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The tumor protein D52 (TPD52) is an oncogene overexpressed in breast cancer. Although the oncogenic effects of TPD52 are well recognized, how its expression and the role in migration/invasion is still not clear. This study tried to explore the regulative role of microRNA-34a (miR-34a), a tumor suppressive miRNA, on TPD52 expression in breast cancer. The expression of miR-34a was found significantly decreased in breast cancer specimens with lymph node metastases and breast cancer cell lines. The clinicopathological characteristics analyzed showed that lower expression levels of miR-34a were associated with advanced clinical stages. Moreover, TPD52 was demonstrated as one of miR-34a direct targets in human breast cancer cells. miR-34a was further found significantly repress epithelial-mesenchymal transition (EMT) and inhibit breast cancer cell migration and invasion via TPD52. These findings indicate that miR-34a inhibits breast cancer progression and metastasis through targeting TPD52. Consequently, our data strongly suggested that oncogenic TPD52 pathway regulated by miR-34a might be useful to reveal new therapeutic targets for breast cancer. [ABSTRACT FROM AUTHOR]

Objective: Abnormally increased somatic cell counts (SCCs) in milk is usually a sign of bovine subclinical mastitis. Mutual interaction between the host and its associated microbiota plays an important role in developing such diseases. The main objective of this study was to explore the difference between cows with elevated SCCs and healthy cattle from the perspective of host-microbe interplay., Methods: A total of 31 milk samples and 23 bovine peripheral blood samples were collected from Holstein dairy cattle to conduct an integrated analysis of transcriptomic and metagenomics., Results: The results showed that Ralstonia and Sphingomonas were enriched in cows with subclinical mastitis. The relative abundance of the two bacteria was positively correlated with the expression level of bovine transcobalamin 1 and uridine phosphorylase 1 encoding gene. Moreover, functional analysis revealed a distinct alternation in some important microbial biological processes., Conclusion: These results reveal the relative abundance of Ralstonia and Sphingomonas other than common mastitis-causing pathogens varied from healthy cows to those with subclinical mastitis and might be associated with elevated SCCs. Potential association was observed between bovine milk microbiota composition and the transcriptional pattern of some genes, thus providing new insights to understand homeostasis of bovine udder.

The promulgation and execution of green credit (GC) policies have had a significant influence on the development of the economy and society, and their impact on low-carbon development (LCD) needs to be taken seriously. On the basis of elaborating the mechanism of the role of GC on LCD, this study constructs a panel fixed effects (FE) model to test the direct impact of GC on LCD by using Chinese provincial-level data from 2007 to 2020. An intermediary effect model is constructed to investigate its indirect effects. A dynamic SDM is further constructed to examine the spatial effects of GC on LCD in neighbouring regions. The results show that GC is helping China to achieve LCD. GC can promote LCD through promoting green innovation, optimizing energy structure and upgrading industrial structure. It is crucial to acknowledge that all three pathways are essential channels of influence and should not be disregarded. GC not only fosters LCD in the local areas, but also has a positive spatial spillover effect in adjacent regions. Based on the above conclusions, this study proposes policy recommendations such as increasing support for GC, smoothing the transmission channel from GC to LCD, and establishing a synergistic linkage mechanism between interregional credit and environmental governance. This study provides valuable insights for China to realize LCD, as well as for other countries to actively engage in energy conservation and emission reduction efforts., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Systemic atherosclerosis and carotid intima-media thickness (IMT) have been widely used in clinical practice for ischemic stroke; however, little is known about the risk factors for unruptured intracranial aneurysms (UIAs) in patients with ischemic stroke (IS). Therefore, we performed this study to identify the risk factors and construct a prediction model for UIA in patients with IS., Methods: Data were retrospectively collected from patients with IS from 2015 to 2022 at the First Hospital of Quanzhou City, Quanzhou, Fujian, China. Risk factors for UIA in patients with IS were identified using a multivariate logistic regression model, and a receiver operating characteristic (ROC) curve was applied to construct the prediction model., Results: Out of the 122 patients with IS, 52 who presented with UIA (ISUIA) were categorized into the study group and the remaining 70 IS patients without UIA into the control group. Patients in the ISUIA group had lower carotid IMT and carotid artery plaque scores than those in the IS group ( P < 0.05). Multivariate analyses found that aspirin use (OR: 12.987; P = 0.031), elevated C-reactive protein (CRP) level (OR: 1.019; P = 0.004), and carotid IMT > 0.09 mm (OR: 0.218; P < 0.001) were significantly associated with the risk of UIA in patients with IS. However, UIA in patients with IS was unaffected by the carotid artery plaque score ( P = 0.114). The constricted prediction model based on the abovementioned factors for UIA in IS patients was 0.79 (95% CI: 0.71-0.87)., Conclusion: The findings revealed that the risk factors for UIA in patients with IS included aspirin use, elevated CRP level, and smaller carotid IMT, and the predictive value of the prediction model was relatively better., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gao, Kang, Zhang, Jiang, He and Wu.)

Background: Folic acid is a water-soluble B vitamin (B9), which is closely related to the body's immune and other metabolic pathways. The folic acid synthesized by rumen microbes has been unable to meet the needs of high-yielding dairy cows. The incidence rate of subclinical mastitis in dairy herds worldwide ranged between 25%~65% with no obvious symptoms, but it significantly causes a decrease in lactation and milk quality. Therefore, this study aims at exploring the effects of folic acid supplementation on the expression profile of lncRNAs, exploring the molecular mechanism by which lncRNAs regulate immunity in subclinical mastitic dairy cows., Results: The analysis identified a total of 4384 lncRNA transcripts. Subsequently, differentially expressed lncRNAs in the comparison of two groups (SF vs. SC, HF vs. HC) were identified to be 84 and 55 respectively. Furthermore, the weighted gene co-expression network analysis (WGCNA) and the KEGG enrichment analysis result showed that folic acid supplementation affects inflammation and immune response-related pathways. The two groups have few pathways in common. One important lncRNA MSTRG.11108.1 and its target genes (ICAM1, CCL3, CCL4, etc.) were involved in immune-related pathways. Finally, through integrated analysis of lncRNAs with GWAS data and animal QTL database, we found that differential lncRNA and its target genes could be significantly enriched in SNPs and QTLs related to somatic cell count (SCC) and mastitis, such as MSTRG.11108.1 and its target gene ICAM1, CXCL3, GRO1., Conclusions: For subclinical mastitic cows, folic acid supplementation can significantly affect the expression of immune-related pathway genes such as ICAM1 by regulating lncRNAs MSTRG.11108.1, thereby affecting related immune phenotypes. Our findings laid a ground foundation for theoretical and practical application for feeding folic acid supplementation in subclinical mastitic cows., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Low-molecular-weight heparin (LMWH) and fondaparinux sodium (FPX) are routinely used to prevent deep vein thrombosis (DVT) after total knee arthroplasty (TKA). In this study, we compared the effects of these agents in preventing post-TKA DVT., Methods: Clinical data of patients who underwent unilateral TKA for unicompartmental knee osteoarthritis at the Ningxia Medical University General Hospital between September 2021 and June 2022 were retrospectively analyzed. Based on the anticoagulation agent used, the patients were divided into LMWH and FPX groups (34 and 37 patients, respectively). Changes in perioperative coagulation-related indicators, d-dimer and platelet count, perioperative complete blood count, amount of blood loss, lower-limb DVT, pulmonary embolism, and allogeneic blood transfusion were determined., Results: Intergroup differences in d-dimer or fibrinogen (FBG) levels before and 1 or 3 days after surgery were not significant (all p > 0.05); within-group pairwise comparisons indicated significant differences (all, p < 0.05). Intergroup differences in preoperative prothrombin time (PT), thrombin time, activated partial PT, and international normalized ratio were not significant (all p > 0.05), whereas significant differences were detected on postoperative days 1 and 3 (all p < 0.05). Intergroup differences in platelet counts before and 1 or 3 days after surgery were not significantly different (all p > 0.05). Pairwise comparisons of hemoglobin and hematocrit levels between patients in the same group before and 1 or 3 days after surgery revealed significant differences in both groups (all p < 0.05); however, intergroup differences were not significant (all p > 0.05). Although intergroup differences in visual analog scale (VAS) scores before and 1 or 3 days after surgery were not significant (p > 0.05), we detected significant intragroup differences in VAS scores before and 1 or 3 days after surgery (p < 0.05). The treatment cost ratio was significantly lower in the LMWH group than in the FPX group (p < 0.05)., Conclusion: Both LMWH and FPX can effectively prevent DVT after TKA. There are some suggestive signals that FPX may have more beneficial pharmacological effects and clinical significance, while LMWH is cheaper and therefore more economical., (© 2023. The Author(s).)

Background: Domestic geese are seasonal breeders and have the lowest reproductive capacity among all poultry species. Magang geese is a topical short-day breeder, short photoperiod exposure stimulates its reproductive activity while long photoperiod inhibits. To explore epigenetic change that could influence reproductive activity, we performed whole genome bisulfite sequencing and transcriptome sequencing in the hypothalamus at three reproductive stages during long-light exposure in male Magang geese., Results: A total number of 10,602 differentially methylated regions (DMRs) were identified among three comparison groups. We observed that the vast majority of DMRs were enriched in intron regions. By integrating the BS-sequencing and RNA-seq data, the correlation between methylation changes of CG DMRs and expression changes of their associated genes was significant only for genes containing CG DMRs in their intron. A total of 278 DMR-associated DEGs were obtained among the three stages. KEGG analysis revealed that the DMR-associated DEGs were mainly involved in 11 pathways. Among them, the neuroactive ligand-receptor interaction pathway was significantly enriched in both two comparisons (RA vs.RD and RD vs.RI); the Wnt signaling pathway, apelin signaling pathway, melanogenesis, calcium signaling pathway, focal adhesion, and adherens junction were significantly enriched in the RA vs. RI comparison. In addition, the expression level of two serotonin-metabolic genes was significantly altered during reproductive axis inactivation by the methylation status of their promoter region (TPH2) and intron region (SLC18A2), respectively. These results were confirmed by Bisulfite sequencing PCR (BSP), pyrosequencing, and real-time qPCR, indicating that serotonin metabolic signaling may play a key role in decreasing the reproductive activity of Magang geese induced by long-light exposure. Furthermore, we performed a metabolomics approach to investigate the concentration of neurotransmitters among the three stages, and found that 5-HIAA, the last product of the serotonin metabolic pathway, was significantly decreased in the hypothalamus during RI., Conclusions: Our study reveals that the methylation status of the serotonin metabolic pathway in the hypothalamus is associated with reproductive inactivation, and provided new insight into the effect of DNA methylation on the reproductive regulation of the hypothalamus in Magang geese., (© 2023. The Author(s).)

The development and application of digital finance has brought profound changes to the real economy, and its impact on industrial green total factor productivity is worthy of attention and evaluation. The industrial green total factor productivity of each province in China is measured by using EBM-ML index with the provincial panel data collected from 2011 to 2020. The panel fixed effects model is used to estimate the impact of digital finance on industrial green total factor productivity. The intermediary effect model is constructed to analyze its conduction mechanisms. The heterogeneity of the impact of digital finance on industrial green total factor productivity is further explored. The results indicate that digital finance makes a significant contribution to the promotion of industrial green total factor productivity. Digital finance indirectly promotes the enhancement of industrial green total factor productivity by promoting technological innovation, driving industrial upgrading and stimulating entrepreneurial dynamism. The impact of digital finance on industrial green total factor productivity has obvious sub-dimension heterogeneity and regional heterogeneity. Based on the above conclusions, we also suggest policy recommendations such as unblocking the conduction channels of digital finance and implementing the differentiated digital finance development strategy. The highlight of this paper is that it takes digital finance as the entry point and shifts the research content to the real economy, broadening the research perspective of "digital finance"., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

To date, digital economy has become an emerging driving force of economic growth in various countries. To further explore the green value of digital economy, full array polygon graphic index method and Global Malmquist productivity index are used to evaluate China's digital economy development and green total factor productivity respectively. Based on a comprehensive explanation of the influence mechanism, spatial econometric model and intermediary effect model are constructed to test the spatial spillover effect and transmission mechanism between digital economy and green total factor productivity. The results show that digital economy has a positive direct impact and spatial spillover effect on green total factor productivity with the significant U-shaped characteristics, and these effects mainly come from the promotion of green technology progress by digital economy. Industrial structure upgrading and factor market distortion respectively account for 22 % and 5.875 % of the impact of digital economy on green total factor efficiency, which means that they are the two primary channels for digital economy to influence green total factor productivity. Results of heterogeneity analysis show that digital economy is the key factor for resource-based cities to break the "resource curse", but the unbalanced development of digital economy leads to the "digital gap" between the central and peripheral cities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Recent studies have increasingly pointed to microRNAs (miRNAs) as the agent of gene regulatory network (GRN) stabilization as well as developmental canalization against constant but small environmental perturbations. To analyze mild perturbations, we construct a Dicer-1 knockdown line (dcr-1 KD) in Drosophila that modestly reduces all miRNAs by, on average, ∼20%. The defining characteristic of stabilizers is that, when their capacity is compromised, GRNs do not change their short-term behaviors. Indeed, even with such broad reductions across all miRNAs, the changes in the transcriptome are very modest during development in stable environment. By comparison, broad knockdowns of other regulatory genes (esp. transcription factors) by the same method should lead to drastic changes in the GRNs. The consequence of destabilization may thus be in long-term development as postulated by the theory of canalization. Flies with modest miRNA reductions may gradually deviate from the developmental norm, resulting in late-stage failures such as shortened longevity. In the optimal culture condition, the survival to adulthood is indeed normal in the dcr-1 KD line but, importantly, adult longevity is reduced by ∼90%. When flies are stressed by high temperature, dcr-1 KD induces lethality earlier in late pupation and, as the perturbations are shifted earlier, the affected stages are shifted correspondingly. Hence, in late stages of development with deviations piling up, GRN would be increasingly in need of stabilization. In conclusion, miRNAs appear to be a solution to weak but constant environmental perturbations., Competing Interests: Conflict of interest statement. The authors declare that they have no competing interests., (© The Author(s) 2023. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.)

Considering that artificial insemination is the most widely used assisted reproductive technique in the dairy industry, the semen quality of bulls is very important for selecting excellent stud bulls. Sperm motility is one of the important traits of semen quality, and related genes may be regulated by environmental factors. Seminal plasma can affect sperm cell transcriptome and further affect sperm motility through exosome or other processes. However, the molecular regulation mechanism of bull sperm motility has not been studied by combining the sperm cell transcriptome with seminal plasma metabolome. The number of motile sperm per ejaculate (NMSPE) is an integrated indicator for assessing sperm motility in stud bulls. In the present study, we selected 7 bulls with higher NMSPE (5,698.55 million +/- 945.40 million) as group H and 7 bulls with lower NMSPE (2,279.76 million +/- 1,305.69 million) as group L from 53 Holstein stud bulls. The differentially expressed genes (DEGs) in sperm cells were evaluated between the two groups (H vs. L). We conducted gene co-expression network analysis (WGCNA) on H and L groups of bulls, as well as two monozygotic twin Holstein bulls with different NMSPE values, to screen candidate genes for NMSPE. The regulatory effect of seminal plasma metabolome on the candidate genes of NMSPE was also investigated. A total of 1,099 DEGs were identified in the sperm cells of H and L groups. These DEGs were primarily concentrated in energy metabolism and sperm cell transcription. The significantly enriched Kyoto encyclopedia of genes and genomes (KEGG) pathways of the 57 differential metabolites were the aminoacyl-tRNA biosynthesis pathway and vitamin B6 metabolism pathway. Our study discovered 14 genes as the potential candidate markers for sperm motility, including FBXO39. We observed a broad correlation between transcriptome of sperm cells and seminal plasma metabolome, such as three metabolites, namely, mesaconic acid, 2-coumaric acid, and 4-formylaminoantipyrine, might regulate FBXO39 expression through potential pathways. The genes related to seminal plasma metabolites expressed in sperm cells are not only located near the quantitative trait loci of reproductive traits, but also enriched in the genome-wide association study signal of sire conception rate. Collectively, this study was the first to investigate the interplays among transcriptome of sperm cells and seminal plasma metabolome from Holstein stud bulls with different sperm motility., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Society of Animal Science.)

Objectives: Poor adherence among patients with chronic diseases including inflammatory rheumatic diseases (IRDs) is a complex and serious global health care problem. This study aimed to develop an intelligent nomogram using retrospectively collected patient clinical data for predicting nonadherence to biologic treatment in rheumatoid arthritis (RA) patients., Methods: The clinical characteristics of 102 RA patients were collected from outpatients and inpatients at the Orthopedic Departments of Ningxia General Hospital of Ningxia Medical University and Ningxia Hui Autonomous Region People's Hospital from October 2020 to September 2021. Adherence was evaluated using the proportion of treatment days covered within 6 months as the outcome event. A least absolute shrinkage and selection operator (LASSO) regression analysis was used to identify risk predictors, and then multivariate logistic regression analysis was applied to construct the risk prediction model. Furthermore, the nomogram was plotted by multivariable logistic regression., Results: Among the 102 patients analyzed, 43 patients did not adhere to biologic therapy for various reasons. LASSO regression analysis identified age, sex, education level, disease activity, monthly income, medical insurance, and adverse drug reactions as the significant risk predictors. By incorporating these factors, the nomogram was plotted which showed good discrimination, calibration, and clinical value. The C-index was 0.759 (95% CI: 0.665-0.853), and the area under the receiver operating characteristic (ROC) curve was 0.7416 with a good calibration ability. Decision curve analysis showed that the prediction effect of this model could benefit about 75% of the patients without compromising the interests of other patients., Conclusions: This nomogram could help medical staff identify patients with higher risk of nonadherence early, so that intervention measures can be taken in time., Competing Interests: None., (AJTR Copyright © 2022.)

Although chromosomal mosaic embryos detected by trophectoderm (TE) biopsy offer healthy embryos available for transfer, high-resolution postnatal karyotyping and chromosome testing of the transferred embryos are insufficient. Here, we applied single-cell multi-omics sequencing for seven infants with blastula chromosomal mosaicism detected by TE biopsy. The chromosome ploidy was examined by single-cell genome analysis, with the cellular identity being identified by single-cell transcriptome analysis. A total of 1616 peripheral leukocytes from seven infants with embryonic chromosomal mosaicism and three control ones with euploid TE biopsy were analyzed. A small number of blood cells showed copy number alterations (CNAs) on seemingly random locations at a frequency of 0%-2.5% per infant. However, none of the cells showed CNAs that were the same as those of the corresponding TE biopsies. The blastula chromosomal mosaicism may be fully self-corrected, probably through the selective loss of the aneuploid cells during development, and the transferred embryos can be born as euploid infants without mosaic CNAs corresponding to the TE biopsies. The results provide a new reference for the evaluations of transferring chromosomal mosaic embryos in certain situations., (Copyright © 2022 Beijing Institute of Genomics. Published by Elsevier B.V. All rights reserved.)

Based on the panel data of 30 Chinese provinces, the Cobb-Douglas production function and GML index were constructed to measure the degree of land price distortion and green development efficiency, respectively, in China, and the System Generalised Method of Moments model was employed to explore the relationship between land price distortion and green development efficiency, and a mediating effect model was further constructed to analyse the transmission mechanism. The results show that, first, land price in China is characterised by a negative distortion, but the degree of negative distortion tends to decrease after 2010. Second, land price distortion significantly inhibits the improvement of green development efficiency; this conclusion still holds after a series of robustness tests, and land price distortion significantly promotes the progress of green technology, while significantly inhibiting the improvement of green technology efficiency. Third, the results of the mediating effect show that the inhibiting effect of land price distortion on green development efficiency is mainly achieved through three channels: house price, industrial structure and infrastructure. Finally, policy recommendations for green sustainable development are put forward from the aspects of land supply structure adjustment and so on., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The aim of this study was to investigate the effect of coenzyme Q10 (CoQ10), a commonly used nutritional supplement, on intracranial aneurysm (IA) initiation and progression in a mouse model, as well as the mechanism., Methods: Hydrogen peroxide (H 2 O 2 ) was used to treat mouse-derived vascular smooth muscle cells (VSMCs) to induce oxidative injury, followed by incubation with CoQ10. In the mouse IA model established by elastase injection, CoQ10 was orally administered at 10 mg/kg every other day for 14 days, during which the incidence of IA, rupture rate, symptom-free survival, and systolic blood pressure were recorded., Results: CoQ10 promoted the expression of nuclear factor erythroid 2-related factor 2 and antioxidant enzymes. In H 2 O 2 -treated VSMCs, reactive oxygen species and cell apoptosis were reduced by CoQ10. In IA mice, CoQ10 treatment decreased the rupture rate of IA, improved the symptom-free survival, and reduced systolic blood pressure. Macrophage infiltration and expression of pro-inflammatory cytokines in the cerebral arteries were mitigated by CoQ10 treatment., Conclusions: CoQ10 is effective in reducing oxidative stress in VSMCs, thereby attenuating IA formation and rupture in mice. CoQ10 also alleviates inflammation and restores normal phenotypes of VSMCs in the cerebral arteries. Our data suggest that CoQ10 is a potentially effective drug for managing IA., Impact: To investigate the effect of CoQ10, a commonly used nutritional supplement, on IA initiation and progression in a mouse model, as well as the mechanism. CoQ10 promoted the expression of Nrf2 and antioxidant enzymes. In H 2 O 2 -treated VSMCs, ROS and cell apoptosis were reduced by CoQ10. CoQ10 is effective in reducing oxidative stress in VSMCs, thereby attenuating IA formation and rupture in mice., (© 2021. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Background: Staphylococcus aureus (S. aureus) mastitis is one of the most difficult diseases to treat in lactating dairy cows worldwide. S. aureus with different lineages leads to different host immune responses. Long non-coding RNAs (lncRNAs) are reported to be widely involved in the progress of inflammation. However, no research has identified stable lncRNAs among different S. aureus strain infections. In addition, folic acid (FA) can effectively reduce inflammation, and whether the inflammatory response caused by S. aureus can be reduced by FA remains to be explored., Methods: lncRNA transcripts were identified from Holstein mammary gland tissues infected with different concentrations of S. aureus (in vivo) and mammary alveolar cells (Mac-T cells, in vitro) challenged with different S. aureus strains. Differentially expressed (DE) lncRNAs were evaluated, and stable DE lncRNAs were identified in vivo and in vitro. On the basis of the gene sequence conservation and function conservation across species, key lncRNAs with the function of potentially immune regulation were retained for further analysis. The function of FA on inflammation induced by S. aureus challenge was also investigated. Then, the association analysis between these keys lncRNA transcripts and hematological parameters (HPs) was carried out. Lastly, the knockdown and overexpression of the important lncRNA were performed to validate the gene function on the regulation of cell immune response., Results: Linear regression analysis showed a significant correlation between the expression levels of lncRNA shared by mammary tissue and Mac-T cells (P < 0.001, R 2  = 0.3517). lncRNAs PRANCR and TNK2-AS1 could be regarded as stable markers associated with bovine S. aureus mastitis. Several HPs could be influenced by SNPs around lncRNAs PRANCR and TNK2-AS1. The results of gene function validation showed PRANCR regulates the mRNA expression of SELPLG and ITGB2 within the S. aureus infection pathway and the Mac-T cells apoptosis. In addition, FA regulated the expression change of DE lncRNA involved in toxin metabolism and inflammation to fight against S. aureus infection., Conclusions: The remarkable association between SNPs around these two lncRNAs and partial HP indicates the potentially important role of PRANCR and TNK2-AS1 in immune regulation. Stable DE lncRNAs PRANCR and TNK2-AS1 can be regarded as potential targets for the prevention of bovine S. aureus mastitis. FA supplementation can reduce the negative effect of S. aureus challenge by regulating the expression of lncRNAs., (© 2021. The Author(s).)

Intracranial aneurysm (IA) is a common type of refractory cerebrovascular diseases. Inflammatory responses have been reported to be associated with the pathogenesis of IA. We aimed to study the role of STAT3 on IA formation and inflammatory response. STAT3 expression and clinicopathological factors were analyzed in IA and normal cerebral arteries. mRNA level of STAT3 was detected in normal, unruptured, and ruptured IA tissues by RT-PCR and Western blot. Inflammatory cytokines were examined by ELISA in unruptured, ruptured IA tissues, as well as cells with STAT3 overexpression or knockdown. mRNA of phenotypic modulation-related factors was tested by RT-PCR in STAT3 overexpressing or knockdown VSMCs. STAT3 expression was upregulated in ruptured IA tissues and highly associated with IA diameter and IA type. Inflammatory cytokine secretion was increased in ruptured IA samples and positively correlated with STAT3 expression. STAT3 overexpression led to enhanced expression of SM-α actin, SM-MHC, MMP2, and MMP9, and increased secretion of inflammatory cytokines. Our findings have demonstrated that STAT3 is a key regulator in IA formation by modulating inflammatory cytokine expression., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Intracranial aneurysm rupture is the main cause of subarachnoid hemorrhage, leading to high disability and mortality. This study aimed to evaluate the clinical treatment effects of multiple overlapping stent-assisted coiling for complex intracranial aneurysms., Methods: We conducted a randomized, controlled, single-blinded clinical trial among 168 patients diagnosed with complex intracranial aneurysms. Treatment allocation to either single stent (SS) group or multiple stent (MS) group was randomized at 1:1 ratio using a Web-based platform. The O'Kelly-Marotta (OKM) grading scale was used to evaluate the degree of aneurysm occlusion after operation and during follow-up. Good aneurysm occlusion was defined as OKM grade C-D. The modified Rankin Scale (mRS) was used to evaluate the neurological status and the clinical outcome of patients., Results: Efficacy comparative analysis demonstrated that major recurrence of aneurysms was significantly reduced in the MS group (P = 0.012). In addition, the MS group displayed significantly reduced number of patients with mRS between 3 and 6 (P = 0.007) and increased number of patients with mRS between 0 and 1 (P = 0.034). Furthermore, the MS group showed increased percentage of patients with OKM grade C-D (P = 0.041). Compared with the SS group, the MS group exhibited decreased mortality (P = 0.037) and morbidity (P = 0.035)., Conclusions: Multiple overlapping stent-assisted coiling significantly improved the clinical treatment effects and provided a new method for complex intracranial aneurysms., (© 2021. The Author(s).)

Background: To investigate the expression and clinical significance of EFNA1 in broad-spectrum tumors, and to evaluate its relationship with prognosis and biological functions of esophageal carcinoma (ESCA)., Methods: EFNA1 expression in various cancers was analyzed according to the data in the TCGA database. The clinical data were integrated, to analyze the relationship with ESCA clinical parameters and prognosis, and EFNA1 expression in ESCA tissue samples was detected by immunohistochemistry (IHC). Based on bioinformatics, the functional background of EFNA1 overexpression was analyzed. EFNA1 knockout cell model was established by EFNA1-shRNA transfecting ESCA cells, and the effect of knocking down EFNA1 on the proliferation of ESCA cells was detected by MTT., Results: Among 7563 samples from TCGA, the EFNA1 gene highly expressed in 15 samples with common cancers and endangered the prognosis of patients with tumors. Its overexpression in ESCA and its influence on the prognosis were most significant. EFNA1 expression in 80 samples with ESCA and their paired samples was tested by IHC to verify its high expression (paired t test, P < 0.001) in ESCA tissues. It was found that EFNA1 expression was related to clinical factors (TNM staging, P = 0.031; lymph node metastasis, P = 0.043; infiltration, P = 0.016). Meanwhile, EFNA1 was found to be an independent risk factor based on the COX multi-factor analysis. And to further explore the importance of EFNA1 in tumors, EC-9706 and ECA109 cells were screened from 8 ESCA-related cell lines to build EFNA1 knockdown cell models. The results showed that EFNA1 knockdown significantly inhibited the proliferation of tumor cells (P < 0.05). In terms of molecular mechanism, EFNA1 related genes were significantly enriched in the proliferative pathway according to the pathway enrichment analysis. It was found that knocking down EFNA1 did inhibit cell proliferation based on cell experiments., Conclusions: EFNA1 overexpression in ESCA tissue is related to the prognosis of patients. Knocking down EFNA1 can significantly inhibit the proliferation of ESCA cells., (© 2021. The Author(s).)

Traumatic brain injury (TBI) causes permanent neurological and cognitive impairments. Effective pharmacological interventions remain elusive. Spermidine is a polyamine compound found in our body that may play a role in brain development and congenital function. In this study, we aimed to investigate the therapeutic potential of spermidine for TBI. We employed experimental closed head injury (CHI) model to evaluate the protective function of spermidine on brain injury. We assessed the neurobehavioral function recovery using Neurologic Severity Score (NSS) and Morris water maze test. At histological level, we evaluated the improvement on brain edema, brain-blood barrier integrity, and cell apoptosis. We also measured inflammatory cytokines and brain injury biomarkers to monitor the treatment outcomes. Last, we correlated the level of spermidine with CHI animal model and TBI patients with different levels of severity. Spermidine administration post-CHI was found effectively to accelerate NSS improvement and shorten latency in maze test. We observed consistent improvements in brain edema, BBB function, and cell death in spermidine-treated group. Inflammatory cytokines and TBI biomarkers, e.g., S100B, MBP and CFAP were reduced significantly in treatment group. Interestingly, inhibiting spermidine synthesis influenced the neurobehavioral recovery in CHI mice. ODC1, a rate-limiting enzyme for spermidine synthesis, was found lower in CHI mice. Serum level of spermidine was significantly lower in TBI patients with severe pathological scores. Spermidine pathway may carry an endogenous role in pathophysiological process of CHI. For the first time, we demonstrated that administrating spermidine may provide a new treatment for TBI.

The tumor protein D52 (TPD52) is an oncogene overexpressed in breast cancer. Although the oncogenic effects of TPD52 are well recognized, how its expression and the role in migration/invasion is still not clear. This study tried to explore the regulative role of microRNA-34a (miR-34a), a tumor suppressive miRNA, on TPD52 expression in breast cancer. The expression of miR-34a was found significantly decreased in breast cancer specimens with lymph node metastases and breast cancer cell lines. The clinicopathological characteristics analyzed showed that lower expression levels of miR-34a were associated with advanced clinical stages. Moreover, TPD52 was demonstrated as one of miR-34a direct targets in human breast cancer cells. miR-34a was further found significantly repress epithelial-mesenchymal transition (EMT) and inhibit breast cancer cell migration and invasion via TPD52. These findings indicate that miR-34a inhibits breast cancer progression and metastasis through targeting TPD52. Consequently, our data strongly suggested that oncogenic TPD52 pathway regulated by miR-34a might be useful to reveal new therapeutic targets for breast cancer.

Objective: To summarize the clinical experiences of microsurgical and endovascular treatments of complicated arteriovenous malformation (AVM) in the conditions of hybrid operating room., Methods: The clinical data were collected and analyzed for 8 patients of complex AVM between June 2012 to June 2013. There were Spetzler grade III (n = 2) and grade IV (n = 6). And the lesions were complicated with intracranial aneurysms (n = 3) and located in motor area (n = 2) and basal ganglia (n = 2). Five cases of AVM with cerebral hemorrhage underwent emergency surgery, including digital subtraction angiography (DSA) plus intraoperative embolization plus surgical resection of AVM plus intraoperative DSA (iDSA). Two cases underwent embolization plus aneurysm surgery while another had AVM embolization plus AVM resection and γ knife treatment., Results: All surgical procedures, including iDSA, were completed in the same hybrid operating room. There was no change of surgical position or intraoperative mortality. Five patients of AVM hemorrhage undergoing emergency hematoma evacuation had no residue of AVM on iDSA. Their postoperative consciousness improved without neurological dysfunction. Two patients of limb paralysis recovered to paresis at 3 months postoperation. One case with blurry vision improved somewhat. Two cases undergoing elective surgery had a complete resection of AVM after embolization., Conclusion: Surgery plus endovascular treatment in hybrid operating room is efficacious for complex cerebral AVM. It avoids multiple surgeries and inspections. And any lesion residue may be assessed immediately with postoperative DSA.