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Yun Seob Jung,1 Byung Hak Jin,2 Ju Eun Choi,2 Min Soo Park,2 Young-Woo Kim,3 Hyung Won Kang,4 Sunyoung Cho,5 Choon Ok Kim2 1Department of Pharmacology, Yonsei University College of Medicine, Seoul, Korea; 2Department of Clinical Pharmacology, Severance Hospital, Yonsei University Health System, Seoul, Korea; 3School of Korean Medicine, Dongguk University, Gyeongju, Korea; 4College of Korean Medicine, Wonkwang University, Iksan, Korea; 5IntegroMediLab Co., Ltd, Seoul, KoreaCorrespondence: Choon Ok Kim, Department of Clinical Pharmacology, Severance Hospital, Yonsei University Health System, Seoul, Korea, Tel +82-2-2228-0455, Fax +82-2-2227-7890, Email delivery98@yuhs.acPurpose: Herbal medicines are occasionally used in combination with conventional antidepressants to mitigate various depression-associated symptoms. However, there is limited information on herb–antidepressant interactions. In this study, we investigated the pharmacokinetic (PK) effects of four herbal medicines (Gami-soyosan, Banhasasim-tang, Ojeok-san, and Bojungikgi-tang) on escitalopram, a commonly used antidepressant.Patients and Methods: In this open-label, fixed-sequence, three-period, crossover study, 18 participants were enrolled and divided into two groups. Each group received a 10 mg oral dose of escitalopram in period 1. Participants took escitalopram once daily and their assigned herbal medicines thrice a day for 7 d in periods 2 (group 1: Gami-soyosan, group 2: Ojeok-san) and 3 (group 1: Banhasasim-tang; group 2: Bojungikgi-tang). The primary endpoints were Cmax,ss and AUCtau,ss of escitalopram. Cmax,ss and AUCtau,ss in period 1 were obtained using nonparametric superposition from single-dose data. The PK endpoints were classified according to the CYP2C19 phenotype.Results: Of 18 participants, 16 completed the study. Systemic exposure to escitalopram resulted in a minor increase in the presence of each herbal medicine. The geometric mean ratios (GMRs, combination with herbal medicines/escitalopram monotherapy) and their 90% confidence intervals (CIs) for Cmax,ss and AUCtau,ss were as follows: Gamisoyosan– 1.1454 (0.9201, 1.4258) and 1.0749 (0.8084, 1.4291), Banhasasim-tang– 1.0470 (0.7779, 1.4092) and 1.0465 (0.7035, 1.5568), Ojeok-san– 1.1204 (0.8744, 1.4357) and 1.1267 (0.8466, 1.4996), and Bojungikgi-tang– 1.1264 (0.8594, 1.4762) and 1.1400 (0.8515, 1.5261), respectively. Furthermore, no significant differences in the GMRs of Cmax,ss and AUCtau,ss were observed across different CYP2C19 phenotypes in any of the groups.Conclusion: The co-administration of escitalopram with Gami-soyosan, Banhasasim-tang, Ojeok-san, or Bojungikgi-tang did not exert significant PK effects on escitalopram. These findings provide valuable insights into the safe use of herbal medicines along with escitalopram.Keywords: CYP2C19 phenotype, herb–drug interaction, antidepressant, geometric mean ratio

Ha Na Woo1*, Hye Kyung Chung2*, Eun Jin Ju1, Joohee Jung1,3, Hye-Won Kang4, Sa-Won Lee4, Min-Hyo Seo4, Jin Seong Lee5, Jung Shin Lee1,6, Heon Joo Park7, Si Yeol Song1,8, Seong-Yun Jeong1, Eun Kyung Choi1,2,81Institute for Innovative Cancer Research, 2Center for Development and Commercialization of Anti-cancer Therapeutics, Asan Medical Center, Seoul, 3College of Pharmacy, Duksung Women's University, Seoul, 4Department of Parenteral Delivery Program, Samyang Pharmaceuticals R&D, Daejeon, 5Department of Radiology and Research Institute of Radiology, 6Department of Internal Medicine, Asan Medical Center, Seoul, 7Department of Microbiology, College of Medicine, Inha University, Inchon, 8Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea*These authors contributed equally to this studyAbstract: Nanoparticles are useful delivery vehicles for promising drug candidates that face obstacles for clinical applicability. Sirolimus, an inhibitor of mammalian target of rapamycin has gained attention for targeted anticancer therapy, but its clinical application has been limited by its poor solubility. This study was designed to enhance the feasibility of sirolimus for human cancer treatment. Polymeric nanoparticle (PNP)–sirolimus was developed as an injectable formulation and has been characterized by transmission electron microscopy and dynamic light scattering. Pharmacokinetic analysis revealed that PNP–sirolimus has prolonged circulation in the blood. In addition, PNP–sirolimus preserved the in vitro killing effect of free sirolimus against cancer cells, and intravenous administration displayed its potent in vivo anticancer efficacy in xenograft tumor mice. In addition, PNP–sirolimus enhanced the radiotherapeutic efficacy of sirolimus both in vitro and in vivo. Clinical application of PNP–sirolimus is a promising strategy for human cancer treatment.Keywords: sirolimus, polymeric nanoparticle, anticancer, radiotherapy

The transcriptional repressor Rex plays important roles in regulating the expression of respiratory genes by sensing the reduction–oxidation (redox) state according to the intracellular NAD+/NADH balance. Previously, we reported on crystal structures of apo, NAD+-bound, and NADH-bound forms of Rex from Thermotoga maritima to analyze the structural basis of transcriptional regulation depending on either NAD+ or NADH binding. In this study, the crystal structure of Rex in ternary complex with NAD+ and operator DNA revealed that the N-terminal domain of Rex, including the helix-turn-helix motif, forms extensive contacts with DNA in addition to DNA sequence specificity. Structural comparison of the Rex in apo, NAD+-bound, NADH-bound, and ternary complex forms provides a comprehensive picture of transcriptional regulation in the Rex. These data demonstrate that the conformational change in Rex when binding with the reduced NADH or oxidized NAD+ determines operator DNA binding. The movement of the N-terminal domains toward the operator DNA was blocked upon binding of NADH ligand molecules. The structural results provide insights into the molecular mechanism of Rex binding with operator DNA and cofactor NAD+/NADH, which is conserved among Rex family repressors. Structural analysis of Rex from T. maritima also supports the previous hypothesis about the NAD+/NADH-specific transcriptional regulation mechanism of Rex homologues.

Veterinarians use flumequine (FLU) widely but its toxicological effects are still unclear.

We have investigated the intensities and full width at half maximum (FWHM) of the high dispersion spectroscopic N III emission lines of AG Peg, observed with the Hamilton Echelle Spectrograph (HES) in three different epochs at Mt. Hamilton’s Lick Observatory. The earlier theoretical Bowen line study assumed the continuum fluorescence effect, presenting a large discrepancy with the present data. Hence, we analyzed the observed N III lines assuming line fluorescence as the only suitable source: (1) The O III and N III resonance line profiles near λ 374 were decomposed, using the Gaussian function, and the contributions from various O III line components were determined. (2) Based on the theoretical resonant N III intensities, the expected N III Bowen intensities were obtained to fit the observed values. Our study shows that the incoming line photon number ratio must be considered to balance at each N III Bowen line level in the ultraviolet radiation according to the observed lines in the optical zone. We also found that the average FWHM of the N III Bowen lines was about 5 km·s-1 greater than that of the O III Bowen lines, perhaps due to the inherently different kinematic characteristics of their emission zones.

Background: Deguelin, a naturally occurring rotenoid, is known to be an Akt inhibitor and to have an anti-tumor effect on several cancers.Aims: This study was performed to elucidate the effect of deguelin on apoptotic pathways related to NF-κB signaling in colon cancer cells and on the anti-tumor effect in colon cancer xenograft mice.Methods: We studied COLO 205 and HCT116 cells in the presence or absence of deguelin. NF-κB signaling was examined by real-time RT-PCR for interleukin (IL)-8, by Western blotting for IκB phosphorylation/degradation, and by the electrophoretic mobility shift assay. Cell death was determined by the MTT assay, and apoptosis by Annexin V-FITC staining and caspase-3 activity. We also assessed the expression of antiapoptotic and proapoptotic factors by use of RT-PCR. In colon cancer xenograft mice, we evaluated the effect of deguelin on inoculated tumor growth, and apoptotic index was measured by the in vivo TUNEL assay.Results: Deguelin significantly inhibited IL-8 gene expression, IκB phosphorylation/degradation, and DNA binding activity of NF-κB in colon cancer cells. Deguelin induced cell death and apoptosis in colon cancer cells in a dose and time-dependent manner. Deguelin down-regulated expression of NF-κB-mediated antiapoptotic factors such as cFLIP, Bcl-2, and Bcl-X(L). In the colon cancer xenograft model, the volume of the tumor treated with deguelin was significantly lower than that of the control, and the apoptotic index for deguelin-treated mice was much higher.Conclusion: Deguelin might be a potential therapeutic agent for treatment of colorectal cancer. [ABSTRACT FROM AUTHOR]

We investigated the inhibitory pathways that mediate the antinociceptive effects of heterotopic electro-acupuncture (EA) on formalin injection-induced pain in rats. EA (2 ms, 10 Hz, 3 mA) was delivered to heterotopic acupoints HT(7) and PC(7) for 30 min; this was followed immediately by subcutaneous injection of formalin into the left hind paw of rats. Naltrexone (10 mg/kg, i.p.), an opioid receptor antagonist, was administered to evaluate the involvement of endogenous opioids. The dorsolateral funiculus (DLF), which is a descending pathway that inhibits pain, was transected at the ipsilateral T10-11 level of the thoracic spinal cord. EA inhibited behavioral responses to formalin injection-induced pain and prevented the pain-induced increase in cFos expression in the lumbar spinal cord. Pretreatment with naltrexone did not inhibit the antinociceptive effects of EA on formalin injection-induced pain. Transection of the DLF ipsilateral to the acupuncture site eliminated the antinociceptive effects of EA. These results suggest that the antinociceptive effects of heterotopic EA are mediated by the DLF and not by endogenous opioids. [ABSTRACT FROM AUTHOR]

The manganese transport regulator MntR is a metal-ion activated transcriptional repressor of manganese transporter genes to maintain manganese ion homeostasis. MntR, a member of the diphtheria toxin repressor (DtxR) family of metalloregulators, selectively responds to Mn2+ and Cd2+ over Fe2+, Co2+ and Zn2+. The DtxR/MntR family members are well conserved transcriptional repressors that regulate the expression of metal ion uptake genes by sensing the metal ion concentration. MntR functions as a homo-dimer with one metal ion binding site per subunit. Each MntR subunit contains two domains: an N-terminal DNA binding domain, and a C-terminal dimerization domain. However, it lacks the C-terminal SH3-like domain of DtxR/IdeR. The metal ion binding site of MntR is located at the interface of the two domains, whereas the DtxR/IdeR subunit contains two metal ion binding sites, the primary and ancillary sites, separated by 9 Å. In this paper, we reported the crystal structures of the apo and Mn2+-bound forms of MntR from Bacillus halodurans, and analyze the structural basis of the metal ion binding site. The crystal structure of the Mn2+-bound form is almost identical to the apo form of MntR. In the Mn2+-bound structure, one subunit contains a binuclear cluster of manganese ions, the A and C sites, but the other subunit forms a mononuclear complex. Structural data about MntR from B. halodurans supports the previous hypothesizes about manganese-specific activation mechanism of MntR homologues.

Objectives: Modified regular ginseng extract (MRGX) has stronger anti-cancer activity-possessing gensenoside profiles. Methods: To investigate changes in gene expression in the MRGX-treated lung cancer cells (A549), we examined genomic data with cDNA microarray results. After completing the gene-ontology-based analysis, we grouped the genes into up-and down-regulated profiles and into ontology-related regulated genes and proteins through their interaction network. Results: One hundred nine proteins that were up- and down-regulated by MRGX were queried by using IPA. IL8, MMP7 and PLAUR and were found to play a major role in the anti-cancer activity in MRGX-treated lung cancer cells. These results were validated using a Western blot analysis and a semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis. Conclusions: Most MRGX-responsive genes are up-regulated transiently in A549 cells, but down-regulated in a sustained manner in lung cancer cells.

Nanoemulsion based nanomaterial (NE) was carried out in the present study to evaluate the efficacy and its antitumor potential of the gastric cancer cells. NE was prepared with astaxanthin/alpha-tocopherol- cellulose nanocrystals/cellulose nanofibrils based nanoemulsions for gastric cancer treatment. The cytotoxic potential was tested against cancer cells and evaluated in terms of its cell proliferation, migration, and cellular uptake by the standard methods. NE was examined for its synergetic effect with photodynamic therapy (PDT) in a xenograft mouse model. The results confirmed the synergetic effect of PDT and NEs in the in vivo animal model. The regulated expression of proteins manifested the reduced toxicity and inhibition of cell proliferation and migration. The antitumor study showed that NE inhibited the growth of human colon cancer in vivo. Immunohistological analysis confirmed the regulation of PI3K/AKT signaling pathway. The present study demonstrates that NEs can enhance anti-cancer effect against human gastric cancer through the immunomodulatory signaling pathway., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The development of effective scaffolds for bone regeneration is crucial given the increasing demand for innovative solutions to address bone defects and enhance healing process. In this study, a polycaprolactone/fish collagen/alginate (P/FC/A) 3D scaffold incorporating phlorotannin was developed to promote bone tissue regeneration. While the efficacy of the P/FC/A scaffold has been demonstrated through in vitro and in vivo experiments, its sub-chronic toxicity in animal models remains understudied, raising concerns regarding its safety in clinical application. Therefore, this study assessed the sub-chronic toxicity of the P/FC/A scaffold over 12 week using a New Zealand White rabbit model. Our results indicate no significant adverse effects in the group exposed to the P/FC/A scaffold compared with the negative control group implanted with a high-density polyethylene scaffold. These findings underscore the non-toxicity and safety profile of the P/FC/A scaffold, further supporting its potential suitability for clinical use in bone regeneration., Competing Interests: Declaration of competing interest Won-Kyo Jung reports financial support was provided by National Research Foundation of Korea. Won-Kyo Jung reports financial support was provided by Korea Ministry of Oceans and Fisheries. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: We have previously reported anatomical, histological, and gene expression characteristics of the nodal structure of rat skin surface and suggested its potential as an acupuncture point. However, the specific characteristics of the interactions among the genes expressed in this structure remain unclear., Objective: We aimed to determine gene expression changes by analyzing interaction networks of genes up-regulated in nodal structures and to explore relationships with acupuncture points., Methods: We investigated the relationship between the nodal structures and acupuncture points by analyzing the interactions of up-regulated genes, their Gene Ontology biological functions, and the characteristics of Kyoto Encyclopedia of Genes and Genomes pathways. RNA-seq and STRING analysis provided comprehensive information on these gene groups., Results: Interactions between up-regulated genes in nodal structures were classified into three groups. The first group, which includes Wnt7b, Wnt3, and Wnt16, showed significant interactions in pathways such as Wnt signaling, Alzheimer's disease, and regulation of stem cell pluripotency. The second group, composed of Fos, Dusp1, Pla2g4e, Pla2g4f, and Fgfr3, demonstrated a notable association with the MAPK signaling pathway. Lastly, the third group, consisting of Adcy1, Pla2g4e, Pla2g4f, and Dusp1 exhibited effective interactions with the inflammatory mediator regulation of TRP channels and serotonergic synapse., Conclusion: Continued research on nodal structures where these genes are expressed is needed to improve our understanding of skin anatomy and physiology as well as their potential clinical utility as acupuncture points., (© 2024. The Author(s) under exclusive licence to The Genetics Society of Korea.)

Autologous fat is widely used in soft tissue reconstruction; however, significant volume reduction owing to necrosis and degradation of the transplanted adipose tissue (AT) remains a major challenge. To address this issue, a novel live AT micro-fragment-based bio-ink (ATmf bio-ink) compatible with precision 3D printing, is developed. Live AT micro-fragments of ≈280 µm in size are prepared using a custom tissue micronizer and they are incorporated into a fibrinogen/gelatin mixture to create the ATmf bio-ink. AT micro-fragments exhibit high viability and preserve the heterogeneous cell population and extracellular matrix of the native AT. The developed bio-ink enables precise micropatterning and provides an excellent adipo-inductive microenvironment. AT grafts produced by co-printing the bio-ink with polycaprolactone demonstrate a 500% improvement in volume retention and a 300% increase in blood vessel infiltration in vivo compared with conventional microfat grafts. In vivo engraftment of AT grafts is further enhanced by using a stem cell-laden ATmf bio-ink. Last, it is successfully demonstrated that the bio-ink is enabled for the creation of clinically relevant and patient-specific AT grafts for patients undergoing partial mastectomy. This novel ATmf bio-ink for volumetric soft tissue reconstruction offers a pioneering solution for addressing the limitations of existing clinical techniques., (© 2024 The Author(s). Advanced Healthcare Materials published by Wiley-VCH GmbH.)

Background: Obesogenic diets cause intestinal inflammation and dysfunction. Polyphenols have shown a positive impact on reducing inflammation in in vitro studies. However, their bioactivity may not be the same in the in vivo system due to structural alteration by the gastrointestinal digestive process. The purpose of this study was to investigate the anti-inflammatory effect of onion peel and its major bioactive compound, quercetin, in the intestine and further examine the impact of intestinal digestion on this effect., Methods: Onion peel extract (OPE) and quercetin (Q) were digested using gastrointestinal digestive enzymes in vitro and then treated into lipopolysaccharide (LPS)-stimulated Caco-2/HT-29 cells. Genes and proteins related to tight junction, inflammation, and epithelial integrity were measured., Results: OPE and digested OPE (DOPE) had a higher protective effect on LPS-induced tight junction and inflammatory genes and paracellular permeability than Q and digested Q (DQ). DOPE was more effective than OPE, while digestion did not change the activity of Q. The anti-inflammatory effect of OPE and Q with or without digestion was achieved by inhibiting nuclear factor kappa B through AMP-activated protein kinase-activated silent mating-type information regulation 2 homolog 1., Conclusions: It was the first to find that a crude extract, after undergoing gastrointestinal digestion, demonstrated a notably superior anti-inflammatory effect in the cell study, suggesting the consumption of onion peels could potentially yield similar benefits in the human intestine. This discovery underscores the potential of onion peel polyphenols in combating intestinal inflammation, making them a compelling area of research for future therapeutic applications using food byproducts.

Prostate-specific antigen (PSA) remains a key biomarker for the diagnosis and monitoring of prostate cancer (PCa). For patients within the 'PSA gray zone', the positive predictive value (PPV) of PSA for PCa detection by biopsy is estimated to be between 30 and 42%. In the present study, a single-center, retrospective, evaluator-blinded, pilot and pivotal clinical trial was performed to assess the clinical performance of the mirCaP kit (Urotech, Inc.), which measures the herpes simplex virus 2-microRNA (miR)-H9/hsa-miR-3659 ratio, with respect to helping physicians make appropriate decisions regarding further assessment of patients with PSA levels within this gray zone. For the patients in the initial clinical trial group who were in the PSA gray zone, the sensitivity, specificity, accuracy, PPV and negative predictive value (NPV) of the mirCaP kit were 94.29, 77.50, 85.33, 78.57 and 93.94%, respectively. For those in the pivotal clinical trial, these values were 94.50, 82.73, 87.90, 81.10 and 95.04%, respectively. These results suggest that the mirCaP kit may be an effective non-invasive diagnostic marker for PCa in patients with PSA levels in the gray zone. Thus, the mirCaP kit is a promising tool that can help physicians make a decision regarding the need for prostate biopsy in these patients. Of note, the NPV of >90% indicates that the mirCaP kit could prevent unnecessary prostate biopsies in >90% of these cases., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2024, Spandidos Publications.)

Background : Proximal humeral bone deficiency in revision shoulder arthroplasty is an emerging and challenging problem as the use of reverse shoulder arthroplasty (RSA) increases. This paper presents a technical note discussing our detailed preoperative planning steps, surgical techniques, and their rationale in carrying out the use of an allograft prosthetic composite (APC) to address proximal humeral bone deficiency in revision RSA. The outcomes of this technique are also presented. This paper also presents a systematic review to further discuss the existing literature on RSA with APCs. Methods : The preoperative surgical planning and the surgical technique employed to execute proximal humeral reconstruction using APC during revision arthroplasty are discussed in the technical note. The preliminary clinical and radiological results of five patients who underwent revision shoulder arthroplasty with proximal humeral reconstruction using APCs are presented. The PRISMA guidelines were followed to perform the systematic review. A systematic search using PubMed, Embase, and Cochrane databases was conducted. All studies involving RSA and APCs were pooled, and the data were extracted and analyzed. Results : A total of 14 studies were eligible for inclusion in the systematic review, with a total of 255 patients and a mean follow-up of 57 months. All studies in the systematic review and the patients included in the author's case series showed improvements in the level of pain, range of motion, function, and satisfaction. Graft incorporation in the systematic review was 84%. Conclusions : Based on the available literature and the results of our case series, the use of an APC construct is a viable option for proximal humeral bone deficiency in revision shoulder arthroplasty.

Recent studies have identified a urinary microbiome, dispelling the myth of urine sterility. Intravesical bacillus Calmette-Guérin (BCG) therapy is the preferred treatment for intermediate to high-risk non-muscle-invasive bladder cancer (BCa), although resistance occurs in 30-50% of cases. Progression to muscle-invasive cancer necessitates radical cystectomy. Our research uses 16S rRNA gene sequencing to investigate how the urinary microbiome influences BCa and its response to BCG therapy. Urine samples were collected via urethral catheterization from patients with benign conditions and non-muscle-invasive BCa, all of whom underwent BCG therapy. We utilized 16S rRNA gene sequencing to analyze the bacterial profiles and metabolic pathways in these samples. These pathways were validated using a real metabolite dataset, and we developed predictive models for malignancy and BCG response. In this study, 87 patients participated, including 29 with benign diseases and 58 with BCa. We noted distinct bacterial compositions between benign and malignant samples, indicating the potential role of the toluene degradation pathway in mitigating BCa development. Responders to BCG had differing microbial compositions and higher quinolone synthesis than non-responders, with two Bifidobacterium species being prevalent among responders, associated with prolonged recurrence-free survival. Additionally, we developed highly accurate predictive models for malignancy and BCG response. Our study delved into the mechanisms behind malignancy and BCG responses by focusing on the urinary microbiome and metabolic pathways. We pinpointed specific beneficial microbes and developed clinical models to predict malignancy and BCG therapy outcomes. These models can track recurrence and facilitate early predictions of treatment responses.

In plants, balancing growth and environmental responses is crucial for maximizing fitness. Close proximity among plants and canopy shade, which negatively impacts reproduction, elicits morphological adjustments such as hypocotyl growth and leaf hyponasty, mainly through changes in light quality and auxin levels. However, how auxin, synthesized from a shaded leaf blade, distally induces elongation of hypocotyl and petiole cells remains to be elucidated. We demonstrated that ASYMMETRIC LEAVES1 (AS1) promotes leaf hyponasty through the regulation of auxin biosynthesis, polar auxin transport, and auxin signaling genes in Arabidopsis (Arabidopsis thaliana). AS1 overexpression leads to elongation of the abaxial petiole cells with auxin accumulation in the petiole, resulting in hyponastic growth, which is abolished by the application of an auxin transport inhibitor to the leaf blade. In addition, the as1 mutant exhibits reduced hypocotyl growth under shade conditions. We observed that AS1 protein accumulates in the nucleus in response to shade or far-red light. Chromatin immunoprecipitation analysis identified the association of AS1 with the promoters of YUCCA8 (YUC8) and INDOLE-3-ACETIC ACID INDUCIBLE 19 (IAA19). In addition, AS1 forms complexes with PHYTOCHROME INTERACTING FACTORs in the nucleus and synergistically induces YUC8 and IAA19 expression. Our findings suggest that AS1 plays a crucial role in facilitating phenotypic plasticity to the surroundings by connecting light and phytohormone action., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Laryngeal cancer is the second most common cancer in the upper aerodigestive tract, with its incidence increasing across all ages. The conventional treatments for laryngeal cancer include surgical procedure, radiation, and chemotherapy; however, these treatments can lead to various complications. Photothermal therapy (PTT) using laser light has been employed form cancer effective treatment because of its minimal invasion and short operation time. The current study aims to investigate the feasibility of 532 nm PTT on laryngeal cancer in an invivo tumor model. Ex vivo dosimetry evaluation was conducted to determine the laser irradiation conditions, and HEP-2 tumor bearing mice were used to demonstrate in vivo photothermal effects. In addition, histology and western blot analysis were conducted to verify tumor necrosis and any changes in cancer-associated factors in the tumor tissues. The current in vivo results showed that PTT at 5 W for 40 s and 20 W for 10 s had comparable effects in terms of temperature increase and tumor removal. The 532 nm PTT significantly decreased the remaining tumor and downregulated the expression levels of MMP- 9 and ERK. The current study demonstrated that the 532 nm PTT could be a feasible option for treatment of laryngeal tumor with high power delivery for a short exposure time. Further investigations will confirm the endoscopic application of the 532 nm PTT for the treatment of intralaryngeal tissue prior to clinical translation., (© 2024. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Pancreatic islet macroencapsulation systems for subcutaneous transplantation have garnered significant attention as a therapy for Type I diabetes due to their minimal invasiveness and low complication rates. However, the low vascular density of subcutaneous tissue threatens the long-term survival of islets. To address this issue, prevascularized systems are introduced but various challenges remain, including system complexity and vascular-cell immunogenicity. Here, a novel prevasculature-free macroencapsulation system designed as a multilayer sheet, which ensures sufficient mass transport even in regions with sparse vasculature, is presented. Islets are localized in top/bottom micro-shell layers (≈300 µm thick) to maximize proximity to the surrounding host vasculature. These sheets, fabricated via bioprinting using rat islets and alginate-based bio-ink, double islet viability and optimize islet density, improving insulin secretion function by 240%. The subcutaneous transplantation of small islet masses (≈250 islet equivalent) into diabetic nude mice enable rapid (<1 day) recovery of blood glucose, which remain stable for >120 days. Additionally, antifibrotic drug-loaded multilayer sheets facilitate blood glucose regulation by rat islets at the subcutaneous sites of diabetic immunocompetent mice for >35 days. Thus, this macroencapsulation system can advance the treatment of Type I diabetes and is also effective for islet xenotransplantation in subcutaneous tissue., (© 2024 The Author(s). Advanced Materials published by Wiley‐VCH GmbH.)

Meniscus injuries present significant therapeutic challenges due to their limited self-healing capacity and diverse biological and mechanical properties across meniscal tissue. Conventional repair strategies neglect to replicate the complex zonal characteristics within the meniscus, resulting in suboptimal outcomes. In this study, we introduce an innovative, age- and stiffness-tunable meniscus decellularized extracellular matrix (DEM)-based hydrogel system designed for precision repair of heterogeneous, zonal-dependent meniscus injuries. By synthesizing age-dependent DEM hydrogels, we identified distinct cellular responses: fetal bovine meniscus-derived DEM promoted chondrogenic differentiation, while adult meniscus-derived DEM supported fibrochondrogenic phenotypes. The incorporation of methacrylate hyaluronic acid (MeHA) further refined the mechanical properties and injectability of the DEM-based hydrogels. The combination of age-dependent DEM with MeHA allowed for precise stiffness tuning, influencing cell differentiation and closely mimicking native tissue environments. In vivo tests confirmed the biocompatibility of hydrogels and their integration with native meniscus tissues. Furthermore, advanced 3D bioprinting techniques enabled the fabrication of hybrid hydrogels with biomaterial and mechanical gradients, effectively emulating the zonal properties of meniscus tissue and enhancing cell integration. This study represents a significant advancement in meniscus tissue engineering, providing a promising platform for customized regenerative therapies across a range of heterogeneous fibrous connective tissues., Competing Interests: Competing interests The authors declare no competing interests.

exo-6b 2 -Methyl-substituted pentabenzocorannulene (exo-PBC-Me) was synthesized by the palladium-catalyzed cyclization of 1,2,3-triaryl-1H-cyclopenta[l]phenanthrene. Its bowl-shaped geometry with an sp 3 carbon atom in the backbone and a methyl group located at the convex (exo) face was verified by X-ray crystallography. According to DFT calculations, the observed conformer is energetically more favorable than the endo one by 39.9 kcal/mol. Compared to the nitrogen-doped analogs with intact π-conjugated backbones (see the main text), exo-PBC-Me displayed a deeper bowl depth (avg. 1.93 Å), redshifted and broader absorption (250-620 nm) and emission (from 585 to more than 850 nm) bands and a smaller optical HOMO-LUMO gap (2.01 eV). exo-PBC-Me formed polar crystals where all bowl-in-bowl stacking with close π ⋅ ⋅ ⋅ π contacts is arranged unidirectionally, providing the potential for applications as organic semiconductors and pyroelectric materials. This unusual structural feature, molecular packing, and properties are most likely associated with the assistance of the methyl group and the sp 3 carbon atom in the backbone., (© 2024 Wiley-VCH GmbH.)

Background Context: Adjacent segment degeneration (ASD) following lumbar fusion operation is common and can occur at varying timepoints after index surgery. An early revision operation for ASD, however, signifies a short symptom-free period and might increase the risk of successive surgeries., Purpose: We aimed to elucidate the overall risk factors associated with revision surgeries for ASD with distinct attention to early revisions., Study Design/setting: Retrospective, case-control study., Patient Sample: The study included 86 patients who underwent revision operations for ASD after lumbar fusion in the revision group and 166 patients who did not for at least 5 years after index surgery., Outcome Measures: Sagittal parameters, Pfirrmann grading, facet degeneration grading, and disc space height (DSH) of adjacent segments were assessed., Methods: Revision operations within 5 years postsurgery were defined as early revision. We compared the revision and no-revision groups as well as the early- and late-revision groups., Results: The revision group demonstrated a significantly greater preoperative C7-S1 sagittal vertical axis (SVA) (p=.001), postoperative C7-S1 SVA (p<.001), and postoperative pelvic incidence (PI)-lumbar lordosis (LL) (p<.001) than those in the no-revision group. Preoperative DSH of the proximal adjunct segment (p=.001), postoperative PI-LL (p=.014), and postoperative C7-S1 SVA (p=.037) exhibited significant association with ASD in logistic regression analysis. The early-revision group had a significantly higher patient age (p=.001) and a greater number of levels fused (p=.030) than those in the late-revision group. Multivariate Cox regression analysis demonstrated that old age (p=.045), a significant number of levels fused (p=.047), and a narrow preoperative DSH of the proximal adjacent level (p=.011) were risk factors for early revision., Conclusions: Postoperative sagittal imbalance, including significant PI-LL and C7-S1 SVA were risk factors for revision operation for ASD but not for early revision. These factors are likely to affect the long-term risk of revision operation due to ASD and thus are not considered risk factors for early revision. Narrow DSH of the proximal adjacent level increased the risks of both revision and early revision surgeries. Moreover, old age and a significant number of levels fused further increased the risk for early revision for ASD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Objectives: Renal denervation (RDN) is an emerging surgical treatment for resistant hypertension. However, the current RDN using radiofrequency can cause undesirable thermal damage to the medial and luminal layers due to direct contact between the arterial lumen and energy source. The aim of this study is to evaluate the feasibility of the new laser-assisted RDN by exploring the potential treatment conditions., Methods: For ex vivo testing, six different treatment conditions (10 and 20 W applied for delivery of 300, 450, and 600 J) were tested on the porcine liver and renal artery (RA) by using a continuous wave 1064 nm laser wavelength. The ablated area in the liver tissue was measured to estimate the extent of the coagulated area. Histological evaluation was performed on the treated RA tissues to confirm the extent of thermal nerve damage., Results: The ablated depth, length, and area in the liver tissue increased with laser power and total energy. According to the histological results, 20 W groups yielded more significant damage to the RA nerves than 10 W groups at the total energy of 300 J (0.0 ± 0.0 mm for 10 W vs. 2.9 ± 1.0 mm for 20 W), 450 J (1.9 ± 0.6 mm for 10 W vs. 6.8 ± 1.5 mm for 20 W), and 600 J (2.9 ± 0.4 mm for 10 W vs. 7.3 ± 0.8 mm for 20 W). The treated RA exhibited insignificant medial injury in depth (medial thinning ≤ 25%), and no difference in the medial thinning was found among the six groups (p = 0.4)., Conclusion: The current study demonstrated that the 1064 nm laser at 20 W with delivery of 450 J could effectively damage the RA nerves with no or minimal injury to the surrounding tissue. The proposed laser-assisted RDN may enhance physiological effects with insignificant complications in in vivo situations. Further in vivo studies will be conducted to validate the current findings by evaluating the extent of blood pressure reduction and norepinephrine changes after the laser-assisted RDN on a large animal model., (© 2024 Wiley Periodicals LLC.)

Photobiomodulation (PBM) has widely been used to effectively treat complications associated with cancer treatment, including oral mucositis, radiation dermatitis, and surgical wounds. However, the safety of PBM against cancer still needs to be validated as the effects of PBM on cancer cells and their mechanisms are unclear. The current study investigated the wavelength-dependent PBM effects by examining four different laser wavelengths (405, 532, 635, and 808 nm) on B16F10 melanoma tumor cells. In vitro tests showed that PBM with 808 nm promoted both proliferation and migration of B16F10 cells. In vivo results demonstrated that PBM with 808 nm significantly increased the relative tumor volume and promoted angiogenesis with overexpression of VEGF and HIF-1α. In addition, PBM induced the phosphorylation of factors closely related to cancer cell proliferation and tumor growth and upregulated the related gene expression. The current result showed that compared to the other wavelengths, 808 nm yielded a significant tumor-stimulating effect the malignant melanoma cancer. Further studies will investigate the in-depth molecular mechanism of PBM on tumor stimulation in order to warrant the safety of PBM for clinical cancer treatment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Human liver-type phosphofructokinase 1 (PFKL) has been shown to regulate glucose flux as a scaffolder arranging glycolytic and gluconeogenic enzymes into a multienzyme metabolic condensate, the glucosome. However, it has remained elusive of how phase separation of PFKL is governed and initiates glucosome formation in living cells, thus hampering to understand a mechanism of glucosome formation and its functional contribution to human cells. In this work, we developed a stochastic model in silico using the principle of Langevin dynamics to investigate how biological properties of PFKL contribute to the condensate formation. The significance of an intermolecular interaction between PFKLs, an effective concentration of PFKL at a region of interest, and its own self-assembled filaments in formation of PFKL condensates and control of their sizes were demonstrated by molecular dynamics simulation using the Large-scale Atomic/Molecular Massively Parallel Simulator (LAMMPS). Such biological properties that define intracellular dynamics of PFKL appear to be essential for phase separation of PFKL, which may represent an initiation step for the formation of glucosome condensates. Collectively, our computational study provides mechanistic insights of glucosome formation, particularly an initial stage through the formation of PFKL condensates in living human cells., (© 2024. The Author(s).)

As a technique in artificial intelligence, a convolution neural network model has been utilized to extract average surface roughness from the geometric characteristics of a membrane image featuring micro- and nanostructures. For surface roughness measurement, e.g. atomic force microscopy and optical profiler, the previous methods have been performed to analyze a porous membrane surface on an interest of region with a few micrometers of the restricted area according to the depth resolution. However, an image from the scanning electron microscope, combined with the feature extraction process, provides clarity on surface roughness for multiple areas with various depth resolutions. Through image preprocessing, the geometric pattern is elucidated by amplifying the disparity in pixel intensity values between the bright and dark regions of the image. The geometric pattern of the binary image and magnitude spectrum confirmed the classification of the surface roughness of images in a categorical scatter plot. A group of cropped images from an original image is used to predict the logarithmic average surface roughness values. The model predicted 4.80 % MAPE for the test dataset. The method of extracting geometric patterns through a feature map-based CNN, combined with a statistical approach, suggests an indirect surface measurement. The process is achieved through a bundle of predicted output data, which helps reduce the randomness error of the structural characteristics. A novel feature extraction approach of CNN with statistical analysis is a valuable method for revealing hidden physical characteristics in surface geometries from irregular pixel patterns in an array of images., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Hyun Wook Kang reports was provided by Chonnam National University. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Tissues on a chip are sophisticated three-dimensional (3D) in vitro microphysiological systems designed to replicate human tissue conditions within dynamic physicochemical environments. However, the current fabrication methods for tissue spheroids on a chip require multiple parts and manual processing steps, including the deposition of spheroids onto prefabricated "chips." These challenges also lead to limitations regarding scalability and reproducibility. To overcome these challenges, we employed 3D printing techniques to automate the fabrication process of tissue spheroids on a chip. This allowed the simultaneous high-throughput printing of human liver spheroids and their surrounding polymeric flow chamber "chips" containing inner channels in a single step. The fabricated liver tissue spheroids on a liver-on-a-chip (LOC) were subsequently subjected to dynamic culturing by a peristaltic pump, enabling assessment of cell viability and metabolic activities. The 3D printed liver spheroids within the printed chips demonstrated high cell viability (>80%), increased spheroid size, and consistent adenosine triphosphate (ATP) activity and albumin production for up to 14 days. Furthermore, we conducted a study on the effects of acetaminophen (APAP), a nonsteroidal anti-inflammatory drug, on the LOC. Comparative analysis revealed a substantial decline in cell viability (<40%), diminished ATP activity, and reduced spheroid size after 7 days of culture within the APAP-treated LOC group, compared to the nontreated groups. These results underscore the potential of 3D bioprinted tissue chips as an advanced in vitro model that holds promise for accurately studying in vivo biological processes, including the assessment of tissue response to administered drugs, in a high-throughput manner.

Colorectal cancer (CRC) is one of the top five most common and life-threatening malignancies worldwide. Most CRC develops from advanced colorectal adenoma (ACA), a precancerous stage, through the adenoma-carcinoma sequence. However, its underlying mechanisms, including how the tumor microenvironment changes, remain elusive. Therefore, we conducted an integrative analysis comparing RNA-seq data collected from 40 ACA patients who visited Dongguk University Ilsan Hospital with normal adjacent colons and tumor samples from 18 CRC patients collected from a public database. Differential expression analysis identified 21 and 79 sequentially up- or down-regulated genes across the continuum, respectively. The functional centrality of the continuum genes was assessed through network analysis, identifying 11 up- and 13 down-regulated hub-genes. Subsequently, we validated the prognostic effects of hub-genes using the Kaplan-Meier survival analysis. To estimate the immunological transition of the adenoma-carcinoma sequence, single-cell deconvolution and immune repertoire analyses were conducted. Significant composition changes for innate immunity cells and decreased plasma B-cells with immunoglobulin diversity were observed, along with distinctive immunoglobulin recombination patterns. Taken together, we believe our findings suggest underlying transcriptional and immunological changes during the adenoma-carcinoma sequence, contributing to the further development of pre-diagnostic markers for CRC., (© 2024. The Author(s).)

Here, the simultaneous effect of chemo- and photothermal therapy against epidermoid carcinoma (EC) was investigated. A novel hydrogel, termed bionanogel (BNG), was designed using psyllium mucilage polysaccharide and bacterial gellan gum, incorporated with nanocomplex carrying caffeic acid (CA) and IR-820, and further characterized. The dual effect of BNG and 808 nm laser (BNG + L) on EC was investigated. Staining and scratch assays were performed to analyze their therapeutic effect on EC. In vivo evaluations of BNG + L in xenograft models were performed. Rapid transition, limited swelling, degradability and high tensile strength indicated BNG stability and sustained drug release. Irradiation with 808 nm laser light at 1.25 W /cm 2 for 4 min resulted in a temperature increase of 53 °C and facilitated cell ablation. The in vitro studies showed that BNG + L suppressed cancer progression via a late apoptotic effect. The in vivo study showed that the slow release of CA from BNG + L significantly attenuated EC with low mitotic index and downregulation of proteins involved in cancer proliferation such as EGFR, AKT, PI3K, ERK, mTOR and HIF-1α. Thus, BNG could be a novel medium for targeted and controlled drug delivery for the treatment of epidermoid cancer when triggered by NIR light., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Key Message: FKF1 dimerization is crucial for proper FT levels to fine-tune flowering time. Attenuating FKF1 homodimerization increased CO abundance by enhancing its COP1 binding, thereby accelerating flowering under long days. In Arabidopsis (Arabidopsis thaliana), the blue-light photoreceptor FKF1 (FLAVIN-BINDING, KELCH REPEAT, F-BOX 1) plays a key role in inducing the expression of FLOWERING LOCUS T (FT), encoding the main florigenic signal in plants, in the late afternoon under long-day conditions (LDs) by forming dimers with FT regulators. Although structural studies have unveiled a variant of FKF1 (FKF1 I160R) that disrupts homodimer formation in vitro, the mechanism by which disrupted FKF1 homodimer formation regulates flowering time remains elusive. In this study, we determined that the attenuation of FKF1 homodimer formation enhances FT expression in the evening by promoting the increased stability of CONSTANS (CO), a primary activator of FT, in the afternoon, thereby contributing to early flowering. In contrast to wild-type FKF1, introducing the FKF1 I160R variant into the fkf1 mutant led to increased FT expression under LDs. In addition, the FKF1 I160R variant exhibited diminished dimerization with FKF1, while its interaction with GIGANTEA (GI), a modulator of FKF1 function, was enhanced under LDs. Furthermore, the FKF1 I160R variant increased the level of CO in the afternoon under LDs by enhancing its binding to COP1, an E3 ubiquitin ligase responsible for CO degradation. These findings suggest that the regulation of FKF1 homodimerization and heterodimerization allows plants to finely adjust FT expression levels around dusk by modulating its interactions with GI and COP1., (© 2024. The Author(s).)

Leisure plays a key role in the happiness of youth. Studies have shown that various factors of leisure, such as the type, the time, the cost, and the space, have an influence on the adolescents' happiness. However, little is known about which of these factors is a major factor in youth's happiness. The purpose of this study is to explore the leisure factors that determine happiness in adolescents by examining the relationship between happiness and various leisure factors. The study used the method of machine learning to analyze national statistical data, National Leisure Activity Survey. The data used in this study were from the National Leisure Activity Survey 2019, which is a national statistic produced by the Ministry of Culture, Sports and Tourism in the Republic of Korea. The analysis found that leisure perceptions, academic and leisure balance, and public leisure space have a very important impact on the adolescents' well-being. The findings of this research may contribute to a better understanding of leisure and happiness in adolescents, and will also help adolescents make better use of their leisure time, leading to better leisure lives, and ultimately contribute to raising their level of happiness., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The use of reverse shoulder arthroplasty as a primary and revision implant is increasing. Advances in implant design and preoperative surgical planning allow the management of complex glenoid defects. As the demand for treating severe bone loss increases, custom allograft composites are needed to match the premorbid anatomy. Baseplate composite structural allografts are used in patients with eccentric and centric defects to restore the glenoid joint line. Preserving bone stock is important in younger patients where a revision surgery is expected. The aim of this article is to present the assessment, planning, and indications of femoral head allografting for bony defects of the glenoid. Methods: The preoperative surgical planning and the surgical technique to execute the plan with a baseplate composite graft are detailed. The preliminary clinical and radiological results of 29 shoulders which have undergone this graft planning and surgical technique are discussed. Clinical outcomes included visual analogue score of pain (VAS), American Shoulder and Elbow Surgeons score (ASES), Constant-Murley score (CS), satisfaction before and after operation, and active range of motion. Radiological outcomes included graft healing and presence of osteolysis or loosening. Results: The use of composite grafts in this series has shown excellent clinical outcomes, with an overall graft complication rate in complex bone loss cases of 8%. Conclusion: Femoral head structural allografting is a valid and viable surgical option for glenoid bone defects in reverse shoulder arthroplasty.

Vitamin D may have anticancer effects against colorectal cancer (CRC). Bone mineral density (BMD) reflects the long-term vitamin D status. This study investigated the association between osteoporosis and colorectal neoplasms (CRN). The data were obtained from the National Health Insurance Service sample cohort, which included 60,386 osteoporosis patients and 8224 controls who underwent BMD in 2002-2019. The logistic regression models included age, sex, income level, and comorbidity. Sensitivity tests were performed using the data from the National Health Screening Program. In total, 7706 (11.2%) patients were diagnosed with CRN, and the proportion was significantly higher in osteoporosis patients than in controls (11.7% vs. 8.1%). In the multivariate analysis, osteoporosis was associated with an increased risk of CRN (odds ratio (OR) = 1.91, 95% confidence interval = 1.75-2.09, p < 0.0001), which was significant for both colorectal adenomas and CRC (OR = 1.88 and 1.83, respectively). A subgroup analysis by sex revealed a significant association between osteoporosis and CRN in both women and men (OR = 2.06 and 1.66, respectively). The sensitivity tests revealed results similar to those of the original dataset. In conclusion, osteoporosis is significantly associated with CRN risk in both sexes. In high-risk patients with low BMD, appropriate screening for CRN and vitamin D supplementation are required, regardless of sex.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive solid malignancies. A specific mechanism of its metastasis has not been established. In this study, we investigated whether Neural Wiskott-Aldrich syndrome protein (N-WASP) plays a role in distant metastasis of PDAC. We found that N-WASP is markedly expressed in clinical patients with PDAC. Clinical analysis showed a notably more distant metastatic pattern in the N-WASP-high group compared to the N-WASP-low group. N-WASP was noted to be a novel mediator of epithelial-mesenchymal transition (EMT) via gene expression profile studies. Knockdown of N-WASP in pancreatic cancer cells significantly inhibited cell invasion, migration, and EMT. We also observed positive association of lysyl oxidase-like 2 (LOXL2) and focal adhesion kinase (FAK) with the N-WASP-mediated response, wherein EMT and invadopodia function were modulated. Both N-WASP and LOXL2 depletion significantly reduced the incidence of liver and lung metastatic lesions in orthotopic mouse models of pancreatic cancer. These results elucidate a novel role for N-WASP signaling associated with LOXL2 in EMT and invadopodia function, with respect to regulation of intercellular communication in tumor cells for promoting pancreatic cancer metastasis. These findings may aid in the development of therapeutic strategies against pancreatic cancer., Competing Interests: The authors declare no conflict of interest., (© 2024 Kim et al.)

Super Typhoon Mangkhut, which traversed the North Equatorial Current (NEC; 8-17 °N) in the western North Pacific in 2018, was the most intense Category-5 tropical cyclone (TC) with the longest duration in history-3.5 days. Here we show that the combination of two factors-high ocean heat content (OHC) and increased stratification - makes the NEC region the most favored area for a rapid intensification (RI) of super typhoons, instead of the Eddy Rich Zone (17-25 °N), which was considered the most relevant for RI occurrence. The high OHC results from a northward deepening thermocline in geostrophic balance with the westward-flowing NEC. The stratification is derived from precipitation associated with the Inter-Tropical Convergence Zone in the summer peak typhoon season. These factors, which are increasingly significant over the past four decades, impede the TC-induced sea surface cooling, thus enhancing RI of TCs and simultaneously maintaining super typhoons over the NEC region., (© 2024. The Author(s).)

Surgeons have been reluctant to perform crossed-pin fixation for displaced pediatric supracondylar humeral (SCH) fractures because it carries a risk of iatrogenic ulnar nerve injury. This study aimed to introduce lateral-exit crossed-pin fixation for displaced pediatric SCH fractures and to evaluate its clinical and radiological outcomes, with a particular focus on iatrogenic ulnar nerve injuries. Children who underwent lateral-exit crossed-pin fixation for displaced SCH fractures between 2010 and 2015 were retrospectively reviewed. Lateral-exit crossed-pin fixation involved the introduction of a medial pin from the medial epicondyle, as in the conventional method, followed by pulling the pin through the lateral skin until the distal and medial aspects of the pin were just under the cortex of the medial epicondyle. The time to union and loss of fixation were assessed. Flynn's clinical criteria (cosmetic and functional factors) and complications including iatrogenic ulnar nerve injury were investigated. A total of 81 children with displaced SCH fractures were treated with lateral-exit crossed-pin fixation. All but one patient achieved union with good alignment, with an average time to union of 7.9 weeks (3.9-10.3 weeks). Only one patient exhibited cubitus varus deformity associated with loss of reduction. All patients recovered to almost their full range of motion. No case of iatrogenic ulnar nerve injury developed; however, iatrogenic radial nerve injury developed in one patient. Lateral-exit crossed-pin fixation provides sufficient stability with a lower risk of iatrogenic ulnar nerve injury in children with displaced SCH fractures. This method is an acceptable technique for crossed-pin fixation., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Hydrogels are widely used as scaffold materials for constructing in vitro three-dimensional microphysiological systems. However, their high sensitivity to various external cues hinders the development of hydrogel-laden, microscale, and high-throughput chips. Here, we have developed a long-term storable gel-laden chip composite built in a multi-well plate, which enables in situ cell encapsulation and facilitates high-throughput analysis. Through optimized chemical crosslinking and freeze-drying method (C/FD), we have achieved a high-quality of gel-laden chip composite with excellent transparency, uniform porosity, and appropriate swelling and mechanical characteristics. Besides collagen, decellularized extracellular matrix with tissue-specific biochemical compound has been applied as chip composite. As a ready-to-use platform, in situ cell encapsulation within the gel has been achieved through capillary force generated during gel reswelling. The liver-mimetic chip composite, comprising HepG2 cells or primary hepatocytes, has demonstrated favorable hepatic functionality and high sensitivity in drug testing. The developed fabrication process with improved stability of gels and storability allows chip composites to be stored at a wide range of temperatures for up to 28 d without any deformation, demonstrating off-the-shelf products. Consequently, this provides an exceptionally simple and long-term storable platform that can be utilized for an efficient tissue-specific modeling and various biomedical applications., (© 2024 IOP Publishing Ltd.)

Alzheimer's disease (AD) is a representative cause of dementia and is caused by neuronal loss, leading to the accumulation of aberrant neuritic plaques and the formation of neurofibrillary tangles. Oxidative stress is involved in the impaired clearance of amyloid beta (Aβ), and Aβ-induced oxidative stress causes AD by inducing the formation of neurofibrillary tangles. Hwangryunhaedok-tang (HHT, Kracie K-09 ® ), a traditional herbal medicine prescription, has shown therapeutic effects on various diseases. However, the studies of HHT as a potential treatment for AD are insufficient. Therefore, our study identified the neurological effects and mechanisms of HHT and its key bioactive compounds against Alzheimer's disease in vivo and in vitro. In a 5xFAD mouse model, our study confirmed that HHT attenuated cognitive impairments in the Morris water maze (MWM) test and passive avoidance (PA) test. In addition, the prevention of neuron impairment, reduction in the protein levels of Aβ, and inhibition of cell apoptosis were confirmed with brain tissue staining. In HT-22 cells, HHT attenuates tBHP-induced cytotoxicity, ROS generation, and mitochondrial dysfunction. It was verified that HHT exerts a neuroprotective effect by activating signaling pathways interacting with Nrf2, such as MAPK/ERK, PI3K/Akt, and LKB1/AMPK. Among the components, baicalein, a bioavailable compound of HHT, exhibited neuroprotective properties and activated the Akt, AMPK, and Nrf2/HO-1 pathways. Our findings indicate a mechanism for HHT and its major bioavailable compounds to treat and prevent AD and suggest its potential.