Enhancement of ANN-based wind power forecasting by modification of surface roughness parameterization over complex terrain.

Wind energy plays an important role in the sustainable energy transition towards a low-carbon society. Proper assessment of wind energy resources and accurate wind energy prediction are essential prerequisites for balancing electricity supply and demand. However, these remain challenging, especially for onshore wind farms over complex terrains, owing to the interplay between surface heterogeneities and intermittent turbulent flows in the planetary boundary layer. This study aimed to improve wind characteristic assessment and medium-term wind power forecasts over complex hilly terrain using a numerical weather prediction (NWP) model. The NWP model reproduced the wind speed distribution, duration, and spatio-temporal variabilities of the observed hub-height wind speed at 24 wind turbines in onshore wind farms when incorporating more realistic surface roughness effects, such as the subgrid-scale topography, roughness sublayer, and canopy height. This study also emphasizes the good features for machine learning that represent heterogeneities in the surface roughness elements in the atmospheric model. We showed that medium-term forecasting using the NWP model output and a simple artificial neural network (ANN) improved day-ahead wind power forecasts by 14% in terms of annual normalized mean absolute error. Our results suggest that better parameterizations of surface friction in atmospheric models are important for wind power forecasting and resource assessment using NWP models, especially when combined with machine learning techniques, and shed light on onshore wind power forecasting and wind energy assessment in mountainous regions.

The absence of thioredoxin-interacting protein in alveolar cells exacerbates asthma during obesity.

Obesity is associated with an increased incidence of asthma. However, the mechanisms underlying this association are not fully understood. In this study, we investigated the role of thioredoxin-interacting protein (TXNIP) in obesity-induced asthma. Asthma was induced by intranasal injection of a protease from Aspergillus oryzae in normal diet (ND)- or high fat diet (HFD)-fed mice to investigate the symptoms. We measured TXNIP expression in the lungs of patients with asthma and in ND or HFD asthmatic mice. To explore the role of TXNIP in asthma pathogenesis, we induced asthma in the same manner in alveolar type 2 cell-specific TXNIP deficient (TXNIPCre) mice. In addition, the expression levels of pro-inflammatory cytokines were compared based on TXNIP gene expression in A549 cells stimulated with recombinant human tumor necrosis factor alpha. Compared to ND-fed mice, HFD-fed mice had elevated levels of free fatty acids and adipokines, resulting in high reactive oxygen species levels and more severe asthma symptoms. TXNIP expression was increased in both, asthmatic patients and HFD asthmatic mice. However, in experiments using TXNIPCre mice, despite being TXNIP deficient, TXNIPCre mice exhibited exacerbated asthma symptoms. Consistent with this, in vitro studies showed highest expression levels of pro-inflammatory cytokines in TXNIP-silenced cells. Overall, our findings suggest that increased TXNIP levels in obesity-induced asthma is compensatory to protect against inflammatory responses.

Green tea extract suppresses airway inflammation via oxidative stress-driven MAPKs/MMP-9 signaling in asthmatic mice and human airway epithelial cells.

Introduction: The anti-inflammatory effect of green tea extract (GTE) has been confirmed in asthmatic mice, however, the pharmacological mechanism is not fully elucidated. Methods: To investigate the therapeutic efficacy of GTE in asthma and identify specific pathways, murine model of allergic asthma was established by ovalbumin (OVA) sensitization and the challenge for 4 weeks, with oral treatment using GTE and dexamethasone (DEX). Inflammatory cell counts, cytokines, OVA-specific IgE, airway hyperreactivity, and antioxidant markers in the lung were evaluated. Also, pulmonary histopathological analysis and western blotting were performed. In vitro, we established the model by stimulating the human airway epithelial cell line NCI-H292 using lipopolysaccharide, and treating with GTE and mitogen-activated protein kinases (MAPKs) inhibitors. Results: The GTE100 and GTE400 groups showed a decrease in airway hyperresponsiveness and the number of inflammatory cells in the bronchoalveolar lavage fluid (BALF) compared to the OVA group. GTE treatment also reduced interleukin (IL)-13, IL-5, and IL-4 levels in the BALF, and OVA-specific immunoglobulin E levels in the serum compared to those in the OVA group. GTE treatment decreased OVA-induced mucus secretion and airway inflammation. In addition, GTE suppressed the oxidative stress, and phosphorylation of MAPKs, which generally occurs after exposure to OVA. GTE administration also reduced matrix metalloproteinase-9 activity and protein levels. Conclusion: GTE effectively inhibited asthmatic respiratory inflammation and mucus hyperproduction induced by OVA inhalation. These results suggest that GTE has the potential to be used for the treatment of asthma.

PAR2-mediated cellular senescence promotes inflammation and fibrosis in aging and chronic kidney disease.

Cellular senescence contributes to inflammatory kidney disease via the secretion of inflammatory and profibrotic factors. Protease-activating receptor 2 (PAR2) is a key regulator of inflammation in kidney diseases. However, the relationship between PAR2 and cellular senescence in kidney disease has not yet been described. In this study, we found that PAR2-mediated metabolic changes in renal tubular epithelial cells induced cellular senescence and increased inflammatory responses. Using an aging and renal injury model, PAR2 expression was shown to be associated with cellular senescence. Under in vitro conditions in NRK52E cells, PAR2 activation induces tubular epithelial cell senescence and senescent cells showed defective fatty acid oxidation (FAO). Cpt1α inhibition showed similar senescent phenotype in the cells, implicating the important role of defective FAO in senescence. Finally, we subjected mice lacking PAR2 to aging and renal injury. PAR2-deficient kidneys are protected from adenine- and cisplatin-induced renal fibrosis and injury, respectively, by reducing senescence and inflammation. Moreover, kidneys lacking PAR2 exhibited reduced numbers of senescent cells and inflammation during aging. These findings offer fresh insights into the mechanisms underlying renal senescence and indicate that targeting PAR2 or FAO may be a promising therapeutic approach for managing kidney injury.

Korean Red Ginseng suppresses emphysematous lesions induced by cigarette smoke condensate through inhibition of macrophage-driven apoptosis pathways.

Background: Cigarette smoke is generally accepted as a major contributor to chronic obstructive pulmonary disease (COPD), which is characterized by emphysematous lesions. In this study, we investigated the protective effects of Korean Red Ginseng (KRG) against cigarette smoke condensate (CSC)-induced emphysema. Methods: Mice were instilled with 50 mg/kg of CSC intranasally once a week for 4 weeks, KRG was administered to the mice once daily for 4 weeks at doses of 100 or 300 mg/kg, and dexamethasone (DEX, positive control) was administered to the mice once daily for 2 weeks at 3 mg/kg. Results: KRG markedly decreased the macrophage population in bronchoalveolar lavage fluid and reduced emphysematous lesions in the lung tissues. KRG suppressed CSC-induced apoptosis as revealed by terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling staining and Caspase 3 immunohistochemistry. Additionally, KRG effectively inhibited CSC-mediated activation of Bcl-2-associated X protein/Caspase 3 signaling, followed by the induction of cell survival signaling, including vascular endothelial growth factor/phosphoinositide 3-kinase/protein kinase B in vivo and in vitro. The DEX group also showed similar improved results in vivo and in vitro. Conclusion: Taken together, KRG effectively inhibits macrophage-mediated emphysema induced by CSC exposure, possibly via the suppression of pro-apoptotic signaling, which results in cell survival pathway activation. These findings suggest that KRG has therapeutic potential for the prevention of emphysema in COPD patients.

Step-by-Step Nanoscale Top-Down Blocking and Etching Lead to Nanohexapods with Cartesian Geometry.

In this research, we designed a stepwise synthetic method for Au@Pt hexapods where six elongated Au pods are arranged in a pairwise perpendicular fashion, sharing a common point (the central origin in a Cartesian-coordinate-like hexapod shape), featured with tip-selectively decorated Pt square nanoplates. Au@Pt hexapods were successfully synthesized by applying three distinctive chemical reactions in a stepwise manner. The Pt adatoms formed discontinuous thin nanoplates that selectively covered six concave facets of a Au truncated octahedron and served as etching masks in the succeeding etching process, which prevented underlying Au atoms from being oxidized. The subsequent isotropic etching proceeded radially, starting from the bare Au surface, carving the central nanocrystal in a concave manner. By controlling the etching conditions, Au@Pt hexapods were successfully fabricated, wherein the core Au domain is connected to six protruding arms, which hold Pt nanoplates at the ends. Due to their morphology, Au@Pt hexapods feature distinctive optical properties in the near-infrared region, as a proof of concept, allowing for surface-enhanced Raman spectroscopy (SERS)-based monitoring of in situ CO electrooxidation. We further extended our synthetic library by tailoring the size of the Pt nanoplates and neck widths of Au branches, demonstrating the validity of selective blocking and etching-based colloidal synthesis.

Korean red ginseng suppresses mitochondrial apoptotic pathway in denervation-induced skeletal muscle atrophy.

Background: Skeletal muscle denervation leads to motor neuron degeneration, which in turn reduces muscle fiber volumes. Recent studies have revealed that apoptosis plays a role in regulating denervation-associated pathologic muscle wasting. Korean red ginseng (KRG) has various biological activities and is currently widely consumed as a medicinal product worldwide. Among them, ginseng has protective effects against muscle atrophy in in vivo and in vitro. However, the effects of KRG on denervation-induced muscle damage have not been fully elucidated. Methods: We induced skeletal muscle atrophy in mice by dissecting the sciatic nerves, administered KRG, and then analyzed the muscles. KRG was administered to the mice once daily for 3 weeks at 100 and 400 mg/kg/day doses after operation. Results: KRG treatment significantly increased skeletal muscle weight and tibialis anterior (TA) muscle fiber volume in injured areas and reduced histological alterations in TA muscle. In addition, KRG treatment reduced denervation-induced apoptotic changes in TA muscle. KRG attenuated p53/Bax/cytochrome c/Caspase 3 signaling induced by nerve injury in a dose-dependent manner. Also, KRG decreases protein kinase B/mammalian target of rapamycin pathway, reducing restorative myogenesis. Conclusion: Thus, KRG has potential protective role against denervation-induced muscle atrophy. The effect of KRG treatment was accompanied by reduced levels of mitochondria-associated apoptosis.

Transaortic removal of a large primary sarcoma from the left ventricle assisted by strategic partial resection and endoscopic guidance: a case report.

BACKGROUND: Surgical resection remains the mainstay of treatment for cardiac sarcoma, a rare but lethal disease. Achieving complete removal of a large-sized left ventricular sarcoma remains a challenge even with various surgical approaches that have been employed. CASE PRESENTATION: We present a case of a 74-year-old woman with shortness of breath who underwent surgical removal of a primary cardiac sarcoma, measuring 6 × 3.5 × 3 cm, attached to the septum of the left ventricle and caused sub-aortic valve obstruction. Transaortic approach was chosen and the access to this entire huge mass was enabled by using interim partial resection which created a space for further dissection and subsequent deeper endoscopic views. The further dissection was finally able to be advanced on the apex, and the residual mass was completely resected with gross tumor-free margins. CONCLUSION: Interim partial resection and endoscopic guidance can highly facilitate the transaortic removal of even large left ventricular sarcomas.

Oral bioavailability and egg drug residue of lincomycin in laying hens after different treatment.

Lincomycin (LCM) is an antibiotic used to treat severe bacterial infections in livestock and companion animals. In this study, we aimed to investigate the oral bioavailability of LCM with PK data after IV and PO administration and to compare differences in drug residue patterns in eggs. To ensure food safety, an additional study on egg residue was conducted using 3 different commercial LCM drugs. For bioavailability study, laying hens were divided into oral and intravenous (n = 8/group) groups and received single dose (10 mg/kg) of LCM. The limits of quantification for LCM were 0.729 µg/mL and 0.009 mg/kg in plasma and eggs, respectively. The oral group exhibited a significantly lower average serum drug concentration than the IV group, with a bioavailability of 2.6%. Furthermore, the egg residue profiles confirmed reduced systemic drug exposure after oral administration. For the commercial LCM drug egg residue experiment, laying hens were divided into low- and high-dose groups (n = 12/group) for each drug and treated with the recommended dosage and administration method for each respective drug. The eggs were collected and analyzed until 14 d after the last drug treatment. Despite differences in the LCM content and formulation among commercial drugs, all the tested commercial drugs showed average concentrations below the MRL in eggs within approximately 3 d after the last drug treatment. In this study, we have confirmed that LCM has a low oral absorption rate in laying hens, and this was consistent with the findings from the egg residue profiles. Further studies are requested to elucidate the exact reasons for evidently low oral drug absorption in laying hens.

Circularly Polarized Light Emission from Nonchiral Perovskites Incorporated into Nanoporous Cholesteric Polymer Templates.

Chiral perovskites have garnered significant attention, owing to their chiroptical properties and emerging applications. Current fabrication methods often involve complex chemical synthesis routes. Herein, an alternative approach for introducing chirality into nonchiral hybrid organic-inorganic perovskites (HOIPs) using nanotemplates composed of cholesteric polymeric networks is proposed. This method eliminates the need for additional molecular design. In this process, HOIP precursors are incorporated into a porous cholesteric polymer film, and two-dimensional (2D) HOIPs grow inside the nanopores. Circularly polarized light emission (CPLE) was observed even though the selective reflection band of the cholesteric polymer films containing a representative HOIP deviated from the emission wavelength of the 2D HOIP. This effect was confirmed by the induced circular dichroism (CD) observed in the absorbance band of the HOIP. The observed CPLE and CD are attributed to the chirality induced by the template in the originally nonchiral 2D HOIP. Additionally, the developed 2D HOIP exhibited a long exciton lifetime and good stability under harsh conditions. These findings provide valuable insights into the development and design of innovative optoelectronic materials.

Thiobarbiturate-Derived Compound MHY1025 Alleviates Renal Fibrosis by Modulating Oxidative Stress, Epithelial Inflammation, and Fibroblast Activation.

Chronic kidney disease (CKD) is a kidney structure and function abnormality. CKD development and progression are strongly influenced by oxidative stress and inflammatory responses, which can lead to tubulointerstitial fibrosis. Unfortunately, there are no effective or specific treatments for CKD. We investigated the potential of the thiobarbiturate-derived compound MHY1025 to alleviate CKD by reducing oxidative stress and inflammatory responses. In vitro experiments using NRK52E renal tubular epithelial cells revealed that MHY1025 significantly reduced LPS-induced oxidative stress and inhibited the activation of the NF-κB pathway, which is involved in inflammatory responses. Furthermore, treatment with MHY1025 significantly suppressed the expression of fibrosis-related genes and proteins induced by TGFß in NRK49F fibroblasts. Furthermore, we analyzed the MHY1025 effects in vivo. To induce kidney fibrosis, mice were administered 250 mg/kg folic acid (FA) and orally treated with MHY1025 (0.5 mg/kg/day) for one week. MHY1025 effectively decreased the FA-induced inflammatory response in the kidneys. The group treated with MHY1025 exhibited a significant reduction in cytokine and chemokine expression and decreased immune cell marker expression. Decreased inflammatory response was associated with decreased tubulointerstitial fibrosis. Overall, MHY1025 alleviated renal fibrosis by directly modulating renal epithelial inflammation and fibroblast activation, suggesting that MHY1025 has the potential to be a therapeutic agent for CKD.

Green tea extract improves cyclophosphamide-induced immunosuppression in mouse spleen and enhances the immune activity of RAW 264.7 cells.

Cyclophosphamide (CP) is mainly used to treat autoimmune diseases and cancer; however, it damages normal immune cells. Therefore, the effects of chemotherapy on CP are limited. Notably, green tea has been reported to effectively modulate immune function. Here, given the pharmacological properties of green tea, we evaluated the ability of green tea extract (GTE) to restore immunity suppressed by CP in vivo and to activate macrophages in vitro. GTE significantly improved the suppressed immune function, including spleen index and proliferation of spleen T lymphocytes, as revealed by histopathological examination and flow cytometry analysis. Moreover, GTE effectively activated RAW 264.7, as represented by the induction of nitric oxide, reactive oxygen species, and cytokine levels. GTE also increased the phosphorylation of mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B in RAW 264.7 cells. In conclusion, GTE ameliorated CP-induced immunosuppression in mice and stimulated immune activity in RAW 264.7 cells, possibly by activating the MAPK signaling pathway. These findings suggest that GTE has the potential to be used as a supplementary agent in chemotherapy for CP.

Pharmacokinetic profiles and egg residue patterns of levamisole in laying hens at two dosing rates and two routes of administration.

The levamisole maximum residue limit for edible fat, kidney, and muscle of chickens is 0.01 mg/kg. However, no maximum residue limit has been established for eggs. In the present study, the pharmacokinetic profile and levamisole residue in the eggs from laying hens were investigated using ultra-performance liquid chromatography-tandem mass spectrometry. A single dose of levamisole (30 mg/kg) was administered via the intramuscular or oral route, and an additional egg residue study was performed with 300 or 600 mg/kg commercial LEV drug (30 or 60 mg/kg as levamisole) orally. The limit of quantification was 0.0056 µg/mL and 0.0015 mg/kg for plasma and eggs, respectively. The plasma concentration was below the limit of quantification 10 and 12 h after intramuscular and oral administration, respectively. The half-life of the absorption phase was comparable between the intramuscular and oral routes, which was approximately 1 h, and the mean maximum concentration value was significantly higher in intramuscular (2.29 ± 0.30 µg/mL) than in oral (1.45 ± 0.38 µg/mL) route. The relative oral bioavailability after intramuscular administration was 92.3%. In the egg residue study, dose-dependent area under concentration and maximum concentration were observed after single oral administration of 30 and 60 mg/kg egg residue, and the calculated withdrawal period for both 30 and 60 mg/kg groups based on the positive list system standard (0.01 mg/kg) was 7 d after the treatment.

Integrated CO2 capture and electrochemical upgradation: the underpinning mechanism and techno-chemical analysis.

Coupling post-combustion CO2 capture with electrochemical utilization (CCU) is a quantum leap in renewable energy science since it eliminates the cost and energy involved in the transport and storage of CO2. However, the major challenges involved in industrial scale implementation are selecting an appropriate solvent/electrolyte for CO2 capture, modeling an appropriate infrastructure by coupling an electrolyser with a CO2 point source and a separator to isolate CO2 reduction reaction (CO2RR) products, and finally selection of an appropriate electrocatalyst. In this review, we highlight the major difficulties with detailed mechanistic interpretation in each step, to find out the underpinning mechanism involved in the integration of electrochemical CCU to achieve higher-value products. In the past decades, most of the studies dealt with individual parts of the integration process, i.e., either selecting a solvent for CO2 capture, designing an electrocatalyst, or choosing an ideal electrolyte. In this context, it is important to note that solvents such as monoethanolamine, bicarbonate, and ionic liquids are often used as electrolytes in CO2 capture media. Therefore, it is essential to fabricate a cost-effective electrolyser that should function as a reversible binder with CO2 and an electron pool capable of recovering the solvent to electrolyte reversibly. For example, reversible ionic liquids, which are non-ionic in their normal forms, but produce ionic forms after CO2 capture, can be further reverted back to their original non-ionic forms after CO2 release with almost 100% efficiency through the chemical or thermal modulations. This review also sheds light on a focused techno-economic evolution for converting the electrochemically integrated CCU process from a pilot-scale project to industrial-scale implementation. In brief, this review article will summarize a state-of-the-art argumentation of challenges and outcomes over the different segments involved in electrochemically integrated CCU to stimulate urgent progress in the field.

TLR7 activation by miR-21 promotes renal fibrosis by activating the pro-inflammatory signaling pathway in tubule epithelial cells.

BACKGROUND: Toll-like receptor 7 (TLR7) is an endosomal TLR activated by single-stranded RNA, including endogenous microRNAs. Although TLR7 is known to promote inflammatory responses in pathophysiological conditions, its role in renal fibrosis has not been investigated. Here, we aim to investigate the inflammatory roles of TLR7 in kidney inflammation and fibrosis. METHODS: TLR7 knockout mice (Tlr7 -/-) subjected to AD-induced kidney injury were utilized to examine the role of TLR7 in kidney fibrosis. To elucidate the role of TLR7 in renal epithelial cells, NRK52E rat renal tubule epithelial cells were employed. RESULTS: Under fibrotic conditions induced by an adenine diet (AD), TLR7 was significantly increased in damaged tubule epithelial cells, where macrophages were highly infiltrated. TLR7 deficiency protected against AD-induced tubular damage, inflammation, and renal fibrosis. Under in vitro conditions, TLR7 activation increased NF-κB activity and induced chemokine expression, whereas TLR7 inhibition effectively blocked NF-κB activation. Furthermore, among the known TLR7 endogenous ligands, miR-21 was significantly upregulated in the tubular epithelial regions. In NRK52E cells, miR-21 treatment induced pro-inflammatory responses, which could be blocked by a TLR7 inhibitor. When the TLR7 inhibitor, M5049, was administered to the AD-induced renal fibrosis model, TLR7 inhibition significantly attenuated AD-induced renal inflammation and fibrosis. CONCLUSIONS: Overall, activation of TLR7 by endogenous miR-21 in renal epithelial cells contributes to inflammatory responses in a renal fibrosis model, suggesting a possible therapeutic target for the treatment of renal fibrosis. Video Abstract.

Graft Patency of No-Touch Saphenous Veins Used as Aortocoronary Bypass Grafts.

Background: This study evaluated the early, 1-year, and 3-year graft patency rates and mid-term clinical outcomes after no-touch saphenous veins (NT-SVs) were used as aortocoronary grafts in coronary artery bypass grafting (CABG). Methods: In total, 101 patients who underwent CABG using NT-SVs as aortocoronary grafts were included. The 2 most common indications for performing aortocoronary grafting with NT-SVs were unavailability of the left internal thoracic artery (n=36) and moderate lesions where flow competition was expected (n=27). Early (median, 1 day; interquartile range [IQR], 1-2 days), 1-year (median, 13 months; IQR, 11-16 months), and 3-year (median, 34 months; IQR, 27-41 months) graft angiography was performed in 98 (97.0%), 84 (83.2%), and 40 patients (39.6%), respectively. The median follow-up duration was 43 months (IQR, 13-76 months). Overall survival rates and the cumulative incidence of major adverse cardiac events were evaluated. Results: The operative mortality rate was 2% (2 of 101 patients). Early postoperative patency rates for overall and aortocoronary NT-SV grafts were 98.2% (223 of 227 distal anastomoses) and 98.2% (164 of 167), respectively. The 1- and 3-year patency rates for aortocoronary SV grafts were 94.9% (131 of 138) and 90.6% (58 of 64), respectively. The overall survival rates at 5 and 10 years were 81.7% and 59%, respectively. The cumulative incidence of major adverse cardiac events at 5 and 10 postoperative years was 20.7% and 39%, respectively. Conclusion: The feasibility of using NT-SVs as aortocoronary grafts in CABG was shown in this study, based on the graft patency rates up to 3 years and the mid-term clinical outcomes.

Gene Therapy Using Efficient Direct Lineage Reprogramming Technology for Neurological Diseases.

Gene therapy is an innovative approach in the field of regenerative medicine. This therapy entails the transfer of genetic material into a patient's cells to treat diseases. In particular, gene therapy for neurological diseases has recently achieved significant progress, with numerous studies investigating the use of adeno-associated viruses for the targeted delivery of therapeutic genetic fragments. This approach has potential applications for treating incurable diseases, including paralysis and motor impairment caused by spinal cord injury and Parkinson's disease, and it is characterized by dopaminergic neuron degeneration. Recently, several studies have explored the potential of direct lineage reprogramming (DLR) for treating incurable diseases, and highlighted the advantages of DLR over conventional stem cell therapy. However, application of DLR technology in clinical practice is hindered by its low efficiency compared with cell therapy using stem cell differentiation. To overcome this limitation, researchers have explored various strategies such as the efficiency of DLR. In this study, we focused on innovative strategies, including the use of a nanoporous particle-based gene delivery system to improve the reprogramming efficiency of DLR-induced neurons. We believe that discussing these approaches can facilitate the development of more effective gene therapies for neurological disorders.

Plasmonic Double-Walled Nanoframes with Face-to-Face Nanogaps for Strong SERS Activity.

A synthesis method for plasmonic double-walled nanoframes was developed, where single-walled truncated octahedral nanoframes with (111) open facets and (100) solid flat planes are nested in a core-shell manner. By applying multiple chemical toolkits to Au cuboctahedrons as a starting template, Au double-walled nanoframes with controllable face-to-face nanogaps were successfully synthesized in high homogeneity in size and shape. Importantly, when the gap distance between inner and outer flat walled frames became closer, augmentation of electromagnetic near-field focusing was achieved, leading to generation of hot-zones, which was verified by surface-enhanced Raman spectroscopy. The unique optical property of Au double-walled nanoframes with high structural intricacy was carefully investigated and the SERS substrates comprising Au double-walled nanoframes with the narrowest nanogaps exhibited much improved near-field enhancement toward strongly and/or weakly adsorbing analytes, allowing for gas phase detection in chemical warfare agents, which is a huge challenge in early warning systems.

PPAR Pan Agonist MHY2013 Alleviates Renal Fibrosis in a Mouse Model by Reducing Fibroblast Activation and Epithelial Inflammation.

The peroxisome proliferator-activated receptor (PPAR) nuclear receptor has been an interesting target for the treatment of chronic diseases. Although the efficacy of PPAR pan agonists in several metabolic diseases has been well studied, the effect of PPAR pan agonists on kidney fibrosis development has not been demonstrated. To evaluate the effect of the PPAR pan agonist MHY2013, a folic acid (FA)-induced in vivo kidney fibrosis model was used. MHY2013 treatment significantly controlled decline in kidney function, tubule dilation, and FA-induced kidney damage. The extent of fibrosis determined using biochemical and histological methods showed that MHY2013 effectively blocked the development of fibrosis. Pro-inflammatory responses, including cytokine and chemokine expression, inflammatory cell infiltration, and NF-κB activation, were all reduced with MHY2013 treatment. To demonstrate the anti-fibrotic and anti-inflammatory mechanisms of MHY2013, in vitro studies were conducted using NRK49F kidney fibroblasts and NRK52E kidney epithelial cells. In the NRK49F kidney fibroblasts, MHY2013 treatment significantly reduced TGF-ß-induced fibroblast activation. The gene and protein expressions of collagen I and α-smooth muscle actin were significantly reduced with MHY2013 treatment. Using PPAR transfection, we found that PPARγ played a major role in blocking fibroblast activation. In addition, MHY2013 significantly reduced LPS-induced NF-κB activation and chemokine expression mainly through PPARß activation. Taken together, our results suggest that administration of the PPAR pan agonist effectively prevented renal fibrosis in both in vitro and in vivo models of kidney fibrosis, implicating the therapeutic potential of PPAR agonists against chronic kidney diseases.

Green tea extract ameliorates macrophage-driven emphysematous lesions in chronic obstructive pulmonary disease induced by cigarette smoke condensate.

Chronic obstructive pulmonary disease (COPD) is an important lung disease characterized by complicated symptoms including emphysema. We aimed to explore the mechanisms underlying the protective effect of green tea extract (GTE) on cigarette smoke condensate (CSC)-induced emphysema by demonstrating the reduction of macrophage-induced protease expression through GTE treatment in vivo and in vitro. Mice were intranasally administered 50 mg/kg CSC once a week for 4 weeks, and doses of 100 or 300 mg/kg GTE were administered orally once daily for 4 weeks. GTE significantly reduced macrophage counts in bronchoalveolar lavage fluid and emphysematous lesions in lung tissues in CSC-exposed mice. In addition, GTE suppressed CSC-induced extracellular signal-regulated kinase (ERK)/activator protein (AP)-1 phosphorylation followed by matrix metalloproteinases (MMP)-9 expression as revealed by western blotting, immunohistochemistry, and zymography in CSC-instilled mice. These underlying mechanisms related to reduced protease expression were confirmed in NCI-H292 cells stimulated by CSC. Taken together, GTE effectively inhibits macrophage-driven emphysematous lesions induced by CSC treatment, and these protective effects of GTE are closely related to the ERK/AP-1 signaling pathway, followed by a reduced protease/antiprotease imbalance. These results suggest that GTE can be used as a supplementary agent for the prevention of emphysema progression in COPD patients.