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Abstract Background Missing data in confounding variables present a frequent challenge in generating evidence using real-world data, including electronic health records (EHR). Our objective was to apply a recently published toolkit for characterizing missing data patterns and based on the toolkit results about likely missingness mechanisms, illustrate the decision-making process for analyses in an empirical case example. Methods We utilized the Structural Missing Data Investigations (SMDI) toolkit to characterize missing data patterns in the context of a pharmacoepidemiology study comparing cardiovascular outcomes of initiating sodium-glucose-cotransporter-2 inhibitors (SGLT2i) and dipeptidyl peptidase‐4 inhibitors (DPP‐4i) among older adults. The study used a linked EHR-Medicare claims dataset from Duke Health patients (2015–2017), focusing on partially observed confounders from EHR data (HbA1c lab and body mass index [BMI] values). Our analysis incorporated SMDI's descriptive functions and diagnostic tests to explore missingness patterns and determine missingness mitigation approaches. We used findings from these investigations to inform estimation of adjusted hazard ratios comparing the two classes of medications. Results High levels of missingness were noted for important confounding variables including HbA1c (63.6%) and BMI (16.5%). Diagnostic tests resulted in output that described: 1) the distributions of patient characteristics, exposure, and outcome between patients with or without an observed value of the partially observed covariate, 2) the ability to predict missingness based on observed covariates, and 3) estimate if the missingness of a partially observed covariate is differential with respect to the outcome. There was evidence that missingness could be sufficiently described using observed data, which allowed multiple imputation by chained equations using random forests to address missing confounder data in estimating treatment effects. Multiple imputation resulted in improved alignment of effect estimates with previous studies. Conclusions We were able to demonstrate the practical application of the SMDI toolkit in a real-world setting. Application of the SMDI toolkit and the resulting insights of potential missingness patterns can inform the choice of appropriate analytic methods and increase transparency of research methods in handling missing data. This type of approach can inform analytic decision making and may increase our ability to generate evidence from real-world data.

AIM: To assess and compare the variations and agreements across different ocular biometric parameters using swept-source optical coherence tomography (SS-OCT) and Scheimpflug tomography in patients diagnosed with cataract. METHODS: This prospective case series was conducted at Tianjin Medical University Eye Hospital. In total, 212 eyes from 212 patients scheduled for phacoemulsification were included. Eyes were evaluated preoperatively using two SS-OCT devices (IOLMaster700 and CASIA2) and Scheimpflug tomography (Pentacam). Central corneal thickness (CCT), anterior chamber depth (ACD), aqueous depth (AQD), white-to-white distance (WTW), flat simulated keratometry (Kf), steep simulated keratometry (Ks), mean keratometry (Km), and total corneal keratometry (TKm) were measured. Intraclass correlation coefficient (ICC), 95% confidence intervals (CI) and limits of agreement (LoA) widths were conducted to assess differences and correlations between devices. RESULTS: All parameters, except for Ks, were significantly different. Pairwise comparison revealed no significant differences between keratometry obtained by IOLMaster 700 and Pentacam. LoA widths of all paired comparisons for Ks were >0.80 D. Except for WTW between IOLMaster 700 and CASIA2 and between CASIA2 and Pentacam, other Pearson's coefficients between devices showed a strong correlation (all r>0.95). The ICC of WTW (ICC=0.438, 95%CI 0.167-0.625) showed poor reliability. The reliability of CCT, ACD, and AQD was excellent (all ICC>0.95), whereas that of TKm was good (ICC=0.827, 95%CI 0.221-0.939). A significant linear correlation was also observed among devices. CONCLUSION: The ocular parameters derived from the use of IOLMaster700, CASIA2, and Pentacam exhibit significant discrepancies; as such, measurements from these devices should not be deemed as interchangeable.

Abstract Introduction The purpose of the study was to explore the possible correlations between the anterior segment parameters derived from anterior segment swept-source optical coherence tomography (AS-SS-OCT) with the surgically induced corneal astigmatism (CSIA) calculated from total keratometry (TK) measured by AS-SS-OCT. Methods Seventy-one eyes of 67 patients with age-related cataract who underwent phacoemulsification combined with intraocular lens implantation with 2.2-mm incision were included. The CSIA values were calculated from anterior keratometry (CSIAKant) and TK (CSIATK) measured by AS-SS-OCT, respectively. Hotelling’s T 2 test was used to evaluate the difference. The correlation of CSIA with various parameters derived from AS-SS-OCT was tested with the Spearman correlation coefficient. Results The centroid of CSIAKant and of CSIATK were 0.31 ± 0.55 D @ 54° and 0.41 ± 0.59 D @ 51°, with no significant difference (F = 1.283, p = 0.281, Hotelling’s T 2). The mean absolute CSIAKant and CSIATK were 0.58 ± 0.24 D and 0.65 ± 0.28 D. Spearman test showed that the magnitude of CSIAKant was negatively correlated with preoperative peripheral corneal thickness (PCT, p = 0.045) and the magnitude of anterior keratometry (p = 0.044). The magnitude of CSIATK was negatively correlated with preoperative central corneal thickness (CCT, p = 0.003) and preoperative PCT (p = 0.015). Conclusions The increased thickness of the peripheral cornea is correlated with the decrease in the magnitude of the CSIA. The correlation we identified between the corneal thickness and the CSIA indicated that certain preoperative parameters should be considered for the prediction of CSIA for a more precise refractive outcome.

Abstract Background International student education has become an important part of higher education and an important symbol to measure the level of higher education. To change the traditional teaching model, here we introduced a combination of Case-Based Learning (CBL)and Flipped Classroom (FC) into the pathophysiology course for international students. This study aimed to explore whether the active learning ability and critical thinking ability of international students can be improved, based on this new teaching model, improving the innovation ability of teachers’ team and students’ attitude to the reform. Methods The two chapters of Cardiac Insufficiency and Apoptosis in Pathophysiology are designed as a CBL + FC teaching method. Distribute the Self-assessment Scale on Active Learning and Critical Thinking (SSACT) and satisfaction questionnaire to international students to evaluate teaching reform based on CBL + FC. Results Compared with the traditional classroom, the online flipped classroom based on CBL has significantly improved the learning enthusiasm, as these students are required to independently complete literature review, actively participate in classroom teaching, learn to use multiple learning strategies, and collaborate with other students to complete PowerPoint (PPT)production. At the same time, the students’ ability to raise problems and solve problems has been greatly improved by analyzing clinical cases; By consulting the literature, the theoretical knowledge learned can be better applied to clinical analysis. The results of the satisfaction survey also show that international students are more likely to accept the flipped classroom teaching mode. Conclusions This teaching mode will stimulate the learning motivation of international students, enhance teaching attraction and increase teaching interaction; At the same time, the CBL + FC teaching method can strengthen the evaluation of international students’ in and out of class and online learning, enhance students’ active learning ability and critical thinking ability, promote the development of personalized learning, and integrate with international medical education.

Abstract Active artificial bone substitutes are crucial in bone repair and reconstruction. Calcium phosphate bone cement (CPC) is known for its biocompatibility, degradability, and ability to fill various shaped bone defects. However, its low osteoinductive capacity limits bone regeneration applications. Effectively integrating osteoinductive magnesium ions with CPC remains a challenge. Herein, we developed magnesium malate-modified CPC (MCPC). Incorporating 5% magnesium malate significantly enhances the compressive strength of CPC to (6.18 ± 0.49) MPa, reduces setting time and improves disintegration resistance. In vitro, MCPC steadily releases magnesium ions, promoting the proliferation of MC3T3-E1 cells without causing significant apoptosis, proving its biocompatibility. Molecularly, magnesium malate prompts macrophages to release prostaglandin E2 (PGE2) and synergistically stimulates dorsal root ganglion (DRG) neurons to synthesize and release calcitonin gene-related peptide (CGRP). The CGRP released by DRG neurons enhances the expression of the key osteogenic transcription factor Runt-related transcription factor-2 (RUNX2) in MC3T3-E1 cells, promoting osteogenesis. In vivo experiments using minipig vertebral bone defect model showed MCPC significantly increases the bone volume fraction, bone density, new bone formation, and proportion of mature bone in the defect area compared to CPC. Additionally, MCPC group exhibited significantly higher levels of osteogenesis and angiogenesis markers compared to CPC group, with no inflammation or necrosis observed in the hearts, livers, or kidneys, indicating its good biocompatibility. In conclusion, MCPC participates in the repair of bone defects in the complex post-fracture microenvironment through interactions among macrophages, DRG neurons, and osteoblasts. This demonstrates its significant potential for clinical application in bone defect repair.

Abstract A retrospective cohort study was conducted to observe the correction effect of Toric intraocular lens (IOL) implantation in cataract eyes with specific types of irregular corneal astigmatism. Thirty-four eyes with either the "asymmetric bow-tie" pattern (Type I) or the "angled bow-tie" pattern (Type II) were included. Corneal topography was assessed using Pentacam HR, and changes in preoperative corneal astigmatism, visual acuity, manifest refraction, and objective visual quality were measured and compared. The average uncorrected distance visual acuity improved significantly from 0.86 ± 0.40 logMAR to 0.22 ± 0.15 logMAR (P

Abstract VPS37A, an ESCRT-I complex component, is required for recruiting a subset of ESCRT proteins to the phagophore for autophagosome closure. However, the mechanism by which VPS37A is targeted to the phagophore remains obscure. Here, we demonstrate that the VPS37A N-terminal domain exhibits selective interactions with highly curved membranes, mediated by two membrane-interacting motifs within the disordered regions surrounding its Ubiquitin E2 variant-like (UEVL) domain. Site-directed mutations of residues in these motifs disrupt ESCRT-I localization to the phagophore and result in defective phagophore closure and compromised autophagic flux in vivo, highlighting their essential role during autophagy. In conjunction with the UEVL domain, we postulate that these motifs guide a functional assembly of the ESCRT machinery at the highly curved tip of the phagophore for autophagosome closure. These results advance the notion that the distinctive membrane architecture of the cup-shaped phagophore spatially regulates autophagosome biogenesis.

This study provides the first investigation of the complete group of variables in the expanded theory of uses and gratifications on consumer engagement in an all-service social media platform. Consumer engagement is measured both from a psychological state and behavioral perspective, an approach which is important since the antecedent variables in uses and gratifications theory have both psychological and behavioral manifestations. A survey is conducted in Mainland China on WeChat with 805 respondents. Antecedent variables and consumer engagement are measured using previously validated scales. Regression analyses find that the antecedent variables of entertainment, integration/social interaction, personal identity, information, remuneration, and empowerment are significantly associated with consumer engagement on WeChat. Age and gender relationships are also explored in correlation and regression analyses, with associations strongest among males and older groups. The results give added support to the relevance of the uses and gratifications theoretical framework.

ObjectiveBoth 5:2 IF diet (intermittent fasting) and daily caloric restriction eating had been suggested for management of MAFLD (Metabolic-Associated Fatty Liver Disease), this study aimed to evaluate the effects of 5:2 IF diet on body weight and metabolic parameters in adults with MAFLD, in comparison to daily caloric restriction eating.MethodsThis single-center, double-blind, prospective, randomized controlled trial included 60 patients with MAFLD, who were administered either a 5:2 IF diet limited calories consumed for 2 days each week with no restrictions on the remaining 5 (Group 5:2 IF diet) or a daily calorie restriction eating (Group daily calorie restriction). Fibrotouch-B instrument assessment, ultrasound assessment of hepatic steatosis, anthropometric indices and body composition analysis, blood sample measurements were conducted during two distinct visits: initially on the day of study commencement (T1), and subsequently at the conclusion of the 12-week intervention period (T2).ResultsIn comparison to daily calorie restriction eating, the 5:2 IF diet significantly decreased the proportion of hepatic steatosis ≥moderate (29.6% vs. 59.3%, p = 0.028) and the degree of hepatic fibrosis F ≥ 2 (3.7% vs. 25.9%, p = 0.05), and fewer percentage of patients were diagnosed with fatty liver via upper abdominal ultrasound in the 5:2 intermittent fasting diet group (33.3% vs. 63.0%, p = 0.029). Additionally, the CAP (controlled attenuation parameter) and LSM (liver stiffness measurements) value were significantly lower in the 5:2 IF diet group (p 0.05).ConclusionIn summary, although both 5:2 IF diet and daily caloric restriction eating achieved similar effect on body weight, liver enzymes, lipid profile and glycemic indices after 12 weeks treatment, 5:2 IF diet demonstrates better improvement in fibrosis and steatosis scores independently from weight regulation. Consequently, it is anticipated to emerge as a viable dietary modality for lifestyle intervention among patients diagnosed with MAFLD.Clinical trial registrationhttps://www.crd.york.ac.uk/PROSPERO, identifier ChiCTR2400080292.

Abstract Objective In vascular dementia (VD), memory impairment caused by the damage of synaptic plasticity is the most prominent feature that afflicts patients and their families. Treadmill exercise has proven beneficial for memory by enhancing synaptic plasticity in animal models including stroke, dementia, and mental disorders. The aim of this study was to examine the effects of treadmill exercise on recognition memory and structural synaptic plasticity in VD rat model. Methods Male Sprague‐Dawley rats were randomly assigned into four groups: control group (C group, n = 6), vascular dementia group (VD group, n = 6), treadmill exercise and vascular dementia group (Exe‐VD group, n = 6), and treadmill exercise group (Exe group, n = 6). Four‐week treadmill exercise was performed in the Exe‐VD and Exe groups. Then, the common carotid arteries of rats in the VD and Exe‐VD groups were identified to establish the VD model. Behavior tests (open‐field test and novel recognition memory test) were adopted to evaluate anxiety‐like behavior and recognition memory. Transmission electron microscopy and Golgi staining were performed to observe synaptic ultrastructure and spine density in the hippocampus. Results Our study demonstrated that VD rat exhibited significantly anxiety‐like behavior and recognition impairment (p

Meteorological prediction is crucial for various sectors, including agriculture, navigation, daily life, disaster prevention, and scientific research. However, traditional numerical weather prediction (NWP) models are constrained by their high computational resource requirements, while the accuracy of deep learning models remains suboptimal. In response to these challenges, we propose a novel deep learning-based model, the Spatiotemporal Fusion Model (STFM), designed to enhance the accuracy of meteorological predictions. Our model leverages Fifth-Generation ECMWF Reanalysis (ERA5) data and introduces two key components: a spatiotemporal encoder module and a spatiotemporal fusion module. The spatiotemporal encoder integrates the strengths of convolutional neural networks (CNNs) and recurrent neural networks (RNNs), effectively capturing both spatial and temporal dependencies. Meanwhile, the spatiotemporal fusion module employs a dual attention mechanism, decomposing spatial attention into global static attention and channel dynamic attention. This approach ensures comprehensive extraction of spatial features from meteorological data. The combination of these modules significantly improves prediction performance. Experimental results demonstrate that STFM excels in extracting spatiotemporal features from reanalysis data, yielding predictions that closely align with observed values. In comparative studies, STFM outperformed other models, achieving a 7% improvement in ground and high-altitude temperature predictions, a 5% enhancement in the prediction of the u/v components of 10 m wind speed, and an increase in the accuracy of potential height and relative humidity predictions by 3% and 1%, respectively. This enhanced performance highlights STFM’s potential to advance the accuracy and reliability of meteorological forecasting.

Moderate organic acids can make fermented alcohol beverage produce comfortable flavor and delicate taste, but during the fermentation process, the content of organic acids in fermented alcohol beverage is unstable. Too high can easily result in astringent and bitter taste and poor flavor, while too low can make the wine bland and tasteless. The type of organic acid also has important influence on the flavor of fermented alcohol beverage. Some methods of acid degradation are frequently used to accurately reduce the level of the primary organic acids in fermented alcohol beverage in order to improve its flavor and quality. This helps to better maintain the volatile flavor components in fermented alcohol beverage and control its flavor. In order to provide a theoretical foundation for improving the quality of fermented alcohol beverage and optimizing the brew processing, and promoting the large-scale sustainable development of fermented alcohol beverage industry, this paper describes the main acid degradation processes and their principles in fermented alcohol beverage, analyzes the benefits, drawbacks, and limitation of various processes, discusses the effects of acid degradation processes on the types of flavor substances in fermented alcohol beverage, and offers an outlook on future research for flavor regulation of fermented alcohol beverage.

Abstract Autophagosome formation, a crucial step in macroautophagy (autophagy), requires the covalent conjugation of LC3 proteins to the amino headgroup of phosphatidylethanolamine (PE) lipids. Atg3, an E2-like enzyme, catalyzes the transfer of LC3 from LC3-Atg3 to PEs in targeted membranes. Here we show that the catalytically important C-terminal regions of human Atg3 (hAtg3) are conformationally dynamic and directly interact with the membrane, in collaboration with its N-terminal membrane curvature-sensitive helix. The functional relevance of these interactions was confirmed by in vitro conjugation and in vivo cellular assays. Therefore, highly curved phagophoric rims not only serve as a geometric cue for hAtg3 recruitment, but also their interaction with hAtg3 promotes LC3-PE conjugation by targeting its catalytic center to the membrane surface and bringing substrates into proximity. Our studies advance the notion that autophagosome biogenesis is directly guided by the spatial interactions of Atg3 with highly curved phagophoric rims.

Abstract The application of pesticides in mixtures often exerts multiple pressures on agricultural soils in the short term. Therefore, it is necessary to assess the effects of mixed application on the environmental behavior and ecotoxicity of pesticides in soil. In this study, we assessed the effects of three common pesticides through mixed application on soil degradation and toxicity toward the earthworm Eisenia fetida. Compared with the degradation half-lives (DT50) the single pesticide, the DT50 values of avermectin, imidacloprid and carbendazim in the binary mixtures were similar. However, their DT50 values in the ternary mixtures were approximately 1.5 times longer than those in the individual applications, enhancing their stable in soil after two or three applications. The ternary mixtures of the pesticides showed significantly synergistic toxicity toward E. fetida, while their binary mixtures exhibited a changing interaction throughout the entire effect level range. The ternary mixtures activated higher SOD and CAT activities in E. fetida than the individual treatments, confirming their synergistic effects. By conducting avoidance tests with E. fetida, ternary toxic interactions were effectively assessed within a relatively short testing period. In summary, the three pesticides in ternary mixtures exhibited longer degradation half-lives and synergistic toxicity toward earthworms compared to individual or binary mixtures.

BackgroundFlurochloridone (FLC) is toxic to male reproduction and can induce apoptosis of testicular tissue and supporting cells under oxidative stress. Of particular concern is whether nuclear factor-erythrocyte 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) signaling pathway and nuclear factor kappa B (NFκB) signaling pathway participate this process. ObjectiveTo observe apoptosis of testicular tissue and sertoli TM4 cells and alterations of Nrf2/HO-1 and NFκB signaling pathways in mice treated with FLC in vivo/in vitro. Methods(1) Animal experiment. Testis samples were harvested from male C57BL/6 mice after 28-day FLC (0, 3, 15, 75, and 375 mg·kg−1 per day) exposure via oral route. Malondialdehyde (MDA) and superoxide dismutase (SOD) in homogenate of testicular tissue were measured by colorimetry. Apoptosis of testicular tissue was evaluated by TUNEL staining. Expression and distribution of Nrf2 and NFκB were detected by immunohistochemistry. Protein expression levels of Nrf2, HO-1, NAD(P)H: quinone oxidoreductase 1 (NQO1), NFκB, inhibitor of nuclear factor kappa-B kinase subunit beta (IKKβ), and phosphorylated recombinant inhibitory subunit of nuclear factor kappa-B alpha (P-IκBα) in testicular tissue homogenate were determined by Western blotting. (2) Cell experiment. TM4 cell lines were treated with 40, 80, 120, 160, and 200 μmol·L−1 FLC for 6 h, and cell viability was detected by CCK-8. After 6 h exposure to 40, 80, and 160 μmol·L−1 FLC, the apoptosis rate was detected by flow cytometry, and the protein expression levels of Nrf2, HO-1, NQO1, NFκB, IKKβ, and IκBα were detected by Western blotting. Results(1) Animal experiment. Apoptosis occurred in the interstitial and basal parts of spermatogenic tubules in male C57BL/6 mice after 28 days of oral FLC exposure. Compared with the control group, the MDA level in testicular tissue of the 375 mg·kg−1 FLC-treated group was significantly increased (P

Chronic kidney disease (CKD) is characterized by fibrosis and inflammation in renal tissues. Several types of cell death have been implicated in CKD onset and progression. Unlike traditional forms of cell death, PANoptosis is characterized by the crosstalk among programmed cell death pathways. However, the interaction between PANoptosis and CKD remains unclear. Here, we used bioinformatics methods to identify differentially expressed genes and differentially expressed PANoptosis-related genes (DE-PRGs) using data from the GSE37171 dataset. Following this, we further performed gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and gene set enrichment analysis using the data. We adopted a combined approach to select hub genes, using the STRING database and CytoHubba plug-in, and we used the GSE66494 as a validation dataset. In addition, we constructed ceRNA, transcription factor (TF)-gene, and drug-gene networks using Cytoscape. Lastly, we conducted immunohistochemical analysis and western blotting to validate the hub genes. We identified 57 PANoptosis-associated genes as DE-PRGs. We screened nine hub genes from the 57 DE-PRGs. We identified two hub genes (FOS and PTGS2) using the GSE66494 database, Nephroseq, immunohistochemistry, and western blotting. A common miRNA (Hsa-miR-101-3p) and three TFs (CREB1, E2F1, and RELA) may play a crucial role in the onset and progression of PANoptosis-related CKD. In our analysis of the drug-gene network, we identified eight drugs targeting FOS and 52 drugs targeting PTGS2.

Salt substitute has been widely used to prepare low-salt foods due to potential health benefits, though the role of CaCl2 in salt substitute and its unique impacts on food quality have been rarely investigated. In this study, comprehensive research has been conducted to elucidate the effects of replacing NaCl with varying concentrations of CaCl2 on the surimi gel characteristics. The introduction of CaCl2 interacted with surimi proteins differently from NaCl, thus leading to difference in protein aggregation behaviors and surimi gel properties. It has been found that a proper proportion of CaCl2 for NaCl substitution could create salt bridges between surimi proteins more effectively, resulting in an ordered, smooth and dense gel network with an increased water holding capacity (WHC) and improved gel strength. Furthermore, TGase activated by Ca2+ boosted the formation of ε-(γ-glutamyl) lysine bonds, which cross-linked surimi proteins to form a firm gel with a better three-dimensional structure. However, replacing NaCl with excessive amount of CaCl2 as divalent salts induced more serious protein aggregation, leading to water loss and gel properties deterioration. More specially, replacing NaCl with CaCl2 at 50% showed the best performance, as evidenced by the most abundant disulfide bonds and hydrophobic interactions, highest hardness and chewiness, and greatest storage modulus. This study provided new insights on developing high-quality surimi gels with significantly reduced salt concentration and improved gel characteristics.

BackgroundLonger outpatient studies have demonstrated that hybrid closed loop (HCL) use has led to a concomitant reduction in glycated hemoglobin(HbA1c) by 0.3%-0.7%. However, reports have also indicated that HbA1c levels are not declined in the long-term use of HCL. Therefore, we wonder that 3 months use of HCL could improve glycated hemoglobin levels in adolescents and children with T1D.MethodsRelevant studies were searched electronically in the Cochrane Library, PubMed, and Embase utilizing the key words "Pediatrics or Child or Adolescent", "Insulin Infusion Systems" and "Diabetes Mellitus" from inception to 17th March 2024 to evaluate the performance of HCL on HbA1c in adolescents, and children with T1D.ResultsNine studies involving 927 patients were identified. Three months use of HCL show a beneficial effect on HbA1c management (p 0.05). The overall percentage of hyperglycemic time was significantly decreased in HCL group compared to the control group when it was defined as >180 mg/dL (p 250 mg/dL (p = 0.007, I2 = 86%) and >300 mg/dL (p = 0.005; I2 = 76%). The mean glucose level was significantly decreased by HCL (p ConclusionsHCL had a beneficial effect on HbA1c management and TIR without increased hypoglycemic time as compared to standard of care in adolescents and children with T1D when therapy duration of HCL was not less than three months.Trial number and registry urlCRD42022367493; https://www.crd.york.ac.uk/PROSPERO, Principal investigator: Zhen-feng Zhou, Date of registration: October 30, 2022.

Efficient thawing can preserve the quality of frozen hairtail (Trichiurus lepturus) close to that of fresh hairtail. In contrast to air thawing (AT) and radio-frequency thawing (RT), this study looked at how graphene oxide (GO) and graphene magnetic (GM) nanoparticles paired with RT affect the microstructure and protein conformation of hairtails after thawing. The results suggested that GM-RT can reduce the myofibrillar protein (MP) damage and be more effective than other thawing treatments, like AT, RT, and GO-RT, in maintaining the microstructure of hairtail. The particle size and zeta potential showed that GM-RT could reduce the aggregation of MP during the thawing process compared to other thawing methods. Moreover, the texture of the hairtail after GM-RT exhibited higher hardness (1185.25 g), elasticity (2.25 mm), and chewiness (5.75 mJ) values compared to other thawing treatments. Especially compared with RT, the GM-RT treatment displayed significant improvements in hardness (27.24%), a considerable increase in springiness (92.23%), and an increase in chewiness (57.96%). GO-RT and GM-RT significantly reduced the centrifugal loss. The scanning electron microscopy results demonstrated that the effect of GM-RT was more akin to that of a fresh sample (FS) and characterized by a well-organized microstructure. In conclusion, GM-RT effectively diminished the MP aggregation and improved the texture of thawed fish. It can be regarded as a viable alternative thawing technique to enhance MP stability, which is vital for preserving meat quality.

Investigation of cell-to-cell variability holds critical physiological and clinical implications. Thus, numerous new techniques have been developed for studying cell-to-cell variability, and these single-cell techniques can also be used to investigate rare cells. Moreover, for studying protein-protein interactions (PPIs) in single cells, several techniques have been developed based on the principle of the single-molecule pulldown (SiMPull) assay. However, the applicability of these single-cell SiMPull (sc-SiMPull) techniques is limited because of their high technical barrier and special requirements for target cells and molecules. Here, we report a highly innovative nanobead-based approach for sc-SiMPull that is based on our recently developed microbead-based, improved version of SiMPull for cell populations. In our sc-SiMPull method, single cells are captured in microwells and lysed in situ, after which commercially available, pre-surface-functionalized magnetic nanobeads are placed in the microwells to specifically capture proteins of interest together with their binding partners from cell extracts; subsequently, the PPIs are examined under a microscope at the single-molecule level. Relative to previously published methods, nanobead-based sc-SiMPull is considerably faster, easier to use, more reproducible, and more versatile for distinct cell types and protein molecules, and yet provides similar sensitivity and signal-to-background ratio. These crucial features should enable universal application of our method to the study of PPIs in single cells.

IntroductionUnderstanding the variations of oligosaccharide in breast milk contribute to better study how human milk oligosaccharides (HMOs) play a role in health-promoting benefits in infants.MethodsSix abundant HMOs, 2’-fucosyllactose (2’-FL), 3-fucosyllactose (3-FL), Lacto-N-tetraose (LNT), Lacto-N-neotetraose (LNnT), 3’-sialyllactose (3’-SL) and 6’-sialyllactose (6’-SL), in breast milk collected at 0–5 days, 10–15 days, 40–45 days, 200–240 days, and 300–400 days postpartum from six locations across China were analyzed using high-performance anion-exchange chromatography-pulsed amperometric detector.ResultsThe concentration of individual HMO fluctuated dynamically during lactational stages. The median ranges of 2’-FL, 3-FL, LNT, LNnT, 3’-SL, and 6’-SL across the five lactational stages were 935–2865 mg/L, 206–1325 mg/L, 300–1473 mg/L, 32–317 mg/L, 106–228 mg/L, and 20–616 mg/L, respectively. The prominent variation was observed in the content of 6’-SL, which demonstrates a pattern of initial increase followed by a subsequent decrease. Among the five lactational stages, the transitional milk has the highest concentration, which was 31 times greater than the concentration in mature milk at 300–400 days postpartum, where the content is the lowest. Geographical location also influenced the content of HMOs. LNT and LNnT were the highest in mature milk of mothers from Lanzhou among the six sites at 40–240 days postpartum. Breast milks were categorized into two groups base on the abundance of 2’-FL (high and low). There was no significant difference in the proportions of high and low 2’-FL phenotypes among the six sites, and the percentages of high and low 2’-FL phenotypes were 79% and 21%, respectively, across all sites in China.DiscussionThis study provided a comprehensive dataset on 6 HMOs concentrations in Chinese breast milk during the extended postpartum period across a wide geographic range and stratified by high and low 2’-FL phenotypes.

Purpose: To investigate the influence of posterior corneal astigmatism on the prediction accuracy of toric multifocal intraocular lens (IOL) calculation. Methods: The keratometric astigmatism measured by Lenstar LS 900 (KCAL), keratometric astigmatism (KCAP) and total corneal astigmatism (TCA) measured by Scheimpflug camera (Pentacam HR) were documented and analyzed accordingly. Three deduction models using different parameters were compared. Model 1: KCAL ​+ ​keratometric corneal surgically induced astigmatism (KCSIA, 0.30 D @ 50°); Model 2: KCAP ​+ ​KCSIA); Model 3: TCA ​+ ​total CSIA (TCSIA, 0.23 D @ 50°). The prediction errors of each model as the difference vector between the actual and the intended residual astigmatism were compared. Results: Seventy-six eyes implanted with toric multifocal IOLs were included in this study. The vector differences of the actual KCSIA and TCSIA were statistically significant in the total sample and against-the-rule (ATR) subgroup (both P ​

Can Xue is a representative of Chinese women's literature of the late 20th and early 21st centuries. Her works are one of the most interesting literary phenomena. The author discusses the poetics of the “anti-aesthetics” in Can Xue’s works, based on the violation of classical aesthetic norms. To achieve a new aesthetic impact, Can Xue employs such artistic means as fantasy, metaphor, symbol, synesthesia in a new way. Possessing a rich and unbridled imagination, the writer strives to depict something that exists “in the zone of non-existence.” Besides, Can Xue creates anti-aesthetic, ugly, incomprehensible, and metaphorical images, invents illogical dialogues, refers to the phenomena of the interweaving of dreams and reality, peeping, etc. It is concluded that Can Xue breaks the frame of traditional aesthetic, seeks ugly, irrational, and unacceptable to popular standards of beauty. But despite all the ugliness, she draws attention to the hidden depths of human consciousness and soul, shows another truth of life. An analysis of the poetics of Can Xue allows a deeper and more comprehensive understanding of the writings of Chinese authors of the late 20th and early 21st centuries.

Crowd intelligence based transaction network (CIbTN) is a new generation of e-commerce. In a CIbTN, buyers, sellers, and other institutions are all independent and intelligent agents. Each agent stores the commodity information in a local node. The agents interconnect through a circle of friends and construct an unstructured network. To conduct the commodity search task in a network more efficiently and in an energy-saving manner when a buyer presents a commodity demand, a hybrid breadth-depth search algorithm (HBDA) is proposed, which combines the search logic of the breadth-first search algorithm and the depth-first search algorithm. We defined the correlation degree of nodes in a network, optimized the rules of search and forwarding paths using the correlation degree between a node and its neighboring nodes in the circle of friends, and realized the HBDA based on the PeerSim simulation tool and Java. Experimental results show that, in general, the proposed HBDA has a better search success rate, search time, commodity matching degree, and search network consumption over the two blind search algorithms. The HBDA also has good expansibility, thus allowing it to be used for commodity search efficiently with a high success rate in large-scale networks.

Abstract Objective To evaluate the effect of gentamicin in surgical perfusion solution on endophthalmitis incidence after cataract surgery. Methods A retrospective analysis of endophthalmitis incidence was conducted in two groups of patients who underwent cataract surgery, with (Group B) or without gentamicin (Group A) in the surgical perfusion solution. Endophthalmitis incidence, the isolated pathogenic bacteria strains and their antibiotic sensitivity, and the drug-resistant genotype of the pathogens were examined. Results The incidence of endophthalmitis in patients of group A was 0.8‰. Thirteen pathogenic bacterial strains were isolated from the patient samples in group A, including 8 strains of Staphylococcus epidermidis, 1 Staphylococcus aureus, 1 Streptococcus pneumoniae, 1 Streptococcus bovis, 1 Enterococcus faecium and 1 Morganella sp. The incidence of endophthalmitis in group B patients was 0.2‰, which was significantly lower than that in group A (P 0.05). However, the proportion of Enterococci isolated in group B samples was higher than that in group A (P

The crowd intelligence-based e-commerce transaction network (CIeTN) is a distributed and unstructured network structure. Smart individuals, such as buyers, sellers, and third-party organizations, can store information in local nodes and connect and share information via moments. The purpose of this study is to design a product search algorithm on the basis of ant colony optimization (ACO) to achieve an efficient and accurate search for the product demand of a node in the network. We introduce the improved ideas of maximum and minimum ants to design a set of heuristic search algorithms on the basis of ACO. To reduce search blindness, additional relevant heuristic factors are selected to define the heuristic calculation equation. The pheromone update mechanism integrating into the product matching factor and forwarding probability is used to design the network search rules among nodes in the search algorithm. Finally, the search algorithm is facilitated by Java language programming and PeerSim software. Experimental results show that the algorithm has significant advantages over the flooding method and the random walk method in terms of search success rate, search time, product matching, search network consumption, and scalability. The search algorithm introduces the idea of improving the maximum and minimum ant colony system and proposes new ideas in the design of heuristic factors in the heuristic equation and the pheromone update strategy. The search algorithm can search for product information effectively.

This study aims to identify hot spots, research limitations and future research directions in tourism environmental impact assessment (TEIA). We analyzed studies from the core database of Web of Science (WoS) based on their coauthorship, keyword co-occurrence and timeline with VOSviewer and CiteSpace. It was found that China, the United States, the United Kingdom, Australia and Spain are the major contributors to TEIA, and relatively stable cooperative groups have been formed among the authors. Research hotspots in the past 20 years mainly include: the impact of tourism activities in different tourist destinations on the environment, the approaches to assess the impact of tourism on the environment, and strategies on reducing the negative impact of tourism on the environment. We also found TEIA deficiency in the following five aspects: 1) insufficient studies on macro decision-making; 2) insufficient dynamic interaction analysis; 3) insufficient tourism heat footprint research; 4) insufficient studies on the positive effects of tourism on the environment; and 5) insufficient interdisciplinary innovation. Based on the findings, we suggest that 1) further studies be conducted on tourism activity type, time scale, macro pattern, environmental process and policy effect of tourism impact assessment with more variables and factors considered; 2) the impact of different types of tourism on each subsystem of the environment and the paths of the interaction among subsystems be explored from the perspective of system governance; 3) the study of thermal footprint generated by tourism activities be given more attention, especially large-scale tourism activities; 4) the positive impact of tourism activities on the ecological environment be studied, especially ecotourism; 5) the applicability of TEIA evaluation results be increased by means of interdisciplinary methods such as big data analysis.

Modified macroporous structures and active osteogenic substances are necessary to overcome the limited bone regeneration capacity and low degradability of self-curing calcium phosphate cement (CPC). Curcumin (CUR), which possesses strong osteogenic activity and poor aqueous solubility/bioavailability, esterifies the side chains in hyaluronic acid (HA) to form a water-soluble CUR-HA macromolecule. In this study, we incorporated the CUR-HA and glucose microparticles (GMPs) into the CPC powder to fabricate the CUR-HA/GMP/CPC composite, which not only retained the good injectability and mechanical strength of bone cements, but also significantly increased the cement porosity and sustained release property of CUR-HA in vitro. CUR-HA incorporation greatly improved the differentiation ability of bone marrow mesenchymal stem cells (BMSCs) to osteoblasts by activating the RUNX family transcription factor 2/fibroblast growth factor 18 (RUNX2/FGF18) signaling pathway, increasing the expression of osteocalcin and enhancing the alkaline phosphatase activity. In addition, in vivo implantation of CUR-HA/GMP/CPC into femoral condyle defects dramatically accelerated the degradation rate of cement and boosted local vascularization and osteopontin protein expression, and consequently promoted rapid bone regeneration. Therefore, macroporous CPC based composite cement with CUR-HA shows a remarkable ability to repair bone defects and is a promising translational application of modified CPC in clinical practice.

Cargo transfer vessels (CTVs) are designed to transfer cargo from a floating production storage and offloading (FPSO) unit into conventional tankers. The dynamic positioning system allows the CTV to maintain a safe position relative to the FPSO unit using a flexible cargo transmission pipe, and the CTV tows the tanker during operating conditions. The operation mode can be considered a synchronization tracking control problem. In this paper, a synchronization control strategy is presented based on the virtual leader–follower configuration and an adaptive backstepping control method. The position and heading of the following vessel are proven to be able to globally exponentially converge to the virtual ship by the contraction theorem. Then, the optimization problem of the desired thrust command from the controller is solved through an improved firefly algorithm, which fully considers the physical characteristics of the azimuth thruster and the thrust forbidden zone caused by hydrodynamic interference. To validate the effectiveness of the presented synchronous following strategy and thrust allocation algorithm, a scale model experiment is carried out under a sea state of 4 in a seakeeping basin. The experimental results show that the CTV can effectively maintain a safe distance of 100 m with a maximum deviation of 3.78 m and an average deviation of only 0.99 m in the wave heading 180°, which effectively verifies that the control strategy proposed in this paper can achieve safe and cooperative operation between the CTV and the FPSO unit. To verify the advantages of the SAF algorithm in the thrust allocation, the SQP algorithm and PSO algorithm are used to compare the experimental results. The SAF algorithm outperforms the SQP and PSO algorithms in longitudinal and lateral forces, with the R-squared (R2) values of 0.9996 (yaw moment), 0.9878 (sway force), and 0.9596 (surge force) for the actual thrusts and control commands in the wave heading 180°. The experimental results can provide technical support to improve the safe operation of CTVs.

A new fermentation method for kiwi wine was explored by developing the well-known medicinal and edible plant Cyclocarya paliurus (C. paliurus) to create more value with undersized kiwifruits. In this study, the changes in bioactive substances during the C. paliurus–kiwi winemaking process were analyzed on the basis of response surface optimization results, and the antioxidant capacity, aromatic compounds, and sensory quality of the C. paliurus–kiwi composite wine with kiwi wine and two commercial kiwi wines were compared. The results showed that DPPH radical, OH− radical, and ABTS+ scavenging rates remained at over 60.0%, 90.0%, and 70.0% in C. paliurus–kiwi wine, respectively. The total flavonoid content (TFC) and total polyphenol content (TPC) of C. paliurus–kiwi wine were significantly higher than those of the other three kiwi wines. C. paliurus–kiwi wine received the highest score and detected 43 volatile compounds. Ethyl hexanoate, which showed stronger fruity and sweet aromas, was one of the main aroma components of C. paliurus–kiwi wine and different from commercial wines. This wine has a good flavor with a natural and quality feeling of C. paliurus–kiwifruit extract, low-cost processing, and great market potential.

Based on the present situation of usage based insurance (UBI) research and application, this paper puts forward the UBI rating model based on driving behavior classification, and applies the technology of data mining to the evaluation of driving behavior. The actual driving behavior data and the risk data of 400 drivers are used as experimental data. Finally, an example shows that the driving behavior classification model is superior to the driving behavior score model for the identification of accident risk, which can make UBI rate more scientific and reasonable.

AIM: To assess the changes in the peripapillary vasculature and macular thickness after cataract surgery using two phacoemulsification systems with optical coherence tomography angiography (OCTA). METHODS: Fifty-two eyes of 52 patients with age-related cataract were randomized into two groups for phacoemulsification: Infiniti group (26 patients) using the Infiniti phacoemulsification system with gravity-fluidics and Centurion group (26 patients) using the Centurion phacoemulsification system with active-fluidics. The peripapillary vessel density (PVD) and macular thickness were examined using OCTA at baseline and at 1d, 1 and 3mo after cataract surgery. RESULTS: In the Infiniti group, the PVD was significantly reduced at 1d after the cataract surgery (P0.05). In the Centurion group, the VD and thickness in the optic papilla and macula did not significantly change in all regions during the follow-up (all P>0.05). The best-corrected visual acuity (BCVA) significantly improved in both groups postoperatively (P

Objective To investigate the related viral markers of HBV DNA reactive samples among voluntary blood donors in Shiyan area, so as to provide some reference for donor re-entry. Methods From August 2019 to June 2021, 78 samples with HBV DNA reactivity from voluntary blood donors in our blood station were collected, and they were further detected for HBV viral markers(using chemiluminescence assays), nucleic acid testing(NAT) of virus quantification and sequencing analysis. Results Forty-seven (60.3%)out of 78 HBV DNA reactive samples were from repeated blood donors, and 56.4%(44/78)of them were over 45 years old. Among the five viral markers of hepatitis B, 37.2%(29/78) were positive for anti-HBs alone, 19.2%(15/78) were positive for anti-HBe+ anti-HBc and anti-HBs+ anti-HBe+ anti-HBc, and 11.5% (9/78) were all items negative.A total of 62.8%(49/78) of samples were detected by NAT quantification and seven samples had been successfully sequenced for HBV. Conclusion NAT can effectively minimize the missed detection of HBsAg methodology and reduce the risk of HBV transmission through blood. The re-entry of HBV DNA reactive blood donors should be treated with care.

Abstract Objective The aim of this study was to investigate the pro-angiogenic potential of olfactory ensheathing cells (OECs) activated by curcumin (CCM) and lipopolysaccharide (LPS) and the possible underlying mechanisms. Methods Vascular endothelial cells or tissues were cultured and treated with conditioned medium (CM) extracted from activated OECs activated through the addition of LPS and CCM or unactivated controls. Concomitantly, the pro-angiogenic potential of OECs was assessed in vitro by aortic ring sprouting assay, endothelial wound healing assay, CCK-8 assay, and tube formation assay. Subsequently, the OECs were co-cultured with endothelial cells to evaluate their promoting effect on endothelial cell proliferation and migration following a mechanical scratch. Moreover, the spinal cord injury (SCI) model in rats was established, and the number of endothelial cells and vascular structure in the injured area after SCI was observed with OEC transplantation. Finally, the underlying mechanism was investigated by western blot analysis of phosphorylated kinase expression with or without the MK-2206 (Akt-inhibitor). Result The present results showed that the activated OECs can effectively promote vascular endothelial cells' proliferation, migration, and vessel-like structure formation. Strikingly, several pro-angiogenic growth factors such as VEGF-A and PDGF-AA, which facilitate vessel formation, were found to be significantly elevated in CM. In addition, the PI3K/Akt signaling pathway was found to be involved in pro-angiogenic events caused by activated OEC CM, displaying higher phosphorylation levels in cells. In contrast, the delivery of MK2206 can effectively abrogate all the positive effects. Conclusions OECs activated by LPS and CCM have a pro-angiogenic effect and can effectively promote angiogenesis and improve the microenvironment at the injury site when transplanted in the injured spinal cord. This potentiated ability of OECs to provide pro-angiogenic effects is likely mediated through the PI3K/Akt pathway.

In this paper, some rational high-accuracy compact finite difference schemes on nonuniform grids (NRHOC) are introduced for solving convection–diffusion equations. The derived NRHOC schemes not only can suppress the oscillatory property of numerical solutions but can also obtain a high-accuracy approximate solution, and they can effectively solve the convection–diffusion problem with boundary layers by flexibly adjusting the discrete grid, which can be obtained with the singularity in the computational region. Three numerical experiments with boundary layers are conducted to verify the accuracy of the proposed NRHOC schemes. We compare the computed results with the analytical solutions, the results of the rational high-accuracy compact finite difference schemes on uniform grids (RHOC), and the other schemes in the literature. For all test problems, good computed results are obtained with the presented NRHOC schemes. It is shown that the presented NRHOC schemes have a better resolution for the solution of convection-dominated problems.

Plant miRNAs are a class of noncoding RNA with a length of 21–24 nt that play an important role in plant responses to biotic and abiotic stresses. Bacterial blight (BB) caused by Xanthomonas oryzae pv. oryzae (Xoo) is one of the most serious bacterial diseases in rice. Our previous work showed that osa-miR2118b/n was induced by Xoo infection. However, the biological function of miR2118 has not yet been characterized in experiments. Herein, we constructed MIR2118b OE, as well as single and double mutants of MIR2118b/n using CRISPR/Cas9. Further results showed that osa-MIR2118b OE plants exhibited longer lesion lengths than the wild type after Xoo inoculation, while MIR2118 CRISPR plants exhibited shorter lesion lengths than the wild type after Xoo inoculation. Co-transformation experiments in rice protoplasts indicated that osa-miR2118 negatively regulated the transcripts of three nucleotide-binding sites and leucine-rich repeat (NLR) genes (LOC_Os08g42700.1, LOC_Os01g05600.1, and LOC_Os12g37290.1) which are predicted target genes of miR2118, but not the mutated NLR genes with a 3 bp insertion at the center of the binding sites. The transcriptional level of the three NLR genes was reversed relative to osa-miR2118 in the MIR2118b OE and MIR2118b CRISPR plants. The above results demonstrate that osa-miR2118b/n negatively regulates the resistance to bacterial blight through negatively regulating several NLR genes.

Background: Flurochloridone (FLC), a selective herbicide used on a global scale, has been reported to have male reproductive toxicity whose evidence is limited, but its mechanism remains unclear. The present study was conducted to systematically explore the male reproductive toxicity of FLC, including sperm quality, spermatogenesis, toxicity targets, and potential mechanisms. Methods: Male C57BL/6 mice aged 6–7 weeks received gavage administration of FLC (365/730 mg/kg/day) for 28 consecutive days. Then, the tissue and sperm of mice were collected for analysis. We measured the gonadosomatic index and analyzed sperm concentration, motility, malformation rate, and mitochondrial membrane potential (MMP). Spermatocyte immunofluorescence staining was performed to analyze meiosis. We also performed pathological staining on the testis and epididymis tissue and TUNEL staining, immunohistochemical analysis, and ultrastructural observation on the testicular tissue. Results: Results showed that FLC caused testicular weight reduction, dysfunction, and architectural damage in mice, but no significant adverse effect was found in the epididymis. The exposure interfered with spermatogonial proliferation and meiosis, affecting sperm concentration, motility, kinematic parameters, morphology, and MMP, decreasing sperm quality. Furthermore, mitochondrial damage and apoptosis of testicular Sertoli cells were observed in mice treated with FLC. Conclusion: We found that FLC has significant adverse effects on spermatogonial proliferation and meiosis. Meanwhile, apoptosis and mitochondrial damage may be the potential mechanism of Sertoli cell damage. Our study demonstrated that FLC could induce testicular Sertoli cell damage, leading to abnormal spermatogenesis, which decreased sperm quality. The data provided references for the toxicity risk and research methods of FLC application in the environment.

BackgroundTraumatic spinal cord injuries (TSCIs) are worldwide public health problems that are difficult to cure and impose a substantial economic burden on society. There has been a lack of extensive multicenter review of TSCI epidemiology in northwest China during the Corona Virus Disease 2019 (COVID-19) pandemic.MethodA multicenter retrospective study of 14 selected hospitals in two provinces in northwest China was conducted on patients admitted for TSCI between 2017 and 2020. Variables assessed included patient demographics, etiology, segmental distribution, treatment, waiting time for treatment, and outcomes.ResultsThe number of patients with TSCI showed an increasing trend from 2017 to 2019, while there were 12.8% fewer patients in 2020 than in 2019. The male-to-female ratio was 3.67:1, and the mean age was 48 ± 14.9 years. The primary cause of TSCI was high falls (38.8%), slip falls/low falls (27.7%), traffic accidents (23.9%), sports (2.6%), and other factors (7.0%). The segmental distribution showed a bimodal pattern, peak segments were C6 and L1 vertebra, L1 (14.7%), T12 (8.2%), and C6 (8.2%) were the most frequently injured segments. In terms of severity, incomplete injury (72.8%) occurred more often than complete injury (27.2%). The American Spinal Injury Association impairment scale of most patients did not convert before and after treatment in the operational group (71.6%) or the conservative group (80.6%). A total of 975 patients (37.2%) from urban and 1,646 patients (62.8%) from rural areas were included; almost all urban residents could rush to get treatment after being injured immediately (

A key prerequisite for the establishment of digitalized sheep farms and precision animal husbandry is the accurate identification of each sheep’s identity. Due to the uncertainty in recognizing sheep faces, the differences in sheep posture and shooting angle in the recognition process have an impact on the recognition accuracy. In this study, we propose a deep learning model based on the RepVGG algorithm and bilinear feature extraction and fusion for the recognition of sheep faces. The model training and testing datasets consist of photos of sheep faces at different distances and angles. We first design a feature extraction channel with an attention mechanism and RepVGG blocks. The RepVGG block reparameterization mechanism is used to achieve lossless compression of the model, thus improving its recognition efficiency. Second, two feature extraction channels are used to form a bilinear feature extraction network, which extracts important features for different poses and angles of the sheep face. Finally, features at the same scale from different images are fused to enhance the feature information, improving the recognition ability and robustness of the network. The test results demonstrate that the proposed model can effectively reduce the effect of sheep face pose on the recognition accuracy, with recognition rates reaching 95.95%, 97.64%, and 99.43% for the sheep side-, front-, and full-face datasets, respectively, outperforming several state-of-the-art sheep face recognition models.

Abstract The aim of the study is to explore the distribution patterns and internal correlations of the morphological parameters of the cornea in patients with age-related cataract. The Pentacam HR was used to measure anterior corneal astigmatism (ACA), posterior corneal astigmatism (PCA), total corneal astigmatism (TCA) and keratometric corneal astigmatism (KCA). With age, the proportion of with-the-rule (WTR) ACA decreased from 65.31% to 23.63%, while the against-the-rule (ATR) ACA increased from 26.53% to 56.20%. PCA exceeded 0.50 D in 9.14% of eyes, while 76.35% of them were ATR. The magnitude of ACA was positively correlated with PCA in the whole sample, with a more significant correlation in WTR eyes (sr = 0.349, P

Purpose: The incidence of uric acid (UA)-induced kidney injury is increasing owing to the high incidence of hyperuricemia in recent years. The flower of Abelmoschus manihot (Linneus) Medik is a traditional Chinese medicinal herb widely used in the treatment of some kidney diseases. In our previous study, we reported that the total extract of A. manihot L. flower (TEA) attenuated adriamycin-induced renal tubular cell injury. In this study, we aimed to evaluate the role of TEA in UA-induced tubular cell injury.Methods: Normal rat proximal epithelial NRK-52E cells were incubated with UA to mimic hyperuricemia conditions. The role of TEA in the renal tubular cells was also assessed. The cellular morphology was observed using phase-contrast microscopy, and cell viability was analyzed using the Cell Counting kit-8. Living and dead cells were stained using a Calcein-AM/PI double stain kit. The release of lactate dehydrogenase (LDH) was analyzed by LDH cytotoxicity Assay Kit. The expression of target proteins was analyzed using western blot analysis.Results: UA triggered NRK-52E cell injury, as evidenced by morphological changes, detachment of cells from the bottom, cell swelling, large bubbles blowing from cell membrane and loss of cell viability. UA increased release of LDH. UA induced the expression of p-ERK1/2 and the subsequent activation of caspase-8, caspase-3, and NLRP3 inflammasomes. Pyroptosis was elicited by UA after gasdermin E N-terminal (GSDME-NT) was cleaved from gasdermin E (GSDME). Z-DEVD-FMK, a caspase-3 inhibitor, suppressed the expression of both NLRP3 and GSDME-NT, but not that of caspase-8. INF39, an NLRP3 inhibitor, altered the expression of GSDME-NT expression, but not that caspase-3 and caspase-8. TEA alleviated UA-induced cell injury by suppressing ERK1/2/caspase-8/caspase-3/NLRP3/GSDME signaling.Conclusion: GSDME-mediated pyroptosis was involved in UA-induced renal tubular cell injury. This is the first study to report that TEA protects renal tubular epithelial cells against UA by inhibiting the ERK/1/2/caspase-8/caspase-3/NLRP3/GSDME pathway.

Background: Cuproptosis is a newly identified form of non-apoptotic cell death that is associated with the progression and treatment responses in pancreatic adenocarcinoma (PAAD). However, its impact on oncology and tumor microenvironment (TME) remains unclear.Methods: Hub genes were identified using least absolute shrinkage and selection operator (LASSO) Cox regression for 25 newly reported cuproptosis-related regulators and subjected to stepwise regression to obtain cuproptosis-related score (CuRS). Additionally, the clinical significance, functional status, role on TME, and genomic variation of CuRS were further examined systematically.Results: A CuRS model incorporating TRAF2, TRADD, USP21, FAS, MLKL, TNFRSF10B, MAPK8, TRAF5, and RIPK3 was developed. The stability and accuracy of this risk model as an independent prognostic factor for PAAD were confirmed in the training and external validation cohorts. Patients in the high-CuRS group had “cold” tumors with active tumor proliferation and immunosuppression, whereas those in the low-CuRS group comprised “hot” tumors with active immune function and cell killing capacity. Additionally, patients in the high-CuRS group carried fewer genomic copy number variations (CNVs) and greater somatic mutations. Furthermore, patients in the low- and high-CuRS groups exhibited increased sensitivity to immunotherapy and chemotherapy, respectively.Conclusion: We developed and validated a robust CuRS model based on cuproptosis to assess patients’ prognoses and guide clinical decision-making. Overall, the findings of this study are expected to contribute to the comprehensive understanding of cuproptosis and facilitate precise treatment of PAAD.

BackgroundEpidermal growth factor receptor (EGFR) exon 20 insertion mutations are uncommon EGFR mutations and generally resistant to first- and second-generation EGFR-tyrosine kinase inhibitors (TKIs). In precision oncology, treatment regimens are tested for improving the clinical outcomes. Zebrafish embryo tumor transplant models are used in cancer research.MethodsWe report two Chinese females who were diagnosed with stage IV lung adenocarcinoma and shown to harbor EGFR exon 20 insertion mutations by next-generation sequencing (NGS). Then, we established lung cancer patient-derived xenografts using a zebrafish model. The tumor cells were isolated from the patient. For case one, tumor cells were collected from lymph node biopsy, while the tumor cells were obtained from the pleural effusion. Zebrafish were inoculated with tumor cells and placed in the culture medium containing the third-generation EGFR-TKI, osimertinib. Fluorescence microscope photographs were used to record the red fluorescence area, which represented the proliferation and migration of tumor cells in the zebrafish.ResultsCase one was diagnosed with lung adenocarcinoma (cT4N3M1b, stage IVB) and had an EGFR exon 20 mutation (p. N771delinsHH [abundance 14.08%]). Tumor cell proliferation and migration were significantly reduced in the osimertinib group compared with the control group. The patient received first-line osimertinib (160 mg). According to RECIST v1.1, she achieved a partial response. Case two had stage IVA lung adenocarcinoma with a pleural effusion. The pleural effusion sample was selected to obtain tumor cells for injection, and the zebrafish lung cancer model was established. The proliferation of tumor cells in the osimertinib group was significantly reduced compared to the control group. The migration of tumor cells was not significantly reduced compared to the control group. The patient also received first-line osimertinib (160 mg). The lung lesions were stable, but the pleural effusion was poorly controlled.ConclusionOur study demonstrates the applicability of a zebrafish embryos model as an innovative platform to targeted drug testing. More precise methods are needed to select treatment options in the future.

As the recent permafrost thawing of northern Asia proceeds due to anthropogenic climate change, precise and detailed palaeoecological records from past warm periods are essential to anticipate the extent of future permafrost variations. Here, based on the modern relationship between permafrost and vegetation (represented by pollen assemblages), we trained a Random Forest model using pollen and permafrost data and verified its reliability to reconstruct the history of permafrost in northern Asia during the Holocene. An early Holocene (12–8 cal ka BP) strong thawing trend, a middle-to-late Holocene (8–2 cal ka BP) relatively slow thawing trend, and a late Holocene freezing trend of permafrost in northern Asia are consistent with climatic proxies such as summer solar radiation and Northern Hemisphere temperature. The extensive distribution of permafrost in northern Asia inhibited the spread of evergreen coniferous trees during the early Holocene warming and might have decelerated the enhancement of the East Asian summer monsoon (EASM) by altering hydrological processes and albedo. Based on these findings, we suggest that studies of the EASM should consider more the state of permafrost and vegetation in northern Asia, which are often overlooked and may have a profound impact on climate change in this region.

Background: Maternal exposure to ambient fine particulate matters (PM2.5) is associated with low birth weight (LBW) in offspring, but the underlying biological mechanisms are not yet fully understood. As the bridge that connects mother and fetus, the placenta plays a crucial role in fetal development by providing the fetus with nutrients and oxygen. However, whether PM2.5 exposure would impact the placental development and the related mechanisms are unclear. Results: In the present study, female C57Bl/6j mice were exposed to filtered air (FA) or concentrated ambient PM2.5 (CAP) during pregestational and gestational periods, and the fetal development and placental structure were investigated. Our results showed that maternal exposure to CAP induced fetal growth restriction (FGR) and LBW. The placenta from CAP-exposed mice exhibited abnormal development including significant decrease of surface area, smaller junctional zone and impaired spiral artery remodeling. Meanwhile, CAP exposure altered trophoblast lineage differentiation and disrupted the balance between angiogenic and angiostatic factors in placenta. In addition, the inflammatory cytokines levels in lung, placenta and serum were significantly increased after ambient PM2.5 exposure. Conclusion: Our findings indicate that maternal exposure to PM2.5 disrupts normal structure and spiral artery remodeling of placenta and further induces FGR and LBW. This effect may be caused by the placental inflammation response subsequent to the pulmonary and systemic inflammation induced by ambient PM2.5 exposure.

Plant height and tillering are the key traits of tall fescue (Festuca arundinacea Schreb.), a perennial turf grass widely used for forage and turf worldwide. It exhibits excellent abiotic stress tolerance. However, the investigation of these traits at the genetic level is limited by the lack of a completely sequenced genome of tall fescue. Here, we generated genome-wide transcriptome data using PacBio isoform sequencing (Iso-Seq) technology. We obtained 73,628 transcripts with an average length of 2410 bp. Among these transcripts, 42,265 (60.09%) were predicted as complete full-length open reading frames. The dataset contained 11,520 simple sequence repeats; 737 bp long non-coding RNAs; and 1599 alternative splicing sites in unigenes. Sixty-three unigenes involved in abscisic acid biosynthesis, catabolism, and signaling pathways were identified. The Illumina-sequencing analysis results, further verified using qRT-PCR, revealed the significant upregulation of nine unigenes under drought stress. Ninety-three unigenes involved in controlling plant height and tillering were also identified, of which FaMAX1 was functionally verified to regulate plant tillering. Our results provide a valuable genetic resource about the complete transcriptome of tall fescue; the identified candidate genes can aid in improving the drought tolerance and agronomic traits in tall fescue and other related plants.

To predict the resonance frequency of the real liquefied natural gas (LNG) tank, a Cartesian grid based three-dimensional (3D) multiphase flow model is used to simulate violent sloshing in a prismatic tank at different filling levels and excitation frequencies. In this model, a semi-implicit finite difference method is adopted to solve the incompressible two-phase flow Navier-Stokes (N-S) equations on a staggered Cartesian grid. Besides, a radial basis function ghost cell method (RBFGCM) is used to treat the irregular tank walls and a 3D gradient-augmented level set (GALS) method is used to capture highly nonlinear free surfaces. Based on the present model, the violent sloshing induced by rolling excitations in the 3D prismatic tank is simulated. Satisfactory convergences of grid sizes and time steps demonstrate the high accuracy and reliability of the present method. Moreover, the present results of the impulsive pressure and wave elevation agree well with the experimental data for different filling water depths. In addition, violent sloshing phenomena are captured such as wave rolling. Furthermore, the relationship between the pressure amplitude on the tank wall and the excitation frequency at four filling levels are investigated to identify the resonance frequency of the prismatic tank, to provide theorical guides for structrual design of the tanks.