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In the present work, cast iron was used as the carbon source to fabricate WC particle gradient-reinforced W–Cu composites. The results revealed that the surface layer of W–Cu composites after carbonization can be divided into a complete carbonization zone and core-shell structure transition zone, the thickness of the carbonized layer increased gradually with the extension of treatment time. In addition to the W phase and Cu phase, WC and Fe3W3C phases are formed in the surface layer. The hardness and compressive strength of the surface layer show a trend of first increasing and then decreasing, and the arc erosion resistance of the surface layer gradually improves with the treatment time extending. The C atoms diffusion relationship between carbonization layer thickness (D), sintering temperature (T), and treatment time (t) of W–Cu composites with cast iron can be fitted as follows: D=1.9287×1013texp(‐929231RT).

As a well-known classical Chinese medicine prescription, Shengxian Decoction (SXD) has been applied for a century to treat cardiovascular diseases, especially coronary heart disease (CHD), but the potentially effective compounds and underlying mechanisms remain unclear. With ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry (UPLC-Q-TOF/MS) and network pharmacology analysis, the potential effective compounds of SXD and their pharmacological mechanisms against CHD were identified and revealed. 57 effective compounds with favorable pharmacokinetic characteristics and biological activities were screened through UPLC-Q-TOF/MS analysis, database and literature mining, interacting with 96 CHD-related targets to support potential synergistic therapeutic actions. Systematic analysis of the PPI network and microarray data further revealed six core targets, including TNF, IL-1β, IL-6, TP53, VEGFA and PTGS2, which were mainly involved in fluid shear stress and atherosclerosis, lipid and atherosclerosis, PI3K-Akt signaling pathway et al. Moreover, the proposed contribution indexes of effective compounds indicated these compounds, including isoferulic acid, quercetin, calycosin, ferulic acid, kaempferol, calycosin 7-O-glycoside, formononetin, astragaloside IV and saikosaponin D, as the core compounds of SXD. The molecular docking results confirmed that those core compound-target pairs exhibited strong binding energy. Furthermore, we validated that SXD significantly alleviated myocardial tissue injury in CHD rats and reversed H/R-induced decreases in H9c2 cell viability by attenuating the production of TNF, IL-6 and IL-1β, and reducing cardiomyocyte apoptosis via down-regulating the TP53, caspase3 and cytochrome C mRNA expression levels as well as caspase3, caspase9 and cytochrome C protein expression levels according to RT-qPCR and Western blot results. Our findings explained the pharmacological mechanisms underlying the effectiveness of SXD in the treatment of CHD, and laid a foundation for future basic and clinical research of SXD.

Summary: Both therapeutic hypothermia and neural stem cells (NSCs) transplantation have shown promise in neuroprotection and neural repair after brain injury. However, the effects of therapeutic hypothermia on neuronal differentiation of NSCs are not elucidated. In this study, we aimed to investigate whether mild hypothermia promoted neuronal differentiation in cultured and transplanted human NSCs (hNSCs). A significant increase in neuronal differentiation rate of hNSCs was found when exposed to 35°C, from 33% to 45% in vitro and from 7% to 15% in vivo. Additionally, single-cell RNA sequencing identified upregulation of RNA-binding motif protein 3 (RBM3) in neuroblast at 35°C, which stabilized the SRY-box transcription factor 11 (SOX11) mRNA and increased its protein expression, leading to an increase in neuronal differentiation of hNSCs. In conclusion, our study highlights that mild hypothermia at 35°C enhances hNSCs-induced neurogenesis through the novel RBM3-SOX11 signaling pathway, and provides a potential treatment strategy in brain disorders.

Aiming at the problem of long slopes and weak power grids along the railway in high altitude mountainous areas, an optimization method of power supply mode and access to external power grid of CZ railway traction station is proposed. First, combined with the terrain and altitude along the railway and the characteristics of the regional power grid, a sample library of the power supply mode and access to external power grid of CZ railway traction station is designed. Secondly, combined with the train operation diagram and line ramp parameters, the full-day periodic load of each power supply arm is simulated. Then, according to the sample library, a “source-net-load” integrated simulation model is constructed in Simulink. Then, the three-phase voltage unbalance evaluation model of the power system is constructed in combination with relevant standards. Finally, the optimal wiring scheme is selected by using the evaluation model and the simulated voltage unbalance index.

In order to reduce the sintering temperature of the Mo–Cu composites, solution combustion synthesis was used to fabricate ultrafine Mo–Cu composite powders, in which Mo and Cu mixed uniformly. Firstly, solution combustion synthesis was conducted to prepared molybdenum and copper oxides composite powders. However, the residual carbon in the as-synthesized precursors requires additional calcination in nitrogen atmosphere during the reduction process to obtain pure Mo–Cu composite powders. Then the Mo–Cu composites were fabricated by liquid phase sintering at low temperatures of 1050–1180 °C using the Mo–Cu composite powders. The Mo–20Cu and Mo–30Cu composites can reach a relative density of >95% after sintering at a low temperature of 1100 °C, which may be attributed to both the small particle size of Mo and the high uniformity of Mo and Cu distribution.

Summary: TRPA1 is pivotal in cold hypersensitivity, but its regulatory mechanisms in inflammatory cold hyperalgesia remain poorly understood. We show here that the upregulation of SUMO1-conjugated protein levels in a complete Freund’s adjuvant (CFA)-induced inflammatory pain model enhances TRPA1 mRNA stability, ultimately leading to increased expression levels. We further demonstrate that hnRNPA1 binds to TRPA1 mRNA, and its SUMOylation, upregulated in CFA-induced inflammatory pain, contributes to stabilizing TRPA1 mRNA by accumulating hnRNPA1 in the cytoplasm. Moreover, we find that wild-type hnRNPA1 viral infection in dorsal root ganglia neurons, and not infection with the SUMOylation-deficient hnRNPA1 mutant, can rescue the reduced ability of hnRNPA1-knockdown mice to develop inflammatory cold pain hypersensitivity. These results suggest that hnRNPA1 is a regulator of TRPA1 mRNA stability, the capability of which is enhanced upon SUMO1 conjugation at lysine 3 in response to peripheral inflammation, and the increased expression of TRPA1 in turn underlies the development of chronic inflammatory cold pain hypersensitivity.

Ethnopharmacological relevance: Pinellia ternata (Thunb.) Breit. is a well-known perennial herb that is used in traditional medicine in China, Japan and Korea. It's drawing worldwide interests in medicinal applications owing such as anti-diarrhea, lipid-lowering, anti-tumor, anti-cough, expectorant, anti-gastric ulcer, etc. Aim of the study: This review aims to provide useful information on the botany, traditional uses, phytochemistry, pharmacology, toxicity and quality control of Pinellia ternata to help increase its efficiency. In addition, this review will discuss the future research trends and development prospects of this plant. Materials and methods: Data was obtained through a systematic search of published literature and online databases such as Google Scholar, Web of Science, PubMed, Science Direct, and Sci-Finder. The botanical names were confirmed using the World Flora Online and chemical structures were drawn using the ChemBio Draw Ultra Version 19.0 Software. Results: Pinellia ternata is distributed in regions of China and other areas. Pinellia ternata and its compound preparations can be used for cough, vomiting, gastric ulcer and other diseases. Approximately 212 chemical constituents have been isolated from Pinellia ternata, including alkaloids, volatile oils, amino acids, organic acids, flavonoids, cerebrosides, phenylpropanoids and other compounds. Considerable pharmacological experiments in vitro and in vivo have demonstrated that Pinellia ternata possessed antitumor effect, antitussive effects, antiasthmatic effects, increasing resistance to gastric ulcer, and antidiarrheal effect. However, these extracts can also lead to various toxicities such as irritant toxicity, cardiotoxicity, hepatotoxicity and embryonic toxicity. Considerable experiments have demonstrated that different processing methods and suitable compatibility with other herbs can effectively reduce the toxicities and increase the efficiency of Pinellia ternata. Conclusions: Pinellia ternata is an ancient herbal medicine with a broad spectrum of pharmacological activities that has been used for thousands of years in China. Future studies should perform an in-depth analyses of the pharmacokinetics and mechanisms of toxicity of Pinellia ternata. Quality standards should be developed to correspond to the various application methods to ensure the efficacy of drugs in actual treatment.

In this study, the hydrolysis products of chitin, COS1 and COS2, had degrees of deacetylation of 5.9% and 85.7%, respectively. Notably, 50 mg/(kg·d) COS1 and COS2 significantly increased the levels of immunoglobulins (IgG and IgM), cytokines (IL-6 and IFN-γ), and the antioxidant activities (SOD and CAT) in cyclophosphamide-induced mice, and upregulated the mRNA expression of cytokines in the spleen. COS1 activated the MAPK signaling pathways of related proteins (ERK, p-ERK, JNK, and p-JNK). After COS1 and COS2 intervention, the gut microbial structure of immunosuppressed mice changed, increasing the abundance of key bacteria such as, Dubosiella, Romboutsia, and Turicibacter, and decreasing the abundance of key bacteria such as, Escherichia-Shigella and Helicobacter. Notably, COS1 exhibited a higher immunoregulatory activity than COS2, which may be associated with the acetyl groups in COS1. COS1 can be developed as an immunomodulatory agent in functional foods and medicine to improve immunity.

Summary: Background: Severe community-acquired pneumonia (SCAP) results in high mortality as well as massive economic burden worldwide, yet limited knowledge of the bio-signatures related to prognosis has hindered the improvement of clinical outcomes. Pathogen, microbes and host are three vital elements in inflammations and infections. This study aims to discover the specific and sensitive biomarkers to predict outcomes of SCAP patients. Methods: In this study, we applied a combined metagenomic and transcriptomic screening approach to clinical specimens gathered from 275 SCAP patients of a multicentre, prospective study. Findings: We found that 30-day mortality might be independent of pathogen category or microbial diversity, while significant difference in host gene expression pattern presented between 30-day mortality group and the survival group. Twelve outcome–related clinical characteristics were identified in our study. The underlying host response was evaluated and enrichment of genes related to cell activation, immune modulation, inflammatory and metabolism were identified. Notably, omics data, clinical features and parameters were integrated to develop a model with six signatures for predicting 30-day mortality, showing an AUC of 0.953 (95% CI: 0.92–0.98). Interpretation: In summary, our study linked clinical characteristics and underlying multi-omics bio-signatures to the differential outcomes of patients with SCAP. The establishment of a comprehensive predictive model will be helpful for future improvement of treatment strategies and prognosis with SCAP. Funding: National Natural Science Foundation of China (No. 82161138018), Shanghai Municipal Key Clinical Specialty (shslczdzk02202), Shanghai Top-Priority Clinical Key Disciplines Construction Project (2017ZZ02014), Shanghai Key Laboratory of Emergency Prevention, Diagnosis and Treatment of Respiratory Infectious Diseases (20dz2261100).

To avoid the problem of insufficient flexibility of the power grid along the cz railway due to source-load fluctuations, a distributionally robust optimization method considering flexibility is proposed in this paper. Firstly, Wasserstein distance is used to establish the uncertainty set of flexibility demand caused by source-load fluctuation, and a risk-cost model of insufficient flexibility is constructed to couple to the objective function. Combined with the flexibility chance constraint, the flexibility over-limit probability is limited to a certain confidence level in the fuzzy set, and a distributionally robust chance constraint optimization model based on Wasserstein distance is established. Then, the proposed model is transformed into a linear programming problem to be solved by dual theory and inner approximation transformation. Finally, a simulation study of the power grid along the CZ railway is carried out to verify the correctness and effectiveness of the model. The experimental results show that the proposed method can improve the flexibility capacity of the system without sacrificing economy.

Ozone (O3) is an important urban air pollutant having strong correlations with respiratory diseases. Several lines of evidence suggest that O3 exposure causes airway hyperresponsiveness (AHR) and pulmonary inflammation. Inhibitory innate immune receptors, such as NLRP12, have been demonstrated to alleviate inflammation, but the functional role for NLRP12 in O3-induced lung inflammatory inflammation remains to be reported. Here, we determined whether NLRP12 took a protective role in O3-induced AHR and pulmonary inflammation via the suppression of canonical NF-κB. C57BL/6 J mice were exposed to filtered air (FA) or 0.25, 0.50 and 1.00 ppm (3 h/day for 5 consecutive days) followed by detection of airway resistance, white blood cells, total proteins, and cytokines. Meanwhile, NLRP12 in lung tissue were detected by real time PCR. Moreover, we also examined protein expression of NLRP12 and key biomarkers of NF-κB pathway. It was shown that 24 h post O3 exposure, AHR as wells as total cells, proteins, and cytokines contents in BALF of mice were increased compare to those of FA controls in a dose-dependent manner. Notably, O3-induced AHR and lung inflammation were associated with significant decrease in pulmonary NLRP12 and upregulation of phosphorylated IRAK1, p65 and IκBα in canonical NF-κB pathway. Intratracheal administration of NLRP12-overexpresing adenovirus 4 days prior to O3 exposure alleviated AHR and lung inflammation, and inhibited canonical NF-κB pathway activation. The findings from this study indicate that NLRP12 attenuates O3-induced AHR and pulmonary inflammation, possibly through regulating canonical NF-κB pathway. This provides a novel target for the prevention and treatment of lung diseases induced by O3 exposure.

Nitrogen-doped carbon quantum dots (N-CQDs) are nanocomposites that can be synthesized by the hydrothermal method. In this work, N-CQDs with the size of 3.2 ± 1.7 nm was prepared from 1 g citric acid and 2 g urea precursor in 10 mL water. Electrochemiluminescence (ECL) of the prepared N-CQDs with K2S2O8 as a coreactant was found to reach a high ECL efficiency up to 109% relative to that of the Ru(bpy)32+/K2S2O8, coreactant system, revealing their great potential for electroanalysis. It is probably because that N elements were doped well in this N-CQDs and increased presence of surface states per mass of N-CQDs. From the spooling ECL spectroscopy, it can be found that the ECL spectra exhibited both a red shift compared with their photoluminescence (PL) spectrum and a wavelength shift during the potentiodynamic scan in the ECL evolution and devolution processes, due to various emissive excited states of N-CQDs leading to higher ECL efficiency. This work gives an insight into development of high ECL efficiency N-CQDs for bioanalytical and light emitting applications.

The correlation between functional connectivity (FC) network segregation, glucose metabolism and cognitive decline has been recently identified. The coupling relationship between glucose metabolism and the intensity of neuronal activity obtained using hybrid PET/MRI techniques can provide additional information on the physiological state of the brain in patients with AD and mild cognitive impairment (MCI). It is a valuable task to use the above rules for constructing biomarkers that are closely related to the cognitive ability of individuals to monitor the pathological status of patients. This study proposed the concept of the energy connectivity (EC) network and its construction method. We hypothesized that the dissociation between energy connectivity and functional connectivity of brain regions is a valid indicator of cognitive ability in patients with dementia. The number of EC-attenuated brain regions (EC-AR) and the number of FC-attenuated brain regions (FC-AR) are obtained by comparison with the normal group, and the dissociation between functional connectivity and energy connectivity is indicated using the ratio of FC-AR to EC-AR for individuals in the disease group. The findings suggest that FC-AR/EC-AR values are accurate predictors of cognitive performance, while taking into account the cognitive recovery due to compensatory effects of the brain. The cognitive ability of some patients with cognitive recovery can also be predicted more accurately. This also indicates that lower functional connectivity and higher energy connectivity between network modules may be one of the important features that maintain cognitive performance. The concept of energy connectivity also has potential to help explore the pathological state of AD.

To solve the problem of inaccurate prediction of the stack life of proton exchange membrane fuel cells, this paper first proposed a fuel-cell aging prediction method based on method Savitzky–Golay Smoothing and Group Method of Data, which was based on the data drive. Savitzky–Golay Smoothing is an optimal piecewise fitting method based on polynomial in the time domain and using the least square method through moving window, which is widely used in data flow smoothing and denoising. Group Method of Data is a modeling method of the complex nonlinear dynamic system. The inner criterion and outer criterion are used in the training set and test set respectively, and the optimal solution is finally solved by iterative screening. The method presented in this paper was verified by 1020 h fuel cell aging experiment. The experimental results show that: the MSE, RMSE, R of the test data are respectively 6.3935e−05, 0.0079959, and 0.99616. The data-driven prediction method proposed in this paper can be used for fuel cell aging prediction and fault warning.

Background: There is an increasing trend of Metabolic syndrome (MetS) prevalence, which has been considered as an important contributor for cardiovascular disease (CVD), cancers and diabetes. However, there is often a long asymptomatic phase of MetS, resulting in not diagnosed and intervened so timely as needed. It would be very helpful to explore tools to predict the probability of suffering from MetS in daily life or routinely clinical practice. Objective: To develop models that predict individuals’ probability of suffering from MetS timely with high efficacy in general population. Methods: The present study enrolled 8964 individuals aged 40–75 years without severe diseases, which was a part of the REACTION study from October 2011 to February 2012. We developed three prediction models for different scenarios in hospital (Model 1, 2) or at home (Model 3) based on LightGBM (LGBM) technique and corresponding logistic regression (LR) models were also constructed for comparison. Model 1 included variables of laboratory tests, lifestyles and anthropometric measurements while model 2 was built with components of MetS excluded based on model 1, and model 3 was constructed with blood biochemical indexes removed based on model 2. Additionally, we also investigated the strength of association between the predictive factors and MetS, as well as that between the predictors and each component of MetS. Results: In this study, 2714 (30.3%) participants suffer from MetS accordingly. The performances of the LGBM models in predicting the probability of suffering from MetS produced good results and were presented as follows: model 1 had an area under the curve (AUC) value of 0.993 while model 2 indicated an AUC value of 0.885. Model 3 had an AUC value of 0.859, which is close to that of model 2. The AUC values of LR model 1 and 2 for the scenario in hospital and model 3 at home were 0.938, 0.839 and 0.820 respectively, which seemed lower than that of their corresponding machine learning models, respectively. In both LGBM and logistic models, gender, height and resting pulse rate (RPR) were predictors for MetS. Women had higher risk of MetS than men (OR 8.84, CI: 6.70–11.66), and each 1-cm increase in height indicated 3.8% higher risk of suffering from MetS in people over 58 years, whereas each 1- Beat Per Minute (bpm) increase in RPR showed 1.0% higher risk in individuals younger than 62 years. Conclusion: The present study showed that the prediction models developed by machine learning demonstrated effective in evaluating the probability of suffering from MetS, and presented prominent predicting efficacies and accuracies. Additionally, we found that women showed a higher risk of MetS than men, and height in individuals over 58 years was important factor in predicting the probability of suffering from MetS while RPR was of vital importance in people aged 40–62 years.

The objective of this study is to explore the effect and mechanism of ultrasound on chitin extraction from shrimp shells powder (SSP) by the co-fermentation of Bacillus subtilis and Acetobacter pasteurianus. After pre-treating the SSP with high-intensity ultrasound (HIU) at 800 W, the protease activity in the fermentation solution reached 96.9 U/mL on day 3, which was significantly higher than for SSP that had not been pre-treated with ultrasound (81.8 U/mL). The fermentation time of the chitin extraction process was 5.0 d without ultrasound pre-treatment, while it was shortened to 4.5 d when using ultrasound at 800 W to treat SSP. However, there were no obvious differences when we applied ultrasound at low power (200 W, 400 W). Furthermore, chitin purified from shrimp shells pre-treated with HIU at 800 W exhibited lower molecular weight (11.2 kDa), higher chitin purity (89.8%), and a higher degree of deacetylation (21.1%) compared to SSP with no ultrasound pre-treatment (13.5 kDa, 86.6%, 18.5%). Results indicate that HIU peels off the protein/CaCO3 matrix that covers the SSP surface. About 9.1% of protein and 4.7% of Ca2+ were released from SSP pre-treated with HIU at 800 W. These figures were both higher than with no ultrasound pre-treatment (4.5%, 3.2%). Additionally, the amount of soluble protein extracted from SSP through HIU at 800 W was 50% higher than for the control sample. SDS-PAGE analysis indicated that the soluble protein was degraded to the micromolecule. It also revealed that HIU (600, 800 W) induced the secondary and tertiary structure destruction of protein extracted from SSP. In conclusion, HIU-induced degradation and structural damage of protein enhances the protein/CaCO3 matrix to be peeled off from SSP. Also, in the co-fermentation process, an increase of protease activity further accelerates deproteinization.

Benzo(a)pyrene [B(a)P], a ubiquitous environmental pollutant, causes lung inflammatory damage. Pyroptosis，a new inflammation-dependent programmed cell death, happened when pyroptosis-related GSDMD is activated mediated by NLRP3 inflammasome. microRNA-223 (miRNA-223) is involved in inflammatory diseases by regulating NLRP3. However, whether GSDMD regulate NLRP3 inflammasome through miR-223 in B(a)P induced lung inflammatory injury remain unknown. In this study, alveolar epithelial cells (A549) were stimulated with 0, 2, 4, 8 μM B(a)P for 12 h or 24 h. The inflammatory injury and pyroptosis were determined. And the activation of NLRP3 inflammasomes and the level of miRNA-223 were detected. Then, the change of inflammatory injury and activation of NLRP3 inflammasomes in B(a)P-induced A549 cells were detected after inhibiting of GSDMD or miR-223 using siRNA-GSDMD (siGSDMD) or miR-223 inhibitor, respectively. Our results indicated that after B(a)P exposure, TNF-α and IL-6 in the supernatant were increased. Transmission electron microscope (TEM) results showed that A549 cells were obviously swollen and the cell membrane ruptured. Hoechest33342/PI staining showed that pyroptosis occurred. NLRP3, IL-1β, IL-18, GSDMD, GSDMD-N, pro caspase-1 and cleaved caspase-1 were significantly increased. Additionally, after transfecting with siGSDMD in B(a)P-induced A549 cells, the expression level of miR-223 was significantly increased. But IL-6 and TNF-α in the supernatant, the expression of NLRP3, IL-1β, IL-18 and cleaved caspase-1 protein were also decreased. And after inhibiting miR-223 in B(a)P-induced A549 cells, the expression of TNF-α and IL-6 in the supernatant, the protein expression of NLRP3, IL-1β, IL-18 and cleaved caspase-1 were increased. In conclusion, GSDMD may regulate NLRP3 inflammasome through miR-223, which is involved in B(a)P induced inflammatory damage in A549 cells.

Single modality MRI data is not enough to depict and discern the cause of the underlying brain pathology of Alzheimer's disease (AD). Most existing studies do not perform well with multi-group classification. To reveal the structural, functional connectivity and functional topological relationships among different stages of mild cognitive impairment (MCI) and AD, a novel method was proposed in this paper for the analysis of regional importance with an improved deep learning model. Obvious drift of related cognitive regions can be observed in the prefrontal lobe and surrounding the cingulate area in the right hemisphere when comparing AD and healthy controls (HC) based on absolute weights in the classification mode. Alterations of these regions being responsible for cognitive impairment have been previously reported. Different parcellation atlases of the human cerebral cortex were compared, and the fine-grained multimodal parcellation HCPMMP performed the best with 180 cortical areas per hemisphere. In multi-group classification, the highest accuracy achieved was 96.86% with the utilization of structural and functional topological modalities as input to the training model. Weights in the trained model with perfect discriminating ability quantify the importance of each cortical region. This is the first time such a phenomenon is discovered and weights in cortical areas are precisely described in AD and its prodromal stages to the best of our knowledge. Our findings can establish other study models to differentiate the patterns in various diseases with cognitive impairments and help to identify the underlying pathology.

Background/purpose: Oral squamous cell carcinoma (OSCC) is one of the most lethal malignancies which accounts for approximately 90% of all malignant oral tumours. SAMMSON is a lncRNA located on chromosome 3p13–3p14 and is known to act as an oncogene in several malignancies. However, its expression and clinical significance in oral squamous cell carcinoma (OSCC) remain mostly unclear. In this study, we investigated the expression and clinical relevance of lncRNA SAMMSON in human OSCC. Materials and methods: Human OSCC cell lines (Tca8113, SCC9, SCC25, CAL27, HN12, HSU3, FADU) and a human normal oral keratinocyte cell line (HNOK) were used to detect the difference of SAMMSON expression. A total of 90 OSCC patients confirmed by pathological and clinical diagnoses at the Hospital of Stomatology, Department of Periodontology, Shandong University were enrolled. The mRNA expression level was analyzed by reverse transcription PCR (QRT-PCR). Statistical analyses including Student's t-test, chi-square method, Kaplan-Meier method, Univariate and, Multivariate Cox regression analysis were performed to analyse all data. Results: This study showed that the expression of SAMMSON was significantly increased in OSCC tissues and cell lines. High SAMMSON expression was significantly associated with TMN stage, tumour differentiation, lymph node metastasis distant metastasis and neighboring tissue infiltration. Patients with high expression of SAMMSON had poor overall survival and disease-free survival compared to those with low levels. Cox regression analysis showed that SAMMSON could act as an independent prognostic factor in OSCC. Conclusion: Serum SAMMSON expression was associated with tumour SAMMSON expression. ROC curve analysis indicated the high diagnostic sensitivity and specificity of serum SAMMSON expression in OSCC patients as compared to other traditional serum biomarker SCCA, TSGF, and CEA. These results indicated that SAMMSON might play an essential role in OSCC progression and could serve as a novel prognostic and diagnostic biomarker in OSCC.

The paper dealt with the thermoelastic responses of biological tissues subjected to an abrupt input of temperature load in the context of generalized thermoelasticity with three phase lag times. A modified thermoelastic model with three phase lag times was proposed to resolve the discrepancy between the three-phase-lag thermoelastic model and existing models in propagation of thermal wave. The Laplace transform and numerical inverse transform methods were applied to acquire the distributions of temperature, displacement and stresses. The effects of rate of thermal conductivity, phase lag times and rate of blood perfusion on thermoelastic behaviors were discussed specifically. The rate of thermal conductivity plays a crucial role in determining the propagation speed of thermal wave in the framework of Three-Phase-Lag (TPL) or Green-Naghdi (G-N) thermoelasticity.

The fractional derivative (FD) and memory-dependent derivative (MDD) are efficient methods to predict the transient thermal responses. In the present paper, for the first time, the FD and MDD are introduced into classical Pennes bio-heat conduction equation with single phase-lag and the corresponding bio-heat transfer models have been formulated with the aids of thermal energy conservation equation. The Laplace transform and numerical inverse transform method are adopted to get access to thermal responses due to temperature shock. Reductions of the present models to classical Pennes and single phase-lag bio-heat transfer models are presented and comparison between different FD and MDD in transient bio-heat transfer is carried out firstly. An approximate formulation of propagation speed of thermal signal in FD models is given according to results firstly. Influences of fractional derivative parameter and tempered parameter in FD, delay time in MDD, phase-lag time and rate of blood perfusion on temperature variation and distribution are carried out numerically. Both fractional derivative and memory-dependent derivative have the ability to predict thermal response between diffusion and wave behavior and CF fractional derivative and MDD with K3 may be suitable methods.

Based on the joint HCPMMP parcellation method we developed before, which divides the cortical brain into 360 regions, the concept of ordered core features (OCF) is first proposed to reveal the functional brain connectivity relationship among different cohorts of Alzheimer's disease (AD), late mild cognitive impairment (LMCI), early mild cognitive impairment (EMCI) and healthy controls (HC). A set of core network features that change significantly under the specifically progressive relationship were extracted and used as supervised machine learning classifiers. The network nodes in this set mainly locate in the frontal lobe and insular, forming a narrow band, which are responsible for cognitive impairment as suggested by previous finding. By using these features, the accuracy ranged from 86.0% to 95.5% in binary classification between any pair of cohorts, higher than 70.1%–91.0% when using all network features. In multi-group classification, the average accuracy was 75% or 78% for HC, EMCI, LMCI or EMCI, LMCI, AD against baseline of 33%, and 53.3% for HC, EMCI, LMCI and AD against baseline of 25%. In addition, the recognition rate was lower when combining EMCI and LMCI patients into one group of mild cognitive impairment (MCI) for classification, suggesting that there exists a big difference between early and late MCI patients. This finding supports the EMCI/LMCI inclusion criteria introduced by ADNI based on neuropsychological assessments.

Laser has become a well-accepted technique for surgical procedures. To fit the physically irradiated area to the clinically planned target area, a multifibre laser system can be used. This paper theoretically investigated the temperature distribution in a three-dimensional biological tissue when irradiated by multifibre lasers with the aids of the dual-phase-lag (DPL) bio-heat conduction model. First, four laser beams located on the corners of a square are used as the heat sources. The method of separation of variables is adopted to obtain the analytical expression of temperature. The characteristics of DPL bio-heat transfer model and the difference with Pennes model were checked graphically. It is found that the effect of multiple laser beams on temperature response differs from those of single laser beam distinctly. A second heating phenomenon occurs and the contour of a square with curved corners are obtained. Then the laser beams are located to form a triangle and a trapezoid and the corresponding temperature responses are studied. Different irradiated zone can be obtained and accomplished by changing the spot size, the arrangement layout and the interval distance of the laser beams.

Background: The anti-tumor properties of Alpinia oxyphylla Miquel (A. oxyphylla) extracts and their petroleum ether (PE) fractions have long attracted scientific attention. These extracts’ anti-tumor activity and mechanisms in vivo are still unclear. This study was designed to investigate the anti-tumor activity and the underlying mechanism of PE’s effect on hepatocellular carcinoma (HCC) in vitro and in vivo. Materials and method: The anti-tumor activity of PE was evaluated by MTT assay and xenograft study. Mechanistic studies of PE were analyzed by Hoechst 33342 staining, Annexin V-FITC/PI double-staining assay, immunohistochemical staining and western blot assay. The toxicity of the PE treatment was verified by the levels of liver and kidney function in nude mice and the H&E staining of their liver and kidney tissues. Result: PE significantly inhibited the growth of HepG2, BEL-7402, SMMC-7721 and Hep3B cells in a concentration- and time-dependent manner. Specifically, PE inhibited the growth of Hep3B cells by inducing apoptosis. PE treatment at the doses of 0.25, 0.5 and 1 g/kg for 21 days caused a respective 35.7 percent, 49.3 percent and 58.8 percent inhibition of the tumor volume, and a 14.8 percent, 40.2 percent and 55.6 percent decrease in the tumor weight, respectively, as compared with the vehicle group in tumor-loaded mice in vivo. PE promoted the release of cytochrome c from mitochondria to cytosol in a concentration-dependent manner. The expression levels of BAX (p

In the present work, the ultrafine-grained W-25 wt.%Cu composites doped with multi-walled carbon nanotubes (CNTs) have been prepared through combined processes of high-energy ball-milling, liquid-phase sintering and infiltration. Furthermore, the microstructure, hardness and electrical conductivity of the ultrafine-grained W-Cu composites doped with different contents of CNTs were investigated. Meanwhile, the wear resistance, compressive performance at different temperatures and arc erosion resistance were evaluated in comparison with the W-Cu composite without CNTs. The results revealed that the hardness, wear resistance, compressive performance and arc erosion resistance of the W-Cu composites doped with CNTs were enhanced dramatically due to the introduction of tungsten carbide phases after sintering and infiltration. Keywords: W-Cu composite, CNTs, Tungsten carbide, Wear resistance, Compressive performance

In this study, we mainly aimed at developing the Ifosfamide-loaded-lipid-core nanocapsules (IFS-LNC) to increase the therapeutic efficacy in osteosarcoma. The nanoparticle was prepared and evaluated in terms of physical, chemical and biological parameters. The lipid-core-nanocapsules were nanosized with narrow particle size distribution and exhibited a high loading capacity. The LNC displayed a sustained release profile of the drug suggesting its potential application in biomedical field and prolonged anticancer therapy. The LNC showed an endocytosis-mediated cellular uptake in MG63 cancer cells which may lead to an accelerated disruption of the acidic endolysosomal vesicles with release of IFS into the cytoplasm. Specifically, IFS-LNC exhibited a significantly higher cytotoxicity than free IFS used at the same concentration. The indiscriminate ability of the drug-loaded formulation increased the apoptosis of cancer cells by increasing the expression levels of caspase-3 and caspase-9 in MG63 cells. Overall, nanoparticulate formulations of Ifosfamide enhanced the therapeutic efficacy in osteosarcoma. Keywords: Osteosarcoma, Nanocapsules, Ifosfamide, Apoptosis, Chemotherapy

Intracellular nicotinamide phosphoribosyltransferase (iNAMPT) is the rate-limiting enzyme of the mammalian NAD+ biosynthesis salvage pathway. Using inducible and conditional knockout (cKO) mice, we show that Nampt gene deletion in adult projection neurons leads to a progressive loss of body weight, hypothermia, motor neuron (MN) degeneration, motor function deficits, paralysis, and death. Nampt deletion causes mitochondrial dysfunction, muscle fiber type conversion, and atrophy, as well as defective synaptic function at neuromuscular junctions (NMJs). When treated with nicotinamide mononucleotide (NMN), Nampt cKO mice exhibit reduced motor function deficits and prolonged lifespan. iNAMPT protein levels are significantly reduced in the spinal cord of amyotrophic lateral sclerosis (ALS) patients, indicating the involvement of NAMPT in ALS pathology. Our findings reveal that neuronal NAMPT plays an essential role in mitochondrial bioenergetics, motor function, and survival. Our study suggests that the NAMPT-mediated NAD+ biosynthesis pathway is a potential therapeutic target for degenerative MN diseases.

To investigate whether probiotic supplementation could reduce the risk of fungal infection in preterm neonates in neonatal intensive care units (NICUs), we systematically searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials databases for randomized controlled trials (RCTs) focusing on the effect of probiotics on fungal infection in preterm neonates. The outcomes of interest were Candida colonization and invasive fungal sepsis. Seven trials involving 1371 preterm neonates were included. Meta-analysis (fixed-effects model) showed that probiotic supplementation was significantly associated with a lower risk of Candida colonization (2 RCTs, n = 329; relative risk (RR), 0.43; 95% confidence interval (CI), 0.27–0.67; p = 0.0002; I2 = 0%), and invasive fungal sepsis (7 RCTs, n = 1371; RR, 0.64; 95% CI, 0.46–0.88; p = 0.006; I2 = 13%). After excluding one study with a high baseline incidence (75%) of fungal sepsis, the effect of probiotics on invasive fungal sepsis became statistically insignificant (RR, 0.88; 95% CI, 0.44–1.78; p = 0.72; I2 = 15%). When using the random-effects model, the effect of probiotics remained favorable for Candida colonization (RR, 0.43; 95% CI 0.27–0.68; p = 0.0002; I2 = 0%) but not for fungal sepsis (RR, 0.64; 95% CI 0.38–1.08; p = 0.10; I2 = 13%). Current evidence indicates that probiotics can reduce the risk of Candida colonization in preterm neonates in NICUs. Limited data support that probiotic supplementation prevents invasive fungal sepsis in preterm neonates. High-quality and adequately powered RCTs are warranted.

Extreme meteorological disaster effects on grain production is mainly determined by the interaction between danger degree of hazard-induced factors and vulnerability degree of hazard-affected bodies. This paper treats physical exposure, sensitivity of the response to the impact, and capabilities of disaster prevention and mitigation as a complex system for vulnerability degree of hazard-affected bodies, which included the external shocks and internal stability mechanism. Hazard-induced factors generate external shocks on grain production systems though exposure and sensitivity of hazard-affected body, and the result can be represented as affected area of grain. By quantile regression model, this paper depicts the quantitative relationship between hazard-induced factors of extreme meteorological disaster and the affected area in the tail of the distribution. Moreover, the model of production function have also been utilized to expound and prove the quantitative relationship between the affected area and final grain output under the internal stability mechanism of the agricultural natural resources endowment, the input factors of agricultural production, and the capacity of defending disaster. The empirical study of this paper finds that impact effects of drought disaster to grain production system presents the basic law of “diminishing marginal loss”, namely, with the constant improvement of the grade of drought, marginal affected area produced by hazard-induced factors will be diminishing. Scenario simulation of extreme drought impact shows that by every 1% reduction in summer average rainfall, grain production of Jilin Province will fell 0.2549% and cut production of grain 14.69% eventually. In response to ensure China's grain security, the construction of the long-term mechanism of agricultural disaster prevention and mitigation, and the innovation of agricultural risk management tools should be also included in the agricultural policy agenda.

β-site amyloid precursor protein cleaving enzyme 1 (BACE1) is the rate-limiting enzyme in the formation of β-amyloid peptides (Aβ), which are important in the development of Alzheimer's disease. It has been demonstrated that albiflorin can alleviate Aβ aggregation. However, the mechanism behind this effect is unknown. In our previous work, albiflorin and its four analogues were isolated from Paeonia lactiflora Pall. This study aims to investigate the relationship of these four compounds with BACE1. Our results show that the albiflorin analogue 4-O-galloylalbiflorin (4-O-GA) had the strongest BACE1 inhibitory effect and was also selective for BACE1. Furthermore, docking study of BACE1 with these analogues yielded similar results, whereby 4-O-GA treatment caused the greatest decreases in both the generation of Aβ1–42 and Aβ1–40 and in the expression of BACE1 and HIF-1α. Our findings indicate that 4-O-GA exerted significant and selective inhibitory activities against BACE1, potentially providing a useful agent for developing BACE1 inhibitor drugs.

Objective: Explicating the property and action of traditional Chinese medicine (TCM) in the perspectives of modern science deepens the insight into the property of TCM, and provides the basis for new drug discovery and clinical therapy. In this study, we investigated the relationship between transient receptor potential melastatin 8 (TRPM8) and pungent flavor using three-dimensional pharmacophores based on virtual screening methods. Methods: Firstly, an inhouse database was established to identify the related pharmacological action according to the traditional Chinese herbs expressing an action of promoting blood circulation. Then, several therapeutic targets, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoAR), cholesteryl ester transfer protein (CETP), Niemann-Pick C1-Like 1 (NPC1L1) and platelet-activating factor receptor (PAFR), were selected to screen traditional Chinese herbs, and the common virtual screening hits with various hit scores providing data to reveal the correlation among TRPM8 and therapeutic targets. Results: According to the screening results, TRPM8 agonists were able to identify the effective components of pungent herbs and TRPM8, which shares the common virtual screening hits with the therapeutic targets, was considered to be related to the action of pungent taste. Conclusion: The novel ideas and methods in this study are beneficial to unveil the scientific relationship between a TCM property and its action.

Objective: Lipid droplet (LD) deposition in adipose tissue is a critical factor leading to metabolic dysfunction. Various herbal medicines in traditional Chinese medicine (TCM) are used to treat hyperlipidemia, type 2 diabetes, obesity, and other diseases. The objective of this study was to identify potential anti-adipogenic agents from TCM herbal compounds. Methods: One hundred and twenty compounds were evaluated in terms of their effect on adipocyte differentiation through image-based high content screening. Anti-adipogenic effects of identified hits were further confirmed at various concentrations. In addition, drug-induced liver injury assay was performed with HepG2 cells to test the hepatotoxicity of hit compounds. Results: Berbamine (BBM), a chemical isolated from barberry, and a derivative of BBM, berbamine dihydrochloride (BBMD), reduced LDs formation by more than 50%. Dose-dependent effects were observed and the IC50 values of the two hits, BBM and BBMD, were determined as 1.88 μM and 0.95 μM, respectively. Moreover, BBM induced mild HepG2 cell injury, while its dihydrochloride—BBMD did not exhibit hepatotoxicity within 40 μM. Conclusion: This study demonstrates that BBMD may be a potential therapeutic candidate for disorders associated with elevated LDs accumulation.

Purpose: Drug resistance has been recognized to be a major obstacle to the chemotherapy for osteosarcoma. And the potential importance of hypoxia as a target to reverse drug resistance in osteosarcoma has been indicated, though the mechanism underlining such role is not clarified. The present study aims to investigate the role of hypoxia in the drug resistance in osteosarcoma cells via activating AMP-activated protein kinase (AMPK) signaling. Experimental design: We investigated the promotion of the resistance to doxorubicin of osteosarcoma MG-63 and U2-os cells in vitro, and then determined the role of hypoxia-inducible factor-1 (HIF-1)α and HIF-1β, the activation and regulatory role of AMPK in the osteosarcoma U2-os cells which were treated with doxorubicin under hypoxia. Results: It was demonstrated that hypoxia significantly reduced the sensitivity of MG-63 and U2-os cells to doxorubicin, indicating an inhibited viability reduction and a reduced apoptosis promotion. And such reduced sensitivity was not associated with HIF-1α, though it was promoted by hypoxia in U2-os cells. Interestingly, the AMPK signaling was significantly promoted by hypoxia in the doxorubicin-treated U2-os cells, with a marked upregulation of phosphorylated AMPK (Thr 172) and phosphorylated acetyl-CoA carboxylase (ACC) (Ser 79), which were sensitive to the AMPK activator, AICAR and the AMPK inhibitor, Compound C. Moreover, the promoted AMPK activity by AICAR or the downregulated AMPK activity by Compound C significantly reduced or promoted the sensitivity of U2-os cells to doxorubicin. Conclusion: The present study confirmed the AMPK signaling activation in the doxorubicin-treated osteosarcoma cells, in response to hypoxia, and the chemical upregulation or downregulation of AMPK signaling reduced or increased the chemo-sensitivity of osteosarcoma U2-os cells in vitro. Our study implies that AMPK inhibition might be a effective strategy to sensitize osteocarcoma cells to chemotherapy.

This paper aims to evaluate the effectiveness of the Chinese crop insurance program in terms of farmers' utility and welfare. A simulation model based on the power utility function was first developed to evaluate the effectiveness of crop insurance. Then, the Monte Carlo approach was used to generate the datasets of area, price, yield, cost, and income based on the characteristics of representative farmers, which were clustered and calibrated using the farm-level data of 574 individual farmers from five Chinese provinces. Finally, the effectiveness of Chinese crop insurance was evaluated by comparing the certainty equivalence (CE) of farmers’ utility/welfare under alternative crop insurance scenarios. Government subsidy is a necessary premise for implementing the crop insurance program. The government should subsidize more than 50% of the crop insurance premium to motivate more farmers to participate in the program. The findings also show that the current crop insurance program in China has increased the farmers’ welfare but still need to be improved to achieve the Pareto improvement and to make full use of the financial fund of the government. This paper is believed to not only extend academic research but also has significant implications for policymakers, especially in the context of rapid development of Chinese crop insurance with much issues such as rate, subsidy and coverage level needed to be improved.

Flood catastrophe risk assessment is imperative for the steady development of agriculture under the context of global climate change, and meanwhile, it is an urgent scientific issue need to be solved in agricultural risk assessment discipline. This paper developed the methodology of flood catastrophe risk assessment, which can be shown as the standard process of crop loss calculation, Monte Carlo simulation, the generalized extreme value distribution (GEV) fitting, and risk evaluation. Data on crop loss were collected based on hectares covered by natural disasters, hectares affected by natural disasters, and hectares destroyed by natural disasters using the standard equation. Monte Carlo simulation based on appropriate distribution was used to expand sample size to overcome the insufficiency of crop loss data. Block maxima model (BMM) approach based on the extreme value theory was for modeling the generalized extreme value distribution (GEV) of flood catastrophe loss, and then flood catastrophe risk at the provincial scale in China was calculated. The Type III Extreme distribution (Weibull) has a weighted advantage of modeling flood catastrophe risk for grain production. The impact of flood catastrophe to grain production in China was significantly serious, and high or very high risk of flood catastrophe mainly concentrates on the central and eastern regions of China. Given the scenario of suffering once-in-a-century flood disaster, for majority of the major-producing provinces, the probability of 10% reduction of grain output is more than 90%. Especially, the probabilities of more than 15% decline in grain production reach up to 99.99, 99.86, 99.69, and 91.60% respectively in Anhui, Jilin, Liaoning, and Heilongjiang. Flood catastrophe assessment can provide multifaceted information about flood catastrophe risk that can help to guide management of flood catastrophe.

High-molecular-weight glutenin subunits (HMW-GSs) play a critical role in determining the viscoelastic properties of wheat dough. The HMW-GSs are encoded by Glu-A1, Glu-B1, and Glu-D1 loci on the long arms of chromosomes 1A, 1B, and 1D, respectively. In the present study, four near-isogenic lines with different HMW-GS deletions and compositions at the Glu-A1 and Glu-D1 loci in Yangmai 18 background were used for quality analysis. Deletion in Glu-D1 showed much weaker gluten quality and dough strength than null Glu-A1 genotype and wild genotype (WT), based on the measurements of sodium dodecyl sulfate (SDS)-sedimentation, lactic acid solvent retention capacity (SRC), gluten index, development time, stability time, and alveograph P and L values. The deletion of Glu-D1 did not significantly affect grain hardness, grain protein content, water SRC, sodium carbonate SRC, and sucrose SRC. Double null genotype in Glu-A1 and Glu-D1 and single null genotype in Glu-D1 showed significantly higher cookie diameter, crispness, and lower cookie height compared with single null genotype in Glu-A1 and WT. These indicate that the null Glu-D1 genotype is useful for improvement of biscuit quality, and use of this germplasm would be a viable strategy to develop new wheat varieties for biscuit processing.