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Binding activity of steroidogenic factor-1 (SF-1) to promoters of the majority of steroidogenic genes in response to gonadotropins is a critical mechanism that regulates steroidogenesis in gonads. Thus, the modulation of SF-1 action may be essential for the differential regulation of formation of sex steroids in the ovary. Aromatase P450 (P450arom) is the rate-limiting enzyme for estrogen formation. In this study, we characterize another nuclear receptor half site in the gonadal aromatase promoter which we show to be important for aromatase regulation. We also show herein that the stimulation of P450arom promoter activity by SF-1 in ovarian granulosa, testicular Sertoli and JEG-3 choriocarcinoma cells is inhibited by two transcription factors, Wilms’ tumor suppressor gene (WT1) and dosage sensitive sex reversal adrenal hypoplasia congenita critical region on the X chromosome gene 1 (DAX-1). Given the characterized roles of these transcription factors in gonadal development and function, modulation of SF-1 action by WT1 and DAX-1 may represent an important key mechanism in steroidogenesis. [Copyright &y& Elsevier]

Estrogen is produced in a number of human tissues including the ovary, placenta and extraglandular sites such as adipose tissue, skin and the brain. Aromatase is the key enzyme that regulates estrogen formation in these tissues. Aromatase activity is not detectable in normal endometrium. In contrast, aromatase is expressed aberrantly in endometriosis and is stimulated by PGE2. This results in local production of estrogen, which induces PGE2 formation and establishes a positive feedback cycle. Another abnormality in endometriosis, i.e. deficient 17β-hydroxysteroid dehydrogenase (17β-HSD) type 2 expression, impairs the inactivation of estradiol to estrone. These molecular aberrations collectively favor accumulation of increasing quantities of estradiol and PGE2 in endometriosis. The clinical relevance of these findings was exemplified by the successful treatment of an unusually aggressive case of postmenopausal endometriosis using an aromatase inhibitor. [Copyright &y& Elsevier]

[Display omitted] • Spinel outer layer containing Ni3+ is successfully prepared via artificial surface reconstruction. • The spinel outer layer substantially promotes the lithium ion diffusion coefficient. • The reversible capacity of the modified samples reaches up to 193.1 mAh g−1 after 200 cycles at 1 C. • Surface side reaction of the cathode particle is remarkable suppressed. To achieve cathode materials with satisfactory electrochemical performances, the in-situ artificial reconstruction of spinel shell on Li-rich layer cathode is explored via surface pretreatment strategy. A series of physical characterizations prove that the in-situ evolution of the spinel outer layer containing a certain amount of Ni3+ guarantees the evenly distribution and closely connection with the layered matrix. When the amount of surface pretreatment agent ammonium persulfate reaches 2%, the cathode material exhibits remarkable electrochemical performances with a discharge capacity of 280.2 mAh g−1 at 0.1 C, discharge capacity of 141.9 mAh g−1 at 5 C, and capacity retention of 90.1% after 200 cycles at 1 C. The further exploration reveals that the enhanced electrochemical performance is attributed to the accelerated of Li+ diffusion (D Li+ =6.06 × 10−15 cm2 s−1) and reduced the internal impedance of the battery. In addition, the spinel outer layer can prevent the active material from contacting the electrolyte, inhibit the formation of an inert layer, and alleviate the spinel structure penetration into the interior. The robust modification strategy is believed to be an effective approach for promoting the discharge capacity, rate performance, and cycle stability of the cathode material and retarding the voltage decay. [ABSTRACT FROM AUTHOR]

The produced inactive interface during the cycle and poor rate performance are the inevitable obstacles for the practicability of lithium-rich layered cathode. Here, we report that in-situ surface pretreatment technique with hydrazine hydrate can reconstruct epitaxial spinel possessing the rapid lithium ions diffusion path, which primarily includes the leaching of Li+/Ni2+ and redistribution of the metal ions. We confirm the generation of epitaxial spinel heterostructure on the layered matrix by kinds of characterization methods such as transmission electron microscopy and Raman spectroscopy. As a result, the epitaxial spinel substantially promotes the lithium ion diffusion coefficient from 1.98 × 10−11 cm2 s−1 to 3.76 × 10−11 cm2 s−1. Even under a discharge current 5 C, the reversible capacity still reaches up to 171.1 mAh g−1. After 200 cycles at 1 C, the modified cathode delivers a capacity retention of 84.2% with the discharge capacity of 197.8 mAh g−1. The presence of the epitaxial spinel layer exerts a positive effect on the stability of the cathode structure and suppression of side reactions at the interface via exploring the morphology and composition of the cycled cathodes. The in-situ surface reconstruction technology to generate spinel is appealing for promise prospect application of lithium-rich layered cathodes in the future. [Display omitted] • Nickel-poor spinel epitaxial layer is prepared via in-situ surface reconstruction. • The modified cathode delivers a discharge capacity of 302.1 mAh g−1 at 0.1 C. • The epitaxial spinel substantially promotes the lithium ion diffusion coefficient. • The reversible capacity of the modified samples reaches up to 171.1 mAh g−1 at 5 C. • Surface side reactions and cracking of the cathode particle is remarkable suppressed. [ABSTRACT FROM AUTHOR]

Carbon fiber reinforced composites (CFRC) are in huge demand in aviation industry for reducing the fuel consumption, despite the unfavorable electromagnetic interference (EMI) shielding property. In this work, carbon fiber fabrics (CF) were coated by a thin layer of nickel (Ni) using electroless plating to increase the electrical conductivity of the composites. Dopamine was then self-polymerized on Ni coated CF (CF-Ni) surfaces to enhance the interfacial interactions between fibers and epoxy matrix. The results showed that the introduction of 0.39 wt% of polydopamine (PDA) content leads to a significant increase of interlaminar shear strength (ILSS), tensile strength and modulus by 70.7%, 22.7% and 15.3%, respectively, compared with CF-Ni/epoxy composites with free of PDA. The dominant facture mechanisms changed from fiber pulling-out and/or debonding to fiber breakage after the introduction of PDA. Compared with CF/epoxy composites, the EMI shielding effectiveness (SE) of CF-Ni/epoxy composites increased by 77.2% and slightly decreased with the increase of the PDA content. In order to further optimize the overall performances of the composites, the laminates structures were specially designed by replacing 2 plies of CF-Ni-PDA with CF-PDA in the middle according to EMI shielding mechanisms. The composites with special laminate stacking exhibited outstanding ILSS (61.2 MPa) and EMI SE (31.0 dB), which are dominant over most reported structural composites. The effects of humidity on the mechanical and EMI shielding properties were evaluated as well, indicating that the composites played a huge application potential in aircraft. [Display omitted] [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor T (CAR T) cell immunotherapy has shown remarkable efficacy in non-Hodgkin's lymphoma (NHL) patients. Minimal residual disease (MRD) monitoring in NHL is essential after CAR T cell therapy, which can be achieved by monitoring circulating tumor DNA (ctDNA). The mutation of TP53 in NHL has been suggested to be associated with a poor prognosis. However, whether TP53-mutated ctDNA can be used as a biomarker remains undetermined. In this study, a total of 40 patients with mutated TP53 who received CAR T cell treatment were analyzed, and specific probes targeting 29 different TP53 mutation sites in the 40 patients were designed and verified. Then, the presence of TP53-mutated ctDNA in longitudinal plasma samples was tracked by droplet digital PCR. Patients were stratified into two groups, favorable or unfavorable, based on their highest ctDNA level using a MAF cutoff of 3.15% according to the ROC curve. The unfavorable group had significantly worse PFS than the favorable group (p < 0.001). Our results suggest that patients with mutated TP53 with a favorable ctDNA profile in the first trimester have better prognostic outcomes than patients with an unfavorable profile, and ctDNA can be a reliable predictor of the subsequent clinical outcome. [ABSTRACT FROM AUTHOR]

• Validated a low-cost solution for plant phenotyping in greenhouse. • Identified novel image features to quantify plant variations due to salt stress. • An automated data processing and analytic pipeline was developed and validated. • Salt-resistant soybean lines were identified. Plant high-throughput phenotyping technology is taking more and more important roles in soybean breeding and genetic research thanks to the advance in sensing and data analytic technologies. However, commercial high-throughput phenotyping systems of general purpose are expensive and complicated for many research groups, and their data analytic methods are designed for specific research projects. The goal of this study was to develop and validate a customized image-based phenotyping system that was used to automatedly collect, process and analyze imagery data of soybean cultivars to evaluate their response to salt stress in controlled environments. The imaging system consisted of a consumer-grade digital camera and an automated platform was used to take sequential images of soybean plants of five cultivars under salt stress during the experimental period. An image processing and analytic pipeline was developed to automatically extract image features and evaluate their tolerance to salt stress. Results indicated that two image features, i.e. canopy area and ExV (the difference of excess green and excess red) were highly correlated with salinity tolerance trait of soybean. The image saturation and blue channel values were able to extract salt stress characteristics and identify different types of salt stress characteristics. In addition, the ratio of damaged leaf area to canopy area was extracted as a novel image feature to quantify the salinity tolerance grade. The overall results indicated that the automatic plant phenotyping system based on low-cost image sensors and automation platform was able to quantify plant stress due to salt stress and would be useful in soybean breeding programs. [ABSTRACT FROM AUTHOR]

DNA methylation alters the expression of certain genes without any alteration to the DNA sequence and is a dynamic process during normal hematopoietic differentiation. As an epigenetic regulator, methyl-CpG-binding domain protein 2 (MBD2) is an important member of the MBD protein family and is acknowledged as a "reader" of DNA methylation. We used a mouse model to study the effects of MBD2 on the early development of T cells. Here, we found that MBD2 deficiency led to retardation of T cell differentiation at the DN3 stage. Meanwhile, decreased proliferative capacity and increased apoptosis were detected in Mbd2 −/− DN thymocytes. Furthermore, we found the WNT pathway was significantly down-regulated in Mbd2 −/− DN thymocytes: DKK1 (Dickkopf-1) expression was significantly increased, while TCF7 (transcription factor 7) and c-MYC were down-regulated. Thus, these findings established that MBD2 acted as a dominant regulator to imprint DN T cell development via the WNT pathway. • MBD2 deficiency resulted in retardation of T cell differentiation at the DN3 stage. • Decreased proliferative capacity and increased apoptosis were detected in Mbd 2 −/− DN thymocytes. • MBD2 affects early T cell development by regulating the expression of key genes of WNT pathway. [ABSTRACT FROM AUTHOR]

Recent research has identified some risk factors for phubbing behavior. However, scarce research has examined the potential influence of emotional support from social media on phubbing behavior, and little is known regarding the mediating mechanisms underlying this relationship. The present study examined the predictive role of emotional support from social media on phubbing behavior among college students and investigated whether fear of missing out and problematic social media use both mediated the relationship between emotional support from social media and phubbing behavior. A sample of 501 Chinese college students (aged 17-23, Mage = 19.6 years, SD = 1.24) completed questionnaires regarding emotional support from social media, fear of missing out, problematic social media use, and phubbing behavior. The results indicated that (a) emotional support from social media was positively associated with phubbing behavior; (b) both fear of missing out and problematic social media use mediated the relationship between emotional support from social media and phubbing behavior; and (c) fear of missing out and problematic social media use sequentially mediated the relationship between emotional support from social media and phubbing behavior. These findings have important implications for the prevention and intervention of phubbing behavior among college students. [ABSTRACT FROM AUTHOR]

Li-rich Mn-based layered cathode materials are subjected to unsatisfactory cycle stability, rate performance and voltage fading from the undesirable structure evolution during cycling despite its ultrahigh specific capacity. In this paper, Na-doped Li 1.15 Na 0.05 [Mn 0.54 Ni 0.13 Co 0.13 O 2 is prepared via introducing larger ionic radius Na ion into the lithium layer of the Li-rich layered cathode material via co-precipitation and high temperature soild-state reaction method. As prepared Na-doped cathode exhibits excellent electrochemical performances, including initial discharge capacity as high as 281 mAh g−1 at 0.1 C and good rate capacity with reversible discharge capacity of 142 mAh g−1 at 5 C. Furthermore, the Na ion substitution substantially suppresses the occurrence of Li+/Ni2+ mixing and phase transformation of layered Li-rich Mn-based oxide materials during continuous cycling, stabilizing the host layered structure. Higher capacity retention of 93.4% can be maintained on Na-doped cathode material after 100 cycles at 1 C rate compared with the undoped cathode (86.3%). Besides, the Na ion substitution also effectively reduces the internal charge transfer impedance and promotes the Li-ion diffusion kinetics, manifesting a promising cathode alternative for new-generation Li-ion battery benefiting from the outstanding performances and simple procedure. Image 1 • Na-doped Li 1.15 Na 0.05 [Mn 0.54 Ni 0.13 Co 0.13 O 2 is synthesized by a facile method. • Na ion substitution substantially suppresses the occurrence of Li+/Ni2+ mixing and structural phase transformation. • Improved discharge capacity, rate capacity and cycle durability could be achieved. • The modification mechanism of layered cathode material is clarified. [ABSTRACT FROM AUTHOR]

Following publication of the original article [1], the authors reported the following error is the article. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B virus (HBV) reactivation is commonly seen in HBsAg-positive hematologic patients undergoing immunosuppressive chemotherapy. Little is known about the risk of HBV reactivation after chimeric antigen receptor T-cell (CAR T) immunotherapy for the treatment of refractory/relapsed malignant B-cell lymphoma. Case presentation: We report a patient who underwent antiviral prophylaxis for 26 months and who discontinued treatment by herself 1 month after the sequential infusion of two specific, third-generation anti-CD19 and anti-CD22 CAR T cell immunotherapies for refractory/relapsed diffuse large B-cell lymphoma. Remission of the primary disease was achieved after two and half months, but she was admitted with a 7-day history of vomiting, jaundice, itching and dark urine. After excluding other possible causes of acute liver damage, HBV reactivation was suspected. HBV-DNA was 4,497,000 IU/mL at that time. Following the reintroduction of entecavir, a decline in the HBV-DNA copies was observed, but ALT, AST and bilirubin were elevated, and there was no improvement of the clinical conditions. She passed away because of hepatic encephalopathy and multiple organ dysfunction syndrome 40 days after admission. Conclusions: Our study provides the first report of the severe, early reactivation of an inactive HBsAg carrier after CAR T cell therapy in DLBCL. Trial registration: ChiCTR-OPN-16008526. [ABSTRACT FROM AUTHOR]

Background: Chimeric antigen receptor-modified (CAR) T-cell immunotherapy is a novel promising therapy for treatment of B-cell malignancy. Cytokine release syndrome (CRS) and infection are the most common adverse events during CAR T-cell therapy. Similar clinical presentation of concurrent CRS and infection makes it difficult to differentially diagnose and timely treat the condition. Methods: We analyzed the features of infection events during the first 30 days after CAR T-cell infusion (CTI) in 109 patients from three clinical trials (ChiCTR-OPN-16008526, ChiCTR-OPC-16009113, ChiCTR-OPN-16009847). Based on the dynamic changes of interleukin (IL)-6 and ferritin, we proposed the "double peaks of IL-6" pattern as a feature of life-threatening infection during the first 30 days after CTI. Meanwhile, we screened candidate biomarkers from 70-biomarker panel to establish a prediction model for life-threatening infection. Results: In this study, 19 patients (17.4%) experienced a total of 19 infection events during the first 30 days after CAR T-cell infusion. Eleven patients (10.1%) had grade 4–5 infection, which were all bacterial infection and predominantly sepsis (N = 9). "Double peaks of IL-6" appeared in 9 out of 11 patients with life-threatening infection. The prediction model of three-cytokines (IL-8, IL-1β and interferon-γ) could predict life-threatening infection with high sensitivity (training: 100.0%; validation: 100.0%) and specificity (training: 97.6%; validation: 82.8%). On base of the aforementioned methods, we proposed a workflow for quick identification of life-threatening infection during CAR T-cell therapy. Conclusions: In this study, we worked out two diagnostic methods for life-threatening infection during CAR T-cell therapy by analyzing inflammatory signatures, which contributed to reducing risks of infection-induced death. [ABSTRACT FROM AUTHOR]

In the original publication of this manuscript [1], Fig. 5E lower panel was incorrect due to an error in the preparation of these figures for publication. It was noticed that in the lower panel of Fig. 5E, one mouse image of ApoE−/− + PBS group (upper) was a photograph coming from ApoE−/− + BAPN pre-treatment group (lower). The corrected figure appears below. We apologize for any confusion this may have caused. [ABSTRACT FROM AUTHOR]

Physiological maturity date is a critical parameter for the selection of breeding lines in soybean breeding programs. The conventional method to estimate the maturity dates of breeding lines uses visual ratings based on pod senescence by experts, which is subjective by human estimation, labor-intensive and time-consuming. Unmanned aerial vehicle (UAV)-based phenotyping systems provide a high-throughput and powerful tool of capturing crop traits using remote sensing, image processing and machine learning technologies. The goal of this study was to investigate the potential of predicting maturity dates of soybean breeding lines using UAV-based multispectral imagery. Maturity dates of 326 soybean breeding lines were taken using visual ratings from the beginning maturity stage (R7) to full maturity stage (R8), and the aerial multispectral images were taken during this period on 27 August, 14 September and 27 September, 2018. One hundred and thirty features were extracted from the five-band multispectral images. The maturity dates of the soybean lines were predicted and evaluated using partial least square regression (PLSR) models with 10-fold cross-validation. Twenty image features with importance to the estimation were selected and their changing rates between each two of the data collection days were calculated. The best prediction (R2 = 0.81, RMSE = 1.4 days) was made by the PLSR model using image features taken on 14 September and their changing rates between 14 September and 27 September with five components, leading to the conclusion that the UAV-based multispectral imagery is promising and practical in estimating maturity dates of soybean breeding lines. [ABSTRACT FROM AUTHOR]

Flood has an important effect on plant growth by affecting their physiologic and biochemical properties. Soybean is one of the main cultivated crops in the world and the United States is one of the largest soybean producers. However, soybean plant is sensitive to flood stress that may cause slow growth, low yield, small crop production and result in significant economic loss. Therefore, it is critical to develop soybean cultivars that are tolerant to flood. One of the current bottlenecks in developing new crop cultivars is slow and inaccurate plant phenotyping that limits the genetic gain. This study aimed to develop a low-cost 3D imaging system to quantify the variation in the growth and biomass of soybean due to flood at its early growth stages. Two cultivars of soybeans, i.e. flood tolerant and flood sensitive, were planted in plant pots in a controlled greenhouse. A low-cost 3D imaging system was developed to take measurements of plant architecture including plant height, plant canopy width, petiole length, and petiole angle. It was found that the measurement error of the 3D imaging system was 5.8% in length and 5.0% in angle, which was sufficiently accurate and useful in plant phenotyping. Collected data were used to monitor the development of soybean after flood treatment. Dry biomass of soybean plant was measured at the end of the vegetative stage (two months after emergence). Results show that four groups had a significant difference in plant height, plant canopy width, petiole length, and petiole angle. Flood stress at early stages of soybean accelerated the growth of the flood-resistant plants in height and the petiole angle, however, restrained the development in plant canopy width and the petiole length of flood-sensitive plants. The dry biomass of flood-sensitive plants was near two to three times lower than that of resistant plants at the end of the vegetative stage. The results indicate that the developed low-cost 3D imaging system has the potential for accurate measurements in plant architecture and dry biomass that may be used to improve the accuracy of plant phenotyping. [ABSTRACT FROM AUTHOR]

Background: The aggressive form of Mantle cell non-hodgkin B cell lymphoma (MCL) has a dismal prognosis. Dual targeting BTK and BCL2 with ibrutinib and venetoclax has improved outcomes in MCL patients who were predicted not to respond to conventional therapy, but it is unlikely to be curative. Chimeric antigen receptor-modified T (CAR T) cells exhibit very effective function in elimination of relapsed/refractory B-cell lymphoid malignancies, we investigated their use in a patient with relapsed MCL. Case presentation: Here, we report a case of a refractory MCL in a patient who had relapsed after conventional chemotherapy and autologous CAR T cell therapy. The patient received multiple molecularly targeted therapies, including targeting BTK and BCL2, and haplo-identical CAR T (haplo-CAR T) cells from her daughter without previous allo-hematopoietic stem cell transplantation. Haplo-CAR T cells could effectively proliferate in vivo and had a clinically significant antitumor activity without serious side effects. The patient achieved a partial remission, with minimal residual disease. Conclusions: This case suggests that haplo-CAR T cell therapy can be effective in controlling lymphoma that failed to respond to autologous CAR T cell therapy and overcome limitation of autologous CAR T cells, thus may be one possible regimen before the era of off-the-shelf "universal" CAR T cell therapy. Trial registration: ChiCTR-OPN-16008526. http://www.chictr.org.cn/showproj.aspx?proj=13798; ChiCTR1800019385. http://www.chictr.org.cn/showproj.aspx?proj=32805; ChiCTR1800019449. http://www.chictr.org.cn/showproj.aspx?proj=32778. [ABSTRACT FROM AUTHOR]

Background: POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome still has no standard treatment. On the basis that both POEMS syndrome and myeloma have an underlying plasma cell dyscrasia, anti-myeloma therapy can be expected to be useful for POEMS syndrome. Chimeric antigen receptor T (CAR-T) cells targeting B cell maturation antigen (BCMA) has been used in the treatment of relapsed and refractory multiple myeloma (RRMM). No POEMS syndrome cases treated with anti-BCMA CAR-T cells have been reported. Case presentation: Here, we, for the first time, report a POEMS syndrome case treated with anti-BCMA CAR-T cells. A 49-year-old female with incapacitating POEMS syndrome that progressed on lenalidomide treatment was enrolled in a phase I study involving anti-BCMA CAR-T cells (ChiCTR-OPC-16009113). Another patient with RRMM who had undergone six prior lines treatments was also enrolled in the study. They received infusions of anti-BCMA CAR-T cells. Both patients achieved a stringent complete response. Complete remission persisted in the patient with POEMS syndrome and lasted for 7.6 months before a relapse in RRMM patient. Both patients had toxicity consistent with the grade 1 cytokine release syndrome. Conclusions: This is the first report of treatment by anti-BCMA CAR-T cells in POEMS syndrome. Our findings demonstrate the anti-BCMA CAR-T cell treatment may be a feasible therapeutic option for patients with POEMS syndrome and RRMM who do not respond well to traditional therapies. Trial registration: ChiCTR-OPC, ChiCTR-OPC-16009113. Registered 29 August 2016. [ABSTRACT FROM AUTHOR]

Geometric dimensions of plants are significant parameters for showing plant dynamic responses to environmental variations. An image-based high-throughput phenotyping platform was developed to automatically measure geometric dimensions of plants in a greenhouse. The goal of this paper was to evaluate the accuracy in geometric measurement using the Structure from Motion (SfM) method from images acquired using the automated image-based platform. Images of nine artificial objects of different shapes were taken under 17 combinations of three different overlaps in x and y directions, respectively, and two different spatial resolutions (SRs) with three replicates. Dimensions in x, y and z of these objects were measured from 3D models reconstructed using the SfM method to evaluate the geometric accuracy. A metric power of unit (POU) was proposed to combine the effects of image overlap and SR. Results showed that measurement error of dimension in z is the least affected by overlap and SR among the three dimensions and measurement error of dimensions in x and y increased following a power function with the decrease of POU (R2 = 0.78 and 0.88 for x and y respectively). POUs from 150 to 300 are a preferred range to obtain reasonable accuracy and efficiency for the developed image-based high-throughput phenotyping system. As a study case, the developed system was used to measure the height of 44 plants using an optimal POU in greenhouse environment. The results showed a good agreement (R2 = 92% and Root Mean Square Error = 9.4 mm) between the manual and automated method. [ABSTRACT FROM AUTHOR]

Background: Extracellular matrix (ECM) is a mediator of tumor progression. However, whether the alterations of the intraperitoneal ECM prior to tumor establishment affects the malignant progression of ovarian cancer remains elusive. Methods: Apolipoprotein (ApoE) knock-out mice was used to analyze the intraperitoneal ECM alterations by quantification of the major components of ECM. ID8 cells were implanted in vivo to generate allografts and human ovarian cancer cell lines were characterized in vitro to assess the effects of ECM alterations on the malignant progression of ovarian cancer. Adhesion assay, immunochemistry, cytokines profile, proliferation assay, transwell invasion assay and western blot were used to determine the malignant phenotype of ovarian cancer cells. Results: ApoE loss induced increased ECM deposition, which stimulated the adhesions of ovarian cancer cells. The adhesion-mediated focal adhesion kinase (FAK) signaling enhanced the invasive behaviors of ovarian cancer cells through activation of a ERK-MMP linkage. This ECM-induced signaling cascade was further confirmed in human ovarian cancer cell lines in vitro. Furthermore, reversal of the ECM accumulation with BAPN or abrogation of adhesion-induced ERK activation in ovarian cancer cells with MEK inhibitors (MEKi) was found to effectively delay ovarian cancer progression. Conclusions: These findings identify the FAK-ERK activation in cell/matrix adhesion in the malignant progression of ovarian cancer and the efficiency of BAPN or MEKi for tumor suppression, providing an impetus for further studies to explore the possibility of new anticancer therapeutic combinations. [ABSTRACT FROM AUTHOR]

A correction to the article "Loss of Mdb2 Protects Mice Against High-Fat Diet-Induced Obesity and Insulin Resistance by Regulating the Homeostasis of Energy Storage and Expenditure" by Jia Cheng and colleagues, published in a previous issue is presented.

The present study was conducted to explore the mechanisms leading to differences among fishes in the ability to biosynthesize long-chain polyunsaturated fatty acids (LC-PUFAs). Replacement of fish oil with vegetable oil caused varied degrees of increase in 18-carbon fatty acid content and decrease in n-3 LC-PUFA content in the muscle and liver of rainbow trout (Oncorhynchus mykiss), Japanese seabass (Lateolabrax japonicus) and large yellow croaker (Larimichthys crocea), suggesting that these fishes have differing abilities to biosynthesize LC-PUFAs. Fish oil replacement also led to significantly up-regulated expression of FADS2 and SREBP-1 but different responses of the two PPAR-α homologues in the livers of these three fishes. An in vitro experiment indicated that the basic transcription activity of the FADS2 promoter was significantly higher in rainbow trout than in Japanese seabass or large yellow croaker, which was consistent with their LC-PUFA biosynthetic abilities. In addition, SREBP-1 and PPAR-α up-regulated FADS2 promoter activity. These regulatory effects varied considerably between SREBP-1 and PPAR-α, as well as among the three fishes. Taken together, the differences in regulatory activities of the two transcription factors targeting FADS2 may be responsible for the different LC-PUFA biosynthetic abilities in these three fishes that have adapted to different ambient salinity. [ABSTRACT FROM AUTHOR]

Engrafting the bone marrow cells of a patient with M5 acute myeloid leukemia into immunocompromised mice (AM7577) resulted in serially transferrable stable AML and eventual mortality. The disease starts in the bone marrow and then expands to peripheral areas, which is typical of M5 leukemogenesis, where high leukemic burden in blood is coincident with symptoms/mortality. The leukemic cells in the mice had myeloid morphology, phenotypes, and genotypes (including the internal tandem duplication of FMS-like tyrosine kinase receptor 3 gene [FLT3-ITD]) similar to those of the original patient. Autocrine mechanisms of human granulocyte–macrophage colony-stimulating factor/interleukin-3 likely support AM7577 growth in mice. Treatment with FLT3 TKI (AC220) caused complete remission in peripheral blood, spleen, and bone, along with relief of symptoms and extended life, hinting that FLT3-ITD may be a key leukemogenic driver maintaining the disease. Interestingly, withdrawal of AC220 (high dose) did not result in relapse of disease, suggesting cure. These results, however, are in contrast to cytarabine (AraC) induction treatment: First, although AraC significantly suppresses the diseases in blood, and to a lesser degree in bone marrow and spleen, the suppression is temporary and does not prevent eventual onset of disease/death. Second, the withdrawal of AraC always resulted in rapid relapse in peripheral blood and eventually death. Our observation in this patient-derived model may provide useful information for clinical applications of the two drugs. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to evaluate the effectiveness of the treatment of fibular osteomyelitis by Ilizarov bone transport.Methods: We retrospectively reviewed 5 patients with fibular osteomyelitis treated by Ilizarov bone transport. Our study included 4 males and 1 female with a mean of age 29.2 years. The average length of the bone defects after radical debridement was 7.6 cm (range 6.5-10 cm).Results: The mean follow-up was 24.8 months (range 14-34 months). No patient was lost to follow-up. All the patients had bone union and no recurrence of infection was observed. The mean external fixation time was 8.8 months (range 8-10 months), and the mean external fixation index was 1.18 months/cm (range 0.90-1.43 months/cm). There was no sign of knee or ankle instability by clinical examination in all the patients. According to Association for the Study and Application of the Method of Ilizarov (ASAMI) classification, bone results were excellent in 3 patients, good in 2 patients; functional results were excellent in 3 patients, good in 2 patients.Conclusions: Our study suggested that Ilizarov bone transport may be a good choice for the treatment of fibular osteomyelitis, especially for the patient with distal fibular loss. [ABSTRACT FROM AUTHOR]

Cervical cancer cells exhibit an increased requirement for ubiquitin-dependent protein degradation associated with an elevated metabolic turnover rate. Ubiquitin, which is a small, highly conserved protein expressed in all eukaryotic cells, can be covalently linked to certain target proteins to mark them for degradation by the ubiquitin-proteasome system. Previous studies highlight the essential role of Ubiquitin B (UbB) and UbB-dependent proteasomal protein degradation in histone deacetylase inhibitor (HDACi) -induced tumor selectivity. We hypothesized that UbB plays a critical role in the function of cervical cancer stem cells. We measured endogenous UbB levels in mammospheres in vitro by real-time PCR and Western blotting. The function of UbB in cancer stem-like cells was assessed after knockdown of UbB expression in prolonged Trichostatin A-selected HeLa cells (HeLa/TSA) by measuring in vitro cell proliferation, cell apoptosis, invasion, and chemotherapy resistance as well as by measuring in vivo growth in an orthotopic model of cervical cancer. We also assessed the cancer stem cell frequency, tumorsphere formation, and in vivo growth of human cervical cancer xenografts after UbB silencing. We found that HeLa/TSA were resistant to chemotherapy, highly expressed the UbB gene and the stem cell markers Sox2, Oct4 and Nanog. These cells also displayed induced differentiation abilities, including enhanced migration/invasion/malignancy capabilities in vitro and in vivo. Furthermore, an elevated expression of UbB was shown in the tumor samples of chemotherapy patients. Silencing of UbB inhibited tumorsphere formation, lowered the expression of stem cell markers and decreased cervical xenograft growth. Our results demonstrate that UbB was significantly increased in prolonged Trichostatin A-selected HeLa cells and it played a key role in the maintenance of cervical cancer stem-like cells. [ABSTRACT FROM AUTHOR]