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Dan Liu, Li Zhang, Mengna Shou, Hong Yu, Yanqing Yang, Hong Cheng Shaoxing Maternity and Child Health Care Hospital, Shaoxing University, Shaoxing, Zhejiang, People’s Republic of ChinaCorrespondence: Dan Liu, Email marcia1981@126.comBackground: The presence of abnormal vision during early childhood has been shown to have a substantial impact on the development of visual, motor, and cognitive functions, potentially resulting in long-term adverse psychosocial outcomes. The objective of this study was to examine the prevalence and associated risk factors of abnormal vision among preschool children aged 4– 6 years in Shaoxing, China.Methods: A cross-sectional study was conducted from March to May 2023 in Shaoxing, involving a sample of 9913 children within the specified age range. Parents were interviewed using a structured questionnaire that gathered information on sociodemographic characteristics and other relevant factors.Results: The study revealed that 14.4% of participants had abnormal vision. Logistic regression analysis indicated that individuals who watched TV for more than 3 hours daily had a 2.206 times higher likelihood of developing abnormal vision (P< 0.05). Additional risk factors for abnormal vision included watching TV at a distance of less than 3 meters, misalignment of eyes and screen while watching TV, early exposure to electronic devices before the age of 2, parents are unaware of the impact of chewing on eye development, and lack of promotion of good eye habits in children (P < 0.05). An association was found between parent’s and children’s refractive error (P < 0.05), with good family lighting and a balanced dietary structure being identified as protective factors against abnormal vision.Conclusion: The study concluded that exposure to electronic products was a significant factor in the development of abnormal vision among children aged 4– 6. Furthermore, family environment and genetic predisposition were also found to influence vision. Regular ocular screenings and early interventions may be effective in preventing abnormal vision.Keywords: risk factors, abnormal vision, preschool children, China

Immunotherapy that targets N-linked glycans has not yet been developed due in large part to the lack of specificity of N-linked glycans between normal and malignant cells. N-Glycan chains are synthesized by the sequential action of glycosyl transferases in the Golgi apparatus. It is an overwhelming task to discover drug-like inhibitors of glycosyl transferases that block the synthesis of specific branching processes in cancer cells, killing tumor cells selectively. It has long been known that N-glycan biosynthesis can be inhibited by disruption of the first committed enzyme, dolichyl-phosphate N-acetylglucosaminephosphotransferase 1 (DPAGT1). Selective DPAGT1 inhibitors have the promising therapeutic potential for certain solid cancers that require increased branching of N-linked glycans in their growth progressions. Recently, we discovered that an anti-Clostridium difficile molecule, aminouridyl phenoxypiperidinbenzyl butanamide (APPB) showed DPAGT1 inhibitory activity with the IC50 value of 0.25 μM. It was confirmed that APPB inhibits N-glycosylation of β-catenin at 2.5 nM concentration. A sharp difference between APPB and tunicamycin was that the hemolytic activity of APPB is significantly attenuated (IC50 > 200 μM RBC). Water solubility of APPB is >350-times greater than that of tunicamycin (78.8 mg/mL for APPB, 60 min) for in vivo studies (PK/PD, safety profiles, and in vivo efficacy) using animal models. We have refined all steps in the previously reported synthesis for APPB for larger-scale. This article summarizes protocols of gram-scale synthesis of APPB and its physicochemical data, and a convenient DPAGT1 assay. • Remember that the abstract is what readers see first in electronic abstracting & indexing services. • This is the advertisement of your article. Make it interesting, and easy to be understood. • Be accurate and specific, keep it as brief as possible. Protocol name: A practical synthesis of a novel DPAGT1 inhibitor, aminouridyl phenoxypiperidinbenzyl butanamide (APPB) for in vivo studies, Keywords: Selective dolichyl-phosphate, N-Acetylglucosaminephosphotransferase 1, DPAGT1 inhibitor, Gram-scale synthesis

Abstract Background Combination therapy is required for the treatment of moderate acne vulgaris. However, patient compliance in applying multiple topical formulations is poor. Objective To assess the efficacy and safety of a fixed-dose combination gel with adapalene 0.1% and clindamycin 1% (adapalene-clindamycin) relative to adapalene 0.1% monotherapy and clindamycin 1% monotherapy in patients with moderate facial acne vulgaris. Methods This was a randomized, controlled, assessor-blind, phase III study conducted in patients with moderate facial acne vulgaris. Results A total of 1617 patients were enrolled. At week 12, patients in the adapalene–clindamycin gel treatment group showed a significant reduction in the percentage change from baseline in total lesion count (− 66.85%), compared with adapalene alone (− 50.82%) or clindamycin gel alone (− 57.61%). The difference in the least square means of the adapalene–clindamycin gel group and adapalene group, or clindamycin gel group was − 16.08% (95% CI − 19.95% to − 12.21%) and − 9.38% (95% CI − 13.25% to − 5.51%;), respectively. At week 12, 19.28% of participants who received adapalene–clindamycin gel achieved at least 2-grade improvement in IGA, versus 7.74% with adapalene gel (OR 3.05, 95% CI 1.93, 4.80) and 14.77% with clindamycin gel (OR 1.42, 95% CI 0.97, 2.07). The study also achieved all its secondary endpoints. Adverse event rates were mostly mild to moderate and comparable across the three treatment groups. Conclusion Adapalene 0.1%–clindamycin 1% combination gel is well tolerated and demonstrated superior efficacy over 0.1% adapalene gel monotherapy and 1% clindamycin gel monotherapy for the treatment of moderate acne vulgaris. Trial Registration ClinicalTrials.gov identifier NCT03615768.

Abstract As an unconventional oil and gas resource, coalbed methane has become a key area of unconventional oil and gas exploration worldwide, and hydraulic fracturing is the critical technology for the efficient stimulation of coalbed methane. However, due to the strong heterogeneity of deep coal seam reservoirs and the development of natural cleat fractures, the fracture propagation path is quite complex and difficult to capture. In this study, we propose a hydraulic fracture propagation simulation method using the ABAQUS Software for natural cleat fracture networks and a fluid–solid fully coupled two‐dimensional finite element model with the global embedded cohesive zone model (CZM). CZM is established to simulate the propagation of hydraulic fractures in the heterogeneous combination of coal rock and mudstone. The accuracy of this model is verified by using Blanton's experiment criterion. Finally, the model is used to simulate the influence of cleat angle, cleat density, length ratio of coal rock and mudstone combination, and construction displacement on the propagation behavior of hydraulic fractures. This study aims to deepen the understanding of the mechanism of hydraulic fracture propagation in deep coal seams and provides guidance for deep coal seam fracturing and hydraulic fracturing design.

Kinetic models were constructed for a variety of cytochrome P450-catalyzed reactions involving drug metabolism. The kinetic parameters observed were explained using a two-site model of the enzyme. In this model of cytochrome P450, atypical kinetics from the binding of at least two substrates in the enzyme's binding site is described. This model is used to explain the atypical kinetics of various isoforms of cytochrome P450.

The stereoselective epoxidation and regioselective hydration at the K-region of benz(a)anthracene (BA), 7,12-dimethylbenz(a)anthracene (DMBA), chrysene (CR), benzo(a)pyrene (B(a)P), dibenz(a,h)anthracene (DB(a,h)A) and benzo(c)phenanthrene (B(c)Ph) were characterized using cDNA-expressed human and mouse P450s 1A1 and 1A2 and epoxide hydrolase. Findings revealed that all P450 isoforms preferentially produced major K-region S,R-epoxides of BA, DMBA, B(a)P, DB(a,h)A, and B(c)Ph, and major R,S-epoxide of CR in the presence of 3,3,3-trichloropropylene 1,2-oxide.

Activation and inhibition of the metabolism of polycylic aromatic hydrocarbons suggest that the substrate and the activator, having access to the active oxygen, bind to the same site simultaneously. Activation changes the effective sides of the active sites and activator presence narrows the effective substrate binding site. Hydrocarbon metabolism requires the presence of CYP3A.

Androstene dione metabolism is examined by isolating the microsomes of Chinese hamster ovary cells that express human aromatase. The restriction of electron flux from NADPH-cytochrome P450 reductase to aromatase results in enhanced quantities of smaller metabolites. The reactions of aromatase and oxidoreductase are indicated by the metabolite ratios.

The measurement of cellular forces, which reflect crucial biological attributes, has the potential to replace conventional cell assessment methods, such as morphology, proliferation, and molecular expression analysis, in medical cell diagnosis and cell culture studies. In medical cell evaluations, force inference techniques have gained prominence due to their non-invasiveness and lack of requirement for specialized equipment. Among those techniques, the method proposed by Ishihara et al., which estimates forces in densely packed cells based only on cell geometry, is a promising method. However, its applicability range of this method has not been fully established. In this study, we employed a two-dimensional vertex model to numerically assess the applicability of this method on homogeneous and heterogeneous cells. Our comparisons between the true values from numerical simulations and the estimated values from the inference method revealed a significant correlation between estimation accuracy and cell roundness in systems of homogeneous cell. Moreover, the method demonstrated efficient force estimations in heterogeneous-cell systems. These findings may be useful when the force inference method is employed to evaluate medical cells.

Under complex conditions, the vertical, lateral and longitudinal dynamics of vehicles have obvious coupling and interaction. This paper aims to provide a suitable driver cab and a vehicle model for the study of vehicle coupling dynamic performance. In modeling the cab and body kinetic equation, two shock absorbers are considered in the front axle suspension system. In addition, the vertical, roll and pitch motion of the diver cab, vehicle body, the vertical and roll behavior of three wheel axles, the pitch angles of the left and right balancing pole on rear suspension, and roll angle the of each tire are considered. Finally, based on the above coupled motion characteristics, a diver cab and a vehicle model for three-axles heavy-duty vehicle with 26 degrees of freedom (DOF) are proposed.

Understanding the mechanical properties of rock is of great significance for the development of unconventional reservoirs. However, a large number of bedding makes the mechanical laws of rock unclear. To investigate the effect of bedding properties on the uniaxial mechanical properties of rock, the coal model containing bedding is developed based on the continuous–discontinuous method, and the effect of bedding angle, bedding strength, bedding number, and loading rate on the uniaxial mechanical properties of rock is investigated. The failure morphology, stress–strain evolution, peak stress, and fracture degrees are analyzed and discussed in detail. The reliability of the numerical model in this paper has been verified by comparison with the indoor experiments. The results show that when the bedding angle is 0°, the peak stress of the rock is maximum, 8.16 MPa, and when the bedding angle is 90°, the fracture degree of the rock is maximum, 3.74%. For the different bedding strengths, the peak stress first decreases linearly with the decrease of the bedding strength. The peak stress barely varies when the bedding strength is less than 0.5 MPa. The fracture degree of the rock shows a nonlinear increase with the increase in bedding strength. For different bedding numbers, the activation of the bedding is not related to the bedding number. The loading speed also has a great influence on the mechanical properties of rock. With the increase in loading rate, the difficulty of bedding activation gradually increases, and the complexity of fractures gradually increases. This study aims to further improve the understanding of the effect of bedding properties on the uniaxial mechanical properties of rock.

Our previous studies have shown that 2,3-epoxy-4-hydroxynonanal, a reactive epoxy aldehyde capable of forming etheno adducts with DNA bases, is mutagenic and tumorigenic (Carcinogenesis, 14, 2073). The epoxy aldehyde can be generated from trans-4-hydroxy-2-nonenal, a lipid peroxidation product of ω-6 polyunsaturated fatty acids, by autoxidation or by incubation with fatty acid hydroperoxides or hydrogen peroxides (Chem. Res. Toxicol., 9, 306). These are plausible in vivo pathways for the formation of 2,3-epoxy-4-hydroxynonanal. The possibility that 2,3-epoxy-4-hydroxynonanal is a tumorigen of endogenous oritin is suggested by recent observations that etheno bases are detected as background DNA lesions in untreated rodents and humans. A metabolic pathway critical for detoxification of 2,3-epoxy-4-hydroxynonanal involves the ring-opening by epoxide hydrolase, which abolishes its ability to form cyclic etheno DNA adducts. In this study we examined whether 2,3-epoxy-4-hydroxynonanal is a substrate of cDNA expressed human epoxide hydrolase. Human epoxide hydrolase was expressed in TK- 143 cells (thymidine kinase-deficient human embryoblast) infected with recombinant vaccinia virus encoding human epoxide hydrolase cDNA. Controls consisted of the cells infected with vaccinia virus in the absence of human epoxide hydrolase cDNA. No hydrolysis occurred when [2,3-3H]2,3-epoxy-4-hydroxynonanal was incubated at 37°C for 30 min at pH 7.4 with cells expressing human epoxide hydrolase as indicated by the presence of a pair of radioactive peaks in reverse-phase HPLC chromatography, which comigrated with the UV standards of the two diastereomers of the epoxy aldehyde. The identity of these compounds as the intact epoxy aldehyde was further supported by derivatization to the 2,4-dinitrophenylhydrazones followed by reversed phase HPLC analysis. Similar results were observed with the control cells or with the heat deactivated human epoxide hydrolase. The epoxide hydrolase activity in the expressed cells was demonstrated by their ability to convert benzo[a]pyrene-4,5-dihydroepoxide to benzo[a]pyrene-trans-4,5-dihydrodiol under the same conditions. These results clearly indicate that 2,3-epoxy-4-hydroxynonanal is not a substrate of human epoxide hydrolase, and, thus strengthen its possible endogenous role in the formation of promutagenic exocyclic etheno adducts in vivo. [ABSTRACT FROM PUBLISHER]

In geochemical sample analysis, some elements such as Ag, B, Sn are difficult to analyze. Traditional alternating current Arc Emission Spectrometry is used to analyze them, for example Spectrograph and Multi-channel Arc Emission Spectrometer. However, due to their complex operation, the increasing demands of geochemical samples and requirement of analysis quality, makes these methods unsuitable for a large number of samples requiring daily analyses. A new Full Spectrum Direct Reading Emission Spectrometer E5000 has been developed, based on newly designed arc source and Paschen-Runge type CCD spectrometer. E5000 Emission Spectrometer has many innovations and is described in this paper. An electrode is positioned by laser diode and driven by a motor to achieve a high precision electrode position. With E5000, a photo plate is unnecessary, so the spectrum will not be influenced by emulsion characteristics of a photo plate. Also with CCD type full spectrum technology, inference element correction and spectrum background correction can be easily achieved. Stream sediments and soils samples have been tested with the E5000 Spectrometer, and the detection limits of Ag, B, Sn are 0.01 μg/g, 0.65 μg/g, 0.16 μg/g, and analysis precision of stream sediments and soils samples are less than 10%, demonstrating that this method meets the analysis quality requirement for geochemical samples.