Hepatocyte leukotriene B4 receptor 1 promotes NAFLD development in obesity.

BACKGROUND AND AIMS: NAFLD is the most prevalent chronic liver disease worldwide and has emerged as a serious public health issue with no approved treatment. The development of NAFLD is strongly associated with hepatic lipid content, and patients with NAFLD have significantly higher rates of hepatic de novo lipogenesis (DNL) than lean individuals. Leukotriene B4 (LTB4), a metabolite of arachidonic acid, is dramatically increased in obesity and plays important role in proinflammatory cytokine production and insulin resistance. But the role of liver LTB4/LTB4 receptor 1 (Ltb4r1) in lipid metabolism is unclear. APPROACH AND RESULTS: Hepatocyte-specific knockout (HKO) of Ltb4r1 improved hepatic steatosis and systemic insulin resistance in both diet-induced and genetically induced obese mice. The mRNA level of key enzymes involved in DNL and fatty acid esterification decreased in Ltb4r1 HKO obese mice. LTB4/Ltb4r1 directly promoted lipogenesis in HepG2 cells and primary hepatocytes. Mechanically, LTB4/Ltb4r1 promoted lipogenesis by activating the cAMP-protein kinase A (PKA)-inositol-requiring enzyme 1α (IRE1α)-spliced X-box-binding protein 1 (XBP1s) axis in hepatocytes, which in turn promoted the expression of lipogenesis genes regulated by XBP1s. In addition, Ltb4r1 suppression through the Ltb4r1 inhibitor or lentivirus-short hairpin RNA delivery alleviated the fatty liver phenotype in obese mice. CONCLUSIONS: LTB4/Ltb4r1 promotes hepatocyte lipogenesis directly by activating PKA-IRE1α-XBP1s to promote lipogenic gene expression. Inhibition of hepatocyte Ltb4r1 improved hepatic steatosis and insulin resistance. Ltb4r1 is a potential therapeutic target for NAFLD.

Study of Allergy and Sensitization Relationship in Children and Parents in Southern China.

INTRODUCTION: The incidence of allergic diseases has increased globally, with genetics playing an essential role in these conditions' development. However, there is still a gap in understanding of how parental allergy status affects children's allergies. METHODS: An electronic questionnaire was used to assess allergy-related symptoms in kindergarten children and their parents, with a clinical diagnosis and concurrent serum allergen-specific immunoglobulin E (IgE), total IgE, and blood cell counts obtained. RESULTS: 88 family groups were enrolled, with allergy prevalence of 85.2% in children, 50% in fathers, and 42% in mothers. Allergic rhinoconjunctivitis was the most common allergic disease. When the mother had an allergy, the children's allergy diagnosis rate was 91.3%; 86.67% when the father had an allergy; and 85.71% when both parents had allergies. The child sensitization rate was 78.26% when the father had sensitization, 59.09% just as the mother had sensitization, and 84.21% when both parents had sensitization. Paternal allergies affected children's quality of life due to allergic rhinitis but not their rhinitis symptoms. Maternal allergies or sensitization did not significantly affect children's symptoms or quality-of-life scores. CONCLUSION: The study found a positive correlation between childhood and parental allergies, and further studies are needed to confirm the findings.

Two FGF Receptor Kinase Molecules Act in Concert to Recruit and Transphosphorylate Phospholipase Cγ.

The molecular basis by which receptor tyrosine kinases (RTKs) recruit and phosphorylate Src Homology 2 (SH2) domain-containing substrates has remained elusive. We used X-ray crystallography, NMR spectroscopy, and cell-based assays to demonstrate that recruitment and phosphorylation of Phospholipase Cγ (PLCγ), a prototypical SH2 containing substrate, by FGF receptors (FGFR) entails formation of an allosteric 2:1 FGFR-PLCγ complex. We show that the engagement of pTyr-binding pocket of the cSH2 domain of PLCγ by the phosphorylated tail of an FGFR kinase induces a conformational change at the region past the cSH2 core domain encompassing Tyr-771 and Tyr-783 to facilitate the binding/phosphorylation of these tyrosines by another FGFR kinase in trans. Our data overturn the current paradigm that recruitment and phosphorylation of substrates are carried out by the same RTK monomer in cis and disclose an obligatory role for receptor dimerization in substrate phosphorylation in addition to its canonical role in kinase activation.

A retrospective comparison of Sun's tip-flexible semirigid ureterorenoscopy, super-mini percutaneous nephrolithotomy and flexible ureteroscopy applied to treat upper urinary tract calculi.

BACKGROUND: This retrospective study was conducted to compare the safety and efficacy of Sun's tip-flexible semirigid ureterorenoscopy (tf-URS), super-mini percutaneous nephrolithotomy (SMP) and flexible ureteroscopy (FURS) in treating upper urinary tract calculi, including upper ureteral or renal calculi. METHODS: We included patients with upper ureteral calculi or renal calculi 1.0-2.0 cm in size, who underwent tf-URS, SMP or FURS, respectively. The indicators reflecting safety and efficacy were compared among the three surgical techniques. RESULTS: SMP presented with higher single stone crushing success rate, but longer operation time and postoperative hospital stay, more blood loss, and higher postoperative pain score compared with FURS and tf-URS (P < 0.05). The hospitalization cost of tf-URS group was lower than that of SMP and FURS groups (P < 0.05). The incidence of postoperative fever in tf-URS group was significantly higher than that in SMP group (P < 0.05). No significant difference was found in mucosal injury, perirenal hematoma, and stone-free rate at 3 months after surgery (P > 0.05). CONCLUSIONS: tf-URS and FURS have the advantages in minimal invasion, hospitalization cost, patient comfort, and hospital stay while SMP has higher stone-free rate. These three surgical techniques are safe, reliable and complementary, which should be selected according to the actual situation.

Aminophylline suppresses chronic renal failure progression by activating SIRT1/AMPK/mTOR-dependent autophagy.

Chronic renal failure (CRF) is a severe syndrome affecting the urinary system for which there are no effective therapeutics. In this study, we investigate the effects and mechanisms of aminophylline in preventing CRF development. A rat model of chronic renal failure is established by 5/6 nephrectomy. The levels of serum creatinine (SCR), urinary protein (UPR), and blood urea nitrogen (BUN) are detected by ELISA. Histological evaluations of renal tissues are performed by H&E, Masson staining, and PAS staining. Functional protein expression is detected by western blot analysis or immunofluorescence microscopy. Glomerular cell apoptosis is determined using the TUNEL method. Results show that Aminophylline significantly reduces the levels of SCR, UPR, and BUN in the CRF model rats. Histological analyses show that aminophylline effectively alleviates renal tissue injuries in CRF rats. The protein expression levels of nephrin, podocin, SIRT1, p-AMPK, and p-ULK1 are greatly increased, while p-mTOR protein expression is markedly decreased by aminophylline treatment. Additionally, the protein level of LC3B in CRF rats is significantly increased by aminophylline. Moreover, aminophylline alleviates apoptosis in the glomerular tissues of CRF rats. Furthermore, resveratrol promotes SIRT1, p-AMPK, and p-ULK1 protein expressions and reduces p-mTOR and LC3B protein expressions in CRF rats. Selisistat (a SIRT1 inhibitor) mitigates the changes in SIRT1, p-AMPK, p-ULK1, p-mTOR, and LC3B expressions induced by aminophylline. Finally, RAPA alleviates renal injury and apoptosis in CRF rats, and 3-MA eliminates the aminophylline-induced inhibition of renal injury and apoptosis in CRF rats. Aminophylline suppresses chronic renal failure progression by modulating the SIRT1/AMPK/mTOR-mediated autophagy process.

Evaluation of the clinical performance of multiple serum sIgE detection systems based on component-resolved diagnosis.

BACKGROUND: Serum allergen-specific IgE (sIgE) detection is an important tool in the diagnosis of allergic diseases. However, the absence of international standards for sIgE detection systems raises questions about the comparability of different systems. OBJECTIVE: This study aims to evaluate three common allergen sIgE detection systems, with a primary focus on detecting dust mite allergens. METHODS: We recruited 85 children with rhinitis and 15 healthy control children. The subjects underwent testing with three different sIgE detection systems, including magnetic particle flow fluorescence, magnetic particle chemiluminescence, and protein chip, to detect sIgE levels to HDM extracts. In addition, skin prick testing (SPT) was conducted, and protein chip technology was performed to measure sIgE levels to component proteins. RESULTS: Our findings reveal strong consistency between SPT and the three in vitro detection systems, with consistency exceeding 71.76% for dust mite allergens. Moreover, there was excellent consistency and RAST class consistency among the three in vitro detection systems, with scores exceeding 94.12% and 89.00%, respectively. And for the 13 additional allergens crude extracts sIgE simultaneously detected by systems 1 and 2, the results showed that the consistency of both systems was above 87.00%, and the RAST class consistency was above 82.00%. CONCLUSION: The three serum sIgE detection systems exhibited an approximate 80% concordance rate with SPT in identifying dust mite allergens. Furthermore, these systems demonstrated excellent consistency and RAST class consistency among themselves. These findings suggest that the three assays introduced in this study are interchangeable in allergen diagnosis.

Effects of clinical nursing pathway on the surgical site wound infection in patients undergoing knee or hip replacement surgery: A meta-analysis.

To explore the effect of clinical nursing pathway on wound infection in patients undergoing knee or hip replacement surgery. Computerised searches of PubMed, Web of Science, Cochrane Library, Embase, Wanfang, China Biomedical Literature Database, China National Knowledge Infrastructure databases were conducted, from database inception to September 2023, on the randomised controlled trials (RCTs) of application of clinical nursing pathway to patients undergoing knee and hip arthroplasty. Literature was screened and evaluated by two researchers based on inclusion and exclusion criteria, and data were extracted from the final included literature. RevMan 5.4 software was employed for data analysis. Overall, 48 RCTs involving 4139 surgical patients were included, including 2072 and 2067 in the clinical nursing pathway and routine nursing groups, respectively. The results revealed, compared with routine nursing, the use of clinical nursing pathways was effective in reducing the rate of complications (OR = 0.17, 95%CI: 0.14-0.21, p < 0.001) and wound infections (OR = 0.29, 95%CI: 0.16-0.51, p < 0.001), shortens the hospital length of stay (MD = -4.11, 95%CI: -5.40 to -2.83, p < 0.001) and improves wound pain (MD = -1.34, 95%CI: -1.98 to -0.70, p < 0.001); it also improve patient satisfaction (OR = 7.13, 95%CI: 4.69-10.85, p < 0.001). The implementation of clinical nursing pathways in clinical care after knee or hip arthroplasty can effectively reduce the incidence of complications and wound infections, and also improve the wound pain, while also improving treatment satisfaction so that patients can be discharged from the hospital as soon as possible.

Synthesis, Structures and Properties of Trioxa[9]circulene and Diepoxycyclononatrinaphthalene.

This article presents trioxa[9]circulene (3) as a novel member of hetero[n]circulenes. Its synthesis began with the synthesis of dimethoxydioxa[8]helicene (5) and used dimethoxydiepoxycyclononatrinaphthalene (4) as a key intermediate, despite the condensation reaction predominantly yielding a 1,4-addition byproduct. The structures and properties of 3-5 were extensively investigated using experimental and computational methods. Analysis of the crystal structures reveal elongation of the internal C-C bonds in the nine-membered ring of 3 compared to 4 and 5. Computational studies demonstrate the remarkable flexibility of trioxa[9]circulene's saddle-shaped polycyclic framework, while the other two compounds are rigid with large racemization barriers. Optically pure forms of 4 and 5 exhibit absorption and luminescence dissymmetry factors on the order of 10-2, with smaller values observed for compound 4. In the crystal structures, molecules of 3 stack to form columns with remarkable π-π overlap, and the π-π interactions of 4 exhibit short intermolecular C-to-C contacts. Consequently, the solution-processed film of 4 functioned as a p-type organic semiconductor in field effect transistors.

Cyclodextrin Incorporation into Covalent Organic Frameworks Enables Extensive Liquid and Gas Chromatographic Enantioseparations.

The separation of enantiomers using high-performance chromatography technologies represents great importance and interest. In this aspect, ß-cyclodextrin (ß-CD) and its derivatives have been extensively studied as chiral stationary phases (CSPs). Nevertheless, ß-CD that was immobilized on a traditional matrix often exhibited low stabilities and limited operating ranges. Recently, covalent organic frameworks (COFs) with highly ordered nanopores are emerging as promising CSPs for enantioseparations, but their practical applications are still hampered by the difficulty of monomer and COF synthesis. Herein, two ß-CD-driven COFs are synthesized via a fast and facile plasma-induced polymerization combined postsynthesis modification strategy. The precisely defined COF channels enhanced the accessibility of the accommodated ß-CD to the analytes and acted as robust protective barriers to safeguard the ß-CD from harsh environments. Therefore, the ß-CD-modified COFs can be potentially general CSPs for extensive enantioseparation in both gas chromatography and high-performance liquid chromatography, and a wide range of racemates were separated. Compared to the commonly employed commercial chiral columns, these COF-based columns exhibited comparable resolution capability and superior application versatility. This work integrates the advantages and overcomes the defects of COFs and ß-CD, thus advancing COFs as platforms for chiral selector modification and giving great promise for practical chromatographic enantioseparation.

Synthesis of Bitten Gold Nanoparticles with Single-Particle Chiroptical Responses.

The introduction of structural complexity to nanoparticles brings them interesting properties. Regularity breaking has been challenging in the chemical synthesis of nanoparticles. Most reported chemical methods for synthesizing irregular nanoparticles are complicated and laborious, largely hindering the exploration of structural irregularity in nanoscience. In this study, the authors have combined seed-mediated growth and Pt(IV)-induced etching to synthesize two types of unprecedented Au nanoparticles, bitten nanospheres and nanodecahedrons, with size control. Each nanoparticle has an irregular cavity on it. They exhibit distinct single-particle chiroptical responses. Perfect Au nanospheres and nanorods without any cavity do not show optical chirality, which demonstrates that the geometrical structure of the bitten opening plays a decisive role in the generation of chiroptical responses.

FGF4 protects the liver from nonalcoholic fatty liver disease by activating the AMP-activated protein kinase-Caspase 6 signal axis.

BACKGROUND AND AIMS: NAFLD represents an increasing health problem in association with obesity and diabetes with no effective pharmacotherapies. Growing evidence suggests that several FGFs play important roles in diverse aspects of liver pathophysiology. Here, we report a previously unappreciated role of FGF4 in the liver. APPROACH AND RESULTS: Expression of hepatic FGF4 is inversely associated with NAFLD pathological grades in both human patients and mouse models. Loss of hepatic Fgf4 aggravates hepatic steatosis and liver damage resulted from an obesogenic high-fat diet. By contrast, pharmacological administration of recombinant FGF4 mitigates hepatic steatosis, inflammation, liver damage, and fibrogenic markers in mouse livers induced to develop NAFLD and NASH under dietary challenges. Such beneficial effects of FGF4 are mediated predominantly by activating hepatic FGF receptor (FGFR) 4, which activates a downstream Ca2+ -Ca2+ /calmodulin-dependent protein kinase kinase beta-dependent AMP-activated protein kinase (AMPK)-Caspase 6 signal axis, leading to enhanced fatty acid oxidation, reduced hepatocellular apoptosis, and mitigation of liver damage. CONCLUSIONS: Our study identifies FGF4 as a stress-responsive regulator of liver pathophysiology that acts through an FGFR4-AMPK-Caspase 6 signal pathway, shedding light on strategies for treating NAFLD and associated liver pathologies.

Component-Resolved Analyses for Diagnosis of Food Allergies in Infants and Young Children in Southern China.

INTRODUCTION: Chicken eggs and cow's milk are two of the most common foods that cause allergic reactions in infants and young children, and there is a lack of precise diagnostic methods to identify the allergic state of these patients. The recently developed food allergen component-resolved diagnosis (CRD) may be a more accurate diagnosis method for food allergies. METHODS: One hundred children sensitized to egg white and milk crude extracts and diagnosed with or suspected allergic disease were included. The specific immunoglobulin E (sIgE) (s) of animal food allergen crude extracts (egg yolk, milk, shrimp, crab, cod, beef) and the main components of egg white and milk were tested. The sensitization characteristics, cross-reactivity, and clinical relevance were analyzed. RESULTS: The results of egg white-sensitized patients showed that ovalbumin (Gal d 2) had the highest positive rate of 100%. Compared with other pairwise combinations of egg allergens, the combination of egg white and Gal d 2 had higher diagnostic accuracy, with an AUC of 0.876 (95% CI: 0.801-0.951), a sensitivity of 88.9%, and a specificity of 75.9%. The positive rates of beta-lactoglobulin (Bos d 5) and alpha-lactoglobulin (Bos d 4) in the milk-sensitized children were comparable, 92% and 91%, respectively. The combination of crude milk extract and Bos d 4 had the highest diagnostic accuracy, with an AUC of 0.969 (95% CI: 0.938-0.999), a sensitivity of 100%, and a specificity of 82.7%. CONCLUSION: Among these subjects, our study found the main allergenic component of egg white was Gal d 2, and the main allergenic components of milk were Bos d 4 and Bos d 5. CRD may help identify egg/milk allergies and non-allergies.

Association of Ureaplasma infection pattern and azithromycin treatment effect with bronchopulmonary dysplasia in Ureaplasma positive infants: a cohort study.

BACKGROUND: It is unclear whether Ureaplasma-associated pneumonia and azithromycin treatment affect the risk for bronchopulmonary dysplasia (BPD). METHODS: A retrospective cohort study was performed in very low birth weight (VLBW) infants who tested positive for Ureaplasma within 72 h after birth in a tertiary unit. Chest X-ray (CXR) and laboratory test were performed before and after azithromycin treatment. Multivariate logistic regression analysis was used to identify the independent association between BPD and Ureaplasma-associated pneumonia, as well as BPD and effective azithromycin treatment. RESULTS: A total of 118 infants were included in the current study, of whom 36 developed BPD (defined as supplemental oxygen needed at postmenstrual age 36 weeks or discharge). The rate of BPD was significantly higher in infants with Ureaplasma-associated pneumonia (44.6%) compared to infants with Ureaplasma colonization (17.7%, P = 0.002). After adjusting for confounders, an effective azithromycin treatment was significantly associated with reduced risk of BPD [odd ratio (OR) 0.011; 95% confidence interval (CI): 0.000-0.250), whereas Ureaplasma-associated pneumonia was not significantly associated with BPD (OR 1.835; 95% CI: 0.548-6.147). CONCLUSION: Effective Azithromycin treatment in Ureaplasma positive VLBW infants was associated with a reduced risk of BPD.

Curtailing FGF19's mitogenicity by suppressing its receptor dimerization ability.

As a physiological regulator of bile acid homeostasis, FGF19 is also a potent insulin sensitizer capable of normalizing plasma glucose concentration, improving lipid profile, ameliorating fatty liver disease, and causing weight loss in both diabetic and diet-induced obesity mice. There is therefore a major interest in developing FGF19 as a therapeutic agent for treating type 2 diabetes and cholestatic liver disease. However, the known tumorigenic risk associated with prolonged FGF19 administration is a major hurdle in realizing its clinical potential. Here, we show that nonmitogenic FGF19 variants that retain the full beneficial glucose-lowering and bile acid regulatory activities of WT FGF19 (FGF19WT) can be engineered by diminishing FGF19's ability to induce dimerization of its cognate FGF receptors (FGFR). As proof of principle, we generated three such variants, each with a partial defect in binding affinity to FGFR (FGF19ΔFGFR) and its coreceptors, i.e., ßklotho (FGF19ΔKLB) or heparan sulfate (FGF19ΔHBS). Pharmacological assays in WT and db/db mice confirmed that these variants incur a dramatic loss in mitogenic activity, yet are indistinguishable from FGF19WT in eliciting glycemic control and regulating bile acid synthesis. This approach provides a robust framework for the development of safer and more efficacious FGF19 analogs.

Effects of evidence-based nursing in preventing pressure ulcers in intensive care unit patients: A meta-analysis.

To systematically analyse the effects of evidence-based nursing (EBN) in preventing the development of pressure ulcers (PUs) in intensive care unit (ICU) patients. We conducted a computerised search of the Embase, PubMed, Cochrane Library, Web of Science, China National Knowledge Infrastructure and Wanfang databases for randomised controlled trials on the prevention of PUs in ICU patients by EBN, published before the respective databases were established until September 2023. Two investigators independently performed literature screening, data extraction and quality assessment. A meta-analysis was performed using Stata 17.0. Eighteen papers were included, comprising 2593 patients, of whom 1297 and 1296 received EBN and conventional nursing, respectively. The incidence of PUs was 2.70% and 12.04% in the EBN and conventional nursing groups, respectively. Meta-analysis showed a statistically significantly lower incidence of PUs in the EBN group than that in the conventional nursing group (risk ratio = 0.22, 95% confidence interval: 0.16-0.32, p < 0.001). EBN interventions are more effective than conventional nursing in preventing PUs in ICU patients. However, since the literature included in this study was from China, the conclusions require further confirmation via higher-quality studies.

Durable High-Temperature Proton Exchange Membrane Fuel Cells Enabled by the Working-Temperature-Matching Palladium-Hydrogen Buffer Layer.

The durability degradation during stack-operating conditions seriously deteriorates the lifetime and performance of the fuel cell. To alleviate the rapid potential rise and performance degradation, an anode design is proposed to match the working temperature of high-temperature proton exchange membrane fuel cells (HT-PEMFCs) with the release temperature of hydrogen from palladium. The result is significantly enhanced hydrogen oxidation reaction (HOR) activity of Pd and superior performance of the Pd anode. Furthermore, Pd as hydrogen buffer and oxygen absorbent layer in the anode can provide additional in situ hydrogen and absorb infiltrated oxygen during local fuel starvation to maintain HOR and suppress reverse-current degradation. Compared with the traditional Pt/C anode, the Pd/C also greatly improved HT-PEMFCs durability during start-up/shut-down and current mutation. The storage/release of hydrogen provides innovative guidance for improving the durability of PEMFCs.

Preoperative posterior tilt can be a risk factor of fixation failure in nondisplaced femoral neck fracture: a systematic review and meta-analysis.

PURPOSE: This systematic review and meta-analysis aimed to identify whether posterior tilt increases the risk of treatment failure in nondisplaced femoral neck fractures. METHODS: We searched the databases of the PubMed, Embase, and Cochrane Library from 1980 to 2022. The search strategy was based on the combination of keywords "nondisplaced," "hip fracture," "femoral neck fracture," and "internal fixation." Cohort studies enrolled patients with nondisplaced (Garden I and Garden II) femoral neck fractures were included. Two investigators independently extracted data and the other two assessed the methodological quality. Data were analyzed using Review Manager software. RESULTS: We analyzed 13 cohort trials with a pooled sample of 4818 patients, with posterior tilt ≥ 20° in 698 patients and < 20° in 3578 patients in 11 trials, and posterior tilt ≥ 10° in 483 patients and < 10° in 496 patients in 4 trials. All studies were of high quality based on Newcastle-Ottawa Scale evaluation. Treatment failure was reported in 24.4% (170/698) of patients with posterior tilt ≥ 20° and 10.9% (392/3578) of patients with posterior tilt < 20°, indicating that posterior tilt ≥ 20° was significantly associated with a higher risk of treatment failure (Risk ratio, 2.73; 95% confidence interval [CI], 1.77-4.21). Posterior tilt ≥ 10° was not found to be a risk factor for fixation failure (risk ratio, 1.92; 95% CI 0.76-4.83). CONCLUSION: Nondisplaced femoral neck fractures with posterior tilt ≥ 20° were associated with an increasing rate of failure when treated with internal fixation. LEVEL OF EVIDENCE : III, Systematic review and meta-analysis.

Nanohelix-Induced Optical Activity of Liquid Metal Nanoparticles.

Liquid metals (such as gallium or Ga) exist in liquid states under ambient conditions and are hardly sculpted in chiral structures. Herein, through electron-beam evaporation of Ga, hemispherical achiral Ga nanoparticles (NPs) are randomly immobilized along helical surfaces of SiO2 nanohelices (NHs), functioning as a chiral template. Helical assembly of Ga NPs shows chiroplasmonic optical activity owing to collective plasmon-plasmon interactions, which can be tuned as a function of a helical SiO2 pitch (P) and the amount of Ga evaporated. At a P of ≈150 nm, the chiroplasmonic optical activity, evaluated with anisotropic g-factor, can be as large as ≈0.1. Because the SiO2 NHs and Ga NPs have high environmental stability of nanostructures, the chiroplasmonic optical activity shows excellent anti-aging stability, despite slight blue shift and chiroplasmonic degradation for the first 2 weeks. Spontaneous oxidation of the Ga NPs enables the formation of dense Ga2 O3 layers covering Ga cores to prevent further oxidation and thus to stabilize the chiroplasmonic optical activity. This work devises an alternative approach to impose optical activity onto Ga NPs, providing an additional degree of freedom (i.e., chirality) for Ga-based flexible electronic devices to develop advanced applications of 3D display, circular polarizers, bio-imaging, and bio-detection.

Chiral Nanoparticles with Enhanced Thermal Stability of Chiral Structures through Alloying.

Metallic chiral nanoparticles (CNPs) promisingly function as asymmetric catalysts but lack an important study in thermal stability of optical activity that stems from metastable chiral lattices. In this work, annealing is applied to silver (Ag) CNPs, fabricated by glancing angle deposition (GLAD), and causes elimination of optical activity at 200 °C, mainly ascribed to chiral-to-achiral lattice transformation. The Ag CNPs are remarkedly enhanced in thermal stability through an alloying with aluminum (Al) via layer-by-layer GLAD to generate binary Ag0.5 Al0.5 CNPs composed of solid-state liquids, whose optical activity vanishes at 700 °C. Ease in the diffusion of Al atoms in the host Ag CNPs and thermal insulation from the Al2 O3 layers partially covering the binary CNPs effectively prohibit structural relaxation of the metastable chiral lattices, accounting for the significant enhancement in thermal stability of chiral lattices. This is a pioneering work to investigate the fundamental principles determining the thermal stability of metallic CNPs in terms of chiral structures and optical activity. It paves the way toward applying metallic CNPs to asymmetric catalysis at high temperature to accelerate an asymmetric synthesis of enantiomers with designable chirality, which is one of the most important topics in modern chemistry.

Activating Adenosine Monophosphate-Activated Protein Kinase Mediates Fibroblast Growth Factor 1 Protection From Nonalcoholic Fatty Liver Disease in Mice.

BACKGROUND AND AIMS: Fibroblast growth factor (FGF) 1 demonstrated protection against nonalcoholic fatty liver disease (NAFLD) in type 2 diabetic and obese mice by an uncertain mechanism. This study investigated the therapeutic activity and mechanism of a nonmitogenic FGF1 variant carrying 3 substitutions of heparin-binding sites (FGF1△HBS ) against NAFLD. APPROACH AND RESULTS: FGF1△HBS administration was effective in 9-month-old diabetic mice carrying a homozygous mutation in the leptin receptor gene (db/db) with NAFLD; liver weight, lipid deposition, and inflammation declined and liver injury decreased. FGF1△HBS reduced oxidative stress by stimulating nuclear translocation of nuclear erythroid 2 p45-related factor 2 (Nrf2) and elevation of antioxidant protein expression. FGF1△HBS also inhibited activity and/or expression of lipogenic genes, coincident with phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and its substrates. Mechanistic studies on palmitate exposed hepatic cells demonstrated that NAFLD-like oxidative damage and lipid accumulation could be reversed by FGF1△HBS . In palmitate-treated hepatic cells, small interfering RNA (siRNA) knockdown of Nrf2 abolished only FGF1△HBS antioxidative actions but not improvement of lipid metabolism. In contrast, AMPK inhibition by pharmacological agent or siRNA abolished FGF1△HBS benefits on both oxidative stress and lipid metabolism that were FGF receptor (FGFR) 4 dependent. Further support of these in vitro findings is that liver-specific AMPK knockout abolished therapeutic effects of FGF1△HBS against high-fat/high-sucrose diet-induced hepatic steatosis. Moreover, FGF1△HBS improved high-fat/high-cholesterol diet-induced steatohepatitis and fibrosis in apolipoprotein E knockout mice. CONCLUSIONS: These findings indicate that FGF1△HBS is effective for preventing and reversing liver steatosis and steatohepatitis and acts by activation of AMPK through hepatocyte FGFR4.