Novel PIKfyve/Tubulin Dual-target Inhibitor as a Promising Therapeutic Strategy for B-cell Acute Lymphoblastic Leukemia

Objective:In B-cell acute lymphoblastic leukemia(B-ALL),current intensive chemotherapies for adult patients fail to achieve durable responses in more than 50%of cases,underscoring the urgent need for new therapeutic regimens for this patient population.The present study aimed to determine whether HZX-02-059,a novel dual-target inhibitor targeting both phosphatidylinositol-3-phosphate 5-kinase(PIKfyve)and tubulin,is lethal to B-ALL cells and is a potential therapeutic for B-ALL patients.Methods:Cell proliferation,vacuolization,apoptosis,cell cycle,and in-vivo tumor growth were evaluated.In addition,Genome-wide RNA-sequencing studies were conducted to elucidate the mechanisms of action underlying the anti-leukemia activity of HZX-02-059 in B-ALL.Results:HZX-02-059 was found to inhibit cell proliferation,induce vacuolization,promote apoptosis,block the cell cycle,and reduce in-vivo tumor growth.Downregulation of the p53 pathway and suppression of the phosphoinositide 3-kinase(PI3K)/AKT pathway and the downstream transcription factors c-Myc and NF-κB were responsible for these observations.Conclusion:Overall,these findings suggest that HZX-02-059 is a promising agent for the treatment of B-ALL patients resistant to conventional therapies.

Expression of vascular endothelial growth factors A and C in human pancreatic cancer

AIM： To study the expression of vascular endothelial growth factor A （VEGF-A） and VEGF-C and to determine whether the presence of VEGF-A and VEGF-C was associated with the clinicopathologic characteristics of pancreatic cancer. METHODS： VEGF-A and VEGF-C mRNA transcripts were examined by Northern blot in 6 human pancreatic cancer cell lines and 8 normal pancreatic tissues and 8 pancreatic carcinoma specimens. The expression of VEGF-A and VEGF-C proteins was examined by Western blot in the tested cell lines and by immunohistochemical stain in 50 pancreatic carcinoma samples. RESULTS： VEGF-A and VEGF-C mRNA transcripts were present in all the 6 human pancreatic cancer cell lines. Immunoblotting revealed the presence of VEGF-A and VEGF-C proteins in all the cell lines. Northern blot analysis of total RNA revealed 3.0-fold and 3.6-fold increase in VEGF-A and VEGF-C mRNA transcript in the cancer samples, respectively. Immunohistochemical analysis confirmed the expression of VEGF-A and VEGF-C in cancer cells within the tumor mass. Immunohistochemical analysis of 50 pancreatic cancer tissue samples revealed the presence of VEGF-A and VEGF-C immunoreactivity in 50% and 80% of the cancer tissue samples, respectively. The presence of VEGF-A in these cells was associated with larger tumor size and enhanced local spread （x^2= 6.690, P= 0.035〈0.05） but was not associated with decreased patient survival. However, the presence of VEGF-C in the cancer cells was associated with increased lymph node metastasis （x^2= 5.710, P= 0.017〈0.05）,but was not associated with decreased patient survival. There was no correlation between the expression of VEGF-A and VEGF-C in the same cancer cells. CONCLUSION： VEGF-A and VEGF-C are commonly overexpressed in human pancreatic cancer and may contribute to tumor growth and lymph node metastasis, There is no relationship between the expression of VEGF-A and VEGF-C in pancreatic cancer.

Ankle-brachial index as a predictor of all-cause and cardio- vascular disease mortality in 3733 Chinese patients with high cardiovascular risk

Objective To assess the association between 1-year risk of all-cause and cardiovascular disease （CVD） mortality and ankle-brachial index （ABI） in Chinese patients who were at high CVD risk. Methods Totally 3733 patients with high CV risk had bilateral ABI measurements at baseline and were followed up for 1-1.5 years. Patients were divided to four groups： 1） coronary heart disease （CHD）; 2） ischemic stroke （IS）; 3） diabetes mellitus （DM）; 4） very high risk group（VHR）, low ABI was defined as 〈0.9. Results A total of 3179 patients were analyzed. The prevalence of low ABI was 28.1%. At 1 year, all-cause mortality was 8.7%, and 27.6% was attributable to CVD; mortality due to CV events was 4.8% and 1.5%. After adjusting other risk factors the hazard ratio of low ABI was 1.623 for all-cause mortality and 2.304 for CVD mortality. Similar in patient with and without low ABI, respectively were found in four groups.Conclusion ABI is a strong and independent predictor ofrnortality. Patients with a low ABI have a substantially increased risk of all-cause mortality and CVD mortality （J Geriatr Cardio12010; 7：17-20）.

Auxiliary ball milling to prepare WS_(2)/graphene nanosheets composite for lithium-ion battery anode materials

A novel nano-WS_(2)/graphene nanosheets(GNSs)composite is obtained by ball milling with xylitol as auxiliary agent and hightemperature sintering.Xylitol improves the shear force during ball milling and well overcomes the van der Waals interactions between the interlayer of graphite and WS_(2).Through high-temperature calcination,GNSs and WS_(2) nanosheets can form tight interface contact.The produced WS_(2)/GNSs composites can be used as anode materials for lithium-ion batteries,while maintaining a high reversible specific capacity of 705 mAh·g^(-1)with the capacity retention of 95%at a current density of 250 mA·g^(-1)after 200 cycles,mainly because WS_(2)/GNSs composites have a higher Li^(+)diffusion coefficient of 2.2×10^(-9)cm^(2)·s^(-1)and a higher specific surface area of 70.10 m^(2)·g^(-1).As a result,the xylitol-assisted ball milling method designed in this work is suitable for extended preparation of peeling of two-dimensional layer materials into nanosheets.

Left epigastric isolated tumor fed by the inferior phrenic artery diagnosed as ectopic hepatocellular carcinoma:A case report

BACKGROUND Hepatocellular carcinoma(HCC)is one of the most frequent cancers and the main cause of cancer-related death worldwide.Ectopic HCC,an extremely rare type of HCC,exhibits a wide range of clinical signs and radiographic features,making preoperative identification challenging.CASE SUMMARY A 47-year-old man underwent routine abdominal color ultrasonography,which identified an asymptomatic tumor in the left upper abdomen.The patient had no history of hepatitis,did not drink alcohol,and had no family history of cancer.Abdominal contrast-enhanced computed tomography(CT)revealed a heterogeneously enhanced lesion between the spleen and stomach that had invaded the diaphragm,with blood supplied by the left inferior phrenic artery.The patient underwent laparoscopic surgery,and HCC was identified by postoperative pathology.Additionally,specific immunohistochemical staining was performed to assess the molecular biological characteristics of the HCC.The patient underwent two rounds of hepatic arterial interventional chemotherapy after surgery.Abdominal plain and enhanced magnetic resonance imaging and lung CT 3 mo postoperatively revealed no signs of local recurrence or distant metastasis.CONCLUSION This asymptomatic ectopic HCC case described achieved an excellent result due to early detection,radical resection,and systematic surveillance.

结肠腺癌组织中CDX2、OPN的表达及意义

目的探讨尾型同源盒转录因子2(CDX2)与骨桥蛋白(OPN)在结肠腺癌组织的表达及其临床意义。方法采用免疫组织化学链霉菌抗生物素蛋白-过氧化物酶连接法检测CDX2和OPN在58例结肠腺癌组织、30例结肠腺瘤组织、30例癌旁正常结肠组织中的表达,了解CDX2、OPN与结肠腺癌患者临床病理特征的关系,并分析两者的相关性。结果 CDX2在结肠腺癌、结肠腺瘤、正常结肠组织中阳性表达率分别为62.1%(36/58)、86.7%(26/30)和93.3%(28/30),结肠腺癌组织中的阳性表达率低于结肠腺瘤和正常结肠组织(P<0.05)。OPN在结肠腺癌、结肠腺瘤、正常结肠组织中阳性表达率分别为74.1%(43/58)、40.0%(12/30)和26.7%(8/30),OPN在结肠腺癌组织中的表达阳性表达率高于结肠腺瘤和正常结肠组织(P<0.05)。CDX2阳性表达率与患者肿瘤浸润深度、分化程度相关(P<0.05);OPN阳性表达率与浸润深度、有无淋巴结转移相关(P<0.05),与患者年龄、性别、肿瘤形态无关(P>0.05)。通过Spearman相关分析,结肠腺癌组织中CDX2与OPN的表达呈负相关(P<0.05)。结论 CDX2、OPN的表达可能与结肠腺癌的发生、发展及预后相关,且两者在结肠腺癌组织的表达呈负相关,联合检测可能对结肠癌早期诊断、预后评估具有一定指导意义。

Burnup analysis for the pebble-bed fluoride-salt-cooled high-temperature reactor based on the energy-dependent elastic scattering cross-sectional model

To carry out accurate burnup calculations for a pebble-bed fluoride-salt-cooled high-temperature reactor,the energy-dependent cross-sectional model based on the Doppler broadening rejection correction method has been proposed to develop the energy-dependent elastic scattering cross-sectional model. In this study, the Monte Carlo continuous energy code PSG2/Serpent was used to examine the difference between the constant cross-sectional model and the energy-dependent cross-sectional model during burnup. For the cases analyzed in this study,numerical simulations show that the multiplication coefficient was improved by hundreds pcm and ^(239)Pu concentration was improved by approximately 1–2% during burnup when the energy-dependent elastic scattering crosssectional model is considered.

Effects of Al contents on microstructure and properties of hot-dip Zn-Al alloy coatings on hydrogen reduced hot-rolled steel without acid pickling

A new hot-dip galvanizing method was employed on hot-rolled low carbon steel.The effects of Al contents on microstructure,micro-hardness and corrosion resistance of Zn-Al alloy coatings were systematically investigated.Phase composition,microstructure and element distribution in Zn-Al alloy coatings were analyzed using X-ray diffraction（XRD）and electron probe micro analysis（EPMA）,respectively.It is found that Al content（0.6-6.0 wt.%）in galvanizing zinc affects surface quality and adhesion between coatings and matrix in the newly developed method.In addition,with increasing Al content,micro-hardness significantly increased due to the increase in Zn-Al eutectoid phases.Potentiodynamic polarization and electrochemical impedance spectroscopy（EIS）also revealed that increase in Al plays a noticeable role in improving the corrosion resistance of Zn-Al alloy coatings.

Effects of Coiling Temperature and Cooling Condition on Transformation Behavior of Tertiary Oxide Scale

The influences of coiling temperature and cooling condition on structural transformation of the hot-rolled tertiary oxide scale formed under continuous cooling conditions were studied by thermal gravimetric analyzer. The fourth oxide scale formed under different conditions were classified and plotted. Because the oxide scale structure transformation is diffusion-controlled and the transformation law is similar to ＂C＂ curve, the eutectoid transformation nose temperature is 450 ℃. Under condition of low temperature and high cooling rate, ion diffusion behavior is restricted so that the eutectoid reaction is suppressed, resulting in that the fourth oxide scale is mainly made up of pre-eutectoid Fe304 and FeO without eu- tectoid products. From scale structure transition diagram, the eutectoid reaction process was affected by coiling temperature and cooling rate, leading to various scale structures.

Effective and Robust Detection of Adversarial Examples via Benford-Fourier Coefficients

Adversarial example has been well known as a serious threat to deep neural networks(DNNs).In this work,we study the detection of adversarial examples based on the assumption that the output and internal responses of one DNN model for both adversarial and benign examples follow the generalized Gaussian distribution(GGD)but with different parameters(i.e.,shape factor,mean,and variance).GGD is a general distribution family that covers many popular distributions(e.g.,Laplacian,Gaussian,or uniform).Therefore,it is more likely to approximate the intrinsic distributions of internal responses than any specific distribution.Besides,since the shape factor is more robust to different databases rather than the other two parameters,we propose to construct discriminative features via the shape factor for adversarial detection,employing the magnitude of Benford-Fourier(MBF)coefficients,which can be easily estimated using responses.Finally,a support vector machine is trained as an adversarial detector leveraging the MBF features.Extensive experiments in terms of image classification demonstrate that the proposed detector is much more effective and robust in detecting adversarial examples of different crafting methods and sources compared to state-of-the-art adversarial detection methods.