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In order to load fish oil for potential encapsulation of fat-soluble functional active substances, fish oil-loaded multicore submillimeter-sized capsules were prepared with a combination method of three strategies (monoaxial electrospraying, chitosan-tripolyphosphate ionotropic gelation, and Tween blending). The chitosan-tripolyphosphate/Tween (20, 40, 60, and 80) capsules had smaller and evener fish oil cores than the chitosan-tripolyphosphate capsules, which resulted from that Tween addition induced smaller and evener fish oil droplets in the emulsions. Tween addition decreased the water contents from 56.6 % to 35.0 %–43.4 %, increased the loading capacities from 10.4 % to 12.7 %–17.2 %, and increased encapsulation efficiencies from 97.4 % to 97.8 %–99.1 %. In addition, Tween addition also decreased the highest peroxide values from 417 meq/kg oil to 173–262 meq/kg oil. These properties' changes might result from the structural differences between the chitosan-tripolyphosphate and chitosan-tripolyphosphate/Tween capsules. All the results suggested that the obtained chitosan-tripolyphosphate/Tween capsules are promising carriers for fish oil encapsulation. This work also provided useful knowledge to understand the preparation, structural, and physicochemical properties of the chitosan-tripolyphosphate capsules. [ABSTRACT FROM AUTHOR]

• The defect-rich VS 4 nanosheets are obtained via microwave-induced fabrication method. • The sulfur vacancies promote the desorption of Mg2+. • V3+ self-doping maintains the structural stability of the active material. • Cation-anionic synergistic redox achieve a high specific capacity. Vanadium sulfide (VS 4) demonstrates the most prospect as the cathode materials for rechargeable magnesium battery due to its special one-dimensional linear crystal structure. However, VS 4 cathode still suffers from sluggish kinetics, irreversible structural change, short cycle life, and low capacity. Herein, a microwave-induced synthesis method is presented to fabricate VS 4 nanosheets with rich sulfur vacancies and high V3+/V4+ ratio. When serviced as the cathode material for rechargeable magnesium battery, the VS 4 nanosheets display excellent electrochemical performances with large specific capacity of 701 mAh/g at 200 mA g−1 current density. In addition, the VS 4 nanosheets cathodes also show long-term operating stability over 600 cycles at 1.0 A/g current density with only 0.3 % capacity decay per cycle. Our experimental results show that the improved electrochemical reaction kinetics is ascribed to the defect-rich structure and the reversible anionic redox reactions between S2−/S 2 2− of the VS 4 nanosheets. This work offers a meaningful way to design high-performance Mg2+ ion storage cathode materials with favorable diffusion kinetics. [ABSTRACT FROM AUTHOR]

To evaluate the safety and efficacy of an enhanced recovery after surgery (ERAS) program for intraspinal tumors in a single-institutional prospective randomized controlled trial. A multimodal and multidisciplinary ERAS protocol for intraspinal tumor surgery was developed. A total of 94 enrolled patients were randomized into 2 groups: 48 were managed following the ERAS protocol (ERAS group), and 46 received conventional perioperative care (control group). The primary end point was postoperative length of stay (LOS). The secondary outcomes included postoperative pain score and pain medication use, urinary catheterization, ambulation, mortality, reoperation/readmission rates, complication rates, patient satisfaction, and overall cost. A significant reduction in LOS was achieved in patients undergoing ERAS protocol compared with the controls (5 vs. 8 days; P < 0.0001). Moreover, patients in the ERAS group had better postoperative pain scores (1.0 ± 1.3 vs. 1.9 ± 1.3; P = 0.007), decreased use of patient-controlled analgesia (4.2% vs. 19.6%; P = 0.020) and oral opioid (37.5% vs. 58.7%; P = 0.040), early urinary catheter removal (58.3% vs. 6.5%; P < 0.0001), greater ambulation (68.8% vs. 17.4%; P < 0.0001), and higher satisfaction scores (91.8 ± 4.4 vs. 88.2 ± 6.8; P = 0.022) than did the control group. There were no deaths or 30-day readmission/reoperation in both groups, nor did the postoperative complication rates differ between groups. The ERAS protocol for intraspinal tumor surgery seems to be feasible, effective, and safe in shortening postoperative LOS, improving postoperative pain control with reduced opioid use, and accelerating functional recovery without increasing rates of complications or reoperation/readmission. Adoption of spine ERAS programs could be encouraged in practice, although validation with larger-scale multicenter trials is warranted. [ABSTRACT FROM AUTHOR]

We sought to assess whether controlled, intraoperative lumbar drainage (LD) of cerebrospinal fluid (CSF) could facilitate resection of pituitary macroadenomas and reduce the rate of CSF leak. A retrospective cohort study from a prospective database was conducted on 189 patients with pituitary macroadenoma who received endoscopic transsphenoidal surgery between 2013 and 2017. Patients were classified into 2 groups: 119 patients received an intraoperative LD (LD group) and 70 patients underwent routine endoscopic surgery without LD (control group). In the LD group, lumbar catheters were placed preoperatively and CSF was drained intermittently during tumor resection. The rates of gross total resection (GTR) and CSF leaks were assessed both intraoperatively and postoperatively. Intraoperative LD was associated with a higher rate of GTR (92.4% in the LD group vs. 78.6% in the control group, P = 0.006), especially in macroadenomas with suprasellar extension (90.3% vs. 75.0%, P = 0.012). Both intraoperative and postoperative CSF leak rates were significantly decreased in the LD group (intraoperative: 10.1% vs. 31.4%, P < 0.001; postoperative: 3.4% vs. 11.4%, P = 0.035). In functioning adenomas, a better remission rate of excess-hormone secretion was observed in the LD group compared with the controls (89.1% vs. 60.6%, P = 0.001). Patients in the LD group also had an enhanced recovery with a shorter postoperative length of stay (7 days vs. 5 days, P = 0.020). Intraoperative LD may assist surgeons during endoscopic transsphenoidal resection of pituitary macroadenomas by achieving a higher rate of GTR and a lower rate of perioperative CSF leaks. Validation in prospective randomized controlled studies is needed. [ABSTRACT FROM AUTHOR]

• Dark carbon fixation (DCF) is an important organic C source in intertidal wetlands. • Reductive sulfur in intertidal sediments was a key factor controlling DCF. • cbbM -harboring bacteria were the dominant DCF microbes in intertidal sediments. • DCF may play an important role in linking C-N-S cycles in intertidal wetlands. Dark carbon fixation (DCF) contributes approximately 0.77 Pg C y−1 to oceanic primary production and the global carbon budget. It is estimated that nearly half of the DCF in marine sediments occurs in estuarine and coastal regions, but the environmental factors controlling DCF and the microorganisms responsible for its production remain under exploration. In this study, we investigated DCF rates and the active chemoautotrophic microorganisms in intertidal sediments of the Yangtze Estuary, using 14C-labeling and DNA-stable isotope probing (DNA-SIP) techniques. The measured DCF rates ranged from 0.27 to 3.37 mmol C m−2 day−1 in intertidal surface sediments. The rates of DCF were closely related to sediment sulfide content, demonstrating that the availability of reductive substrates may be the dominant factor controlling DCF in the intertidal sediments. A significant positive correlation was also observed between the DCF rates and abundance of the cbbM gene. DNA-stable isotope probing (DNA-SIP) results further confirmed that cbbM -harboring bacteria, rather than cbbL -harboring bacteria, played a dominant role in DCF in intertidal sediments. Phylogenetic analysis showed that the predominant cbbM -harboring bacteria were affiliated with Burkholderia, including Sulfuricella denitrificans, Sulfuriferula, Acidihalobacter, Thiobacillus , and Sulfurivermis fontis. Moreover, metagenome analyses indicated that most of the potential dark-carbon-fixing bacteria detected in intertidal sediments also harbor genes for sulfur oxidation, denitrification, or dissimilatory nitrate reduction to ammonium (DNRA), indicating that these chemoautotrophic microorganisms may play important roles in coupled carbon, nitrogen, and sulfur cycles. These results shed light on the ecological importance and the underlying mechanisms of the DCF process driven by chemoautotrophic microorganisms in intertidal wetlands. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: Flower-like ZnO particles were fabricated from zinc nitrate and urea via the microwave-induced combustion technique (MICT). The structure and morphology of the products were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and selected area electron diffraction (SAED). The effects of growth conditions such as microwave power, radiation time, and molar ratio of urea/Zn2+ were investigated. Results show that the morphologies and particle sizes of the final products depend on the molar ratio of urea/Zn2+. The SEM images of ZnO flowers grown in different periods were employed to explain the formation mechanism. This study provides a simple and efficient approach for synthesizing flower-like ZnO heterostructures. [ABSTRACT FROM AUTHOR]

Three types of tilapia scale gelatins (hot water-pretreated gelatin, HWG; acetic acid-pretreated gelatin, AAG; and pepsin enzyme-pretreated gelatin, PEG) were extracted and their gel strength, foaming properties, and emulsifying properties were analyzed. They had different gel strength values: AAG (370 ± 10 g Bloom) > HWG (320 ± 10 g Bloom) > PEG (280 ± 10 g Bloom). The creaming index values of tilapia scale gelatin-stabilized fish oil-loaded emulsions were dependent on gelatin type (HWG ≈ AAG > PEG) at low gelatin concentration (2 mg/mL), whereas they were similar and low (8–10 %) at high gelatin concentration (10 mg/mL). Extraction methods had no consistently significant effects on the gelatin foaming properties. In summary, tilapia scale gelatins had better gel strength and foaming properties and similar or even better emulsifying properties than mammalian gelatins. Therefore, tilapia scales could be a potential source of gelatins to replace mammalian gelatins. • Tilapia scale gelatins were extracted using three different pretreatment methods. • Hot water- and pepsin-pretreated gels were the finest and coarsest, respectively. • These gelatins had better or comparable gel strength than commercial mammalian ones. • These gelatins had better foaming properties than some reported mammalian ones. • These gelatins had comparable emulsifying properties to some reported mammalian ones. [ABSTRACT FROM AUTHOR]

Elevated expression of HER3, which interacts with HER2 in breast cancer cells, confers chemoresistance via phosphoinositide 3-kinase (PI-3K)/Akt-dependent upregulation of Survivin. However, the underlying mechanism is not clear. Ectopic expression or specific knockdown of HER3 in HER2-overexpressing breast cancer cells did not alter Survivin mRNA levels and Survivin protein stability, supporting the notion that HER3 signaling may regulate specific miRNAs that target Survivin to alter its protein translation. Here we showed that overexpression and specific knockdown of HER3 reduced and enhanced expression of two Survivin-targeting miRNAs, miR-203 and miR-542-3p, in breast cancer cells, respectively. While the specific inhibitor of either miR-203 or miR-542-3p attenuated an anti-HER3 antibody-induced downregulation of Survivin, inhibition of miR-542-3p exhibited a better efficacy than miR-203 inhibition did. Consistently, miR-542-3p mimic was much more effective than miR-203 mimic not only in inhibition of Survivin, but also in enhancement of paclitaxel-induced apoptosis in HER2-overexpressing breast cancer cells. Moreover, the combination of miR-542-3p mimic and paclitaxel, as compared with either agent alone, significantly inhibited in vivo tumor growth of HER2-overexpressing breast cancer cells. Collectively, our data indicated that the HER3/PI-3K/Akt signaling upregulates Survivin via suppression of miR-203 and miR-542-3p. Because miR-542-3p has three binding sites on the 3'-UTR of Survivin mRNA, its mimic was able to effectively downregulate Survivin in vitro and in vivo. Thus, miR-542-3p-replacement therapy is an excellent approach to overcome HER3-mediated paclitaxel resistance and significantly enhances the antitumor activity of paclitaxel against HER2-overexpressing breast cancer. [ABSTRACT FROM AUTHOR]

Coastal wetlands are hotspots for nitrogen (N) cycling and a significant natural source of the potent greenhouse gas nitrous oxide (N 2 O). Burrowing benthos are known to transform N in intertidal marsh soils, but their contribution to N 2 O emissions and the underlying molecular mechanisms remain unclear. Here, the effects of crab bioturbation on N 2 O emissions in coastal marshes, where Chiromantes dehaani and Helice tridens tientsinensis were the dominant crab species, were investigated in field and indoor experiments. The N 2 O emissions increased significantly in the presence of crabs, being positively correlated with the intensity of crab bioturbation but differing among crab species. Natural-abundance isotope analyses indicated that crab bioturbation greatly promoted the contribution of hydroxylamine oxidation to N 2 O production; nevertheless, bacterial denitrification (including heterotrophic denitrification and nitrifier denitrification) remained the dominant pathway. Molecular analyses suggested that the increased N 2 O emissions in crab-disturbed habitats might be driven by underlying changes to microbial communities, especially by the disproportionate stimulation of nitric oxide reductase-carrying microbes over nitrous oxide reductase-carrying microbes. This study highlights the importance of considering the burrowing activity, density, and species of benthos when evaluating the N cycle in coastal wetlands. [Display omitted] • Crab bioturbation greatly accelerates N 2 O emission in intertidal marsh soils. • Increase of N 2 O emission is closely related to reshaped microbial community by crab. • Different species of crabs exhibit different promoting effects on N 2 O emission. • Crab bioturbation affects N 2 O production pathways based on N 2 O isotopic signatures. • Activity and species of crabs should be considered when restoring coastal wetlands. [ABSTRACT FROM AUTHOR]

Overexpression of survivin is observed in various hematological malignancies, including acute myeloid leukemia (AML). Studies show that elevated expression of survivin correlates with a worse clinic outcome in AML patients. It remains unclear whether inhibition of survivin may alter the efficacy of chemotherapy against AML. Here, we evaluate the effects of specific knockdown of survivin on AML cells' sensitivity to chemotherapy, and investigate the therapeutic potential of the transcription inhibitor of survivin YM155 either alone or in combination with chemotherapeutic agents. We found Kasumi-1 and HL-60 cells had relatively higher expression levels of survivin among all AML cell lines tested. Specific knockdown of survivin in Kasumi-1 and HL-60 cells resulted in: inhibition of cell proliferation; cell cycle G2/M arrest; induction of DNA damage response and apoptosis. Downregulation of survivin enhanced etoposide- or doxorubicin-induced anti-proliferative/anti-survival activity in AML cells. The small molecule inhibitor YM155 reduced survivin in a dose- and time-dependent manner and trigged apoptosis in Kasumi-1 and HL-60 cells. The combinatorial effects of YM155 and chemotherapeutics were either synergetic or antagonistic, depending upon the drugs used for combination and the type of AML cells being treated. Collectively, our data demonstrate that survivin plays an important role in the maintenance and proliferation of AML cells. While specific knockdown of survivin enhances chemosensitivity, the combinations of YM155 and chemotherapeutic agents exhibit synergetic or antagonistic effects on AML cells. Our findings provide a rationale for further assessment of survivin-targeted therapy in the treatment of patients with AML. [ABSTRACT FROM AUTHOR]

"Turn on" fluorescence immunoassay of endocrine diethyl phthalate. [Display omitted] • Fluorescence turn-on immunoassay of endocrine diethyl phthalate. • Red carbon dots can reduce interference of autofluorescence. • Red carbon dots as tags can improve the sensitivity of immunoassay. • "Turn-on" probe can reduce the interference of actual sample medium. Diethyl phthalate (DEP), as the environmental endocrine, would interfere with people's endocrine system and has greatly harm in health. Here a sensitivity, eco-friendly fluorescence immunoassay technique was established based on "turn-on" red carbon dots (R-CDs) conjugated anti-DEP antibody (Ab) as the immunoprobe for the detection of DEP in daily supplies. The R-CDs will "turn-on" fluorescence when it in formamide solution, due to the change of the electron distribution on the surface and electronic charge transfer of the red carbon dots. The use of "turn-on" R-CDs as immunoprobe effectively increased the sensitivity of the immunoassay. Moreover, the R-CDs conjugated anti-DEP Ab without any additional embellishment. Under the optimal conditions, a good linear was established with the DEP concentration range of 5 × 10−2 ng/mL–10 ng/mL, the low limit of detection (LOD) of the proposed method was 0.0056 ng/mL. This project has satisfactory accuracy with recoveries ranging from 96.0% to 115.1%. Our research provides an accurately, simply and sensitivity strategy to detect the content of environmental endocrine DEP in daily supplies. [ABSTRACT FROM AUTHOR]

The defect-rich unconventional phase Cu 7.2 S 4 Nanotubes are fabricated by a facile microwave-induced selective etching method. Benefitting from the unique one-dimensional crystal structure and lattice defect-rich hollow structure, the Cu 7.2 S 4 nanotubes exhibit high reversible capacity and remarkable cycling stability. [Display omitted] • The defect-rich Cu 7.2 S 4 nanotubes are fabricated for the first time. • The unique microwave-induced selective etching method is demonstrated. • The record cycling stability is achieved over the Cu 7.2 S 4 nanotube cathode. • The multistep reaction kinetics of the Cu 7.2 S 4 nanotube cathode are confirmed. Copper sulfide is promising great potential for capable cathode in rechargeable magnesium batteries. However, divalent Mg2+ diffusion in its host lattice is subject to high lattice strain and mechanical stress mainly due to strong Coulombic interaction. Herein, a microwave-induced selective etching strategy is reported to construct non-stoichiometric-phase robust Cu 7.2 S 4 nanotubes with rich lattice defects, which can proceed with ultra-long-cycling stability over 1600 cycles with ultra-low capacity decay of 0.0109 % per cycle at 1.0 A g−1. Furthermore, the Cu 7.2 S 4 nanotube cathode can also exhibit a large specific capacity of 314 mAh g−1 at 0.1 A g−1 as well as an excellent rate capability of 91.7 mAh g−1 at 1.0 A g−1. The present electrochemical performances greatly surpass those of Cu 7.2 S 4 nanowire, Cu 7.2 S 4 nanoparticle, and conventional phase CuS nanotubes and at least are comparable to the conversion-type cathode materials reported so far. The generated lattice defect combined with the optimized robust nanotube structure can effectively buffer lattice strain and mechanical stress to provide a favorable diffusion kinetic. Our designed microwave-induced selective etching system demonstrates significant superiority in morphology, phase, and defect engineering of Cu 7.2 S 4 nanotubes to accommodate reversible Mg2+ storage for high-performance rechargeable magnesium batteries. [ABSTRACT FROM AUTHOR]

Abstract: Ultrasound (US) is used widely in the context of breast cancer. While it is advantageous for a number of reasons, it has low specificity and requires the use of a contrast agent. Its use as a standalone diagnostic and real-time imaging modality could be achieved by development of a tumor-targeted ultrasound contrast agent (UCA); functionalizing the UCA with a tumor-targeting agent would also allow the targeted administration of anti-cancer drugs at the tumor site. In this article, clinical US techniques are used to show that mesoporous silica nanoparticles (MSNs), functionalized with the monoclonal antibody Herceptin®, can be used as an effective UCA by increasing US image contrast. Furthermore, in vitro assays show the successful localization and binding of the MSN-Herceptin conjugate to HER2+ cancer cells, resulting in tumor-specific cytotoxicity. These results demonstrate the potential of MSNs as a stable, biocompatible, and effective therapeutic and diagnostic (“theranostic”) agent for US-based breast cancer imaging, diagnosis, and treatment. [Copyright &y& Elsevier]

Abstract: Bendamustine, a hybrid molecule of purine analog and alkylator, induces cell death by activation of apoptosis, DNA damage response, and mitotic catastrophe. Entinostat, a selective class I inhibitor of histone deacetylase (HDAC), exerts anti-tumor activity in various cancer types, including multiple myeloma (MM). We sought to determine the combinatorial effects of bendamustine and entinostat on MM cells. Cell growth assays showed that bendamustine or entinostat inhibited proliferation in a dose-dependent manner, and their combinations synergistically induced growth inhibition in all MM cells tested. An apoptotic-ELISA and western blot assays on PARP cleavage and caspase-8 and caspase-3 revealed that bendamustine in combination with entinostat exhibited a much more potent activity than either agent alone to promote the MM cells undergoing apoptosis in a dose-dependent manner. Flow cytometric analysis found that entinostat exhibited distinct effects on cell cycle progression in different lines and bendamustine mainly arrested the cells at S phase, whereas their combinations dramatically blocked the S cells entering G2/M phase. Furthermore, studies on DNA damage response indicated that phospho-histone H2A.X (P-H2A.X), a hall marker of DNA double strand break, along with phosphorylated CHK2 (P-CHK2) was significantly enhanced by the combinations of bendamustine and entinostat as compared to either agent alone. These molecular changes were correlated with the increases in mitotic catastrophe. Collectively, our data demonstrate that bendamustine in combination with entinostat exhibit potent anti-proliferative/anti-survival activity in MM cells via induction of apoptosis and DNA damage response. Regimens consisting of bendamustine and/or entinostat may represent novel therapeutic strategies against MM. [Copyright &y& Elsevier]

Abstract: Trastuzumab (or Herceptin), as the first erbB2-targeted therapy, has been successfully used to treat breast cancer patients with erbB2-overexpressing tumors. However, resistances to trastuzumab frequently occur, and novel strategies/agents are urgently needed to abrogate the resistant phenotype. Our current study explores the potential of SNDX-275, a class I HDAC inhibitor, to overcome trastuzumab resistance and investigates the combinational effects of SNDX-275 and trastuzumab on both sensitive and resistant breast cancer cells. Cell proliferation assays showed that SNDX-275 significantly enhanced trastuzumab-induced growth inhibition in trastuzumab-sensitive, erbB2-overexpressing breast cancer cells. Importantly, SNDX-275 at its therapeutic range re-sensitized trastuzumab-resistant cells to trastuzumab-mediated growth inhibition. SNDX-275 in combination with trastuzumab resulted in a dramatic reduction of erbB3 and its phosphorylation (P-erbB3), and inhibition of Akt signaling. Apoptotic-ELISA and western blot analyses confirmed that the combinations of SNDX-275 and trastuzumab as compared to SNDX-275 alone significantly enhanced DNA fragmentation and induced more PARP cleavage and caspase-3 activation in both trastuzumab-sensitive and -resistant breast cancer cells. Furthermore, co-immunoprecipitation assays revealed that SNDX-275 mainly attenuated the interactions of erbB2 and erbB3 receptors, but had no significant effect on erbB2/IGF-1R or erbB3/IGF-1R associations in the trastuzumab-resistant breast cancer cells. These data indicated that SNDX-275 enhanced trastuzumab efficacy against erbB2-overexpressing breast cancer cells, and exhibited potential to overcome trastuzumab resistance via disrupting erbB2/erbB3 interactions and inactivating PI-3K/Akt signaling. SNDX-275 may be included in erbB2-targeted regimen as a novel strategy to treat breast cancer patients whose tumors overexpress erbB2. [Copyright &y& Elsevier]

Abstract: Cerebral white matter lesions (WMLs) are frequently observed in vascular dementia and Alzheimer''s disease and are believed to be responsible for cognitive dysfunction. The cerebral WMLs are most likely caused by chronic cerebral hypoperfusion and can be experimentally induced by permanent bilateral common carotid artery occlusion (BCCAO) in rats. Previous studies found the involvement of oxidative stress and astrocytic activation in the cerebral WMLs of BCCAO rats. Gypenoside (GP), a pure component extracted from the Gyrostemma pentaphyllum Makino, a widely reputed medicinal plants in China, has been reported to have some neuroprotective effects via anti-oxidative stress and anti-inflammatory mechanisms. In the present study, we investigated the protective effect of GP against cerebral WMLs and the underlying mechanisms for its inhibition of cognitive decline in BCCAO rats. Adult male Sprague–Dawley rats were orally administered daily doses of 200 and 400mg/kg GP for 33days after BCCAO, and spatial learning and memory were assessed using the Morris water maze. Following behavioral testing, oxygen free radical levels and antioxidative capability were measured biochemically. The levels of lipid peroxidation and oxidative DNA damage were also assessed by immunohistochemical staining for 4-hydroxynonenal and 8-hydroxy-2′-deoxyguanosine, respectively. Activated astrocytes were also assessed by immunohistochemical staining and Western blotting with GFAP antibodies. The morphological changes were stained with Klüver–Barrera. Rats receiving 400mg/kg GP per day performed significantly better in tests for spatial learning and memory than saline-treated rats. GP 400mg/kg per day were found to markedly scavenge oxygen free radicals, enhance antioxidant abilities, decrease lipid peroxide production and oxidative DNA damage, and inhibit the astrocytic activation in corpus callosum and optic tract in BCCAO rats. However, GP 200mg/kg per day had no significant effects. GP may have therapeutic potential for treating dementia induced by chronic cerebral hypoperfusion and further evaluation is warranted. [Copyright &y& Elsevier]

Abstract: Histone deacetylase (HDAC) inhibitors induce chromatin destabilization. We sought to determine whether HDAC inhibition may amplify alkylator-induced mitotic cell death in multiple myeloma (MM) cells. The combination of SNDX-275, a class I HDAC inhibitor, with melphalan, showed a powerful synergism on growth inhibition with the combination index ranged from 0.27 to 0.75 in MM1.S and RPMI8226 cells. Their combinations as compared with either agent alone promoted much more caspase-dependent apoptosis. Flow cytometry analysis showed that SNDX-275 had minimal effects on cell cycle progression of MM1.S cells, but clearly increased the percentage of S phase in RPMI8226 cells associated with an upregulation in p21waf1 and a reduction in cyclin D1 and E2F1. Melphalan alone significantly arrested both MM1.S and RPMI8226 cells at S phase and enhanced expression of p53 and p21waf1. Furthermore, studies on DNA damage response revealed that phospho-histone H2A.X (γH2A.X), a hall marker of DNA double strand break, along with phosphorylated CHK1 (P-CHK1) and CHK2 (P-CHK2) was dramatically induced by SNDX-275 or melphalan. The increase in γH2A.X and P-CHK1 was considerably higher on combination than either agent alone. These molecular changes correlated well with the significant increase in mitotic catastrophe. Our data indicate that SNDX-275 synergistically enhances melphalan-induced apoptosis in MM cells via intensification of DNA damage, suggesting that SNDX-275 in combination with melphalan may be a novel therapeutic strategy for MM. [ABSTRACT FROM AUTHOR]

Abstract: FRAT1 was originally characterized as a protein frequently rearranged in advanced T cell lymphoma, which inhibits GSK-3-mediated phosphorylation of β-catenin and positively regulates the Wnt signaling pathway. FRAT1 has been identified as a proto-oncogene involved in tumorigenesis. Previous studies have shown that FRAT1 is strikingly overexpressed in some human cancers. However, the relationship between FRAT1 and human gliomas is unclear. In this study, we detected the expression of FRAT1 in human gliomas by immunohistochemistry, Western blot and RT-PCR. FRAT1 was found to be specifically expressed in the majority of glioma samples, and their expression levels increased markedly with the increase of WHO grades. In addition, there was a positive correlation between FRAT1 immunoreactivity score (IRS) and β-catenin IRS. Our results suggest that FRAT1 may be an important factor in the tumorigenesis and progression of gliomas, and could be used as a potential molecular marker for pathological diagnosis and a target for biological therapy. [Copyright &y& Elsevier]

• An algorithm for detecting the main fruit bearing branch of litchi in the natural environment was proposed. • A method for calculating the picking point of litchi's main fruit bearing branch was proposed. • The Precision of picking points calculation was 89.7%. • The roll angle error of the main fruit bearing branch was 11.28° ± 23.70°. The accurate identification of picking points is the key to the intelligent operation of litchi picking robot. To pick fruit, the robot must detect the location of picking point at first. To locate the location of picking points more accurately, this paper proposes a method of locating picking points based on the detection of litchi's main fruit bearing branch (MFBB). In the natural environment, the MFBB of litchi are similar to non-MFBB, so it is easy to get incorrect MFBB visual detection result that leads to the failure of robot picking. To identify litchi's MFBB in the natural environment quickly and accurately, this paper proposed a litchi's MFBB detection method based on the YOLACT. Firstly, litchi fruit and MFBB were connected as a litchi cluster label, and the data set of litchi cluster and MFBB was established, so the YOLACT model could learn the connection relationship between fruit and MFBB from the data set. Then, based on the detection result of litchi cluster and MFBB segmentation mask by this model, the pixel width difference between fruit and MFBB was used to segment the part of litchi cluster mask belonging to the MFBB, to obtain a more complete MFBB and improve the recall rate of MFBB. Finally, the middle point of the MFBB mask was taken as the picking point, and the angle of the MFBB was determined by skeleton extraction and the least square fitting method to provide a reference for robot picking posture. The experimental results showed that the precision of picking points calculated by this method was 89.7%, the F1 score was 83.8%, and the average running time of a single image was 0.154 s. Indicating that the proposed method has a good detection performance for the litchi picking points, and it can provide technical support for the visual recognition of the litchi picking robot. [ABSTRACT FROM AUTHOR]