In vivo magnetogenetics for cell-type-specific targeting and modulation of brain circuits.

Neuromodulation technologies are crucial for investigating neuronal connectivity and brain function. Magnetic neuromodulation offers wireless and remote deep brain stimulations that are lacking in optogenetic- and wired-electrode-based tools. However, due to the limited understanding of working principles and poorly designed magnetic operating systems, earlier magnetic approaches have yet to be utilized.

Nanoarchitectonics of MXene Derived TiO /Graphene with Vertical Alignment for Achieving the Enhanced Supercapacitor Performance.

Structural engineering and hybridization of heterogeneous 2D materials can be effective for advanced supercapacitor. Furthermore, architectural design of electrodes particularly with vertical construction of structurally anisotropic graphene nanosheets, can significantly enhance the electrochemical performance. Herein, MXene-derived TiO nanocomposites hybridized with vertical graphene is synthesized via CO laser irradiation on MXene/graphene oxide nanocomposite film.

Post-translational regulation of proto-oncogene ZBTB7A expression by p53 status in cancer cells: HSP90-dependent stabilization vs. p53-KLHL20-ubiquitin proteasomal degradation.

ZBTB7A overexpressed in many human cancers is a major oncogenic driver. ZBTB7A promotes tumorigenesis by regulating transcription of the genes involved in cell survival and proliferation, apoptosis, invasion, and migration/metastasis. One unresolved issue is the mechanism underlying the aberrant overexpression of ZBTB7A in cancer cells.

Cancer Statistics in Korea: Incidence, Mortality, Survival, and Prevalence in 2020.

Purpose: The current study provides national cancer statistics and their secular trends in Korea, including incidence, mortality, survival, and prevalence in 2020.

Materials And Methods: Incidence, survival, and prevalence rates of cancer were calculated using the Korea National Cancer Incidence Database, from 1999 to 2020, with survival follow-up until December 31, 2021. Deaths from cancer were assessed using causes-of-death data obtained from Statistics Korea.

An immunocompetent rectal cancer model to study radiation therapy.

We describe a mouse model of rectal cancer (RC) involving rapid tumor organoid engraftment via orthotopic transplantation in an immunocompetent setting. This approach uses simple mechanical disruption to allow engraftment, avoiding the use of dextran sulfate sodium. The resulting RC tumors invaded from the mucosal surface and metastasized to distant organs.

Adherens junctions organize size-selective proteolytic hotspots critical for Notch signalling.

Adherens junctions (AJs) create spatially, chemically and mechanically discrete microdomains at cellular interfaces. Here, using a mechanogenetic platform that generates artificial AJs with controlled protein localization, clustering and mechanical loading, we find that AJs also organize proteolytic hotspots for γ-secretase with a spatially regulated substrate selectivity that is critical in the processing of Notch and other transmembrane proteins. Membrane microdomains outside of AJs exclusively organize Notch ligand-receptor engagement (LRE microdomains) to initiate receptor activation.

Genomic and transcriptomic determinants of response to neoadjuvant therapy in rectal cancer.

The incidence of rectal cancer is increasing in patients younger than 50 years. Locally advanced rectal cancer is still treated with neoadjuvant radiation, chemotherapy and surgery, but recent evidence suggests that patients with a complete response can avoid surgery permanently. To define correlates of response to neoadjuvant therapy, we analyzed genomic and transcriptomic profiles of 738 untreated rectal cancers.

KRAS Mutants Upregulate Integrin β4 to Promote Invasion and Metastasis in Colorectal Cancer.

Unlabelled: KRAS mutation in colorectal cancer is associated with aggressive tumor behavior through increased invasiveness and higher rates of lung metastases, but the biological mechanisms behind these features are not fully understood. In this study, we show that KRAS-mutant colorectal cancer upregulates integrin α6β4 through ERK/MEK signaling. Knocking-out integrin β4 (ITGB4) specifically depleted the expression of integrin α6β4 and this resulted in a reduction in the invasion and migration ability of the cancer cells.

An antibody against L1 cell adhesion molecule inhibits cardiotoxicity by regulating persistent DNA damage.

Targeting the molecular pathways underlying the cardiotoxicity associated with thoracic irradiation and doxorubicin (Dox) could reduce the morbidity and mortality associated with these anticancer treatments. Here, we find that vascular endothelial cells (ECs) with persistent DNA damage induced by irradiation and Dox treatment exhibit a fibrotic phenotype (endothelial-mesenchymal transition, EndMT) correlating with the colocalization of L1CAM and persistent DNA damage foci. We demonstrate that treatment with the anti-L1CAM antibody Ab417 decreases L1CAM overexpression and nuclear translocation and persistent DNA damage foci.

Proto-oncoprotein Zbtb7c and SIRT1 repression: implications in high-fat diet-induced and age-dependent obesity.

Zbtb7c is a proto-oncoprotein that controls the cell cycle and glucose, glutamate, and lipid metabolism. Zbtb7c expression is increased in the liver and white adipose tissues of aging or high-fat diet-fed mice. Knockout or knockdown of Zbtb7c gene expression inhibits the adipocyte differentiation of 3T3-L1 cells and decreases adipose tissue mass in aging mice.

KRAS mutant rectal cancer cells interact with surrounding fibroblasts to deplete the extracellular matrix.

Somatic mutations in the KRAS oncogene are associated with poor outcomes in locally advanced rectal cancer but the underlying biologic mechanisms are not fully understood. We profiled mRNA in 76 locally advanced rectal adenocarcinomas from patients that were enrolled in a prospective clinical trial and investigated differences in gene expression between KRAS mutant (KRAS-mt) and KRAS-wild-type (KRAS-wt) patients. We found that KRAS-mt tumors display lower expression of genes related to the tumor stroma and remodeling of the extracellular matrix.

Cell fate decisions by c-Myc depend on ZBTB5 and p53.

The oncoprotein, c-Myc, not only promotes cell proliferation, but can also induce or sensitize cells to apoptosis. However, how c-Myc decides cell fate and which c-Myc downstream target genes are involved remain unknown. Previously, we showed that ZBTB5 (zinc finger and BTB domain-containing 5) is a proto-oncogene that stimulates cell proliferation.

Pharmacologic Inhibition of HIF-1α Attenuates Radiation-Induced Pulmonary Fibrosis in a Preclinical Image Guided Radiation Therapy.

Purpose: Radiation-induced pulmonary fibrosis (RIPF) is a long-term side effect of thoracic radiation therapy. Hypoxia-induced vascular endothelial mesenchymal transition (EndMT) can occur during the development of RIPF. Here, we examined the direct contribution of endothelial HIF-1α (EC-HIF1α) on RIPF.

KLHL4, a novel p53 target gene, inhibits cell proliferation by activating p21.

KLHL4 is a member of the KLHL protein family, many of whom bind the Cul3 E3 ligase, and mediate the ubiquitination of interacting proteins. The KLHL4 gene, localized on the X chromosome, associates with a disorder known as X-linked cleft palate (CPX). However, the biological functions of KLHL4 are largely unknown.

Important Consideration in Choosing Antipsychotics in the Treatment of Patients with 22q11.2 Deletion Syndrome: Risk of Convulsion.

The prevalence of epilepsy and psychosis in 22q11.2 deletion syndrome (22q11.2DS) is higher than in the general population.

Endothelial-to-mesenchymal transition in anticancer therapy and normal tissue damage.

Endothelial-to-mesenchymal transition (EndMT) involves the phenotypic conversion of endothelial-to-mesenchymal cells, and was first discovered in association with embryonic heart development. EndMT can regulate various processes, such as tissue fibrosis and cancer. Recent findings have shown that EndMT is related to resistance to cancer therapy, such as chemotherapy, antiangiogenic therapy, and radiation therapy.

A rectal cancer organoid platform to study individual responses to chemoradiation.

Rectal cancer (RC) is a challenging disease to treat that requires chemotherapy, radiation and surgery to optimize outcomes for individual patients. No accurate model of RC exists to answer fundamental research questions relevant to patients. We established a biorepository of 65 patient-derived RC organoid cultures (tumoroids) from patients with primary, metastatic or recurrent disease.

Temporal and differential regulation of KAISO-controlled transcription by phosphorylated and acetylated p53 highlights a crucial regulatory role of apoptosis.

Transcriptional regulator KAISO plays a critical role in cell cycle arrest and apoptosis through modulation of p53 acetylation by histone acetyltransferase p300. KAISO potently stimulates apoptosis in cells expressing WT p53, but not in p53-mutant or p53-null cells. Here, we investigated how KAISO transcription is regulated by p53, finding four potential p53-binding sites (p53-responsive DNA elements; p53REs) located in a distal 5'-upstream regulatory element, intron 1, exon 2 coding sequence, and a 3'-UTR region.

Hypoxia-induced RelA/p65 derepresses SLC16A3 (MCT4) by downregulating ZBTB7A.

Overexpressed Solute Carrier Family 16 Member 3 (SLC16A3, also called MCT4) plays a critical role in hypoxic cancer cell growth and proliferation, by expelling glycolysis-derived lactate across the plasma membrane. However, how SLC16A3 expression is regulated, under hypoxic conditions, is poorly understood. FBI-1, encoded by ZBTB7A, is a proto-oncoprotein.

The Influence of Depression and School Life on the Quality of Life of Korean Child and Adolescent Patients with Attention-Deficit/Hyperactivity Disorder:A Comparison of the Perspectives of the Patients and Their Caregivers.

Objectives: This study aimed to compare the quality of life reported by patients with attention-deficit/hyperactivity disorder (ADHD) to the patients' quality of life as reported by their caregivers. In addition, it aimed to examine how emotional problems, including depression and anxiety, and the severity of the symptoms affect the quality of life reported by the patients and their caregivers.

Methods: The patients' quality of life and their degree of depression and anxiety were measured using the Pediatric Quality of Life Inventory (PedsQL) 4.

Tumour-vasculature development via endothelial-to-mesenchymal transition after radiotherapy controls CD44v6 cancer cell and macrophage polarization.

It remains controversial whether targeting tumour vasculature can improve radiotherapeutic efficacy. We report that radiation-induced endothelial-to-mesenchymal transition (EndMT) leads to tumour vasculature with abnormal SMANG2 pericyte recruitment during tumour regrowth after radiotherapy. Trp53 (but not Tgfbr2) deletion in endothelial cells (ECs) inhibited radiation-induced EndMT, reducing tumour regrowth and metastases with a high CD44v6 cancer-stem-cell (CSC) content after radiotherapy.

ZNF509S1 downregulates PUMA by inhibiting p53K382 acetylation and p53-DNA binding.

Expression of the POK family protein ZNF509L, and -its S1 isoform, is induced by p53 upon exposure to genotoxic stress. Due to alternative splicing of the ZNF509 primary transcript, ZNF509S1 lacks the 6 zinc-fingers and C-terminus of ZNF509L, resulting in only one zinc-finger. ZNF509L and -S1 inhibit cell proliferation by activating p21/CDKN1A and RB transcription, respectively.