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Yu-Chi Tu,* Yu-Mei Wang,* Li-Jun Yao Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li-Jun Yao, Email ljyao@hust.edu.cnAbstract: DNA can be used for precise construction of complex and flexible micro-nanostructures, including DNA origami, frame nucleic acids, and DNA hydrogels. DNA nanomaterials have good biocompatibility and can enter macrophages via scavenger receptor-mediated endocytosis. DNA nanomaterials can be uniquely and flexibly designed to ensure efficient uptake by macrophages, which represents a novel strategy to regulate macrophage function. With the development of nanotechnology, major advances have been made in the design and manufacturing of DNA nanomaterials for clinical therapy. In diseases accompanied by macrophage disturbances including tumor, infectious diseases, arthritis, fibrosis, acute lung injury, and atherosclerosis, DNA nanomaterials received considerable attention as potential treatments. However, we lack sufficient information to guarantee precise targeting of macrophages by DNA nanomaterials, which precludes their therapeutic applications. In this review, we summarize recent studies of macrophage-targeting DNA nanomaterials and discuss the limitations and challenges of this approach with regard to its potential use as a biological therapy.Keywords: macrophages, DNA nanomaterials, therapy, macrophage-related diseases

Background: It is essential for nurses to have a solid understanding of what may influence the quality of life (QOL) among elderly residents within nursing homes. Although many factors have been demonstrated to be related to the QOL among elderly people, the relationship between perceived empowerment care and QOL among elderly residents within nursing homes has not been investigated thoroughly. Objectives: The aim of this study is to explore how demographic characteristics, perceived empowerment care and functional status affect perceived QOL among the elderly residents who reside in nursing homes. Design: This study employed a cross-sectional design. Settings: Eight nursing homes throughout southern Taiwan were recruited into this study. Participants: One hundred and two residents aged 65 years or older residing in nursing homes for at least 6 months, who did not have moderate to severe obstacles in cognitive ability, were recruited as participants. Methods: A questionnaire including demographic data, a physical function scale, an activity of daily living (ADL) scale, a patient empowerment scale, and a QOL index was used in this study. Results: The results showed a medium rating level of QOL among elderly residents. Elderly residents did not feel excessively disempowered care. Perceived empowering care, ADLs and marital status were significant predictors of QOL, which explained 45.3% of the total amount of variance in QOL. Perceived empowering care was the most important predictor of QOL. Conclusions: Nurses should pay attention to the effect of empowering care on QOL of elderly residents within nursing homes. Empowering care should be considered as a strategy of nursing care in nursing homes. [ABSTRACT FROM AUTHOR]

Myeloproliferative neoplasms (MPN) are a group of malignant myeloid tumors caused by hematopoietic stem cell proliferation. The discovery of gene mutations has elucidated the pathogenesis of MPN and provided molecular diagnostic criteria for MPN. Recent studies have shown that there are cytokine disorders in MPN patients, and the changes in the microenvironment caused by these cytokine disorders may have great significance for the pathophysiology and pathogenesis of MPN, which may lead to corresponding clinical symptoms and different prognosis in patients. In this review, the latest research progress on the role and status of cytokines in MPN will be summarized.

Chronic neutrophil leukemia (CNL) is a rare and life-threatening disease. Cases of CNL combined with lymphoma are rare. Here, we report a case of CNL with T-acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) in a 28-year-old male. After a regimen of ruxolitinib, VICLP (Vincristine, Idarubicin, Cyclophosphamide, Prednisone, Peg-asparaginase) regimen, high-dose cytarabine, and methotrexate regimens, the patient's bone marrow condition partially resolved. However, when the disease relapsed four months later, despite attempts with selinexor, venetoclax, and CAG(aclarubicin hydrochloride, Algocytidine, Granulocyte Stimulating Factor) chemotherapy, the leukocytes and peripheral blood primitive cells reduced, but the bone marrow did not achieve remission. This pathogenesis may be related to microenvironmental immune escape under prolonged inflammatory stimulation and gene disruption affecting protein function due to colony-stimulating factor 3 receptor gene (CSF3R) mutations. For this type of disease, early intervention may delay disease progression., (© 2024. The Author(s).)

Enhanced Sensorimotor Rhythm activity has been linked to increased automation in motor execution. Although existing research demonstrates the positive effects of SMR neurofeedback training on improving golf putting performance, its influence on golf long-game performance remains unexplored. This study sought to address this gap by involving seventeen professional female golfers (Age =24.63 ± 3.24 years, Handicap＝2.06 ± 1.18) in a crossover-designed experiment incorporating both NFT and a no-training control condition. During the study, participants executed 40 150-yard swings while receiving continuous SMR neurofeedback. Pre- and post-testing included visual analog scales to assess psychological processes associated with SMR activities, including attention engagement, conscious motor control, and physical relaxation levels. The results revealed that a single session of NFT effectively heightened SMR power irrespective of T1 (p = .02) or T2 (p = .03), which was observed with improved swing accuracy compared to the control conditions, particularly in "To Pin" (p = .04, the absolute distance to the hole after the ball comes to a stop). Subjective assessments further indicated that SMR NFT contributed to a sense of ease and tranquility during motor preparation for the golf swing (attention engagement: p = .01, conscious motor control: p = .033, physical relaxation: p = .013), and which offered valuable insights into the potential mechanisms underlying the impact of SMR NFT on long-game performance. Additionally, in such practical applications professional athletes can utilize our single-session neurofeedback protocol to train efficiently and cost-effectively before competitions, thereby enhancing their opportunity to achieve a higher rank., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Half of NSCLC patients harbor epidermal growth factor receptor (EGFR) mutations, and their therapeutic responses are remarkably different from patients with wild-type EGFR (EGFR-WT) NSCLC. We previously demonstrated that the hedgehog inhibitor vismodegib (Vis) potentiates paclitaxel (PTX)-induced cytotoxicity via suppression of Bax phosphorylation, which promotes accumulation of mitochondrial damage and apoptosis in EGFR-WT NSCLC cells. In this study, we further delineated the anticancer activity and underlying mechanisms of this combination treatment in EGFR-mutant NSCLC cells. MTS/PMS activity and trypan blue exclusion assays were used to assess cell viability. Apoptosis was monitored by chromosome condensation, annexin V staining, and cleavage of PARP and caspase-3. Western blots were conducted to track proteins of interest after treatment. Reactive oxygen species (ROS) level was monitored by 2',7'-dichlorodihydrofluorescein diacetate. Mitochondrial status was analyzed by tetramethylrhodamine, ethyl ester. Hedgehog signaling was induced by PTX, which rendered H1975 and PC9 cells insensitive to PTX-induced mitochondrial apoptosis via suppression of Bak. However, Vis enhanced PTX-induced Bak activation, leading to mitochondrial damage, ROS accumulation, and subsequent apoptosis. Our findings suggest that the combination of Vis and PTX could be a potential therapeutic strategy to increase PTX sensitivity of EGFR-mutant NSCLC., Competing Interests: Compliance with Ethical Standards Conflict of interest The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This study collected 80 samples of suspected kratom plant powder. A polymerase chain reaction sequence analysis was conducted using two sets of DNA barcode primers for plant ribosomal (r)DNA internal transcribed spacers (ITSs), namely, ITS3/ITS4 and ITS-p3/ITS-u4. Among the 80 samples, 40 were analyzed using the ITS3/ITS4 primer pair, and then DNA sequences were subjected to a National Center for Biotechnology Information-Basic Local Alignment Search Tool (NCBI-BLAST) comparison. Results showed that 29 samples had a 100% match (364/364) with Mitragyna speciosa (kratom), and 6 samples had a 99.73% match (363/364) with M. speciosa, whereas 5 samples had disordered and unreadable sequences. The 5 unreadable samples and an additional 40 suspected kratom samples were then analyzed using the ITS-p3/ITS-u4 primer pair, followed by an NCBI-BLAST comparison. Among these, 32 samples had a 100% match (404/404) with M. speciosa, and 11 samples had a 99.75% match (403/404) with M. speciosa. Among the samples with sequences matching M. speciosa, three distinct types were observed (no variance/404, 287M/404, and 287A/404). One sample had a 99.51% match (404/406) with Neolamarckia cadamba, and another sample had a sequencing length of 305 bp, with 25 positions showing mixed base pairs, indicating a mixture of different species. Analysis of the mixed base pair pattern suggested a possible mixture of M. speciosa and N. cadamba. Actually, M. speciosa and N. cadamba have very similar external morphologies. This indicates that the ITS-p3/ITS-u4 primer pair is effective in distinguishing mixtures of M. speciosa and N. cadamba and is thus more suitable than ITS3/ITS4 for identifying and analyzing samples of suspected kratom plant powder., (© 2024 Wiley‐VCH GmbH.)

Non-small cell lung cancer (NSCLC) is a common cancer with several accepted treatments, such as chemotherapy, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, and immune checkpoint inhibitors. Nevertheless, NSCLC cells often become insensitive to these treatments, and therapeutic resistance is a major reason NSCLC still has a high mortality rate. The induction of therapeutic resistance in NSCLC often involves hedgehog, and suppression of hedgehog can increase NSCLC cell sensitivity to several conventional therapies. In our previous work, we demonstrated that the marine antimicrobial peptide tilapia piscidin 4 (TP4) exhibits potent anti-NSCLC activity in both EGFR-WT and EGFR-mutant NSCLC cells. Here, we sought to further explore whether hedgehog might influence the sensitivity of NSCLC cells to TP4. Our results showed that hedgehog was activated by TP4 in both WT and EGFR-mutant NSCLC cells and that pharmacological inhibition of hedgehog by vismodegib, a Food and Drug Administration-approved hedgehog inhibitor, potentiated TP4-induced cytotoxicity. Mechanistically, vismodegib acted by enhancing TP4-mediated increases in mitochondrial membrane potential and intracellular reactive oxygen species (ROS). MitoTempo, a specific mitochondrial ROS scavenger, abolished vismodegib/TP4 cytotoxicity. The combination of vismodegib with TP4 also reduced the levels of the antioxidant proteins catalase and superoxide dismutase, and it diminished the levels of chemoresistance-related proteins, Bcl-2 and p21. Thus, we conclude that hedgehog regulates the cytotoxic sensitivity of NSCLC cells to TP4 by protecting against mitochondrial dysfunction and suppressing oxidative stress. These findings suggest that combined treatment of vismodegib and TP4 may be a promising therapeutic strategy for NSCLC., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

High glucose (HG)-induced endothelial cell (EC) and smooth muscle cell (SMC) dysfunction is critical in diabetes-associated atherosclerosis. However, the roles of heme oxygenase-1 (HO-1), a stress-response protein, in hemodynamic force-generated shear stress and HG-induced metabolic stress remain unclear. This investigation examined the cellular effects and mechanisms of HO-1 under physiologically high shear stress (HSS) in HG-treated ECs and adjacent SMCs. We found that exposure of human aortic ECs to HSS significantly increased HO-1 expression; however, this upregulation appeared to be independent of adenosine monophosphate-activated protein kinase, a regulator of HO-1. Furthermore, HSS inhibited the expression of HG-induced intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and reactive oxygen species (ROS) production in ECs. In an EC/SMC co-culture, compared with static conditions, subjecting ECs close to SMCs to HSS and HG significantly suppressed SMC proliferation while increasing the expression of physiological contractile phenotype markers, such as α-smooth muscle actin and serum response factor. Moreover, HSS and HG decreased the expression of vimentin, an atherogenic synthetic phenotypic marker, in SMCs. Transfecting ECs with HO-1-specific small interfering (si)RNA reversed HSS inhibition on HG-induced inflammation and ROS production in ECs. Similarly, reversed HSS inhibition on HG-induced proliferation and synthetic phenotype formation were observed in co-cultured SMCs. Our findings provide insights into the mechanisms underlying EC-SMC interplay during HG-induced metabolic stress. Strategies to promote HSS in the vessel wall, such as continuous exercise, or the development of HO-1 analogs and mimics of the HSS effect, could provide an effective approach for preventing and treating diabetes-related atherosclerotic vascular complications., (© 2024 Wiley Periodicals LLC.)

Ischemia-reperfusion injury (IRI) is a complex phenomenon. Although researchers have long been aware of IRI, its complex signaling events and potential therapeutic targets are still an active research area. The role of reactive oxygen species in IRI has garnered great interest among scientists. Recent studies have found that reactive oxygen species produced by IRI can activate redox-sensitive transient receptor potential channels (redox TRPs). The discovery of redox TRPs provides a new perspective for understanding the mechanism of IRI., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Published by IMR Press.)

Background and Aims: Besides hospital size, clinical diagnosis and severity of patient cases determine the total platelet usage. Therefore, the appropriateness of platelet usage could not be compared simply with the total units of platelet usage in each hospital. This study aimed to objectively monitor and analyze platelet usage after implementing a single-unit issuing policy for each platelet transfusion in our hospital in October 2020., Materials and Methods: We used three objective indices, X, Y, and Z, to monitor platelet usage and compared it with other hospitals. Three indices were generated by dividing the annual total units of platelet usage by the total annual reimbursement, total number of admissions, and average total reimbursement per admission for each hospital., Results: The new indices X and Y alleviated hospital size-dependent differences. Index Y was preferred over X because its value fluctuated less during the COVID-19 pandemic. The Z index was adjusted for the average total reimbursement per admission, and the results showed that more patients with higher disease complexity did not have increased platelet usage during the COVID-19 pandemic. In our hospital (H1), index Z decreased from 2019 to 2021 due to a policy of issuing a single unit for each platelet transfusion., Conclusion: These three objective indices are suitable for peer comparison and monitoring platelet usage in hospitals, irrespective of their size. They could be applied to promote patient blood management and provide an early response to the gradual shortage of blood resources owing to the aging population and declining birth rate in Taiwan., Competing Interests: The authors declare no conflict of interest., (© 2024 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

Objective: Various prediction scores have been developed to predict mortality in trauma patients, such as the shock index (SI), modified SI (mSI), age-adjusted SI (aSI), and the shock index (SI) multiplied by the alert/verbal/painful/unresponsive (AVPU) score (SIAVPU). The SIAVPU is a novel scoring system but its prediction accuracy for trauma outcomes remains in need of further validation. Therefore, we investigated the accuracy of four scoring systems, including SI, mSI, aSI, and SIAVPU, in predicting mortality, admission to the intensive care unit (ICU), and prolonged hospital length of stay ≥ 30 days (LOS)., Methods: This retrospective multicenter study used data from the Tzu Chi Hospital trauma database. The area under the receiver operating characteristic curve (AUROC) was determined for each outcome to assess their discrimination capabilities and comparing by Delong's test. Subgroup analyses were conducted to investigate the prediction accuracy of the SIAVPU in different patient populations., Results: In total, 5355 patients were included in the analysis. The median of SIAVPU were significantly higher among patients at those with major injury (1.47 vs 0.63), those admitted to the ICU (0.73 vs 0.62), those with prolonged hospital LOS≥ 30 days (0.83 vs 0.64), and those with mortality (1.08 vs 0.64). The AUROC of the SIAVPU was significantly higher than that of the SI, mSI, and aSI for 24-h mortality (AUROC: 0.845 vs 0.533, 0.540, and 0.678), 3-day mortality (AUROC: 0.803 vs 0.513, 0.524, and 0.688), 7-day mortality (AUROC: 0.755 vs 0.494, 0.505, and 0.648), in-hospital mortality (AUROC: 0.722 vs 0.510, 0.524, and 0.667), ICU admission (AUROC: 0.635 vs 0.547, 0.551, and 0.563). At the optimal cutoff value of 0.9, the SIAVPU had an accuracy of 82.2% for predicting 24-h mortality, 82.8% for predicting 3-day mortality, of 82.8% for predicting 7-day mortality, of 82.5% for predicting in-hospital mortality, of 73.9% for predicting Intensive Care Unit (ICU) admission, and of 81.7% for predicting prolonged hospital LOS ≥30 days., Conclusions: Our results reveal that SIAVPU has better accuracy than the SI, mSI, and aSI for predicting 24-h, 3-day, 7-day, and in-hospital mortality; ICU admission; and prolonged hospital LOS ≥30 days among patients with traumatic injury.

Rationale: Vascular calcification (VC) is a life-threatening complication in patients with chronic kidney disease (CKD) caused mainly by hyperphosphatemia. However, the regulation of VC remains unclear despite extensive research. Although serum- and glucocorticoid-induced kinase 3 (SGK3) regulate the sodium-dependent phosphate cotransporters in the intestine and kidney, its effect on VC in CKD remains unknown. Additionally, type III sodium-dependent phosphate cotransporter-1 (Pit-1) plays a significant role in VC development induced by high phosphate in vascular smooth muscle cells (VSMCs). However, it remains unclear whether SGK3 regulates Pit-1 and how exactly SGK3 promotes VC in CKD via Pit-1 at the molecular level. Thus, we investigated the role of SGK3 in the certified outflow vein of arteriovenous fistulas (AVF) and aortas of uremic mice. Methods and Results: In our study, using uremic mice, we observed a significant upregulation of SGK3 and calcium deposition in certified outflow veins of the AVF and aortas, and the increase expression of SGK3 was positively correlated with calcium deposition in uremic aortas. In vitro , the downregulation of SGK3 reversed VSMCs calcification and phenotype switching induced by high phosphate. Mechanistically, SGK3 activation enhanced the mRNA transcription of Pit-1 through NF-κB, downregulated the ubiquitin-proteasome mediated degradation of Pit-1 via inhibiting the activity of neural precursor cells expressing developmentally downregulated protein 4 subtype 2 (Nedd4-2), an E3 ubiquitin ligase. Moreover, under high phosphate stimulation, the enhanced phosphate uptake induced by SGK3 activation was independent of the increased protein expression of Pit-1. Our co-immunoprecipitation and in vitro kinase assays confirmed that SGK3 interacts with Pit-1 through Thr468 in loop7, leading to enhanced phosphate uptake. Conclusion: Thus, it is justifiable to conclude that SGK3 promotes VC in CKD by enhancing the expression and activities of Pit-1, which indicate that SGK3 could be a therapeutic target for VC in CKD., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

In June 2021, a yellow-throated marten (Martes flavigula chrysospila) submitted for postmortem examination was diagnosed as rabid through laboratory testing. The rabies virus detected was closest phylogenetically to viruses of ferret badgers (Melogale moschata subaurantiaca) in Taiwan, indicating spillover infection from the primary reservoir in this area, the ferret badger., (© Wildlife Disease Association 2024.)

Background: Osimertinib is the first-line therapy for patients with non-small cell lung cancer harboring epidermal growth factor receptor-activating alterations. Although osimertinib has been shown to elicit profound patient responses, cancer cells frequently develop additional alterations that sustain their proliferation capacity. This acquired resistance represents a substantial hurdle in precision medicine for patients with lung cancer., Methods: The biological and cellular properties of the G-quadruplex ligand BMVC-8C3O and its anticancer activities were evaluated in non-small cell lung carcinomas. In addition, combined treatment with BMVC-8C3O and osimertinib was evaluated for its effects on the growth of osimertinib-resistant tumors in vivo., Results: We demonstrate that BMVC-8C3O effectively suppresses c-FOS expression by stabilizing G-rich sequences located at the c-FOS promoter. The suppression c-FOS expression by BMVC-8C3O increases the sensitivity of acquired resistant cancer cells to osimertinib. Combining BMVC-8C3O and osimertinib has a synergistic effect in inhibiting the growth of acquired resistant cancers both in vitro and in mouse models. The combined inhibitory effect is not limited to BMVC-8C3O, either: several G-quadruplex ligands show varying levels of inhibition activity. We also show that simultaneous inhibition of both the c-FOS and PI3K/AKT pathways by BMVC-8C3O and osimertinib synergistically inhibits the growth of acquired resistant cancer cells., Conclusion: These findings unveil a synthetic lethal strategy to prevent and inhibit epidermal growth factor receptor-altered lung cancers with acquired osimertinib resistance. G-quadruplex ligands have the potential to be integrated into current osimertinib-based treatment regimens., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Calcium (Ca2+) plays a critical role in podocyte function. The Ca2+-sensitive receptors on the cell surface can sense changes in Ca2+ concentration, and Ca2+ flow into podocytes, after activation of Ca2+ channels (such as transient receptor potential canonical (TRPC) channels and N-type calcium channels) by different stimuli. In addition, the type 2 ryanodine receptor (RyR2) and the voltage-dependent anion channel 1 (VDAC1) on mitochondrial store-operated calcium channels (SOCs) on the endoplasmic reticulum maintain the Ca2+ homeostasis of the organelle. Ca2+ signaling is transmitted through multiple downstream signaling pathways and participates in the morphogenesis, structural maintenance, and survival of podocytes. When Ca2+ is dysregulated, it leads to the occurrence and progression of various diseases, such as focal segmental glomerulosclerosis, diabetic kidney disease, lupus nephritis, transplant glomerulopathy, and hypertensive renal injury. Ca2+ signaling is a promising therapeutic target for podocyte-related diseases. This review first summarizes the role of Ca2+ sensing, Ca2+ channels, and different Ca2+-signaling pathways in the biological functions of podocytes, then, explores the status of Ca2+ signaling in different podocyte-related diseases and its advances as a therapeutic target., Competing Interests: The authors declare no conflict of interest., (© 2023 The Author(s). Published by IMR Press.)

Non-small cell lung carcinomas (NSCLCs) commonly harbor activating mutations in the epidermal growth factor receptor (EGFR). Drugs targeting the tyrosine kinase activity of EGFR have shown effectiveness in inhibiting the growth of cancer cells with EGFR mutations. However, the development of additional mutations in cancer cells often leads to the persistence of the disease, necessitating alternative strategies to overcome this challenge. We explored the efficacy of stabilizing the G-quadruplex structure formed in the promoter region of EGFR as a means to suppress its expression and impede the growth of cancer cells with EGFR mutations. We revealed that the carbazole derivative BMVC-8C3O effectively suppressed EGFR expression and demonstrated significant growth inhibition in EGFR-mutated NSCLC cells, both in cell culture and mouse xenograft models. Importantly, the observed repression of EGFR expression and growth inhibition were not exclusive to carbazole derivatives, as several other G-quadruplex ligands exhibited similar effects. The growth-inhibitory activity of BMVC-8C3O is attributed, at least in part, to the repression of EGFR, although it is possible that additional cellular targets are also affected. Remarkably, the growth-inhibitory effect was observed even in osimertinib-resistant cells, indicating that BMVC-8C3O holds promise for treating drug-resistant NSCLC. Our findings present a promising and innovative approach for inhibiting the growth of NSCLC cells with EGFR mutations by effectively suppressing EGFR expression. The demonstrated efficacy of G-quadruplex ligands in this study highlights their potential as candidates for further development in NSCLC therapy., 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.)

Focal segmental glomerulosclerosis (FSGS), a podocyte disease, is the leading cause of end-stage renal disease (ESRD). Nevertheless, the current effective treatment for FSGS is deficient. Curcumin (CUR) is a principal curcuminoid of turmeric, which is a member of the ginger family. Previous studies have shown that CUR has renoprotective effects. However, the mechanism of CUR in anti-FSGS is not clear. This study aimed to explore the mechanism of CUR against FSGS through a combination of network pharmacological methods and verification of experiments. The analysis identified 98 shared targets of CUR against FSGS, and these 98 targets formed a network of protein-protein interactions (PPI). Of these 98 targets, AKT1, TNF, IL-6, VEGFA, STAT3, MAPK3, HIF1A, CASP3, IL1B, and JUN were identified as the hub targets. Molecular docking suggested that the best binding to CUR is MAPK3 and AKT1. Apoptotic process and cell proliferation were identified as the main biological processes of CUR against FSGS by gene ontology (GO) analysis. The most enriched signaling pathway in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was the PI3K-AKT signaling pathway. Western blots and flow cytometry showed that CUR could inhibit adriamycin (ADR) induced apoptosis, oxidative stress damage, and attenuate podocyte epithelial-mesenchymal transition (EMT) by repressing the AKT signaling pathway. Collectively, our study demonstrates that CUR can attenuate apoptosis, oxidative stress damage, and EMT in FSGS in vitro. These results supply a compelling basis for future studies of CUR for the clinical treatment of FSGS., Competing Interests: Declaration of competing interest 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 Elsevier Inc. All rights reserved.)

SLIT ligand and its receptor ROBO were initially recognized for their role in axon guidance in central nervous system development. In recent years, as research has advanced, the role of the SLIT-ROBO signaling pathway has gradually expanded from axonal repulsion to cell migration, tumor development, angiogenesis, and bone metabolism. As a secreted protein, SLIT regulates various pathophysiological processes in the kidney, such as proinflammatory responses and fibrosis progression. Many studies have shown that SLIT-ROBO is extensively involved in various aspects of kidney development and maintenance of structure and function. The SLIT-ROBO signaling pathway also plays an important role in different types of kidney disease. This article reviews the advances in the study of the SLIT-ROBO pathway in various renal pathophysiological and kidney disorders and proposes new directions for further research in this field., 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., (Copyright © 2023 Feng, Shu, Sun, Tu, Liao and Yao.)

Mesembryanthemum crystallinum L. (ice plant) develops salt tolerance during the transition from the juvenile to the adult stage through progressive morphological, physiological, biochemical, and molecular changes. Myo -inositol is the precursor for the synthesis of compatible solute D-pinitol and promotes Na+ transport in ice plants. We previously showed that supplying myo -inositol to 9-day-old seedlings alleviates salt damage by coordinating the expression of genes involved in inositol synthesis and transport, affecting osmotic adjustment and the Na/K balance. In this study, we examined the effects of myo -inositol on physiological parameters and inositol-related gene expression in early- and late-stage juvenile plants. The addition of myo -inositol to salt-treated, hydroponically grown late juvenile plants had no significant effects on growth or photosynthesis. In contrast, supplying exogenous myo -inositol to salt-treated early juvenile plants increased leaf biomass, relative water content, and chlorophyll content and improved PSII activity and CO2 assimilation. The treatment combining high salt and myo -inositol synergistically induced the expression of myo -inositol phosphate synthase (INPS ), myo -inositol O -methyltransferase (IMT ), and inositol transporters (INTs ), which modulated root-to-shoot Na/K ratio and increased leaf D-pinitol content. The results indicate that sufficient myo -inositol is a prerequisite for high salt tolerance in ice plant.

This study was to investigate three agents possible protective effect against DM-induced cardiovascular dysfunction in spontaneously hypertensive rats (SHR). Control group was fed normal diet, DM group was injected with STZ/NA and fed high fat diet (HFD), and treatment groups were given STZ/NA, fed HFD, and then oral gavaged with eugenosedin-A (Eu-A), glibenclamide (Gli), or pioglitazone (Pio) 5 mg/kg/per day for 4-week, respectively. Eu-A, Gli, and Pio clearly ameliorated the changes of body weight, cardiac weight, and the biochemical parameters, cardiovascular disorders and inflammation. Like Gli and Pio, Eu-A may be effectively to control DM and the cardiovascular dysfunction.

The mitochondrial calcium uniporter is a Ca 2+ channel that imports cytoplasmic Ca 2+ into the mitochondrial matrix to regulate cell bioenergetics, intracellular Ca 2+ signaling, and apoptosis. The uniporter contains the pore-forming MCU subunit, an auxiliary EMRE protein, and the regulatory MICU1/MICU2 subunits. Structural and biochemical studies have suggested that MICU1 gates MCU by blocking/unblocking the pore. However, mitoplast patch-clamp experiments argue that MICU1 does not block, but instead potentiates MCU via allosteric mechanisms. Here, we address this direct clash of the proposed MICU1 function. Supporting the MICU1-occlusion mechanism, patch-clamp demonstrates that purified MICU1 strongly suppresses MCU Ca 2+ currents, and this inhibition is abolished by mutating the MCU-interacting K126 residue. Moreover, a membrane-depolarization assay shows that MICU1 prevents MCU-mediated Na + flux into intact mitochondria under Ca 2+ -free conditions. Examining the observations underlying the potentiation model, we found that MICU1 occlusion was not detected in mitoplasts not because MICU1 cannot block, but because MICU1 dissociates from the uniporter complex. Furthermore, MICU1 depletion reduces uniporter transport not because MICU1 can potentiate MCU, but because EMRE is down-regulated. These results firmly establish the molecular mechanisms underlying the physiologically crucial process of uniporter regulation by MICU1.

Efficient diode-pumped passively Q-switched Nd:YVO 4 yellow and orange lasers are developed with the pulse pumping scheme and the intracavity stimulated Raman scattering (SRS) and second harmonic generation (SHG). A Np-cut KGW is exploited in the SRS process to generate the yellow 579 nm laser or the orange 589 nm laser in a selectable way. The high efficiency is achieved by designing a compact resonator to include a coupled cavity for intracavity SRS and SHG and to provide a focused beam waist on the saturable absorber for reaching an excellent passive Q-switching. The output pulse energy and peak power can reach 0.08 mJ and 50 kW for the orange laser at 589 nm. On the other hand, the output pulse energy and peak power can be up to 0.10 mJ and 80 kW for the yellow laser at 579 nm.

The prevalence rate of hyperuricemia remains high in Taiwan, at 21.6% in men and 9.57% in women. Both metabolic syndrome (MetS) and hyperuricemia can cause many complications; however, few studies have evaluated the correlation between MetS and hyperuricemia. Therefore, in this observational cohort study, we explored associations between metabolic syndrome (MetS) and its components and new-onset hyperuricemia. Of 27,033 individuals in the Taiwan Biobank who had complete follow-up data, we excluded those with hyperuricemia at baseline ( n = 4871), those with gout at baseline ( n = 1043), those with no data on baseline uric acid ( n = 18), and those with no data on follow-up uric acid ( n = 71). The remaining 21,030 participants (mean age 50.8 ± 10.3 years) were enrolled. We found a significant association between new-onset hyperuricemia with MetS and the components of MetS (hypertriglyceridemia, abdominal obesity, low high-density lipoprotein cholesterol, hyperglycemia, and high blood pressure). Furthermore, compared to those without any MetS components, those with one MetS component (OR = 1.816), two MetS components (OR = 2.727), three MetS components (OR = 3.208), four MetS components (OR = 4.256), and five MetS components (OR = 5.282) were significantly associated with new-onset hyperuricemia (all p < 0.001). MetS and its five components were associated with new-onset hyperuricemia in the enrolled participants. Further, an increase in the number of MetS components was associated with an increase in the incidence rate of new-onset hyperuricemia., Competing Interests: The authors declare no conflict of interest.

Classical swine fever (CSF) is a systemic hemorrhagic disease affecting domestic pigs and wild boars. The modified live vaccine (MLV) induces quick and solid protection against CSF virus (CSFV) infection. Maternally derived antibodies (MDAs) via colostrum could interfere with the MLV's efficacy, leading to incomplete protection against CSFV infection for pigs. This study investigated CSFV transmission among experimental piglets with various post-MLV immune statuses. Nineteen piglets, 18 with MDAs and 1 specific-pathogen-free piglet infected with CSFV that served as the CSFV donor, were cohabited with piglets that had or had not been administered the MLV. Five-sixths of the piglets with MDAs that had been administered one dose of MLV were fully protected from contact transmission from the CSFV donor and did not transmit CSFV to the piglets secondarily exposed through cohabitation. Cell-mediated immunity, represented by the anti-CSFV-specific interferon-γ-secreting cells, was key to viral clearance and recovery. After cohabitation with a CSFV donor, the unvaccinated piglets with low MDA levels exhibited CSFV infection and spread CSFV to other piglets through contact; those with high MDA levels recovered but acted as asymptomatic carriers. In conclusion, MLV still induces solid immunity in commercial herds under MDA interference and blocks CSFV transmission within these herds.

Ischemia-reperfusion injury (IRI) contributes to acute kidney injury (AKI) and development of chronic kidney disease. We describe an IRI protocol for mice via flank incisions approach, using a pedicle clamp to cause ischemic injury. Compared with trans-abdominal approach, it is technically easier with lesser fluid loss and organ injury. Technical challenges during the dissection of renal pedicles are highlighted. For complete details on the execution of this protocol, please refer to Lai et al. (2014)., Competing Interests: Declaration of interests The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Serum- and glucocorticoid-induced kinase 3 (SGK3), which is ubiquitously expressed in mammals, is regulated by estrogens and androgens. SGK3 is activated by insulin and growth factors through signaling pathways involving phosphatidylinositol-3-kinase (PI3K), 3-phosphoinositide-dependent kinase-1 (PDK-1), and mammalian target of rapamycin complex 2 (mTORC2). Activated SGK3 can activate ion channels (TRPV5/6, SOC, Kv1.3, Kv1.5, Kv7.1, BKCa, Kir2.1, Kir2.2, ENaC, Nav1.5, ClC-2, and ClC Ka), carriers and receptors (Npt2a, Npt2b, NHE3, GluR1, GluR6, SN1, EAAT1, EAAT2, EAAT4, EAAT5, SGLT1, SLC1A5, SLC6A19, SLC6A8, and NaDC1), and Na + /K + -ATPase, promoting the transportation of calcium, phosphorus, sodium, glucose, and neutral amino acids in the kidney and intestine, the absorption of potassium and neutral amino acids in the renal tubules, the transportation of glutamate and glutamine in the nervous system, and the transportation of creatine. SGK3-sensitive transporters contribute to a variety of physiological and pathophysiological processes, such as maintaining calcium and phosphorus homeostasis, hydro-salinity balance and acid-base balance, cell proliferation, muscle action potential, cardiac and neural electrophysiological disturbances, bone density, intestinal nutrition absorption, immune function, and multiple substance metabolism. These processes are related to kidney stones, hypophosphorous rickets, multiple syndromes, arrhythmia, hypertension, heart failure, epilepsy, Alzheimer's disease, amyotrophic lateral sclerosis, glaucoma, ataxia idiopathic deafness, and other diseases., 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., (Copyright © 2022 Liao, Dong, Zhang, Shu, Tu and Yao.)

Background: Ischemic stroke poses a major threat to human health and represents the third leading cause of death worldwide and in Taiwan. Post-acute care (PAC) training has been reported to be beneficial for post-index stroke events. However, knowledge is still lacking on the outcome of stroke events with cardiac origin. The focus of the current study is to investigate the effectiveness of PAC in this subgroup of patients as well as identify key baseline pointers that are capable of early prediction of patients' physical recovery. In addition, the authors hypothesize that the routinely arranged non-invasive carotid duplex that evaluates the characteristics of the carotid lumen could play a significant role in providing an early outcome prediction., Methods: For the current research, 142 ischemic stroke patients with underlying cardiac arrhythmia (atrial fibrillation) were retrospectively recruited. The patients' basic demographics, neuroimaging, carotid duplex, and basic biochemistry datasets were accurately documented. The pre and post-admission National Institutes of Health Stroke Scale (NIHSS) (6-month follow-ups), Barthel Index, and mRS score (12-month follow-ups) were also recorded. All statistical analyses were performed using R for Windows (version 3.6.3). Barthel Index, NIHSS, and mRS scores obtained before and after hospitalization were compared to determine the patients' outcomes and were classified as improved or unimproved. A multivariate logistic analysis was designed and applied to assess the significance of risk factors and to obtain the odds ratios (ORs). The receiver operating characteristic (ROC) curve and the Youden Index was used to find the important cut-off point information, and the area under the curve (AUC) was calculated to provide accuracy., Results: The average age of the 142 ischemic stroke patients enrolled in the current study was about 66 years, of which 88 patients were male and 54, female. Many of them had other comorbidities: 86 patients had mixed hyperlipidemia (60.56%), 115 had hypertension (80.99%), and 49 suffered from diabetes mellitus (34.51%). The mRS showed an improvement in the condition of only 40 patients (28.175%), whereas the Barthel Index showed improvement in 71 patients (50%), and 68 patients (47.89%) showed recovery on the NIHSS. The Barthel Index and NIHSS were selected because they already had an almost equal number of samples among the improved and unimproved groups (50%), rather than mRS, which had a lower number (28.17%) of improved cases. While conducting the EuroQol-5 Dimension (EQ-5D) assessment, anxiety/depression stood out as the most prominent issue, affecting 44 patients (30.99%). Self-care was another factor that was involved in the ongoing improvement of 36 patients (25.35%). Multivariate logistic analysis of both NIHSS and Barthel Index showed improvement with a contralateral plaque index statistical significance (P<0.05), whereas NIHSS showed a relevant significance in anxiety/depression and Barthel Index registered usual activity in the data analysis (P<0.05). ROC curve and Youden index analysis showed similar results in both NIHSS and Barthel Index of contralateral plaque index of 4.5, this being the cutoff point value for this group of patients., Conclusion: In the current study, nearly half of the enrolled patients showed favorable functional recovery. The outcome assessments seem to correlate well with NIHSS and Barthel Index scores, rather than mRS. The anxiety/depression and usual activities domains of the EQ-5D results are associated with and have a great impact after the patients undertake the PAC rehabilitative strategy. Moreover, the variables obtained through carotid duplex and plaque index might also play a significant role in determining the patient's functional outcome., 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., (Copyright © 2022 Liu, Hsu, Tu, Lin, Wang, Lee, Shih, Chou and Lin.)

Lumpy skin disease is an arthropod-borne bovine disease caused by lumpy skin disease virus. A suspect lumpy skin disease case in a breeding cattle farm on Kinmen Island, Taiwan was reported on July 8, 2020 and later confirmed the first occurrence of lumpy skin disease in the country by molecular biological detections, electron microscopy, and sequence comparison. Implementation of control measures including blanket vaccination on the island effectively ceased the outbreaks. Phylogenetic analyses revealed that the virus discovered in the outbreaks was most similar to those identified in China in 2019. Identifying this virus in the coastal areas in East Asia indicated the rapid eastward spread of lumpy skin disease in Asia.

Objective: T-LAK-cell-originated protein kinase (TOPK), a PSD95-Disc large-ZO1 (PDZ) binding kinase (PBK), is a novel member of the mitogen-activated protein kinase (MAPK) family. Studies have shown that TOPK plays a critical role in the function of tumor cells, including apoptosis and mitosis. However, little is known on the effect of TOPK in cisplatin-induced acute kidney injury (CP-AKI). This study aimed to investigate the role and mechanism of TOPK in CP-AKI., Methods: Cisplatin was administered to C57BL/6 mice and cultured kidney tubular epithelial cells (TECs) to establish the CP-AKI murine or cellular models. TECs were then stimulated with the specific inhibitor of TOPK OTS514 or transfected with the recombinant-activated plasmid TOPK-T9E to inhibit or activate TOPK. The TECs were treated with AKT inhibitor VIII following stimulation with OTS514 or cisplatin. Western blotting and flow cytometry were used to evaluate the cell cycle and apoptosis of TECs., Results: The analysis revealed that the TOPK activity was significantly suppressed by cisplatin, both in vivo and in vitro. Furthermore, the pharmacological inhibition of TOPK by OTS514, a specific inhibitor of TOPK, exacerbated the cisplatin-induced cell cycle arrest in the G2/M phase and apoptosis of cultured TECs. Moreover, the TOPK activation via the TOPK-T9E plasmid transfection could partially reverse the cell cycle arrest at the G2/M phase and apoptosis of cisplatin-treated TECs. In addition, AKT/protein kinase B (PKB), as a TOPK target protein, was inhibited by cisplatin in cultured TECs. The pharmaceutical inhibition of AKT further aggravated the apoptosis of TECs induced by cisplatin or TOPK inhibition. TOPK systematically mediated the apoptosis via the AKT pathway in the CP-AKI cell model., Conclusion: These results indicate that TOPK activation protects against CP-AKI by ameliorating the G2/M cell cycle arrest and cell apoptosis., (© 2022. The Author(s).)

Bat lyssaviruses were identified in Taiwan's bat population during 2016-2017. The lyssavirus surveillance system was continuously conducted to understand the epidemiology. Through this system, the found dead bats were collected for lyssavirus detection by direct fluorescent antibody test and reverse transcription polymerase chain reaction. Three bats were identified as positive during 2018-2021. A novel lyssavirus, designated as Taiwan bat lyssavirus 2, was detected in a Nyctalus plancyi velutinus . This lyssavirus had less than 80% nucleotide identity in the nucleoprotein (N) gene with other lyssavirus species, forming a separate branch in the phylogenetic analysis. The other two cases were identified in Pipistrellus abramus (Japanese pipistrelles); they were identified to be similar to the former lyssavirus identified in 2016-2017, which was renominated as Taiwan bat lyssavirus 1 (TWBLV-1) in this study. Even though one of the TWBLV-1 isolates showed high genetic diversity in the N gene compared with other TWBLV-1 isolates, it may be a TWBLV-1 variant but not a new species based on its high amino acid identities in the nucleoprotein, same host species, and same geographic location as the other TWBLV-1.

Bacteria commonly form aggregates in a range of coral species [termed coral-associated microbial aggregates (CAMAs)], although these structures remain poorly characterized despite extensive efforts studying the coral microbiome. Here, we comprehensively characterize CAMAs associated with Stylophora pistillata and quantify their cell abundance. Our analysis reveals that multiple Endozoicomonas phylotypes coexist inside a single CAMA. Nanoscale secondary ion mass spectrometry imaging revealed that the Endozoicomonas cells were enriched with phosphorus, with the elemental compositions of CAMAs different from coral tissues and endosymbiotic Symbiodiniaceae, highlighting a role in sequestering and cycling phosphate between coral holobiont partners. Consensus metagenome-assembled genomes of the two dominant Endozoicomonas phylotypes confirmed their metabolic potential for polyphosphate accumulation along with genomic signatures including type VI secretion systems allowing host association. Our findings provide unprecedented insights into Endozoicomonas -dominated CAMAs and the first direct physiological and genomic linked evidence of their biological role in the coral holobiont.

We demonstrate the interplay of pure spin current, spin-polarized current, and spin fluctuation in 3d Ni&#95;{x}Cu&#95;{1-x}. By tuning the compositions of the Ni&#95;{x}Cu&#95;{1-x} alloys, we separate the effects due to the pure spin current and spin-polarized current. By exploiting the interaction of spin current with spin fluctuation in suitable Ni-Cu alloys, we obtain an unprecedentedly high spin Hall angle of 46%, about 5 times larger than that in Pt, at room temperature. Furthermore, we show that spin-dependent thermal transport via anomalous Nernst effect can serve as a sensitive magnetometer to electrically probe the magnetic phase transitions in thin films with in-plane anisotropy. The enhancement of spin Hall angle by exploiting spin current fluctuation via composition control makes 3d magnets functional materials in charge-to-spin conversion for spintronic application.

In past researches, we had been proved the action mechanism of pre-germinated brown rice (PGBR) to treat metabolic syndrome and diabetes mellitus. This study was to investigate the protective effect of PGBR in high fructose and high fat-induced non-alcoholic fatty liver disease (NAFLD) in rodents. WKY rats were divided into: Control group was fed normal drinking water and diet; FLD group was fed 10% high-fructose-water (HFW) and high-fat-diet (HFD); PGBR group was given HFW, and HFD mixed PGBR. After four weeks, the body, hepatic and cardiac weight gains of FLD group had significant increases than that of Control group. The enhanced blood pressure and heart rate, hypertriglyceridemia, hyperuricemia, and higher liver function index (GPT levels) were observed; meanwhile, the IL-6 and TNF-α levels of serum, and TG level of liver were also elevated in FLD group. The related protein expressions of lipid synthesis, inflammation, cardiac fibrosis, and hypertrophy were deteriorated by HFW/HFD. However, in treatment group, PGBR decreased all above influenced parameters, additionally GOT; and related protein expressions. PGBR treated HFW/HFD-induced NAFLD and cardiac complications might be via improving lipid homeostasis, and inhibiting inflammation. Together, PGBR could be used as a healthy food for controlling NAFLD and its' cardiac dysfunction., Competing Interests: No potential conflicts of interest were disclosed., (Copyright © 2022 JCBN.)

Background: Vaccination is an important intervention to prevent the incidence and spread of serious diseases. Many factors including information obtained from the internet influence individuals' decisions to vaccinate. Misinformation is a critical issue and can be hard to detect, although it can change people's minds, opinions, and decisions. The impact of misinformation on public health and vaccination hesitancy is well documented, but little research has been conducted on the relationship between the size of the population reached by misinformation and the vaccination decisions made by that population. A number of fact-checking services are available on the web, including the Islander news analysis system, a free web service that provides individuals with real-time judgment on web news. In this study, we used such services to estimate the amount of fake news available and used Google Trends levels to model the spread of fake news. We quantified this relationship using official public data on COVID-19 vaccination in Taiwan., Objective: In this study, we aimed to quantify the impact of the magnitude of the propagation of fake news on vaccination decisions., Methods: We collected public data about COVID-19 infections and vaccination from Taiwan's official website and estimated the popularity of searches using Google Trends. We indirectly collected news from 26 digital media sources, using the news database of the Islander system. This system crawls the internet in real time, analyzes the news, and stores it. The incitement and suspicion scores of the Islander system were used to objectively judge news, and a fake news percentage variable was produced. We used multivariable linear regression, chi-square tests, and the Johnson-Neyman procedure to analyze this relationship, using weekly data., Results: A total of 791,183 news items were obtained over 43 weeks in 2021. There was a significant increase in the proportion of fake news in 11 of the 26 media sources during the public vaccination stage. The regression model revealed a positive adjusted coefficient (β=0.98, P=.002) of vaccine availability on the following week's vaccination doses, and a negative adjusted coefficient (β=-3.21, P=.04) of the interaction term on the fake news percentage with the Google Trends level. The Johnson-Neiman plot of the adjusted effect for the interaction term showed that the Google Trends level had a significant negative adjustment effect on vaccination doses for the following week when the proportion of fake news exceeded 39.3%., Conclusions: There was a significant relationship between the amount of fake news to which the population was exposed and the number of vaccination doses administered. Reducing the amount of fake news and increasing public immunity to misinformation will be critical to maintain public health in the internet age., (©Yen-Pin Chen, Yi-Ying Chen, Kai-Chou Yang, Feipei Lai, Chien-Hua Huang, Yun-Nung Chen, Yi-Chin Tu. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 26.04.2022.)

Objective: To investigate the effect of RUNX2 gene overexpression vector modified exosomes derived from bone marrow mesenchymal stem cells (BMSCs) combined with calcium carbonate scaffold system in bone defect., Methods: Rabbit BMSCs were used as the research object, and BMSCs were identified by flow cytometry. Construct RUNX2 gene overexpression vector, transfect BMSCs with lentivirus, and collect exosomes by ultracentrifugation. The morphology of exosomes was observed by transmission electron microscope, the expression of exosome marker CD63 was detected by Western blot, and the calcium carbonate scaffold was constructed by three chamber parallel automatic temperature control reaction system. According to whether the RUNX2 gene overexpression vector was transfected or not, the complex of BMSCs and calcium carbonate scaffold was divided into three groups, namely BMSCs group, RUNX2 overexpression group and exosome group. The osteogenic differentiation of BMSCs was detected by oil red O staining and RT-PCR. There were 9 clean adult healthy male New Zealand white rabbits, aged (12.97±1.21) months, with a body weight of (19.3±3.6) kg, with 3 rabbits in each group. The animal model of skull defect was constructed by surgical method, and the repair of bone defect was evaluated by imaging, he staining and Masson staining., Results: The results of flow cytometry showed that the expression of CD29 protein, CD44 protein, CD11b protein and CD45 protein on the surface of BMSCs were 99.5%, 100%, 0.1% and 0.1%, respectively. Transmission electron microscopy showed that the exosomes were bilayer vesicles with a diameter of 50 to 150 nm. Western blot showed that the molecular marker CD63 of exosomes was positive. Oil red O staining showed that the osteogenic differentiation of BMSCs in exosome group was significantly higher than that in RUNX2 overexpression group and BMSCs group. The results of RT-PCR showed that the relative expressions of RUNX2, BMP-2 and ALP mRNA in BMSCs in exosome group were significantly higher than those in RUNX2 overexpression group and BMSCs group ( P <0.05). The imaging results showed that the repair effect of skull defect in exosome group was better than that in RUNX2 overexpression group. HE staining and Masson staining showed that the repair effect of skull defect in exosome group was better than that in RUNX2 overexpression group ( P <0.05). MSCs in exosome group was significantly higher than that in RUNX2 overexpression group and BMSCs group. The results of RT-PCR showed that the relative expressions of RUNX2, BMP-2 and ALP mRNA in BMSCs in exosome group were significantly higher than those in RUNX2 overexpression group and BMSCs group( P <0.05). The imaging results showed that the repair effect of skull defect in exosome group was better than that in RUNX2 overexpression group. HE staining and Masson staining showed that the repair effect of skull defect in exosome group was better than that in RUNX2 overexpression group( P <0.05)., Conclusion: Compared with RUNX2 gene overexpression vector transfection, extraction of exosomes directly can promote the differentiation of BMSCs into osteoblasts more efficiently, and the combination with calcium carbonate scaffold can better promote the healing of bone defects. So as to provide new ideas and methods for the clinical treatment of bone defects.

The use of medium cut-off (MCO) polyarylethersulfone and polyvinylpyrrolidone blend membrane is an emerging mode in hemodialysis. Recent studies have shown that MCO membranes exhibit a middle high molecular weight uremic toxin clearance superior to standard high flux hemodialysis. We conducted a systematic literature review and meta-analysis of randomized controlled trials to investigate whether MCO membranes efficiently increase the reduction ratio of middle molecules, and to explore the potential clinical applications of MCO membranes. We selected articles that compared beta 2-microglobulin (β2M), kappa free light chain (κFLC), lambda free light chain (λFLC), interleukin-6 (IL-6), and albumin levels among patients undergoing hemodialysis. Five randomized studies with 328 patients were included. The meta-analysis demonstrated a significantly higher reduction ratio of serum β2M (p < 0.0001), κFLC (p < 0.0001), and λFLC (p = 0.02) in the MCO group. No significant difference was found in serum IL-6 levels after hemodialysis. Albumin loss was observed in the MCO group (p = 0.04). In conclusion, this meta-analysis study demonstrated the MCO membranes’ superior ability to clear β2M, κFLC, and λFLC. Serum albumin loss is an issue and should be monitored. Further studies are expected to identify whether MCO membranes could significantly improve clinical outcomes and overall survival.

Chamaecyparis formosensis is an endemic species of Taiwan, threatened from intensive use and illegal felling. An individual identification system for C. formosensis is required to provide scientific evidence for court use and deter illegal felling. In this study, 36 polymorphic simple sequence repeat markers were developed. By applying up to 28 non-linked of the developed markers, it is calculated that the cumulative random probability of identity (CP I ) is as low as 1.652 × 10 -12 , and the identifiable population size is up to 60 million, which is greater than the known C. formosensis population size in Taiwan. Biogeographical analysis data show that C. formosensis from four geographic areas belong to the same genetic population, which can be further divided into three clusters: SY (Eastern Taiwan), HV and GW (Northwestern Taiwan), and MM (Southwestern Taiwan). The developed system was applied to assess the provenance of samples with 88.44% accuracy rate and therefore can serve as a prescreening tool to reduce the range required for comparison. The system developed in this study is a potential crime-fighting tool against illegal felling., (© 2022. The Author(s).)

Non-small cell lung cancer (NSCLC) is one of the most common and deadly cancers worldwide. Among NSCLC patients, almost half have wild-type epidermal growth factor receptor (EGFR WT). The primary therapeutic option for these EGFR WT NSCLC patients is chemotherapy, while NSCLC patients with EGFR mutations have more diverse therapeutic options, including EGFR tyrosine kinase inhibitors. Moreover, NSCLC patients with EGFR WT have worse chemotherapy response than EGFR mutant NSCLC patients. Thus, an urgent need exists for novel therapeutic strategies to improve chemotherapy response in EGFR WT NSCLC patients. Hedgehog signaling is known to be highly active in NSCLC; however, its potential role in chemoresistance is not fully understood. In the present study, we found that paclitaxel (PTX) treatment induces hedgehog signaling in EGFR WT NSCLC cells, and inhibition of hedgehog signaling with GDC-0449 (Vismodegib) increases sensitivity to PTX-stimulated apoptosis. Furthermore, GDC-0449 potentiates PTX-induced reactive oxygen species and mitochondrial dysfunction. In contrast, a hedgehog agonist, Hh-Ag1.5, attenuates PTX-induced apoptosis. Mechanistic experiments revealed that hedgehog induces phosphorylation of Akt at Ser473. Akt then phosphorylates Bax at Ser184, which can switch its activity from pro-apoptosis to anti-apoptosis. Taken together, our findings suggest that inhibition of hedgehog signaling might be a promising therapeutic strategy to improve PTX response in EGFR WT NSCLC., 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., (Copyright © 2022 Tu, Yeh, Yu, Lee and Su.)

Serum and glucocorticoid-inducible kinase 3 (SGK3) is involved in maintaining podocyte function by regulating the protein levels of podocin and CD2-associated protein. Nephrin is also one of the slit diaphragm proteins of podocytes, but whether SGK3 participates in podocyte injury by regulating the levels of nephrin remains unclear. In this study, we focused on whether SGK3 affects nephrin levels and the mechanisms involved in the same. In the kidneys of adriamycin (ADR)-induced podocyte injury mouse model, the protein levels of SGK3 and nephrin were significantly decreased. Furthermore, the expression of SGK3 was negatively correlated with the output of proteinuria, and positively correlated with the levels of nephrin. In ADR-treated conditionally immortalized mouse podocyte cells (MPCs), the protein levels of nephrin and SGK3 were inhibited, while the constitutive expression of SGK3 reversed the ADR-induced decline in nephrin protein levels. Furthermore, ADR treatment or SGK3 inactivation enhanced the ubiquitin-proteasome degradation of nephrin in MPCs, and dramatically activated downstream effector proteins of SGK3, neural precursor cells expressing developmentally downregulated protein 4 subtype 2 (Nedd4-2) and glycogen synthase kinase-3 β (GSK3β). Similarly, Nedd4-2 or GSK3β overexpression resulted in increased activity of Nedd4-2 or GSK3β, and significantly downregulated nephrin levels. Interestingly, ubiquitin-mediated protein degradation of nephrin was regulated by Nedd4-2, rather than by GSK3β. In summary, SGK3 inactivation downregulated the levels of nephrin by increasing Nedd4-2 and GSK3β activity in ADR-induced podocyte injury model; in particular, the SGK3/Nedd4-2 signaling pathway was found to be involved in ubiquitin-mediated proteasome degradation of nephrin., 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., (Copyright © 2022 Dong, Li, Zhang, Shu, Tu, Liao and Yao.)

Cisplatin-induced acute kidney injury (CP-AKI) is a severe complication in patients receiving CP chemotherapy. However, effective therapies for CP-AKI are currently lacking. Curcumin (CUR), a natural polyphenol, is extracted from the rhizome of turmeric and has been reported to have nephroprotective activity. However, the role of CUR in CP-AKI remains unclear. This study aimed to explore the mechanism of CUR in CP-AKI by combining a network pharmacology approach with experimental validations. The analysis revealed 176 potential targets of CUR based on the HERB database and 1,286 related targets of CP-AKI from the GeneCards, DrugBank, and OMIM databases. Further, 106 common targets of CUR against CP-AKI were obtained, and these common targets constructed a protein-protein interaction (PPI) network. In addition, the core targets were screened from the PPI network using Cytoscape. Molecular docking revealed that CUR displayed the best binding to AKT1. Gene Ontology (GO) analysis indicated that the primary biological processes of CUR against CP-AKI included cellular response to chemical stress and apoptotic regulation. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis suggested that the PI3K-Akt signaling pathway was most significantly enriched in CUR against CP-AKI. Western blotting and flow cytometry showed that CUR inhibited apoptosis induced by CP by activating the Akt signaling pathway in human kidney tubular epithelial cells (HK-2). Altogether, our findings demonstrated that CUR alleviated apoptosis by activating the Akt signaling pathway in CP-AKI in vitro . These data provide a scientific basis for future investigations into the clinical application of CUR against CP-AKI.

Objective: To explore the effects of siRNA hsa-circ-0000885 modified bone marrow mesenchymal stem cells (BMSCs) on osteogenic differentiation, cell proliferation and apoptosis in order to provide new ideas and methods for the clinical treatment of osteoporosis (OP)., Methods: From September 2018 to February 2020, 13 patients with osteoporosis admitted to our hospital were selected as the research objects, including 11 females and 2 males, with an age of (65.45±10.77) years old. After obtaining the informed consent of patients, peripheral blood tissues were extracted. Then the expression level of cir-cRNA in peripheral blood mononuclear cells(PBMC) was detected by circ RNA chip. The expression of circ RNA was silenced by siRNA technology. The BMSCs were transfected with lentivirus. According to the siRNA interference plasmid hsa-circ-0000885, the cells were divided into the blank group, the empty vector group and the siRNA interference group. After 72 hours of treatment, the cell cycle was detected by flow cytometry, the apoptosis level was detected by AV-PI kit, and the osteogenic differentiation ability of BMSCs was detected by ALP staining., Results: The expression of hsa-circ-0000885 in PBMC of patients with osteoporosis was significantly higher than that of healthy controls ( t =2.119, P <0.05). ALP staining showed that siR-NA hsa-circ-0000885 could promote the osteogenic differentiation of BMSCs, which was obviously too much in the blank group and blank plasmid group ( F =9.132, q =2.995, 2.897; P =0.009, 0.012<0.05). The results of CCK-8 showed that siRNA hsa-circ-0000885 could promote the proliferation of BMSCs, which was significantly higher than that of the blank group and blank plasmid group ( F =9.881, q =2.457, 2.904; P =0.032, 0.016<0.05). The results of AV-PI showed that the apoptosis rate of siRNA interference group was significantly lower than that of blank group and blank plasmid group( F =10.208; q =2.885, 3.001; P =0.019, 0.011<0.05)., Conclusion: The lentivirus mediated siRNA hsa-circ-0000885 plasmid transfected into BMSCs and osteoclast co culture system can promote cell proliferation, inhibit apoptosis and promote osteogenic differentiation of BMSCs, which can be used as a potential therapeutic target for OP patients.

Objectives: To examine whether urinary excretion of cysteine-rich protein 61 (Cyr61), an acknowledged proinflammatory factor in kidney pathologies, increases in chronic kidney disease (CKD) and is associated with subsequent rapid kidney function decline., Design: An observational cohort study., Setting: In the nephrology outpatient clinics of a tertiary hospital in Taiwan., Participants: We enrolled 138 adult CKD outpatients (n=12, 32, 18, 18, 29 and 29 in stages 1, 2, 3a, 3b, 4 and 5 CKD, respectively) between February and October 2014 and followed them for 1 year. Their mean age was 60.46±13.16 years, and 51 (37%) of them were women., Primary Outcome Measures: Urinary Cyr61 levels were measured by ELISA. Rapid kidney function decline was defined as an estimated glomerular filtration rate (eGFR) decline rate ≥ 4 mL/min/1.73 m 2 /year or developing end-stage renal disease during subsequent 3-month or 1-year follow-up period. Models were adjusted for demographic and clinical variables., Results: The urine Cyr61-to-creatinine ratio (UCyr61CR) increased significantly in patients with stage 4 or 5 CKD. Multivariable linear regression analysis showed that log(UCyr61CR) was positively correlated with log(urine protein-to-creatinine ratio) (p<0.001) but negatively correlated with baseline eGFR (p<0.001) and hypertension (p=0.007). Complete serum creatinine data during the follow-up were available for 112 patients (81.2%). Among them, multivariable logistic regression identified log(UCyr61CR) was independently associated with rapid kidney function decline (adjusted OR 2.29, 95% CI 1.27 to 4.15) during the subsequent 3 months. UCyr61CR improved the discriminative performance of clinical models to predict 3-month rapid kidney function decline. In contrast, log(UCyr61CR) was not associated with rapid eGFR decline during the entire 1-year follow-up., Conclusions: Elevated urinary Cyr61 excretion is associated with rapid short-term kidney function deterioration in patients with CKD. Measuring urinary Cyr61 excretion is clinically valuable for monitoring disease trajectory and may guide treatment planning., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

People are constantly exposed to blue light while engaging in work. It is thus crucial to understand if vast exposure to blue light influences cognitive control, which is essential for working efficiently. Previous studies proposed that the stimulation of intrinsically photosensitive retinal ganglion cells (ipRGCs), a newly discovered photoreceptor that is highly sensitive to blue light, could modulate non-image forming functions. Despite studies that showed blue light (or ipRGCs) enhances brain activations in regions related to cognitive control, how exposure to blue light changes our cognitive control behaviorally remains elusive. We examined whether blue light influences cognitive control through three behavioral tasks in three studies: the sustained attention to response task (SART), the task-switching paradigm, and the Stroop task. Classic effects of the SART, switch cost, and the Stroop effect were found, but no differences were observed in results of different background lights across the six experiments. Together, we conclude that these domains of cognitive control are not influenced by blue light and ipRGCs, and whether the enhancement of blue light on brain activities extends to the behavioral level should be carefully re-examined., (© 2021. The Author(s).)

This study involved a simulation of transportation and basic life support on ambulances carrying coronavirus disease 2019 (COVID-19) patients, using a specially modified mannequin. The mannequin used can spew a fluorescent solution from its mouth to simulate the droplets or vomitus made by the patient and can be detected using ultraviolet light illumination. We determined that the most frequently contaminated areas of an ambulance in the driver's cabin are the left front door's outer handle, driver's handler, gear lever, and mat. The most frequently contaminated area in the rear patient's cabin is the rear door, rear door lining, and handle over the roof. The most frequently contaminated areas before the removal of personal protective equipment (PPE) are the lower chest to the belly area, bilateral hands, lower rim of the gown, and shoes. After the removal of PPE, traces of fluorescence were observed over the neck, hands, and legs. We therefore suggest taking a bath immediately after PPE removal., Competing Interests: There is no conflics of interest., (Copyright © 2021 by Taiwan Society of Emergency Medicine & Ainosco Press. All Rights Reserved.)