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Elucidating the complex dynamic cellular organization in the hypothalamus is critical for understanding its role in coordinating fundamental body functions. Over the past decade, single-cell and spatial omics technologies have significantly evolved, overcoming initial technical challenges in capturing and analyzing individual cells. These high-throughput omics technologies now offer a remarkable opportunity to comprehend the complex spatiotemporal patterns of transcriptional diversity and cell-type characteristics across the entire hypothalamus. Current single-cell and single-nucleus RNA sequencing methods comprehensively quantify gene expression by exploring distinct phenotypes across various subregions of the hypothalamus. However, single-cell/single-nucleus RNA sequencing requires isolating the cell/nuclei from the tissue, potentially resulting in the loss of spatial information concerning neuronal networks. Spatial transcriptomics methods, by bypassing the cell dissociation, can elucidate the intricate spatial organization of neural networks through their imaging and sequencing technologies. In this review, we highlight the applicative value of single-cell and spatial transcriptomics in exploring the complex molecular-genetic diversity of hypothalamic cell types, driven by recent high-throughput achievements.

Abstract Cellular senescence, recognized as a key hallmark of aging, leads to the accumulation of senescent cells in various tissues over time. While the detrimental effects of these cells on age-related pathological conditions are well-documented, there is still limited information about how senescent cells are distributed in normal tissues of both young and aged organs. Our research indicates that fully senescent p16INK4A+ cells are rarely identified in the parenchyma of organic tissues and in the stromal cells crucial for structural maintenance, such as fibroblasts and smooth muscle cells. Instead, p16INK4A+ cells are more commonly found in immune cells, whether they reside in the organ or are infiltrating. Notably, p16INK4A+ senescent T cells have been observed to induce apoptosis and inflammation in colonic epithelial cells through Granzyme A-PARs signaling, compromising the integrity of the epithelial lining. This study showed that the senescence of immune cells could affect the phenotypical change of the parenchymal cells in the elderly and suggests that targeting immunosenescence might be a strategy to control functional decline in this population.

Abstract Mitochondrial dysfunction induced by mitochondrial DNA (mtDNA) mutations has been implicated in various human diseases. A comprehensive analysis of mitochondrial genetic disorders requires suitable animal models for human disease studies. While gene knockout via premature stop codons is a powerful method for investigating the unique functions of target genes, achieving knockout of mtDNA has been rare. Here, we report the genotypes and phenotypes of heteroplasmic MT-ND5 gene-knockout mice. These mutant mice presented damaged mitochondrial cristae in the cerebral cortex, hippocampal atrophy, and asymmetry, leading to learning and memory abnormalities. Moreover, mutant mice are susceptible to obesity and thermogenetic disorders. We propose that these mtDNA gene-knockdown mice could serve as valuable animal models for studying the MT-ND5 gene and developing therapies for human mitochondrial disorders in the future.

Abstract Hepatocellular carcinoma (HCC) presents a major health issue worldwide. This study introduces the HepScope gene set, developed through a hybrid approach that utilizes single-cell RNA sequencing (scRNA-seq), spatial transcriptomics (stRNA-seq), bulk RNA-seq, and proteomics data, along with the adaptation of Convolutional Neural Network (CNN) techniques. Comprising 113 genes significantly upregulated in malignant hepatocytes, HepScope gene set includes 77 genes unique to this set compared to other HCC-related gene sets. Unlike existing solutions, HepScope gene set demonstrated superior discriminatory power in distinguishing malignant from non-malignant hepatocytes, as validated by Seurat's module score, outperforming five other gene sets across multiple datasets. A 1D-CNN model, specifically adapted for the HepScope gene set, achieved superior accuracy (0.71), AUROC (0.82), and F1 score (0.85) compared to models trained on other gene sets, underscoring its enhanced predictive precision and robustness. Rigorous cross-validation and benchmarking against alternative models confirmed HepScope’s consistent performance. Additionally, we evaluated the prognostic capability of the HepScope gene set across two independent cohorts, demonstrating that the HepScope-based risk score is a strong independent predictor of overall and disease-free survival, making it a valuable tool for patient prognosis. Collectively, our findings position HepScope as a promising gene set for both diagnostic and prognostic applications in HCC, highlighting its potential in precision medicine for HCC and offering insights into personalized therapy development.

This study delineates the development of a versatile and flexible heater achieved through the sequential coating of polycaprolactone (PCL) fibers with MXene, silver nanowires (AgNW), and Aerosil/polydimethylsiloxane (AP). The primary innovation of this research lies in the concurrent realization of self-healability at low temperatures and exceptional mechanical flexibility, biocompatibility, and robust superhydrophobicity-based waterproof properties. PCL, recognized for its biocompatibility, demonstrates self-healing capabilities under mild thermal conditions, while the MXene layer mitigates damage and deformation during the healing process by providing thermal stability and efficient heat dissipation. AgNW significantly enhances electrical conductivity, thereby facilitating efficient Joule heating. The AP layer, introduced for the first time in wearable fibrous devices, imparts superior water-repellent properties by forming a hydrophobic surface that repels water and prevents moisture penetration, effectively safeguarding the electrode material from humid environments and acidic solutions. Comprehensive evaluations indicate that the heater maintains stable electrical and thermal properties, even after enduring 50,000 cycles of bending at a radius of curvature of 500 μm, 100 h of washing, and multiple cycles of cutting and healing. The fabric-based heaters were seamlessly integrated into commercially available arm sleeves, preserving their heating functionality despite being subjected to bending motions.

Abstract T cell immunoglobulin and mucin-containing molecule 3 (TIM-3) exhibits unique, cell type- and context-dependent characteristics and functions. Here, we report that TIM-3 on myeloid cells plays essential roles in modulating lung inflammation. We found that myeloid cell-specific TIM-3 knock-in (FSF-TIM3/LysM-Cre+) mice have lower body weight and shorter lifespan than WT mice. Intriguingly, the lungs of FSF-TIM3/LysM-Cre+ mice display excessive inflammation and features of disease-associated pathology. We further revealed that galectin-3 levels are notably elevated in TIM-3-overexpressing lung-derived myeloid cells. Furthermore, both TIM-3 blockade and GB1107, a galectin-3 inhibitor, ameliorated lung inflammation in FSF-TIM3/LysM-Cre+/− mice. Using an LPS-induced lung inflammation model with myeloid cell-specific TIM-3 knock-out mice, we demonstrated the association of TIM-3 with both lung inflammation and galectin-3. Collectively, our findings suggest that myeloid TIM-3 is an important regulator in the lungs and that modulation of TIM-3 and galectin-3 could offer therapeutic benefits for inflammation-associated lung diseases.

Abstract Background This study aimed to produce Odontoglossum ringspot virus (ORSV)-free Cymbidium orchid ‘New True’ plants from ORSV-infected mother plants by culturing their meristems and successively repeating subcultures of protocorm-like bodies (PLBs) derived from the meristems. Results Initially, ORSV was confirmed as the causative agent of viral symptoms in orchid leaves via reverse transcription-polymerase chain reaction (RT-PCR) analysis. Meristems from infected plants were cultured to generate PLBs, which in sequence were repeatedly subcultured up to four times. RT-PCR and quantitative RT-PCR analyses revealed that while ORSV was undetectable in shoots derived from the first subculture, complete elimination of the virus required at least a second subculture. Genetic analysis using inter-simple sequence repeat markers indicated no somaclonal variation between regenerated plants and the mother plant, suggesting that genetic consistency was maintained. Conclusion Overall, our findings demonstrate that subculturing PLBs for a second time is ideal for producing genetically stable, ORSV-free Cymbidium orchids, thus offering a practical means of generating genetically stable, virus-free plants and enhancing plant health and quality in the orchid industry.

Abstract Hepatocellular carcinoma (HCC) is known to be lethal disease. However, its prognosis remains poor, primarily because the precise oncogenic mechanisms underlying HCC progression remain elusive, thus hampering effective treatment. Here, we aimed to identify the potential oncogenes in HCC and elucidate the underlying mechanisms of their action. To identify potential candidate genes, an integrative analysis of eight publicly available genomic datasets was performed, and the functional implications of the identified genes were assessed in vitro and in vivo. Sortilin 1 (SORT1) was identified as a potential candidate oncogene in HCC, and its overexpression in HCC cells was confirmed by analyzing spatial transcriptomic and single-cell data. Silencing SORT1 in Huh-7 and Hep3B cells significantly reduced HCC progression in vitro and in vivo. Functional analyses of oncogenic pathways revealed that SORT1 expression regulated the Notch signaling pathway activation and CD133 expression. Furthermore, analysis of epigenetic regulation of the candidate gene and its clinical implications using The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA LIHC) and our HCC cohort (AJOU_HCC cohort) data demonstrated an inverse correlation between the methylation status of the SORT1 promoter region, specifically at the cg16988986 site, and SORT1 mRNA expression, indicating the epigenetic regulation of SORT1 in HCC. In addition, the distinct methylation status of cg16988986 was significantly associated with patient survival. In conclusion, SORT1 plays a pivotal role in HCC by activating the Notch signaling pathway and increasing CD133 expression. These findings suggest SORT1 as a promising therapeutic target for HCC.

Background/Aims Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality worldwide. Despite identification of several biomarkers for HCC diagnosis, challenges such as low sensitivity and intratumoral heterogeneity have impeded early detection, highlighting the need for etiology-specific blood biomarkers. Methods We generated whole-transcriptome sequencing (WTS) and targeted proteome data from buffy coat and plasma samples from HCC patients. By integrating etiological information on viral infection, we investigated the etiology-specific gene expression landscape at the blood level. Validation of differentially expressed genes (DEGs) was performed using publicly available RNA-seq datasets and qRT‒PCR with AUC analyses. Results Differential expression analyses with multiomics data revealed distinct gene expression profiles between HBV-associated HCC and nonviral HCC, indicating the presence of etiology-specific blood biomarkers. The identified DEGs were validated across multiple independent datasets, underscoring their utility as biomarkers. Additionally, single-cell RNA-seq analysis of HCC confirmed differences in DEG expression across distinct immune cell types. Conclusions Our buffy coat WTS data and plasma proteome data may serve as reliable sources for identifying etiology-specific blood biomarkers of HCC and might contribute to discovery of therapeutic targets for HCC across different etiologies.

Abstract The arginyl-transferase ATE1 is a tRNA-dependent enzyme that covalently attaches an arginine molecule to a protein substrate. Conserved from yeast to humans, ATE1 deficiency in mice correlates with defects in cardiovascular development and angiogenesis and results in embryonic lethality, while conditional knockouts exhibit reproductive, developmental, and neurological deficiencies. Despite the recent revelation of the tRNA binding mechanism and the catalytic cycle of yeast ATE1, the structure-function relationship of ATE1 in higher organisms is not well understood. In this study, we present the three-dimensional structure of human ATE1 in an apo-state and in complex with its tRNA cofactor and a peptide substrate. In contrast to its yeast counterpart, human ATE1 forms a symmetric homodimer, which dissociates upon binding of a substrate. Furthermore, human ATE1 includes a unique and extended loop that wraps around tRNAArg, creating extensive contacts with the T-arm of the tRNA cofactor. Substituting key residues identified in the substrate binding site of ATE1 abolishes enzymatic activity and results in the accumulation of ATE1 substrates in cells.

In this study, pitch-based carbon (PC) was modified with polyethylenimine (PEI) to produce PEI-modified PC (PEI-PC) for wastewater treatment. PEI, containing amine groups, shows advantages in adsorbing ionic dyes. The adsorption and desorption properties of PEC-PC for dyes were evaluated through pH edge, experiments, adsorption kinetics, isotherm studies, and desorption tests. We selected Cibacron Brilliant Yellow 3G-P (Reactive Yellow 2: RY2) as the model dye for our study. pH edge experiments were conducted in a pH range of 2-12 with an initial dye concentration of 100 mg/L. The results showed that dye uptake on PEI-PC increased as the pH value decreased. Adsorption kinetic experiments confirmed that adsorption equilibrium at pHs 2 and 7 was achieved within 30 min. The adsorption isotherm experiments, conducted at initial dye concentrations ranging from 10 to 300 mg/L, revealed that the experimental data fit well with the Langmuir model. The dye-loaded PEI-PC was desorbed using a 0.05 M NaOH solution, and this adsorption-desorption process was repeated. It was observed that when the adsorption-desorption cycles were repeated from 1 to 5 times, the adsorption efficiency decreased by 29 %.

Pancreatic cancer is among the most lethal cancers with limited treatment options. Traditional herbal medicines have been explored as potential adjunct therapies for enhancing the effectiveness of standard chemotherapies. In this study, we investigated the safety and efficacy of Rhus verniciflua Stokes (RVS) in combination with first-line chemotherapy for unresectable locally advanced and metastatic pancreatic cancer in a prospective setting. This prospective observational pilot study enrolled patients with confirmed inoperable stage III or IV pancreatic cancer undergoing or scheduled to receive 5-fluorouracil-based or gemcitabine-based first-line chemotherapy with RVS treatment and were followed up for up to 20 months. The primary endpoint was the safety profile of RVS, which was assessed through adverse events. The secondary endpoints included overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Cox regression analysis identified possible prognostic factors for PFS and OS. Of the enrolled 25 patients, 18 completed the follow-up. The median RVS treatment duration was 6.14 months (range 2.23–8.01 months) and the median RVS daily dose was 3.8 capsules/day (range 2.1–5.7 capsules/day). RVS showed a favorable safety profile, with only one case of non-severe pruritus possibly related to RVS treatment. No hepatotoxicity and nephrotoxicity related to RVS was reported. The ORR and DCR were 5.6% and 72.2%, respectively. The median PFS and OS were 7.24 months (95% CI: 3.15–12.9) and 13.9 months (95% CI: 1.14–27.72), respectively. Cox regression analysis showed that baseline CA19-9 level was an independent prognostic factor for OS, and the daily dose of RVS was an independent prognostic factor for PFS and OS. In conclusion, RVS can be administered safely to patients with unresectable locally advanced metastatic pancreatic cancer who are undergoing first-line chemotherapy, and the daily dose was an independent prognostic factor for cancer survival. Further randomized controlled studies are warranted to confirm the exact benefits of RVS treatment.Clinical trial registrationhttps://cris.nih.go.kr, identifier KCT0007496.

Abstract N 6-adenosine methylation (m6A) is critical for controlling cancer cell growth and tumorigenesis. However, the function and detailed mechanism of how m6A methyltransferases modulate m6A levels on specific targets remain unknown. In the current study, we identified significantly elevated levels of RBM15, an m6A writer, in basal-like breast cancer (BC) patients compared to nonbasal-like BC patients and linked this increase to worse clinical outcomes. Gene expression profiling revealed correlations between RBM15 and serine and glycine metabolic genes, including PHGDH, PSAT1, PSPH, and SHMT2. RBM15 influences m6A levels and, specifically, the m6A levels of serine and glycine metabolic genes via direct binding to target RNA. The effects of RBM15 on cell growth were largely dependent on serine and glycine metabolism. Thus, RBM15 coordinates cancer cell growth through altered serine and glycine metabolism, suggesting that RBM15 is a new therapeutic target in BC.

Abstract The emergence of high-form-factor electronics has led to a demand for high-density integration of inorganic thin-film devices and circuits with full stretchability. However, the intrinsic stiffness and brittleness of inorganic materials have impeded their utilization in free-form electronics. Here, we demonstrate highly integrated strain-insensitive stretchable metal-oxide transistors and circuitry (442 transistors/cm2) via a photolithography-based bottom-up approach, where transistors with fluidic liquid metal interconnection are embedded in large-area molecular-tailored heterogeneous elastic substrates (5 × 5 cm2). Amorphous indium-gallium-zinc-oxide transistor arrays (7 × 7), various logic gates, and ring-oscillator circuits exhibited strain-resilient properties with performance variation less than 20% when stretched up to 50% and 30% strain (10,000 cycles) for unit transistor and circuits, respectively. The transistors operate with an average mobility of 12.7 ( ± 1.7) cm2 V−1s−1, on/off current ratio of > 107, and the inverter, NAND, NOR circuits operate quite logically. Moreover, a ring oscillator comprising 14 cross-wired transistors validated the cascading of the multiple stages and device uniformity, indicating an oscillation frequency of ~70 kHz.

Memristors are promising candidates for next-generation non-volatile memory devices, offering low power consumption and high-speed switching capabilities. However, conventional metal oxide-based memristors are constrained by fabrication complexity and high costs, limiting their commercial viability. Organic–inorganic hybrid perovskites (OIHPs), known for their facile solution processability and unique ionic–electronic conductivity, provide an attractive alternative. This study presents a conjugated polyelectrolyte (CPE), PhNa-1T, as an interlayer for OIHP memristors to enhance the high-resistance state (HRS) performance. A post-treatment process using n-octylammonium bromide (OABr) was further applied to optimize the interlayer properties. Devices treated with PhNa-1T/OABr achieved a significantly improved ON/OFF ratio of 2150, compared to 197 for untreated devices. Systematic characterization revealed that OABr treatment improved film morphology, reduced crystallite strain, and optimized energy level alignment, thereby reinforcing the Schottky barrier and minimizing current leakage. These findings highlight the potential of tailored interlayer engineering to improve OIHP-based memristor performance, offering promising prospects for applications in non-volatile memory technologies.

Abstract The Hippo pathway’s main effector, Yes-associated protein (YAP), plays a crucial role in tumorigenesis as a transcriptional coactivator. YAP’s phosphorylation by core upstream components of the Hippo pathway, such as mammalian Ste20 kinase 1/2 (MST1/2), mitogen-activated protein kinase kinase kinase kinases (MAP4Ks), and their substrate, large tumor suppressor 1/2 (LATS1/2), influences YAP’s subcellular localization, stability, and transcriptional activity. However, recent research suggests the existence of alternative pathways that phosphorylate YAP, independent of these core upstream Hippo pathway components, raising questions about additional means to inactivate YAP. In this study, we present evidence demonstrating that TSSK1B, a calcium/calmodulin-dependent protein kinase (CAMK) superfamily member, is a negative regulator of YAP, suppressing cellular proliferation and oncogenic transformation. Mechanistically, TSSK1B inhibits YAP through two distinct pathways. Firstly, the LKB1–TSSK1B axis directly phosphorylates YAP at Ser94, inhibiting the YAP–TEAD complex’s formation and suppressing its target genes’ expression. Secondly, the TSSK1B–LATS1/2 axis inhibits YAP via phosphorylation at Ser127. Our findings reveal the involvement of TSSK1B-mediated molecular mechanisms in the Hippo–YAP pathway, emphasizing the importance of multilevel regulation in critical cellular decision-making processes.

Abstract This study delves into the development of a novel 10 by 10 sensor array featuring 100 pressure sensor pixels, achieving remarkable sensitivity up to 888.79 kPa−1, through the innovative design of sensor structure. The critical challenge of strain sensitivity inherent is addressed in stretchable piezoresistive pressure sensors, a domain that has seen significant interest due to their potential for practical applications. This approach involves synthesizing and electrospinning polybutadiene‐urethane (PBU), a reversible cross‐linking polymer, subsequently coated with MXene nanosheets to create a conductive fabric. This fabrication technique strategically enhances sensor sensitivity by minimizing initial current values and incorporating semi‐cylindrical electrodes with Ag nanowires (AgNWs) selectively coated for optimal conductivity. The application of a pre‐strain method to electrode construction ensures strain immunity, preserving the sensor's electrical properties under expansion. The sensor array demonstrated remarkable sensitivity by consistently detecting even subtle airflow from an air gun in a wind sensing test, while a novel deep learning methodology significantly enhanced the long‐term sensing accuracy of polymer‐based stretchable mechanical sensors, marking a major advancement in sensor technology. This research presents a significant step forward in enhancing the reliability and performance of stretchable piezoresistive pressure sensors, offering a comprehensive solution to their current limitations.

This article reported a case of a patient with schizophrenia who experienced self-perceived fever and discomfort after taking atypical antipsychotic drugs with strong alpha 1 receptor antagonism， which included olanzapine， risperidone， paliperidone and clozapine. Such phenomenon was believed to be a medication side effect. Therefore， the patient switched to aripiprazole and the fever disappeared. This case report is intended to remind psychiatrists to pay attention to the side effects caused by atypical antipsychotic drugs with strong alpha 1 receptor antagonism as well as to suggest that various factors should be considered， including mechanisms of drug action， patient pathophysiology and individual differences， in order to improve treatment compliance and prognosis.

In this paper, we present a sensitive and highly reproducible fluorescence immunosensor for detecting PSA in human serum. A unique feature of this study is that it uses creatively designed paddle screw-type devices and their custom-made rotating system for PSA immunoassay. The paddle screw devices were designed to maximize the surface-to-volume ratio over which the immunoassay reaction could occur to improve detection sensitivity. This paddle screw-based immunoassay offers an accessible and efficient method with a short analysis time of less than 30 min. Active rotation of the paddle screw plays a crucial role in fast and accurate analysis of PSA. Additionally, a paddle screw-based immunoassay and subsequent fluorescence detection using a custom prototype fluorescence detection system were compared to a typical well plate-based immunoassay system. Results of PSA detection in human serum showed that the detection sensitivity through the paddle screw-based analysis improved about five times compared to that with a well plate-based analysis.

Abstract Despite the importance of hypothalamic neurocircuits in regulating homeostatic and survival-related behaviors, our understanding of the intrinsic molecular identities of neural components involved in these complex multi-synaptic interactions remains limited. In this study, we constructed a Cre recombinase-dependent pseudorabies virus (PRVs) capable of crossing synapses, coupled with transcriptome analysis of single upstream neurons post-infection. By utilizing this retrograde nuclear Connect-seq (nuConnect-seq) approach, we generated a single nuclei RNA-seq (snRNA-seq) dataset of 1,533 cells derived from the hypothalamus of CRH-IRES-Cre (CRH-Cre) mice. To ensure the technical validity of our nuConnect-seq dataset, we employed a label transfer technique against an integrated reference dataset of postnatal mouse hypothalamus comprising 152,524 QC-passed cells. The uniqueness of our approach lies in the integration of diverse datasets for validation, providing a more nuanced diversity of hypothalamic cell types. The presented validated dataset may deepen our understanding of hypothalamic neurocircuits and underscore the essential role of comprehensive integrated transcriptomic data for technical validity.

Abstract Background Cancer cells undergo cellular adaptation through metabolic reprogramming to sustain survival and rapid growth under various stress conditions. However, how brain tumors modulate their metabolic flexibility in the naturally serine/glycine (S/G)-deficient brain microenvironment remain unknown. Methods We used a range of primary/stem-like and established glioblastoma (GBM) cell models in vitro and in vivo. To identify the regulatory mechanisms of S/G deprivation-induced metabolic flexibility, we employed high-throughput RNA-sequencing, transcriptomic analysis, metabolic flux analysis, metabolites analysis, chromatin immunoprecipitation (ChIP), luciferase reporter, nuclear fractionation, cycloheximide-chase, and glucose consumption. The clinical significances were analyzed in the genomic database (GSE4290) and in human GBM specimens. Results The high-throughput RNA-sequencing and transcriptomic analysis demonstrate that the de novo serine synthesis pathway (SSP) and glycolysis are highly activated in GBM cells under S/G deprivation conditions. Mechanistically, S/G deprivation rapidly induces reactive oxygen species (ROS)-mediated AMP-activated protein kinase (AMPK) activation and AMPK-dependent hypoxia-inducible factor (HIF)-1α stabilization and transactivation. Activated HIF-1α in turn promotes the expression of SSP enzymes phosphoglycerate dehydrogenase (PHGDH), phosphoserine aminotransferase 1 (PSAT1), and phosphoserine phosphatase (PSPH). In addition, the HIF-1α-induced expression of glycolytic genes (GLUT1, GLUT3, HK2, and PFKFB2) promotes glucose uptake, glycolysis, and glycolytic flux to fuel SSP, leading to elevated de novo serine and glycine biosynthesis, NADPH/NADP+ ratio, and the proliferation and survival of GBM cells. Analyses of human GBM specimens reveal that the levels of overexpressed PHGDH, PSAT1, and PSPH are positively correlated with levels of AMPK T172 phosphorylation and HIF-1α expression and the poor prognosis of GBM patients. Conclusion Our findings reveal that metabolic stress-enhanced glucose-derived de novo serine biosynthesis is a critical metabolic feature of GBM cells, and highlight the potential to target SSP for treating human GBM.

Abstract The biological process of aging is thought to result in part from accumulation of senescent cells in organs. However, the present study identified a subset of fibroblasts and smooth muscle cells which are the major constituents of organ stroma neither proliferative nor senescent in tissues of the elderly, which we termed “mid-old status” cells. Upregulation of pro-inflammatory genes (IL1B and SAA1) and downregulation of anti-inflammatory genes (SLIT2 and CXCL12) were detected in mid-old cells. In the stroma, SAA1 promotes development of the inflammatory microenvironment via upregulation of MMP9, which decreases the stability of epithelial cells present on the basement membrane, decreasing epithelial cell function. Remarkably, the microenvironmental change and the functional decline of mid-old cells could be reversed by a young cell-originated protein, SLIT2. Our data identify functional reversion of mid-old cells as a potential method to prevent or ameliorate aspects of aging-related tissue dysfunction.

Abstract Cryotherapy leverages controlled freezing temperature interventions to engender a cascade of tumor‐suppressing effects. However, its bottleneck lies in the standalone ineffectiveness. A promising strategy is using nanoparticle therapeutics to augment the efficacy of cryotherapy. Here, a cold‐responsive nanoplatform composed of upconversion nanoparticles coated with silica – chlorin e6 – hyaluronic acid (UCNPs@SiO2‐Ce6‐HA) is designed. This nanoplatform is employed to integrate cryotherapy with photodynamic therapy (PDT) in order to improve skin cancer treatment efficacy in a synergistic manner. The cryotherapy appeared to enhance the upconversion brightness by suppressing the thermal quenching. The low‐temperature treatment afforded a 2.45‐fold enhancement in the luminescence of UCNPs and a 3.15‐fold increase in the photodynamic efficacy of UCNPs@SiO2‐Ce6‐HA nanoplatforms. Ex vivo tests with porcine skins and the subsequent validation in mouse tumor tissues revealed the effective HA‐mediated transdermal delivery of designed nanoplatforms to deep tumor tissues. After transdermal delivery, in vivo photodynamic therapy using the UCNPs@SiO2‐Ce6‐HA nanoplatforms resulted in the optimized efficacy of 79% in combination with cryotherapy. These findings underscore the Cryo‐PDT as a truly promising integrated treatment paradigm and warrant further exploring the synergistic interplay between cryotherapy and PDT with bright upconversion to unlock their full potential in cancer therapy.

Abstract Nicotinamide phosphoribosyltransferase (NAMPT) is a metabolic enzyme with key roles in inflammation. Previous studies have examined the consequences of its upregulated expression in cancer cells themselves, but studies are limited with respect to its role in the other cells within the tumor microenvironment (TME) during colorectal cancer (CRC) progression. Using single‐cell RNA sequencing (scRNA‐seq) data, it is founded that NAMPT is highly expressed in SPP1+ tumor‐associated macrophages (TAMs), a unique subset of TAMs associated with immunosuppressive activity. A NAMPThigh gene signature in SPP1+ TAMs correlated with worse prognostic outcomes in CRC patients. The effect of Nampt deletion in the myeloid compartment of mice during CRC development is explored. NAMPT deficiency in macrophages resulted in HIF‐1α destabilization, leading to reduction in M2‐like TAM polarization. NAMPT deficiency caused significant decreases in the efferocytosis activity of macrophages, which enhanced STING signaling and the induction of type I IFN‐response genes. Expression of these genes contributed to anti‐tumoral immunity via potentiation of cytotoxic T cell activity in the TME. Overall, these findings suggest that NAMPT‐initiated TAM‐specific genes can be useful in predicting poor CRC patient outcomes; strategies aimed at targeting NAMPT may provide a promising therapeutic approach for building an immunostimulatory TME in CRC progression.

Biological and molecular characterization of a Korean isolate of Orthotospovirus chrysanthinecrocaulis (for-merly known as chrysanthemum stem necrosis virus, CSNV) isolated from Chrysanthemum morifolium was determined using host range and sequence analysis in this study. Twenty-three species of indicator plants inoculated mechanically CSNV-Kr was investigated for determination of host range. CSNV-Kr induced various local and systemic symptoms in the inoculated plant species. CSNV-Kr could not infect three plant species and induced symptomless in systemic leaves in Nicotiana tabacum cultivars, though the plant samples reacted positively with the antiserum to CSNV by double-antibody sandwich–enzyme-linked immunosorbent assay. The complete genome sequence of CSNV-Kr was determined. The L RNA of CSNV-Kr consists of 8,959 nucleotides (nt) and encodes a putative RNA-dependent RNA polymerase. The M RNA of CSNV-Kr consists of 4,835 nt and encodes the movement protein (NSm) and the glycoprotein precursor (Gn/Gc protein). The S RNA of CNSV-Kr consists of 2,836 nt and encodes NSs protein and N protein. The Gn/Gc and N sequence of CSNV-Kr were compared with those of previously published CSNV isolates originating from different countries at nucleotide and amino acid levels. The Gn/GC sequence of CSNV-Kr shared 98.8−99.5% identity with CSNV isolated from other countries and the N sequence of CSNV-Kr shared 98.8−99.6% identity. No particular region of variability could be found in either grouping of viruses. All of the CSNV isolates did not show any relationship according to geographical origins and isolation hosts, suggesting no distinct segregation of the CSNV isolates.

Bioinformatic analysis of large and complex omics datasets has become increasingly useful in modern day biology by providing a great depth of information, with its application to neuroscience termed neuroinformatics. Data mining of omics datasets has enabled the generation of new hypotheses based on differentially regulated biological molecules associated with disease mechanisms, which can be tested experimentally for improved diagnostic and therapeutic targeting of neurodegenerative diseases. Importantly, integrating multi-omics data using a systems bioinformatics approach will advance the understanding of the layered and interactive network of biological regulation that exchanges systemic knowledge to facilitate the development of a comprehensive human brain profile. In this review, we first summarize data mining studies utilizing datasets from the individual type of omics analysis, including epigenetics/epigenomics, transcriptomics, proteomics, metabolomics, lipidomics, and spatial omics, pertaining to Alzheimer's disease, Parkinson's disease, and multiple sclerosis. We then discuss multi-omics integration approaches, including independent biological integration and unsupervised integration methods, for more intuitive and informative interpretation of the biological data obtained across different omics layers. We further assess studies that integrate multi-omics in data mining which provide convoluted biological insights and offer proof-of-concept proposition towards systems bioinformatics in the reconstruction of brain networks. Finally, we recommend a combination of high dimensional bioinformatics analysis with experimental validation to achieve translational neuroscience applications including biomarker discovery, therapeutic development, and elucidation of disease mechanisms. We conclude by providing future perspectives and opportunities in applying integrative multi-omics and systems bioinformatics to achieve precision phenotyping of neurodegenerative diseases and towards personalized medicine.

Given the persistent occurrence of foodborne illnesses linked to both raw and processed vegetables, understanding microbial behavior in these foods under distribution conditions is crucial. This study aimed to develop predictive growth models for Salmonella spp. and Listeria monocytogenes in raw (mung bean sprouts, onion, and cabbage) and processed vegetables (shredded cabbage salad, cabbage and onion juices) at various temperatures, ranging from 4 to 36 °C. Growth models were constructed and validated using isolated strains of Salmonella spp. (S. Bareilly, S. Enteritidis, S. Typhimurium) and L. monocytogenes (serotypes 1/2a and 1/2b) from diverse food sources. The minimum growth temperatures for Salmonella varied among different vegetable matrices: 8 °C for mung bean sprouts, 9 °C for both onion and cabbage, and 10 °C for ready-to-eat (RTE) shredded cabbage salad. Both pathogens grew in cabbage juice at temperatures above 17 °C, while neither demonstrated growth in onion juice, even at 36 °C. Notably, Salmonella spp. exhibited faster growth than L. monocytogenes in all tested samples. At 8 °C, the lag time (LT) and specific growth rate (SGR) for Salmonella spp. in mung bean sprouts were approximately tenfold longer and threefold slower, respectively, compared to those at 10 °C. A decrease in refrigerator storage temperature by 1 or 2 degrees significantly prevented the growth of Salmonella in raw vegetables. These findings offer valuable insights into assessing the risk of foodborne illness associated with the consumption of raw and processed vegetables and inform management strategies in mitigating these risks.

The investigation into the implementation and widespread adoption of oyster shell recycling methods aimed at restoring coastal ecosystems and enhancing water quality is currently limited. In this study, we investigated the utilization of oyster shell powder (OSP) as a cost-effective and environmentally sustainable method for treating high-fluoride-concentration wastewater, a byproduct of industrial processes. We conducted extensive laboratory testing to determine the optimal conditions for fluoride removal. This involved variations in OSP doses, particle sizes, and initial wastewater pH levels. The results of these tests showed that OSP achieved fluoride removal efficiencies exceeding 98% at an optimal dosage of 5 g/L. In addition, OSP effectively adjusted the wastewater pH from highly acidic (pH 2) to almost neutral (pH 6.87), demonstrating its effectiveness in real-world industrial wastewater treatment. OSP, derived from oyster shell waste, is rich in calcium carbonate and offers a novel approach to wastewater management by leveraging a natural waste product. This study demonstrates the potential of OSP as a waste management strategy and contributor to the circular economy by repurposing industrial byproducts.

Exosomes are small extracellular vesicles produced by almost all cell types in the human body, and exosomal microRNAs (miRNAs) are small non-coding RNA molecules that are known to serve as important biomarkers for diseases such as cancer. Given that the upregulation of miR-106b is closely associated with several types of malignancies, the sensitive and accurate detection of miR-106b is important but difficult. In this study, a surface acoustic wave (SAW) biosensor was developed to detect miR-106b isolated from cancer cells based on immunoaffinity separation technique using our unique paddle screw device. Our novel SAW biosensor could detect a miR-106b concentration as low as 0.0034 pM in a linear range from 0.1 pM to 1.0 μM with a correlation coefficient of 0.997. Additionally, we were able to successfully detect miR-106b in total RNA extracted from the exosomes isolated from the MCF-7 cancer cell line, a model system for human breast cancer, with performance comparable to commercial RT-qPCR methods. Therefore, the exosome isolation by the paddle screw method and the miRNA detection using the SAW biosensor has the potential to be used in basic biological research and clinical diagnosis as an alternative to RT-qPCR.

Summary: In this study, we explore the dynamic process of colorectal cancer progression, emphasizing the evolution toward a more metastatic phenotype. The term “evolution” as used in this study specifically denotes the phenotypic transition toward a higher metastatic potency from well-formed glandular structures to collective invasion, ultimately resulting in the development of cancer cell buddings at the invasive front. Our findings highlight the spatial correlation of this evolution with tumor cell senescence, revealing distinct types of senescent tumor cells (types I and II) that play different roles in the overall cancer progression. Type I senescent tumor cells (p16INK4A+/CXCL12+/LAMC2−/MMP7−) are identified in the collective invasion region, whereas type II senescent tumor cells (p16INK4A+/CXCL12+/LAMC2+/MMP7+), representing the final evolved form, are prominently located in the partial-EMT region. Importantly, type II senescent tumor cells associate with local invasion and lymph node metastasis in colorectal cancer, potentially affecting patient prognosis.

Blue light can reach the epidermis, dermis, and hypodermis of the skin and affect the physiology of each cell type. However, thus far, most studies have focused on the effects of blue light on the epidermis and dermis; no studies have been conducted on the effects of blue light on the hypodermis. In this study, we attempted to elucidate the effects of blue light on the hypodermis. Specifically, we investigated the effects of blue light on 3T3-L1 adipogenesis and its mechanism of action. In this study, we found that blue light reduced lipid accumulation and GPDH activity, indicating its antiadipogenic properties. Furthermore, blue light inhibited the mRNA and protein levels of peroxisome proliferator-activated receptor γ (PPARγ) and its target genes, such as Fasn and FABP4, and the luciferase activity of the PPRE promoter, suggesting that blue light downregulates the expression of adipogenic genes, leading to suppression of 3T3-L1 adipogenesis. Furthermore, blue light increased the phosphorylation of PPARγ, indicating its anti-adipogenic effect through PPARγ degradation. Blue light upregulates the expression and phosphorylation of transient receptor potential vanilloid 1 (TRPV1). Furthermore, blue light restored calcium influx, which was attenuated by adipogenesis. These data suggest that TRPV1 is involved in the anti-adipogenic effects of blue light. Blue light induced the phosphorylation of AMPK, ACC, and MAPKs, whereas capsazepine, an antagonist of TRPV1, attenuated the effects of blue light. Capsazepine treatment also reduced the blue light-induced anti-adipogenic effects. These results indicate that TRPV1 operates upstream of AMPK or MAPKs in the blue light-induced anti-adipogenesis process, which is mediated by activating the TRPV1-AMPK/MAPK signaling pathways. Meanwhile, inhibition of AMPK and MAPKs reduced the phosphorylation level of PPARγ, indicating that AMPK/MAPK signaling contributes to the phosphorylation of PPARγ. These results suggest the possibility of using blue light as an antiadipogenic agent.

Background: Cancer is one of the leading causes of death in most countries with an expected increased burden on healthcare systems. Since integrative medical treatments are not collected within the scope of existing cancer registries, the establishment of the Korean Medicine Cancer Registry (KMCARE), gathering integrative therapies, including conservative care and Korean medicine, is warranted. Methods: A prospective observational study based on the registry will be conducted in 5 Korean medical hospitals. A total of 650 eligible participants undergoing Korean medicine treatments within 1 month of a diagnosis of lung, colorectal, stomach, or breast cancer are anticipated to be enrolled in the registry. Data collected in the KMCARE can be classified into patient information, received treatments, and outcomes. The primary outcome is the Functional Assessment of Cancer Therapy-General Questionnaire score at 3 months. Secondary outcomes include the MD Anderson Symptom Inventory-Core and the Body Constitution Questionnaire at 3 and 6 months. After 6 months of follow-up periods, survival surveillance will be continued for additional 18 months. Descriptive and statistical analysis of primary and secondary outcomes, baseline data, safety, survival, and prognostic factors will be performed. Discussion: This is the first prospective, multi-centered, registry-based observational study of cancer patients in Korean medicine hospitals, which could reveal the current status of cancer patients receiving integrative cancer therapies, and provide better insight into the role of Korean medicine in palliative care for patients with cancer. Trial registration: Clinical Research Information Service (CRIS), KCT0007447.

Abstract Background Cancer‐associated fibroblasts (CAFs) play an important role in the induction of chemo‐resistance. This study aimed to clarify the mechanism underlying CAF‐mediated resistance to two tyrosine kinase inhibitors (TKIs), sorafenib and lenvatinib, and to identify a novel therapeutic target for overcoming TKI resistance in hepatocellular carcinoma (HCC). Methods We performed a systematic integrative analysis of publicly available gene expression datasets and whole‐transcriptome sequencing data from 9 pairs of CAFs and para‐cancer fibroblasts isolated from human HCC and para‐tumor tissues, respectively, to identify key molecules that might induce resistance to TKIs. We then performed in vitro and in vivo experiments to validate selected targets and related mechanisms. The associations of plasma secreted phosphoprotein 1 (SPP1) expression levels before sorafenib/lenvatinib treatment with progression‐free survival (PFS) and overall survival (OS) of 54 patients with advanced HCC were evaluated using Kaplan‐Meier and Cox regression analysis. Results Bioinformatic analysis identified CAF‐derived SPP1 as a candidate molecule driving TKI resistance. SPP1 inhibitors reversed CAF‐induced TKI resistance in vitro and in vivo. CAF‐derived SPP1 activated rapidly accelerated fibrosarcoma (RAF)/mitogen‐activated protein kinase (MAPK) and phosphatidylinositol 3‐kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) through the integrin‐protein kinase C‐alpha (PKCα) signaling pathway and promoted epithelial‐to‐mesenchymal transition (EMT). A high plasma SPP1 level before TKI treatment was identified as an independent predictor of poor PFS (P = 0.026) and OS (P = 0.047) in patients with advanced HCC after TKI treatment. Conclusions CAF‐derived SPP1 enhances TKI resistance in HCC via bypass activation of oncogenic signals and EMT promotion. Its inhibition represents a promising therapeutic strategy against TKI resistance in HCC. Moreover, plasma SPP1 level before TKI treatment represents a potential biomarker for treatment response prediction.

Abstract As single-cell RNA sequencing (scRNA-seq) has emerged as a great tool for studying cellular heterogeneity within the past decade, the number of available scRNA-seq datasets also rapidly increased. However, reuse of such data is often problematic due to a small cohort size, limited cell types, and insufficient information on cell type classification. Here, we present a large integrated scRNA-seq dataset containing 224,611 cells from human primary non-small cell lung cancer (NSCLC) tumors. Using publicly available resources, we pre-processed and integrated seven independent scRNA-seq datasets using an anchor-based approach, with five datasets utilized as reference and the remaining two, as validation. We created two levels of annotation based on cell type-specific markers conserved across the datasets. To demonstrate usability of the integrated dataset, we created annotation predictions for the two validation datasets using our integrated reference. Additionally, we conducted a trajectory analysis on subsets of T cells and lung cancer cells. This integrated data may serve as a resource for studying NSCLC transcriptome at the single cell level.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made significant impacts on global public health, including the development of several skin diseases that have arisen primarily as a result of the pandemic. Owing to the widespread expansion of coronavirus disease 19 (COVID-19), the development of effective treatments for these skin diseases is drawing attention as an important social issue. For many centuries, ginseng and its major active ingredients, ginsenosides and saponins, have been widely regarded as herbal medicines. Further, the anti-viral action of ginseng suggests its potential effectiveness as a therapeutic agent against COVID-19. Thus, the aim of this review was to examine the association of skin lesions with COVID-19 and the effect of ginseng as a therapeutic agent to treat skin diseases induced by COVID-19 infection. We classified COVID-19-related skin disorders into three categories: caused by inflammatory, immune, and complex (both inflammatory and immune) responses and evaluated the evidence for ginseng as a treatment for each category. This review offers comprehensive evidence on the improvement of skin disorders induced by SARS-CoV-2 infection using ginseng and its active constituents.

Abstract Background This study validated the Korean version of the Readiness to Return to Work (RRTW) scale, as an assessment measure, following a musculoskeletal, work-related injury and as a measure of following return to work. Methods The participants of this study were workers with experience in rehabilitation programs at the Workers’ Compensation and Welfare Service (KCOMWEL) Hospital in Korea. Factor analyses were employed to ensure the validity and reliability of the RRTW scale in claimants who were in treatment without working (the not-working group) or who had already returned to work (the working group). To test structural validity, we analyzed exploratory factor analysis (EFA) respectively for the not working group (exploratory factor analysis (EFA) (n = 200), confirmatory factor analysis (CFA) (n = 109), and the working group (n = 123). To verify concurrent validity (multidimensional and assignment approach), the variables that were identified as relevant variables in previous studies were analyzed. Results The not working group EFA, as shown in the original scale, had four dimensions, and one item was deleted: (1) Precontemplation (PC), (2) Contemplation (C), (3) Prepared for Action-Self-evaluative (PAS), and (4) Prepared for Action-Behavioral (PAB). The CFA revealed that a good model fit and reliability were suitable. Regarding the working group of EFA, it appeared in two dimensions as in the original scale, one item was modified from the UM scale to the PM scale, and the reliability was appropriate. Concurrent validity was satisfied based on the correlation between the RRTW factor and related variables. Conclusions RRTW in the Korean version of the instrument was similar to those reported for the original scale, indicating that it may be used in research and clinical settings.

Triboelectric nanogenerators (TENGs) have become a significant player in the expanding wearable electronics arena due to their high output voltage, diverse material compatibility, and straightforward design. For optimal performance in wearables, TENGs need specific characteristics like air permeability, durability, washability, and self-healing capability. In a novel approach, we utilized polybutadiene-based urethane (PBU), equipped with Diels-Alder networks, as a triboelectric material. This choice lends our design washability, self-healing capabilities, and considerable mechanical strength. PBU's abundant amine groups are key to enhancing its triboelectric properties, facilitating electron transfer between materials and contributing to high charge density. We also used polyvinylidene fluoride (PVDF) electrospun fibers as the negative layer, chosen for their electron-attracting ability and flexibility. These components were electrospun onto a conductive fabric coated with copper-nickel to optimize the contact area and increase wearability. Our device, measuring 2500 mm2, generated approximately 113 V and a rectified current of around 8 μA at 0.98 kPa external pressure and a 5 Hz frequency. Impressively, it maintained performance despite thousands of wash cycles and various deformities, demonstrating unique self-healing abilities following severe surface damage. The TENG has demonstrated its real-world potential by powering up to 150 LEDs, efficiently operating calculators, thermometers, hygrometers, and even functioning as a warning device through normal walking motion. Moreover, its air permeability allows for electricity generation from the wearer's breath when attached to a regular mask, as evidenced by successful LED lighting by human normal breathing.

In the contemporary epoch, distinguished by a transition from the internet-of-things (IoT) to the artificial intelligence of things (AIoT), individual electronic appliances necessitate inherent power-generation, independence from internet connectivity, and an imbued degree of intellect. Devices governed by pressure or strain sensors particularly demand such attributes. Responding to this technological imperative, our study endeavored to conceive an intelligent door security apparatus grounded on the universally adopted numerical input system. Despite the commercialization of identification systems such as fingerprint, iris, or facial recognition, these mechanisms suffer from susceptibility to a variety of functional aberrations. Consequently, our investigation concentrated on a security system predicated on numerical input. This necessitated the formulation of a swift, self-powered pressure sensor characterized by sensitivity to minute pressure changes. As such, we engineered a triboelectric pressure sensor incorporating a composite of Ti3C2-based MXene and polydimethylsiloxane (PDMS) as the electronegative stratum, and Nylon functioning as the electropositive layer. Addressing the sensor's intrinsic deficiency in sensitivity to pressure, we augmented the MXene-PDMS composite's surface with an out-of-plane wavy structure, and utilized a Nylon stratum composed of nanofibers, thereby amplifying the contact area under pressurized conditions. This meticulously developed sensor displayed a sensitivity metric of 0.604 kPa−1 at 15 kPa, and notably, the swiftest response times recorded amongst triboelectric pressure sensors to date. Post attachment of the sensor to a numeric keypad (ranging from 0 to 9), we meticulously measured the signal alterations contingent on each key press, resulting in a comprehensive dataset. Employing a multitude of machine learning algorithms, we realized an exemplary degree of precision in both training and testing phases. The pragmatic implications of this work are noteworthy. Not only does our technology facilitate the unlocking of a door by entering the correct numerical code, but it is capable of recognizing distinct triboelectric signal patterns, corresponding to the specific manner of key entry by an authorized user, offering an additional dimension of security.

In this study, spent coffee grounds (SCG) were treated using sodium hypochlorite (NaClO) to remove organics. The NaClO-treated SCG was modified with 3-aminopropyltriethoxysilane (APTES) to improve its adsorption performance. To understand the characteristics of the prepared adsorbents, samples were characterized by Fourier transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). The pH edge, kinetic, and isotherm experiments were conducted to evaluate the adsorption performance of APTES-SCG for Reactive Black 5 (RB5), Reactive Orange 16 (RO16), and Reactive Yellow 2 (RY2). The pH edge experiments were carried out in the pH range of 2-12 at an initial dye concentration of 100 mg/L. The results showed that the dye uptakes on APTES-SCG increased with decreasing pH value. The adsorption experiments for kinetics confirmed that the equilibrium time was reached within 30 min at pH 2. The adsorption isotherm experiments were performed at initial dye concentrations of 30 to 300 mg/L, and the experimental data were well-fitted by the Langmuir model. The dye-loaded APTES-SCG was desorbed using 0.01 M NaOH solution and repeated adsorption-desorption experiments showed that APTES-SCG could be reused at least 3 times.

Abstract Tumor cells often overexpress immune checkpoint proteins, including CD47, for immune evasion. However, whether or how oncogenic activation of receptor tyrosine kinases, which are crucial drivers in tumor development, regulates CD47 expression is unknown. Here, it is demonstrated that epidermal growth factor receptor (EGFR) activation induces CD47 expression by increasing the binding of c‐Src to CD47, leading to c‐Src‐mediated CD47 Y288 phosphorylation. This phosphorylation inhibits the interaction between the ubiquitin E3 ligase TRIM21 and CD47, thereby abrogating TRIM21‐mediated CD47 K99/102 polyubiquitylation and CD47 degradation. Knock‐in expression of CD47 Y288F reduces CD47 expression, increases macrophage phagocytosis of tumor cells, and inhibits brain tumor growth in mice. In contrast, knock‐in expression of CD47 K99/102R elicits the opposite effects compared to CD47 Y288F expression. Importantly, CD47‐SIRPα blockade with an anti‐CD47 antibody treatment significantly enhances EGFR‐targeted cancer therapy. In addition, CD47 expression levels in human glioblastoma (GBM) specimens correlate with EGFR and c‐Src activation and aggravation of human GBM. These findings elucidate a novel mechanism underlying CD47 upregulation in EGFR‐activated tumor cells and underscore the role of the EGFR‐c‐Src‐TRIM21‐CD47 signaling axis in tumor evasion and the potential to improve the current cancer therapy with a combination of CD47 blockade with EGFR‐targeted remedy.

Temporal lobe epilepsy (TLE) is one of the most common neurological disorders, but still one-third of patients cannot be properly treated by current medication. Thus, we investigated the therapeutic effects of a novel small molecule, NecroX-7, in TLE using both a low [Mg2+]o-induced epileptiform activity model and a mouse model of pilocarpine-induced status epilepticus (SE). NecroX-7 post-treatment enhanced the viability of primary hippocampal neurons exposed to low [Mg2+]o compared to controls in an MTT assay. Application of NecroX-7 after pilocarpine-induced SE also reduced the number of degenerating neurons labelled with Fluoro-Jade B. Immunocytochemistry and immunohistochemistry showed that NecroX-7 post-treatment significantly alleviated ionized calcium-binding adaptor molecule 1 (Iba1) intensity and immunoreactive area, while the attenuation of reactive astrocytosis by glial fibrillary acidic protein (GFAP) staining was observed in cultured hippocampal neurons. However, NecroX-7-mediated morphologic changes of astrocytes were seen in both in vitro and in vivo models of TLE. Finally, western blot analysis demonstrated that NecroX-7 post-treatment after acute seizures could decrease the expression of mixed lineage kinase domain-like pseudokinase (MLKL) and phosphorylated MLKL (p-MLKL), markers for necroptosis. Taken all together, NecroX-7 has potential as a novel medication for TLE with its neuroprotective, anti-inflammatory, and anti-necroptotic effects.

Abstract Cancer cells in secondary tumors are found to form metastases more efficiently as compared to their primary tumor counterparts. This is partially due to the unfavorable microenvironments encountered by metastasizing cancer cells that result in the survival of a more metastatic phenotype from the original population. However, the role of deleterious mechanical stresses in this change of metastatic potential is unclear. Here, by forcing cancer cells to flow through small capillary‐sized constrictions, it is demonstrated that mechanical deformation can select a tumor cell subpopulation that exhibits resilience to mechanical squeezing‐induced cell death. Transcriptomic profiling reveals up‐regulated proliferation and DNA damage response pathways in this subpopulation, which are further translated into a more proliferative and chemotherapy‐resistant phenotype. These results highlight a potential link between the microenvironmental physical stresses and the enhanced malignancy of metastasizing cancer cells which may be utilized as a therapeutic strategy in preventing the metastatic spread of cancer cells.

Background: Radiation-induced dermatitis (RID) is one of the most prevalent side-effects of conventional cancer therapies; however, there is no standard treatment for its prevention. Therefore, this study aimed to evaluate the comparative efficacy and safety of Jaungo (mainly composed of Lithospermum erythrorhizon Siebold & Zucc. and Angelica sinensis (Oliv.) Diel) and the water-in-oil-type non-steroidal moisturizer for the prevention of RID in patients with breast cancer (BC).Methods: This is a prospective, single-blind, pilot randomized controlled trial. Between March 2021 and July 2022, 50 patients were randomly selected to use Jaungo or the moisturizer while undergoing postoperative radiation therapy (RT). Assessments were conducted nine times—every week while the patients underwent RT and 2 weeks after the end of therapy. The primary outcome was the incidence rate of RID grade ≥2. The secondary outcomes were the incidence rate of maximum grade RID, time to RID onset, RID-related quality of life (QOL) score, pain intensity, and adverse events.Results: The incidence rate of RID grade ≥2 was 24.0% and 20.0% in the Jaungo and the moisturizer groups, respectively, with no significant difference between the groups (p = 0.733). Regarding the secondary outcomes, the incidence rate of maximum grade RID (p = 0.890), mean time to RID onset (p = 0.092), cumulative incidence rate of RID (p = 0.280), RID-related QOL score, and maximum pain intensity (p = 0.844) also did not differ significantly between the groups. None of the subjects in either group experienced severe adverse effects, although one participant in the moisturizer group had mild fever and insomnia.Conclusion: These findings suggest that Jaungo has preventive efficacy without severe side-effects against RID in patients with BC that is comparable to that of the water-in-oil type non-steroidal moisturizer. Further extensive randomized controlled trials with larger sample sizes are warranted to validate our findings.Clinical Trial Registration: Clinical Research Information Service (CRIS), https://cris.nih.go.kr, identifier KCT0005971.

We present a surface acoustic wave (SAW) sensor array for microRNA (miRNA) detection that utilizes photocatalytic silver staining on titanium dioxide (TiO2) nanoparticles as a signal enhancement technique for high sensitivity with an internal reference sensor for high reproducibility. A sandwich hybridization was performed on working sensors of the SAW sensor array that could simultaneously capture and detect three miRNAs (miRNA-21, miRNA-106b, and miRNA-155) known to be upregulated in cancer. Sensor responses due to signal amplification varied depending on the concentration of synthetic miRNAs. It was confirmed that normalization (a ratio of working sensor response to reference sensor response) screened out background interferences by manipulating data and minimized non-uniformity in the photocatalytic silver staining step by suppressing disturbances to both working sensor signal and reference sensor signal. Finally, we were able to successfully detect target miRNAs in cancer cell-derived exosomal miRNAs with performance comparable to the detection of synthetic miRNAs.

Background: The purpose of this systematic review and meta-analysis was to evaluate the efficacy and safety of traditional herbal medicine (THM) for improving anorexia in patients with cancer.Methods: We searched for randomized controlled trials (RCTs) that evaluated orally administered THM for cancer-related anorexia using 10 databases from the inception to 1 August 2021. The primary outcome was an improvement in anorexia, measured with the total effective rate (TER) or visual analog scale (VAS). The secondary outcomes were the changes in body weight, the Karnofsky performance scale, acylated ghrelin, and adverse events. We used the Cochrane risk of bias assessment tool and the Grading of Recommendations Assessment, Development, and Evaluation method to assess the quality of the studies and the quality of the evidence.Results: A total of 26 RCTs were included, of which 23 were subjected to quantitative analysis. THM showed a significant improvement in anorexia measured with the TER [risk ratio (RR) 1.12, 95% confidence intervals (CI) 1.04–1.20] than appetite stimulants with moderate quality evidence and in the Karnofsky performance scale (RR 1.38, 95% CI 1.12–1.70) with low quality evidence but not in body weight gain (RR 0.98, 95% CI 0.80–1.20). THM showed a significant improvement in anorexia measured with the TER (RR 1.74, 95% CI 1.23–2.48) compared with usual care with low-quality evidence but did not significantly improve the VAS score (mean difference 0.72, 95% CI 0.00–1.43) or the level of acylated ghrelin (mean difference 0.94, 95% CI 1.08–2.97). There were no serious adverse events.Conclusion: This review suggests that THM may be considered a safe alternative therapeutic option for improving anorexia in patients with cancer. Nonetheless, more rigorous RCTs are needed due to methodological limitations.Systematic Review Registration:https://www.crd.york.ac.uk/prospero, identifier CRD42021276508.