Therapeutic challenge for immunotherapy targeting cold colorectal cancer: A narrative review

Cold colorectal tumors are not likely to trigger a robust immune response and tend to suppress the immune response.There may be three reasons.First,the complex tumor microenvironment of cold colorectal cancer(CRC)leads to tolerance and clearance of immunotherapy.Second,the modification and concealment of tumor-specific targets in cold CRC cause immune escape and immune response interruption.Finally,the difference in number and function of immune cell subsets in patients with cold CRC makes them respond poorly to immunotherapy.Therefore,we can only overcome the challenges in immunotherapy of cold CRC through in-depth research and understanding the changes and mechanisms in the above three aspects of cold CRC.

Dyslipidemia： evidence of efficacy of the pharmacological and non-pharmacological treatment in the elderly

The clinical decision to control risk factors for cardiovascular disease （CVD） in the elderly takes the followings into consideration： （1） the elderly life expectancy; （2） the elderly biological age and functional capacity; （3） the role of cardiovascular disease in the elderly group; （4） the prevalence of risk factors in the elderly; and （5） The effectiveness of treatment of risk factors in the elderly. A large number of studies showed the efficacy of secondary and primary prevention of dyslipidemia in the elderly. However, the only trial that included patients over 80 years was the Heart Protection Study （HPS）. Statins are considered the first line therapy for lowering low-density lipoprotein cholesterol （LDL-C）. Because lifestyle changes are very difficult to achieve, doctors in general tend to prescribe many drugs to control cardiovascular risk factors. However, healthy food consumption remains a cornerstone in primary and secondary cardiovascular prevention and should be implemented by everyone.

Promotive Effects of Yokukansan, a Traditional Japanese Medicine, on Proliferation and Differentiation of Cultured Mouse Cortical Oligodendrocytes

Effects of yokukansan, a traditional Japanese medicine, on proliferation and differentiation of oligodendrocytes were examined using purified mouse cortical oligodendrocyte precursor cells (OPCs). OPCs were cultured for four days, and proliferation was evaluated by counting A2B5 (a specific antibody to OPC)-reactive cells on the second day of cell culture. Differentiation from OPC to oligodendrocyte was evaluated by counting O4 (a specific antibody to detect differentiated cells in various stages)-reactive cells on the fourth day of culture. The effects of yokukansan (final concentration: 100 or 200 μg/ml) on proliferation and differentiation were examined by adding it to the medium for four days. Yokukansan increased not only the number of A2B5-positive cells on the second day but also the number of O4-positive cells on the fourth day compared to those in the corresponding controls. A WST-8 assay was used to identify active components from seven components of Uncaria Hook (UH), one of the constituent galenicals of yokukansan. Geissoschizine methyl ether (GM: 0.1 - 3.0 μM) was identified by this screening assay and increased the number of A2B5-positive cells on the second day and O4-positive cells on the fourth day as yokukansan did. These results suggest that yokukansan promotes the proliferation and differentiation of oligodendrocytes, and also that GM contained in UH is one of active components responsible for this effect of yokukansan.

Assessment of the Viability of the Reuse of Sedibeng District Municipal Secondary Effluent in Southern Gauteng, South Africa

Population growth, urbanization, water resources pollution, environmental awareness, uneven distribution of water resources and water scarcity have necessitated water reuse especially in arid and semi-arid countries. Influent and effluent data of chemical and biological analyses from four wastewater treatment plants (WWTPs) in the Sedibeng district municipality (SDM) were used to assess the viability of water reuse. Available worldwide water reuse criteria of Water Reclamation Plants (WRPs) for different reuse options were used to characterize the SDM’s four WWTPs for potable water, power and steel industrial water reuse. Only WWTP4 does not meet the influent design criteria of the New Goreangab WRP in Windhoek, Namibia of 43 mg/l and the DWAF general limit of discharge of 75 mg/l used by Beaufort West WRP in South Africa for COD. WWTP2 and 4 do not meet the DWAF general limit of 25 mg/l for suspended solids. Some of the water quality parameters of the effluents from these plants were non-compliant to the requirements for reuse in power generation and steel manufacturing. However, the implementation of advance treatment technologies such as membrane or advanced oxidation processes (AOPs) as part of the treatment train in a potential WRP would address the water quality issues. Water reclamation of SDM effluent either through direct (DPR) or indirect potable (IPR) water reuse, power generation and steel manufacturing industry has the potential of reuse in the Southern Gauteng region. The success of the selected option would be depended on cost effectiveness, stakeholder commitment and public acceptance of the reuse strategy.

Tibetan herbal formula Padma Digestin modulates gastrointestinal motility in vitro

AIM:To examine the effects of Padma Digestin on the smooth muscle motility of different gastrointestinal segments in vitro . METHODS:The effects of the ethanolic extract of Padma Digestin (at 8.16 mg/mL or 81.6mg/mL) on the contractility and susceptibility to acetylcholine (ACh) of muscle strips from the cardia, antrum, pylorus, duodenum, jejunum, ileum and colon of male Wistar rats were analyzed.RESULTS:Compared with the control treatment, the Padma Digestin extract had a procontractile effect on the antral smooth muscle strips. Padma Digestin decreased ACh sensitivity in cardia muscle strips and increased it in those from the antrum and pylorus. In the intestinal segments, spontaneous contractility was inhibited in both the duodenal and jejunal strips, whereas reactivity to ACh was inhibited in the jejunal strips only. In the colonic samples, Padma Digestin inhibited spontaneous and ACh-stimulated contractility at a low dose but seems to have increasing effects at a high dose. CONCLUSION:Padma Digestin extract has regionspecific effects on the contractility and excitability of gastrointestinal smooth muscle. Our results support the traditional use of Padma Digestin for maldigestion and functional gastrointestinal disorders.

Zinc Oxide Composites of Doxorubicin in the Form of Coating, Composite Films and Gels with a High Antitumor Activity and Low Toxicity

This work is devoted to the formation doxorubicin (DOX) zinc oxide composites in the form of coating (DOX + ZnO), hydrogels and composite films of DOX with polyvinyl alcohol (DOX + PVA + ZnO) by DC-magnetron deposition of ZnO nanoscale particles (ZnO NPs) on their surfaces (DOX, DOX + PVA) with higher (two times and more) antitumor activity and considerable smaller toxicity at low doses of DOX in compositions compared to the initial drug. Using the methods of spectroscopy, atomic force microscopy (AFM), scanning electron microscopy (SEM) and X-ray Powder Diffraction (XRD), the role of ZnO NPs size on the antitumor activity of doxorubicin zinc oxide compositions is shown. AFM shows presence of many ZnO NPs on the surface DOX. A comparison of the FTIR spectra of DOX and its zinc oxide compositions has shown the presence of new bands of OH valence and deformation vibrations. It is possible to assume that interaction between ZnO and DOX takes place in the form of hydrogen bond, promoting the complexes formation. It is possible that both synergic and hydrogen-bonding ZnO with DOX increase the antitumor activity.

Analysis of OECD/NEA medium 1000 MWth sodium-cooled fast reactor using the Monte Carlo serpent code and ENDF/B-VIII.0 nuclear data library

This study presents a benchmark evaluation of the new ENDF/B-VIII.0 nuclear data library for the Organization for Economic Co-operation and Development/Nuclear Energy Agency Medium 1000 MWth sodium-cooled fast reactor(SFR).The study presented herein covers both SFR core types,i.e.,metallic fueled(MET-1000)and oxide fueled(MOX-1000),simulated using the continuous-energy Monte Carlo Serpent2 code.The neutronics performances of the ENDF/B-VIII.0-based simulations were compared mainly to two libraries:ENDF/B-VII.1 and JENDL-4.0.The comparison includes several neutronics parameters evaluated for the beginning and end of the cycle conditions.These parameters include the effective multiplication factor keff,total effective delayed neutron fraction beff,sodium void reactivity(DqNa),Doppler constant(DqDoppler),and control rod worth(DqCR).In addition,a sensitivity study was used to reveal the major isotope/reaction pairs contributing to the discrepancy observed in the performance of the three libraries using 33 and 44-energy-group structures.

Quality Study of Rice Husk Ash (RHA) Brick Using Neutron Radiography Technique

A powerful non-destructive testing (NDT) technique is adopted to study the quality of RHA brick-1 and RHA brick-2. In that case, rice husk ash has been utilized for the preparation of bricks in full replacement of clay. In these studies, homogeneity of elemental distribution, water absorption and size and shape of the pores have been observed. From the studies, it was observed that elemental distribution is very good at various level, large number of porosity is presented with little bit size, initial rate of absorption (IRA) due to first five minutes immersion of water is higher compared to other immersion time (>5 minute), incremental water intrusion area increases very slowly with the increasing immersion time and the water absorption for RHA brick-2 becomes saturated very early than that of the RHA brick-1.

Chemical Fingerprinting of Counterfeits of Viagra and Cialis Tablets and Analogues via Electrospray Ionization Mass Spectrometry

Direct infusion electrospray ionization mass spectrometry (ESI-MS) is shown to provide an efficient tech- nique for the investigation of polar composition of forensic tablets for male erectile dysfunction. ESI-MS fingerprinting of 41 commercial sildenafil samples (Viagra?, Cialis?, Lazar?, Libiden?, , Maxfil?, , Plenovit?, Potent 75?, Rigix?, V-50?, Vimax?, Pramil 75? and Pramil?) and 56 counterfeit samples (Viagra and Cialis) were obtained. The spectra for the authentic Viagra? tablets showed abundant ions exclusively corresponding to the sildenafil (SLD) molecule: [SLD + H]+ of m/z 475;[SLD + Na]+ of m/z 497;and [2SLD + H]+ of m/z 949. The spectra for com-mercial sildenafil samples also showed predominat SLD ions. Tablets of authentic Cialis? showed mainly ions of m/z 343, 365 and 707 from the lactose molecule (the excipient);as well as a minor ion of m/z 390 corresponding to the active ingredient tadalafil (TAD) in its protonated form [TAD + H]+. For counterfeit Cialis samples, how-ever, normally TAD ions of much high abundances was observed, together with ions corresponding to sildenafil analogues such as those of m/z 489 (homosildenafil) and 505 (hydroxyhomosildenafil). Principal component analysis was applied to ESI-MS fingerprint data, placing samples according to their contents of active ingredients hence authentic and counterfeit samples are easily recognized.

Use of a calibrated SWAT model to evaluate the effects of agricultural BMPs on sediments of the Kalaya river basin (North of Morocco)

Soil erosion from agricultural fields is a worldwide problem,to influence water quality,soil fertility and reservoir sedimentation especially in Mediterranean countries such as Morocco.In fact,this work assesses the effects of Best Management Practices (BMPs) on sediments using the Soil and Water Assessment Tool (SWAT) model in the Kalaya watershed in Northem Morocco,to recommend the most appropriate practice.This study is based on the use of three most usable practices:contouring,stripcropping and terracing,by the calibrated SWAT model.The general parameters of the model have been modified to reflect the implementation of different agricultural BMPs used.Resulting sediment yield were compared with the baseline scenario,for validation.However,the effective measures to reduce sediment losses at the watershed level are organized according to their effectiveness,and these are terracing (28% reduction and the value is 15t/ha/yr) followed by strip-cropping (9% reduction and the value is 5t/ha/yr).In contrast,measurements performed by the contouring are inappropriate for the study area because they have contributed to increasing the soil erosion (more than 31% of losses and the value is 17t/ha/yr more than existing conditions).Therefore,the model illustrates that the terrace is effective for reducing sediment losses and limiting soil erosion especially on steep slopes.Thus,the results provide useful information for targeted management in order to implement the most effective agricultural BMPs in the watershed.

Designing interfaces in energy materials applications with firstprinciples calculations

Materials for energy-related applications,which are crucial for a sustainable energy economy,rely on combining materials that form complex heterogenous interfaces.Simultaneously,progress in computational materials science in describing complex interfaces is critical for improving the understanding and performance of energy materials.Hence,we present an in-depth review of the physical quantities regulating interfaces in batteries,photovoltaics,and photocatalysts,that are accessible from modern electronic structure methods,with a focus on density functional theory calculations.For each energy application,we highlight unique approaches that have been developed to calculate interfacial properties and explore the possibility of applying some of these approaches across disciplines,leading to a unified overview of interface design.Finally,we identify a set of challenges for further improving the theoretical description of interfaces in energy devices.

Assessing sediment yield in Kalaya gauged watershed(Northern Morocco)using GIS and SWAT model

An efficient design for erosion-control structures of any watershed in the world is entrusted with the delicate forecasting of sediment yields.These outlook yields are usually inferred by extrapolations from past observations.Because runoff,as the transporting vehicle,is more closely correlated with sediment yields than any other variable.So,calibration as well as validation of process-based hydrological models are two major processes while estimating the sediment yield in watershed.The actual survey is fulfilled with the aim of developing a trustworthy hydrologic model simulating stream flow discharge and sediment concentration with least uncertainty among the parameters picked out for calibration so as to verify the effect of the scenarios on the spatial distribution of sediment yield(sediments transported from sub-basins to the main channel during the step of time).Soil and Water Assessment Tool(SWAT,version 2012)model integrated with Geographic Information System(GIS,version 10.1)was used to simulate the stream flow and sediment concentration of Kalaya catchment situated in north of Morocco for the period from 1971 to 1993.Model calibration and validation were performed for monthly time periods using Sequential Uncertainty Fitting 2(SUFI-2,version 2)within SWAT-CUP using 16 parameters.Our calibration outputs for monthly simulation for the period from 1976 to 1984 showed a good model performance for flow rates with NSE and PBIAS values of 0.76 and
11.80,respectively;also a good model performance for sediment concentration with NSE and PBIAS values of 0.69 and 7.12,respectively.Nonetheless,during validation period(1985–1993)for monthly time step,the NSE and PBIAS values were 0.67 and
14.44,respectively for flow rates and these statistical values were 0.70 and 15.51,respectively for sediment concentration;which also means a good model performance for both.Following calibration,the inclusive effect of each parameter used was ranked using global sensitivity function in SWAT-CUP.From our analysis,the effective hydraulic conductivity in main channel alluvium(CH_K2),USLE support practice factor(USLE_P)and manning's"n"value for the main channel(CH_N2)were found to be the most sensitive parameters during different iterations with different number of simulation but with the same inputs.The least sensitive parameter were found to be different in either cases unlike the most sensitive parameters.As a result,the global evaluated soil erosion rate in the study area varied from 20 to 120 t/ha/yr.It was summarized that the entire knowledge of the hydrologic processes happens within the watershed and the consciousness about acceptable meaningful range of the parameters is crucial while developing reliable hydrologic model.

NURBS-based DEM for non-spherical particles

The discrete element method(DEM)is used to analyze complex practical granular systems;however,the representation of real shapes is an important consideration because behavior of non-spherical particles is unlike that of spherical particles both individually and collectively.In this study,we use non-uniform rational basis-splines(NURBS)to describe the shapes of non-spherical particles and introduce a contact detection scheme based on quadratic convergence,to simulate the behaviors of elliptical particles.The simulation results are compared with those based on polygons,in terms of the shape description and contact treatment,to demonstrate the high accuracy and efficiency of NURBS-based DEM.

Disentangling multiple scattering with deep learning:application to strain mapping from electron diffraction patterns

A fast,robust pipeline for strain mapping of crystalline materials is important for many technological applications.Scanning electron nanodiffraction allows us to calculate strain maps with high accuracy and spatial resolutions,but this technique is limited when the electron beam undergoes multiple scattering.Deep-learning methods have the potential to invert these complex signals,but require a large number of training examples.We implement a Fourier space,complex-valued deep-neural network,FCU-Net,to invert highly nonlinear electron diffraction patterns into the corresponding quantitative structure factor images.FCU-Net was trained using over 200,000 unique simulated dynamical diffraction patterns from different combinations of crystal structures,orientations,thicknesses,and microscope parameters,which are augmented with experimental artifacts.We evaluated FCU-Net against simulated and experimental datasets,where it substantially outperforms conventional analysis methods.Our code,models,and training library are open-source and may be adapted to different diffraction measurement problems.

Conventional Acupuncture for Cardiac Arrhythmia：A Systematic Review of Randomized Controlled Trials

Objective：To exam the effect and safety of conventional acupuncture（CA） on cardiac arrhythmia.Methods：Nine medical databases were searched until February 2016 for randomized controlled trials.Heterogeneity was measured by Cochran Q test.Meta-analysis was conducted if I2 was less than 85% and the characteristics of included trials were similar.Results：Nine qualified studies involving 638 patients were included.Only 1 study had definitely low risk of bias,while 7 trials were rated as unclear and 1 as high.Meta-analysis of CA alone did not have a significant benefit on response rate compared to amiodarone in patients with atrial fibrillation（Af） and atrial flutter（AF） [relative risk（RR）：1.09;95% confidence interval（CI）：0.79–1.49;P=0.61;I2=61%,P=0.11].However,1 study with higher methodological quality detected a lower recurrence rate of Af in CA alone as compared with sham acupuncture plus no treatment,and benefits on ventricular rate and time of conversion to normal sinus rhythm were found in CA alone group by 1 study,as well as the response rate in CA plus deslanoside group by another study.Meta-analysis of CA plus anti-arrhythmia drug（AAD） was associated with a significant benefit on the response rate when compared with AAD alone in ventricular premature beat（VPB） patients（RR,1.19,95% CI：1.05–1.34;P=0.005;I2=13%,P=0.32）,and an improvement in quality-of-life score（QOLS） of VPB also showed in 1 individual study.Besides,a lower heart rate was detected in the CA alone group by 1 individual study when compared with no treatment in sinus tachycardia patients（MD –21.84 [–27.21,–16.47]） and lower adverse events of CA alone were reported than amiodarone.Conclusions：CA may be a useful and safe alternative or additive approach to AADs for cardiac arrhythmia,especially in VPB and Af patients,which mainly based on a pooled estimate and result from 1 study with higher methodological quality.However,we could not reach a robust conclusion due to low quality of overall evidence.

A deep convolutional neural network for real-time full profile analysis of big powder diffraction data

We present Parameter Quantification Network(PQ-Net),a regression deep convolutional neural network providing quantitative analysis of powder X-ray diffraction patterns from multi-phase systems.The network is tested against simulated and experimental datasets of increasing complexity with the last one being an X-ray diffraction computed tomography dataset of a multi-phase Ni-Pd/CeO_(2)-ZrO_(2)/Al_(2)O_(3) catalytic material system consisting of ca.20,000 diffraction patterns.It is shown that the network predicts accurate scale factor,lattice parameter and crystallite size maps for all phases,which are comparable to those obtained through full profile analysis using the Rietveld method,also providing a reliable uncertainty measure on the results.The main advantage of PQNet is its ability to yield these results orders of magnitude faster showing its potential as a tool for real-time diffraction data analysis during in situ/operando experiments.

Designing the Financing System of the New-type Cooperative Medi-cal Service in Rural Areas

A total of 310 counties （and county-level cities） in 30 provinces, autonomous regions and municipalities directly under the central government in China had conducted experiments of new-type cooperative medical service in the rural areas by October 2004, coveting 95.04 million rural people. The actual number of peasants who joined the service is 68.99 million, accounting for 72.6% of the total, and 3.021 billion yuan was raised.