Extracellular vesicles containing circMYBL1 induce CD44 in adenoid cystic carcinoma cells and pulmonary endothelial cells to promote lung metastasis.

Adenoid cystic carcinoma (ACC) is a rare malignant epithelial neoplasm that arises in secretory glands and commonly metastasizes to the lungs. MYBL1 is frequently overexpressed in ACC and has been suggested to be a driver of the disease. Here, we identified a circRNA derived from MYBL1 pre-mRNA that accompanied overexpression of MYBL1 in ACC. Overexpression of circMYBL1 was correlated with increased lung metastasis and poor overall survival in ACC patients. Ectopic circMYBL1 overexpression promoted malignant phenotypes and lung metastasis of ACC cells. Mechanistically, circMYBL1 formed a circRNA-protein complex with CCAAT enhancer binding protein beta (CEBPB), which inhibited ubiquitin-mediated degradation and promoted nuclear translocation of CEBPB. In the nucleus, circMYBL1 increased the binding of CEBPB to the CD44 promoter region and enhanced its transcription. In addition, circMYBL1 was enriched in small extracellular vesicles (sEVs) isolated from the plasma of ACC patients. Treatment with sEVs containing circMYBL1 in sEVs enhanced pro-metastatic phenotypes of ACC cells, elevated the expression of CD44 in human pulmonary microvascular endothelial cells (HPMECs), and enhanced the adhesion between HPMECs and ACC cells. Moreover, circMYBL1 encapsulated in sEVs increased the arrest of circulating ACC cells in the lung and enhanced the lung metastatic burden. This data suggests that circMYBL1 is a tumor-promoting circRNA that could serve as a potential biomarker and therapeutic target in ACC.

Catalase-templated nanozyme-loaded microneedles integrated with polymyxin B for immunoregulation and antibacterial activity in diabetic wounds.

Diabetic wounds are characterized by chronic trauma, with long-term non-healing attributed to persistent inflammation and recurrent bacterial infections. Exacerbation of the inflammatory response is largely due to increased levels of reactive oxygen species (ROS). In this study, catalase (CAT) was used as a biological template to synthesize nanozyme-supported natural enzymes (CAT-Mn(SH)x) using a biomimetic mineralization method. Subsequently, polymyxin B (CAT-Mn(SH)x@PMB) was immobilized on its surface through electrostatic assembly. CAT-Mn(SH)x@PMB demonstrates the ability for slow and sustained release of hydrogen sulfide (H2S). Finally, CAT-Mn(SH)x@PMB loaded microneedles (MNs) substrate were synthesized using polyvinyl alcohol (PVA) and hydroxyethyl methacrylate (HEMA), and named CAT-(MnSH)x@PMB-MNs. It exhibited enhanced enzyme and antioxidant activities, along with effective antibacterial properties. Validation findings indicate that it can up-regulate the level of M2 macrophages and reduce the level of pro-inflammatory cytokine tumor necrosis factor-α (TNF-α). Additionally, it promotes angiogenesis and rapid nerve regeneration, thereby facilitating wound healing through its dual anti-inflammatory and antibacterial effects. Hence,this study introduces a time-space tissue-penetrating and soluble microneedle patch with dual anti-inflammatory and antibacterial effects for the treatment of diabetic wounds.

ALMS1-IT1: A Key Player in the Novel Disulfidptosis-Related LncRNA Prognostic Signature for Head and Neck Squamous Cell Carcinoma.

Disulfidptosis is a newly discovered form of programmed cell death that is induced by disulfide stress. It is closely associated with various cancers, including head and neck squamous cell carcinoma (HNSCC). However, the factors involved in the modulation of disulfidptosis-related genes (DRGs) still remain unknown. In this study, we established and validated a novel risk score model composed of 11 disulfidptosis-related lncRNAs (DRLs) based on 24 DRGs in HNSCC. The results revealed strong correlations between the 11-DRL prognostic signature and clinicopathological features, immune cell infiltration, immune-related functions, and disulfidptosis-associated pathways, including NADPH and disulfide oxidoreductase activities. Furthermore, we studied and verified the involvement of ALMS1-IT1, one of the 11 model DRLs, in the disulfidptosis of HNSCC cell lines. A series of assays demonstrated that ALMS1-IT1 modulated cell death under starvation conditions in a pentose phosphate pathway (PPP)-dependent manner. Knockdown of ALMS1-IT1 inhibited the PPP, contributing to a decline in NADPH levels, which resulted in the formation of multiple intermolecular disulfide bonds between actin cytoskeleton proteins and the collapse of F-actin in the cytoplasm. Therefore, ALMS1-IT1, which is highly expressed in SLC7A11high cells, can be considered a promising therapeutic target for disulfidptosis-focused treatment strategies for cancer and other diseases.

Epidemiological investigation of Cryptosporidium in children with diarrhea in middle Inner Mongolia, China.

Cryptosporidia (Cryptosporidium) is a protozoan that is widely parasitic in the intestinal cells of humans and animals, and it is also an important zoonotic parasite. However, there is no epidemiological investigation on Cryptosporidium spp. infection in infants with diarrhea of Inner Mongolia, the largest livestock region in China. To investigate the prevalence of Cryptosporidium, 2435 fresh fecal samples were collected from children with diarrhea in Inner Mongolia Maternal and Child Health Care Hospital. Molecular characterization of Cryptosporidium was carried out based on its 18S rRNA and gp60 gene sequences. The overall prevalence was 12.85% (313/2435), and in Hohhot (12.15%), it was lower than that in the surrounding city (14.87%) (P < 0.05). Moreover, Cryptosporidium was detected in different seasons and sexes. Concerning the age of children with diarrhea, the prevalence of those age groups between 0 and 1 was obviously lower than others, and there were significant differences in the prevalence at different ages (P < 0.001). Analysis of the 18S rRNA gene sequence revealed that all the positive samples were Cryptosporidium parvum, and there were 5 subtypes (IIdA23G3, IIdA24G3, IIdA24G4, IIdA25G3, and IIdA25G4). To the best of our knowledge, the above subtypes have not been reported. Our results provide a relevant basis for control and education on food safety and foodborne illness prevention.

Design Synthesis of Low-Silica SAPO-34 Nanocrystals by Constructing Isomorphous Core-Shell Structure: An Effective Catalyst for Improving Catalytic Performances in Methanol-to-Olefins Reaction.

It is well known that low-silica SAPO-34, with an extra porosity (meso- and/or macropores) system, affords excellent catalytic performance in the methanol-to-olefins (MTO) reaction, while the direct synthesis of low-silica SAPO-34 with a hierarchical structure is difficult to achieve, principally because the crystal impurities are usually formed under a low silica content in a gel precursor. Herein, low-silica SAPO-34 nanocrystals were successfully fabricated for the first time by constructing an isomorphous core-shell structure in an epitaxial growth manner. In which, low-silica, ultrasmall nanosquare-shaped SAPO-34 crystals with the same growth orientation along the (100) crystal plane compactly grow on the monocrystal SAPO-34 cores. Crucially, the external surface acid properties of the core SAPO-34 with the Si-rich outer layer are effectively modified by the low-silica SAPO-34 shell. Furthermore, the growth process and Si-substitution mechanism of the shell zeolite were comprehensively investigated. It was found that with the prolonged crystallization time, more and more coordinated Si(4Al) and Si(3Al) structures via two substitution mechanisms (SM2 and SM3) are generated in the nanocrystalline SAPO-34 shell, which endow moderate acidity of the core-shell SAPO-34. Compared to the uncoated SAPO-34, the core-shell SAPO-34 performs a longer lifespan and a higher average selectivity of light olefins (ethylene plus propylene) when applied to the MTO reaction, which is attributed to the positive effects of the luxuriant interstitial pores offering a fast diffusion channel and the moderate acid density depressing the hydrogen transfer reaction of light olefins. This work provides new insights into the fabrication of low-silica SAPO-34 nanocrystals, which are based on the rational design of the isomorphous core-shell zeolite.

Efficient production of peptidylglycine α-hydroxylating monooxygenase in yeast for protein C-terminal functionalization.

Peptidylglycine α-hydroxylating monooxygenase (PHM) is pivotal for C-terminal amidation of bioactive peptides in animals, offering substantial potential for customized protein synthesis. However, efficient PHM production has been hindered by the complexity of animal cell culture and the absence of glycosylation in bacterial hosts. Here, we demonstrate the recombinant expression of Caenorhabditis elegans PHM in the yeast Pichia pastoris, achieving a remarkable space-time yield of 28.8 U/L/day. This breakthrough surpasses prior PHM production rates and eliminates the need for specialized cultivation equipment or complex transfection steps. Mass spectrometry revealed N-glycosylation at residue N182 of recombinant CePHM, which impacts the enzyme's activity as indicated by biochemical experiments. To showcase the utility of CePHM, we performed C-terminal amidation on ubiquitin at a substrate loading of 30 g/L, a concentration meeting the requirements for pharmaceutical peptide production. Overall, this work establishes an efficient PHM production method, promising advancements in scalable manufacturing of C-terminally modified bioactive peptides and probe proteins.

Health risks from extreme heat in China: Evidence from health insurance.

Global warming has accentuated the effects of extreme heat on health. Health insurance, functioning as a risk management tool, has the potential to alleviate these impacts. Consequently, this paper investigates the correlation between extreme heat events and the demand for health insurance in China. Using data from the China Health and Nutrition Survey, we have observed a substantial increase in the likelihood of residents purchasing health insurance during extreme heat events. To be specific, for every extra day of extreme heat events annually, there is a 0.3% increase in the probability of purchasing health insurance. This effect is not uniform across different demographic groups. It is particularly pronounced among middle-aged and elderly individuals, rural residents, those with lower educational levels, higher income brackets, and individuals residing in underprivileged areas with limited access to green spaces and healthcare facilities. Furthermore, our study indicates that the increased frequency of extreme heat events not only impacts individuals' physical health but also triggers negative emotions, which in turn drive risk-averse behavior related to health insurance purchases. These findings carry substantial policy implications for mitigating the economic consequences of climate change.

Predictive value of serum TBA for 2-year MACEs in ACS patients undergoing PCI: a prospective cohort study.

Bile acids play important roles in lipid metabolism and glucose homeostasis. Limited research exist on the association between serum total bile acid (TBA) levels and major adverse cardiovascular events (MACEs) in patients with acute coronary syndrome (ACS), particularly those with comorbid type 2 diabetes mellitus (T2DM). This study was conducted to examine the relationship between baseline serum TBA level and T2DM status in patients with ACS after percutaneous coronary intervention (PCI) and to identify the predictive value of TBA levels for a 2-year risk of MACEs. 425 ACS patients underwent PCI were recruited and divided into three groups based on baseline serum TBA concentration. An analysis of the association between the T2DM status and baseline serum TBA levels was conducted using univariate linear regression and multivariate linear regression. The predictive relevance of serum TBA levels was evaluated using the receiver operating characteristic (ROC) curve and Cox regression. Kaplan-Meier curves were employed to analyze the differences among groups in predicting MACEs over a 2-year follow-up period. Baseline serum TBA levels were higher in ACS patients who were diagnosed with T2DM (the median 3.6 µmol/L) than those without T2DM (the median 3.0 µmol/L). T2DM status in ACS patients was positively correlated with baseline serum TBA concentrations (ß: 1.7, 95% confidence interval [CI] 0.3-3.0), particularly in the male (ß: 2.0, 95% CI 0.3-3.6) and 50-69-year-old (ß: 2.5, 95% CI 0.6-4.4) populations. The areas under the ROC curve of baseline serum TBA levels predicted MACEs in ACS and ACS-T2DM patients following PCI were 0.649 (95% CI 0.595-0.703) and 0.783 (95% CI 0.685-0.881), respectively. Furthermore, Cox regression analysis showed that baseline serum TBA level was associated with the occurrence of MACEs in patients with ACS after PCI over a 2-year follow-up period, especially in those diagnosed with T2DM, whose baseline TBA concentration was lower than 10.0 µmol/L. ACS Patients with T2DM had higher serum TBA levels. TBA level at baseline was an independent predictor of MACEs in ACS patients who underwent PCI, especially with comorbid T2DM.

The trend of allogeneic tendon decellularization: literature review.

Tendon injuries repair is a significant burden for orthopaedic surgeons. Finding a proper graft material to repair tendon is one of the main challenges in orthopaedics, for which the requirement of substitute for tendon repair would be different for each clinical application. Among biological scaffolds, the use of decellularized tendon increasingly represents an interesting approach to treat tendon injuries and several articles have investigated the approaches of tendon decellularization. To understand the outcomes of the the approaches of tendon decellularization on effect of tendon transplantation, a literature review was performed. This review was conducted by searching in Pubmed and Embase and 64 studies were included in this study. The findings revealed that the common approaches to decellularize tendon include chemical, physical, and enzymatic decellularization methods or their combination. With the development of tissue engineering, researchers also put forward new theories such as automatic acellular machine, 3D printing technology to manufacture acellular scaffold.

A multiclass extreme gradient boosting model for evaluation of transcriptomic biomarkers in Alzheimer's disease prediction.

BACKGROUND: Patients with young-onset Alzheimer's disease (AD) (before the age of 50 years old) often lack obvious imaging changes and amyloid protein deposition, which can lead to misdiagnosis with other cognitive impairments. Considering the association between immunological dysfunction and progression of neurodegenerative disease, recent research has focused on identifying blood transcriptomic signatures for precise prediction of AD. METHODS: In this study, we extracted blood biomarkers from large-scale transcriptomics to construct multiclass eXtreme Gradient Boosting models (XGBoost), and evaluated their performance in distinguishing AD from cognitive normal (CN) and mild cognitive impairment (MCI). RESULTS: Independent testing with external dataset revealed that the combination of blood transcriptomic signatures achieved an area under the receiver operating characteristic curve (AUC of ROC) of 0.81 for multiclass classification (sensitivity = 0.81; specificity = 0.63), 0.83 for classification of AD vs. CN (sensitivity = 0.72; specificity = 0.73), and 0.85 for classification of AD vs. MCI (sensitivity = 0.77; specificity = 0.73). These candidate signatures were significantly enriched in 62 chromosome regions, such as Chr.19p12-19p13.3, Chr.1p22.1-1p31.1, and Chr.1q21.2-1p23.1 (adjusted p < 0.05), and significantly overrepresented by 26 transcription factors, including E2F2, FOXO3, and GATA1 (adjusted p < 0.05). Biological analysis of these signatures pointed to systemic dysregulation of immune responses, hematopoiesis, exocytosis, and neuronal support in neurodegenerative disease (adjusted p < 0.05). CONCLUSIONS: Blood transcriptomic biomarkers hold great promise in clinical use for the accurate assessment and prediction of AD.

Visualizing the Birth and Monitoring the Life of a Bimetallic Methanation Catalyst.

Well-defined bimetallic heterogeneous catalysts are not only difficult to synthesize in a controlled manner, but their elemental distributions are also notoriously challenging to define. Knowledge of these distributions is required for both the as-synthesized catalyst and its activated form under reaction conditions, where various types of reconstruction can occur. Success in this endeavor requires observation of the active catalyst via in situ analytical methods. As a step toward this goal, we present a composite material composed of bimetallic nickel-ruthenium nanoparticles supported on a protonated zeolite (Ni-Ru/HZSM-5) and probe its evolution and function as a photoactive carbon dioxide methanation catalyst using in situ X-ray absorption spectroscopy (XAS). The working Ni-Ru/HZSM-5, as a selective and durable photothermal CO2 methanation catalyst, comprises a corona of Ru nanoparticles decorating a Ni nanoparticle core. The specific Ni-Ru interactions in the bimetallic particles were confirmed by in situ XAS, which reveals significant electron transfer from Ni to Ru. The light-harvesting Ni nanoparticle core and electron-accepting Ru nanoparticle corona serve as the CO2 and H2 dissociation centers, respectively. These Ni and Ru nanoparticles also promote synergistic photothermal and hydrogen atom transfer effects. Collectively, these effects enable an associative CO2 methanation reaction pathway while hindering coking and fostering high selectivity toward methane.

ViT-MVT: A Unified Vision Transformer Network for Multiple Vision Tasks.

In this work, we seek to learn multiple mainstream vision tasks concurrently using a unified network, which is storage-efficient as numerous networks with task-shared parameters can be implanted into a single consolidated network. Our framework, vision transformer (ViT)-MVT, built on a plain and nonhierarchical ViT, incorporates numerous visual tasks into a modest supernet and optimizes them jointly across various dataset domains. For the design of ViT-MVT, we augment the ViT with a multihead self-attention (MHSE) to offer complementary cues in the channel and spatial dimension, as well as a local perception unit (LPU) and locality feed-forward network (locality FFN) for information exchange in the local region, thus endowing ViT-MVT with the ability to effectively optimize multiple tasks. Besides, we construct a search space comprising potential architectures with a broad spectrum of model sizes to offer various optimum candidates for diverse tasks. After that, we design a layer-adaptive sharing technique that automatically determines whether each layer of the transformer block is shared or not for all tasks, enabling ViT-MVT to obtain task-shared parameters for a reduction of storage and task-specific parameters to learn task-related features such that boosting performance. Finally, we introduce a joint-task evolutionary search algorithm to discover an optimal backbone for all tasks under total model size constraint, which challenges the conventional wisdom that visual tasks are typically supplied with backbone networks developed for image classification. Extensive experiments reveal that ViT-MVT delivers exceptional performances for multiple visual tasks over state-of-the-art methods while necessitating considerably fewer total storage costs. We further demonstrate that once ViT-MVT has been trained, ViT-MVT is capable of incremental learning when generalized to new tasks while retaining identical performances for trained tasks. The code is available at https://github.com/XT-1997/vitmvt.

Point-NAS: A Novel Neural Architecture Search Framework for Point Cloud Analysis.

Recently, point-based networks have exhibited extraordinary potential for 3D point cloud processing. However, owing to the meticulous design of both parameters and hyperparameters inside the network, constructing a promising network for each point cloud task can be an expensive endeavor. In this work, we develop a novel one-shot search framework called Point-NAS to automatically determine optimum architectures for various point cloud tasks. Specifically, we design an elastic feature extraction (EFE) module that serves as a basic unit for architecture search, which expands seamlessly alongside both the width and depth of the network for efficient feature extraction. Based on the EFE module, we devise a searching space, which is encoded into a supernet to provide a wide number of latent network structures for a particular point cloud task. To fully optimize the weights of the supernet, we propose a weight coupling sandwich rule that samples the largest, smallest, and multiple medium models at each iteration and fuses their gradients to update the supernet. Furthermore, we present a united gradient adjustment algorithm that mitigates gradient conflict induced by distinct gradient directions of sampled models and supernet, thus expediting the convergence of the supernet and assuring that it can be comprehensively trained. Pursuant to the provided techniques, the trained supernet enables a multitude of subnets to be incredibly well-optimized. Finally, we conduct an evolutionary search for the supernet under resource constraints to find promising architectures for different tasks. Experimentally, the searched Point-NAS with weights inherited from the supernet realizes outstanding results across a variety of benchmarks. i.e., 94.2% and 88.9% overall accuracy under ModelNet40 and ScanObjectNN, 68.6% mIoU under S3DIS, 63.6% and 69.3% mAP@0.25 under SUN RGB-D and ScanNet V2 datasets.

Modifiable risk factors for subsequent lethal prostate cancer among men with an initially negative prostate biopsy.

BACKGROUND: Previously suggested modifiable risk factors for prostate cancer could have resulted from detection bias because diagnosis requires a biopsy. We investigated modifiable risk factors for a subsequent cancer diagnosis among men with an initially negative prostate biopsy. METHODS: In total, 10,396 participants of the Health Professionals Follow-up Study with an initial negative prostate biopsy after 1994 were followed for incident prostate cancer until 2017. Potential risk factors were based on previous studies in the general population. Outcomes included localised, advanced, and lethal prostate cancer. RESULTS: With 1851 prostate cancer cases (168 lethal) diagnosed over 23 years of follow-up, the 20-year risk of any prostate cancer diagnosis was 18.5% (95% CI: 17.7-19.3). Higher BMI and lower alcohol intake tended to be associated with lower rates of localised disease. Coffee, lycopene intake and statin use tended to be associated with lower rates of lethal prostate cancer. Results for other risk factors were less precise but compatible with and of similar direction as for men in the overall cohort. CONCLUSIONS: Risk factors for future prostate cancer among men with a negative biopsy were generally consistent with those for the general population, supporting their validity given reduced detection bias, and could be actionable, if confirmed.

HNEAP Regulates Necroptosis of Cardiomyocytes by Suppressing the m5 C Methylation of Atf7 mRNA.

PIWI-interacting RNAs (piRNAs) are highly expressed in various cardiovascular diseases. However, their role in cardiomyocyte death caused by ischemia/reperfusion (I/R) injury, especially necroptosis, remains elusive. In this study, a heart necroptosis-associated piRNA (HNEAP) is found that regulates cardiomyocyte necroptosis by targeting DNA methyltransferase 1 (DNMT1)-mediated 5-methylcytosine (m5 C) methylation of the activating transcription factor 7 (Atf7) mRNA transcript. HNEAP expression level is significantly elevated in hypoxia/reoxygenation (H/R)-exposed cardiomyocytes and I/R-injured mouse hearts. Loss of HNEAP inhibited cardiomyocyte necroptosis and ameliorated cardiac function in mice. Mechanistically, HNEAP directly interacts with DNMT1 and attenuates m5 C methylation of the Atf7 mRNA transcript, which increases Atf7 expression level. ATF7 can further downregulate the transcription of Chmp2a, an inhibitor of necroptosis, resulting in the reduction of Chmp2a level and the progression of cardiomyocyte necroptosis. The findings reveal that piRNA-mediated m5 C methylation is involved in the regulation of cardiomyocyte necroptosis. Thus, the HNEAP-DNMT1-ATF7-CHMP2A axis may be a potential target for attenuating cardiac injury caused by necroptosis in ischemic heart disease.

BCL6 promotes a stem-like CD8+ T cell program in cancer via antagonizing BLIMP1.

Overcoming CD8+ T cell exhaustion is critical in cancer immunotherapy. Recently, an intratumor stem/progenitor-like CD8+ T cell (Tprog cell) population that mediates the persistence of antitumor responses has been defined, which can further develop into a terminally differentiated CD8+ T cell (Tterm cell) subpopulation with potent cytotoxic functions. Tprog cells are the main responders to immune checkpoint blockade therapies, yet how extrinsic signals via transcription factors control Tprog cell generation and persistence in tumors is unclear. Here, we found that BCL6 inhibits tumor-specific Tterm cell generation from Tprog cell downstream of TCF1. We show that Bcl6 deficiency reduced the persistence of Tprog cells, without affecting their generation, thus abrogating long-term tumor control. High-level BCL6 expression was observed in tumor-specific T cells in draining lymph nodes (LNs) and was associated with T cell exhaustion. This was observed in TOX+TCF1+ Tprog cells in both LNs and tumors. BCL6 expression in CD8+ T cells was up-regulated by TGF-ß-SMAD2 signaling but down-regulated by the IL-2-STAT5 pathway. Mechanistically, BCL6 transcriptionally repressed the expression of Tterm cell-associated genes and induced those of Tprog cell-related genes, in a manner antagonistic to BLIMP1. Prdm1 deficiency also promoted the Tprog cell program and greatly improved the efficacy of anti-PD-1 therapy. Thus, we identified the TGF-ß-BCL6 and IL-2-BLIMP1 antagonistic pathways in regulation of antitumor CD8+ T cells, which may benefit the development of long-lasting and effective cancer immunotherapy.

Formation and modulation of multi-pulse femtosecond laser-induced periodic surface structures by electromagnetic and partial differential equation simulations.

In order to demonstrate the formation of laser-induced periodic surface structures (LIPSS), simulations were performed to investigate the effect of multiple femtosecond laser pulses with different laser energy densities on a Ti6Al4V surface. In this work, a set of partial differential equations calculating the electron and lattice temperature variations, followed by coupling with an electric field, is used to analyze the evolution of the periodic surface structure induced by the interaction of the femtosecond laser with the material. As the number of pulses increases, the surface structure of the material changes from none to produce LIPSS structure and from low spatial frequency LIPSS (LSFL) structure to high spatial frequency LIPSS (HSFL) structure. In order to compare the results, single-point laser scanning ablation experiments were carried out at femtosecond laser energy. The experimental results are consistent with the simulation results.

Comparison of intraoperative blood loss and perioperative complications between preoperative embolization and nonembolization combined with spinal tumor surgeries: a systematic review and meta-analysis.

PURPOSE: The present study aimed to comparatively evaluate intraoperative blood loss (IBL) and perioperative complications between preoperative embolization (PE) and nonembolization (NE) combined with spinal tumor surgeries as well as to determine the subgroup of spinal tumor surgeries suitable for PE. METHODS: A systematic search in PubMed and EMBASE and an additional search by reference lists of the retrieved studies were undertaken by two reviewers. The mean IBL and perioperative complication rate were employed as the effect size in the general quantitative synthesis through direct calculation. Meta-analysis was performed using standardized mean difference (SMD) and weighted mean difference (WMD) of IBL and the odds ratio (OR) of complications. Heterogeneity was assessed using the I2 statistic. RESULTS: The reviewers selected 17 published studies for the general quantitative synthesis and meta-analyses. The mean IBL of spinal tumor surgeries was 1786.3 mL in the NE group and 1716.4 mL in the PE group. The mean IBL between the two groups was similar. The pooled WMD and SMD of IBL in spinal tumor surgeries was 324.15 mL (95% CI 89.50-1640.9, p = 0.007) and 0.398 (95% CI 0.114-0.682, p = 0.006), respectively. The reduction of the PE group compared with the NE group for the rates of major complications and major hemorrhagic complications were 7.80% and 5.71%, respectively. The risk of PE-related complications in the PE group was only 1.53% more than in the PE group. The pooled OR of major complications in spinal tumor surgeries was 1.426 (95% CI 0.760-2.674; p = 0.269). CONCLUSIONS: PE may be suitable for spinal tumor surgeries and some subgroups. From the perspective of complications, PE may also be a feasible option for spinal tumor surgeries.

Association of dietary fatty acids with the risk of atherosclerotic cardiovascular disease in a prospective cohort of United States veterans.

BACKGROUND: Atherosclerotic cardiovascular diseases (ASCVDs) are the leading cause of worldwide adult mortality. Although broad classes of dietary fats have been shown to alter ASCVD risk, the roles that individual dietary fatty acids play in influencing ASCVD risk are unclear. OBJECTIVES: The aim of this prospective cohort study was to examine the relationships of the total fat classes and individual fatty acids with the risk of ASCVD. METHODS: The Million Veteran Program is a prospective cohort whereby dietary intake of fatty acids was assessed in 158,198 participants that had enrolled between January 2011 and November 2018 and were free of ASCVD at baseline. Incident ASCVD was ascertained from the Veterans Affairs electronic health records and the National Death Index. Multivariable-adjusted hazard ratios (HRs) for the relationship between fat intake and ASCVD risk were computed using Cox regression models. RESULTS: The mean age was 61 years, 88% were males. A total of 11,771 ASCVD events were identified during the follow-up. When compared with the lowest quintile, participants in the highest quintile of dietary trans-monounsaturated fats and conjugated linoleic acids had an increased risk (HR [95% CI]) of ASCVD events: 1.10 (1.04, 1.17) and 1.11 (1.05, 1.18), respectively. When compared with low consumers, participants in the highest quintile of total cis-polyunsaturated fatty acid intake had a lower risk of experiencing an ASCVD event 0.93 (0.87, 0.99). CONCLUSION: Although higher intakes of specific trans-fatty acids and conjugated linoleic were associated with an increased risk of ASCVD, the same cannot be said for all other fat classes. This work suggests that care must be taken when drawing general conclusions regarding the health effects of dietary individual fatty acids.

TMEM11 regulates cardiomyocyte proliferation and cardiac repair via METTL1-mediated m7G methylation of ATF5 mRNA.

The mitochondrial transmembrane (TMEM) protein family has several essential physiological functions. However, its roles in cardiomyocyte proliferation and cardiac regeneration remain unclear. Here, we detected that TMEM11 inhibits cardiomyocyte proliferation and cardiac regeneration in vitro. TMEM11 deletion enhanced cardiomyocyte proliferation and restored heart function after myocardial injury. In contrast, TMEM11-overexpression inhibited neonatal cardiomyocyte proliferation and regeneration in mouse hearts. TMEM11 directly interacted with METTL1 and enhanced m7G methylation of Atf5 mRNA, thereby increasing ATF5 expression. A TMEM11-dependent increase in ATF5 promoted the transcription of Inca1, an inhibitor of cyclin-dependent kinase interacting with cyclin A1, which suppressed cardiomyocyte proliferation. Hence, our findings revealed that TMEM11-mediated m7G methylation is involved in the regulation of cardiomyocyte proliferation, and targeting the TMEM11-METTL1-ATF5-INCA1 axis may serve as a novel therapeutic strategy for promoting cardiac repair and regeneration.