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Cerebral venous sinus thrombosis (CVST) and hyperlipidemia are severe complications of L-Asparaginase (L-Asp) during the treatment of B-cell acute lymphoblastic leukemia (B-ALL). Herein, we reported a 9-year-old B-ALL boy who underwent abnormal hypertriglyceridemia and CVST presenting as seizures and disturbance of consciousness twice during the induction therapy. Fortunately, he survived treatment with anticoagulant and lipid-lowering therapy. No thrombophilia-related gene mutation was detected, but a heterozygous mutation in lipoprotein lipase (LPL) gene was identified. His neurological symptoms were managed with short-term anticoagulant therapy and long-term lipid-lowering therapy. This case illustrated the manifestation and potential pathogenesis of CVST and highlighted the essentiality of screening baseline lipid profile and dyslipidemia- and thrombophilia-related gene mutation.

Abstract Objective Traditional Chinese exercises (Taichi, Wuqinxi, Liuzijue, and Baduanjin) are considered effective alternative treatments for improving symptoms in the stable phase of COPD. However, the most effective exercise remains unknown. This study compared the effectiveness of different traditional Chinese exercises on pulmonary function in patients with stable chronic obstructive pulmonary disease (COPD) using a network meta-analysis. Methods From database establishment until September 2023, eligible randomized controlled trials (RCTs) were searched. Two reviewers performed the risk of bias assessment of the included studies using the Cochrane Collaboration tool, and the evidence level was suggested using the GRADE system. Results Fifty-seven studies comprising 4294 patients were included. The results of the network meta-analysis show that Baduanjin was most effective in improving the forced expiratory volume in the first second (FEV1). However, Liuzijue significantly improved the first–second forced vital capacity percentage of expected value (FEV1%) and the ratio of the forced expiratory volume in the first second to the forced vital capacity (FEV1/FVC). The probability ranking results indicated that Liuzijue was the most effective, followed by Baduanjin, Wuqinxi, and Taichi. Subgroup analysis in conjunction with intervention duration revealed that Liuzijue had a significant advantage over other interventions for improving FEV1, FEV1%, and FEV1/FVC within 6 months and improved FEV1% and FEV1/FVC for ≥ 6 months. Moreover, Subgroup analysis based on baseline pulmonary function revealed that Liuzijue had a significant advantage over other interventions for improving FEV1% within severe and moderate groups. Finally, Subgroup analysis based on the frequency of interventions showed that Liuzijue was still more effective in improving FEV1, FEV1%, and FEV1/FVC in the ≥ three times one week. Conclusion Liuzijue was more effective than Taichi, Wuqinxi, Liuzijue, and Baduanjin in improving pulmonary function in patients with stable COPD.

IntroductionSichuan south-road dark tea (SSDT) is generally produced through a series of processes, including fixing, rolling, pile fermentation, and drying, with microbial action during pile fermentation playing a crucial role in determining tea quality. The air within the SSDT pile fermentation plant (SSDTPP) is considered an important source of these microbes, but research in this area has been limited.MethodsIn this study, air samples from SSDTPP were collected on the 1st (SSDT1), 12th (SSDT2), and 24th (SSDT3) days of pile fermentation and comprehensively analyzed by high-throughput sequencing.Results and discussionThe results revealed the presence of 2 and 24 phyla, 9 and 49 classes, 18 and 88 orders, 28 and 153 families, 38 and 253 genera, and 47 and 90 species of fungi and bacteria, respectively, across all samples. SSDT1 and SSDT2 individually had the highest fungal and bacterial diversity, while Aspergillus was the dominant genus throughout the pile fermentation with an abundance of 34.6%, 91.17%, and 67.86% in SSDT1, SSDT2, and SSDT3, respectively. Microbial populations in SSDT1 were predominantly involved in xenobiotic biodegradation and metabolism, amino acid metabolism, the biosynthesis of other secondary metabolites, etc. However, SSDT2 exhibited a higher prevalence of human disease-related functions. SSDT3 primarily focused on the metabolism of other amino acids and carbohydrate metabolism. Additionally, 104 genera and 22 species coexisted in both SSDTPP air and piled SSDT, suggesting that frequent microbial exchange may occur between them. These findings pave the way for microbial traceability during SSDT production and provide a foundation for further functional microbial research.

The increasing wind power penetration and proliferation of induction motor loads, of which dynamic impact cannot be revealed through steady-state analysis, bring challenges to the short-term voltage stability of modern power systems. This study proposes a hybrid model-data-driven approach for dynamic VAR source planning to enhance the short-term voltage stability of wind-penetrated power systems to reduce the computation burden of electro-mechanical transient models. Firstly, the theoretical background of Stochastic Spectral Embedding (SSE) is introduced. Then, a surrogate model for the electromechanical transient model is established using SSE following efficient expansion coefficient calculation and a designed partition strategy for the studied problem. Furthermore, a hybrid model-data-driven VAR deployment optimization model is established with 3 objectives, which is solved by a dual-population-based evolutionary algorithm (DPEA). The accuracy and effectiveness of the model are verified on a modified New England 39-bus system. Simulation results prove that the computational cost is reduced significantly in comparison with conventional model-based method without a compromise in accuracy and the proposed method is also more accurate than methods based on other surrogate models. The proposed SSE-based model can be applied to other power system analysis with electro-mechanical transient models to alleviate the computational cost.

To schedule power sources operated by different entities in a short-time scale considering nonconvex generation cost and deep peak regulation (DPR) service constraints, this paper proposes an FRL-based multiple power sources coordination framework in wind-solar-thermal power network. In the studied power transmission network (TN), renewable energy sources and thermal power units connected to the same bus are aggregated as a wind-solar-thermal virtual power plant (WSTVPP). The transmission system operator (TSO) sends dispatch instructions to each WSTVPP by optimal power flow program, and allocates the cost of DPR service in TN. Based on the dispatch instruction, the internal power sources of each WSTVPP are scheduled by its local center control agent to achieve local economic operation while maximizing the overall DPR service revenue for the WSTVPP from the auxiliary service market. The multiple WSTVPPs operation is modeled as a partially observable Markov decision process, and solved by a designed FRL algorithm. The FRL algorithm employs a global neural network (NN) model for coordination, heterogeneous local NN models and data to efficiently train each WSTVPP control agent with individual objectives for handling multiple power sources scheduling in TN while preserving local privacy. Numerical studies validate the effectiveness of the proposed framework for handling the short-time scale power sources operation with nonconvex constraints.

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Juvenile myelomonocytic leukemia (JMML) is a disorder characterized by the simultaneous presence of myeloproliferative and myelodysplastic features, primarily affecting infants and young children. Due to the heterogeneous genetic background among patients, the current clinical and laboratory prognostic features are insufficient for accurately predicting outcomes. Thus, there is a pressing need to identify novel prognostic indicators. Red cell distribution width (RDW) is a critical parameter reflecting the variability in erythrocyte size. Recent studies have emphasized that elevated RDW serves as a valuable predictive marker for unfavorable outcomes across various diseases. However, the prognostic role of RDW in JMML remains unclear. Patients with JMML from our single-center cohort between January 2008 and December 2019 were included. Overall, 77 patients were eligible. Multivariate Cox proportional hazard models showed that patients with red cell distribution width coefficient of variation (RDW-CV) >17.35% at diagnosis were susceptible to much worse overall survival rate (hazard ratio [HR] = 5.22, confidence interval [CI] = 1.50–18.21, P = .010). Besides, the combination of RDW elevation and protein phosphatase non-receptor type 11 (PTPN11) mutation was likely to predict a subgroup with the worst outcomes in our cohort. RDW is an independent prognostic variable in JMML subjects. RDW may be regarded as an inexpensive biomarker to predict the clinical outcome in patients with JMML.

The advancement in performance in the domain of flexible wearable strain sensors has become increasingly significant due to extensive research on laser-induced graphene (LIG). An innovative doping modification technique is required owing to the limited progress achieved by adjusting the laser parameters to enhance the LIG’s performance. By pre-treating with AgNO3, we successfully manufactured LIG with a uniform dispersion of silver nanoparticles across its surface. The experimental results for the flexible strain sensor exhibit exceptional characteristics, including low resistance (183.4 Ω), high sensitivity (426.8), a response time of approximately 150 ms, and a relaxation time of about 200 ms. Moreover, this sensor demonstrates excellent stability under various tensile strains and remarkable repeatability during cyclic tests lasting up to 8000 s. Additionally, this technique yields favorable results in finger bending and hand back stretching experiments, holding significant reference value for preserving the inherent characteristics of LIG preparation in a single-step and in situ manner.

The distinctive quality of Sichuan south-road dark tea (SSDT) is gradually disappearing with processing innovation. Here, near-infrared (NIR) spectroscopy (NIRS) and spectrofluorometric techniques were utilized to determine the spectral characteristics of dried SSDT and its brew, respectively. Combined with chemical analysis, the multidimensional quality characteristics of SSDT will be presented. Finally, the NIR spectral fingerprint of dried SSDT was observed, with Kangzhuan (KZ) and Jinjian (JJ) showing a very similar NIR spectrum. The SiPLS models effectively predicted the levels of theabrownin, caffeine, and epigallocatechin gallate, based on the NIR spectrum, with root-mean-square errors of calibration of 0.15, 0.12, and 0.02 for each chemical compound, root-mean-square errors of prediction of 0.20, 0.09, and 0.03, and both corrected and predicted correlation coefficients greater than 0.90. Meanwhile, the fluorescence characteristics of the SSDT brew were identified based on the parallel factor analysis for the fluorescence excitation–emission matrix (EEM). The KZ and JJ brews could be classified with 100% accuracy using extreme-gradient-boosting discriminant analysis. The integration of NIRS and fluorometric EEM seems to be a powerful technique for characterizing SSDTs, and the results can greatly benefit the production and quality control of SSDTs.

Abstract Background For the unclear pathogenesis of Sjogren's syndrome (SS), further exploration is necessary. Mesenchymal stem cells (MSCs) and derived exosomes (MSCs‐exo) have exhibited promising results in treating SS. Object This study aimed to investigate the effect and mechanism of human umbilical cord MSCs (UC‐MSCs) on SS. Methods Nonobese Diabetic (NOD) mouse splenic T cells were co‐cultured with UC‐MSCs and UC‐MSCs‐exo, and interferon‐gamma (IFN‐γ), interleukin (IL)‐6, IL‐10, prostaglandin E2 (PGE2), and transforming growth factor‐β1 (TGF‐β1) levels in the supernatant were assessed by quantitative real‐time polymerase chain reaction and enzyme‐linked immunosorbent assay. Co‐cultured T cells were injected into NOD mice via the tail vein. The inflammatory cell infiltration in the intestine and the submandibular gland was characterized by hematoxylin‐eosin staining. Treg/Th17 homeostasis within the spleen was determined by flow cytometry. Gut microbiota was detected by 16S rRNA sequencing, and the relationship between differential microbiota and Treg/Th17 cytokines was analyzed by the Pearson correlation coefficient. Results UC‐MSCs, UC‐MSCs‐exo, and NOD mouse splenic T cells were successfully cultured and identified. After T cells were co‐cultured with UC‐MSCs and UC‐MSCs‐exo, both IFN‐γ and IL‐6 were decreased while IL‐10, PGE2, and TGF‐β1 were increased in transcriptional and translational levels. UC‐MSCs and UC‐MSCs‐exo partially restored salivary secretion function, reduced Ro/SSA antibody and α‐Fodrin immunoglobulin A levels, reduced inflammatory cell infiltration in the intestine and submandibular gland, raised proportion of Treg cells, decreased IFN‐γ, IL‐6, IL‐2, IL‐17, lipopolysaccharide, and tumor necrosis factor‐alpha levels, and raised IL‐10, Foxp3, and TGF‐β1 levels by affecting co‐cultured T cells. The intervention of UC‐MSCs and UC‐MSCs‐exo improved intestinal homeostasis in NOD mice by increasing microbiota diversity and richness. Additionally, differential microbiota was significantly associated with Treg/Th17 cytokine levels. Conclusion Human UC‐MSCs and UC‐MSCs‐exo improved disease characterization of SS in NOD mice through regulation of gut microbiota and Treg/Th17 cellular immunity.

Abstract Background Neutropenic children with hematological diseases were associated with higher morbidity of carbapenem-resistant enterobacteriaceae (CRE) blood-stream infection (BSI) or colonization. But it was still murky regarding clinical characteristics, antimicrobial susceptibility, and outcomes of CRE-BSI in these patients. We aimed to identify the potential risk factors for subsequent bacteremia and clinical outcome caused by CRE-BSI. Methods Between 2008 and 2020, 2,465 consecutive neutropenic children were enrolled. The incidence and characteristics of CRE-BSI were explored in CRE-colonizers versus non-colonizers. Survival analysis was performed and risk factors for CRE-BSI and 30-day mortality were evaluated. Results CRE-carriers were identified in 59/2465 (2.39%) neutropenic children and19/59 (32.2%) developed CRE-BSI, while 12/2406 (0.5%) of non-carriers developed CRE-BSI (P

Lysine methyltransferase 2A-rearranged acute myeloid leukemia (KMT2A-r AML) is a special entity in the 2022 World Health Organization classification of myeloid neoplasms, characterized by high relapse rate and adverse outcomes. Current risk stratification was established on the treatment response and translocation partner of KMT2A. To study the transcriptomic feature and refine the current stratification of pediatric KMT2A-r AML, we analyzed clinical and RNA sequencing data of 351 patients. By implementing least absolute shrinkage and selection operator algorithm, we identified 7 genes (KIAA1522, SKAP2, EGFL7, GAB2, HEBP1, FAM174B, and STARD8) of which the expression levels were strongly associated with outcomes. We then developed a transcriptome-based score, dividing patients into 2 groups with distinct gene expression patterns and prognosis, which was further validated in an independent cohort and outperformed the LSC17 score. We also found cell cycle, oxidative phosphorylation, and metabolism pathways were upregulated in patients with inferior outcomes. By integrating clinical characteristics, we proposed a simple-to-use prognostic scoring system with excellent discriminability, which allowed us to distinguish allogeneic hematopoietic stem cell transplantation candidates more precisely. In conclusion, pediatric KMT2A-r AML is heterogenous on transcriptomic level and the newly proposed scoring system combining clinical characteristics and transcriptomic features can be instructive in clinical routines.

Raw dark tea (RDT) usually needs to be stored for a long time to improve its quality under suitable relative humidity (RH). However, the impact of RH on tea quality is unclear. In this study, we investigated the metabolites and microbial diversity, and evaluated the sensory quality of RDT stored under three RH conditions (1%, 57%, and 88%). UHPLC-Q-TOF-MS analysis identified 144 metabolites, including catechins, flavonols, phenolic acids, amino acids, and organic acids. 57% RH led to higher levels of O-methylated catechin derivatives, polymerized catechins, and flavonols/flavones when compared to 1% and 88% RH. The best score in sensory evaluation was also obtained by 57% RH. Aspergillus, Gluconobacter, Kluyvera, and Pantoea were identified as the core functional microorganisms in RDT under different RH storage conditions. Overall, the findings provided new insights into the variation of microbial communities and chemical components under different RH storage conditions.

The penetration of distributed energy resources (DERs) and energy-intensive resources is gradually increasing in active distribution networks (ADNs), which leads to frequent and severe voltage violation problems. As a densely distributed flexible resource in the future distribution network, 5G base station (BS) backup battery is used to regulate the voltage profile of ADN in this paper. First, the dispatchable potential of 5G BS backup batteries is analyzed. Considering the spatial-temporal characteristics of electric load for 5G BS, the dispatchable capacity of backup batteries at different time intervals is evaluated based on historical heat map data. Then, a voltage profile optimization model for ADN is established, consisting of 5G BS backup batteries and other voltage regulation resources. In this model, the charging/discharging behavior of backup batteries is based on its evaluation result of dispatchable capacity. Finally, the range of charging/discharging cost coefficients of 5G BS that benefits ADN and 5G operators are analyzed respectively. Further, an incentive policy for 5G operators is proposed. Under this policy, the charging/discharging cost coefficients of 5G BS can achieve a win-win situation for ADN and 5G operators. As an emerging flexible resource in ADN, the effectiveness and economy of 5G BS backup batteries participating in voltage profile optimization are verified in a test distribution network.

Thermal power units (TPUs) play a crucial role in accommodating the high penetration of renewable energy sources (RESs) like wind turbines (WTs) and photovoltaics (PVs). This paper proposes an evaluation framework to quantitatively analyze the flexibility potential of retrofitted TPUs in enhancing the accommodate capability of RESs through coupling integration and optimal scheduling. Firstly, the coordination framework for coupling TPUs with RESs is outlined, including a comprehensive analysis of benefits and implementation strategies. Secondly, an annual optimal scheduling model for TPUs and RESs is developed, incorporating deep peak regulation services, ladder-type constraints for retrofitted TPUs, and their operational characteristics before and after the coupling integration. Thirdly, indices to evaluate RES accommodation levels and TPU regulation capacities are proposed to quantify the performance of power sources. Finally, a real-world case study is conducted to demonstrate that integrating retrofitted TPUs with RESs through coupling significantly enhances RES utilization by 3.6% and boosts TPUs’ downward regulation capabilities by 32%.

The exceptional performance of graphene has driven the advancement of its preparation techniques and applications. Laser-induced graphene (LIG), as a novel graphene preparation technique, has been applied in various fields. Graphene periodic structures created by the LIG technique exhibit superhydrophobic characteristics and can be used for deicing and anti-icing applications, which are significantly influenced by the laser parameters. The laser surface treatment process was simulated by a finite element software analysis (COMSOL Multiphysics) to optimize the scanning parameter range, and the linear array surface structure was subsequently fabricated by the LIG technique. The generation of graphene was confirmed by Raman spectroscopy and energy-dispersive X-ray spectroscopy. The periodic linear array structure was observed by scanning electron microscopy (SEM) and confocal laser imaging (CLSM). In addition, CLSM testings, contact angle measurements, and delayed icing experiments were systematically performed to investigate the effect of scanning speed on surface hydrophobicity. The results show that high-quality and uniform graphene can be achieved using the laser scanning speed of 125 mm/s. The periodic linear array structures can obviously increase the contact angle and suppress delayed icing. Furthermore, these structures have the enhanced ability of the electric heating deicing, which can reach 100 °C and 240 °C within 15 s and within 60 s under the DC voltage power supply ranging from 3 to 7 V, respectively. These results indicate that the LIG technique can be developed to provide an efficient, economical, and convenient approach for preparing graphene and that the hydrophobic surface array structure based on LIG has considerable potential for deicing and anti-icing applications.

There has been a significant shift in research focus in recent years toward laser-induced graphene (LIG), which is a high-performance material with immense potential for use in energy storage, ultrahydrophobic water applications, and electronic devices. In particular, LIG has demonstrated considerable potential in the field of high-precision human motion posture capture using flexible sensing materials. In this study, we investigated the surface morphology evolution and performance of LIG formed by varying the laser energy accumulation times. Further, to capture human motion posture, we evaluated the performance of highly accurate flexible wearable sensors based on LIG. The experimental results showed that the sensors prepared using LIG exhibited exceptional flexibility and mechanical performance when the laser energy accumulation was optimized three times. They exhibited remarkable attributes, such as high sensitivity (~41.4), a low detection limit (0.05%), a rapid time response (response time of ~150 ms; relaxation time of ~100 ms), and excellent response stability even after 2000 s at a strain of 1.0% or 8.0%. These findings unequivocally show that flexible wearable sensors based on LIG have significant potential for capturing human motion posture, wrist pulse rates, and eye blinking patterns. Moreover, the sensors can capture various physiological signals for pilots to provide real-time capturing.

IntroductionSome studies have shown the effectiveness of tea in reducing depression. Gut flora dysfunction is strongly associated with depression. The mechanism by which Ziyan green tea ameliorates depression is not clear.MethodsIn this study, we examined the impact of Ziyan green tea on mice exhibiting symptoms similar to depression. We specifically focused on the role of intestinal flora and its metabolites. We first established a chronic unpredictable mild stress (CUMS) mouse model to induce depressive symptoms and conducted behavioural tests, biochemical tests, and pathological tissue analysis. We also investigated gut microbiota changes by 16S rRNA sequencing and measured faecal metabolites in mice using UHPLC-MS/MS.ResultsThe results showed that Ziyan green tea intervention improved depression-like behaviour, neurobiochemical factors, and reduced levels of pro-inflammatory factors in CUMS mice. Spearman’s correlation analysis showed that different microbial communities (Corynebacterium, Faecalibaculum, Enterorhabdus, Desulfovibrio) correlation with differential metabolites (Cholic acid, Deoxycholic acid, etc.) and depression-related biochemical indicators (5-HT, DA, BDNF, IL-6, and TNF-α).DiscussionIn conclusion, our findings suggest that both low and high-dose interventions of Ziyan green tea have positive preventive effects on CUMS mice without dose dependence, partly because they mainly affect intestinal Purine Metabolism, Bile Acid Biosynthesis and Cysteine Metabolism in CUMS mice, thus stimulating brain 5-HT, DA and BDNF, and decreasing the inflammatory factors IL-6, TNF-α, activate the composition of intestinal flora, improve the intestinal flora environment and thus promote the production of intestinal metabolites, which can be used for depression treatment. It is suggested that Ziyan green tea may achieve an antidepressant effect through the gut-microbiota-brain axis.

Microbes are crucial to the quality formation of Sichuan South-road Dark Tea (SSDT) during pile-fermentation, but their mechanism of action has not yet been elucidated. Here, the glycoside hydrolase (GH) gene family and microbial function of Debaryomyces hansenii Y4 during solid-state fermentation were analyzed, and the results showed that many GH genes being distributed in comparatively abundant GH17, GH18, GH76, GH31, GH47, and GH2 were discovered in D. hansenii. They encoded beta-galactosidase, alpha-D-galactoside galactohydrolase, alpha-xylosidase, mannosidase, etc., and most of the GHs were located in the exocellular space and participated in the degradation of polysaccharides and oligosaccharides. D. hansenii Y4 could develop the mellow mouthfeel and “reddish brown” factors of SSDT via increasing the levels of water extracts, soluble sugars and amino acids but decreasing the tea polyphenols and caffeine levels, combined with altering the levels of thearubiins and brown index. It may facilitate the isomerization between epicatechin gallate and catechin gallate. Moreover, the expression levels of DEHA2G24860g (Beta-galactosidase gene) and DEHA2G08602g (Mannan endo-1,6-alpha-mannosidase DFG5 gene) were sharply up-regulated in fermentative anaphase, and they were significantly and negatively correlated with epicatechin content, especially, the expression of DEHA2G08602g was significantly and negatively correlated with catechin gallate level. It was hypothesized that D. hansenii Y4 is likely to be an important functional microbe targeting carbohydrate destruction and catechin transformation during SSDT pile-fermentation, with DEHA2G08602g as a key thermotolerant functional gene.

ObjectiveBrain neuroplasticity in which sleep affects the speed of information processing in the elderly population has not been reported. Therefore, this study was conducted to explore the effects of sleep on information processing speed and its central plasticity mechanism in the elderly.MethodsA total of 50 individuals aged 60 and older were enrolled in this case control study. All subjects were divided into two groups according to the sleep time: short sleep duration (< 360 min) (6 men and 19 women; mean age: 66.96 ± 4.28 years old), and non-short sleep duration (> 360 min) (13 men and 12 women). Resting-state functional magnetic resonance imaging (rs-fMRI) data were collected, and the amplitude of low frequency fluctuation (ALFF), regional homogeneity (ReHo), and degree centrality (DC) were calculated for each participant. Two-sample t-tests were performed to compare the ALFF, ReHo, and DC maps between the two groups. Then, the relationships among clinical features, fMRI and cognitive function were analyzed using general linear model.ResultsShort sleep duration group showed significantly increased ALFF value in the bilateral middle frontal gyrus and right insula; significantly increased ReHo value in the left superior parietal gyrus, and decreased ReHo value in the right crebellum; significantly decreased DC value in the left inferior occipital gyrus, left superior parietal gyrus and right cerebellum (p

Abstract Background Intestinal bacteria of mammal can be influenced by many factors, environmental bacteria is an important factor. However, there are few studies on the interactions between environmental bacteria and intestinal bacteria in wild mammals. To explore the associations between the intestinal bacteriome and the related environmental bacteriome, the intestinal bacterial communities of Eospalax cansus at three different sites and the bacterial communities of the surrounding soil (outside and inside the cave) at each site were investigated by 16S rRNA sequencing. Results The composition and structure between zokor intestinal bacteria and related soil bacteria were distinct, and the soil of zokor habitat harbored significantly higher diversity than that of zokor intestinal bacteria. We have found that host factors may be more important than environmental factors in shaping intestinal bacteriome. In addition, it was found that the relative abundances of shared OTUs between zokors and related soil were significantly negatively related. These shared OTUs were present in the soil at relatively low abundance. However, these shared OTUs between zokors and soil were affiliated with diverse bacterial taxa, and they were related to the degradation of complex carbohydrates. Conclusions These results suggested that the zokor gut may mainly select for low-abundance but diverse soil bacteria, which may be a host- specific choice for zokor to meet the needs of its phytophagous dietary.

The fermentation is the main process to form the unique flavor and health benefits of dark tea. Numerous studies have indicated that the microorganisms play a significant part in the fermentation process of dark tea. Dark tea has the quality of “The unique flavor grows over time,” but unscientific storage of dark tea might cause infestation of harmful microorganisms, thereby resulting in the remaining of fungi toxins. Mycotoxins are regarded as the main contributor to the quality of dark tea, and its potential mycotoxin risk has attracted people’s attention. This study reviews common and potential mycotoxins in dark tea and discusses the possible types of masked mycotoxins in dark tea. A summary of the potential risks of mycotoxins and masked mycotoxins in dark tea is presented, intending to provide a reference for the prevention and risk assessment of harmful fungi in dark tea.

Instant dark teas (IDTs) were individually liquid-state fermented using the fungi Aspergillus cristatus, Aspergillus niger, and Aspergillus tubingensis. To understand how the chemical constituents of IDTs were affected by the fungi, samples were collected and measured by liquid chromatography-tandem mass-tandem mass spectrometry (LC-MS/MS). Untargeted metabolomics analysis revealed that 1,380 chemical constituents were identified in positive and negative ion modes, and 858 kinds of chemical components were differential metabolites. Through cluster analysis, IDTs were different from the blank control, and their chemical constituents mostly included carboxylic acids and their derivatives, flavonoids, organooxygen compounds, and fatty acyls. And the metabolites of IDTs fermented by A. niger and A. tubingensis had a high degree of similarity and were classified into one category, which showed that the fungus used to ferment is critical to the formation of certain qualities of IDTs. The biosynthesis of flavonoids and phenylpropanoid, which involved nine different metabolites such as p-coumarate, p-coumaroyl-CoA, caffeate, ferulate, naringenin, kaempferol, leucocyanidin, cyanidin, and (-)-epicatechin, were significant pathways influencing the quality formation of IDTs. Quantification analysis indicated that the A. tubingensis fermented-IDT had the highest content of theaflavin, theabrownin, and caffeine, while the A. cristatus fermented-IDT had the lowest content of theabrownin, and caffeine. Overall, the results provided new insights into the relationship between the quality formation of IDTs and the microorganisms used in liquid-state fermentation.

Business failure prediction is very important for the sustainable development of enterprises. Machine learning algorithms, especially ensemble algorithms, have shown great economic benefits in enterprise financial early warning. However, the highly imbalanced class distribution of financial risk data and the inexplainable of most machine learning-based early distress warning models limit their commercial application. To address the above limitations, we enhance the business failure prediction performance by tree-ensemble in a boosting manner. Moreover, to solve the class imbalanced issue in business failure datasets, a weighted objective function, weighted cross-entropy, is embedded into the boosted tree framework, making the weighted XGBoost a cost-sensitive business failure prediction model. Besides, to tackle the second issue, we explore the intrinsic interpretability of the proposed method by visualizing the feature importance and incorporating a partial dependence plot technique to locally interpret the individual business failure event. Experimental results on business failure datasets with different predictive horizons collected from China Security Market Accounting Research (CSMAR) database show the proposed weighted XGBoost is a good solution to reduce the error on recognizing firms in business failure. Furthermore, the visualized feature importance score and partial dependence plot result both demonstrate that the cost-sensitive tree-based ensemble can be a good tool to guide the investors in making rational as well as provide interpretable business prediction results as a reference for the policy-making of the regulators.

Flexible wearable strain sensors based on laser-induced graphene (LIG) have attracted significant interest due to their simple preparation process, three-dimensional porous structure, excellent electromechanical characteristics, and remarkable mechanical robustness. In this study, we demonstrated that LIG with various defects could be prepared on the surface of polyimide (PI) film, patterned in a single step by adjusting the scanning speed while maintaining a constant laser power of 12.4 W, and subjected to two repeated scans under ambient air conditions. The results indicated that LIG produced at a scanning speed of 70 mm/s exhibited an obvious stacked honeycomb micropore structure, and the flexible strain sensor fabricated with this material demonstrated stable resistance. The sensor exhibited high sensitivity within a low strain range of 0.4–8.0%, with the gauge factor (GF) reaching 107.8. The sensor demonstrated excellent stability and repeatable response at a strain of 2% after approximately 1000 repetitions. The flexible wearable LIG-based sensor with a serpentine bending structure could be used to detect various physiological signals, including pulse, finger bending, back of the hand relaxation and gripping, blinking eyes, smiling, drinking water, and speaking. The results of this study may serve as a reference for future applications in health monitoring, medical rehabilitation, and human–computer interactions.

Abstract Background Children with acute lymphoblastic leukemia (ALL) undergoing chemotherapy experience a relatively high risk of infection. And the disturbance of gut microbiota is generally believed to impair intestinal barrier function and may induce bacterial infections and inflammation. The study aimed to investigate the alterations in the gut microbiota and assess its relationship with chemotherapy-induced pneumonia in pediatric ALL patients. Methods We conducted a case–control study with 14 cases affected by pneumonia and 44 unaffected subjects and characterized the physiological parameters and gut microbiota by microarray-based technique. Results There were significant differences in α- and β-diversity in the affected group compared with the control group. At species level, the LEfSe analysis revealed that Enterococcus malodoratus, Ochrobactrum anthropi and Actinomyces cardiffensis were significantly abundant in the affected subjects. A receiver operating characteristic (ROC) curve yielded the area under the curve (AUC) of 0.773 for classification between the two groups. In addition, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways involved in the bacterial secretion system were more enriched in the affected group than in the control group. Conclusions Gut microbiota alteration was associated with chemotherapy-induced pneumonia in pediatric ALL patients, which provided a new perspective on the personalized clinical care of pediatric ALL.

In recent years, there has been an increasingly heated debate on whether Chinese dark tea is contaminated with mycotoxins and whether it poses health risks to consumers. In this study, a rapid method based on high-performance liquid chromatography was used to detect ochratoxin A (OTA) in Chinese dark tea samples from different regions of China and different years. Of the 228 Chinese dark tea samples tested, 21 were detected for OTA contamination, with a concentration ranging from 2.51 ± 0.16 to 12.62 ± 0.72 μg/kg. Subsequently, a dark tea drinking risk assessment was conducted, and the hazard quotient for each group was far below the acceptable level of 1.0. Of the 12 Aspergillus spp. strains isolated, one strain of Aspergillus niger had the ability to produce OTA. We also found that tea polyphenols and epigallocatechin gallate inhibited the growth of ochratoxin-producing Aspergillus niger and the expression of non-ribosomal peptide synthetase (NRPS), a key gene for ochratoxin synthesis. Thus, OTA contamination of dark tea is at an acceptable risk level, and the inhibition of ochratoxigenic Aspergillus niger by polyphenols provides new insights into the safety of dark tea consumption.

The NOD-like receptor pyrin domain 3 (NLRP3) inflammasome is activated during atherogenesis, but how this occurs is unclear. Here, we explored the mechanisms activating and regulating NLRP3 inflammasomes via the acid sphingomyelinase (ASM)-ceramide signaling pathway. As a neointima formation model, partial left carotid ligations were performed on endothelial cell (EC)-specific ASM transgene mice (Smpd1trg/ECcre) and their control littermates (Smpd1trg/WT and WT/WT) fed on the Western diet (WD). We found neointima formation remarkably increased in Smpd1trg/ECcre mice over their control littermates. Next, we observed enhanced colocalization of NLRP3 versus adaptor protein ASC (the adaptor molecule apoptosis-associated speck-like protein containing a CARD) or caspase-1 in the carotid ECs of WD-treated Smpd1trg/ECcre mice but not in their control littermates. In addition, we used membrane raft (MR) marker flotillin-1 and found more aggregation of ASM and ceramide in the intima of Smpd1trg/ECcre mice than their control littermates. Moreover, we demonstrated by in situ dihydroethidium staining, carotid intimal superoxide levels were much higher in WD-treated Smpd1trg/ECcre mice than in their control littermates. Using ECs from Smpd1trg/ECcre and WT/WT mice, we showed ASM overexpression markedly enhanced 7-ketocholesterol (7-Ket)-induced increases in NLRP3 inflammasome formation, accompanied by enhanced caspase-1 activity and elevated interleukin-1β levels. These 7-Ket-induced increases were significantly attenuated by ASM inhibitor amitriptyline. Furthermore, we determined that increased MR clustering with NADPH oxidase subunits to produce superoxide contributes to 7-Ket-induced NLRP3 inflammasome activation via a thioredoxin-interacting protein-mediated controlling mechanism. We conclude that ceramide from ASM plays a critical role in NLRP3 inflammasome activation during hypercholesterolemia via MR redox signaling platforms to produce superoxide, which leads to TXNIP dissociation.

Non-Down’s syndrome acute megakaryocytic leukemia (non-DS-AMKL) is a subtype of childhood acute myeloid leukemia (AML), whose prognosis, prognostic factors and treatment recommendations have not yet to be defined in children. We conducted a retrospective study with 65 newly diagnosed non-DS-AMKL children from August 2003 to June 2020 to investigate the clinical impact of factors and clinical outcome. Among all 65 patients, 47 of them were treated at our center who received three different regimens due to time point of admission (CAMS-another, CAMS-2009 and CAMS-2016 protocol), and the efficacy were compared. Patients with newly diagnosed non-DS-AMKL accounted for 7.4% of pediatric AML cases. The median age of the patients was 18 months at diagnosis, and over 90% of them were under three-years-old. The overall survival (OS) rates were 33.3% ± 1.7%, 66.7% ± 24.4% and 74.2% ± 4.0% for three groups (CAMS-another, CAMS-2009 and CAMS-2016 regimen), respectively. In CAMS-2016 group, the complete remission (CR) rate after induction was 67.7% (21/31), while the total CR rate after all phases of chemotherapy was 80.6% (25/31). The 2-year survival probability did not significantly improve in patients underwent HSCT when compared with non-HSCT group (75.0% ± 4.7% vs. 73.9% ± 4.6%, p=0.680). Those who had a “dry tap” during BM aspiration at admission had significantly worse OS than those without “dry tap” (33.3% ± 8.6% vs. 84.0% ± 3.6%, p=0.006). Moreover, the results also revealed that patients with CD34+ had significantly lower OS (50.0% ± 6.7% vs. 89.5% ± 3.5%, p=0.021), whereas patients with CD36+ had significantly higher OS than those who were negative (85.0% ± 4.0% vs. 54.5% ± 6.6%, p=0.048). In conclusion, intensive chemotherapy resulted in improved prognosis of non-DS-AMKL children and subclassification may base on “dry tap” and immunophenotypic. Although some progress has been made, outcomes of non-DS-AMKL children remain unsatisfactory, especially in HSCT group, when compared with other AML types.

Abstract Background The intestinal microbes in mammals play a key role in host metabolism and adaptation. As a subterranean rodent, zokor digs tunnels for foraging and mating. These digging activities of zokors increase the energy expenditure relative to their aboveground counterparts. However, relatively little is known regarding intestinal microbes of zokor and how they make full use of limited food resources underground for high energy requirements. Results Eospalax cansus and Eospalax rothschildi had distinct intestinal microbes. Although the composition of intestinal microbes is similar in two species, the proportion of bacterium are distinctly different between them. At phylum level, 11 phyla were shared between two species. Firmicutes and Bacteroidota were two dominant microbes in both of two species, while Eospalax cansus have a significantly high proportion of Firmicutes/Bacteroidota than that of Eospalax rothschildi. At genus level, norank_f_Muribaculaceae were dominant microbes in both of two zokor species. The relative abundance of 12 genera were significantly different between two species. Some bacterium including unclassified_f__Lachnospiraceae, Lachnospiraceae_NK4A136_group, Ruminococcus and Eubacterium_siraeum_group associated with cellulose degradation were significantly enriched in Eospalax cansus. Although alpha diversity was with no significant differences between Eospalax cansus and Eospalax rothschildi, the intestinal microbes between them are significant distinct in PCoA analysis. We have found that trapping location affected the alpha diversity values, while sex and body measurements had no effect on alpha diversity values. PICRUSt metagenome predictions revealed significant enrichment of microbial genes involved in carbohydrate metabolism in Eospalax cansus rather than Eospalax rothschildi. Conclusions Our results demonstrate that Eospalax cansus harbor a stronger ability of fermentation for dietary plants than Eospalax rothschildi. The stronger ability of fermentation and degradation of cellulose of intestinal microbes of Eospalax cansus may be a long-time adaptation to limited food resources underground.

Microbes are critical in the Sichuan South-road Dark Tea (SSDT) organoleptic quality development during pile-fermentation. Piled tea center at fermenting metaphase is crucial for the conversion of its quality components. In this study, we investigated the microbial community of piled SSDT center below the stacked tea surface of 15 cm (SSDTB), 50 cm (SSDTX), and 85 cm (SSDTH) on the second turning time of pile-fermentation, respectively. Results showed that SSDTH and SSDTB had a higher similarity in the microbial community. Pantoea (36.8%), Klebsiella (67.7%), and Aspergillus (35.3%) were the most abundant in SSDTH, SSDTB, and SSDTX, respectively. We found 895 species were common among all samples, but 86, 293, and 36 species were unique to SSDTB, SSDTX, and SSDTH, respectively. Aspergillus niger showed high co-occurrence and was positively correlated with numerous microbes in SSDT samples, and Aspergillus niger M10 isolated from SSDTX was excellent at enhancing soluble sugar (SS), amino acids (AAs), theaflavin (TF), and thearubigins (TR) contents, while decreasing catechin (Cat), tea polyphenols (TPs)/AA, Caf/SS, Cat/SS, TPs/SS, and (TPs + Caf)/SS levels in AM10 post-fermentation, as compared with the control. Moreover, it also produced a noticeable difference in the CIELab parameters in dried, liquor, and infused tea colors between AM10 and control during fermentation. When it was further inoculated on differential mediums, we detected glycoside hydrolases, namely, β-glucosidase, mannosidase, pectinase, cellulase, amylase, and α-galactosidase being secreted by Aspergillus niger M10. Taken together, SSDXT presented a more unique microbial community. Aspergillus niger M10 probably improved the sweet and mellow taste, and the yellow brightness and red color of SSDT during fermentation. It also provided new insights into the microbial profile and organoleptic quality development mechanism of SSDT during pile-fermentation.

To further emphasize the clinical–genetic features and prognosis of CDKN2A/B deletions in childhood acute lymphoblastic leukemia (ALL), we retrospectively analyzed 819 consecutive B-ALL patients treated with the Chinese Children’s Cancer Group ALL-2015 (CCCG-ALL-2015) protocol, and fluorescence in situ hybridization (FISH) analysis on CDKN2A/B deletion was available for 599 patients. The prevalence of CDKN2A/B gene deletions was 20.2% (121/599) of B-ALL. CDKN2A/B deletions were significantly associated with older age, higher leukocyte counts, a higher percentage of hepatosplenomegaly, and a higher frequency of BCR-ABL (p < 0.05). Those patients achieved similar minimal residual disease (MRD) clearance and complete remission compared to patients without CDKN2A/B deletion. The CDKN2A/B deletions were correlated with inferior outcomes, including a 3-year event-free survival (EFS) rate (69.8 ± 4.6 vs. 89.2 ± 1.6%, p = 0.000) and a 3-year overall survival (OS) rate (89.4% ± 2.9% vs. 94.7% ± 1.1%, p = 0.037). In multivariable analysis, CDKN2A/B deletion was still an independent prognostic factor for EFS in total cohorts (p < 0.05). We also detected a multiplicative interaction between CDKN2A/B deletions and TP53 deletion on dismal prognosis (p-interaction < 0.05). In conclusion, CDKN2A/B deletion is associated with distinct characteristics and serves as a poor prognostic factor in pediatric ALL, especially in TP53 deletion carriers.

Abstract This paper proposes an active fault‐tolerant control (FTC) strategy for a class of non‐linear Lipschitz systems. The proposed FTC approach employs the integral sliding mode control (ISMC) technique due to its inherent capability of dealing with system uncertainties. First, under the nominal fault‐free condition, the linear matrix inequality technique is introduced to design the primary controller for the non‐linear Lipschitz system. To accommodate the actuator faults/failures, the ISMC law is combined with a control allocation scheme that distributes the control signals to the redundant actuators. A non‐linear octorotor system is then used as a test bench to validate the tolerance performance of the proposed FTC strategy. In particular, the proposed FTC strategy is applied for the inner‐loop control, while in the outer loop, a fractional‐order control approach is used to achieve the precise longitude and latitude control. Finally, various simulations are performed to justify the effectiveness of the proposed control scheme.

Abstract Background The preferred salvage treatment for children with relapsed/refractory acute myeloid leukemia (R/R‐AML) remains unclear. The combination of cladribine/Ara‐C/granulocyte‐colony stimulating factor and mitoxantrone (CLAG‐M) shown promising results in adult R/R‐AML. We aim to investigate the efficacy and safety of CLAG‐M versus mitoxantrone/etoposide/cytarabine (MEC) or idarubicin/etoposide/cytarabine (IEC) in R/R‐AML children. Methods Fifty‐five R/R‐AML children were analyzed. The overall response rate (ORR), overall survival (OS), and progression‐free survival (PFS) at 3‐year were documented. Karyotype or mutations status were summarized as different risk groups. Results The ORR was achieved in 80% (16/20) and 51% (18/35) of patients after one‐cycle of CLAG‐M and MEC/IEC treatment (p

Abstract. Next-generation sequencing technology has been widely utilized for the diagnosis of Fanconi anemia (FA). However, mixed cell sequencing and chimerism of FA patients may lead to unconfirmed genetic subtypes. Herein, we introduced two novel diagnostic methods, including single-cell sequencing and capillary nano-immunoassay. One FA case with FANCM c.4931G>A p.R1644Q and FANCD1 c.6325G>A p.V2109I was studied. The DNA of 28 cells was amplified and eight types of cells were observed after Sanger sequencing. There were two homozygous mutations (FANCM/FANCD1). Furthermore, the capillary nano-immunoassay was conducted to analyze the expression profile of FA-associated proteins. Abnormal FANCM and FANCD1 expressions simultaneously existed. This case was thus diagnosed as FA-D1/FA-M dual subtype. Compared with mixed cell sequencing, single-cell sequencing data shows more accuracy for the FA subtype evaluation, while the capillary nano-immunoassay is a good method to detect the expression profile of abnormal or modified FA protein.

In this paper, we investigate finite-time bounded (FTB) tracking control for a class of neutral systems. Firstly, the dynamic equation of the tracking error signal is given based on the original neutral system. Then, we combine it with the equations of the state vector to construct an error system, where the reference signal and the disturbance signal are fused in a new vector. Next, about the error system, we study the input–output finite-time stability problem of the closed-loop system by utilizing the Lyapunov–Krasovskii functional. We also give a finite-time stability condition in the form of linear matrix inequalities (LMIs). Furthermore, the delay-dependent and delay-independent finite-time bounded tracking controllers are designed separately for the original system. Finally, a realistic example is given to show the effectiveness of the controller design method in the paper.

Neutrophils constitute abundant cellular components in atherosclerotic plaques. Most of the current studies are focused on the roles of granular proteins released by neutrophils in atherosclerosis. Here, we revealed a unique subset of neutrophils which exhibit the characteristics of antigen-presenting cell (APC) (which were called APC-like neutrophils afterwards) in atherosclerosis. The roles of APC-like neutrophils and relevant mechanisms were investigated in hyperlipidemic patients and atherosclerotic mice. Higher percentages of neutrophils and APC-like neutrophils were found in peripheral blood of hyperlipidemic patients than that of healthy donors. Meanwhile, we also identified higher infiltration of neutrophils and APC-like neutrophils in atherosclerotic mice. Ox-LDL induced Phorbol-12-myristate-13-acetate (PMA)-activated neutrophils to acquire the APC-like phenotype. Importantly, upon over-expression of APC-like markers, neutrophils acquired APC functions to promote the proliferation and interferon-γ production of CD3+ T cells via HLA-DR/CD80/CD86. In accordance with what found in vitro, positive correlation between neutrophils and CD3+ T cells was observed in hyperlipidemic patients. In conclusion, our work identifies a proinflammatory neutrophil subset in both hyperlipidemic patients and atherosclerotic mice. This unique phenotype of neutrophils could activate the adaptive immune response to promote atherosclerosis progression. Thus, this neutrophil subset may be a new target for immunotherapy of atherosclerosis.

ObjectiveT-cell acute lymphoblastic leukemia (T-ALL) is a rare hematological malignancy with a poor prognosis. The present study aims to identify the precise risk grouping of children with T-ALL.MethodsWe analyzed the outcomes for 105 consecutive patients treated using the Chinese Children’s Cancer Group ALL-2015 (CCCG-ALL-2015) protocol registered with the Chinese Clinical Trial Registry (ChiCTR-IPR-14005706) between 2015 and 2020 in our center. Nine out of 21 clinical and biological indicators were selected for the new scoring system based on the analysis in this study.ResultsThe 5-year overall survival (OS), event-free survival (EFS), and disease-free survival (DFS) rates for the 105 patients were 83.1 ± 4.8%, 72.4 ± 5.6%, and 78.4 ± 3.6%, respectively. Based on the new scoring system, 90 evaluable children were regrouped into low-risk (n=22), intermediate-risk (n=50), and high-risk (n=18) groups. The 5-year survival (OS, EFS, and RFS) rates for all patients in the low-risk group were 100%, significantly higher than the rates for those in the intermediate-risk group (91.2 ± 5.2%, 74.4 ± 8.6%, and 82.5 ± 6.2%, respectively) and high-risk group (59.0 ± 13.2%, 51.9 ± 12.4%, and 51.9 ± 12.4%, respectively) (all P values < 0.01).ConclusionThe CCCG-ALL-2015 program significantly improved the treatment outcomes for childhood T-ALL as compared with the CCCG-ALL-2008 protocol. Our new refined risk grouping system showed better stratification among pediatric T-ALL patients and better potential in evaluating therapeutic efficacy.

ObjectiveA type of rodent called a zokor causes great harm to agriculture and forestry production due to its large and sophisticated diet. As this rodent lives subterrane for most of its life, researchers know little about its dietary habits. Further understanding of its diet is important for developing green and sustainable control strategies for the zokor.MethodsChloroplast trnL gene and internal transcription spacer 1 primers were selected for high-throughput sequencing of stomach contents of captured zokor by DNA metabarcoding.ResultsA total of 25 zokors were selected, the food list of 32 families, 80 genera, and 154 species was obtained. At the family level, it was found that zokors mainly fed on Asteraceae, Poaceae, Rosaceae, Pinaceae, Brassicaceae, and Apiaceae. At the genus level, zokors mainly fed on Echinops, Littledalea, Artemisia, Picea, Cirsium, and Elymus. The diet alpha diversity of Eospalax cansus was slightly higher than that of Eospalax cansus (P>0.05). The zokor's diet is highly phconsistent with the resources of its habitat. Most food choices tend to be the same between the two zokors. They fed primarily on Calamagrostis, Cirsium, Echinops, Medicago, Sanguisorba, and Taraxacum. Zokors mainly fed on the roots of perennial herbs, which are important source of energy.ConclusionHigh-throughput sequencing-based DNA metabarcoding technology has effectively revealed the diet of zokors and indicated that zokors are food generalists.

Abstract Background The prognosis of children with acute monocytic leukemia (AML‐M5) remains unsatisfactory and the risk profile is still controversial. We aim to investigate the prognostic value of clinical and cytogenetic features and propose a new risk stratification in AML‐M5 children. Methods We included 132 children with AML‐M5. Overall survival (OS) and progression‐free survival (PFS) were documented. Cox regression was performed to evaluate the potential risk factors of prognosis. Results The 5‐year‐OS was 46.0% (95% confidence intervals, 41.6%‐50.4%) in all patients. There was significantly lower OS in the age ≤ 3 years old (P = .009) and hyperleukocytosis (P

Relapse of childhood AML1-ETO (AE) acute myeloid leukemia is the most common cause of treatment failure. Optimized minimal residual disease monitoring methods is required to prevent relapse. In this study, we used next-generation sequencing to identify the breakpoints in the fusion gene and the DNA-based droplet digital PCR (ddPCR) method was used for dynamic monitoring of AE-DNA. The ddPCR technique provides more sensitive and precise quantitation of the AE gene during disease progression and relapse. Quantification of the AE fusion gene by ddPCR further contributes to improved prognosis. Our study provides valuable methods for dynamic surveillance of AE fusion DNA and assistance in determining the prognosis.

BackgroundThe aim of the study was to validate the diagnostic role of circulating tumor DNA (ctDNA) in genetics aberration on the basis of next-generation sequencing (NGS) in pediatric acute myeloid leukemia (AML).MethodsBone marrow (BM) and peripheral blood (PB) were collected from 20 AML children at the time of initial diagnosis, and a ctDNA sample was isolated from PB. Detection of mutation was performed on ctDNA, BM, and peripheral blood mononuclear cell (PBMC) by NGS based on a 185-gene panel.ResultsAmong 185 genes sequenced by the NGS platform, a total of 82 abnormal genes were identified in 20 patients. Among them, 61 genes (74.39%) were detected in ctDNA, PBMC, and BM samples, while 11 (13.41%) genes were found only in ctDNA and 4 (4.88%) were detected only in the BM sample, and 2 (2.44%) were detected only in PBMC. A total of 239 mutations were detected in three samples, while 209 in ctDNA, 180 in bone marrow, and 184 in PBMC. One hundred sixty-four mutations in ctDNA were shared by matched BM samples, and the median variant allelic frequency (VAF) of these mutations was 41.34% (range, 0.55% to 99.96%) and 44.36% (range, 0.56% to 99.98%) in bone marrow and ctDNA. It was found that 65.79% (75/114) of mutations with clinical significance were detected in three samples, with 9 mutations detected both in ctDNA and BM, and 2 mutations detected both in PBMC and BM. The consistency of mutations with clinical significance between ctDNA and BM was 77.06% (84/109). Among the 84 mutations with clinical significance detected in both sources, the concordance of VAF assessment by both methods was high (R2 = 0.895).ConclusionThis study demonstrates that ctDNA was a reliable sample in pediatric AML and can be used for mutation detection. Consistency analysis showed that ctDNA can mirror the genomic information from BM. In addition, a subset of mutations was exclusively detected in ctDNA. These data support the fact that monitoring ctDNA with next-generation sequencing-based assays can provide more information about gene mutations to guide precision treatment in pediatric AML.

Flapping-wing aircraft (FWA) operates in a flight mode that mimics natural flyers, such as birds, bats and insects. For large scale bird-inspired flapping wings aircraft, the design of airfoil parameters is crucial to improving the aerodynamic performance. In order to study the effect of camber on the aerodynamic characteristics, we developed four different airfoils with a chord length of 12 cm. The cambers of airfoils are respectively 30 mm, 25 mm, 20 mm and 15 mm. A numerical investigation into the effects of camber on aerodynamic performance is carried out through COMSOL Multiphysics software using Fluid–Structure Interaction (FSI) module. In this work, the fluid–structure module employs the Navier–Stokes equations coupled with a solid stress–strain physics module and a moving mesh module. The three-dimensional (3D) flapping wing computational models with different cambers are built. The results show that certain camber of airfoil can improve the aerodynamic characteristics of flapping wing.

Atherosclerosis is a chronic inflammatory disease. Interleukin-17-producing CD4+ T cells (Th17 cells) play important roles in the progression of atherosclerosis. However, most of the studies were focused on the advanced stage of atherosclerosis. In the current study, we investigated the roles of Th17 cells, relevant mechanisms in hyperlipidemic patients, and different stages of atherosclerotic mice. Human blood samples were collected, and percentages of Th17 cells, macrophages, and neutrophils were analyzed by flow cytometry. ApoE−/− mice were fed with high-fat diet (HFD) and sacrificed at different time points to evaluate the infiltration of inflammatory cells at different stages of atherosclerosis. Furthermore, essential mechanisms of IL-17A in atherosclerotic inflammatory milieu formation were studied in vivo by intraperitoneal injection with monoclonal anti-murine IL-17 antibody. Our study reveals the higher percentages of Th17 cells, monocytes, and neutrophils in hyperlipidemic patients compared to healthy donors. Meanwhile, we also identify an infiltration of Th17 cells in the early stage of atherosclerosis (4 weeks after HFD), which maintains at high level until late stage of atherosclerosis (20 weeks after HFD). What is more, inflammatory cells including macrophages and neutrophils were also accumulated in atherosclerotic lesions. Neutralization of IL-17 in ApoE−/− mice resulted in less infiltration of macrophages and neutrophils and smaller atherosclerotic lesions. Importantly, in accordance with what is found in the mouse model, positive correlations between Th17 cells and macrophages or neutrophils were observed in hyperlipidemic patients. In conclusion, our clinical and mouse model data together reveal a pro-atherogenic role of Th17 cells through the promotion of inflammation in hyperlipidemic conditions and different stages of atherosclerosis, which further supports the notion that IL-17 may be a therapy target for the treatment of atherosclerosis.

Credit scoring is an effective tool for banks and lending companies to manage the potential credit risk of borrowers. Machine learning algorithms have made grand progress in automatic and accurate discrimination of good and bad borrowers. Notably, ensemble approaches are a group of powerful tools to enhance the performance of credit scoring. Random forest (RF) and Gradient Boosting Decision Tree (GBDT) have become the mainstream ensemble methods for precise credit scoring. RF is a Bagging-based ensemble that realizes accurate credit scoring enriches the diversity base learners by modifying the training object. However, the optimization pattern that works on invariant training targets may increase the statistical independence of base learners. GBDT is a boosting-based ensemble approach that reduces the credit scoring error by iteratively changing the training target while keeping the training features unchanged. This may harm the diversity of base learners. In this study, we incorporate the advantages of the Bagging ensemble training strategy and boosting ensemble optimization pattern to enhance the diversity of base learners. An extreme learning machine-based supervised augmented GBDT is proposed to enhance the discriminative ability for credit scoring. Experimental results on 4 public credit datasets show a significant improvement in credit scoring and suggest that the proposed method is a good solution to realize accurate credit scoring.

Previous studies have shown that gut microbiota can affect human immune system in many ways. Our aim was to investigate quantitative differences in fecal bacterial compositions of childhood acute lymphoblastic leukemia (ALL) patients compared to those of healthy children, so as to identify individual bacterial species that are related to the etiology of ALL. We recruited 81 subjects, including 58 patients with ALL and 23 healthy controls. Fecal samples were collected and examined by 16S rRNA quantitative arrays and bioinformatics analysis. Both Principal Coordinates Analysis (PCoA) and Non-metric Multidimensional scaling (NMDS) demonstrated that the microbial composition of ALL patients deviated from the tight cluster of healthy controls. Multiple bacterial species exhibited significant changes (e.g., Roseburia faecis, Edwardsiella tarda, and Fusobacterium naviforme) in the ALL samples. Some of the differentially abundant taxa were correlated with the level of interleukin-10. The ALL cases could be efficiently distinguished from healthy controls by the random forest model based on differential species (area under ROC curve = 0.843). Taken together, the composition of gut microbiota differed from healthy controls to pediatric ALL patients. Our study identified a series of ALL-related species in the gut microbiota, providing a new direction for future studies aiming to understand the host-gut microbiota interplay in ALL pathogenesis.

Abstract Background The combination of all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) has been suggested to be safe and effective for adult acute promyelocytic leukaemia (APL). As of 2010, the role of cytarabine (Ara-C) in APL was controversial. The aim of this study was to test the efficacy and safety of ATRA and ATO in paediatric APL patients. Also, we assessed whether Ara-C could be omitted in ATO and ATRA- based trials in children. Methods We performed a randomized controlled trial in paediatric APL patients (≤14 years of age) in our hospital from May 2010 to December 2016. All of the patients were assigned to receive ATRA plus ATO for induction followed by one course of idarubicin (IDA) and ATO (28 days). The patients were then randomly assigned to receive two courses of daunorubicin (DNR, no- Ara-C group) or DNR + Ara-C (Ara-C group). All of the patients were followed with maintenance therapy with oral ATRA, 6-mercaptopurine, and methotrexate for 1.5 years. Results Among the 66 patients, 43 were male and 23 were female. All of the patients achieved complete remission (CR) with the exception of one who gave up the treatment. During induction therapy, all toxicity events were reversed after appropriate management. Thirty patients in the Ara-C group underwent 57 courses of treatment, and 35 patients in the no-Ara-C group underwent 73 courses of treatment. No significant differences in age, genders, white blood cell counts, haemoglobin levels, and platelet counts were found between the Ara-C and no-Ara-c groups. Greater myelosuppression and sepsis were observed in the Ara-C group during the consolidation courses. No patient died at consolidation, and only one patient relapsed. No differences were found in event-free survival, disease-free survival and overall survival between the two groups. Additionally, our analysis of the arsenic levels in the plasma, urine, hair and nails of the patients indicated that no significant accumulation of arsenic occurred after ATO was discontinued for 12 months. Conclusions Overall, ATO and ATRA are safe and effective for paediatric APL patients and Ara-C could be omitted when ATO is used for two courses. Trial registration ClinicalTrials.gov (NCT01191541, retrospectively registered on 18 August 2010).