This study aimed to synthesize Ti
3
C
2
T
x
(MXene) through selective etching of Ti
3
AlC
2
(MAX) using the in situ hydrofluoric acid method. ZnO was then grown on the Ti
3
C
2
T
x
surface to form Ti
...3
C
2
T
x
(MXene)/ZnO composites (M-ZnO) using the hydrothermal method. To increase adhesion between the M-ZnO sensing composite and the laser-patterned interdigitated electrode surface, PEDOT:PSS was used as an adhesive layer to obtain PEDOT:PSS/M-ZnO-based gas sensors. The surface morphology, cross-sectional profile, elemental analysis, and structural and chemical compositions of M-ZnO composites were characterized using scanning electron microscope with energy-dispersive X-ray spectroscopy, X-ray diffractometer, X-ray photoelectron spectroscopy, and Fourier transform infrared spectroscopy. The results of the sensing test indicated that the responses of the gas sensors were 3.66%, 6.62%, 8.12%, and 10.23% when PEDOT:PSS/M-ZnO were exposed to 400, 600, 800, and 1000 ppb NO
2
concentrations, respectively. The sensitivity of the PEDOT:PSS/ZnO-, PEDOT:PSS/MXene-, and PEDOT:PSS/M-ZnO-based gas sensors was 0.67, 1.37, and 10.61, respectively. The PEDOT:PSS/M-ZnO-based gas sensor had the highest sensitivity of 10.61, which was 15.8 times higher than the PEDOT:PSS/ZnO-based gas sensor. Additionally, the PEDOT:PSS/M-ZnO-based gas sensor displayed good stability and excellent sensing selectivity for NO
2
gas at room temperature.
Mesenchymal stem cells (MSCs) have promising potential in clinical application, whereas their limited amount and sources hinder their bioavailability. Embryonic stem cells (ESCs) and induced ...pluripotent stem cells (iPSCs) have become prominent options in regenerative medicine as both possess the ability to differentiate into MSCs.
Recently, our research team has successfully developed human leukocyte antigen (HLA)-homozygous iPSC cell lines with high immune compatibility, covering 13.5% of the Taiwanese population. As we deepen our understanding of the differences between these ESCs and HLA-homozygous iPSCs, our study focused on morphological observations and flow cytometry analysis of specific surface marker proteins during the differentiation of ESCs and iPSCs into MSCs.
The results showed no significant differences between the two pluripotent stem cells, and both of them demonstrated the equivalent ability to further differentiate into adipose, cartilage, and bone cells.
Our research revealed that these iPSCs with high immune compatibility exhibit the same differentiation potential as ESCs, enhancing the future applicability of highly immune-compatible iPSCs.
This paper attempts to explore the feasibility of using cholesteric liquid crystals (CLCs) for reflective displays in active matrix (AM) driving. The study focuses on reverse mode polymer-stabilized ...cholesteric liquid crystals (PSCLCs) to overcome the inherent bistability of CLCs and achieve faster response times for switching between bright and dark states. Key parameters such as cell gap, monomer concentration, polymerization temperature, and different monomer types and liquid crystal hosts are systematically investigated to optimize the electro-optical properties of the liquid crystals for active matrix driving. The research demonstrates that PSCLCs can operate within a 15 V driving voltage range while maintaining a good bright-dark state contrast ratio (>10) and a response time of less than 42 ms. This suggests significant potential for their application in dynamic reflective display technologies.
Mesenchymal stem cells (MSCs) have garnered significant attention in the field of cell-based therapy owing to their remarkable capabilities for differentiation and self-renewal. However, primary ...tissue-derived MSCs are plagued by various limitations, including constrained tissue sources, arduous and invasive retrieval procedures, heterogeneous cell populations, diminished purity, cellular senescence, and a decline in self-renewal and proliferative capacities after extended expansion. Addressing these challenges, our study focuses on establishing a robust differentiation platform to generate mesenchymal stem cells derived from induced pluripotent stem cells (iMSCs).
To achieve this, we used a comprehensive methodology involving the differentiation of induced pluripotent stem cells into MSCss. The process was meticulously designed to ensure the expression of key MSC positive markers (CD73, CD90, and CD105) at elevated levels, coupled with the minimal expression of negative markers (CD34, CD45, CD11b, CD19, and HLA-DR). Moreover, the stability of these characteristics was evaluated across 10th generations.
Our findings attest to the success of this endeavor. iMSCs exhibited robust expression of positive markers and limited expression of negative markers, confirming their MSC identity. Importantly, these characteristics remained stable even up to the 10th generation, signifying the potential for sustained use in therapeutic applications. Furthermore, our study demonstrated the successful differentiation of iMSCs into osteocytes, chondrocytes, and adipocytes, showcasing their multilineage potential.
In conclusion, the establishment of induced pluripotent stem cell-derived mesenchymal stem cells (iMSCs) presents a significant advancement in overcoming the limitations associated with primary tissue-derived MSCs. The remarkable stability and multilineage differentiation potential exhibited by iMSCs offer a strong foundation for their application in regenerative medicine and tissue engineering. This breakthrough paves the way for further research and development in harnessing the full therapeutic potential of iMSCs.
It has been shown recently that deep learning based models are effective on speech quality prediction and could outperform traditional metrics in various perspectives. Although network models have ...the potential to be a surrogate for complex human hearing perception, they may contain instabilities in predictions. This work shows that deep speech quality predictors can be vulnerable to adversarial perturbations, where the prediction can be changed drastically by unnoticeable perturbations as small as −30 dB compared with speech inputs. In addition to exposing the vulnerability of deep speech quality predictors, we further explore and confirm the viability of adversarial training for strengthening robustness of models.
Siglec-7 (sialic acid–binding immunoglobulin-like lectin 7) is an immune checkpoint-like glycan recognition protein on natural killer (NK) cells. Cancer cells often upregulate Siglec ligands to ...subvert immunosurveillance, but the molecular basis of Siglec ligands has been elusive. In this study, we investigated Siglec-7 ligands on chronic lymphocytic leukemia (CLL) B cells. CLL B cells express higher levels of Siglec-7 ligands compared with healthy donor B cells, and enzymatic removal of sialic acids or sialomucins makes them more sensitive to NK cell cytotoxicity. Gene knockout experiments have revealed that the sialyltransferase ST6GalNAc-IV is responsible for the biosynthesis of disialyl-T (Neu5Acα2–3Galβ1–3Neu5Acα2–6GalNAcα1–), which is the glycotope recognized by Siglec-7, and that CD162 and CD45 are the major carriers of this glycotope on CLL B cells. Analysis of public transcriptomic datasets indicated that the low expression of
GCNT1
(encoding core 2 GlcNAc transferase, an enzyme that competes against ST6GalNAc-IV) and high expression of
ST6GALNAC4
(encoding ST6GalNAc-IV) in CLL B cells, together enhancing the expression of the disialyl-T glycotope, are associated with poor patient prognosis. Taken together, our results determined the molecular basis of Siglec-7 ligand overexpression that protects CLL B cells from NK cell cytotoxicity and identified disialyl-T as a potential prognostic marker of CLL.
•A situational awareness Bayesian network is developed based on expert knowledge.•It enables exploring biophysical pathways starting with the expert knowledge.•It allows physicians to conduct their ...familiar “what if” counterfactual inference.•It outperforms other credible models for the joint prediction of treatment outcomes.•It has the potential to be a key component of personalized adaptive radiotherapy.
A situational awareness Bayesian network (SA-BN) approach is developed to improve physicians’ trust in the prediction of radiation outcomes and evaluate its performance for personalized adaptive radiotherapy (pART).
118 non-small-cell lung cancer patients with their biophysical features were employed for discovery (n = 68) and validation (n = 50) of radiation outcomes prediction modeling. Patients’ important characteristics identified by radiation experts to predict individual’s tumor local control (LC) or radiation pneumonitis with grade ≥ 2 (RP2) were incorporated as expert knowledge (EK). Besides generating an EK-based naïve BN (EK-NBN), an SA-BN was developed by incorporating the EK features into pure data-driven BN (PD-BN) methods to improve the credibility of LC or / and RP2 prediction. After using area under the free-response receiver operating characteristics curve (AU-FROC) to assess the joint prediction of these outcomes, their prediction performances were compared with a regression approach based on the expert yielded estimates (EYE) penalty and its variants.
In addition to improving the credibility of radiation outcomes prediction, the SA-BN approach outperformed the EYE penalty and its variants in terms of the joint prediction of LC and RP2. The value of AU-FROC improves from 0.70 (95% CI: 0.54–0.76) using EK-NBN, to 0.75 (0.65–0.82) using a variant of EYE penalty, to 0.83 (0.75–0.93) using PD-BN and 0.83 (0.77–0.90) using SA-BN; with similar trends in the validation cohort.
The SA-BN approach can provide an accurate and credible human–machine interface to gain physicians’ trust in clinical decision-making, which has the potential to be an important component of pART.
The potential of induced pluripotent stem cells (iPSCs) in revolutionizing regenerative medicine cannot be overstated. iPSCs offer a profound opportunity for therapies involving cell replacement, ...disease modeling, and cell transplantation. However, the widespread application of iPSC cellular therapy faces hurdles, including the imperative to regulate iPSC differentiation rigorously and the inherent genetic disparities among individuals. To address these challenges, the concept of iPSC super donors emerges, holding exceptional genetic attributes and advantageous traits. These super donors serve as a wellspring of standardized, high-quality cell sources, mitigating inter-individual variations and augmenting the efficacy of therapy.
In pursuit of this goal, our study embarked on the establishment of iPSC cell lines specifically sourced from donors possessing the HLA type (A33:03-B58:01-DRB1*03:01). The reprogramming process was meticulously executed, resulting in the successful generation of iPSC lines from these carefully selected donors. Subsequently, an extensive characterization was conducted to comprehensively understand the features and attributes of these iPSC lines.
The outcomes of our research were highly promising. The reprogramming efforts culminated in the generation of iPSC lines from donors with the specified HLA type. These iPSC lines displayed a range of distinctive characteristics that were thoroughly examined and documented. This successful generation of iPSC lines from super donors possessing advantageous genetic traits represents a significant stride towards the realization of their potential in therapeutic applications.
In summary, our study marks a crucial milestone in the realm of regenerative medicine. The establishment of iPSC lines from super donors with specific HLA types signifies a paradigm shift in addressing challenges related to iPSC cellular therapy. The standardized and high-quality cell sources derived from these super donors hold immense potential for various therapeutic applications. As we move forward, these findings provide a solid foundation for further research and development, ultimately propelling the field of regenerative medicine toward new horizons of efficacy and accessibility.
A maternal inheritance disorder called Leber's hereditary optic neuropathy (LHON) is the most common primary mitochondrial deoxyribonucleic acid (DNA) disorder. In most studies, there are more male ...patients than female patients, which contradicts the usual pattern in mitochondrial hereditary diseases. This suggests that nuclear DNA (nDNA) may influence the degeneration of retinal ganglion cells (RGCs) in LHON. The primary cause of this is dysfunction in complex I of the electron transport chain, leading to ineffective adenosine triphosphate (ATP) production. In addition to MT-ND4 or MT-ND1 mutations, genes such as PRICKLE3 , YARS2 , and DNAJC30 , which come from nDNA, also play a role in LHON. These three genes affect the electron chain transport differently. PRICKLE3 interacts with ATP synthase (complex V) at Xp11.23, while YARS2 is a tyrosyl-tRNA synthetase 2 involved in mitochondria . DNAJC30 mutations result in autosomal recessive LHON (arLHON). Understanding how genes impact the disease is crucial for developing new treatments. Idebenone has been approved for treating LHON and has shown safety and efficacy in clinical trials. Mesenchymal stem cell-based therapy has also emerged as a potential treatment for LHON by transferring mitochondria into target cells. Gene therapy research focuses on specific gene mutations, and the wild-type ND4 gene target in the adeno-associated viruses (AAV) vector has shown promise in clinical trials as a potential treatment for LHON.
Immunoglobulin-related genes are associated with the favorable prognosis of triple-negative breast cancer (TNBC) patients. We aimed to analyze the function and prognostic value of immunoglobulin ...lambda constant 2 (IGLC2) in TNBC patients.
We knocked down the gene expression of IGLC2 (IGLC2-KD) in MDA-MB-231 cells to evaluate the proliferation, migration, and invasion of tumors
3-(4,5-Dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, wound healing, and transwell cell migration assay respectively. Relapse-free survival (RFS) and distant metastasis-free survival (DMFS) analyses were conducted using the KM plotter online tool. The GSE76275 data set was used to analyze the association of IGLC2 and clinical characteristics. A pathway enrichment analysis was conducted using the next-generation sequencing data of wild-type and IGLC2-KD MDA-MB-231 cells.
The low gene expression of IGLC2 was related to unfavorable RFS, DMFS. The high expression of IGLC2 was exhibited in the basal-like immune-activated (BLIA) TNBC molecular subtype, which was immune-activated and showed excellent response to immune therapy. IGLC2 was positively correlated with programmed death-ligand 1 (PD-L1) as shown by Spearman correlation (r = 0.25, p < 0.0001). IGLC2 had a strong prognostic effect on lymph node-negative TNBC (RFS range: 0.31, q value= 8.2e-05; DMFS = 0.16, q value = 8.2e-05) but had no significance on lymph node-positive ones. The shRNA-mediated silencing of IGLC2 increased the proliferation, migration, and invasion of MDA-MB-231 cells. The results of pathway enrichment analysis showed that IGLC2 is related to the PI3K-Akt signaling pathway, MAPK signaling pathway, and extracellular matrix-receptor interaction. We confirmed that MDA-MB-231 tumor cells expressed IGLC2, subverting the traditional finding of generation by immune cells.
IGLC2 linked with the proliferation, migration, and invasion of MDA-MB-231 cells. A high expression of IGLC2 was related to favorable prognosis for TNBC patients. IGLC2 may serve as a biomarker for the identification of TNBC patients who can benefit the most from immune checkpoint blockade treatment.