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Abstract Background Babesia duncani is a pathogen within the phylum Apicomplexa that causes human babesiosis. It poses a significant threat to public health, as it can be transmitted not only through tick bites but also via blood transfusion. Consequently, an understanding of the gene functions of this pathogen is necessary for the development of drugs and vaccines. However, the absence of conditional gene knockdown tools has hindered the research on this pathogen. The auxin-inducible degron (AID) system is a rapid, reversible conditional knockdown system widely used in gene function studies. Thus, there is an urgent need to establish the AID system in B. duncani to study essential gene functions. Methods The endogenous genes of the Skp1-Cullin-F-box (SCF) complex in B. duncani were identified and confirmed through multiple sequence alignment and conserved domain analysis. The expression of the F-box protein TIR1 from Oryza sativa (OsTIR1) was achieved by constructing a transgenic parasite strain using a homologous recombination strategy. Polymerase chain reaction (PCR), western blot, and indirect immunofluorescence assay (IFA) were used to confirm the correct monoclonal parasite strain. The degradation of enhanced green fluorescent protein (eGFP) tagged with an AID degron was detected through western blot and live-cell fluorescence microscopy after treatment of indole-3-acetic acid (IAA). Results In this study, Skp1, Cul1, and Rbx1 of the SCF complex in B. duncani were identified through sequence alignment and domain analysis. A pure BdTIR1 strain with expression of the OsTIR1 gene was constructed through homologous recombination and confirmed. This strain showed no significant differences from the wild type (WT) in terms of growth rate and proportions of different parasite forms. The eGFP tagged with an AID degron was successfully induced for degradation using 500 μM IAA. Grayscale analysis of western blot indicated a 61.3% reduction in eGFP expression levels, while fluorescence intensity analysis showed a 77.5% decrease in fluorescence intensity. Increasing the IAA concentration to 2 mM accelerated eGFP degradation and enhanced the extent of degradation. Conclusions This study demonstrated the functionality of the AID system in regulating protein levels by inducing rapid degradation of eGFP using IAA, providing an important research tool for studying essential gene functions related to invasion, egress, and virulence of B. duncani. Moreover, it also offers a construction strategy for apicomplexan parasites that have not developed an AID system. Graphical Abstract

Abstract This study aimed to investigate the effect and potential mechanism of evodiamine (EVO) on proliferation and apoptosis of nasopharyngeal carcinoma (NPC) cells. EVO inhibited proliferation, blocked cell cycle progression, and induced apoptosis of NPC cells. There are 27 known anti-NPC targets of EVO, of which eight are core targets, namely SRC, ERBB2, STAT3, MAPK8, NOS3, CXCL8, APP, and HDAC1. Molecular docking analysis showed that the binding of EVO with its key targets (SRC, ERBB2) was good. EVO also reduced the expression of SRC and ERBB2, the key proteins p-MEK and p-ERK1/2 of the MAPK/ERK signaling pathway, and the downstream proteins PCNA and XIAP. EVO inhibited the growth of NPC xenografts in nude mice and reduced the expression levels of SRC, ERBB2, ERK1/2, p-ERK1/2, PCNA and XIAP in NPC tissue. When the MAPK/ERK signaling pathway was activated by epidermal growth factor (EGF), the expression levels of PCNA and XIAP increased, the cell proliferation index increased, and the apoptosis rate decreased in the EGF + EVO treatment group compared to treatment with EVO alone. These changes indicated that the inhibitory effect of EVO on proliferation and apoptosis of NPC cells was related to the down-regulation of SRC and ERBB2 expression, and further inhibition of the MAPK/ERK signaling pathway.

This study aims at developing a dataset for determining the presence of carotid artery plaques in ultrasound images, composed of 1761 ultrasound images from 1165 participants. A deep learning architecture that combines bilinear convolutional neural networks with residual neural networks, known as the single-input BCNN-ResNet model, was utilized to aid clinical doctors in diagnosing plaques using carotid ultrasound images. Following training, internal validation, and external validation, the model yielded an ROC AUC of 0.99 (95% confidence interval: 0.91 to 0.84) in internal validation and 0.95 (95% confidence interval: 0.96 to 0.94) in external validation, surpassing the ResNet-34 network model, which achieved an AUC of 0.98 (95% confidence interval: 0.99 to 0.95) in internal validation and 0.94 (95% confidence interval: 0.95 to 0.92) in external validation. Consequently, the single-input BCNN-ResNet network model has shown remarkable diagnostic capabilities and offers an innovative solution for the automatic detection of carotid artery plaques.

Abstract Breast cancer (BC) significantly contributes to cancer-related mortality in women, underscoring the criticality of early detection for optimal patient outcomes. Mammography is a key tool for identifying and diagnosing breast abnormalities; however, accurately distinguishing malignant mass lesions remains challenging. To address this issue, we propose a novel deep learning approach for BC screening utilizing mammography images. Our proposed model comprises three distinct stages: data collection from established benchmark sources, image segmentation employing an Atrous Convolution-based Attentive and Adaptive Trans-Res-UNet (ACA-ATRUNet) architecture, and BC identification via an Atrous Convolution-based Attentive and Adaptive Multi-scale DenseNet (ACA-AMDN) model. The hyperparameters within the ACA-ATRUNet and ACA-AMDN models are optimized using the Modified Mussel Length-based Eurasian Oystercatcher Optimization (MML-EOO) algorithm. The performance is evaluated using a variety of metrics, and a comparative analysis against conventional methods is presented. Our experimental results reveal that the proposed BC detection framework attains superior precision rates in early disease detection, demonstrating its potential to enhance mammography-based screening methodologies.

Abstract Objective To investigate the distribution and activation of B-cell subpopulations in rheumatoid arthritis (RA) patients treated with Janus kinase inhibitors (JAKis) and to analyze their correlation with disease remission. Methods Peripheral blood samples were collected from 23 adult healthy controls and 58 RA patients, 31 of whom were treated with JAKis and assessed during a 24-month follow-up. The number of peripheral B-cell subpopulations (including naive B cells, nonswitched memory B (NSMB) cells, switched memory B cells, and double-negative B cells), their activation, and phosphorylation of SYK and AKT upon B-cell receptor (BCR) stimulation in each population were analyzed by flow cytometry. Results Compared with that in healthy controls, the frequency of NSMB cells was significantly lower in new-onset untreated RA patients. However, expression of CD40, CD80, CD95, CD21low and pAKT significantly increased in these NSMB cells. Additionally, the number of NSMB cells correlated negatively with DAS28-ESR and IgG and IgA levels in these patients; expression of CD80, CD95 and CD21low on NSMB cells correlated positively with DAS28-ESR and IgG and IgA levels. After treatment with JAKis, the serum IgG concentration significantly decreased in RA patients in remission, but CD40, CD95 and pAKT levels in NSMB cells significantly decreased. Conclusion RA patients present different B-cell subpopulations, in which the frequency of NSMB cells is negatively associated with disease activity. However, treatment with JAKis can inhibit activation of NSMB cells, restore the balance of kinase phosphorylation, and facilitate disease remission in RA patients.

Excess weight gain is a growing concern worldwide, fueled by increased consumption of calorie-dense foods and more sedentary lifestyles. Obesity in China is also becoming increasingly problematic, developing into a major public health concern. Obesity not only increases the risk of associated disease but also imposes a burden on health care systems, and it is thus imperative that an effective intervention approach be identified. Recent studies have demonstrated that the polyphenol-rich Mediterranean diet has considerable potential in this regard. Polyphenols can inhibit the production of adipocytes and reduce adverse reactions, such as inflammation, insulin resistance, and gut microflora imbalance. In this review, we examine four polyphenols (curcumin, ellagic acid, ferulic acid, and quercetin) in terms of their potential as interventions targeting obesity. The mechanisms that help promote adipocyte browning, increase thermogenic factors, increase thermogenesis, and regulate adipocyte differentiation are summarized, and key signaling pathways, including PPARγ, C/EBP-, and others, are reviewed.

T follicular helper cells (Tfh) were initially identified nearly two decades ago as critically important in directing B-cell maturation and antibody generation in the germinal centers of secondary lymphoid tissues. Since then, Tfh cells have become the center of sustained investigation in oncology due to their unique, often paradoxical roles in tumour immunity. Specifically, Tfh cells in the tumour microenvironment can enhance anti-tumour immune response or promote, through the same mechanisms, tumour progression. These dual roles largely result from Tfh cells controlling unique cytokine secretions and, in turn, shifting the net effect of the Tfh-driven immune response (by directly and indirectly affecting the activities of other cytotoxic T cells and natural killer cells). The dual nature of the Tfh is the basis for our commentary, which highlights their simultaneous identity as a curse and a gift to oncology. Indeed, the curtain calls for a better understanding Tfh cell biology, so that their potential can be used to benefit oncology. We discuss how prevalent Tfh cells in tumors can be beneficial in directing potent anti-tumour immune responses. We also review how the characterization of Tfh cells in tumors has now led to their identification as candidate biomarkers of response to immunotherapy, and how they are now being evaluated as targets for new immunotherapies leading to new clinical trials. The study concludes by emphasizing how the unique biological properties of Tfh cells can be leveraged to advance cancer treatment, ultimately aiming to enhance the effectiveness of clinical oncology practices.

BackgroundThe association between Estradiol (E2) levels and abdominal aortic calcification (AAC) in postmenopausal women remains unclear.Methods614 postmenopausal women from the 2013-2014 NHANES survey cycle were included in this study. The study population was divided into 3 groups according to E2 tertiles: Tertile1 (2.12-3.57pg/mL), Tertile2 (3.60-7.04pg/mL), and Tertile3 (7.06-38.4pg/mL). Estrogen concentration data were natural logarithmically transformed. A Kauppila score > 5 was regarded as prominent arterial calcification and was used to define (EAAC). Logistic regression models were used to assess the association between E2 levels and EAAC prevalence. Subgroup analyses were performed to test whether the association between E2 levels and EAAC prevalence was consistent in different groups. Sensitivity analyses tested the stability of the model in women older than 45 years.ResultsEAAC prevalence was significantly higher in Tertile1 (16.6%) than in Tertile2 (9.8%) and Tertile3 (8.3%). On a continuous scale, the adjusted model showed a 58% [OR (95%CI), 1.58 (1.02, 2.54)] increase in the risk of EAAC prevalence for per unit decrease in ln(E2). On a categorical scale, the adjusted model showed that Tertile1 and Tertile2 were 2.55 [OR (95%CI), 2.55 (1.10, 5.92)] and 1.31[OR (95%CI), 1.31(1.03, 2.57)] times higher risk of suffering from EAAC than Tertile3, respectively.ConclusionThis study found that a higher prevalence of AAC in postmenopausal women is closely associated with lower serum E2 levels. Our research further underscores the importance of E2 in maintaining cardiovascular health in postmenopausal women and suggests that monitoring E2 levels may aid in the early prevention and management of AAC and related cardiovascular diseases.

Objective: To evaluate the application value of combining spectral imaging and metal artifact reduction (MAR) in head and neck CTA after the embolization of intracranial aneurysms. Methods: We collected 37 patients who experienced embolization of intracranial aneurysms then received spectral imaging of head and neck CTA. Monochromatic images with energy ranging from 70～140 keV, 120 kVp-like mixed energic images, 70～140 keV MAR images, and 120 kVp-like MAR images were generated. The region of interest was placed on the area near the coil and with the most serious metal artifact. CT attenuation and standard deviation were measured, and artifact index (AI) and signal-noise ratio (SNR) were calculated. Two radiologists independently subjectively evaluated the metal artifact and the display of surrounding vessels using Likert 5 scales. The subjective scores and objective parameters between MAR and non-MAR images were compared. The Wilcoxon ranking test, paired sample t test, and independent sample t test were utilized to compare parameters between the groups. Results: MAR images had significantly lower AI than did non-MAR images for all eight monochromatic energies. When energies ranged from 80~110 keV, SNR was higher for MAR images than for non-MAR images, and the difference was statistically significant. With same energies, MAR images had higher artifact and vessel display scores than did non-MAR images. For non-MAR images, the different coil diameters did not make a statistical difference in AI and vessel display scores. For MAR images, a larger coil diameter (>8.79 mm) led to higher AI and lower vessel display scores than did normal diameters (≤8.79 mm). Conclusion: The combination of spectral imaging and MAR could effectively reduce the metal artifact of implants for the embolization of intracranial aneurysms and improve the surrounding vessel display. Moreover, the metal artifact reduction effect was more significant for the coils with smaller diameters.

ObjectiveThis study aims to assess the current research status, focus areas, and developmental trends in nasopharyngeal carcinoma (NPC) through a bibliometric analysis. MethodsArticles focusing on NPC published from 2000 to 2023 were retrieved from the Web of Science database. VOSviewer and CiteSpace were used for bibliometric and visual analysis. ResultsA total of 14516 related publications were retrieved. There has been a steady increase in the number of NPC-related publications from 2000 to 2023. China was the dominant country in this field with 8948 papers (61.64%), followed by the USA (2234, 15.39%). Sun Yat-sen University was the most influential institution, while Ma J was the most prolific author. Furthermore, Head And Neck-journal For The Sciences And Specialties Of The Head And Neck was the most prolific journal. International Journal of Radiation Oncology Biology Physics had the highest total citation counts. "Introduction chemotherapy", "Concurrent chemotherapy", "Epithelial-mesenchymal transition", "Cancer stem cells", "MicroRNAs", "LncRNA", "Exosomes", and "Biomarker" were the most common keywords. The reference "Chen YP, 2019, Lancet" had the highest citations and strong outbreak value. ConclusionThe past two decades have witnessed a significant increase in research on NPC. The optimization of treatment mode is the most widely studied aspect at present. The mechanism of occurrence and development and the most favorable diagnostic and therapeutic targets are the research hotspots in the future.

Human babesiosis is a tick-borne disease caused by Babesia pathogens. The disease, which presents with malaria-like symptoms, can be life-threatening, especially in individuals with weakened immune systems and the elderly. The worldwide prevalence of human babesiosis has been gradually rising, prompting alarm among public health experts. In other pathogens, genetic techniques have proven to be valuable tools for conducting functional studies to understand the importance of specific genes in development and pathogenesis as well as to validate novel cellular targets for drug discovery. Genetic manipulation methods have been established for several non-human Babesia and Theileria species and, more recently, have begun to be developed for human Babesia parasites. We have previously reported the development of a method for genetic manipulation of the human pathogen Babesia duncani. This method is based on positive selection using the hDHFR gene as a selectable marker, whose expression is regulated by the ef-1aB promoter, along with homology regions that facilitate integration into the gene of interest through homologous recombination. Herein, we provide a detailed description of the steps needed to implement this strategy in B. duncani to study gene function. It is anticipated that the implementation of this method will significantly improve our understanding of babesiosis and facilitate the development of novel and more effective therapeutic strategies for the treatment of human babesiosis.

BackgroundCarotid plaques are major risk factors for stroke. Carotid ultrasound can help to assess the risk and incidence rate of stroke. However, large-scale carotid artery screening is time-consuming and laborious, the diagnostic results inevitably involve the subjectivity of the diagnostician to a certain extent. Deep learning demonstrates the ability to solve the aforementioned challenges. Thus, we attempted to develop an automated algorithm to provide a more consistent and objective diagnostic method and to identify the presence and stability of carotid plaques using deep learning.MethodsA total of 3,860 ultrasound images from 1,339 participants who underwent carotid plaque assessment between January 2021 and March 2023 at the Shanghai Eighth People’s Hospital were divided into a 4:1 ratio for training and internal testing. The external test included 1,564 ultrasound images from 674 participants who underwent carotid plaque assessment between January 2022 and May 2023 at Xinhua Hospital affiliated with Dalian University. Deep learning algorithms, based on the fusion of a bilinear convolutional neural network with a residual neural network (BCNN-ResNet), were used for modeling to detect carotid plaques and assess plaque stability. We chose AUC as the main evaluation index, along with accuracy, sensitivity, and specificity as auxiliary evaluation indices.ResultsModeling for detecting carotid plaques involved training and internal testing on 1,291 ultrasound images, with 617 images showing plaques and 674 without plaques. The external test comprised 470 ultrasound images, including 321 images with plaques and 149 without. Modeling for assessing plaque stability involved training and internal testing on 764 ultrasound images, consisting of 494 images with unstable plaques and 270 with stable plaques. The external test was composed of 279 ultrasound images, including 197 images with unstable plaques and 82 with stable plaques. For the task of identifying the presence of carotid plaques, our model achieved an AUC of 0.989 (95% CI: 0.840, 0.998) with a sensitivity of 93.2% and a specificity of 99.21% on the internal test. On the external test, the AUC was 0.951 (95% CI: 0.962, 0.939) with a sensitivity of 95.3% and a specificity of 82.24%. For the task of identifying the stability of carotid plaques, our model achieved an AUC of 0.896 (95% CI: 0.865, 0.922) on the internal test with a sensitivity of 81.63% and a specificity of 87.27%. On the external test, the AUC was 0.854 (95% CI: 0.889, 0.830) with a sensitivity of 68.52% and a specificity of 89.49%.ConclusionDeep learning using BCNN-ResNet algorithms based on routine ultrasound images could be useful for detecting carotid plaques and assessing plaque instability.

Abstract Mitochondrial transcription termination factor 3 (MTERF3) negatively regulates mitochondrial DNA transcription. However, its role in hepatocellular carcinoma (HCC) progression remains elusive. Here, we investigate the expression and function of MTERF3 in HCC. MTERF3 is overexpressed in HCC tumor tissues and higher expression of MTERF3 positively correlates with poor overall survival of HCC patients. Knockdown of MTERF3 induces mitochondrial dysfunction, S-G2/M cell cycle arrest and apoptosis, resulting in cell proliferation inhibition. In contrast, overexpression of MTERF3 promotes cell cycle progression and cell proliferation. Mechanistically, mitochondrial dysfunction induced by MTERF3 knockdown promotes ROS accumulation, activating p38 MAPK signaling pathway to suppress HCC cell proliferation. In conclusion, ROS accumulation induced by MTERF3 knockdown inhibits HCC cell proliferation via p38 MAPK signaling pathway suggesting a promising target in HCC patients.

Abstract Copy number variations (CNVs) play a vital role in regulating genes expression and tumorigenesis. We explored the copy number alterations in early-stage lung adenocarcinoma using high-throughput sequencing and nucleic acid flight mass spectrometry technology, and found that 8q22.1-22.2 is frequently amplified in lung adenocarcinoma tissues. COX6C localizes on the region and its expression is notably enhanced that driven by amplification in lung adenocarcinoma. Knockdown of COX6C significantly inhibits the cell proliferation, and induces S-G2/M cell cycle arrest, mitosis deficiency and apoptosis. Moreover, COX6C depletion causes a deficiency in mitochondrial fusion, and impairment of oxidative phosphorylation. Mechanistically, COX6C-induced mitochondrial deficiency stimulates ROS accumulation and activates AMPK pathway, then leading to abnormality in spindle formation and chromosome segregation, activating spindle assemble checkpoint, causing mitotic arrest, and ultimately inducing cell apoptosis. Collectively, we suggested that copy amplification-mediated COX6C upregulation might serves as a prospective biomarker for prognosis and targeting therapy in patients with lung adenocarcinoma.

Abstract Hepatocellular carcinoma (HCC) is the third leading cause of cancer‐related death worldwide. Functionally uncharacterized genes are an attractive repository to explore candidate oncogenes. It is demonstrated that C21orf58 displays an oncogenic role in promoting cell growth, tumorigenesis and sorafenib resistance of HCC cells by abnormal activation of STAT3 signaling. Mechanistically, a novel manner to regulate STAT3 signaling that adaptor C21orf58 forms a ternary complex is reveal with N‐terminal domain of STAT3 and SH2 domain of JAK2, by which C21orf58 overactivates wild‐type STAT3 by facilitating its phosphorylation mediated by JAK2, and hyper‐activates of constitutively mutated STAT3 due to preferred binding with C21orf58 and JAK2. Moreover, it is validated that inhibition of C21orf58 with drug alminoprofen, selected by virtual screening, could effectively repress the viability and tumorigenesis of HCC cells. Therefore, it is identified that C21orf58 functions as an oncogenic adaptor, reveal a novel regulatory mechanism of JAK2/STAT3 signaling, explain the cause of abnormal activity of activated mutants of STAT3, and explore the attractive therapeutic potential by targeting C21orf58 in HCC.

Understanding the spatial heterogeneity of bird community distribution within urban greenways is crucial for optimizing ecological functions and supporting urban biodiversity. While ecological corridors enhance connectivity and biodiversity, specific mechanisms by which landscape composition and configuration influence bird diversity remain unclear. This study examines bird community distribution along the Qingshan Lake Greenway in Hangzhou during autumn and winter, using 17 observation points across wetlands, forests, and mixed habitats. The key findings indicate that wetlands have significantly higher species richness compared to forests and mixed habitats, underscoring wetlands’ critical role in supporting diverse bird communities. Greenways primarily facilitate short-distance bird movement with limited permeability between habitats. Additionally, greenway effectiveness in enhancing bird diversity depends heavily on design and structural characteristics. This research highlights the necessity of incorporating microhabitat design and diverse habitat configurations in greenway planning to enhance ecological connectivity and biodiversity. It provides essential insights for urban planners and ecologists, emphasizing detailed landscape composition and configuration analyses. Future research should include year-round studies and advanced ecological monitoring technologies to validate and expand these findings, ultimately contributing to more effective urban biodiversity conservation and sustainable development strategies.

Babesia duncani (B. duncani), a protozoan parasite prevalent in North America, is a significant threat for human health. Given the regulatory role of pyruvate kinase I (PyK I) in glycolytic metabolism flux and ATP generation, PyK I has been considered the target for drug intervention for a long time. In this study, B. duncani PyK I (BdPyK I) was successfully cloned, expressed, and purified. Polyclonal antibodies were confirmed to recognize the native BdPyK I protein (56 kDa) using Western blotting. AlphaFold software predicted the three-dimensional structure of BdPyK I, and molecular docking with small molecules was conducted to identify potential binding sites of inhibitor on BdPyK I. Moreover, inhibitory effects of six inhibitors (tannic acid, apigenin, shikonin, PKM2 inhibitor, rosiglitazone, and pioglitazone) on BdPyK I were examined under the optimal enzymatic conditions of 3 mM PEP and 3 mM ADP, and significant activity reduction was found. Enzyme kinetics and growth inhibition assays further confirmed the reliability of these inhibitors, with PKM2 inhibitor, tannic acid, and apigenin exhibiting the highest selectivity index as specific inhibitors for B. duncani. Subsequently, key amino acid residues were mutated in both BdPyK I and Homo sapiens pyruvate kinase I (HPyK I), and two differential amino acid residues (isoleucine and phenylalanine) were identified between HPyK I and BdPyK I through PyK activity detection experiments. These findings lay foundation for understanding the role of PyK I in the growth and development of B. duncani, providing insights for babesiosis prevention and drug development.

Abstract Background Babesia gibsoni, the causative agent of canine babesiosis, belongs to the phylum Apicomplexa. The development of in vitro culture technology has driven research progress in various kinds of omics studies, including transcriptomic analysis of Plasmodium spp. between in vitro and in vivo environments, which has prompted the observation of diagnostic antigens and vaccine development. Nevertheless, no information on Babesia spp. could be obtained in this respect, which greatly hinders the further understanding of parasite growth and development in the blood stage. Methods In this study, considerable changes in the morphology and infectivity of continuous in vitro cultured B. gibsoni (Wuhan isolate) were observed compared to in vivo parasites. Based on these changes, B. gibsoni (Wuhan isolate) was collected from both in vivo and in vitro cultures, followed by total RNA extraction and Illumina transcriptome sequencing. The acquired differentially expressed genes (DEGs) were validated using qRT-PCR, and then functionally annotated through several databases. The gene with the greatest upregulation after in vitro culture was cloned from the genome of B. gibsoni (Wuhan isolate) and characterized by western blotting and indirect immunofluorescence assay for detecting the native form and cellular localization. Results Through laboratory cultivation, multiple forms of parasites were observed, and the infectivity of in vitro cultured parasites in dogs was found to be lower. Based on these changes, Illumina transcriptome sequencing was conducted, showing that 377 unigenes were upregulated and 334 unigenes were downregulated. Notably, an AP2 transcription factor family, essential for all developmental stages of parasites, was screened, and the transcriptional changes in these family members were tested. Thus, the novel AP2 transcription factor gene (BgAP2-M) with the highest upregulated expression after in vitro adaptation was selected. This gene comprises an open reading frame (ORF) of 1989 base pairs encoding a full-length protein of 662 amino acids. BgAP2-M contains one AP2 domain and one ACDC conserved domain, which may be involved in the nuclear biology of parasites. The prepared polyclonal antibodies against the BgAP2-M peptides further detected a native size of ~ 73 kDa and were localized to the nuclei of B. gibsoni. Conclusion This study presents a thorough transcriptome analysis of B. gibsoni in vivo and in vitro for the first time, contributing to a detailed understanding of the effects of environmental changes on the growth and development of parasites in the blood stage. Moreover, it also provides a deeper investigation for the different members of the ApiAP2 transcription factor family as various life stage regulators in Babesia spp. Graphical Abstract

The rapid development of urbanization and urban land-use intensification have substantially reduced biodiversity and ecosystem services. Wildflower mixtures can improve regional biodiversity and habitat heterogeneity by establishing flower-rich habitats and providing multiple ecosystem services, which were considered one of the most favorable landscape ecological restoration technologies approaches. How to design wildflower mixtures to achieve optimal eco-efficiency is currently unclear. In China, wildflower mixture is one of landscape architecture’s most popular methods for establishing herbaceous vegetation. Currently, there is a notable lack of systematic research regarding species selection, and concerns have been raised about the design approach that introduces convergent species, which may potentially become invasive. This research integrated a wildflower mixture design database currently published in China and discovered community composition and construction methods. Based on this, we compared the species composition of wildflower mixtures in China and assessed the potential invasive species. Additionally, we attempted to explore the distribution over time and space, their potential invasion risk, and the main factors influencing species selection through modeling approaches. The results highlighted that species selection of mixture converged with different spatiotemporal attributes and design intentions, despite designed wildflower mixtures in China having gradually increased in recent years. A large number of species from North America and Europe have been causing an increase in potential invasion annually. Furthermore, the research confirmed that the convergence contributes to the homogenization of urban landscape vegetation communities, which leads to biological invasion from the design level, and revealed the possibility that ineffective ecological restoration techniques may cause adverse environmental impacts.

Abstract Background The associations between short- and long-term exposure to ambient fine particulate matter with an aerodynamic diameter ≤ 2.5 µm (PM2.5) and allergic symptoms in middle-aged and elderly populations remain unclear, particularly in China, where most cities have severe air pollution. Methods Participants (n = 10,142; age = 40–75 years) were recruited from ten regions in China from 2018 to 2021 for the Predictive Value of Inflammatory Biomarkers and Forced Expiratory Volume in 1 s (FEV1) for Chronic Obstructive Pulmonary Disease (PIFCOPD) study. Short-term (lag0 and lag0–7 day) and long-term (1-, 3- and 5-year) PM2.5 concentrations at residences were extracted from the air pollutant database known as Tracking Air Pollution (TAP) in China. Multivariate logistic regression models were used to estimate associations for short- and long-term PM2.5 exposure concentrations and long-term exposure models were additionally adjusted for short-term deviations. Results A 10 µg/m3 increase in PM2.5 on the day the allergic symptoms questionnaire was administered (lag0 day) was associated with higher odds of allergic nasal (1.09, 95% CI 1.05, 1.12) and eye symptoms (1.08, 95% CI 1.05, 1.11), worsening dyspnea caused by allergens (1.06, 95% CI 1.02, 1.10), and ≥ 2 allergic symptoms (1.07, 95% CI 1.03, 1.11), which was similar in the lag0–7 day concentrations. A 10 µg/m3 increase in the 1-year average PM2.5 concentration was associated with an increase of 23% for allergic nasal symptoms, 22% for eye symptoms, 20% for worsening dyspnea caused by allergens, and 21% for ≥ 2 allergic symptoms, similar to the 3- and 5-year average PM2.5 concentrations. These associations between long-term PM2.5 concentration and allergic symptoms were generally unchanged after adjustment for short-term deviations. Conclusions Short- and long-term exposure to ambient PM2.5 was associated with an increased risk of allergic nasal and eye symptoms, worsening dyspnea caused by allergens, and ≥ 2 allergic symptoms. Trial registration Clinical trial ID: NCT03532893 (29 Mar 2018).

Abstract Objectives The aim of this work is to verify the non-inferior efficacy and safety of CMAB008 compared with innovator infliximab in rheumatoid arthritis patients combined with methotrexate. Methods We conducted a randomized, double-blinded, parallel, positive control design, multicenter study, with a stable dose of methotrexate. Patients were enrolled randomly with a ratio of 1:1 to receive intravenously CMAB008 3 mg/kg or innovator infliximab 3 mg/kg at weeks 0, 2, 6, 14, 22 and 30. The primary efficacy endpoint was American College of Rheumatology 20% improvement criteria (ACR20) response rate at week 30. The non-inferiority was established if the lower limit of the one-sided 97.5% confidence interval (CI) for the difference was more than − 15% and the equivalence was established if the two-sided 95% CI was within ± 15% in an exploratory equivalence analysis. The secondary endpoints included other efficacy assessment parameters, as well as immunogenicity, safety, and pharmacokinetics. Results In the full analysis population (FAS), 110 (57.6%) of 191 patients in the CMAB008 group and 120 (62.2%) of 193 patients in the innovator infliximab group reached the primary outcome of ACR20 at week 30. The differences of the rates were − 4.6% and the lower limit of one-sided 97.5% confidence interval was − 14.29%, not less than the lower limit of the non-inferiority margin (− 15%); so CMAB008 was non-inferior to innovator infliximab. Further, CMAB008 was equivalent to innovator infliximab both in FAS (difference − 4.6%, 95% CI − 14.29% to 5.12%) and PPS (difference – 3.3%, 95% CI – 13.18% to 6.62%). The efficacy, safety, immunogenicity, and pharmacokinetics are highly similar between CMAB008 and innovator infliximab. Conclusions Non-inferior efficacy of CMAB008 to innovator infliximab is illustrated with similar early and lasting therapeutic effects, and the equivalence is further demonstrated. CMAB008 is well tolerated and has semblable safety compared with the innovator infliximab. Trial registration number NCT03478111.

Nasopharyngeal carcinoma (NPC) is an aggressive head and neck tumor that is influenced by a variety of molecular factors during its pathogenesis. Among these, the phosphatase and tensin homolog (PTEN) plays a crucial role in regulatory networks. This article systematically reviews the multifaceted functions of PTEN in NPC, including its roles in inhibiting cell proliferation, regulating migration and invasion, promoting autophagy and apoptosis, and influencing resistance to radiotherapy. Molecular factors such as long non-coding RNA, microRNA (miRNA), and circular RNA can modulate PTEN through various pathways, thereby impacting the biological behavior of NPC. In addition, PTEN is involved in regulating the tumor microenvironment of NPC, and its interaction with the Epstein-Barr virus has also recently become a focus of research. A comprehensive understanding of the PTEN regulatory network provides a foundation for future personalized and targeted therapeutic strategies. This study expands our understanding of the pathogenesis of NPC and suggests new directions in the field of tumor biology and NPC treatment.

Background: This study aimed to investigate the association between abdominal aortic calcification (AAC) and coronary heart disease (CHD) in essential hypertension (EH). Methods: This study included patients diagnosed with EH during the 2013–2014 NHANES survey cycle. The study cohort was categorized into the following four groups based on their AAC-24 score: no AAC (0); mild AAC (1–4); moderate AAC (5–15); and severe AAC (16–24). Logistic regression models were used to assess the association between AAC and CHD. Restricted cubic spline curves (RCS) were used to explore possible nonlinear relationships between AAC and CHD. Results: The prevalence of CHD was found to be higher in the moderate AAC and severe AAC groups than in the group without AAC (40.1% versus 30.9%, 47.7% versus 30.9%). On a continuous scale, the fully adjusted model showed a 7% increase in the risk of CHD prevalence per score increase in AAC [OR (95% CI) = 1.07 (1.03–1.11)]. On a categorical scale, the fully adjusted model showed the risk of CHD prevalence in EH patients with moderate AAC and severe AAC was 2.06 (95%CI, 1.23–3.45) and 2.18 (1.09–5.25) times higher than that in patients without AAC, respectively. The RCS curve suggested a dose-response linear relationship between AAC and CHD. Conclusion: These findings highlight that in patients with EH, a higher severity of AAC is associated with a higher risk of CHD prevalence.

Curcumin (CUR) is a lipophilic natural polyphenol that can be isolated from the rhizome of turmeric. Studies have proposed that CUR possesses a variety of biological activities. Due to its anti-inflammatory and antioxidant properties, CUR shows promise in the treatment of inflammatory bowel disease, while its anti-obesity effects make it a potential therapeutic agent in the management of obesity. In addition, curcumin’s ability to prevent atherosclerosis and its cardiovascular benefits further expand its potential application in the treatment of cardiovascular disease. Nevertheless, owing to the limited bioavailability of CUR, it is difficult to validate its specific mechanism of action in the treatment of diseases. However, the restricted bioavailability of CUR makes it challenging to confirm its precise mode of action in disease treatment. Recent research indicates that the oral intake of curcumin may lead to elevated levels of residual curcumin in the gastrointestinal system, hinting at curcumin’s potential to directly influence gut microbiota. Furthermore, the ecological dysregulation of the gut microbiota has been shown to be critical in the pathogenesis of human diseases. This review summarizes the impact of gut dysbiosis on host health and the various ways in which curcumin modulates dysbiosis and ameliorates various diseases caused by it through the administration of curcumin.

Two-dimensional (2D) materials have received significant attention for their potential use in next-generation electronics, particularly in nonvolatile memory and neuromorphic computing. This is due to their simple metal–insulator–metal (MIM) sandwiched structure, excellent switching performance, high-density capability, and low power consumption. In this work, using comprehensive material simulations and device modeling, the thinnest monolayer hexagonal boron nitride (h-BN) atomristor is studied by using a MIM configuration with Ta electrodes. Our first-principles calculations predicted both a high resistance state (HRS) and a low resistance state (LRS) in this device. We observed that the presence of van der Waals (vdW) gaps between the Ta electrodes and monolayer h-BN with a boron vacancy (VB) contributes to the HRS. The combination of metal electrode contact and the adsorption of Ta atoms onto a single VB defect (TaB) can alter the interface barrier between the electrode and dielectric layer, as well as create band gap states within the band gap of monolayer h-BN. These band gap states can shorten the effective tunneling path for electron transport from the left electrode to the right electrode, resulting in an increase in the current transmission coefficient of the LRS. This resistive switching mechanism in monolayer h-BN atomristors can serve as a theoretical reference for device design and optimization, making them promising for the development of atomristor technology with ultra-high integration density and ultra-low power consumption.

Regulatory T cells (Tregs) are instrumental in maintaining immune tolerance and preventing destructive autoimmunity, but how heterogeneous Treg populations are established remains largely unknown. Here, we show that Zfp335 deletion in Tregs failed to differentiate into effector Tregs (eTregs) and lose Treg-suppressive function and that KO mice exhibited early-onset lethal autoimmune inflammation with unrestricted activation of conventional T cells. Single-cell RNA-Seq analyses revealed that Zfp335-deficient Tregs lacked a eTreg population and showed dramatic accumulation of a dysfunctional Treg subset. Mechanistically, Zfp335-deficient Tregs displayed reduced oxidative phosphorylation and dysfunctional mitochondrial activity. Further studies revealed that Zfp335 controlled eTreg differentiation by regulating fatty acid oxidation (FAO) through direct targeting of the FAO enzyme Hadha. Importantly, we demonstrate a positive correlation between ZNF335 and HADHA expression in human eTregs. Our findings reveal that Zfp335 controls FAO-driven eTreg differentiation to establish immune tolerance.

Deubiquitination is an important form of post-translational modification that regulates protein homeostasis. Ovarian tumor domain-containing proteins (OTUDs) subfamily member OTUD3 was identified as a deubiquitinating enzyme involved in the regulation of various physiological processes such as immunity and inflammation. Disturbances in these physiological processes trigger diseases in humans and animals, such as cancer, neurodegenerative diseases, diabetes, mastitis, etc. OTUD3 is aberrantly expressed in tumors and is a double-edged sword, exerting tumor-promoting or anti-tumor effects in different types of tumors affecting cancer cell proliferation, metastasis, and metabolism. OTUD3 is regulated at the transcriptional level by a number of MicroRNAs, such as miR-520h, miR-32, and miR101-3p. In addition, OTUD3 is regulated by a number of post-translational modifications, such as acetylation and ubiquitination. Therefore, understanding the regulatory mechanisms of OTUD3 expression can help provide insight into its function in human immunity and disease, offering the possibility of its use as a therapeutic target to diagnose or treat disease.

Geological storage of CO2 is an effective measure to reduce carbon emission and mitigate greenhouse effect. Through geothermal exploration and comprehensive research，it is found that the sandstone stratified strata of the Third and Fourth Member of the Quantou Formation，the Qingshankou Formation and the Yaojia Formation of the Cretaceous age in the Lindian area of Heilongjiang Province，with the burial depth of about 940−2062 m，contain rich saline water with TDS of 2000−9000 mg/L，and are of well-developed pores and slow groundwater flow. The caprock is dominated by pelite stratified strata of the Nenjiang Formation，Sifangtai Formation and Mingshui Formation of the Cretaceous age，with a thickness of about 800−1300 m. It has not been penetrated by major fault zones and is well closed，which determines that it can be used as a good geological reservoir for CO2 storage. At the same time, Lindian is close to the city of Daqing, with numerous chemical enterprises, concentrated and sufficient carbon sources, and large scale and short distance, providing favorable conditions for CO2 geological storage in the study area. Due to the lack of oil and gas resources and oil wells in the Lindian area, this work uses geothermal exploration wells for the first time. According to the mechanism of CO2 geological storage technology and the international authoritative potential assessment formula, the potential assessment of CO2 geological storage of deep saline aquifers in this area is carried out. The results show that the theoretical CO2 storage in the deep salt aquifers is 478.91×108 t，the effective CO2 storage is 11.49×108 t, which is of large storage potential. In the future, it can provide geological storage sites for carbon reduction in Daqing, Qiqihar and other neighboring cities. The implementation of this work provides technical support for the next implementation of CO2 geological storage suitability evaluation, objective target area and site selection and demonstration projects in the Lindian area.

Abstract This case reports describe a rare disease, mid‐aortic syndrome (MAS), that can cause severe heart failure and hypertension in infancy. The typical images, key points of diagnosis, and therapy methods of the disease have also been presented. We report two critical thoracoabdominal aortic coarctation cases in infants aged 2 and 11 months with severe heart failure. The patients were initially misdiagnosed as dilated myocardiopathy, with the correct diagnosis confirmed through imaging. Both patients underwent balloon angioplasty; one patient also had bare‐metal stents implanted. The patient treated with balloon angioplasty alone died after the procedure, whereas the other patient recovered well. In conclusion, careful physical examinations, especially upper and lower extremity blood pressure differences and palpation of upper and lower limb pulses, are critical in unexplained infant heart failure cases. Stent implantation may be a safer and more effective treatment than simple balloon angioplasty in infants with MAS.

Abstract Background Babesia gibsoni is one of the causative agents of canine babesiosis worldwide. Some dogs infected with B. gibsoni show severe clinical signs with progressive anemia, hemoglobinuria and splenomegaly. However, most infected dogs present a state of chronic infection and thereby may be a persistent pathogen carrier, increasing the risk of pathogen spreading. To date, little is known about this pathogen, with genomic and transcriptomic data in particular generally unavailable. This lack of knowledge extensively limits the development of effective diagnostic strategies and vaccines. Methods High-throughput RNA sequencing of total RNA of B. gibsoni asexual stages collected from infected beagles was performed. The unigenes were annotated in seven databases. The genes were sorted according to their fragments per kilobase per million (FPKM) value, which was used as an indicator for expression level. The gene with the highest FPKM value was cloned from the genome of B. gibsoni and further tested for immunogenicity, cellular localization and efficacy as a potential diagnostic candidate for detecting B. gibsoni in sera collected from beagles. Results A total of 62,580,653 clean reads were screened from the 64,336,475 raw reads, and the corresponding 70,134 transcripts and 36,587 unigenes were obtained. The gene with the highest FPKM value was screened from the unigenes; its full length was 1276 bp, and it was named BgP30. The BgP30 gene comprised three exons and two introns, with a 786-bp open reading frame, and encoded 261 amino acids with a predicted molecular weight of 30 kDa. The cellular localization assay confirmed the existence of P30 protein in B. gibsoni parasites. Moreover, P30 was detected in the serum of experimentally B. gibsoni-infected beagles, from 15 days up to 422 days post-infection, suggesting its usefulness as a diagnostic candidate for both acute and chronic infections. Conclusions We sequenced the transcriptome of B. gibsoni asexual stages for the first time. The BgP30 gene was highly expressed in the transcriptome screening experiments, with further studies demonstrating that it could induce immune response in B. gibsoni-infected dogs. These results lead us to suggest that bgP30 may be a good diagnostic candidate marker to detect both acute and chronic B. gibsoni infections. Graphical Abstract

Highlights The proportion of CD4+CD25−Foxp3+ T cells was elevated in untreated RA. CD4+CD25−Foxp3+ T cells expressed decreased Helios compared with Treg cells in both RA patients and HCs. CD4+CD25−Foxp3+ T cells produced increased IFN-γ compared with Tregs in RA patients. Elevated CD4+CD25−Foxp3+ T cells were positively correlated with DAS28 score, anti-IgG titer and anti-CCP titer.

ABSTRACT The intracellular protozoan parasite Babesia gibsoni infects canine erythrocytes and causes babesiosis. The hazards to animal health have increased due to the rise of B. gibsoni infections and medication resistance. However, the lack of high-quality full-genome sequencing sets has expanded the obstacles to the development of pathogeneses, drugs, and vaccines. In this study, the whole genome of B. gibsoni was sequenced, assembled, and annotated. The genomic size of B. gibsoni was 7.94 Mbp in total. Four chromosomes with the size of 0.69 Mb, 2.10 Mb, 2.77 Mb, and 2.38 Mb, respectively, 1 apicoplast (28.4 Kb), and 1 mitochondrion (5.9 Kb) were confirmed. KEGG analysis revealed 2,641 putative proteins enriched on 316 pathways, and GO analysis showed 7,571 annotations of the nuclear genome in total. Synteny analysis showed a high correlation between B. gibsoni and B. bovis. A new divergent point of B. gibsoni occurred around 297.7 million years ago, which was earlier than that of B. bovis, B. ovata, and B. bigemina. Orthology analysis revealed 22 and 32 unique genes compared to several Babesia spp. and apicomplexan species. The metabolic pathways of B.gibsoni were characterized, pointing to a minimal size of the genome. A species-specific secretory protein SA1 and 19 homologous genes were identified. Selected specific proteins, including apetala 2 (AP2) factor, invasion-related proteins BgAMA-1 and BgRON2, and rhoptry function proteins BgWH_04g00700 were predicted, visualized, and modeled. Overall, whole-genome sequencing provided molecular-level support for the diagnosis, prevention, clinical treatment, and further research of B. gibsoni. IMPORTANCE The whole genome of B. gibsoni was first sequenced, annotated, and disclosed. The key part of genome composition, four chromosomes, was comparatively analyzed for the first time. A full-scale phylogeny evolution analysis based on the whole-genome-wide data of B. gibsoni was performed, and a new divergent point on the evolutionary path was revealed. In previous reports, molecular studies were often limited by incomplete genomic data, especially in key areas like life cycle regulation, metabolism, and host-pathogen interaction. With the whole-genome sequencing of B. gibsoni, we provide useful genetic data to encourage the exploration of new terrain and make it feasible to resolve the theoretical and practical problems of babesiosis.

ABSTRACT The establishment of in vitro culture methods has greatly facilitated the research of Babesia. However, the current Babesia gibsoni in vitro culture medium requires high concentrations of canine serum, which intensively limits the culture and is unable to satisfy the demands of long-term studies. In this study, AlbuMAX I (2 mg/mL) and 2.5% dog serum (vol/vol) were added to VP-SFM medium to develop a low-concentration serum culture medium named VP-SFMAD (2.5%), and the effectiveness of this medium was assessed by the growth of B. gibsoni. The results showed that VP-SFMAD (2.5%) could support the continuous growth of the parasite, and the parasitemia has no difference with the cultivation in RPMI 1640 with 20% dog serum. In contrast, either a low concentration of dog serum or absence of AlbuMAX I will significantly lower the parasite growth or fail to maintain B. gibsoni growth in the long term. The strategy of reducing the hematocrit was also evaluated, and VP-SFMAD (2.5%) improved the parasitemia to over 50% within 5 days. The high parasitemia is helpful for larger numbers of parasite collection, which is valuable for studying the biology, pathogenesis, and virulence of Babesia and other intraerythrocytic parasites. In addition, VP-SFMAD (2.5%) medium was successfully used for monoclonal parasite screening, which obtained monoclonal strains with parasitized erythrocytes about 3%, which is similar to RPMI-1640D (20%) medium that obtains monoclonal strains on the 18th day. Those results showed that VP-SFMAD can be applied to B. gibsoni continuous long-term, expansion culture, and subclone culture. IMPORTANCE The VP-SFM as a base medium supplemented with AlbuMAX I and a low concentration of canine serum (2.5%) allowed the continuous in vitro culture of Babesia gibsoni at both small and large volumes, which was to meet different experimental needs, such as long-term culture and obtaining high parasitemia and subclone culture. The establishment of in vitro culture systems allows researchers to better understand the metabolism and growth patterns of Babesia. Importantly, several technical problems impeding such studies have been overcome.

The aim of this study is to explore the active components and potential molecular mechanism of action of Rubia cordifolia L. against nasopharyngeal carcinoma (NPC). We used network pharmacology, molecular docking, and bioinformatics analysis to identify the active components and their role against NPC. The experimental verification was detected by MTT, AnnexinV-FITC/PI double fluorescence staining and Western blotting method. Network pharmacology identified that mollugin is one of the most effective components inRubia cordifolia L. Important NPC targets included HSP90AA1, CDK1, EGFR, PIK3CA, MAPK14, and CDK2. Molecular docking revealed considerable binding activity of mollugin with either of the 6 important NPC targets. Bioinformatics analysis showed that these 6 important targets were mutated in NPC, and the expression of HSP90AA1, PIK3CA, and CDK2 in cancer tissues was significantly different from that in normal tissues. MTT detection and AnnexinV-FITC/PI double fluorescence staining showed that mollugin inhibited the proliferation and induced apoptosis of NPC cells. Western blotting indicated that the molecular mechanism of mollugin against NPC was related to the regulation of the expression of Survivin and XIAP. This study predicted and partially verified the pharmacological and molecular mechanism of action of Rubia cordifolia L. against NPC. Mollugin was identified as a potential active ingredient against NPC. These results prove the reliability of network pharmacology approaches and provide a basis for further research and application of Rubia cordifolia L. against NPC.

The effect of structure on the vibration response was explored for four piano soundboards with different but commonly adopted structures. The vibration response was obtained using the free-vibration method, and the values of the dynamic modulus of elasticity and dynamic shear modulus obtained using the free-vibration frequency method (EF and GF) were compared with the dynamic modulus of elasticity obtained using the Euler beam method (EE) and dynamic shear modulus obtained using the free-plate torsional vibration method (GT), respectively. It was found that the soundboards with different structures had different vibration modes and that excitation at different locations highlighted different vibration modes. For all the soundboards analyzed, the EE and GT were higher than EF and GF by 2.2% and 24.3%, respectively. However, the trends of the results of these methods were the same. The four piano soundboards with different structures possessed varying dynamic moduli of elasticity and dynamic shear moduli. These rules are consistent with the grain directions of the soundboards and the anisotropy of the wood (the direction of the units of the soundboards). The results show that the vibration mode of the piano soundboard is complex. The dynamic elastic modulus of the soundboard can be calculated using the Euler beam method. The results provide a reference for studies on the vibration response, material selection, production technology, and testing of piano soundboards.

Abstract Background The rates of hepatitis B virus (HBV) infection in rheumatoid arthritis (RA) patients are controversial when considering the reported outcomes. It was speculated that HBV infection status was altered after RA, and variations inn HBV infection rates became apparent. Methods To compare the positive proportions of hepatitis B e antigen (HBeAg) and HBV DNA, a retrospective case–control study was performed between 27 chronic hepatitis B (CHB) patients with RA and 108 age- and gender-matched CHB patients. In addition, the positivity rates of hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) were surveyed among the 892 RA patients. Results Compared to CHB patients, CHB patients with RA exhibited lower rates of HBeAg positivity (11.1% vs. 35.2%, P = 0.003), HBV DNA positivity (37.0% vs. 63.9%, P = 0.007) and ALT elevation (11.1% vs. 35.2%, P = 0.024). In the 892 RA patients, the prevalence of HBsAg (3.0%) was lower than that reported in the Chinese national data (7.2%), whereas the anti-HBc positivity rate of 44.6% was higher than that of 34.1%. Conclusion HBV infection status was altered after suffering from RA. Compared to the matched CHB patients, low positive proportions of HBeAg and HBV DNA were observed for CHB patients with RA.

ObjectiveThis study aims to compare the value of a gadolinium contrast-enhanced 1.5-T three-dimensional (3D) steady-state free precession (SSFP) sequence with that of a noncontrast 3D SSFP sequence for magnetic resonance coronary angiography in a pediatric population.Materials and methodsSeventy-nine patients from 1 month to 18 years old participated in this study. A 3D SSFP coronary MRA at 1.5-T was applied before and after gadolinium-diethylenetriaminepentaaceticacid (DTPA) injection. The detection rates of coronary arteries and side branches were assessed by McNemar's χ2 test. The image quality, vessel length, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) of the coronary arteries were analyzed by the Wilcoxon signed-rank test. The intra- and interobserver agreements were evaluated with a weighted kappa test or an intraclass correlation efficient test.ResultsA contrast-enhanced scan detected more coronary arteries than a noncontrast-enhanced scan in patients under 2 years old (P 0.05). The contrast-enhanced 3D SSFP protocol detected longer lengths for the left anterior descending coronary artery in children younger than 2 years and the left circumflex coronary artery (LCX) in children younger than 5 years (P

The acoustic vibration performance of wood affects the quality of many musical instruments, and the variability of wood causes obvious differences between individual timber samples. To mitigate the variations among the individual timber samples intended for musical instruments, in this study, we combined finite element simulation with experimental testing to investigate the effect of the periodic annular groove structure on the comprehensive acoustic vibration characteristics of wood. The results revealed that there are discernible correlations between the structural parameters of the periodic annular groove and the key acoustic parameters of wood, including the resonant frequency, equivalent dynamic modulus of elasticity, equivalent specific dynamic modulus of elasticity, equivalent acoustic radiation quality constant, and equivalent acoustic impedance. These relationships can be used to fine-tune the overall acoustic vibration performance of wood and harmonize the acoustic vibration characteristics among different timber specimens. The effects of the periodic annular groove structure on the five acoustic vibration parameters obtained through finite element simulations exhibited minimal differences to the corresponding results from experimental tests. Furthermore, there was a remarkably strong correlation between the outcomes of the finite element simulations and the experimental test results, with the coefficient of determination exceeding 0.99.

(1) Background: Epidemiological studies on the relationship between serum copper and hypertension are contradictory. We assessed the relationship between serum copper and blood pressure among adults in the United States. (2) Methods: We divided hypertension into two categories: treated hypertension and untreated hypertension. Linear or logistic regression analysis was applied to investigate the association between serum copper concentrations and blood pressure levels. (3) Results: As compared to quartile 1, the odds ratios (ORs) for untreated hypertension in quartiles 2, 3, and 4 were 1.02 (0.74–1.42), 1.23 (0.88–1.72), and 1.08 (0.74–1.58), respectively, in multivariable analysis (all p > 0.05). In non-hypertension, as compared with quartile 1, the β (95% CI) of systolic blood pressure for quartiles 2, 3, and 4 was −0.92 (−2.07–0.23), −0.05 (−1.30–1.20), and −0.48 (−1.83–0.88), respectively, in multivariable analysis (all p > 0.05). As compared to quartile 1, the ORs for treated hypertension in quartiles 2, 3, and 4 were 1.36 (0.88–2.10), 1.35 (0.87–2.09), and 1.56 (0.98–2.47), respectively, upon multivariable analysis including antihypertensive medication use as a covariate (all p > 0.05). Furthermore, 1SD increase in serum copper was non-significantly associated with 1.16 (0.97–1.37)-fold increased risk of hypertension in multivariable analysis (p = 0.096). (4) Conclusion: In the present study, we discovered that the serum copper concentration was not related with hypertension or blood pressure levels. Antihypertensive drug use may distort the correlation between copper and blood pressure levels. Information on antihypertensive drug use may be taken into account when identifying new risk factors for hypertension.

Objective: To examine the kinetics of B cell subsets and activation markers in the early stage of belimumab treatment and their correction with treatment response.Methods: We enrolled 27 systemic lupus erythematosus (SLE) patients receiving 6 months belimumab treatment. Flow cytometry was used to test their B cell subsets and activation markers (including CD40, CD80, CD95, CD21low, CD22, p-SYK and p-AKT).Results: During belimumab treatment, SLEDAI-2K declined, the proportions of CD19+ B cells and naïve B cells decreased, whereas the switched memory B cells and non-switched B cells increased. The larger variations of the B cell subsets and the activation markers were in the first 1 month than the other later time frames. The ratio of p-SYK/p-AKT on non-switched B cell at 1 month was associated with the SLEDAI-2K decline rate in the 6 months of belimumab treatment.Conclusion: B cell hyperactivity was rapidly inhibited in the early stage of belimumab treatment, and the ratio of p-SYK/p-AKT may predict SLEDAI-2K decline.Clinical Trial Registration:https://www.clinicaltrials.gov/ct2/show/NCT04893161?term=NCT04893161&draw=2&rank=1; identifier: NCT04893161.

Abstract Background Kawasaki disease (KD) is an acute systemic vasculitis of unclear etiology that mainly affects infants and young children. Strategies to reduce the incidence and severity of coronary artery lesions (CALs), the determinant factor in the long-term prognosis of KD, are currently a focus of studies on KD. Corticosteroids, preferred in the treatment of the majority of vasculitides, are controversial in the treatment of acute KD. In this trial, we will evaluate whether the addition of prednisolone to standard intravenous immunoglobulin (IVIG) plus aspirin therapy can reduce the occurrence of CAL in Chinese patients with KD. Methods This is a multicenter, prospective, open-label, randomized controlled trial, which is expected to be conducted in more than 20 hospitals in China and aims to assess the efficacy and safety of IVIG + prednisolone treatment versus standard treatment. Patients with KD who fulfill the inclusion and exclusion criteria will be recruited and randomized (1:1) to receive either a large dose of IVIG (2 g/kg over 12–24 h with a maximum dose of 60 g) + aspirin 30 mg/kg/d or IVIG (2 g/kg over 12–24 h) + aspirin 30 mg/kg/d + prednisolone (2 mg/kg/d with a maximum dose of 60 mg tapered over 15 days after normalization of C-reactive protein concentration). The primary outcome will be the occurrence of CAL at 1 month of illness. The follow-up duration for each participant will be set as 1 year. Patients and treating physicians will be unmasked to group allocation. Discussion This will be the first multicenter randomized controlled trial to evaluate the efficacy of IVIG + aspirin + prednisolone in Chinese pediatric patients with KD, which may provide high-level evidence for improving the initial treatment for acute KD. Trial registration ClinicalTrials.gov NCT04078568 . Registered on 16 August 2018.

A 6-year-old girl was diagnosed with Kawasaki disease and bilateral giant coronary artery aneurysms at four months old and was subsequently referred to our hospital due to chest pain and T wave changes on electrocardiography. After admission, stress myocardial perfusion imaging showed reversible ischemia in multiple areas of the left ventricle. Coronary angiography revealed complete proximal segment occlusion of the left circumflex artery (LCX). The occluded LCX was recanalized by a Gaia 3rd micro-wire successfully passing through the occluded section to the distal end of the LCX, followed by sequential balloon dilation and drug-coated balloon angioplasty. Coronary angiography immediately after post-dilation and one-year follow-up angiography showed that the structure and blood flow of LCX was good. Although percutaneous coronary intervention (PCI) in pediatric patients with Kawasaki disease is limited in practice, PCI remains one of the treatment options for selected patients.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that requires long-term treatment and monitoring. Inhibition of inflammatory gene expression by gene therapy is a significant breakthrough in RA treatment, but the lack of a safe and effective gene delivery system hinders its application. Since oral administration can significantly reduce wound infection caused by parenteral administration, it also has the advantages of high patient compliance and convenience. Therefore, oral administration may be the best option for the treatment of this chronic disease. In this study, we developed a novel oral drug system by delivering tumor necrosis factor-α (TNF-α) short hairpin RNA (shRNA) mediated by non-pathogenic yeast to evaluate its regulation of systemic immune inflammation and safety in RA. Non-pathogenic yeast can resist the destruction of the gastrointestinal acid-base environment and can be recognized by the intestinal macrophages and act on systemic inflammatory lesions. Oral administration of yeast-mediated TNF-α shRNA significantly reduced the expression of TNF-α predominant pro-inflammatory factors in intestinal macrophages and joint synovium, and up-regulated the expression of anti-inflammatory cytokine IL-10 and M2 macrophages, systematically regulating the inflammatory response. This yeast-mediated oral gene delivery system can not only significantly inhibit knee joint synovial inflammation, but also has no toxic effects on peripheral blood and major organs. Therefore, yeast-mediated oral delivery of TNF-α shRNA may be used as a novel gene therapy strategy to treat RA through immunomodulating the mononuclear phagocyte system from the intestine to the joint synovium, and ultimately regulating systemic and local immune inflammation, providing new ideas for the clinical treatment of RA.

Abstract Background Kawasaki disease (KD) is a systemic vasculitis that predominantly affects medium-sized arteries. In addition to well-known coronary artery aneurysms (CAAs), peripheral systemic artery aneurysms (SAAs) have also been sporadically reported. In the literatures, SAAs occurred mainly in untreated, intravenous immunoglobin (IVIG)-resistant, or severe refractory KD, and thrombotic events in SAAs were rarely reported. Case presentation A 10-month-old boy with a history of KD was referred to our hospital for suspected pseudoaneurysm of the axillary arteries. Four months prior to presentation, he had persistent fever, conjunctival congestion, and rash. On the 10th day of fever echocardiogram showed biliteral CAAs. He was then diagnosed with KD and given IVIG 2 g/kg and aspirin at a local hospital. His fever and symptoms soon subsided and he was discharged with low dose aspirin and dipyridamole. One month prior to presentation, his parents incidentally palpated swellings in his bilateral axillae. On admission, physical examination revealed a pulsatile swelling in his right axilla and a non-pulsatile swelling in the left with impalpable left brachial and radial pulses, cooler and less active left upper limb than the right one. While the pulses of other three limbs were normal. Ultrasound examination revealed giant bilateral axillary artery aneurysms (AAAs) with massive thrombus in the left. Angiography confirmed giant bilateral AAAs with left AAAs completely occluded and fine collateral vessels connecting to the distal brachial artery, in addition to giant bilateral multiple CAAs without stenoses. The patient was given intravenous prostaglandin for 10 days to allow for formation of collateral circulation, as well as aspirin, low molecular weight heparin (which was switched to warfarin before discharge) and metoprolol. At discharge, the temperature and movement of his left upper limb improved significantly. On follow-up at 7 months, his left upper limb further improved and was similar to the right with no occurrence of cardiovascular events. The images of CAAs and AAAs on echocardiogram and computerized tomography remained the same. Conclusions This case highlights the importance of evaluating peripheral SAAs in KD patients with CAAs, even if their course of treatment appears smooth. For both large non-aortic SAAs and CAAs in KD patients, antithrombotic therapy is of utmost importance.

Abstract Babesiosis is a tick-borne disease with global impact caused by parasites of the phylum Apicomplexa, genus Babesia. Typically, acute bovine babesiosis (BB) is characterized by fever, anemia, hemoglobinuria, and high mortality. Surviving animals remain persistently infected and become reservoirs for parasite transmission. Bovids in China can be infected by one or more Babesia species endemic to the country, including B. bovis, B. bigemina, B. orientalis, B. ovata, B. major, B. motasi, B. U sp. Kashi and B. venatorum. The latter may pose a zoonotic risk. Occurrence of this wide diversity of Babesia species in China may be due to a combination of favorable ecological factors, such as the presence of multiple tick vectors, including Rhipicephalus and Hyalomma, the coexistence of susceptible bovid species, such as domestic cattle, yaks, and water buffalo, and the lack of efficient measures of tick control. BB is currently widespread in several regions of the country and a limiting factor for cattle production. While some areas appear to have enzootic stability, others have considerable cattle mortality. Research is needed to devise solutions to the challenges posed by uncontrolled BB. Critical research gaps include risk assessment for cattle residing in endemic areas, understanding factors involved in endemic stability, evaluation of parasite diversity and pathogenicity of regional Babesia species, and estimation of whether and how BB should be controlled in China. Research should allow the design of comprehensive interventions to improve cattle production, diminish the risk of human infections, and increase the availability of affordable animal protein for human consumption in China and worldwide. In this review, we describe the current state of BB with reference to the diversity of hosts, vectors, and parasite species in China. We also discuss the unique risks and knowledge gaps that should be taken into consideration for future Babesia research and control strategies.

BackgroundBlood flowing in the arterial lumen acts on the surface of the vessel wall to form wall shear stress (WSS). To date, there has been limited research on the utility of non-invasive technology in the accurate quantification of carotid WSS in patients with hypertension (HP).ObjectiveThe present study aimed to explore the usage of vascular vector flow mapping (VFM) in the quantitative assessment of carotid WSS in hypertensive patients at an early stage and to validate its clinical utility.MethodsA total of 50 individuals confirmed without carotid plaques were grouped into a HP group (n = 25) and a control (CON) group (n = 25) according to blood pressure. An ALOKA LISENDO 880 Color Doppler Ultrasound with a L441 3–15 MHZ probe was used to obtain a longitudinal section scan to determine the regions of interests (ROIs) of the common carotid artery. VFM-based WSS measurements were obtained by selecting the ROI with optimal image quality from three full cardiac cycles. WSS-derived measurements, including WSSmax, WSSmin, and WSSmean, were analyzed and compared between the HP and CON groups. In addition, the correlations between WSS-derived measurements and the carotid artery intima-media thickness (IMT) were also analyzed.ResultsThere were significant statistical differences in WSSmax and WSSmean between patients in the HP and CON groups. Specifically, the HP group had significantly decreased WSSmax and WSSmean compared to the CON group (WSSmax: 1.781 ± 0.305 Pa vs. 2.286 ± 0.257 Pa; WSSmean: 1.276 ± 0.333 Pa vs. 1.599 ± 0.293 Pa, both p < 0.001). However, there was no statistical difference in WSSmin between the groups (0.79 ± 0.36 vs. 0.99 ± 0.42, p = 0.080). Additionally, Spearman’s correlation analysis indicated that the WSS-derived parameters were negatively correlated with the IMT (p < 0.001).ConclusionVascular VFM technology shows promising results in the quantitative assessment of difference in hemodynamics of the vascular flow field between patients with HP and normal controls. Difference in WSS may serve as a potential predictor for the development of arteriosclerosis risks.

According to the difference in temperature, thermotherapy can be divided into thermal ablation and mild hyperthermia. The main advantage of thermal ablation is that it can efficiently target tumors in situ, while mild hyperthermia has a good inhibitory effect on distant metastasis. There are some similarities and differences between the two therapies with respect to inducing anti-tumor immune responses, but neither of them results in sustained systemic immunity. Malignant tumors (such as breast cancer, pancreatic cancer, nasopharyngeal carcinoma, and brain cancer) are recurrent, highly metastatic, and highly invasive even after treatment, hence a single therapy rarely resolves the clinical issues. A more effective and comprehensive treatment strategy using a combination of hyperthermia and immune checkpoint inhibitor (ICI) therapies has gained attention. This paper summarizes the relevant preclinical and clinical studies on hyperthermia combined with ICI therapies and compares the efficacy of two types of hyperthermia combined with ICIs, in order to provide a better treatment for the recurrence and metastasis of clinically malignant tumors.