Predictors of length of hospital stay after pediatric Ebstein anomaly corrective surgery: a retrospective cohort study.

BACKGROUND: The remarkable advancements in surgical techniques over recent years have shifted the clinical focus from merely reducing mortality to enhancing the quality of postoperative recovery. The duration of a patient's hospital stay serves as a crucial indicator in evaluating postoperative recovery and surgical outcomes. This study aims to identify predictors of the length of hospital stay for children who have undergone corrective surgery for Ebstein Anomaly (EA). METHODS: We conducted a retrospective cohort study on children (under 18 years of age) diagnosed with EA who were admitted for corrective surgery between January 2009 and November 2021 at Fuwai Hospital. The primary outcome was the Time to Hospital Discharge (THD). Cox proportional hazard models were utilized to identify predictors of THD. In the context of time-to-event analysis, discharge was considered an event. In cases where death occurred before discharge, it was defined as an extended THD, input as 100 days (exceeding the longest observed THD), and considered as a non-event. RESULTS: A total of 270 children were included in this study, out of which three died in the hospital. Following the Cox proportional hazard analysis, six predictors of THD were identified. The hazard ratios and corresponding 95% confidence intervals were as follows: age, 1.030(1.005,1.055); C/R > 0.65, 0.507(0.364,0.707); Carpentier type C or D, 0.578(0.429,0.779); CPB time, 0.995(0.991,0.998); dexamethasone, 1.373(1.051,1.795); and transfusion, 0.680(0.529,0.875). The children were categorized into three groups based on the quartile of THD. Compared to children in the ≤ 6 days group, those in the ≥ 11 days group were associated with a higher incidence of adverse outcomes. Additionally, the duration of mechanical ventilation and ICU stay, as well as hospital costs, were significantly higher in this group. CONCLUSION: We identified six predictors of THD for children undergoing corrective surgery for EA. Clinicians can utilize these variables to optimize perioperative management strategies, reduce adverse complications, improve postoperative recovery, and reduce unnecessary medical expenses.

The inoculum dose of Zika virus can affect the viral replication dynamics, cytokine responses and survival rate in immunocompromised AG129 mice.

Zika virus, a mosquito-borne arbovirus, has repeatedly caused large pandemics with symptoms worsening from mild and self-limiting diseases to Guillain-Barré syndrome in adults and fetal microcephaly in newborns. In recent years, Zika virus diseases have posed a serious threat to human health. The shortage of susceptible small animal models makes it difficult to study pathogenic mechanisms and evaluate potential therapies for Zika virus infection. Therefore, we chose immunocompromised mice (AG129 mice) deficient in IFN-α/ß and IFN-γ receptors, which can abolish the innate immune system that prevents Zika virus infection early. AG129 mice were infected with the Zika virus, and this mouse model exhibited replication dynamics, tissue tropism, pathological lesion and immune activation of the Zika virus. Our results suggest that the inoculum dose of Zika virus can affect the viral replication dynamics, cytokine responses and survival rate in AG129 mice. By testing the potential antiviral drug favipiravir, several critical indicators, including replication dynamics and survival rates, were identified in AG129 mice after Zika virus infection. It is suggested that the model is reliable for drug evaluation. In brief, this model provides a potential platform for studies of the infectivity, virulence, and pathogenesis of the Zika virus. Moreover, the development of an accessible mouse model of Zika virus infection will expedite the research and deployment of therapeutics and vaccines.

An engineered lactate oxidase based electrochemical sensor for continuous detection of biomarker lactic acid in human sweat and serum.

Lactate levels in humans reveal intensity and duration of exertion and provide a critical readout for the severity of life-threatening illnesses such as pediatric sepsis. Using the lactate oxidase enzyme (Lox) from Aerococcus viridians, we demonstrated its functionality for lactate electrochemical sensing in physiological fluids in a lab setting. The structure and dynamics of LOx were validated by crystallography, X-ray scattering, and hydroxyl radical protein footprinting. This provided a validated protein template for understanding and designing an enzyme-based electrochemical sensing elements. Using this template, LOx enzyme variants were generated and compared. Comparison of the variants demonstrates that one exhibits effective lactate sensing at significantly reduced operating voltages. Additionally, we demonstrate that the four hexahistidine-tags on each enzyme tetramer are sufficient for immobilization to create a durable, functional sensor, with no need for a covalent attachment, enabling self-immobilization and eliminating the need for additional immobilization steps. The functionality of the LOx enzyme variants was verified at physiological lactate concentrations in both human serum (0-4 mM) and artificial sweat (0-100 mM) using 3-electrode setups for analysis of the three variants in parallel. Accuracy of measurement in both artificial sweat and human serum were high. Employing a microfluidic flow cell, we successfully monitored varying lactate levels in physiological fluids continuously over a 2h period. Overall, this optimized LOx enzyme, which self-immobilizes onto gold sensing electrodes, facilitates efficient and reliable lactate detection and continuous monitoring at reduced operating voltages suitable for further development towards commercial use.

Motion blur microscopy: in vitro imaging of cell adhesion dynamics in whole blood flow.

Imaging and characterizing the dynamics of cellular adhesion in blood samples is of fundamental importance in understanding biological function. In vitro microscopy methods are widely used for this task but typically require diluting the blood with a buffer to allow for transmission of light. However, whole blood provides crucial signaling cues that influence adhesion dynamics, which means that conventional approaches lack the full physiological complexity of living microvasculature. We can reliably image cell interactions in microfluidic channels during whole blood flow by motion blur microscopy (MBM) in vitro and automate image analysis using machine learning. MBM provides a low cost, easy to implement alternative to intravital microscopy, for rapid data generation where understanding cell interactions, adhesion, and motility is crucial. MBM is generalizable to studies of various diseases, including cancer, blood disorders, thrombosis, inflammatory and autoimmune diseases, as well as providing rich datasets for theoretical modeling of adhesion dynamics.

Exploring the heart-brain and brain-heart axis: Insights from a bidirectional Mendelian randomization study on brain cortical structure and cardiovascular disease.

INTRODUCTION: The bidirectional relationship between the brain cortex and cardiovascular diseases (CVDs) remains inadequately explored. METHODS: This study employed bidirectional Mendelian randomization (MR) analysis to investigate the interaction between nine phenotypes, namely hypertension, heart failure, atrial fibrillation (AF), and coronary heart disease (CHD), and brain cortex measurements, including total surface area (SA), average thickness (TH), and the SA and TH of 34 regions based on the Desikan-Killiany atlas. The nine traits were obtained from sources such as the UK Biobank and FinnGen, etc., while MRI-derived traits of cortical structure were sourced from the ENIGMA Consortium. The primary estimate was obtained using the inverse-variance weighted approach. False discovery rate adjustment was applied to p-values (q-values) in the analyses for regional cortical structure. RESULTS: A total of 1260 two-sample MR analyses were conducted. Existing CHD demonstrated an influence on the SA of the banks of the superior temporal sulcus (bankssts) (q = 0.018) and the superior frontal lobe (q = 0.018), while hypertension was associated with changes in the TH of the lateral occipital region (q = 0.02). Regarding the effects of the brain cortex on CVD incidence, total SA was significantly associated with the risk of CHD. Additionally, 15 regions and four areas exhibited significant effects on blood pressure and AF risk, respectively (q < 0.05). These regions were primarily located in the frontal, temporal, and cingulate areas, which are responsible for cognitive function and mood regulation. CONCLUSION: The detection of cortical changes through MRI could aid in screening for potential neuropsychiatric disorders in individuals with established CVD. Moreover, abnormalities in cortical structure may predict future CVD risk, offering new insights for prevention and treatment strategies.

Sulfate Derivatives with Heteroleptic Tetrahedra: New Deep-ultraviolet Birefringent Materials in which Weak Interactions Modulate Functional Module Ordering.

Deep-ultraviolet (UV) birefringent materials are urgently needed to facilitate light polarization in deep-UV lithography. Maximizing anisotropy by regulating the alignment of functional modules is essential for improving the linear optical performance of birefringent materials. In this work, we proposed a strategy to design deep-UV birefringent materials that achieve functional module ordering via weak interactions. Following this strategy, four compounds CN4H7SO3CF3, CN4H7SO3CH3, C(NH2)3SO3CH3, and C(NH2)3SO3CF3 were identified as high-performance candidates for deep-UV birefringent materials. The millimeter-sized crystals of CN4H7SO3CF3, CN4H7SO3CH3, and C(NH2)3SO3CH3 were grown, and the transmittance spectra show that their cutoff edges are below 200 nm. CN4H7SO3CF3 exhibits the largest birefringence (0.149 @ 546 nm, 0.395 @ 200 nm) in the deep-UV region among reported sulfates and sulfate derivatives. It reveals that the hydrogen bond can modulate the module ordering of the heteroleptic tetrahedra and planar π-conjugated cations, thus greatly enhancing the birefringence. Our study not only discovers new deep-UV birefringent materials but also provides an upgraded strategy for optimizing optical anisotropy to achieve efficient birefringence.

Acute liver failure: A clinically severe syndrome characterized by intricate mechanisms.

Acute liver failure presents as a clinical syndrome characterized by swift deterioration and significant mortality rates. Its underlying mechanisms are intricate, involving intricate interplays between various cells. Given the current scarcity of treatment options, there's a pressing need to diligently uncover the disease's core mechanisms and administer targeted therapies accordingly.

The prognostic role of lymphocyte-to-monocyte ratio in patients with resectable pancreatic cancer: a systematic review and meta-analysis.

Objectives: This systematic review and meta-analysis examined whether the lymphocyte-to-monocyte ratio (LMR) can serve as an indicator for predicting the prognosis of patients with resectable pancreatic cancer. Patients and Methods: This meta-analysis was registered with PROSPERO: CRD42023461260. A systematic literature search was conducted in the PubMed, Embase, Cochrane, and Web of Science databases up to September 2023 to assess whether LMR can predict the prognosis of patients with resectable pancreatic cancer. The outcomes measured included subgroup analyses of overall survival (OS) with hazard ratios (HR) and confidence intervals of geographical region, patient population, and LMR threshold. A sensitivity analysis was also performed for OS and HR and confidence intervals were calculated for recurrence-free survival (RFS). Results: A total of 14 eligible articles, comprising 4,019 patients, were included in the comprehensive analysis. The results of this comprehensive analysis indicate that LMR is a robust predictor of OS, demonstrating strong prognostic significance (HR = 0.55, 95% CI [0.44-0.69], I2 = 79%, P < 0.00001). This predictive significance extended to various types of pancreatic cancer, such as pancreatic ductal adenocarcinoma (HR = 0.73, 95% CI [0.57-0.93], I2 = 46%, P = 0.01), pancreatic neuroendocrine neoplasms (HR = 0.81, 95% CI [0.66-0.99], P = 0.04) and other subtypes (HR = 0.40, 95% CI [0.22-0.72], I2 = 89%, P < 0.00001), but not to pancreatic head cancer (HR = 0.46, 95% CI [0.16-1.13], I2 = 59%, P = 0.12). LMR retained its predictive value across different regions, including Asia (HR = 0.62, 95% CI [0.47-0.76], I2 = 68%, P < 0.0001), Europe (HR = 0.78, 95% CI [0.67-0.91], I2 = 0%, P = 0.002), and the Americas (HR = 0.14, 95% CI [0.08-0.24], I2 = 0%, P < 0.00001). Notably, both LMR cut-off values greater than or equal to three (HR = 0.62, 95% CI [0.47-0.82], I2 = 67%, P = 0.0009) and less than three (HR = 0.47, 95% CI [0.32-0.69], I2 = 85%, P = 0.0001) exhibited prognostic significance. The sensitivity analysis for OS confirmed the strong predictive value of LMR, whereas LMR did not exhibit predictive significance for RFS (HR = 0.35, 95% CI [0.09-1.32], I2 = 95%, P = 0.12). In both subgroups categorized by Newcastle-Ottawa Scale (NOS) scores of ≥7 (HR = 0.66, 95% CI [0.54-0.80], I2 = 53%, P = 0.04) and <7 (HR = 0.41, CI [0.23-0.72], I2 = 89%, P < 0.00001), LMR was demonstrated to have predictive value. Conclusion: Despite the observed heterogeneity and potential biases in the included studies, the findings of this study suggest that LMR may serve as a valuable predictor of OS in patients with resectable pancreatic cancer.

Forensic significance of VOCs profiling in decayed ante- and post-mortem injuries by GC×GC-TOF/MS.

Accurately identifying and differentiating the types of injuries in decomposed corpses is a major challenge in forensic identification. Forensic investigations involving decomposed cadavers pose challenges in determining the cause of death. Traditional methods often lack conclusive evidence. However, the implementation of advanced analytical techniques, such as comprehensive two-dimensional gas chromatography coupled with time-of-flight mass spectrometry (GC × GC-TOF/MS), shows promise in overcoming these limitations, but the potential in this area remains limited. Therefore, this study aims to bridge this gap by exploring the potential of GC × GC-TOF/MS in the analysis of volatile organic compounds (VOCs) changes within decaying ante- and post-mortem injuries.The research emphasizes the forensic significance of VOCs changes in decomposed cadavers. We used GC × GC-TOF/MS analysis to identify the specific volatile compounds in putrefied corpse tissue samples from mice. The GC × GC-TOF/MS analysis results showed that under winter conditions, PC1 explained 57.16% of the variance, and PC2 explained 25.23% of the variance; while under summer conditions, PC1 explained 71.89% of the variance, and PC2 explained 24.49% of the variance. This demonstrates the potential of GC × GC-TOF/MS in identifying specific VOCs present in tissue samples that can serve as potential biomarkers for distinguishing between antemortem and postmortem injury. GC × GC-TOF/MS analysis revealed distinct VOC patterns in both conditions. Comprehensive use of GC × GC-TOF/MS analysis enhances accuracy in identifying and characterizing ante- and post-mortem injuries in decomposed cadavers. This study can significantly contribute to the field of forensic medicine and improve the accuracy of forensic investigations.

Single-cell view into the role of microbiota shaping host immunity in the larynx.

Microbiota play a critical role in the development and training of host innate and adaptive immunity. We present the cellular landscape of the upper airway, specifically the larynx, by establishing a reference single-cell atlas, while dissecting the role of microbiota in cell development and function at single-cell resolution. We highlight the larynx's cellular heterogeneity with the identification of 16 cell types and 34 distinct subclusters. Our data demonstrate that commensal microbiota have extensive impact on the laryngeal immune system by regulating cell differentiation, increasing the expression of genes associated with host defense, and altering gene regulatory networks. We uncover macrophages, innate lymphoid cells, and multiple secretory epithelial cells, whose cell proportions and expressions vary with microbial exposure. These cell types play pivotal roles in maintaining laryngeal and upper airway health and provide specific guidance into understanding the mechanism of immune system regulation by microbiota in laryngeal health and disease.

Deep learning-based image quality assessment for optical coherence tomography macular scans: a multicentre study.

AIMS: To develop and externally test deep learning (DL) models for assessing the image quality of three-dimensional (3D) macular scans from Cirrus and Spectralis optical coherence tomography devices. METHODS: We retrospectively collected two data sets including 2277 Cirrus 3D scans and 1557 Spectralis 3D scans, respectively, for training (70%), fine-tuning (10%) and internal validation (20%) from electronic medical and research records at The Chinese University of Hong Kong Eye Centre and the Hong Kong Eye Hospital. Scans with various eye diseases (eg, diabetic macular oedema, age-related macular degeneration, polypoidal choroidal vasculopathy and pathological myopia), and scans of normal eyes from adults and children were included. Two graders labelled each 3D scan as gradable or ungradable, according to standardised criteria. We used a 3D version of the residual network (ResNet)-18 for Cirrus 3D scans and a multiple-instance learning pipline with ResNet-18 for Spectralis 3D scans. Two deep learning (DL) models were further tested via three unseen Cirrus data sets from Singapore and five unseen Spectralis data sets from India, Australia and Hong Kong, respectively. RESULTS: In the internal validation, the models achieved the area under curves (AUCs) of 0.930 (0.885-0.976) and 0.906 (0.863-0.948) for assessing the Cirrus 3D scans and Spectralis 3D scans, respectively. In the external testing, the models showed robust performance with AUCs ranging from 0.832 (0.730-0.934) to 0.930 (0.906-0.953) and 0.891 (0.836-0.945) to 0.962 (0.918-1.000), respectively. CONCLUSIONS: Our models could be used for filtering out ungradable 3D scans and further incorporated with a disease-detection DL model, allowing a fully automated eye disease detection workflow.

[Intraperitoneal injection of human-derived anti-c-Met single-chain antibody inhibits the growth of transplanted tumours in A549 lung adenocarcinoma-loaded mice].

Objective To verify the anti-tumor effect of the mesenchymal-epithelial transition single-chain antibody (Met scFv) on subcutaneously transplanted tumors in nude mice. Methods A tumor model was established in nude mice by subcutaneous injection of A549 lung adenocarcinoma cells. Once the tumors were formed, IRDye680 LT N-hydroxysuccinimide (NHS) ester-labeled Met scFv was administered intraperitoneally. Real-time monitoring was conducted using a small animal imager to observe the dynamic distribution of the antibody in tumor-bearing mice. The affinity between c-Met and the antibody in tumor cells was detected. Tumor volume changes were observed and the tumor growth curve were plotted following regular tail vein injections of Met scFv. Immunohistochemical staining was employed to determine whether Met scFv could effectively bind to the c-Met antigen in tumor tissues. Results The distribution of Met scFv in nude mice showed that it was primarily located in the peritoneal cavity within the first 3 hours. After approximately 48 hours, fluorescent signals began to accumulate in the tumor tissue. Immunohistochemical staining of the tumors revealed high expression of c-Met in the tumor tissues; regular tail vein injections of Met scFv significantly slowed down the growth of tumors in mice. Conclusion Met scFv specifically recognizes tumor cells in vivo and exhibites significant anti-tumor activity.

A Machine-Learning-Assisted Crystalline Structure Prediction Framework To Accelerate Materials Discovery.

Modern crystal structure prediction methods based on structure generation algorithms and first-principles calculations play important roles in the design of new materials. However, the cost of these methods is very expensive because their success mostly relies on the efficient sampling of structures and the accurate evaluation of energies for those sampled structures. Herein, we develop a Machine-learning-Assisted CRYStalline Materials sAmpling sysTem (MAXMAT) aiming to accelerate the prediction of new crystal structures. For a given chemical composition, MAXMAT can generate efficient crystal structures with the help of a Python package for crystal structure generation (PyXtal) and can quickly evaluate the energies of these generated structures using a well-developed machine learning interaction potential model (M3GNET). We have used MAXMAT to perform crystal structure searches for three different chemical systems (TiO2, MgAl2O4, and BaBOF3) to test its accuracy and efficiency. Furthermore, we apply MAXMAT to predict new nonlinear optical materials, suggesting several thermodynamically synthesizable structures with high performance in LiZnGaS3 and CaBOF3 systems.

Acupoints for Headache with Blood Stasis Syndrome: a Literature Study Based on Data Mining Technology.

Objective: This study aimed to investigate the features and underlying principles of acupuncture points used in the treatment of headaches associated with blood stasis syndrome. Methods: Literature on the treatment of blood stasis headache with acupuncture and moxibustion was searched across three Chinese databases and one English database from January 1st, 2000, to January 1st, 2024. Relevant data including titles, journals, authors, keywords, interventions, main acupoints, and outcomes were extracted for further analysis. Results: A total of 112 papers with 102 complete prescriptions were analyzed. Of the 77 acupoints examined, 72 were meridian points, and 5 were extraordinary points, used 699 times in total. The top ten acupoints by frequency were Fengchi (GB20), Taiyang (EX-HN5), Baihui (GV20), Hegu (LI4), Shuaigu (GB8), Taichong (LR3), Xuehai (SP10), Touwei (ST8), Geshu (BL17), and Waiguan (TE5). Yang meridian points were used more frequently than Yin meridian points (82.8% vs 17.2%), with the Gallbladder Meridian of Foot Shaoyang being the most common. Nearly half of the acupoints (49.9%) were on the head and neck, and 23.1% on the lower limbs. Specific acupoints accounted for 53.5% of the total frequency. Fengchi (GB20) and Taiyang (EX-HN5) showed the highest correlation. Association rule mining highlighted combinations like Fengchi (GB20) with Taiyang (EX-HN5) and Baihui (GV20). Cluster analysis yielded five clusters. Conclusion: The study provides insights into selecting effective acupoints and combinations for clinical acupuncture practice and experimental studies in treating blood stasis headaches. Acupoints like Fengchi (GB20), Taiyang (EX-HN5), and Baihui (GV20) may be effective for clinical treatment, but further studies are needed to validate their efficacy.

Chitosan-based biomaterials promote bone regeneration by regulating macrophage fate.

The development of various osteogenic biomaterials has not only promoted the development of bone tissue engineering but also provided more possibilities for bone defect repair. However, most previous studies have focused on the interaction of biomaterials on endogenous or exogenous stem cells involved in the bone regeneration process while neglecting the effect of changes in the immune microenvironment of bone defect sites on bone regeneration after biomaterial implantation into the host. With the development of bone immunology, the role of various immune cells, especially macrophages, in bone regeneration has gradually attracted the attention of researchers. An increasing number of studies have begun to target macrophages to better promote bone regeneration by modulating the fate of macrophages in a spatiotemporally ordered manner to mimic the changes in the immune microenvironment of bone defect sites during the natural repair process of bone tissue. Chitosan is one of the most abundant natural polysaccharides in the world. In recent years, various chitosan-based biomaterials have been widely used in macrophage fate modulation and bone regeneration. In this review, we review the interaction between macrophages and scaffold materials, general information about chitosan, the modulation of macrophage fate by chitosan-based biomaterials, and their application in bone regeneration.

Association of the PCSK6 rs1531817(C/A) polymorphism with the prognosis and coronary stenosis in premature myocardial infarction patients: a prospective cohort study.

BACKGROUND: Proprotein convertase subtilisins/kexin 6 (PCSK6) polymorphisms have been shown to be associated with atherosclerosis progression. This research aimed to evaluate the relationship of PCSK6 rs1531817 polymorphisms with coronary stenosis and the prognosis in premature myocardial infarction (PMI) patients. METHODS: This prospective cohort analysis consecutively included 605 PMI patients who performed emergency percutaneous coronary intervention (PCI) at Tianjin Chest Hospital sequentially between January 2017 and August 2022, with major adverse cardiovascular events (MACEs) as the outcome. Analyses assessed the relationships among PCSK6 rs1531817 polymorphism, Gensini score (GS), triple vessel disease (TVD), and MACEs. RESULTS: 92 (16.8%) patients experienced MACEs with an average follow-up of 25.7 months. Logistic analysis revealed that the PCSK6 rs1531817 CA + AA genotype was an independent protective factor against high GS and TVD. Cox analysis revealed that the PCSK6 rs1531817 CA + AA genotype was an independent protective factor against MACEs. The mediation effect results showed that apolipoprotein A1/apolipoprotein B (ApoA1/ApoB) partially mediated the association between PCSK6 rs1531817 polymorphism and coronary stenosis and that total cholesterol/high-density lipoprotein (TC/HDL) and TVD partially and in parallel mediated the association between the PCSK6 rs1531817 polymorphism and MACEs. CONCLUSION: Patients with the PCSK6 CA + AA genotype have milder coronary stenosis and a better long-term prognosis; according to the mediation model, ApoA1/ApoB and TC/HDL partially mediate. These results may provide a new perspective on clinical therapeutic strategy for anti-atherosclerosis and improved prognosis in PMI patients.

Clinical and Molecular Characteristics of Megakaryocytes in Myelodysplastic Syndrome.

Objective Myelodysplastic syndrome (MDS) is a malignant clonal disorder of hematopoietic stem cells which is characterized by morphologic dysplasia. However, the pathological characteristics of megakaryocytes (MKs) in MDS patients with gene mutation are not well established. Methods Bone marrow MK specimens from 104 patients with primary MDS were evaluated, and all patients were distributed into two groups according to gene mutation associated with functional MKs. The morphologic and cellular characteristics of MKs and platelets were recorded and compared. Results The more frequently mutated genes in MDS patients were TUBB1 (11.54%), VWF (8.65%), NBEAL2 (5.77%), and the most common point mutation was TUBB1 p.(R307H) and p.(Q43P). Patients with MK mutation showed a decrease in adenosine diphosphate-induced platelet aggregation, high proportion of CD34 + CD61 + MKs (10.00 vs. 4.00%, p = 0.012), and short overall survival (33.15 vs. 40.50 months, p = 0.013). Further, patients with a higher percent of CD34 + CD61 + MKs (≧20.00%) had lower platelet counts (36.00 × 10 9 /L vs. 88.50 × 10 9 /L, p = 0.015) and more profound emperipolesis ( p = 0.001). By analyzing RNA-sequencing of MKs, differentially expressed mRNA was involved in physiological processes including platelet function and platelet activation, especially for MDS patients with high percent of CD34 + CD61 + MKs. The high levels of expression of CD62P, CXCL10, and S100A9 mRNA, shown by RNA sequencing, were validated by PCR assay. Conclusion High proportion of CD34 + CD61 + MKs was a poor prognostic factor in MDS patients with MK mutation. CD62P, CXCL10, and S100A9 may be the potential targets to evaluate the molecular link between gene defects and platelet function.

Comparative Analysis of Structural and Functional Properties of Dietary Fiber from Four Grape Varieties.

Muscadine grapes are characterized by their large and abundant seeds and hard and thick skins that contain significant amounts of dietary fiber (DF). The current study investigated the chemical constituents, molecular architecture, and physicochemical attributes of DF derived from Muscadine grapes (Granny Val and Alachua) and compared them with those derived from Shine Muscat and Kyoho. Using a combined enzymatic method, the total dietary fiber (TDF) was extracted and divided into two parts: soluble dietary fiber (SDF) and insoluble dietary fiber (IDF). TDF (mainly IDF, with a small fraction of SDF) was dominated by cellulose, followed by pectin and hemicellulose. In addition, Granny Val and Alachua had a significantly higher abundance of TDF and IDF compared with Shine Muscat and Kyoho. Moreover, Shine Muscat had significantly the highest abundance of SDF among the four grape varieties. Of note, IDF from Granny Val and Alachua exhibited a complex and dense texture on its surface, and notably outperformed Shine Muscat and Kyoho in terms of cholesterol, fatty acid, heavy metal adsorption, and antioxidant activity. Collectively, Muscadine grapes, i.e., Granny Val and Alachua in the current study, possessed elevated DF levels (predominantly IDF), and their enhanced bioactivity underscored their potential as a potential food ingredient for further use.

Identification of stable reference genes for relative quantification of long RNA expression in urinary extracellular vesicles.

Urinary extracellular vesicles (uEVs) are rich in valuable biomolecule information which are increasingly recognized as potential biomarkers for various diseases. uEV long RNAs are among the critical cargos capable of providing unique transcriptome information of the source cells. However, consensus regarding ideal reference genes for relative long RNAs quantification in uEVs is not available as of date. Here we explored stable reference genes through profiling the long RNA expression by RNA-seq following unsupervised analysis and validation studies. Candidate reference genes were identified using four algorithms: NormFinder, GeNorm, BestKeeper and the Delta Ct method, followed by validation. RNA profile showed uEVs contained abundant long RNAs information and the core transcriptome was related to cellular structures, especially ribosome which functions mainly as translation, protein and RNA binding molecules. Analysis of RNA-seq data identified RPL18A, RPL11, RPL27, RACK1, RPSA, RPL41, H1-2, RPL4, GAPDH, RPS27A as candidate reference genes. RT-qPCR validation revealed that RPL41, RPSA and RPL18A were reliable reference genes for long RNA quantification in uEVs from patients with diabetes mellitus (DM), diabetic nephropathy (DN), IgA nephropathy (IgAN) and prostate cancer (PCA). Interestingly, RPL41 also outperformed traditional reference genes in renal tissues of DN and IgAN, as well as in plasma EVs of several types of cancers. The stable reference genes identified in this study may facilitate development of uEVs as novel biomarkers and increase the accuracy and comparability of biomarker studies.

Characterization of the key flavor compounds in cream cheese by GC-MS, GC-IMS, sensory analysis and multivariable statistics.

The aroma types of cream cheese affect its commercial value and consumer acceptability. However, the types of volatile substances and sensory characteristics of cream cheese at different fermentation stages are still unclear. Therefore, in this study, headspace solid-phase microextraction gas chromatography-mass spectrometry (HS-SPME-GC-MS) and headspace gas chromatography-ion mobility spectrometry (HS-GC-IMS) were used to analyze the volatile substances in cream cheese fermentation. Orthogonal partial least squares discriminant analysis (OPLS-DA), odor activity value (OAV), relative odor activity value (ROAV) and variable projection importance (VIP) were used to identify the characteristic flavor substances in cream cheese fermentation. Finally, the relationship between key flavor substances and sensory characteristics was determined by partial least squares (PLS) analysis. A total of 34 and 36 volatile organic compounds were identified by HS-SPME-GC-MS and HS-GC-MS, respectively, and 14 characteristic flavor substances were found, based on VIP, ROAV and OAV models. Combined with sensory analysis and flavor substance changes, it was found that the cream cheese fermented for 15 d had the best flavor and taste. This study reveals the characteristics and contribution of volatile substances in cream cheese at different fermentation stages, which provides new insights into improving flavor and quality control.