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Abstract Proteasome inhibition emerges as a promising strategy for cancer prevention. PNO1, pivotal for colorectal cancer (CRC) progression, is involved in proteasome assembly in Saccharomyces cerevisiae. Hence, we aimed to explore the role of PNO1 in proteasome assembly and its up- and down-streams in CRC. Here, we demonstrated that PNO1 knockdown suppressed CRC cells growth, proteasome activities and assembly, as well as CDKN1B/p27Kip1 (p27) degradation. Moreover, p27 knockdown partially attenuated the inhibition of HCT116 cells growth by PNO1 knockdown. The up-stream studies of PNO1 identified miR-326 as a candidate miRNA directly targeting to CDS-region of PNO1 and its overexpression significantly down-regulated PNO1 protein expression, resulting in suppression of cell growth, decrease of proteasome activities and assembly, as well as increasing the stability of p27 in CRC cells. These findings indicated that miR-326 overexpression can suppress CRC cell growth, acting as an endogenous proteasome inhibitor by targeting PNO1.

Abstract Background Pien Tze Huang (PZH), a traditional Chinese medicine formulation, is recognized for its therapeutic effect on colitis and colorectal cancer. However, its protective role and underlying mechanism in colitis-associated colorectal cancer (CAC) remain to be elucidated. Methods A CAC mouse model was established using AOM/DSS. Twenty mice were randomly divided into four groups (n = 5/group): Control, PZH, AOM/DSS, and AOM/DSS + PZH groups. Mice in the PZH and AOM/DSS + PZH group were orally administered PZH (250 mg/kg/d) from the first day of experiment, while the control and AOM/DSS group received an equivalent volume of distilled water. Parameters such as body weight, disease activity index (DAI), colon weight, colon length, colon histomorphology, intestinal tumor formation, serum concentrations of pro-inflammatory cytokines, proliferation and apoptosis in colon tissue were assessed. RNA sequencing was employed to identify the differentially expressed transcripts (DETs) in colonic tissues and related signaling pathways. Wnt/β-Catenin Pathway-Related genes in colon tissue were detected by QPCR and immunohistochemistry (IHC). Results PZH significantly attenuated AOM/DSS-induced weight loss, DAI elevation, colonic weight gain, colon shortening, histological damage, and intestinal tumor formation in mice. PZH also notably decreased serum concentration of IL-6, IL-1β, and TNF-α. Furthermore, PZH inhibited cell proliferation and promote apoptosis in tumor tissues. RNA-seq and KEGG analysis revealed key pathways influenced by PZH, including Wnt/β-catenin signaling pathway. IHC staining confirmed that PZH suppressed the expression of β-catenin, cyclin D1 and c-Myc in colonic tissues. Conclusions PZH ameliorates AOM/DSS-induced CAC in mice by suppressing the activation of Wnt/β-catenin signaling pathway.

Abstract Background The study evaluated the performance of the Mindray N-terminal pro-B-type natriuretic peptide (NT-proBNP) in a healthy population in China, focusing on creating a reference range for future clinical applications adjusted according to different demographics. Methods The study measured NT-proBNP in 2277 healthy individuals. We analyzed age and sex-stratified data, performed precision, accuracy, linearitcvy, and detection limit studies, and evaluated method comparison and consistency between Roche and Mindray assays on 724 serum samples. We used Excel 2010, Medcalc, and GraphPad Prism 9. Results In males, the 97.5th centile NT-proBNP concentration at age

ObjectiveOur study was conducted to explore the link between oxidative balance score (OBS) and rheumatoid arthritis (RA).MethodsA total of 21,415 participants were included in our research from five cycles (2011–2012, 2013–2014, 2015–2016, 2017–2018, and 2017–2020) of the National Health and Nutrition Examination Survey (NHANES). Moreover, 20 elements related to diet as well as lifestyle were combined to calculate OBS. The relationship between OBS and RA was assessed by employing multivariable regression analysis, and further exploration was carried out through subgroup analysis, restricted cubic spline analysis, and sensitivity analysis. Multiple covariates were selected to adjust the model for more robust results.ResultsIn our cross-sectional study, a higher OBS has a protective effect on the development of RA (OR = 0.98, 95% CI: 0.97 to 0.99). In contrast to individuals aged ≥60, the result is more prominent in the population aged 20–60 (OR = 0.97, 95% CI: 0.96 to 0.98). Marital status appears to introduce interference in the relationship between OBS and RA, and unmarried individuals exhibited different outcomes (OR = 1.02, 95% CI: 0.99 to 1.04) compared to others. The positive influence of OBS was more evident in patients with chronic kidney disease and cardiovascular disease, while it was stronger in individuals without diabetes and liver disease.ConclusionA higher OBS correlates with a reduced odd of RA. Further studies are needed to shoot more sights on improving dietary habits and lifestyles to gain proper OBS and explore whether OBS can be one of the measurements utilized to measure the risk of RA.

Highland barley is the main food of Tibetan people, which is rich in starch, fat, protein, vitamins, dietary fiber, β-glucan, polyphenol, amino acid, etc. Highland barley has widely healthy functions such as hypolipidemic, hypoglycemic, cholesterol lowing, antioxidation, and gastrointestinal regulation, etc. Due to the special characteristics including bran thickness, taste bad, and indigestible of the crude material, as a result that highland barley could be edible after processing. Superheated steam, baking, frying, steaming, boiling, and other hot processing methods as well as germination are common processing methods for highland barley. Different processing steps of highland barley would have a certain impact on the contents and structures of its nutritional compositions, and the biological activities such as hypolipidemic and hypoglycemic are also varied. Therefore, this paper reviews the effects of different processing methods on nutrients and bioactivities of highland barley in recent 10 years, and its variable regular and influencing factors are also discussed. Finally, the development of functional food products of highland barley is prospected. It has certain reference value for the in-depth digging, quality improvement, technological innovation and new product development of highland barley.

ABSTRACT Tail fat deposition of Altay sheep not only increased the cost of feeding but also reduced the economic value of meat. Currently, because artificial tail removal and gene modification methods cannot solve this problem, it is maybe to consider reducing tail fat deposition from the path of intestinal microbiota and metabolite. We measured body weight and tail fat weight, collected the serum for hormone detection by enzyme-linked immunosorbent assay, and collected colon contents to 16S rRNA sequence and liquid chromotography with mass spectrometry detection to obtain colon microbiota and metabolite information, from 12 3-month-old and 6-month-old Altay sheep. Subsequently, we analyzed the correlation between colon microbiota and tail fat weight, hormones, and metabolites, respectively. We identified that the tail fat deposition of Altay sheep increased significantly with the increase of age and body weight, and the main microbiota that changed were Verrucomicrobia, Cyanobacteria, Akkermansia, Bacteroides, Phocaeicola, Escherichia-Shigella, and Clostridium_sensu_stricto_1. The results indicated that the diversities of metabolites in the colon contents of 3-months old and 6-months old were mainly reflected in phosphocholine (PC) and phosphatidylethanolamine (PE) in the lipid metabolism pathway. The correlations analyzed showed that Verrucomicrobia, Chlamydiae, Akkermansia, Ruminococcaceae_UCG-005, Bacteroides, and Phocaeicola were negatively correlated with tail fat deposition. Verrucomicrobia, Akkermansia, and Bacteroides were negatively correlated with growth hormone (GH). Verrucomicrobia was positively correlated with L-a-lysophosphatidylserine and PE(18:1(9Z)/0:0). Our results showed that tail fat deposition of Altay sheep was probably correlated with the abundance of Verrucomicrobia, Akkermansia, Bacteroides of colon microbiota, PC, PE of metabolites, and GH of serum.IMPORTANCEExcessive tail fat deposition of Altay sheep caused great economic losses, and the current research results could not solve this problem well. Now, our research speculates that the tail fat deposition of Aletay sheep may be related to the abundance of Verrucomicrobia, Akkermansia, Bacteroides, metabolites phosphocholine, phosphatidylethanolamine, and growth hormone of serum. Further investigation of the interaction mechanism between these microbiota or metabolites and tail fat deposition is helpful in reducing tail fat deposition of Altay sheep and increasing the economic benefits of breeding farms.

To handle the low frequency oscillations of the three-phase four-wire inverter grid-connected system caused by small phase-locked range, slow locking speed and large steady-state error of the traditional phase-locked loop, an improved phase-locked loop is proposed to suppress low frequency oscillation. Firstly, the paper established a sequence impedance model of three-phase four-wire inverter, and analyzed the impact of the phase-locked loop on low frequency stability in a weak power grid and the mechanism of low frequency oscillations. Secondly, based on the cross-coupling method of the Complex Filter Matrix (CFM)-Orthogonal Signal Generator (OSG), the paper combined a first-order complex filter with a positive-negative sequence voltage component relationship matrix to form an improved phase-locked loop. The improved phase-locked loop is used to reshape the positive sequence, negative sequence and zero sequence impedance of the inverter, which not only increased the impedance amplitude of the inverter system, but also realized low frequency oscillations suppression. Finally, applying the simulation and experimentation, the paper verified the validity of the established sequence impedance and the effectiveness of the proposed improved phase-locked loop to suppress low frequency oscillation in the three-phase four-wire weak power grid.

Abstract Objective Investigating the utility of serum exosomal markers CA125, HE4, and C5a, both individually and in combination, for distinguishing between benign and malignant ovarian tumors. Methods In this study, we selected a total of 234 patients diagnosed with ovarian tumors, including 34 with malignant tumors, 10 with borderline ovarian tumors, and 190 with benign tumors. This study conducted comparisons of exosomal levels of CA125, HE4, and C5a among distinct groups, as well as making comparisons between serum and exosomal levels of CA125 and HE4. Furthermore, the diagnostic performance was assessed through Receiver Operating Characteristic (ROC) curve analysis. The Area Under the Curve (AUC) was computed, and a comparative evaluation of sensitivity and specificity was conducted to ascertain their effectiveness in determining the nature of ovarian tumors across different markers. Results Serum CA125 and HE4 levels, the ROMA index, exosomal CA125, HE4, C5a levels, and their combined applied value (OCS value) were notably elevated in the ovarian non-benign tumor group compared to the benign tumor group, with statistical significance (P < 0.05). Exosomal and serum levels of CA125 and HE4 exhibited a positive correlation, with concentrations of these markers in serum surpassing those in exosomes. The combined OCS (AUC = 0.871) for CA125, HE4, and C5a in exosomes demonstrated superior sensitivity (0.773) and specificity (0.932) compared to serum tumor markers (CA125, HE4) and the ROMA index. The tumor stage represents an autonomous risk factor influencing the prognosis of individuals with ovarian malignancies. Conclusion The stage of ovarian malignancy is an independent risk factor for its prognosis. The combination of exosomal CA125, HE4 and C5a has a higher clinical value for the identification of the nature of ovarian tumours.

Abstract Background Although the majority of Ghanaian women receive antenatal care (ANC), many exhibit low health literacy by misinterpreting and incorrectly operationalizing ANC messages, leading to poor maternal and newborn health outcomes. Prior research in low-resource settings has found group antenatal care (G-ANC) feasible for women and providers. This study aims to determine the effect of G-ANC on increasing maternal health literacy. We hypothesized that pregnant women randomized into G-ANC would exhibit a greater increase in maternal health literacy than women in routine, individual ANC. Methods A 5-year cluster randomized controlled trial was conducted in 14 rural and peri-urban health facilities in the Eastern Region of Ghana. Facilities were paired based on patient volume and average gestational age at ANC enrollment and then randomized into intervention (G-ANC) vs. control (routine, individual ANC); 1761 pregnant women were recruited. Data collection occurred at baseline (T0) and post-birth (T2) using the Maternal Health Literacy scale, a 12-item composite scale to assess maternal health literacy. Logistic regression compared changes in health literacy from T0 to T2. Results Overall, women in both the intervention and control groups improved their health literacy scores over time (p

The extra-interfacial manifestations induced by the waveguide resonance properties of monolayer colloidal crystals (MCCs) have been well discovered by symmetrically probing their reflectance spectra. To clearly analyze the origin of the resonance peaks in the spectra obtained by reflection probing, experimental and calculated values were compared and the results for monolayers with different arrangement structures were compared. The different contributions to the resonance modes by different light bands entering the MCC were elucidated. In addition, the experimental results visualize that changing the incident angle, lattice and polarization can effectively modulate the wavelength position and intensity of the characteristic peaks induced by the resonance of the monolayer waveguide.

Slow transit constipation (STC) is a common and debilitating condition characterized by delayed colonic transit and difficulty in fecal expulsion, significantly impacting patients’ physical and mental wellbeing as well as their overall quality of life. This study investigates the therapeutic potential of Liqi Tongbian Decoction (LTD) in the treatment of STC, especially in cases involving the context of Qi stagnation, through a multifaceted approach involving the modulation of intestinal flora and short-chain fatty acids (SCFAs). We employed a rat model of STC with Qi Stagnation Pattern, established using the “loperamide + tail-clamping provocation method,” to explore the effects of LTD on fecal characteristics, intestinal motility, and colonic pathology. Importantly, LTD exhibited the ability to increase the richness, diversity, and homogeneity of intestinal flora while also modulating the composition of microorganisms. It significantly increased the production of SCFAs, especially butyric acid. Moreover, LTD exerted a substantial influence on the synthesis of serotonin (5-HT) by modulating the expression of tryptophan hydroxylase (TPH) and interacting with the 5-HT4 receptor (5-HT4R), resulting in enhanced colonic motility. Correlation analyses revealed a positive correlation between certain bacterial genera, such as Lachnospiraceae_NK4A136 spp. and Clostridiales spp. and the concentrations of butyric acid and 5-HT. These results suggest a mechanistic link between microbiome composition, SCFAs production, and 5-HT synthesis. These findings highlight the potential of LTD to alleviate STC by facilitating a beneficial interplay among intestinal flora, SCFAs production, and 5-HT-mediated colonic motility, providing novel insights into the management of STC with Qi Stagnation Pattern.

Abstract The precise modification or functionalization of the protein C-terminus is essential but full of challenges. Herein, a chemical approach to modify the C-terminus is developed by fusing a cysteine protease domain on the C-terminus of the protein of interest, which could achieve the non-enzymatic C-terminal functionalization by InsP6-triggered cysteine protease domain self-cleavage. This method demonstrates a highly efficient way to achieve protein C-terminal functionalization and is compatible with a wide range of amine-containing molecules and proteins. Additionally, a reversible C-terminal de-functionalization is found by incubating the C-terminal modified proteins with cysteine protease domain and InsP6, providing a tool for protein functionalization and de-functionalization. Last, various applications of protein C-terminal functionalization are provided in this work, as demonstrated by the site-specific assembly of nanobody drug conjugates, the construction of a bifunctional antibody, the C-terminal fluorescent labeling, and the C-terminal transpeptidation and glycosylation.

To clarify the effects of different frying temperatures and grain colors on volatile organic compounds (VOCs) in highland barley (HB) tsampa flour, gas chromatography-ion mobility spectrometry (GC-IMS) was used to analyze the VOCs in two types of HB with two colors, Goumangzi and Kunlun-15. The VOCs were analyzed at different frying temperatures (160, 180, 200, 220 and 240 ℃). The results showed that a total of 62 compounds was detected, among which 44 organic compounds could be accurately identified, including 19 aldehydes, 10 alcohols, 5 ketones, 5 esters, 4 pyrazines and 1 furan. Frying had a significant effect on the composition of VOCs in tsampa flour, with the increase of frying temperature, the total amount of alcohol VOCs tended to decrease gradually, while aldehydes, ketones, esters, pyrazines and furans VOCs tended to increase. Pyrazines, aldehydes and ketones were the characteristic and main flavor substances of HB tsampa flour, and frying at higher temperature (220, 240 ℃) was favorable to their production. The variation of VOCs with frying temperature was more significant in WHB, except for furan VOCs, the relative changes of other compounds were higher than those in BHB. The principal component analysis showed that there were significant differences in the flavor of BHB and WHB tsampa flour, which could be classified into two different flavor types. This study was expected to provide a theoretical basis for the development of technical specifications for the production of highland barley tsampa flour.

Electrohydrodynamic processing technology, as an innovative non-thermal processing technology, is gradually applied in food science and technology field with the assistance of future food industry development. This article reviews principle, classification, accessible factors, biological materials and application, summarizes and discusses future developments in food field of electrohydrodynamic processing technology. Electrohydrodynamic processing technology consistes of electrospinning and electrospraying techniques, and could produce complex function micron/nano fibrosome or particle, which may be adopted in microencapsulation of food functional components, immobilized enzyme, biosensor, active food packaging, assistant technique of food 3D printing developments. Future work should be carried out in increasing yield of fibrosome/particle, decreasing solvent residual toxicity and integrating 3D printing for future food industry development.

This study investigated the improvement effects of beta-glucanase (BGS) on the specific volume, texture, and volatile flavor compounds of bread prepared with 30% and 50% whole highland barley flour. The changes in specific volume, texture, crumb structure and color, and sensory while the BGS levels ranging from 0.02% to 0.10% were analyzed. The volatile flavor compounds in highland barley bread were tested by gas chromatography-ion mobility spectrometry. The results showed that the specific volume, elasticity, and gas cell numbers of highland barley bread all improved significantly (P

This study evaluated the effects of four highland barley proteins (HBPs), namely, albumin, globulin, gliadin and glutenin, on the short-term retrogradation of highland barley starch (HBS). The findings reveal that HBPs could reduce the viscosity, storage modulus and hardness of HBS, with albumin and globulin showing more prominent effects. Furthermore, with the addition of HBPs, the loss tangent (tan δ) of HBS loss increased from 0.07 to 0.10, and the enthalpy of gelatinization decreased from 8.33 to 7.23. The degree of retrogradation (DR%) of HBS was 5.57%, and the DR% decreased by 26.65%, 38.78%, 11.67% and 20.29% with the addition of albumin, globulin, gliadin and glutenin, respectively. Moreover, the relative crystallinity (RC) and the double helix structures were inhibited with the HBPs’ incorporation. Meanwhile, the HBPs also could inhibit water migration and improve the structure of HBS gels. In summary, HBPs could inhibit the retrogradation behavior of HBS, which provides new theoretical insights for the production studies of highland barley foods.

This research was performed to investigate the impacts of different processing methods on phenols in hulless barley for the purpose of achieving furthest retention of the antioxidant and hypoglycemic bioactives. Using Hainan Kunlun 17 hulless barley as experimental material, the hulless barley grains were thermally processed by six different processing methods, including steaming, boiling, frying, microwave, baking and air fryer, and the contents of free polyphenols, bound polyphenols, free flavonoids and bound flavonoids, as well as the changes of antioxidant and hypoglycaemic activities in hulless barley before and after processing were analysed. The results showed that the contents of polyphenols and flavonoids in hulless barley were varied after preparing by different processing methods. Compared with unprocessed hulless barley, the contents of free polyphenols and free flavonoids from other processing methods were significantly decreased (P

In this study, the effects of inulin, as a fat substitute, on the quality of mung bean protein low-fat plant yogurt were investigated. The mung bean protein yogurt with 3% of sunflower oil was taken as a high-fat yogurt control, the fat-replacement effect of inulin was evaluated by analyzing the effects of different concentrations of inulin (2%, 4% and 6%) on the viscoelasticity, texture, water holding capacity, microstructure and sensory quality of mung bean protein low-fat yogurt (with 1% of sunflower oil). The results indicated that compared with the mung bean protein high-fat yogurt, the viscoelasticity, hardness, chewiness, water holding capacity, and sensory quality of mung bean protein low-fat plant yogurt with 2% of inulin were equal to those of mung bean protein high-fat yogurt (P>0.05), with a uniform and dense protein network structure. The hardness and chewiness of mung bean protein low-fat yogurt with 4% inulin were significantly improved by 21.56% and 32.34% (P

Sonic vibration sampling technology is widely used due to its high sample fidelity, low disturbance to the stratum and environmental protection. The influence of the diameter variation of sonic drill string caused by the sampling tube on the axial vibration of the system is still unclear, which restricts the improvement of coring efficiency. In this study, an axial vibration model of a sonic drilling string with a sampling tool is established, which takes into account the section variation. Adopting numerical simulations, the influence of the drill string on the vibration characteristics of the system, the relationship between the excitation and the amplitude of the sampling bit, and the effect of the cross-sectional area on the bearing capacity of the drill string with the sampling tube are obtained. With the longer the sampling tube and the thicker the wall thickness, the lower the inherent frequency and the higher the bearing capacity. The results show that the discontinuity of the drill string section caused by the sampling tube inevitably affects the natural frequency and response of the drill string system. The model can provide a theoretical basis for the research of sonic vibration sampling engineering. Properly balancing parameters can improve drilling and sampling performance.

Human‐like and creature‐like systems are one of the most representative imaginary blueprints of future robots. To fulfill this blueprint, the development of high‐performance actuators across different length scales is indispensable. Owing to their mechanical compliance and conformability to curvy surfaces of living organisms, flexible actuators have emerged as an essential direction of next‐generation actuators. This review focuses on thin‐film‐shaped flexible actuators (TFFAs), a rising family of flexible actuators, aiming to provide an overview of the state‐of‐art status in this exciting direction. The designs, manufacturing, and mechanisms of various TFFAs are summarized, according to their key composing materials/mechanisms, including, for example, nanomaterials, liquid crystal elastomers, shape memory polymers/alloys, hydrogels, biohybrids, and other mechanisms/materials. The representative applications of TFFAs are introduced, ranging from biomedical uses, robots for environment explorations, to haptic interfaces and reconfigurable electronics. Finally, the grand challenges and open opportunities are discussed in detail.

Background: Qing Hua Chang Yin (QHCY) is a famous formula of traditional Chinese medicine (TCM) and has been proven to have protective effect on ulcerative colitis. However, its protective effect and potential therapeutic mechanisms in chronic colitis remain unclear. The purpose of this study is to explore the effects and underlying mechanisms of QHCY on dextran sulfate sodium (DSS)-induced chronic colitis mice model.Methods: The chronic colitis model was established by administration of 2% DSS for three consecutive cycles of 7 days with two intervals of 14 days for recovery by drinking water. The experiment lasted 49 days. The DSS + QHCY group received QHCY administration by oral gavage at doses of 1.6 g/kg/d, DSS + Mesalazine group was administrated Mesalazine by oral gavage at doses of 0.2 g/kg/d. The control and DSS group were given equal volume of distilled water. The body weight, stool consistency and blood in stool were monitored every 2 days. The disease activity index (DAI) was calculated. The colon length was measured after the mice were sacrificed. The histomorphology of colonic tissues was checked by the HE and PAS staining. Immunohistochemistry was performed to detect the expressions of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6), tight junction proteins (ZO-1, occludin) and Mucin2 (MUC2). 16S rRNA sequencing analysis was conducted to study the diversity and abundance of gut microbiota changes.Results: QHCY treatment not only significantly attenuated DSS-induced the weight loss, DAI score increase, colon shortening and histological damage in mice, but also decreased the expression of pro-inflammatory cytokines in colonic tissues and increased the expression of ZO-1, occludin, and MUC2. Furthermore, QHCY enhanced the diversity of gut microbes and regulated the structure and composition of intestinal microflora in mice with chronic colitis.Conclusion: QHCY has a therapeutic effect on a murine model of chronic colitis. It can effectively reduce the clinical and pathological manifestations of colitis and prevent alterations in the gut microbiota.

Background: 5-Fluorouracil (5-FU) is one of the most commonly prescribed anticancer agents. However, intestinal mucositis is a well-known adverse event, which limits its therapeutic use. Refined Baohe formula (RBF) is derived from Baohe Pills with a potent gastrointestinal protective effect. However, the effects of RBF on 5-FU-induced intestinal mucositis remain unknown. Thus, this study investigated the effects and mechanism of RBF on 5-FU-induced intestinal mucositis in a CT-26 xenograft mice colorectal cancer (CRC) model. Methods: The composition of the RBF preparation was analyzed by high-pressure liquid chromatography. CT-26 cells bearing mice were intraperitoneally administered 150 mg/kg of 5-FU on day 1 to construct a 5-FU-induced intestinal injury model. Mice in the 5-FU + RBF group were intragastrically administrated with RBF (12.4 g/kg) for 4 days. Tumor volume and weight were determined, body weight and diarrhea scores were monitored, leukocytes were calculated, and hematoxylin-eosin staining, immunohistochemistry, and terminal deoxynucleotidyl transferase dUTP nick end labeling were performed to investigate the therapeutic efficiency and underlying mechanisms of RBF on 5-FU-induced intestinal mucositis mice. Results: RBF didn`t affect the effect of tumor suppression, while attenuated diarrhea associated with 5-FU-induced intestinal mucositis and significantly reduced leucocyte toxicity. Additionally, RBF significantly promoted cell proliferation and inhibited cell apoptosis, and up-regulated CDK4, c-Myc, and B-cell lymphoma-2 expression, while down-regulated Bax expression, as well as enhanced both p-AKT and AKT expression in intestinal crypts of 5-FU-treated mice. Conclusions: RBF attenuated 5-FU-induced intestinal mucositis by inhibiting apoptosis and promoting cell proliferation by modulating the AKT pathway and its downstream effectors in a CT-26 xenograft mouse CRC model.

In order to prevent the oxidative rancidity of highland barley, three common treatment methods of microwave, roasting and superheated steam were used to inactivate the enzyme of black highland barley. Then the changes of microstructure, nutrient composition, phenolic compounds and antioxidant capacity before and after inactivation of enzymes treatment were evaluated when the same enzyme inactivation effect was achieved. The experimental results showed that different methods of inactivating enzyme resulted in different degrees of expansion and browning of highland barley. The color change and equivalent radius of highland barley roasted at 175 ℃ for 20 min was the largest，the equivalent radius of highland barley grain was similar after microwave and superheated steam treatment. By observing the electron microscope of highland barley treated with different methods of inactivating enzyme, it could be found that there were gaps and pores in the cross section of grain, and even large holes in vascular bundles. In addition, total phenols (decreased by 14.71%~20.52%) and total flavonoids (decreased by 11.39%~45.15%) decreased significantly after three treatments, and the content of flavonoids and phenols in highland barley roasted at 150 ℃ for 20 min was the lowest. While the effect of microwave treatment on the content of total phenols was lower than the other two treatments, and the effect of superheated steam treatment on the content of total flavonoids was the least. But DPPH free radical scavenging rate, ABTS+ scavenging rate and antioxidant activity increased except microwave treatment. However, the change trend of antioxidant capacity of highland barley after different enzyme inactivation treatments was not completely consistent with the change trend of total phenol and total flavonoids. Under the treatment conditions of enzyme inactivation rate of 50% and 60%, the antioxidant capacity of highland barley treated with superheated steam was the highest, followed by roasting treatment, and the antioxidant capacity of microwave treatment was the lowest. In summary, it can be concluded that the three treatments can be used to inactivate enzyme and can effectively improve the nutritional quality of highland barley. However, the comprehensive evaluation shows that superheated steam treatment is the best choice among the three treatments.

We set up a general equilibrium model of Chinese wealth management products (WMPs), which are deeply rooted in traditional Chinese commercial banks. According to this model, we proposed two hypotheses, namely, the regulatory arbitrage and information asymmetry hypotheses. We tested the hypotheses by using data on Chinese WMPs during the 2006–2015 period. We found that regulatory arbitrage was the main driver of WMPs’ rapid expansion. The greater the pressure from regulation was, the greater the incentive for commercial banks to issue off-balance sheet WMPs and take risks. When the regulatory standard became strict or loose, the effect of regulatory arbitrage on marginal risk-taking behavior became reinforced or reduced, respectively. We also argue that transparency can moderate drive-up behavior. Some relevant suggestions are provided for solving the problems of overexpansion and risk-taking behavior according to the results.

This study investigated the effect of barley vinegar on constipation by regulating the structure of intestinal microbiota and the level of short-chain fatty acids (SCFAs). BALB/c mice with loperamide-induced constipation were treated with barley vinegar in the intervention. After treatment, constipation-related factors were identified. The effect of barley vinegar on the composition of the intestinal microbiota was evaluated by means of 16S rDNA gene sequencing, and the content of SCFAs in enteral feces was determined via the GC-MS method. Treating constipated mice with barley vinegar accelerated gastrointestinal peristalsis, inhibited the inflammatory response, protected the intestinal barrier, upregulated the production of beneficial intestinal bacteria, and downregulated the production of harmful intestinal bacteria. These therapeutic effects are attributed to reversed gut microbiota dysfunction, which favors the production of intestinal metabolites such as SCFAs. The purgative function of highland barley vinegar may improve the intestinal environment by regulating the balance of intestinal flora and the concentration of SCFAs. In addition, LC-MS metabolomics was used to analyze the effect of barley vinegar on intestinal metabolites in mice with constipation. The results show that the treatment of barley vinegar inhibited the decrease in aspartate, L-threonine, L-serine, L-proline, 3,4-dihydroxymandelic acid, epinephrine, glyceric acid, and 3,4-dihydroxymandelic acid content in intestinal metabolites caused by constipation. 4-2 hydroxy benzene acetic acid and fumaric acid content increased. KEGG pathway analysis showed that digestive system, amino acid and lipid metabolism pathways were important pathways for highland barley vinegar relieving constipation. This study proves that highland barley vinegar mainly regulates lipid metabolism, the digestive system and amino acid metabolism to maintain a steady state, prevent intestinal injury, and improve constipation. In short, this study demonstrates that highland barley vinegar can alleviate constipation in mice and repair colitis damage.

IntroductionExposure to ambient air pollutants is associated with an increased incidence of respiratory diseases such as pneumonia and asthma, especially in younger children. We investigated the relationship between rates of hospitalization of children aged under 5 years for pneumonia and asthma and the concentration of air pollutants in Ningbo between January 1, 2015 and August 29, 2017.MethodsData were obtained from the Ningbo Air Quality Data Real-time Publishing System and the big data platform of the Ningbo Health Information Center. A generalized additive model was established via logarithmic link function and utilized to evaluate the effect of pollutant concentration on lag dimension and perform sensitivity analysis.ResultsA total of 10,301 cases of pneumonia and 115 cases of asthma were identified over the course of this study. Results revealed that PM2.5, PM10, SO2 and NO2 were significantly associated with hospitalization for pneumonia and asthma in children under 5 years of age. For every 10-unit increase in lag03 air pollutant concentration, hospitalization for pneumonia and asthma due to PM2.5, PM10, SO2 and NO2 increased by 2.22% (95%CI: 0.64%, 3.82%), 1.94% (95%CI: 0.85%, 3.04%), 11.21% (95%CI: 4.70%, 18.10%) and 5.42% (95%CI: 3.07%, 7.82%), respectively.DiscussionAdverse effects of air pollutants were found to be more severe in children aged 1 to 5 years and adverse effects due to PM2.5, PM10 and SO2 were found to be more severe in girls. Our findings underscore the need for implementation of effective public health measures to urgently improve air quality and reduce pediatric hospitalizations due to respiratory illness.

Abstract Background Colorectal cancer (CRC) is one of the most highly malignant tumors and has a complicated pathogenesis. A preliminary study identified syntrophin beta 1 (SNTB1) as a potential oncogene in CRC. However, the clinical significance, biological function, and underlying mechanisms of SNTB1 in CRC remain largely unknown. Thus, the present study aimed to investigate the role of SNTB1 in CRC. Methods The expression profile of SNTB1 in CRC samples was evaluated by database analysis, cDNA array, tissue microarray, quantitative real-time PCR (qPCR), and immunohistochemistry. SNTB1 expression in human CRC cells was silenced using short hairpin RNAs (shRNA)/small interfering RNAs (siRNA) and its mRNA and protein levels were assessed by qPCR and/or western blotting. Cell viability, survival, cell cycle, and apoptosis were determined by the CCK-8 assay, colony formation, and flow cytometry assays, respectively. A xenograft nude mouse model of CRC was established to validate the roles of SNTB1 in vivo. Immunohistochemistry and TUNEL staining were used to determine the expression of SNTB1, PCNA, and cell apoptosis in tissue samples. Isobaric tag for relative and absolute quantification (iTRAQ) was used to analyze the differentially expressed proteins after knockdown of SNTB1 in CRC cells. Silence of protein kinase N2 (PKN2) using si-PNK2 was performed for rescue experiments. Results SNTB1 expression was increased in CRC tissues compared with adjacent noncancerous tissues and the increased SNTB1 expression was associated with shorter overall survival of CRC patients. Silencing of SNTB1 suppressed cell viability and survival, induced cell cycle arrest and apoptosis in vitro, and inhibited the growth of CRC cells in vivo. Further elucidation of the regulation of STNB1 on CRC growth by iTRAQ analysis identified 210 up-regulated and 55 down-regulated proteins in CRC cells after SNTB knockdown. A PPI network analysis identified PKN2 as a hub protein and was up-regulated in CRC cells after SNTB1 knockdown. Western-blot analysis further confirmed that SNTB1 knockdown significantly up-regulated PKN2 protein expression in CRC cells and decreased the phosphorylation of both ERK1/2 and AKT. Moreover, rescue experiments indicated that PKN2 knockdown significantly rescued SNTB1 knockdown-mediated decrease in cell viability, survival, and increase of cell cycle arrest at G0/G1 phase and apoptosis of CRC cells. Conclusions These findings indicate that SNTB1 is overexpressed in CRC. Elevated SNTB1 levels are correlated with shorter patient survival. Importantly, SNTB1 promotes tumor growth and progression of CRC, possibly by reducing the expression of PKN2 and activating the ERK and AKT signaling pathway. Our study highlights the potential of SNTB1 as a new prognostic factor and therapeutic target for CRC.

Floral thermogenesis is coupled with odor emission in known thermogenic plants. It is widely accepted that elevation in floral temperature can help release of volatile organic compounds (VOCs). However, no information is available about whether floral thermogenesis is associated with VOC biosynthesis. Here, we used RNA-Sequencing (RNA-Seq) to draw a gene expression atlas of floral thermogenesis in Magnolia denudata and captured an upregulation of Alternative Oxidase (AOX) during floral thermogenesis. Western blot analyses also suggested upregulation of AOX during floral thermogenesis. Moreover, oxygen consumption analyses revealed increased activity of the AOX respiration pathway during floral thermogenesis. Using HPLC analyses, we further found that increased AOX respiration substantially promoted production of citric acid by 1.35 folds, which provided fundamental metabolite skeletons for biosynthesis of VOCs. RNA-Seq also showed upregulation of genes regulating lignin catabolism, which was in agreement with in situ Raman chemical imaging of lignin. Taken together, our results suggest the central role of AOX by coupling heat production and VOC biosynthesis in floral thermogenesis of M. denudata.

Background: In southwest China, especially in Nujiang, lacquer oil from the drupes of Toxicodendron vernicifluum (Stokes) F. A. Barkley, including black lacquer oil (BLO) and white lacquer oil (WLO), is one of the most important edible oils for the local people. Through the field investigation, the locals believe that lacquer oil has benefits for parturient women and for the treatment of “Yuezi” disease. However, studies on bioactivities and the chemical compositions of lacquer oil are limited.Purpose: This study was designed to reveal the mystery of lacquer oil for the treatment of “Yuezi” disease by testing its anti-inflammatory and anti-postpartum depressant activities and related bioactive compounds.Methods: The anti-inflammatory effects of lacquer oil were examined by establishing a lipopolysaccharide (LPS)-induced RAW264.7 cell inflammation model and detecting the level of pro-inflammatory factors such as NO, IL-6 and TNF-α. The antidepressant effects of lacquer oil were studied by building a mouse model of postpartum depression (PPD), and the animal behavior changes of PPD model mice were assessed by open field test (OFT), forced swimming test (FST) and tail suspension test (TST). The chemical profiles of BLO and WLO were detected by lipidomic and the untargeted metabolomic research methods based on UPLC-MS/MS.Results: The results showed that BLO and WLO exerted anti-inflammatory effects by reducing the release of pro-inflammatory factors and BLO had better anti-inflammatory effects than WLO. While only BLO had anti-postpartum depressant activities, as evidenced by the significantly reduced the immobility time of the BLO-treated PPD mice in TST and FST compared to the PPD model mice. The comparative lipidomic analysis revealed that BLO contained high levels of Diacylglycerols (DAG) and Diacylglyceryl trimethylhomoserines (DGTS) but low level of ceramides (Cer), sphingomyelines (SM), phosphatidylcholines (PC) and phosphatidylethanolamines (PE) compared with WLO. Metabolomics analysis showed that there were 57 chemical markers between BLO and WLO, of which 17 potential biomarkers have been declared to possess anti-inflammatory and/or antidepressant activities.Conclusion: The findings of this study furnish a scientific support for the traditional uses of lacquer oil for the treatment of “Yuezi” disease from anti-inflammation and anti-postpartum depression perspective.

This study investigated the effect of oat β-glucan as a fat substitute on the structure formation, texture, and sensory properties of pea protein yogurt. The results showed that the incorporation of 0.5% β-glucan significantly accelerated the lactic acid bacteria-induced fermentation, with the time for reaching the target pH of 4.6 shortened from 3.5 h to 3 h (p < 0.05); increased the plastic module (G′) from 693 Pa to 764 Pa when fermenting 3 h (p < 0.05); and enhanced the water-holding capacity from 77.29% to 82.15% (p < 0.05). The identification of volatile organic compounds (VOCs) in low-fat pea protein yogurt by GC-IMS revealed a significant decrease in aldehydes and a significant increase in alcohols, ketones and acids in the pea yogurt after fermentation (p < 0.05). Among them, the levels of acetic acid, acetone, 2,3-butanedione, 3-hydroxy-2-butanone, and ethyl acetate all significantly increased with the addition of oat β-glucan (p < 0.05), thereby providing prominent fruity, sweet, and creamy flavors, respectively. Combined with the results of sensory analysis, the quality characteristics of pea protein yogurt with 1% oil by adding 1% oat β-glucan were comparable to the control sample with 3% oil. Therefore, oat β-glucan has a good potential for fat replacement in pea protein yogurt.

Abstract Objectives For patients presenting with adnexal mass, it is important to correctly distinguish whether the mass is benign or malignant for the purpose of precise and timely referral and implication of correct line of management. The objective of this study was to evaluate the performance of Risk of malignancy Indexes (RMI) 1–4, Human Epididymis Protein 4 (HE4) and Risk of Malignancy Algorithm (ROMA) in differentiating the adnexal mass into benign and malignant. Methods A retrospective study using 155 patients diagnosed with adnexal mass between January 2014 to December 2014 in The First Affiliated Hospital of Zhengzhou University was conducted. The patient records were assessed for age, menopausal status, serum CA125 and HE4 levels, ultrasound characteristics of the pelvic mass and the final pathological diagnosis of the mass. RMI1, RMI2, RMI3, RMI4, ROMA were calculated for each patient and the sensitivity, specificity and the Receiver Operating Characteristics (ROC) curves were determined for each test to evaluate their performance. Results Among 155 patients with adnexal masses meeting inclusion criteria, 120 (77.4%) were benign, 8 (5.2%) borderline and 27 (17.4%) were malignant. RMI2 and RMI4 had the highest sensitivity (66.7%) while HE4 had the highest specificity (96.9%).Although ROMA had the highest area under the curve (AUC) of 0.886 it was not found to be statistically superior to the other tests. For epithelial ovarian cancers, ROMA (80%), HE4 (96.9%) and RMI 4 (0.868) had the highest sensitivity, specificity and AUC respectively however, the AUC characteristics were not statistically significant between any groups. Compared to the postmenopausal group (sensitivity 72.2–77.8%) all the tests showed lower sensitivity (42.9%) for the premenopausal group of patients. Conclusions RMI 1–4, ROMA and HE4 were all found to be useful for differentiating benign/borderline adnexal masses from malignant ones for deciding optimal therapy, however no test was found to be significantly better than the other. None were able to differentiate between benign and borderline tumors. All of the tests demonstrated increased sensitivity when borderline tumors were considered low-risk, and when only epithelial ovarian cancers were considered.

We assessed the role of the protein-coding gene chaperonin-containing TCP1 subunit 6A (CCT6A) in osteosarcoma, as this is currently unknown. Using data from the R2 online genomic analysis and visualization application, we found that CCT6A messenger ribonucleic acid (RNA) expression is increased in osteosarcoma tissue and cells. Transfection of CCT6A small interfering RNA into cultured osteosarcoma cells revealed that CCT6A knockdown attenuates cell growth, cell viability, cell survival, and induced apoptosis and cell cycle progression at the G0/G1 phases. Moreover, CCT6A knockdown downregulated phospho-protein kinase B (p-Akt), cyclinD1 and B-cell lymphoma-2, whereas upregulated Bcl-2-associated X-protein expression. Thus, CCT6A knockdown inhibits cell proliferation, induces cell apoptosis, and suppresses the Akt pathway.

This paper presents a new method of intelligent control for vehicle suspension. First, the suspension system is modeled with all the details, and then based on the obtained model, the sliding mode control is designed for it. The controller parameters and coefficients are calculated and updated by a type-2 fuzzy system. The chattering phenomenon is eliminated with a unique technique. In order to evaluate the performance of the proposed control system, two-model uncertainty of the road is applied. Simulations have been performed for both active and passive modes. The simulation results show the high efficiency of the proposed control system.

Background: HAUS6 participates in microtubule-dependent microtubule amplification, but its role in malignancies including colorectal cancer (CRC) has not been explored. We therefore assessed the potential oncogenic activities of HAUS6 in CRC.Results: HAUS6 mRNA and protein expression is higher in CRC tissues, and high HAUS6 expression is correlated with shorter overall survival in CRC patients. HAUS6 knockdown in CRC cell lines suppressed cell growth in vitro and in vivo by inhibiting cell viability, survival and arresting cell cycle progression at G0/G1, while HAUS6 over-expression increased cell viability. We showed that these effects are dependent on activation of the p53/p21 signalling pathway by reducing p53 and p21 degradation. Moreover, combination of HAUS6 knockdown and 5-FU treatment further enhanced the suppression of cell proliferation of CRC cells by increasing activation of the p53/p21 pathway.Conclusion: Our study highlights a potential oncogenic role for HAUS6 in CRC. Targeting HAUS6 may be a promising novel prognostic marker and chemotherapeutic target for treating CRC patients.

Objectives: To investigate the effects of swimming on cancer induced muscle wasting and explore its underlying mechanism in CT-26 bearing mice.Methods: BALB/c mice (n = 16) injected with CT-26 cells were divided into two groups, including Tumor group (n = 8) and Swimming group (n = 8). Another 8 un-injected mice were set as Control group. Mice in Swimming group were subjected to physical training for swimming twice per day for 30 min intervals and 6 days per week for a total of 4 weeks. The tumor volume was monitored every 3 days and tumor weight was measured at the end of experiment. The changes of muscle function, pathological and cell apoptosis of quadriceps muscles were further assessed, and its underlying mechanisms were further explored using multiple biological technologies.Results: Swimming obviously alleviated tumor volume and weight in CT-26 bearing mice. Moreover, swimming attenuated the decrease of muscle tension, autonomic activities, and increase of muscle atrophy, pathological ultrastructure, as well as cell apoptosis of quadriceps muscles in CT-26 bearing mice. Furthermore, swimming significantly down-regulated the protein expression of NF-κB, p-NF-κB, TNF-α, IL-1β, IL-6 and Bax, while up-regulated the expression of Bcl-2. Further differential expressed metabolites (DEMs) analysis identified a total of 76 (in anion mode) and 330 (in cationic mode) DEMs in quadriceps muscles of CT-26 bearing mice after swimming, including taurochenodeoxycholic acid, taurocholic acid, ascorbic acid and eicosapentaenoic acid.Conclusion: Swimming attenuates tumor growth and muscle wasting, and by suppressing the activation of NF-κB signaling pathway mediated inflammation, reducing the level of Bax medicated cell apoptosis, as well as modulating multiple metabolites might be the importantly underlying mechanisms.

As an essential trace element in the human body, selenium (Se) has various physiological activities, such as antioxidant and anticancer activity. Selenium-enriched proteins/peptides (SePs/SePPs) are the primary forms of Se in plants and animals, and they are the vital carriers of its physiological activities. On the basis of current research, this review systematically describes the extraction methods (aqueous, alkaline, enzymatic, auxiliary, etc.) and detection methods (HPLC–MS/MS, GC–ICP-MS, etc.) for SePs/SePPs in plants. Their bioavailability and bioactivity, and the effect of processing are also included. Our review provides a comprehensive understanding and theoretical guidance for the utilization of selenium-enriched proteins/peptides.

Sonic drilling technology uses the longitudinal vibration of a drill string to realize fast and effective drilling. By setting the top and bottom boundary conditions of the drill string during drilling, a dynamic model of flexible sonic string percussive drilling is established in this article. At a certain drilling depth, with the excitation frequencies as the control parameters, the maximum impact force and rock breaking energy utilization rate are used to evaluate the rock breaking capability of the sonic drilling system under the linear bit–rock model. A surface diagram of the maximum breaking force reached within the working frequencies and at varying drilling depths is obtained. The curve graph of the rock breaking energy utilization rate varying with drilling depth under the first six orders of resonance is also calculated. Analysing the influence of changing drilling parameters on the rock breaking capability of sonic drilling systems can provide theoretical guidance for the actual drilling process.

Summary: Plant proteins exert effects of reducing cardio-cerebrovascular disease-related mortality partly via cholesterol-lowering, which was associated with gut microbiota. Here, we verify that there are significant differences in cholesterol levels among hamsters consuming different proteins. The decisive roles of gut microbiota in regulating host cholesterol are illustrated by the fact that the difference in serum cholesterol levels between hamsters feeding with pea protein and pork protein disappeared when treated with antibiotics. The results of cross-over intervention of pea and pork protein show that serum cholesterol levels are reversed with dietary exchange. The corresponding changes in microbiota suggest that Muribaculaceae are responsible for the inhibitory effect of pea protein on serum cholesterol level, whereas the opposite effect of pork protein is due to Erysipelotrichaceae. Moreover, pea protein supplement alters cecal metabolites including arginine/histidine pathway, primary bile acid biosynthesis, short-chain fatty acids, and other lipid-like molecules involved in cholesterol metabolism.

The purpose of this study was to compare the gelatinization and retrogradation properties of highland barley starch (HBS) using different extraction methods. We obtained HBS by three methods, including alkali extraction (A-HBS), ultrasound extraction (U-HBS) and enzyme extraction (E-HBS). An investigation was carried out using a rapid viscosity analyzer (RVA), texture profile analysis (TPA), differential scanning calorimetry (DSC), X-ray diffraction (XRD) and Fourier-transform infrared spectrometry (FTIR). It is shown that the different extraction methods did not change the crystalline type of HBS. E-HBS had the lowest damaged starch content and highest relative crystallinity value (p < 0.05). Meanwhile, A-HBS had the highest peak viscosity, indicating the best water absorption (p < 0.05). Moreover, E-HBS had not only higher G′ and G″ values, but also the highest gel hardness value, reflecting its strong gel structure (p < 0.05). These results confirmed that E-HBS provided better pasting stability and rheological properties, while U-HBS provides benefits of reducing starch retrogradation.

NUFIP1 is an RNA-binding protein that interacts with fragile X mental retardation protein (FMRP) in the messenger ribonucleoprotein particle (mRNP). We previously showed that NUFIP1 was upregulated in colorectal cancer (CRC), but how the protein may contribute to the disease and patient prognosis is unknown. Here we combine database analysis, microarray, quantitative PCR, and immunohistochemistry of patients’ samples to confirm our previous findings on NUFIP1 overexpression in CRC, and to reveal that increased expression of NUFIP1 in CRC tissues correlated with worse overall, recurrence-free, event-free and disease-free survival in patients, as well as with more advanced CRC clinicopathological stage. Loss of function analysis demonstrated that NUFIP1 knockdown suppressed cell growth in vitro and in vivo, inhibited cell viability and survival, and induced cell cycle arrest and apoptosis in vitro, as well as up-regulated Bax and down-regulated Bcl-2 protein expression. In addition, as a natural anticancer triterpene from various fruits and vegetables, ursolic acid (UA) treatment suppressed cell proliferation, down-regulated NUFIP1 protein expression, and further enhanced the effects of NUFIP1 knockdown in CRC cells in vitro. NUFIP1 knockdown up-regulated the expression of 136 proteins, down-regulated the expression of 41 proteins, and enriched multiple signaling pathways including the senescence-associated heterochromatin foci (SAHF) pathway. Furthermore, NUFIP1 knockdown enhanced the expression of senescence-associated-β-galactosidase (SA-β-gal), the SAHF markers HP1γ and trimethylation (H3k9me3), and the senescence-related protein HMGA2, as well as both p53 and its downstream p21 protein expression. Our findings suggest that NUFIP1 is overexpressed in CRC and correlates with disease progression and poor patient survival. NUFIP1 may exert oncogenic effects partly by altering senescence. UA may show potential to treat CRC by down-regulating NUFIP1.

Objective: As a well-known traditional Chinese medicine formula prescribed by academician Ke-ji Chen, Qingda granule (QDG) lowered the blood pressure of spontaneously hypertensive rats and attenuated hypertensive cardiac remodeling and inflammation. However, its functional role and underlying mechanisms on hypertensive vascular function remain largely unclear. This study aims to assess the effects of QDG treatment on Angiotensin II- (AngII-) induced hypertension and vascular function and explore its underlying mechanisms both in vitro and in vivo.Methods: In an in vivo study, 25 male C57BL/6 mice were randomly divided into five groups, including Control, AngII, AngII + QDG-L, AngII + QDG-M, and AngII + QDG-H groups (n = 5 for each group). Mice in AngII and AngII + QDG-L/-M/-H groups were infused with AngII (500 ng/kg/min), while in the Control group, they were infused with saline. Mice in AngII + QDG were intragastrically given different concentrations of QDG (0.5725, 1.145, or 2.29 g/kg/day), while in Control and AngII groups, they were intragastrically given equal volumes of double distilled water for 2 weeks. Blood pressure was determined at 0, 1, and 2 weeks of treatment. Ultrasound was used to detect the pulse wave velocity (PWV) and HE staining to detect the pathological change of the abdominal aorta. RNA sequencing (RNA-seq) was performed to identify the differentially expressed transcripts (DETs) and related signaling pathways. IHC was used to detect the expression of p-ERK in the abdominal aorta. Primary isolated rat vascular smooth muscle cells (VSMCs) were used to assess the cellular Ca2+ release and activation of the ERK pathway by confocal microscope and western blotting analysis, respectively.Results: QDG treatment significantly alleviated the elevated blood pressure, the PWV, and the thickness of the abdominal aorta in AngII-induced hypertensive mice. RNA-seq and KEGG analyses identified 1,505 DETs and multiple enriched pathways (including vascular contraction and calcium signaling pathway) after QDG treatment. Furthermore, confocal microscope showed that QDG treatment partially attenuated the increase of Ca2+ release with the stimulation of AngII in cultured VSMCs. In addition, IHC and western blotting indicated that QDG treatment also partially alleviated the increase of phospho-ERK levels in abdominal aorta tissues of mice and cultured VSMCs after the infusion or stimulation of AngII.Conclusion: QDG treatment attenuated the elevation of blood pressure, abdominal aorta dysfunction, pathological changes, Ca2+ release, and activation of the ERK signaling pathway.

Abstract Objective To investigate the mechanism of LncRNA H19 in Th17 cell differentiation and endometrial stromal cells (ESCs) proliferation in endometriosis (EMS). Methods LncRNA H19, miR-342-3p and IER3 expressions were detected by qRT-PCR and western blot. The percentage of Th17 cells/CD4+ T cells was detected by flow cytometry. IL-17 level was measured by ELISA. The interaction of miR-342-3p and IER3 was confirmed by Luciferase reporter assay. Results LncRNA H19 and IER3 expressions were down-regulated in mononuclear cells from peritoneal fluid (PFMCs) of patients with EMS or under Th17 differentiation conditions, whereas miR-342-3p expression was up-regulated and the percentage of Th17 cells was increased in PFMCs of patients with EMS or under Th17 differentiation conditions. Over-expression of LncRNA H19 decreased IL-17 level and the percentage of Th17 cells/CD4+ T cells. Besides, we confirmed that miR-342-3p could target to IER3 and negatively regulate IER3 expression. LncRNA H19 over-expression suppressed Th17 differentiation and ESC proliferation through regulating miR-342-3p/IER3. In vivo experiments showed LncRNA H19 over-expression suppressed the growth of Th17 cell differentiation-induced endometriosis-like lesions. Conclusion LncRNA H19 was down-regulated in PFMC of patients with EMS or under Th17 polarizing conditions, and LncRNA H19 over-expression suppressed Th17 cell differentiation and ESCs proliferation through miR-342-3p/IER3 pathway.

Smoking cessation prolongs survival and decreases mortality of patients with non‐small‐cell lung cancer (NSCLC). In addition, epigenetic alterations of some genes are associated with survival. However, potential interactions between smoking cessation and epigenetics have not been assessed. Here, we conducted an epigenome‐wide interaction analysis between DNA methylation and smoking cessation on NSCLC survival. We used a two‐stage study design to identify DNA methylation–smoking cessation interactions that affect overall survival for early‐stage NSCLC. The discovery phase contained NSCLC patients from Harvard, Spain, Norway, and Sweden. A histology‐stratified Cox proportional hazards model adjusted for age, sex, clinical stage, and study center was used to test DNA methylation–smoking cessation interaction terms. Interactions with false discovery rate‐q ≤ 0.05 were further confirmed in a validation phase using The Cancer Genome Atlas database. Histology‐specific interactions were identified by stratification analysis in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) patients. We identified one CpG probe (cg02268510SIPA1L3) that significantly and exclusively modified the effect of smoking cessation on survival in LUAD patients [hazard ratio (HR)interaction = 1.12; 95% confidence interval (CI): 1.07–1.16; P = 4.30 × 10–7]. Further, the effect of smoking cessation on early‐stage LUAD survival varied across patients with different methylation levels of cg02268510SIPA1L3. Smoking cessation only benefited LUAD patients with low methylation (HR = 0.53; 95% CI: 0.34–0.82; P = 4.61 × 10–3) rather than medium or high methylation (HR = 1.21; 95% CI: 0.86–1.70; P = 0.266) of cg02268510SIPA1L3. Moreover, there was an antagonistic interaction between elevated methylation of cg02268510SIPA1L3 and smoking cessation (HRinteraction = 2.1835; 95% CI: 1.27–3.74; P = 4.46 × 10−3). In summary, smoking cessation benefited survival of LUAD patients with low methylation at cg02268510SIPA1L3. The results have implications for not only smoking cessation after diagnosis, but also possible methylation‐specific drug targeting.

The structural and functional properties of physical modified rice flour, including ultrasound treated rice flour (US), microwave treated rice flour (MW) and hydrothermal treated rice flour (HT) were investigated with wet-milled rice flour (WF) used as a positive control. The results showed the presence of small dents and pores on the rice flour granules of US and MW while more fragments and cracks were showed in HT. XRD and FTIR revealed that moderate ultrasonic treatment promoted the orderly arrangement of starch while hydrothermal treatment destroyed the crystalline structure of rice flour. In addition, the significant decrease of gelatinization enthalpy and the narrowing gelatinization temperature were observed in US. Compared to that of SF, adding physical modified rice flour led to a batter with higher viscoelasticity and lower tan δ. However, the batter added HT exhibited highest G′ and G″ values and lowest tan δ, which led to a harder texture of bread. Texture analysis demonstrated that physical modified rice flour (except HT) reduced the hardness, cohesion, and gumminess of rice bread. Especially, the specific volume of bread with US increased by 15.6% and the hardness decreased by 17.6%. This study suggested that ultrasound treatment of rice flour could improve texture properties and appearance of rice bread.

Resveratrol is a natural polyphenol found in various plants. It has been widely studied on cardiovascular disorders. It is known that resveratrol can activate Sirtuin proteins and participate in cellular energy metabolism through a Sirtuin-dependent pathway. Here, we hypothesized that resveratrol may protect against myocardial ischemia/reperfusion injury (MIRI) through the target of Sirt1/Sirt3 on mitochondrial dynamics, cardiac autophagy, bioenergetics and oxidative damage in hypoxia/reoxygenation (H/R)-induced neonatal rat cardiomyocytes. We observed that resveratrol could activate the Sirt1/Sirt3-FoxO pathway on myocardial mitochondria in H/R cardiomyocytes. Subsequently, we found that resveratrol repaired the fission–fusion balance, autophagic flux and mitochondrial biosynthesis compared by H/R group. These changes were followed by increased functional mitochondrial number, mitochondrial bioenergetics and a better mitochondrial antioxidant enzyme system. Meanwhile, these effects were antagonized by co-treatment with Selisistat (Ex527), a Sirtuin inhibitor. Together, our findings uncover the potential contribution of resveratrol in reestablishing a mitochondrial quality control network with Parkin, Mfn2 and PGC-1α as the key nodes.

Abstract Background Inflammation may be a key pathophysiological mechanism in diabetic nephropathy (DN). Intercellular adhesion molecule 1 (ICAM1) is an acute phase marker of inflammation. ICAM1 rs5498 has been reported to be associated with the risk of DN. However, the previous findings were conflicting due to the limited sample sizes, different methodologies and ethnicities. Therefore, this study aimed to investigate the genetic association between ICAM1 rs5498 and the risk of DN. Methods Two investigators independently searched the studies from the databases PubMed, Web of Science, the Cochrane Library, Chinese National Knowledge Infrastructure (CNKI) and Embase. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the associations. Results No significant association was detected between ICAM1 rs5498 and DN susceptibility in allelic and recessive models (p > 0.05). However, significant reduction of frequencies of the dominant model of ICAM1 rs5498 was only detected in the Caucasian subgroup (OR = 0.80; 95% CI = [0.65, 0.99], p = 0.04) and type 1 diabetes mellitus subgroup (OR = 0.80; 95% CI = [0.65, 0.99], p = 0.04). Conclusions Thus, ICAM1 rs5498 might be a risk factor for DN in Caucasians and type 1 diabetes mellitus patients, which suggested that ICAM1 rs5498 might help in early diagnosis and prevention of this disease. Further studies were needed to clarify the biochemical function and pathological role of ICAM1 rs5498 in the risk of DN.

Cardiac fibrosis plays an important role in hypertension-related contractile dysfunction and heart failure. Qingda granule (QDG), derived from the Qingxuan Jiangya decoction, has been used clinically for more than 60 years to treat hypertension. However, the effect of QDG on hypertensive cardiac fibrosis remains largely unknown. The objective of this study was to investigate the effect of QDG on cardiac fibrosis and explore the underlying mechanism in vivo and in vitro. For in vivo experiments, 30 male spontaneously hypertensive rats were randomly divided into groups that received no QDG or one of three doses (0.45, 0.9 or 1.8 g/kg/day). Positive-control animals received valsartan (VAL, 7.2 mg/kg/day). Treatments were administered by gavage for 10 weeks. All three doses of QDG and VAL led to significantly lower blood pressure than in SHR animals. Besides, all three doses of QDG and VAL attenuated pathological changes in SHR animals. However, only intermediate, high concentrations of QDG and VAL led to significantly lower left ventricle ejection fraction and left ventricle fractional shortening than in SHR animals. Therefore, the minimum and effective QDG dose (intermediate concentration of QDG) was selected for subsequent animal experiments in this study. Our results showed that intermediate concentration of QDG also significantly mitigated the increases in levels of α-smooth muscle actin (α-SMA), proliferating cell nuclear antigen (PCNA), collagen III, transforming growth factor-β1 (TGF-β1) and in the ratio of phospho-Smad2/3 to total Smad2/3 protein in cardiac tissue, based on immunohistochemistry, Western blotting, and Masson staining. For in vitro experiments, primary cardiac fibroblasts were stimulated with 100 nM angiotensin II in the presence or absence of QDG. And we tested different concentrations of QDG (3.125, 6.25, 12.5, 25, 50 μg/mL) in the cell viability experiment. Our results showed that 3.125, 6.25 and 12.5 μg/mL of QDG treatment for 24 h didn’t affect the cell viability of cardiac fibroblasts. Consistently, QDG at 6.25 or 12.5 μg/mL significantly reduced cell viability and down-regulated α-SMA in primary cardiac fibroblasts were stimulated with 100 nM angiotensin II. Therefore, QDG at 12.5 μg/mL was chosen for the following cell experiment. Our results showed that QDG at 12.5 μg/mL alleviated the increase of PCNA, collagen Ⅲ, TGF-β1 expression, and the ratio of phospho-Smad2/3 to total Smad2/3 protein. Our studies in vitro and in vivo suggest that QDG reduces blood pressure and cardiac fibrosis as well as protecting cardiac function, and that it exerts these effects in part by suppressing TGF-β1/Smad2/3 signaling.

Presently, optimal proportions and synergistic mechanisms of component-based Chinese medicines are critical for developing novel strategies to treat cardiovascular diseases (CVDs). A new multi-objective optimization algorithm based on uniform design (UD) and stepwise regression (SR) modeling is proposed to find the synergistic effect of orientin (Ori), quercitrin (Que) and vitexin (Vit), the three effective components from Polygonum orientale L., using the H9c2 cells injury induced by hypoxia/reoxygenation (H/R). The optimal proportion of these three components was calculated by simulated annealing (SA). In this research, the excellent combination named OQV-e (Ori: Que: Vit =12.55 μM: 39.99 μM: 19.99 μM) could exert significant cardioprotection against the H9c2 cells injury induced by H/R through increasing cell viability, decreasing leakage rate of lactate dehydrogenase (LDH) and the level of nitric oxide (NO). Moreover, western blot analysis revealed that OQV-e could activate autophagy by inhibiting the p-JNK/JNK signaling pathway, which showed that the method (UD-SR-SA) was a feasible strategy. Mathematical system modeling may be a considerable approach for the powerful mathematical analysis of the complex pharmacological effects of component-based Chinese medicines from herbal medicines, which might greatly enhance the efficiency to find new modern Chinese drugs for CVDs based on Chinese herbal medicine (CHM) with affirmative therapeutic effect.

Qingda granule (QDG), simplified from Qingxuan Jiangya Decoction, is a well-known traditional Chinese medicine formula that has been used for decades to treat hypertension. However, the cardioprotective effects of QDG on Ang II-induced hypertension remain unknown. This study aimed to investigate the effects of QDG on hypertension-induced cardiac hypertrophy and apoptosis, as well as explore its underlying mechanisms. Mice were infused with Ang II (500 ng/kg/min) or saline solution as control, then administered oral QDG (1.145 g/kg/day) or saline for two weeks. QDG treatment attenuated the elevation in blood pressure caused by Ang II, as well as the decreased left ventricle ejection fractions and fractional shortening. Moreover, QDG treatment significantly alleviated the Ang II-induced elevation of the ratio of heart weight to tibia length, as well as cardiac injury, hypertrophy, and apoptosis. In cultured H9C2 cells stimulated with Ang II, QDG partially reversed the increase in cell surface area and number of apoptotic cells, up-regulation of hypertrophy markers ANP and BNP, and activation of caspases-9 and -3. QDG also partially reversed Ang II-induced accumulation of reactive oxygen species (ROS), depolarization of the mitochondrial membrane, release of cytochrome C, up-regulation of Bax, and decrease in levels of p-PI3K, p-AKT, and Bcl-2. These results suggest that QDG can significantly attenuate Ang II-induced hypertension, cardiac hypertrophy and apoptosis, and it may exert these effects in part by suppressing ROS production and activating the PI3K/AKT signaling pathway.