A review of the literature on the use of CRISPR/Cas9 gene therapy to treat hepatocellular carcinoma

Noncoding RNAs instruct the Cas9 nuclease to site speifillyl cleave DNA in the CRISPR/Cas9 system.Despite the high incidence of hepatocellular carcinoma(HCC),the patient's outcome is poor.As a result of the emergence of therapeutic resistance in HCC patients,dlinicians have faced difficulties in treating such tumor.In addition,CRISPR/Cas9 screens were used to identify genes that improve the dlinical response of HCC patients.It is the objective of this article to summarize the current understanding of the use of the CRISPR/Cas9 system for the treatment of cancer,with a particular emphasis on HCC as part of the current state of knowledge.Thus,in order to locate recent developments in oncology research,we examined both the Scopus database and the PubMed database.The ability to selectively interfere with gene expression in combinatorial CRISPR/Cas9 screening can lead to the discovery of new effective HCC treatment regimens by combining clinically approved drugs.Drug resistance can be overcome with the help of the CRISPR/Cas9 system.HCC signature genes and resistance to treatment have been uncovered by genome-scale CRISPR activation screening although this method is not without limitations.It has been extensively examined whether CRISPR can be used as a tool for disease research and gene therapy.CRISPR and its applications to tumor research,particularly in HCC,are examined in this study through a review of the literature.

Statistical analysis of physico-mechanical parameters of sandstones occurring in orogenic settings

In northeastern Sicily(Italy),sandstone rock masses widely crop out as cover deposits over crystalline terrains belonging to the orogenic belt.Despite being part of the same geological formation,these sandstones are characterized by highly different features in terms of texture and physico-mechanical properties.This poses a scientific question on the possibility of tracing these rocks to a single statistical model,which could be representative of their main engineering geological properties.Therefore,it is worth investigating on the possible reasons of such differences,that should be searched either in the current geographical sandstone distribution or in the rock texture.For this study,sandstone samples were collected from different sites and were analyzed at both the hand and thin section scales.Three sandstone types were recognized,characterized by a different texture.Then,the laboratory characterization allowed estimating their main physico-mechanical and ultrasonic properties,such as porosity,density,mechanical strength,deformability,and ultrasonic velocities.The rock mechanical strength proved linked to the rock compactness and to the presence of lithic fragments,while pores and a pseudo-matrix between grains represent weakening features.Rock data were also statistically analyzed by grouping the specimens according to a geographical criterion,with respect to their sampling area,but no link was found between location and rock properties.Finally,with the aim of achieving mathematical laws that could be used to predict some rock properties from others,useful for practical purposes when dealing with such a high property variability,single and multiple regression analyses were carried out.Results show that the Uniaxial Compressive Strength,porosity,and P-wave velocity are the best predictors for a quick,indirect estimation of the main physico-mechanical parameters.The methodological approach developed for this research can be taken as reference to study other worldwide cases,involving rocks characterized by a wide range of physico-mechanical properties and covering large regional territories.

The potential for an old-growth forest to store carbon in the topsoil:A case study at Sasso Fratino,Italy

There is considerable interest devoted to oldgrowth forests and their capacity to store carbon(C)in biomass and soil.Inventories of C stocks in old-growth forests are carried out worldwide,although there is a lack of information on their actual potential for C sequestration.To further understand this,soil organic carbon(SOC)was measured in one of Italy's best-preserved old-growth forests,the Sasso Fratino Integral Nature Reserve.This reserve is on the World Heritage List along with other ancient beech forests of Europe,and it is virtually untouched due to the steepness of the terrain,even before legal constraints were imposed.Although the sandstone-derived soils are often shallow,they are rich in organic matter.However,no quantification had been carried out.By systematically sampling the topsoil across the forest,we accurately determined the average amount of SOC(62.0±16.9 Mg ha^(–1))and nitrogen(4.0±1.2 Mg ha^(–1))in the top 20 cm.Using the CENTURY model,future dynamics of SOC stocks were predicted to 2050 according to two climate scenarios,A1F1 and B2,the first of high concern and the second more optimistic.The model projected an increase of 0.2 and 0.3 Mg ha^(–1)a^(–1)by 2030 under the A1F1 and B2 scenarios,respectively,suggesting that the topsoil in old-growth forests does not reach equilibrium but continues accumulating SOC.However,from 2030 to 2050,a decline in SOC accumulation is predicted,indicating SOC net loss at high altitudes under the worst-case scenario.This study confirms that soils in oldgrowth forests play a significant role in carbon sequestration.It also suggests that climate change may affect the potential of these forests to store SOC not only in the long term but also in the coming years.

A novel approach to the dynamic response analysis of Euler-Bernoulli beams resting on a Winkler soil model and subjected to impact loads

This work presents a novel approach to the dynamic response analysis of a Euler-Bernoulli beam resting on a Winkler soil model and subjected to an impact loading.The approach considers that damping has much less importance in controlling the maximum response to impulsive loadings because the maximum response is reached in a very short time,before the damping forces can dissipate a significant portion of the energy input into the system.The development of two sine series solutions,relating to different types of impulsive loadings,one involving a single concentrated force and the other a distributed line load,are presented.This study revealed that when a simply supported Euler-Bernoulli beam,resting on a Winkler soil model,is subject to an impact load,the resulting vertical displacements,bending moments and shear forces produced along the span of the beam are considerably affected.In particular,the quantification of this effect is best observed,relative to the corresponding static solution,via an amplification factor.The computed impact amplification factors,for the sub-grade moduli used in this study,were in magnitude greater than 2,thus confirming the multiple-degree-of-freedom nature of the problem.

Complementary memtransistors for neuromorphic computing: How, what and why

Memtransistors in which the source-drain channel conductance can be nonvolatilely manipulated through the gate signals have emerged as promising components for implementing neuromorphic computing.On the other side,it is known that the complementary metal-oxide-semiconductor(CMOS)field effect transistors have played the fundamental role in the modern integrated circuit technology.Therefore,will complementary memtransistors(CMT)also play such a role in the future neuromorphic circuits and chips?In this review,various types of materials and physical mechanisms for constructing CMT(how)are inspected with their merits and need-to-address challenges discussed.Then the unique properties(what)and poten-tial applications of CMT in different learning algorithms/scenarios of spiking neural networks(why)are reviewed,including super-vised rule,reinforcement one,dynamic vision with in-sensor computing,etc.Through exploiting the complementary structure-related novel functions,significant reduction of hardware consuming,enhancement of energy/efficiency ratio and other advan-tages have been gained,illustrating the alluring prospect of design technology co-optimization(DTCO)of CMT towards neuro-morphic computing.

Introduction to the Special Issue on Recent Developments on Computational Biology-I

In modern time,experts started to use interdisciplinary properties with the development of technology and science.Thus,these disciplines provide more sophisticated properties of real-world problems.In this sense,some models need to be investigated by using revised and modified traditional methods.The first discipline is the applied sciences such as physics,engineering,mechanics,electricity,biology,economy and mathematical applications[1-5].In this stage,many methods[5-10]are developed and modified.To uncover the deep properties of problems is to use the main properties of such interdisciplinary properties.Furthermore,works conducted on such mathematical models including non-local operators,partial,ordinary and integer order have introduced a deeper investigation of problems for experts.By using technological tools,expertsmay observe more realistic and exact results of models.

Effectiveness of Sodium Silicate on the Corrosion Protection of AA7075-T6 Aluminium Alloy in Sodium Chloride Solution

The influence of sodium silicate on the corrosion behaviour of aluminium alloy 7075-T6 in 0.1 M sodium chloride solution was studied by open circuit potential (OCP) and electrochemical impedance spectroscopy (EIS) techniques. Scanning electron microscopy (SEM) was used to characterize the AA7075-T6 surface. Silicate can significantly reduce corrosion deterioration and the inhibition efficiency increases with the concentration of Na2SiO3. The corrosion inhibition mechanism involves the formation of a protective film over the alloy surface by adsorption of aluminosilicate anions from solution, as has also been suggested by others in literature.

Final results of the first phase of the PROTO-SPHERA experiment: obtainment of the full current stable screw pinch and first evidences of the jet + torus combined plasma configuration

In astrophysics, the boundary conditions for plasma phenomena are provided by nature and the astronomer faces the problem of understanding them from a variety of observations [Hester J J et al 1996 Astrophys. J. 456 225], on the other hand, in laboratory plasma experiments the electromagnetic boundary conditions become a major problem in the set-up of the machine that produces the plasma, an issue that has to be investigated step by step and to be modified and adapted with great patience, in particular in the case of an innovative plasma confinement experiment. The PROTO-SPHERA machine [Alladio F et al 2006 Nucl. Fusion 46 S613] is a magnetic confinement experiment, that emulates in the laboratory the jet + torus plasma configurations often observed in astrophysics: an inner magnetized jet of plasma centered on the(approximate) axis of symmetry and surrounded by a magnetized plasma torus orthogonal to this jet. The PROTO-SPHERA plasma is simply connected, i.e., no metal current conducting rod is linked to the plasma torus, while instead it is the inner magnetized plasma jet(in the following always called the plasma centerpost) that is linked to the torus. It is mandatory that no spurious plasma current path modifies the optimal shape of the plasma centerpost. Moreover, as the plasma torus is produced and sustained, in absence of any applied inductive electric field, by the inner plasma centerpost through magnetic reconnections [Taylor J B and Turner M F 1989 Nucl.Fusion 29 219], it is required as well that spurious current paths do not surround the torus on its outboard, in order not to lower the efficiency of the magnetic reconnections that maintain the plasma torus at the expense of the plasma centerpost. Boundary conditions have been corrected,up to the point that the first sustainment in steady state has been achieved for the combined plasma.

Transanal eco-Doppler evaluation after hemorrhoidal artery embolization

BACKGROUND Hemorrhoidal artery embolization(Emborrhoid)is a novel method for the treatment of severe hemorrhoidal bleeding.Despite having a technical success rate of 93%-100%,the clinical success ranges between 63%and 94%,with a rebleeding rate of 13.6%.AIM To evaluate the effectiveness of this procedure in reducing hemorrhoidal flow and hemorrhoidal bleeding.METHODS This prospective observational pilot study was conducted at Division of General Surgery 1 and Tertiary Referral Pelvic Floor Center,Treviso Regional Hospital,Italy.In a 2 months period(February-March 2022),consecutive patients with hemorrhoidal bleeding scores(HBSs)≥4,Goligher scores of II or III,failure of non-operative management,and a candidate for Emborrhoid were included.Endoanal ultrasound with eco-Doppler was performed preoperatively and 1 month after the procedure.The primary endpoint was to quantify the changes in arterial hemorrhoidal flow after treatment.The secondary endpoint was to evaluate the correlation between the flow changes and the HBS.RESULTS Eleven patients underwent Emborrhoid.The overall pretreatment mean systolic peak(MSP)was 14.66 cm/s.The highest MSP values were found in the anterior left lateral(17.82 cm/s at 1 o’clock and 15.88 cm/s at 3 o’clock)and in the posterior right lateral(14.62 cm/s at 7 o’clock and 16.71 cm/s at 9 o’clock)quadrants of the anal canal.After treatment,the overall MSP values were significantly reduced(P=0.008)although the correlation between MSP and HBS changes was weak(P=0.570).A statistical difference was found between distal embolization compared with proximal embolization(P=0.047).However,the coil landing zone was not related to symptoms improvement(P=1.000).A significant difference in MSP changes was also reported between patients with type 1 and type 2 superior rectal artery(SRA)anatomy(P=0.040).No relationship between hemorrhoidal grades(P=1.000),SRA anatomy(P=1.000)and treatment outcomes was found.CONCLUSION The preliminary findings of this pilot study confirm that Emborrhoid was effective in reducing the arterial hemorrhoidal flow in hemorrhoidal disease.However,the correlation between the post-operative MSP and HBS changes was weak.Hemorrhoidal grade,SRA anatomy and type of embolization were not related to treatment outcomes.

A Number Theoretic Analysis of the Enthalpy, Enthalpy Energy Density, Thermodynamic Volume, and the Equation of State of a Modified White Hole, and the Implications to the Quantum Vacuum Spacetime, Matter Creation and the Planck Frequency

In this paper, we analyze the enthalpy, enthalpy energy density, thermodynamic volume, and the equation of state of a modified white hole. We obtain new possible mathematical connections with some sectors of Number Theory, Ramanujan Recurring Numbers, DN Constant and String Theory, that enable us to extract the quantum geometrical properties of these thermodynamic equations and the implication to the quantum vacuum spacetime geometry of our early universe as they act as the constraints to the nature of quantum gravity of the universe.

Profiles of the Headspace Volatile Organic and Essential Oil Compounds from the Tunisian Cardaria draba (L.) Desv. and Its Leaf and Stem Epidermal Micromorphology

In this work, we investigated aroma volatiles emanated by dry roots, stems, leaves, flowers, and fruits of Cardariadraba (L.) Desv. growing wild in Tunisia and its aerial part essential oils (EOs) composition. A total of 37 volatileorganic compounds (96.7%–98.9%) were identified;4 esters, 4 alcohols, 7 hydrocarbons, 12 aldehydes, 5 ketones,1 lactone, 1 organosulfur compound, 2 organonitrogen compounds, and 1 acid. The hydrocarbons form the maingroup, representing 49.5%–84.6% of the total detected volatiles. The main constituent was 2,2,4,6,6-pentamethylheptane(44.5%–76.2%) reaching the highest relative percentages. Forty-two compounds were determined in thetwo fractions of EOs, representing 98.8% and 97.2% of the total oil composition, respectively. The principal componentswere hexadecanoic acid (34.6%), 6-methyl-5-hepten-2-one (18.3%), decanal (15.0%), 6,10,14-trimethyl-2-pentadecanone (13.2%), and n-pentacosane (13%). Micromorphological details of the leaf and stem epidermisusing light microscopy revealed polygonal cells with sinuous walls in the adaxial and abaxial leaf surfaces andnearly rectangular and long ones with linear and thick walls for the stem epidermis. The stomata complexes wereanisocytic in the leaf epidermis and mainly anisocytic and rarely paracytic in the stem epidermis. Non-glandulartrichomes were unbranched and long with an acute apex or short with a convex apex. The glandular ones wereidentified for the first time in this species. They were short-stalked with a large secretory head. The highest stomatalindex (17.02%) was recorded in the abaxial leaf surface. The identification of headspace volatiles and essentialoil compounds can be used to characterize this species, and the various epidermis micromorphologicalfeatures are very useful for biosystematics taxonomic studies within Brassicaceae.

Reconsidering the role of depression and common psychiatric disorders as partners in the type 2 diabetes epidemic

Common psychiatric disorders(CPDs)and depression contribute significantly to the global epidemic of type 2 diabetes(T2D).We postulated a possible pathophysiological mechanism that through Bridge-Symptoms present in depression and CPDs,promotes the establishment of emotional eating,activation of the reward system,onset of overweight and obesity and,ultimately the increased risk of developing T2D.The plausibility of the proposed pathophysiological mechanism is supported by the mechanism of action of drugs such as naltrexonebupropion currently approved for the treatment of both obesity/overweight with T2D and as separate active pharmaceutical ingredients in drug addiction,but also from initial evidence that is emerging regarding glucagon-like peptide 1 receptor agonists that appear to be effective in the treatment of drug addiction.We hope that our hypothesis may be useful in interpreting the higher prevalence of CPDs and depression in patients with T2D compared with the general population and may help refine the integrated psychiatric-diabetic therapy approach to improve the treatment and or remission of T2D.

This pain drives me crazy:Psychiatric symptoms in women with interstitial cystitis/bladder pain syndrome

BACKGROUND Interstitial cystitis/bladder pain syndrome(IC/BPS)is an at least 6-mo noninfectious bladder inflammation of unknown origin characterized by chronic suprapubic,abdominal,and/or pelvic pain.Although the term cystitis suggests an inflammatory or infectious origin,no definite cause has been identified.It occurs in both sexes,but women are twice as much affected.AIM To systematically review evidence of psychiatric/psychological changes in persons with IC/BPS.METHODS Hypothesizing that particular psychological characteristics could underpin IC/BPS,we investigated in three databases the presence of psychiatric symptoms and/or disorders and/or psychological characteristics in patients with IC/BPS using the following strategy:("interstitial cystitis"OR"bladder pain syndrome")AND("mood disorder"OR depressive OR antidepressant OR depression OR depressed OR hyperthymic OR mania OR manic OR rapid cyclasterisk OR dysthymiasterisk OR dysphoriasterisk).RESULTS On September 27,2023,the PubMed search produced 223 articles,CINAHL 62,and the combined PsycLIT/PsycARTICLES/PsycINFO/Psychology and Behavioral Sciences Collection search 36.Search on ClinicalTrials.gov produced 14 studies,of which none had available data.Eligible were peer-reviewed articles reporting psychiatric/psychological symptoms in patients with IC/BPS,i.e.63 articles spanning from 2000 to October 2023.These studies identified depression and anxiety problems in the IC/BPS population,along with sleep problems and the tendency to catastrophizing.CONCLUSION Psychotherapies targeting catastrophizing and life stress emotional awareness and expression reduced perceived pain in women with IC/BPS.Such concepts should be considered when implementing treatments aimed at reducing IC/BPS-related pain.

含混合储能直流微电网混合势函数建模及稳定性分析

针对含恒功率负荷的混合储能直流微电网大扰动稳定及储能变换器建模问题,在推导混合储能(hybrid energy storage system,HESS)脉宽调制开关网络等效模型基础上,提出了一种基于混合势函数理论的含HESS直流微电网稳定性判据及分析方法。首先,计及HESS充放电特性,将含HESS直流微电网系统的工作状态划分为buck和boost工作模式;接着,分别建立上述两种工作模式下基于脉宽调制开关网络等效模型的直流微电网系统混合势函数模型;最后,应用混合势函数理论第3稳定性定理,分别推导得到buck和boost工作模式下的直流微电网大扰动稳定性判据,并对比基于开关平均模型的系统稳定性判据,提出的稳定性判据推导方法对系统动态行为预测更为准确。仿真验证了所提稳定性分析方法的合理性以及混合势函数判据的先进性。

考虑电动汽车灵活储能的交直流混合微电网功率协调控制策略

孤立交直流混合微电网集中储能荷电状态趋近充、放电临界值,容易引发微电网及其子网功率越限,从而导致系统供电不可靠。在此背景下,该文提出了一种考虑电动汽车灵活储能的交直流混合微电网功率协调控制策略。首先,根据交直流混合微电网及其子网功率盈缺状态,同时考虑混合储能中传统集中和灵活储能之间协调配合,将交直流混合微电网运行模式划分为正常、临界平衡和功率越限3种。在此基础上,根据储能荷电状态不均衡或异常、子微网越限等非正常状态进一步划分工况,以将控制目标进行细分。接着,通过分析电动汽车灵活储能、传统集中储能与互联接口变换器在同一时间尺度下的响应优先级,设计混合储能功率分配和互联接口变换器功率传输原则,并提出系统运行模式及工况间平滑切换方法。最后,基于MATLAB/Simulink搭建的交直流混合微电网仿真模型验证了所提控制策略的有效性。

A novel way to study the nuclear collective excitations

Typically, the unambiguous determination of the quantum numbers of nuclear states is a challenging task. Recently, it has been proposed to utilize to this aim vortex photons in the MeV energy region and, potentially, this could revolutionize nuclear spectroscopy because of the new and enhanced selectivity of this probe. Moreover, nuclei may become diagnostic tools for vortex photons. Still, some open questions have to be dealt with.Nuclei exhibit intricate excitation spectra. Indeed, not all states within these spectra are equally significant. Some are not sensitive to specific terms in the nuclear Hamiltonian or do not display novel features, so that investigating them is not helpful to enhance our overall understanding of nuclear structure. On the other hand, there are states that manifest themselves as prominent peaks, e.g., in the inelastic scattering spectra. Among the best examples are the so-called Giant Resonances that lie at energies of the order of tens of MeV [1].

Preparation of aromatic hydrocarbons from catalytic pyrolysis of digestate

Catalytic pyrolysis of digestate to produce aromatic hydrocarbons can be combined with anaerobic fermentation to effectively transform and utilize all biomass components,which can achieve the meaningful purpose of transforming waste into high-value products.This study explored whether catalytic pyrolysis of digestate is feasible to prepare aromatic hydrocarbons by analyzing the thermogravimetric characteristics,pyrolysis characteristics,and catalytic pyrolysis characteristics of digestate.For digestate pyrolysis,an increase in temperature was found to elevate the CO,CH_4,and monocyclic aromatic hydrocarbon(benzene,toluene,and xylene;BTX)content,whereas it decreased the contents of phenols,acids,aldehydes,and other oxygenates.Furthermore,the catalytic pyrolysis process effectively inhibited the acids,phenols,and furans in the liquid,whereas the yield of BTX increased from 25.45%to 45.99%,and the selectivity of xylene was also increased from 10.32%to 28.72%after adding ZSM-5.ZSM-5 also inhibited the production of nitrogenous compounds.

A Quorum Sensing Active Matter in a Confined Geometry

Inspired by the problem of biofilm growth,we numerically investigate clustering in a two-dimensional suspension of active(Janus)particles of finite size confined in a circular cavity.Their dynamics is regulated by a non-reciprocal mechanism that causes them to switch from active to passive above a certain threshold of the perceived near-neighbor density(quorum sensing).A variety of cluster phases,i.e.,glassy,solid(hexatic)and liquid,are observed,depending on the particle dynamics at the boundary,the quorum sensing range,and the level of noise.

One-and Multi-dimensional CWENOZ Reconstructions for Implementing Boundary Conditions Without Ghost Cells

We address the issue of point value reconstructions from cell averages in the context of third-order finite volume schemes,focusing in particular on the cells close to the boundaries of the domain.In fact,most techniques in the literature rely on the creation of ghost cells outside the boundary and on some form of extrapolation from the inside that,taking into account the boundary conditions,fills the ghost cells with appropriate values,so that a standard reconstruction can be applied also in the boundary cells.In Naumann et al.(Appl.Math.Comput.325:252–270.https://doi.org/10.1016/j.amc.2017.12.041,2018),motivated by the difficulty of choosing appropriate boundary conditions at the internal nodes of a network,a different technique was explored that avoids the use of ghost cells,but instead employs for the boundary cells a different stencil,biased towards the interior of the domain.In this paper,extending that approach,which does not make use of ghost cells,we propose a more accurate reconstruction for the one-dimensional case and a two-dimensional one for Cartesian grids.In several numerical tests,we compare the novel reconstruction with the standard approach using ghost cells.

Quinpi:Integrating Conservation Laws with CWENO Implicit Methods

Many interesting applications of hyperbolic systems of equations are stiff,and require the time step to satisfy restrictive stability conditions.One way to avoid small time steps is to use implicit time integration.Implicit integration is quite straightforward for first-order schemes.High order schemes instead also need to control spurious oscillations,which requires limiting in space and time also in the linear case.We propose a framework to simplify considerably the application of high order non-oscillatory schemes through the introduction of a low order implicit predictor,which is used both to set up the nonlinear weights of a standard high order space reconstruction,and to achieve limiting in time.In this preliminary work,we concentrate on the case of a third-order scheme,based on diagonally implicit Runge Kutta(DIRK)integration in time and central weighted essentially non-oscillatory(CWENO)reconstruction in space.The numerical tests involve linear and nonlinear scalar conservation laws.