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Metabolic‐associated fatty liver disease (MAFLD) has become one of the most widespread metabolic diseases nowadays, while no definitive agent is approved for practical treatment. Given excessive lipid deposition and cellular oxidative stress are two main inducers of MAFLD, developing synergistic therapeutic agents that enhance lipid metabolism and antioxidative ability are effective routes for MAFLD therapy. Herein, a novel kind of bio‐functional carbon dots (MTCDs) derived from metformin and tea polyphenols based on a fused pharmacophore strategy is developed. The surface of MTCDs retains abundant phenolic hydroxyl and guanidine groups, which are designed to reduce both lipid deposition and oxidative stress in the liver. Moreover, by finely controlling the surface charge, MTCDs exhibit excellent lysosome targeting functionality with favorable biocompatibility and low biotoxicity. Mechanistical studies further reveal that MTCDs treatment protects lysosomes from oxidative stress damage and activates hepatocyte AMP‐activated protein kinase signaling, which initiates lipophagy progress to accelerate lipolysis and lipid consumption. Collectively, these studies propose an effective "two birds with one stone" tool for MAFLD synergistic therapy and suggest a viable strategy for multi‐pharmacophore agent development. [ABSTRACT FROM AUTHOR]

Diagnosis of intravascular large B‐cell lymphoma (IVLBCL) is a challenge due to its heterogeneous clinical presentation and lack of specific markers. This retrospective study investigated the utility of circulating tumour DNA (ctDNA) sequencing for diagnosing IVLBCL and analysing its mutation landscape. A cohort of 34 IVLBCL patients enrolled and underwent plasma ctDNA targeted sequencing. The median plasma ctDNA concentration was 135.0 ng/mL, significantly higher than that in diffuse large B‐cell lymphoma (DLBCL) controls. Correlations were found between ctDNA concentration and disease severity indicators, LDH and SF. Mutation analysis revealed frequent mutations in B‐cell receptor and NF‐κB signalling pathways, including MYD88 (56%), CD79B (44%), TNFAIP3 (38%) and IRF4 (29%). CNS involvement was significantly related with BCL6 and CD58 mutation. Patients with complicated hemophagocytic lymphohistiocytosis had significantly higher mutation rates in B2M. Comparison with DLBCL subtypes showed distinctive mutation profiles in IVLBCL. Moreover, plasma ctDNA detected more mutations with higher variant allele fraction than tissue DNA, suggesting its superiority in sensitivity and accessibility. Dynamic monitoring of ctDNA during treatment correlated with therapeutic responses. This study revealed the role of ctDNA in IVLBCL diagnosis, mutation analysis, and treatment monitoring, offering a promising avenue for improving patient diagnosis in this rare lymphoma subtype. [ABSTRACT FROM AUTHOR]

Thermal evaporation can significantly facilitate scalable, uniform, and conformal perovskite film, particularly well‐suited for the preparation of perovskite/silicon (Si) tandem solar cells. However, the perovskite material easily induces a phase transition from a photoactive phase to a photoinactive phase, limiting the development of the stability and efficiency of tandem cells. Introducing lead chloride (PbCl2) into wide‐bandgap perovskite materials is beneficial for the fabrication of efficient and stable light‐absorbing materials, but the microscopic mechanism of the effect of PbCl2 on perovskite is still unclear. The study here reports evidences that the addition of PbCl2 to improve perovskite film stability and optoelectronic performance is due to the minor octahedral tilting of the perovskite structure are reported. It also demonstrates that this strategy accelerates interfacial charge transfer and carrier diffusion in the perovskite bulk and heterojunction interfaces. Therefore, the wide‐bandgap perovskite solar cells (PSCs) prepared by adding PbCl2 exhibit a champion power conversion efficiency (PCE) of 17.80%. The PSCs retain 97% of their performance following 200 h of operation at the maximum power point under full 1‐sun illumination. Finally, monolithic perovskite/Si tandem cells with record PCEs of 27.43% and an open‐circuit voltage of 1.817 V are fabricated. [ABSTRACT FROM AUTHOR]

Diffusion Tensor Imaging (DTI) is a new technique to characterize the brain structure. It is a special modality for Magnetic Resonance (MRI) which provides the information of fiber orientation. By quantitatively comparing the difference of the fiber information of different image pairs, one can effectively track the status of the nerve diseases. For this purpose, it is necessary to deform the DTI image of the patient (floating image) to the same shape of the template image (target image). This is so called DTI registration, which is usually formulated by a 3D variational problem. However, the numerical implementation for 3D variational problem costs too much CPU consumption. To reduce CPU consumption, it is meaningful to give some research on the structure of the solution for DTI registration. In this paper, the structure of the solution for DTI registration is mainly focused on. For this purpose, an explicit representation of the solution for a DTI registration model is presented. Based on this representation, a new DTI registration algorithm is induced. Several numerical experiments are also performed to show the efficiency of the proposed algorithm in DTI registration. [ABSTRACT FROM AUTHOR]

Combined chemotherapy and targeted therapy holds immense potential in the management of advanced gastric cancer (GC). GC tissues exhibit an elevated expression level of protein kinase B (AKT), which contributes to disease progression and poor chemotherapeutic responsiveness. Inhibition of AKT expression through an AKT inhibitor, capivasertib (CAP), to enhance cytotoxicity of paclitaxel (PTX) toward GC cells is demonstrated in this study. A cathepsin B‐responsive polymeric nanoparticle prodrug system is employed for co‐delivery of PTX and CAP, resulting in a polymeric nano‐drug BPGP@CAP. The release of PTX and CAP is triggered in an environment with overexpressed cathepsin B upon lysosomal uptake of BPGP@CAP. A synergistic therapeutic effect of PTX and CAP on killing GC cells is confirmed by in vitro and in vivo experiments. Mechanistic investigations suggested that CAP may inhibit AKT expression, leading to suppression of the phosphoinositide 3‐kinase (PI3K)/AKT signaling pathway. Encouragingly, CAP can synergize with PTX to exert potent antitumor effects against GC after they are co‐delivered via a polymeric drug delivery system, and this delivery system helped reduce their toxic side effects, which provides an effective therapeutic strategy for treating GC. [ABSTRACT FROM AUTHOR]

Catalytic hydrothermolysis (CH) is a sustainable aviation fuel (SAF) pathway that has been recently approved for use in aircraft fuel production. In alignment with broader sustainable aviation goals, SAF production through CH requires a quantitative assessment of carbon intensity (CI) impacts. In this study, a current‐day life‐cycle analysis (LCA) was performed on SAF produced via CH to determine the CI. Various oily feedstocks were considered, including vegetable oils (soybean, carinata, camelina and canola) and low‐burden oils and greases (corn oil, yellow grease and brown grease). Life‐cycle inventory data were collected on all processes within the CH LCA boundary: feedstock cultivation and/or collection, preprocessing, hydrothermal cleanup and CH, biocrude refining, fuel transportation and end use through combustion. Baseline results show that the CH‐produced SAF can be generated with CI reductions ranging from 48 to 82% compared with conventional jet fuel. Modest improvements to CI can be achieved through incremental changes to the brown grease CH process, such as relaxing the dewatering specification and implementing renewable natural gas and electricity, which could decrease the CI from 22.9 to 7.9 g CO2e/MJ. Total CH fuel production potential was also assessed on the basis of current or near‐future feedstock availability and CI. The total biofuel production potential of CH (SAF and renewable fuel co‐products) in the US sums to approximately 3487 million gallons per year, with 97% of these volumes having a CI below 50% of that for petroleum jet fuel. The study shows that from an LCA perspective, CH offers a viable SAF pathway that is comparable with existing SAF pathways like hydroprocessed esters and fatty acids. [ABSTRACT FROM AUTHOR]

Blue–violet phosphor is an essential component to realize full spectrum lighting on the basis of commercial 365 nm N‐UV chip excitation. However, its development falls behind since the phosphor with small stokes‐shift (ΔS) is hard to realize. Herein, a new blue–violet phosphor SrSc4Si5O17:Ce3+ with small ΔS (∼30 nm) is presented. SrSc4Si5O17:Ce3+ emits bright blue–violet luminescence peaking at 390 nm, and the internal/external quantum efficiency can reach 73.4%/50.4% under 365 nm excitation. The unique luminescence performance of the phosphor is related closely to its crystal structure. The host‐referred bind energy (HRBE) diagram is also successfully constructed to illustrate its thermal quenching behavior. Finally, the packaged white light‐emitting diodes based on the 365 nm N‐UV chip, SrSc4Si5O17:Ce3+, and other high‐performance phosphors have an ultra‐high color rendering index (Ra = 95.9), indicating that SrSc4Si5O17:Ce3+ is a potential candidate for various applications, including indoor healthy lighting and agricultural lighting. [ABSTRACT FROM AUTHOR]

Since the rapid development of nanomedicine in oncotherapy, multiple nanomaterials are adopted to regulate the immune system in cancer individuals. Tumor immunotherapy enhances the immune function of patients to achieve the purpose of killing tumor cells by utilizing the organism immune mechanism. As emerging inorganic carbon nanoparticles, carbon dots (CDs) have been found as photosensitizers, vaccines, immunoadjuvants, and so on for cancer treatment due to their unique structure and property, such as effective platforms for drug delivery, immunomodulation, and phototherapy. In this review, we mainly discuss the recent application of CDs in tumor immunotherapy and the prospects of CDs in the field of immune medicine. By assessing the achievements and challenges of CDs in tumor immunotherapy, our review would provide mechanistic insights into the evolution of future nanomedicine. [ABSTRACT FROM AUTHOR]

For the conventional persistent luminescence (PersL) charging processes, carriers are photo‐pumped to the conduction band (CB) or high‐energy excited states (HES) under short‐wavelength UV or coherent near‐infrared (NIR) laser excitation. Herein, electron tunneling charging behavior is reported in Cr3+, Sm3+ co‐doped NIR PersL magnetoplumbite SrGa12O19, which allows for efficient charging by incoherent visible light. First, the electrons are efficiently captured by the neighboring GaII‐O2− electron–hole trap centers via a tunneling process, and then these excited electrons are transferred to shallow traps via a persistently energetic optical pump. This work further optimizes the PersL performance via engineering the energy band through partial substitution of In3+ for Ga3+. Consequently, tunneling charging occurring near the neighboring Cr3+‐traps dimers enables Sr(Ga,In)12O19:Cr3+,Sm3+ to display brighter NIR PersL (≈760 nm, peak; ≈100 nm, FWHM) than gallate spinel under sunlight irradiation. This work provides insights into electron tunneling charging under low‐energy excitation for NIR PersL, which may inspire more PersL explorations for practical applications. [ABSTRACT FROM AUTHOR]

Energy storage devices become an indispensable part of modern power systems with high renewable energy penetration level. To reduce the operating costs, it is a promising way to allow the sharing and leasing of energy storage devices. In this paper, a bi‐lever optimized dispatch scheme is proposed to improve the usage efficiency of cloud energy storage in multi microgrids (MMG) system. Minimizing the operating costs of shared cloud energy storage is the main task of the upper lever while maximizing the profits of MMG is the goal of the lower lever. Moreover, the transaction cost and benefit between the two levers play an important role in system level optimization. This leads to a hybrid optimization problem with both discrete decision variables and continuous decision variables. To solve the problem, a relaxation‐based bi‐lever reformulation and decomposition algorithm is developed. The effectiveness of the proposed bi‐lever dispatch optimization model is verified by carrying out numerical experiments in three scenarios. It is shown that the proposed cloud energy storage service can effectively reduce the operating cost of MMG. [ABSTRACT FROM AUTHOR]

Wearable devices, biomaterials, and tissue engineering have all gained from the development of flexible materials. Hydrogels are made up of the polymer matrix in an amount of water and are now being explored extensively. Ascribed to their high hydrophilicity, conventional hydrogels are difficult to deal with high humidity, being easily swell and even decompose. The utilization of hydrogel underwater is influenced by two key factors: the hydrogel absorbs water and swells easily to depress the mechanical characteristics, and the hydration layer at the contact interface also prevents the hydrogel from making close contact with the target surface, preventing conformal and accurate smart perception. So far, many researchers have proposed satisfying improvements for underwater applications from these two perspectives. This review first summarizes the general mechanisms of underwater adhesion hydrogels. Then, various anti‐swelling strategies of the reported hydrogel are described. Finally, the existing challenges and prospects of underwater adhesion and anti‐swelling hydrogels are provided. [ABSTRACT FROM AUTHOR]

Salamanders possess a pair of lungs for active air breathing, but the lung respiration is fully operational only during the late stage of development, particularly after metamorphosis. Larval salamanders mainly exchange air through the gills and skin, thus sparing the developing lungs. Salamanders can repair their lungs after injury, but a comparative analysis of regenerative responses between the lungs of young and adult animals is lacking. In this study, lung resections were performed in both larval and adult newts (Pleurodeles waltl). The cellular dynamics, tissue morphology and organ function during lung regeneration were examined and the Yap mutants were produced with CRISPR tools. We found that salamander switches the regenerative strategies from morphological replication through the blastema formation to compensatory growth via resident epithelial cells proliferation upon pulmonary resection injury as it transitions beyond metamorphosis. The larval animals achieve lung regeneration by forming a transient blastema‐like structure and regrowing full‐sized developing lungs, albeit unventilated. The adults repair injured lungs via massive proliferating epithelial cells and by expanding the existing alveolar epithelium without neo‐alveolarization. Yap signalling promotes epithelial cell proliferation and prevents epithelial‐to‐mesenchymal transition to restore functional respiration. The salamanders have evolved distinct regenerative strategies for lung repair during different phases of life. Our results demonstrate a novel strategy for functional lung recovery by inducing epithelial cell proliferation to strengthen the remaining alveoli without rebuilding new alveoli. [ABSTRACT FROM AUTHOR]

Tumor immunotherapy is only effective in a fraction of patients due to a low response rate and severe side effects, and these challenges of immunotherapy in clinics can be addressed through induction of immunogenic cell death (ICD). ICD is elicited from many antitumor therapies to release danger associated molecular patterns (DAMPs) and tumor‐associated antigens to facilitate maturation of dendritic cells (DCs) and infiltration of cytotoxic T lymphocytes (CTLs). The process can reverse the tumor immunosuppressive microenvironment to improve the sensitivity of immunotherapy. Nanostructure‐based drug delivery systems (NDDSs) are explored to induce ICD by incorporating therapeutic molecules for chemotherapy, photosensitizers (PSs) for photodynamic therapy (PDT), photothermal conversion agents for photothermal therapy (PTT), and radiosensitizers for radiotherapy (RT). These NDDSs can release loaded agents at a right dose in the right place at the right time, resulting in greater effectiveness and lower toxicity. Immunotherapeutic agents can also be combined with these NDDSs to achieve the synergic antitumor effect in a multi‐modality therapeutic approach. In this review, NDDSs are harnessed to load multiple agents to induce ICD by chemotherapy, PDT, PTT, and RT in combination of immunotherapy to promote the therapeutic effect and reduce side effects associated with cancer treatment. [ABSTRACT FROM AUTHOR]

Efficient bioconversion of methanol, which can be generated from greenhouse gases, into valuable resources contributes to achieving climate goals and developing a sustainable economy. The methylotrophic yeast Ogataea methanolica is considered to be a suitable host for efficient methanol bioconversion because it has outstanding characteristics for the better adaptive potential to a high methanol environment (i.e., greater than 5%). This capacity represents a huge potential to construct an innovative carbon‐neutral production system that converts methanol into value‐added chemicals under the control of strong methanol‐induced promoters. In this review, we discuss what is known about the regulation of methanol metabolism and adaptation mechanisms for 5% methanol conditions in O. methanolica in detail. We also discuss about the potential to breed "super methylotrophic yeast," which has potent growth characteristics under high methanol conditions. Take‐away: •Ogataea methanolica has a high capacity to adapt to high methanol conditions (≥5%).•Alcohol oxidase isozymes regulate intracellular formaldehyde levels to adapt to high methanol levels.•Ogataea methanolica coordinates methanol metabolism in response to external methanol.•Strictly regulating methanol metabolism maintains energy homeostasis. [ABSTRACT FROM AUTHOR]

Delivery of biologics via cerebrospinal fluid (CSF) has demonstrated potential to access the tissues of the central nervous system (CNS) by circumventing the blood‐brain barrier and blood‐CSF barrier. Developing an effective CSF drug delivery strategy requires optimization of multiple parameters, including choice of CSF access point, delivery device technology, and delivery kinetics to achieve effective therapeutic concentrations in the target brain region, whereas also considering the biologic modality, mechanism of action, disease indication, and patient population. This review discusses key preclinical and clinical examples of CSF delivery for different biologic modalities (antibodies, nucleic acid‐based therapeutics, and gene therapy) to the brain via CSF or CNS access routes (intracerebroventricular, intrathecal‐cisterna magna, intrathecal‐lumbar, intraparenchymal, and intranasal), including the use of novel device technologies. This review also discusses quantitative models of CSF flow that provide insight into the effect of fluid dynamics in CSF on drug delivery and CNS distribution. Such models can facilitate delivery device design and pharmacokinetic/pharmacodynamic translation from preclinical species to humans in order to optimize CSF drug delivery to brain regions of interest. [ABSTRACT FROM AUTHOR]

In this study, we analysed the intracellular fatty acid profiles of Komagataella phaffii during methylotrophic growth. K. phaffii grown on methanol had significantly lower total fatty acid contents in the cells compared with glucose‐grown cells. C18 and C16 fatty acids were the predominant fatty acids in K. phaffii, although the contents of odd‐chain fatty acids such as C17 fatty acids were also relatively high. Moreover, the intracellular fatty acid composition of K. phaffii changed in response to not only carbon sources but also methanol concentrations: C17 fatty acids and C18:2 content increased significantly as methanol concentration increased, whereas C18:1 and C18:3 contents were significantly lower in methanol‐grown cells. The intracellular content of unidentified compounds (CnH2nO4), on the other hand, was significantly greater in cells grown on methanol. As the intracellular contents of these CnH2nO4 compounds were significantly higher in a gene‐disrupted strain for glutathione peroxidase (gpx1Δ) than in the wild‐type strain, we presume that the CnH2nO4 compounds are fatty acid peroxides. These results indicate that K. phaffii can coordinate intracellular fatty acid composition during methylotrophic growth in order to adapt to high‐methanol conditions and that certain fatty acid species such as C17:0, C17:1, C17:2 and C18:2 may be related to the physiological functions by which K. phaffii adapts to high‐methanol conditions. [ABSTRACT FROM AUTHOR]

Broadband near‐infrared phosphors are essential to realize nondestructive analysis in food industry and biomedical areas. Efficient long‐wavelength (>830 nm) phosphors are strongly desired for practical applications. Herein, we demonstrate an efficient broadband NIR phosphor LiInGe2O6:Cr3+, which exhibits a broad NIR emission peaking at ~880 nm with a full width at half maximum of 172 nm upon 460 nm excitation. The internal/external quantum efficiencies of LiInGe2O6:Cr3+ are measured to be 81.2% and 39.8%, respectively. The absorption of the phosphor matches well with commercial blue LEDs. Using the fabricated phosphor converted LED illuminating human palm, distribution of blood vessels can be clearly recognized under a NIR camera. These results indicate that LiInGe2O6:Cr3+ is a promising candidate to be used in future non‐destructive biological applications. [ABSTRACT FROM AUTHOR]

Summary: Since methylotrophic yeasts such as Ogataea methanolica can use methanol as a sole carbon feedstock, they could be applied to produce valuable products from methanol, a next‐generation energy source synthesized from natural gases, using genetic engineering tools. In this study, metabolite profiling of O. methanolica was conducted under glucose (Glc) and low and high methanol (L‐ and H‐MeOH) conditions to show the adaptation mechanism to a H‐MeOH environment. The yeast strain responded not only to the presence of methanol but also to its concentration based on the growth condition. Under H‐MeOH conditions, O. methanolica downregulated the methanol utilization, glycolytic pathway and alcohol oxidase (AOD) isozymes and dihydroxyacetone synthase (DAS) expression compared with L‐MeOH‐grown cells. However, levels of energy carriers, such as ATP, were maintained to support cell survival. In H‐MeOH‐grown cells, reactive oxygen species (ROS) levels were significantly elevated. Along with increasing ROS levels, ROS scavenging system expression was significantly increased in H‐MeOH‐grown cells. Thus, we concluded that formaldehyde and H2O2, which are products of methanol oxidation by AOD isozymes in the peroxisome, are overproduced in H‐MeOH‐grown cells, and excessive ROS derived from these cells is generated in the cytosol, resulting in upregulation of the antioxidant system and downregulation of the methanol‐utilizing pathway to suppress overproduction of toxic intermediates. [ABSTRACT FROM AUTHOR]

Paeonia ludlowii, a plant of the Paeoniaceae family, has abundant genetic diversity in different populations, and the seed oil can be used in a diverse number of activities. However, its neuroprotective effect is not clear. We investigated the memory‐improving effects and associated mechanisms of Paeonia ludlowii seed oil (PLSO) on amyloid beta (Aβ)25–35‐induced Alzheimer's disease (AD) in rats. The Morris water maze test was undertaken, and subsequently, the content of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and acetylcholinesterase (ACHE) in the hippocampus was detected by biochemical analyses. To further study PLSO, we examined the pathologic structure and apoptosis of hippocampal tissue by staining. Immunohistochemical analysis was used to detect expression of IBA‐1 and GFAP in the hippocampus. Detection of proinflammatory factors was achieved by reverse transcription–quantitative polymerase chain reaction and Western blotting. High‐dose PLSO inhibited expression of GFAP and IBA‐1. We demonstrated that high‐dose PLSO can regulate activation of glial cells and mediate apoptosis of hippocampal cells, and significantly improve learning and memory deficits in AD rats. PLSO could be developed as a nutritional supplement and sold as a drug for AD prevention and/or treatment. [ABSTRACT FROM AUTHOR]

Fibroblast growth factor 21 (FGF21) is a regulator of glucose and lipid metabolism. It has been widely considered as a promising candidate for the treatment of type 2 diabetes mellitus (T2DM) and other related metabolic disorders. However, lack of structural and dynamic information has limited FGF21‐based drug development. Here, using nuclear magnetic resonance (NMR) spectroscopy, we determine the structure of FGF21 and find that its non‐canonical flexible β‐trefoil conformation affects the folding of β2‐β3 hairpin and further overall protein stability. To modulate folding dynamics, we designed an FGF21‐FGF19 chimera, FGF21SS. As expected, FGF21SS shows better thermostability without inducing hepatocyte proliferation. Functional characterization of FGF21SS shows its better insulin sensitivity, reduced inflammation in 3T3‐L1 adipocytes, and lower blood glucose and insulin levels in ob/ob mice compared with wild type. Our dynamics‐based rational design provides a promising approach for FGF21‐based therapeutic development against T2DM. Synopsis: NMR structural analysis of FGF21 reveals a flexible conformation that affects heparan sulfate binding and β2‐β3 hairpin folding dynamics. A folding dynamic modulated variant, FGF21SS, improves protein thermostability and anti‐diabetic activity. FGF21 structure reveals a non‐canonical flexible β‐trefoil conformation that is unfavorable for heparan sulfate and receptor interaction.The untypical β10‐β11 region of FGF21 affects the folding dynamics of the β2‐β3 hairpin and overall protein stability.Dynamic folding modulation of the β2‐β3 hairpin by SS bond mutation and loop replacement improves FGF21 variant's thermostability and anti‐diabetic activity. [ABSTRACT FROM AUTHOR]

In order to fully predict the performance of variable displacement vane oil pump (VDVP) during concept design phase， one-dimensional simulation software AMESim is used to model the centralised parameters of VDVP. Several important performance indexes of VDVP are predicted, including the flow, pressure, torque and initial variable point, it is proved by the bench test that the simulation results have a good correlation with the test results. In addition, the effect of leakage on volumetric efficiency is studied, external leakage is smaller than internal leakage, and the higher the temperature, the larger the leakage. The force characteristics of VDVP are studied. Under extreme conditions, the maximum pressure of the internal chamber is about 15.9 bar, and the maximum forces of the stator and rotor are 1920 and 1653 N, respectively. The effect of temperature on the frictional power is studied. Under low-temperature conditions, the viscous frictional power is much greater than the dry frictional power, while the high temperature is the opposite. [ABSTRACT FROM AUTHOR]

A stimuli‐responsive polymeric prodrug‐based nanotheranostic system with imaging agents (cyanine5.5 and gadolinium‐chelates) and a therapeutic agent paclitaxel (PTX) is prepared via polymerization and conjugating chemistry. The branched polymeric PTX‐Gd‐based nanoparticles (BP‐PTX‐Gd NPs) demonstrate excellent biocompatibility, and high stability under physiological conditions, but they stimuli‐responsively degrade and release PTX rapidly in a tumor microenvironment. The in vitro behavior of NPs labeled with fluorescent dyes is effectively monitored, and the NPs display high cytotoxicity to 4T1 cells similar to free PTX by impairing the function of microtubules, downregulating anti‐apoptotic protein Bcl‐2, and upregulating the expression of Bax, cleaved caspase‐3, cleaved caspase‐9, cleaved‐PARP, and p53 proteins. Great improvement in magnetic resonance imaging (MRI) is demonstrated by these NPs, and MRI accurately maps the temporal change profile of the tumor volume after injection of NPs and the tumor treatment process is also closely correlated with the T1 values measured from MRI, demonstrating the capability of providing real‐time feedback to the chemotherapeutic treatment effectiveness. The imaging‐guided chemotherapy to the 4T1 tumor in the mice model achieves an excellent anti‐tumor effect. This stimuli‐responsive polymeric nano‐agent opens a new door for efficient breast cancer treatment under the guidance of fluorescence/MRI. [ABSTRACT FROM AUTHOR]

In the present study, thermal starved elastohydrodynamic lubrication (EHL) model is developed for a helical gear pair. The influences of inlet oil‐supply layer, input speed, lubricant viscosity, and surface roughness on the lubrication behaviour are investigated. The minimum film thickness, temperature rise of teeth surfaces and oil film, and the friction coefficient are predicted along the line of action (LOA). Results show that the effects of inlet oil‐supply layer, input speed, and lubrication viscosity on the tribological performance are remarkable. Under the starved lubrication, the influence of inlet oil supply on the temperature rise is insignificant. Meanwhile, the effect of surface roughness has been discussed. It reveals that the roughness texture along the entrainment velocity direction has significant influence on the lubrication characteristics. The results provide the tribological guidance for design of a helical gear pair in engineering. [ABSTRACT FROM AUTHOR]

Background and Purpose: It has been extensively reported that the leading anti-diabetic drug, metformin, exerts significant anticancer effects. This hydrophilic, cationic drug requires cation transporters for cellular entry where it activates its intracellular target, the AMPK signalling pathway. However, clinical results on metformin therapy (used at antidiabetic doses) for breast cancer are ambiguous. It is likely that the antidiabetic dose is inadequate in patients that have breast tumours with low cation transporter expression, resulting in non-responsiveness to the drug. We postulate that cation transporter expression and metformin dose are key determinants in its antitumour efficacy in breast cancer.Experimental Approach: Antitumour efficacy of metformin was compared between low cation transporter-expressing MCF-7 breast tumours and MCF-7 tumours overexpressing organic cation transporter 3 (OCT3-MCF7). A dose-response relationship of metformin in combination with standard-of-care paclitaxel (for oestrogen receptor-positive MCF-7 breast tumours) or carboplatin (for triple-negative MDA-MB-468 breast tumours) was investigated in xenograft mice.Key Results: Metformin had greater efficacy against tumours with higher cation transporter expression, as observed in OCT3-MCF7 versus MCF-7 tumours and MDA-MB-468 versus MCF-7 tumours. In MCF-7 tumours, a threefold higher metformin dose was required to achieve intratumoural exposure that was comparable to exposure in MDA-MB-468 tumours and enhance antitumour efficacy of standard-of-care in MCF-7 tumours versus MDA-MB-468 tumours. Antitumour efficacy correlated with intratumoural AMPK activation and metformin concentration.Conclusions and Implications: An efficacious metformin dose for breast cancer varies among tumour subtypes based on cation transporter expression, which provides a useful guide for dose selection. [ABSTRACT FROM AUTHOR]

Tumor angiogenesis is one of the hallmarks of cancer as well as an attractive target for cancer therapy. Characterization of novel pathways that act in parallel with the VEGF/VEGFR axis to promote tumor angiogenesis may provide insights into novel anti‐angiogenic therapeutic targets. We found that the expression level of Nogo‐B is positively correlated with tumor vessel density in hepatocellular carcinoma (HCC). While Nogo‐B depletion inhibited tumor angiogenesis, Nogo‐B overexpression promoted tumor angiogenesis in a tumor xenograft subcutaneous model of the human HCC cell line. Mechanically, Nogo‐B regulates tumor angiogenesis based on its association with integrin αvβ3 and activation of focal adhesion kinase. Moreover, Nogo‐B antibody successfully abolished the function of Nogo‐B in tumor angiogenesis in vitro and in vivo. Collectively, our results strongly suggest that Nogo‐B is an important tumor angiogenic factor and blocking Nogo‐B selectively inhibits tumor angiogenesis. We found that the expression level of Nogo‐B is positively correlated with tumor vessel density in hepatocellular carcinoma and promotes tumor angiogenesis in vitro and in vivo, while Nogo‐B antibody inhibited tumor angiogenesis in vitro and in vivo. Collectively, our results strongly suggest that Nogo‐B is an important tumor angiogenic factor and blocking Nogo‐B selectively inhibits tumor angiogenesis. [ABSTRACT FROM AUTHOR]

Abstract: New integrated biorefinery (IBR) concepts are being investigated to co‐produce hydrocarbon fuels and high‐value bio‐based chemicals to improve the economic viability of IBRs, to enhance biomass resource utilization efficiencies, and to maximize potential greenhouse gas (GHG) emission reductions. Unlike fuel‐only biorefineries, IBRs may co‐produce a significant amount of bio‐based chemicals, whose emission implications for specific biorefinery products and the biorefinery as a whole need to be evaluated. We discuss this in principle and apply three sets of co‐product handling methods to conduct life‐cycle analysis (LCA) of modeled IBRs with co‐production of two bioproduct examples – succinic acid and adipic acid – alongside a renewable diesel blendstock fuel product. The LCA results for the specific co‐product handling methods that were examined shed light on potential artifacts of product‐specific LCA with selected co‐product methods. We discuss the advantages and limitations of each method and conclude that (i) a system‐level or ‘black‐box’ LCA allocation method is too simplistic to reflect appropriately the GHG burdens of distinctly different processing trains for fuels and chemicals in the IBR context, and (ii) the displacement method is the only co‐product handling method that accounts fully for the emission effects of both the fuel product and the non‐fuel bio‐based co‐products in the IBRs within the context of the existing fuel‐focused GHG regulatory framework. Alternatively, biorefinery system‐level LCA combines benefits of individual products to offer a complete picture. This system‐level LCA approach offers a holistic LCA without somewhat arbitrary decisions either on an allocation basis or by the selection of an evaluation metric based on specific products. © 2018 Society of Chemical Industry and John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Abstract: Eucommiae Cortex is a classical traditional Chinese medicine, which needs to be processed by “sweating” methods. To select the suitable processing method and “sweating” processing condition for Eucommiae Cortex, in this study, the quality of Eucommiae Cortex was evaluated based on simultaneous determination of multiple bioactive constituents combined with gray relational analysis. The contents of lignans, iridoids, penylpropanoids, flavonoids, and phenols in samples were simultaneously determined using ultra‐fast performance liquid chromatography coupled with triple quadrupole‐linear ion trap tandem mass spectrometry. The chromatographic separation was performed on a Synergiۛ Hydro‐RP 100 Å column (100 mm × 2.0 mm, 2.5 μm) at 30°C with a gradient elution of acetonitrile with 0.1% formic acid/0.1% aqueous formic acid as the mobile phase. Furthermore, gray relational analysis was performed to evaluate and sort the samples according to the contents of 14 constituents by calculating the relative correlation degree of each sample. The results demonstrated that the quality of Eucommiae Cortex “sweating” at source area was better and the better “sweating” condition was to scrape off the cork layer before “sweating” with straw covering and sun drying. The developed method could provide the foundation and support for “sweating” processing method of Eucommiae Cortex in normalization and standardization. [ABSTRACT FROM AUTHOR]

This paper is the summation of several analyses to assess the size and benefits of a Billion Ton Bioeconomy, a vision to enable a sustainable market for producing and converting a billion tons of US biomass to bio-based energy, fuels, and products by 2030. Two alternative biomass availability scenarios in 2030, defined as the (i) Business-as-usual (598 million dry tons) and (ii) Billion Ton (1042 million dry tons), establish a range of possible outcomes for the future bioeconomy. The biomass utilized in the current (2014) (365 million dry tons) economy is estimated to displace approximately 2.4% of fossil energy consumption and avoid 116 million tons of CO2-equivalent ( CO2e) emissions, whereas the Billion Ton bioeconomy of 2030 could displace 9.5% of fossil energy consumption and avoid as much as 446 million tons of CO2 equivalent emissions annually. Developing the integrated systems, supply chains, and infrastructure to efficiently grow, harvest, transport, and convert large quantities of biomass in a sustainable way could support the transition to a low-carbon economy. Bio-based activities in the current (2014) economy are estimated to have directly generated more than $48 billion in revenue and 285 000 jobs. Our estimates show that developing biomass resources and addressing current limitations to achieve a Billion Ton bioeconomy could expand direct bioeconomy revenue by a factor of 5 to contribute nearly $259 billion and 1.1 million jobs to the US economy by 2030. © 2016 Society of Chemical Industry and John Wiley & Sons, Ltd [ABSTRACT FROM AUTHOR]

Rhubarb is one of the most popular traditional Chinese medicines and has been used for thousands of years in many Asian countries. Prepared rhubarb is obtained by steaming raw rhubarb with glutinous rice wine until it turned black in appearance both inside and outside. After processing, the therapeutic effects of prepared rhubarb change a lot. To find out the exact compound changes of the chemical profile in a decoction of rhubarb after processing and to clarify the material basis of the changed therapeutic effects, an ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry method coupled with automated data analysis software and statistical strategy was developed. As a result, 63 peaks in raw rhubarb and 54 peaks in prepared rhubarb were detected, and a total of 45 chemical compounds were identified. The analysis data were subjected to a principle component analysis and a t-test. Based on the results, 16 peaks were found to be the main contributors to the significant difference ( p < 0.05) between raw and prepared rhubarb. Compared with raw rhubarb, the content of 15 components in prepared rhubarb was lower, while only rhein (1,8-dihydroxy-3-carboxy anthraquinone) showed a higher intensity. [ABSTRACT FROM AUTHOR]

POEMS syndrome is a rare plasma cell dyscrasia. Serum concentrations of the monoclonal protein in this disorder are typically low, and inapplicable to monitor disease activity in most cases, resulting in limited practical and prognostic values. Novel immunoassays measuring isotype-specific heavy/light chain ( HLC) pairs showed its utility in disease monitoring and outcome prediction in several plasma cell dyscrasias. We report results of HLC measurements in 90 patients with POEMS syndrome. Sixty-six patients (73%; 95% confidence interval, 63-82%) had an abnormal HLC ratio at baseline. It could stratify the risk of disease relapse and was strongly associated with worse progression-free survival in a multivariate analysis ( P = 0.021; hazard ratio [ HR] 6.89, 95% CI 1.34-35.43). After therapy, HLC ratios improved, with 43 patients (48%) remaining abnormal. The post-therapeutic HLC ratio, if abnormal, also remained as an independent prognostic factor associated with worse progression-free survival ( P = 0.019; HR 4.30, 95% CI 1.27-14.56). These results suggest the prognostic utility of HLC ratios in clinical management of POEMS patients. [ABSTRACT FROM AUTHOR]

Water hampers the formation of strong and durable bonds between adhesive polymers and solid surfaces, in turn hindering the development of adhesives for biomedical and marine applications. Inspired by mussel adhesion, a mussel foot protein homologue (mfp3S-pep) is designed, whose primary sequence is designed to mimic the pI, polyampholyte, and hydrophobic characteristics of the native protein. Noticeably, native protein and synthetic peptide exhibit similar abilities to self-coacervate at given pH and ionic strength. 3,4-dihydroxy- l-phenylalanine (Dopa) proves necessary for irreversible peptide adsorption to both TiO2 (anatase) and hydroxyapatite (HAP) surfaces, as confirmed by quartz crystal microbalance measurements, with the coacervate showing superior adsorption. The adsorption of Dopa-containing peptides is investigated by attenuated total reflection infrared spectroscopy, revealing initially bidentate coordinative bonds on TiO2, followed by H-bonded and eventually long-ranged electrostatic and Van der Waals interactions. On HAP, mfp3s-pep-3Dopa adsorption occurs predominantly via H-bond and outersphere complexes of the catechol groups. Importantly, only the Dopa-bearing compounds are able to remove interfacial water from the target surfaces, with the coacervate achieving the highest water displacement arising from its superior wetting properties. These findings provide an impetus for deve­loping coacervated Dopa-functionalized peptides/polymers adhesive formulations for a variety of applications on wet polar surfaces. [ABSTRACT FROM AUTHOR]

The antidiabetic drug metformin exerts antineoplastic effects against breast cancer and other cancers. One mechanism by which metformin is believed to exert its anticancer effect involves activation of its intracellular target, adenosine monophosphate-activated protein kinase (AMPK), which is also implicated in the antidiabetic effect of metformin. It is proposed that in cancer cells, AMPK activation leads to inhibition of the mammalian target of rapamycin (mTOR) and the downstream pS6K that regulates cell proliferation. Due to its hydrophilic and cationic nature, metformin requires cation-selective transporters to enter cells and activate AMPK. This study demonstrates that expression levels of cation-selective transporters correlate with the antiproliferative and antitumor efficacy of metformin in breast cancer. Metformin uptake and antiproliferative activity were compared between a cation-selective transporter-deficient human breast cancer cell line, BT-20, and a BT-20 cell line that was engineered to overexpress organic cation transporter 3 (OCT3), a representative of cation-selective transporters and a predominant transporter in human breast tumors. Metformin uptake was minimal in BT-20 cells, but increased by >13-fold in OCT3-BT20 cells, and its antiproliferative potency was >4-fold in OCT3-BT20 versus BT-20 cells. This increase in antiproliferative activity was associated with greater AMPK phosphorylation and decreased pS6K phosphorylation in OCT3-BT20 cells. In vitro data were corroborated by in vivo observations of significantly greater antitumor efficacy of metformin in xenograft mice bearing OCT3-overexpressing tumors versus low transporter-expressing wildtype tumors. Collectively, these findings establish a clear relationship between cation-selective transporter expression, the AMPK-mTOR-pS6K signaling cascade, and the antiproliferative activity of metformin in breast cancer. [ABSTRACT FROM AUTHOR]

Although autologous stem cell transplantation or melphalan-based chemotherapy has significantly improved the prognosis of POEMS syndrome, a few patients will relapse or be refractory to primary therapy, and there is a lack of studies regarding these patients. In this study, we used low-dose lenalidomide (10 mg daily) and dexamethasone (40 mg, once weekly) to treat twelve patients with relapsed ( n = 8) or refractory ( n = 4) POEMS syndrome. After a median follow-up time of 20 months, the overall hematologic response rate was 77% with 44% having a complete response. Eight (67%) patients had neurological response, and the median overall neuropathy limitation scale score was reduced from 3 (range, 1-9) to 2 (range, 0-6). Serum vascular endothelial growth factor response rate was 91% and 46% of patients had normal serum VEGF levels. One patient had progression of the disease 3 months after the end of treatment and subsequently died from the disease. Therefore, the estimated 2 year overall survival and progression-free survival were 92%. The low-dose lenalidomide and dexamethasone regimen was well tolerated, with no treatment-related death or any grade 3 or 4 toxicity. In conclusion, low-dose lenalidomide plus dexamethasone therapy is an effective and safe regimen for patients with relapsed or refractory POEMS syndrome. [ABSTRACT FROM AUTHOR]

Aims Among patients with neuromyelitis optica spectrum disorder ( NMOSD), fatigue is commonly complained about and is one of the most debilitating symptoms. This study aimed to investigate the incidence of fatigue and explore impacting factors attributed to fatigue in NMOSD. Methods Thirty-three patients with NMOSD and twenty matched healthy controls were enrolled. A battery of self-reported questionnaires was conducted to assess quality of sleep, daytime sleepiness, fatigue, depression, and level of activity of daily life. The structure of sleep was assessed by polysomnography with blood oxygen saturation monitored by noninvasive pulse oximeter. Brain and spinal cord lesions were evaluated by MRIs. Results Fatigue was more severe and more prevalent among the patients with NMOSD compared with controls (fatigue score which ranges from 0 to 11 with higher scores indicating more severe fatigue: 6.4 ± 0.6 vs. 3.8 ± 0.4, P = 0.002; incidence, 64% vs. 35%, P = 0.043), and it was negatively associated with daily activity level (r = 0.455, P = 0.008). The patients with fatigue had higher Pittsburgh Sleep Quality Index score, higher Epworth Sleepiness Scale score, lower blood oxygen state, and higher depression score than patients without fatigue; blood oxygen was especially negatively correlated with fatigue (nadir SpO2, r = −0.558, P = 0.001; mean SpO2, r = −0.457, P = 0.007); depression was also positively correlated with fatigue (r = 0.599, P < 0.001). Conclusion Patients with NMOSD experienced significant fatigue, which had an obvious impact on their daily activity. Fatigue in these patients was related to hypoxemia, sleep disturbances, and depression. [ABSTRACT FROM AUTHOR]

In traditional Chinese medicine, raw and processed herbs are used to treat different diseases. Suitable quality assessment methods are crucial for the discrimination between raw and processed herbs. The dried fruit of Arctium lappa L. and their processed products are widely used in traditional Chinese medicine, yet their therapeutic effects are different. In this study, a novel strategy using high-performance liquid chromatography and diode array detection coupled with multivariate statistical analysis to rapidly explore raw and processed Arctium lappa L. was proposed and validated. Four main components in a total of 30 batches of raw and processed Fructus Arctii samples were analyzed, and ten characteristic peaks were identified in the fingerprint common pattern. Furthermore, similarity evaluation, principal component analysis, and hierachical cluster analysis were applied to demonstrate the distinction. The results suggested that the relative amounts of the chemical components of raw and processed Fructus Arctii samples are different. This new method has been successfully applied to detect the raw and processed Fructus Arctii in marketed herbal medicinal products. [ABSTRACT FROM AUTHOR]

A rapid, sensitive, and reliable analytical method based on ultra high performance liquid chromatography with tandem mass spectrometry has been developed for the simultaneous determination of fangchinoline and tetrandrine in rat plasma. Plasma samples were pretreated by protein precipitation with acetonitrile. The analysis was performed on a C18 reversed-phase ultra high performance liquid chromatography column (2.1 mm × 100 mm, 3.5 μm, Agilent), and the flow rate was set at 0.4 mL/min. Under the experimental conditions, extraction recoveries from plasma were 68.1-72.8% for fangchinoline and 69.2-76.5% for tetrandrine. The plasma concentrations of tetrandrine and fangchinoline in rats at assigned time points were all successfully detected through exactly validated method. Good linearities were obtained in the range of 0.92-184 ng/mL for tetrandrine and in the range of 0.83-166 ng/mL for fangchinoline. The intra- and interday precisions for both analytes were within 11.1% and the accuracies were within the range of -10.7 to 11.3%. The developed method was then successfully applied to investigate the pharmacokinetic properties of these two alkaloids after oral administration of Stephania tetrandra S. Moore extracts and Fangji Huangqi Tang. The comparative results provided a meaningful basis for a better understanding of the practical value of the compatibility theory of traditional Chinese medicine in the clinic. [ABSTRACT FROM AUTHOR]

An improved high-performance liquid chromatography with diode array detection combined with accelerated solvent extraction method was used to simultaneously determine six compounds in crude and processed Radix Scrophulariae samples. Accelerated solvent extraction parameters such as extraction solvent, temperature, number of cycles, and analysis procedure were systematically optimized. The results indicated that compared with crude Radix Scrophulariae samples, the processed samples had lower contents of harpagide and harpagoside but higher contents of catalpol, acteoside, angoroside C, and cinnamic acid. The established method was sufficiently rapid and reliable for the global quality evaluation of crude and processed herbal medicines. [ABSTRACT FROM AUTHOR]

Sulfur fumigation may induce the decrease or the chemical transformation of some active ingredients of traditional Chinese medicines in vitro. Whether sulfur fumigation can cause the pharmacokinetic changes of the active ingredients in vivo is related to the efficacy and the safety of Chinese medicines' application clinically. A sensitive, specific, and accurate method for the simultaneous determination of paeoniflorin, ferulic acid, senkyunolide A, and senkyunolide I in rat plasma by ultra high performance liquid chromatography coupled with triple quadrupole mass spectrometry was developed to evaluate the influence of sulfur fumigation to Si Wu Tang for the first time. Each compound was extracted from plasma samples by liquid-liquid extraction with ethyl acetate, and the chromatographic separation was accomplished on an Agilent Extend C18 column with a linear gradient elution. The mass spectrometric detection and analysis were performed by using an AB Sciex triple quadrupole 5500 mass spectrometer in multiple reaction monitoring mode. The validated method was successfully applied to a pharmacokinetic study of four compounds in rats after oral administration of sun-dried and sulfur-fumigated Si Wu Tang. The results provided a meaningful basis for evaluating the affection of sulfur fumigation to the clinical application and the efficacy of Si Wu Tang. [ABSTRACT FROM AUTHOR]

Direct β-to-β linked branched and cyclic porphyrin trimers and pentamers have been synthesized by the Suzuki-Miyaura coupling of β-borylporphyrins and β-bromoporphyrins. The cyclic porphyrin trimer, the smallest directly linked cyclic porphyrin wheel to date, and its twined pentamer, exhibit small electrochemical HOMO-LUMO gaps, broad nonsplit Soret bands, and red-shifted Q-bands, thus indicating large electronic interactions between the constituent porphyrin units. [ABSTRACT FROM AUTHOR]

Sulfur-fumigation is known to reduce volatile compounds that are the main active components in herbs used in herbal medicine. We investigated changes in chemical composition between sun-dried and sulfur-fumigated Radix Angelicae Dahuricae using a purge and trap technique to capture volatile compounds, and two-dimensional gas chromatography/time-of-flight mass spectrometry for identification. Using sun-dried Radix Angelicae Dahuricae samples as a reference, the results showed that 73 volatile compounds, including 12 sulfide compounds, were found to be present only in sulfur-fumigated samples. Furthermore, 32 volatile compounds that were found in sun-dried Radix Angelicae Dahuricae samples disappeared after sulfur-fumigation. The proposed method can be applied to accurately discriminate sulfur-fumigated Radix Angelicae Dahuricae from different commercial sources. [ABSTRACT FROM AUTHOR]

ABSTRACT A rapid and sensitive high-performance liquid chromatography-mass spectrometric (HPLC-MS) method was developed and validated for simultaneous determination of benzoylhypaconine (BHA), benzoylmesaconine (BMA), benzoylaconine (BAC) and hypaconitine (HA) in rat plasma for the first time. The analytes were separated on a Kromasil C18 column with a total running time of 11 min. The validation data demonstrated a sound feasibility for the newly developed method and it was then applied to the pharmacokinetic study of these analytes in rats. Pharmacokinetic behaviors of BHA, BMA, BAC and HA in rats were studied after oral administration of Radix Aconiti Lateralis Praeparata extract (FZ) and Dahuang Fuzi Decoction (DFD). The main parameters for the two groups of subjects were compared, and significant differences between Radix Aconiti Lateralis Praeparata extract group and Dahuang Fuzi Decoction group in calculated parameters, such as the area under the plasma concentration-time from zero to the last quantifiable time-point (AUC0- t), the area under the plasma concentration-time curve from zero to infinity (AUC0-∞), peak plasma concentration ( Cmax), half-life of elimination ( T1/2), mean retention time (MRT0- t), plasma clearance ( CL), volume of distribution ( Vd) and time to reach Cmax ( Tmax), were found. After oral administration of DFD, the AUC0- t, AUC0-∞ and Cmax of BHA, BMA, BAC and HA decreased remarkably ( p < 0.05) compared with those of the FZ extract group. Vd and CL values of BHA, BMA, BAC and HA increased, two of which showed significant difference ( p < 0.05). T1/2 and MRT0- t values of BHA, BMA and BAC in the DFD group were significantly delayed compared with those of FZ extract group. Only the Tmax of HA, the toxic ingredient in FZ, delayed significantly in DFD group compared with the value of FZ group. All these pharmacokinetic parameters were statistically compared, and the rationality of the combination for DFD was clearly demonstrated. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

In the present study, comprehensive 2 D GC- TOF-MS combined with multivariate data analysis was applied to analyze the differences of the volatile components in crude and processed Atractylodis Macrocephalae Rhizoma ( AMR) samples. As a result, 26 compounds that were found in crude AMR samples disappeared in processed AMR samples, and 19 compounds were newly generated and identified in AMR after processing with wheat bran. Meanwhile, principal component analysis demonstrated that there were significant chemical differences between crude and processed AMR samples, and processing procedure caused obvious quantitative and qualitative changes of volatile components in AMR. The established method could be used to explain the chemical differentiation between crude and processed AMR, and to further understand the processing mechanism of herbal medicines. [ABSTRACT FROM AUTHOR]

Stomatin is an important lipid raft-associated protein which interacts with membrane proteins and plays a role in the membrane organization. However, it is unknown whether it is involved in the response to hypoxia and glucocorticoid ( GC) in alveolar epithelial cells ( AEC). In this study we found that hypoxia and dexamethasone (dex), a synthetic GC not only up-regulated the expression of stomatin alone, but also imposed additive effect on the expression of stomatin in A549 cells, primary AEC and lung of rats. Then we investigated whether hypoxia and dex transcriptionally up-regulated the expression of stomatin by reporter gene assay, and found that dex, but not hypoxia could increase the activity of a stomatin promoter-driven reporter gene. Further deletion and mutational studies demonstrated that a GC response element ( GRE) within the promoter region mainly contributed to the induction of stomatin by dex. Moreover, we found that hypoxia exposure did not affect membrane-associated actin, but decreased actin in cytoplasm in A549 cells. Inhibiting stomatin expression by stomatin si RNA significantly decreased dense of peripheral actin ring in hypoxia or dex treated A549 cells. Taken all together, these data indicated that dex and/or hypoxia significantly up-regulated the expression of stomatin in vivo and in vitro, which could stabilize membrane-associated actin in AEC. We suppose that the up-regulation of stomatin by hypoxia and dex may enhance the barrier function of alveolar epithelia and mediate the adaptive role of GC to hypoxia. [ABSTRACT FROM AUTHOR]