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Quantum entanglement serves as an essential resource across various fields, including quantum communication, quantum computing, and quantum precision measurement. Quantum microscope, as one of the significant applications in quantum precision measurement, could bring revolutionary advancements in both signal-to-noise ratio (SNR) and spatial resolution of imaging. Here, we present a quantum microscopy system that relies on a fully fiber-integrated high-performance energy-time entangled light source operating within the near-infrared II (NIR-II) window. Complemented by tailored real-time data acquisition and processing software, we successfully demonstrate the quantum imaging of a standard target, achieving a SNR of 131.51 ± 6.74 and a spatial resolution of 4.75 ± 0.27 µm. Furthermore, we showcase quantum imaging of cancer cells, unveiling the potential of quantum entanglement in biomedical applications. Our fiber-integrated quantum microscope, characterized by high imaging SNR, instantaneous image capture, and analysis capabilities, marks an important step toward the practical application in life sciences.

An integrated quantum light source is increasingly desirable in large-scale quantum information processing. Despite recent remarkable advances, a new material platform is constantly being explored for the fully on-chip integration of quantum light generation, active and passive manipulation, and detection. Here, for the first time, we demonstrate a gallium nitride (GaN) microring based quantum light generation in the telecom C-band, which has potential toward the monolithic integration of quantum light source. In our demonstration, the GaN microring has a free spectral range of 330 GHz and a near-zero anomalous dispersion region of over 100 nm. The generation of energy-time entangled photon pair is demonstrated with a typical raw two-photon interference visibility of 95.5±6.5%, which is further configured to generate a heralded single photon with a typical heralded second-order autocorrelation g_{H}^{(2)}(0) of 0.045±0.001. Our results pave the way for developing a chip-scale quantum photonic circuit.

The emerging sample pretreatment technique of magnetic solid-phase extraction (MSPE) has drawn the attention of researchers owing to its advantages of less reagent consumption, fast separation/enrichment process, high adsorption capacity, and simple operation. This paper presents a review of synthesis techniques, classification, and analysis procedures for MSPE in the detection of heavy metals in food. Magnetic adsorbents derived from silica, metal oxides, carbon, polymers, etc. , are applied for the detection of heavy metals in food. Then, the recent development of the technology of MSPE for the analysis of heavy metal extraction in food is summarized in detail. Finally, the future outlook for the improvement of MSPE is also discussed.

Two-dimensional (2D) bismuth oxyhalides (BiOX) have attracted much attention as potential optoelectronic materials. To explore their application diversity, we herewith systematically investigate the tunable properties of 2D BiOX using first-principles calculations. Their electronic and optical properties can be modulated by changing the number of monolayers, applying strain, and/or varying the halogen composition. The band gap shrinks monotonically and approaches the bulk value, the optical absorption coefficient increases, and the absorption spectrum redshifts as the layer number of 2D BiOX increases. The carrier transport property can be improved by applying tensile strain, and the ability of photocatalytic hydrogen evolution can be obtained by applying compressive strain. General strain engineering will be effective in linearly tuning the band gap of BiOX in a wide strain range. Strain, together with halogen composition variation, can tune the optical absorption spectrum to be on demand in the range from visible to ultraviolet. This suggests that 2D BiOX materials can potentially serve as tunable novel photodetectors, can be used to improve clean energy techniques, and have potential in the field of flexible optoelectronics.

Parkinson's disease (PD) is a neurodegenerative disorder associated with α-synuclein aggregation and dopaminergic neuron loss in the midbrain. There is evidence that psychological stress promotes PD progression by enhancing glucocorticoids-related oxidative damage, however, the mechanisms involved are unknown. The present study demonstrated that plasma membrane phospholipid peroxides, as determined by phospholipidomics, triggered ferroptosis in dopaminergic neurons, which in turn contributed to stress exacerbated PD-like motor disorder in mice overexpressing mutant human α-synuclein. Using hormonomics, we identified that stress stimulated corticosteroid release and promoted 15-lipoxygenase-1 (ALOX15)-mediated phospholipid peroxidation. ALOX15 was upregulated by α-synuclein overexpression and acted as a fundamental risk factor in the development of chronic stress-induced parkinsonism and neurodegeneration. Further, we demonstrated the mechanism by which corticosteroids activated the PKC pathway and induced phosphatidylethanolamine-binding protein-1 (PEBP1) to form a complex with ALOX15, thereby facilitating ALOX15 to locate on the plasma membrane phospholipids. A natural product isolated from herbs, leonurine, was screened with activities of inhibiting the ALOX15/PEBP1 interaction and thereby attenuating membrane phospholipid peroxidation. Collectively, our findings demonstrate that stress increases the susceptibility of PD by driving membrane lipid peroxidation of dopaminergic neurons and suggest the ALOX15/PEBP1 complex as a potential intervention target., (© 2023 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Two-dimensional (2D) antiferromagnetic semiconductor chromium thiophosphate (CrPS 4 ) has gradually become a major candidate material for low-dimensional nanoelectromechanical devices due to its remarkable structural, photoelectric characteristics and potentially magnetic properties. Here, we report the experimental study of a new few-layer CrPS 4 nanomechanical resonator demonstrating excellent vibration characteristics through the laser interferometry system, including the uniqueness of resonant mode, the ability to work at the very high frequency, and gate tuning. In addition, we demonstrate that the magnetic phase transition of CrPS 4 strips can be effectively detected by temperature-regulated resonant frequencies, which proves the coupling between magnetic phase and mechanical vibration. We believe that our findings will promote the further research and applications of the resonator for 2D magnetic materials in the field of optical/mechanical signal sensing and precision measurement.

Constructing two-dimensional (2D) van der Waals (vdW) heterostructures is an effective strategy for tuning and improving the characters of 2D-material-based devices. Four trilayer vdW heterostructures, BP/BP/MoS 2 , BlueP/BlueP/MoS 2 , BP/graphene/MoS 2 and BlueP/graphene/MoS 2 , were designed and simulated using the first-principles calculation. Structural stabilities were confirmed for all these heterostructures, indicating their feasibility in fabrication. BP/BP/MoS 2 and BlueP/BlueP/MoS 2 lowered the bandgaps further, making them suitable for a greater range of applications, with respect to the bilayers BP/MoS 2 and BlueP/MoS 2 , respectively. Their absorption coefficients were remarkably improved in a wide spectrum, suggesting the better performance of photodetectors working in a wide spectrum from mid-wave (short-wave) infrared to violet. In contrast, the bandgaps in BP/graphene/MoS 2 and BlueP/graphene/MoS 2 were mostly enlarged, with a specific opening of the graphene bandgap in BP/graphene/MoS 2 , 0.051 eV, which is much larger than usual and beneficial for optoelectronic applications. Accompanying these bandgap increases, BP/graphene/MoS 2 and BlueP/graphene/MoS 2 exhibit absorption enhancement in the whole infrared, visible to deep ultraviolet or solar blind ultraviolet ranges, implying that these asymmetrically graphene-sandwiched heterostructures are more suitable as graphene-based 2D optoelectronic devices. The proposed 2D trilayer vdW heterostructures are prospective new optoelectronic devices, possessing higher performance than currently available devices.

Bolometers based on graphene have demonstrated outstanding performance with high sensitivity and short response time. In situ adjustment of bolometers is very important in various applications, but it is still difficult to implement in many systems. Here we propose a gate-tunable bolometer based on two strongly coupled graphene nanomechanical resonators. Both resonators are exposed to the same light field, and we can measure the properties of one bolometer by directly tracking the resonance frequency shifts, and indirectly measure the other bolometer through mechanical coupling. We find that the sensitivity and the response bandwidth of both bolometers can be independently adjusted by tuning the corresponding gate voltages. Moreover, the properties of the indirectly measured bolometer show a dependence on the coupling between the two resonators, with other parameters being fixed. Our method has the potential to optimize the design of large-scale bolometer arrays, and open new horizons in infrared/terahertz astronomy and communication systems.

Bladder cancer (BC) is a familiar malignancy with high morbidity and mortality. The effect of treatment is unsatisfactory after the metastasis and invasion of BC. Hence, more studies should be carried out to explore the metastasis of BC. RT-qPCR or/and western blot was conducted to evaluate miR-494-3p, KLF9, and RGS2 expression. Cell proliferation and invasion were estimated by MTT assay and transwell assay, respectively. Cell migration was tested by wound healing assay and transwell assay. Dual-luciferase reporter gene assay was employed to validate the interplay between miR-494-3p and KLF9 mRNA. The interaction between KLF9 and RGS2 promoter was verified using dual-luciferase reporter gene assay and chromatin immunoprecipitation (ChIP) assay. miR-494-3p expression was upregulated, whereas KLF9 and RGS2 were downregulated in BC cells. miR-494-3p inhibition was competent to limit the growth of BC cells. KLF9 knockdown abolished the miR-494-3p depletion-mediated inhibitory growth of BC cells. Mechanistically, we found that KLF9 was a downstream gene of miR-494-3p and could bind to the promoter region of RGS2 to promote the expression of RGS2. Moreover, RGS2 knockdown abrogated the suppressive effects of miR-494-3p knockdown on the proliferation, migration, and invasion of BC cells. Notably, miR-494-3p inhibition obstructed the tumor growth in nude mice. miR-494-3p silencing inhibited the progression of BC by regulating the KLF9/RGS2 axis in vitro and in vivo, which laid the foundation for experiments of miR-494-3p in BC and provided therapeutic targets for BC., (© 2022 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.)

Two-dimensional (2D) materials provide a new strategy for developing photodetectors at the nanoscale. The electronic and optical properties of black phosphorus (BP), indium selenide (InSe) monolayer and BP/InSe heterojunction were investigated via first-principles calculations. The geometric characteristic shows that the BP, InSe monolayer and BP/InSe heterojunction have high structural symmetry, and the band gap values are 1.592, 2.139, and 1.136 eV, respectively. The results of band offset, band decomposed charge and electrostatic potential imply that the heterojunction structure can effectively inhibit the recombination of electron--hole pairs, which is beneficial for carrier mobility of photoelectric devices. Moreover, the optical properties, including refractive index, reflectivity, electron energy loss, extinction coefficient, absorption coefficient and photon optical conductivity, show excellent performance. These findings reveal the optimistic application potential for future photoelectric devices. The results of the present study provide new insight into challenges related to the peculiar behavior of the aforementioned materials with applications.

As an inherent property of the device itself, nonlinearity in micro-/nano- electromechanical resonators is difficult to eliminate, and it has shown a wide range of applications in basic research, sensing and other fields. While many application scenarios require tunability of the nonlinearity, inherent nonlinearity of a mechanical resonator is difficult to be changed. Here, we report the experimental observation of a Joule heating induced tuning effect on the nonlinearity of graphene mechanical resonators. We fabricated multiple graphene mechanical resonators and detected their resonant properties by an optical interference method. The mechanical vibration of the resonators will enter from the linear to the nonlinear intervals if we enhance the external driving power to a certain value. We found that at a fixed drive power, the nonlinearity of a mechanical resonator can be tuned by applying a dc bias current on the resonator itself. The tuning mechanism could be explained by the nonlinear amplitude-frequency dependence theory. Our results may provide a research platform for the study of mechanical nonlinearity by using atomic-thin layer materials., (© 2022 IOP Publishing Ltd.)

The number of semiconducting MXenes with direct band gaps is extremely low; thus, it is highly desirable to broaden the MXene family beyond carbides and nitrides to expand the palette of desired chemical and physical properties. Here, we theoretically report the existence of the single-layer (SL) dititanium oxide 2H-Ti 2 O MOene (MXene-like 2D transition oxides), showing an Ising superconducting feature. Moreover, SL halogenated 2H- and 1T-Ti 2 O monolayers display tunable semiconducting features and strong light-harvesting ability. In addition, the external strains can induce Weyl fermions via quantum phase transition in 2H-Ti 2 OF 2 and Ti 2 OCl 2 monolayers. Specifically, 2H- and 1T-Ti 2 OF 2 are direct semiconductors with band gaps of 0.82 and 1.18 eV, respectively. Furthermore, the carrier lifetimes of SL 2H- and 1T-Ti 2 OF 2 are evaluated to be 0.39 and 2.8 ns, respectively. This study extends emerging phenomena in a rich family of 2D MXene-like MOene materials, which provides a novel platform for next-generation optoelectronic and photovoltaic fields.

Recently, two-dimensional (2D) metal halides have brought out an intensive interest for their unique mechanical, electronic, magnetic, and topological properties. Here, we theoretically report the existence of the single-layer (SL) zirconium dihalide materials ZrX 2 (X = Cl, Br, and I) using first-principles calculations. SL ZrX 2 , which can be obtained from its bulk phase through simple mechanical exfoliation, shows the dynamic, thermodynamic, and mechanical stability. Halogen atoms can effectively tune the electronic structure, dipole moment transition, band alignment, and light absorption. Specifically, ZrX 2 monolayers intrinsically exhibit a ferroelasticity with an abnormal 120° orientation rotation, possessing a moderate switching barrier of 24-39 meV/atom. Importantly, we observe superior anisotropic light absorption responses on SL ZrX 2 in the visible region. Besides, a series of ZrX 2 -based excitonic solar cells have been proposed, which hold a large power conversion efficiency limit of 12.4-18.7%.

Graphene has been considered as one of the best materials to implement mechanical resonators due to their excellent properties such as low mass, high quality factors and tunable resonant frequencies. Here we report the observation of phonon lasing induced by the photonthermal pressure in a few-layer graphene resonator at room temperature, where the graphene resonator and the silicon substrate form an optical cavity. A marked threshold in the oscillation amplitude and a narrowing linewidth of the vibration mode are observed, which confirms a phonon lasing process in the graphene resonator. Our findings will stimulate the studies on phononic phenomena, help to establish new functional devices based on graphene mechanical resonators, and might find potential applications in classical and quantum sensing fields, as well as in information processing.

GM1 ganglioside is particularly abundant in the mammalian central nervous system and has shown beneficial effects on neurodegenerative diseases. In this study, we investigated the therapeutic effect of GM1 ganglioside in experimental models of Parkinson's disease (PD) in vivo and in vitro. Mice were injected with MPTP (30 mg·kg -1 ·d -1 , i.p.) for 5 days, resulting in a subacute model of PD. PD mice were treated with GM1 ganglioside (25, 50 mg·kg - 1 ·d -1 , i.p.) for 2 weeks. We showed that GM1 ganglioside administration substantially improved the MPTP-induced behavioral disturbance and increased the levels of dopamine and its metabolites in the striatal tissues. In the MPP + -treated SH-SY5Y cells and α-synuclein (α-Syn) A53T-overexpressing PC12 (PC12 α-Syn A53T ) cells, treatment with GM1 ganglioside (40 μM) significantly decreased α-Syn accumulation and alleviated mitochondrial dysfunction and oxidative stress. We further revealed that treatment with GM1 ganglioside promoted autophagy, evidenced by the autophagosomes that appeared in the substantia nigra of PD mice as well as the changes of autophagy-related proteins (LC3-II and p62) in the MPP + -treated SH-SY5Y cells. Cotreatment with the autophagy inhibitor 3-MA or bafilomycin A1 abrogated the in vivo and in vitro neuroprotective effects of GM1 ganglioside. Using GM1 ganglioside labeled with FITC fluorescent, we observed apparent colocalization of GM1-FITC and α-Syn as well as GM1-FITC and LC3 in PC12 α-Syn A53T cells. GM1 ganglioside significantly increased the phosphorylation of autophagy regulatory proteins ATG13 and ULK1 in doxycycline-treated PC12 α-Syn A53T cells and the MPP + -treated SH-SY5Y cells, which was inhibited by 3-MA. Taken together, this study demonstrates that the anti-PD role of GM1 ganglioside resulted from activation of autophagy-dependent α-Syn clearance.

Recently, two-dimensional (2D) metal halides have triggered an enormous interest for their tunable mechanical, electronic, magnetic, and topological properties, greatly enriching the family of 2D materials. Here, based on first-principles calculations, we report a systematic study of group 11 transition-metal halide MX (M = Cu, Ag, Au; X = Cl, Br, I) monolayers. Among them, CuBr, CuI, AgBr, and AgI monolayers exhibit high thermodynamic, dynamic, and mechanic stability. The four stable monolayers have a direct band gap of ∼3.12-3.36 eV and possess high carrier mobility (∼10 3 cm 2 V -1 s -1 ), suggestive of future photocatalysts for water splitting applications. What is more, the simulations of optical properties confirm that the stable MX monolayers hold the potential for further applications in ultraviolet optical devices and quantum cutting solar materials.

Background: Hypernatremic donors was regarded as the expanded criteria donors in liver transplantation. The study was to investigate the effects of donor hypernatremia on the outcomes of liver transplantation and identify the prognostic factors possibly contributing to the poor outcomes., Methods: Donor serum sodium levels before procurement were categorized as normal sodium (< 155 mmol/L), moderate high sodium (155-170 mmol/L), and severe high sodium (≥ 170 mmol/L). Furthermore, we subdivided the 142 hypernatremic donors (≥ 155 mmol/L) into two subgroups: subgroup A, the exposure time of liver grafts from hypernatremia to reperfusion was < 36 h; and subgroup B, the exposure time was ≥ 36 h. The outcomes included initial graft function, survival rates of grafts and recipients, graft loss and early events within the first year following liver transplantation., Results: There were no significant differences in the 1-year survival rates of grafts and recipients, 1-year graft loss rates and early events among the normal, moderate high and severe high sodium groups. However, the overall survival rates of grafts and recipients in subgroup A were significantly higher than those in subgroup B. Cox model showed that the exposure time (HR = 1.117; 95% CI: 1.053-1.186; P < 0.001), cold ischemia time (HR = 1.015; 95% CI: 1.006-1.024; P = 0.001) and MELD (HR = 1.061; 95% CI: 1.003-1.121; P = 0.037) were the important prognostic factors contributing to the poor outcomes of recipients with hypernatremic donors., Conclusions: The level of donor sodium immediately before organ procurement does not have negative effects on the early outcomes following adult liver transplantation. For hypernatremia liver donors, minimization of the exposure time from hypernatremia to reperfusion is critical to prevent graft loss., (Copyright © 2020. Published by Elsevier B.V.)

Ethnopharmacological Relevance: Tianma Gouteng granules (TG), a clinical prescription of traditional Chinese medicine, has been clinically applied to treat Parkinson's disease (PD) in combination with Madopar, as included in the Chinese Pharmacopoeia (2015). TG has the potential to decrease the susceptibility of PD pharmacologically, however the mechanisms need detailed demonstration., Aim of the Study: To evaluate the pharmacological activities, as well as the possible mechanism of TG in diverse models of PD., Materials and Methods: 6-OHDA-treated rats, MPTP-treated mice, and α-synuclein A53T overexpressed mice, were utilized as PD animal models. Rotarod, locomotor activity, inclined plane and traction tests were used for behavioral assessment. Immunohistochemistry was used for tyrosine hydrolase determination. Western blot were conducted for detection of 4-HNE and 15-lipoxygenase-1 (ALOX15). The interactions of ALOX15 with the components in TG were predicted by molecular docking approach., Results: Lipid peroxidation was involved in dopaminergic neuron damage in 6-OHDA-induced rat models. In MPTP-treated mice, the inhibition of lipid peroxidation improved behavioral and pathological symptoms of PD. The lipid peroxidation-related protein, ALOX15 was found to be the key factor in PD process in diverse PD models including 6-OHDA-treated rats, MPTP-treated mice, and α-synuclein A53T overexpressed mice. TG treatment significantly relieved behavioral and pathological symptoms of MPTP-induced PD mouse models with a potential mechanism of alleviating ALOX15-induced lipid peroxidation. Moreover, the results of molecular docking analysis show that compounds in TG might have interactions with ALOX15., Conclusions: TG effectively improved the behavioral and dopaminergic neuron damage in diverse PD models. The mechanism of this action may be related to the direct inhibition of ALOX15 and the relief of lipid peroxidation., Competing Interests: Declaration of competing interest The authors declared no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Based on the latest monthly data of moderate resolution imaging spectroradiometer (MODIS)/Terra C6.1 aerosol optical depth (AOD), the temporal-spatial distribution and variability trend in AOD over China during 2001-2017 are analyzed to explore the distribution and variation characteristics of AOD in China. Regarding the spatial characteristics, the first prominent high-value center of the annual mean AOD was located in the industrially and economically developed areas of the North China Plain, Central China, the Yangtze River Delta region, the Pearl River Delta region, and the Sichuan Basin. The second prominent high-value center of the annual mean AOD was located in the dust aerosol-dominated areas of Taklimakan Desert. Two low-value centers of the annual mean AOD were located in the eastern part of Inner Mongolia to the north of Northeast China and the Tibet Plateau. Regarding the temporal characteristics, the AOD value peaked in eight areas in spring and summer. The annual mean AOD values in the Taklimakan Desert, Sichuan Basin, and Pearl River Delta peaked from March to May, and those in the North China Plain, Central China, and Yangtze River Delta peaked from May to July. The trend characteristics showed that during 2001-2006, the AOD in Northwest China and Inner Mongolia showed a downtrend, and that in the east-central China and the eastern part of southwest China showed a growth trend. During 2007-2012, the trend of AOD in the Tibetan Plateau and the Taklimakan Desert changed from decreasing to increasing. The growth trend of AOD in the North China Plain and the Sichuan Basin was weakened, and the AOD in the Yangtze River Delta showed a weak downward trend. During 2013-2017, the AOD in most areas of China showed a significant downward trend.

1,8-Cineole (eucalyptol), a monoterpene, has been widely reported for the anti-inflammatory effects. Our previous data confirmed that 1,8-cineole ameliorated the inflammatory phenotype of human umbilical vein endothelial cells (HUVECs) by mediating NF-κB expression in vitro . At present, we investigated the protection effects of 1,8-cineole on vascular endothelium in lipopolysaccharide (LPS)-induced acute inflammatory injury mice and the potential mechanisms involved in the protection in HUVECs. Results from enzyme linked immunosorbent assays revealed that 1,8-cineole suppressed the secretion of interleukin (IL)-6 and IL-8 and increased the expression of IL-10 in the serum of LPS-induced mice. 1,8-Cineole reduced the inflammatory infiltration and the expression of vascular cell adhesion molecular 1 (VCAM-1) in the sections of thoracic aorta in LPS-induced acute inflammatory mice. Western blotting indicated that 1,8-cineole significantly decreased the phosphorylation of NF-κB p65 and increased the expression of PPAR-γ in the thoracic aorta tissue. 1,8-Cineole increased the expression of PPAR-γ in LPS-induced HUVECs. 1,8-Cineole and rosiglitazone reduced the protein and mRNA levels of VCAM-1, E-selectin, IL-6, and IL-8 in LPS-induced HUVECs, which could be reversed by the action of GW9662 (inhibitor of PPAR-γ). 1,8-Cineole and rosiglitazone blocked the LPS-induced IκBα degradation and NF-κB p65 nucleus translocation, which could be reversed by the pretreatment of GW9662 or silence of PPAR-γ gene. In conclusion, 1,8-cineole attenuated LPS-induced vascular endothelial cells injury via PPAR-γ dependent modulation of NF-κB.

Hepatocellular carcinoma (HCC) is known for its high mortality rate worldwide. Based on intensive studies, microRNA (miRNA) expression functions in tumor suppression. Therefore, we aimed to evaluate the contribution of miR-146a-5p to radiosensitivity in HCC through the activation of the DNA damage repair pathway by binding to replication protein A3 (RPA3). First, the limma package of R was performed to differentially analyze HCC expression chip, and regulative miRNA of RPA3 was predicted. Expression of miR-146a-5p, RPA3, and DNA damage repair pathway-related factors in tissues and cells was determined. The effects of radiotherapy on the expression of miR-146a-5p and RPA3 as well as on cell radiosensitivity, proliferation, cell cycle, and apoptosis were also assessed. The results showed that there exists a close correlation between miR-146a and the radiotherapy effect on HCC progression through regulation of RPA3 and the DNA repair pathway. The positive rate of ATM, pCHK2, and Rad51 in HCC tissues was higher when compared with that of the paracancerous tissues. SMMC-7721 and HepG2 cell proliferation were significantly inhibited following 8 Gy 6Mv dose. MiR-146a-5p restrained the expression of RPA3 and promoted the expression of relative genes associated with the DNA repair pathway. In addition, miR-146a-5p overexpression suppresses cell proliferation and enhances radiosensitivity and cell apoptosis in HCC cells. In conclusion, the present study revealed that miR-146a-5p could lead to the restriction of proliferation and the promotion of radiosensitivity and apoptosis in HCC cells through activation of DNA repair pathway and inhibition of RPA3.

Increasing evidence indicates that DNA damage and p53 activation play major roles in the pathological process of motor neuron death in amyotrophic lateral sclerosis (ALS). Human SpeedyA1 (Spy1), a member of the Speedy/Ringo family, enhances cell proliferation and promotes tumorigenesis. Further studies have demonstrated that Spy1 promotes cell survival and inhibits DNA damage-induced apoptosis. We showed that the Spy1 expression levels were substantially decreased in ALS motor neurons compared with wild-type controls both in vivo and in vitro by qRT-PCR, western blotting, and Immunoassay tests. In addition, we established that over-expression of human SOD1 mutant G93A led to a decreased expression of Spy1. Furthermore, DNA damage response was activated in SOD1 G93A -transfected cells (mSOD1 cells). Moreover, decreased Spy1 expression reduced cell viability and further activated the DNA damage response in mSOD1 cells. In contrast, increased Spy1 expression improved cell viability and inhibited the DNA damage response in mSOD1 cells. These results suggest that Spy1 plays a protective role in ALS motor neurons. Importantly, these findings provide a novel direction for therapeutic options for patients with ALS as well as for trial designs, such as investigating the role of oncogenic proteins in ALS., (Copyright © 2018 Elsevier B.V. All rights reserved.)

To assess the health-related quality of life (HRQOL) of Han Chinese people with systemic lupus erythematosus (SLE) using a Chinese version of the Systemic Lupus Erythematosus-Specific Quality of Life Questionnaire (SLEQOL-C) and explore the factors influencing HRQOL of people with SLE. Participants were Han Chinese people with SLE. The SLEQOL-C and 36-item Short Form Health Survey (SF-36) were used to estimate the HRQOL. Disease activity was determined using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and fatigue using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F). Participant factors included age, gender, educational background, disease duration, erythrocyte sedimentation rate (ESR), and complement C3 and C4 levels. The results showed that higher SLEQQL-C scores correlated with lower SF-36 both measures are essential for HRQQL prediction. The SLEQOL-C scores were correlated with educational level,age, FACIT-F score, SLEDAI score, and ESR, which suggests that poor educational background, old-age, and increased fatigue, disease activity, and ESR might represent poor HRQOL. Although disease duration did not significantly correlate with the scores on the SLEQOL-C; those whose disease duration was 12-24 months had higher SLEQOL-C summary scores and physical functioning, symptoms, and treatment subscale scores than did those whose duration was less than 6 months. The FACIT-F score, education level, age, disease duration, SLEDAI score, and ESR contributed to SLEQOL-C scores. The SLEQOL-C is reliable for assessing HRQOL of Han Chinese people with SLE. Fatigue, educational level, age, disease duration, ESR, and disease activity mainly influenced HRQOL of SLE patients.

Wernicke encephalopathy (WE) is an acute neurological disorder resulting from vitamin B1 deficiency, which is common in chronic alcoholism and is rare in acute liver failure. So far, there are 2 cases of WE reported after liver transplantation. Here, we report a case of a 45-year-old nonalcoholic male patient who developed psychiatric and neurological disturbance 15 d after receiving orthotopic liver transplantation because of hepatitis B-related cirrhosis and portal hypertension. Brain magnetic resonance imaging (MRI) showed symmetric high-signal intensities in the periaqueductal area. The patient was diagnosed with WE and given intravenous high-dose vitamin B1 immediately. His neurological disturbance resolved in 7 d after receiving the vitamin B1. Brain MRI after 5 mo showed nearly complete recovery. Most WE cases may be misdiagnosed in patients after liver transplantation, and we should pay more attention to its onset., Competing Interests: Conflict-of-interest statement: All the authors have no conflicts of interest to declare.

SnO 2 nanobelts (NBs) have unique structural and functional properties which attract great attention in gas detecting. In this work, Eu doping is adopted to improve the gas sensitivity of pure SnO 2 , especially to enhance the response to one single gas. The Eu-doped SnO 2 NBs, pure-SnO 2 NBs, and their single NB devices are fabricated by simple techniques. The sensing properties of the two sensors have been experimentally investigated. It is found that the two sensors possess long-term stability with rapid response performance, and Eu doping improves the electronic performance and the gas-sensing response, particularly to acetone. In addition, the effects aroused by Eu have been theoretically calculated, which indicates that Eu doping enhances the sensing performance of SnO 2 . Consequently, Eu-doped SnO 2 NBs show great potential applications in the detection of acetone.

Objective: To investigate the clinical characteristics of 31 acute myeloid leukemia (AML) patients with chromosome 21 aberrations., Methods: Karyotypes of 168 newly diagnosed AML patients in Second Xiangya Hospital from Jan 2014 to July 2016 were reviewed for the presence of chromosome 21 aberrations (accounting for 18.45%). Clinical manifestation, as well as prognostic gene mutations distribution and immune classification were analyzed., Results: Out of 168 AML newly diagnosed patients, 31 cases with chromosome 21 aberrations including t(8;21) accounting for 67.74% (21/31), and trisomy 21 (16.13%,5/31), 2 variants were found as t(1; 21) and t(1; 21; 8); 77 cases had normal karyotype, and 60 cases possessed other chromosomes aberrations. Statistically significant differences did not exist among age, sex and white blood cell count (P>0.05). However, the 21 cases in chromosome aberrations group were predisposed to lower hemoglobin and platelet count(P<0.05). 5 cases of Trisomy 21 were characterized by M5 2 cases, M1 one case, M2 one case M4 one case. And the rate of C-kit/D816V mutation was higher in t(8;21) aberrations group when 7 prognostic genes including FLT3/ITD, C-kit/D816V, NPM1, DNMT3A, TET2 were analyzed, and the immune classification of t(8; 21) aberration group inclined to CD19 + , CD34 + but CD33 - , CD64 - . And trisomy 21 displayed a trend to CD34 + and CD7 + ., Conclusion: Chromosome 21 is easily involved in acute myeloid leukemia. The patients with involvement of this aberration have characteristic clinic changes.

Objective: To study the effect of Taoren Quyu Decoction (TQD) on endometrial cells in patients with endometriosis (EMs) and EMs in rats., Methods: A total of 60 female Wistar rats were randomly divided into 4 groups, namely, normal group, model group, positive group and TQD group, each group having 15 rats. Except the normal group, EMs model was established in the other three groups by transplanting the rat autologous endometrium. After 4 weeks of intragastric administration, blood, eutopic and ectopic endometrial tissues of rats in each group were collected to detect the serum levels of estrogen (E2), cancer antigen 125 (CA125), endometrial antibody (EMAb), and expressions of microvessel density (MVD), vascular endothelial growth factor (VEGF) and angiopoietin (Ang-2). The volume of endometriosis cyst was determined simultaneously. For the in vitro culture of human endometrial cells, 4 groups, namely, normal group, model group, positive group and TQD group were used. The positive group and TQD group were treated with danazol and TQD respectively. Then 24 h after the treatment, the expressions of survivin and tumor suppressor gene (p53) of each group were detected., Results: The volumes of the endometriosis cysts in the positive group and the TQD group were significantly reduced compared with the model group (P < 0.05). The serum levels of E2, CA125 and EMAb, and the expressions of MVD, VEGF and Ang-2 in the model group were significantly increased compared with the normal group (P < 0.05); while they were all significantly reduced in the positive group and TQD group (P < 0.05). Compared with the normal group, the expression of survivin in the model group was significantly up-regulated (P < 0.05), and expression of p53 was significantly reduced (P < 0.05); compared with the model group, the expressions of survivin in the positive and TQD groups were significantly decreased (P < 0.05), and expression of p53 was significantly up-regulated (P < 0.05). The difference between positive group and TQD group was not statistically significant (P > 0.05)., Conclusions: TQD has a significant anti-EMs effect, and its mechanism of action may be related to anti-angiogenesis and promoting apoptosis of ectopic endometrial cell., (Copyright © 2017 Hainan Medical University. Production and hosting by Elsevier B.V. All rights reserved.)

Background: Mutations in the Cu/Zn superoxide dismutase ( SOD1 ) gene have been linked to amyotrophic lateral sclerosis (ALS). However, the molecular mechanisms have not been elucidated yet. Homer family protein Homer1b/c is expressed widely in the central nervous system and plays important roles in neurological diseases. In this study, we explored whether Homer1b/c was involved in SOD1 mutation-linked ALS., Results: In vitro studies showed that the SOD1 G93A mutation induced an increase of Homer1b/c expression at both the mRNA and protein levels in NSC34 cells. Knockdown of Homer1b/c expression using its short interfering RNA (siRNA) (si-Homer1) protected SOD1 G93A NSC34 cells from apoptosis. The expressions of Homer1b/c and apoptosis-related protein Bax were also suppressed, while Bcl-2 was increased by lithium and valproic acid (VPA) in SOD1 G93A NSC34 cells. In vivo, both the mRNA and protein levels of Homer1b/c were increased significantly in the lumbar spinal cord in SOD1 G93A transgenic mice compared with wild type (WT) mice. Moreover, lithium and VPA treatment suppressed the expression of Homer1b/c in SOD1 G93A mice., Conclusion: The suppression of SOD1 G93A mutation-induced Homer1b/c upregulation protected ALS against neuronal apoptosis, which is a novel mechanism of the neuroprotective effect of lithium and VPA. This study provides new insights into pathogenesis and treatment of ALS., Competing Interests: The authors declare no conflict of interest.

Objective: To compare the mid- to long-term outcomes of patients receiving isolated coronary artery bypass grafting (CABG) versus surgical ventricular restoration (SVR) plus CABG for left ventricular aneurysms., Methods: The clinical data were retrospectively analyzed in 205 patients with left ventricular aneurysms admitted to our hospital between January, 1997 and December, 2012, including 115 patients receiving SVR plus CABG and 90 undergoing isolated CABG. By matching preoperative echocardiographic parameters including aneurysm size, left ventricular ejection fraction (LVEF), left ventricular end-systolic volume index (LVESVI) and EuroSCORE risk factors, 32 patients receiving SVR plus CABG and another 32 with isolated CABG were enrolled in this study. The patients were compared for survival rates, major adverse cardiac or cerebrovascular events (MACCEs), left ventricular geometry and function at 1, 3 and 5 years of follow-up., Results: Compared with the patients receiving isolated CABG, those receiving SVR and CABG showed greater improvements in echocardiographic parameters and NYHA functional class. The differences in the echocardiographic parameters between the two groups gradually reduced with time and became comparable at 5 years after the operation (P>0.05). No significant difference was found in the mid- to long-term survival or the incidence of MACCEs between the two groups (P>0.05)., Conclusion: Compared with isolated CABG, SVR plus CABG does not reduce the incidence of MACCEs or improve the mid- to long-term survival rate of patients with left ventricular aneurysm with a LVESVI <60 mL/m(2).

Antibody-drug conjugate (ADC) is a new class of therapeutics composed of a monoclonal antibody and small cytotoxin moieties conjugated through a chemical linker. ADC molecules bind to the target antigens expressed on the tumor cell surfaces guided by the monoclonal antibody component. The binding ADC molecules can be internalized and subsequently the toxin moieties can be released within the tumor cells via chemical and/or enzymatic reactions to kill the target cells. The conjugation combines the merits of both components, i.e., the high target specificity of the monoclonal antibody and the highly potent cell killing activity of the cytotoxin moieties. However, such complexities make the pharmacokinetic and metabolic studies of ADCs highly challenging. The major challenges should include characterization of absorption, distribution, metabolism and excretion, investigation of underlying mechanisms, assessment of pharmacokinetic- pharmacodynamic relationship, and analytical method development of ADC drugs. This review will discuss common pharmacokinetic issues and considerations, as well as tools and strategies that can be utilized to characterize the pharmacokinetic and metabolic properties of ADCs.

We theoretically demonstrate high quality(Q)-factor micropillar cavities at 1.55-μm wavelength based on Si/SiO(2)-InP hybrid structure. An adiabatic design in distributed Bragg reflectors (DBRs) improves Q-factor for upto 3 orders of magnitude, while reducing the diameter to sub-micrometer. A moderate Q-factor of ~3000 and a Purcell factor of ~200 are realized by only 2 taper segments and fewer conventional DBR pairs, enabling single photon generation at GHz rate. As the taper segment number is increased, Q-factor can be boosted to ~10(5)-10(6), enabling coherent exchange between the emitter and the optical mode at 1.55 μm, which is applicable in quantum information networks.

Background: Portal hypertension is one of the most important clinical conditions that cause intraoperative intensive hemorrhage in cirrhotic patients undergoing liver transplantation. Pre-transplant portal decompression may reduce the intraoperative bleeding during liver transplantation., Methods: Splenic artery trunk embolization (SATE) was performed one month prior to liver transplantation. Platelet count, prealbumin, international normalized ratio, and blood flow in the portal vein and hepatic artery were monitored before and one month after SATE. The measurements above were collected on admission and before surgery in the non-SATE patients, who served as controls. We also recorded the intraoperative blood loss, operating time, required transfusion, post-transplant ascites, and complications within three months after operation in all patients., Results: SATE significantly reduced portal venous blood flow, increased hepatic arterial blood flow, normalized platelet count, and improved prealbumin and international normalized ratio in the patients before liver transplantation. Compared to the non-SATE patients, the pre-transplant SATE significantly decreased the operating time, intraoperative bleeding, post-transplant ascites and severe surgical complications., Conclusion: Pre-transplant SATE decreases portal pressure, improves liver function reserve, and reduces the surgical risk of liver transplantation effectively in patients with severe portal hypertension.

An efficient screening assay was developed and validated for simultaneous assessment of compound-mediated inhibition of six major human cytochrome P450 (CYP) enzymes. This method employed a cocktail of six probe substrates (i.e., phenacetin, amodiaquine, diclofenac, S-mephenytoin, dextromethorphan and midazolam for CYP1A2, 2C8, 2C9, 2C19, 2D6 and 3A4, respectively) as well as individual prototypical inhibitors of the six CYP enzymes in human liver microsomes under optimized incubation conditions. The corresponding marker metabolites (i.e., acetaminophen, N-desethylamodiaquine, 4-OH-diclofenac, 4-OH-S-mephenytoin, dextrorphan and 1-OH-midazolam) in the incubates were quantified using LC-MS/MS methods either by an internal standard (IS) calibration curve or a simplified analyte-to-IS peak area ratio approach. The results showed that the IC 50 values determined by the cocktail approach were in good agreement with those obtained by the individual substrate approach as well as those reported in the literature. Besides, no remarkable difference was observed between the two quantification approaches. In conclusion, this new cocktail assay can be used for reliable screening of compound-mediated CYP inhibition.

The disposition of a single oral dose of 5 mg (100 μCi) of [(14)C]axitinib was investigated in fasted healthy human subjects (N = 8). Axitinib was rapidly absorbed, with a median plasma Tmax of 2.2 hours and a geometric mean Cmax and half-life of 29.2 ng/ml and 10.6 hours, respectively. The plasma total radioactivity-time profile was similar to that of axitinib but the AUC was greater, suggesting the presence of metabolites. The major metabolites in human plasma (0-12 hours), identified as axitinib N-glucuronide (M7) and axitinib sulfoxide (M12), were pharmacologically inactive, and with axitinib comprised 50.4%, 16.2%, and 22.5% of the radioactivity, respectively. In excreta, the majority of radioactivity was recovered in most subjects by 48 hours postdose. The median radioactivity excreted in urine, feces, and total recovery was 22.7%, 37.0%, and 59.7%, respectively. The recovery from feces was variable across subjects (range, 2.5%-60.2%). The metabolites identified in urine were M5 (carboxylic acid), M12 (sulfoxide), M7 (N-glucuronide), M9 (sulfoxide/N-oxide), and M8a (methylhydroxy glucuronide), accounting for 5.7%, 3.5%, 2.6%, 1.7%, and 1.3% of the dose, respectively. The drug-related products identified in feces were unchanged axitinib, M14/15 (mono-oxidation/sulfone), M12a (epoxide), and an unidentified metabolite, comprising 12%, 5.7%, 5.1%, and 5.0% of the dose, respectively. The proposed mechanism to form M5 involved a carbon-carbon bond cleavage via M12a, followed by rearrangement to a ketone intermediate and subsequent Baeyer-Villiger rearrangement, possibly through a peroxide intermediate. In summary, the study characterized axitinib metabolites in circulation and primary elimination pathways of the drug, which were mainly oxidative in nature.

Background: The vitreous has been shown to induce epithelial-mesenchymal transdifferentiation because it induces fibroblast-like morphology, enhanced migration and invasion in retinal pigment epithelial cells in proliferative vitreoretinopathy. Rac1 is the principal mediator of cell migration. In the current study, the relationship between Rac1 and cell migration, and invasion in vitreous-transformed retinal pigment epithelial cells was investigated using NSC23766, a specific inhibitor of Rac guanosine-5'-triphosphatase activity, and the involvement of a Rac1 guanosine-5'-triphosphatase-dependent pathway was detected., Design: One-way design with multiple levels and repeated measurement design., Participants and Samples: The vitreous humor was collected from 20 healthy donor eyes and the retinal pigment epithelial cells were obtained from 9 healthy donor eyes., Methods: Human low-passage retinal pigment epithelial cells were treated with normal medium or 25% vitreous medium. Rac1 activity was measured using a pull-down assay. The cytotoxicity of NSC23766 was measured using the trypan blue dye exclusion test. Cell migration was measured using a wound healing assay. Cell invasion was determined using a transwell invasion assay. Protein expression of Rac1 and phosphorylation of LIM kinase 1 and cofilin were detected by Western blot analysis., Main Outcome Measures: Cell migration, invasion, Rac1 activity and phosphorylation of LIM kinase 1 and cofilin., Results: Rac1guanosine-5'-triphosphatase was activated in vitreous-transformed retinal pigment epithelial cells. A Rac inhibitor suppressed vitreous-induced migration and invasion in retinal pigment epithelial cells. Cofilin phosphorylation was activated by vitreous treatment but blocked by NSC23766., Conclusions: Rac1 mediates vitreous-transformed retinal pigment epithelial cells' plasticity of mesenchymal movement via Rac1 guanosine-5'-triphosphatase-dependent pathways that modulate LIM kinase 1 and cofilin activity. Rac inhibition may be considered a novel treatment for proliferative vitreoretinopathy., (© 2013 The Authors. Clinical and Experimental Ophthalmology © 2013 Royal Australian and New Zealand College of Ophthalmologists.)

The data in literature of acupuncture and moxibustion on treatment of diarrhea from pre-Qin period to Qing dynasty was collected to establish prescription database and characteristics and rules of ancient acupuncture and moxibustion for diarrhea were analyzed with data mining technology. Totally 235 papers were collected and 76 acupoints were involved with 439 times of selection. The number and times of special acupoints were 72.37% (55/76) and 76.99% (338/439), respectively, which was more seen in front-mu acupoint and back-shu acupoint. The acupoints were distributed among 11 meridians. Moxibustion was applied in 53 papers while combination of acupuncture and moxibustion was used in 1 literature. As a result, acupuncture and moxibustion for diarrhea in ancient pay much attention on acupoint in back and abdomen, in which Tianshu (ST 25), Shen-que (CV 8), Guanyuan (CV 4) and Dachangshu (BL 25) were the most frequently used. The compatibility of front-mu acupoint and back-shu acupoint was very common. Selection of special acupoint was dominant. Besides crossing points that has the most intersection of meridian qi in the back and abdomen, acupoints below the elbow and knee joints, such as five-shu points, source point, luo-connecting point, eight confluence point and lower he-sea point were also taken into account. As for compatibility of special acupoints, the supportive degree between back-shu acupoint and confluence points or front-mu acupoint was the highest; the selections of meridians mainly were Bladder Meridian, Conception Vessel and Spleen Meridian; and application of moxibustion was highly valued. In conclusion, it is feasible to apply data mining technology to the clinical literature research of ancient acupuncture and moxibustion, which can provide evidence for summary of the traditional classical theory.

Numerical simulations were carried out on micropillar cavities consisting of Si/SiO2 distributed Bragg reflectors (DBRs) with an InP spacer layer. Owing to a large refractive index contrast of ~2 in DBRs, cavities with just 4/6.5 top/bottom DBR pairs that give a low pillar height (~4.5 μm), have noticeable Purcell-enhancement effect in the 1.55-μm band. With careful designs on cavities with diameters of ~2.30 μm, a quality factor of up to 3300, a nominal Purcell factor of up to 110, and an output efficiency of ~60% are obtainable. These results ensure improvement of operation frequency and enhancement of photon indistinguishability for 1.55-μm single photon sources based on InAs/InP quantum dots.

ABSTRACT Clinical application of standards for reporting interventions in clinical trials of acupuncture (STRICTA) is introduced in this article, and improving opinions are proposed as well. STRICTA has already been extensively applied in designation of acupuncture clinical trials, composition of articles and quality assessment of acupuncture literature. According to the present version of STRICTA, it is suggested that items such as "standards and methods on acupoint selection and location", "angle and direction of needle insertion" and "whether the subjects ever have been acupunctured" should be further perfected. Individuated treat protocols which is highlighted on treatment according to differentiation of syndromes according to different opportunities and stages of diseases should be promoted so as to give better expression to the characteristics of Chinese medicine and enhance the clinical value of the relative literature.

Purpose: This study aims to analyze the clinical-pathological characteristics of multifocal and multicentric breast cancer (MMBC) in Chinese women., Methods: Sixty-seven cases with MMBC were randomly collected and reviewed at seven hospitals in representative districts of China during 1999 to 2008., Results: The incidence of MMBC in breast cancer in China was 1.75%. Compared to those with unifocal breast cancer, women with MMBC were more likely to have larger tumor size, lymph node metastasis (59.70% vs. 45.62%) and stage III to IV (46.26% vs. 21.10%). The peak age at onset of MMBC was 40 to 49 years old and has been gradually increasing during 1999 to 2008. Most of the MMBC women were treated with surgery and adjuvant therapy., Conclusion: In China, the incidence of MMBC in breast cancer is significantly lower than that in Western countries. Compared to unifocal breast cancer, MMBC is biologically more aggressive. Most MMBC women underwent mastectomy, instead of breast conservation surgery.

Objective: To observe the effect of Kupffer cells on immune tolerance in liver transplantation., Methods: The rats were randomly divided into A, B and C groups. A group was sham operation group. The donor rats of group B had intraperitoneal injection of 1 nmol Kuppffer cells every other day for three days before liver transplantation. Rats of group C were injected with equal saline. The rat liver transplantation models were established by modified Kamada's two-cuff technique. The rats were sacrificed after 24 hours. The concentrations of ALT and AST in serum were measured with the biochemical analyzer. The level of IL-2 and TNF-α in serum were measured by ELISA method. The apoptotic indexes were detected by immunohistochemical assay., Results: The concentration of ALT, AST, IL-1 and TNF-α in A, B and C groups were increased successively. The levels of group C were significantly higher than that of group B and A (P<0.05), and the levels of group B were significantly higher than that of group A (P<0.05). The apoptotic indexes of three groups were 3.40±0.37, 14.70±2.54 and 26.33±3.65, respectively, with significant difference among three groups (P<0.05)., Conclusions: Pretreatment with Kupffer cells can reduce liver injury and raise liver transplantation immune tolerance., (Copyright © 2012 Hainan Medical College. Published by Elsevier B.V. All rights reserved.)

To investigate the association between p53 codon 72 polymorphisms and gastric cancer risk, a meta-analysis published in 2007 was updated with new data. Relevant literature was retrieved by searching PubMed and statistical analysis conducted using Review Manager software. Twenty-eight case-control studies were included in this meta-analysis, with 6,859 cases and 9,277 controls. The pooled results for all included studies showed that patients with gastric cancer had a borderline lower frequency of the Arg/Arg phenotype (odds ratio (OR) = 0.91, 95 % CI = 0.83-1.00, p = 0.04). When stratified for race, the difference in Arg/Arg frequency was significant among Asians (OR = 0.87, 95 % CI = 0.78-0.97, p = 0.01). On stratifying the various studies we found that, among Asians: (i) patients with cardial gastric cancer had a significantly higher frequency of the Pro/Pro genotype (OR = 1.35, 95 % CI = 1.03-1.77, p = 0.04) than those with non-cardial gastric cancer; (ii) patients with advanced (stage III/IV) gastric cancer had a significantly higher frequency of Arg/Arg (OR = 1.30, 95 % CI = 1.06-1.61, p = 0.01) than those with early (stage I/II) cancer; and (iii) patients with metastasis had a significantly higher frequency of Pro/Pro (OR = 3.31, 95 % CI = 1.31-8.41) than those without metastasis. Our study suggests that, among Asians, the p53 codon 72 Arg/Arg genotype is associated with a modestly decreased risk of gastric cancer, and that this difference in genotype distribution may be associated with cancer stage, location, differentiation and metastasis.

Sunitinib is an oral multitargeted tyrosine kinase inhibitor approved for the treatment of advanced renal cell carcinoma, imatinib-refractory gastrointestinal stromal tumor, and advanced pancreatic neuroendocrine tumors. The current studies were conducted to characterize the pharmacokinetics, distribution, and metabolism of sunitinib after intravenous and/or oral administrations of [(14)C]sunitinib in rats (5 mg/kg i.v., 15 mg/kg p.o.), monkeys (6 mg/kg p.o.), and humans (50 mg p.o.). After oral administration, plasma concentration of sunitinib and total radioactivity peaked from 3 to 8 h. Plasma terminal elimination half-lives of sunitinib were 8 h in rats, 17 h in monkeys, and 51 h in humans. The majority of radioactivity was excreted to the feces with a smaller fraction of radioactivity excreted to urine in all three species. The bioavailability in female rats was close to 100%, suggesting complete absorption of sunitinib. Whole-body autoradioluminography suggested radioactivity was distributed throughout rat tissues, with the majority of radioactivity cleared within 72 h. Radioactivity was eliminated more slowly from pigmented tissues. Sunitinib was extensively metabolized in all species. Many metabolites were detected both in urine and fecal extracts. The main metabolic pathways were N-de-ethylation and hydroxylation of indolylidene/dimethylpyrrole. N-Oxidation/hydroxylation/desaturation/deamination of N,N'-diethylamine and oxidative defluorination were the minor metabolic pathways. Des-ethyl metabolite M1 was the major circulating metabolite in all three species.

Objective: To investigate the role of Thl7 cells and the cytokine interleukin-17 (IL-17) in acute allograft rejection in mice., Methods: Mouse models of kidney transplantation were randomly divided into rejection group and isograft group. On the post-operative day (POD) 3 and 7, we tested the serum IL-17 level using enzyme-linked immunosorbent assay and measured the number of Th17 cells in the renal grafts by flow cytometry. The grafts were harvested and fixed in 10% formalin to prepare paraffin sections for routine pathological inspection., Results: Compared to isograft group, the allograft group showed a significantly higher level of serum IL-17 on POD3 and POD7 (P<0.05), and the level of IL-17 is significantly higher on POD7 than on POD3 (P<0.05). The allograft group showed more infiltrating Th17 cells in the grafts on POD3 and POD7 (P<0.05), and the cell number was significantly greater on POD7 (P<0.05). Pathological examination also showed an increased severity of graft rejection with the post-transplantation time., Conclusion: Thl7 cells may play an important role in the development of renal graft rejection. IL-17 may serve as a potential specific indicator for predicting allograft rejection.

Objective: To investigate glycometabolism of patients with depression at first episode., Methods: Oral glucose tolerance test (OGTT) was performed in 100 patients with depression at first episode and 50 healthy subjects; the levels of fast blood plasma insulin were also measured., Result: There were no statistically significant differences in fast blood plasma insulin levels and postprandial blood glucose levels at 0 h, 1 h and 3 h (P>0.05); the fasting blood glucose (FBS), postprandial blood glucose levels in 2 h and area under OGTT curve of depression patients were significantly higher than those of healthy controls. The frequency of impaired glucose tolerance (IGT) in depression patients was higher than that in controls (P<0.05)., Conclusion: Depression patients at the first episode are abnormal in glycometabolism, which may have clinical implication.

Background: Interleukin 10 (IL-10), a Th2 type cytokine, modulates inflammatory responses by inhibiting the production of proinflammatory cytokines. This study was designed to investigate the protective effects of adenovirus-mediated human IL-10 (Ad-hIL-10) gene transfer on protecting grafts from cold ischemia-reperfusion injury following orthotopic liver transplantation in rats., Methods: Adenoviruses encoding hIL-10 or beta-galactosidase (Ad-lacZ) were injected via the superior mesenteric vein into prospective donor animals. The donor liver was harvested 48 hours after transduction, and stored for 12 hours at 4 degree centigrade in lactated Ringer's solution prior to transplantation. The rats were divided into saline, Ad-lacZ, and Ad-hIL-10 groups. Liver function test, histopathological examination, reverse transcriptase-polymerase chain reaction (RT-PCR), and Western blotting were performed at 24 hours after transplantation in the three groups., Results: Liver function (ALT and AST) was significantly improved, and the Suzuki score was significantly decreased in the Ad-hIL-10 group. The levels of hepatic TNF-alpha, MIP-2, ICAM-1 mRNA, and NF-kappaB protein in the Ad-hIL-10 group were significantly decreased. The expression of hIL-10 mRNA was detected by RT-PCR in Ad-hIL-10-treated grafts but not in controls treated with saline or Ad-lacZ., Conclusions: Donor pretreatment with Ad-hIL-10 down-regulates the expression of proinflammatory cytokines TNF-alpha, MIP-2, and ICAM-1 mRNA. hIL-10 protects against hepatic cold ischemia-reperfusion injury, at least in part, by suppressing NF-kappaB activation and subsequent expression of proinflammatory mediators.