Novel in-situ encapsulation of tin phosphide particles in MXene conductive networks as anode materials of the durable sodium-ion battery.

Sodium-ion battery (SIB) is one of potential alternatives to lithium-ion battery, because of abundant resources and lower price of sodium. High electrical conductivity and long-term durability of MXene are advantageous as the anode material of SIB, but low energy density restricts applications. Tin phosphide possesses high theoretical capacity, low redox potential, and large energy density, but volume expansion reduces its cycling stability. In this study, tin phosphide particles are in-situ encapsulated into MXene conductive networks (SnxPy/MXene) by hydrothermal and phosphorization processes as novel anode materials of SIB. MXene amounts and hydrothermal durations are investigated to evenly distribute SnxPy in MXene. After 100 cycles, SnxPy/MXene reaches high specific capacities of 438.8 and 314.1 mAh/g at 0.2 and 1.0 A/g, respectively. The capacity retentions of 6.0% and 73.6% at 0.2 A/g are respectively obtained by SnxPy and SnxPy/MXene. The better specific capacity and cycling stability of SnxPy/MXene are attributed to less volume expansion of SnxPy during charge/discharge processes and relieved self-stacking of MXene by encapsulating SnxPy particles between MXene layers. Electrochemical impedance spectroscopy and Galvanostatic intermittent titration technique are also applied to analyze the charge storage mechanism in SIB. Higher sodium ion diffusion coefficient and smaller charge-transfer resistance are obtained by SnxPy/MXene.

Maternal exposure to hyperbaric oxygen at the preimplantation stages increases apoptosis and ectopic Cdx2 expression and decreases Oct4 expression in mouse blastocysts via Nrf2-Notch1 upregulation and Nf2 downregulation.

BACKGROUND: The environmental oxygen tension has been reported to impact the blastocyst quality and cell numbers in the inner cell mass (ICM) during human and murine embryogenesis. While the molecular mechanisms leading to increased ICM cell numbers and pluripotency gene expression under hypoxia have been deciphered, it remains unknown which regulatory pathways caused the underweight fetal body and overweight placenta after maternal exposure to hyperbaric oxygen (HBO). RESULTS: The blastocysts from the HBO-exposed pregnant mice revealed significantly increased signals of reactive oxygen species (ROS) and nuclear Nrf2 staining, decreased Nf2 and Oct4 expression, increased nuclear Tp53bp1 and active caspase-3 staining, and ectopic nuclear signals of Cdx2, Yap, and the Notch1 intracellular domain (N1ICD) in the ICM. In the ICM of the HBO-exposed blastocysts, both Nf2 cDNA microinjection and Nrf2 shRNA microinjection significantly decreased the ectopic nuclear expression of Cdx2, Tp53bp1, and Yap whereas increased Oct4 expression, while Nrf2 shRNA microinjection also significantly decreased Notch1 mRNA levels and nuclear expression of N1ICD and active caspase-3. CONCLUSION: We show for the first time that maternal exposure to HBO at the preimplantation stage induces apoptosis and impairs ICM cell specification via upregulating Nrf2-Notch1-Cdx2 expression and downregulating Nf2-Oct4 expression.

Identification of Potential Protein Targets in Extracellular Vesicles Isolated from Chemotherapy-Treated Ovarian Cancer Cells.

Despite the ongoing clinical trials and the introduction of novel treatments over the past few decades, ovarian cancer remains one of the most fatal malignancies in women worldwide. Platinum- and paclitaxel-based chemotherapy is effective in treating the majority of patients with ovarian cancer. However, more than 70% of patients experience recurrence and eventually develop chemoresistance. To improve clinical outcomes in patients with ovarian cancer, novel technologies must be developed for identifying molecular alterations following drug-based treatment of ovarian cancer. Recently, extracellular vesicles (EVs) have gained prominence as the mediators of tumor progression. In this study, we used mass spectrometry to identify the changes in EV protein signatures due to different chemotherapeutic agents used for treating ovarian cancer. By examining these alterations, we identified the specific protein induction patterns of cisplatin alone, paclitaxel alone, and a combination of cisplatin and paclitaxel. Specifically, we found that drug sensitivity was correlated with the expression levels of ANXA5, CD81, and RAB5C in patients receiving cisplatin with paclitaxel. Our findings suggest that chemotherapy-induced changes in EV protein signatures are crucial for the progression of ovarian cancer.

Investigating brain aging trajectory deviations in different brain regions of individuals with schizophrenia using multimodal magnetic resonance imaging and brain-age prediction: a multicenter study.

Although many studies on brain-age prediction in patients with schizophrenia have been reported recently, none has predicted brain age based on different neuroimaging modalities and different brain regions in these patients. Here, we constructed brain-age prediction models with multimodal MRI and examined the deviations of aging trajectories in different brain regions of participants with schizophrenia recruited from multiple centers. The data of 230 healthy controls (HCs) were used for model training. Next, we investigated the differences in brain age gaps between participants with schizophrenia and HCs from two independent cohorts. A Gaussian process regression algorithm with fivefold cross-validation was used to train 90, 90, and 48 models for gray matter (GM), functional connectivity (FC), and fractional anisotropy (FA) maps in the training dataset, respectively. The brain age gaps in different brain regions for all participants were calculated, and the differences in brain age gaps between the two groups were examined. Our results showed that most GM regions in participants with schizophrenia in both cohorts exhibited accelerated aging, particularly in the frontal lobe, temporal lobe, and insula. The parts of the white matter tracts, including the cerebrum and cerebellum, indicated deviations in aging trajectories in participants with schizophrenia. However, no accelerated brain aging was noted in the FC maps. The accelerated aging in 22 GM regions and 10 white matter tracts in schizophrenia potentially exacerbates with disease progression. In individuals with schizophrenia, different brain regions demonstrate dynamic deviations of brain aging trajectories. Our findings provided more insights into schizophrenia neuropathology.

Ligand Incorporating Sequence-dependent ZIF67 Derivatives as Active Material of Supercapacitor: Competition between Ammonia Fluoride and 2-Methylimidazole.

The zeolitic imidazolate framework 67 (ZIF67) derivative is a potential active material of supercapacitors (SC), owing to high specific surface area and porosity and possible formation of cobalt compounds. A novel ZIF67 derivative is synthesized using a one-step solution process with cobalt precursor 2-methylimidazole (2-Melm) and ammonia fluoride in our previous work. Due to its facile synthesis and excellent electrocapacitive behavior, it is crucial to understand the competition between ammonia fluoride and 2-Melm on forming derivatives with cobalt ions and to create more efficient ZIF67 derivatives for charge storage. In this work, several ZIF67 derivatives are designed using a one-step solution process with 2-Melm and ammonia fluoride incorporated in different sequences. The reaction durations for a single ligand and two ligands are controlled. The largest capacity of 176.33 mAh/g corresponding to the specific capacitance of 1057.99 F/g is achieved for the ZIF67 derivative electrode prepared by reacting ammonia fluoride and a cobalt precursor for 0.5 h and then incorporating 2-Melm for another 23.5 h of reaction (NM0.5). This derivative composed of highly conductive CoF2, NiF2, Co(OH)F, and Ni(OH)F presents high specific surface area and porosity. The relevant SC presents a maximum energy density of 19.5 Wh/kg at 430 W/kg, a capacity retention of 92%, and Coulombic efficiency of 96% in 10000 cycles.

Novel design of Sulfur-doped nickel cobalt layered double hydroxide and polypyrrole nanotube composites from zeolitic imidazolate Framework-67 as efficient active material of battery supercapacitor hybrids.

Nickel and cobalt layered double hydroxide (NiCo-LDH) has large specific surface area and interlayer spacing, multiple redox states and high ion-exchange capability, but poor electrical conductivity, severe agglomerations and structural defect restrict energy storage ability of NiCo-LDH as active materiel of battery supercapacitor hybrids (BSH). In this study, it is the first time to design sulfur-doped NiCo-LDH and polypyrrole nanotubes composites (NiCo-LDH-S/PNTs) from zeolitic imidazolate framework-67 (ZIF-67) as the efficient active material of BSH using electrospinning and hydrothermal processes. Effects of sulfur doping amounts are investigated. The one-dimensional hollow polypyrrole decorated with NiCo-LDH-S sheets with high aspect ratio provides straight charge-transfer routes and abundant contacts with electrolyte. The highest specific capacitance (CF) of 1936.3 F/g (specific capacity of 322.8 mAh/g) is achieved for the NiCo-LDH-S/PNTs with sulfur doping amount of 7% at 10 mV/s. The BSH comprising graphene LDH negative electrode and NiCo-LDH-S/PNTs positive electrode shows the maximum energy density of 16.28 Wh/kg at 650 W/kg. The CF retention of 74% and Coulombic efficiency of 90% are also achieved after 8000 charge/discharge cycles.

Prognostic and Genomic Analysis of Proteasome 20S Subunit Alpha (PSMA) Family Members in Breast Cancer.

The complexity of breast cancer includes many interacting biological processes, and proteasome alpha (PSMA) subunits are reported to be involved in many cancerous diseases, although the transcriptomic expression of this gene family in breast cancer still needs to be more thoroughly investigated. Consequently, we used a holistic bioinformatics approach to study the PSMA genes involved in breast cancer by integrating several well-established high-throughput databases and tools, such as cBioPortal, Oncomine, and the Kaplan-Meier plotter. Additionally, correlations of breast cancer patient survival and PSMA messenger RNA expressions were also studied. The results demonstrated that breast cancer tissues had higher expression levels of PSMA genes compared to normal breast tissues. Furthermore, PSMA2, PSMA3, PSMA4, PSMA6, and PSMA7 showed high expression levels, which were correlated with poor survival of breast cancer patients. In contrast, PSMA5 and PSMA8 had high expression levels, which were associated with good prognoses. We also found that PSMA family genes were positively correlated with the cell cycle, ubiquinone metabolism, oxidative stress, and immune response signaling, including antigen presentation by major histocompatibility class, interferon-gamma, and the cluster of differentiation signaling. Collectively, these findings suggest that PSMA genes have the potential to serve as novel biomarkers and therapeutic targets for breast cancer. Nevertheless, the bioinformatic results from the present study would be strengthened with experimental validation in the future by prospective studies on the underlying biological mechanisms of PSMA genes and breast cancer.

Novel Insights into the Prognosis and Immunological Value of the SLC35A (Solute Carrier 35A) Family Genes in Human Breast Cancer.

According to statistics 2020, female breast cancer (BRCA) became the most commonly diagnosed malignancy worldwide. Prognosis of BRCA patients is still poor, especially in population with advanced or metastatic. Particular functions of each members of the solute carrier 35A (SLC35A) gene family in human BRCA are still unknown regardless of awareness that they play critical roles in tumorigenesis and progression. Using integrated bioinformatics analyses to identify therapeutic targets for specific cancers based on transcriptomics, proteomics, and high-throughput sequencing, we obtained new information and a better understanding of potential underlying molecular mechanisms. Leveraging BRCA dataset that belongs to The Cancer Genome Atlas (TCGA), which were employed to clarify SLC35A gene expression levels. Then we used a bioinformatics approach to investigate biological processes connected to SLC35A family genes in BRCA development. Beside that, the Kaplan-Meier estimator was leveraged to explore predictive values of SLC35A family genes in BCRA patients. Among individuals of this family gene, expression levels of SLC35A2 were substantially related to poor prognostic values, result from a hazard ratio of 1.3 (with 95 percent confidence interval (95% CI: 1.18-1.44), the p for trend (ptrend) is 3.1 × 10-7). Furthermore, a functional enrichment analysis showed that SLC35A2 was correlated with hypoxia-inducible factor 1A (HIF1A), heat shock protein (HSP), E2 transcription factor (E2F), DNA damage, and cell cycle-related signaling. Infiltration levels observed in specific types of immune cell, especially the cluster of differentiation found on macrophages and neutrophils, were positively linked with SLC35A2 expression in multiple BRCA subclasses (luminal A, luminal B, basal, and human epidermal growth factor receptor 2). Collectively, SLC35A2 expression was associated with a lower recurrence-free survival rate, suggesting that it could be used as a biomarker in treating BRCA.

Potential Prognostic Biomarkers of NIMA (Never in Mitosis, Gene A)-Related Kinase (NEK) Family Members in Breast Cancer.

Breast cancer remains the most common malignant cancer in women, with a staggering incidence of two million cases annually worldwide; therefore, it is crucial to explore novel biomarkers to assess the diagnosis and prognosis of breast cancer patients. NIMA-related kinase (NEK) protein kinase contains 11 family members named NEK1-NEK11, which were discovered from Aspergillus Nidulans; however, the role of NEK family genes for tumor development remains unclear and requires additional study. In the present study, we investigate the prognosis relationships of NEK family genes for breast cancer development, as well as the gene expression signature via the bioinformatics approach. The results of several integrative analyses revealed that most of the NEK family genes are overexpressed in breast cancer. Among these family genes, NEK2/6/8 overexpression had poor prognostic significance in distant metastasis-free survival (DMFS) in breast cancer patients. Meanwhile, NEK2/6 had the highest level of DNA methylation, and the functional enrichment analysis from MetaCore and Gene Set Enrichment Analysis (GSEA) suggested that NEK2 was associated with the cell cycle, G2M checkpoint, DNA repair, E2F, MYC, MTORC1, and interferon-related signaling. Moreover, Tumor Immune Estimation Resource (TIMER) results showed that the transcriptional levels of NEK2 were positively correlated with immune infiltration of B cells and CD4+ T Cell. Collectively, the current study indicated that NEK family genes, especially NEK2 which is involved in immune infiltration, and may serve as prognosis biomarkers for breast cancer progression.

Prognostic and immune infiltration signatures of proteasome 26S subunit, non-ATPase (PSMD) family genes in breast cancer patients.

The complexity of breast cancer includes many interacting biological processes that make it difficult to find appropriate therapeutic treatments. Therefore, identifying potential diagnostic and prognostic biomarkers is urgently needed. Previous studies demonstrated that 26S proteasome delta subunit, non-ATPase (PSMD) family members significantly contribute to the degradation of damaged, misfolded, abnormal, and foreign proteins. However, transcriptional expressions of PSMD family genes in breast cancer still remain largely unexplored. Consequently, we used a holistic bioinformatics approach to explore PSMD genes involved in breast cancer patients by integrating several high-throughput databases, including The Cancer Genome Atlas (TCGA), cBioPortal, Oncomine, and Kaplan-Meier plotter. These data demonstrated that PSMD1, PSMD2, PSMD3, PSMD7, PSMD10, PSMD12, and PSMD14 were expressed at significantly higher levels in breast cancer tissue compared to normal tissues. Notably, the increased expressions of PSMD family genes were correlated with poor prognoses of breast cancer patients, which suggests their roles in tumorigenesis. Meanwhile, network and pathway analyses also indicated that PSMD family genes were positively correlated with ubiquinone metabolism, immune system, and cell-cycle regulatory pathways. Collectively, this study revealed that PSMD family members are potential prognostic biomarkers for breast cancer progression and possible promising clinical therapeutic targets.

Potential Therapeutic and Prognostic Values of LSM Family Genes in Breast Cancer.

In recent decades, breast cancer (BRCA) has become one of the most common diseases worldwide. Understanding crucial genes and their signaling pathways remain an enormous challenge in evaluating the prognosis and possible therapeutics. The "Like-Smith" (LSM) family is known as protein-coding genes, and its member play pivotal roles in the progression of several malignancies, although their roles in BRCA are less clear. To discover biological processes associated with LSM family genes in BRCA development, high-throughput techniques were applied to clarify expression levels of LSMs in The Cancer Genome Atlas (TCGA)-BRCA dataset, which was integrated with the cBioPortal database. Furthermore, we investigated prognostic values of LSM family genes in BCRA patients using the Kaplan-Meier database. Among genes of this family, LSM4 expression levels were highly associated with poor prognostic outcomes with a hazard ratio of 1.35 (95% confidence interval 1.21-1.51, p for trend = 3.4 × 10-7). MetaCore and GlueGo analyses were also conducted to examine transcript expression signatures of LSM family members and their coexpressed genes, together with their associated signaling pathways, such as "Cell cycle role of APC in cell cycle regulation" and "Immune response IL-15 signaling via MAPK and PI3K cascade" in BRCA. Results showed that LSM family members, specifically LSM4, were significantly correlated with oncogenesis in BRCA patients. In summary, our results suggested that LSM4 could be a prospective prognosticator of BRCA.

Expression Profile and Prognostic Value of Wnt Signaling Pathway Molecules in Colorectal Cancer.

Colorectal cancer (CRC) is a heterogeneous disease with changes in the genetic and epigenetic levels of various genes. The molecular assessment of CRC is gaining increasing attention, and furthermore, there is an increase in biomarker use for disease prognostication. Therefore, the identification of different gene biomarkers through messenger RNA (mRNA) abundance levels may be useful for capturing the complex effects of CRC. In this study, we demonstrate that the high mRNA levels of 10 upregulated genes (DPEP1, KRT80, FABP6, NKD2, FOXQ1, CEMIP, ETV4, TESC, FUT1, and GAS2) are observed in CRC cell lines and public CRC datasets. Moreover, we find that a high mRNA expression of DPEP1, NKD2, CEMIP, ETV4, TESC, or FUT1 is significantly correlated with a worse prognosis in CRC patients. Further investigation reveals that CTNNB1 is the key factor in the interaction of the canonical Wnt signaling pathway with 10 upregulated CRC-associated genes. In particular, we identify NKD2, FOXQ1, and CEMIP as three CTNNB1-regulated genes. Moreover, individual inhibition of the expression of three CTNNB1-regulated genes can cause the growth inhibition of CRC cells. This study reveals efficient biomarkers for the prognosis of CRC and provides a new molecular interaction network for CRC.

A New Light on Potential Therapeutic Targets for Colorectal Cancer Treatment.

The development and progression of colorectal cancer (CRC) involve changes in genetic and epigenetic levels of oncogenes and/or tumor suppressors. In spite of advances in understanding of the molecular mechanisms involved in CRC, the overall survival rate of CRC still remains relatively low. Thus, more research is needed to discover and investigate effective biomarkers and targets for diagnosing and treating CRC. The roles of long non-coding RNAs (lncRNAs) participating in various aspects of cell biology have been investigated and potentially contribute to tumor development. Our recent study also showed that CRNDE was among the top 20 upregulated genes in CRC clinical tissues compared to normal colorectal tissues by analyzing a Gene Expression Omnibus (GEO) dataset (GSE21815). Although CRNDE is widely reported to be associated with different types of cancer, most studies of CRNDE were limited to examining regulation of its transcription levels, and in-depth mechanistic research is lacking. In the present study, CRNDE was found to be significantly upregulated in CRC patients at an advanced TNM stage, and its high expression was correlated with poor outcomes of CRC patients. In addition, we found that knocking down CRNDE could reduce lipid accumulation through the miR-29b-3p/ANGPTL4 axis and consequently induce autophagy of CRC cells.

Expression Profiles and Prognostic Value of FABPs in Colorectal Adenocarcinomas.

Colorectal cancer (CRC) is one of the world's leading causes of cancer-related deaths; thus, it is important to detect it as early as possible. Obesity is thought to be linked to a large rise in the CRC incidence as a result of bad dietary choices, such as a high intake of animal fats. Fatty acid-binding proteins (FABPs) are a set of molecules that coordinate intracellular lipid responses and are highly associated with metabolism and inflammatory pathways. There are nine types of FABP genes that have been found in mammals, which are FABP1-7, FABP9, and FABP12. Each FABP gene has its own roles in different organs of the body; hence, each one has different expression levels in different cancers. The roles of FABP family genes in the development of CRC are still poorly understood. We used a bioinformatics approach to examine FABP family gene expression profiles using the Oncomine, GEPIA, PrognoScan, STRING, cBioPortal, MetaCore, and TIMER platforms. Results showed that the FABP6 messenger (m)RNA level is overexpressed in CRC cells compared to normal cells. The overexpression of FABP6 was found to be related to poor prognosis in CRC patients' overall survival. The immunohistochemical results in the Human Protein Atlas showed that FABP1 and FABP6 exhibited strong staining in CRC tissues. An enrichment analysis showed that high expression of FABP6 was significantly correlated with the role of microRNAs in cell proliferation in the development of CRC through the insulin-like growth factor (IGF) signaling pathway. FABP6 functions as an intracellular bile-acid transporter in the ileal epithelium. We looked at FABP6 expression in CRC since bile acids are important in the carcinogenesis of CRC. In conclusion, high FABP6 expression is expected to be a potential biomarker for detecting CRC at the early stage.

Identification of Dipeptidyl Peptidase (DPP) Family Genes in Clinical Breast Cancer Patients via an Integrated Bioinformatics Approach.

Breast cancer is a heterogeneous disease involving complex interactions of biological processes; thus, it is important to develop therapeutic biomarkers for treatment. Members of the dipeptidyl peptidase (DPP) family are metalloproteases that specifically cleave dipeptides. This family comprises seven members, including DPP3, DPP4, DPP6, DPP7, DPP8, DPP9, and DPP10; however, information on the involvement of DPPs in breast cancer is lacking in the literature. As such, we aimed to study their roles in this cancerous disease using publicly available databases such as cBioportal, Oncomine, and Kaplan-Meier Plotter. These databases comprise comprehensive high-throughput transcriptomic profiles of breast cancer across multiple datasets. Furthermore, together with investigating the messenger RNA expression levels of these genes, we also aimed to correlate these expression levels with breast cancer patient survival. The results showed that DPP3 and DPP9 had significantly high expression profiles in breast cancer tissues relative to normal breast tissues. High expression levels of DPP3 and DPP4 were associated with poor survival of breast cancer patients, whereas high expression levels of DPP6, DPP7, DPP8, and DPP9 were associated with good prognoses. Additionally, positive correlations were also revealed of DPP family genes with the cell cycle, transforming growth factor (TGF)-beta, kappa-type opioid receptor, and immune response signaling, such as interleukin (IL)-4, IL6, IL-17, tumor necrosis factor (TNF), and interferon (IFN)-alpha/beta. Collectively, DPP family members, especially DPP3, may serve as essential prognostic biomarkers in breast cancer.

Prognoses and genomic analyses of proteasome 26S subunit, ATPase (PSMC) family genes in clinical breast cancer.

Breast cancer is a complex disease, and several processes are involved in its development. Therefore, potential therapeutic targets need to be discovered for these patients. Proteasome 26S subunit, ATPase gene (PSMC) family members are well reported to be involved in protein degradation. However, their roles in breast cancer are still unknown and need to be comprehensively researched. Leveraging publicly available databases, such as cBioPortal and Oncomine, for high-throughput transcriptomic profiling to provide evidence-based targets for breast cancer is a rapid and robust approach. By integrating the aforementioned databases with the Kaplan-Meier plotter database, we investigated potential roles of six PSMC family members in breast cancer at the messenger RNA level and their correlations with patient survival. The present findings showed significantly higher expression profiles of PSMC2, PSMC3, PSMC4, PSMC5, and PSMC6 in breast cancer compared to normal breast tissues. Besides, positive correlations were also revealed between PSMC family genes and ubiquinone metabolism, cell cycle, and cytoskeletal remodeling. Meanwhile, we discovered that high levels of PSMC1, PSMC3, PSMC4, PSMC5, and PSMC6 transcripts were positively correlated with poor survival, which likely shows their importance in breast cancer development. Collectively, PSMC family members have the potential to be novel and essential prognostic biomarkers for breast cancer development.

Analysis of LAGEs Family Gene Signature and Prognostic Relevance in Breast Cancer.

Breast cancer (BRCA) is one of the most complex diseases and involves several biological processes. Members of the L-antigen (LAGE) family participate in the development of various cancers, but their expressions and prognostic values in breast cancer remain to be clarified. High-throughput methods for exploring disease progression mechanisms might play a pivotal role in the improvement of novel therapeutics. Therefore, gene expression profiles and clinical data of LAGE family members were acquired from the cBioportal database, followed by verification using the Oncomine and The Cancer Genome Atlas (TCGA) databases. In addition, the Kaplan-Meier method was applied to explore correlations between expressions of LAGE family members and prognoses of breast cancer patients. MetaCore, GlueGo, and GluePedia were used to comprehensively study the transcript expression signatures of LAGEs and their co-expressed genes together with LAGE-related signal transduction pathways in BRCA. The result indicated that higher LAGE3 messenger (m)RNA expressions were observed in BRCA tissues than in normal tissues, and they were also associated with the stage of BRCA patients. Kaplan-Meier plots showed that overexpression of LAGE1, LAGE2A, LAGE2B, and LAGE3 were highly correlated to poor survival in most types of breast cancer. Significant associations of LAGE family genes were correlated with the cell cycle, focal adhesion, and extracellular matrix (ECM) receptor interactions as indicated by functional enrichment analyses. Collectively, LAGE family members' gene expression levels were related to adverse clinicopathological factors and prognoses of BRCA patients; therefore, LAGEs have the potential to serve as prognosticators of BRCA patients.

Comprehensive Analysis of Prognostic and Genetic Signatures for General Transcription Factor III (GTF3) in Clinical Colorectal Cancer Patients Using Bioinformatics Approaches.

Colorectal cancer (CRC) has the fourth-highest incidence of all cancer types, and its incidence has steadily increased in the last decade. The general transcription factor III (GTF3) family, comprising GTF3A, GTF3B, GTF3C1, and GTFC2, were stated to be linked with the expansion of different types of cancers; however, their messenger (m)RNA expressions and prognostic values in colorectal cancer need to be further investigated. To study the transcriptomic expression levels of GTF3 gene members in colorectal cancer in both cancerous tissues and cell lines, we first performed high-throughput screening using the Oncomine, GEPIA, and CCLE databases. We then applied the Prognoscan database to query correlations of their mRNA expressions with the disease-specific survival (DSS), overall survival (OS), and disease-free survival (DFS) status of the colorectal cancer patient. Furthermore, proteomics expressions of GTF3 family members in clinical colorectal cancer specimens were also examined using the Human Protein Atlas. Finally, genomic alterations of GTF3 family gene expressions in colorectal cancer and their signal transduction pathways were studied using cBioPortal, ClueGO, CluePedia, and MetaCore platform. Our findings revealed that GTF3 family members' expressions were significantly correlated with the cell cycle, oxidative stress, WNT/ß-catenin signaling, Rho GTPases, and G-protein-coupled receptors (GPCRs). Clinically, high GTF3A and GTF3B expressions were significantly correlated with poor prognoses in colorectal cancer patients. Collectively, our study declares that GTF3A was overexpressed in cancer tissues and cell lines, particularly colorectal cancer, and it could possibly step in as a potential prognostic biomarker.

Development of an Al-Based Web Diagnostic System for Phenotyping Psychiatric Disorders.

Background: Artificial intelligence (AI)-based medical diagnostic applications are on the rise. Our recent study has suggested an explainable deep neural network (EDNN) framework for identifying key structural deficits related to the pathology of schizophrenia. Here, we presented an AI-based web diagnostic system for schizophrenia under the EDNN framework with three-dimensional (3D) visualization of subjects' neuroimaging dataset. Methods: This AI-based web diagnostic system consisted of a web server and a neuroimaging diagnostic database. The web server deployed the EDNN algorithm under the Node.js environment. Feature selection and network model building were performed on the dataset obtained from two hundred schizophrenic patients and healthy controls in the Taiwan Aging and Mental Illness (TAMI) cohort. We included an independent cohort with 88 schizophrenic patients and 44 healthy controls recruited at Tri-Service General Hospital Beitou Branch for validation purposes. Results: Our AI-based web diagnostic system achieved 84.00% accuracy (89.47% sensitivity, 80.62% specificity) for gray matter (GM) and 90.22% accuracy (89.21% sensitivity, 91.23% specificity) for white matter (WM) on the TAMI cohort. For the Beitou cohort as an unseen test set, the model achieved 77.27 and 70.45% accuracy for GM and WM. Furthermore, it achieved 85.50 and 88.20% accuracy after model retraining to mitigate the effects of drift on the predictive capability. Moreover, our system visualized the identified voxels in brain atrophy in a 3D manner with patients' structural image, optimizing the evaluation process of the diagnostic results. Discussion: Together, our approach under the EDNN framework demonstrated the potential future direction of making a schizophrenia diagnosis based on structural brain imaging data. Our deep learning model is explainable, arguing for the accuracy of the key information related to the pathology of schizophrenia when using the AI-based web assessment platform. The rationale of this approach is in accordance with the Research Domain Criteria suggested by the National Institute of Mental Health.

Polymorphisms in the Human Aquaporin 4 Gene Are Associated With Schizophrenia in the Southern Chinese Han Population: A Case-Control Study.

BACKGROUND: In psychiatric illness, pathogenic role of neuroinflammation has been supported by multiple lines of evidence. Astrocytes contribute to the blood-brain barrier (BBB) with formation of the "glymphatic" drainage system of the central nervous system (CNS) through perivascular processes. Found primarily at the end-feet of astrocytes, the aquaporin 4 (AQP4) gene has been suspected to play putative roles in the development of psychiatric disorders as well as the clearance of the glymphatic system. However, there remain many uncertainties because of the limited research on AQP4. The present study is focused on the association between AQP4 gene polymorphisms and schizophrenia (SCZ) in the Southern Chinese Han population. METHODS: Two hundred ninety-two patients and 100 healthy controls were enrolled in this study. To study the relationship of AQP4 gene polymorphisms and SCZ, genetic information was drawn from a cohort of 100 healthy controls and 100 matched patients with SCZ of Southern Han Chinese descent. Comparisons of the allele and genotype distributions between control and case groups were made using the χ2 test. Two-group comparisons were made to assess the linkage equilibrium and haplotype. RESULTS: Three SNPs were found. In comparison to healthy controls, patients had higher T-allele frequencies at rs1058424 and G-allele frequencies at rs3763043 (p = 0.043 and p = 0.045, respectively). Furthermore, there is an association between the decreased risk of SCZ and the AA genotype at both rs1058424 (p = 0.021, OR = 2.04) and rs3763043 (p = 0.018, OR = 2.25) The TCG haplotype (p = 0.036) was associated with a potential risk of SCZ, while the ACA haplotype (p = 0.0007) was associated with a decreased risk of SCZ and retained statistical significance after Bonferroni correction (p = 0.006). CONCLUSIONS: An etiological reference for SCZ is provided by the association between AQP4 gene polymorphisms and SCZ in Southern Han Chinese population.