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The mining of shallow coal seams in Shendong Mining Area has resulted in well-developed surface fractures and complex three-dimensional air leakage. In order to study the distribution characteristics and dynamic evolution laws of surface fractures in Shendong Mining Area, take the shallow burial mining of Huojitu Well in Daliuta Coal Mine and Bulianta Coal Mine as the engineering background, a combination of on-site UAV fixed-point observation, infrared, geological radar and other technologies was used to study the distribution characteristics of macroscopic and hidden fractures on the surface, and to analyze the dynamic evolution laws of fractures. Research has shown that the goaf of the shallow coal seam mining face in Shendong Mining Area has a greater impact on surface strike fractures compared to inclined fractures. Among them, the effective influence range of 101 fissures in 12 lower 206 working face in Huojitu Well is 35 m, and 122 fissures in 22310 working face of Bulianta Coal Mine is 62 m. The maximum width of strike fissures is 80 cm, and dip fissures are generally less than 10 cm. The maximum width of strike fractures reaches 80 cm, and inclined fractures are generally below 10 cm; with the advance of the working surface, the width of the crack increases gradually until it is fully developed, and the spacing of the discontinuous section of the crack becomes larger and the drop increases. If the crack with a larger width (the crack width is greater than 10 cm) is close to the working face, the crack width will gradually shrink with the advance of the working face, and may even be closed.

Abstract Background Mitochondrial diseases (MDs) can be caused by single nucleotide variants (SNVs) and structural variants (SVs) in the mitochondrial genome (mtDNA). Presently, identifying deletions in small to medium-sized fragments and accurately detecting low-percentage variants remains challenging due to the limitations of next-generation sequencing (NGS). Methods In this study, we integrated targeted long-range polymerase chain reaction (LR-PCR) and PacBio HiFi sequencing to analyze 34 participants, including 28 patients and 6 controls. Of these, 17 samples were subjected to both targeted LR-PCR and to compare the mtDNA variant detection efficacy. Results Among the 28 patients tested by long-read sequencing (LRS), 2 patients were found positive for the m.3243 A > G hotspot variant, and 20 patients exhibited single or multiple deletion variants with a proportion exceeding 4%. Comparison between the results of LRS and NGS revealed that both methods exhibited similar efficacy in detecting SNVs exceeding 5%. However, LRS outperformed NGS in detecting SNVs with a ratio below 5%. As for SVs, LRS identified single or multiple deletions in 13 out of 17 cases, whereas NGS only detected single deletions in 8 cases. Furthermore, deletions identified by LRS were validated by Sanger sequencing and quantified in single muscle fibers using real-time PCR. Notably, LRS also effectively and accurately identified secondary mtDNA deletions in idiopathic inflammatory myopathies (IIMs). Conclusions LRS outperforms NGS in detecting various types of SNVs and SVs in mtDNA, including those with low frequencies. Our research is a significant advancement in medical comprehension and will provide profound insights into genetics.

Abstract Traditional village toponyms contain rich vernacular geographical information, profound cultural connotations, and social group memories. Studying the meanings and spatial distribution characteristics of traditional village toponyms and their formation mechanism is significant for the sustainable development and protection of the intangible culture of traditional villages. However, previous studies mainly focused on qualitative description combined with geospatial analysis techniques to explore their spatial distribution and influencing factors, but there has yet to be an in-depth study on why such a pattern is formed. Thus, this study employs statistics, a GIS kernel density estimation method, a geodetector, and historical data to examine the spatial distribution, influence factors, and formation mechanisms of various toponyms in traditional villages in western Hunan, China. The results show that (1) the toponyms in traditional villages in western Hunan can be categorized into natural and cultural landscape toponyms. Natural landscape toponyms predominate in the northwest, whereas cultural landscape toponyms are more concentrated in the southeast, with Huayuan, Longshan, and Dong Autonomous Counties as the primary focal points; (2)Natural toponyms are shaped by terrain, river proximity, and vegetation, whereas cultural toponyms cluster due to natural features and historic trail influence, mirroring the historical migration and settlement patterns in the development of western Hunan; (3)Multiple influencing factors, regulatory powers, and curing processes reveal the formation mechanism of the spatial patterns of toponyms. This study offers a novel lens for recognizing and understanding the characteristics of human settlement environments and culture in traditional villages. Moreover, the results of this study can provide scientific guidance for the cultural protection of traditional villages on a cross-regional scale.

Abstract Wolfiporia cocos is a medicinal mushroom used in China. It biosynthesizes pachymic acid (PA), a main therapeutic triterpene associated with therapies. Nowadays, the unknown PA biosynthesis leads to difficulties in increasing its content in W. cocos. Herein, we report sequencing, assembling, and characterization of the genome and several transcriptomes of W. cocos. Sequence mining determined candidate genes that encode lanosterol synthase, sterol O-acyltransferase, and sterol C-24 methyltransferase likely involved in the steps from lanosterol to PA. Gene cluster analysis identified four CYP450 cDNAs likely involved in the biosynthesis of PA, namely WcCYP64-1, WcCYP64-2, WcCYP52, and WcCYP_FUM15, which were subjected to both overexpression and silencing in mycelia. The overexpression of each of WcCYP64-1, WcCYP52 and WcCYP_FUM15 increased the content of PA, 16α-hydroxytrametenolic acid, eburicoic acid, and tumulosic acid, while the silencing of each gene either significantly or slightly decreased the contents of these four compounds, indicating their involvement in the PA biosynthesis. In addition, different temperatures affected the expression of these genes and the formation of PA. By contrast, the overexpression and silencing of WcCYP64-2 did not alter the formation of these compounds. Taken together, these findings determine more potential steps in the biosynthetic pathway of PA for metabolic engineering.

Abstract The chromatin modifier GRAIN WEIGHT 6a (GW6a) enhances rice grain size and yield. However, little is known about its gene network determining grain size. Here, we report that MITOGEN-ACTIVED PROTEIN KINASE 6 (OsMAPK6) and E3 ligase CHANG LI GENG 1 (CLG1) interact with and target GW6a for phosphorylation and ubiquitylation, respectively. Unexpectedly, however, in vitro and in vivo assays reveal that both of the two post-translational modifications stabilize GW6a. Furthermore, we uncover two major GW6a phosphorylation sites (serine142 and threonine186) targeted by OsMAPK6 serving an important role in modulating grain size. In addition, our genetic and molecular results suggest that the OsMAPK6-GW6a and CLG1-GW6a axes are crucial and operate in a non-additive manner to control grain size. Overall, our findings identify a previously unknown mechanism by which phosphorylation and ubiquitylation non-additively stabilize GW6a to enhance grain size, and reveal correlations and interactions of these posttranslational modifications during rice grain development.

Purpose This study evaluated the elastic characteristics of the pulmonary trunk and distal branches in fetuses diagnosed with tetralogy of Fallot (TOF) using Doppler echocardiography. Methods Data on 42 fetuses diagnosed with TOF and 84 gestational age–matched normal fetuses were prospectively collected from the Second Xiangya Hospital of Central South University between August 2022 and January 2023. The severity of TOF was classified into three categories based on the z-score of the pulmonary annulus diameter: mild (z-score ≥-2), moderate (-40.05). Conclusion Fetuses diagnosed with TOF exhibited increased vascular stiffness in the MPA and reduced stiffness in the distal pulmonary artery (PA). Larger-scale follow-up studies are required to elucidate the relationships between these changes in vascular stiffness and PA development in patients with TOF.

Abstract Introduction Previous studies have reported controversial relationships between circulating vascular endothelial growth factors (VEGF) and ischemic stroke (IS). This study aims to demonstrate the causal effect between VEGF and IS using Mendelian randomization (MR). Methods Summary statistics data from two large-scale genome-wide association studies (GWAS) for 16,112 patients with measured VEGF levels and 40,585 patients with IS were downloaded from public databases and included in this study. A published calculator was adopted for MR power calculation. The primary outcome was any ischemic stroke, and the secondary outcomes were large-artery stroke, cardioembolic stroke, and small-vessel stroke. We used the inverse variance-weighted (IVW) method for primary analysis, supplemented by MR-Egger regression and the weighted median method. Results Nine SNPs were included to represent serum VEGF levels. The IVW method revealed no strong causal association between VEGF and any ischemic stroke (odds ratio [OR] 1.01, 95% CI 0.99–1.04, p = 0.39), cardioembolic stroke (OR 1.04, 95% CI 0.97–1.12, p = 0.28), large-artery stroke (OR 1.02, 95% CI 0.95–1.09, p = 0.62), and small-vessel stroke (OR 0.98, 95% CI 0.91–1.04, p = 0.46). These findings remained robust in sensitivity analyses. MR-Egger regression suggested no horizontal pleiotropy. Conclusions This Mendelian randomization study found no relationship between genetically predisposed serum VEGF levels and risks of IS or its subtypes.

Abstract Background Benign prostatic hyperplasia (BPH) is a prevalent disease affecting elderly men, with chronic inflammation being a critical factor in its development. Omentin-1, also known as intelectin-1 (ITLN-1), is an anti-inflammatory protein primarily found in the epithelial cells of the small intestine. This study aimed to investigate the potential of ITLN-1 in mitigating BPH by modulating local inflammation in the prostate gland. Methods Our investigation involved two in vivo experimental models. Firstly, ITLN-1 knockout mice (Itln-1 −/− ) were used to study the absence of ITLN-1 in BPH development. Secondly, a testosterone propionate (TP)-induced BPH mouse model was treated with an ITLN-1 overexpressing adenovirus. We assessed BPH severity using prostate weight index and histological analysis, including H&E staining, immunohistochemistry, and enzyme-linked immunosorbent assay. In vitro, the impact of ITLN-1 on BPH-1 cell proliferation and inflammatory response was evaluated using cell proliferation assays and enzyme-linked immunosorbent assay. Results In vivo, Itln-1 −/− mice exhibited elevated prostate weight index, enlarged lumen area, and higher TNF-α levels compared to wild-type littermates. In contrast, ITLN-1 overexpression in TP-induced BPH mice resulted in reduced prostate weight index, lumen area, and TNF-α levels. In vitro studies indicated that ITLN-1 suppressed the proliferation of prostate epithelial cells and reduced TNF-α production in macrophages, suggesting a mechanism involving the inhibition of macrophage-mediated inflammation. Conclusion The study demonstrates that ITLN-1 plays a significant role in inhibiting the development of BPH by reducing local inflammation in the prostate gland. These findings highlight the potential of ITLN-1 as a therapeutic target in the management of BPH.

Background Tumor deposits (TD) was a significant risk factor impacting the prognosis of patients diagnosed with gastric cancer (GC), yet it was not currently incorporated into TNM staging systems. The objective of this research was to develop a predictive model for assessing the prognosis of patients with TD-positive GC. Methods Retrospective analysis was performed on the data of 4,972 patients treated for GC with D2 radical gastrectomy at Wannan Medical College’s Yijishan Hospital between January 2012 and December 2021. The patients were categorized based on the number of TD (L1: 1, L2: 2–3, L3: ≥4) and the anatomical location of TD (Q1: single area, Q2: multiple areas). In a 3:1 ratio, patients were randomly assigned to one of two groups: training or validation. Results The study included a total of 575 patients who were divided into the training group (n = 432) and validation group (n = 143). Survival analysis showed that the number and anatomical location of TD had a significant impact on the prognosis of patients with TD-positive GC. Univariate analysis of the training group data revealed that tumor size, T-stage, N-stage, histological grade, number and distribution of TD, neural invasion, and postoperative chemotherapy were associated with prognosis. Multivariate Cox regression analysis identified poor histological grade, T4 stage, N3 stage, number of TD, neural invasion, and postoperative chemotherapy as independent prognostic factors for GC patients with TD. A nomogram was developed using these variables, demonstrating well predictive ability for 1, 3, and 5-year overall survival (OS) in the validation set. The DCA curve shows that the constructed model shows a large positive net gain compared to the eighth edition Tumour, Node, Metastasis (TNM) staging system. Conclusion The prognostic model developed for patients with TD-positive GC has a higher clinical utility compared to the eighth edition of TNM staging.

BackgroundElevated PPP4C expression has been associated with poor prognostic implications for patients suffering from lung adenocarcinoma (LUAD). The extent to which PPP4C affects immune cell infiltration in LUAD, as well as the importance of associated genes in clinical scenarios, still requires thorough investigation.MethodsIn our investigation, we leveraged both single-cell and comprehensive RNA sequencing data, sourced from LUAD patients, in our analysis. This study also integrated datasets of immune-related genes from InnateDB into the framework. Our expansive evaluation employed various analytical techniques; these included pinpointing differentially expressed genes, constructing WGCNA, implementing Cox proportional hazards models. We utilized these methods to investigate the gene expression profiles of PPP4C within the context of LUAD and to clarify its potential prognostic value for patients. Subsequent steps involved validating the observed enhancement of PPP4C expression in LUAD samples through a series of experimental approaches. The array comprised immunohistochemistry staining, Western blotting, quantitative PCR, and a collection of cell-based assays aimed at evaluating the influence of PPP4C on the proliferative and migratory activities of LUAD cells.ResultsIn lung cancer, elevated expression levels of PPP4C were observed, correlating with poorer patient prognoses. Validation of increased PPP4C levels in LUAD specimens was achieved using immunohistochemical techniques. Experimental investigations have substantiated the role of PPP4C in facilitating cellular proliferation and migration in LUAD contexts. Furthermore, an association was identified between the expression of PPP4C and the infiltration of immune cells in these tumors. A prognostic framework, incorporating PPP4C and immune-related genes, was developed and recognized as an autonomous predictor of survival in individuals afflicted with LUAD. This prognostic tool has demonstrated considerable efficacy in forecasting patient survival and their response to immunotherapeutic interventions.ConclusionThe involvement of PPP4C in LUAD is deeply intertwined with the tumor’s immune microenvironment. PPP4C’s over-expression is associated with negative clinical outcomes, promoting both tumor proliferation and spread. A prognostic framework based on PPP4C levels may effectively predict patient prognoses in LUAD, as well as the efficacy of immunotherapy strategy. This research sheds light on the mechanisms of immune interaction in LUAD and proposes a new strategy for treatment.

IntroductionSalt stress is a major environmental factor that constrains soybean growth, development, and productivity. Flavonoids are key secondary metabolites that play a crucial role in enhancing plant resistance to both biotic and abiotic stress. However, a comprehensive understanding of the regulatory mechanisms underlying flavonoid biosynthesis under salt stress in soybean is lacking.MethodsIn this study, an integrative analysis of soybean metabolome and transcriptome was conducted using two soybean lines, FQ03 (salt-sensitive, SS) and FQ07 (salt-tolerant, ST).ResultsA total of 650 significantly changed metabolites were identified in SS and ST after salt stress treatment. Among them, 151 flavonoids were categorized into nine classes, with flavones and flavonols being the predominant flavonoid types in soybean. Heatmap analysis showed higher contents of most flavonoid metabolites in ST than in SS under salt stress, and the total flavonoid content in ST was significantly higher than that in SS. In addition, transcriptome analysis revealed a higher number of differentially expressed genes (DEGs) in ST than in SS under salt stress. KEGG enrichment analysis revealed that DEGs were mainly enriched in pathways related to phenylpropanoid biosynthesis, isoflavonoid biosynthesis, flavonoid biosynthesis, as well as flavone and flavonol biosynthesis. Notably, 55 DEGs that were mapped to the flavonoid biosynthetic pathway were identified, with most showing higher expression levels in ST than in SS. Weighted gene correlation network analysis identified eight structural genes and six transcription factor genes as key regulators of flavonoid biosynthesis within the blue module. Furthermore, qRT-PCR results confirmed the accuracy of the transcriptomic data and reliability of the identified candidate genes.DiscussionThis study provides insights into the regulatory mechanisms underlying salt stress responses in soybean and highlights hub genes as potential targets for developing salt-tolerant soybean varieties.

Abstract Disulfidptosis is a condition where dysregulated NAPDH levels and abnormal accumulation of cystine and other disulfides occur in cells with high SLC7A11 expression under glucose deficiency. This disrupts normal formation of disulfide bonds among cytoskeletal proteins, leading to histone skeleton collapse and triggering cellular apoptosis. However, the correlation between disulfidptosis and immune responses in relation to glioblastoma survival rates and immunotherapy sensitivity remains understudied. Therefore, we utilized The Cancer Genome Atlas and The Chinese Glioma Genome Atlas to identify disulfidptosis-related immune checkpoint genes and established an overall survival (OS) prediction model comprising six genes: CD276, TNFRSF 14, TNFSF14, TNFSF4, CD40, and TNFRSF18, which could also be used for predicting immunotherapy sensitivity. We identified a cohort of glioblastoma patients classified as high-risk, which exhibited an upregulation of angiogenesis, extracellular matrix remodeling, and epithelial-mesenchymal transition as well as an immunosuppressive tumor microenvironment (TME) enriched with tumor associated macrophages, tumor associated neutrophils, CD8 + T-cell exhaustion. Immunohistochemical staining of CD276 in 144 cases further validated its negative correlation with OS in glioma. Disulfidptosis has the potential to induce chronic inflammation and an immunosuppressive TME in glioblastoma.

In response to the current situation in which an imbalance in educational redistribution has led to an inefficient and slow educational environment in the long-term, difficulty in satisfying the interests of subjects, and a lack of effective targeting of school policy measures, an SD evolutionary game model targeting educational reform, with schools, administrative institutions, and professors as the three parties, was established. Based on expected utility theory and Lyapunov’s first law, a feedback regulation simulation study was conducted on subjects’ decision making behavior. The research results show that: the evolutionary trajectory of the subjects in the game is affected by the redistribution of education funding benefits, but the evolution of the final system is in a state of stable equilibrium (push, reform, reform); the decision-making behavior of the pushing party plays a decisive role in the stability of the system, and if the education subsidies of university professors and the income from the value of research results are greater than the education subsidies before the education reform, evolution over time is conducive to prompting the professor group to prefer the education reform strategy, while the effect of school push on the stability of the educational reform system is significant in schools with lower returns on the value of research funding.

Abstract Background As a key regulatory enzyme in the glycolysis pathway, pyruvate kinase (PK) plays crucial roles in multiple physiological processes during plant growth and is also involved in the abiotic stress response. However, little information is known about PKs in soybean. Results In this study, we identified 27 PK family genes against the genome of soybean cultivar Zhonghuang13. They were classified into 2 subfamilies including PKc and PKp. 22 segmental duplicated gene pairs and 1 tandem duplicated gene pair were identified and all of them experienced a strong purifying selective pressure during evolution. Furthermore, the abiotic stresses (especially salt stress) and hormone responsive cis-elements were present in the promoters of GmPK genes, suggesting their potential roles in abiotic stress tolerance. By performing the qRT-PCR, 6 GmPK genes that continuously respond to both NaCl and ABA were identified. Subsequently, GmPK21, which represented the most significant change under NaCl treatment was chosen for further study. Its encoded protein GmPK21 was localized in the cytoplasm and plasma membrane. The transgenic Arabidopsis overexpressing GmPK21 exhibited weakened salinity tolerance. Conclusions This study provides genomic information of soybean PK genes and a molecular basis for mining salt tolerance function of PKs in the future.

Abstract Background Effective conservation and utilization of farm animals are fundamental for realizing sustainable increases in food production. In situ and ex situ conservation are the two main strategies that are currently used to protect the genetic integrity of Chinese domestic chicken breeds. However, genomic diversity and population structure have not been compared in these conserved populations. Results Three hundred and sixty-one individuals from three Chinese domestic chicken breeds were collected from populations conserved in situ and ex situ and genotyped using genotyping-by-sequencing (GBS). First, we used different parameters based on heterozygosity, genomic inbreeding, and linkage disequilibrium to estimate the genomic diversity of these populations, and applied principal component analysis (PCA), neighbor-joining tree, and ADMIXTURE to analyze population structure. We found that the small ex situ conserved populations, which have been maintained in controlled environments, retained less genetic diversity than the in situ conserved populations. In addition, genetic differentiation was detected between the in situ and ex situ conserved populations of the same breed. Next, we analyzed signatures of selection using three statistical methods (fixation index (FST), nucleotide diversity (Pi), and cross-population extended haplotype homozygosity (XP-EHH) to study the genetic footprints that underlie the differentiation between in situ and ex situ conserved populations. We concluded that, in these small populations, differentiation might be caused by genetic drift or by mutations from the original populations. The differentiation observed in the population of Beijing You chicken probably reflects adaptation to environmental changes in temperature and humidity that the animals faced when they were moved from their place of origin to the new site for ex situ conservation. Conclusions Conservation programs of three Chinese domestic chicken breeds have maintained their genomic diversity to a sustainable degree. The small ex situ conserved populations, which are maintained in controlled environments, retain less genetic diversity than populations conserved in situ. In addition, the transfer of populations from their place of origin to another site for conservation purposes results in genetic differentiation, which may be caused by genetic drift or adaptation. This study provides a basis for further optimization of in situ and ex situ conservation programs for domestic chicken breeds in China.

Vectors incorporating the human H1 (hH1) promoter are being applied for RNA interference (RNAi) experiments and genome editing. Although extensive studies have been conducted on the hH1 promoter, our understanding of the mouse H1 promoter remains limited. In this study, we predicted the 163 bp mouse H1 (mH1) promoter and 84 bp mouse H1 core (mH1 core) promoter through global alignment and detected its RNA polymerase II (Pol II) and III activities through the expression of the EGFP and the abundance of artificial sequence, which were generally slightly weaker than those of the hH1 promoter. Furthermore, to boost its Pol III activity, we engineered various promoter mutants by introducing mutations or systematically swapping elements. Surprisingly, the Pol II activity of mH1 core mut5 with AT stretch was at least 2-fold greater than that of the wild type, making it a potential candidate for target protein expression purposes. Fortunately, the Pol III activities of mH1 mut1 and mH1 core mut5 were at least 1.5 times stronger than those of the parental promoters in human and mouse cell lines on account of AT stretch, as did the mH1 mut4 with AT stretch and proximal sequence element (PSE) and TATA box insertion mutations. We highly recommend these three promoters as valuable supplements to the type 3 Pol III promoter toolbox.

BackgroundOsteomyelitis is characterized by an inflammatory process initiated by microorganisms, leading to infection and subsequent degradation of bone tissue. Several studies have indicated a potential link between gut microbiota and the occurrence of osteomyelitis. Utilizing the benefits of Mendelian randomization, which mitigates issues of confounding and reverse causation, we employed this approach to ascertain the presence of a causal connection between gut microbiota and osteomyelitis. Additionally, we aimed to pinpoint gut microbiota that could potentially exert substantial influence.MethodsWe performed a rigorous screening of single nucleotide polymorphisms in GWAS summary statistics for gut microbiota and osteomyelitis. The 2,542 instrumental variables obtained after screening were subjected to MR analyses, including inverse variance weighting, weighted median, weighted mode, MR-Egger, and Mendelian randomization pleiotropy residual sum and outlier test. We then validated the reliability of the results by performing sensitivity analyses on the MR of 196 well-defined gut microbiota.ResultWe established a causal relationship between gut microbiota and osteomyelitis through MR analysis. Additionally, we identified a taxon of significant importance and six taxons with nominal significance. Specifically, the family Bacteroidales S24.7 group exhibited an association with a diminished risk of osteomyelitis development. Conversely, the class Bacilli, class Bacteroidia, order Bacteroidales, order Lactobacillales, family Streptococcaceae, and genus Coprococcus3 displayed an increased risk of developing osteomyelitis. The MR outcomes for these seven taxa remained stable throughout a series of sensitivity analyses.ConclusionThis study demonstrated a causal relationship between gut microbiota and osteomyelitis by Mendelian randomization. We hope that this study will provide a new direction for the treatment of osteomyelitis, which has a paucity of therapeutic options.

Summary: Seed size is controlled not only by intrinsic genetic factors but also by external environmental signals. Here, we report a major quantitative trait locus (QTL) gene for seed size and weight on chromosome 1 (SSW1) in Arabidopsis, and we found SSW1 acts maternally to positively regulate seed size. Natural variation in SSW1 contains three types of alleles. The SSW1Cvi allele produces larger seeds with more amino acid and storage protein contents than the SSW1Ler allele. SSW1Cvi displays higher capacity for amino acid transport than SSW1Ler due to the differences in transport efficiency. Under low nitrogen supply, the SSW1Cvi allele exhibits increased seed yield and nitrogen use efficiency (NUE). Locations of natural variation alleles of SSW1 are associated with local soil nitrogen contents, suggesting that SSW1 might contribute to geographical adaptation in Arabidopsis. Thus, our findings reveal a mechanism that coordinates seed growth and NUE, suggesting a potential target for improving seed yield and NUE in crops.

BackgroundA substantial percentage of the US population is not up to date on guideline-recommended cancer screenings. Identifying interventions that effectively improve screening rates would enhance the delivery of such screening. Interventions involving health IT (HIT) show promise, but much remains unknown about how HIT is optimized to support cancer screening in primary care. ObjectiveThis scoping review aims to identify (1) HIT-based interventions that effectively support guideline concordance in breast, cervical, and colorectal cancer screening provision and follow-up in the primary care setting and (2) barriers or facilitators to the implementation of effective HIT in this setting. MethodsFollowing scoping review guidelines, we searched MEDLINE, CINAHL Plus, Web of Science, and IEEE Xplore databases for US-based studies from 2015 to 2021 that featured HIT targeting breast, colorectal, and cervical cancer screening in primary care. Studies were dual screened using a review criteria checklist. Data extraction was guided by the following implementation science frameworks: the Reach, Effectiveness, Adoption, Implementation, and Maintenance framework; the Expert Recommendations for Implementing Change taxonomy; and implementation strategy reporting domains. It was also guided by the Integrated Technology Implementation Model that incorporates theories of both implementation science and technology adoption. Reporting was guided by PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews). ResultsA total of 101 studies met the inclusion criteria. Most studies (85/101, 84.2%) involved electronic health record–based HIT interventions. The most common HIT function was clinical decision support, primarily used for panel management or at the point of care. Most studies related to HIT targeting colorectal cancer screening (83/101, 82.2%), followed by studies related to breast cancer screening (28/101, 27.7%), and cervical cancer screening (19/101, 18.8%). Improvements in cancer screening were associated with HIT-based interventions in most studies (36/54, 67% of colorectal cancer–relevant studies; 9/14, 64% of breast cancer–relevant studies; and 7/10, 70% of cervical cancer–relevant studies). Most studies (79/101, 78.2%) reported on the reach of certain interventions, while 17.8% (18/101) of the included studies reported on the adoption or maintenance. Reported barriers and facilitators to HIT adoption primarily related to inner context factors of primary care settings (eg, staffing and organizational policies that support or hinder HIT adoption). Implementation strategies for HIT adoption were reported in 23.8% (24/101) of the included studies. ConclusionsThere are substantial evidence gaps regarding the effectiveness of HIT-based interventions, especially those targeting guideline-concordant breast and colorectal cancer screening in primary care. Even less is known about how to enhance the adoption of technologies that have been proven effective in supporting breast, colorectal, or cervical cancer screening. Research is needed to ensure that the potential benefits of effective HIT-based interventions equitably reach diverse primary care populations.

Background: Carotid arterial atherosclerotic stenosis is a well-recognized pathological basis of ischemic stroke; however, its underlying molecular mechanisms remain unknown. Vascular smooth muscle cells (VSMCs) play fundamental roles in the initiation and progression of atherosclerosis. Organelle dynamics have been reported to affect atherosclerosis development. However, the association between organelle dynamics and various cellular stresses in atherosclerotic progression remain ambiguous. Methods: In this study, we conducted transcriptomics and bioinformatics analyses of stable and vulnerable carotid plaques. Primary VSMCs were isolated from carotid plaques and subjected to histopathological staining to determine their expression profiles. Endoplasmic reticulum (ER), mitochondria, and lysosome dynamics were observed in primary VSMCs and VSMC cell lines using live-cell imaging. Moreover, the mechanisms underlying disordered organelle dynamics were investigated using comprehensive biological approaches. Results: ER whorls, a representative structural change under ER stress, are prominent dynamic reconstructions of VSMCs between vulnerable and stable plaques, followed by fragmented mitochondria and enlarged lysosomes, suggesting mitochondrial stress and lysosomal defects, respectively. Induction of mitochondrial stress alleviated ER stress and autophagy in an eukaryotic translation initiation factor (eIF)-2α-dependent manner. Furthermore, the effects of eIF2α on ER stress, mitochondrial stress, and lysosomal defects were validated using clinical samples. Conclusion: Our results indicate that morphological and functional changes in VSMC organelles, especially in ER whorls, can be used as reliable biomarkers for atherosclerotic progression. Moreover, eIF2α plays an important role in integrating multiple stress-signaling pathways to determine the behavior and fate of VSMCs.

Abstract The prevalence of cardiometabolic diseases in the United States is presumably linked to an obesogenic retail food environment that promotes unhealthy dietary habits. Past studies, however, have reported inconsistent findings about the relationship between the two. One underexplored area is how humans interact with food environments and how to integrate human activity into scalable measures. In this paper, we develop the retail food activity index (RFAI) at the census tract level by utilizing Global Positioning System tracking data covering over 94 million aggregated visit records to approximately 359,000 food retailers across the United States over two years. Here we show that the RFAI has significant associations with the prevalence of multiple cardiometabolic diseases. Our study indicates that the RFAI is a promising index with the potential for guiding the development of policies and health interventions aimed at curtailing the burden of cardiometabolic diseases, especially in communities characterized by obesogenic dietary behaviors.

Abstract Background The Begonia species are common shade plants that are mostly found in southwest China. They have not been well studied despite their medicinal and decorative uses because gene penetration, decreased adaptability, and restricted availability are all caused by frequent interspecific hybridization. Result To understand the patterns of mutation in the chloroplast genomes of different species of Begonia, as well as their evolutionary relationships, we collected seven Begonia species in China and sequenced their chloroplast genomes. Begonia species exhibit a quadripartite structure of chloroplast genomes (157,634 − 169,694 bp), consisting of two pairs of inverted repeats (IR: 26,529 − 37,674 bp), a large single copy (LSC: 75,477 − 86,500 bp), and a small single copy (SSC: 17,861 − 18,367 bp). 128–143 genes (comprising 82–93 protein-coding genes, 8 ribosomal RNAs, and 36–43 transfer RNAs) are found in the chloroplast genomes. Based on comparative analyses, this taxon has a relatively similar genome structure. A total of six substantially divergent DNA regions (trnT-UGU-trnL-UAA, atpF-atpH, ycf4-cemA, psbC-trnS-UGA, rpl32-trnL-UAG, and ccsA-ndhD) are found in the seventeen chloroplast genomes. These regions are suitable for species identification and phylogeographic analysis. Phylogenetic analysis shows that Begonia species that were suited to comparable environments grouped in a small clade and that all Begonia species formed one big clade in the phylogenetic tree, supporting the genus’ monophyly. In addition, positive selection sites were discovered in eight genes (rpoC1, rpoB, psbE, psbK, petA, rps12, rpl2, and rpl22), the majority of which are involved in protein production and photosynthesis. Conclusion Using these genome resources, we can resolve deep-level phylogenetic relationships between Begonia species and their families, leading to a better understanding of evolutionary processes. In addition to enhancing species identification and phylogenetic resolution, these results demonstrate the utility of complete chloroplast genomes in phylogenetically and taxonomically challenging plant groupings.

Knowledge on spatial distribution, provenance and delivery mode of surface sediment aids in interpretation of nearby sediment records for paleoenvironmental reconstruction. Such knowledge, however, remains largely unknown for the modern Ross Sea, Antarctica: a key region for understanding the dynamical behavior of Antarctic Ice Sheet over geological past. In this study, we address this gap by analyzing the grain-size distribution, coarse fraction (>250 μm) lithology, and clay mineralogy of a set of surface sediment samples covering the whole Ross Sea continental shelf. Our data reveals that the sediments were mostly delivered by icebergs and bottom currents. Iceberg delivery was significantly controlled by factors such as water depth, proximity to the iceberg sources, and invasion of the Modified Circumpolar Deep Water. Bottom current activity was stronger in the Western Ross Sea (WRS) than in the Eastern Ross Sea (ERS), controlled by the formation and transport of Dense Shelf Water. Three major sorts of coarse fraction were identified, including the quartz-rich Iceberg Rafted Detritus (IRD) originating from West Antarctic glaciers and primarily distributed in the ERS, the mafic rocks-rich IRD from the Ferrar Group as well as the McMurdo Volcanic Group and mainly found in the WRS, and deformed silt traced back to the grounding zone of the David Glacier-Dragalski Ice Tongue system. The distribution of clay minerals is dominated by a distinct binary mixing pattern. Smectite and kaolinite are mainly present in the ERS, derived from beneath the West Antarctic Ice Sheet. Higher illite and chlorite contents were found offshore of the Southern Victoria Land, derived from the East Antarctic craton. Overall, these results demonstrate that the glaciers draining into Ross Sea from both the East and West Antarctic Ice Sheets are highly dynamical in the context of modern climate conditions, with implications for potential contribution to future sea level rise.

Introduction: Surgical training traditionally adheres to the apprenticeship paradigm, potentially exposing trainees to an increased risk of complications stemming from their limited experience. To mitigate this risk, augmented and virtual reality have been considered, though their effectiveness is difficult to assess. Research question: The PASSION study seeks to investigate the improvement of manual dexterity following intensive training with neurosurgical simulators and to discern how surgeons' psychometric characteristics may influence their learning process and surgical performance. Material and methods: Seventy-two residents were randomized into the simulation group (SG) and control group (CG). The course spanned five days, commencing with assessment of technical skills in basic procedures within a wet-lab setting on day 1. Over the subsequent core days, the SG engaged in simulated procedures, while the CG carried out routine activities in an OR. On day 5, all residents' technical competencies were evaluated. Psychometric measures of all participants were subjected to analysis. Results: The SG demonstrated superior performance (p

BackgroundFreezing of gait (FOG) is a common and disabling phenomenon in patients with Parkinson’s disease (PD), but effective treatment approach remains inconclusive. Dysfunctional emotional factors play a key role in FOG. Since primary motor cortex (M1) connects with prefrontal areas via the frontal longitudinal system, where are responsible for emotional regulation, we hypothesized M1 may be a potential neuromodulation target for FOG therapy. The purpose of this study is to explore whether high-frequency rTMS over bilateral M1 could relieve FOG and emotional dysregulation in patients with PD.MethodsThis study is a single-center, randomized double-blind clinical trial. Forty-eight patients with PD and FOG from the Affiliated Hospital of Xuzhou Medical University were randomly assigned to receive 10 sessions of either active (N = 24) or sham (N = 24) 10 Hz rTMS over the bilateral M1. Patients were evaluated at baseline (T0), after the last session of treatment (T1) and 30 days after the last session (T2). The primary outcomes were Freezing of Gait Questionnaire (FOGQ) scores, with Timed Up and Go Test (TUG) time, Standing-Start 180° Turn (SS-180) time, SS-180 steps, United Parkinson Disease Rating Scales (UPDRS) III, Hamilton Depression scale (HAMD)-24 and Hamilton Anxiety scale (HAMA)-14 as secondary outcomes.ResultsTwo patients in each group dropped out at T2 and no serious adverse events were reported by any subject. Two-way repeated ANOVAs revealed significant group × time interactions in FOGQ, TUG, SS-180 turn time, SS-180 turning steps, UPDRS III, HAMD-24 and HAMA-14. Post-hoc analyses showed that compared to T0, the active group exhibited remarkable improvements in FOGQ, TUG, SS-180 turn time, SS-180 turning steps, UPDRS III, HAMD-24 and HAMA-14 at T1 and T2. No significant improvement was found in the sham group. The Spearman correlation analysis revealed a significantly positive association between the changes in HAMD-24 and HAMA-14 scores and FOGQ scores at T1.ConclusionHigh-frequency rTMS over bilateral M1 can improve FOG and reduce depression and anxiety in patients with PD.

Background: Food pantries are an important source of food for those facing food insecurity. The Charitable Food Nutrition Index (CFNI) was developed for research and practice to measure the nutritional quality of assortments of foods in this setting. Objective: The study assessed the construct validity of the CFNI using secondary data from a group-randomized food pantry intervention in Minnesota. Methods: The CFNI was calculated for each client cart post-intervention (n = 187; 85 intervention, 102 control). CFNI scores were based on the proportion of items in each client cart ranked “green,” “yellow,” or “red” using the Healthy Eating Research Nutrition Guidelines for the Charitable Food System. An implementation score assessing intervention fidelity was measured for each pantry (n = 11; 5 intervention, 6 control) based on the four intervention subcomponents: aesthetics/use of space; healthy food prominence and appeal; unhealthy food de-emphasis; and stocking standards. Mixed linear models were used to test whether: (a) client carts from pantries in the intervention condition had higher CFNI scores than those in the control condition, and (b) higher implementation scores were associated with higher CFNI scores. Results: In adjusted models, clients from intervention group pantries had higher CFNI scores, reflecting a healthier assortment of foods compared with clients from control group pantries (p = 0.022). CFNI scores were positively associated with greater fidelity to the intervention (p = 0.020). Conclusions: The CFNI was sensitive enough to detect the effects of the intervention in the expected directions. These findings support its construct validity and utility as a measure in the charitable food system.

Abstract Background Stroke is a heavy burden in modern society, and carotid artery disease is a major cause. The role of the extracellular matrix (ECM) in the development and progression of carotid artery disease has become a popular research focus. However, there is no published bibliometric analysis to derive the main publication features and trends in this scientific area. We aim to conduct a bibliometric analysis to reveal current status of ECM in carotid artery disease and to predict future hot spots. Methods We searched and downloaded articles from the Web of Science Core Collection with “Carotid” and “Extracellular Matrix” as subject words from 1990 to 2021. The complete bibliographic data were analyzed by Bibliometrics, BICOMB, gCLUTO and CiteSpace softwares. Results Since 1990, the United States has been the leader in the number of publications in the field of ECM in carotid artery disease, followed by China, Japan and Germany. Among institutions, Institut National De La Sante Et De La Recherche Medicale Inserm, University of Washington Seattle and Harvard University are in the top 3. “Arteriosclerosis Thrombosis and Vascular Biology” is the most popular journal and “Circulation” is the most cited journal. “Clowes AW”, “Hedin Ulf” and “Nilsson Jan” are the top three authors of published articles. Finally, we investigated the frontiers through the strongest citation bursts, conducted keyword biclustering analysis, and discovered five clusters of research hotspots. Our research provided a comprehensive analysis of the fundamental data, knowledge organization, and dynamic evolution of research about ECM in carotid artery disease. Conclusions The field of ECM in carotid artery disease has received increasing attention. We summarized the history of the field and predicted five future hotspots through bibliometric analysis. This study provided a reference for researchers in this fields, and the methodology can be extended to other fields.

Abstract Lung adenocarcinoma (LUAD) is a malignant tumor in the respiratory system. The efficacy of current treatment modalities varies greatly, and individualization is evident. Therefore, finding biomarkers for predicting treatment prognosis and providing reference and guidance for formulating treatment options is urgent. Cancer immunotherapy has made distinct progress in the past decades and has a significant effect on LUAD. Immunogenic Cell Death (ICD) can reshape the tumor’s immune microenvironment, contributing to immunotherapy. Thus, exploring ICD biomarkers to construct a prognostic model might help individualized treatments. We used a lung adenocarcinoma (LUAD) dataset to identify ICD-related differentially expressed genes (DEGs). Then, these DEGs were clustered and divided into subgroups. We also performed variance analysis in different dimensions. Further, we established and validated a prognostic model by LASSO Cox regression analysis. The risk score in this model was used to evaluate prognostic differences by survival analysis. The treatment prognosis of various therapies were also predicted. LUAD samples were divided into two subgroups. The ICD-high subgroup was related to an immune-hot phenotype more sensitive to immunotherapy. The prognostic model was constructed based on six ICD-related DEGs. We found that high-risk score patients responded better to immunotherapy. The ICD prognostic model was validated as a standalone factor to evaluate the ICD subtype of individual LUAD patients, which might contribute to more effective therapies.

Objective: To explore the changes of the total flavonoids, free amino acids and quercetin extraction amount with the brewing time and temperature during the brewing process of Penthorum chinense Pursh （PCP） leaf tea and fit the extraction kinetics equation of the three and calculate the kinetics parameters. Methods: The total flavonoids, free amino acids and quercetin were determined by ultraviolet spectrophotometry and high performance liquid chromatography （HPLC）. The second-order kinetic model and Arrhenius formula were used to fit the kinetics and calculate the kinetic parameters. Results: The leaching amount of total flavonoids and quercetin increased with the increase of the temperature and the brewing time in the range of 60~100 ℃ for 60 min. When brewing for 60 min at 60~90 ℃, the free amino acids had the same leaching law. When the temperature rised to 100 ℃, the heat loss of free amino acids was large after brewing for 20 min. The second-order kinetic model could fit the leaching amount of the three substances well with the high correlation coefficient. Linear relationship between temperature and second-order rate constant k was good. The activation energies of total flavonoids, free amino acids and quercetin were 16 628.201, 23 415.139 and 14 975.396 J/mol. Conclusion: The extraction amount of total flavonoids, free amino acids and quercetin in PCP leaf tea changed significantly with the brewing time and temperature, and the extraction amount of the three was in line with the second-order kinetic model in the range of 60~90 ℃, which can be used to predict the extraction amount.

Abstract Background Bicuspid aortic valve (BAV) is the most prevalent congenital valvular heart defect, and around 50% of severe isolated calcific aortic valve disease (CAVD) cases are associated with BAV. Although previous studies have demonstrated the cellular heterogeneity of aortic valves, the cellular composition of specific BAV at the single-cell level remains unclear. Methods Four BAV specimens from aortic valve stenosis patients were collected to conduct single-cell RNA sequencing (scRNA-seq). In vitro experiments were performed to further validate some phenotypes. Results The heterogeneity of stromal cells and immune cells were revealed based on comprehensive analysis. We identified twelve subclusters of VICs, four subclusters of ECs, six subclusters of lymphocytes, six subclusters of monocytic cells and one cluster of mast cells. Based on the detailed cell atlas, we constructed a cellular interaction network. Several novel cell types were identified, and we provided evidence for established mechanisms on valvular calcification. Furthermore, when exploring the monocytic lineage, a special population, macrophage derived stromal cells (MDSC), was revealed to be originated from MRC1+ (CD206) macrophages (Macrophage-to-Mesenchymal transition, MMT). FOXC1 and PI3K-AKT pathway were identified as potential regulators of MMT through scRNA analysis and in vitro experiments. Conclusions With an unbiased scRNA-seq approach, we identified a full spectrum of cell populations and a cellular interaction network in stenotic BAVs, which may provide insights for further research on CAVD. Notably, the exploration on mechanism of MMT might provide potential therapeutic targets for bicuspid CAVD.

Grain size has an important effect on rice yield. Although several key genes that regulate seed size have been reported in rice, their molecular mechanisms remain unclear. In this study, a rice small grain size 2 (sms2) mutant was identified, and MutMap resequencing analysis results showed that a 2 bp insertion in the second exon of the LOC_Os02g01590 gene resulted in a grain length and width lower than those of the wild-type Teqing (TQ). We found that SMS2 encoded vacuolar acid invertase, a novel allele of OsINV3, which regulates grain size. GO and KEGG enrichment analyses showed that SMS2 was involved in endoplasmic reticulum protein synthesis, cysteine and methionine metabolism, and propionic acid metabolism, thereby regulating grain size. An analysis of sugar content in young panicles showed that SMS2 reduced sucrose, fructose, and starch contents, thus regulating grain size. A haplotype analysis showed that Hap2 of SMS2 had a longer grain and was widely present in indica rice varieties. Our results provide a new theoretical basis for the molecular and physiological mechanisms by which SMS2 regulates grain size.

The advent of deep learning has provided solutions to many challenges posed by the Internet. However, efficient localization and recognition of vulgar segments within videos remain formidable tasks. This difficulty arises from the blurring of spatial features in vulgar actions, which can render them indistinguishable from general actions. Furthermore, issues of boundary ambiguity and over-segmentation complicate the segmentation of vulgar actions. To address these issues, we present the Boundary-Match U-shaped Temporal Convolutional Network (BMUTCN), a novel approach for the segmentation of vulgar actions. The BMUTCN employs a U-shaped architecture within an encoder–decoder temporal convolutional network to bolster feature recognition by leveraging the context of the video. Additionally, we introduce a boundary-match map that fuses action boundary inform ation with greater precision for frames that exhibit ambiguous boundaries. Moreover, we propose an adaptive internal block suppression technique, which substantially mitigates over-segmentation errors while preserving accuracy. Our methodology, tested across several public datasets as well as a bespoke vulgar dataset, has demonstrated state-of-the-art performance on the latter.

The DA1-like gene family plays a crucial role in regulating seed and organ size in plants. The DA1 gene family has been identified in several species but has not yet been reported in sweet potatoes. In this study, nine, eleven, and seven DA1s were identified in cultivated sweet potato (Ipomoea batatas, 2n = 6x = 90) and its two diploid wild relatives, I. trifida (2n = 2x = 30) and I. triloba (2n = 2x = 30), respectively. The DA1 genes were classified into three subgroups based on their phylogenetic relationships with Arabidopsis thaliana and Oryza sativa (rice). Their protein physiological properties, chromosomal localization, phylogenetic relationships, gene structure, promoter cis-elements, and expression patterns were systematically analyzed. The qRT-PCR results showed that the expression levels of four genes, IbDA1-1, IbDA1-3, IbDA1-6, and IbDA1-7, were higher in the sweet potato leaves than in the roots, fiber roots, and stems. In our study, we provide a comprehensive comparison and further the knowledge of DA1-like genes in sweet potatoes, and provide a theoretical basis for functional studies.

Abstract Rad51 maintains genome integrity, whereas Rad52 causes non-canonical homologous recombination leading to gross chromosomal rearrangements (GCRs). Here we find that fission yeast Srr1/Ber1 and Skb1/PRMT5 promote GCRs at centromeres. Genetic and physical analyses show that srr1 and skb1 mutations reduce isochromosome formation mediated by centromere inverted repeats. srr1 increases DNA damage sensitivity in rad51 cells but does not abolish checkpoint response, suggesting that Srr1 promotes Rad51-independent DNA repair. srr1 and rad52 additively, while skb1 and rad52 epistatically reduce GCRs. Unlike srr1 or rad52, skb1 does not increase damage sensitivity. Skb1 regulates cell morphology and cell cycle with Slf1 and Pom1, respectively, but neither Slf1 nor Pom1 causes GCRs. Mutating conserved residues in the arginine methyltransferase domain of Skb1 greatly reduces GCRs. These results suggest that, through arginine methylation, Skb1 forms aberrant DNA structures leading to Rad52-dependent GCRs. This study has uncovered roles for Srr1 and Skb1 in GCRs at centromeres.

Resistance of FLT3-ITD acute myeloid leukaemia (AML) patients to FLT3 inhibitors (FLT3i) remains an urgent clinical challenge. Here, the authors identify C/EBPα activation as a mechanism of FLT3i resistance and therapeutically target C/EBPα activation in combination with FLT3i in preclinical models FLT3-ITD AML.

High incidence of traditional and emerging Fusarium mycotoxins in cereal grains and silages can be a potential threat to feed safety and ruminants. Inadequate biodegradation of Fusarium mycotoxins by rumen microflora following ingestion of mycotoxin-contaminated feeds can lead to their circulatory transport to target tissues such as mammary gland. The bovine udder plays a pivotal role in maintaining milk yield and composition, thus, human health. However, toxic effects of Fusarium mycotoxins on bovine mammary gland are rarely studied. In this study, the bovine mammary epithelial cell line was used as an in-vitro model of bovine mammary epithelium to investigate effects of deoxynivalenol (DON), enniatin B (ENB) and beauvericin (BEA) on bovine mammary gland homeostasis. Results indicated that exposure to DON, ENB and BEA for 48 h significantly decreased cell viability in a concentration-dependent manner (P

As stage IIIC non-small cell lung cancer (NSCLC) is not recommended for surgical resection, the survival and prognosis for stage IIIC NSCLC remain poor. More powerful and individualized therapies are urgently needed to improve the prognosis of stage IIIC NSCLC. Recently, immunotherapeutics have been increasingly considered in the neoadjuvant therapy of NSCLC. This study presents a patient with stage IIIC NSCLC achieving a pathological complete response (pCR) following conversion therapy with immunotherapy plus chemotherapy. This case also presents a histologic transformation from squamous cell carcinoma to adenocarcinoma after prolonged progression-free survival (PFS) following surgery. Collectively, this case suggests that conversion immunotherapy with chemotherapy and subsequent surgery can be considered and benefits a subset of unresectable stage IIIC NSCLC.

Introduction Stroke remains the second leading cause of death worldwide, a common cause of which is intracranial atherosclerotic stenosis (ICAS). Medical treatment is recommended as first-line therapy for treating ICAS, but the recurrence rate remains high. Drug-coated balloon (DCB) angioplasty has been designed to lower the risk of recurrent stenosis, holding therapeutic promise in the treatment of ICAS. However, the benefits of DCB require further evaluation.Methods and analysis The Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols was followed to develop this protocol. We will systematically search online databases including Cochrane Central Register of Controlled Trials, PubMed, Web of Science, EMBASE, China Biological Medicine Database, ClinicalTrials.gov and WHO ICTRP from 1 January 2011 to the date of search. This will be supplemented by a manual search of unpublished and ongoing trials to manually select articles for inclusion. Inclusion criteria are randomised or quasi-randomised clinical trials and observational studies that investigated DCB or medical treatment for patients with a symptomatic ICAS of 50%–99%. The primary outcome is short-term composite safety including death of any cause, or non-fatal stroke. Secondary outcomes include long-term death or stroke, restenosis, neurological rehabilitation, quality of life and other complications. The available data will be analysed using meta-analysis, if appropriate. The evaluation of heterogeneity and biases will be guided by the Cochrane Handbook for Systematic Reviews of Interventions.Ethics and dissemination This systematic review does not require ethical approval as all available data from eligible studies will be anonymous with no concerns regarding privacy. Our findings will be disseminated through international conferences and peer-reviewed publications. Additional data from the study are available on request to corresponding authors via email.PROSPERO registration number CRD42022341607.

ObjectiveImpaired elasticity of aorta has been observed in fetuses with congenital cardiac disease, while the orientation of left ventricle outflow tract has been found to influence the blood flow in the ascending aorta. Therefore, the objective of this study is to examine the left ventricle inflow and outflow tract angle (LIOA) in healthy fetuses.MethodA total of 668 fetuses were enrolled in this prospective study. The LIOA were measured with two-line method at left ventricle inflow and outflow tract view. Pearson's correlation coefficient was utilized to assess the associations between LIOA and estimated fetal weight (EFW) and cardiac dimensions, including cardiac axis and diameters of aortic valve (AV), pulmonary artery valve (PAV), mitral valve (MV) and tricuspid valve (TV).ResultsThe LIOA was determined to be 44 ± 7.5° (mean ± SD). No significant difference was observed in the LIOA across different gestational ages (GAs). A mild positive correlation was observed between LIOA and cardiac axis. However, no significant associations were found between LIOA and parameters such as EFW, as well as diameters of AV, PAV, MV and TV.ConclusionThe LIOA remained constant during the mid-third trimester and was mildly positively correlated with cardiac axis in normal fetuses.

BackgroundCancer indeed represents a significant public health challenge, and unplanned extubation of peripherally inserted central catheter (PICC-UE) is a critical concern in patient safety. Identifying independent risk factors and implementing high-quality assessment tools for early detection in high-risk populations can play a crucial role in reducing the incidence of PICC-UE among patients with cancer. Precise prevention and treatment strategies are essential to improve patient outcomes and safety in clinical settings. ObjectiveThis study aims to identify the independent risk factors associated with PICC-UE in patients with cancer and to construct a predictive model tailored to this group, offering a theoretical framework for anticipating and preventing PICC-UE in these patients. MethodsProspective data were gathered from January to December 2022, encompassing patients with cancer with PICC at Xiangya Hospital, Central South University. Each patient underwent continuous monitoring until the catheter’s removal. The patients were categorized into 2 groups: the UE group (n=3107) and the non-UE group (n=284). Independent risk factors were identified through univariate analysis, the least absolute shrinkage and selection operator (LASSO) algorithm, and multivariate analysis. Subsequently, the 3391 patients were classified into a train set and a test set in a 7:3 ratio. Utilizing the identified predictors, 3 predictive models were constructed using the logistic regression, support vector machine, and random forest algorithms. The ultimate model was selected based on the receiver operating characteristic (ROC) curve and TOPSIS (Technique for Order Preference by Similarity to Ideal Solution) synthesis analysis. To further validate the model, we gathered prospective data from 600 patients with cancer at the Affiliated Hospital of Qinghai University and Hainan Provincial People’s Hospital from June to December 2022. We assessed the model’s performance using the area under the curve of the ROC to evaluate differentiation, the calibration curve for calibration capability, and decision curve analysis (DCA) to gauge the model’s clinical applicability. ResultsIndependent risk factors for PICC-UE in patients with cancer were identified, including impaired physical mobility (odds ratio [OR] 2.775, 95% CI 1.951-3.946), diabetes (OR 1.754, 95% CI 1.134-2.712), surgical history (OR 1.734, 95% CI 1.313-2.290), elevated D-dimer concentration (OR 2.376, 95% CI 1.778-3.176), targeted therapy (OR 1.441, 95% CI 1.104-1.881), surgical treatment (OR 1.543, 95% CI 1.152-2.066), and more than 1 catheter puncture (OR 1.715, 95% CI 1.121-2.624). Protective factors were normal BMI (OR 0.449, 95% CI 0.342-0.590), polyurethane catheter material (OR 0.305, 95% CI 0.228-0.408), and valved catheter (OR 0.639, 95% CI 0.480-0.851). The TOPSIS synthesis analysis results showed that in the train set, the composite index (Ci) values were 0.00 for the logistic model, 0.82 for the support vector machine model, and 0.85 for the random forest model. In the test set, the Ci values were 0.00 for the logistic model, 1.00 for the support vector machine model, and 0.81 for the random forest model. The optimal model, constructed based on the support vector machine, was obtained and validated externally. The ROC curve, calibration curve, and DCA curve demonstrated that the model exhibited excellent accuracy, stability, generalizability, and clinical applicability. ConclusionsIn summary, this study identified 10 independent risk factors for PICC-UE in patients with cancer. The predictive model developed using the support vector machine algorithm demonstrated excellent clinical applicability and was validated externally, providing valuable support for the early prediction of PICC-UE in patients with cancer.

Background: Our previous study reported that histamine H2 receptor antagonists (H2RAs) exposure was associated with decreased mortality in critically ill patients with heart failure (HF) through the same pharmacological mechanism as β-blockers. However, population-based clinical study directly comparing the efficacy of H2RAs and β-blockers on mortality of HF patients are still lacking. This study aims to compare the association difference of H2RAs and β-blockers on mortality in critically ill patients with HF using the Medical Information Mart for Intensive Care III database (MIMIC-III).Methods: Study population was divided into 4 groups: β-blockers + H2RAs group, β-blockers group, H2RAs group, and Non-β-blockers + Non-H2RAs group. Kaplan–Meier curves and multivariable Cox regression models were employed to evaluate the differences of all-cause mortalities among the 4 groups. Propensity score matching (PSM) was used to increase comparability of four groups.Results: A total of 5593 patients were included. After PSM, multivariate analyses showed that patients in H2RAs group had close all-cause mortality with patients in β-blockers group. Furthermore, 30-day, 1-year, 5-year and 10-year all-mortality of patients in β-blockers + H2RAs group were significantly lower than those of patients in β-blockers group, respectively (HR: 0.64, 95%CI: 0.50–0.82 for 30-day; HR: 0.80, 95%CI: 0.69–0.93 for 1-year mortality; HR: 0.83, 95%CI: 0.74–0.93 for 5-year mortality; and HR: 0.85, 95%CI: 0.76–0.94 for 10-year mortality, respectively).Conclusion: H2RAs exposure exhibited comparable all-cause mortality-decreasing effect as β-blockers; and, furthermore, H2RAs and β-blockers had additive or synergistic interactions to improve survival in critically ill patients with HF.

As the most common type of refractive error, myopia has become one of the leading causes of visual impairment. With the increasing prevalence of myopia, there is a growing need to better understand the factors involved in its development. Inflammation, one of the most fundamental pathophysiological processes in humans, is a rapid response triggered by harmful stimuli and conditions. Although controlled inflammatory responses are necessary, over-activated inflammation is the common soil for many diseases. The impact of inflammation on myopia has received rising attention in recent years. Elevated inflammation may contribute to myopia progression either directly or indirectly by inducing scleral remodeling, and myopia development may also increase ocular inflammation. This article provides a comprehensive review of the interplay between inflammation and myopia and the potential biological mechanisms, which may present new targets for understanding the pathology of myopia and developing myopia therapies.

BackgroundRecent studies have suggested a possible association between gut microbiota and bipolar disorder (BD). However, observational studies are limited and there are variations between the gut microbiota taxa found in different studies. Therefore, we aimed to explore whether there is a causal relationship between gut microbiota and bipolar disorder at the genetic level and to reveal trends in the effect of influential gut microbiota on the development of bipolar disorder.MethodsWe conducted a Mendelian randomisation (MR) study of summary statistics from a genome-wide association study (GWAS) of gut microbiota and bipolar disorder. Inverse variance weighting (IVW) was used as the primary method of statistical analysis, while results from the MR-Egger method, weighted median, weighted mode, and MR multiplicity residuals and outliers (MR-PRESSO) tests were used for additional validation.Cochrane’s Q test, MR-Egger intercept test, and MR-PRESSO global test were used to test MR results for stability and reliability.ResultWe identified 13 gut microbial taxa causally associated with bipolar disorder. Betaproteobacteria, Acidaminococcaceae, Eubacterium xylanophilum group, Butyricimonas, Peptococcus, Prevotella 7, Roseburia, Terrisporobacter, Burkholderiales and Desulfovibrionales increased the risk of BD, whereas Candidatus Soleaferrea, Ruminiclostridium 5 and Victivallis decreased the risk of BD. The results of the MR analysis were shown to be reliable in the sensitivity analysis.ConclusionWith the MR study, we analysed the causal relationship between 196 gut microbial taxa and bipolar disorder and also identified gut microbiota associated with the risk of developing bipolar disorder. Our findings provide new biomarkers and potential therapeutic targets for the prevention and treatment of BD.

To solve the problem of large torque ripple of interior permanent magnet synchronous motor (IPMSM), the rotor surface notch design method was used for V-type IPMSM. In order to accurately obtain the optimal parameter values to improve the torque performance of the motor, this paper takes the output torque capacity and torque ripple as the optimization objectives, and proposes a multi-objective layered optimization method based on the parameter hierarchical design combined with Taguchi method and response surface method (RSM). The conclusion can be drawn by comparing the electromagnetic performance of the motor before and after optimization, the proposed IPMSM based on the rotor surface notch design can not only improve the output torque, but also play an obvious inhibition effect on the torque ripple.

Abstract Background BMPR1B (Bone morphogenetic protein receptor type-1B) is a receptor in the bone morphogenetic protein (BMP) family and has been identified as a candidate gene for reproductive traits in pigs. Our previous study in Taihu pigs found a specific estrogen response element (ERE) in the first intron of the BMPR1B gene that is associated with the number born alive trait. However, little is known about the mechanism by which the ERE regulates the expression of BMPR1B in the endometrium. Results Here, a 15-bp InDel (insertion/deletion) (AGCCAGAAAGGAGGA) was identified as a unique variation in Taihu pigs, and was shown to be responsible for the binding of the type I receptor of estrogen (ESR1) to the ERE using dual-luciferase assays. Four BMPR1B transcripts (T1, T2, T3, and T4) were identified by 5′ RACE in endometrial tissue. Expression of T3 and T4 in the endometrium of Meishan pigs was significantly higher than in Duroc pigs during pregnancy. Luciferase assays showed that three distinct BMPR1B promoters may drive expression of T1, T3, and T4. Interestingly, ERE-mediated enhancement of T4 promoter activity significantly increased expression of Transcript T4 in the endometrium of Taihu pigs (P

Herein, a series of novel O-alkyl ferulamide derivatives were designed and synthesised through the multi-target-directed ligands (MTDLs) strategy. The biological activities in vitro showed that compounds 5a, 5d, 5e, 5f, and 5h indicated significantly selective MAO-B inhibitory potency (IC50 = 0.32, 0.56, 0.54, 0.73, and 0.86 μM, respectively) and moderate antioxidant activity. Moreover, compounds 5a, 5d, 5e, 5f, and 5h showed potent anti-inflammatory properties, remarkable effects on self-induced Aβ1-42 aggregation, and potent neuroprotective effect on Aβ1-42-induced PC12 cell injury. Furthermore, compounds 5a, 5d, 5e, 5f, and 5h presented good blood–brain barrier permeation in vitro and drug-like properties. More interesting, the PET/CT images with [11C]5f demonstrated that [11C]5f could penetrate the BBB with a high brain uptake and exhibited good brain clearance kinetic property. Therefore, compound 5f would be a promising multi-functional agent for the treatment of AD.

The external morphology and morphological variations of Sepiella inermis vary across regions, necessitating investigation. However, the histological information on the subcutaneous gland has been insufficient to describe it. In this study, specimens were systematically collected and characterized from the Gulf of Thailand. Regarding external morphology, female cuttlebones exhibit greater width and more pronounced curves compared to males, while males feature 17–19 white dots along the fin margins. The presence of the subcutaneous gland was discerned during the embryonic stage at stage 19. A histological study of the subcutaneous gland illustrated the structure and development of the gland in both embryonic and adult stages, with four layers of membranes covering the gland. In the adult stage, trabeculae are dispersed throughout the gland, whereas in the embryonic stage, they form four distinct lines. The morphometric analysis revealed significant differences between males and females (p < 0.05) and the morphological variations within both sexes across the seven study areas exhibit significant differences (p < 0.05). According to the discriminant analysis results, there were significant differences (p < 0.05) between the groups in Surat Thani Province. Examining the length–weight relationship between dorsal mantle length and body weight showed significant differences between the sexes, indicating an allometric growth.

This paper studies a long short-term memory (LSTM)-based coherent mortality forecasting method for developing countries or regions. Many of such developing countries have experienced a rapid mortality decline over the past few decades. However, their recent mortality development trend is not necessarily driven by the same factors as their long-term behavior. Hence, we propose a time-varying mortality forecasting model based on the life expectancy and lifespan disparity gap between these developing countries and a selected benchmark group. Here, the mortality improvement trend for developing countries is expected to converge gradually to that of the benchmark group during the projection phase. More specifically, we use a unified deep neural network model with LSTM architecture to project the life expectancy and lifespan disparity difference, which further controls the rotation of the time-varying weight parameters in the model. This approach is applied to three developing countries and three developing regions. The empirical results show that this LSTM-based coherent forecasting method outperforms classical methods, especially for the long-term projections of mortality rates in developing countries.