High persistence rate of hepatitis B virus in a hydrodynamic injection-based transfection model in C3H/He N mice

AIM: To optimize the viral persistence rate in a hydrodynamic injection(HI) based hepatitis B virus(HBV) transfection mouse model.METHODS:(1) 5-6-wk-old male C3H/He N and C57BL/6 mice were hydrodynamically injected with 10 μg endotoxin-free p AAV/HBV1.2 plasmid DNA via the tail vein. Hepatitis B surface antigen(HBs Ag), hepatitis B e antigen(HBe Ag) and HBV DNA, both in the serum and liver, were detected at different time points post HI by ELISA, immunohistochemical staining or quantitative polymerase chain reaction(PCR);(2) male C3H/He N and C57BL/6 mice, either hydrodynamically injected mice at 10 wk post HI or na?ve mice, were all immunized subcutaneously with 5 μg HBs Ag formulated in complete Freund's adjuvant three times at a 2-wk interval. Two weeks after the final immunization, splenocytes were isolated for T cell function analysis by ELISPOT assay; and(3) five weeks post HI, C3H/He N mice were intragastrically administered 0.1 mg/kg entecavir once a day for 14 d, or were intraperitoneally injected with 1 mg/kg interferon(IFN)-α twice a week for 2 wk, or were treated with PBS as controls. The sera were collected and assayed for HBV DNA on days 0, 7 and 14 after drug treatment. RESULTS:(1) Approximately 90%(22/25) of the injected C3H/He N mice were still HBs Ag-positive at 46 wk post HI, whereas HBs Ag in C57BL/6 mice were completely cleared at 24 wk. Serum levels of HBe Ag in C3H/He N mice were higher than those in C57BL/6 mice from 4 wk to 46 wk. HBV DNA levels in the hydrodynamically injected C3H/He N mice were higher than those in the C57BL/6 mice, both in the serum(from 4 wk to 46 wk) and in the liver(detected at 8 wk and 46 wk post HI). Histology showed that hepatitis B core antigen and HBs Ag were expressed longer in the liver of C3H/He N mice than in C57BL/6;(2) HBs Ag specific T cell responses after HBs Ag vaccination in hydrodynamically injected C3H/He N and C57BL/6 mice, or naive control mice were detected by ELISPOT assay. After stimulation with HBs Ag, the frequencies of IFN-γ producing splenocytes in the hydrodynamically injected C3H/He N mice were significantly lower than those in hydrodynamically injected C57BL/6 mice, control C3H/He N and control C57BL/6 mice, which were 0, 17 ± 7, 18 ± 10, and 41 ± 10 SFCs/106 splenocytes, respectively, and the mean spot sizes showed the same pattern. Even just stimulated with PMA and ionomysin, T-cell responses elicited in the vaccinated control C3H/He N were much higher than those in hydrodynamically injected C3H/He N mice; and(3) For drug treatment experiments on the hydrodynamically injected C3H/He N mice, serum HBV DNA levels in the entecavir treatment group declined(131.2 folds, P < 0.01) on day 7 after treatment and kept going down. In the group of IFN-α treatment, serum HBV DNA levels declined to a lowest point(6.42 folds, P < 0.05) on 7 d after treatment and then rebounded.CONCLUSION: We have developed a novel HI-based HBV transfection model using C3H/He N mice, which had a higher HBV persistence rate than the classic C57BL/6 mouse model.

Modified Bfat-1 gene and its biological verification in mice by hydrodynamic tail vein injection

Omega-3 polyunsaturated fatty acids （w-3 PUFAs） are essential components required for normal cellular function and have been shown to have important therapeutic and nutritional benefits in humans. But humans or mammals cannot naturally produce w-3 PUFAs, due to the lack of the co-3 fatty acid desaturase gene （fat-1 gene）. Previously, fat-1 gene has been cloned from Caenorhabditis elegans and transferred into mice, pigs and sheep, but not yet into beef cattle. We attempt to transfer it into beef cattle. The object of this paper is to edit the fat-1 gene from C. elegans to express more efficiently in beef cattle and verify its biological function in mice model. As a result, the fat-1 gene from C. elegans was modified by synonymous codon usage and named it Bfat-l. We have demonstrated that degree of codon bias of Brat-1 gene was in- creased in beef cattle. Moreover, Bfat-1 gene could be transiently expressed in mouse liver and muscle, the w-6/co-3 PUFAs ratio of 18 and 20 carbon was decreased significantly in liver （P〈0.05）, and the ratio of 20 carbon decreased significantly in muscle 24 and 72 h after injection （P〈0.05）. This confirms that the Bfat-1 gene modification was successful, and the protein encoded was able to catalyze the conversion of w-6 PUFAs to e0-3 PUFAs.

Influence of Feed Injection on Hydrodynamic Behavior in FCC Riser

This paper studies the influence of feed injection on the hydrodynamic behavior of fluid catalytic cracking riser reactors. Experiments were conducted in a cold model of 186 mm ID with two oppositely inclined secondary air feed nozzles. The flow structure was determined by means of the axial static pressure measurements and local radial optic fiber probe measurements on different levels with emphasis on the sections downstream of the secondary injection. The measurements reveal that the secondary injection plays a crucial role on riser hydrodynamics. Just above the secondary injection, the flow and mixing are strongly affected, while below the secondary injection the effect is weak. The radial profile just downstream of secondary injection demonstrates wavy features. The effective region of secondary injection could be estimated by the axial pressure gradient profiles and/or the radial profiles of local solids velocity and density.

Numerical Simulation of Asphaltene Precipitation and Deposition during Natural Gas and CO_(2) Injection

Asphaltene deposition is a significant problem during gas injection processes,as it can block the porous medium,the wellbore,and the involved facilities,significantly impacting reservoir productivity and ultimate oil recovery.Only a few studies have investigated the numerical modeling of this potential effect in porous media.This study focuses on asphaltene deposition due to natural gas and CO_(2) injection.Predictions of the effect of gas injection on asphaltene deposition behavior have been made using a 3D numerical simulation model.The results indicate that the injection of natural gas exacerbates asphaltene deposition,leading to a significant reduction in permeability near the injection well and throughout the reservoir.This reduction in permeability strongly affects the ability of gas toflow through the reservoir,resulting in an improvement of the displacement front.The displacement effi-ciency of the injection gas process increases by up to 1.40%when gas is injected at 5500 psi,compared to the scenario where the asphaltene model is not considered.CO_(2) injection leads to a miscible process with crude oil,extracting light and intermediate components,which intensifies asphaltene precipitation and increases the viscosity of the remaining crude oil,ultimately reducing the recovery rate.

Shenqi Fuzheng injection alleviates chemotherapy-induced cachexia by restoring glucocorticoid signaling in hypothalamus

Chemotherapy-induced cachexia(CIC)is a debilitating condition characterized by weight loss,muscle atrophy,and anorexia[1].While peripheral mechanisms of cachexia have been extensively studied,the involvement of the central nervous system(CNS)in CIC is often overlooked.Chemotherapeutic drugs cause stress responses and inflammation,which may impact the hypothalamus and disrupt systemic energy and neuroendocrine functions.Understanding hypothalamic roles in regulating these processes can provide insights into CIC's mechanisms and aid in developing novel therapies.

Does HSP27 injection induce glaucoma damage in mice?

In a further aging society,excellent eyesight is an integral part of overall well-being and quality of life.Preserving good vision is crucial to maintaining mobility,independence,and mental health.There can be several reasons for visual impairment in elderly people,these include age-related macular degeneration,the leading cause of vision loss among older adults,cataract,glaucoma,diabetic retinopathy,retinal detachment,and others.

Tofacitinib combined with local low-dose ixekizumab injection benefits those with peripheral psoriatic arthritis

Dear Editor,Treating psoriatic arthritis(PsA)is always difficult.Systemic treatments can be administered either orally or through intramuscular and intra-articular injection,including conventional synthetics,biologics and targeted synthetic disease-modifying antirheumatic drugs[1].The alternatives,topical external therapies,are not effective on joint lesions due to drug permeability issues.Drugs injected into the articular cavity are also unsuitable for small peripheral joint lesions,the most common manifestations of PsA.The limited treatment options for PsA present a challenge.

Experimental study of the influencing factors and mechanisms of the pressure-reduction and augmented injection effect by nanoparticles in ultra-low permeability reservoirs

Nanoparticles(NPs)have gained significant attention as a functional material due to their ability to effectively enhance pressure reduction in injection processes in ultra-low permeability reservoirs.NPs are typically studied in controlled laboratory conditions,and their behavior in real-world,complex environments such as ultra-low permeability reservoirs,is not well understood due to the limited scope of their applications.This study investigates the efficacy and underlying mechanisms of NPs in decreasing injection pressure under various injection conditions(25—85℃,10—25 MPa).The results reveal that under optimal injection conditions,NPs effectively reduce injection pressure by a maximum of 22.77%in core experiment.The pressure reduction rate is found to be positively correlated with oil saturation and permeability,and negatively correlated with temperature and salinity.Furthermore,particle image velocimetry(PIV)experiments(25℃,atmospheric pressure)indicate that the pressure reduction is achieved by NPs through the reduction of wall shear resistance and wettability change.This work has important implications for the design of water injection strategies in ultra-low permeability reservoirs.

Background diseases and the number of previous intravitreal aflibercept injections on immediate intraocular pressure increase and vitreous reflux rate in phakic eyes

●AIM:To evaluate the effect of background diseases and number of previous intravitreal aflibercept injections(IVAIs)on immediate intraocular pressure(IOP)increase and vitreous reflux(VR)rate and to evaluate the correlation of both age and axial length with immediate IOP increase and VR rate.●METHODS:This study included 105 patients with cystoid macular edema secondary to retinal vein occlusion,35 patients with diabetic macular edema,69 patients with neovascular age-related macular degeneration(nAMD),and 12 patients with myopic choroidal neovascularization,which underwent first-time IVAI.The correlation of immediate IOP increase and VR rates with the four background diseases was investigated.Moreover,the correlation of age with immediate IOP increase and VR rate as well as correlation of axial length with immediate IOP increase and VR rate were evaluated.Further,54 patients with nAMD were treated with IVAI>10 times(multiple IVAIs).Moreover,the correlation of immediate IOP increase and VR rates with first-time and multiple IVAIs in nAMD was determined.●RESULTS:The immediate IOP increase(P=0.16)and VR rates(P=0.50)were almost similar among the four background diseases.The immediate postinjection IOP and age,VR rate and age,immediate postinjection IOP and axial length,or VR rate and axial length were not correlated in the four background diseases.The immediate IOP increase(P=0.66)and VR rates(P=0.28)did not significantly differ between first-time and multiple IVAIs in nAMD.●CONCLUSION:Background diseases and number of previous IVAIs have no effect on immediate IOP increase and VR rate.Further,age and axial length have no correlation on immediate IOP increase and VR rate.

Oxygen variation in titanium powder and metal injection molding

The control of oxygen is paramount in achieving high-performance titanium(Ti)parts by powder metallurgy such as metal in-jection molding(MIM).In this study,we purposely selected the Ti and Ti-6Al-4V powders as the reference materials since these two are the most representative Ti materials in the industry.Herein,hydride-dehydride(HDH)Ti powders were pre-oxidized to examine the ef-fect of oxygen variation on the characteristics of oxide layer on the particle surface and its resultant color feature.The results indicate that the thickness and Ti oxide level(Ti^(0)→Ti^(4+))of the oxide layer on the HDH Ti powders increased as the oxygen content increased,lead-ing to the transition of color appearance from grey,brown to blue.This work aids in the powder feedstock selection at the initial stage in powder metallurgy.In addition,the development of oxygen content was comprehensively studied during the MIM process using the gas-atomized(GA)Ti-6Al-4V powders.Particularly,the oxygen variation in the form of oxide layer,the change of oxygen content in the powders,and the relevant parts were investigated during the processes of kneading,injection,debinding,and sintering.The oxygen vari-ation was mainly concentrated in the sintering stage,and the content increased with the increase of sintering temperature.The variation of oxygen content during the MIM process demonstrates the crucial role of powder feedstock and sintering stage in controlling oxygen con-tent.This work provides a piece of valuable information on oxygen detecting,control,and manipulation for the powder and processing in the industry of Ti and its alloys by powder metallurgy.

An Innovative Coupled Common-Node Discrete Element Method-Smoothed Particle Hydrodynamics Model Developed with LS-DYNA and Its Applications

In this study,a common-node DEM-SPH coupling model based on the shared node method is proposed,and a fluid–structure coupling method using the common-node discrete element method-smoothed particle hydrodynamics(DS-SPH)method is developed using LS-DYNA software.The DEM and SPH are established on the same node to create common-node DEM-SPH particles,allowing for fluid–structure interactions.Numerical simulations of various scenarios,including water entry of a rigid sphere,dam-break propagation over wet beds,impact on an ice plate floating on water and ice accumulation on offshore structures,are conducted.The interaction between DS particles and SPH fluid and the crack generation mechanism and expansion characteristics of the ice plate under the interaction of structure and fluid are also studied.The results are compared with available data to verify the proposed coupling method.Notably,the simulation results demonstrated that controlling the cutoff pressure of internal SPH particles could effectively control particle splashing during ice crushing failure.

Intravitreal injection practice patterns among Chinese ophthalmologists

AIM:To describe the practice patterns of intravitreal injections(IVIs)among ophthalmologists in China.METHODS:This was a cross-sectional online survey.Ophthalmologists who had performed accumulated more than 100 injections were contacted by the Brightness Center,a hospital-based national network,to complete an anonymous,24-question,internet-based survey.They were surveyed on practices in injection techniques,pre-,and post-injections procedures.RESULTS:A total of 333 ophthalmologists from 28 provinces/municipalities/autonomous regions responded to the survey(50.68%response rate).The 91.29%of the respondents evaluated systemic risk factors by medical history,electrocardiogram(ECG)and blood test.All the respondents used pre-injection prophylactic antibiotics.Most checked intraocular pressure(IOP,99.1%)and blood pressure(96.1%)before injections.A majority of the respondents performed injections in the operating room(98.8%),wore masks(99.7%),gloves(99.4%)and sterile surgical clothing(96.1%),performed topical anesthetics(97.9%),and applied povidone-iodine(95.8%)pre-injection.The 61.26%of the respondents dilated pupil.About half of the respondents(51.05%)performed bilateral injections in the same setting.Superior temporal quadrant(40.54%)was the most frequent site of injection.Around three quarters used 30-gauge needles.Most respondents(97.9%)measured the site of injection from limbus.More than half(53.45%)performed conjunctiva displacement prior to injection.The 32.43%of the respondents checked IOP post-injection and 87.99%physicians checked hand motion(HM)or counting fingers(CF)after injection,while 36.94%observed optic nerve perfusion.All participants used topical antibiotics post-injections.Most physicians(91.89%)reviewed patients on the following day.CONCLUSION:This study provides a description of the real-world practice patterns in IVIs in China and offers critical information regarding education and training of ophthalmologists and amendment of local society guidelines.

Simulation of nanofluid natural convection based on single-particle hydrodynamics in energy-conserving dissipative particle dynamics(eDPD)

In the present study,the nanofliud natural convection is investigated by the energy-conserving dissipative particle dynamics(eDPD)method,where the nanoparticles are considered at the single-particle level.The thermal expansion coefficientβand the viscosityμof the simulated system containing nanoparticles are calculated and found to be in close alignment with the previous simulation results.The single-particle hydrodynamics in e DPD enables simulations of nanofluid natural convection with higher Rayleigh numbers and greater nanoparticle volume fractions.Additionally,this approach is utilized to simulate the nanoparticle distribution during the enhanced heat transfer process in the nanofluid natural convection.The localized aggregation of nanoparticles enhances the heat transfer performance of the nanofluid under specific Rayleigh numbers and nanoparticles volume fractions.

A modified smoothed particle hydrodynamics method considering residual stress for simulating failure and its application in layered rock mass

Residual strength is an indispensable factor in evaluating rock fracture,yet the current Smoothed Particle Hydrodynamics(SPH)framework rarely considers its influence when simulating fracture.An improved cracking strategy considering residual stress in the base bond SPH method was proposed to simulate failures in layered rocks and slopes and verified by experimental results and other simulation methods(i.e.,the discrete element method).Modified Mohr–Coulomb failure criterion was applied to distinguish the mixed failure of tensile and shear.Bond fracture markψwas introduced to improve the kernel function after tensile damage,and the calculation of residual stress after the damage was derived after shear damage.Numerical simulations were carried out to evaluate its performance under different stress and scale conditions and to verify its effectiveness in realistically reproducing crack initiation and propagation and coalescence,even fracture and separation.The results indicate that the improved cracking strategy precisely captures the fracture and failure pattern in layered rocks and rock slopes.The residual stress of brittle tock is correctly captured by the improved SPH method.The improved SPH method that considers residual strength shows an approximately 13%improvement in accuracy for the safety factor of anti-dip layered slopes compared to the method that does not consider residual strength,as validated against analytical solutions.We infer that the improved SPH method is effective and shows promise for applications to continuous and discontinuous rock masses.

Cross-upgrading of biomass hydrothermal carbonization and pyrolysis for high quality blast furnace injection fuel production:Physicochemical characteristics and gasification kinetics analysis

The paper proposes a biomass cross-upgrading process that combines hydrothermal carbonization and pyrolysis to produce high-quality blast furnace injection fuel.The results showed that after upgrading,the volatile content of biochar ranged from 16.19%to 45.35%,and the alkali metal content,ash content,and specific surface area were significantly reduced.The optimal route for biochar pro-duction is hydrothermal carbonization-pyrolysis(P-HC),resulting in biochar with a higher calorific value,C=C structure,and increased graphitization degree.The apparent activation energy(E)of the sample ranges from 199.1 to 324.8 kJ/mol,with P-HC having an E of 277.8 kJ/mol,lower than that of raw biomass,primary biochar,and anthracite.This makes P-HC more suitable for blast furnace injection fuel.Additionally,the paper proposes a path for P-HC injection in blast furnaces and calculates potential environmental benefits.P-HC of-fers the highest potential for carbon emission reduction,capable of reducing emissions by 96.04 kg/t when replacing 40wt%coal injec-tion.

Efficacy of acupoint injection in the treatment of chronic eczema and its influence on peripheral blood T cells

BACKGROUND Chronic eczema significantly impacts daily life,social interactions,and quality of life;however,no curative treatment has been identified.AIM To determine the clinical efficacy of acupoint injection for chronic eczema and its influence on peripheral blood T cells.METHODS Eighty patients with chronic eczema treated at our hospital between June 2022 and March 2023 were randomly assigned to a control group(n=40),which received conventional Western medicine treatment,or an observation group(n=40),which received routine Western medicine treatment plus acupoint injection of triamcinolone acetonide.Response and adverse reaction rates,as well as differences in the levels of serum cytokines IFN-γ,IL-2,IL-4,and IL-10 before and after treatment were investigated.RESULTS No difference in overall response rates were found between the observation and control groups(100%vs 90%,respectively;P>0.05);however,the observation group had a higher marked response rate than the control group(87.5%vs 52.5%;P<0.05).Both groups had decreased Eczema Area and Severity Index scores and increased pruritus after treatment(P<0.05),particularly in the observation group(P<0.05).The observation group had an adverse reaction rate of 2.5%(1/40),which did not differ significantly from that of the control group(P>0.05).The observation group exhibited higher post-treatment INF-γand IL-2 but lower IL-4 levels than the control group(P<0.05);however,no significant inter-group difference was observed in post-treatment IL-10 levels(P>0.05).CONCLUSION Acupoint injection of triamcinolone acetonide is safe and effective in treating chronic eczema.Its therapeutic mechanism is related to the regulation of peripheral blood T cell levels,inhibition of inflammatory reactions,and mitigation of immune imbalance.

Self-expanding metal stent for relieving the stricture after endoscopic injection for esophageal varices

BACKGROUND Esophageal stricture is one of the complications after esophageal varices sclero-therapy injection(ESI),and the incidence rate is between 2%-10%.AIM To explore the efficacy of self-expanding metal stent(SEMS)for the stricture after endoscopic injection with cyanoacrylate(CYA)and sclerotherapy for esophageal varices.METHODS We retrospectively analyzed the efficacy of SEMS to improve the stricture after endoscopic injection with CYA and sclerotherapy for esophageal varices in 4 patients from February 2023 to June 2023.RESULTS The strictures were improved in four patients after stenting.The stent was removed after two weeks because of chest pain with embedding into esophageal mucosa in one patient.The stent was removed after one month,however,the stent was reinserted because of the strictures happening again in two patients.The stent was removed after three months,however,the stent was reinserted because of the strictures happening again in one patient.The stent embedded into esophageal mucosa in three patients.There were 3 patients suffered reflux esophagitis,and the acid reflux was relieved by taking hydrotalcite.There was no other complication of esophageal perforation,bleeding from varices or infection.CONCLUSION SEMS may relieve the stricture which happened after endoscopic injection with CYA and sclerotherapy for esophageal varices.However,when we should remove the stent still needs to be explored.

An Updated Lagrangian Particle Hydrodynamics (ULPH)-NOSBPD Coupling Approach forModeling Fluid-Structure Interaction Problem

A fluid-structure interaction approach is proposed in this paper based onNon-Ordinary State-Based Peridynamics(NOSB-PD)and Updated Lagrangian Particle Hydrodynamics(ULPH)to simulate the fluid-structure interaction problem with large geometric deformation and material failure and solve the fluid-structure interaction problem of Newtonian fluid.In the coupled framework,the NOSB-PD theory describes the deformation and fracture of the solid material structure.ULPH is applied to describe the flow of Newtonian fluids due to its advantages in computational accuracy.The framework utilizes the advantages of NOSB-PD theory for solving discontinuous problems and ULPH theory for solving fluid problems,with good computational stability and robustness.A fluidstructure coupling algorithm using pressure as the transmission medium is established to deal with the fluidstructure interface.The dynamic model of solid structure and the PD-ULPH fluid-structure interaction model involving large deformation are verified by numerical simulations.The results agree with the analytical solution,the available experimental data,and other numerical results.Thus,the accuracy and effectiveness of the proposed method in solving the fluid-structure interaction problem are demonstrated.The fluid-structure interactionmodel based on ULPH and NOSB-PD established in this paper provides a new idea for the numerical solution of fluidstructure interaction and a promising approach for engineering design and experimental prediction.

Horizontal well spacing optimization and gas injection simulation for the ultra-low-permeability Yongjin reservoir

Optimal spacing for vertical wells can be effectively predicted with several published methods,but methods suitable for assessing the proper horizontal well spacing are rare.This work proposes a method for calculating the optimal horizontal well spacing for an ultra-low permeability reservoir e the Yongjin reservoir in the Juggar Basin,northwestern China.The result shows that a spacing of 640m is the most economical for the development of the reservoir.To better develop the reservoir,simulation approaches are used and a new model is built based on the calculated well spacing.Since the reservoir has an ultralow permeability,gas injection is regarded as the preferred enhanced oil recovery(EOR)method.Injection of different gases including carbon dioxide,methane,nitrogen and mixed gas are modelled.The results show that carbon dioxide injection is the most efficient and economical for the development of the reservoir.However,if the reservoir produces enough methane,reinjecting methane is even better than injecting carbon dioxide.

A New Heat Transfer Model for Multi-Gradient Drilling with Hollow Sphere Injection

Multi-gradient drilling is a new offshore drilling method.The accurate calculation of the related wellbore temperature is of great significance for the prediction of the gas hydrate formation area and the precise control of the wellbore pressure.In this study,a new heat transfer model is proposed by which the variable mass flow is properly taken into account.Using this model,the effects of the main factors influencing the wellbore temperature are analyzed.The results indicate that at the position where the separation injection device is installed,the temperature increase of the fluid in the drill pipe is mitigated due to the inflow/outflow of hollow spheres,and the temperature drop of the fluid in the annulus also decreases.In addition,a lower separation efficiency of the device,a shallower installation depth and a smaller circulating displacement tend to increase the temperature near the bottom of the annulus,thereby helping to reduce the hydrate generation area and playing a positive role in the prevention and control of hydrates in deepwater drilling.