Profile of Peanut Sensitization in Children Attending a Pneumo-Allergology Consultation at the Teaching Hospital Campus of Lomé, Togo

Introduction: Food allergies are on the constant increase worldwide. Among them is peanut allergy, which also affects children. The aim of this study was to determine the profile of peanut sensitization in children attending a pneumo-allergology consultation. Methods: This was a cross-sectional study, which ran from January 1, 2018, to December 31, 2022, on children sensitized to peanuts seen in pneumo-allergology consultations at the Teaching Hospital Campus of Lomé. Results: The sample included 137 children aged 3 months to 18 years. The frequency of peanut sensitization was 25.3%. The mean age of patients was 6.3 ± 4.3 years (minimum 6 months and maximum 18 years). The 6 months to 5 years age group was the most represented (43.1%). The sex ratio was 1.3. The main reasons for consultation were rhinorrhea (67.9%), sneezing (36.5%) and cough (35.8%). Allergic rhinitis was identified as a personal history in 75.2% of patients. Peanut allergy was manifested as rhinorrhea (62.5%), asthma (26.8%) and eczema (8.9%). The risk of onset of symptoms within 15 - 30 minutes was 1.87 times (p = 0.001, CI = [1.2 - 2.1]) for peanuts consumed in roasted form with shell. Severe clinical signs such as Quincke’s Edema and anaphylactic shock were found in 1.4% of cases. Conclusion: Peanut allergy was common in children. Severe clinical signs were rare.

Mass transfer process of peanut protein extracted by bis(2-ethylhexyl)sodium sulfosuccinate reverse micelles

The liquid-liquid extraction method using reverse micelles can simultaneously extract lipid and protein of oilseeds,which have become increasingly popular in recent years.However,there are few studies on mass transfer processes and models,which are helpful to better control the extraction process of oils and proteins.In this paper,mass transfer process of peanut protein extracted by bis(2-ethylhexyl)sodium sulfosuccinate(AOT)/isooctane reverse micelles was investigated.The effects of stirring speed(0,70,140,and 210 r/min),temperature of extraction(30,35,40,45,and 50℃),peanut flour particle size(0.355,0.450,0.600,and 0.900 mm)and solidliquid ratio(0.010,0.0125,0.015,0.0175,and 0.020 g/mL)on extraction rate were examined.The results showed that extraction rate increased with temperature rising,particle size reduction as well as solid-liquid ratio increase respectively,while little effect of stirring speed(P>0.05)was observed.The apparent activation energy of extraction process was calculated as 10.02 kJ/mol and Arrhenius constant(A)was 1.91 by Arrhenius equation.There was a linear relationship between reaction rate constant and the square of the inverse of initial particle radius(1/r_(0)^(2))(P<0.05).This phenomenon and this shrinking core model were anastomosed.In brief,the extraction process was controlled by the diffusion of protein from the virgin zone interface of particle through the reacted zone and it was in line with the first order reaction.Mass transfer kinetics of peanut protein extracted by reverse micelles was established and it was verified by experimental results.The results provide an important theoretical guidance for industrial production of peanut protein separation and purification.

Dual ligand-targeted Pluronic P123 polymeric micelles enhance the therapeutic effect of breast cancer with bone metastases

Bone metastasis secondary to breast cancer negatively impacts patient quality of life and survival.The treatment of bone metastases is challenging since many anticancer drugs are not effectively delivered to the bone to exert a therapeutic effect.To improve the treatment efficacy,we developed Pluronic P123(P123)-based polymeric micelles dually decorated with alendronate(ALN)and cancer-specific phage protein DMPGTVLP(DP-8)for targeted drug delivery to breast cancer bone metastases.Doxorubicin(DOX)was selected as the anticancer drug and was encapsulated into the hydrophobic core of the micelles with a high drug loading capacity(3.44%).The DOX-loaded polymeric micelles were spherical,123 nm in diameter on average,and exhibited a narrow size distribution.The in vitro experiments demonstrated that a pH decrease from 7.4 to 5.0 markedly accelerated DOX release.The micelles were well internalized by cultured breast cancer cells and the cell death rate of micelle-treated breast cancer cells was increased compared to that of free DOX-treated cells.Rapid binding of the micelles to hydroxyapatite(HA)microparticles indicated their high affinity for bone.P123-ALN/DP-8@DOX inhibited tumor growth and reduced bone resorption in a 3D cancer bone metastasis model.In vivo experiments using a breast cancer bone metastasis nude model demonstrated increased accumulation of the micelles in the tumor region and considerable antitumor activity with no organ-specific histological damage and minimal systemic toxicity.In conclusion,our study provided strong evidence that these pH-sensitive dual ligand-targeted polymeric micelles may be a successful treatment strategy for breast cancer bone metastasis.

Linear-like polypeptide-based micelle with pH-sensitive detachable PEG to deliver dimeric camptothecin for cancer therapy

Nano drug delivery systems have made significant progress in delivering anticancer drugs camptothecin(CPT).However,many challenges for CPT delivery remain,including low drug loading efficiency,premature drug leakage,and poor cellular internalization.Herein,we report a novel dual-sensitive polypeptide-based micelle with remarkably high drug loading of CPT for cancer therapy.This self-assembled micelle possesses the following essential components for CPT:(1)pH-sensitive PEG(OHC-PEG-CHO)for prolonging blood circulation and allowing biocompatibility by shielding the cationic micelles,which can be detached under the tumor acidic microenvironment and facilitates the cellular uptake;(2)polypeptide polylysine-polyphenylalanine(PKF)synthesized via ring-opening polymerization for micelle formation and CPT analogue loading;(3)dimeric CPT(DCPT)with redox-sensitive linker for increasing CPT loading and ensuring drug release at tumor sites.Interestingly,the linear-like morphology of PEG-PKF/DCPT micelles was able to enhance their cellular internalization when compared with the spherical blank PKF micelles.Also,the anticancer efficacy of DCPT against lung cancer cells was significantly improved by the micelle formation.In conclusion,this work provides a promising strategy facilitating the safety and effective application of CPT in cancer therapy.

近红外无创血糖浓度的Label Sensitivity算法和支持向量机回归

近红外光谱分析技术在生物医学工程领域具有广阔应用前景。无创且持续性地测量能实时监控人体血糖水平,给糖尿病患者带来极大便利性、提高生存质量、降低糖尿病并发症发生率具有很大的社会效益。无创血糖监测的想法提出较早,但仍然存在预测精度低、预测值与标签值相关性不高等难点,至今没有达到临床要求。近年来,光谱检测技术发展迅猛且机器学习技术在智能信息处理方面具有明显优势,两者结合可以有效提高人体无创血糖医学监测模型的精度和普适性。提出了一种标签敏感度算法(LS),并结合支持向量机方法建立了人体血糖含量预测模型。使用近红外光谱仪采集了4名志愿者食指处动态血液光谱数据(每名志愿者28组数据),并使用多元散射矫正(MSC)方法消除了部分光散射的影响。考虑血糖对不同波长光的吸收有差异,提出了基于血糖浓度标签差的特征波长挑选方法,并构建了标签敏感度支持向量机(LSSVR)预测模型。设计实验,对比该模型与偏最小二乘回归(PLSR)和区分度支持向量机(FSSVR)算法。结果表明,LS算法的最佳特征波长数为32,经特征波长选择后的LSSVR表现最佳,其均方误差降低至0.02 mmol·L^(-1),明显优于全谱段PLSR模型,血糖浓度的预测值与标签值的相关系数提升至99.8%,预测值全部位于可容许误差的克拉克网格A区内。LSSVR模型的优异表现为早日实现血糖的无创监测提供了新思路。

Construction of curcumin-loaded micelles and evaluation of the anti-tumor effect based on angiogenesis

Objective:Inhibition of tumor angiogenesis has become a new targeted tumor therapy.In this study,we established a micellar carrier with a tumor neovascularization-targeting effect modified by the neovascularization-targeting peptide NGR.Methods:The targeted polymer poly(ethylene glycol)-b-poly(lactide-co-glycolide)(PEG-PLGA)modified with Asn–Gly–Arg(NGR)peptide was prepared and characterized by 1H nuclear magnetic resonance and Fourier-transform infrared spectrometry.NGR-PEG-PLGA was used to construct curcumin(Cur)-loaded micelles by the solvent evaporation method.The physicochemical properties of the micelles were also investigated.Additionally,we evaluated the antitumor efficacy of the polymer micelles(PM)using in vitro cytology experiments and in vivo animal studies.Results:The particle size of Cur-NGR-PM was 139.70±2.51 nm,and the drug-loading capacity was 14.37±0.06%.In vitro cytological evaluation showed that NGR-modified micelles showed higher cellular uptake through receptor-mediated endocytosis pathways than did unmodified micelles,leading to the apoptosis of tumor cells.Then,in vivo antitumor experiments showed that the modified micelles significantly inhibited tumor growth and were safe.Conclusions:NGR-modified micelles significantly optimized the therapeutic efficacy of Cur.This strategy offers a viable avenue for cancer treatment.

Preparation and evaluation of poly(L-histidine) based pH-sensitive micelles for intracellular delivery of doxorubicin against MCF-7/ADR cells

In this study, a p H-sensitive micelle self-assembled from poly(L-histidine) based triblock copolymers of poly(ethylene glycol)–poly(D,L-lactide)–poly(L-histidine)(mPEG-PLA-PHis) was prepared and used as the intracellular doxorubicin(Dox) delivery for cancer chemotherapy. Dox was loaded into the micelles by thin-film hydration method and a Box–Behnken design for three factors at three levels was used to optimize the preparations. The optimized mPEG-PLA-Phis/Dox micelles exhibited good encapsulation efficiency of 91.12%,a mean diameter of 45 nm and narrow size distribution with polydispersity index of 0.256.In vitro drug release studies demonstrated that Dox was released from the micelles in a p Hdependent manner. Furthermore, the cellular evaluation of Dox loaded micelles displayed that the micelles possessed high antitumor activity in vitro with an IC50 of 35.30 μg/ml against MCF-7/ADR cells. The confocal microscopy and flow cytometry experiments indicated that m PEG-PLA-Phis micelles mediated efficient cytoplasmic delivery of Dox with the aid of poly(Lhistidine) mediated endosomal escape. In addition, blank m PEG-PLA-Phis micelles were shown to be nontoxic to MCF-7/ADR cells even at a high concentration of 200 μg/ml. The pHsensitive mPEG-PLA-PHis micelles have been demonstrated to be a promising nanosystem for the intracellular delivery of Dox for MDR reversal.

pH-sensitive polymeric micelles triggered drug release for extracellular and intracellular drug targeting delivery

Most of the conventional chemotherapeutic agents used for cancer chemotherapy suffer from multidrug resistance of tumor cells and poor antitumor efficacy.Based on physiological differences between the normal tissue and the tumor tissue,one effective approach to improve the efficacy of cancer chemotherapy is to develop pH-sensitive polymeric micellar delivery systems.The copolymers with reversible protonationedeprotonation core units or acid-liable bonds between the therapeutic agents and the micelle-forming copolymers can be used to form pH-sensitive polymeric micelles for extracellular and intracellular drug smart release.These systems can be triggered to release drug in response to the slightly acidic extracellular fluids of tumor tissue after accumulation in tumor tissues via the enhanced permeability and retention effect,or they can be triggered to release drug in endosomes or lysosomes by pH-controlled micelle hydrolysis or dissociation after uptake by cells via the endocytic pathway.The pH-sensitive micelles have been proved the specific tumor cell targeting,enhanced cellular internalization,rapid drug release,and multidrug resistance reversal.The multifunctional polymeric micelles combining extracellular pH-sensitivity with receptor-mediated active targeting strategies are of great interest for enhanced tumor targeting.The micelles with receptor-mediated and intracellular pH targeting functions are internalized via receptor-mediated endocytosis followed by endosomal-pH triggered drug release inside the cells,which reverses multidrug resistance.The pH sensitivity strategy of the polymeric micelles facilitates the specific drug delivery with reduced systemic side effects and improved chemotherapeutical efficacy,and is a novel promising platform for tumor-targeting drug delivery.

Evaluation of micelles incorporated into thermosensitive hydrogels for intratumoral delivery and controlled release of docetaxel:A dual approach for in situ treatment of tumors

The in situ gelling hybrid hydrogel system has been reported to effectively concentratechemotherapeutic drugs at the tumor site and sustain their release for a long period. DTX-micelles(docetaxel-loaded mixed micelles) are able to increase the solubility of DTX inwater, and then a high drug loading rate of hydrogels can be achieved by encapsulatingthe docetaxel-loaded mixed micelles into the hydrogels. The thermosensitive nature ofDTX-MM-hydrogels(thermosensitive hydrogels incorporated with docetaxel-loaded mixedmicelles) can accelerate the formation of a depot of this drug-loaded system at the siteof administration. Therefore, the hydrogels provide a much slower release compared withDTX-micelles and DTX-injection. An in vivo retention study has demonstrated that the DTX-MM-hydrogels can prolong the drug retention time and in viv o trials have shown that theDTX-MM-hydrogels have a higher antitumor efficacy and systemic safety. In conclusion, theDTX-MM-hydrogels prepared in this study have considerable potential as a drug deliverysystem, with higher tumor inhibition effects and are less toxic to normal tissues.

A semi-analytical model for coupled flow in stress-sensitive multi-scale shale reservoirs with fractal characteristics

A large number of nanopores and complex fracture structures in shale reservoirs results in multi-scale flow of oil. With the development of shale oil reservoirs, the permeability of multi-scale media undergoes changes due to stress sensitivity, which plays a crucial role in controlling pressure propagation and oil flow. This paper proposes a multi-scale coupled flow mathematical model of matrix nanopores, induced fractures, and hydraulic fractures. In this model, the micro-scale effects of shale oil flow in fractal nanopores, fractal induced fracture network, and stress sensitivity of multi-scale media are considered. We solved the model iteratively using Pedrosa transform, semi-analytic Segmented Bessel function, Laplace transform. The results of this model exhibit good agreement with the numerical solution and field production data, confirming the high accuracy of the model. As well, the influence of stress sensitivity on permeability, pressure and production is analyzed. It is shown that the permeability and production decrease significantly when induced fractures are weakly supported. Closed induced fractures can inhibit interporosity flow in the stimulated reservoir volume (SRV). It has been shown in sensitivity analysis that hydraulic fractures are beneficial to early production, and induced fractures in SRV are beneficial to middle production. The model can characterize multi-scale flow characteristics of shale oil, providing theoretical guidance for rapid productivity evaluation.

Antibiotic-based small molecular micelles combined with photodynamic therapy for bacterial infections

The appearance of multidrug-resistant bacteria and the formation of bacterial biofilms have necessitated the development of alternative antimicrobial therapeutics.Antibiotics conjugated with or embedded in nano-drug carriers show a great potential and advantage over free drugs,but the mass proportion of carriers generally exceeds 90%of the nano-drug,resulting in low drug loading and limited therapeutic output.Herein,we fabricated a nanocarrier using antibiotics as the building blocks,minimizing the use of carriermaterials,significantly increasing the drug loading content and treatment effect.Firstly,we conjugated betaine carboxylate with ciprofloxacin(CIP)through an ester bond to form the amphiphilic conjugate(CIP-CB),which self-assembled into micelles(CIP-CBMs)in aqueous solutions,with a CIP loading content as high as 65.4%and pH-induced surface charge reversal properties.Secondly,a model photosensitizer(5,10,15,20-tetraphenylporphyrin(TPP))was encapsulated in CIP-CBMs,generating infection-targeted photodynamic/antibiotic combined nanomedicines(denoted as TPP@CIP-CBMs).Upon accumulation at infection sites or in deep bacterial biofilms,the ester bond between the betaine carboxylate and CIP is cleaved to release free TPP and CIP,leading to a synergetic antibacterial and antibiofilm activity in vitro and in vivo.

Identification, pathogenicity, and fungicide sensitivity of Eutiarosporella dactylidis associated with leaf blight on maize in China

Maize(Zea mays L.) is an economically vital grain crop that is cultivated worldwide. In 2011, a maize foliar disease was detected in Lingtai and Lintao counties in Gansu Province, China. The characteristic signs and symptoms of this disease include irregular chlorotic lesions on the tips and edges of infected leaves and black punctate fruiting bodies in dead leaf tissues. Given favourable environmental conditions, this disease spread to areas surrounding Gansu. In this study, infected leaves were collected from Gansu and Ningxia Hui Autonomous Region between 2018and 2020 to identify the disease-causing pathogen. Based on morphological features, pathogenicity tests, and multilocus phylogenetic analysis involving internal transcribed spacer(ITS), 18S small subunit rDNA(SSU), 28S large subunit rDNA(LSU), translation elongation factor 1-alpha(TEF), and β-tubulin(TUB) sequences, Eutiarosporella dactylidis was identified as the causative pathogen of this newly discovered leaf blight. Furthermore, an in vitro bioassay was conducted on representative strains using six fungicides, and both fludioxonil and carbendazim were found to significantly inhibit the mycelial growth of E. dactylidis. The results of this study provide a reference for the detection and management of Eutiarosporella leaf blight.

Future changes in precipitation and water availability over the Tibetan Plateau projected by CMIP6 models constrained by climate sensitivity

Precipitation projections over the Tibetan Plateau(TP)show diversity among existing studies,partly due to model uncertainty.How to develop a reliable projection remains inconclusive.Here,based on the IPCC AR6–assessed likely range of equilibrium climate sensitivity(ECS)and the climatological precipitation performance,the authors constrain the CMIP6(phase 6 of the Coupled Model Intercomparison Project)model projection of summer precipitation and water availability over the TP.The best estimates of precipitation changes are 0.24,0.25,and 0.45 mm d^(−1)(5.9%,6.1%,and 11.2%)under the Shared Socioeconomic Pathway(SSP)scenarios of SSP1–2.6,SSP2–4.5,and SSP5–8.5 from 2050–2099 relative to 1965–2014,respectively.The corresponding constrained projections of water availability measured by precipitation minus evaporation(P–E)are 0.10,0.09,and 0.22 mm d^(−1)(5.7%,4.9%,and 13.2%),respectively.The increase of precipitation and P–E projected by the high-ECS models,whose ECS values are higher than the upper limit of the likely range,are about 1.7 times larger than those estimated by constrained projections.Spatially,there is a larger increase in precipitation and P–E over the eastern TP,while the western part shows a relatively weak difference in precipitation and a drier trend in P–E.The wetter TP projected by the high-ECS models resulted from both an approximately 1.2–1.4 times stronger hydrological sensitivity and additional warming of 0.6℃–1.2℃ under all three scenarios during 2050–2099.This study emphasizes that selecting climate models with climate sensitivity within the likely range is crucial to reducing the uncertainty in the projection of TP precipitation and water availability changes.

Preparation of adhesive resveratrol micelles and determination of drug content

Objective:Resveratrol polymer micelles with tissue adhesion were prepared and the content of resveratrol in the micelles was determined by HPLC.Method:The micelle adhesion experiment was carried out by polylysine orifice plate experiment and small animal fluorescence imaging method,and the micelle prescription was optimized to obtain resveratrol micelles with good adhesion.The separation was performed on a Shiseido SPOLAR C18 column(150 mm×4.6 mm,5μm)with methanol-water(42:58)as the mobile phase.The flow rate was 1.0 mL·min^(-1),the detection wavelength was 305 nm,the column temperature was 35℃,and the injection volume was 10μL.Results:Resveratrol micelles prepared with F127 alone had the best adhesion.The peak area and concentration of resveratrol had a good linear relationship in the concentration range of 10~200μg/mL(r=0.9996).The specificity,precision,recovery and stability all met the methodological requirements.Conclusion:In this experiment,resveratrol micelles with tissue adhesion were successfully prepared,and a method for the determination of resveratrol content in micelles was established.The method is accurate,rapid and simple.

Prevalence and Sensitization and Intestinal Parasitic Infestation of Vernal Keratoconjunctivitis in School Children of Kinshasa

Background: There is no study that estimates the prevalence of vernal keratoconjunctivitis and the association between vernal keratoconjunctivitis and intestinal parasitic infestation in our setting. Purpose: This study aimed to estimate the vernal keratoconjunctivitis prevalence, describe the profile of sensitization and determine the association between vernal keratoconjunctivitis disease and intestinal parasitic infestation in school children of Kinshasa during the scholar year from 2022 to 2023. Methods: An observational, cross-sectional study was performed from September 2022 to June 2023. The children with vernal keratoconjunctivitis were recruited by using the four-stage probability sampling technique. Children attending in the school children of Kinshasa with vernal keratoconjunctivitis were enrolled in the classroom and underwent a clinical examination and skin prick test for 11 allergens and stool examination direct with microscope in the Laboratory. Data were entered in Microsoft Sheets using SPSS version 20.0. The Chi-square test was used to compare the sex, age groups, home environment (grow trees and/or flowers around the yard), dampness in the house, keeping pets (cat and/or dog), number of people per household, number of people sharing a bedroom and intestinal parasitic infestation. The significant level was set to a value of p Results: A total of 28,800 students from four-stage probabilist sampling technique in school of Kinshasa were included, and 2100 students had symptoms according to the vernal keratoconjunctivitis-related symptom questionnaire. Children with vernal keratoconjunctivitis were enrolled and the mean age ± standard was 7.2 ± 3.7 years, with a prevalence of 7.2% and gender was three boys for one girl. All vernal keratoconjunctivitis children recruited in urban and rural part had 33.1% positive skin prick test (SPT) and 67.9% showed polysensitization. Children an urban part was more sensitized than rural respectively with Dermatophagoides pteronyssinus 28.1% vs 28.9%, p = 0.00001, Blomia tropicalis. 15.9% vs 14.9%, p = 0.00001 and cockroach 12% vs 13%, p = 0.00001 in both parts. Vernal keratoconjunctivitis children in rural part were more affected to the intestinal parasite than urban with Ascaris lumbricoides 14% vs 18.3%, p = 0.0006, followed by Ancylostoma duodenale 9.5% vs 12.5%, p = 0.003, Anguillule 7.9% vs 10.1%, p = 0.001, Oxyure 5.7% vs 8.2%, p = 0.0001 and Trichuris trichiura 2.6% vs 3.3%, p = 0.0009. Conclusion: This study outlines that the prevalence of vernal keratoconjunctivitis was 7.2% and 33.1% of children attending for vernal keratoconjunctivitis in school children had a positive skin prick test to at least one allergen, in particular for Dermatophagoides pteronyssinus, Blomia tropicalis and cockroach. The most common intestinal parasitic infestation was Ascaris lumbricoides, Ancylostoma duodenale, Anguillule and Trichuris trichiura.

Assessment of immune responses and intestinal flora in BALB/c mice model of wheat food allergy via different sensitization methods

Increasing incidences showed that food allergies have attracted more and more attention from researchers.BALB/c mice were sensitized with wheat gluten combined with aluminum hydroxide adjuvant via intraperitoneal injection,transdermal sensitization,and oral gavage sensitization route.Results showed that all the three sensitization methods could induce allergic symptoms;increase the serum antibody(total immunoglobulin E(IgE),specific IgE,IgG,IgA)and histamine content;promote the secretion of Th2 cytokines(interleukin(IL)-4,IL-5,IL-13)and inflammatory factors(IL-6,IL-17 A,IL-10);and inhibit the production of Th1 cytokines(IFN-γ,IL-2).However,the allergic symptoms of mice sensitized by intraperitoneal injection were the most obvious among the three models.The level of serum antibodies in intraperitoneal injection group was significantly higher than control.Subsequently,16 S rRNA sequencing technology was used to analyze the intestinal flora of mice.The results showed that the abundance of Firmicutes in the wheat protein sensitized group was lower than that in the normal group,while the abundance of Bacteroidetes was higher,and Lactobacillus was the difference marker in normal group.Bacterial species diversity analysis showed that the species richness and diversity of intestinal flora in mice were decreased,the difference between mice induced by intraperitoneal injection and normal control group mice was the most significant.Taken together,these results show that among three sensitization methods used to build a mouse model with aluminum hydroxide as adjuvant,intraperitoneal injection is the comparably best way to build a mouse sensitization mode.

MEAN SENSITIVITY AND BANACH MEAN SENSITIVITY FOR LINEAR OPERATORS

Let(X,T)be a linear dynamical system,where X is a Banach space and T:X→X is a bounded linear operator.This paper obtains that(X,T)is sensitive(Li-Yorke sensitive,mean sensitive,syndetically mean sensitive,respectively)if and only if(X,T)is Banach mean sensitive(Banach mean Li-Yorke sensitive,thickly multi-mean sensitive,thickly syndetically mean sensitive,respectively).Several examples are provided to distinguish between different notions of mean sensitivity,syndetic mean sensitivi`ty and mean Li-Yorke sensitivity.

Integrated Use of Alternative Methods for Evaluating the Skin Sensitization Potencies of Five Frequently Used Preservatives in Cosmetics

In vitro skin sensitization testing methods based on the adverse outcome pathway(AOP)were used to evaluate the skin sensitization potencies of 5 commonly used preservatives.According to the“2 out of 3”principle of the integrated approaches to testing and assessment(IATA)the direct peptide reactivity assay(DPRA)and the human cell line activation test(h-CLAT)were used to detect the preservatives commonly used in cosmetics,including phenoxyethanol.methyl paraben,propyl paraben,imidazolidinyl urea and DMDM hydantoin.The DPRA and the h-CLA were carried out according to the OEC442C and 442E guidelines,respectively.The results show that.phenoxyethanol and methyl paraben are both negative in DPRA and h-CLAT while imidazolidinyl urea and DMDM hydantoin are both positive in these two tests.Propyl paraben has negative result in DPRA but positive result in h-CLAT.Therefore,imidazolidiny urea and DMDM hydantoin are sensitizers,while phenoxyethanol and methylparaben are non-sensitizers.Taken animal and human data into consideration,it is predicted that propyl paraben should be a non-sensitizer.The combination of DPRA and h-CLAT can make up for the limitations of using a single method,and it is suitable for the preliminary screening of cosmetic raw materials according to skin sensitization.

Application of in Vitro Alternative Tests Based on AOP in Skin Sensitization Evaluation of Cosmetics

To evaluate and discuss two novels in vitro alternative tests which based on the 2nd and 4th event of the AOP in skin sensitization and their application in skin sensitization evaluation of cosmetics in vitro.The DSens(DSens method)and Jurkat(TCPA method)were used as the test models and 9 of reference chemicals and 12 kinds of cosmetic products were used to confirm and assess the application capability in skin sensitization.The results showed that the DSens method was more sensitive to the reference chemicals compare to the TCPA method.All the results of cosmetic products showed a high consistency between these two assays and h-CLAT or in vivo assay.As the new screening method for skin sensitization evaluation of cosmetics,the in vitro alternative tests based on AOP have certain effectiveness.The reasonable combination strategy can bring a bright future for the development and application of animal alternative test in China.

High-Precision Flow Numerical Simulation and Productivity Evaluation of Shale Oil Considering Stress Sensitivity

Continental shale oil reservoirs,characterized by numerous bedding planes and micro-nano scale pores,feature significantly higher stress sensitivity compared to other types of reservoirs.However,research on suitable stress sensitivity characterization models is still limited.In this study,three commonly used stress sensitivity models for shale oil reservoirs were considered,and experiments on representative core samples were conducted.By fitting and comparing the data,the“exponential model”was identified as a characterization model that accurately represents stress sensitivity in continental shale oil reservoirs.To validate the accuracy of the model,a two-phase seepage mathematical model for shale oil reservoirs coupled with the exponential model was introduced.The model was discretely solved using the finite volume method,and its accuracy was verified through the commercial simulator CMG.The study evaluated the productivity of a typical horizontal well under different engineering,geological,and fracture conditions.The results indicate that considering stress sensitivity leads to a 13.57%reduction in production for the same matrix permeability.Additionally,as the fracture half-length and the number of fractures increase,and the bottomhole flowing pressure decreases,the reservoir stress sensitivity becomes higher.