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Abstract Background This study aimed to investigate the difference between cycloplegic and noncycloplegic refraction and evaluate the pseudomyopia prevalence in Chinese preschool children during the outbreak of COVID-19. Methods A cross-sectional study was conducted in the Tongzhou District of Beijing, China. Refractive error was measured under both noncycloplegic and cycloplegic conditions with autorefraction. The difference between noncycloplegic and cycloplegic spherical equivalent refraction (SER) and pseudomyopia prevalence were analyzed. Pseudomyopia was defined as SER ≤-0.50D in precycloplegic assessments and >-0.50D in post-cycloplegic assessments. Results Out of the 1487 participants who were enrolled in the study, 1471 individuals (98.92%) between the ages of 3–6 years completed all required procedures. A statistically significant difference in refraction was observed between noncycloplegic and cycloplegic measurements, the median of difference in spherical equivalent refraction (SER) of 0.88D (dioptre)(0.50,1.38). There was a high intraclass correlation (ICC) between these two methods for cylinders (ICC = 0.864; 95% CI, 0.850–0.877). The median DSE for myopia, emmetropia and hyperopia were 0.25D (0.00, 0.38),0.25D (0.06, 0.50) and 1.00D (0.62, 1.38), an hypermetropes showed considerably greater differences than myopes and emmetropes (Kruskal-Wallis test, H = 231.023, P = 0.000). Additionally, girls displayed a greater DSE than boys. Furthermore, when comparing against-the-rule (ATR) and oblique astigmatism, it was found that with-the-rule (WTR) astigmatism had the largest DSE. The study found varying prevalence rates of myopia, emmetropia, and hyperopia with and without cycloplegia, which were 1.90% vs. 10.06%, 11.49% vs. 50.31%, and 86.61% vs. 39.63%, respectively. Additionally, the overall prevalence of pseudomyopia was determined to be 8.29%. Participants with pseudomyopia had a significantly higher mean difference in SER (DSE) compared to non-pseudomyopic participants. Conclusions Cycloplegic refraction is more sensitive than a noncycloplegic one for measuring refractive error in preschool children. Pseudomyopia is prevalent in preschool children during the COVID-19 outbreak period. Our study indicates the possibility that cycloplegic refraction should be performed in preschool children routinely.

As the most common internal modification of mRNA, N6-methyladenosine (m6A) and its regulators modulate gene expression and play critical roles in various biological and pathological processes including tumorigenesis. It was reported previously that m6A methyltransferase (writer), methyltransferase-like 3 (METTL3) adds m6A in primary microRNAs (pri-miRNAs) and facilitates its processing into precursor miRNAs (pre-miRNAs). However, it is unknown whether m6A modification also plays a role in the maturation process of pre-miRNAs and (if so) whether such a function contributes to tumorigenesis. Here, we found that YTHDF2 is aberrantly overexpressed in acute myeloid leukemia (AML) patients, especially in relapsed patients, and plays an oncogenic role in AML. Moreover, YTHDF2 promotes expression of miR-126-3p (also known as miR-126, as it is the main product of precursor miR-126 (pre-miR-126)), a miRNA that was reported as an oncomiRNA in AML, through facilitating the processing of pre-miR-126 into mature miR-126. Mechanistically, YTHDF2 recognizes m6A modification in pre-miR-126 and recruits AGO2, a regulator of pre-miRNA processing, to promote the maturation of pre-miR-126. YTHDF2 positively and negatively correlates with miR-126 and miR-126's downstream target genes, respectively, in AML patients, and forced expression of miR-126 could largely rescue YTHDF2/Ythdf2 depletion-mediated suppression on AML cell growth/proliferation and leukemogenesis, indicating that miR-126 is a functionally important target of YTHDF2 in AML. Overall, our studies not only reveal a previously unappreciated YTHDF2/miR-126 axis in AML and highlight the therapeutic potential of targeting this axis for AML treatment, but also suggest that m6A plays a role in pre-miRNA processing that contributes to tumorigenesis.

There is an interdependent symbiotic relationship between humans and water; scientific and effective assessment of the human–water symbiosis relationship is of great significance for the promotion of sustainable development. This study developed a novel framework of the human–water symbiosis relationship under an integrated perspective, which included theoretical interpretation, quantitative assessment, pattern discrimination, and an attribution analysis. Based on the symbiosis theory, the theoretical analysis of the human–water relationship was carried out to analyze the three basic elements of the human–water system, and then the evaluation index system of the human–water symbiosis system was constructed to quantitatively assess the development level of the human system and the water system. The Lotka–Volterra model was used to identify the symbiotic pattern, and the human–water symbiosis index was calculated to characterize the health state of the human–water symbiosis system. The main influencing factors of the human–water symbiosis system were further identified through an attribution analysis. Finally, a case study was carried out with 18 cities in Henan Province. Results reveal that (a) the proposed method can effectively realize the quantitative characterization of the human–water symbiosis relationship, with good applicability and obvious advantages; (b) the human–water symbiosis pattern of cities in Henan Province is dominated by the “human system parasitizes water system (H+W−)” pattern, and more attention should be paid to the water system in the subsequent development of it; and (c) the main factors influencing the human system, the water system, and the human–water symbiosis system are the research and development (R&D) personnel equivalent full-time (H7), per capita water resources (W1), and proportion of water conservancy and ecological water conservancy construction investment (W6), respectively. The findings can provide theoretical and methodological support for the study of the human–water symbiosis relationship and sustainable development in other regions.

Abstract Recombinant proteins are gaining increasing popularity for treating human diseases. The clinical effectiveness of recombinant proteins is directly related to their biological activity, which is an important indicator in drug development and quality control. However, certain recombinant proteins have unclear or complex signal pathways, making detecting their activity in vitro difficult. For instance, recombinant human endostatin (endostatin), a new antitumor drug developed in China, lacks a sensitive and stable assay for its biological activity since being market approval. To address this issue, we performed a genome‐wide screening of immortalized human umbilical vein endothelial cells (HUVECs) using a CRISPR/Cas9 knockout library containing 20,000 targeted genes. We identified two potential endostatin‐resistant genes, NEPSPP and UTS2, and successfully constructed a highly sensitive cell line, HUVEC‐UTS2‐3#, by knocking down the UTS2 gene. Based on the optimized parameters of HUVEC‐UTS2‐3# cells, we established a new method for detecting the biological activity of endostatin. The method was validated, and it produced results consistent with primary HUVEC cells but with higher sensitivity and more stable data. The use of gene‐editing technology provides a novel solution for detecting the biological activity of recombinant proteins that other methods cannot detect.

This study considers the superior mechanical properties of carbon nanotube concrete (CNC) and conducts corrosion tests over varying durations to investigate key aspects such as corrosion depth, strength loss, ion migration patterns, and microscopic morphological changes in CNC under the influence of stray current in a salt brine environment. Through compressive strength test, chloride ion color test, ion content titration test, microscopic detection test and molecular dynamics simulation, the results show that in an environment where multiple erosive ions coexist, sulfate ions are the most erosive ions to CNC, and are easily combined with calcium ions. The electric field speeds up the transmission of ions, especially chloride ions. Carbon nanotube has a certain adsorption effect on sulfate ions. The main corrosion products are ettringite, gypsum and magnesium hydroxide. Among them, ettringite and gypsum mainly cause expansion and corrosion.

This paper proposes the design of the Zhejiang opera culture gene map using the Zhejiang opera culture gene and gene map. Secondly, it focuses on the application of data mining algorithms in managing opera culture resources, including indexing and querying of dissemination track data and mining Zhejiang opera culture data resources. Finally, the application effect of data mining in Zhejiang opera culture gene mapping is demonstrated through an example analysis. The results show that for the multi-valued attribute dataset of trajectory data of Zhejiang opera culture, the execution time of the optimized algorithm is reduced by 848 ms under a 1% support rate and 88 ms under a 10% support rate compared with the Apriori algorithm. This paper reveals the inner connections and characteristics of Zhejiang opera culture through a data mining algorithm for cultural gene mapping, providing a scientific basis.

Recombinant adeno-associated virus (rAAV) has emerged as a prominent vector for in vivo gene therapy, owing to its distinct advantages. Accurate determination of the rAAV genome titer is crucial for ensuring the safe and effective administration of clinical doses. The evolution of the rAAV genome titer assay from quantitative PCR (qPCR) to digital PCR (dPCR) has enhanced accuracy and precision, yet practical challenges persist. This study systematically investigated the impact of various operational factors on genome titration in a single-factor manner, aiming to address potential sources of variability in the quantitative determination process. Our findings revealed that a pretreatment procedure without genome extraction exhibits superior precision compared with titration with genome extraction. Additionally, notable variations in titration results across different brands of dPCR instruments were documented, with relative standard deviation (RSD) reaching 23.47% for AAV5 and 11.57% for AAV8. Notably, optimal operations about DNase I digestion were identified; we thought treatment time exceeding 30 min was necessary, and there was no need for thermal inactivation after digestion. And we highlighted that thermal capsid disruption before serial dilution substantially affected AAV genome titers, causing a greater than ten-fold decrease. Conversely, this study found that additive components of dilution buffer are not significant contributors to titration variations. Furthermore, we found that repeated freeze–thaw cycles significantly compromised AAV genome titers. In conclusion, a comprehensive dPCR titration protocol, incorporating insights from these impact factors, was proposed and successfully tested across multiple serotypes of AAV. The results demonstrate acceptable variations, with the RSD consistently below 5.00% for all tested AAV samples. This study provides valuable insights to reduce variability and improve the reproducibility of AAV genome titration using dPCR.

The complexity of finite element analysis for composite structures can be significantly reduced by representing the connector and adjacent concrete as a macroscopic element. Nevertheless, the prevailing macroscopic models for shear connections predominantly employ nonlinear elastic theory. This approach introduces inaccuracies in estimating structural stiffness and load-bearing capabilities, primarily due to its inability to precisely capture the cumulative effects of plastic damage. In response, this study introduces a novel macroscopic elastoplastic model grounded in plasticity theory, aimed at accurately characterizing the nonlinear behavior of stud connections subjected to concurrent shear and tensile forces. This paper meticulously delineates the implementation of the elastoplastic constitutive model using the backward Euler method for numerical integration. It further articulates the derivation of the consistent tangent stiffness, which aligns with the convergence efficiency of the Newton–Raphson iterative approach. The computation of the element stiffness matrix for a two-node element is executed via the governing equation inherent to the finite element method. An exemplar macroelement test conducted in ABAQUS affirms the implicit backward Euler scheme’s stability and consistency across varying tolerances. Validation of the elastoplastic model against empirical test outcomes corroborates its efficacy, demonstrating the model’s precision in predicting the load–displacement behavior of stud connections under the influence of shear and tensile forces.

Objective: To investigate the therapeutic effect of Xingnao Kaiqiao acupuncture combined with modern rehabilitation therapy on cognitive dysfunction after acute ischemic stroke (AIS). Methods: Totally 140 patients with cognitive impairment after AIS admitted to Sichuan Provincial Rehabilitation Hospital from September 2016 to May 2021 were included in this prospective randomized controlled trial. After admission, patients were randomly divided into the trial group and the control group based on a computer-generated random number table. Patients in the trial group were treated with Xingnao Kaiqiao acupuncture combined with modern rehabilitation therapy, and those in the control group were treated with modern rehabilitation therapy alone. Before and after treatment, Mini-Mental State Examination (MMSE) and Barthel index (BI) were used to evaluate the cognitive function and daily living activities, and event-related potentials (ERP) were also measured in both groups. Statistical analyses were performed to compare the results between the two groups. Results: Finally 135 patients were included, 67 in the trial group and 68 in the control group. After treatment, the MMSE score and BI were significantly improved in both groups as compared with those before treatment (both P < .001). In the trial group, the BI and the MMSE subscores in the domains of orientation, registration, recall, and language were significantly higher than those in the control group (all P < 0.05). The global MMSE score of the trial group was higher than that of the control group both after 2 and 4 weeks of treatment, and the differences were statistically significant (P = 0.000/0.001). In the analysis of time effect alone, time had significant effects on the MMSE score in both groups (P < 0.001). After treatment, the latencies of P3 waves were significantly shorter and the amplitudes of P3 waves were significantly higher in the trial group as compared with the control group (both P < 0.05). Conclusion: Xingnao Kaiqiao acupuncture combined with modern rehabilitation therapy may be associated with a better efficacy in treating cognitive dysfunction after AIS. The effect of Xingnao Kaiqiao acupuncture on ERP may play a role in the mechanism underlying such a therapeutic effect. [ABSTRACT FROM AUTHOR]

Thyroid hormone (TH) plays an essential role in cell proliferation, differentiation, and metabolism. Experimental and clinical studies have shown a potential association between TH signaling and retinal degeneration. The suppression of TH signaling protects cone photoreceptors in mouse models of retinal degeneration, whereas excessive TH signaling induces cone degeneration, manifested as reduced light response and a loss of cones. This work investigates the genes/transcriptomic alterations that might be involved in TH-induced cone degeneration in mice using single-cell RNA sequencing (scRNAseq) analysis. One-month-old C57BL/6 mice received triiodothyronine (T3, 20 µg/mL in drinking water) for 4 weeks as a model of hyperthyroidism/excessive TH signaling. At the end of the experiments, retinal cells were dissociated, and cell viability was analyzed before being subjected to scRNAseq. The resulting data were analyzed using the Seurat package and visualized using the Loupe browser. Among 155,866 single cells, we identified 14 cell clusters, representing various retinal cell types, with rod and cone clusters comprising 76% and 4.1% of the total cell population, respectively. Cone cluster transcriptomes demonstrated the most alterations after the T3 treatment, with 450 differentially expressed genes (DEGs), accounting for 38.5% of the total DEGs. Statistically significant changes in the expression of genes in the cone cluster revealed that phototransduction and oxidative phosphorylation were impaired after the T3 treatment, along with mitochondrial dysfunction. A pathway analysis also showed the activation of the sensory neuronal/photoreceptor stress pathways after the T3 treatment. Specifically, the eukaryotic initiation factor-2 signaling pathway and the cAMP response element-binding protein signaling pathway were upregulated. Thus, excessive TH signaling substantially affects cones at the transcriptomic level. The findings from this work provide an insight into how excessive TH signaling induces cone degeneration. [ABSTRACT FROM AUTHOR]

The paper aims at predicting the remaining useful life of highly reliable and long-life products with multiple and multi-stage characteristics in the degradation process. Considering the unit-to-unit variability among the product units, a new bivariate and two-phase Wiener process model with random effects is established. Schwarz Information Criterion is used to identify the change points of the degradation model, and the analytical expressions of life and remaining useful life are given by the concept of first hitting time. Furthermore, the appropriate Copula function is selected to describe the correlation between the two quality characteristics based on Akaike Information Criterion. A bivariate degradation model is established and the unknown parameters of the model are estimated by Markov Chain Monte Carlo method. Finally, the applicability and effectiveness of the proposed method are verified by the comparative analysis of turbine engine. [ABSTRACT FROM AUTHOR]

Background: Neurogenic bladder (NB) is a form of neurological bladder dysfunction characterized by excessive contraction of the bladder detrusor. Protein kinase A (PKA) signaling is involved in the contraction of the detrusor muscle. Aims: To investigate whether PKA signaling mediates the effect of electroacupuncture (EA) on the excessive contraction of the bladder detrusor in NB. Methods: Sixty rats were randomly divided into control, sham, NB, NB + EA, and NB + EA + H89 (a PKA receptor antagonist) groups. The modified Hassan Shaker spinal cord transection method was used to generate a NB model. After EA intervention for one week, urodynamic tests were used to evaluate bladder function, hematoxylin and eosin staining was conducted to assess morphological changes, enzyme-linked immunosorbent assay (ELISA) was performed to measure the concentration of PKA, and Western blotting was conducted to measure the protein levels of phosphorylated myosin light chain kinase (p-MLCK)/p-MLC. Results: The results showed that NB resulted in morphological disruption, impairment of urodynamics, and decreases in the concentration of PKA and the protein levels of p-MLCK/p-MLC. EA reversed the changes induced by NB dysfunction. However, the improvement in urodynamics and the increases in the concentration of PKA and the protein levels of p-MLCK/p-MLC were inhibited by H89. Conclusion: Our findings indicate that the PKA signaling pathway mediates the beneficial effect of EA on excessive contraction of the bladder detrusor in a rat model of NB. [ABSTRACT FROM AUTHOR]

Rapid point-of-care tests that diagnose gonococcal infections and identify susceptibility to antibiotics enable individualized treatment. This could improve patient outcomes and slow the emergence and spread of antibiotic resistance. However, little is known about the long-term impact of such diagnostics on the burden of gonorrhea and the effective life span of antibiotics. We used a mathematical model of gonorrhea transmission among men who have sex with men in the United States to project the annual rate of reported gonorrhea cases and the effective life span of ceftriaxone, the recommended antibiotic for first-line treatment of gonorrhea, as well as 2 previously recommended antibiotics, ciprofloxacin and tetracycline, when a rapid drug susceptibility test that estimates susceptibility to ciprofloxacin and tetracycline is available. The use of a rapid drug susceptibility test with ≥50% sensitivity and ≥95% specificity, defined in terms of correct ascertainment of drug susceptibility and nonsusceptibility status, could increase the combined effective life span of ciprofloxacin, tetracycline, and ceftriaxone by at least 2 years over 25 years of simulation. If test specificity is imperfect, however, the increase in the effective life span of antibiotics is accompanied by an increase in the rate of reported gonorrhea cases even under perfect sensitivity. [ABSTRACT FROM AUTHOR]

In order to investigate the composition and changing pattern of metabolites during the brewing process of goji wine, this study analyzed the changes of metabolites at three stages (pretreatment, primary fermentation and aging) during the brewing process using the widely targeted metabolomics based on ultra-high performance liquid chromatography-electrospray-triple quadrupole linear ion trap-tandem mass spectrometry (UPLC-ESI-QTRAP-MS/MS). The results showed that a total of 1 092 metabolites, including 195 flavonoids, 193 phenolic acids, 174 alkaloids, 121 lipids, 85 organic acids, 80 amino acids and their derivatives, 48 nucleotides and their derivatives, 45 lignans and coumarins, 35 terpenoids, 10 steroids, and 106 other substances were identified during the brewing process of goji wine. Volcano plots identified 260, 619 and 130 differential metabolites for the pretreatment, primary fermentation and aging stages, respectively. These differential metabolites were dominated by lipids, phenolic acids, flavonoids and alkaloids. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the lysine degradation pathway, the valine, leucine and isoleucine biosynthesis pathways, the phytohormone signal transduction pathway, and the flavonoid biosynthesis pathway were significantly enriched during the brewing process of goji wine. This study provides data support for understanding the changes of metabolites during the brewing process of goji wine, and provides a theoretical basis for optimizing the brewing process of goji wine and developing goji-based functional products.

Abstract Discovering new treatments for melanoma will benefit human health. The mechanism by which deoxyhypusine synthase (DHPS) promotes melanoma development remains elucidated. Multi‐omics studies have revealed that DHPS regulates m6A modification and maintains mRNA stability in melanoma cells. Mechanistically, DHPS activates the hypusination of eukaryotic translation initiation factor 5A (eIF5A) to assist METTL3 localizing on its mRNA for m6A modification, then promoting METTL3 expression. Structure‐based design, synthesis, and activity screening yielded the hit compound GL‐1 as a DHPS inhibitor. Notably, GL‐1 directly inhibits DHPS binding to eIF5A, whereas GC‐7 cannot. Based on the clarification of the mode of action of GL‐1 on DHPS, it is found that GL‐1 can promote the accumulation of intracellular Cu2+ to induce apoptosis, and antibody microarray analysis shows that GL‐1 inhibits the expression of several cytokines. GL‐1 shows promising antitumor activity with good bioavailability in a xenograft tumor model. These findings clarify the molecular mechanisms by which DHPS regulates melanoma proliferation and demonstrate the potential of GL‐1 for clinical melanoma therapy.

Thyroid hormone (TH) plays an essential role in cell proliferation, differentiation, and metabolism. Experimental and clinical studies have shown a potential association between TH signaling and retinal degeneration. The suppression of TH signaling protects cone photoreceptors in mouse models of retinal degeneration, whereas excessive TH signaling induces cone degeneration, manifested as reduced light response and a loss of cones. This work investigates the genes/transcriptomic alterations that might be involved in TH-induced cone degeneration in mice using single-cell RNA sequencing (scRNAseq) analysis. One-month-old C57BL/6 mice received triiodothyronine (T3, 20 µg/mL in drinking water) for 4 weeks as a model of hyperthyroidism/excessive TH signaling. At the end of the experiments, retinal cells were dissociated, and cell viability was analyzed before being subjected to scRNAseq. The resulting data were analyzed using the Seurat package and visualized using the Loupe browser. Among 155,866 single cells, we identified 14 cell clusters, representing various retinal cell types, with rod and cone clusters comprising 76% and 4.1% of the total cell population, respectively. Cone cluster transcriptomes demonstrated the most alterations after the T3 treatment, with 450 differentially expressed genes (DEGs), accounting for 38.5% of the total DEGs. Statistically significant changes in the expression of genes in the cone cluster revealed that phototransduction and oxidative phosphorylation were impaired after the T3 treatment, along with mitochondrial dysfunction. A pathway analysis also showed the activation of the sensory neuronal/photoreceptor stress pathways after the T3 treatment. Specifically, the eukaryotic initiation factor-2 signaling pathway and the cAMP response element-binding protein signaling pathway were upregulated. Thus, excessive TH signaling substantially affects cones at the transcriptomic level. The findings from this work provide an insight into how excessive TH signaling induces cone degeneration.

Background: The South West Thames Centre for Genomics implemented a wider diagnostic Next Generation Sequencing (NGS) gene panel for eligible cancer patients undergoing diagnostic testing whilst restricting data analysis and reporting for BRCA1/BRCA2/PALB2/CHEK2 1100delC only as per contemporaneous guidelines. This study investigated the cost-utility of reanalyzing existing diagnostic grade extended panel data for truncating germline pathogenic variants (GPVs) in known moderate risk cancer susceptibility genes (CSGs) and performing follow-up genetic testing for first-degree relatives if patients have an identified CSG allele., Methods: Reanalysis of existing NGS data was undertaken in 889 samples from cancer patients contemporaneously eligible through the NHS England National Genomic Test Directory (NGTD) codes R207 (ovarian) or R208 (breast) who had tested negative for BRCA1/BRCA2/PALB2 and CHEK2 1100delC founder variant. We modeled the cost and health outcomes for comparisons between: 1. Extending reanalysis to ATM truncating GPVs (partial extended testing) versus historical genetic testing, and 2. Extending analysis to ATM truncating GPV/BRIP1 truncating GPV/CHEK2 truncating GPV excluding CHEK2 1100delC/RAD51C truncating GPV/RAD51D truncating GPV (full extended testing) versus historical genetic testing., Results: For partial extended testing, the ICER compared with historical genetic testing was UK£49,671/QALY. For full extended testing, the ICER compared with historical genetic testing of historical genetic testing was UK£5716/QALY. The full extended testing remained cost-effective with a 30% increase in genetic testing cost., Conclusion: Where existing NGS data for cancer susceptibility genes is stored to diagnostic standard in UK laboratories, this study suggests it is cost-effective to analyze, report and clinically manage patients and relatives by extended analysis to an 8-gene panel compared to the historical genetic testing., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)