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Ta-Liang Chen,1,2,* Chao-Shun Lin,2–4 Jui-An Lin,1,2 Chun-Chieh Yeh,5,6 Li-Chin Sung,7 Yi-Cheng Chang,8 Chun-Chuan Shih,9,10,* Chien-Chang Liao2–4,11,12 1Department of Anesthesiology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; 2Department of Anesthesiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 3Department of Anesthesiology, Taipei Medical University Hospital, Taipei, Taiwan; 4Anesthesiology and Health Policy Research Center, Taipei Medical University Hospital, Taipei, Taiwan; 5Department of Surgery, China Medical University Hospital, Taichung, Taiwan; 6Department of Surgery, University of Illinois, Chicago, IL, USA; 7Division of Cardiology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan; 8Division of Endocrinology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; 9School of Chinese Medicine for Post-Baccalaureate, College of Medicine, I-Shou University, Kaohsiung, Taiwan; 10Ph.D. Program in Clinical Drug Development of Herbal Medicine, College of Pharmacy, Taipei Medical University, Taipei, Taiwan; 11Research Center of Big Data and Meta-Analysis, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; 12School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan*These authors contributed equally to this workCorrespondence: Chien-Chang LiaoDepartment of Anesthesiology, Taipei Medical University Hospital, 252 Wuxing St., Taipei 11031, TaiwanTel +886-2-2737-2181, ext. 8310Fax +886-2-2736-7344Email jacky48863027@yahoo.com.twObjective: This study aimed to evaluate the risk of incident diabetes between people who used lovastatin and red yeast rice (RYR) prescriptions.Methods: A retrospective cohort study was performed to analyze the real-world database of Taiwan’s National Health Insurance. We identified the RYR cohort, which included 34,504 persons age 20 years or older who began their use of a RYR prescription in 2010–2014. A comparison cohort of 34,504 adults beginning the use of lovastatin was selected from the same dataset, which was matched by age and sex. Both cohorts had no diabetes before the use of the medications. Events of incident diabetes in 2000–2015 were ascertained from medical claims. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of incident diabetes associated with the use of RYR prescriptions were calculated.Results: The incidences of diabetes for the RYR cohort and the lovastatin cohort were 1.01 and 2.59 per 100 person-years, respectively (P < 0.0001). Compared with the lovastatin cohort, the adjusted HR of incident diabetes was 0.46 (95% CI 0.43–0.50) for people who used RYR prescriptions. The association between reduced incident diabetes and use of RYR prescriptions was significant in various subgroups. There was a dose-response relationship between RYR prescriptions and the reduced risk of incident diabetes.Conclusion: We raised the possibility that people who used RYR prescriptions may have a lower risk of incident diabetes compared with the lovastatin cohort.Keywords: diabetes, lovastatin, red yeast rice, risk

Fai Lam,1–4 Chun-Chuan Shih,5 Ta-Liang Chen,4,6 Chao-Shun Lin,2–4 Hsiao-Ju Huang,7 Chun-Chieh Yeh,8,9 Yu-Chen Huang,10,11 Hung-Yi Chiou,1,* Chien-Chang Liao2–4,11,12,* 1School of Public Health, College of Public Health, Taipei Medical University, Taipei, Taiwan; 2Department of Anesthesiology, Taipei Medical University Hospital, Taipei, Taiwan; 3Anesthesiology and Health Policy Research Center, Taipei Medical University Hospital, Taipei, Taiwan; 4Department of Anesthesiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 5School of Chinese Medicine for Post-Baccalaureate, I-Shou University, Kaohsiung, Taiwan; 6Department of Anesthesiology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; 7Devision of Chinese Medicine, An Nan Hospital, China Medical University, Tainan, Taiwan; 8Department of Surgery, China Medical University Hospital, Taichung, Taiwan; 9Department of Surgery, University of Illinois, Chicago, IL, USA; 10Department of Dermatology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; 11Research Center of Big Data and Meta-Analysis, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; 12School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan*These authors contributed equally to this workCorrespondence: Chien-Chang LiaoDepartment of Anesthesiology, Taipei Medical University Hospital, Taipei 110, TaiwanTel +886-2-27372181 ext. 8310Fax +886-2-27367344Email jacky48863027@yahoo.com.twObjective: Urticaria is a mast cell-related disease caused severe itching and the lifetime prevalence of urticaria is about 20% in general population. Our purpose is to evaluate risk of urticaria in geriatric stroke patients received influenza vaccination (IV).Methods: In a cohort of 192,728 patients with newly diagnosed stroke aged over 65 years obtained from 23 million people in Taiwan’s National Health Insurance between 2000 and 2008, we identified 9890 stroke patients who received IV and 9890 propensity score-matched stroke patients who did not receive IV. Controlling for immortal time bias, both the IV and non-IV groups were followed for one year. Urticaria events were identified during the follow-up period. We calculated the adjusted rate ratios (RRs) and 95% confidence intervals (CIs) of the one-year risk of urticaria associated with IV.Results: During the follow-up period of one year, stroke patients with IV had a significantly higher risk of urticaria compared with non-IV stroke patients (RR 1.81, 95% CI 1.47–2.23). An increased risk of urticaria in stroke patients with IV was noted in both sexes, patients 65–84 years of age, patients with comorbid medical conditions, and various time intervals of follow-up. Vaccinated stroke patients with hemorrhage (RR 4.00, 95% CI 1.76–9.10) and those who received intensive care (RR 5.14, 95% CI 2.32–11.4) had a very high risk of urticaria compared with those without IV.Conclusion: Receiving IV may be associated with an increased risk of urticaria in stroke patients. We could not infer the causality from the current results because of this study’s limitations. Future investigations are needed to evaluate the possible mechanism underlying the association between IV and urticaria.Keywords: urticaria, stroke, influenza vaccination

Shu-Wen Weng,1,* Ta-Liang Chen,2–4 Chun-Chieh Yeh,5,6 Hsin-Long Lane,7 Chien-Chang Liao,2–4,8,* Chun-Chuan Shih7,9 1Department of Chinese Medicine, Taichung Hospital, Ministry of Health and Welfare, Taichung, Taiwan; 2Department of Anesthesiology, Taipei Medical University Hospital, Taipei, Taiwan; 3Anesthesiology and Health Policy Research Center, Taipei Medical University Hospital, Taipei, Taiwan; 4Department of Anesthesiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 5Department of Surgery, China Medical University Hospital, Taichung, Taiwan; 6Department of Surgery, University of Illinois, Chicago, IL, USA; 7School of Chinese Medicine for Post-Baccalaureate, I-Shou University, Kaohsiung, Taiwan; 8School of Chinese Medicine, China Medical University, Taichung, Taiwan; 9Program for the Clinical Drug Discovery from Botanical Herbs, Taipei Medical University, Taipei, Taiwan *These authors contributed equally to this work Objective: To compare the long-term risk of epilepsy in stroke patients who use Bu Yang Huan Wu Tang (BYHWT) and those who do not. Methods: In the Taiwanese national insurance claims data, we identified newly diagnosed stroke patients receiving inpatient care in the years 2000–2004. Using propensity score-matched pairs to balance the baseline characteristics, we selected eligible stroke patients who did (n=8,971) and did not (n=8,971) receive BYHWT. These two groups were followed up until the end of 2009 to track the occurrence of epilepsy. We used Cox proportional hazard models to calculate the adjusted HRs and 95% CIs for post-stroke epilepsy during the follow-up period according to BYHWT use. Results: Compared with the control group, stroke patients with BYHWT had a reduced risk of epilepsy during the 5–9 years of the follow-up period (HR 0.69, 95% CI 0.61–0.77). The association between BYHWT and reduced post-stroke epilepsy was significant in various subgroups of stroke patients. There was a dose-dependent decrease in the frequency of epilepsy with increasing quantities of BYHWT use from 1 package (HR 0.77, 95% CI 0.66–0.90) to ≥6 packages (HR 0.52, 95% CI 0.42–0.65). Conclusion: Stroke patients who received BYHWT therapy had a reduced long-term risk of epilepsy, and the beneficial effect could be observed in various subgroups. However, future clinical trials will be necessary to corroborate the present findings and identify the biochemical mechanism involved. Keywords: stroke, epilepsy, Bu Yang Huan Wu Tang, long-term risk

High uniformity enhancement-mode (E-mode) and depletion-mode (D-mode) InGaP/InGaAs pseudomorphic high electron mobility transistors (pHEMTs) have been developed on 6 inch GaAs substrate using a selective succinic acid gate recess process. The 0.5 µm long gate fingers of E-mode and D-mode pHEMTs are deposited simultaneously in this process simplification. The InGaP/InGaAs E-mode pHEMT exhibits a maximum drain-to-source current (Ids) of 460 mA mm−1, and a maximum transconductance (gm) of 430 mS mm−1. At 5.2 GHz operation, 216 mW mm−1 power density, 40% power-added efficiency and a 0.81 dB minimum noise figure (NFmin) are also achieved for the E-mode device. In this study, D-mode pHEMTs are applied for a switch monolithic microwave integrated circuit which provides an insertion loss of −1.8 dB and isolation of −9.2 dB under 28 dBm input power (Pin) and 5.5 GHz operation. From these measured results, this uniform E/D-mode InGaP/InGaAs pHEMT technology exhibits a high potential for WLAN applications. [ABSTRACT FROM AUTHOR]

GaAs-based pseudomorphic high electron mobility transistors (pHEMTs) in which the field-plate (FP) is connected to the gate terminal and the source terminal, were developed and evaluated experimentally to determine their microwave and power performance. The small gate-to-drain feedback capacitance (Cgd) and the stable FP-induced depletion region at high input power (Pin) of the source-terminated FP pHEMT (FP-S pHEMT) greatly improve the power and linearity of the FP-S pHEMT above those of the gate-terminated FP pHEMT (FP-G pHEMT). The power ratio of the fundamental to the third-order inter-modulation product (IM3) is 18.8 dBc for FP-S pHEMT for Pin = 0 dBm; the corresponding value for FP-G pHEMT is 12.4 dBc. These experimental results indicate that the FP architecture is more effective at high-power operation and exhibits high linearity in high-power pHEMT applications. [ABSTRACT FROM AUTHOR]

Introduction: Sepsis-induced immunosuppression may result in death. The mechanisms of immune suppression include loss of macrophage and monocyte expression of the major histocompatibility complex, increased anti-inflammatory cytokine expression and decreased expression of proinflammatory cytokines. In this study, we sought to determine the mechanisms of immune suppression in severe sepsis by repeated detection.Methods: We designed this prospective observational study to measure monocyte human leukocyte antigen (HLA)-DR expression, plasma cytokine levels and cytokine responses on days 1 and 7 in stimulated peripheral blood mononuclear cells (PBMCs) of healthy controls and patients with severe sepsis.Results: Of the 35 enrolled patients, 23 survived for 28 days and 12 died, 6 of whom died within 7 days. Plasma levels of IL-1β, IL-6, IL-10, IL-17, transforming growth factor (TGF)-β1 and TNF-α were higher, but plasma IL-12 level was lower in septic patients than those in controls. Day 1 plasma levels of IL-1β, IL-6, IL-10 and TGF-β1 in nonsurvivors were higher than those in survivors. Day 7 plasma IL-10 levels in nonsurvivors were higher than in survivors. IL-1β response was higher, but IL-12 and TNF-α responses were lower in septic patients than in controls. Day 1 IL-6 response was lower, but day 1 TGF-β1 response was higher in nonsurvivors than in survivors. Plasma IL-6 and IL-10 levels were decreased in survivors after 6 days. IL-6 response was decreased in survivors after 6 days, but IL-12 response was increased. Monocyte percentage was higher, but positive HLA-DR percentage in monocytes and mean fluorescence intensity (MFI) of HLA-DR were lower in septic patients than in controls. MFI of HLA-DR was increased in survivors after 6 days.Conclusions: Monocyte HLA-DR expression and IL-12 response from PBMCs are restored in patients who survive severe sepsis. [ABSTRACT FROM AUTHOR]

With the rise of skin-like electronics, devices are increasingly coming into close contact with the human body, creating a demand for polymer semiconductors (PSCs) that combine stretchability with reliable electrical performance. However, balancing mechanical robustness with high carrier mobility remains a challenge. To address this, tris(pentafluorophenyl)borane (BCF) for Lewis acid doping is proposed to improve charge mobility while enhancing stretchability by increasing structural disorder. Through systematic investigation, several key structural principles have been identified to maximize the effectiveness of BCF doping in stretchable PSCs. Notably, increasing the lamellar stacking distance and reducing crystallinity facilitate the incorporation of BCF into the alkyl side-chain regions, thereby enhancing both mobility and stretchability. Conversely, stronger Lewis base groups in the main chain negatively impact these improvements. These results demonstrate that with a small addition of BCF, a two-fold increase in carrier mobility is achieved while simultaneously enhancing the crack onset strain to 100%. Furthermore, doped PSCs exhibit stable mobility retention under repeated 30% strains over 1000 cycles. This method of decoupling carrier mobility from mechanical properties opens up new avenues in the search for high-mobility stretchable PSCs., (© 2024 Wiley‐VCH GmbH.)

Cerebral reperfusion injury in stroke, stemming from interconnected thrombotic and inflammatory signatures, often involves platelet activation, aggregation and its interaction with various immune cells, contributing to microvascular dysfunction. However, the regulatory mechanisms behind this platelet activation and the resulting inflammation are not well understood, complicating the development of effective stroke therapies. Utilizing animal models and platelets from hemorrhagic stroke patients, our research demonstrates that human cerebral dopamine neurotrophic factor (CDNF) acts as an endogenous antagonist, mitigating platelet aggregation and associated neuroinflammation. CDNF moderates mitochondrial membrane potential, reactive oxygen species production, and intracellular calcium in activated platelets by interfering with GTP binding to Rap1b, thereby reducing Rap1b activation and downregulating the Rap1b-MAPK-PLA2 signaling pathway, which decreases release of the pro-inflammatory mediator thromboxane A2. In addition, CDNF reduces the inflammatory response in BV2 microglial cells co-cultured with activated platelets. Consistent with ex vivo findings, subcutaneous administration of CDNF in a rat model of ischemic stroke significantly reduces platelet activation, aggregation, lipid mediator production, infarct volume, and neurological deficits. In summary, our study highlights CDNF as a promising therapeutic target for mitigating platelet-induced inflammation and enhancing recovery in stroke. Harnessing the CDNF pathway may offer a novel therapeutic strategy for stroke intervention., Competing Interests: Declaration of interests M.S. is one of inventors of the CDNF-related patent (7452969), which is owned by the Herantis Pharma Company (Espoo, Finland)., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Adult height has been associated with handgrip strength, which is a surrogate marker of physical frailty. However, it is uncertain if this association is causative or due to confounding bias., Methods: We evaluated pairwise associations among handgrip strength, adult height, and genetically determined height (using a polygenic score [PGS] for height in a mediation framework and a 2-sample Mendelian randomization approach) by means of a multivariable regression model using a prospective cohort of Chinese living in Singapore. We additionally evaluated pathway enrichments of height-related genes in relation to increased handgrip strength to discover common biological mechanisms underlying associations of genetically determined height with handgrip strength., Results: Height PGS exhibited a positive association with handgrip strength at late life after adjusting for midlife body weight and other baseline exposures (cigarette smoking, education, and physical activity status, p = 1.2 × 10-9). Approximately 66.4% of the total effect of height PGS on handgrip strength was mediated through adult height (βindirect-effect = 0.034, pindirect-effect = 1.4 × 10-40). Two-sample Mendelian randomization evaluations showed a consistent causal relationship between increased height and increased handgrip strength in late life (p between 6.6 × 10-4 and 3.9 × 10-18), with insignificant horizontal pleiotropic effects (pMR-Egger intercept = 0.853). Pathway analyses of genes related to both increased adult height and handgrip strength revealed enrichment in ossification and adipogenesis pathways (padj between .034 and 6.8 × 10-4)., Conclusions: The study highlights a potentially causal effect between increased adult height and increased handgrip strength in late life, which may be explained by related biological processes underlying the preservation of muscle mass and strength in aging., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Industrial wastewater management is a significant global challenge. Sludge microbiota from swine farms may play a crucial role in enhancing wastewater treatment processes, thereby reducing water pollution from industrial activities. A deeper understanding of this complex community could lead to innovative approaches for improving wastewater treatment methods. Sludge samples were collected from the anaerobic, sedimentation, and thickening tanks of ten swine farms. The microbiota communities were analyzed using 16S rRNA full-length sequencing on the PacBio platform, with subsequent data analysis conducted on the QIIME2 platform utilizing the SILVA database. Compared to anaerobic and thickening tanks, the sedimentation tanks exhibited a unique profile of sludge microbiota, with higher abundances of the phyla Proteobacteria, Bacteroidota, and Caldatribacteriota. Additionally, sludges from farms already utilized in processing industrial water-specifically farms B, G, and J-contained higher concentrations of bacteria (>20 ng/μL), indicating the robustness of the bacterial load for practical industrial use. Furthermore, sludge from farms with higher alpha diversity, such as E, G, I, and J, exhibited enriched degradation profiles, including the degradation of aromatic compounds, polymers, industrial compounds, toluene, and vanillin. The farms were categorized based on wastewater ammonia nitrogen degradation levels, revealing a clustering effect of the microbiota from the sedimentation tanks in the Principal Coordinates Analysis (PCoA) plot. A higher relative abundance of the families Rhodocyclaceae , AKYH767 , and Comamonadaceae , and a lower abundance of the families Anaerolineaceae and Christensenellaceae , were found in groups with high ammonia nitrogen reduction, suggesting potential targets for bioaugmentation strategies. In conclusion, this study underscores the critical role of microbial abundance, composition, and biodiversity in optimizing wastewater treatment and advocates for comprehensive microbiota analysis to identify suitable sludge for industrial applications., Competing Interests: 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., (© 2024 The Authors. Published by Elsevier Ltd.)

Conjugated polymer sorting is recognized as an efficient and scalable method for the selective extraction of semiconducting single-walled carbon nanotubes (s-SWCNTs). However, this process typically requires the use of nonpolar and aromatic solvents as the dispersion medium, which are petroleum-based and carry significant production hazards. Moreover, there is still potential for improving the efficiency of batch purification. Here, this study presents fluorene-based conjugated polymer that integrates diamines containing ethylene glycol chains (ODA) as linkers within the main chain, to effectively extract s-SWCNTs in bio-renewable solvents. The introduction of ODA segments enhances the solubility in bio-renewable solvents, facilitating effective wrapping of s-SWCNTs in polar environments. Additionally, the ODA within the main chain enhances affinity to s-SWCNTs, thereby contributing to increased yields and purity. The polymer achieves a high sorting yield of 55% and a purity of 99.6% in dispersion of s-SWCNTs in 2-Methyltetrahydrofuran. Thin-film transistor arrays fabricated with sorted s-SWCNTs solution through slot-die coating exhibit average charge carrier mobilities of 20-23 cm 2  V⁻¹ s⁻¹ and high on/off current ratios exceeding 10 5 together with high spatial uniformity. This study highlights the viability of bio-renewable solvents in the sorting process, paving the way for the eco-friendly approach to the purification of SWCNTs., (© 2024 Wiley‐VCH GmbH.)

We planned to explore the protective activities of extract of Phyllanthus emblica L. (EPE) on insulin resistance and metabolic disorders including hyperlipidemia, visceral obesity, and renal dysfunction in high-fat diet (HFD)-progressed T2DM mice. Mice treatments included 7 weeks of HFD induction followed by EPE, fenofibrate (Feno), or metformin (Metf) treatment daily for another 4-week HFD in HFD-fed mice. Finally, we harvested blood to analyze some tests on circulating glycemia and blood lipid levels. Western blotting analysis was performed on target gene expressions in peripheral tissues. The present findings indicated that EPE treatment reversed the HFD-induced increases in blood glucose, glycosylated HbA1 C , and insulin levels. Our findings proved that treatment with EPE in HFD mice effectively controls hyperglycemia and hyperinsulinemia. Our results showed that EPE reduced blood lipid levels, including a reduction in blood triglyceride (TG), total cholesterol (TC), and free fatty acid (FFA); moreover, EPE reduced blood leptin levels and enhanced adiponectin concentrations. EPE treatment in HFD mice reduced BUN and creatinine in both blood and urine and lowered albumin levels in urine; moreover, EPE decreased circulating concentrations of inflammatory NLR family pyrin domain containing 3 (NLRP3) and kidney injury molecule-1 (KIM-1). These results indicated that EPE displayed antihyperglycemic and antihyperlipidemic activities but alleviated renal dysfunction in HFD mice. The histology examinations indicated that EPE treatment decreased adipose hypertrophy and hepatic ballooning, thus contributing to amelioration of lipid accumulation. EPE treatment decreased visceral fat amounts and led to improved systemic insulin resistance. For target gene expression levels, EPE enhanced AMP-activated protein kinase (AMPK) phosphorylation expressions both in livers and skeletal muscles and elevated the muscular membrane glucose transporter 4 (GLUT4) expressions. Treatment with EPE reduced hepatic glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK) expressions to suppress glucose production in the livers and decreased phosphorylation of glycogen synthase kinase 3β (GSK3β) expressions to affect hepatic glycogen synthesis, thus convergently contributing to an antidiabetic effect and improving insulin resistance. The mechanism of the antihyperlipidemic activity of EPE involved a decrease in the hepatic phosphorylation of mammalian target of rapamycin complex C1 (mTORC1) and p70 S6 kinase 1 (S6K1) expressions to improve insulin resistance but also a reduction in hepatic sterol regulatory element binding protein (SREBP)-1c expressions, and suppression of ACC activity, thus resulting in the decreased fatty acid synthesis but elevated hepatic peroxisome proliferator-activated receptor (PPAR) α and SREBP-2 expressions, resulting in lowering TG and TC concentrations. Our results demonstrated that EPE improves insulin resistance and ameliorates hyperlipidemia in HFD mice.

Introduction: Dysregulated host response to infection causes life-threatening organ dysfunction. Excessive inflammation and abnormal blood coagulation can lead to disseminated intravascular coagulation (DIC) and multiple-organ failure in the late sepsis stages. Platelet function impairment in sepsis contributes to bleeding, secondary infection, and tissue injury. Platelet transfusion is considered in patients with sepsis with DIC and bleeding; however, its benefits are limited and of low quality. Fibrinogen plays a crucial role in platelet function, and establishing a fibrin network binds to activated integrin αIIbβ3 and promotes outside-in signaling that amplifies platelet functions. However, the role of fibrinogen in sepsis-induced platelet dysfunction remains unclear., Materials and Methods: We evaluated the effects of fibrinogen on platelet hyporeactivity during septic shock in adult male Wistar rats using lipopolysaccharide (LPS) injection and cecal ligation and puncture (CLP) surgery. Changes in the hemodynamic, biochemical, and coagulation parameters were examined. Platelet activation and aggregation were measured using whole-blood assay, 96-well plate-based aggregometry, and light-transmission aggregometry. Additionally, platelet adhesion, spreading, and fibrin clot retraction were evaluated., Results: Rats with LPS- and CLP-induced sepsis displayed considerable decreases in plasma fibrinogen levels and platelet aggregation, adhesion, spreading, and clot retraction. The aggregation of platelets obtained from rats with sepsis was markedly augmented by fibrinogen supplementation. Additionally, fibrinogen administration improved platelet adhesion, spreading, and clot retraction in rats with sepsis., Conclusions: Fibrinogen supplementation could serve as a potential therapeutic intervention for alleviating platelet hyporeactivity in patients with sepsis and bleeding., Competing Interests: Declaration of competing interest All authors declared that they have no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Heatstroke is a critical heat-related condition characterized by coagulopathy and multiple organ dysfunction. One of the most severe complications of heatstroke is disseminated intravascular coagulation. This condition manifests as excessive clot formation and bleeding that are primarily due to platelet depletion and dysfunction. Fibrinogen plays a crucial role in hemostasis because it links integrin αIIbβ3 on adjacent platelets, thereby promoting the platelet activation and aggregation necessary for clot formation. However, reduced fibrinogen levels may impair the formation of the initial platelet plug and increase the risk of bleeding. The current study explored the effect of fibrinogen on platelet dysfunction in a heatstroke model., Materials and Methods: Male Wistar rats were subjected to heat stress, and subsequent changes in hemodynamic, biochemical, and coagulation parameters were analyzed. Platelet viability, aggregation, adhesion, spreading and fibrin clot retraction were assessed., Results: The rats with heatstroke exhibited a variety of clinical symptoms, including hypotension, tachycardia, multiple organ dysfunction, and coagulopathy. Platelet viability in the heatstroke group was comparable to that in the healthy control group. However, the heatstroke group exhibited significant reductions in plasma fibrinogen levels and platelet aggregation, adhesion, spreading, and fibrin clot retraction. Notably, fibrinogen supplementation markedly augmented the aggregation responses of platelets in the heatstroke group. The impairment of platelet adhesion, spreading, and fibrin clot retraction in the rats with heatstroke was partially ameliorated by fibrinogen supplementation., Conclusions: An early use of fibrinogen replacement may serve as a therapeutic intervention to alleviate platelet hyporeactivity and prevent the complications in patients with heatstroke., Competing Interests: Declaration of competing interest All authors declared that they have no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: The effects of thoracic endovascular aneurysm repair (TEVAR) with additional distal bare metal stents (BMSs) in patients with subacute complicated type B aortic dissection (cTBAD) are unclear and are investigated in this retrospective study., Methods: The medical records of 67 patients who received TEVAR due to subacute cTBAD were reviewed. Areas of true lumen (TL) and false lumen at five levels-pulmonary artery (PA), diaphragm, renal artery (RA), middle of the infrarenal aorta, and aortic bifurcation-were measured using computed tomography before and 3, 6, and 12 months after surgery. The TL ratio (TL area/total aortic area) and total aortic area at each time point were compared between the TEVAR + BMS (n = 37) and TEVAR-only (n = 30) groups. The effects of BMS use and time were evaluated using generalized estimating equations and generalized linear regression models., Results: Baseline characteristics, remodeling types, and clinical outcomes did not differ significantly between the two groups. Postoperative TL ratios at the diaphragm and RA were significantly higher in the TEVAR + BMS group than in the TEVAR-only group ( p < 0.05). BMS use and time had significant interaction effects at the PA, diaphragm, and RA (all p < 0.05), but effects on total aortic area were not significant at any of the five parts. TL ratios at the diaphragm and RA exhibited greater improvement in the TEVAR + BMS group than in the TEVAR-only group at postoperative months 6 and 12 (all p < 0.001). Aortic diameters at all five parts were significantly smaller in the TEVAR + BMS group than in the TEVAR-only group (all p < 0.05)., Conclusion: In patients with subacute cTBAD, TEVAR with BMS implantation effectively expands the TL from the thoracic aorta to the RA but neither enhances aortic remodeling nor elicits any change in total aortic area in whole dissected aorta relative to TEVAR only., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2024, the Chinese Medical Association.)

Polymer-wrapped single-walled carbon nanotubes (SWNTs) are a potential method for obtaining high-purity semiconducting ( sc ) SWNT solutions. Conjugated polymers (CPs) can selectively sort sc -SWNTs with different chiralities, and the structure of the polymer side chains influences this sorting capability. While extensive research has been conducted on modifying the physical, optical, and electrical properties of CPs through side-chain modifications, the impact of these modifications on the sorting efficiency of sc -SWNTs remains underexplored. This study investigates the introduction of various conjugated side chains into naphthalene diimide-based CPs to create a biaxially extended conjugation pattern. The CP with a branched conjugated side chain ( P3 ) exhibits reduced aggregation, resulting in improved wrapping ability and the formation of larger bundles of high-purity sc -SWNTs. Grazing incidence X-ray diffraction analysis confirms that the potential interaction between sc -SWNTs and CPs occurs through π-π stacking. The field-effect transistor device fabricated with P3 / sc -SWNTs demonstrates exceptional performance, with a significantly enhanced hole mobility of 4.72 cm 2 V -1 s -1 and high endurance/bias stability. These findings suggest that biaxially extended side-chain modification is a promising strategy for improving the sorting efficiency and performance of sc -SWNTs by using CPs. This achievement can facilitate the development of more efficient and stable electronic devices.

Oil-Gan is the fruit of the genus Phyllanthus emblica L. The fruits have excellent effects on health care and development values. There are many methods for the management of diabetic nephropathy (DN). However, there is a lack of effective drugs for treating DN throughout the disease course. The primary aim of this study was to examine the protective effects (including analyses of urine and blood, and inflammatory cytokine levels) and mechanisms of the ethyl acetate extract of P. emblica (EPE) on db/db mice, an animal model of diabetic nephropathy; the secondary aim was to examine the expression levels of p- protein kinase Cα (PKCα)/t-PKCα in the kidney and its downregulation of vascular endothelial growth factor (VEGF) and fibrosis gene transforming growth factor-β1 (TGF-β1) by Western blot analyses. Eight db/m mice were used as the control group. Forty db/db mice were randomly divided into five groups. Treatments included a vehicle, EPE1, EPE2, EPE3 (at doses of 100, 200, or 400 mg/kg EPE), or the comparative drug aminoguanidine for 8 weeks. After 8 weeks of treatment, the administration of EPE to db/db mice effectively controlled hyperglycemia and hyperinsulinemia by markedly lowering blood glucose, insulin, and glycosylated HbA1c levels. The administration of EPE to db/db mice decreased the levels of BUN and creatinine both in blood and urine and reduced urinary albumin excretion and the albumin creatine ratio (UACR) in urine. Moreover, EPE treatment decreased the blood levels of inflammatory cytokines, including kidney injury molecule-1 (KIM-1), C-reactive protein (CRP), and NLR family pyrin domain containing 3 (NLRP3). Our findings showed that EPE not only had antihyperglycemic effects but also improved renal function in db/db mice. A histological examination of the kidney by immunohistochemistry indicated that EPE can improve kidney function by ameliorating glomerular morphological damage following glomerular injury; alleviating proteinuria by upregulating the expression of nephrin, a biomarker of early glomerular damage; and inhibiting glomerular expansion and tubular fibrosis. Moreover, the administration of EPE to db/db mice increased the expression levels of p- PKCα/t-PKCα but decreased the expression levels of VEGF and renal fibrosis biomarkers (TGF-β1, collagen IV, p-Smad2, p-Smad3, and Smad4), as shown by Western blot analyses. These results implied that EPE as a supplement has a protective effect against renal dysfunction through the amelioration of insulin resistance as well as the suppression of nephritis and fibrosis in a DN model.

Natto contains a potent fibrinolytic enzyme called nattokinase (NK), which has thrombolytic, antihypertensive, antiatherosclerotic and lipid-lowering effects. Although NK has been recognized for its beneficial effect on humans with atherosclerotic cardiovascular disease (ASCVD), the underlying mechanisms involved in vascular inflammation-atherosclerosis development remain largely unknown. The current study aimed to explore the effects of NK on gene regulation, autophagy, necroptosis and inflammasome in vascular inflammation. The transcriptional profiles of NK in endothelial cells (ECs) by RNA sequencing (RNA-seq) revealed that NK affected THBS1, SRF and SREBF1 mRNA expression. In Q-PCR analysis, SRF and THBS1 were upregulated but SREBF1 was unaffected in ECs treated with NK. NK treatment induced autophagy and inhibited NLRP3 inflammasome and necroptosis in ECs. Furthermore, the inhibition of SRF or THBS1 by siRNA suppressed autophagy and enhanced the NLRP3 inflammasome and necroptosis. In a mouse model, NK reduced vascular inflammation by activating autophagy and inhibiting NLRP3 inflammasome and necroptosis. Our findings provide the first evidence that NK upregulates SRF and THBS1 genes, subsequently increasing autophagy and decreasing necroptosis and NLRP3 inflammasome formation to reduce vascular inflammation. Therefore, NK could serve as nutraceuticals or adjuvant therapies to reduce vascular inflammation and possible atherosclerosis progression., Competing Interests: Declaration of competing interest All authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Chitosan acts as a versatile carrier in polymeric nanoparticle (NP) for diverse drug administration routes. Delivery of antioxidants, such as quercetin (Qu) showcases potent antioxidant and anti-inflammatory properties for reduction of various cardiovascular diseases, but low water solubility limits uptake. To address this, we developed a novel layer-by-layer zein/gamma-polyglutamic acid (γPGA)/low-molecular-weight chitosan (LC)/fucoidan NP for encapsulating Qu and targeting inflamed vessel endothelial cells. We used zein (Z) and γPGA (r) to encapsulate Qu (Qu-Zr NP) exhibited notably higher encapsulation efficiency compared to zein alone. Qu-Zr NP coated with LC (Qu-ZrLC2 NP) shows a lower particle size (193.2 ± 2.9 nm), and a higher zeta potential value (35.2 ± 0.4 mV) by zeta potential and transmission electron microscopy analysis. After coating Qu-ZrLC2 NP with fucoidan, Qu-ZrLC2Fa NP presented particle size (225.16 ± 0.92 nm), zeta potential (-25.66 ± 0.51 mV) and maintained antioxidant activity. Further analysis revealed that Qu-ZrLC2Fa NP were targeted and taken up by HUVEC cells and EA.hy926 endothelial cells. Notably, we observed Qu-ZrLC2Fa NP targeting zebrafish vessels and isoproterenol-induced inflamed vessels of rat. Our layer-by-layer formulated zein/γPGA/LC/fucoidan NP show promise as a targeted delivery system for water-insoluble drugs. Qu-ZrLC2Fa NP exhibit potential as an anti-inflammatory therapeutic for blood vessels., 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. Availability of data and materials. All data used to support the findings of this study are available from the corresponding author upon request., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Contrast-enhanced ultrasound (CEUS) is considered as an efficient tool for focal liver lesion characterization, given it allows real-time scanning and provides dynamic tissue perfusion information. An accurate diagnosis of liver lesions with CEUS requires a precise interpretation of CEUS images. However,it is a highly experience dependent task which requires amount of training and practice. To help improve the constrains, this study aims to develop an end-to-end method based on deep learning to make malignancy diagnosis of liver lesions using CEUS., Methods: A total of 420 focal liver lesions with 136 benign cases and 284 malignant cases were included. A deep learning model based on a two-dimensional convolution neural network, a long short-term memory (LSTM), and a linear classifier (with sigmoid) was developed to analyze the CEUS loops from different contrast imaging phases. For comparison, a 3D-CNN based method and a machine-learning (ML)-based time-intensity curve (TIC) method were also implemented for performance evaluation., Results: Results of the 4-fold validation demonstrate that the mean AUC is 0.91, 0.88, and 0.78 for the proposed method, the 3D-CNN based method, and the ML-based TIC method, respectively., Conclusions: The proposed CNN-LSTM method is promising in making malignancy diagnosis of liver lesions in CEUS without any additional manual features selection., (© 2024. The Author(s).)

Intrinsically stretchable electronics with skin-like mechanical properties have been identified as a promising platform for emerging applications ranging from continuous physiological monitoring to real-time analysis of health conditions, to closed-loop delivery of autonomous medical treatment 1-7 . However, current technologies could only reach electrical performance at amorphous-silicon level (that is, charge-carrier mobility of about 1 cm 2  V -1  s -1 ), low integration scale (for example, 54 transistors per circuit) and limited functionalities 8-11 . Here we report high-density, intrinsically stretchable transistors and integrated circuits with high driving ability, high operation speed and large-scale integration. They were enabled by a combination of innovations in materials, fabrication process design, device engineering and circuit design. Our intrinsically stretchable transistors exhibit an average field-effect mobility of more than 20 cm 2  V -1  s -1 under 100% strain, a device density of 100,000 transistors per cm 2 , including interconnects and a high drive current of around 2 μA μm -1 at a supply voltage of 5 V. Notably, these achieved parameters are on par with state-of-the-art flexible transistors based on metal-oxide, carbon nanotube and polycrystalline silicon materials on plastic substrates 12-14 . Furthermore, we realize a large-scale integrated circuit with more than 1,000 transistors and a stage-switching frequency greater than 1 MHz, for the first time, to our knowledge, in intrinsically stretchable electronics. Moreover, we demonstrate a high-throughput braille recognition system that surpasses human skin sensing ability, enabled by an active-matrix tactile sensor array with a record-high density of 2,500 units per cm 2 , and a light-emitting diode display with a high refreshing speed of 60 Hz and excellent mechanical robustness. The above advancements in device performance have substantially enhanced the abilities of skin-like electronics., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Whether early HIV diagnosis is beneficial for HIV patients themselves remains uncertain, given the stigma and social discrimination associated with an HIV diagnosis. This study aimed to measure the impact of early HIV diagnosis on quality-adjusted life expectancy (QALE) in comparison with late HIV diagnosis, from real-world data in Taiwan under universal access to antiretroviral therapy (ART)., Methods: This population-based cohort study included 14,570 men who have sex with men (MSM) in the national HIV registry and a quasi-random sample (n = 127) of MSM patients to measure quality of life using the EQ-5D health utility instrument. We integrated quality of life data into the extrapolated cohort survival curve to estimate the QALE in patients with early versus late HIV diagnosis (≤30 days before AIDS diagnosis). Loss-of-QALE were estimated by comparing the cohort with age-, sex-, and calendar-year-matched referents simulated from vital statistics. Difference-in-differences was estimated to quantify the effect of early HIV diagnosis., Results: Early HIV diagnosis is associated with a loss-of-life expectancy of 3.11 years, with an average health utility of 0.95, in contrast to those diagnosed late (loss-of-life expectancy 8.47 years, with an average health utility of 0.86). After integration of survival and life quality, early HIV diagnosis results in a reduction of loss-of-QALE by 8.28 quality-adjusted life years among MSM living with HIV., Conclusions: Under universal access to ART, early HIV diagnosis is highly beneficial for people living with HIV themselves, with a net gain of 8.28 healthy life years compared with those diagnosed late., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2024. Published by Elsevier B.V.)

This work aims to explore the utility of wearable inertial measurement units (IMUs) for quantifying movement in Romberg tests and investigate the extent of movement in adults with vestibular hypofunction (VH). A cross-sectional study was conducted at an academic tertiary medical center between March 2021 and April 2022. Adults diagnosed with unilateral vestibular hypofunction (UVH) or bilateral vestibular hypofunction (BVH) were enrolled in the VH group. Healthy controls (HCs) were recruited from community or outpatient clinics. The IMU-based instrumented Romberg and tandem Romberg tests on the floor were applied to both groups. The primary outcomes were kinematic body metrics (maximum acceleration [ACC], mean ACC, root mean square [RMS] of ACC, and mean sway velocity [MV]) along the medio-lateral (ML), cranio-caudal (CC), and antero-posterior (AP) axes. A total of 31 VH participants (mean age, 33.48 [SD 7.68] years; 19 [61%] female) and 31 HCs (mean age, 30.65 [SD 5.89] years; 18 [58%] female) were recruited. During the eyes-closed portion of the Romberg test, VH participants demonstrated significantly higher maximum ACC and increased RMS of ACC in head movement, as well as higher maximum ACC in pelvic movement along the ML axis. In the same test condition, individuals with BVH exhibited notably higher maximum ACC and RMS of ACC along the ML axis in head and pelvic movements compared with HCs. Additionally, BVH participants exhibited markedly increased maximum ACC along the ML axis in head movement during the eyes-open portion of the tandem Romberg test. Conversely, no significant differences were found between UVH participants and HCs in the assessed parameters. The instrumented Romberg and tandem Romberg tests characterized the kinematic differences in head, pelvis, and ankle movement between VH and healthy adults. The findings suggest that these kinematic body metrics can be useful for screening BVH and can provide goals for vestibular rehabilitation., (© 2023 The Authors.)

(1) Background: Many studies have revealed a relationship between serum 25-hydroxy vitamin D and physical activity. This study aimed to investigate the relationship between self-reported sitting time and serum 25-hydroxy vitamin D levels in middle-aged and elderly adults in Taiwan. (2) Methods: A total of 396 people were enrolled in our study during a community health examination in Taiwan in 2019. We grouped participants from low to high according to their tertile of serum 25-hydroxy vitamin D levels, using the following categories: deficiency, insufficiency, and sufficiency. Parameters including self-reported sitting time were analyzed between each group. Pearson correlation coefficients were calculated to explore the relationships of serum 25-hydroxy vitamin D levels with age-adjusted risk factors. A scatter plot demonstrated the relationship between serum 25-hydroxy vitamin D levels and self-reported sitting time. The association between serum 25-hydroxy vitamin D levels and self-reported sitting time was assessed by multivariate linear regression with adjustment for age, sex, waist circumference, low-density lipoprotein, triglycerides, and smoking and drinking status. (3) Results: We analyzed the data from 396 participants. A total of 41.4% of participants were male, and the average age of all participants was 64.91 (±8.80) years. The participants in the high serum 25-hydroxy vitamin D group were more likely to have shorter self-reported sitting time. Serum 25-hydroxy vitamin D was negatively correlated (Pearson's r) with self-reported sitting time, even after adjustment for age. According to the results of multivariate linear regression, vitamin D levels showed a negative association with self-reported sitting time (β = -0.131, p = 0.006) after adjustment for age, sex, waist circumference, low-density lipoprotein, triglycerides, and smoking and drinking status. (4) Conclusions: According to our research, self-reported sitting time was inversely correlated with serum 25-hydroxy vitamin D in middle-aged and elderly people in Taiwan. Meanwhile, longer self-reported sitting time can be an independent risk factor for lower serum 25-hydroxy vitamin D levels.

The manipulation of the polymer backbone structure has a profound influence on the crystalline behavior and charge transport characteristics of polymers. These strategies are commonly employed to optimize the performance of stretchable polymer semiconductors. However, a universal method that can be applied to conjugated polymers with different donor-acceptor combinations is still lacking. In this study, we propose a universal strategy to boost the stretchability of polymers by incorporating the nonlinear conjugated linker (NCL) into the main chain. Specifically, we incorporate meta-dibromobenzene (MB), characterized by its asymmetric linkage sites, as the NCL into the backbone of diketopyrrolopyrrole-thiophene-based (DPP-based) polymers. Our research demonstrates that the introduction of MB prompts chain-kinking, thereby disrupting the linearity and central symmetry of the DPP conjugated backbone. This modification reshapes the polymer conformation, decreasing the radius of gyration and broadening the free volume, which consequently adjusts the level of crystallinity, leading to a considerable increase in the stretchability of the polymer. Importantly, this method increases stretchability without compromising mobility and exhibits broad applicability across a wide range of donor-acceptor pair polymers. Leveraging this strategy, fully stretchable transistors were fabricated using a DPP polymer that incorporates 10 mol % of MB. These transistors display a mobility of approximately 0.5 cm 2 V -1 s -1 and prove remarkably durable, maintaining 90% of this mobility even after enduring 1000 cycles at 25% strain. Overall, we propose a method to systematically control the main-chain conformation, thereby enhancing the stretchability of conjugated polymers in a widely applicable manner.

The amygdala plays crucial roles in emotional processing, motivated behaviors, and stress responses. It receives sensory information and modulates fear- and anxiety-related behaviors. Neuronal activations are induced in the basolateral complex of the amygdala (BLA) and the central nucleus of the amygdala (CeA) when exposing to acute stress, leading to increased alertness and proper behavioral adaptation. Previous studies have shown that animals displayed a decrease in appetitive motivated behaviors under stress conditions. However, whether the hyperactive amygdala is responsible for the decrease in appetitive motivated behaviors remains unknown. In this study, we aimed to examine the role of BLA or CeA activation in effort-based motivated behavior. We pharmacologically activated the BLA or the CeA with N-methyl- D -aspartate (NMDA) before the lever-pressing for food reward test on different fixed-ratio (FR) schedules (FR1, FR16, or FR32) in male Long-Evans rats. Our data showed that activation of either the BLA or the CeA with NMDA (0.05 μg in 0.5 μl per site) decreased the lever-pressing behavior on higher FR schedules of FR16 and FR32, but not on the FR1 test. Importantly, locomotor activity and free-feeding food intake were intact under amygdala activation, suggesting that the decrease in lever-pressing behavior was not due to motor disablement or decreased appetite. These results suggested that activation of the BLA or the CeA negatively impaired the effort-based motivated behavior that the animals were less willing to work for food reward., Competing Interests: Competing interests The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: The fruits of Phyllanthus emblica L. are high in nutrients and have excellent health care function and developmental value. There are many management strategies available for diabetes and hyperlipidemia. Nevertheless, there is a lack of an effective and nontoxic drug., Objective: The present study was designed to first screen four extracts of P. emblica L. on insulin signaling target gene expression levels, including glucose transporter 4 (GLUT4) and p-Akt/t-Akt. The ethyl acetate extract of P. emblica L. (EPE) exhibited the most efficient activity among the four extracts and was thus chosen to explore the antidiabetic and antihyperlipidemic activities in streptozotocin (STZ)-induced type 1 diabetic mice., Design: All mice (in addition to one control (CON) group) were administered STZ injections (intraperitoneal) for 5 consecutive days, and then STZ-induced mice were administered EPE (at 100, 200, or 400 mg/kg body weight), fenofibrate (Feno) (at 250 mg/kg body weight), glibenclamide (Glib) (at 10 mg/kg body weight), or vehicle by oral gavage once daily for 4 weeks. Finally, histological examination, blood biochemical parameters, and target gene mRNA expression levels were measured, and liver tissue was analyzed for the levels of malondialdehyde (MDA), a maker of lipid peroxidation., Results: EPE treatment resulted in decreased levels of blood glucose, HbA1C, triglycerides (TGs), and total cholesterol and increased levels of insulin compared with the vehicle-treated STZ group. EPE treatment decreased blood levels of HbA1C and MDA but increased glutathione levels in liver tissue, implying that EPE exerts antioxidant activity and could prevent oxidative stress and diabetes. The EPE-treated STZ mice displayed an improvement in the sizes and numbers of insulin-expressing β cells. EPE treatment increased the membrane expression levels of skeletal muscular GLUT4, and also reduced hepatic mRNA levels of glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase thereby inhibiting hepatic gluconeogenesis. This resulted in a net glucose lowering effect in EPE-treated STZ mice. Furthermore, EPE increased the expression levels of p-AMPK/t-AMPK in both the skeletal muscle and liver tissue compared with vehicle-treated STZ mice. EPE-treated STZ mice showed enhanced expression levels of fatty acid oxidation enzymes, including peroxisome proliferator-activated receptor α (PPARα), but reduced expression levels of lipogenic genes including fatty acid synthase, as well as decreased mRNA levels of sterol regulatory element binding protein 1c (SREBP1c), apolipoprotein-CIII (apo-CIII), and diacylglycerol acyltransferase-2 (DGAT2). This resulted in a reduction in plasma TG levels. EPE-treated STZ mice also showed reduced expression levels of PPAR γ. This resulted in decreased adipogenesis, fatty acid synthesis, and lipid accumulation within liver tissue, and consequently, lower TG levels in liver tissue and blood. Furthermore, EPE treatment not only displayed an increase in the Akt activation in liver tissue, but also in C2C12 myotube in the absence of insulin. These results implied that EPE acts as an activator of AMPK and /or as a regulator of the insulin (Akt) pathway., Conclusions: Taken together, EPE treatment exhibited amelioration of the diabetic and hyperlipidemic state in STZ-induced diabetic mice., Competing Interests: The authors have not received any funding or benefits from industry or elsewhere to conduct this study., (© 2023 Shin-Ming Huang et al.)

The scaling of transistors with thinner channel thicknesses has led to a surge in research on two-dimensional (2D) and quasi-2D semiconductors. However, modulating the threshold voltage (V T ) in ultrathin transistors is challenging, as traditional doping methods are not readily applicable. In this work, we introduce a optical-thermal method, combining ultraviolet (UV) illumination and oxygen annealing, to achieve broad-range V T tunability in ultrathin In 2 O 3 . This method can achieve both positive and negative V T tuning and is reversible. The modulation of sheet carrier density, which corresponds to V T shift, is comparable to that obtained using other doping and capacitive charging techniques in other ultrathin transistors, including 2D semiconductors. With the controllability of V T , we successfully demonstrate the realization of depletion-load inverter and multi-state logic devices, as well as wafer-scale V T modulation via an automated laser system, showcasing its potential for low-power circuit design and non-von Neumann computing applications., (© 2023. Springer Nature Limited.)

Background: Persistent false lumen (FL) perfusion with aneurysmal formation is common after thoracic endovascular aortic repair (TEVAR) for typical extended aortic dissection and is associated with poor outcomes. Endovascular FL embolization (FLE) has recently been tried for treatment of postdissection aortic aneurysm (PDAA). However, most reports address thoracic rather than abdominal FLE. In this study, we present the results of abdominal FLE in patients with residual patent abdominal FL following stent-graft repair for aortic dissection., Methods: Between 2015 and 2019, 24 patients (mean age: 56.7 ± 11.8 years, range: 40-84 years, 18 male) received endovascular abdominal FLE using vascular plugs, coils, or candy plugs as the main surgery (5 patients) or auxiliary procedure (19 patients) after earlier stent-graft repair for aortic dissection (Type A: 9, Type B: 15). The medical records were reviewed and aortic remodeling was examined comparing the preembolization computed tomography (CT) and the most recent CT before reintervention., Results: Technical success was achieved without any intraoperative complications, early morbidity, or mortality. Median follow-up was 34.4 months (range: 12-71). Regarding thoracic FL, 15 patients exhibited complete thrombosis before the procedure and did not change status thereafter except for 1 patient with distal stent-graft-induced new entry. In the other 9 patients, 6 exhibited increased thrombosis. With regard to the abdominal aorta, increased FL thrombosis only occurred in 8 patients with 3 (12.5%) achieving complete thrombosis. The maximal thoracic aortic diameter did not change (1.4 ± 5.6 mm) statistically, but the abdominal diameter increased significantly (4.3 ± 3.7 mm, p < 0.005)., Conclusion: From our results, abdominal FLE is a safe procedure. However, covering all the re-entry tears is complex and the possibility of complete FL thrombosis is low. The abdominal aortic diameter appears to become enlarged in these patients. Continuous follow-up is necessary after FLE., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2023, the Chinese Medical Association.)

Background: Both inflammation and oxidative stress contribute to the pathogenesis of sepsis and its associated organ damage. Angiotensin-(1-7), acting through the Mas receptor and angiotensin II-type 2 receptors (AT2R), could attenuate organ dysfunction and improve survival in rats with sepsis. However, the role of AT2R in inflammation and oxidative stress in rats with sepsis is unclear. Therefore, this study examined the modulatory effects and molecular mechanism of AT2R stimulation in rats with polymicrobial sepsis., Methods: Male Wistar rats underwent cecal ligation and puncture (CLP) or sham surgery followed by the administration of saline or CGP42112 (a selective, high-affinity agonist of AT2R, 50 μg/kg intravenously) at 3 hours after sham surgery or CLP. The changes in hemodynamics, biochemical variables, and plasma levels of chemokines and nitric oxide were detected during the 24-hour observation. Organ injury was evaluated by histological examination., Results: We found that CLP evoked delayed hypotension, hypoglycemia, and multiple organ injuries, characterized by elevated plasma biochemical parameters and histopathological changes. These effects were attenuated by treatment with CGP42112. CGP42112 significantly attenuated plasma chemokines and nitric oxide production and reduced liver inducible nitric oxide synthase and nuclear factor kappa-B expression. More importantly, CGP42112 significantly improved the survival of rats with sepsis (50% vs. 20% at 24 h after CLP, p < 0.05)., Conclusion: The protective effects of CGP42112 may be related to anti-inflammatory responses, suggesting that the stimulation of AT2R is a promising therapeutic candidate for the treatment of sepsis., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interests related to the subject matter or materials discussed in this article., (Copyright © 2023, the Chinese Medical Association.)

This retrospective study compared the effectiveness of different materials used in Uvulopalatopharyngoplasty (UPPP) for snoring or obstructive sleep apnea treatment, focusing on the impact on bleeding control, pain control, and healing ability. The study population comprised 213 patients who underwent UPPP at Wan-Fang Hospital between July 2018 and October 2022 divided into four groups based on the postoperative material used: No Material Use Group, Tissue Glue Group, Platelet-Rich Plasma (PRP) Group, and Polyglycolic Acid (PGA) Sheet Group. Results showed significant differences in operation time and intraoperative bleeding amount among the groups, with the Tissue Glue Group demonstrating the shortest operation time. While no significant differences in postoperative pain at 24 h were observed, PRP and PGA Sheet groups exhibited lower average pain scores in cases with higher pain levels. Postoperative complications and emergency room visits due to pain or bleeding varied among the groups, with the No Material Use Group having the highest incidence, although no statistical significance was achieved. This study provides insights into the potential benefits of using advanced materials in UPPP, guiding future research and clinical practice to improve patient care and outcomes.

Graphene oxide-based materials (GOBMs) have been widely explored as nano-reinforcements in cementitious composites due to their unique properties. Oxygen-containing functional groups in GOBMs are crucial for enhancing the microstructure of cementitious composites. A better comprehension of their surface chemistry and mechanisms is required to advance the potential applications in cementitious composites of functionalized GOBMs. However, the mechanism by which the oxygen-containing functional groups enhance the response of cementitious composites is still unclear, and controlling the surface chemistry of GOBMs is currently constrained. This review aims to investigate the reactions and mechanisms for functionalized GOBMs as additives incorporated in cement composites. A variety of GOBMs, including graphene oxide (GO), hydroxylated graphene (HO-G), edge-carboxylated graphene (ECG), edge-oxidized graphene oxide (EOGO), reduced graphene oxide (rGO), and GO/silane composite, are discussed with regard to their oxygen functional groups and interactions with the cement microstructure. This review provides insight into the potential benefits of using GOBMs as nano-reinforcements in cementitious composites. A better understanding of the surface chemistry and mechanisms of GOBMs will enable the development of more effective functionalization strategies and open up new possibilities for the design of high-performance cementitious composites.

Oil-Gan, also known as emblica, is the fruit of the genus Phyllanthus emblica L. The fruits are high in nutrients and display excellent health care functions and development values. The primary aim of this study was to investigate the activities of ethyl acetate extract from Phyllanthus emblica L. (EPE) on type 1 diabetes mellitus (T1D) and immunoregulatory activities in non-obese diabetes (NOD) mice with spontaneous and cyclophosphamide (Cyp)-accelerated diabetes. EPE was vehicle-administered to spontaneous NOD (S-NOD) mice or Cyp-accelerated NOD (Cyp-NOD) mice once daily at a dose of 400 mg/kg body weight for 15 or 4 weeks, respectively. At the end, blood samples were collected for biological analyses, organ tissues were dissected for analyses of histology and immunofluorescence (IF) staining (including expressions of Bcl and Bax), the expression levels of targeted genes by Western blotting and forkhead box P3 (Foxp3), and helper T lymphocyte 1 (Th1)/Th2/Th17/Treg regulatory T cell (Treg) cell distribution by flow cytometry. Our results showed that EPE-treated NOD mice or Cyp-accelerated NOD mice display a decrease in levels of blood glucose and HbA1c, but an increase in blood insulin levels. EPE treatment decreased blood levels of IFN-γ and tumor necrosis α (TNF-α) by Th1 cells, and reduced interleukin (IL)-1β and IL-6 by Th17 cells, but increased IL-4, IL-10, and transforming growth factor-β1 (TGF-β1) by Th2 cells in both of the two mice models by enzyme-linked immunosorbent assay (ELISA) analysis. Flow cytometric data showed that EPE-treated Cyp-NOD mice had decreased the CD4 + subsets T cell distribution of CD4 + IL-17 and CD4 + interferon gamma (IFN-γ), but increased the CD4 + subsets T cell distribution of CD4 + IL-4 and CD4 + Foxp3. Furthermore, EPE-treated Cyp-NOD mice had decreased the percentage per 10,000 cells of CD4 + IL-17 and CD4 + IFNγ, and increased CD4 + IL-4 and CD4 + Foxp3 compared with the Cyp-NOD Con group ( p < 0.001, p < 0.05, p < 0.05, and p < 0.05, respectively). For target gene expression levels in the pancreas, EPE-treated mice had reduced expression levels of inflammatory cytokines, including IFN-γ and TNF-α by Th1 cells, but increased expression levels of IL-4, IL-10, and TGF-1β by Th2 cells in both two mice models. Histological examination of the pancreas revealed that EPE-treated mice had not only increased pancreatic insulin-expressing β cells (brown), and but also enhanced the percentage of Bcl-2 (green)/Bax (red) by IF staining analyses of islets compared with the S-NOD Con and the Cyp-NOD Con mice, implying that EPE displayed the protective effects of pancreas β cells. EPE-treated mice showed an increase in the average immunoreactive system (IRS) score on insulin within the pancreas, and an enhancement in the numbers of the pancreatic islets. EPE displayed an improvement in the pancreas IRS scores and a decrease in proinflammatory cytokines. Moreover, EPE exerted blood-glucose-lowering effects by regulating IL-17 expressions. Collectively, these results implied that EPE inhibits the development of autoimmune diabetes by regulating cytokine expression. Our results demonstrated that EPE has a therapeutic potential in the preventive effects of T1D and immunoregulation as a supplementary.

Artificial skin that simultaneously mimics sensory feedback and mechanical properties of natural skin holds substantial promise for next-generation robotic and medical devices. However, achieving such a biomimetic system that can seamlessly integrate with the human body remains a challenge. Through rational design and engineering of material properties, device structures, and system architectures, we realized a monolithic soft prosthetic electronic skin (e-skin). It is capable of multimodal perception, neuromorphic pulse-train signal generation, and closed-loop actuation. With a trilayer, high-permittivity elastomeric dielectric, we achieved a low subthreshold swing comparable to that of polycrystalline silicon transistors, a low operation voltage, low power consumption, and medium-scale circuit integration complexity for stretchable organic devices. Our e-skin mimics the biological sensorimotor loop, whereby a solid-state synaptic transistor elicits stronger actuation when a stimulus of increasing pressure is applied.

Asthma is often characterized by tissue-level mechanical phenotypes that include remodeling of the airway and an increase in airway tightening, driven by the underlying smooth muscle. Existing therapies only provide symptom relief and do not improve the baseline narrowing of the airway or halt progression of the disease. To investigate such targeted therapeutics, there is a need for models that can recapitulate the 3D environment present in this tissue, provide phenotypic readouts of contractility, and be easily integrated into existing assay plate designs and laboratory automation used in drug discovery campaigns. To address this, we have developed DEFLCT, a high-throughput plate insert that can be paired with standard labware to easily generate high quantities of microscale tissues in vitro for screening applications. Using this platform, we exposed primary human airway smooth muscle cell-derived microtissues to a panel of six inflammatory cytokines present in the asthmatic niche, identifying TGF-β1 and IL-13 as inducers of a hypercontractile phenotype. RNAseq analysis further demonstrated enrichment of contractile and remodeling-relevant pathways in TGF-β1 and IL-13 treated tissues as well as pathways generally associated with asthma. Screening of 78 kinase inhibitors on TGF-β1 treated tissues suggests that inhibition of protein kinase C and mTOR/Akt signaling can prevent this hypercontractile phenotype from emerging, while direct inhibition of myosin light chain kinase does not. Taken together, these data establish a disease-relevant 3D tissue model for the asthmatic airway, which combines niche specific inflammatory cues and complex mechanical readouts that can be utilized in drug discovery efforts., Competing Interests: Yes, all authors are current or prior employees (were employees at the time of their contributions to the paper) of Novartis., (© 2023 Author(s).)

Graphene oxide (GO) has been widely used in biological sensing studies because of its excellent physical and chemical properties. In particular, the rich functional groups on the surface of GO can effectively enhance the bonding of biomolecules and serve as an efficient sensing substrate. However, when biomolecules are labeled with fluorescence, the GO interface affects the biomolecules by reducing the fluorescence properties and limiting their applications in biosensing. Here, we establish an annealed GO (aGO) substrate through the annealing process, which can effectively increase the bonding amount of a DNA probe because of the accumulation of oxygen atoms on the surface without significantly damaging the nanosheet structure. Furthermore, we prove that the aGO substrate can effectively maintain its fluorescence performance and stability by exposing more graphic domains. Overall, this study successfully verifies that GO's interface annealing modification can be used as an alternative innovative interface application in biosensing.

Global warming increases the incidence of heat stroke (HS) and HS causes the reduction of visceral blood flow during hyperthermia, leading to intestinal barrier disruption, microbial translocation, systemic inflammation and multiple organ failure. Cathelicidin LL-37 exhibits antimicrobial activities, helps innate immunity within the gut to maintain intestinal homeostasis, and augments intestinal wound healing and barrier function. Thus, we evaluated the effects and possible mechanisms of cathelicidin LL-37 on HS. Wistar rats were placed in a heating-chamber of 42 ̊C to induce HS. Changes in rectal temperature, hemodynamic parameters, and survival rate were measured during the experimental period. Blood samples and ilea were collected to analyze the effects of LL-37 on systemic inflammation, multiple organ dysfunction, and intestinal injury. Furthermore, LS174T and HT-29 cells were used to assess the underlying mechanisms. Our data showed cathelicidin LL-37 ameliorated the damage of intestinal cells induced by HS. Intestinal injury, systemic inflammation, and nitrosative stress (high nitric oxide level) caused by continuous hyperthermia were attenuated in HS rats treated with cathelicidin LL-37, and hence, improved multiple organ dysfunction, coagulopathy, and survival rate. These beneficial effects of cathelicidin LL-37 were attributed to the protection of intestinal goblet cells (by increasing transepithelial resistance, mucin-2 and Nrf2 expression) and the improvement of intestinal barrier function (less cyclooxygenase-2 expression and FITC-dextran translocation). Interestingly, high cathelicidin expression in the ileal samples of inflammatory bowel disease patients was associated with better clinical outcome. These results suggest that cathelicidin LL-37 could prevent heat stress-induced intestinal damage and heat-related illnesses., Competing Interests: Conflict of interest statement The authors have declared that no conflict of interest exists., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

'Smart' bandages based on multimodal wearable devices could enable real-time physiological monitoring and active intervention to promote healing of chronic wounds. However, there has been limited development in incorporation of both sensors and stimulators for the current smart bandage technologies. Additionally, while adhesive electrodes are essential for robust signal transduction, detachment of existing adhesive dressings can lead to secondary damage to delicate wound tissues without switchable adhesion. Here we overcome these issues by developing a flexible bioelectronic system consisting of wirelessly powered, closed-loop sensing and stimulation circuits with skin-interfacing hydrogel electrodes capable of on-demand adhesion and detachment. In mice, we demonstrate that our wound care system can continuously monitor skin impedance and temperature and deliver electrical stimulation in response to the wound environment. Across preclinical wound models, the treatment group healed ~25% more rapidly and with ~50% enhancement in dermal remodeling compared with control. Further, we observed activation of proregenerative genes in monocyte and macrophage cell populations, which may enhance tissue regeneration, neovascularization and dermal recovery., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Patients bitten by Protobothrops mucrosquamatus typically experience significant pain, substantial swelling, and potentially blister formation. The appropriate dosage and efficacy of FHAV for alleviating local tissue injury remain uncertain. Between 2017 and 2022, 29 snakebite patients were identified as being bitten by P. mucrosquamatus . These patients underwent point-of-care ultrasound (POCUS) assessments at hourly intervals to measure the extent of edema and evaluate the rate of proximal progression (RPP, cm/hour). Based on Blaylock's classification, seven patients (24%) were classified as Group I (minimal), while 22 (76%) were classified as Group II (mild to severe). In comparison to Group I patients, Group II patients received more FHAV (median of 9.5 vials vs. two vials, p -value < 0.0001) and experienced longer median complete remission times (10 days vs. 2 days, p -value < 0.001). We divided the Group II patients into two subgroups based on their clinical management. Clinicians opted not to administer antivenom treatment to patients in Group IIA if their RPP decelerated. In contrast, for patients in Group IIB, clinicians increased the volume of antivenom in the hope of reducing the severity of swelling or blister formation. Patients in Group IIB received a significantly higher median volume of antivenom (12 vials vs. six vials; p -value < 0.001) than those in Group IIA. However, there was no significant difference in outcomes (disposition, wound necrosis, and complete remission times) between subgroups IIA and IIB. Our study found that FHAV does not appear to prevent local tissue injuries, such as swelling progression and blister formation, immediately after administration. When administering FHAV to patients bitten by P. mucrosquamatus , the deceleration of RPP may serve as an objective parameter to help clinicians decide whether to withhold FHAV administration.

Background: Few studies have compared intraoperative oxygenation and perioperative outcomes between non-intubated video-assisted thoracic surgery (NIVATS) with supraglottic airway devices (SADs) and NIVATS with high flow nasal oxygenation (HFNO). The aim of this retrospective study was to compare the intraoperative desaturation rate and postoperative outcomes between NIVATS with SADs and NIVATS with HFNO., Methods: Data regarding NIVATS performed for lung cancer from January 2020 to December 2021 were collected. Intraoperative anesthetic results, post-anesthetic adverse effects, and surgical outcomes for patients who received SAD or HFNO were analyzed using propensity score-matched and unmatched analysis., Results: In total, 199 patients with i-gel™ and 95 patients with HFNO were included. Significantly more female patients (91.6 vs. 82.4%, p = 0.0378) and fewer wedge resections (78.9 vs. 85.4%, p = 0.0258) were observed in the HFNO group. Among 250 patients who underwent NIVATS wedge resections under total intravenous anesthesia, those who received HFNO had a significantly higher desaturation event rate (19.8% vs. 7.9% in i-gel™ group; p = 0.0063), lower nadir SPO 2 (94.0% vs. 96.1% in i-gel™ group; p = 0.0012), and longer hospitalization (4.0 ± 0.8 vs. 3.6 ± 0.6 in i-gel™ group; p < 0.0001). However, propensity score matching analysis revealed no significant between-group difference in the desaturation rate. A log-rank test revealed that smoking (p = 0.0005) and HFNO (p = 0.0074) were associated with intraoperative desaturation., Conclusion: The rate of SAD use in NIVATS was twice the rate of HFNO use, especially for wedge resections. There is uncertain airway patency and limited flow through HFNO during one-lung ventilation, whereas SADs like i-gel™ presented a significantly less intraoperative desaturation rate over time and similar postoperative outcomes., (Copyright © 2022. Published by Elsevier B.V.)

Genomic researchers increasingly utilize commercial cloud service providers (CSPs) to manage data and analytics needs. CSPs allow researchers to grow Information Technology (IT) infrastructure on demand to overcome bottlenecks when combining large datasets. However, without adequate security controls, the risk of unauthorized access may be higher for data stored on the cloud. Additionally, regulators are mandating data access patterns and specific security protocols for the storage and use of genomic data. While CSP provides tools for security and regulatory compliance, building the necessary controls required for cloud solutions is not trivial. Research Assets Provisioning and Tracking Online Repository (RAPTOR) by the Genome Institute of Singapore is a cloud-native genomics data repository and analytics platform that implements a "five-safes" framework to provide security and governance controls to data contributors and users, leveraging CSP for sharing and analysis of genomic datasets without the risk of security breaches or running afoul of regulations., Competing Interests: The authors declare no competing interests., (© 2023 The Author(s).)

(1) Background: Metabolic syndrome has become a serious health problem in society. Homocysteine is a biomarker for cardiovascular disease. We investigated the relationship between homocysteine levels and metabolic syndrome. (2) Methods: A total of 398 middle-aged and elderly individuals were included in our study. First, we divided the participants into two groups: the metabolic syndrome group and the nonmetabolic syndrome group. Second, according to tertiles of homocysteine levels from low to high, the participants were divided into first, second, and third groups. Pearson's correlation was then calculated for homocysteine levels and metabolic factors. Scatterplots are presented. Finally, the risk of metabolic syndrome in the second and third groups compared with the first group was assessed by multivariate logistic regression. (3) Results: In our study, the metabolic syndrome group had higher homocysteine levels, and the participants in the third group were more likely to have metabolic syndrome. Multivariate logistic regression revealed that the third group, which had the highest homocysteine level, was associated with metabolic syndrome with an odds ratio of 2.32 compared with the first group after adjusting for risk factors. (4) Conclusions: We concluded that high plasma homocysteine levels were independently associated with MetS in our study population.

Background: Association of sedentary behavior and plasma leptin levels is a popular topic in recent research. Aged populations often suffer from cardiometabolic diseases, and leptin is considered a novel marker for many cardiometabolic diseases. To further explore this topic, our research investigates the relationship between sedentary time and serum leptin levels in middle-aged and older populations., Methods: A total of 396 middle-aged and older adult Taiwanese participants were included in this study. We recorded their self-reported sitting time as sedentary time. Participants were categorized into low leptin, medium leptin group, and high leptin groups according to the tertile of serum leptin level in the study. We also analyzed the anthropometric and cardiometabolic parameters between the three groups. Spearman's correlation coefficient was used to analyze the correlation between leptin level, sedentary time, and other cardiometabolic risk factors. The relationsip between leptin and sedentary time was also shown in a scatter plot. Multivariate linear regression was performed to determine the association between serum leptin levels and sedentary time after adjusting for age, sex, alcohol consumption, smoking, triglycerides, body mass index (BMI), fasting plasma glucose, systolic blood pressure, uric acid, creatinine, and alanine transaminase (ALT)., Results: In our study, data from a total of 396 participants were analyzed. The average age of participants was 64.75 (±8.75) years, and ~41.4% were male. A longer period of sedentary time was observed in the high leptin group. A positive correlation was found between serum leptin level and sedentary time in Spearman's correlation, in all BMI groups. Serum leptin levels were positively associated with sedentary time (B = 0.603, p = 0.016) in the multivariate linear regression after adjusting for age, sex, alcohol consumption, smoking, triglycerides, BMI, fasting plasma glucose, systolic blood pressure, uric acid, creatinine, and ALT., Conclusion: Prolonged sedentary time can be an independent risk factor for high serum leptin levels, and high leptin levels can be a novel marker in future healthcare to screen the individual with prolonged sedentary time. Furthermore, based on our study, future research can further explore the relationship between leptin levels and health promotion, especially decreasing sedentary time in the middle-aged and elder population, which is vulnerable to cardiometabolic 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 © 2023 Shih, Shih, Huang, Shih and Chen.)

Background: Plasma leptin is considered a risk factor for obesity and cardio-metabolic disease, but the link between serum leptin and renal function is still under evaluation. In our study, we focused on the relationship between serum leptin and renal function, and we investigated the relationship in more detail., Methods: The 396 middle-aged and elderly Taiwanese adults recruited for our health survey were the subject of our research. All participants agreed to participate and signed a consent form before they joined and completed our study. We divided the participants into three groups according to eGFR tertiles and analyzed the parameters between each group. Then, we used Pearson's correlation test to investigate the relationship between eGFR levels and cardio-metabolic risk factors with adjustment for age. The scatter plot indicates the trend between serum leptin levels and eGFR levels. Participants were reclassified into three subgroups according to their leptin levels and the bar chart reveals the prevalence of chronic kidney disease (CKD) in each group. Finally, we used multivariate linear regression to evaluate the relationship between serum leptin and eGFR levels with adjustment for age, sex, smoking status, drinking status, body mass index (BMI), uric acid levels, hypertension (HTN), diabetes mellitus (DM), and dyslipidemia., Results: In our study, we analyzed the data from 396 eligible participants. A total of 41.4% of the participants were male, and the average age of all participants was 64.81 years ( ± 8.78). The participants in the high eGFR group were more likely to have lower serum leptin levels. Furthermore, eGFR values were negatively correlated with serum leptin levels even after adjustment for age. The prevalence of CKD in the high serum leptin group was higher than that in the low serum leptin group. Serum leptin levels showed significant negative correlations with eGFR levels (β=-0.14, p<0.01) in the multivariate linear regression after adjusting for age, sex, smoking status, drinking status, BMI, uric acid levels, HTN, DM, and dyslipidemia., Conclusion: According to our study, serum leptin levels show a negative relationship with eGFR levels in middle-aged and elderly people in Taiwan. In addition, high serum leptin levels could be an novel marker to survey kidney failure in clinical practices., 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 Shih, Shih, Chen and Chen.)

Ecotoxicity assessments based on bacteria as model organisms are widely used for routine toxicity screening because it has the advantages of time-saving, high sensitivity, cost-effectiveness, and less ethical responsibility. Determination of ecotoxicity effect via bacterial growth can avoid the restriction of model bacteria selection and unique equipment requirements, but traditional viable cell count methods are relatively labor- and time-intensive. The Start Growth Time method (SGT) is a high-throughput and time-conserving method to determine the amount of viable bacterial cells. However, its usability and stability for ecotoxicity assessment are rarely studied. This study confirmed its applicability in terms of bacterial types (gram-positive and gram-negative), growth phases (middle exponential and early stationary phases), and simultaneous existence of dead cells (adjustment by flow cytometry). Our results verified that the stability of establishing SGT correlation is independent of the bacterial type and dead-cell portion. Moreover, we only observed the effect of growth phases on the slope value of established SGT correlation in Shewanella oneidensis, which suggests that preparing inoculum for the SGT method should be consistent in keeping its stability. Our results also elucidate that the SGT values and the live cell percentages meet the non-linear exponential correlation with high correlation coefficients from 0.97 to 0.99 for all the examined bacteria. The non-linear exponential correlation facilitates the application of the SGT method in the ecotoxicity assessment. Finally, applying the exponential SGT correlation to evaluate the ecotoxicity effect of copper ions on E. coli was experimentally validated. The SGT-based method would require about 6 to 7 h to finish the assessment and obtain an estimated EC 50 at 2.27 ± 0.04 mM. This study demonstrates that the exponential SGT correlation can be a high-throughput, time-conversing, and wide-applicable method for bacterial ecotoxicity assessment., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aims: Heat stroke is a life-threatening disorder triggered by thermoregulatory failure. Hyperthermia-induced splanchnic hypoperfusion has been reported to induce intestinal barrier dysfunction and systemic immune response that ultimately cause multiple-organ failure and death. Intestinal goblet cells contribute greatly to the formation of mucus barrier, which hinders translocation of gut microorganisms. Studies have reported that misoprostol can not only alleviate ischemic injury but also protect GI mucosal layer. Therefore, we evaluated the effects of misoprostol on intestinal goblet cells after heat stress and on multiple-organ dysfunction in heat stroke rats., Main Methods: Heat stress was established in the heating chamber and followed by misoprostol treatment. Changes in hemodynamics, organ function indices, inflammation, oxidative stress, and survival rate were analyzed. Furthermore, ilea and LS174T cells were used to examine intestinal functions., Key Findings: Heat stress caused dysfunction of intestinal goblet cells and damage to ilea by increasing oxidative stress and apoptosis. Increased nitrosative stress and inflammation accompanied by hypotension, hypoperfusion, tachycardia, multiple-organ dysfunction, and death were observed in the heat stroke rat model. Treatment of LS174T cells with misoprostol not only decreased oxidative stress and apoptosis but also reduced cytotoxicity caused by heat stress. Moreover, misoprostol prevented disruption of the enteric barrier, multiple-organ injury, and death in rats with heat stroke., Significance: This study indicates that misoprostol could alleviate intestinal damage and organ injury caused by heat stress and be a potential therapy for heat-related illnesses., Competing Interests: Declaration of competing interest All authors have read the journal's policy on disclosure of potential conflicts of interest and have no conflicts of interest to declare., (Copyright © 2022 Elsevier Inc. All rights reserved.)