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Yu-Jhou Chen,1,2,* Chen-June Seak,2– 4,* Chien-Cheng Chen,2,5,6 Tsung-Hsing Chen,1,2,5 Shih-Ching Kang,7 Chip-Jin Ng,2,4 Chao-Wei Lee,8 Ming-Yao Su,2,9,10 Hsin-Chih Huang,1,2,9 Chun-Hsiang Ooyang,7 Sen-Yung Hsieh,1,2 Hao-Tsai Cheng1,2,5,9 1Department of Gastroenterology and Hepatology, Linkou Medical Center, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan; 2College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan; 3Department of Emergency Medicine, New Taipei Municipal Tucheng Hospital, New Taipei City 23652, Taiwan; 4Department of Emergency Medicine, Linkou Medical Center, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan; 5College of Medicine, Graduate Institute of Clinical Medicine, Chang Gung University, Taoyuan 33302, Taiwan; 6Department of Medical Image and Intervention, Linkou Medical Center, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan; 7Division of Trauma and Emergent Surgery, Department of Surgery, Linkou Medical Center, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan; 8Division of General Surgery, Department of Surgery, Linkou Medical Center, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan; 9Department of Gastroenterology and Hepatology, Department of Internal Medicine, New Taipei Municipal Tucheng Hospital, New Taipei City 23652, Taiwan; 10Board of Directors and Supervisors, Taiwan Association for the Study of Small Intestinal Disease (TASSID), Taoyuan 33305, Taiwan*These authors contributed equally to this workCorrespondence: Hao-Tsai ChengDepartment of Gastroenterology and Hepatology, New Taipei Municipal TuCheng Hospital, No 6, Sec. 2, Jincheng Road, Tucheng Dist., New Taipei City 236, Taiwan (Republic Of China)Tel +886-2-22630588 ext. 6185Fax +886-2-22732688Email hautai@adm.cgmh.org.twPurpose: High prevalence of psychiatric comorbidities (PCs) has been widely documented in caustic substance ingestion cases. However, their effect on the clinical features and prognostic outcomes remains unclear due to the paucity of discussion. We report on detailed clinical courses with long-term multifaceted outcomes and review the association between caustic ingestion and each specific PC.Patients and Methods: The retrospective chart review included 396 adults (median follow-up, 16.6 months) with and 377 without (control group) PCs treated between 1999 and 2018 at Chang Gung Memorial Hospital. All PCs were diagnosed/confirmed by psychiatrists through face-to-face interviews.Results: The PCs predicted serious esophagogastroduodenoscopy grading, higher rates of admission/surgery/intensive care unit stay, increments of systemic/gastrointestinal complications, and poorer 5-year overall survival rates. The poor survival among patients with PCs was highly consistent with their baseline characteristics. Significantly advanced age, more non-PCs, alcoholism, illicit drug abuse, and baseline unhealthy status resulted in statistically higher risks of severe complications and limited recovery.Conclusion: PCs changed clinical patterns and had critical roles in the survival outcomes of caustic injury victims. Clinical awareness achieves benefit by limiting injuries in mild cases or allowing emergent interventions in severe cases. Future studies based on worldwide populations are essential for realizing geographic differences.Keywords: caustic, corrosive, psychiatric, endoscopy, complications, long-term survival

Abhishek Dubey,1,* Dae Won Park,2,* Jung Eun Kwon,2 Yong Joon Jeong,2 Taegeun Kim,1 Inhye Kim,3 Se Chan Kang,2 Ki-Whan Chi1 1Department of Chemistry, University of Ulsan, Ulsan, 2Department of Life Science, Gachon University, Seongnam, 3Laboratory of Bio-Resources, Yongin-si, Gyeonggi-Do, Republic of Korea *These authors contributed equally to this work Abstract: Three new large hexanuclear metalla-prisms 9–11 incorporating 1,3,5-tris(pyridin-4-ylethynyl)benzene (tpeb) 4 and one of the dinuclear arene ruthenium clips [Ru2(p-iPrC6H4Me)2(OO∩OO)][CF3SO3]2 (OO∩OO =2,5-dioxydo-1,4-benzoquinonato [dobq] 1, 5,8-dihydroxy-1,4-naphthaquinonato (donq) 2, and 6,11-dihydroxy-5,12-naphthacenedionato [dotq] 3), which encapsulate the guest molecule ellagic acid (2,3,7,8-tetrahydroxy-chromeno[5,4,3-cde]chromene-5,10-dione, 5) were prepared. All complexes were isolated as triflate salts in good yields and were fully characterized by 1H NMR spectroscopy and electrospray ionization mass spectrometry. The photophysical properties of these metalla-prisms were also investigated. Compounds 9 and 10 showed potent antioxidant activity, but 10 had the superior ORACPE value (1.30±0.020). Ellagic acid (5) and compound 11 showed weaker activity than that of Trolox. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed that the metalla-prism compounds exhibit anticancer properties in vitro. Compound 10 inhibited the growth of all cancer cell lines at micromolar concentrations, with the highest cytotoxicity observed against A549 human lung cancer cells (IC50 =25.9 µM). However, these compounds had a lower anti-cancer activity than that of doxorubicin. In a tumoricidal assay, ellagic acid (5) and compound 10 induced cytotoxicity in tumor cells, while doxorubicin did not. While free ellagic acid had no effect on the granulocyte-colony stimulating factor and regulated on activation normal T cell expressed and secreted protein, the encapsulated metalla-prism 10 stimulated granulocyte-colony stimulating factor and reduced regulated on activation normal T cell expressed and secreted protein expression in the RAW264.7 macrophage line. Our results show that ellagic acid encapsulated in metalla-prisms inhibited cancer cells via the modulation of mRNA induction and protein expression levels of the granulocyte-colony stimulating factor and regulated on activation normal T cell expressed and secreted protein in macrophages. Keywords: metalla-prism, antioxidant, tumoricidal assay, G-CSF, Rantes

Inhye Kim,1,* Young Ho Song,2,* Nem Singh,2 Yong Joon Jeong,3 Jung Eun Kwon,3 Hyunuk Kim,4 Young Mi Cho,3 Se Chan Kang,3 Ki-Whan Chi2 1Laboratory of Bio-Resources, Yongin-si, Gyeonggi-Do, 2Department of Chemistry, University of Ulsan, Ulsan, 3Department of Life Science, Gachon University, Seongnam, 4Energy Materials Lab, Korea Institute of Energy Research, Daejeon, Republic of Korea *These authors contributed equally to this work Abstract: Nano-sized multinuclear ruthenium complexes have rapidly emerged as promising therapeutic candidates with unique anticancer activities. Here, we describe the coordination-driven self-assembly and anticancer activities of a set of three organometallic tetranuclear Ru(II) molecular bowls. [2+2] Coordination-driven self-assembly of 3,6-bis(pyridin-3-ylethynyl)phenanthrene (bpep) (1) and one of the three dinuclear arene ruthenium clips, [(ƞ6-p-iPrC6H4Me)2Ru2-(OO\OO)][OTf]2 (OO\OO =2,5-dioxido-1,4-benzoquinonato, OTf = triflate) (2), 5,8-dioxido-1,4-naphthoquinonato (3), or 6,11-dioxido-5,12-naphthacenediona (4), resulted in three molecular bowls 5–7 of general formula [{(ƞ6-p-iPrC6H4Me)2Ru2-(OO\OO)}2(bpep)2][OTf]4. All molecular bowls were obtained as triflate salts in very good yields (>90%) and were fully characterized using multinuclear nuclear magnetic resonance (NMR), electrospray ionization–mass spectrometry (ESI-MS), and elemental analysis. The structure of the representative molecular bowl 5 was confirmed by single-crystal X-ray diffraction analysis. The anticancer activities of molecular bowls 5–7 were determined by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide, autophagy, and Western blot analysis. Bowl 6 showed the strongest cytotoxicity in AGS human gastric carcinoma cells and was more cytotoxic than doxorubicin. In addition, autophagic activity and the ratio of apoptotic cell death increased in AGS cells by treatment with bowl 6. Bowl 6 also induced autophagosome formation via upregulation of p62 and promotion of the conversion of LC3-I to LC3-II. Moreover, bowl 6 promoted apoptotic cell death through downregulation of Akt/mTOR activation, followed by increased caspase-3 activity. These results suggest that bowl 6 induces gastric cancer cell death via modulation of autophagy and apoptosis. Bowl 6 is a potent anticancer agent and a potential treatment for human gastric cancer that merits further study. Keywords: phenanthrene, ruthenium, coordination self-assembly, gastric cancer, Akt/mTOR

Sangwha Lee,1,* Jongsung Kim,1,* Chung Wung Bark,2 Bonghee Lee,3 Heongkyu Ju,4 Se Chan Kang,5 TaeYoung Kim,6 Moon Il Kim,6 Young Tag Ko,3 Jeong-Seok Nam,3 Hyon Hee Yoon,1 Kyu-Sik Yun,1,6 Young Soo Yoon,1 Seong Soo A An,1,6 John Hulme6 1BioNano Sensor Research Center, 2Department of Electrical Engineering, Gachon University, Seongnam-si, 3Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, 4Department of Nano-Physics, 5Department of Life Science, Gachon University, 6Department of BioNano Technology, Gachon BioNano Research Institute, Seongnam-si, South Korea *These authors contributed equally to this work Abstract: From the synergistic integration and the multidisciplinary strengths of the BioNano Sensor Research Center, Gachon Bionano Research Institute, and Lee GilYa Cancer and Diabetes Institute, researchers, students, and faculties at Gachon University in collaboration with other institutions in Korea, Australia, France, America, and Japan have come together to produce a special issue on the diverse applications of nano-theranostics in nanomedicine. This special issue will showcase new research conducted by various scientific groups in Gyonggi-do and Songdo/Incheon, South Korea. The objectives of this special issue are as follows: 1) to bring together and demonstrate some of the latest research results in the field, 2) to introduce new multifunctional nanomaterials and their applications in imaging and detection methods, and 3) to stimulate collaborative interdisciplinary research at both national and international levels in nanomedicine. Keywords: cancer, imaging and therapeutics, antibacterial, disease, neurodegenerative

Devasier Bennet,1 Se Chan Kang,2 Jongback Gang,3 Sanghyo Kim1,4 1Department of Bionanotechnology, 2Department of Life Science, 3Department of Nano Chemistry, Gachon University, Bokjeong-Dong, Sujeong-Gu, Seongnam-Si, Gyeonggi-Do, Republic of Korea; 4Graduate Gachon Medical Research Institute, Gil Medical Center, Inchon, Republic of Korea Abstract: Plants contain enriched bioactive molecules that can protect against skin diseases. Bioactive molecules become unstable and ineffective due to unfavorable conditions. In the present study, to improve the therapeutic efficacy of phytodrugs and enhance photoprotective capability, we used poly(D,L-lactide-co-glycolide) as a carrier of apple peel ethanolic extract (APETE) on permeation-enhanced nanoparticles (nano-APETE). The in vitro toxicity of nano-APETE-treated dermal fibroblast cells were studied in a bioimpedance system, and the results coincided with the viability assay. In addition, the continuous real-time evaluations of photodamage and photoprotective effect of nano-APETE on cells were studied. Among three different preparations of nano-APETE, the lowest concentration provided small, spherical, monodispersed, uniform particles which show high encapsulation, enhanced uptake, effective scavenging, and sustained intracellular delivery. Also, the nano-APETE is more flexible, allowing it to permeate through skin lipid membrane and release the drug in a sustained manner, thus confirming its ability as a sustained transdermal delivery. In summary, 50 µM nano-APETE shows strong synergistic photoprotective effects, thus demonstrating its higher activity on target sites for the treatment of skin damage, and would be of broad interest in the field of skin therapeutics. Keywords: apple peel ethanolic extract, antioxidant, cellular uptake, electric cell-substrate impedance sensing, phyto-drugs, light-induced damage

Introduction: While angioembolization is occasionally required for craniofacial fracture patients who experience massive maxillofacial hemorrhage, complications such as headache, temporal-facial pain, soft tissue necrosis, and embolic material migration leading to stroke or blindness can arise. Few studies have explored delayed or progressive intracerebral hemorrhage (ICH) following angioembolization for craniofacial fractures., Methods: A retrospective review of craniofacial fracture patients from January 1, 2015, to December 31, 2022 at our institution was conducted. We applied univariate and multivariable logistic regression (MLR) analyses to assess whether angioembolization served as an independent factor for delayed or progressive ICH. Propensity score matching (PSM) was used to balance the groups of patients who underwent angioembolization with those who did not. Outcome measurements included delayed or progressive ICH occurring within 72 hours, the need for additional neurosurgical interventions, and the length of stay (LOS) in the intensive care unit (ICU) and hospital., Results: Of the 2,519 craniofacial fracture patients studied over an 8-year period, 21 (0.8%) underwent angioembolization for maxillofacial hemorrhage. MLR analysis revealed that angioembolization was an independent factor for delayed or progressive ICH (odds ratio=5.71, p = 0.028). After 1:2 PSM, patients who underwent angioembolization had greater rates of delayed or progressive ICH (28.6% vs. 7.1%, p = 0.023), an extended hospital LOS (17.0 vs. 15.0 days, p = 0.009) and a longer ICU LOS (10.0 vs. 4.0 days, p = 0.004)., Conclusions: A greater probability of delayed or progressive ICH was observed in craniofacial fracture patients who underwent angioembolization for maxillofacial hemostasis., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Colon cancer remains a significant global health concern, necessitating the continuous exploration of novel therapeutic strategies. Cisplatin is a first-line chemotherapy medication that is frequently used to treat patients for a variety of malignancies, including colon cancer. However, a major obstacle to its clinical usefulness is acquired resistance. This research investigates the synergistic effects of kaempferol, a natural flavonoid with known anti-cancer properties, in combination with cisplatin, in colon cancer cells. Our study employed colon cancer cell lines to evaluate the individual and combined cytotoxic effects of kaempferol and cisplatin. The results demonstrated a notable enhancement in the cytotoxicity of colon cancer cells when treated with a combination of kaempferol and cisplatin compared to individual treatments. This synergistic effect was further characterized by an increase in apoptosis, as evidenced by morphological changes and biochemical markers of apoptosis and cell cycle. The investigations revealed that the combined treatment led to the modulation of key apoptotic pathways, including the upregulation of pro-apoptotic factors and downregulation of anti-apoptotic factors. Additionally, the synergistic effect was associated with the inhibition of cell proliferation and induction of cell cycle arrest. The findings of this study suggest that the combination of kaempferol and cisplatin holds promise as a potent therapeutic strategy for colon cancer treatment, potentially enhancing the efficacy of conventional chemotherapy while minimizing adverse effects. Further in-depth investigations, including in vivo studies, are warranted to validate these findings and explore the translational potential of this synergistic approach in clinical settings., Competing Interests: CONFLICTS OF INTEREST No potential conflicts of interest were disclosed., (Copyright © 2024 Korean Society of Cancer Prevention.)

Abeliophyllum distichum (Oleaceae), endemic to the Korean Peninsula and the sole member of its genus and species, possesses high scarcity value, escalating its importance under the Nagoya Protocol. Despite its significance, their metabolites and activities of A. distichum flowers remain unexplored. This study employs an integrated metabolomic approach utilizing NMR, LC/MS, GC/MS, and FTIR techniques to comprehensively analyze the metabolite profile of A. distichum flowers. By combining these methods, we identified 35 metabolites, 43 secondary metabolites, and 108 hydrophobic primary metabolites. Notably, distinct concentration patterns of these compounds were observed across five variants, classified based on morphological characteristics. Correlation analyses of primary and secondary metabolites unveiled varietal metabolic flux, providing insights into A. distichum flower metabolism. Additionally, the reconstruction of metabolic pathways based on dissimilarities in morphological traits elucidates variant-specific metabolic signatures. These findings not only enhance our understanding of chemical differences between varieties but also underscore the importance of considering varietal differences in future research and conservation efforts., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 The Author(s). Plant Direct published by American Society of Plant Biologists and the Society for Experimental Biology and John Wiley & Sons Ltd.)

Purpose: To assess the impact of pre-existing cirrhosis on the outcomes of non-operatively managed blunt liver trauma within the Trauma Quality Improvement Program (TQIP) database., Methods: A study of non-operatively managed blunt liver injury patients from 2016 to 2019 was conducted. Propensity score matching analyzed mortality, complications, and hospital length of stay (LOS) for patients with and without cirrhosis. The effect of transcatheter arterial embolization (TAE) was determined using multivariate logistic regression., Results: Out of 63,946 patients, 767 (1.2%) had pre-existing cirrhosis. Following 1:1 matching, those with cirrhosis experienced more hemorrhage (TAE need: 5.7% vs. 2.7%; transfusion volume: 639.1 vs. 259.3 ml), complications (acute kidney injury: 5.1% vs. 2.8%; sepsis: 2.4% vs. 1.0%), and poorer outcomes (mortality: 19.5% vs. 10.2%; hospital LOS: 11.6 vs. 8.4 days; ICU LOS: 12.1 vs. 7.4 days; ventilator days: 7.6 vs. 1.6). Notably, TAE was associated with increased mortality in cirrhotic patients (odds ratio: 4.093) but did not significantly affect mortality in patients without cirrhosis., Conclusions: Within TQIP, pre-existing cirrhosis is a significant negative determinant for outcomes in blunt liver trauma. Cirrhotic patients undergoing TAE for hemostasis face greater mortality risk than non-cirrhotic counterparts., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Forsythia koreana Nakai is an ornamental plant widely cultivated in East Asia. The essential oil of F. koreana flowers (FEO) was extracted by hydrodistillation process and the volatile components were determined with gas chromatography coupled with mass spectrometry. The anti-inflammatory activity of FEO was investigated by using TPA-induced mouse ear inflammation model. The major components of FEO were identified as n -tetracosane (29.85%), n -heneicosane (17.45%), myristic acid (8.46%) and palmitaldehyde (6.22%). The TPA-induced mouse ear edema, water content, dermis thickness, epidermis thickness and nitric oxide production were decreased by FEO. Our findings suppose that the flower essential oil of F. koreana exerted anti-inflammatory activity, and may be used in the development of anti-inflammatory products in future.

Background: Obesity may serve as a protective factor in blunt abdominal trauma (BAT) patients due to a "cushion effect". In this study, we aim to use computed tomography (CT) scans to measure abdominal adiposity and its correlation with injury severity in BAT patients., Methods: We conducted a retrospective analysis of male BAT patients who had undergone CT scans. Subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) were manually measured and height-normalized for analysis at lumbar levels L2 and L3. Statistical methods were used to compare differences in adiposity between patients with and without severe abdominal injuries. For controls, we also compared adipose tissue in patients with and without severe trauma to the chest, where less fat typically accumulates., Results: We included 361 male participants and conducted a comparative analysis of their demographic and injury characteristics. Patients without severe abdominal injuries had significantly higher SAT and VAT indices at both L2 and L3 (p < 0.05). However, these measures showed no significant differences between patients with and without severe chest trauma. Solid organ injuries, particularly liver injuries, were associated with decreased SAT and VAT., Conclusion: Increase abdominal adiposity was linked to lower abdominal injury severity and solid organ injuries, particularly liver injuries. In addition to conventional BMI for evaluating obesity, either subcutaneous or visceral adipose tissue over lumbar levels L2 and L3 can be used to assess the "cushion effect.", Competing Interests: Declaration of competing interest This study was approved by the Institutional Research Board of Our Institution (202100283B0) on 2022/05/03 for ethics approval and consent to participate. The consent was not obtained because the patients’ information is deidentified and downloaded under privacy protection in Chang Gung database. The authors have no commercial associations or sources of support that might pose a conflict of interest. All the authors have made substantive contributions to the study and endorse the data and conclusions., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Research quality can be improved with reliable and reproducible experimental results when animal experiments are conducted using laboratory animals with guaranteed microbiological and genetic quality through health monitoring. Therefore, health monitoring requires the rapid and accurate diagnosis of infectious diseases in laboratory animals., Methods: This study presents a performance evaluation of a commercially available multiplex real-time PCR (mRT-PCR) assay for the rapid detection of 12 infectious pathogens (Set 1: Sendai virus [SeV, formally murine respirovirus], Mycoplasma spp., Rodentibacter pneumotropicus , and Rodentibacter heylii ; Set 2: Helicobacter spp., Murine norovirus [MNV], Murine hepatitis virus [MHV], and Salmonella spp.; Set 3: Staphylococcus aureus , Streptobacillus moniliformis , Corynebacterium kutscheri , and Pseudomonas aeruginosa ). To evaluate the efficacy of the mRT-PCR assay, 102 clinical samples encompassing fecal and cecal specimens were analyzed. The resulting data were then compared with the findings from sequence analysis for validation., Results: The assay's detection limit ranged from 1 to 100 copies per reaction. Specificity testing involving various viruses and bacteria indicated no cross-reactivity between strains. Additionally, the assay exhibited good reproducibility, with mean coefficients of variation for inter- and intra assay variation below 3%. The overall positive rate was 52.9% ( n  = 54), with the mRT-PCR assay findings matching sequence analysis results ( κ  = 1). MHV ( n  = 29, 28.4%) was the most prevalent pathogen, followed by Helicobacter spp. ( n  = 28, 27.5%), R. heylii ( n  = 18, 17.6%), Mycoplasma spp. ( n  = 14, 13.7%), MNV ( n  = 12, 11.8%), S. aureus ( n  = 9, 8.8%), P. aeruginosa ( n  = 4, 3.9%), and R. pneumotropicus ( n  = 1, 0.9%)., Discussion: This assay offers a rapid turnaround time of 100 min, including 30 min for DNA preparation and 70 min for target DNA/RNA amplification. It ensures accuracy, minimizing false positives or negatives, making it a convenient tool for the simultaneous detection of infectious diseases in many samples. Overall, the propose‑d assay holds promise for the effective detection of the most important pathogens in laboratory animal health monitoring., Competing Interests: H-yW, JA, JL, SK, and HK were employed by Optipharm, Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Ahn, Lee, Kang and Kim.)

The rhizome of Zingiber officinale (Z. officinale), commonly known as ginger, has been characterized as a potential drug candidate due to its antitumor effects. However, the chemotherapeutic effect of ginger on human oral cancer remains poorly understood. In this study, we examined the effects of an ethanol extract of Z. officinale rhizomes (ZOE) on oral cancer and identified the components responsible for its pharmacological activity. ZOE exerts its inhibitory activity in oral cancer by inducing both autophagy and apoptosis simultaneously. Mechanistically, ZOE-induced autophagy and apoptosis in oral cancer are attributed to the reactive oxygen species (ROS)-mediated endoplasmic reticulum stress response. Additionally, we identified two active components of ZOE, 1-dehydro-6-gingerdione and 8-shogaol, which were sufficient to stimulate autophagy initiation and apoptosis induction by enhancing CHOP expression. These results suggest that ZOE and its two active components induce ROS generation, upregulate CHOP, initiate autophagy and apoptosis, and hold promising therapeutics against human oral cancer., (© 2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Interleukin-2 (IL-2), a cytokine with pleiotropic immune effects, was the first approved cancer immunotherapy agent. However, IL-2 is associated with systemic toxicity due to binding with its ligand IL-2Rα, such as vascular leakage syndrome, limiting its clinical applications. Despite efforts to extend the half-life of IL-2 and abolish IL-2Rα interactions, the risk of toxicity remains unresolved. In this study, we developed the bispecific fusion protein MB2033, comprising a novel IL-2 variant (IL-2v) connected to anti-programmed death ligand 1 (PD-L1) via a silenced Fc domain. The IL-2v of MB2033 exhibits attenuated affinity for IL-2Rβγ without binding to IL-2Rα. The binding affinity of MB2033 for PD-L1 is greater than that for IL-2Rβγ, indicating its preferential targeting of PD-L1 + tumor cells to induce tumor-specific immune activation. Accordingly, MB2033 exhibited significantly reduced regulatory T cell activation, while inducing comparable CD8 + T cell activation to recombinant human IL-2 (rhIL-2). MB2033 induced lower immune cell expansion and reduced cytokine levels compared with rhIL-2 in human peripheral blood mononuclear cells, indicating a decreased risk of peripheral toxicity. MB2033 exhibited superior anti-tumor efficacy, including tumor growth inhibition and complete responses, compared with avelumab monotherapy in an MC38 syngeneic mouse model. In normal mice, MB2033 was safer than non-α IL-2v and tolerable up to 30 mg/kg. These preclinical results provide evidence of the dual advantages of MB2033 with an enhanced safety and potent clinical efficacy for cancer treatment., (© 2024. The Author(s).)

PTEN germline mutations account for ~0.2-1% of all autism spectrum disorder (ASD) cases, as well as ~17% of ASD patients with macrocephaly, making it one of the top ASD-associated risk genes. Individuals with germline PTEN mutations receive the molecular diagnosis of PTEN Hamartoma Tumor Syndrome (PHTS), an inherited cancer predisposition syndrome, about 20-23% of whom are diagnosed with ASD. We generated forebrain organoid cultures from gene-edited isogenic human induced pluripotent stem cells (hiPSCs) harboring a PTEN G132D (ASD) or PTEN M134R (cancer) mutant allele to model how these mutations interrupt neurodevelopmental processes. Here, we show that the PTEN G132D allele disrupts early neuroectoderm formation during the first several days of organoid generation, and results in deficient electrophysiology. While organoids generated from PTEN M134R hiPSCs remained morphologically similar to wild-type organoids during this early stage in development, we observed disrupted neuronal differentiation, radial glia positioning, and cortical layering in both PTEN-mutant organoids at the later stage of 72+ days of development. Perifosine, an AKT inhibitor, reduced over-activated AKT and partially corrected the abnormalities in cellular organization observed in PTEN G132D organoids. Single cell RNAseq analyses on early-stage organoids revealed that genes related to neural cell fate were decreased in PTEN G132D mutant organoids, and AKT inhibition was capable of upregulating gene signatures related to neuronal cell fate and CNS maturation pathways. These findings demonstrate that different PTEN missense mutations can have a profound impact on neurodevelopment at diverse stages which in turn may predispose PHTS individuals to ASD. Further study will shed light on ways to mitigate pathological impact of PTEN mutants on neurodevelopment by stage-specific manipulation of downstream PTEN signaling components., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

We herein describe a novel electrochemical strategy to detect hydrogen peroxide (H 2 O 2 ) by utilizing the peroxidase-mimicking activity of cerium oxide nanoparticles (CeO 2 NP) and reduced graphene oxide (rGO). Particularly, CeO 2 NP/rGO nanocomposites were deposited on the commercial electrode by a very convenient and direct electrochemical reduction of graphene oxide. Due to the peroxidase-mimicking activity of CeO 2 NP and the outstanding electrochemical properties of reduced graphene oxide, the reduction current of H 2 O 2 was greatly enhanced. Based on this strategy, we reliably determined H 2 O 2 down to 1.67 μM with excellent specificity and further validated its practical capabilities by robustly detecting H 2 O 2 present in heterogeneous human serum samples. We believe that this work could serve as a new facile platform for H 2 O 2 detection., 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.)

Elaeocarpus sylvestris var. ellipticus (ES), which our research group had confirmed inhibits influenza A and SARS-CoV-2 viruses, was investigated to identify new potent and selective inhibitors of herpes simplex virus-1 (HSV-1) replication. To clarify the optimal condition for ES extract (ESE), ES was extracted at different concentrations of 0, 30, 50, 70, and 100%, to screen for its anti-HSV-1 effect. Among these ESE samples, ESE50 (50% concentration) exhibited the strongest inhibition of HSV-1 replication (EC 50 23.2 μg/mL) while showing low cytotoxicity on host cells (IC 50 342.8 μg/mL). The treatment of ESE50 clearly demonstrated a decrease in the expression of ICP0 in the lungs of HSV-1-infected BALB/c nude mice, compared to the MOCK group. Geraniin, which was isolated from ESE50 and analyzed using ESI-MS and 1D-( 1 H- and 13 C-) and 2D-NMR, showed greater potency in inhibiting HSV-1 replication, as determined by the plaque reduction assay (EC 50 8.3 μg/mL) and luciferase inhibition (EC 50 36.9 μg/mL). The results demonstrate that ESE50 and geraniin show great potential as candidates for new drug discovery in the treatment of HSV-1 and related diseases.

Cnidium monnieri fructus is widely used in traditional Oriental medicine for treating female genital disorders, male impotence, frigidity, and skin-related conditions in East Asia. However, the role of C. monnieri fructus extract (CMFE) in melanin synthesis is not well elucidated. This study aimed to investigate the anti-melanogenesis effect and mechanism of action of CMFE in α-MSH-stimulated B16F10 cells. Intracellular melanin content and tyrosinase activity were measured in α-MSH-stimulated B16F10 cells treated with various concentrations of CMFE (0.5-5 μg/mL). mRNA and protein levels of tyrosinase and MITF were evaluated using qRT-PCR and ting. CMFE's effect on the proteasomal degradation of tyrosinase was confirmed using a proteasomal degradation inhibitor, MG132. CMFE treatment activated p38, a protein associated with proteasomal degradation. Treatment with CMFE at up to 5 μg/mL showed no significant cytotoxicity. CMFE significantly reduced α-MSH-stimulated melanin production (43.29 ± 3.55% decrease, p < 0.05) and cellular tyrosinase activity (31.14 ± 3.15% decrease, p < 0.05). Although mRNA levels of MITF and tyrosinase increased, CMFE suppressed tyrosinase protein levels. The suppressive effect of CMFE on tyrosinase protein was blocked by MG132. CMFE inhibited melanogenesis by promoting the proteasome degradation of tyrosinase through p38 activation. These findings suggest that CMFE has the potential to be a natural whitening agent for inhibiting melanogenesis.

Diagnostic imaging is essential in modern trauma care for initial evaluation and identifying injuries requiring intervention. Deep learning (DL) has become mainstream in medical image analysis and has shown promising efficacy for classification, segmentation, and lesion detection. This narrative review provides the fundamental concepts for developing DL algorithms in trauma imaging and presents an overview of current progress in each modality. DL has been applied to detect free fluid on Focused Assessment with Sonography for Trauma (FAST), traumatic findings on chest and pelvic X-rays, and computed tomography (CT) scans, identify intracranial hemorrhage on head CT, detect vertebral fractures, and identify injuries to organs like the spleen, liver, and lungs on abdominal and chest CT. Future directions involve expanding dataset size and diversity through federated learning, enhancing model explainability and transparency to build clinician trust, and integrating multimodal data to provide more meaningful insights into traumatic injuries. Though some commercial artificial intelligence products are Food and Drug Administration-approved for clinical use in the trauma field, adoption remains limited, highlighting the need for multi-disciplinary teams to engineer practical, real-world solutions. Overall, DL shows immense potential to improve the efficiency and accuracy of trauma imaging, but thoughtful development and validation are critical to ensure these technologies positively impact patient care., Competing Interests: Declaration of Competing Interest The authors have no financial conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: To develop a rib and clavicle fracture detection model for chest radiographs in trauma patients using a deep learning (DL) algorithm., Materials and Methods: We retrospectively collected 56 145 chest X-rays (CXRs) from trauma patients in a trauma center between August 2008 and December 2016. A rib/clavicle fracture detection DL algorithm was trained using this data set with 991 (1.8%) images labeled by experts with fracture site locations. The algorithm was tested on independently collected 300 CXRs in 2017. An external test set was also collected from hospitalized trauma patients in a regional hospital for evaluation. The receiver operating characteristic curve with area under the curve (AUC), accuracy, sensitivity, specificity, precision, and negative predictive value of the model on each test set was evaluated. The prediction probability on the images was visualized as heatmaps., Results: The trained DL model achieved an AUC of 0.912 (95% CI 87.8 to 94.7) on the independent test set. The accuracy, sensitivity, and specificity on the given cut-off value are 83.7, 86.8, and 80.4, respectively. On the external test set, the model had a sensitivity of 88.0 and an accuracy of 72.5. While the model exhibited a slight decrease in accuracy on the external test set, it maintained its sensitivity in detecting fractures., Conclusion: The algorithm detects rib and clavicle fractures concomitantly in the CXR of trauma patients with high accuracy in locating lesions through heatmap visualization., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

This study aimed to identify substances including Lactobacillus rhamnosus vitaP1 (KACC 92054P) that alleviate hangover-induced emotional anxiety and liver damage. The association between emotional anxiety caused by hangover and the genes P2X4, P2X7, SLC6A4 was investigated. In vitro and in vivo analyses were conducted to assess the influence of free-panica on alcohol-induced upregulated gene expression. Additionally, the concentration of AST, ALT, alcohol, and acetaldehyde in blood was measured. Free-panica, consisting of five natural products (Phyllanthus amarus, Phoenix dactylifera, Vitis vinifera, Zingiber officinale, and Lactobacillus rhamnosus), were evaluated for their regulatory effects on genes involved in alcohol-induced emotional anxiety and liver damage. The combination of these natural products in free-panica successfully restored emotional anxiety, and the concentration of AST, ALT, alcohol, and acetaldehyde in blood to those of the normal control group. These findings support the potential development of free-panica as a health functional food or medicinal intervention for relieving hangover symptoms and protecting liver from alcohol consumption., (© 2024. The Author(s).)

Rare ginsenoside compound K (CK) is an intestinal microbial metabolite with a low natural abundance that is primarily produced by physicochemical processing, side chain modification, or metabolic transformation in the gut. Moreover, CK exhibits potent biological activity compared to primary ginsenosides, which has raised concerns in the field of ginseng research and development, as well as ginsenoside-related dietary supplements and natural products. Ginsenosides Rb1, Rb2, and Rc are generally used as a substrate to generate CK via several bioconversion processes. Current research shows that CK has a wide range of pharmacological actions, including boosting osteogenesis, lipid and glucose metabolism, lipid oxidation, insulin resistance, and anti-inflammatory and anti-apoptosis properties. Further research on the bioavailability and toxicology of CK can advance its medicinal application. The purpose of this review is to lay the groundwork for future clinical studies and the development of CK as a therapy for metabolic disorders. Furthermore, the toxicology and pharmacology of CK are investigated as well in this review. The findings indicate that CK primarily modulates signaling pathways associated with AMPK , SIRT1 , PPARs , WNTs , and NF-kB . It also demonstrates a positive therapeutic effect of CK on non-alcoholic fatty liver disease (NAFLD), obesity, hyperlipidemia, diabetes, and its complications, as well as osteoporosis. Additionally, the analogues of CK showed more bioavailability, less toxicity, and more efficacy against disease states. Enhancing bioavailability and regulating hazardous variables are crucial for its use in clinical trials.

BACKGROUND The gut microbial metabolites demonstrate significant activity against metabolic diseases including osteoporosis (OP) and obesity, but active compounds, targets, and mechanisms have not been fully identified. Hence, the current investigation explored the mechanisms of active metabolites and targets against OP and obesity by using network pharmacology approaches. MATERIAL AND METHODS The gutMGene database was used to collect gut microbial targets-associated metabolites; DisGeNET and OMIM databases were used to identify targets relevant to OP and obesity. A total of 63 and 89 overlapped targets were considered the final OP and obesity targets after creating a Venn diagram of metabolites-related targets and disease-related targets. Furthermore, the top 20% of degrees, betweenness, and closeness were used to form the sub-network of protein-protein interaction of these targets. Finally, the biotransformation-increased receptors and biological mechanisms were identified and validated using ADMET properties analysis, molecular docking, and molecular dynamic simulation. RESULTS GO, KEGG pathway analysis, and protein-protein interactions were performed to establish metabolites and target networks. According to the enrichment analysis, OP and obesity are highly linked to the lipid and atherosclerosis pathways. Moreover, ADMET analysis depicts that the major metabolites have drug-likeliness activity and no or less toxicity. Following that, the molecular docking studies showed that compound K and TP53 target have a remarkable negative affinity (-8.0 kcal/mol) among all metabolites and targets for both diseases. Finally, the conformity of compound K against the targeted protein TP53 was validated by 250ns MD simulation. CONCLUSIONS Therefore, we summarized that compound K can regulate TP53 and could be developed as a therapy option for OP and obesity.

The prevalence of metabolic syndrome is increasing globally due to behavioral and environmental changes. There are many therapeutic agents available for the treatment of chronic metabolic diseases, such as obesity and diabetes, but the data on their efficacy and safety are lacking. Through a pilot study by our group, Zingiber officinale rhizomes used as a spice and functional food were selected as an anti-obesity candidate. In this study, steam-processed ginger extract (GGE) was used and we compared its efficacy at alleviating metabolic syndrome-related symptoms with that of conventional ginger extract (GE). Compared with GE, GGE (25-100 μg/mL) had an increased antioxidant capacity and α-glucosidase inhibitory activity in vitro. GGE was better at suppressing the differentiation of 3T3-L1 adipocytes and lipid accumulation in HepG2 cells and promoting glucose utilization in C2C12 cells than GE. In 16-week high-fat-diet (HFD)-fed mice, GGE (100 and 200 mg/kg) improved biochemical profiles, including lipid status and liver function, to a greater extent than GE (200 mg/kg). The supplementation of HFD-fed mice with GGE (200 mg/kg) resulted in the downregulation of SREBP-1c and FAS gene expression in the liver. Collectively, our results indicate that GGE is a promising therapeutic for the treatment of obesity and metabolic syndrome.

Introduction: Patients with subdural hemorrhage (SDH) and a Glasgow Coma Scale (GCS) score of 13-15 are typically categorized as having mild traumatic brain injury. We hypothesize that patients without a maximum GCS score - specifically, patients with GCS scores of 13 and 14 - may exhibit poorer neurological outcomes., Method: Between January 1, 2019, and December 31, 2020, SDH patients with GCS scores ranging from 13 to 15 were retrospectively studied. We compared outcomes between patients with a maximum GCS score of 15 and those with scores of either 13 or 14. Independent factors associated with neurological deterioration among patients with a GCS score of 15 were evaluated using multivariate logistic regression (MLR) analysis., Results: During the study period, 470 patients with SDH and GCS scores between 13 and 15 were examined. Compared to patients with a maximum GCS score (N = 375), those in the GCS 13-14 group (N = 95) showed significantly higher rates of neurological deterioration (33.7% vs. 10.4%, p value <0.001) and neurosurgical interventions (26.3% vs. 16.3%, p value <0.024). Moreover, the GCS 13-14 group had a significantly poorer prognosis than patients with a GCS score of 15 [mortality rate: 7.4% vs. 2.4%, p value <0.017; rate of impaired consciousness at discharge: 21.1% vs. 4.0%, p value <0.001; and rate of neurological disability at discharge: 29.5% vs. 6.9%, p value <0.001]. The MLR analysis revealed that SDH thickness (odds ratio = 1.127, p value = 0.006) was an independent risk factor for neurological disability at discharge in patients with a GCS score of 15., Conclusion: Among SDH patients with mild TBI, those with GCS scores of 13-14 exhibited poorer neurological outcomes than those with a maximum GCS score. The thickness of the SDH is positively associated with neurological disability in SDH patients with a maximum GCS score., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Lung cancer is the predominant cause of cancer-related fatalities. This prompted our exploration into the anti-lung cancer efficacy of Labisia pumila , a species meticulously selected from the preliminary screening of 600 plants., Methods: Through the strategic implementation of activity-guided fractionation, ardisiacrispin A (1) was isolated utilizing sequential column chromatography. Structural characterization was achieved employing various spectroscopic methods, including nuclear magnetic resonance (NMR), mass spectrometry (MS), and infrared spectroscopy (IR)., Results: L. pumila 70% EtOH extract showed significant toxicity in A549 lung cancer cells, with an IC 50 value of 57.04 ± 10.28 µg/mL, as well as decreased expression of oncogenes and induced apoptosis. Compound 1 , ardisiacrispin A, induced a 50% cell death response in A549 cells at a concentration of 11.94 ± 1.14 µg/mL., Conclusions: The present study successfully investigated ardisiacrispin A extracted from L. pumila leaves, employing a comprehensive spectroscopic approach encompassing NMR, IR, and MS analyses. The anti-lung cancer efficacy of ardisiacrispin A and L. pumila extract was successfully demonstrated for the first time, to the best of our knowledge.

Obesity is a well-established risk factor for cancer, significantly impacting both cancer incidence and mortality. However, the intricate molecular mechanisms connecting adipose tissue to cancer cell metabolism are not fully understood. This Review explores the historical context of tumor energy metabolism research, tracing its origins to Otto Warburg's pioneering work in 1920. Warburg's discovery of the "Warburg effect", wherein cancer cells prefer anaerobic glycolysis even in the presence of oxygen, laid the foundation for understanding cancer metabolism. Building upon this foundation, the "reverse Warburg effect" emerged in 2009, elucidating the role of aerobic glycolysis in cancer-associated fibroblasts (CAFs) and its contribution to lactate accumulation in the tumor microenvironment, subsequently serving as a metabolic substrate for cancer cells. In contrast, within high-adiposity contexts, cancer cells exhibit a unique metabolic shift termed the "inversion of the Warburg effect". This phenomenon, distinct from the stromal-dependent reverse Warburg effect, relies on increased nutrient abundance in obesity environments, leading to the generation of glucose from lactate as a metabolic substrate. This Review underscores the heightened tumor proliferation and aggressiveness associated with obesity, introducing the "inversion of the Warburg effect" as a novel mechanism rooted in the altered metabolic landscape within an obese milieu. The insights presented here open promising avenues for therapeutic exploration, offering fresh perspectives and opportunities for the development of innovative cancer treatment strategies., Competing Interests: The authors declare no competing financial interest., (© 2024 American Chemical Society.)

Introduction: Transarterial embolization (TAE) or nephrectomy for patients with blunt renal trauma might result in acute kidney injury (AKI). Thus, we analyzed the American College of Surgeons - Trauma Quality Improvement Program (TQIP) to validate this. We hypothesized that nephrectomy, and not TAE, would be a risk factor for AKI in patients with blunt renal trauma., Material and Methods: Adult patients with blunt injuries from the TQIP between 2017 and 2019 were eligible for inclusion. The patients were divided into three treatment groups: conservative treatment, TAE, and nephrectomy. Multivariable logistic regression was used to clarify the AKI predictors., Results: The study included 12,843 patients, wherein 12,373 (96.3 %), 229 (1.8 %), and 241 (1.9 %) patients were in the conservative, TAE, and nephrectomy groups, respectively. A total of 269 (2.2 %), 20 (8.7 %), and 29 (12.0 %) patients had AKI in the three groups, respectively. Both TAE (odds ratio [OR], 2.367; 95 % confidence interval [CI], 1.372-3.900; p = 0.001) and Nephrectomy (OR, 2.745; 95 % CI, 1.629-4.528; p < 0.001) were a statistically significant predictor for AKI in the multivariable logistic regression., Conclusions: TAE and nephrectomy were statistically associated with AKI in patients with blunt renal trauma. This result differs from our previous research findings that nephrectomy, but not TAE, was a risk factor for AKI in patients with blunt renal trauma. Further prospective and well-designed research may be needed., Competing Interests: Declaration of Competing Interest Jen-Fu Huang has received Grant no. MOST 111–2314-B-182A-019 from the Ministry of Science and Technology, Taiwan, R.O.C.. Other authors declare that they have no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Quantum-dot light-emitting diodes (QD-LEDs) have gained attention as potential display technologies. However, the solvents used to dissolve a polymeric hole transport layer (HTL) are hazardous to both humans and the environment. Additionally, intermixing the HTL and QD layers presents a significant challenge when fabricating inverted QD-LEDs. Here, a green solvent selection procedure to achieve good device performance and environmental safety in QD-LEDs is established. This procedure utilizes Hansen solubility parameters and surface roughness to identify a set of solvents that do not lower the device performance by avoiding interlayer mixing or a rough interface. The CHEM21 solvent selection guide is used to screen for environmentally hazardous solvents. Finally, cyclopentanone (CPO) is selected as the optimal HTL solvent from among 16 candidates. Using CPO improves the maximum luminescence by ≈1.6 times and the maximum current efficiency by ≈12.6 times, compared to that of conventional devices using hazardous chlorobenzene. Solvent selection is critical for the fabrication of green and high-performance inverted QD-LEDs, particularly for large display panels that require n-type oxide thin-film transistors., (© 2023 Wiley-VCH GmbH.)

Individuals with a PTEN germline mutation receive the molecular diagnosis of PTEN hamartoma tumor syndrome (PHTS). PHTS displays a complex spectrum of clinical phenotypes including harmartomas, predisposition to cancers, and autism spectrum disorder (ASD). Clear-cut genotype-phenotype correlations are yet to be established due to insufficient information on the PTEN function being impacted by mutations. To fill this knowledge gap, we compared functional impacts of two selected missense PTEN mutant alleles, G132D and M134R, each respectively being associated with distinct clinical phenotype, ASD or thyroid cancer without ASD using gene-edited human induced pluripotent stem cells (hiPSCs). In homozygous hiPSCs, PTEN expression was severely reduced by M134R mutation due to shortened protein half-life. G132D suppressed PTEN expression to a lesser extent than Μ134R mutation without altering protein half-life. When challenged with γ-irradiation, G132D heterozygous cells exited radiation-induced G2 arrest earlier than wildtype and M134R heterozygous hiPSCs despite the similar DNA damage levels as the latter two. Immunoblotting analyses suggested that γ-irradiation induced apoptosis in G132D heterozygous cells to lesser degrees than in the hiPSCs of other genotypes. These data suggest that ASD-associated G132D allele promotes genome instability by premature cell cycle reentry with incomplete DNA repair., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Purpose: The association between appendicular skeletal muscle mass (ASM) and cardiometabolic risk has been emphasized. We estimated reference values of the percentage of ASM (PASM) and investigated their association with metabolic syndrome (MS) in Korean adolescents., Methods: Data from the Korea National Health and Nutrition Examination Survey performed between 2009 and 2011 were used. Tables and graphs of reference PASM were generated using 1,522 subjects, 807 of whom were boys aged 10 to 18. The relationship between PASM and each component of MS in adolescents was further analyzed in 1,174 subjects, 613 of whom were boys. Moreover, the pediatric simple MS score (PsiMS), the homeostasis model assessment of insulin resistance (HOMA-IR), and the triglyceride-glucose (TyG) index were analyzed. Multivariate linear and logistic regressions adjusting for age, sex, household income, and daily energy intake were performed., Results: In boys, PASM increased with age; the trend was different in girls, in whom PASM declined with age. PsiMS, HOMA-IR, and TyG index showed inverse associations with PASM (PsiMS, β=-0.105, P<0.001; HOMA-IR, β=-0.104, P<0.001; and TyG index, β=-0.013, P<0.001). PASM z-score was negatively associated with obesity (adjusted odds ratio [aOR], 0.22; 95% CI, 0.17-0.30), abdominal obesity (aOR, 0.27; 95% CI, 0.20-0.36), hypertension (aOR, 0.65; 95% CI, 0.52-0.80), and elevated triglycerides (aOR, 0.67; 95% CI, 0.56-0.79)., Conclusion: The probability of acquiring MS and insulin resistance decreased as PASM values increased. The reference range may offer clinicians information to aid in the effective management of patients. We urge clinicians to monitor body composition using standard reference databases.

Quantum-dot (QDs) polymer composite films, which are key components in recent display applications, require improved photoluminescence (PL) intensity and color conversion efficiency for better display quality and low power consumption. In this study, we developed a novel approach to improve the photoluminescence (PL) of quantum dot (QDs)-polymer nanocomposite films. This was achieved by incorporating CO 2 micropores and scattering particles into QD-embedded photopolymerizable polymer films. CO 2 micropores were generated by the decomposition of KHCO 3 in the film. The CO 2 micropores, along with the partially decomposed KHCO 3 microparticles, act as a scattering medium that increases the photon absorbance and improves the PL intensity. The effect of KHCO 3 annealing temperature on various optical properties is investigated, and it is found that a large number of uniform micropores are created in the film at an optimal temperature, 110 ℃. Compared to an ordinary QD-polymer film, the PL of the QD-hybrid-foamed polymer film increases by 4.2 times. This method is fast and economically efficient, and provides insights into the design of high-performance optoelectronic devices., 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 © 2023 Elsevier Inc. All rights reserved.)

The major reason for multidrug resistance is the failure of chemotherapy in many tumors, including colon cancer. Hypoxia-inducible factor (HIF)-1α is a crucial transcription factor that simulates multiple cellular response to hypoxia. HIF-1α has been known to play a vital role towards tumor resistance; however, its mechanism of action is still not fully elucidated. N this study, we found that HIF-1α remarkably modulated drug resistance-associated proteins upon CopA3 peptide treatment against colon cancer cells. Abnormal rates of tumor growth along with high metastatic potential lacks the susceptibility towards cellular signals is a key characteristic in many tumor types. Moreover, in growing tumors, cells are exposed to insufficient nutrient supply and low oxygen availability. These stress force them to switch into adaptable and aggressive phenotypes. Our study investigated the interaction of HIF-1α and MDR gene association upon CopA3 treatment in the tumor microenvironment. We demonstrate that the multidrug resistance gene is associated with tumor resistance to chemotherapeutics, which upon CopA3 treatment promotes p53 activation and proteasomal degradation of HIF-1α, effecting the angiogenesis response to hypoxia. p53 downregulation augments HIF-1-dependent transcriptional activation of VEGF in response to oxygen deprivation., Competing Interests: Declaration of competing interest I, Prof., Sun Chul Kang, would like to state that, the authors of the manuscript do not have any conflict of interest neither in terms of data nor money., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: There are insufficient studies on the effect of dietary salt intake on cardiovascular (CV) outcomes in chronic kidney disease (CKD) patients, and there is no consensus on the sodium (Na) intake level that increases the risk of CV disease in CKD patients. Therefore, we investigated the association between dietary salt intake and CV outcomes in CKD patients., Methods: In the Korean cohort study for Outcome in patients with CKD (KNOW-CKD), 1,937 patients were eligible for the study, and their dietary Na intake was estimated using measured 24h urinary Na excretion. The primary outcome was a composite of CV events and/or all-cause death. The secondary outcome was a major adverse cardiac event (MACE)., Results: Among 1,937 subjects, there were 205 (10.5%) events for the composite outcome and 110 (5.6%) events for MACE. Compared to the reference group (urinary Na excretion< 2.0g/day), the group with the highest measured 24h urinary Na excretion (urinary Na excretion ≥ 8.0g/day) was associated with increased risk of both the composite outcome (hazard ratio 3.29 [95% confidence interval 1.00-10.81]; P = 0.049) and MACE (hazard ratio 6.28 [95% confidence interval 1.45-27.20]; P = 0.013) in a cause-specific hazard model. Subgroup analysis also showed a pronounced association between dietary salt intake and the composite outcome in subgroups of patients with abdominal obesity, female, lower estimated glomerular filtration rate (< 60 ml/min per 1.73m 2 ), no overt proteinuria, or a lower urinary potassium-to-creatinine ratio (< 46 mmol/g)., Conclusion: A high-salt diet is associated with CV outcomes in non-dialysis CKD patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors EK and K-HO declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Kang, Kang, Ryu, Kim, Kim, Kang, Jeong, Kim, Kim, Kim, Kim and Oh.)

Colorectal cancer (CRC) was the second most commonly diagnosed cancer worldwide and the second most common cause of cancer-related deaths in Europe in 2020. After CRC patients' recovery, in many cases a patient's tumor returns and develops chemoresistance, which has remained a major challenge worldwide. We previously published our novel findings on the role of DA in inhibiting the activity of GDH1 using in silico and enzymatic assays. No studies have been conducted so far to explain the inhibitory role of DA against glutamate dehydrogenase in MDR-CRC cells. We developed a multidrug-resistant colorectal cancer cell line, HCT-116 MDR , after treatment with cisplatin and 5-fluorouracil. We confirmed the MDR phenotype by evaluating the expression of MDR1, ABCB5, extracellular vesicles, polyploidy, DNA damage response markers and GDH1 in comparison with parental HCT-116 WT (HCT-116 wild type). Following confirmation, we determined the IC 50 and performed clonogenic assay for the efficacy of decursinol angelate (DA) against HCT-116 MDR (HCT-116 multidrug resistant). Subsequently, we evaluated the novel interactions of DA with GDH1 and the expression of important markers regulating redox homeostasis and cell death. DA treatment markedly downregulated the expression of GDH1 at 50 and 75 μM after 36 h, which directly correlated with reduced expression of the Krebs cycle metabolites α-ketoglutarate and fumarate. We also observed a systematic dose-dependent downregulation of MDR1, ABCB5, TERT, ERCC1 and γH2AX. Similarly, the expression of important antioxidant markers was also downregulated. The markers for intrinsic apoptosis were notably upregulated in a dose-dependent manner. The results were further validated by flow cytometry and TUNEL assay. Additionally, GDH1 knockdown on both HCT-116 WT and HCT-116 MDR corresponded to a decreased expression of γH2AX, catalase, SOD1 and Gpx-1, and an eventual increase in apoptosis markers. In conclusion, inhibition of GDH1 increased ROS production, decreased cell proliferation and increased cell death.

Background: The prevalence of obesity in children and adolescents is increasing worldwide, which is of concern because obesity can lead to various complications such as metabolic syndrome (MS). Waist circumference (WC) and waist-height ratio (WHtR) are useful indicators of abdominal obesity and MS. In this study, we investigate trends in the prevalence of abdominal obesity and MS using two different references., Methods: Data from the Korea National Health and Nutrition Examination Survey (2007 to 2020) were used. In total, 21,652 participants aged 2 to 18 years and 9,592 participants aged 10 to 18 years were analyzed for abdominal obesity and MS, respectively. The prevalence of abdominal obesity and that of MS were compared using the Korean National Growth Chart in 2007 (REF2007) and the newly published WC and WHtR reference values in 2022 (REF2022)., Results: Both WC and WHtR showed an increasing trend. The prevalence of abdominal obesity was 14.71% based on REF2022, 5.85% points higher than that of 8.86% based on REF2007. MS based on REF2022 had a higher prevalence for both the National Cholesterol Education Program definition (3.90% by REF2007, 4.78% by REF2022) and the International Diabetes Federation definition (2.29% by REF2007, 3.10% by REF2022). The prevalence of both abdominal obesity and MS increased over time., Conclusion: The prevalence of abdominal obesity and MS increased in Korean children and adolescents from 2007 to 2020. When analyzed by REF2022, both abdominal obesity and MS showed higher prevalence rates than when using REF2007, indicating that previous reports were underestimated. Follow-up for abdominal obesity and MS using REF2022 is needed.

The gut microbiome is the community of healthy, and infectious organisms in the gut and its interaction in the host gut intestine (GI) environment. The balance of microbial richness with beneficial microbes is very important to perform healthy body functions like digesting food, controlling metabolism, and precise immune function. Alternately, this microbial dysbiosis occurs due to changes in the physiochemical condition, substrate avidity, and drugs. Moreover, various categories of diet such as "plant-based", "animal-based", "western", "mediterranean", and various drugs (antibiotic and common drugs) also contribute to maintaining microbial flora inside the gut. The imbalance (dysbiosis) in the microbiota of the GI tract can cause several disorders (such as diabetes, obesity, cancer, inflammation, and so on). Recently, the major interest is to use prebiotic, probiotic, postbiotic, and herbal supplements to balance such microbial community in the GI tract. But, there has still a large gap in understanding the microbiome function, and its relation to the host diet, drugs, and herbal supplements to maintain the healthy life of the host. So, the present review is about the updates on the microbiome concerns related to diet, drug, and herbal supplements, and also gives research evidence to improve our daily habits regarding diet, drugs, and herbal supplements. Because our regular dietary plan and traditional herbal supplements can improve our health by balancing the bacteria in our gut., Competing Interests: Conflict of interest statement The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023. Published by Elsevier GmbH.)

Long-standing scarcity of efficacious treatments and tumor heterogeneity have contributed to triple-negative breast cancer (TNBC), a subtype with a poor prognosis and aggressive behavior that accounts for 10-15% of all new cases of breast cancer. TNBC is characterized by the absence of progesterone and estrogen receptor expression and lacks gene amplification or overexpression of HER2. Genomic sequencing has detected that the unique mutational profile of both the somatic and germline modifications in TNBC is staggeringly dissimilar from other breast tumor subtypes. The clinical utility of sequencing germline BRCA1/2 genes has been well established in TNBC. Nevertheless, reports regarding the penetrance and risk of other susceptibility genes are relatively scarce. Recurring mutations (e.g., TP53 and PI3KCA mutations) occur together with rare mutations in TNBC, and the shared effects of genomic modifications drive its progression. Given the heterogeneity and complexity of this disease, a clinical understanding of the genomic modifications in TNBC can pave an innovative way toward its therapy. In this review, we summarized the most recent discoveries associated with the underlying biology of developmental signaling pathways in TNBC. We also summarize the recent advancements in genetics and epidemiology and discuss state-of-the-art vaccine-based therapeutic strategies for TNBC that will enable tailored therapeutics., 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 © 2023 Elsevier Inc. All rights reserved.)

Clostridium perfringens is a constituent of the normal gut microbiome in pigs; however, it can potentially cause pre- and post-weaning diarrhea. Nevertheless, the importance of this bacterium as a primary pathogen of diarrhea in piglets needs to be better understood, and the epidemiology of C. perfringens in Korean pig populations is unknown. To study the prevalence and typing of C. perfringens, 203 fecal samples were collected from diarrheal piglets on 61 swine farms during 2021-2022 and examined for the presence of C. perfringens and enteric viruses, including porcine epidemic diarrhea virus (PEDV). We determined that the most frequently identified type of C. perfringens was C. perfringens type A (CPA; 64/203, 31.5%). Among the CPA infections, single infections with CPA (30/64, 46.9%) and coinfections with CPA and PEDV (29/64, 45.3%) were the most common in diarrheal samples. Furthermore, we conducted animal experiments to investigate the clinical outcome of single infections and coinfections with highly pathogenic (HP)-PEDV and CPA in weaned piglets. The pigs infected with HP-PEDV or CPA alone showed mild or no diarrhea, and none of them died. However, animals that were co-inoculated with HP-PEDV and CPA showed more-severe diarrheal signs than those of the singly infected pigs. Additionally, CPA promoted PEDV replication in coinfected piglets, with high viral titers in the feces. A histopathological examination revealed more-severe villous atrophy in the small intestine of coinfected pigs than in singly infected pigs. This indicates a synergistic effect of PEDV and CPA coinfection on clinical disease in weaned piglets., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Our previous study revealed that tissue culture-adapted porcine epidemic diarrhea virus (PEDV) strains, namely KNU-141112-S DEL2/ORF3 and -S DEL5/ORF3, were attenuated to different extents in vivo, suggesting that their independent deletion (DEL) signatures, including 2-amino acid (aa; residues 56-57) or 5-aa (residues 56-60) DEL in the N-terminal domain (NTD) of the spike (S) protein, may contribute to the reduced virulence of each strain. To investigate whether each DEL in the NTD of the S1 subunit is a determinant for the virulence of PEDV, we generated two mutant viruses, named icS DEL2 and icS DEL5, by introducing the identical double or quintuple aa DEL into S1 using reverse genetics with an infectious cDNA clone of KNU-141112 (icKNU-141112). We then orally inoculated conventional suckling piglets with icKNU-141112, icS DEL2, or icS DEL5 to compare their pathogenicities. The virulence of both DEL mutant viruses was significantly diminished compared to that of icKNU-141112, which causes severe clinical signs and 100 % mortality. Interestingly, the degree of attenuation differed between the two mutant viruses: icS DEL5 caused neither diarrhea nor mortality, whereas icS DEL2 caused mild to moderate diarrhea, higher viral titers in feces and intestinal tissues, and 25 % mortality. Furthermore, the icS DEL5-infected piglets displayed no remarkable macroscopic and microscopic intestinal lesions, while the icS DEL2-infected piglets showed histopathological changes in small intestine tissues, including moderate-to-severe villous atrophy. Our data indicate that the loss of the pentad ( 56 GENQG 60 ) residues in S alone can be sufficient to give rise to an attenuated phenotype of PEDV., 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 © 2023 Elsevier B.V. All rights reserved.)

The diverse expression patterns of the tumor suppressor p53 in cancer cells reflect the regulatory efficiency of multiple cellular pathways. By contrast, many human tumors are reported to develop in the presence of wild-type p53. Recently, several oncogene inhibitors have been used clinically to suppress tumor development by functionally reactivating other oncoproteins. On the other hand, p53 reactivation therapies have not been well established, as few of the p53-MDM2 complex inhibitors such as Nutlin-3 induces mutation in p53 gene upon prolonged usage. Therefore, in this study CopA3, a 9-mer dimeric D-type peptide with anticancer activity against the human colorectal cancer cells, was used to explore the efficacy of p53 reactivation in-vitro and in-vivo. The anticancer activity of CopA3 was more selective towards the wild-type p53 expressing cells than the p53 deficient or mutant colorectal cancer cells. In response to this, this study investigated the signaling pathway in vitro and validated its anti-tumor activity in-vivo. The protein-peptide interaction and molecular docking efficiently provided insight into the specific binding affinity of CopA3 to the p53-binding pocket of the MDM2 protein, which efficiently blocked the p53 and MDM2 interaction. CopA3 plays a crucial role in the binding with MDM2 and enhanced the nuclear translocation of the p53 protein, which sequentially activated the downstream targets to trigger the autophagic mediated cell death machinery through the JNK/Beclin-1 mediated pathway. Collectively, CopA3 affected the MDM2-p53 interaction, which suppressed tumor development. This study may provide a novel inhibitor candidate for the MDM2-p53 complex, which could ultimately suppress the growth of colorectal cancer cells without being cytotoxic to the healthy neighboring cells present around the tumor microenvironment., Competing Interests: Declaration of competing interest We would like to state that, the authors of the manuscript do not have any conflict of interest neither in terms of data nor money., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Breast cancer (BC) is known to be the most common malignancy among women throughout the world. Plant-derived natural products have been recognized as a great source of anticancer drugs. In this study, the efficacy and anticancer potential of the methanolic extract of Monotheca buxifolia leaves using human breast cancer cells targeting WNT / β-catenin signaling was evaluated. We used methanolic and other (chloroform, ethyl acetate, butanol, and aqueous) extracts to discover their potential cytotoxicity on breast cancer cells (MCF-7). Among these, the methanol showed significant activity in the inhibition of the proliferation of cancer cells because of the presence of bioactive compounds, including phenols and flavonoids, detected by a Fourier transform infrared spectrophotometer and by gas chromatography mass spectrometry. The cytotoxic effect of the plant extract on the MCF-7 cells was examined by MTT and acid phosphatase assays. Real-time PCR analysis was performed to measure the mRNA expression of WNT-3a and β-catenin , along with Caspase-1,-3,-7, and -9 in MCF-7 cells. The IC50 value of the extract was found to be 232 μg/mL and 173 μg/mL in the MTT and acid phosphatase assays, respectively. Dose selection (100 and 300 μg/mL) was performed for real-time PCR, Annexin V/PI analysis, and Western blotting using Doxorubicin as a positive control. The extract at 100 μg/mL significantly upregulated caspases and downregulated the WNT-3a and β-catenin gene in MCF-7 cells. Western blot analysis further confirmed the dysregulations of the WNT signaling component (*** p< 0.0001). The results showed an increase in the number of dead cells in methanolic extract-treated cells in the Annexin V/PI analysis. Our study concludes that M. buxifolia may serve as an effective anticancer mediator through gene modulation that targets WNT / β-catenin signaling, and it can be further characterized using more powerful experimental and computational tools.