Constant-gain nonlinear adaptive observers revisited: an application to chemostat systems

This study deals with constant-gain adaptive observers for nonlinear systems,for which relatively few solutions are available for some particular cases.We introduce an asymptotic observer of constant gain for nonlinear systems that have linear input.This allows the observer design to be formulated within the linear matrix inequality paradigm provided that a strictly positive real condition bet ween the inpu t disturbance and the output is fulfilled.The proposed observer is t hen applied to a large class of nonlinear chemos tat dynamical systems that are widely used in the fermentation process,cell cultures,medicine,etc.In fact,under standard practical assumptions,the necessary change of the chemos tat state coordinates exis ts,allowing use of the const ant-gain observer.Finally,the developed theory is illustrated by estimating pollutant concentration in a Spirulina maxima wastewater treatment facility.

以新视角观察p53家族在肺癌发生及治疗中的独特作用

P53作为转录因子,其转录激活功能维持了基因组的稳定性,对防止肿瘤的形成起着重要作用,是目前研究得最为广泛、深入的抑癌基因,被称为"基因卫士"。P53家族的成员p63、p73与p53在DNA结合结构域上有高度的同源性,某些p53家族亚型可以与p53-反应基因相结合起着转录激活的作用,另外一些则起着负性调节作用。肺癌是世界上患病率最高的恶性肿瘤之一,p53家族成员在肺癌中的异常表达与肺癌的发生有密切联系,并导致不良的预后及对放疗、化疗的抵抗。对p53家族成员在肺癌致病机制的深入研究可有助于为临床提供合理的化疗方案及靶向治疗策略。本文着重回顾总结p53家族成员在肺癌发生、化疗敏感性以及肺癌靶向治疗中的独特的作用。

CCXCKR、VEGF-A及VEGF-C在人直肠癌中的表达及其与转移的关系

目的:研究Chemo Centryx趋化因子受体(Chemo Centryx chemokine receptor,CCXCKR)、血管内皮生长因子(vascular endothelial growth factor,VEGF)A和C在直肠癌组织、癌旁组织、正常直肠组织中的表达,探讨其与淋巴结转移的关系.方法:应用免疫组织化学SP法检测50例手术切除的直肠癌组织、癌旁组织和11例正常直肠组织中CCXCKR、VEGF-A、VEGF-C的表达情况.将50例直肠癌患者根据有无淋巴结转移分为:淋巴结转移组(19例)与无淋巴结转移组,并采用免疫组织化学方法分别检测CCXCKR、VEGF-A及VEGF-C在有无淋巴结转移的直肠癌组织中的表达情况,以探讨CCXCKR、VEGF-A及VEGF-C与淋巴结转移的关系.结果:CCXCKR在正常直肠组织、癌旁组织中表达明显高于直肠癌组织(P<0.01),在淋巴结转移组CCXCKR的表达明显低于淋巴结未转移组(P<0.01).而直肠癌组织、癌旁组织中VEGF-A和VEGF-C表达阳性率明显高于正常直肠组织(P<0.01),其中在淋巴结转移组两者的表达明显高于淋巴结未转移组(P<0.05).VEGF-A和VEGF-C在直肠癌组织中的表达呈正相关(r=0.703,P<0.0l),而CCXCKR与V E G F-A及V E G F-C在直肠癌组织中的表达均分别呈负相关(r=-0.360,P<0.05、r=-0.326,P<0.05).结论:直肠癌中CCXCKR低表达、VEGF-A与VEGF-C高表达与直肠癌淋巴结转移密切相关,CCXCKR可能对直肠癌的发生和转移有抑制作用,CCXCKR、VEGF-A与V E G F-C联合检测,对直肠癌预后的判断具有实际意义.

Locoregional treatments for hepatocellular carcinoma: Current evidence and future directions

Liver cancers are the second most frequent cause of global cancer-related mortality of which 90%are attributable to hepatocellular carcinoma(HCC).Despite the advent of screening programmes for patients with known risk factors,a substantial number of patients are ineligible for curative surgery at presentation with limited outcomes achievable with systemic chemotherapy/external radiotherapy.This has led to the advent of numerous minimally invasive options including but not limited to trans-arterial chemoembolization,radiofrequency/microwave ablation and more recently selective internal radiation therapy many of which are often the first-line treatment for select stages of HCC or serve as a conduit to liver transplant.The authors aim to provide a comprehensive overview of these various image guided minimally invasive therapies with a brief focus on the technical aspects accompanied by a critical analysis of the literature to assess the most up-to-date evidence from comparative systematic reviews and meta-analyses finishing with an assessment of novel combination regimens and future directions of travel.

A survey on herbal management of hepatocellular carcinoma

In this review we outline the different mechanisms mediating hepatocarcinogenesis. We also discuss possible targets of bioactive herbal agents at different stages of hepatocarcinogenesis and highlight their role at each individual stage. We gathered information on the most common herbal prescriptions and extracts thought to be useful in prevention or sensitization for chemotherapy in management of hepatocellular carcinoma (HCC). The value of this topic may seem questionable compared to the promise offered for HCC management by chemotherapy and radiation. However, we would recommend the use of herbal preparations not as alternatives to common chemo /and or radiotherapy, but rather for prevention among atrisk individuals, given that drug/herb interactions are still in need of extensive clarification. The bioactive constituents of various herbs seem to be promising targets for isolation, cancer activity screening and clinical evaluation. Finally, herbal preparations may offer a cost effective protective alternative to individuals known to have a high risk for HCC and possibly other cancers, through maintaining cell integrity, reversingoxidative stress and modulating different molecular pathways in preventing carcinogenesis.

Determination of creatinine level in patient blood samples by Fourier NIR spectroscopy and multivariate analysis in comparison with biochemical assay

In this paper,in vivo spectra from 23 patients'blood samples with various Creatinine(Cr)concentration levels ranging from 0.96 to 12.5 mg/dL were measured using Fourier transform near-infrared spectrometer(FT-NIRS)and spectrum quantitative analysis method.Since Cr undergoes passive filtration,it serves as a key biomarker of kidneys function via the estimation of glomerular filtration rate.Thus,increased blood Cr concentration reflects impaired renal func-tion.After spectra pre processing and outlier exclusion,a spectral model was developed based on partial least squares regression(PLSR)method,wherein Cr concentrations correlated with filtered NIR spectra across several peaks,where Cr is know n to absorb NIR light.Several statistical metrics were applied to estimate the model efficiency during data analysis.Comparison of spectra-derived concentrations to reference Cr measurements by the current gold-standard Jaffe's method held in hospital lab revealed a Cr prediction accuracy of 1.64 mg/dL with good corre-lation of R=0.9.Bland-Altman plots were used to compare between our calculations and ref-erence lab values and reveal minimal bias between the two.The finding presented the potential of FT-NIRS coupled with PLSR technique for Cr determination.

A Revisited Definition of the Three Solute Descriptors Related to the Van der Waals Forces in Solutions

It is currently admitted that the intermolecular forces implicated in Gas Liquid Chromatography (GLC) can be expressed as a product of parameters (or descriptors) of solutes and of parameters of solvents. The present study is limited to those of solutes, and among them the three ones are involved in the Van der Waals forces, whereas the two ones involved in the hydrogen bonding are left aside at this stage. These three studied parameters, which we call δ, ω and ε, respectively reflect the three types of Van der Waals forces: dispersion, orientation or polarity strictly speaking, and induction-polarizability. These parameters have been experimentally obtained in previous studies for 121 Volatile Organic Compounds (VOC) via an original Multiplicative Matrix Analysis (MMA) applied to a superabundant and accurate GLC data set. Then, also in previous studies, attempts have been made to predict these parameters via a Simplified Molecular Topology procedure (SMT). Because these last published results have been somewhat disappointing, a promising new strategy of prediction is developed and detailed in the present article.

Chemo-selective couplings of anilines and acroleins/enones under substrate control and condition control

Rh(III)‐catalyzed C–H activation of N‐protected anilines and chemo‐divergent couplings with acroleins/enones have been realized for synthesis of three classes of heterocycles.The oxidative coupling of N‐pyridylaniline afforded dihydroquinolones with the acrolein being a major hydrogen acceptor.When the directing group was replaced by pyrimidyl in the same system,redox‐neutral coupling occurred to afford hemiaminal ethers.Oxidative annulation of N‐pyridylanilines with enones using AgBF4 oxidant afforded atropisomeric quinolinium salts.

Updated Definition of the Three Solvent Descriptors Related to the Van der Waals Forces in Solutions

Innovative viewpoint on the older topic of the van der Waals forces, is of interesting and significant issue to be concerned in both the fields related to the fundamental investigation and thus valuable in guiding the new physiochemical phenomena and processes for both academic research and practical applications. The intermolecular Van der Waals forces involved in solutions have been recently deeply reconsidered as far as the solute side is concerned. More precisely, the solute descriptors (or parameters) experimentally established, have been accurately related to molecular features of a Simplified Molecular Topology. In the present study, an equivalent result is reached on the solvent side. Both experimental parameters have been obtained simultaneously in previous Gas Liquid Chromatographic studies for 121 Volatile Organic Compounds and 11 liquid stationary phases, via an original Multiplicative Matrix Analysis. In that experimental step, five groups of forces were identified, two of hydrogen bonding and three of Van der Waals: 1) dispersion (London), 2) orientation or polarity strictly speaking (Keesom), and 3) induction-polarizability (Debye). At this stage, an attempt of characterization the solvent parameters via the SMT procedure has been limited to those related to the Van der Waals forces, those related to the hydrogen bonding being for now left aside.

Competing Causes of Death in 138 Patients with Loco-Regionally Advanced Head and Neck Cancer Treated with Multi-Modality Treatment

Introduction: The goal of this study was to analyze the causes of death in patients with loco-regionally advanced squamous cell carcinoma (HNSCC) of the head and neck treated with multimodality treatment. Materiel: The mortality records of 138 advanced head and neck patients treated in our department with surgery and adjuvant (chemo) radiotherapy from 2007 to 2013 were collected and reviewed in this study.?Results: From May 2007 to January 2013, 138 patients were followed up with a median follow-up duration of 25 months. The 5-year overall survival (OS), disease-free survival (DFS) were 45%, and 56.1%, respectively. A total of 39 patients (28%) died during the follow-up period. Clearly, in this population, loco-regional relapse accounted for one of the most cause of death but acute and late or chronic treatment-associated causes leading to death occurred in almost 8% of the patients. Furthermore, the risk of death from head and neck squamous cell carcinoma (HNSCC) was greater in patients with hypopharynx cancer. Univariate analysis indicated that patients with N2b disease and above and vascular tumor embolism had a lower overall survival (p = 0.001 and p = 0.007 respectively). The multivariate analysis showed that N2b disease and above was an independent prognostic factor for poorer loco-regional control (p = 0.001). Conclusions: Patients with locally advanced head and neck cancer treated with surgery and adjuvant (chemo) radiotherapy are potentially curable but face significant risks of mortality from causes other than disease progression.

Analysis of Clinical Effect of Concurrent Chemo/radiotherapy in the Treatment of Advanced Cervical Cancer

The study aimed to analyze the efficacy and adverse effects of concurrent chemo/radiotherapy in the treatment of advanced cervical cancer,and the efficacy and safety of concurrent chemo/radiotherapy were evaluated to standardize the treatment.First of all,retrospective analysis was carried out,and 30 cases of advanced cervical cancer treated in hospitals from 2013 to 2018 were included in the study.30 cases of concurrent chemo/radiotherapy were included in the synchronous group,and 30 cases of radical radiotherapy alone were included in the radiotherapy group.The results showed that the CR rate and remission rate in the synchronous group were 43.3%and 93.3%,which were higher than those in the radiotherapy group(26.7%and 80.0%).The 3-year survival rate of the synchronous group was 80.0%,which was higher than that of the radiotherapy group,with a statistically significant difference(P<0.05).There was no significant difference in 3-year all-cause mortality,5-year survival and 5-year allcause mortality between the two groups.The tumor-free survival time in the synchronous group was(24.4±8.2)months,which was higher than that in the radiotherapy group(17.0±8.5)months,and the difference was statistically significant(P<0.05).Therefore,compared with radiotherapy alone,concurrent chemo/radiotherapy in the treatment of advanced cervical cancer can improve the 3-year survival rate and prolong the tumor-free survival time.However,it did not increase 5-year survival rate,and bone marrow suppression and gastrointestinal reactions were increased.

化工建筑、构筑物的防腐与防护

通过对建筑材料腐蚀与防护机理的分析,首先要提高和改善建筑材料本身抗腐蚀性,在碳钢中加一些合金元素,以增加其抗氧化性;对非金属材料进行严格水灰比控制,来提高混凝土致密度,混凝土越致密腐蚀介质就难渗入,被腐蚀可能性就越小。其次在金属材料表面应用保护性的金属镀层;在混凝土外部加覆盖层和贴面材料。这样就能保证建筑结构抗腐蚀性,达到建筑结构合理的使用年限,满足了化工生产的要求。

Pillar[6]arene-based supramolecular self-assemblies for twopronged GSH-consumption-augmented chemo/photothermal therapy

The abundant intracellular glutathione(GSH)in cancer cells severely undermines the therapeutic efficacy of different treatments due to their role in protecting cancer cells from the associated oxidative stress.Developing a highly integrated system to consume GSH would help to improve the therapeutic outcomes.In this study,supramolecular prodrug self-assemblies(SPSAs)with IR825 loaded inside were developed to consume GSH via two-pronged pathways while augmenting the therapeutic potency of chemo/photothermal treatment.SPSAs were prepared using water-soluble pillar[6]arene(WP[6])as host units and H_(2)O_(2)-responsive nitrogen mustard prodrug,chlorambucil-(phenylboronic acid pinacol ester)conjugates(Cb-BE),as the guests.When SPSAs were internalized by cancer cells,the generation of quinone methide(QM)from Cb-BE and singlet oxygen(^(1)O_(2))from irradiation-activated IR825 could consume GSH in a concerted way.As such,the therapeutic efficacies of the released chlorambucil and the accompanied hyperthermia were augmented toward synergistically inhibiting tumor growth.

2-巯基嘧啶与碳酸Morita-Baylis-Hillman酯的选择性S-烯丙基烷基化

发展了一种1,4-二氮杂二环[2.2.2]辛烷(DABCO)催化2-巯基嘧啶与碳酸Morita-Baylis-Hillman(MBH)酯的S-烯丙基烷基化反应新方法.一系列碳酸MBH酯与2-巯基嘧啶反应并以55%~99%的产率得到S-烯丙基烷基化产物.具有专一的化学选择性和良好的区域选择性,反应条件温和,反应时间短,底物适用广泛,有良好的应用前景.

Role of adjuvant(chemo)radiotherapy for resected extrahepatic cholangiocarcinoma:a meta-analysis

Background:Adjuvant(chemo)radiotherapy(A(C)RT)may be an important supplement to surgery for extrahepatic cholangiocarcinoma(EHCC).However,whether all patients would achieve benefits from A(C)RT and which adjuvant regimen,adjuvant radiotherapy(ART)or adjuvant chemoradiotherapy(ACRT),would be preferred,are still undetermined.The low incidence of EHCC makes it difficult to carry out randomized controlled trials(RCTs);therefore,almost all clinical studies on radiotherapy are retrospective.We have conducted a meta-analysis of these retrospective studies.Methods:We conducted a meta-analysis of current retrospective studies using PubMed,Embase,and ClinicalTrials databases.All studies published in English that were related to A(C)RT and which analyzed overall survival(OS),disease-free survival(DFS),or locoregional recurrence-free survival(LRFS)were included.Estimated hazard ratios(HRs)were calculated for OS,DFS,and LRFS.Results:Data from eight studies including 685 patients were included.Our analysis showed that A(C)RT significantly improved OS(HR 0.69,95%confidence interval(CI)0.48–0.97,P=0.03),DFS(HR 0.60,95%CI 0.47–0.76,P<0.0001),and LRFS(HR 0.27,95%CI 0.17–0.41,P<0.00001)of EHCC overall.In subgroups,patients with microscopically positive resection margin(R1)could achieve a benefit from A(C)RT(HR 0.44,95%CI 0.27–0.72,P=0.001).No statistically OS difference was observed in negative resection margin(R0)subgroup(HR 0.98,95%CI 0.30–3.19,P=0.98).Significant OS benefit was found in patients who received concurrent ACRT(HR 0.40,95%CI 0.26–0.62,P<0.0001),while the result of ART without chemotherapy showed no significant benefit(HR 1.14,95%CI 0.29–4.50,P=0.85).In the distal cholangiocarcinoma subgroup,no significant difference was seen when ACRT and ART were included(HR 0.61,95%CI 0.14–2.72,P=0.52),but a significant difference was seen ewOshSpe,enDc iaFanlSla,yl yianzn iddn igsL ttRahlF ep Sca iotinne cEnutHrsr.C eCnt pAaCtieRnTt so,nelys p(eHcRi a0 ll.y2 i9 n,t9 h5 o%s eC Iw i0 t.h13 R–10 r.e6 s4 e,cPti=o0 n.0 m0 a2 r).g iCnso.n AclCusRioT nms:aAy(bCe)RsTu pmeraiyo ri tmop rAoRvTe .

Chemical screen identifies shikonin as a broad DNA damage response inhibitor that enhances chemotherapy through inhibiting ATM and ATR

DNA damage response(DDR)is a highly conserved genome surveillance mechanism that preserves cell viability in the presence of chemotherapeutic drugs.Hence,small molecules that inhibit DDR are expected to enhance the anti-cancer effect of chemotherapy.Through a recent chemical library screen,we identified shikonin as an inhibitor that strongly suppressed DDR activated by various chemotherapeutic drugs in cancer cell lines derived from different origins.Mechanistically,shikonin inhibited the activation of ataxia telangiectasia mutated(ATM),and to a lesser degree ATM and RAD3-related(ATR),two master upstream regulators of the DDR signal,through inducing degradation of ATM and ATR-interacting protein(ATRIP),an obligate associating protein of ATR,respectively.As a result of DDR inhibition,shikonin enhanced the anti-cancer effect of chemotherapeutic drugs in both cell cultures and in mouse models.While degradation of ATRIP is proteasome dependent,that of ATM depends on caspase-and lysosome-,but not proteasome.Overexpression of ATM significantly mitigated DDR inhibition and cell death induced by shikonin and chemotherapeutic drugs.These novel findings reveal shikonin as a pan DDR inhibitor and identify ATM as a primary factor in determining the chemo sensitizing effect of shikonin.Our data may facilitate the development of shikonin and its derivatives as potential chemotherapy sensitizers through inducing ATM degradation.

Photothermo-responsive Cu_7S_4@polymer nanocarriers with small sizes and high efficiency for controlled chemo/photothermo therapy

Drug delivery systems(DDSs) have been getting more and more attention in the field of cancer therapy with the development of nanotechnology. But remote and noninvasive controlled drug release for improving treatment efficacy and reducing side effects faces great challenge. We report a kind of 'smart' nanocomposites(NCs) that is sensitive to the surrounding temperature by grafting a layer of thermosensitive polymer, poly(N-isopropylacrylamide)(pNIPAm),on the surface of single Cu_7S_4 nanoparticle(NP) via atomtransfer radical polymerization(ATRP). These NCs demonstrate a photothermal conversion efficiency of 25.4% under808-nmnear infrared(NIR) light irradiation and a drug loading content of 19.4%(drug/total NCs, w/w) with a lower critical solution temperature(LCST) of ~38°C. At normal physiological temperature(37°C), only 10.8% of the loaded doxorubicin(DOX) was released at physiological pH value(pH7.4) within 10 h. In the presence of 808-nm irradiation, due to the temperature increment as a result of photothermal effects,DOX was rapidly released.

Aptamerized silica/gold nanocapsules for stimulated release of doxorubicin through remote two-photon excitation

Precision-based drug delivery via remote triggering is fast becoming an attractive therapeutic design and is highly useful in complicated clinical situations that may require accurate site-delivery of drug while reducing the risk of collateral damage to surrounding healthy tissue.Of the many strategies available to achieve these desirable effects,silica/gold nano-assemblies offers a practical means to achieving these aims.Herein,as a proof-of-concept,a silica nanocapsule passivated with a gold outer nanoshell had been fabricated to deliver Doxorubicin,and this nano-assembly can be remotely triggered via two-photon excitation(TPE),even under in vivo setting.A polyethylene glycol(PEG)layer as well as AS1411 DNA aptamer had also been grafted to the surface to improve homing specificity toward MDA-MB-231 breast cancer tissue.The assembly of silica/gold nanocapsules was characterized via TEM,FTIR,and UVVis to validate the the nanoconstruct.Upon TPE irradiation,a higher expression level of Annexin V and Caspase-3 was observed in both in vitro and in vivo animal models.A significant reduction in tumor size on mice model was noticed after 21 days,and these results had suggested a viable nano-sized design serving as remotely triggered drug release platform based on current well-established silica nanoparticulate methodologies.