantly intensified by the COVID-19 pandemic, highlights the critical role of surgical videos in medical education. We aimed to identify a straightforward, high-quality approach to recording surgical videos at a low economic cost in the operating room, thereby contributing to enhanced patient care. METHODS: The recording was comprised of six head and neck flap harvesting surgeries using GoPro or two types of digital cameras. Data were extracted from the recorded videos and their subsequent editing process. Some of the participants were subsequently interviewed. RESULTS: Both cameras, set at 4 K resolution and 30 frames per second (fps), produced satisfactory results. The GoPro, worn on the surgeon's head, moves in sync with the surgeon, offering a unique first-person perspective of the operation without needing an additional assistant. Though cost-effective and efficient, it lacks a zoom feature essential for close-up views. In contrast, while requiring occasional repositioning, the digital camera captures finer anatomical details due to its superior image quality and zoom capabilities. CONCLUSION: Merging these two systems could significantly advance the field of surgical video recording. This innovation holds promise for enhancing technical communication and bolstering video-based medical education, potentially addressing the global shortage of specialized surgeons.


Subject(s)
COVID-19 , Video Recording , Humans , COVID-19/epidemiology , Plastic Surgery Procedures/education , Surgical Flaps , SARS-CoV-2 , Head/surgery , Neck/surgery
3.
Lupus Sci Med ; 11(1)2024 05 23.
Article in English | MEDLINE | ID: mdl-38782493

ABSTRACT

OBJECTIVE: Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disorder with no reliable serum biomarkers currently available other than autoantibodies. METHODS: In the present study, isobaric tags for relative and absolute quantitation-based mass spectrometry was used to screen the sera of patients with SLE to uncover potential disease biomarkers. RESULTS: 85 common proteins were identified, with 16 being elevated (≥1.3) and 23 being decreased (≤0.7) in SLE. Of the 16 elevated proteins, serum alpha-1-microglobulin/bikunin precursor (AMBP), zinc alpha-2 glycoprotein (AZGP) and retinol-binding protein 4 (RBP4) were validated in independent cross-sectional cohorts (Cohort I, N=52; Cohort II, N=117) using an orthogonal platform, ELISA. Serum AMBP, AZGP and RBP4 were validated to be significantly elevated in both patients with inactive SLE and patients with active SLE compared with healthy controls (HCs) (p<0.05, fold change >2.5) in Cohort I. All three proteins exhibited good discriminatory power for distinguishing active SLE and inactive SLE (area under the curve=0.82-0.96), from HCs. Serum AMBP exhibited the largest fold change in active SLE (5.96) compared with HCs and correlated with renal disease activity. The elevation in serum AMBP was validated in a second cohort of patients with SLE of different ethnic origins, correlating with serum creatinine (r=0.60, p<0.001). CONCLUSION: Since serum AMBP is validated to be elevated in SLE and correlated with renal disease, the clinical utility of this novel biomarker warrants further analysis in longitudinal cohorts of patients with lupus and lupus nephritis.


Subject(s)
Biomarkers , Lupus Erythematosus, Systemic , Retinol-Binding Proteins, Plasma , Humans , Lupus Erythematosus, Systemic/blood , Biomarkers/blood , Female , Male , Adult , Cross-Sectional Studies , Retinol-Binding Proteins, Plasma/analysis , Middle Aged , Mass Spectrometry/methods , Enzyme-Linked Immunosorbent Assay/methods , Alpha-Globulins/analysis , Cohort Studies , Glycoproteins/blood , Case-Control Studies , Young Adult , Zn-Alpha-2-Glycoprotein
4.
J Drugs Dermatol ; 23(5): e134-e136, 2024 05 01.
Article in English | MEDLINE | ID: mdl-38709689

ABSTRACT

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory disease that generates multiple cytokines. Here, we present an example of the cytokines forming a cytokine storm and its effects on the patient. CASE PRESENTATION: We report the case of a 55-year-old man who had severe but stable HS. Serum samples were collected from the patient and extraordinarily elevated cytokine concentrations were identified in the patient's serum.  Conclusion: Cytokine storms may be a condition associated with HS posing additional risk to patient survival. J Drugs Dermatol. 2024;23(5):e134-e136.     doi:10.36849/JDD.7860R1e.


Subject(s)
Cytokine Release Syndrome , Hidradenitis Suppurativa , Humans , Male , Middle Aged , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/diagnosis , Cytokine Release Syndrome/etiology , Cytokine Release Syndrome/blood , Cytokines/blood , Hidradenitis Suppurativa/blood , Hidradenitis Suppurativa/complications , Hidradenitis Suppurativa/diagnosis , Hidradenitis Suppurativa/immunology , Severity of Illness Index
5.
Sci Rep ; 14(1): 8127, 2024 04 07.
Article in English | MEDLINE | ID: mdl-38584156

ABSTRACT

The traditional lecture-based learning (LBL) method is facing great challenges due to its low efficiency and single proceeding form. We designed a PRI-E learning mode that combined and modified problem-based, case-based, and evidence-based learning with a step-by-step approach. We evaluated the practical learning outcomes of using the PRI-E mode by comparing it with traditional lecture-based learning in oral and maxillofacial oncology education. "PRI-E" consists of the first letters of the English words Passion, Research, Innovation, and Education, and it means "the best Education". This prospective randomized controlled trial included 40 participants. We evenly divided the participants into the PRI-E (n = 20) and LBL group (n = 20) based on the entrance test scores. The same staff group designed and then taught the learning content with different group measures. The evaluation included the final test scores and questionnaire assessments. Without affecting the examination results, the PRI-E teaching method was more satisfactory and popular with participants in terms of ability development and classroom participation. Enacting the PRI-E teaching method required more time, but this did not affect its popularity among the participants. Compared with the LBL learning mode, the PRI-E learning mode was more organized and efficient in oral and maxillofacial oncology education without affecting academic performance. This model has a high degree of satisfaction, which is conducive to training students' comprehensive ability.


Subject(s)
Learning , Problem-Based Learning , Humans , Problem-Based Learning/methods , Prospective Studies , Students , Educational Measurement
6.
Biosensors (Basel) ; 14(3)2024 Mar 18.
Article in English | MEDLINE | ID: mdl-38534254

ABSTRACT

To improve the efficiency and patient coverage of the current healthcare system, user-friendly novel homecare devices are urgently needed. In this work, we developed a smartphone-based analyzing and reporting system (SBARS) for biomarker detection in lupus nephritis (LN). This system offers a cost-effective alternative to traditional, expensive large equipment in signal detection and quantification. This innovative approach involves using a portable and affordable microscopic reader to capture biomarker signals. Through smartphone-based image processing techniques, the intensity of each biomarker signal is analyzed. This system exhibited comparable performance to a commercial Genepix scanner in the detection of two potential novel biomarkers of LN, VISG4 and TNFRSF1b. Importantly, this smartphone-based analyzing and reporting system allows for discriminating LN patients with active renal disease from healthy controls with the area-under-the-curve (AUC) value = 0.9 for TNFRSF1b and 1.0 for VSIG4, respectively, indicating high predictive accuracy.


Subject(s)
Lupus Nephritis , Humans , Lupus Nephritis/diagnosis , Point-of-Care Systems , Biomarkers
7.
Front Immunol ; 15: 1370254, 2024.
Article in English | MEDLINE | ID: mdl-38524134

ABSTRACT

Introduction: Systemic Lupus Erythematosus (SLE) impacts the central nervous system (CNS), leading to severe neurological and psychiatric manifestations known as neuropsychiatric lupus (NPSLE). The complexity and heterogeneity of clinical presentations of NPSLE impede direct investigation of disease etiology in patients. The limitations of existing mouse models developed for NPSLE obstruct a comprehensive understanding of this disease. Hence, the identification of a robust mouse model of NPSLE is desirable. Methods: C57BL/6 mice transgenic for human MeCP2 (B6.Mecp2Tg1) were phenotyped, including autoantibody profiling through antigen array, analysis of cellularity and activation of splenic immune cells through flow cytometry, and measurement of proteinuria. Behavioral tests were conducted to explore their neuropsychiatric functions. Immunofluorescence analyses were used to reveal altered neurogenesis and brain inflammation. Various signaling molecules implicated in lupus pathogenesis were examined using western blotting. Results: B6.Mecp2Tg1 exhibits elevated proteinuria and an overall increase in autoantibodies, particularly in female B6.Mecp2Tg1 mice. An increase in CD3+CD4+ T cells in the transgenic mice was observed, along with activated germinal center cells and activated CD11b+F4/80+ macrophages. Moreover, the transgenic mice displayed reduced locomotor activity, heightened anxiety and depression, and impaired short-term memory. Immunofluorescence analysis revealed IgG deposition and immune cell infiltration in the kidneys and brains of transgenic mice, as well as altered neurogenesis, activated microglia, and compromised blood-brain barrier (BBB). Additionally, protein levels of various key signaling molecules were found to be differentially modulated upon MeCP2 overexpression, including GFAP, BDNF, Albumin, NCoR1, mTOR, and NLRP3. Discussion: Collectively, this work demonstrates that B6.Mecp2Tg1 mice exhibit lupus-like phenotypes as well as robust CNS dysfunctions, suggesting its utility as a new animal model for NPSLE.


Subject(s)
Lupus Vasculitis, Central Nervous System , Humans , Animals , Mice , Female , Mice, Transgenic , Mice, Inbred C57BL , Autoantibodies , Phenotype , Proteinuria , Methyl-CpG-Binding Protein 2/genetics
8.
J Autoimmun ; 143: 103165, 2024 02.
Article in English | MEDLINE | ID: mdl-38194790

ABSTRACT

OBJECTIVE: To identify urinary biomarkers that can distinguish active renal involvement in Lupus Nephritis (LN), a severe manifestation of systemic lupus erythematosus (SLE). METHODS: Urine from 117 subjects, comprised of inactive SLE, active non-renal lupus, active LN, and healthy controls, were subjected to Proximity Extension Assay (PEA) based comprehensive proteomics followed by ELISA validation in an independent, ethnically diverse cohort. Proteomic data is also cross-referenced to renal transcriptomic data to elucidate cellular origins of biomarkers. RESULTS: Systems biology analyses revealed progressive activation of cytokine signaling, chemokine activity and coagulation pathways, with worsening renal disease. In addition to validating 30 previously reported biomarkers, this study uncovers several novel candidates. Following ELISA validation in an independent cohort of different ethnicity, the six most discriminatory biomarkers for active LN were urinary ICAM-2, FABP4, FASLG, IGFBP-2, SELE and TNFSF13B/BAFF, with ROC AUC ≥80%, with most correlating strongly with clinical disease activity. Transcriptomic analyses of LN kidneys mapped the likely origin of these proteins to intra-renal myeloid cells (CXCL16, IL-1RT2, TNFSF13B/BAFF), T/NK cells (FASLG), leukocytes (ICAM2) and endothelial cells (SELE). CONCLUSION: In addition to confirming the diagnostic potential of urine ALCAM, CD163, MCP1, SELL, ICAM1, VCAM1, NGAL and TWEAK for active LN, this study adds urine ICAM-2, FABP4, FASLG, IGFBP-2, SELE, and TNFSF13B/BAFF as additional markers that warrant systematic validation in larger cross-sectional and longitudinal cohorts.


Subject(s)
Lupus Erythematosus, Systemic , Lupus Nephritis , Humans , Lupus Nephritis/diagnosis , Lupus Nephritis/genetics , Insulin-Like Growth Factor Binding Protein 2 , Proteomics , Cross-Sectional Studies , Endothelial Cells , Lupus Erythematosus, Systemic/diagnosis , Lupus Erythematosus, Systemic/genetics , Biomarkers , Kidney , Gene Expression Profiling
9.
Article in English | MEDLINE | ID: mdl-38215315

ABSTRACT

Communication overhead has become one of the major bottlenecks in the distributed training of modern deep neural networks. With such consideration, various quantization-based stochastic gradient descent (SGD) solvers have been proposed and widely adopted, among which signSGD with majority vote shows a promising direction because of its communication efficiency and robustness against Byzantine attackers. However, signSGD fails to converge in the presence of data heterogeneity, which is commonly observed in the emerging federated learning (FL) paradigm. In this article, a sufficient condition for the convergence of the sign-based gradient descent method is derived, based on which a novel magnitude-driven stochastic-sign-based gradient compressor is proposed to address the non-convergence issue of signSGD. The convergence of the proposed method is established in the presence of arbitrary data heterogeneity. The Byzantine resilience of sign-based gradient descent methods is quantified, and the error-feedback mechanism is further incorporated to boost the learning performance Experimental results on the MNIST dataset, the CIFAR-10 dataset, and the Tiny-ImageNet dataset corroborate the effectiveness of the proposed methods.

10.
Clin Oral Investig ; 28(2): 125, 2024 Jan 30.
Article in English | MEDLINE | ID: mdl-38286974

ABSTRACT

OBJECTIVE: The study addresses the long-standing challenge of insufficient length in vascularized fibular flaps when reconstructing large mandibular defects that require dual-barrel grafts. Employing personalized 3D-printed osteotomy guides, the study aims to optimize fibular utilization and minimize the required graft length. MATERIAL AND METHODS: Two reconstruction methods for distal bone defects were compared: a fold-down (FD) group that employed a specialized osteotomy guide for folding down a triangular bone segment, and a traditional double-barrel (DB) group. Metrics for comparison included defect and graft lengths, as well as the graft-to-defect length ratio. Postoperative quality of life was assessed using the University of Washington Quality of Life questionnaire (UW-QoL). RESULT: Both FD and DB groups achieved successful mandibular reconstruction. Despite larger defects in the FD group (117 ± 31.35 mm vs 84 ± 35.34 mm, p = 0.028), the used fibula length was not statistically longer in the FD group. The median ratio of graft-to-defect length was also lower in the FD group (1.327 vs 1.629, p = 0.024), suggesting that FD required only 82.47% of the graft length needed in the DB approach. Quality of life scores post-surgery were comparable between the groups. CONCLUSION: Personalized 3D-printed osteotomy guides enhance fibula graft efficacy for reconstructing larger mandibular defects, necessitating shorter graft lengths while preserving postoperative quality of life. CLINICAL RELEVANCE: This study confirms the utility of 3D printing technology as an effective and precise tool in orthopedic surgery, particularly for complex reconstructions like large mandibular defects. It suggests a viable alternative that could potentially revolutionize current practices in bone grafting.


Subject(s)
Free Tissue Flaps , Mandibular Reconstruction , Fibula/surgery , Quality of Life , Mandible/surgery , Surgical Flaps , Mandibular Reconstruction/methods , Bone Transplantation/methods , Osteotomy
11.
IEEE Trans Pattern Anal Mach Intell ; 45(12): 14727-14744, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37676811

ABSTRACT

This article presents Holistically-Attracted Wireframe Parsing (HAWP), a method for geometric analysis of 2D images containing wireframes formed by line segments and junctions. HAWP utilizes a parsimonious Holistic Attraction (HAT) field representation that encodes line segments using a closed-form 4D geometric vector field. The proposed HAWP consists of three sequential components empowered by end-to-end and HAT-driven designs: 1) generating a dense set of line segments from HAT fields and endpoint proposals from heatmaps, 2) binding the dense line segments to sparse endpoint proposals to produce initial wireframes, and 3) filtering false positive proposals through a novel endpoint-decoupled line-of-interest aligning (EPD LOIAlign) module that captures the co-occurrence between endpoint proposals and HAT fields for better verification. Thanks to our novel designs, HAWPv2 shows strong performance in fully supervised learning, while HAWPv3 excels in self-supervised learning, achieving superior repeatability scores and efficient training (24 GPU hours on a single GPU). Furthermore, HAWPv3 exhibits a promising potential for wireframe parsing in out-of-distribution images without providing ground truth labels of wireframes.

12.
IEEE Trans Pattern Anal Mach Intell ; 45(12): 15233-15248, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37698973

ABSTRACT

This article studies the challenging two-view 3D reconstruction problem in a rigorous sparse-view configuration, which is suffering from insufficient correspondences in the input image pairs for camera pose estimation. We present a novel Neural One-PlanE RANSAC framework (termed NOPE-SAC in short) that exerts excellent capability of neural networks to learn one-plane pose hypotheses from 3D plane correspondences. Building on the top of a Siamese network for plane detection, our NOPE-SAC first generates putative plane correspondences with a coarse initial pose. It then feeds the learned 3D plane correspondences into shared MLPs to estimate the one-plane camera pose hypotheses, which are subsequently reweighed in a RANSAC manner to obtain the final camera pose. Because the neural one-plane pose minimizes the number of plane correspondences for adaptive pose hypotheses generation, it enables stable pose voting and reliable pose refinement with a few of plane correspondences for the sparse-view inputs. In the experiments, we demonstrate that our NOPE-SAC significantly improves the camera pose estimation for the two-view inputs with severe viewpoint changes, setting several new state-of-the-art performances on two challenging benchmarks, i.e., MatterPort3D and ScanNet, for sparse-view 3D reconstruction.

13.
Int J Mol Sci ; 24(16)2023 Aug 17.
Article in English | MEDLINE | ID: mdl-37629087

ABSTRACT

Metabolism plays a critical role in cancer. OLR1 has been implicated in cardiovascular and metabolic disorders, while its association with tumorigenesis and tumor immunity remains poorly defined in the literature. We conducted comprehensive pan-cancer analyses based on the TCGA database to examine OLR1 expression and its prognostic implications. Correlations between OLR1 expression level and tumor immunity and immunotherapy were investigated by immune infiltration, enrichment, and TIDE analysis methods. Immunohistochemistry detected OLR1 expression in HNSCC. We used the GSEA method to explore the potential signaling pathways in which OLR1 is involved, and a correlation analysis to investigate the relationships between OLR1 and epithelial-mesenchymal transition (EMT) and cuproptosis. In addition, the effects of OLR1 knockdown on the EMT process, invasion, stemness, and cuproptosis of HNSCC cells were examined by scratch, Transwell, CCK8, sphere formation, and flow cytometry, while changes in related proteins were detected using the immunoblotting method. OLR1 is highly expressed in most cancers, and it is associated with patient prognosis. OLR1 expression positively correlates with immunosuppressive cell infiltration and immune checkpoint molecules, while being negatively associated with effector T cells. Moreover, significant correlations are observed between OLR1 expression and tumor mutation burden (TMB) and microsatellite instability (MSI) in some cancers. In HNSCC, OLR1 expression is related to advanced clinicopathological factors and unfavorable outcomes. Patients with high OLR1 expression levels are prone to experience immune escape and benefit less from immune checkpoint inhibitor (ICI) therapy. Moreover, OLR1 expression may affect EMT, stemness, and cuproptosis resistance outcomes. OLR1 is an immune-related prognostic biomarker with potential as a prognostic indicator for immunotherapy, and it may also be involved in regulating the EMT process and cuproptosis in HNSCC.


Subject(s)
Apoptosis , Epithelial-Mesenchymal Transition , Head and Neck Neoplasms , Humans , Carcinogenesis , Epithelial-Mesenchymal Transition/genetics , Head and Neck Neoplasms/genetics , Head and Neck Neoplasms/therapy , Prognosis , Scavenger Receptors, Class E , Squamous Cell Carcinoma of Head and Neck/genetics , Squamous Cell Carcinoma of Head and Neck/therapy , Copper
14.
Int J Mol Sci ; 24(15)2023 Aug 06.
Article in English | MEDLINE | ID: mdl-37569875

ABSTRACT

The natural healing process of bone is impaired in the presence of tumors, trauma, or inflammation, necessitating external assistance for bone regeneration. The limitations of autologous/allogeneic bone grafting are still being discovered as research progresses. Bone tissue engineering (BTE) is now a crucial component of treating bone injuries and actively works to promote vascularization, a crucial stage in bone repair. A biomaterial with hydroxyapatite (HA), which resembles the mineral makeup of invertebrate bones and teeth, has demonstrated high osteoconductivity, bioactivity, and biocompatibility. However, due to its brittleness and porosity, which restrict its application, scientists have been prompted to explore ways to improve its properties by mixing it with other materials, modifying its structural composition, improving fabrication techniques and growth factor loading, and co-cultivating bone regrowth cells to stimulate vascularization. This review scrutinizes the latest five-year research on HA composite studies aimed at amplifying vascularization in bone regeneration.


Subject(s)
Biomedical Engineering , Durapatite , Durapatite/chemistry , Tissue Engineering/methods , Bone and Bones , Biocompatible Materials , Bone Regeneration , Tissue Scaffolds/chemistry
15.
Arthritis Rheumatol ; 75(9): 1573-1585, 2023 09.
Article in English | MEDLINE | ID: mdl-37163449

ABSTRACT

OBJECTIVE: To discover novel serum biomarkers that have diagnostic or predictive value in lupus nephritis (LN). METHODS: Using a quantitative protein microarray, we screened for high-abundant proteome expression in the serum of patients with LN compared to healthy controls. Top candidates from this screening were validated using a larger cohort of patients with LN compared to a disease control cohort (subjects with other chronic kidney diseases) and a healthy control cohort. Promising markers were then selected using a machine-learning model and further validated with a larger patient cohort. The corresponding autoantibodies and immune complexes containing these proteins were also examined. RESULTS: In total, 13 proteins were found to be significantly elevated in LN patient serum in the screening, among which 8 proteins were validated by enzyme-linked immunosorbent assay using 81 serum samples from LN patients and control subjects. Three serum markers with LN diagnostic potential were identified using feature importance analysis and further validated using 155 serum samples from LN patients and control subjects. V-set immunoglobulin domain-containing protein 4 (VSIG4) appeared to be the most promising marker in distinguishing LN from healthy controls, with an area under the curve of 0.93. VSIG4 could also discriminate active LN from inactive LN. Furthermore, serum VSIG4 levels were positively correlated with all of the following clinical parameters: the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score (Spearman's rank correlation rs = 0.42, P < 0.001), the renal domain score of the SLEDAI (rs = 0.46, P < 0.001), the urinary protein-to-creatinine ratio (rs = 0.56, P < 0.001), and the serum creatinine level (rs = 0.41, P < 0.001). Importantly, we found that serum VSIG4 levels tracked with LN disease activity longitudinally, and that serum VSIG4 levels reflected the renal pathology activity index (AI), particularly the AI components of crescent formation and hyaline deposits. CONCLUSION: VSIG4 may be a promising novel serum biomarker and therapeutic target in patients with LN.


Subject(s)
Lupus Erythematosus, Systemic , Lupus Nephritis , Renal Insufficiency, Chronic , Humans , Biomarkers , Immunoglobulin Domains , Kidney/pathology , Lupus Nephritis/diagnosis
16.
Biomolecules ; 13(2)2023 02 06.
Article in English | MEDLINE | ID: mdl-36830672

ABSTRACT

BACKGROUND: The CAV family, especially CAV1 and CAV2, is significantly associated with tumor development. In this study, we aimed to explore the pathogenic and prognostic roles of CAV1 and CAV2 in head and neck squamous cell carcinoma (HNSCC) through bioinformatic analysis and verified in human tissue. METHODS: We analyzed expression profiles of CAV1 and CAV2 in HNSCC and in normal tissues via data from The Cancer Genome Altas. Prognostic significance was examined by Kaplan-Meier survival curve obtained from the Xena browser together with Cox regression analysis. Co-expressed genes were uploaded to GeneMANIA and applied to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses, showing interaction networks. Signaling pathways of CAV1 and CAV2 in HNSCC were analyzed by Gene Set Enrichment Analysis to elucidate potential regulatory mechanisms. Gene-drug interaction network was explored via Comparative Toxicogenomics Database. Immunohistochemistry was performed to verify theoretical results. RESULTS: Compared with normal tissues, expression levels of CAV1 and CAV2 were remarkably higher in HNSCC (p < 0.0001), which independently implies poor OS (CAV1: HR: 1.146, p = 0.027; CAV2: HR: 1.408, p = 0.002). Co-expressed genes (PXN, ITGA3, TES, and MET) were identified and analyzed by FunRich with CAV1 and CAV2, revealing a significant correlation with focal adhesion (p < 0.001), which has a vital influence on cancer progression. GSEA also showed cellular protein catabolic process (ES = 0.42) and proteasome complex (ES = 0.72), which is a key degradation system for proteins involved in oxidatively damaging and cell cycle and transcription, closely correlated with high expression of CAV2 in HNSCC. More importantly, we found the relationship between different immune cell infiltration degrees in the immune micro-environment in HNSCC and expression levels of CAV1/CAV2 (p < 0.0001). Gene-drug interaction network was checked via CTD. Moreover, tissue microarrays verified higher expression levels of CAV1/CAV2 in HNSCC (p < 0.0001), and the high expression subgroup indicated significantly poorer clinical outcomes (p < 0.05). CONCLUSIONS: The results revealed that CAV1 and CAV2 are typically upregulated in HNSCC and might predict poor prognosis.


Subject(s)
Computational Biology , Head and Neck Neoplasms , Humans , Squamous Cell Carcinoma of Head and Neck/genetics , Prognosis , Kaplan-Meier Estimate , Head and Neck Neoplasms/genetics , Gene Expression Regulation, Neoplastic , Biomarkers, Tumor/genetics , Tumor Microenvironment
17.
Alzheimers Dement ; 19(2): 456-466, 2023 02.
Article in English | MEDLINE | ID: mdl-35436382

ABSTRACT

BACKGROUND: The misfolding and deposition of amyloid beta (Aß) in human brain is the main hallmark of Alzheimer's disease (AD) pathology. One of the drivers of Alzheimer´s pathogenesis is the production of soluble oligomeric Aß, which could potentially serve as a biomarker of AD. METHODS: Given that the diphenylalanine (FF) at the C-terminus of Aß fragments plays a key role in inducing the AD pathology, based on the hydrophobic structure of FF, we synthesized a near-infrared BF2-dipyrrolmethane fluorescent imaging probe (NB) to detect both soluble and insoluble Aß. RESULTS: We found that NB not only binds Aß, particularly oligomeric Aß, but also interposes self-assembly of Aß through π-π interaction between NB and FF. CONCLUSION: This work holds great promise in the early detection of AD and may also provide an innovative approach to decelerate and even halt AD onset and progression.


Subject(s)
Alzheimer Disease , Amyloid beta-Peptides , Humans , Amyloid beta-Peptides/metabolism , Alzheimer Disease/diagnosis , Brain/pathology , Peptide Fragments/metabolism
18.
Sensors (Basel) ; 22(19)2022 Oct 08.
Article in English | MEDLINE | ID: mdl-36236730

ABSTRACT

This paper presents a system for behavioral, environmental, and physiological monitoring of working dogs using on-body and aerial sensors. The proof of concept study presented here includes two trained dogs performing nine scent detection tasks in an uncontrolled environment encompassing approximately two acres. The dogs were outfitted with a custom designed wearable harness to monitor their heart rate, activity levels and skin temperature. We utilized a commercially available micro-air vehicle to perform aerial sensing by tracking the terrain and movement of the dog in the outdoor space. The dogs were free to explore the space working at maximal speeds to complete a scent-based search-and-retrieval task. Throughout the experiment, the harness data was transferred to a base station via Wi-Fi in real-time. In this work, we also focused on testing the performance of a custom 3D electrode with application specific ergonomic improvements and adaptive filter processing techniques to recover as much electrocardiography data as possible during high intensity motion activity. We were able to recover and use 84% of the collected data where we observed a trend of heart rate generally increasing immediately after successful target localization. For tracking the dogs in the aerial video footage, we applied a state-of-the-art deep learning algorithm designed for online object tracking. Both qualitative and quantitative tracking results are very promising. This study presents an initial effort towards deployment of on-body and aerial sensors to monitor the working dogs and their environments during scent detection and search and rescue tasks in order to ensure their welfare, enable novel dog-machine interfaces, and allow for higher success rate of remote and automated task performance.


Subject(s)
Electrocardiography , Working Dogs , Algorithms , Animals , Dogs , Heart Rate , Monitoring, Physiologic
19.
Chemosensors (Basel) ; 10(8)2022 Aug.
Article in English | MEDLINE | ID: mdl-36072130

ABSTRACT

Fluorescence-based microarray offers great potential in clinical diagnostics due to its high-throughput capability, multiplex capabilities, and requirement for a minimal volume of precious clinical samples. However, the technique relies on expensive and complex imaging systems for the analysis of signals. In the present study, we developed a smartphone-based application to analyze signals from protein microarrays to quantify disease biomarkers. The application adopted Android Studio open platform for its wide access to smartphones, and Python was used to design a graphical user interface with fast data processing. The application provides multiple user functions such as "Read", "Analyze", "Calculate" and "Report". For rapid and accurate results, we used ImageJ, Otsu thresholding, and local thresholding to quantify the fluorescent intensity of spots on the microarray. To verify the efficacy of the application, three antigens each with over 110 fluorescent spots were tested. Particularly, a positive correlation of over 0.97 was achieved when using this analytical tool compared to a standard test for detecting a potential biomarker in lupus nephritis. Collectively, this smartphone application tool shows promise for cheap, efficient, and portable on-site detection in point-of-care diagnostics.

20.
J Stomatol Oral Maxillofac Surg ; 123(6): 666-671, 2022 11.
Article in English | MEDLINE | ID: mdl-35768022

ABSTRACT

The vascular iliac myofascial flap is a compound flap with the deep circumflex iliac artery (DCIA) as the vascular pedicle, carrying the iliac bone and parts of the internal oblique, external oblique and muscle-fascial tissue that cover the surface of the iliac crest and inside the iliac bone. The aim of this study was to advocate a feasible surgical strategy for maxillofacial surgeons through our review of clinical applications and to improve the quality of life of patients after the operation. In recent years, Stomatology Hospital of Wuhan University has performed dozens of vascularized iliac myofascial flaps, not only to repair jaw defects but also to complete the repair of intraoral soft tissue defects. 20 patients were followed up. These patients with jaw tumors who received a vascular iliac myofascial flap to repair compound defects of the jaw from 2018 to 2020. The Quality of Life Questionnaire-Head and Neck Cancer-37 (QLQ-H&N37) was used to evaluate their speech function (Z=-0.061, P>0.05) and postoperative aesthetics (Z=-2.824, P<0.05). All patients obtained good surgical results and satisfaction in terms of aesthetics and function. The successful reconstruction of these cases prove that the vascularized iliac composite flap with myofascial tissue is a reliable flap for the reconstruction of maxillofacial defects.


Subject(s)
Head and Neck Neoplasms , Plastic Surgery Procedures , Humans , Ilium/surgery , Ilium/blood supply , Plastic Surgery Procedures/methods , Quality of Life , Surgical Flaps/surgery
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