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Mechanistic insights into CLNS1A-mediated chemoresistance and tumor progression in non-small cell lung cancer
No full text[[abstract]]CLNS1A is a chloride channel protein and an essential component of the methylosome complex, which additionally comprises PRMT5 and MEP50. In this study, we investigated its contribution to lung cancer and its potential as a therapeutic target. Analysis of transcriptomic datasets and western blotting revealed that CLNS1A, PRMT5, and MEP50 were overexpressed in lung cancer tissues, with elevated CLNS1A expression correlating with poor patient survival. CLNS1A overexpression enhanced platinum clearance from cells, increased the IC(50) values for chemotherapy, and improved cell survival. Conversely, the knockdown of CLNS1A increased drug accumulation, reduced survival, and increased sensitivity to chemotherapy. The 3W mutant, a chloride channel-defective variant with steric hindrance at key bottleneck residues, impaired chloride ion transport, thereby reducing drug resistance, migration, and anchorage-independent growth. Mechanistically, CLNS1A promotes drug efflux through its chloride channel activity and activates the FAK-SRC-RAC1 pathway to enhance motility and clonogenicity. It also facilitates PRMT5-mediated RUVBL1 methylation to support anti-apoptotic DNA damage response signaling. In vivo, CLNS1A overexpression accelerated tumor growth and reduced survival, whereas CLNS1A knockdown sensitized tumors to cisplatin, enhancing therapeutic efficacy. These findings suggest that CLNS1A is a potential biomarker and therapeutic target, and its inhibition offers a strategy to overcome drug resistance and limit the metastatic progression of lung cancer
Functional expression of NMDA receptors in SH-SY5Y neuroblastoma cells following long-term RA/BDNF-induced differentiation
No full text[[abstract]]SH-SY5Y neuroblastoma cells can be effectively differentiated into a neuronal phenotype using retinoic acid (RA) and brain-derived neurotrophic factor (BDNF), making them a valuable in vitro model for studying neuronal differentiation. This study aimed to investigate the electrophysiological properties of SH-SY5Y cells following prolonged differentiation, with a focus on membrane characteristics, evoked action potentials, and the functionality of cellular components such as N-methyl-D-aspartate (NMDA) receptor. Whole-cell patch-clamp recordings were employed to evaluate ionic currents and action potentials in embryonic mouse cortical neurons (mCNs) and in both differentiated and undifferentiated SH-SY5Y neuroblastoma cells. Differentiated SH-SY5Y cells exhibited neurite outgrowth, evoked action potential firing, and functional NMDA receptor-mediated currents. Notably, atorvastatin significantly modulated the duration and firing of action potentials as well as NMDA receptor-mediated currents in differentiated SH-SY5Y cells. These findings highlight that neuronally differentiated SH-SY5Y cells expressing functional NMDA receptor-mediated currents serve as a robust and convenient model for investigating the molecular mechanisms of NMDA receptor function and for screening pharmacological agents targeting these receptors
Associations between children's upper respiratory tract mycobiome, school air mycobiome, and surrounding greenness
No full text[[abstract]]Fungal spores are ubiquitous in the air, shaped by landscape and climate, and are known contributors to respiratory allergy in children. However, the contribution of airborne fungi to the upper respiratory tract (URT) mycobiome in children remains poorly understood, as does the influence of natural landscape on this exposure. This study investigated associations between children's URT mycobiome, the school air mycobiome, and surrounding greenness. Two study waves were conducted one year apart at 44 schools around Taiwan. Each wave included passive air sampling across classrooms to characterize school-wide fungal exposure, along with nasal and oropharyngeal swab collection from 78 boys. Fungal genus abundance was estimated using high-throughput sequencing and quantitative PCR targeting the ITS2 region, with URT data normalized to human DNA content. Greenness was estimated using the normalized difference vegetation index within a 10-km buffer around each school. Pearson correlation and linear mixed-effect models were used to examine associations. Cladosporium and Malassezia were the most abundant genera in nasal and oral samples. Nasal abundance of Cladosporium was positively associated with its school air abundance, and similar associations were observed for Bjerkandera, Curvularia, Phlebia, Scopuloides, Sertulicium, Sporobolomyces, Wallemia, and Xylodon. Oropharyngeal abundances of Cladosporium and Malassezia were more strongly associated with nasal than airborne abundances. Greenness surrounding schools was positively associated with the airborne abundance of Bjerkandera, Scopuloides, Sertulicium, Sporobolomyces, and Xylodon. These findings suggest that the air and nasal mycobiomes may be related and that natural landscape may influence children's respiratory fungal exposure
Pathological primary tumor status, rather than adjuvant therapy, predicts survival outcomes in pT1-3N1M0 oral cavity squamous cell carcinoma: A nationwide cohort study
No full text[[abstract]]Background: The eighth edition of the American Joint Committee on Cancer (AJCC) Staging Manual classifies pT1-3N1M0 oral cavity squamous cell carcinoma (OCSCC) as p-Stage III. However, the prognosis within this group is heterogeneous, and the clinical benefit of adjuvant therapy for patients with a single nodal metastasis remains unclear. Here, we analyzed nationwide data from Taiwan to assess survival outcomes and examine the role of adjuvant therapy in this population. Methods: A retrospective analysis of 1324 pT1-3N1M0 OCSCC patients who underwent surgical resection between 2011 and 2021 was conducted using data from the Taiwan Cancer Registry and National Health Insurance Research Database. Cox proportional hazards models were applied to identify independent prognostic factors for disease-specific survival (DSS) and overall survival (OS). Results: Among the cohort, 247 patients (18.7 %) had pT1N1, 699 (52.8 %) had pT2N1, and 378 (28.5 %) had pT3N1 disease. The 5-year DSS rates for pT1N1, pT2N1, and pT3N1 were 82 %, 79 %, and 69 %, respectively, while OS rates were 73 %, 70 %, and 60 % (both p < 0.0001). No significant differences in DSS or OS were observed between surgery alone and adjuvant therapy. In multivariable analysis, pT3N1 disease was indepen-dently associated with worse survival outcomes (HR: 1.76, p = 0.0011 for DSS; HR: 1.63, p = 0.0005 for OS), whereas adjuvant therapies were not independent prognostic factors. Conclusion: Among patients with pT1-3N1M0 OCSCC, those presenting with pT3N1 disease demonstrated significantly poorer DSS and OS. Notably, in patients lacking additional adverse pathological features, the omission of adjuvant therapy did not adversely impact survival endpoints
Classifying developmental delays with EEG: A comparative study of machine learning and deep learning approaches
No full text[[abstract]]Early detection of developmental delays is crucial for improving children's cognitive, social, and emotional outcomes through timely interventions. This study explores the potential of machine learning (ML) and deep learning (DL) to classify Electroencephalography (EEG) data from an oddball task, distinguishing between children with and without developmental delays. Participants underwent language assessments and EEG recordings, with subsequent analysis using Event-Related Potentials (ERPs), Event-Related Spectral Perturbations (ERSPs), and functional connectivity to characterize group differences. Three methodologies were employed in this research to classify EEG data. Firstly, statistical features are extracted from the EEG data and various ML algorithms are applied for classification, with feature selection techniques utilized to identify the most relevant features and enhance classification accuracy. Secondly, brain dynamics is utilized to incorporate ERP, ERSP, and functional connectivity measures as features for developmental delay detection. Similar to the first approach, feature selection techniques are again employed to enhance classification accuracy. Lastly, DL approaches are explored by implementing multiple convolutional neural networks (CNNs), including a 2D CNN (EEGNet), various hybrid CNN architectures integrating LSTM, GRU, and attention mechanisms, and a novel 1D CNN with a standardized convolutional layer (SCL) for improved stability and training performance. The effectiveness of each approach in accurately classifying EEG data for developmental delay detection is independently analyzed. The results demonstrate that the proposed 1D convolutional neural network outperforms both EEGNet and the employed ML classifiers. This model achieves an impressive accuracy of 96.4% and an F1 score of 96.6%, underscoring its potential as a valuable tool for early and accurate developmental delay detection using EEG data
[[alternative]]Primers, snp markers and method for genotyping mycobacterium tuberculosis
No full text[[abstract]]The present invention relates to a method able to enhance survival and functionality of anti-tumor or anti-viral immune cells through overexpression of Akt molecules in the cells. Akt signaling prevented the expression of immune checkpoints and therefore rescued antigen-specific cytotoxic T lymphocytes from exhaustion in immunosuppressive microenvironment. This present invention also demostrated that AKT genes have the potential to be utilized in T-cell engineering of adoptive T-cell therapy for treatment of chronic viral infection and malignancie
Method for genotyping Mycobacterium tuberculosis
No full text[[abstract]]The present application provides a method for genotyping M. tuberculosis, comprising obtaining amplifying and obtaining a first DNA fragment from a DNA sample by using one or more primer sets selected from the group consisting of primer sets 1 to 25 (SEQ ID Nos. 1 to 50); amplifying and obtaining a second DNA fragment from the obtained first DNA fragment by using one or more extension primers selected from the group consisting of SEQ ID Nos. 51 to 75; and detecting the second DNA fragment by using mass spectrometry, particularly by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS)
Immunosuppressive cells and methods of making and using thereof
No full text[[abstract]]This invention relates to an immunosuppressive cell, and methods of obtaining the cell and using the cell. The immunosuppressive cell is obtained by culturing a precursor cell in a medium that contains a GRO chemokine
[[alternative]]Device and method for single cell isolation and cultivation
No full text[[abstract]]本發明係關於一種用於單細胞擷取與培養之雙微井微流裝置。本發明之裝置係包括一組用以捕捉單細胞之擷取微井；及一組用以於細胞培養期間使細胞擴散與細胞生長之培養微井
Neural stem cells and a monomer or homodimer of il12p40 to enhance nerve regeneration
No full text[[abstract]]The present application provides a composition and methods to enhance nerve regeneration utilizing at least one component of neural stem cells or IL12p40. The composition comprises neural stem cells and a neurotrophic factor, which is constructed by IL12p40 as at least one subunit. The methods to enhance nerve regeneration comprise providing a nerve regeneration composition comprising a neurotrophic factor containing IL12p40 as at least one subunit to a subject. The composition of the methods can further comprise neural stem cells