The enhancing effect and promoting mechanisms of the stereoisomeric monoterpene alcohol esters as enhancers for drugs with different physicochemical properties

To explore the structure-activity connections of amphiphilic permeation enhancers containing the length of the hydrophobic chains as well as the properties of the polar head,O-acylgeraniol and O-acylnerol derivatives were synthesized from geraniol/nerol(cis-isomer of geraniol) and pharmaceutical excipient acids in this research. Their promotion of the percutaneous absorption of three drugs as the model, flurbiprofen(FP), isosorbide dinitrate(ISDN) and donepezil(DNP), which were selected based on their physicochemical properties,was tested by in vitro skin penetration and in vivo. Molecular simulation, ATR-FTIR, CLSM and histological observation were implement to evaluate the mode of action of the enhancers.The results indicated that(E)-3,7-dimethyl-2,6-octadien-1-yl tetradecanoate(GER-C14, trans-)achieved the highest enhancement ability for the three drugs;additionally, the in vivo results obtained were in good correlation with the in vitro data. Molecular docking results suggested that enhancers loosen the hydrogen bonds between ceramides, and the results of molecular simulation indicated that GER-C14, NER-C14 could insert into the middle of the lipid bilayer to form an independent phase. According to ATR-FTIR and histological evaluation, the enhancers extracted lipids and influenced the protein region, thereby disturbing the skin array. In addition, CLSM described the dynamic effects of enhancers on lipids between stratum corneum(SC) cells. In conclusion, GER-C14 had a better penetration promotion effect, which broadened our understanding of stereoisomeric penetration enhancers.

Coherent beam combining of two all‑PM thulium‑doped fiber chirped pulse amplifiers

In this paper,we report a coherent beam combining(CBC)system that involves two thulium-doped all-polarization maintaining(PM)fiber chirped pulse amplifiers.Through phase-locking the two channels via a fiber stretcher by using the stochastic parallel gradient descent(SPGD)algorithm,a maximum average power of 265 W is obtained,with a CBC efficiency of 81%and a residual phase error of λ/17.After de-chirping by a pair of diffraction gratings,the duration of the combined laser pulse is compressed to 690 fs.Taking into account the compression efficiency of 90%and the main peak energy proportion of 91%,the corresponding peak power is calculated to be 4 MW.The laser noise characteristics before and after CBC are examined,and the results indicate that the CBC would degrade the low frequency relative intensity noise(RIN),of which the integration is 1.74%in[100 Hz,2 MHz]at the maximum combined output power.In addition,the effects of the nonlinear spectrum broadening during chirped pulse amplification on the CBC efficiency are also investigated,showing that a higher extent of pulse stretching is effective in alleviating the spectrum broadening and realizing a higher output power with decent combining efficiency.

白细胞介素-37在结肠癌组织中的表达及其对结肠癌细胞增殖、侵袭的作用

目的探讨白细胞介素-37(IL-37)在结肠癌组织中表达的变化,并通过体外实验探讨其对结肠癌细胞增殖、侵袭的作用。方法收集2017年4月—2019年4月在西安市第四医院手术切除的结肠癌组织及对应的癌旁组织,检测其IL-37的表达量;培养结肠癌HT29细胞,随机分为对照组、转染空白pcDNA3.1质粒的空白质粒组、转染表达IL-37的pcDNA3.1重组质粒的IL-37质粒组,MTS检测3组结肠癌HT29细胞的增殖能力,Transwell实验检测细胞的侵袭能力,qRT-PCR检测细胞周期蛋白D1(CyclinD1)、B淋巴细胞瘤-2(Bcl-2)、基质金属蛋白酶2(MMP-2)、基质金属蛋白酶9(MMP-9)mRNA相对表达量,Western blotting法检测IL-37、p-STAT3及p-Akt蛋白相对表达量。结果结肠癌组织中IL-37的蛋白相对表达量低于癌旁组织(P <0.05);3组细胞增殖及侵袭能力,CyclinD1、Bcl-2、MMP-2、MMP-9 mRNA相对表达量,p-STAT3、p-Akt的蛋白相对表达量比较,差异有统计学意义(P <0.05),IL-37质粒组的细胞增殖及侵袭能力,CyclinD1、Bcl-2、MMP-2、MMP-9 mRNA相对表达量,p-STAT3、p-AKT的蛋白相对表达量均低于对照组、空白质粒组。结论 IL-37在结肠癌组织中表达减少,上调IL-37的表达能够抑制结肠癌细胞的增殖、侵袭,该抑制作用可能与抑制STAT3/Akt通路有关。

胃癌组织SOX1和β-catenin的表达及其与临床病理特征、远期预后的相关性

目的探讨胃癌组织性别决定区Y框蛋白1(SOX1)和β-连环蛋白(β-catenin)的表达及其与临床病理特征、远期预后的相关性。方法收集2015年2月—2017年3月在西安市第四医院行胃癌根治术或姑息性切除术患者的胃癌组织及癌旁组织,采用免疫组织化学染色检测SOX-1、β-catenin的阳性表达;Western blotting检测SOX-1、β-catenin蛋白相对表达量;随访患者的总体生存情况。结果胃癌组织SOX1的阳性表达率低于癌旁组织(P<0.05),β-catenin的阳性表达率高于癌旁组织(P<0.05);胃癌组织SOX1蛋白相对表达量低于癌旁组织(P<0.05),β-catenin蛋白相对表达量高于癌旁组织(P<0.05);胃癌组织SOX1蛋白相对表达量与β-catenin蛋白相对表达量呈正相关(r=0.347,P=0.017);低分化,TNMⅢ、Ⅳ期,有淋巴结转移胃癌组织SOX1的阳性表达率低于中、高分化,TNMⅠ、Ⅱ期,无淋巴结转移胃癌组织(P<0.05);低分化,TNMⅢ、Ⅳ期,有淋巴结转移胃癌组织β-catenin的阳性表达率高于中、高分化,TNMⅠ、Ⅱ期,无淋巴结转移胃癌组织(P<0.05);与SOX1阴性表达患者比较,SOX1阳性表达患者的总生存期延长(P<0.05);与β-catenin阴性表达患者比较,β-catenin阳性表达患者的总生存期缩短(P<0.05)。结论胃癌组织中SOX1的低表达与β-catenin的高表达有关且与临床病理特征、远期预后的恶化相关。

Genome-wide comparative analysis of type-A Arabidopsis response regulator genes by overexpression studies reveals their diverse roles and regulatory mechanisms in cytokinin signaling

Cytokinin is a critical growth regulator for various aspects of plant growth and development. In Arabidopsis, cytokinin signaling is mediated by a two-component system-based phosphorelay that transmits a signal from the receptors, through histidine phosphotransfer proteins, to the downstream response regulators （ARRs）. Of these ARRs, type-A ARR genes, whose transcription can be rapidly induced by cytokinin, act as negative regulators of eytokinin signaling. However, because of functional redundancy, the function of type-A ARR genes in plant growth and development is not well understood by analyzing loss-of-function mutants. In this study, we performed a comparative functional study on all ten type-A ARR genes by analyzing transgenic plants overexpressing these ARR genes fused to a MYC epitope tag. Overexpression of ARR genes results in a variety of cytokinin-associated phenotypes. Notably, overexpression of different ARR transgenes causes diverse phenotypes, even between phylogenetically closely-related gene pairs, such as within the ARR3-ARR4 and ARR5-ARR6 pairs. We found that the accumulation of a subset of ARR proteins （ARR3, ARR5, ARR7, ARR16 and ARR17; possibly ARR8 and ARR15） is increased by MG132, a specific proteasomal inhibitor, indicating that stability of these proteins is regulated by proteasomal degradation. Moreover, similar to that of previously characterized ARR5, ARR6 and ARR7, stability of ARR16 and ARR17, possibly including ARR8 and ARR15, is regulated by cytokinin. These results suggest that type-A ARR proteins are regulated by a combinatorial mechanism involving both the cytokinin and proteasome pathways, thereby executing distinctive functions in plant growth and development.

Experimental research on overlying strata movement and fracture evolution in pillarless stress-relief mining

In multiple seams mining, the seam with relatively low gas content （protective seam） is often extracted prior to mining its overlying and/or underlying seams of high gas content and low permeability to minimize the risk of high gas emission and outbursts of coal and gas. A key to success with this mining sequence is to gain a detailed understanding of the movement and fracture evolution of the overlying and underlying strata after the protective seam in extracted. In Zhuji mine, the No. 11-2 seam is extracted as a protective seam with the pillarless mining method by retaining goal-side roadways prior to its overlying No. 13-1 seam. An investigation has been undertaken in the panel 1111 （1） of Zhuji mine to physically simulate the movement and fracture evolution of the overlying strata alter the No. 1 I-2 seam is extracted. In the physical simulation, the displacement, strain, and deformation and failure process of the model for simulation were acquired with various means such as grating displacement meter, strain gauges, and digital photography. The simulation result shows that： （1） Initial caving interval of the immediate roof was 21.6 m, the first weighting interval was 23.5-37.3 m with the average interval of 33.5 m, and the periodic weighting interval of the main roof was in a range of 8.2-20.55 m and averaged at 15.2 m. （2） The maximum height of the caving zone after the extraction of No. 11-2 seam was 8.0 m, which was 4 times of the seam mining height and the internal strata of the caving zone collapsed irregularly. The mining-induced fractures developed 8-30 m above the mined No. 11-2 seam, which was 7.525 times of the seam mining height, the fracture zone was about 65° upward from the seam open-off cut toward the goaf, the height of longitudinal joint growth was 4-20 times of the mining seam height, and the height of lateral joint growth was 20-25 times of the mining seam height. （3） The ＂arch-in-arch＂ mechanical structure of the internal goaf was bounded by an expansion angle of broken strata in the lateral direction of the retained goaf-side roadway. The spatial and temporal evolution regularities of over- burden＇s displacement field and stress field, dynamic development process and distribution of fracture field were analyzed. Based on the simulation results, it is recommended that several goaf drainage methods, i.e. gas drainage with buried pipes in goaf, surface goaf gas drainage, and cross-measure boreholes, should be implemented to ensure the safe mining of the panel 1111 （1）.

支气管肺泡灌洗在老年慢性阻塞性肺疾病合并重症肺炎患者中的价值研究

目的探讨肺泡灌洗术在老年慢性阻塞性肺疾病(COPD)合并重症肺炎患者治疗中的临床价值及预后。方法选取2017年1月—2020年1月永康市第一人民医院重症医学科收治的老年COPD合并重症肺炎患者118例,根据随机数字表法分为对照组和观察组,每组59例。对照组患者给予常规治疗,观察组患者在对照组基础上给予支气管肺泡灌洗(BAL)治疗。比较两组患者临床症状消失时间、抗菌药物使用时间、住院时间、血氧指标、临床疗效及病死率。结果观察组患者临床症状消失时间、抗菌药物使用时间及住院时间均短于对照组(P<0.05)。两组患者治疗前后pH值的差值比较,差异无统计学意义(P>0.05);观察组治疗前后PaO_(2)、SpO_(2)、PaCO_(2)的差值大于对照组(P<0.05)。观察组临床疗效好转率高于对照组(P<0.05),病死率低于对照组(P<0.05)。结论老年COPD合并重症肺炎患者应用BAL治疗,能够有效缩短临床症状消失时间,缩短抗菌药物使用时间及住院时间,改善肺部血液循环,提高患者预后和生存率。

CO_(2)storage with enhanced gas recovery(CSEGR):A review of experimental and numerical studies

CO_(2)emission mitigation is one of the most critical research frontiers.As a promising option of carbon capture,utilization and storage(CCUS),CO_(2)storage with enhanced gas recovery(CSEGR)can reduce CO_(2)emission by sequestrating it into gas reservoirs and simultaneously enhance natural gas production.Over the past decades,the displacement behaviour of CO_(2)—natural gas has been extensively studied and demonstrated to play a key role on both CO_(2)geologic storage and gas recovery performance.This work thoroughly and critically reviews the experimental and numerical simulation studies of CO_(2)displacing natural gas,along with both CSEGR research and demonstration projects at various scales.The physical property difference between CO_(2)and natural gas,especially density and viscosity,lays the foundation of CSEGR.Previous experiments on displacement behaviour and dispersion characteristics of CO_(2)/natural gas revealed the fundamental mixing characteristics in porous media,which is one key factor of gas recovery efficiency and warrants further study.Preliminary numerical simulations demonstrated that it is technically and economically feasible to apply CSEGR in depleted gas reservoirs.However,CO_(2)preferential flow pathways are easy to form(due to reservoir heterogeneity)and thus adversely compromise CSEGR performance.This preferential flow can be slowed down by connate or injected water.Additionally,the optimization of CO_(2)injection strategies is essential for improving gas recovery and CO_(2)storage,which needs further study.The successful K12—B pilot project provides insightful field-scale knowledge and experience,which paves a good foundation for commercial application.More experiments,simulations,research and demonstration projects are needed to facilitate the maturation of the CSEGR technology.

Prognostic significance of systemic immune-inflammation index in patients with intrahepatic cholangiocarcinoma undergoing hepatic resection

BACKGROUND The prognosis of intrahepatic cholangiocarcinoma(ICC)patients following surgical resection remains poor.It is necessary to investigate effective biomarkers or prognostic models for ICC patients.AIM To investigate the prognostic effect of systemic immune-inflammation index(SII)to predict long-term outcomes in ICC patients with undergoing hepatic resection.METHODS Consecutive ICC patients who underwent initial hepatectomy with curative intent from January 2009 to September 2017 were retrospectively reviewed.Receiver-operating characteristic(ROC)curves were used to determine the optimal cut-off values of SII.Kaplan-Meier curves and Cox proportional hazards regression were performed to evaluate the discriminative ability of preoperative SII in predicting overall survival(OS)and recurrence-free survival(RFS).RESULTS A total of 530 patients were included and randomly divided into derivation(n=265)and validation cohort(n=265).The optimal cut-off value for SII was 450.Ata median follow-up of 18 mo(range,1-115.4 mo),317(59.8%)patients died and381(71.9%)patients experienced tumor relapse.Low SII level was associated with better OS and RFS(both P<0.05).Multivariate analyses identified multiple tumors,node invasion and high SII level as independent risk factors for OS,while multiple tumors,node invasion and high SII level were identified as independent risk factors for RFS.Validation cohort confirmed the findings of derivation cohort.CONCLUSION The present study demonstrated the feasibility of preoperative SII as a prognostic indicator for ICC.Patients with increased SII level were associated with worse OS and earlier tumor recurrence.Elevated SII level was an independent risk factor for OS and RFS in patients with ICC after hepatectomy.In the future,the SII could help stratifying patients with ICC,thus guiding therapeutic choices,especially in immunotherapy.

High Rate and Long Lifespan Sodium‑Organic Batteries Using Pseudocapacitive Porphyrin Complexes‑Based Cathode

Sodium-organic batteries utilizing natural abundance of sodium element and renewable active materials gain great attentions for grid-scale applications.However,the development is still limited by lack of suitable organic cathode materials with high electronic conductivity that can be operated stably in liquid electrolyte.Herein,we present 5,15-bis(ethynyl)-10,20-diphenylporphyrin(DEPP)and[5,15-bis(ethynyl)-10,20-diphenylporphinato]copper(II)(CuDEPP)as new cathodes for extremely stable sodium-organic batteries.The copper(II)ion partially contributes the charge storage and significantly stabilizes the structure of porphyrin complex for electrochemical energy storage.In situ electrochemical stabilization of organic cathode with a lower charging current density was identified which enables both improved high energy density and power density.An excellent longterm cycling stability up to 600 cycles and an extremely high power density of 28 kW kg−1 were achieved for porphyrin-based cathode.This observation would open new pathway for developing highly stable sodium-organic cathode for electrochemical energy storage.

膳食纤维对仔猪肠道健康的影响及机制

仔猪健康是养猪生产效益的重要保证。哺乳仔猪在断奶时面临着环境和营养物质来源改变的双重压力,表现出以生长率和营养物质吸收率降低、肠道功能紊乱及敏感性增加、腹泻和高死亡率为主要特征的断奶应激综合征(Aumaitre和Corring,1978)。由断奶应激导致的仔猪胃肠道功能失调往往给养猪业带来巨大的经济损失(Lallès et al.,2007)。随着我国农业农村部第194号公告的出台,饲料药物添加剂抗生素类已于2020年7月1日正式退出我国畜牧业的历史舞台。

Effectiveness of coal mine dust control:A new technique for preparation and efficacy of self-adaptive microcapsule suppressant

This study aims to make full use of the agricultural waste peanut shells to lower material costs and achieve cleaner production at the same time.Cellulose nanofibrils(CNF)extracted from peanut shells were mixed with acrylic acid(AA)and dimethyl diallyl ammonium chloride(DMDAAC)to prepare a new type of capsule core(dust suppressant).Then,the self-adaptive AA-DM-CNF/CA microcapsules were prepared under the action of calcium alginate.The infrared spectroscopy and X-ray diffraction analysis results suggest that AA,DMDAAC and CNF have experienced graft copolymerization which leads to the formation of an amorphous structure.The scanning electron microscopy analysis results demonstrate that the internal dust suppressant can expand and break the wall after absorbing water,featuring a self-adaptive function.Meanwhile,the laser particle size analysis results show that the microcapsules,inside which the encapsulated dust suppressant can be observed clearly,maintain a good shape.The product performance experimental results reveal that the capsule core and the capsule wall achieve synergistic dust suppression,thus lengthening the dust suppression time.The product boasts good dust suppression,weather resistance,degradation and synergistic combustion performances.Moreover,this study,as the first report on the development and analysis of dust-suppressing microcapsules,fills in the research gap on the reaction mechanism between dust-suppressing microcapsules and coal by MS simulation.The proposed AA-DM-CNF/CA dust-suppressing microcapsules can effectively lower the dust concentration in the space and protect the physical and mental health of coal workers.In general,this research provides a new insight into the structure control and performance enhancement of dust suppressants.Expanding the application range of microcapsules is of crucial economic and social benefits.

Backlund transformations, consistent Riccati expansion solvability, and soliton-cnoidal interaction wave solutions of Kadomtsev-Petviashvili equation

The famous Kadomtsev-Petviashvili(KP)equation 1 s a classical equation In soliton tneory.A Backlund transformation between the KP equation and the Schwarzian KP equation is demonstrated by means of the truncated Painlev6 expansion in this paper.One-parameter group transformations and one-parameter subgroup-invariant solutions for the extended KP equation are obtained.The consistent Riccati expansion(CRE) solvability of the KP equation is proved.Some interaction structures between soliton-cnoidal waves are obtained by CRE and several evolution graphs and density graphs are plotted.

Consistent Riccati expansion solvability,symmetries,and analytic solutions of a forced variable-coefficient extended Korteveg-de Vries equation in fluid dynamics of internal solitary waves

We study a forced variable-coefficient extended Korteweg-de Vries(KdV)equation in fluid dynamics with respect to internal solitary wave.Bäcklund transformations of the forced variable-coefficient extended KdV equation are demonstrated with the help of truncated Painlevéexpansion.When the variable coefficients are time-periodic,the wave function evolves periodically over time.Symmetry calculation shows that the forced variable-coefficient extended KdV equation is invariant under the Galilean transformations and the scaling transformations.One-parameter group transformations and one-parameter subgroup invariant solutions are presented.Cnoidal wave solutions and solitary wave solutions of the forced variable-coefficient extended KdV equation are obtained by means of function expansion method.The consistent Riccati expansion(CRE)solvability of the forced variable-coefficient extended KdV equation is proved by means of CRE.Interaction phenomenon between cnoidal waves and solitary waves can be observed.Besides,the interaction waveform changes with the parameters.When the variable parameters are functions of time,the interaction waveform will be not regular and smooth.

First principles study of stability, mechanical, and electronic properties of chromium silicides

Through the first principles calculations, the chemical stability, mechanical, and electronic properties of chromium silicides are predicted. Estimating enthalpies and binding energies, density state density and electron density distribution are combined to analyse the thermodynamic stability and physical properties of chrome-silicon binary compounds. The chromium silicide includes Cr3 Si, Cr5 Si3, CrSi, and CrSi2. The chemical stability and the information about electronic structure, mechanical properties, Debye temperature, and anisotropy properties are obtained by density functional theory and Debye quasi-harmonic approximation. Meanwhile, the calculation of elastic modulus shows that Cr3 Si has the highest body modulus value（251 GPa） and CrSi2 possesses the highest shear modulus（169.5 GPa） and Young＇s modulus（394.9 GPa）. In addition, the Debye temperature and the speed of sound of these Cr–Si compounds are also calculated.Since the calculated bulk modulus is different from Young＇s modulus anisotropy index, and also different from Young＇s modulus of a three-dimensional surface shape, the different mechanical anisotropies of all the compounds are obtained.

High-power all-fiber linearly polarized Yb-doped chirped pulse amplifier based on active polarization control

High-power ultrafast laser amplification based on a non-polarization maintaining fiber chirped pulse amplifier is demonstrated.The active polarization control technology based on the root-mean-square propagation(RMS-prop)algorithm is employed to guarantee a linearly polarized output from the system.A maximum output power of 402.3 W at a repetition rate of 80 MHz is realized with a polarization extinction ratio(PER)of>11.4 dB.In addition,the reliable operation of the system is verified by examining the stability and noise properties of the amplified laser.The M2factor of the laser beam at the highest output power is measured to be less than 1.15,indicating a diffraction-limited beam quality.Finally,the amplified laser pulse is temporally compressed to 755 fs with a highest average power of 273.8 W.This is the first time,to the best of our knowledge,that the active polarization control technology was introduced into the high-power ultrafast fiber amplifier.

Nonlocal symmetries,soliton-cnoidal wave solution and soliton molecules to a(2+1)-dimensional modified KdV system

A(2+1)-dimensional modified KdV(2DmKdV)system is considered from several perspectives.Firstly,residue symmetry,a type of nonlocal symmetry,and the Bäcklund transformation are obtained via the truncated Painlevéexpansion method.Subsequently,the residue symmetry is localized to a Lie point symmetry of a prolonged system,from which the finite transformation group is derived.Secondly,the integrability of the 2DmKdV system is examined under the sense of consistent tanh expansion solvability.Simultaneously,explicit soliton-cnoidal wave solutions are provided.Finally,abundant patterns of soliton molecules are presented by imposing the velocity resonance condition on the multiple-soliton solution.

A Super mKdV Equation： Bosonization, Painlevé Property and Exact Solutions

The symmetry of the fermionic field is obtained by means of the Lax pair of the mKdV equation. A new super mKdV equation is constructed by virtue of the symmetry of the fermionic form. The super mKdV system is changed to a system of coupled bosonic equations with the bosonization approach. The bosonized SmKdV(BSmKdV)equation admits Painlevé property by the standard singularity analysis. The traveling wave solutions of the BSmKdV system are presented by the mapping and deformation method. We also provide other ideas to construct new super integrable systems.

Lump Solutions for Two Mixed Calogero-Bogoyavlenskii-Schiff and Bogoyavlensky-Konopelchenko Equations

Based on the Hirota bilinear operators and their generalized bilinear derivatives, we formulate two new(2+1)-dimensional nonlinear partial differential equations, which possess lumps. One of the new nonlinear differential equations includes the generalized Calogero-Bogoyavlenskii-Schiff equation and the generalized BogoyavlenskyKonopelchenko equation as particular examples, and the other has the same bilinear form with different Dp-operators.A class explicit lump solutions of the new nonlinear differential equation is constructed by using the Hirota bilinear approaches. A specific case of the presented lump solution is plotted to shed light on the charateristics of the lump.

Arginine metabolism: a potential target in pancreatic cancer therapy

Pancreatic ductal adenocarcinoma (PDAC) is an extremely malignant disease, which has an extremely low survival rate of <9% in the United States. As a new hallmark of cancer, metabolism reprogramming exerts crucial impacts on PDAC development and progression. Notably, arginine metabolism is altered in PDAC cells and participates in vital signaling pathways. In addition, arginine and its metabolites including polyamine, creatine, agmatine, and nitric oxide regulate the proliferation, growth, autophagy, apoptosis, and metastasis of cancer cells. Due to the loss of argininosuccinate synthetase 1 (ASS1) expression, the key enzyme in arginine biosynthesis, arginine deprivation is regarded as a potential strategy for PDAC therapy. However, drug resistance develops during arginine depletion treatment, along with the re-expression of ASS1, metabolic dysfunction, and the appearance of anti-drug antibody. Additionally, arginase 1 exerts crucial roles in myeloid-derived suppressor cells, indicating its potential targeting by cancer immunotherapy. In this review, we introduce arginine metabolism and its impacts on PDAC cells. Also, we discuss the role of arginine metabolism in arginine deprivation therapy and immunotherapy for cancer.