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In this study, it was compared the physicochemical properties and cooking taste quality between four different types of compound nutritional rice (rice flour with the addition of other coarse grains, legumes, potatoes, and other powders, extruded as artificial rice grains) and common rice. We found that the protein and apparent amylose contents of compound nutritional rice were higher than that of common rice, up to 9.775% and 19.45% respectively. The γ-aminobutyric acid (GABA) and resistant starch contents were much lower than in common rice, and the dietary fiber content did not differ from that in common rice. The results of Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) analysis revealed that the starch properties and structure of the compound nutritional rice changed due to high temperature and high pressure processing. In particular, the crystalline structures of starch became V-shaped. In addition, the results of artificial tasting and tasting meter showed that the taste of compound nutritional rice was generally inferior to that of common rice. In summary, compound nutritional rice had problems such as nutritional imbalance and poor taste. There was still a lot of room for improving the taste quality of compound nutritional rice. Therefore, the future development of compound nutritional rice should focus on both nutritional balance and taste improvement. The results of this paper also provided a certain theoretical basis for this.

Abstract Background It has been confirmed that the ApoB/ApoA1 ratio is closely associated with the incidence of cardiometabolic diseases (CMD). However, due to uncontrolled confounding factors in observational studies, the causal relationship of this association remains unclear. Methods In this study, we extracted the ApoB/ApoA1 ratio and data on CMD and its associated risk factors from the largest European Genome-Wide Association Study. The purpose was to conduct Mendelian Randomization (MR) analysis. The causal relationship between the ApoB/ApoA1 ratio and CMD was evaluated using both univariable and multivariable MR analyses. Furthermore, bidirectional MR analysis was performed to estimate the causal relationship between the ApoB/ApoA1 ratio and risk factors for CMD. The final verification confirmed whether the ApoB/ApoA1 ratio exhibits a mediating effect in CMD and related risk factors. Results In terms of CMD, a noteworthy correlation was observed between the increase in the ApoB/ApoA1 ratio and various CMD, including ischemic heart disease, major adverse cardiovascular events, aortic aneurysm, cerebral ischemic disease and so on (all P FDR

Introduction Type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) often coexist and increase risk for developing liver fibrosis and diabetes complications if no effective measures are taken. Dietary intervention is known to be able to achieve diabetes remission, while evidence regarding the long-term effect on liver fat is limited for comorbidity management of type 2 diabetes and NAFLD. This study aims to investigate the long-term effect of a Chinese Medical Nutrition Therapy (CMNT) diet accompanied by intermittent energy restriction on reducing liver fat and glycated haemoglobin (HbA1c) in patients with type 2 diabetes and NAFLD.Methods and analysis This is a multicentre two-armed parallel randomised controlled trial study. 120 participants with type 2 diabetes and NAFLD will be recruited from the physical examination centres of multiple hospitals in China. Participants will be randomly allocated 1:1 to either the CMNT group or the usual care group. The CMNT group will be instructed to consume the provided specific meal replacement Chinese medicinal foods consisting of 6 cycles of 5 consecutive days followed by 10 days of regular food intake. The usual care group will be given standard dietary advice. Primary outcomes are changes in the controlled attenuation parameter value by transient elastography and HbA1c level. Secondary outcomes include differences in anthropometrics, clinical blood markers, questionnaires, gut microbiota and metabolomics. Further follow-up will be performed at 6 months, 1 year and 2 years.Ethics and dissemination The study protocol was approved by the Biomedical Research Ethics Committee of Hunan Agricultural University (BRECHAU20200235).The results will be disseminated via relevant peer-reviewed publications and conference presentations.Trial registration number NCT05439226.

Objective: To investigate the effects of Ganoderma lucidum polysaccharides and its flora metabolites on the insulin resistance status of HepG2 cells and its mechanisms. Methods: Insulin resistant HepG2 (IR-HepG2) model was established with the combination of insulin (10−3 µmol/L) and dexamethasone (10 µmol/L). The cytotoxicity of Ganoderma lucidum polysaccharides (GLP) and Ganoderma lucidum polysaccharide flora metabolite (GLP-F) was evaluated using the CCK-8 method. The effects of GLP and GLP-F on glucose consumption and glycogen synthesis in IR-HepG2 cells were evaluated using the glucose kit and glycogen kit methods. Western blot assay was used to detect the effects of GLP and GLP-F on the phosphorylation or expression of IRS-1, AKT, GSK-3β, GLUT2, and PEPCK, key proteins in the insulin signaling cascade in IR-HepG2 cells. Results: Both GLP and GLP-F significantly increased glucose uptake and glycogen synthesis in IR-HepG2 cells (P

Abstract Background Doxorubicin (DOX)-induced cardiotoxicity (DIC) is a major impediment to its clinical application. It is indispensable to explore alternative treatment molecules or drugs for mitigating DIC. WGX50, an organic extract derived from Zanthoxylum bungeanum Maxim, has anti-inflammatory and antioxidant biological activity, however, its function and mechanism in DIC remain unclear. Methods We established DOX-induced cardiotoxicity models both in vitro and in vivo. Echocardiography and histological analyses were used to determine the severity of cardiac injury in mice. The myocardial damage markers cTnT, CK-MB, ANP, BNP, and ferroptosis associated indicators Fe2+, MDA, and GPX4 were measured using ELISA, RT-qPCR, and western blot assays. The morphology of mitochondria was investigated with a transmission electron microscope. The levels of mitochondrial membrane potential, mitochondrial ROS, and lipid ROS were detected using JC-1, MitoSOX™, and C11-BODIPY 581/591 probes. Results Our findings demonstrate that WGX50 protects DOX-induced cardiotoxicity via restraining mitochondrial ROS and ferroptosis. In vivo, WGX50 effectively relieves doxorubicin-induced cardiac dysfunction, cardiac injury, fibrosis, mitochondrial damage, and redox imbalance. In vitro, WGX50 preserves mitochondrial function by reducing the level of mitochondrial membrane potential and increasing mitochondrial ATP production. Furthermore, WGX50 reduces iron accumulation and mitochondrial ROS, increases GPX4 expression, and regulates lipid metabolism to inhibit DOX-induced ferroptosis. Conclusion Taken together, WGX50 protects DOX-induced cardiotoxicity via mitochondrial ROS and the ferroptosis pathway, which provides novel insights for WGX50 as a promising drug candidate for cardioprotection. Graphic abstract

Speaker recognition is an indispensable technology for biometrics. It distinguishes individuals based on their vocal patterns. In this paper, a joint confirmation method based on the Akaike Information Criterion (AIC) of reconstruction error (REE) and time complexity (AIC-Time joint confirmation method) is proposed to select the optimal decomposition rank of NMF. Furthermore, non-negative matrix factorization (NMF) is applied to the spectrogram to generate speaker features. The network for speaker recognition is based on Convolutional Neural Networks combining Squeeze Excitation (SE) blocks with ResNeXt, and the best combination is explored experimentally. The SE block conducts a channel-level adaptive adjustment of the feature maps, reducing redundancy and noise interference while improving feature extraction efficiency and accuracy. The ResNeXt convolutional neural network concurrently executes multiple convolutional kernels, acquiring richer feature information. The experimental results demonstrate that compared to speaker recognition based on Gaussian mixture models (GMM), Visual Geometry Group Network (VGGNet), ResNet, and SE-ResNeXt using spectrograms, this method increases the accuracy by an average of 5.8% and 16.24% under the overlaid of babble and factory1 noise with different signal-to-noise ratios, respectively. In the short speech test, the test set is short speech of 1s and 2s, and the noise is superimposed. Compared with other methods, the recognition rate is increased by an average of 8.67% and 11.72%, respectively.

Objective: To establish the knowledge graph of “disease-syndrome-symptom-method-formula” in Treatise on Febrile Diseases (Shang Han Lun,《伤寒论》) for reducing the fuzziness and uncertainty of data, and for laying a foundation for later knowledge reasoning and its application. Methods: Under the guidance of experts in the classical formula of traditional Chinese medicine (TCM), the method of “top-down as the main, bottom-up as the auxiliary” was adopted to carry out knowledge extraction, knowledge fusion, and knowledge storage from the five aspects of the disease, syndrome, symptom, method, and formula for the original text of Treatise on Febrile Diseases, and so the knowledge graph of Treatise on Febrile Diseases was constructed. On this basis, the knowledge structure query and the knowledge relevance query were realized in a visual manner. Results: The knowledge graph of “disease-syndrome-symptom-method-formula” in the Treatise on Febrile Diseases was constructed, containing 6 469 entities and 10 911 relational triples, on which the query of entities and their relationships can be carried out and the query result can be visualized. Conclusion: The knowledge graph of Treatise on Febrile Diseases systematically realizes its digitization of the knowledge system, and improves the completeness and accuracy of the knowledge representation, and the connection between “disease-syndrome-symptom-treatment-formula”, which is conducive to the sharing and reuse of knowledge can be obtained in a clear and efficient way.

Kidney renal papillary cell carcinoma (KIRP) has a high mortality rate and a poor prognosis. Cu concentrations differed significantly between renal cancer tissues and adjacent normal tissues. Cuproptosis is a newly identified cell death. Long non-coding RNAs (lncRNAs) play a crucial role in the progression of KIRP. In this study, we focused on constructing and validating cuproptosis-related lncRNA signatures to predict the prognosis of KIRP patients and their immune correlation. We created prognosis models using Cox regression analysis and the least absolute shrinkage and selection operator (LASSO) algorithm. We found that patients in the high-risk group had poorer overall survival (OS) and progression-free survival (PFS) and higher mortality. Risk score and stage are prognosis factors independent of other clinical features. Kaplan-Meier analysis, receiver operating characteristic (ROC) curves, and C-index curves showed that cuproptosis-related lncRNA signatures could more accurately predict the prognosis of patients. Functional enrichment analysis suggests that the function of differentially expressed genes (DEGs) is associated with KIRP development and immunity. In immune-related function analysis, we found a significant difference in parainflammation responses between high-risk and low-risk groups. The mutation frequencies of TTN, MET, KMT2C, PKHD1, SETD2, and KMT2D genes in the high-risk group were higher than those in the low-risk group, but the mutation frequencies of MUC16, KIAA109, CUBN, USH2A, DNAH8 and HERC2 genes were significantly lower than those in the low-risk group. Survival analysis of tumor mutation burden (TMB) and combined TMB-risk showed better OS in patients with high TMB. Immune infiltration and immune checkpoint analysis assessed the immune association of six high mutation frequency genes (TTN, MET, KMT2C, PKHD1, SETD2, and KMT2D) with KIRP. Finally, we performed a drug sensitivity analysis and screened 15 potential drugs that differed between high-risk and low-risk patients. In this study, we constructed and validated cuproptosis-related lncRNA signatures that can more accurately predict the prognosis of KIRP patients and provide new potential therapeutic targets and prognosis markers for KIRP patients.

Hepatocellular carcinoma (HCC) is one of the world’s malignant tumors with high morbidity and mortality. Cuproptosis is a novel form of cell death. However, the prognostic evaluation and immune relevance of cuproptosis-related genes (CRGs) in HCC are largely unknown. In our study, we constructed a prognostic model of CRGs in HCC and performed immune infiltration, functional analysis, immune checkpoint and drug sensitivity analysis. Systematically elaborated the prognostic and immune correlation of CRGs in HCC. The results showed that 15 CRGs were up-regulated or down-regulated in HCC, and the mutation frequency of CRGs reached 10.33% in HCC, with CDKN2A having the highest mutation frequency. These 19 CRGs were mainly involved in the mitochondrion, immune response and metabolic pathways. Five selected genes (CDKN2A, DLAT, DLST, GLS, PDHA1) were involved in constructing a prognostic CRGs model that enables the overall survival in HCC patients to be predicted with moderate to high accuracy. Prognostic CRGs, especially CDKN2A, the independent factor of HCC prognosis, may be closely associated with immune-cell infiltration, tumor mutation burden (TMB), microsatellite instability(MSI), and immune checkpoints. CD274, CTLA4, LAG3, PDCD1, PDCD1LG2 and SIGLEC15 may be identified as potential therapeutic targets and CD274 correlated highly with prognostic genes. Quantitative Real-Time PCR (qRT-PCR) and immunohistochemical were performed to validate the mRNA and protein expression levels of CDKN2A in adjacent normal tissues and HCC tissues, and the results were consistent with gene difference analysis. In conclusion, CRGs, especially CDKN2A, may serve as potential prognostic predictors in HCC patients and provide novel insights into cancer therapy.

IntroductionSustained hyperglycemia causes glucotoxicity, which has been regarded as a contributor to hepatocyte damage in type 2 diabetes (T2D) and its metabolic comorbidities. Honokiol is a natural biphenolic component derived from the dietary supplement Magnolia officinalis extract. This study aimed to investigate the effects of honokiol on glucose metabolism disorders and oxidative stress in hepatocytes and the underlying mechanisms.MethodsHepG2 cells were treated with glucosamines (18 mM) to induce glucotoxicity as a diabetic complication model in vitro.Results and discussionHonokiol significantly increased glucose consumption, elevated 2-NBDG uptake, and promoted GLUT2 translocation to the plasma membrane in glucosamine-treated HepG2 cells, indicating that honokiol ameliorates glucose metabolism disorders. Furthermore, glucosamine-induced ROS accumulation and loss of mitochondrial membrane potential were markedly reduced by honokiol, suggesting that honokiol alleviated glucotoxicity-induced oxidative stress. These effects were largely abolished by compound C, an AMPK inhibitor, suggesting an AMPK activation-dependent manner of honokiol function in promoting glucose metabolism and mitigating oxidative stress. Molecular docking results revealed that honokiol could interact with the amino acid residues (His151, Arg152, Lys243, Arg70, Lys170, and His298) in the active site of AMPK. These findings provide new insights into the antidiabetic effect of honokiol, which may be a promising agent for the prevention and treatment of T2D and associated metabolic comorbidities.

Polygonatum sibiricum polysaccharides (PSPs) have important biological functions, such as antioxidation, immunomodulatory, and hypolipidemic functions. Different extraction methods have effects on their structures and activities. In this study, six extraction methods, including hot water extraction (HWE), alkali extraction (AAE), ultrasound-assisted extraction (UAE), enzyme-assisted extraction (EAE), microwave-assisted extraction (MAE), and freeze–thaw-assisted extraction (FAE) were used to extract PSPs, and their structure–activity relationships were analyzed. The results showed that all six PSPs had similar functional group compositions, thermal stability, and glycosidic bond compositions. PSP-As (PSPs extracted by AAE) exhibited better rheological properties due to their higher molecular weight (Mw). PSP-Es (PSPs extracted by EAE) and PSP-Fs (PSPs extracted by FAE) had better lipid-lowering activity due to their lower Mw. PSP-Es and PSP-Ms (PSPs extracted by MAE), which do not contain uronic acid and have a moderate Mw, had better 1,1-diphenyl-2-picrylhydrazyl (DPPH)-radical-scavenging activity. On the contrary, PSP-Hs (PSPs extracted by HWE) and PSP-Fs, with the Mw of uronic acid, had the best OH-radical-scavenging activity. The high-Mw PSP-As had the best Fe2+-chelating ability. In addition, mannose (Man) may play an important role in the immunomodulatory activity. These results indicate that different extraction methods affect the structure and biological activity of polysaccharides to varying degrees, and these results are helpful for understanding the structure–activity relationship of PSPs.

The on-orbit operation of insertion and extraction of space robots is a technology essential to the assembly and maintenance in orbit, satellite fuel filling, failed satellite recovery, especially modular in-orbit assembly of micro-spacecraft. Therefore, the force/posture impedance control for the on-orbit operation of insertion and extraction is studied. Firstly, the dynamic model of space robots’ system in the form of uncontrolled carrier position and controlled attitude is derived by using the momentum conservation principle. Through the kinematic constraints of the replacement component plug, the Jacobi relationship of the plug motion in the base coordinate system is established. Secondly, to achieve the output force control of the plug during the on-orbit operation of insertion and extraction, a second-order linear impedance model is established based on the dynamic relationship between the plug posture and its output force and the impedance control principle. Then, in order to improve the stability, robustness, and adaptability of the controller, an adaptive Radial Basis Function Neural Network (RBFNN) is used to approximate the uncertainties in the dynamic model for the force/posture control of the plug. Finally, the stability of the system is verified by the Lyapunov principle. The simulation results show that the designed neural network impedance control strategy can achieve a control accuracy of less than 10−3 rad for the plug’s attitude tracking error, less than 10−3 m for its position tracking error, and less than 0.5 N for its output force tracking error.

Fu Brick tea is a very popular post-fermented tea that is known for its “golden flower fungus,” Aspergillus cristatus, which becomes the dominant microbe during the maturation process. This study used both culture-dependent methods and high-throughput sequencing to track microbial succession and interactions during the development of the golden flower fungus, a crucial component of the manufacturing process of Fu Brick tea. Among the bacterial communities, Klebsiella and Lactobacillus were consistently cultured from both fresh tea leaves and in post-fermentation Fu Brick tea. Methylobacterium, Pelomonas, and Sphingomonas were dominant genera in fresh tea leaves but declined once fermentation started, while Bacillus, Kluyvera, and Paenibacillus became dominant after piling fermentation. The abundance of A. cristatus increased during the manufacturing process, accounting for over 98% of all fungi present after the golden flower bloom in the Fu Brick tea product. Despite their consistent presence during culture work, network analysis showed Lactobacillus and Klebsiella to be negatively correlated with A. cristatus. Bacillus spp., as expected from culture work, positively correlated with the presence of golden flower fungus. This study provides complete insights about the succession of microbial communities and highlights the importance of co-occurrence microbes with A. cristatus during the manufacturing process of Fu Brick tea.

Polysaccharide is the major biologically active constituent in functional mushroom Ganoderma lucidum. This study was aim to investigate the utilizability of G. lucidum polysaccharide by human fecal microbiota and its prebiotic potential based on the Simulator of Human Intestinal Microbial Ecosystem (SHIME). GLP was obtained from fruiting bodies of G. lucidum with average molecular weight of 133.1 KDa. Short-term colonic fermentation of GLP revealed the continuously decreased contents of total carbohydrates and reducing sugar as well as pH. Gas chromatography analysis indicated that GLP promoted the production of acetic, propionic and butyric acids. The 16S rDNA amplicon sequencing analysis showed that GLP improved the microbial diversity and ratio of Bacteroides to Firmicutes., and sharply enriched Bacteroides ovatus and B. uniformis. Therefore, GLP can be utilized by human fecal microbiota and then modify microbial community and metabolic function, and may serve as novel prebiotics to bring health benefits for human.

BackgroundThe diabetes mellitus prevalence is rapidly increasing in most parts of the world and has become a vital health problem. Probiotic and herbal foods are valuable in the treatment of diabetes.Methods and performanceIn this study, Bacillus licheniformis (BL) and Astragalus membranaceus extract (AE) were given with food to InR[E19]/TM2 Drosophila melanogaster, and the blood glucose, antioxidation activity and intestinal microbiota were investigated. The obtained results showed that BA (BL and AE combination) supplementation markedly decreased the blood glucose concentration compared with the standard diet control group, accompanied by significantly increased enzymatic activities of catalase (CAT), decreased MDA levels and prolonged lifespan of InR[E19]/TM2 D. melanogaster. The treatments with BL, AE and BA also ameliorated intestinal microbiota equilibrium by increasing the population of Lactobacillus and significantly decreasing the abundance of Wolbachia. In addition, clearly different evolutionary clusters were found among the control, BL, AE and BA-supplemented diets, and the beneficial microbiota, Lactobacillaceae and Acetobacter, were found to be significantly increased in male flies that were fed BA. These results indicated that dietary supplementation with AE combined with BL not only decreased blood glucose but also extended the lifespan, with CAT increasing, MDA decreasing, and intestinal microbiota improving in InR[E19]/TM2 D. melanogaster.ConclusionThe obtained results showed that dietary supplementation with BL and AE, under the synergistic effect of BL and AE, not only prolonged the lifespan of InR[E19]/TM2 D. melanogaster, increased body weight, and improved the body's antiaging enzyme activity but also effectively improved the types and quantities of beneficial bacteria in the intestinal flora of InR[E19]/TM2 D. melanogaster to improve the characteristics of diabetes symptoms. This study provides scientific evidence for a safe and effective dietary therapeutic method for diabetes mellitus.

Abstract Background Antimicrobial peptides play important roles in both plant and animal defense systems. Moreover, over-expression of CaAMP1 (Capsicum annuum antimicrobial protein 1), an antimicrobial protein gene isolated from C. annuum leaves infected with Xanthomonas campestris pv. vesicatoria, confers broad-spectrum resistance to hemibiotrophic bacterial and necrotrophic fungal pathogens in Arabidopsis. Phytophthora root and stem rot (PRR), caused by the fungus Phytophthora sojae, is one of the most devastating diseases affecting soybean (Glycine max) production worldwide. Results In this study, CaAMP1 was transformed into soybean by Agrobacterium-mediated genetic transformation. Integration of the foreign gene in the genome of transgenic soybean plants and its expression at the translation level were verified by Southern and western blot analyses, respectively. CaAMP1 over-expression (CaAMP1-OX) lines inoculated with P. sojae race 1 exhibited enhanced and stable PRR tolerance through T2–T4 generations compared with the wild-type Williams 82 plants. Gene expression analyses in the transgenic plants revealed that the expression of salicylic acid-dependent, jasmonic acid-dependent, and plant disease resistance genes (R-genes) were significantly up-regulated after P. sojae inoculation. Conclusions These results indicate that CaAMP1 over-expression can significantly enhance PRR tolerance in soybean by eliciting resistance responses mediated by multiple defense signaling pathways. This provides an alternative approach for developing soybean varieties with improved tolerance against soil-borne pathogenic PRR.

Radiotherapy with or without concurrent chemotherapy is the standard treatment for nasopharyngeal carcinoma (NPC) patients, whose efficacy is limited partly by intrinsic and acquired radioresistance. DNA methyltransferase 3B (DNMT3B) has been reported to participate in tumorigenesis via DNA methylation, but its role in mediating progression and radioresistance of NPC remains unclear. Therefore, we conducted the following studies to explore the relationship between DNMT3B and NPC. Here, we found that DNMT3B was elevated in NPC tissues and predicted the poor prognosis of NPC patients. We demonstrated for the first time that ionizing radiation could induce DNMT3B, which might be one of the reasons for radioresistance. Silencing of DNMT3B inhibited migration and invasion via suppressing epithelial-mesenchymal transition (EMT) in NPC cells. Furthermore, silencing DNMT3B restored and activated p53 and p21 via DNA demethylation, which led to cell cycle arrest and apoptosis, resulting in increased radiosensitivity of NPC both in vitro and in vivo. DNMT3B functions as a novel oncogene in the radioresistance of NPC through regulating EMT, cell cycle, and apoptosis. Therefore, DNMT3B could be a potential target for NPC treatment.

Piezoelectric actuators (PAs) require high precision positioning for the applications of micro electrical mechanical systems, but it exhibits hysteresis nonlinearity which deteriorates positioning accuracy if no proper compensation is given. Hysteresis nonlinear modeling of PAs is a prime choice for hysteresis compensation. This paper proposes a novel intelligent positioning control algorithm based on Bouc-Wen (BW) model for the compensation of a bi-morph type piezoelectric actuator (PA) suffering rate-dependent hysteresis. A region based mixed-species swarm optimization (RMSO) algorithm is proposed for BW modeling to capture the dynamic nonlinearity of a piezoelectric actuator which exhibits rate-dependent hysteresis. Results of numerical simulations have been disclosed to illustrate the performance enhancement of RMSO over classical algorithm while they are applied to the parameter fitting problem of BW model for experimentally acquired datasets. An model based adaptive Fuzzy neural network (Fuzzy-NN) controller of PA is utilized to compensate the hysteresis for the positioning tracking control. Experimental results also illustrate the good performance of the proposed RMSO-BW based control scheme for the hysteresis compensation control of the PA.

The marginal ice zone (MIZ) connects the open ocean and the pack ice, playing significant roles in shaping the ice edge and wave–ice interaction. Spaceborne synthetic aperture radar (SAR) has been demonstrated to be one of the most advantageous sensors for MIZ exploration given its capability to collect images under all weather conditions during day and night. In this study, we take advantage of the Sentinel-1 wave mode vignettes acquired around the Antarctic to quantify the image properties over MIZ. A data set of SAR images covering the ice edge with both open water and sea ice present in the same scene was created by manual inspection. It is found that the radar return over sea ice decreases by an average of approximately 1.78 dB in comparison to its adjacent open water, which is roughly independent of the polarizations and incidence angles. The long ocean waves are barely attenuated right across the ice edge in terms of their comparable azimuth cutoff. Further inside the ice from the edge, the waves are gradually dampened out at distances associated with their wavelengths. The results obtained in this study shall help interpret the radar scattering model validation as well as the wave–ice interaction.

Abstract Radiotherapy is the mainstay and primary curative treatment modality in nasopharyngeal carcinoma (NPC), whose efficacy is limited by the development of intrinsic and acquired radioresistance. Thus, deciphering new molecular targets and pathways is essential for enhancing the radiosensitivity of NPC. SALL4 is a vital factor in the development and prognosis of various cancers, but its role in radioresistance remains elusive. This study aimed to explore the association of SALL4 expression with radioresistance of NPC. It was revealed that SALL4 expression was closely correlated with advanced T classification of NPC patients. Inhibition of SALL4 reduced proliferation and sensitized cells to radiation both in vitro and in vivo. Furthermore, SALL4 silencing increased radiation‐induced DNA damage, apoptosis, and G2/M arrest in CNE2 and CNE2R cells. Moreover, knockdown of SALL4 impaired the expression of p‐ATM, p‐Chk2, p‐p53, and anti‐apoptosis protein Bcl‐2, while pro‐apoptosis protein was upregulated. These findings indicate that SALL4 could induce radioresistance via ATM/Chk2/p53 pathway and its downstream proteins related to apoptosis. Targeting SALL4 might be a promising approach for the development of novel radiosensitizing therapeutic agents for radioresistant NPC patients.

Aiming at the force position control problem of the on-orbit insertion and extraction operation of the free-floating space robot, the system dynamics model is established. According to the interaction between the end of manipulator and the environment, the second-order impedance model is established. In order to improves the calculation efficiency, the above models are reconstructed to avoid the use of acceleration signal by introducing filtering operation. This is also conducive to the application of robot actual control. Then, an estimator requiring only the system inertia matrix is designed to compensate the modeling uncertainty, external bounded disturbance and impact effect in the process of inserting and extracting. Its structure is simple and reliable. Only one control parameter needs to be adjusted, which greatly reduces the amount of calculation. Considering that the on-orbit operation of insertion and extraction is a kind of precision operation, its control system needs to have a high-quality control performance. By introducing the prescribed performance method, the tracking error is constrained within the given range and to ensure the transient performance and steady-state performance of the control system is ensured. Finally, three simulation conditions are designed, and the results are presented to verify that the proposed algorithm has a faster convergence speed compared with traditional sliding mode controller. It can achieve vertically inserting and accurate force tracking of the manipulator end.

One-way carsharing system has been widely adopted in the carsharing field due to its flexible services. However, as one of the main limitations of the one-way carsharing system, the imbalance between supply and demand needs to be solved. Predicting pick-up demand has been studied to achieve the goal, but using returned vehicles to reduce unnecessary relocation is also one of the important methods. Nowadays, trajectory data and other data are available for real-time prediction for return demand. Based on the return demand prediction, the relocation response can be more reasonable. Thus, the balance of demand and supply can be largely improved. The multisource data include trajectory data, user application log data, order data, station data, and user characteristic data. Based on these data, a return demand prediction model was used to predict whether the user will return the vehicle in 15 min in real time, and a destination station prediction model was applied to forecast which station the user will park at. Finally, a case study using ten stations’ one-week field data was conducted to test the benefit of the dynamic return demand prediction. The results showed that the return demand prediction improves the efficiency of the relocations by mitigating the condition that the station parking space is full or empty. The potential application of this study would effectively reduce unnecessary relocation and further formulate an active operation optimization strategy to reduce the system’s operational cost and improve the service quality of the system.

Numerous microbiotas, which play important roles in health, inhabit the human gut. A traditional Chinese medicine dietary therapy (TCMDT) diet, consisted of whole grains and traditional Chinese medicines, is traditionally used to lessen hyperglycemia and reduce obesity. The Simulator of the human intestinal microbial ecosystem (SHIME) was used for studying the effect of the TCMDT diet on gut microbiota and short chain fatty acids. The TCMDT diet increased diabetes-improving microbiota (Coriobacteriaceae, Bacteroidaceae, and Peptostreptococcaceae) by 7–26 times and health-related microbiota (Rikenellaceae, Bifidobacteria, Actinobacteria) by 4–300 times. The short chain fatty acids-producers, Bacteroides and Parabacteroides were elevated after intervention. This diet significantly increased acetate (from 2.23 to 36.77 mmol/L), propionate (from 2.85 to 33.93 mmol/L), and butyrate (from 0.89 to 6.96 mmol/L), which are the major short chain fatty acids. Our study provides novel perspective into the role of gut microbiota modulation during TCMDT diet intervention.

Abstract Background Conventional scientific studies had supported the use of polysaccharides and β-glucans from a number of fungi, including Ganoderma lucidum for the treatment of recurrent oral ulceration (ROU). Our aim of the present study was to evaluate whether freeze-dried powder from G. lucidum mycelia (FDPGLM) prevents ROU in rats. Methods A Sprague-Dawley (SD) rat model with ROU was established by autoantigen injection. The ROU rats were treated with three different dosages of FDPGLM and prednisone acetate (PA), and their effects were evaluated according to the clinical therapeutic evaluation indices of ROU. Results High-dose FDPGLM induced significantly prolonged total intervals and a reduction in the number of ulcers and ulcer areas, thereby indicating that the treatment was effective in preventing ROU. Enzyme-linked immunosorbent assay (ELISA) showed that high-dose FDPGLM significantly enhanced the serum transforming growth factor-β1 (TGF-β1) levels, whereas reduced those of interleukin-6 (IL-6) and interleukin-17 (IL-17). Flow cytometry (FCM) showed that the proportion of CD4+ CD25+ Foxp3+ (forkhead box P3) regulatory T cells (Tregs) significantly increased by 1.5-fold in the high-dose FDPGLM group compared to that in the rat model group (P

Abstract Background Chronic inflammation is causally linked to the carcinogenesis and progression of most solid tumors. LPTS is a well-identified tumor suppressor by inhibiting telomerase activity and cancer cell growth. However, whether and how LPTS is regulated by inflammation signaling is still incompletely elucidated. Methods Real-time PCR and western blotting were used to determine the expression of p65 and LPTS. Reporter gene assay, electrophoretic mobility shift assay and chromatin immunoprecipitation were performed to decipher the regulatory mechanism between p65 and LPTS. Cell counting kit-8 assays and xenograt models were used to detect p65-LPTS-regulated cancer cell growth in vitro and in vivo, respectively. Results Here we for the first time demonstrated that NF-κB could inhibit LPTS expression in the mRNA and protein levels in multiple cancer cells (e.g. cervical cancer and colon cancer cells). Mechanistically, NF-κB p65 could bind to two consensus response elements locating at −1143/−1136 and −888/−881 in the promoter region of human LPTS gene according to EMSA and ChIP assays. Mutation of those two binding sites rescued p65-suppressed LPTS promoter activity. Functionally, NF-κB regulated LPTS-dependent cell growth of cervical and colon cancers in vitro and in xenograft models. In translation studies, we verified that increased p65 expression was associated with decreased LPTS level in multiple solid cancers. Conclusions Taken together, we revealed that NF-κB p65 potentiated tumor growth via suppressing a novel target LPTS. Modulation of NF-κB-LPTS axis represented a potential strategy for treatment of those inflammation-associated malignancies.

A reliable source of Huperzine A (HupA) meets an urgent need due to its wide use in Alzheimer's disease treatment. In this study, we sequenced and characterized the whole genomes of two HupA-producing endophytes, Penicillium polonicum hy4 and Colletotrichum gloeosporioides Cg01, to clarify the mechanism of HupA biosynthesis. The whole genomes of hy4 and Cg01 were 33.92 and 55.77 Mb, respectively. We compared the differentially expressed genes (DEGs) between the induced group (with added extracts of Huperzia serrata) and a control group. We focused on DEGs with similar expression patterns in hy4 and Cg01. The DEGs identified in GO (Gene ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways were primarily located in carbon and nitrogen metabolism and nucleolus, ribosome, and rRNA processing. Furthermore, we analyzed the gene expression for HupA biosynthesis genes proposed in plants, which include lysine decarboxylase (LDC), copper amine oxidase (CAO), polyketides synthases (PKS), etc. Two LDCs, one CAO, and three PKSs in Cg01 were selected as prime candidates for further validation. We found that single candidate biosynthesis-gene knock-out did not influence the HupA production, while both LDC gene knock-out led to increased HupA production. These results reveal that HupA biosynthesis in endophytes might differ from that proposed in plants, and imply that the HupA-biosynthesis genes in endophytic fungi might co-evolve with the plant machinery rather than being acquired through horizontal gene transfer (HGT). Moreover, we analyzed the function of the differentially expressed epigenetic modification genes. HupA production of the histone acetyltransferase (HAT) deletion mutant ΔCgSAS-2 was not changed, while that of the histone methyltransferase (HMT) and histone deacetylase (HDAC) deletion mutants ΔCgClr4, ΔCgClr3, and ΔCgSir2-6 was reduced. Recovery of HupA-biosynthetic ability can be achieved by retro-complementation, demonstrating that HMT and HDACs associated with histone modification are involved in the regulation of HupA biosynthesis in endophytic fungi. This is the first report on epigenetic modification in high value secondary metabolite- producing endophytes. These findings shed new light on HupA biosynthesis and regulation in HupA-producing endophytes and are crucial for industrial production of HupA from fungi.

Diabetes is a metabolic disease, partly due to hypoinsulinism, which affects ∼8% of the world’s adult population. Glibenclamide is known to promote insulin secretion by targeting β cells. Autophagy as a self-protective mechanism of cells has been widely studied and has particular physiological effects in different tissues or cells. However, the interaction between autophagy and glibenclamide is unclear. In this study, we investigated the role of autophagy in glibenclamide-induced insulin secretion in pancreatic β cells. Herein, we showed that glibenclamide promoted insulin release and further activated autophagy through the adenosine 5′-monophosphate (AMP) activated protein kinase (AMPK) pathway in MIN-6 cells. Inhibition of autophagy with autophagy inhibitor 3-methyladenine (3-MA) potentiated the secretory function of glibenclamide further. These results suggest that glibenclamide-induced autophagy plays an inhibitory role in promoting insulin secretion by activating the AMPK pathway instead of altering the mammalian target of rapamycin (mTOR).

This paper discloses the development of the improved Bouc-Wen model which captures the behavior of the rate dependent hysteresis of a piezoelectric actuator. The basic form of the Bouc-Wen model only exhibits symmetric hysteresis loop for a sinusoidal input with no DC offset, whereas the real world bi-morph type actuator occasionally exhibits asymmetric loop for the same stimuli. The present works also proposes the integration of the FIR filter to the model to capture phase lag caused by the structural oscillation of the actuator. Comparison of the modeling accuracy has been given with our recent work of adaptive Preisach model. The result shows that accuracy of the two models are almost the same but the intrinsic difference lies in the number of parameters to be determined to form a computable model: the proposed model has only 25 parameters whereas the adaptive Preisach model includes 5050 discretized distribution function values to establish a single model.

Single molecule, real-time (SMRT) sequencing was used to characterize mitochondrial (mt) genome of Ophiocordyceps sinensis and to analyze the mt genome-wide pattern of epigenetic DNA modification. The complete mt genome of O. sinensis, with a size of 157,539 bp, is the fourth largest Ascomycota mt genome sequenced to date. It contained 14 conserved protein-coding genes (PCGs), 1 intronic protein rps3, 27 tRNAs and 2 rRNA subunits, which are common characteristics of the known mt genomes in Hypocreales. A phylogenetic tree inferred from 14 PCGs in Pezizomycotina fungi supports O. sinensis as most closely related to Hirsutella rhossiliensis in Ophiocordycipitaceae. A total of 36 sequence sites in rps3 were under positive selection, with dN/dS >1 in the 20 compared fungi. Among them, 16 sites were statistically significant. In addition, the mt genome-wide base modification pattern of O. sinensis was determined in this study, especially DNA methylation. The methylations were located in coding and uncoding regions of mt PCGs in O. sinensis, and might be closely related to the expression of PCGs or the binding affinity of transcription factor A to mtDNA. Consequently, these methylations may affect the enzymatic activity of oxidative phosphorylation and then the mt respiratory rate; or they may influence mt biogenesis. Therefore, methylations in the mitogenome of O. sinensis might be a genetic feature to adapt to the cold and low PO2 environment at high altitude, where O. sinensis is endemic. This is the first report on epigenetic modifications in a fungal mt genome.

We explored the expression and function of miR-181d (microRNA-181d) in human pancreatic cancer. Quantitative real-time polymerase chain reaction was used to probe miR-181d expression in both pancreatic cancer cell lines and human pancreatic carcinoma. Pancreatic cancer cell lines, PANC-1 and AsPC-1 cells, were engineered to stably downregulate endogenous miR-181d through lentiviral transduction. The mechanistic effects of miR-181d downregulation on pancreatic cancer development were tested by proliferation, migration, fluorouracil chemosensitivity assays in vitro, and explant assay in vivo. Possible miR-181d downstream gene, NKAIN2 (Na+/K+ transporting ATPase interacting 2), was tested by dual-luciferase activity assay and quantitative real-time polymerase chain reaction. Functional involvement of NKAIN2 in miR-181d-regulated pancreatic cancer development was tested by small interfering RNA–mediated NKAIN2 knockdown in miR-181d-downregulated PANC-1 and AsPC-1 cells. MiR-181d was upregulated in both pancreatic cancer cell lines and human pancreatic carcinoma. Lentivirus-induced miR-181d downregulation decreased pancreatic cancer proliferation, migration, and fluorouracil resistance in vitro and inhibited the growth of cancer explant in vivo. NKAIN2 was directly targeted by miR-181d in pancreatic cancer. Small interfering RNA–mediated NKAIN2 knockdown reversed the inhibition of miR-181d downregulation on pancreatic cancer development. MiR-181d is aberrantly overexpressed in pancreatic cancer. Inhibiting miR-181d may suppress pancreatic cancer development, possibly through the inverse regulation on NKAIN2.

Action video games (AVGs) have attracted increasing research attention as they offer a unique perspective into the relation between active learning and neural plasticity. However, little research has examined the relation between AVG experience and the plasticity of neural network mechanisms. It has been proposed that AVG experience is related to the integration between Salience Network (SN) and Central Executive Network (CEN), which are responsible for attention and working memory, respectively, two cognitive functions essential for AVG playing. This study initiated a systematic investigation of this proposition by analyzing AVG experts’ and amateurs’ resting-state brain functions through graph theoretical analyses and functional connectivity. Results reveal enhanced intra- and internetwork functional integrations in AVG experts compared to amateurs. The findings support the possible relation between AVG experience and the neural network plasticity.

Simo decoction (SMD), as a traditional medicine, is widely used in the treatment of gastrointestinal dysmotility in China. In this study, a combined method of liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS) and ultrafiltration high-performance liquid chromatography molecular docking (UF-HPLC-MD) was efficiently employed to identify and screen bioactive ingredients in SMD. Ninety-four major constituents were identified or tentatively characterized by comparing their retention times and mass spectra with standards or literature data by using LC-Q-TOF-MS, and the ascription of those compounds were classified for the first time. Among them, 13 bioactive ingredients, including norisoboldine, eriocitrin, neoeriocitrin, narirutin, hesperidin, naringin, neohesperidin, hesperitin-7-O-glucoside, linderane, poncirin, costunolide, nobiletin, and tangeretin, were primarily identified as the human serum albumin (HSA) ligands at a range of docking scores from −29.7 to −40.6 kJ/mol by UF-HPLC-MD. The results indicate the systematic identification and screening of HSA ligands from Simo decoction guided by LC-Q-TOF-MS and UF-HPLC-MD represents a feasible and efficient method that could be extended for the identification and screening of other bioactive ingredients from natural medicines.

Fibrinogen can transform fibrin through an agglutination reaction, finally forming fibrin polymer with grid structure. The density and viscosity of the reaction system changes drastically during the course of agglutination. In this research, we apply an independently-developed piezoelectric agglutination sensor to detect the fibrinogen agglutination reaction in patients with coronary heart diseases. The terminal judgment method of determining plasma agglutination reaction through piezoelectric agglutination sensor was established. In addition, the standard curve between plasma agglutination time and fibrinogen concentration was established to determinate fibrinogen content quantitatively. The results indicate the close correlation between the STAGO paramagnetic particle method and the method of piezoelectric agglutination sensor for the detection of Fibrinogen. The correlation coefficient was 0.91 (γ = 0.91). The determination can be completed within 10 minutes. The fibrinogen concentration in the coronary heart disease group was significantly higher than that of the healthy control group (P < 0.05). The results reveal that high fibrinogen concentration is closely correlated to the incurrence, development and prognosis of coronary heart diseases. Compared with other traditional methods, the method of piezoelectric agglutination sensor has some merits such as operation convenience, small size, low cost, quick detecting, good precision and the common reacting agents with paramagnetic particle method.

This paper presents a novel numerical model of the rate-dependent hysteresis. The model has the structure of adaptive linear combiner (ALC) where the states of magnetization of the discretized Preisach plane constitute the input signal sequence of ALC. An adaptive update law with forgetting scheme is designed to update the coefficients of the ALC model to capture rate-dependent behavior of the hysteresis. An input-output behavior of a bimorph type piezo ceramic actuator has been selected as the experimental target to verify accuracy of the proposed hysteresis modeling scheme and the results clarify that the proposed model shows excellent performance for sinusoidal inputs having frequency lower than the resonance of the actuator. Results will be deteriorated for higher frequencies where phase lag might be observed in the corresponding output displacement response of the actuator. However, it has also been shown that appropriate use of FIR filter to the input sequence of ALC largely restores modeling accuracy for those frequencies.

This paper proposes the novel design of a positioning control system of a piezo-ceramic actuator. Piezo-ceramic actuators have been used extensively in many engineering applications which require high precision positioning. However, it is well known that piezo-ceramic actuators exhibit hysteresis in their response to driving input which considerably deteriorates positioning accuracy if no appropriate compensation has been made. Huge efforts have been devoted to the design of control system for positioning control of a piezo-ceramic actuator and a number of different control strategies are proposed for its hysteresis compensation. This paper tackles the problem of the compensation of rate-dependent hysteresis of a piezo-ceramic actuator. Rate-dependence of a hysteresis means that its behavior will vary if the rate or the frequency of the driving signal of the actuator changes. This paper proposes the use of two radial basis function neural networks (RBFNN) to construct a high precision positioning control system of a piezo-ceramic actuator which exhibits rate-dependent hysteresis. The proposed control system takes the form of the internal model control (IMC) system, where one RBFNN is used as the internal model of a piezo-ceramic actuator having rate-dependent hysteresis while the other RBFNN is configured to work as a controller of the system. It is shown in this paper that RBFNN model trained with particle swarm optimization (PSO) algorithm provides good modeling performance for a wide range of driving frequency, and the RBFNN controller is made adaptive with back propagation on-line parameter updater to cope with possible modeling inaccuracy between the actuator and its model. Results of the positioning control experiments indicate that proposed adaptive internal model control system with two RBFNNs shows adequate performance on the compensation of rate-dependent hysteresis to guarantee high precision positioning.

BackgroundGanoderma lucidum (Reishi or Ling Zhi) is one of the most famous Traditional Chinese Medicines and has been widely used in the treatment of various human diseases in Asia countries. It is also a fungus with strong wood degradation ability with potential in bioenergy production. However, genes, pathways and mechanisms of these functions are still unknown.Methodology/principal findingsThe genome of G. lucidum was sequenced and assembled into a 39.9 megabases (Mb) draft genome, which encoded 12,080 protein-coding genes and ∼83% of them were similar to public sequences. We performed comprehensive annotation for G. lucidum genes and made comparisons with genes in other fungi genomes. Genes in the biosynthesis of the main G. lucidum active ingredients, ganoderic acids (GAs), were characterized. Among the GAs synthases, we identified a fusion gene, the N and C terminal of which are homologous to two different enzymes. Moreover, the fusion gene was only found in basidiomycetes. As a white rot fungus with wood degradation ability, abundant carbohydrate-active enzymes and ligninolytic enzymes were identified in the G. lucidum genome and were compared with other fungi.Conclusions/significanceThe genome sequence and well annotation of G. lucidum will provide new insights in function analyses including its medicinal mechanism. The characterization of genes in the triterpene biosynthesis and wood degradation will facilitate bio-engineering research in the production of its active ingredients and bioenergy.

BACKGROUND: Loss of a sensory function is often followed by the hypersensitivity of other modalities in mammals, which secures them well-awareness to environmental changes. Cellular and molecular mechanisms underlying cross-modal sensory plasticity remain to be documented. METHODOLOGY/PRINCIPAL FINDINGS: Multidisciplinary approaches, such as electrophysiology, behavioral task and immunohistochemistry, were used to examine the involvement of specific types of neurons in cross-modal plasticity. We have established a mouse model that olfactory deficit leads to a whisking upregulation, and studied how GABAergic neurons are involved in this cross-modal plasticity. In the meantime of inducing whisker tactile hypersensitivity, the olfactory injury recruits more GABAergic neurons and their fine processes in the barrel cortex, as well as upregulates their capacity of encoding action potentials. The hyperpolarization driven by inhibitory inputs strengthens the encoding ability of their target cells. CONCLUSION/SIGNIFICANCE: The upregulation of GABAergic neurons and the functional enhancement of neuronal networks may play an important role in cross-modal sensory plasticity. This finding provides the clues for developing therapeutic approaches to help sensory recovery and substitution.