High-throughput studies and machine learning for design of β titanium alloys with optimum properties

Based on experimental data,machine learning(ML) models for Young's modulus,hardness,and hot-working ability of Ti-based alloys were constructed.In the models,the interdiffusion and mechanical property data were high-throughput re-evaluated from composition variations and nanoindentation data of diffusion couples.Then,the Ti-(22±0.5)at.%Nb-(30±0.5)at.%Zr-(4±0.5)at.%Cr(TNZC) alloy with a single body-centered cubic(BCC) phase was screened in an interactive loop.The experimental results exhibited a relatively low Young's modulus of(58±4) GPa,high nanohardness of(3.4±0.2) GPa,high microhardness of HV(520±5),high compressive yield strength of(1220±18) MPa,large plastic strain greater than 30%,and superior dry-and wet-wear resistance.This work demonstrates that ML combined with high-throughput analytic approaches can offer a powerful tool to accelerate the design of multicomponent Ti alloys with desired properties.Moreover,it is indicated that TNZC alloy is an attractive candidate for biomedical applications.

The flavonoid glycoside vaccarin inhibits adipogenesis and stimulates lipolysis via Hedgehog signaling in 3T3-L1 adipocytes

Vaccarin,a flavonoid glycoside isolated from Vaccaria segetalis,is non-toxic to 3T3-L1 cells up to concentrations of 200μM.Accordingly,we investigated the effects of this natural product on adipogenesis and lipolysis in 3T3-L1 adipocytes.Our results revealed that vaccarin significantly inhibited lipid accumulation by suppressing the adipogenesis-related transcription factors peroxisome proliferator-activated receptorγ(PPARγ)and the CCAAT/enhancer-binding proteinα(C/EBPα).Specifically,lipid accumulation decreased by up to 27.7±2.7%when 3T3-L1 adipocytes were treated with a 10μM concentration of vaccarin.Mechanistic studies showed that the compound inhibited adipogenesis through activation of the Hedgehog(Hh)signaling pathway and so restoring Smo and Gli1 expression at an early stage of differentiation.In mature 3T3-L1 cells,vaccarin significantly increased the secretion of glycerol into the surrounding medium and thus indicating that it accelerated the degradation of triglycerides.In addition,vaccarin,was shown to enhance lipolysis through stimulation of the transcription levels of lipoprotein lipase,monoglycerides lipase,adipose triacylglyceride lipase,hormone-sensitive lipase and adipose differentiated-related protein.All told,vaccarin suppressed lipid accumulation and enhanced lipolysis during adipocyte differentiation by restoring Hh signaling.As such,it is a phytochemical capable of halting adipocyte hyperplasia and,thereby,ameliorating the effects of obesity.

难熔多组元Ti−Nb−Zr−W合金随成分变化弹塑性和扩散性能的高通量探索

组合材料合成和分析方法能够很好地描述Ti−Nb−Zr−W体系难熔多元合金的弹塑性和扩散特性。在1273 K温度固溶退火25 h后制备6组Ti−Nb−Zr−W四元扩散偶,并对其开展电子探针显微分析和纳米压痕测试。随后,采用Oliver−Pharr和反向分析算法等方法获得Ti−Nb−Zr−W体系宽广成分范围的随成分变化弹塑性。此外,采用机器学习和实用高效数值回归方法分别建立Ti−Nb−Zr−W体系体心立方相的弹塑性和互扩散系数数据库。同时,提出由杨氏模量与主互扩散系数之比所定义的热加工性能参数来评估热加工过程行为。最后,讨论难熔多元合金的耐磨性并进行实验验证。结果表明,低钨含量的富Ti难熔多元合金具有高硬度、良好的耐磨性、高应力和良好的热加工性能,而高钨含量并不能改善富Ti难熔合金的弹塑性。

Effects of cardiopulmonary bypass on tight junction protein expressions in intestinal mucosa of rats

AIM： To investigate the tight junction protein expressions of intestinal mucosa in an experimental model of cardiopulmonary bypass （CPB） in rats. METHODS： Thirty anesthetized rats were randomly divided into two groups： Group S （n = 10） served as sham operation and group C （n = 20） served as CPB which underwent CPB for 1 h. Expression of occludin and zonula occludens-1 （ZO-1） were determined by Western blotting and immunotochemistry, respectively. Plasma levels of diamine oxidase （DAO） and d-lactate were determined using an enzymatic spectrophotometry. RESULTS： Immunohistochemical localization of occludin and ZO-1 showed disruption of the tight junctions in enterocytes lining villi at the end of CPB and 2 h after CPB. The intensities of the occludin and ZO-i at the end of CPB were lower than those of control group （76.4% ± 22.5% vs 96.5% ± 28.5% and 62.4% ± 10.1% vs 85.5% ±25.6%, P 〈 0.05） and were further lower at 2 h after CPB （50.5% ± 10.5% and 45.3% ± 9.5%, P 〈 0.05）. Plasma d-lactate and DAO levels increased significantly （8.688 ± 0.704 vs 5.745 ± 0.364 and 0.898 ± 0.062 vs 0.562 ± 0.035, P 〈 0.05） at the end of CPB compared with control group and were significantly higher at 2 h after CPB than those at the end of CPB （9.377 ± 0.769 and 1.038 ± 0.252, P 〈 0.05）. There were significant negative correlations between occludin or ZO-1 expression and DAO （r^2 = 0.5629,r^2 = 0.5424, P 〈 0.05） or d-lactate levels （r^2 = 0.6512,r^2 = 0.7073, P 〈 0.05） both at the end of CPB and 2 h after CPB. CONCLUSION： CPB markedly down-regulates the expression of occludin and ZO-1 proteins in intestinal mucosa of rats. The close correlation between expression of tight junctions （TJs） and plasma levels of DAO or d-lactate supports the hypothesis that intestinal permeability increases during and after CPB because of decreases in the expressions of TJs.

Lactate Promotes Cancer Stem-like Property of Oral Sequamous Cell Carcinoma

Accumulation of lactate in tumor has been linked to poor prognosis of oral squamous cell carcinoma (OSCC), but the underlying mechanism remained largely uncertain. Previous studies have suggested that presence of cancer stem cells (CSCs) closely correlated with cellular malignancy of OSCC. Here, using 3D organoid culture model, we investigated whether lactate promoted CSCs phenotype in primary OSCC cells. We generated organoids using fresh OSCC specimens and verified that organoids recapitulated histopathology and cellular heterogeneity of parental tumor;Organoids were then transfected with a Wnt reporter to visualize Wnt activity. The sphere forming assay demonstrated that high Wnt activity functionally designated CSCs population in OSCC cells. Further investigations indicated that lactate treatment promoted Wnt activity and increased the expression of CSCs (i.e. CD133^+ cells) in organoids. Moreover, silencing monocarboxylate transporter 1 (MCT1), the prominent path for lactate uptake in human tumor with siRNA significantly impaired organoid forming capacity of OSCC cells. Together, our study demonstrated that lactate can promote CSCs phenotype of OSCC,and MCT1 may be a therapeutic target against OSCC growth.

Investigation of mechanical and diffusion properties in bcc Ti−Nb−Zr−Sn alloys via a high-throughput method

The mechanical and diffusion properties of bcc Ti−Nb−Zr−Sn alloys in the Ti-rich corner were analyzed through a high-throughput method with the combination of nanoindentation and diffusion couple techniques.Nine groups of quaternary Ti−Nb−Zr−Sn diffusion couples were prepared after annealing at 1273 K for 25 h.The composition-dependent mechanical properties were determined by nanoindentation and electron probe microanalysis(EPMA)techniques.Moreover,the corresponding interdiffusion coefficients were confirmed from the composition gradients of the quaternary diffusion couples using a pragmatic numerical inverse method.A composition-dependent database on the mechanical and diffusion properties was utilized to discuss the processability during the hot working.The results reveal that the solute elements Nb and Sn are strictly controlled to increase the hardness and wear resistance of Ti−Nb−Zr−Sn alloys,and the additional element Zr is mainly useful to improve the processability during the hot working.

High-throughput determination of mechanical and diffusion properties of Ti–Ta–Fe alloys

The mechanical and diffusion properties of Ti-Ta-Fe alloys in the Ti-rich region were investigated by utilizing a high-throughput method, with the combination of nanoindentation and diffusion couple techniques.Five groups of ternary Ti-Ta-Fe diffusion couples were prepared after annealing at 1273 K for 25 h. The composition-dependent mechanical properties of bcc Ti-Ta-Fe system were experimentally determined by means of nanoindentation and electron probe microanalysis(EPMA) techniques. Moreover, the interdiffusion coefficients of Ti-Ta-Fe alloys at 1273 K were confirmed from the composition gradients of the ternary diffusion couples with the support of a pragmatic numerical inverse method. A composition-dependent database on the mechanical and diffusion properties of Ti-Ta-Fe alloys was carefully established and utilized for the discussion of the processability during the hot working. The results indicated that the content of Fe should be controlled for the Ti alloys with high hardness and low Young’s modulus.

Localization of Distributed Fiber Sensor Employing a Sub-Ring

A simple distributed optical fiber sensing system used to monitor vibration signal has an additional sub-loop eoupled with main ring by a 3 dB coupler. This paper compares three outputting interfered beams, each of them travels in the sub-ring 0, 1, 2 times, separately. Using the simultaneous equations produced by those three outputs, we find the relation between the interference lights and vibration signal＇s characteristics, such as frequency, amplitude and position. Through simplifying and calculating, the vibration position can be obtained finally.

Primary renal small cell carcinoma:A case report

BACKGROUND Small cell carcinoma(SCC)is a malignant tumour that is frequently accompanied by extensive metastasis.Primary renal SCC has typical characteristics related to SCC and is extremely rare,with no uniform treatment standard.Clinical treatment is mainly based on the literature.Here we report the diagnosis and treatment of an interesting case of primary renal SCC.CASE SUMMARY We report a tortuous course of treatment for a 68-year-old man.Four years before diagnosis,the patient developed continuous gross haematuria,during which he underwent several ureteral biopsies,ureteral stricture relief,and urine exfoliated cell examinations;however,SCC was not confirmed.One month before radical resection of the renal pelvic carcinoma,the severe haematuria recurred.Computed tomography revealed transitional cell carcinoma in the right kidney and right upper ureter.A preoperative examination exluded the possibility of a pulmonary origin of the tumour,and primary renal SCC was diagnosed.The postoperative pathology findings were suggestive of SCC.The patient was treated with combined chemotherapy but died of tumour progression at 7 mo postoperative.CONCLUSION Our patient's disease onset in the context of a succession of regular testing and the fact that it occurred so quickly with perirenal encroachment immediately after diagnosis reveals the cruel and unforgiving side of the disease.Furthermore,patients with poor comprehensive treatment results require new treatment regimens.

Thyroid follicular renal cell carcinoma excluding thyroid metastases:A case report

BACKGROUND Thyroid follicular renal cell carcinoma is a special type of renal cell carcinoma newly recognized in recent years.It has attracted attention because of its unique histology,immunophenotype,and clinical characteristics.It has a very low incidence,and the number of case reports available for review is limited.Moreover,a thyroid mass with type of tumour is rare.CASE SUMMARY We report a case of a renal mass with a bilateral thyroid mass that was accidentally discovered in a 60-year-old man during physical examination.B-mode ultrasound showed a hypoechoic mass in the middle and lower parenchyma of the right kidney,and computed tomography showed an iso-density shadow tumour in the right kidney.Contrast agents had a significant continuous enhancement effect on the tumour,and the enhancement was not uniform.After partial nephrectomy,pathological analysis was performed to rule out the possibility that the renal tumour was caused by thyroid tumour metastasis.Needle biopsy of the thyroid tumour confirmed that the renal cell carcinoma was not related to the thyroid tumour.The patient was alive at the last postoperative follow-up.CONCLUSION This is the third published case in which thyroid tumour biopsy was performed to confirm that thyroid follicular renal cell carcinoma is not thyroid related.

Discovery of a novel EGFR ligand DPBA that degrades EGFR and suppresses EGFR-positive NSCLC growth

Epidermal growth factor receptor(EGFR)activation plays a pivotal role in EGFR-driven non-small cell lung cancer(NSCLC)and is considered as a key target of molecular targeted therapy.EGFR tyrosine kinase inhibitors(TKIs)have been canonically used in NSCLC treatment.However,prevalent innate and acquired resistances and EGFR kinase-independent pro-survival properties limit the clinical efficacy of EGFR TKIs.Therefore,the discovery of novel EGFR degraders is a promising approach towards improving therapeutic efficacy and overcoming drug resistance.Here,we identified a 23-hydroxybetulinic acid derivative,namely DPBA,as a novel EGFR small-molecule ligand.It exerted potent in vitro and in vivo anticancer activity in both EGFR wild type and mutant NSCLC by degrading EGFR.Mechanistic studies disclosed that DPBA binds to the EGFR extracellular domain at sites differing from those of EGF and EGFR.DPBA did not induce EGFR dimerization,phosphorylation,and ubiquitination,but it significantly promoted EGFR degradation and repressed downstream survival pathways.Further analyses showed that DPBA induced clathrin-independent EGFR endocytosis mediated by flotillin-dependent lipid rafts and unaffected by EGFR TKIs.Activation of the early and late endosome markers rab5 and rab7 but not the recycling endosome marker rab11 was involved in DPBA-induced EGFR lysosomal degradation.The present study offers a new EGFR ligand for EGFR pharmacological degradation and proposes it as a potential treatment for EGFR-positive NSCLC,particularly NSCLC with innate or acquired EGFR TKI resistance.DPBA can also serve as a chemical probe in the studies on EGFR trafficking and degradation.

Determination of vanadyl sulfate ion-pair dissociation constant at 298.15 K by Fuoss method

Vanadium battery has fast and large capacity charge and discharge characteristics, and the concentration and stability of the battery electrolyte are the key to the electrolyte performance. In actual, with higher acidity and higher concentration of the vanadium battery electrolyte, the ion-pair is dominant. The ion-pair dissociation constant is one of the important thermodynamic data related to battery performance. The vanadyl sulfate conductivity in aqueous solution was determined using the conductance method at 298.15K. Using the origin data fitting, the limiting molar conductance is obtained, and then by the improved Ostwald dilution law and the Davies equation, the activity coefficient is solved so as to obtain the ionic strength of the true solution. Using the Fuoss method, the dissociation constant of vanadyl sulfate ion-pair was calculated. At last, the vanadyl sulfate limiting molar conductance (Λ 0 ) is 174.8251748 S·dm2·mol?1, and the vanadyl sulfate ion-pair dissociation constant K d is 0.002636367, and then other thermodynamic properties can be studied.

A facile synthesis of cajaninstilbene acid and its derivatives

A four-step synthesis of methyl 6-formyl-2-hydroxy-4-methoxy-3-(3-methylbut-2-en-1-yl)benzoate(11)that can be used as building block for a facile synthesis of cajaninstilbene acid and its derivatives is reported.The synthesis of cajaninstilbene acid was accomplished in six steps with an overall yield of 20%starting from commercial materials by a synthesis whose key steps are TiCl4-mediated[3+3]cyclization and McMurry coupling.

Self-etching adhesives:possible new pulp capping agents to vital pulp therapy

Pulp capping is one of the solving for keeping vital pulp in the case of dentin caries,reversible pulpitis or traumatic pulp exposure.The presence of bacteria on the cavity walls or in the pulp was the major factor that leads to the failure of pulp capping.Traditional pulp capping agent,calcium hydroxide,may not prevent microleakage.Selfetching system is a newly developed adhesive system,which could provide less microleakage and would not break down or dissolve,preventing the oral fluids and bacteria from the pulp along the cavity wall.This may reduce such clinical problems as postoperative sensitivity,secondary caries and marginal discoloration.Researches showed that some kinds of self-etching adhesives induced the mild to moderate inflammatory pulp response,with negative bacterial staining.Inclusion of antibacterial components into self-etching system,such as 12-methacryloyloxydodecylpyridinium bromide(MDPB)may inhibit bacteria and provide better clinical effects.It is speculated that using the self-etching adhesive system containing the antibacterial agent,such as MDPB,to the dental pulp directly or indirectly,may inhibit bacteria after the placement of restoration as well as residual bacteria in the cavity.