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Abstract Background Understanding the stepwise progression of esophageal squamous cell carcinoma (ESCC) is crucial for developing customized strategies for early detection and optimal clinical management. Herein, we aimed to unravel the transcriptional and immunologic alterations occurring during malignant transformation and identify clinically significant biomarkers of ESCC. Methods Digital spatial profiling (DSP) was performed on 11 patients with early-stage ESCC (pT1) to explore the transcriptional alterations in epithelial, immune cell, and non-immune cell stromal compartments across regions of distinct histology, including normal tissues, low- and high-grade dysplasia, and cancerous tissues. Furthermore, single-cell spatial transcriptomics was performed using the CosMx Spatial Molecular Imaging (SMI) system on 4 additional patients with pT1 ESCC. Immunohistochemical (IHC) analysis was performed on consecutive histological sections of 20 pT1 ESCCs. Additionally, public bulk and single-cell RNA-sequencing (scRNA-seq) datasets were analyzed, and in vitro and in vivo functional studies were conducted. Results Spatial transcriptional reprogramming and dynamic cell signaling pathways that determined ESCC progression were delineated. Increased infiltration of macrophages from normal tissues through dysplasia to cancerous tissues occurred. Macrophage subtypes were characterized using the scRNA-seq dataset. Cell–cell communication analysis of scRNA-seq and SMI data indicated that the migration inhibitory factor (MIF)-CD74 axis may exhibit pro-tumor interactions between macrophages and epithelial cells. DSP, SMI, and IHC data demonstrated that DTX3L expression in epithelial cells and BST2 expression in stromal cells increased gradually with ESCC progression. Functional studies demonstrated that DTX3L or BST2 knockdown inhibited ESCC proliferation and migration and decreased M2 polarization of tumor-associated macrophages. Conclusions Spatial profiling comprehensively characterized the molecular and immunological hallmarks from normal tissue to ESCC, guiding the way to a deeper understanding of the tumorigenesis and progression of this disease and contributing to the prevention of ESCC. Within this exploration, we uncovered biomarkers that exhibit a robust correlation with ESCC progression, offering potential new avenues for insightful therapeutic approaches.

Abstract Metal-oxide interfaces with poor coherency have specific properties comparing to bulk materials and offer broad applications in heterogeneous catalysis, battery, and electronics. However, current understanding of the three-dimensional (3D) atomic metal-oxide interfaces remains limited because of their inherent structural complexity and the limitations of conventional two-dimensional imaging techniques. Here, we determine the 3D atomic structure of metal-oxide interfaces in zirconium-zirconia nanoparticles using atomic-resolution electron tomography. We quantitatively analyze the atomic concentration and the degree of oxidation, and find the coherency and translational symmetry of the interfaces are broken. Atoms at the interface have low structural ordering, low coordination, and elongated bond length. Moreover, we observe porous structures such as Zr vacancies and nano-pores, and investigate their distribution. Our findings provide a clear 3D atomic picture of metal-oxide interface with direct experimental evidence. We anticipate this work could encourage future studies on fundamental problems of oxides, such as interfacial structures in semiconductor and atomic motion during oxidation process.

In this paper, liquid-state fermented sauce mash with salt concentrations of 12% and 18% (w/v) was used as the research object, to explore the effect of gradient heating (15 ℃-20 ℃-25 ℃-30 ℃) on the microbial counting and flavor formation of fermented sauce mash. The results showed that the yeast counts of the low-salt sauce mash sample (TC12) using the gradient heating method was about 1.0 log CFU/g higher than that of the constant temperature (30 ℃) control group (C12) at the end of fermentation, which indicated that the yeasts maintained growth and metabolism for a long time in the gradient heating group. This might be related to the fact that the lower temperature in the early stage of fermentation limited the rapid propagation of yeasts. Among them, the amino nitrogen of the fermented soy sauce from TC12 was as high as 1.14 g/100 g, which met the standard of premium-grade brewed soy sauce in China. At the same time, the content of umami (19.03 g/L) and sweet amino acids (19.32 g/L) in TC12 was high, accounting for about 60% of the total amino acids, presenting a better sweet and savory taste. The volatile compound detection data showed that the content of ethanol, ethyl phenylacetate, ethyl palmitate, 3-(methylthiopropionaldehyde) and benzaldehyde in TC12 was relatively high, and the sample showed an overall sweet-fruity aroma and ester-like aroma. On the other hand, the gradient heating sample of the high-salt group (TC18) contained more guaiacol and methyl maltol, showing a smoky incense and saucy aroma. The sensory evaluation results showed that the low-salt gradient heating fermentation samples TC12 had higher aroma and taste scores, as well as better comprehensive tastes than the constant temperature fermentation samples C12. In summary, the gradient heating method is beneficial to limit the excessive growth of yeast in low-salt (12%) fermented sauce mash in the early stage and maintaining a considerable cell count of yeast in the late stage of fermentation, so that the yeast can continuously ferment and generate more flavor substances and improve the overall flavor of low-salt fermented soy sauce.

Abstract When a transformable B2 precipitate is embedded in an amorphous matrix, it is often experimentally observed that the crystalline-amorphous interface not only serves as an initiation site for the martensitic transformation due to local stress concentrations, but also as an inhibitor to stabilize the transformation, the latter being attributed to the “confinement effect” exerted by the amorphous matrix, according to the Eshelby solution. These two seemingly incongruous factors are examined in this study using molecular dynamics simulations from an atomic interaction perspective. An innate strain gradient in the vicinity of the crystalline-amorphous interface is identified. The actual interface, the compressive/dilatative transition, and the interfacial maximum strain are investigated to differentiate from the conventional “interface” located within a distance of a few nanometers. Our innate interfacial elastic strain field model is applicable for the design of materials with a higher degree of martensitic transformation and controllable stress concentration, even in cryogenic environments.

This study aimed to investigate the characteristics of different varieties of camellia oils and their diacylglycerol (DAG)-enriched derivatives in terms of triacylglycerol (TAG) species, bioactive components, volatile compounds, and antioxidant activity. Six types of camellia oils, including C. oleifera (C.O), C. semiserrata (C.S), C. gauchowensis (C.G), along with commercially refined C. oleifera oil (C-C.O) and its DAG-enriched counterparts (at 40% and 80% enrichment), were analyzed and compared. Unique patterns of TAG profiles, fatty acid distributions on different glycerol backbones, tocopherol, squalene, total polyphenols, and volatile compounds were observed, suggesting that these characteristics can be utilized as a criterion to differentiate them. DAG-enriched oils exhibited increased levels of unsaturated fatty acids (UFAs) compared to C-C.O, albeit with decreased contents of tocopherol, squalene, and total polyphenols. Moreover, diverse volatile compounds were identified across all types of camellia oils, among which the DAG-enriched oils had distinct distribution characteristics compared with their crude oils, indicating the influence of the enrichment process on volatile compounds. Furthermore, DAG-enriched oils demonstrated reduced antioxidant activity abilities compared to their counterparts, with the highest activity observed in C.O, followed by C.G. Additionally, strong correlations were observed between antioxidant activity and tocopherol, as well as squalene content.

This paper proposes a weighted large-scale data subspace clustering algorithm to enable it to adapt to the mega-customer environment for financial banks to respond quickly to customer data. Firstly, based on the K-means combined with a genetic algorithm, an improved method for the sensitivity problem of initial clustering center selection of K-means algorithm is proposed. By weighting the variables and streaming data batch processing method as a guide, the improvement method is proposed for the problem that the mean algorithm cannot identify the correct clustering center caused by the ultra-large-scale data environment, leading to the iteration number approaching infinity. The accuracy of the K-mean algorithm, the optimized initial clustering center algorithm, and the algorithm in this paper are 89.61%, 94.37% and 96.94%, respectively. In terms of running time, the highest running time of this algorithm is 10.96 seconds, which is faster than the running time of the other two algorithms. Finally, the financial analysis of the financial bank that completed the digital transformation with the help of the algorithm in this paper, the bank achieved a business of 150.832 billion yuan in 2021, an increase of 11% compared with the end of last year. Net profit achieved 44.883 billion yuan, an increase of 25.8% compared to the end of last year. Therefore, the algorithm in this paper has high advantages in terms of accuracy, efficiency, and practicality, proving that digital transformation can improve bank profits. It also provides a path and direction of transformation for various urban and agricultural commercial banks and other small credit unions.

Abstract Background Biopsies obtained from primary oesophageal squamous cell carcinoma (ESCC) guide diagnosis and treatment. However, spatial intra‐tumoral heterogeneity (ITH) influences biopsy‐derived information and patient responsiveness to therapy. Here, we aimed to elucidate the spatial ITH of ESCC and matched lymph node metastasis (LNmet). Methods Primary tumour superficial (PTsup), deep (PTdeep) and LNmet subregions of patients with locally advanced resectable ESCC were evaluated using whole‐exome sequencing (WES), whole‐transcriptome sequencing and spatially resolved digital spatial profiling (DSP). To validate the findings, immunohistochemistry was conducted and a single‐cell transcriptomic dataset was analysed. Results WES revealed 15.72%, 5.02% and 32.00% unique mutations in PTsup, PTdeep and LNmet, respectively. Copy number alterations and phylogenetic trees showed spatial ITH among subregions both within and among patients. Driver mutations had a mixed intra‐tumoral clonal status among subregions. Transcriptome data showed distinct differentially expressed genes among subregions. LNmet exhibited elevated expression of immunomodulatory genes and enriched immune cells, particularly when compared with PTsup (all P

This paper mainly studies the deployment of hybrid sensors on highways. By constructing the deployment location constraint model, the overall accuracy of sensor deployment can be maximized. In addition, in order to meet the needs of intelligent transportation, the consideration of traffic data communication is added to the work. The highway under study is first divided into several units, and the combination type of sensors is used to represent the possible layout of two adjacent sensors. Then, a 0–1 optimization model reflecting the interaction between the sensor position and the server position is established. Then, a two-step search algorithm is proposed to find the optimal solution of the model and determine the deployment scheme with maximum accuracy. Finally, an example is given to verify the method. The results show that there are significant differences between uniform unit-deployment schemes and non-uniform unit-deployment schemes. Through the sensitivity analysis of each factor, the influence of budget and communication radius on the deployment plan is proven. In addition, the ramp length can also have a negative impact on the target value.

Soft magnetic composites (SMCs) play a pivotal role in the development of high-frequency, miniaturization and complex forming of modern electronics. However, they usually suffer from a trade-off between high magnetization and good magnetic softness (high permeability and low core loss). In this work, utilizing the order modulation strategy, a critical state in a FeSiBCCr amorphous soft magnetic composite (ASMC), consisting of massive crystal-like orders (CLOs, ∼1 nm in size) with the feature of α -Fe, is designed. This critical-state structure endows the amorphous powder with the enhanced ferromagnetic exchange interactions and the optimized magnetic domains with uniform orientation and fewer micro-vortex dots. Superior comprehensive soft magnetic properties at high frequency emerge in the ASMC, such as a high saturation magnetization ( M _s ) of 170 emu g ^−1 and effective permeability ( μ _e ) of 65 combined with a core loss ( P _cv ) as low as 70 mW cm ^−3 (0.01 T, 1 MHz). This study provides a new strategy for the development of high-frequency ASMCs, possessing suitable comprehensive soft magnetic performance to match the requirements of the modern magnetic devices used in the third-generation semiconductors and new energy fields.

Eutectic Sn–Ag–Cu lead-free solder has limited applications due to cost and reliability issues. Sn–Ag–Zn solder has the advantages of low melting point, good mechanical properties and reliable welding interface. However, the research system of low silver content Sn–Ag–Zn solder is incomplete. In this paper, Sn–2.0Ag–1.5Zn low silver content alloy solder is soldered to different substrates. The interfacial reaction after soldering and the microstructure and reliability under different aging treatment conditions are studied. Sn–2.0Ag–1.5Zn solder is made into solder balls by direct melting method. The solder balls are placed in a solder strength tester to be heated and welded to the substrate, and then the solder joints are placed in a heating furnace for aging treatment. The results show that the solder is soldered to the bare Cu substrate, and a dense double-layer Intermetallic Compound (IMC) structure of Cu5Zn8 and Ag3Sn is formed at the interface after aging treatment. The double-layer structure blocks each other, limiting the development of copper-tin IMCs. The solder is soldered with the Cu substrate electroplated with Ni barrier layer, and the soldering interface forms a thin layer of Ni3Sn4 metal compound. After aging for 1000 h, the thickness of Ni3Sn4 is about 1 μm, the thickness of Ni barrier layer is kept at 2–3 μm, and the barrier effect of Ni barrier layer is stable. Sn–2.0Ag–1.5Zn solder has excellent loss performance in long aging treatment. It has good heat-resistance aging treatment, good quality of solder connection, high interface reliability and less environmental pollution. The low silver content in Sn–2.0Ag–1.5Zn solder results in a significant cost reduction. Coarse IMC Ag3Sn is not easily formed. The optimized ratio of Ag and Zn in Sn–2.0Ag–1.5Zn solder improves the strength and toughness of the solder joint. The performance has been improved, and it is a very promising alloy solder.

A series of petroleum coke (petcoke)-derived solid acid catalysts were prepared via nitric acid treatment with or without ball milling pretreatment. The inherent sulfur in petcoke was converted to sulfonic groups, which were active sites for the esterification of octanoic acid and methanol at 60 °C, with ester yields of 14–43%. More specifically, samples without ball milling treated at 120 °C for 3 h had a total acidity of 4.67 mmol/g, which was 1.6 times that of the samples treated at 80 °C, despite their −SO3H acidities being similar (~0.08 mmol/g). The samples treated for 24 h had higher −SO3H (0.10 mmol/g) and total acidity (5.25 mmol/g) but not increased catalytic activity. Ball milling increased the defects and exposed aromatic hydrogen groups on petcoke, which facilitated further acid oxidation (0.12 mmol −SO3H/g for both materials and total acidity of 5.18 mmol/g and 5.01 mmol/g for BP-N-3/120 and BP-N-8/90, respectively) and an increased ester yield. DFT calculations were used to analyze the pathways of sulfonic acid group formation, and the reaction pathway with NO2• was the most thermodynamically and kinetically favourable. The activities of the prepared catalysts were related to the number of −SO3H acid sites, the total acidity, and the oxygen content, with the latter two factors having a negative impact.

Microbial inoculation in moromi fermentation has a great influence on the physicochemical and flavour properties of soy sauces. This work investigated the effect of inoculating Tetragenococcus halophilus and Wickerhamomyces anomalus on the flavour formation of early-stage moromi (30 days) fermented at a lower temperature (22 °C) by determining their physicochemical and aroma changes. The results showed that single yeast or LAB inoculation increased the production of amino nitrogen, lactic acid and acetic acid, as well as free amino acids and key flavour components. Particularly, the sequential inoculation of T. halophilus and W. anomalus produced more free amino acids and aromatic compounds, and there might be synergistic effects between these two strains. More characteristic soy sauce flavour compounds, such as benzaldehyde, HEMF, guaiacol and methyl maltol were detected in the sequentially inoculated moromi, and this sample showed higher scores in savoury, roasted and caramel intensities. These results confirmed that sequential inoculation of T. halophilus and W. anomalus could be a choice for the future production of moromi with good flavour and quality under a lower temperature.

Whey protein (WP) and whey protein hydrolysates (WPH) may have the potency to promote weight loss, preserve muscle and improve gut microbiota composition. The present study explored the effect of WPH vs WP on weight management in obese middle-aged mice in the content of changes in fat mass, muscle mass and gut microbiota composition. The present results showed that WPH significantly reduced energy intake, attenuated weight gain and improved blood lipids and glucose. Moreover, WPH reduced ectopic fat deposition and enhanced antioxidant capacity in muscle, but did not significantly affect muscle mass. WPH failed to reverse the microbial diversity reduction caused by a high-fat diet, but increased Akkermansia and Clostridium XVIII abundances and decreased Alistipes abundance. In conclusion, WPH is expected to have good prospects in weight management in middle age.

Introduction: During the COVID-19 epidemic in Singapore, there was an urgent demand to train more nurses within a short timeframe to perform the Water Swallow Test (WST). The previous training model involved training with actual patients and was time-consuming. Hence, the model was revamped and standardised patients (SPs) were engaged for nurses’ training. This study further investigated nurses’ feedback about the new training model and compared the efficiency and learner-reported outcomes of the previous and new models. Methods: Nurses who completed WST training from January 2018 to July 2020 were enrolled. Training records were accessed to determine the number of nurses trained under the previous and new models. Nurses were invited to complete post-training evaluation forms and their responses were analysed. Descriptive statistics and the Mann-Whitney U test were used for data analysis. Results: Under the previous model, 52 nurses were trained over 2 years, whereas under the new model, 112 nurses were trained over two months. From the evaluation form responses, the majority of nurses trained under the new model agreed that they achieved the learning objectives and were confident in performing the WST. There was also no significant difference (p>0.05) found between learner-reported outcomes for both training models. Conclusion: Our findings demonstrated that the new model that engaged SPs was more efficient in training more nurses. Nurses were also satisfied with the new training model, which achieved similar learner-reported outcomes as the previous model.

Silicon-based kinetic energy converters employing variable capacitors, also known as electrostatic vibration energy harvesters, hold promise as power sources for Internet of Things devices. However, for most wireless applications, such as wearable technology or environmental and structural monitoring, the ambient vibration is often at relatively low frequencies (1–100 Hz). Since the power output of electrostatic harvesters is positively correlated to the frequency of capacitance oscillation, typical electrostatic energy harvesters, designed to match the natural frequency of ambient vibrations, do not produce sufficient power output. Moreover, energy conversion is limited to a narrow range of input frequencies. To address these shortcomings, an impacted-based electrostatic energy harvester is explored experimentally. The impact refers to electrode collision and it triggers frequency upconversion, namely a secondary high-frequency free oscillation of the electrodes overlapping with primary device oscillation tuned to input vibration frequency. The main purpose of high-frequency oscillation is to enable additional energy conversion cycles since this will increase the energy output. The devices investigated were fabricated using a commercial microfabrication foundry process and were experimentally studied. These devices exhibit non-uniform cross-section electrodes and a springless mass. The non-uniform width electrodes were used to prevent pull-in following electrode collision. Springless masses from different materials and sizes, such as 0.5 mm diameter Tungsten carbide, 0.8 mm diameter Tungsten carbide, zirconium dioxide, and silicon nitride, were added in an attempt to force collisions over a range of applied frequencies that would not otherwise result in collisions. The results show that the system operates over a relatively wide frequency range (up to 700 Hz frequency range), with the lower limit far below the natural frequency of the device. The addition of the springless mass successfully increased the device bandwidth. For example, at a low peak-to-peak vibration acceleration of 0.5 g (peak-to-peak), the addition of a zirconium dioxide ball doubled the device’s bandwidth. Testing with different balls indicates that the different sizes and material properties have different effects on the device’s performance, altering its mechanical and electrical damping.

Abstract Background Due to the lack of a sensitive, specific and rapid detection method, aetiological diagnosis of pneumonia caused by Mycoplasma pneumoniae (M. pneumoniae, MP) is a constantly challenging issue. This retrospective study aimed to compare the diagnostic methods for Mycoplasma pneumoniae in children and evaluate their values. Methods From November 2018 to June 2019, 830 children with community-acquired pneumonia were selected from the Department of Respiratory Medicine, Shanghai Children’s Medical Center. On the first day of hospitalization, sputum, throat swab and venous blood samples were collected to analyse MP-IgM (particle agglutination, PA), MP-IgM (immune colloidal gold technique, GICT), MP-DNA, MP-RNA (simultaneous amplification and testing, SAT) and MP-DNA (real-time polymerase chain reaction, RT-PCR). Results Among these 830 children, RT-PCR showed that the positive rate was 36.6% (304/830), in which the positive rate of macrolide resistance (A2063G mutation) accounted for 86.2% of cases (262/304). Using RT-PCR as the standard, MP-RNA (SAT) had the highest specificity (97.5%), and MP-IgM (PA) had the highest sensitivity (74.0%) and Youden index (53.7%). If MP-RNA (SAT) was combined with MP-IgM (PA), its Kappa value (0.602), sensitivity (84.2%), specificity (78.7%) and Youden index (62.9%) were higher than those of single M. pneumoniae detection. Conclusions Our research indicated that a combination of MP-RNA (SAT) plus MP-IgM (PA) might lead to reliable results as an early diagnostic method for children with clinical manifestations of Mycoplasma pneumoniae pneumonia.

Natural killer (NK) cells have been demonstrated as a promising cellular therapy as they exert potent anti-tumor immune responses. However, applications of NK cells to tumor immunotherapy, especially in the treatment of advanced hematopoietic and solid malignancies, are still limited due to the compromised survival and short persistence of the transferred NK cells in vivo. Here, we observed that fucosyltransferase (FUT) 7 and 8 were highly expressed on NK cells, and the expression of CLA was positively correlated with the accumulation of NK cells in clinical B cell lymphoma development. Via enzyme-mediated ex vivo cell-surface fucosylation, the cytolytic effect of NK cells against B cell lymphoma was significantly augmented. Fucosylation also promoted NK cell accumulation in B cell lymphoma-targeted tissues by enhancing their binding to E-selectin. Moreover, fucosylation of NK cells also facilitated stronger T cell anti-tumor immune responses. These findings suggest that ex vivo fucosylation contributes to enhancing the effector functions of NK cells and may serve as a novel strategy for tumor immunotherapy.

To investigate the effect of piperine on pancreatic β cell apoptosis, mice were fed with high-fat diet and injected with 40 mg/kg streptozotoci to establish diabetic model. The mice in the piperine group received 30 mg/kg body weight of piperine by gavage for 12 weeks. Compared with the model group, piperine intervention significantly decreased fasting blooding glucose, and increased homeostasis model assessment (HOMA)-β. Piperine also increased pancreatic superoxide dismutase and decreased malondialdehyde. Piperine significantly decreased the apoptotic rate of pancreatic β-cells, and the protein expression of Bax/Bcl-2 ratio, also up-regulated the protein expression of phosphorylated PI3K and AKT in pancreas. In addition, apoptosis was induced in mouse insulinoma 6 cells by palmitate. Piperine treatment decreased apoptosis, protein expression of Bax/Bcl-2 ratio, and cytochrome C in cells. Thus, piperine plays a beneficial role on diabetic mice by improving pancreatic β-cell dysfunction, this might be associated with regulation on PI3K/Akt-mediated anti-apoptosis signaling.

Metabolic diseases are associated with chronic, low-grade inflammation. Here the authors show that major vault protein (MVP) suppresses NF-κB signalling in macrophages via an IRAK1–TRAF6 axis and that loss of MVP in myeloid cells exacerbates the inflammatory response in mice fed a high fat diet.

Background: Dietary intake of cereal fiber has been reported to benefit lipid metabolism through multiple mechanisms. The present study aimed to discover the potential mechanisms by which cereal fiber could modify the intestinal cholesterol metabolism. Design: Male C57BL/6 mice were fed a reference chow (RC) diet; high-fat, high-cholesterol (HFC) diet; HFC plus oat fiber diet; or HFC plus wheat bran fiber diet for 24 weeks. Serum lipids were measured by enzymatic methods. Western blot was used to determine the protein expressions involved in intestinal cholesterol metabolism. Results: Our results showed that HFC-induced elevations of serum triglycerides, total cholesterol, and low-density lipoprotein cholesterol were normalized in both groups that received cereal fiber. At the protein level, compared with the HFC diet group, the two cereal fibers, especially the oat fiber, significantly increased the protein expression of peroxisome proliferator-activated receptor alpha, liver X receptor alpha, sterol regulatory element-binding protein (SREBP) 2, low-density lipoprotein receptor, adenosine triphosphate (ATP)-binding cassette A1, and ATP-binding cassette G1, while decreasing the protein expression of Niemann-Pick C1-like protein 1, SREBP-1, fatty acid synthase, and acetyl-coenzyme A carboxylase, which were involved in intestinal cholesterol metabolism. Conclusion: Taken together, increased intake of cereal fiber improved blood cholesterol profiles and increased the intestinal cholesterol efflux and cholesterol clearance in C57BL/6 mice fed a HFC diet. Oat fiber had a stronger effect than wheat bran fiber on cholesterol metabolism by modulating the PPARα, LXRα, and SREBP signaling pathways.

Objective: Lung auscultation plays an important role in the diagnosis of pulmonary diseases in children. The objective of this study was to evaluate the use of an artificial intelligence (AI) algorithm for the detection of breath sounds in a real clinical environment among children with pulmonary diseases.Method: The auscultations of breath sounds were collected in the respiratory department of Shanghai Children's Medical Center (SCMC) by using an electronic stethoscope. The discrimination results for all chest locations with respect to a gold standard (GS) established by 2 experienced pediatric pulmonologists from SCMC and 6 general pediatricians were recorded. The accuracy, sensitivity, specificity, precision, and F1-score of the AI algorithm and general pediatricians with respect to the GS were evaluated. Meanwhile, the performance of the AI algorithm for different patient ages and recording locations was evaluated.Result: A total of 112 hospitalized children with pulmonary diseases were recruited for the study from May to December 2019. A total of 672 breath sounds were collected, and 627 (93.3%) breath sounds, including 159 crackles (23.1%), 264 wheeze (38.4%), and 264 normal breath sounds (38.4%), were fully analyzed by the AI algorithm. The accuracy of the detection of adventitious breath sounds by the AI algorithm and general pediatricians with respect to the GS were 77.7% and 59.9% (p < 0.001), respectively. The sensitivity, specificity, and F1-score in the detection of crackles and wheeze from the AI algorithm were higher than those from the general pediatricians (crackles 81.1 vs. 47.8%, 94.1 vs. 77.1%, and 80.9 vs. 42.74%, respectively; wheeze 86.4 vs. 82.2%, 83.0 vs. 72.1%, and 80.9 vs. 72.5%, respectively; p < 0.001). Performance varied according to the age of the patient, with patients younger than 12 months yielding the highest accuracy (81.3%, p < 0.001) among the age groups.Conclusion: In a real clinical environment, children's breath sounds were collected and transmitted remotely by an electronic stethoscope; these breath sounds could be recognized by both pediatricians and an AI algorithm. The ability of the AI algorithm to analyze adventitious breath sounds was better than that of the general pediatricians.

This study aimed to investigate the preventive effects of lactoferrin (Lf) on chronic alcoholic liver injury (ALI) in female mice. Female C57BL/6J mice were randomly divided into four groups: control group (CON), ethanol administration group (EtOH), low-dose Lf treatment group (LLf), and high-dose Lf group (HLf). In the last three groups, chronic ALI was induced by administering 20% ethanol ad libitum for 12 weeks. Mice in the CON and EtOH groups were fed with AIN-93G diet. Meanwhile, 0.4% and 4% casein in the AIN-93G diet were replaced by Lf as the diets of LLf and HLf groups, respectively. HLf significantly reduced hepatic triglyceride content and improved pathological morphology. HLf could inhibit cytochrome P450 2E1 overexpression and promote alcohol dehydrogenase-1 expression. HLf activated protein kinase B and AMP-activated protein kinase (AMPK), as well as upregulating nuclear-factor-erythroid-2-related factor-2 expression to elevate hepatic antioxidative enzyme activities. AMPK activation also benefited hepatic lipid metabolism. Meanwhile, HLf had no obvious beneficial effects on gut microbiota. In summary, Lf could alleviate chronic ALI in female mice, which was associated with redox balance and lipid metabolism regulation.

Osteosarcoma is a primary tumor of bone and its incidence is increasing. Schisandrin B (Sch B), a generally used lignan in Chinese medicine, has been found to repress cancer progression. This study aims to reveal the effects and regulatory mechanism of Sch B in the viability, apoptosis and migration of osteosarcoma cells. In this study, we found circ_0009112 expression was higher and miR-708-5p expression was lower in SaOS2 and U2OS cells than in hFOB1.19 cells. Circ_0009112 expression was downregulated, but miR-708-5p was upregulated by Sch B treatment in a dose-dependent manner in SaOS2 and U2OS cells. Sch B exposure inhibited osteosarcoma development in vitro and in vivo; however, these effects were restored by circ_0009112. Furthermore, circ_0009112 acted as a sponge of miR-708-5p. Circ_0009112 regulated PI3K/AKT pathway after Sch B treatment by associating with miR-708-5p. Sch B exposure inhibited cell viability and migration, whereas promoted cell apoptosis by regulating circ_0009112/miR-708-5p axis through PI3K/AKT pathway in osteosarcoma cells. This study provided a theoretical basis for further studying osteosarcoma therapy with Sch B.

As a special form of culture, Chinese Baijiu culture has its unique position in traditional Chinese culture.Applying visualization technology to the Chinese Baijiu culture plays an important role in spreading and popularizing the rich connotation of Chinese Baijiu culture, enhancing national confidence and promoting international cultural exchange.The application of Chinese Baijiu culture visualization was summarized, then, the basic process of visual analysis using big data in Chinese Baijiu culture was described, after that, the research situation of Chinese Baijiu cultural visualization was analyzed from three dimensions: literature, archaeology and history.And then, application scenarios of several visualization methods in the field of cultural visualization were summarized, including text data visualization, network data visualization, space-time data visualization, multidimensional data visualization and so on.Finally, future hot research issues on Chinese Baijiu culture visualization were discussed.

Background: Leucine supplementation has been reported to improve lipid metabolism. However, lipid metabolism in adipose tissues and liver has not been extensively studied for leucine supplementation in mice fed with a high-fat/cholesterol diet (HFCD). Design: C57BL/6J mice were fed a chow diet, HFCD, HFCD supplemented with 1.5% leucine (HFCD+1.5% Leu group) or 3% leucine (HFCD+3% Leu group) for 24 weeks. The body weight, peritoneal adipose weight, total cholesterol (TC), triglyceride in serum and liver, and serum adipokines were analyzed. In addition, expression levels of proteins associated with hepatic lipogenesis, adipocyte lipolysis, and white adipose tissue (WAT) browning were determined. Results: Mice in the HFCD group developed obesity and deteriorated lipid metabolism. Compared with HFCD, leucine supplementation lowered weight gain and TC levels in circulation and the liver without changing energy intake. The decrease in body fat was supported by histological examination in the WAT and liver. Furthermore, serum levels of proinflammatory adipokines, such as leptin, IL-6, and tumor necrosis factor-alpha, were significantly decreased by supplemented leucine. At the protein level, leucine potently decreased the hepatic lipogenic enzymes (fatty acid synthase and acetyl-coenzyme A carboxylase) and corresponding upstream proteins. In epididymal WAT, the reduced expression levels of two major lipases by HFCD, namely phosphorylated hormone-sensitive lipase and adipose triglyceride lipase, were reversed when leucine was supplemented. Uncoupling protein 1, β3 adrenergic receptors, peroxisome proliferator-activated receptor g coactivator-1α, and fibroblast growth factor 21 were involved in the thermogenic program and WAT browning. Leucine additionally upregulated their protein expression in both WAT and interscapular brown adipose tissue. Conclusion: This study demonstrated that chronic leucine supplementation reduced the body weight and improved the lipid profile of mice fed with a HFCD. This beneficial effect was ascribed to hepatic lipogenesis, adipocyte lipolysis, and WAT browning.

Background: Pycnogenol exhibits many biological activities, including control of blood pressure (BP). However, the reported results are inconsistent because of varied characteristics of participants and quality of studies. Thus, a meta-analysis was conducted to examine the effect of Pycnogenol supplementation on BP. Methods: This literature search of PubMed, the Web of Science and the Cochrane library was performed in May 2016 to identify eligible studies. Reference lists of the retrieved articles were also reviewed. Either a fixed-effects or, in the presence of heterogeneity, a random-effects model was used to calculate the effect of combined treatment. Results: We identified nine trials involving 549 participants who received Pycnogenol supplementation ranging from 150 mg/d to 200 mg/d. Compared with the control, the pooled estimate of change in systolic and diastolic BPs were -3.22 mmHg (95% CI: -6.20, -0.24) and -3.11 mmHg (95% CI: -4.60, -1.62), respectively. Subgroup analyses showed higher BP reduction among hypertensive participants or those who received intervention for more than 12 wk. However, this significant reduction was not observed in well-designed trials. Conclusion: This meta-analysis with nine trials provides better evidence that Pycnogenol exerts beneficial effects on BP.

As an optimization method that has experienced rapid development over the past 20 years, the genetic algorithm has been successfully applied in many fields, but it requires repeated searches based on the characteristics of high-speed computer calculation and conditions of the known relationship between the objective function and independent variables. There are several hundred generations of evolvement, but the functional relationship is unknown in pollution source searches. Therefore, the genetic algorithm cannot be used directly. Certain improvements need to be made based on the actual situation, so that the genetic algorithm can adapt to the actual conditions of environmental problems, and can be used in environmental monitoring and environmental quality assessment. Therefore, a series of methods are proposed for the improvement of the genetic algorithm: (1) the initial generation of individual groups should be artificially set and move from lightly polluted areas to heavily polluted areas; (2) intervention measures should be introduced in the competition between individuals; (3) guide individuals should be added; and (4) specific improvement programs should be put forward. Finally, the scientific rigor and rationality of the improved genetic algorithm are proven through an example.

Wireless Body Area Network (WBAN) is a small-scaled sensor network consisting of a series of medical devices attributed to, around, or implanted in a human body, providing continuous monitoring by different sensors to collect vital signals or motion and GPS. This paper proposes an effective routing algorithm to balance the energy consumption within a WBAN in order to prolong the overall lifetime of the network, called dynamic routing algorithm (DRA) and its improved version based on a multipath choice mechanism. Theoretical analysis and simulation result are demonstrated to evaluate the performance of the algorithm and represent that energy consumption of sensors in the network is reasonably scheduled and life cycle of the network is significantly extended. The routing algorithm proposed in this paper may be potentially applied to significantly save energy of multiple types of sensors during vital signals aggregating and transmitting under the WBAN.

BACKGROUND AND PURPOSE:It has been accepted that AMPK (Adenosine monophosphate-activated protein kinase) activation exhibits many beneficial effects on glucolipid metabolism. Lysophosphatidylcholine (LPC) is an important lysophospholipid which can improve blood glucose levels in diabetic mice and attenuate inflammation by activating AMPK signal pathway in macrophages. Synthetic alkylphospholipids (ALPs), such as miltefosine, is used as an alternate of LPC for the clinical application. Here, we investigated whether miltefosine could have an impact on hepatic steatosis and related metabolic disorders. EXPERIMENTAL APPROACH:Mice were fed with high fat diet (HFD) for 16 weeks to generate an obese model. Next, the obese mice were randomly divided into three groups: saline-treated and miltefosine-treated (2.5 or 5 mg/kg/d) groups. Miltefosine was intraperitoneally administrated into mice for additional 4 weeks plus HFD treatment. KEY RESULTS:It was shown that miltefosine treatment could substantially improve glucose metabolism, prevented hepatic lipid accumulation, and inhibited liver inflammation in HFD-fed mice by activating AMPK signal pathway. In vitro, miltefosine stimulated AMPKα phosphorylation both in time and dose dependent manner and decreased lipid accumulation in liver cells. When a specific AMPK inhibitor compound C was used to treat mice, the antagonistic effects of miltefosine on HFD-induced mouse hyperlipidaemia and liver steatosis were abolished. Treatment with miltefosine also dramatically inhibited the HFD-induced liver inflammation in mice. CONCLUSIONS AND IMPLICATIONS:Here we demonstrated that miltefosine might be a new activator of AMPK signal pathway in vivo and in vitro and be useful for treatment of hepatic steatosis and related metabolic disorders.