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To investigate the regulatory role of the cyp19a1b aromatase gene in the sexual differentiation of largemouth bass (Micropterus salmoides, LMB), we obtained the full-length cDNA sequence of cyp19a1b using rapid amplification of cDNA ends technique. Tissue expression characteristics and feedback with 17-β-estradiol (E2) were determined using quantitative real-time PCR (qRT-PCR), while gonad development was assessed through histological section observations. The cDNA sequence of LMB cyp19a1b was found to be1950 base pairs (bp) in length, including a 5′ untranslated region of 145 bp, a 3′ untranslated region of 278 bp, and an open reading frame encoding a protein consisting of 1527 bp that encoded 508 amino acids. The qRT-PCR results indicated that cyp19a1b abundantly expressed in the brain, followed by the gonads, and its expression in the ovaries was significantly higher than that observed in the testes (P < 0.05). After feeding fish with E2 for 30 days, the expression of cyp19a1b in the pseudo-female gonads (XY-F) was significantly higher than that in males (XY-M) (P < 0.05), whereas expression did not differ significantly between XX-F and XY-F fish (P > 0.05). Although the expression of cyp19a1b in XY-F and XX-F fish was not significantly different after 60 days (P>0.05), both exhibited significantly higher levels than that of XY-M fish (P<0.05). Histological sections analysis showed the presence of oogonia in both XY-F and XX-F fish at 30 days, while spermatogonia were observed in XY-M fish. At 60 days, primary oocytes were abundantly observed in both XY-F and XX-F fish, while a few spermatogonia were visible in XY-M fish. At 90 days, the histological sections' results showed that a large number of oocytes were visible in XY-F and XX-F fish. Additionally, the gonads of XY-M fish contained numerous spermatocytes. These results suggest that cyp19a1b plays a pivotal role in the development of ovaries and nervous system development in LMB. [ABSTRACT FROM AUTHOR]

Objectives: Neurocytomas (NCs) are rare intracranial tumors that can often be surgically resected. However, disease course is unpredictable in many patients and medical therapies are lacking. We have used whole exome sequencing to explore the molecular etiology for neurocytoma and assist in target identification to develop novel therapeutic interventions. Methods: We used whole exome sequencing (WES) to compare the molecular landscape of 21 primary & recurrent NCs to five normal cerebellar control samples. WES data was analyzed using the Qiagen Clinical Insight program, variants of interest (VOI) were interrogated using ConSurf, ScoreCons, & Ingenuity Pathway Analysis Software to predict their potential functional effects, and Copy number variations (CNVs) in the genes of interest were analyzed by Genewiz (Azenta Life Sciences). Results: Of 40 VOI involving thirty-six genes, 7 were pathogenic, 17 likely-pathogenic, and 16 of uncertain-significance. Of seven pathogenic NC associated variants, Glucosylceramidase beta 1 [GBA1 c.703T > C (p.S235P)] was mutated in 5/21 (24%), Coagulation factor VIII [F8 c.3637dupA (p.I1213fs*28)] in 4/21 (19%), Phenylalanine hydroxylase [PAH c.975C > A (p.Y325*)] in 3/21 (14%), and Fanconi anemia complementation group C [FANCC c.1162G > T (p.G388*)], Chromodomain helicase DNA binding protein 7 [CHD7 c.2839C > T (p.R947*)], Myosin VIIA [MYO7A c.940G > T (p.E314*)] and Dynein axonemal heavy chain 11 [DNAH11 c.3544C > T (p.R1182*)] in 2/21 (9.5%) NCs respectively. CNVs were noted in 85% of these latter 7 genes. Interestingly, a Carboxy-terminal domain RNA polymerase II polypeptide A small phosphatase 2 [CTDSP2 c.472G > A (p.E158K)] of uncertain significance was also found in > 70% of NC cases. Interpretation: The variants of interest we identified in the NCs regulate a variety of neurological processes including cilia motility, cell metabolism, immune responses, and DNA damage repair and provide novel insights into the molecular pathogenesis of these extremely rare tumors. [ABSTRACT FROM AUTHOR]

The building quality of the LPBF (laser powder bed fusion)-fabricated component is critical to determine whether it can be applied in the serving condition. However, it is determined not only by process parameters; the powder property and its affecting factors such as average particle sizes and particle size distribution of powder materials have also significant effect on the building quality. In order to investigate the correlation between the building quality and powder properties, five kinds of powder materials with different average particle sizes and particle size distributions of P μ 20 , σ 10 , P μ 35 , σ 10 , P μ 50 , σ 10 , P μ 35 , σ 5 , and P μ 35 , σ 15 are prepared on the basis of the Horsfield filling method. The powder properties such as flowability and apparent density are tested, the build qualities such as dimensional accuracy and surface roughness are measured, and their correlation is analyzed. The results show that the powder material with a narrower particle size distribution benefits flowability. That with medium particle size distribution and average particle size, such as P μ 35 , σ 10 , possesses the highest apparent density and acceptable flowability, and the components manufactured with such powder material have the best surface roughness and dimensional accuracy. Besides, an amount of fine particles is required to optimize component density. The above systematic experiments exhibit the correlation among the particle size distribution and the average particle size, powder properties, and build quality, which is beneficial to preparing the powder materials, improving the irradiation conditions of the laser beam, controlling the LPBF process, and further the building quality of LPBF-fabricated component. [ABSTRACT FROM AUTHOR]

Vagus nerve stimulation (VNS) is a promising neuromodulation technique, which has been demonstrated to promote functional recovery after spinal cord injury (SCI) in our previous study. But the underlying mechanism remains to be explored. Using a compressed SCI model, our present study first demonstrated that activated microglia produce abundant tumor necrosis factor-α (TNF-α) to induce endothelial necroptosis via receptor-interacting protein kinase 1 (RIP1)/RIP3/mixed lineage kinase domain-like protein (MLKL) pathway, thus destroying the blood-spinal cord barrier (BSCB) after SCI. While both TNF-α specifical antibody (infliximab) and necroptosis inhibitor (necrostatin-1) alleviate BSCB disruption. Then our study found that VNS significantly inhibits microglia-derived TNF-α production and reduces expression of p-RIP3 and p-MLKL in endothelial cells. As expected, further results indicated that VNS mitigates the BSCB disruption, thus reducing inflammatory cells infiltration and neural damage. Finally, both electrophysiological evaluation and locomotor test demonstrated that VNS promotes motor function recovery after SCI. In conclusion, our data demonstrated VNS restricts microglia-derived TNF-α to prevent RIP1/RIP3/MLKL mediated endothelial necroptosis, thus alleviating the decisive pathophysiological BSCB disruption to reduce neuroinflammation and neural damage, which ultimately promotes motor function recovery after SCI. Therefore, these results further elaborate that VNS might be a promising therapeutic strategy for SCI. Vagus nerve stimulation prevents microglia-derived TNF-α induced endothelial necroptosis to alleviate blood-spinal cord barrier disruption after spinal cord injury. [ABSTRACT FROM AUTHOR]

The majority of corticotroph adenomas are benign but some are locally invasive, demonstrate high rates of recurrence, and exhibit a relatively poor response to often repeated surgical, medical, and radiation treatment. Herein, we summarize the currently known somatic and genetic mutations and other molecular factors that influence the pathogenesis of these tumors and discuss currently available therapies. Although recent molecular studies have advanced our understanding of the pathogenesis and behavior of these refractory corticotroph adenomas, these insights do not reliably guide treatment choices at present. Development of additional diagnostic tools and novel tumor-directed therapies that offer efficacious treatment choices for patients with refractory corticotroph adenomas are needed. [ABSTRACT FROM AUTHOR]

To explore the influence of cation doping with cation radius variation on LiNi0.8Co0.1Mn0.1O2, a series of layered Li0.99M0.01Ni0.8Co0.1Mn0.1O2 (M-NCM, M=Ca, Sr, Ba) cathode materials were synthesized. Through density functional theory (DFT) calculations, all doped models have low band gaps and more relative electrons near the Fermi energy level than the pristine model. With increasing cation radius, the improvement in electronic conductivity diminishes. X-ray diffraction data and structural refinement results show that lattice parameters and lithium layer increase with increasing doping cation radius. The Ba-NCM sample, which has the largest radius, has the highest initial capacity (246.6 mAh·g−1) at 0.1 C. The Ca-NCM sample, with the least doping cation radius, has the highest capacity retention, which reaches to 90.06% after 100 cycles at 1 C. The Sr-NCM sample exhibits the highest remaining capacity, which could retain 146.5 mAh·g−1 at 5 C and 158.7 mAh·g−1 after 100 cycles at 1 C. This is attributed to the highest Li+ diffusion coefficient (8.49 × 10−11 cm2·s−1) and moderate electronic conductivity and radius of Sr2+. Doping Li sites in LiNi0.8Co0.1Mn0.1O2 with divalent cations of proper radius could be effectively improved the comprehensive electrochemical performance. This effect is based on not only the pillar effect and high electronic conductivity but also the trade-off between the expansion of lithium layer thickness and introduction of steric hindrance, as a consequence of the cations doping. [ABSTRACT FROM AUTHOR]

Na3–2xMgxV2(PO4)3/C (0 ≤ x ≤ 0.2) were synthesized by a sol–gel method. According to X-ray diffraction (XRD) Rietveld refinement and energy dispersive spectroscopy (EDS) mapping results, Mg ions were approved to occupy the Na2 (18e) site in Na3–2xMgxV2(PO4)3/C for the first time. The amount of Mg substitution in Na3–2xMgxV2(PO4)3/C was optimized. The specific discharge capacities of Na2.9Mg0.05V2(PO4)3/C at 10 C, 20 C, and 30 C were 98.9%, 91.5%, and 76.2% of the value obtained at 1 C, respectively. Na2.9Mg0.05V2(PO4)3/C exhibited the highest capacity retention of 80.3% with a discharge capacity of 77.3 mAh·g−1 after 1200 cycles at 10 C. Na2.9Mg0.05V2(PO4)3/C exhibited superior rate performance, resulting from a high sodium diffusion coefficient (DNa) of 3.91 × 10–12 cm2·s−1 and the excellent electrical conductivity (5.7 × 10–2 s·cm−1). Combining the X-ray photoelectron spectroscopy (XPS) and Electrochemical impedance spectroscopy (EIS) results, the mechanism of Mg substitution was investigated. Since two Na+ were replaced by one Mg2+, V Na ′ was produced to maintain valence equilibrium. This phenomenon benefited Na+ migration by broadening the diffusion channel in the structure of Na3V2(PO4)3. According to the EPR results, the signal intensity of Na2.9Mg0.05V2(PO4)3/C was much stronger than that of Na3V2(PO4)2/C, thus confirming the existence of V Na ′ after Mg substitution. When the amount of Mg substitution was further increased to 0.1, the DNa decreased because of the small radius of Mg2+, which led to severe lattice distortion and volumetric shrinkage of the unit cell. [ABSTRACT FROM AUTHOR]

Aluminum-modified Li1.4Mn0.61Ni0.18Co0.18Al0.03O2.4 (LNCMA) and fluorine-modified LiNi0.5Mn1.5O3.9F0.1 (LNMOF) cathode materials were successfully synthesized via a solid-state reaction procedure. The discharge capacity of the LNCMA increased from 175.3 to 192.2 mAh g−1, showing approximately a 9.6% improvement after 50 cycles due to Al doping. For the LNMOF cathode, the discharge capacity increased from 116.9 to 174.9 mAh g−1 after F doping, corresponding to an increase of 49.6% after 50 cycles. The new composite cathode was formed by mixing the two cathode materials at a weight ratio of 1:1, which was selected based on the charge–discharge profiles during the first cycle. When the cells were tested in a voltage range of 2.0–4.85 V, the composite material exhibited initial specific capacities of 229.2 and 215.4 mAh g−1, a coulombic efficiency of 94.0% during the first cycle, and a capacity retention of 94.5% after 50 cycles at 0.2C. The concept of inserting irreversible Li ions from the Li-rich material into the 16c vacancy of the LNMOF was validated. The improved capacity was due to the plateau in the discharge capacity curves due to the Mn3+ → Mn2+ reduction. The charge–discharge capacities of the composite material were higher than those in the literature, as was the coulombic efficiency. The new composite material inherited a high-voltage plateau from the LNMOF and a high specific capacity from the LNCMA, and this material has great potential for future applications. [ABSTRACT FROM AUTHOR]

Boron-modified Li(Ni0.8Co0.1Mn0.1)1−xBxO2 cathode materials(NCM811) were successfully prepared by a nano-milling assisted solid-state approach. X-ray diffraction investigations showed that the materials are solid solutions with a layered structure. SEM observations implied that the doped B ions promoted the growth of the target crystal with well-developed facets since it will form liquid phase at lower temperature. The intensity ratio of I(003)/I(104) raised with the increase in Boron doping concentration, until a maximum value of 1.453 was observed at x = 0.01. Further Rietveld refinements revealed that boron ions occupy the crystal lattice in the transition metal slab which helps to promote the lattice ordering by decreasing the Li/Ni ionic mixing. Such B promoted NCM811 cathode materials were confirmed to have an improved diffusion coefficient with a reduced interfacial resistance by subsequent CV and EIS measurements. From the electrochemical test, those B modified NCM811 cathode materials presented enhanced electrochemical performance. Among the synthesized samples, Li(Ni0.8Co0.1Mn0.1)0.99B0.01O2 exhibited the best specific capacity, with 194.7 mAh g−1 and 166.8 mAh g−1 at 0.1C and 5C respectively. The capacity retention at 0.5C was also confirmed as 98.2% after 100 cycles. Such improvement can be explained by the reduced Li/Ni ionic mixing, the increased Li ionic diffusion and the reduced interfacial resistance caused by the promoted growth of the B doped NCM811 crystals. Compared to those NCM811 materials reported elsewhere, the material obtained by this approach showed high potential for future application. [ABSTRACT FROM AUTHOR]

A cost effective and eco-friendly approach for the preparation of LiFePO4/C cathode material is proposed in this paper. High-purity natural mineral magnetite (Fe3O4 ≥ 99%) was employed as the only ferric source in the synthesis routine. By ultrafine ball milling and subsequent oxidation, the magnetite was converted into FePO4·2H2O. After dehydration, the iron phosphate reacted with Li2CO3 and sucrose to form the target LiFePO4/C composite. Mössbauer result revealed that all the Fe cations exhibited + 2 valence state in the LiFePO4 lattice although redox process of the species occurred during the synthesis. SEM observations indicated that the pure phase LiFePO4 powders with round shape were constructed by fine primary grains with size of 100–200 nm. Such micro-nano structure offered an increased Li diffusion by increasing the surface area and reducing the migration pathway. LiFePO4/C composite synthesized by this magnetite approach exhibited excellent performance with a specific capacity of 161.1 mAh g−1 at 0.1 C and a capacity retention rate of 98.8% after 100 cycles at 1 C. The new approach we proposed presents the remarkable advantages of low cost and environmental friendliness, and therefore suggest significant potential in mass production. [ABSTRACT FROM AUTHOR]

In this work, we report the preparation and the enhanced electrochemical performance of P2-type Na0.67Lix(Mn0.5Fe0.25Co0.25)1−xO2 layered cathode materials with different Li substitutions via a nanomilling-assisted solid-state method. The experimental results show that the introduced lithium ions can greatly improve the performance of the material after entering the transition metal layer. Among these synthesized samples, the Na0.67Li0.03(Mn0.5Fe0.25Co0.25)0.97O2 electrode exhibits an exceptionally high specific capacity of 190.6 mAh g−1 at 0.1 C rate and a capacity retention of 89.5% after 30 cycles. Obviously, the specific capacity retention is improved by 15.3% compared with the pristine Na0.67(Mn0.5Fe0.25Co0.25)O2 without Li incorporation (the specific capacity retention is only 74.2% after 30 cycles). Simultaneously, the sample also shows a large increase in rate performance compared to the pristine material. All of the enhancement can be explained by the fact that the introduced Li ions suppress the phase transition during the charge-discharge process and avoid the volume expansion of the electrode, which significantly reduce the occurrence of micro-cracks within the electrode. The reduced polarization, the decreased internal resistance of the prepared electrodes and the increased sodium ion diffusion coefficient, as confirmed from the CV and EIS measurements, can be regarded as the three major reasons for the enhanced electrochemical performance of the Li ion-substituted materials. [ABSTRACT FROM AUTHOR]

Rubidium modified Ni-rich LiNi0.8Co0.15Al0.05O2 cathode materials were successfully synthesized through a nano-milling assisted solid-state method. Rietveld refinement revealed that the Rb ions were incorporated into the lattice by replacing the original Li ions. It resulted in the enlarging of Li layer spacing together with the reducing of the thickness of the transition metal slab. Such changes in crystal structure led to the increase in the diffusion coefficient of Li ions in the lattice (DLi). Calculated diffusion coefficient presented the highest Li-ion diffusion coefficient of 1.54 × 10−10 cm2 s−1 for the sample Rb0.01Li0.99Ni0.8Co0.15Al0.05O2. It was also in good accordance with the changes in Li slab thickness. Improved electrochemical performance in specific capacity, capacity retention and rate performance were observed. Among the samples synthesized, the Rb0.01Li0.99Ni0.8Co0.15Al0.05O2 sample exhibited the highest initial discharge capacity and the best rate performance. It delivered specific discharge capacities of 190.5, 177, 169, 161 and 151 mAh g−1 at 0.1C, 0.2C, 0.5C, 1C and 5C, respectively. It also showed the best cycle stability with capacity retention of 91.31% after 100 cycles at 2C. [ABSTRACT FROM AUTHOR]

High specific energy olivine LiMn1-xFexPO4/C (0 ≤ x ≤ 0.5) nanoparticles have been synthesized in 20 min at extremely low temperature 160 °C by microwave-solvothermal method. The obtained cathode materials are orthorhombic solid solutions with size of 30–100 nm. Electrochemical test shows that Fe substitution could significantly increase the initial specific capacity and specific energy, as well as cycling performance and rate capability. LiMn0.8Fe0.2PO4/C exhibits the best reversible specific discharge capacity of 165.9 mA h g−1 and specific discharge energy of 643.1 W h kg−1 at 0.1 C. Its discharge capacity remains 95.7% of its initial value of 129.0 mA h g−1 after 50 cycles at 0.5 C. According to the electrochemical impedance spectroscopic analysis, the performance improvement is mainly attributed to the enhancement of Li+ diffusion coefficient (DLi) by Fe substitution. DLi is 4.43 × 10−14 and 1.34 × 10−12 cm2 s−1 for LiMnPO4/C and LiMn0.5Fe0.5PO4/C, respectively. [ABSTRACT FROM AUTHOR]

With the continuous progress of medical technology, intelligent medical diagnosis systems have become an important direction for the development of medical technology. In terms of cerebral vascular examination, magnetic resonance cerebrovascular imaging has become one of the conventional examination methods. It can be used to evaluate cerebrovascular diseases, such as aneurysms, cerebral vascular stenosis, cerebral vascular malformations, etc. The purpose of this article is to study the application value of intelligent medical systems combined with magnetic resonance cerebrovascular imaging technology in the diagnosis of intracranial aneurysms. The researchers selected 50 patients for the experiment. Among them, the experimental group patients used intelligent medical systems for auxiliary diagnosis, while the control group patients used conventional diagnostic methods. By using magnetic resonance cerebrovascular imaging to diagnose patients, researchers compared the diagnostic results of two groups of patients to evaluate the application effect of intelligent medical systems in the diagnosis of intracranial aneurysms. After the experiment, the vascular visualization score of the experimental group was 3.645 ± 0.489, while the score of the control group was 3.598 ± 0.558 (P < 0.05). After the experiment, the saturation artifact score of the experimental group was 3.933 ± 0.249, while the score of the control group was 2.805 ± 0.539 (P < 0.05), indicating that the scanning sequence score of the experimental group was better than that of the control group. The intelligent medical system has optimized the magnetic resonance imaging module to better extract user symptoms and apply it to medical diagnosis. [ABSTRACT FROM AUTHOR]

This paper reports the comparison of photoluminescence and afterglow behavior of Dy in CaSnO and CaSnO phosphors. The samples containing CaSnO and CaSnO were prepared via solid-state reaction. The properties have been characterized and analyzed by utilizing X-ray diffraction (XRD), photoluminescence spectroscope (PLS), X-ray photoelectron spectroscopy (XPS), afterglow spectroscopy (AS) and thermal luminescence spectroscope (TLS). The emission spectra revealed that CaSnO:Dy and CaSnO:Dy phosphors showed different photoluminescence. The CaSnO:Dy phosphor showed a typical F to H energy transition of Dy ions, with three significant emissions centering around 482, 572 and 670 nm. However, the CaSnO:Dy phosphor revealed a broad T → S transitions of Sn ions. The XPS demonstrate the existence of Sn ions in CaSnO phosphor caused by the doping of Dy ions. Both the CaSnO:Dy and CaSnO:Dy phosphors showed a typical triple-exponential afterglow when the UV source switched off. Thermal simulated luminescence study indicated that the persistent afterglow of CaSnO:Dy and CaSnO:Dy phosphors was generated by the suitable electron or hole traps which were resulted from the doping the calcium stannate host with rare-earth ions (Dy). [ABSTRACT FROM AUTHOR]

It is of great importance to thoroughly explore the evolving temperature fields of direct laser metal deposition (abbreviated as LMD) in vertical thin wall manufacturing. It is helpful to control the temperature gradient, and even to adjust to forming microstructures and accumulation of residual stress. In this paper, a comprehensive three-dimensional transient model is developed for evolving temperature fields. The manufactured material is DS superalloy Rene80. The laser-powder interaction during the powder flowing process is simulated first, and its possible effect on the temperature field of the melting pool is analyzed. Then a 3D numerical simulation for the evolving temperature field is carried out based on considering transport phenomena during LMD such as the change in phase, powder injection and liquid flow. The applied deposition parameters are derived from experimental investigation with optimized vertical wall manufacturing. The simulated results explain why a balance between heat input and dissipation could form inside the vertical thin wall. These reconstruct the instability at an early phase of the building process without any temperature control unit and exhibit the influence of parameters such as laser power, deposition velocity and laser beam deposition pattern. The simulation results of temperature evolution are consistent with experimental investigation. [ABSTRACT FROM AUTHOR]

Renilla luciferase reporter is a widely used internal control in dual luciferase reporter assay system, where its transcription is driven by a constitutively active promoter. However, the authenticity of the Renilla luciferase response in some experimental settings has recently been questioned. Testicular receptor 4 (TR4, also known as NR2C2) belongs to the subfamily 2 of nuclear receptors. TR4 binds to a direct repeat regulatory element in the promoter of a variety of target genes and plays a key role in tumorigenesis, lipoprotein regulation, and central nervous system development. In our experimental system using murine pituitary corticotroph tumor AtT20 cells to investigate TR4 actions on POMC transcription, we found that overexpression of TR4 resulted in reduced Renilla luciferase expression whereas knockdown TR4 increased Renilla luciferase expression. The TR4 inhibitory effect was mediated by the TR4 DNA-binding domain and behaved similarly to the GR and its agonist, Dexamethasone. We further demonstrated that the chimeric intron, commonly present in various Renilla plasmid backbones such as pRL-Null, pRL-SV40, and pRL-TK, was responsible for TR4's inhibitory effect. The results suggest that an intron-free Renilla luciferase reporter may provide a satisfactory internal control for TR4 at certain dose range. Our findings advocate caution on the use of Renilla luciferase as an internal control in TR4-directed studies to avoid misleading data interpretation. [ABSTRACT FROM AUTHOR]

A comparison of electrochemical performance between LiFeMnCrPO/C and LiMnPO/C cathode materials was conducted in this paper. The cathode samples were synthesized by a nano-milling-assisted solid-state process using caramel as carbon sources. The prepared samples were investigated by XRD, SEM, TEM, energy-dispersive X-ray spectroscopy (EDAX), powder conductivity test (PCT), carbon-sulfur analysis, electrochemical impedance spectroscopy (EIS), and galvanostatic charge-discharge cycling. The results showed that LiFeMnCrPO/C exhibited high specific capacity and high energy density. The initial discharge capacity of LiFeMnCrPO/C was 163.6 mAh g at 0.1C (1C = 160 mA g), compared to 112.3 mAh g for LiMnPO/C. Moreover, the Fe/Cr-substituted sample showed good cycle stability and rate performance. The capacity retention of LiFeMnCrPO/C was 98.84 % over 100 charge-discharge cycles, while it was only 86.64 % for the pristine LiMnPO/C. These results indicated that Fe/Cr substitution enhanced the electronic conductivity for the prepared sample and facilitated the Li diffusion in the structure. Furthermore, LiFeMnCrPO/C composite presented high energy density (606 Wh kg) and high power density (574 W kg), thus suggested great potential application in lithium ion batteries (LIBs). [ABSTRACT FROM AUTHOR]

Hypoxia-inducible factor-1α (HIF-1α) has been reported to regulate over 100 gene expressions in response to hypoxia and other stress conditions. In the present study, we found that arsenite could induce HIF-1α protein accumulation in both mouse epidermal Cl41 cells and mouse embryonic fibroblasts (MEFs). Knockout of p85α, a regulatory subunit of PI-3K, in MEFs (p85α) dramatically decreased the arsenite-induced HIF-1α accumulation, indicating that p85α is crucial for arsenite effects on the stabilization of HIF-1α protein. Our further studies suggest that arsenite could induce inducible Hsp70 expression, and transfection of inducible Hsp70 into p85α MEFs could restore HIF-1α protein accumulation. Moreover, the results using EMSA and Supershift assays indicate that p85α is crucial for arsenite-induced activation of the heat-shock transcription factor 1 (HSF-1), which is responsible for transcription of inducible Hsp70. Taken together, p85α-mediated HIF-1α stabilization upon arsenite exposure is specifically through HSF-1 activation and subsequent up-regulation of the inducible Hsp70 expression. [ABSTRACT FROM AUTHOR]