Unveiling the Role of Fluorination in Hexacyclic Coordinated Ether Electrolytes for High-Voltage Lithium Metal Batteries.

Fluorinated ethers have become promising electrolyte solvent candidates for lithium metal batteries (LMBs) because they are endowed with high oxidative stability and high Coulombic efficiencies of lithium metal stripping/plating. Up to now, most reported fluorinated ether electrolytes are -CF3-based, and the influence of ion solvation in modifying degree of fluorination has not been well-elucidated. In this work, we synthesize a hexacyclic coordinated ether (1-methoxy-3-ethoxypropane, EMP) and its fluorinated ether counterparts with -CH2F (F1EMP), -CHF2 (F2EMP), or -CF3 (F3EMP) as terminal group. With lithium bis(fluorosulfonyl)imide as single salt, the solvation structure, Li-ion transport behavior, lithium deposition kinetics, and high-voltage stability of the electrolytes were systematically studied. Theoretical calculations and spectra reveal the gradually reduced solvating power from nonfluorinated EMP to fully fluorinated F3EMP, which leads to decreased ionic conductivity. In contrast, the weakly solvating fluorinated ethers possess higher Li+ transference number and exchange current density. Overall, partially fluorinated -CHF2 is demonstrated as the desired group. Further full cell testing using high-voltage (4.4 V) and high-loading (3.885 mAh cm-2) LiNi0.8Co0.1Mn0.1O2 cathode demonstrates that F2EMP electrolyte enables 80% capacity retention after 168 cycles under limited Li (50 µm) and lean electrolyte (5 mL Ah-1) conditions and 129 cycles under extremely lean electrolyte (1.8 mL Ah-1) and the anode-free conditions. This work deepens the fundamental understanding on the ion transport and interphase dynamics under various degrees of fluorination and provides a feasible approach toward the design of fluorinated ether electrolytes for practical high-voltage LMBs.

Zwitterion Dual-Modification Strategy for High-Quality NiOx and Perovskite Films for Solar Cells.

Nickel oxide (NiOx ) has been limited in use as a hole transport layer for its low conduction, surface defects, and redox reactions with the perovskite layer. To address these issues, the incorporation of zwitterion L-tryptophan (Trp) is proposed at the NiOx /Trp interface. The carboxyl group of Trp effectively passivates the surface positive defects of NiOx , thereby improving its optical and electrical properties. The ammonium group of Trp not only passivates negative defects but modulates the growth of the perovskite layer, resulting in an improved perovskite film quality. Furthermore, the Trp layer acts as a buffer layer, suppressing adverse interfacial reactions between the perovskite and NiOx . Consequently, perovskite solar cells with 1.56 and 1.68 eV absorbers achieve the champion power conversion efficiency (PCE) of 23.79% and 20.41%, respectively. Moreover, the unencapsulated devices demonstrate excellent long-term stability, retaining above 80% of the initial PCE value after 1600 h of storage in the air with a humidity of 50-60%.

Aptamer-Functionalized Magnetic Ti3C2 Based Nanoplatform for Simultaneous Enrichment and Detection of Exosomes.

Exosomes are nanovesicles secreted by cells, which play a crucial role in various pathological processes. Exosomes have shown great promise as tumor biomarkers because of the abundant secretion during tumor formation. The development of a convenient, efficient, and cost-effective method for simultaneously enriching and detecting exosomes is of utmost importance for both basic research and clinical applications. In this study, an aptamer-functionalized magnetic Ti3C2 composite material (Fe3O4@Ti3C2@PEI@DSP@aptamer@FAM-ssDNA) is prepared for the simultaneous enrichment and detection of exosomes. CD63 aptamers are utilized to recognize and capture the exosomes, followed by magnetic separation. The exosomes are then released by cleaving the disulfide bonds of DSP. Compared to traditional methods, Fe3O4@Ti3C2@PEI@DSP@aptamer@FAM-ssDNA exhibited superior efficiency in enriching exosomes while preserving their structural and functional integrity. Detection of exosome concentration is achieved through the fluorescence quenching of Ti3C2 and the competitive binding between the exosomes and a fluorescently labeled probe. This method exhibited a low detection limit of 4.21 × 104 particles mL-1, a number that is comparable to the state-of-the-art method in the detection of exosomes. The present study demonstrates a method of simultaneous enrichment and detection of exosomes with a high sensitivity, accuracy, specificity, and cost-effectiveness providing significant potential for clinical research and diagnosis.

Perovskite Solar Cells Based on Polymerized Chlorophyll Films as Environmentally Friendly Hole-Transporting Layers.

Hole-transporting layers (HTLs) play a crucial role in the performance of inverted, p-i-n perovskite solar cells (PSCs). Chlorophylls (Chls) are naturally abundant organic photoconductors on earth, with good charge carrier mobility and appropriate Fermi energy levels that make them promising candidates for use in photovoltaic devices. However, Chls films prepared using the solution method exhibit lower carrier mobility compared to other organic polymer films, which limits their application in PSCs. To address this issue, Chls molecules are chemically linked to reduce the charge transfer barrier, thus the transfer of charges between molecules is transformed to intramolecular charge transfer. This study synthesizes and characterizes two polymerized Chl films, PolyCuChl and PolyNiChl, as HTLs of CH3 NH3 PbI3 -based PSCs. PSCs based on the electrochemical polymerization of PolyChl HTLs demonstrate an enhanced power conversion efficiency (PCE) of up to 19.0%, which is the highest efficiency among devices based on Chl materials. Furthermore, these devices demonstrated exceptional long-term stability. These results highlight the potential of polymerized Chl films as a viable alternative to conventional HTLs in PSCs. The approach utilizes abundant, environmentally friendly, and versatile Chl derivatives, and can be extended to develop next-generation HTL materials for improved PSC performance.

Preferred Orientation Deposition via Multifunctional Gel Electrolyte with Molecular Anchor Enabling Highly Reversible Zn Anode.

The high activity of water molecules results in a series of awful parasitic reaction, which seriously impede the development of aqueous zinc batteries. Herein, a new gel electrolyte with multiple molecular anchors is designed by employing natural biomaterials from chitosan and chlorophyll derivative. The gel electrolyte firmly anchors water molecules by ternary hydrogen bonding to reduce the activity of water molecules and inhibit hydrogen evolution reaction. Meanwhile, the multipolar charged functional groups realize the gradient induction and redistribution of Zn2+ , which drives oriented Zn (002) plane deposition of Zn2+ and then achieves uniform Zn deposition and dendrite-free anode. As a result, it endows the Zn||Zn cell with over 1700 h stripping/plating processes and a high efficiency of 99.4% for the Zn||Cu cell. In addition, the Zn||V2 O5 full cells also exhibit capacity retention of 81.7% after 600 cycles at 0.5 A g-1 and excellent long-term stability over 1600 cycles at 2 A g-1 , and the flexible pouch cells can provide stable power for light-emitting diodes even after repeated bending. The gel electrolyte strategy provides a reference for reversible zinc anode and flexible wearable devices.

Synthesis of Superelastic, Highly Conductive Graphene Aerogel/Liquid Metal Foam and its Piezoresistive Application.

Graphene aerogel (GA) has important application potential as piezoresistive sensors due to its low density, high conductivity, high porosity, and good mechanical properties. However, the fabrication of GA-based sensors with good mechanical properties and excellent sensing performance is still challenging. Herein, liquid- metal-modified GAs (GA/LM) are proposed for the development of an excellent GA-based sensor. GA/LM with three-dimensional interconnected layered structure exhibits excellent compressive stress of 41 KPa and fast response time (<20 ms). While generally flexible GA composites cannot be compressed beyond 80 % strain without plastic deformation, GA/LM demonstrates a high compressive strength of 60 kPa under a strain of 90 %. A real-time pressure sensor was fabricated based on GA/LM-2 to monitor swallowing, pulse beating, finger, wrist and knee bending, and even plantar pressure during walking. These excellent features enable potential applications in health detection.

Discovery of 1,2,3-triazole-based pleuromutilin derivatives as potent gram-positive antibacterial agents.

A novel class of pleuromutilin derivatives possessing 1,2,3-triazole as the linker connected to phenyl analogues were designed. The antibacterial properties of the prepared compounds were assessed in vitro against five strains (E. coli, S. aureus, S. epidermidis, and E. faecalis). Most of the tested compounds displayed potent antibacterial activities against gram-positive bacteria and 14-O-[2-(4-((2,4-dinitrophenoxy)-methyl-1H-1,2,3-triazol-1-yl) acetamide)-2-methylpropan-2-yl) thioacetyl]mutilin (7c) exerted antibacterial activities against S. aureus, MRSA and S. epidermidis with MIC values 0.0625 µg/mL, representing 64-fold, 4-fold and 8-fold higher than tiamulin respectively. Compound 6e, 7c and 8c were chosen to carry out killing kinetics, which exhibited concentration-dependent effect. Subsequently, molecular modeling was conducted to further explore the binding of compound 6e, 7a, 7c, 8c and tiamulin with 50S ribosomal subunit from deinococcus radiodurans. The investigation revealed that the main interactions between compound 7c and the ribosomal residues were three hydrogen bonds, π-π, and p-π conjugate effects. Additionally, the free binding energy and docking score of 7c with the ribosome demonstrated the lowest values of -11.90 kcal/mol and -7.97 kcal/mol, respectively, consistent with its superior antibacterial activities.

The role of 14-3-3ß in acute asthma in children and analysis of the risk factors for asthma exacerbation.

OBJECTIVE: To investigate the role of 14-3-3ß in acute asthma exacerbations in children and analyze the risk factors for asthma exacerbations. METHODS: This study recruited 101 children with acute asthma exacerbations, 101 children with stable asthma, and 65 healthy children. Serum 14-3-3ß was compared among the three groups. Factors such as asthma family history, skin prick test, serum-specific IgE test, coinfections, and clinical indicators (FeNO, FEV1, white blood cells, eosinophils, and serum IgE level) were compared between the asthma groups. Risk factors associated with acute asthma exacerbations were identified using multivariate logistic regression models. ROC curve was drawn to determine the diagnostic sensitivity and specificity of 14-3-3ß. RESULTS: Serum 14-3-3ß was significantly greater in the acute asthma group than in the stable asthma and control groups. Serum 14-3-3ß was higher in severe acute asthma group than in mild-moderate asthma group. There were no significant differences in serum 14-3-3ß levels between stable asthma and control groups (p > .05). Multivariate logistic regression analysis revealed that serum 14-3-3ß level, FeNO, coinfection, and FEV1 z-score significantly increased the odds of acute asthma exacerbations in children. The optimal 14-3-3ß cutoff value (39.79 ng/mL), had a sensitivity of 69.3% and specificity of 94.1% for predicting acute asthma exacerbations. CONCLUSIONS: 14-3-3ß is elevated in children with acute exacerbations of asthma, and increases with exacerbation severity. 14-3-3ß, FeNO, FEV1, and coinfection could be independent risk factors for predicting asthma exacerbations. The optimal 14-3-3ß cutoff value for predicting asthma exacerbations was 39.79 ng/mL.

Modeling and biological evaluation of pegmolesatide, a novel and potent erythropoiesis-stimulating agent.

Pegmolesatide, a synthetic, polyethylene-glycolylated, peptide-based erythropoiesis-stimulating agent (ESA), has been recently approved in China. Pegmolesatide is derived from the structure of endogenous erythropoietin (EPO), a natural product in mammals. This study compared the in vitro effects and selectivity of pegmolesatide to those of recombinant EPO and carbamylated EPO (CEPO) through computer-aided analyses and biological tests. The findings indicate that pegmolesatide exhibited the same stimulating effect on erythropoiesis as EPO with fewer side effects than EPO and CEPO.

Remodeling Zinc Deposition via Multisite Zincophilic Chlorophyll for Powerful Aprotic Zinc Batteries.

The organic electrolyte can resolve the hurdle of hydrogen evolution in aqueous electrolytes but suffers from sluggish electrochemical reaction kinetics due to a compromised mass transfer process. Herein, we introduce a chlorophyll, zinc methyl 3-devinyl-3-hydroxymethyl-pyropheophorbide-a (Chl), as a multifunctional electrolyte additive for aprotic zinc batteries to address the related dynamic problems in organic electrolyte systems. The Chl exhibits multisite zincophilicity, which significantly reduces the nucleation potential, increases the nucleation sites, and induces uniform nucleation of Zn metal with a nucleation overpotential close to zero. Furthermore, the lower LUMO of Chl contributes to a Zn-N-bond-containing SEI layer and inhibits the decomposition of the electrolyte. Therefore, the electrolyte enables repeated zinc stripping/plating up to 2000 h (2 Ah cm-2 cumulative capacity) with an overpotential of only 32 mV and a high Coulomb efficiency of 99.4%. This work is expected to enlighten the practical application of organic electrolyte systems.

Impact of salt content on Douchi metabolites: biogenic amines, non-volatile compounds and volatile compounds.

BACKGROUND: The excessive salt intake associated with Douchi has become a topic of controversy. Addressing this concern and enhancing its market competitiveness necessitates the application of salt reduction fermentation in Douchi. Therefore, to promote the application of salt reduction fermentation in Douchi, a comprehensive study was undertaken aiming to investigate the differences in biogenic amines, volatile compounds and non-volatile compounds in Douchi with varying salt content. RESULTS: The findings unequivocally demonstrate that salt hampers the formation of metabolites in Douchi. As the salt content increased, there was a significant decrease (P < 0.05) in the levels of total acid, amino-type nitrogen and free amino acids in Douchi. Notably, when the salt content exceeded 80 g kg-1, there was a substantial reduction (P < 0.05) in putrescine, lactic acid and malic acid levels. Similarly, when the salt content surpassed 40 g kg-1, ß-phenethylamine and oxalic acid levels exhibited a significant decline (P < 0.05). Furthermore, the results of E-nose and principal component analysis based on headspace solid phase microextraction gas chromatography-mass spectrometry revealed notable discrepancies in the volatile compound content between Douchi samples with relatively low salt content (40 and 80 g kg-1) and those with relatively high salt content (120, 160 and 200 g kg-1) (P < 0.05). By employing partial least squares discriminant analysis, eight distinct volatile compounds, including o-xylene, benzaldehyde and 1-octen-one, were identified. These compounds exhibited higher concentrations in Douchi samples with relatively low salt content (40 and 80 g kg-1). The sensory results showed that Douchi samples with lower salt content exhibited higher scores in the soy sauce-like and Douchi aroma attributes. CONCLUSION: In conclusion, this study significantly enhances our understanding of the impact of salt on metabolites in Douchi and provides invaluable insights for the development of salt reduction fermentation in this context. © 2024 Society of Chemical Industry.

Chemogenetic activation of ventral medullary astrocytes enhances feeding and corticosterone release in response to mild glucoprivation.

To investigate the role of glial cells in the regulation of glucoprivic responses in rats, a chemogenetic approach was used to activate astrocytes neighboring catecholamine (CA) neurons in the ventromedial medulla (VLM) where A1 and C1 CA cell groups overlap (A1/C1). Previous results indicate that activation of CA neurons in this region is necessary and sufficient for feeding and corticosterone release in response to glucoprivation. However, it is not known whether astrocyte neighbors of CA neurons contribute to glucoregulatory responses. Hence, we made nanoinjections of AAV5-GFAP-hM3D(Gq)-mCherry to selectively transfect astrocytes in the A1/C1 region with the excitatory designer receptor exclusively activated by designer drugs (DREADDs), hM3D(Gq). After allowing time for DREADD expression, we evaluated the rats for increased food intake and corticosterone release in response to low systemic doses of the antiglycolytic agent, 2-deoxy-d-glucose (2DG), alone and in combination with the hM3D(Gq) activator clozapine-n-oxide (CNO). We found that DREADD-transfected rats ate significantly more food when 2DG and CNO were coadministered than when either 2DG or CNO was injected alone. We also found that CNO significantly enhanced 2DG-induced FOS expression in the A1/C1 CA neurons, and that corticosterone release also was enhanced when CNO and 2DG were administered together. Importantly, CNO-induced activation of astrocytes in the absence of 2DG did not trigger food intake or corticosterone release. Our results indicate that during glucoprivation, activation of VLM astrocytes cells markedly increases the sensitivity or responsiveness of neighboring A1/C1 CA neurons to glucose deficit, suggesting a potentially important role for VLM astrocytes in glucoregulation.

GPR40 deficiency worsens metabolic syndrome-associated periodontitis in mice.

BACKGROUND AND OBJECTIVE: G protein-coupled receptor 40 (GPR40) is a receptor for medium- and long-chain free fatty acids (FFAs). GPR40 activation improves type 2 diabetes mellitus (T2DM), metabolic syndrome (MetS), and the complications of T2DM and MetS. Periodontitis, a common oral inflammatory disease initiated by periodontal pathogens, is another complication of T2DM and MetS. Since FFAs play a key role in the pathogenesis of MetS which exacerbates periodontal inflammation and GPR40 is a FFA receptor with anti-inflammatory properties, it is important to define the role of GPR40 in MetS-associated periodontitis. MATERIALS AND METHODS: We induced MetS and periodontitis by high-fat diet and periodontal injection of lipopolysaccharide (LPS), respectively, in wild-type and GPR40-deficient mice and determined alveolar bone loss and periodontal inflammation using micro-computed tomography, histology, and osteoclast staining. We also performed in vitro study to determine the role of GPR40 in the expression of proinflammatory genes. RESULTS: The primary outcome of the study is that GPR40 deficiency increased alveolar bone loss and enhanced osteoclastogenesis in control mice and the mice with both MetS and periodontitis. GPR40 deficiency also augmented periodontal inflammation in control mice and the mice with both MetS and periodontitis. Furthermore, GPR40 deficiency led to increased plasma lipids and insulin resistance in control mice but had no effect on the metabolic parameters in mice with MetS alone. For mice with both MetS and periodontitis, GPR40 deficiency increased insulin resistance. Finally, in vitro studies with macrophages showed that deficiency or inhibition of GPR40 upregulated proinflammatory genes while activation of GPR40 downregulated proinflammatory gene expression stimulated synergistically by LPS and palmitic acid. CONCLUSION: GPR40 deficiency worsens alveolar bone loss and periodontal inflammation in mice with both periodontitis and MetS, suggesting that GPR40 plays a favorable role in MetS-associated periodontitis. Furthermore, GPR40 deficiency or inhibition in macrophages further upregulated proinflammatory and pro-osteoclastogenic genes induced by LPS and palmitic acid, suggesting that GPR40 has anti-inflammatory and anti-osteoclastogenic properties.

Successful lexical tone production of Mandarin Chinese autistic children with intellectual impairment.

BACKGROUND: Atypical speech prosody has been commonly found among autistic children. Yet it remains unknown whether prosody impairment originates from poor pitch ability in general or whether it is the result of the difficulty in understanding and using prosody for communicative purposes. AIMS: To investigate whether native Mandarin Chinese-speaking autistic children with intellectual impairment were able to accurately produce native lexical tones, which are pitch patterns that distinguish word meaning lexically and serve little social purpose. METHODS & PROCEDURES: Using a picture-naming task, thirteen 8-13-year-old Mandarin Chinese-speaking autistic children with intellectual impairment were tested on their production of Chinese lexical tones. Chronical age-matched typically developing (TD) children were included as the control group. Perceptual assessment and phonetic analyses were conducted with the produced lexical tones. OUTCOMES & RESULTS: The majority of the lexical tones produced by the autistic children were perceived as accurate by adult judges. Phonetic analysis of the pitch contours found no significant difference between the two groups, and the autistic children and TD children used the phonetic features in comparable ways when differentiating the lexical tones. However, the lexical tone accuracy rate was lower among the autistic children than among the TDs, and the larger individual difference was observed among the autistic children than the TD children. CONCLUSIONS & IMPLICATIONS: These results indicate that autistic children are able to produce the global contours of the lexical tones, and pitch deficits do not seem to qualify as a core feature of autism. WHAT THIS PAPER ADDS: What is already known on the subject Atypical prosody has been considered a maker of the speech of autistic children, and meta-analysis found a significant difference in mean pitch and pitch range between TD children and autistic children. Yet it remains unknown whether the pitch deficits are the result of impaired perceptual-motoric ability or if they reflect failure in learning sentential prosody, which requires an understanding of the interlocutors' mind. In addition, research on pitch ability of autistic children with intellectual disabilities has been scarce, and whether these children are able to produce pitch variation is largely unknown. What this paper adds to existing knowledge We tested native Mandarin Chinese autistic children with intellectual impairment on their production of native lexical tones. The lexical tones in Chinese are pitch variations realized on individual syllables that distinguish lexical meaning, but they do not serve social pragmatic purposes. We found that although these autistic children had only developed limited spoken language, the majority of their lexical tones were perceived as accurate. They were able to use the phonetic features in comparable ways with the TD children when distinguishing the lexical tones. What are the potential or actual clinical implications of this work? It seems unlikely that pitch processing at the lexical level is fundamentally impaired in autistic children, and pitch deficits do not seem to qualify for a core feature of their speech. Practitioners should be cautious when using pitch production as a clinical marker for autistic children.

Giant Malignant Meningioma Penetrates the Skull.

Meningioma is a primary tumor of the central nervous system, most commonly found in the middle-aged and elderly. Most meningiomas are benign, whereas malignant meningiomas account for only 1% of all meningiomas. Meningiomas usually grow slowly, and patients often have headaches and epilepsy as the first symptoms. According to the location of the tumor, there can also be vision, visual field, olfactory, hearing impairment, and so on. Surgery is the main treatment. A case of giant malignant meningioma penetrating the skull is reported. The patient was a 67-year-old male with a left parietal scalp mass about 1 year ago, which gradually enlarged to the size of 6×6 cm and had no other symptoms. Imaging examination showed that the tumor eroded the skull, and the density was uneven. After surgical resection (Simpson grade I), poorly differentiated meningioma (World Health Organization Grade Ⅲ) was returned pathologically. After operation, the patient recovered well.

Efficiency improvement of inverted perovskite solar cells enabled by PTAA/MoS2double hole transporters.

Hole transport layer (HTL) plays a critical role in perovskite solar cells (PSCs). We focus on the improvement of PSCs performance with MoS2nanosheets as the anode buffer layer in the inverted photovoltaic structure. PSC with single MoS2buffer layer shows poor performance in power conversion efficiency (PCE) and the long-term stability. By combination of MoS2and Poly[bis(4-phenyl) (2,4,6-trimethylphenyl) amine] (PTAA) as double-layer HTL, the PCE is improved to 18.47%, while the control device with PTAA alone shows a PCE of 14.48%. The same phenomenon is also found in 2D PSCs. For double-layer HTL devices, the PCE reaches 13.19%, and the corresponding PCE of the control group using PTAA alone is 10.13%. This significant improvement is attributed to the reduced interface resistance and improved hole extraction ability as shown by the electric impedance spectroscopy and fluorescence spectroscopy. In addition, the improved device exhibits better stability because the PCE still maintains 66% of the initial value after 500 h of storage, which is higher than the 47% of the remaining PCE from device based on single PTAA or MoS2. Our results demonstrate the potential of polymer/inorganic nanomaterial as a double-layer buffer material for PSCs.

3D Printed Solutions for Spheroid Engineering and Cancer Research.

In multicellular organisms, cells are organized in a 3-dimensional framework and this is essential for organogenesis and tissue morphogenesis. Systems to recapitulate 3D cell growth are therefore vital for understanding development and cancer biology. Cells organized in 3D environments can evolve certain phenotypic traits valuable to physiologically relevant models that cannot be accessed in 2D culture. Cellular spheroids constitute an important aspect of in vitro tumor biology and they are usually prepared using the hanging drop method. Here a 3D printed approach is demonstrated to fabricate bespoke hanging drop devices for the culture of tumor cells. The design attributes of the hanging drop device take into account the need for high-throughput, high efficacy in spheroid formation, and automation. Specifically, in this study, custom-fit, modularized hanging drop devices comprising of inserts (Q-serts) were designed and fabricated using fused filament deposition (FFD). The utility of the Q-serts in the engineering of unicellular and multicellular spheroids-synthetic tumor microenvironment mimics (STEMs)-was established using human (cancer) cells. The culture of spheroids was automated using a pipetting robot and bioprinted using a custom bioink based on carboxylated agarose to simulate a tumor microenvironment (TME). The spheroids were characterized using light microscopy and histology. They showed good morphological and structural integrity and had high viability throughout the entire workflow. The systems and workflow presented here represent a user-focused 3D printing-driven spheroid culture platform which can be reliably reproduced in any research environment and scaled to- and on-demand. The standardization of spheroid preparation, handling, and culture should eliminate user-dependent variables, and have a positive impact on translational research to enable direct comparison of scientific findings.

GPR40 deficiency is associated with hepatic FAT/CD36 upregulation, steatosis, inflammation, and cell injury in C57BL/6 mice.

G-protein-coupled receptor 40 (GPR40) is highly expressed in pancreatic islets, and its activation increases glucose-stimulated insulin secretion from pancreas. Therefore, GPR40 is considered as a target for type 2 diabetes mellitus (T2DM). Since nonalcoholic fatty liver disease (NAFLD) is associated with T2DM and GPR40 is also expressed by hepatocytes and macrophages, it is important to understand the role of GPR40 in NAFLD. However, the role of GPR40 in NAFLD in animal models has not been well defined. In this study, we fed wild-type or GPR40 knockout C57BL/6 mice a high-fat diet (HFD) for 20 wk and then assessed the effect of GPR40 deficiency on HFD-induced NAFLD. Assays on metabolic parameters showed that an HFD increased body weight, glucose, insulin, insulin resistance, cholesterol, and alanine aminotransferase (ALT), and GPR40 deficiency did not mitigate the HFD-induced metabolic abnormalities. In contrast, we found that GPR40 deficiency was associated with increased body weight, insulin, insulin resistance, cholesterol, and ALT in control mice fed a low-fat diet (LFD). Surprisingly, histology and Oil Red O staining showed that GPR40 deficiency in LFD-fed mice was associated with steatosis. Immunohistochemical analysis showed that GPR40 deficiency also increased F4/80, a macrophage biomarker, in LFD-fed mice. Furthermore, results showed that GPR40 deficiency led to a robust upregulation of hepatic fatty acid translocase (FAT)/CD36 expression. Finally, our in vitro studies showed that GPR40 knockdown by siRNA or a GPR40 antagonist increased palmitic acid-induced FAT/CD36 mRNA in hepatocytes. Taken together, this study indicates that GPR40 plays an important role in homeostasis of hepatic metabolism and inflammation and inhibits nonalcoholic steatohepatitis by possible modulation of FAT/CD36 expression.

Overexpression of CENPF is associated with progression and poor prognosis of lung adenocarcinoma.

Background and aim: The molecular signatures of lung adenocarcinoma (LUAD) are not well understood. Centromere protein F (CENPF) has been shown to promote oncogenesis in many cancers; however, its role in LUAD has not been illustrated. We explored the role of CENPF in LUAD. Methods: CENPF expression level was investigated in public online database firstly, the prognosis of CENPF in LUAD were also assessed by Kaplan-Meier analysis. Then quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed using 13 matched pairs of clinical LUAD tissue samples. Subsequently, the impact of CENPF expression on cell proliferation, cell cycle, apoptosis, colony formation was investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), flow cytometric analysis and colony formation assay, respectively. Finally, experimental xenograft lung cancer model of nude mice armpit of right forelimb to determine the effect of CENPF on LUAD tumorigenesis. Results: CENPF mRNA expression was significantly elevated in LUAD tissues compared with adjacent non-tumor lung tissues in Gene Expression Profiling Interactive Analysis (GEPIA) (P < 0.001). Up-regulated CENPF was remarkably positively associated with pathological stage, relapse free survival (RFS) as well as overall survival (OS) of LUAD patients. Besides, CENPF knockdown greatly suppressed A549 cell proliferation, induced S phase arrest, promoted apoptosis and decreased colony numbers of LUAD cells. Furthermore, knockdown of CENPF significantly inhibited the tumor growth of the LUAD cells in an experimental xenograft lung cancer model of nude mice armpit of right forelimb. Conclusion: Taken together, these results demonstrated that CENPF may serve as a potential biomarker of prognostic relevance and a potential therapeutic target for LUAD.

Leptin receptor-expressing neurons in ventromedial nucleus of the hypothalamus contribute to weight loss caused by fourth ventricle leptin infusions.

Leptin administration into the hindbrain, and specifically the nucleus of the solitary tract, increases phosphorylated signal transducer and activator of transcription 3 (pSTAT3), a marker of leptin receptor activation, in hypothalamic nuclei known to express leptin receptors. The ventromedial nucleus of the hypothalamus (VMH) shows the greatest response, with a threefold increase in pSTAT3. This experiment tested the importance of VMH leptin receptor-expressing neurons in mediating weight loss caused by fourth ventricle (4V) leptin infusion. Male Sprague-Dawley rats received bilateral VMH 75-nL injections of 260 ng/µL of leptin-conjugated saporin (Lep-Sap) or blank-saporin (Blk-Sap). After 23 days they were fitted with 4V infusion cannulas and 1 wk later adapted to housing in a calorimeter before they were infused with 0.9 µg leptin/day for 14 days. There was no effect of VMH Lep-Sap on weight gain or glucose clearance before leptin infusion. Leptin inhibited food intake and respiratory exchange ratio in Blk-Sap but not Lep-Sap rats. Leptin had no effect on energy expenditure or brown adipose tissue temperature of either group. Inguinal and epididymal fat were significantly reduced in leptin-treated Blk-Sap rats, but the response was greatly attenuated in Lep-Sap rats. VMH pSTAT3 was increased in leptin-treated Blk-Sap but not Lep-Sap rats. These results support the concept that leptin-induced weight loss results from an integrated response across different brain areas. They also support previous reports that VMH leptin receptors do not play a significant role in maintaining energy balance in basal conditions but limit weight gain during positive energy balance.