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Postmenopausal osteoporosis (PMOP) is a prevalent condition among elderly women. After menopause, women exhibit decreased iron excretion, which is prone to osteoporosis. To design a specific titanium implant for PMOP, we first analyze miRNAs and DNA characteristics of postmenopausal patients with and without osteoporosis. The results indicate that iron overload disrupts iron homeostasis in the pathogenesis of PMOP. Further experiments confirm that iron overload can cause lipid peroxidation and ferroptosis of MSCs, thus breaking bone homeostasis. Based on the findings above, we have designed a novel Ti implant coated with nanospheres of caffeic acid (CA) and deferoxamine (DFO). CA can bind on the Ti surface through the two adjacent phenolic hydroxyls and polymerize into polycaffeic acid (PCA) dimer, as well as the PCA nanospheres with the repetitive 1,4-benzodioxan units. DFO was grafted with PCA through borate ester bonds. The experimental results showed that modified Ti can inhibit the ferroptosis of MSCs in the pathological environment of PMOP and promote osseointegration in two main ways. Firstly, DFO was released under high oxidative stress, chelating with excess iron and decreasing the labile iron pool in MSCs. Meanwhile, CA and DFO activated the KEAP1/NRF2/HMOX1 pathway in MSCs and reduced the level of intracellular lipid peroxidation. So, the ferroptosis of MSCs is inhibited by promoting the SLC7A11/GSH/GPX4 pathway. Furthermore, the remained CA coating on the Ti surface could reduce the extracellular oxidative stress and glutathione level. This study offers a novel inspiration for the specific design of Ti implants in the treatment of PMOP.

The rheumatoid arthritis (RA) microenvironment is often followed by a vicious circle of high inflammation, endogenous gas levels imbalance, and poor treatment. To break the circle, we develop a dual-gas-mediated injectable hydrogel for modulating the immune microenvironment of RA and simultaneously releasing therapeutic drugs. The hydrogel (DNRS gel) could be broken down on-demand by consuming excessive nitric oxide (NO) and releasing therapeutic hydrogen sulfide (H2S), resulting in endogenous gas restoration, inflammation alleviation, and macrophage polarization to M2 type. Additionally, the hydrogel could suppress osteoclastogenesis and enhance osteogenesis. Furthermore, the intra-articularly injected hydrogel with methotrexate (MTX/DNRS gel) significantly alleviated inflammation and clinical symptoms and promoted the repair of bone erosion in the collagen-induced arthritis rat model. As a result, in vivo results demonstrated that MTX/DNRS gel restored the microenvironment and improved the therapeutic effect of MTX. This study provides a novel understanding of developing versatile smart delivery platforms for RA treatment.

Remnant cholesterol (RC) is highly regarded in the cardiovascular field; however, its relationship with new-onset diabetes remains unclear. This study aimed to investigate the relationship between RC and the risk of developing diabetes, as well as its interaction with low-density lipoprotein cholesterol (LDL-c). This was a secondary analysis of a retrospective cohort study based on a Chinese population. A multivariate Cox proportional hazards regression was initially employed to assess the relationship between RC and newly diagnosed diabetes. This was followed by a subgroup analysis to explore intergroup heterogeneity. A clinical prediction model was then developed. Finally, the study further analyzed the interactions between LDL-c and RC. After adjusting for confounding factors, RC was significantly associated with an increased risk of diabetes (HR = 1.46, 95% confidence interval [CI] 1.36–1.57). Furthermore, this relationship was nonlinear, with an inflection point of 0.48 identified through the piecewise model. Subgroup analysis indicated that the association was more pronounced in individuals under 60 years and those with a body mass index < 24 kg/m2 (P for interaction = 0.0004,

Abstract Background This study explores the intricate relationship between smoking, cardiovascular disease (CVD) risk factors and their combined impact on overall CVD risk, utilizing data from NHANES 2011–2018. Methods Participants were categorized based on the presence of CVD, and we compared their demographic, social, and clinical characteristics. We utilized logistic regression models, receiver operating characteristics (ROC) analysis, and the chi-squared test to examine the associations between variables and CVD risk. Results Significant differences in characteristics were observed between those with and without CVD. Serum cotinine levels exhibited a dose-dependent association with CVD risk. The highest quartile of cotinine levels corresponded to a 2.33-fold increase in risk. Smoking, especially in conjunction with lower HDL-c, significantly increases CVD risk. Combinations of smoking with hypertension, central obesity, diabetes, and elevated triglycerides also contributed to increased CVD risk. Waist-to-Height Ratio, Visceral Adiposity Index, A Body Shape Index, Conicity Index, Triglyceride-Glucose Index, Neutrophil, Mean platelet volume and Neutrophil to Lymphocyte ratio demonstrated significant associations with CVD risk, with varying levels of significance post-adjustment. When assessing the combined effect of smoking with multiple risk factors, a combination of smoking, central obesity, higher triglycerides, lower HDL-c, and hypertension presented the highest CVD risk, with an adjusted odds ratio of 14.18. Conclusion Smoking, when combined with central obesity, higher triglycerides, lower HDL-c, and hypertension, presented the highest CVD risk, with an adjusted odds ratio of 14.18.

Macrophages play a central role in immunological responses to metallic species associated with the localized corrosion of metallic implants, and mediating in peri-implant inflammations. Herein, the pathways of localized corrosion-macrophage interactions were systematically investigated on 316L stainless steel (SS) implant metals. Electrochemical monitoring under macrophage-mediated inflammatory conditions showed a decreased pitting corrosion resistance of 316L SSs in the presence of RAW264.7 cells as the cells would disrupt biomolecule adsorbed layer on the metal surface. The pitting potentials were furtherly decreased when the RAW264.7 cells were induced to the M1 pro-inflammatory phenotype by the addition of lipopolysaccharide (LPS), and pitting corrosion preferentially initiated at the peripheries of macrophages. The overproduction of aggressive ROS under inflammatory conditions would accelerate the localized corrosion of 316L SS around macrophages. Under pitting corrosion condition, the viability and pro-inflammatory polarization of RAW264.7 cells were region-dependent, lower viability and more remarkable morphology transformation of macrophages in the pitting corrosion region than the pitting-free region. The pitting corrosion of 316L SS induced high expression of CD86, TNF-α, IL-6 and high level of intracellular ROS in macrophages. Uneven release of metallic species (Fe2+, Cr3+, Ni2+, etc) and uneven distribution of surface overpotential stimulated macrophage inflammatory responses near the corrosion pits. A synergetic effect of localized corrosion and macrophages was revealed, which could furtherly promote localized corrosion of 316L SS and macrophage inflammatory reactions. Our results provided direct evidence of corrosion-macrophage interaction in metallic implants and disclosed the pathways of this mutual stimulation effect.

Crassulaceae plants are valued for their horticultural, ecological, and economic significance, but their genetic improvement is hindered by the absence of efficient and stable genetic transformation methods. Therefore, the development of a tailored genetic transformation method is crucial for enhancing the progress of the genetic improvement of Crassulaceae plants. The results indicate that, in the transformation experiments conducted on Kalanchoe tetraphylla, the K599 strain exhibited the highest transformation efficiency (76.67%), while C58C1 was least efficient (21.43%). An acetosyringone concentration of 100 μM was optimal for the hairy root transformation, and the immersion method yielded the highest efficiency. Additionally, the Silwet L-77 concentration significantly influenced the transformation efficiency, with 0.05% leading to a decrease. Upon four Crassulaceae species, notable differences were observed, with K. tetraphylla exhibiting the highest efficiency of 100%, and Sedum alfredii displaying the lowest efficiency of 5%. The RUBY reporter gene offers a more distinct advantage over GFP in observing the transformation effects. This study developed a simple, feasible, and cost-effective method for obtaining transgenic roots from leaves of Crassulaceae. The methodology provides technical support for the genetic improvement and gene function research of Crassulaceae plants.

Learning a deep model from small data is an opening and challenging problem. In high-dimensional spaces, few samples only occupy an extremely small portion of the space, often exhibiting sparsity issues. Classifying in this globally sparse sample space poses significant challenges. However, by using a single sample category as a reference object for comparing and recognizing other samples, it is possible to construct a local space. Conducting contrastive learning in this local space can overcome the sparsity issue of a few samples. Based on this insight, we proposed a novel deep learning approach named Local Contrast Learning (LCL). This is analogous to a key insight into human cognitive behavior, where humans identify the objects in a specific context by contrasting them with the objects in that context or from their memory. LCL is used to train a deep model that can contrast the recognized sample with a couple of contrastive samples that are randomly drawn and shuffled. On a one-shot classification task on Omniglot, the deep model-based LCL with 86 layers and 1.94 million parameters, which was trained on a tiny dataset with only 60 classes and 20 samples per class, achieved an accuracy of 98.95%. Furthermore, it achieved an accuracy of 99.24% at 156 classes and 20 samples per class. LCL is a fundamental idea that can be applied to alleviate the parametric model’s overfitting resulting from a lack of training samples.

Abstract B-cell acute lymphoblastic leukemia (B-ALL) is an aggressive hematological disorder with a dismal prognosis. The dysregulation of histone acetylation is of great significance in the pathogenesis and progression of B-ALL. Regarded as a fundamental acetyltransferase gene, the role of HBO1 (lysine acetyltransferase 7/KAT7) in B-ALL has not been investigated. Herein, we found that HBO1 expression was elevated in human B-ALL cells and associated with poor disease-free survival. Strikingly, HBO1 knockdown inhibited viability, proliferation, and G1-S cycle progression in B-ALL cells, while provoking apoptosis. In contrast, ectopic overexpression of HBO1 enhanced cell viability and proliferation but inhibited apoptotic activation. The results of in vivo experiments also certificated the inhibitory effect of HBO1 knockdown on tumor growth. Mechanistically, HBO1 acetylated histone H3K14, H4K8, and H4K12, followed by upregulating CTNNB1 expression, resulting in activation of the Wnt/β-catenin signaling pathway. Moreover, a novel small molecule inhibitor of HBO1, WM-3835, potently inhibited the progression of B-ALL. Our data identified HBO1 as an efficacious regulator of CTNNB1 with therapeutic potential in B-ALL.

Wheat tiller angle (TA) is an important agronomic trait that contributes to grain production by affecting plant architecture. It also plays a crucial role in high-yield wheat breeding. An association panel and a recombinant inbred line (RIL) population were used to map quantitative trait loci (QTL) for TA. Results showed that 470 significant SNPs with 10.4%–28.8% phenotypic variance explained (PVE) were detected in four replicates by a genome-wide association study (GWAS). Haplotype analysis showed that the TA_Hap_4B1 locus on chromosome 4B was a major QTL to regulate wheat TA. Ten QTL were totally detected by linkage mapping with the RIL population, and QTA.hau-4B.1 identified in six environments with the PVE of 7.88%–18.82% was a major and stable QTL. A combined analysis demonstrated that both TA_Hap_4B1 and QTA.hau-4B.1 were co-located on the same region. Moreover, QTA.hau-4B.1 was confirmed by bulked segregant RNA-Seq (BSR-Seq) analysis. Phenotypic analysis showed that QTA.hau-4B.1 was also closely related to yield traits. Furthermore, TraesCS4B02G049700 was considered as a candidate gene through analysis of gene sequence and expression. This study can be potentially used in cloning key genes modulating wheat tillering and provides valuable genetic resources for improvement of wheat plant architecture.

Fine particulate matter (PM2.5) concentration, a crucial indicator reflecting changes in air quality, has frequently been used in previous studies. However, the effects of large-scale ecological restoration (ER) projects on PM2.5 concentrations are often overlooked. Therefore, we used net primary productivity (NPP) as an indicator of ER engineering benefits, used ensemble empirical modal decomposition (EEMD) to reveal the trend of linear and nonlinear relationships of PM2.5 driven by different types and amounts of ER projects, and utilized the Extreme Gradient Boosting (XGBoost) and Shapley's Additive Interpretation (SHAP) values to quantify the impact of each factor on long-term PM2.5 concentrations. The results suggest that: (1) The nonlinear trend better describes the trend of PM2.5 change, with a shift from increasing to decreasing in areas covering 74.15% of China's area, especially in the four major ER zones; (2) PM2.5 concentration exhibits regional effects, L-L and H-H aggregation areas account for a larger proportion of the area, and are distributed in the areas with low and high PM2.5 concentrations, respectively. (3) The year 1990 marks a turning point for 36.8% of the regions. Across four ER regions emerge: a dramatic increase in PM2.5 concentration before ER implementation, followed by a slowing growth trend in the initial stages of the project, and ultimately a gradual decrease. (4) While the contribution of ER to the decrease of PM2.5 concentration is lower than the contribution of the growth caused by human activities and climate change, plant and newly plant areas are the main regions in which the ER project suppresses its growth. These findings highlight the influence of ER projects on PM2.5 concentration in addition to climate and human activities and provide a theoretical basis and scientific and technological support for quantifying the suppression of air pollution by ER projects.

Background. Endothelial barrier disruption of human pulmonary vascular endothelial cells (HPVECs) is an important pathogenic factor for acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Mesenchymal stem cells-exosome (MSCs-Exo) represents an ideal carrier for cell-free therapy. The therapeutic implication and underlying mechanism of human placental MSCs-Exo (HPMSCs-Exo) in ALI/ARDS need to be further explored. Materials and Methods. HPMSCs-Exo was extracted from HPMSCs and characterized. Then, the therapeutic effects of exosomes were evaluated in ALI mice and HPVECs. RNA-sequencing was applied to reveal the miRNA profile of HPMSCs-Exo and differentially expressed genes (DEGs) in HPMSCs-Exo-pretreated HPVECs. The targets of miRNAs were predicted by bioinformatics methods and correlated to DEGs. Finally, the role of hsa-miR-148a-3p/ROCK1 pathway in HPVECs has been further discussed. Results. The results showed that HPMSCs-Exo could downregulate Rho-associated coiled-coil-containing protein kinase 1 (ROCK1), upregulate the expression of zonula occludens-1 (ZO-1) and F-actin, promote HPVECs migration and tube formation, reduce cytoskeletal disorders and cell permeability, and thus improve ALI/ARDS. RNA-sequencing revealed the DEGs were mainly enriched in cell junction, angiogenesis, inflammation, and energy metabolism. HPMSCs-Exo contains multiple miRNAs which are associated with cytoskeletal function; the expression abundance of hsa-miR-148a-3p is the highest. Bioinformatic analysis identified ROCK1 as a target of hsa-miR-148a-3p. The overexpression of hsa-miR-148a-3p in HPMSCs-Exo promoted the migration and tube formation of HPVECs and reduced ROCK1 expression. However, the overexpression of ROCK1 on HPVECs reduced the therapeutic effect of HPMSCs-Exo. Conclusions. HPMSCs-Exo represents a protective regimen against endothelial barrier disruption of HPVECs in ALI/ARDS, and the hsa-miR-148a-3p/ROCK1 pathway plays an important role in this therapeutics implication.

AbstractObjective To investigate the efficacy and adverse effects of focused ultrasound (FU) in the treatment of high-grade squamous intraepithelial lesions (HSIL) and follow up on pregnancy outcomes in patients.Methods This retrospective study recruited 57 patients aged 20–40 years with cervical HSIL combined with HR-HPV infection who received FU treatment between September 2019 and April 2022. Clinical data of the patients were obtained from hospital records. HSIL cure rate and cumulative HR-HPV clearance rate were assessed after treatment. Patients were followed up on fertility and pregnancy outcomes after treatment by telephone interviews until April 1, 2023.Results During a 6-month follow-up, the HSIL cure rate was 73.7%, and a statistical difference between CIN2 and CIN3 (75.6% vs. 66.7%, p = 0.713) was not present. HSIL -recurrence was not observed during the follow-up period, and the median follow-up duration was 12 months. The cumulative HR-HPV clearance rates at the 6- and 12-month follow-ups were 56.1% and 75.4%, respectively. The median clearance time of HR-HPV was 6 (95% confidence interval, 5.46–6.54) months. The clearance rate was higher in HPV16/18 than in non-HPV16/18 (86.7% vs. 62.9%, p = 0.038). After treatment, the successful pregnancy rate in patients with fertility intentions and spontaneous abortion rate were 73.9% and 5.9%, respectively. Preterm birth, preterm premature rupture of membranes, or low-birth-weight infants were not observed.Conclusion FU treatment can regress HSIL and accelerate HR-HPV clearance in young women of childbearing age with cervical HSIL associated with HR-HPV infection, and has no significant adverse effects on pregnancy outcomes.

IntroductionThe coronavirus disease-2019 (COVID-19) pandemic has swept across the world and continues to exert serious adverse effects on vulnerable populations, including pregnant women and neonates. The vaccines available at present were designed to prevent infection from COVID-19 strains and control viral spread. Although the incidence of pregnancy cycle outcomes are not likely to increase patients vaccinated prior to pregnancy compared with unvaccinated patients based on our knowledge of vaccination safety, there is no specific evidence to support this hypothesis. Therefore, the current study aimed to investigate the association between maternal vaccination prior to conception and pregnancy outcomes.MethodsWe retrospectively analyzed 2,614 women who received prenatal care and delivered in the Obstetrical Department of The First Affiliated Hospital of Anhui Medical University between February 2022 and November 2022. Of the 1,380 eligible pregnant women, 899 women who had received preconception vaccination were assigned to a vaccine group and 481 women who were not vaccinated were control group. Of the enrolled patients, 291 women received fertility treatment (141 vaccinated women, 150 unvaccinated women). The primary outcomes were pregnancy complications (hypothyroidism, gestational diabetes mellitus, pregnancy-induced hypertension, polyhydramnios, oligohydramnios, premature rupture of membranes and postpartum hemorrhage), obstetric outcomes (preterm birth rate, cesarean section rate) and neonatal outcomes (birth-weight, body length, low-birth-weight rate, rate of congenital defects, neonatal mortality and admission to the neonatal intensive care unit).ResultsThere was no significant difference in the incidence of complications during pregnancy and delivery when compared between the vaccine group and control group in either univariate- or multivariate-models. The type of vaccine was not associated with the odds of adverse pregnancy outcome. Among the women with infertility treatment, the vaccinated group and the unvaccinated group had similar pregnancy outcomes.ConclusionWomen who received COVID-19 vaccination prior to conception had similar maternal and neonatal outcomes as women who were unvaccinated. Our findings indicate that COVID-19 vaccinations can be safely administered prior to pregnancy in women who are planning pregnancy or assisted reproductive treatment. During new waves of COVID-19 infection, women who are planning pregnancy should be vaccinated as soon as possible to avoid subsequent infections.

Abstract Background Ovarian hyperstimulation syndrome (OHSS) is a rare but serious complication of controlled ovarian stimulation. Frozen-embryo transfer (ET) is prompted to be performed in the next menstrual cycles after cancellation of fresh-ET after occurrence of OHSS. However, effects of frozen-ET in the second menstrual cycle have never been investigated. Therefore, this study aimed to assess this in the menstrual cycle after OHSS. Methods The OHSS group included 342 women with moderate-severe OHSS who underwent the first frozen-ET in the second menstrual cycle in the First Affiliated Hospital of Anhui Medical University from June 2018 to September 2019. A total of 342 women without OHSS who received frozen-ET in the second menstrual cycle were selected as control group matched by age, body mass index, fertility history, ovulation induction scheme. Uni- and multi-variable conditional logistic regression was used to estimate the association between moderate-severe OHSS and pregnancy outcomes. Results There were no significant differences in maternal outcomes (miscarriage, preterm birth and pregnancy complications including gestational diabetes mellitus, pregnancy-induced hypertension, placenta previa, premature rupture of membranes and postpartum hemorrhage) and in neonatal outcome (birth-weight and body length, neonatal congenital diseases and other complications) between the two groups in either uni- or multi-variable models. Conclusions Frozen-ET in the menstrual cycle after OHSS has similar maternal and neonatal outcomes as in women without OHSS. This study indicates that frozen-ET could be performed in the second menstrual cycle in women who recovered from moderate-severe OHSS.

Insufficient osseointegration and biofilm-associated bacterial infection are important challenges for clinical application of titanium (Ti)-based implants. Here, we constructed mesoporous polydopamine (MPDA) nanoparticles (NPs) loaded with luteolin (LUT, a quorum sensing inhibitor), which were further coated with the shell of calcium phosphate (CaP) to construct MPDA-LUT@CaP nanosystem. Then, MPDA-LUT@CaP NPs were immobilized on the surface of Ti implants. Under acidic environment of bacterial biofilm-infection, the CaP shell of MPDA-LUT@CaP NPs was rapidly degraded and released LUT, Ca2+ and PO43− from the surface of Ti implant. LUT could effectively inhibit and disperse biofilm. Furthermore, under near-infrared irradiation (NIR), the thermotherapy induced by the photothermal conversion effect of MPDA destroyed the integrity of the bacterial membrane, and synergistically led to protein leakage and a decrease in ATP levels. Combined with photothermal therapy (PTT) and quorum-sensing-inhibition strategy, the surface-functionalized Ti substrate had an antibacterial rate of over 95.59% against Staphylococcus aureus and the elimination rate of the formed biofilm was as high as 90.3%, so as to achieve low temperature and efficient treatment of bacterial biofilm infection. More importantly, the modified Ti implant accelerated the growth of cell and the healing process of bone tissue due to the released Ca2+ and PO43−. In summary, this work combined PTT with quorum-sensing-inhibition strategy provides a new idea for surface functionalization of implant for achieving effective antibacterial and osseointegration capabilities.

Background and aimsCardiovascular disease and osteoporosis are common diseases in older adults with high morbidity. The study on the interaction between the two in pathogenic mechanisms has been paid much attention by the majority of researchers. This study aimed to explore the relationship between bone mineral density and cardiovascular disease in older adults.MethodsThe primary data was downloaded from the National Health and Nutrition Examination Survey database of the United States. Multivariate logistic regression model, generalized additive model, and smooth curve fitting were used to explore the relationship between bone mineral density and cardiovascular events risk. When a curve relationship was found, a two-piecewise linear model was used to calculate the inflection point. In addition, subgroup analysis was also performed.ResultsA total of 2097 subjects were included in this study. After adjusting for potential confounders, no significant association was found between lumbar bone mineral density and cardiovascular disease, while femur bone mineral density had a non-linear relationship with cardiovascular disease, with an inflection point of 0.741 gm/cm2. When bone mineral density was 0.05) except race.ConclusionOur results indicated that bone mineral density was closely associated with the prevalence of cardiovascular disease in older adults over 60 years old, especially the femur bone mineral density was negatively non-linear associated with cardiovascular disease risk, with an inflection point of 0.741 gm/cm2.

Colchicine (COL), a widely used natural drug, has potent anti-inflammatory effects; however, as a narrow therapeutic index drug, its clinical application is limited by its serious gastrointestinal adverse effects, and only oral formulations are currently marketed worldwide. Recent studies have shown that transdermal, injection, and oral drug delivery are the three main delivery strategies for COL. This article elaborates on the research progress of different delivery strategies in terms of toxicity reduction and efficacy enhancement, depicting that the transdermal drug delivery route can avoid the first-pass effect and the traumatic pain associated with the oral and injection routes, respectively. Therefore, such a dosage form holds a significant promise that requires the development of further research to investigate effective COL delivery formulations. In addition, the permeation-promoting technologies utilized for transdermal drug delivery systems are briefly discussed. This article is expected to provide scientific ideas and theoretical guidance for future research and the exploration of COL delivery strategies.

Beyond traditional endothelium-dependent vessel (EDV), vascular mimicry (VM) is another critical tumor angiogenesis that further forms in many malignant metastatic tumors. However, the existing anti-angiogenesis combined chemotherapeutics strategies are only efficient for the treatment of EDV-based subcutaneous tumors, but remain a great challenge for the treatment of in situ malignant metastatic tumor associated with EDV and VM. Here, we demonstrate a self-assembled nanoparticle (VE-DDP-Pro) featuring self-anti-EDV and -VM capacity enables to significantly enhance the treatment efficacy of cisplatin (DDP) against the growth and metastasis of ovarian cancer. The VE-DDP-Pro is constructed by patching DDP loaded cRGD-folate-heparin nanoparticles (VE) onto the surface of protamine (Pro) nanoparticle. We demonstrated the self-anti-angiogenesis capacity of VE-DDP-Pro was attributed to VE, which could significantly inhibit the formation of EDV and VM by regulating signaling pathway of MMP-2/VEGF, AKT/mTOR/MMP-2/Laminin and AKT/mTOR/EMT, facilitating chemotherapeutics to effectively suppress the development and metastasis of ovarian cancer. Thus, combing with the chemotherapeutics effectiveness of DDP, the VE-DDP-Pro can significantly enhance treatment efficacy and prolong median survival of mice with metastatic ovarian cancer. We believe our self-assembled nanoparticles integrating the anti-EDV and anti-VM capacity provide a new preclinical sight to enhance the efficacy of chemotherapeutics for the treatment malignant metastasis tumor.

Abstract Existing color editing algorithms enable users to edit the colors in an image according to their own aesthetics. Unlike artists who have an accurate grasp of color, ordinary users are inexperienced in color selection and matching, and allowing non-professional users to edit colors arbitrarily may lead to unrealistic editing results. To address this issue, we introduce a palette-based approach for realistic object-level image recoloring. Our data-driven approach consists of an offline learning part that learns the color distributions for different objects in the real world, and an online recoloring part that first recognizes the object category, and then recommends appropriate realistic candidate colors learned in the offline step for that category. We also provide an intuitive user interface for efficient color manipulation. After color selection, image matting is performed to ensure smoothness of the object boundary. Comprehensive evaluation on various color editing examples demonstrates that our approach outperforms existing state-of-the-art color editing algorithms.

IntroductionNitrogen (N) is essential for plant growth and yield production and can be taken up from soil in the form of nitrate or peptides. The NITRATE TRANSPORTER 1/PEPTIDE TRANSPORTER family (NPF) genes play important roles in the uptake and transportation of these two forms of N.MethodsBioinformatic analysis was used to identify and characterize the NPF genes in Setaria. RNA-seq was employed to analyze time-series low nitrate stress response of the SiNPF genes. Yeast and Arabidopsis mutant complementation were used to test the nitrate transport ability of SiNRT1.1B1 and SiNRT1.1B2.ResultsWe identified 92 and 88 putative NPF genes from foxtail millet (Setaria italica L.) and its wild ancestor green foxtail (Setaria viridis L.), respectively. These NPF genes were divided into eight groups according to their sequence characteristics and phylogenetic relationship, with similar intron-exon structure and motifs in the same subfamily. Twenty-six tandem duplication and 13 segmental duplication events promoted the expansion of SiNPF gene family. Interestingly, we found that the tandem duplication of the SiNRT1.1B gene might contribute to low nitrogen tolerance of foxtail millet. The gene expression atlas showed that the SiNPFs were divided into two major clusters, which were mainly expressed in root and the above ground tissues, respectively. Time series transcriptomic analysis further revealed the response of these SiNPF genes to short- and long- time low nitrate stress. To provide natural variation of gene information, we carried out a haplotype analysis of these SiNPFs and identified 2,924 SNPs and 400 InDels based on the re-sequence data of 398 foxtail millet accessions. We also predicted the three-dimensional structure of the 92 SiNPFs and found that the conserved proline 492 residues were not in the substrate binding pocket. The interactions of SiNPF proteins with NO3− were analyzed using molecular docking and the pockets were then identified. We found that the SiNPFs NO3− binding energy ranged from-3.4 to -2.1 kcal/mol.DiscussionTaken together, our study provides a comprehensive understanding of the NPF gene family in Setaria and will contribute to function dissection of these genes for crop breeding aimed at improving high nitrogen use efficiency.

Abstract Background Health-related risky behaviors (HRB) generally refer to behaviors that have a negative influence on health and quality of life. HRB in adolescents with autism have not been well understood so far. We aim to explore health-related risky behaviors and their risk factors with autistic adolescents. Methods In this study, 150 adolescents with autism and 150 neurotypical adolescents were enrolled. Participants in both groups completed the Adolescent Health-Related Risky Behavior Inventory (AHRBI). Autism Spectrum Screening Questionnaire (ASSQ), Wechsler Intelligence Scale, Theory of Mind (ToM) Test, Zung Self-rating Anxiety Scale (SAS), Zung Self-rating Depression Scale (SDS), and Self-Esteem Scale (SES) were also assessed in the autism group to explore risk factors. Results The results showed that the total score of AHRBI and scores of "aggression and violence (AV)", "suicide or self-injury (SS)", "health-compromising behavior (HCB)", and "unprotected sex (US)" subscales in the autism group were significantly higher than those in the control group (Z value = − 4.58 ~ − 2.26, all P

ObjectiveThis paper studied the Epstein–Barr virus (EBV) infection status and influencing factors among children using a combined detection of specific antibodies and DNA.MethodsWe retrospectively analyzed children who visited the Affiliated Hospital of Hangzhou Normal University from January 2019 to December 2020, and correlations between the social environment and clinical data were analyzed.ResultsThe cumulative positive rates of specific antibody, DNA, and combined detection of EBV were 52.4%, 39.5%, and 54.0% (P = 0.001), respectively. The current infection rate was 15.7%, and the peak of infection occurred in the preschool group (P = 0.021). After adjusting for confounding factors, the number of siblings (OR = 1.550) and family members who smoke (OR = 1.524) were independent risk factors for EBV infection, whereas parents with a higher education level (OR = 0.493, OR = 0.316), longer breastfeeding time (OR = 0.578) and dedicated tableware (OR = 0.573) were independent protective factors.ConclusionA combination of antibody and DNA tests may be beneficial for the diagnosis of EBV infection. The EBV infection rate in children at our hospital was lower than the national average. Furthermore, the infection rate is closely related to the number of siblings, regardless of whether family members smoke, the status of parents' education, breastfeeding duration, and meal patterns. Overall, prevention measures should focus on the preschoolers.

Abstract Multidrug resistance remains a great challenge for cancer chemotherapy. Herein, a biomimetic drug delivery system based on lemon‐derived extracellular vesicles (EVs) nanodrugs (marked with heparin‐cRGD‐EVs‐doxorubicin (HRED)) is demonstrated, achieving highly efficient overcoming cancer multidrug resistance. The HRED is fabricated by modifying functional heparin‐cRGD (HR) onto the surface of EVs and then by loading with doxorubicin (DOX). The obtained HRED enable to effectively enter DOX‐resistant cancer cells by caveolin‐mediated endocytosis (main), macropinocytosis (secondary), and clathrin‐mediated endocytosis (last), exhibiting excellent cellular uptake capacity. The diversified endocytosis capacity of HRED can efficiently dissipate intracellular energy and meanwhile trigger downstream production reduction of adenosine triphosphate (ATP), leading to a significant reduction of drug efflux. Consequently, they show excellent anti‐proliferation capacities to DOX‐resistant ovarian cancer, ensuring the efficiently overcoming ovarian cancer multidrug resistance in vivo. The authors believe this strategy provides a new strategy by endocytosis triggered‐energy dissipation and ATP production reduction to design drug delivery system for overcoming cancer multidrug resistance.

Lithium batteries are currently the most popular and promising energy storage system, but the current lithium battery technology can no longer meet people's demand for high energy density devices. Increasing the charge cutoff voltage of a lithium battery can greatly increase its energy density. However, as the voltage increases, a series of unfavorable factors emerges in the system, causing the rapid failure of lithium batteries. To overcome these problems and extend the life of high‐voltage lithium batteries, electrolyte modification strategies have been widely adopted. Under this content, this review first introduces the degradation mechanism of lithium batteries under high cutoff voltage, and then presents an overview of the recent progress in the modification of high‐voltage lithium batteries using electrolyte modification strategies. Finally, the future direction of high‐voltage lithium battery electrolytes is also proposed.

Recurrent spontaneous abortion (RSA) is a common complication of pregnancy that affects the physical and mental health of pregnant women, and approximately 50% of the mechanisms are unclear. Our previous studies have found that high mobility group box 1 (HMGB1) molecules are highly expressed at the maternal-fetal interface of unexplained recurrent spontaneous abortion (URSA) patients. The purpose of this study was to further detect the expression of HMGB1 and pyroptosis in decidual tissue of URSA patients, and explore the potential mechanism of the protective role of HMGB1 in URSA patients and mouse model. The decidua tissues of 75 URSA patients and 75 women who actively terminated pregnancy were collected, and URSA mouse models were established and treated with HMGB1 inhibitor-aspirin. The expression of HMGB1, and their receptors (RAGE, TLR2, TLR4), pyroptosis-associated proteins (NLRP-3, caspase-1, GSDMD) and NF-κB was examined at the maternal-fetal interface of human and mouse. Our study found that HMGB1, NLRP-3, Caspase-1, GSDMD, RAGE, TLR2 and TLR4 were highly expressed and NF-κB signaling pathway were activated in the decidua tissue of URSA group. Moreover, immune cell disorder and co-localization of HMGB1 and macrophages were found at the maternal-fetal interface of URSA mice. However, HMGB1, TLR2, TLR4, NF-κB, and pyroptosis-associated proteins can be down-regulated by administering low-dose aspirin. These data may indicate that highly expressed HMGB1 was actively secreted by macrophages and then activated pyroptosis through the TLR2/TLR4-NF-κB pathway to cause aseptic inflammation, leading to the occurrence and development of URSA. Moreover, low-dose aspirin can reduce HMGB1 protein levels of serum and decidual in URSA.

Poaceae practically dominate staple crops for humans. In addition to the issue of sustenance, there is a growing interest in the secondary metabolites of these staple crops and their functions on health. In this study, metabolomic variations were investigated among six important species of Poaceae with a total of 17 cultivars, including wheat, maize, rice, sorghum, foxtail millet, and broomcorn millet. A total of 201 flavonoid metabolites and 29 carotenoid metabolites were identified based on the UPLC-ESI-MS/MS system. Among them, 114, 128, 101, 179, 113, and 92 flavonoids and 12, 22, 17, 15, 21, and 18 carotenoids were found in wheat, maize, rice, sorghum, foxtail millet, and broomcorn millet, respectively. Only 46 flavonoids and 8 carotenoids were shared by the six crops. Crop-specific flavonoids and carotenoids were identified. Flavone, anthocyanins, flavanone and polyphenol were the major metabolite differences, which showed species specificity. The flavonoid content of the grains from 17J1344 (sorghum), QZH and NMB (foxtail millet) and carotenoids from Mo17 (maize) were higher than the other samples. This study provides a better knowledge of the differences in flavonoid and carotenoid metabolites among Poaceae crops, as well as provides a theoretical basis for the identification of functional metabolites in these grains.

Background: The Aberrant Behavior Checklist (ABC) is a widely used scale in autism clinical intervention research for the assessment of core symptoms and comorbid emotional and behavioral problems among people with autism. The aim of this study was to examine the psychometric properties of the Simplified Chinese version of the Aberrant Behavior Checklist (SC-ABC) using a sample of people with autism in a Chinese population.Methods: In total, we enrolled 799 patients aged 1.5–33 years old. We collected data using the SC-ABC (n = 799), Autism Behavior Checklist (n = 743), Attention Deficit Hyperactivity Disorder Rating Scale-IV (ADHD-RS-IV) (n = 433) and Achenbach Child Behavior Checklist (CBCL) (n = 319). Eighty-four patients were separately assessed with the SC-ABC by two caregivers simultaneously. Forty-four patients were assessed with the SC-ABC again by same caregiver 2 weeks after the first assessment. SC-ABC data from the whole sample were used for confirmatory factor analysis. We evaluated criterion validity using Spearman's correlation coefficient between scores of the SC-ABC and scores of the Autism Behavior Checklist, ADHD-RS-IV and CBCL separately in the whole sample and different age groups. We calculated the intragroup correlation coefficients and Spearman's correlation coefficient for interrater reliability in 84 samples and test-retest reliability in 44 samples. We conducted Cronbach's α for internal consistency.Results: For the SC-ABC, the intragroup correlation coefficients of five subscales and the total score in interrater and test-retest reliability ranged from 0.87 to 0.92 and from 0.93 to 0.97 (all P < 0.01). The Spearman's correlation coefficient of five subscales and the total score in interrater and test-retest reliability ranged from 0.78 to 0.85 and 0.86 to 0.94, respectively (all P < 0.01). Cronbach's α of five subscales and the total score ranged from 0.75 to 0.96 (all P < 0.01). The Spearman's correlation coefficient for criterion validity for the whole sample and different age groups ranged from 0.39 to 0.76 (all P < 0.01). The model fit for the original five factor model was acceptable, with fit indices of SMR = 0.062 and RMSEA = 0.052.Conclusions: The SC-ABC has satisfactory psychometric properties and can be used in the assessment of core symptoms and comorbid emotional and behavioral problems in patients with autism.

Foxtail millet (Setaria italica) is an important minor cereal crop in China. The yellow color of the de-husked grain is the most direct aspect for evaluating the foxtail millet quality. The yellow pigment mainly includes carotenoids (lutein and zeaxanthin) and flavonoids. To reveal the diversity and specificity of flavonoids in foxtail millet, we chose three high eating quality and two poor eating quality varieties as research materials. A total of 116 flavonoid metabolites were identified based on Ultra Performance Liquid Chromatography-Electrospray Ionization-Tandem Mass Spectrometry (UPLC-ESI-MS/MS) system. The tested varieties contained similar levels of flavonoid metabolites, but with each variety accumulating its unique flavonoid metabolites. A total of 33 flavonoid metabolites were identified as significantly discrepant between high eating quality and poor eating quality varieties, which were mainly in the flavonoid biosynthesis pathway and one of its branches, the flavone and flavonol biosynthesis pathway. These results showed the diversified components of flavonoids accumulated in foxtail millets and laid the foundation for further research on flavonoids and the breeding for high-quality foxtail millet varieties.

Respiratory syncytial virus (RSV) is the major cause of pulmonary and bronchial inflammation in infants, young children, and immunocompromised adults, but therapeutic options to control RSV are limited. In the present study a single chain antibody against RSV (GD-scFv) was screened using phage display library panning technology and a full-length monoclonal antibody (GD-mAb) was developed from GD-scFv based on the sequence encoding Ig VH and Ig VL. The anti-RSV potential of GD-mAb was evaluated in vitro and in mice. Our results indicated that both GD-scFv (4.25 ± 2 nM) and GD-mAb (3.13 ± 0.89 nM) showed high binding capability and strong binding specificity to GD protein. GD-mAb effectively neutralized RSV and reduced the plaque number in a concentration-dependent manner through a plaque reduction neutralization assay. In mice, GD-mAb lowered the lung index and reduced the lung virus titer in the mouse lung (p < 0.05). Antibody treatment reduced the phosphorylated protein level in pathways of TLR4/NF-κB, MAPKs, and PI3K/Akt (p < 0.05) and correlated with an absence of pro-inflammatory factors TNF-α, IL-1β, and IL-6 in the mouse lung and serum (p < 0.05). In summary, these data suggest that GD-mAb may be an effective therapeutic agent for the treatment of RSV infections.Importance Currently, only a few therapeutic options are available to control respiratory RSV in humans. In this study, our group developed a full-length monoclonal antibody (GD-mAb) and reported a high binding specificity of the RSV surface glycoproteins G. Moreover, GD-mAb effectively neutralized RSV in vitro, and significantly lowered the lung index and reduced the lung virus titer in an infected mouse lung, which suggests that GD-mAb may serve as an effective antiviral agent for RSV infection.

Given the increasing prevalence of antibiotic resistance among bacterial strains and the side effects caused by synthetic drugs, it is increasingly important to investigate potential herbal alternatives. In the present study, antimicrobial, cell cytotoxicity, and cleaning tests were performed to evaluate the potential of Fufang Bingpeng irrigant as a root canal irrigant, in addition to q-PCR and high-throughput sequencing analyses. Our in vitro results showed a low minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of Fufang Bingpeng irrigant against Porphyromonas gingivalis ATCC 33277 (6.25 and 12.5%, respectively), Prevotella intermedius ATCC 25611 (6.25 and 6.25%, respectively), Fusobacterium nucleatum ATCC 25286 (6.25 and 6.25%, respectively), Enterococcus faecalis ATCC 19433 (25 and 25%, respectively), and Bacteriodes fragilis ATCC 25285 (12.5 and 12.5%, respectively). Furthermore, it effectively removed the remaining debris and increased the number of open dentinal tubules in root canals compared to the NaCl irrigant (p < 0.05). Fufang Bingpeng irrigant also presented low cytotoxicity to L929 cells compared to the NaClO irrigant. The in vivo results indicated that all irrigants used significantly reduced the number of bacteria compared to the number prior to treatment, and only 1/104.95 bacteria remained in the root canal following the use of Fufang Bingpeng irrigant (p < 0.001). Moreover, the high-throughput sequencing results indicated that all irrigants markedly enhanced the α diversity in the root canal compared to the before preparation control group, while Fufang Bingpeng maintained better microbial diversity than other groups. Therefore, Fufang Bingpeng irrigant presents a promising alternative for use as a root canal irrigant in clinical settings.

As one of the core contents of intelligent monitoring, target tracking is the basis for video content analysis and processing. In visual tracking, due to occlusion, illumination changes, and pose and scale variation, handling such large appearance changes of the target object and the background over time remains the main challenge for robust target tracking. In this paper, we present a new robust algorithm (STC-KF) based on the spatio-temporal context and Kalman filtering. Our approach introduces a novel formulation to address the context information, which adopts the entire local information around the target, thereby preventing the remaining important context information related to the target from being lost by only using the rare key point information. The state of the object in the tracking process can be determined by the Euclidean distance of the image intensity in two consecutive frames. Then, the prediction value of the Kalman filter can be updated as the Kalman observation to the object position and marked on the next frame. The performance of the proposed STC-KF algorithm is evaluated and compared with the original STC algorithm. The experimental results using benchmark sequences imply that the proposed method outperforms the original STC algorithm under the conditions of heavy occlusion and large appearance changes.