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Bisphenols (BPs) are widely used in consumer products, and human exposure to BPs is nearly ubiquitous. However, human biomonitoring data are scarce, especially for children. In this study, we quantified eight BPs in the serum of 345 children from a typical coastal city in China. Bisphenol A (BPA), bisphenol F (BPF), and bisphenol S (BPS) were frequently detected (63% BPA, 68% BPF, 43% BPS), with geometric mean (GM) concentrations of 1.6, 0.08, and 0.04 ng/mL, respectively. The other five BPs had low detection frequencies (

We report on fabrication of tapered circular depressed-cladding waveguides in Nd:YAG crystal by femtosecond laser direct writing (FsLDW). Based on the fabricated waveguides, for the first time to the best of our knowledge, efficient Q-switched mode-locked (QML) lasers are realized by employing silver nanoparticles (NPs) embedded in fused silica as saturable absorber (SA) element. Laser pulses as short as 25 ps with a repetition rate of 7.7 GHz are generated at a wavelength of 1064 nm. We systematically explore the influence of incident-output facet and the reduction factors on guiding properties and laser performance by conducting a comparative study of different tapers, and it has been found that the waveguides with tapered structures can suppress multi-mode guiding while ensure fundamental-mode output for waveguide lasers. Our work paves a new way toward developing three-dimensional (3D) waveguide for applications in on-chip ultrafast laser sources.

Hepatocellular carcinoma (HCC) is a common malignancy worldwide. Alpha-fetoprotein (AFP) is still the only serum biomarker widely used in clinical settings. However, approximately 40% of HCC patients exhibit normal AFP levels, including very early HCC and AFP-negative HCC; for these patients, serum AFP is not applicable as a biomarker of early detection. Thus, there is an urgent need to identify novel biomarkers for patients for whom disease cannot be diagnosed early. In this study, we screened and identified novel proteins in AFP-negative HCC and evaluated the feasibility of using autoantibodies to those protein to predict hepatocarcinogenesis. First, we screened and identified differentially expressed proteins between AFP-negative HCC tissue and adjacent non-tumor liver tissue using SWATH-MS proteome technology. In total, 2,506 proteins were identified with a global false discovery rate of 1%, of which 592 proteins were expressed differentially with 175 upregulated and 417 downregulated (adjusted p-value

Disturbances in circadian rhythms are known to affect immune functions. However, the long-term impact of abnormal circadian rhythms on the immune-related functions of the spleen are poorly understood. Hence, we aimed to investigate the immune-related functions of spleen in Per1/Per2 double-knockout (DKO) and wild-type (WT) mice aged 4, 9, and 14 months. Compared to the WT mice, the DKO mice had smaller spleen white pulp (WP) and lymphocyte germinal area, as well as fewer immune cells with age—these differences were especially clear. The spleen lymphocyte mortality, malondialdehyde (MDA) levels, reactive oxygen species (ROS) levels, and ferritin-binding receptor (TFR1) levels were significantly higher in the 14-month-old DKO mice than in WT mice of the same age. Transcriptome analysis showed that most of the differentially expressed mRNAs were enriched in DNA damage repair-related pathways. In DKO mice, spleen cells showed up-regulation of pro-ferroptosis genes, such as Cd36,Atm, and Acsl4, and down-regulation of anti-ferroptosis genes, such as GPX4. We found that long-term abnormalities in the circadian rhythm can induce DNA damage and ferroptosis in mouse spleen.

Background: Joint mechanics are permanently changed using different intensities and running durations. These variations in intensity and duration also influence fatigue during prolonged running. Little is known about the potential interactions between fatigue and joint mechanics in female recreational runners. Thus, the purpose of this study was to describe and examine kinematic and joint mechanical parameters when female recreational runners are subject to fatigue as a result of running.Method: Fifty female recreational runners maintained running on a treadmill to induce fatigue conditions. Joint mechanics, sagittal joint angle, moment, and power were recorded pre- and immediately post fatigue treadmill running.Result: Moderate reductions in absolute positive ankle power, total ankle energy dissipation, dorsiflexion at initial contact, max dorsiflexion angle, and range of motion of the joint ankle were collected after fatigue following prolonged fatigue running. Knee joint mechanics, joint angle, and joint power remained unchanged after prolonged fatigue running. Nevertheless, with the decreased ankle joint work, negative knee power increased. At the hip joint, the extension angle was significantly decreased. The range motion of the hip joint, hip positive work and hip positive power were increased during the post-prolonged fatigue running.Conclusion: This study found no proximal shift in knee joint mechanics in amateur female runners following prolonged fatigue running. The joint work redistribution was associated with running fatigue changes. As for long-distance running, runners should include muscle strength training to avoid the occurrence of running-related injuries.

Oral nutrition interventions are commonly applied as an assistant therapeutic approach, which could affect the balance of the immunological response but with mixed evidence. The objective of this study is to identify the potential of different oral nutrition interventions for blood immune cell parameters in cancer patients. Randomized controlled trials, which were published in peer-reviewed journals in the language of English, and which identified the effects of different oral nutrition interventions on cancer patients, were screened and included in the databases of PubMed, Medline, Embase, and Web of Science. White blood cell count (WBC), lymphocyte count, CD4/CD8, and neutrophil count were selected as outcome measures. For the result, 11 trials were included. The agreement between authors reached a kappa value of 0.78. Beta-carotene supplementation has a high potential in inducing a positive effect on blood immune cell parameters for cancer patients (first positive for WBC and CD4/CD8, second positive for lymphocyte count), as well as a combination of physical exercise and hypocaloric healthy eating intervention (first positive for lymphocyte and neutrophil count, second positive for WBC). Oral nutrition supplementations with a single substance have less potential to provide a positive effect on blood immune cell parameters for cancer patients (glutamine: 0.30 and 0.28 to be the last selection for WBCs and lymphocytes; Omega 3: 0.37 to be the last selection for WBCs; Protein: 0.44 to be the last selection for lymphocytes; Zinc: 0.60 to be the last selection for neutrophils). In conclusion, the programs of immunonutrition therapy for different cancer patients might be different. The past perception that mixed oral nutritional supplementations are superior to oral nutritional supplements with a single substance might be wrong and the selection of oral nutritional supplementation need cautiousness. A combination of physical exercise might have a positive effect but also needs a higher level of evidence. Registration Number: CRD42021286396.

Background: Gender has been considered as an influencing factor in the incidence of sports injuries. But few studies have discussed whether gender differences change after long-distance running. This study aimed at investigating whether the kinematic and ground reaction forces (GRFs) differences between males and females were altered by a 5 km run. Methods: Thirty novice runners (15 males and 15 females) with heel strikes were recruited for this study. In the test before and after the 5 km run, the participants were asked to run through the force plate with their right foot at a speed of 3.3 m/s ± 5%. Kinematics data and GRFs were collected synchronously. Each participant completed five successful running trials for further analysis of data. Results: Gender differences existed in ankle sagittal peak angle (pre: p = 0.059; post: p = 0.013), knee frontal peak angle (pre: p = 0.345; post: p = 0.014), knee horizontal nadir angle (pre: p = 0.056; post: p = 0.005), hip frontal nadir angle (pre: p = 0.103; post: p = 0.001) and peak lateral force (pre: p = 0.564; post: p = 0.001) after a 5 km run, but there were no gender differences before a 5 km run. Gender differences in the knee and hip movement in the frontal plane and horizontal plane and anterior-posterior GRFs changed obviously in the stance phase before and after a 5 km run. Conclusions: The gender difference in lower limb biomechanics during running is not constant. Differences change in peak angle, peak lateral force, knee and hip movement in the frontal plane and horizontal plane, and anterior-posterior GRFs between males and females were associated with the different incidence of running-related injuries, such as patellofemoral joint injuries, anterior cruciate ligament injury and iliotibial band syndrome, etc. These changes can give some concrete details to explore the different incidence rates of lower limb sports injuries between genders.

Background: Mesenchymal stem cell (MSC)-derived exosomes (Exos) are recently proved to be a promising candidate for ulcerative colitis (UC), but the mechanism remains unclear. We investigated the effects of MSC-derived exosomal microRNA-181a (miR-181a) on gut microbiota, immune responses, and intestinal barrier function in UC.Methods: Human bone marrow MSC-derived Exos were extracted and identified via transmission electron microscopy (TEM), Nanoparticle Tracking Analysis (NTA), and Western blotting. Dextran sodium sulfate (DSS)-induced colitis model and lipopolysaccharide (LPS)-induced human colonic epithelial cell (HCOEPIC) model were established to determine the effect of MSC-Exos on gut microbiota, immune responses, and intestinal barrier function in vivo and in vitro. The relationship between miR-181a and UC was analyzed using the Gene Expression Omnibus (GEO) database. MSC-miR-181-inhibitor was used to reveal the role of exosomal miR-181a in DSS-induced colitis.Results: TEM and NTA results showed that Exos of a diameter of about 100 nm with the round and oval vesicle-like structure were successfully extracted. The expressions of the CD63, CD81, and TSG101 proteins were positive in these Exos. After MSC-Exo treatment, the colon length in colitis mice increased; colon inflammatory injury decreased; TNF-α, IL-6, IL-1β, IL-17, and IL-18 levels decreased; and Claudin-1, ZO-1, and IκB levels increased. In addition, the structure of the gut microbiota in DSS-induced colitis mice was changed by MSC-Exos. MSC-Exos showed antiapoptotic effects on LPS-induced HCOEPIC. The protective effects decreased significantly by treatment with MSC-Exos interfered with miR-181a inhibitor in vivo and in vitro.Conclusion: MSC-derived exosomal miR-181a could alleviate experimental colitis by promoting intestinal barrier function. It exerted anti-inflammatory function and affected the gut microbiota. This indicated that MSC exosomal miR-181a may exhibit potential as a disease-modifying drug for UC.

Abstract Background Caspase-1 is an evolutionarily conserved enzyme that proteolytically cleaves the precursors of the inflammatory cytokines interleukin 1β and interleukin 18. However, the role of caspase-1 in determining the severity of acute-on-chronic liver failure (ACLF) has yet to be elucidated. We evaluated the expression levels of caspase-1 in HBV-related liver disease and assessed its utility as a biomarker predicting the severity of ACLF. Methods The gene, protein and activity levels of caspase-1 were measured in the liver and/or serum of subjects with HBV-related disease. We also analysed the correlation between the expression levels of caspase-1 and liver injury of ACLF. Results Compared with the values observed in normal subjects, the relative caspase-1 mRNA and protein levels in livers were decreased in patients with CHB, LC, and HCC but increased in those with ACLF; moreover, ACLF patients had the lowest serum level and hepatic activity of caspase-1 among the five groups. The serum caspase-1 levels in ACLF patients showed a negative correlation with total serum bilirubin and a positive correlation with serum total protein and albumin. Importantly, the serum caspase-1 levels in the surviving group with ACLF were higher than those in the non-surviving group and showed different dynamic trends. Analyses of the area under the receiver operating characteristic curve indicated that caspase-1 (AUC = 0.84, AUC of MELD score = 0.72) may be a useful marker for independently predicting ACLF. Conclusion Caspase-1 is a potential non-invasive biomarker of disease progression and prognosis in ACLF.

Abstract Background Depression is common among chronic heart failure (CHF) patients, and it is associated with significant re-hospitalization and mortality as well as lower quality of life. While psychotherapy is efficacious treatment for depression, the effect for depression among CHF is uncertain. And barriers preclude widely utility of psychotherapy among the elderly. Telephone-delivered psycho-behavioural intervention specifically focuses on depression among the elderly with CHF, and could be a promising alternative to conventional treatment. The present study was designed to prospectively investigate the effect of a telephone-delivered psycho-behavioural intervention on depression in the elderly with chronic heart failure (CHF). Method/design In this prospective, multicentre, parallel, randomized, and controlled trial, 236 participants with depression associated with CHF (New York Heart Association classes II and III) will be enrolled. The study will consist of a 12-week intensive intervention and a 24-week maintenance intervention. Eligible participants will be randomized to either the intervention arm or the control arm. During the intensive phase, participants will receive either a guided telephone psycho-behavioural intervention or regular telephone contacts from the counsellors weekly. During the maintenance phase, participants will receive either psychological behavioural support or regular telephone contacts monthly from counsellors. Depressive symptoms, cardiac outcome and quality of life will be assessed at baseline and weeks 1, 2, 4, 8, 12, 24 and 36. Participants will undergo echocardiography and the plasma concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) tested at baseline, weeks 12 and 36. The primary outcome is the response rate of depression, from baseline to week 12. The second outcomes include the change in cardiac function, quality of life and severity of depressive symptoms during the trial. Discussion To our knowledge, this study is the first prospective randomized trial to test the effective of the telephone-delivered psycho-behavioural intervention on depression in the elderly with CHF. The findings are expected to provide a new and evidence-based approach for depression among the elderly with CHF. Trial registration The trial was registered at www.clinicaltrials.gov (identification number: NCT03233451) on 28 July 2017 and updated on 18 August 2017.

Dandelion polysaccharides (DP) have been reported to possess anticancer activity. In this study, we showed that DP significantly inhibited Hepatocellular carcinoma (HCC) cell proliferation in vitro and in vivo and induced cell apoptosis and arrested cell cycle at the G0/G1 phase. Moreover, RNA sequencing data revealed that DP dampened PI3K-AKT signaling pathway. Western blot results confirmed that DP treatment negatively regulated the levels of p-PI3K, p-AKT, and p-mTOR in HCC cells, suggesting that DP inhibited PI3K/AKT/mTOR pathway. Furthermore, immunophenotyping experiments showed that DP significantly improved the spleen index, spleen germinal center reaction and modulated T cell activation in vivo, which could contribute to the inhibition of tumor growth in animals. In addition, in vivo studies demonstrated that 400 mg/kg DP treatment was well-tolerated by mouse without any adverse systemic toxicological changes. In summary, we propose that DP might be a potential drug candidate for the treatment of HCC.

Abstract Background Seed germination and seedling establishment are two of the most critical phases in plant development. However, the molecular mechanisms underlying the effect of phosphorus on seed germination and post-germinated growth of oilseed rape are unclear so far. Here, we report the role of BnPHT1;4 in seed germination and early seedling development of Brassica napus. Results Our results show that BnPHT1;4 is preferentially expressed in cotyledons of early developing seedlings. Overexpression of BnPHT1;4 in oilseed rape promoted seed germination and seedling growth. Expression levels of the genes related to ABA and GA biosynthesis and signaling were significantly altered in BnPHT1;4 transgenic seedlings. Consequently, active GA level was up-regulated, whereas ABA content was down-regulated in BnPHT1;4 transgenic seedlings. Furthermore, exogenous GA could promote seed germination of wild type, while exogenous ABA could partially recover the advanced-germination phenotype of BnPHT1;4 transgenic seeds. Total phosphorus content in cotyledons of the transgenic seedlings was decreased more rapidly than that in wild type when Pi was supplied or deficient, and Pi contents in shoots and roots of the BnPHT1;4 transgenic plants were higher than those in wild type under high and low Pi conditions. Conclusions Our data suggest that the high-affinity transporter BnPHT1;4 is involved in phosphorus acquisition and mobilization for facilitating seed germination and seedling growth of Brassica napus by modulating ABA and GA biosynthesis.

Kaempferol is a flavonoid compound that has many functions, such as anti-inflammation and antioxidation. Acute liver failure (ALF) is a life-threatening illness accompanied by serious inflammation and extensive hepatocyte apoptosis. The aim of this study was to examine the therapeutic potential of kaempferol and its mechanism in ALF. In a murine ALF model induced by d-galactosamine (d-GalN, 700 mg/kg) / lipopolysaccharide (LPS, 10 μg/kg), mice were pretreated with kaempferol at 2 h before d-GalN/LPS administration and then sacrificed 6 h after d-GalN/LPS injection. Lethality, liver damage, endoplasmic reticulum(ER) stress, hepatocyte viability and apoptosis were evaluated. Whether pretreatment of kaempferol protected hepatocytes from ER stress-induced apoptosis was detected in vitro. Pretreatment of kaempferol decreased lethality, prolonged the survival time and significantly protected against liver injury, which was indicated by decreased transaminase levels and the well-preserved liver structure. The protective effect of kaempferol on the ALF mouse model was achieved by inhibiting hepatocyte apoptosis. Moreover, pretreatment of kaempferol increased the expression of glucose-regulated/binding immunoglobulin protein 78 (Grp78), decreased the expression of C/EBP-homologous protein (CHOP), and protected hepatocytes from ER stress-induced apoptosis in vitro. Our results showed that pretreatment of Grp78 siRNA partially negated the hepatic protection from kaempferol and reversed the inhibition of CHOP protein expression in d-GalN/LPS-induced ALF mice. In conclusion, kaempferol inhibits hepatocyte apoptosis to protect mice from liver failure by regulating the ER stress-Grp78-CHOP signaling pathway. Therefore, kaempferol may be used to treat ALF.

Resonant frequency and impedance matching have great significance for the vibration performance and online monitoring of the rotary ultrasonic machining. Network compensation is a typical solution to match the resonant frequency and the impedance between the rotary ultrasonic holder (RUH) and the ultrasonic transducer. However, the traditional bilateral compensation method could adversely affect the rotary dynamic balance of the RUH. Currently, the existing unilateral compensation methods can only realize the resonant frequency matching. A novel unilateral compensation method that satisfies both the resonant frequency and the impedance matching is proposed. First, the impedance model of the RUH vibrating system is established according to its equivalent circuit. It is found that, without any compensation methods, the resonant frequency and the impedance between the RUH and the transducer have deviated. Second, the primary-series and primary-parallel compensation topologies are applied to the RUH system, and the expressions of compensation capacitance value, voltage gain, power transfer efficiency, and output active power are derived. The deviations of the resonant frequency and the impedance are eliminated with primary-series compensation topology; and as a result, the voltage gain is increased from 0.267 to 0.90, the output active power is 11.3 times than that without compensation. Third, the state-space model of primary-series topology is constructed. Finally, the above theoretical results are verified by the experimental results.

Nonlinear interactions between light and matter give rise to a wide range of applications for both fundamental and applied research. Herein, near‐infrared switching of the optical response based on embedded Ag nanoparticles and laser‐written optical waveguides within yttrium vanadate (YVO4) crystal matrix is demonstrated. Using broadband transient absorption spectroscopy with a combination of femtosecond Z‐scan spectroscopy, the plasmon‐enhanced features of the third‐order optical nonlinearity in Ag:YVO4 nanocomposite at the near‐infrared band are elucidated. Meanwhile, an optical‐lattice‐like microscale waveguide is fabricated with well‐preserved photoluminescence properties by femtosecond laser writing. Taking advantage of the ultrafast on–off switching behavior of Ag:YVO4 saturable absorber, a Q‐switched pulsed laser operation in the waveguide platform, delivering 1 μm light pulses with high peak power of 298 mW, is demonstrated. This work indicates a possible path for the development of chip‐scale ultrafast photonic devices.

Purpose. Examining and understanding the biomechanics of novice runners and experienced runners can further improve our knowledge within the field of running mechanics and running injuries. The purpose of this study was to classify the differences in lower limb biomechanics during a 3.3 m/s running task among both experienced runners and novice runners. Method. Twenty-four participants (12 experienced runners and 12 novice runners) ran at 3.3 m/s across a force plate; kinematics and kinetics data were collected by the Vicon motion system and Kistler force plate. Group comparisons were made using an independent samples t-test to identify differences in the impact peak, loading rate, contact time, ankle, knee, and hip joint kinematics and kinetics during the stance phase. Results. No significant differences were observed between novice and experienced runners for both ankle and knee joint kinetics except that the ankle joint plantar flexion torque was significantly greater in the novice runners. However, the plantar flexion, dorsiflexion, range of motion (ROM), plantar flexion torque, and max angular velocity of ankle joint significantly increased in novice runners than inexperienced runners. Additionally, the flexion angle and range of motion of the hip joint were observed to be larger in the novice runners. Moreover, the maximum extension torque and the maximum extension power in the hip joint were significantly increased in the experienced runners. There were no significant differences in the first peak, contact time, and average vertical loading rate. Novice runners showed a larger vertical instantaneous loading rate than experienced runners. Conclusion. These preliminary findings indicate that novice runners are prone to running injuries in comparison to experienced runners. Novice runners showed larger kinematics and kinetic parameters in the joint of the ankle and hip. Novice runners should enhance muscle strength in the hip and choose scientific training methods.

A high proportion of shoulder injuries in table tennis players are common, which is both a diagnostic and therapeutic challenge. An understanding of the interaction between biomechanical function of the shoulder and mechanisms of shoulder injuries in table tennis players is necessary to prevent injury and to conduct clinical treatment of the shoulder as soon as possible. The purpose of this minireview was to select the available evidence on the biomechanical characteristics of shoulder movement and potential relationships with various shoulder injuries that are common in table tennis players. Five studies revealed interesting biomechanical characteristics of shoulder movement patterns in table tennis players: large internal rotation torque, an increased torsion-rotation movement, and a greater angular velocity of internal rotation were found. Two studies were noted that were related to specific shoulder injury: glenohumeral internal rotation deficit (GIRD) and impingement syndrome. Unfortunately, it is difficult to draw conclusions on the mechanisms of shoulder injury in table tennis players due to the little evidence available that has investigated shoulder injury mechanisms based on biomechanical characteristics. Future studies should focus on the potential relationship between the biomechanical characteristics of the shoulder and injury prevalence to provide valuable reference data for clinical treatment.

Volleyball activities involve several factors such as asymmetrical movements, muscle imbalance, and continual overloading that damage body posture. This study aimed to determine postural changes of volleyball players in spike overhand front set, overhand pass ball, and mat ball motions, and if there is any postural variation difference between short training and long training volleyball players. Methods: Fifteen long training and short training male volleyball players aged 21–23 years were recruited in this study. The upper-thoracic angle, thoracic-lumbar segment angle, lower lumbar-sacral segment, pelvic inclination, and inclination of the acromion were measured using DIERS formetric 3D device in a dynamic way. During the overhand pass motion, long training participants showed a significant larger peak upper-thoracic and peak thoracic-lumbar angles than short training participants. During the mat ball motion, the long training volleyball players demonstrated a significant higher peak upper-thoracic angle, but a smaller peak inclination of the acromion than short trainers. During the spike overhand front set motion, long trainers showed a significant smaller peak upper-thoracic angle than short trainers. Athletes should consider developing an appropriate dynamic trunk stabilization to reduce posture imbalance during volleyball activities.

Objective To study the effects of saikosaponin D (SSD) on proliferation and apoptosis in human non-small cell lung cancer cell lines, and to explore underlying mechanisms. Methods Following treatment with saikosaponin D, A549 and H1299 cells were assessed for anti-proliferation effects using cell cycle kit-8 assays, changes in nuclear morphology using 4′,6-diamidino-2-phenylindole (DAPI) staining, and cell apoptosis using annexin V/propidium iodide double staining. Proliferation- and apoptosis-related proteins were detected by immunoblotting. Results Saikosaponin D had dose-dependent inhibitory effects on A549 cells (IC 50 , 3.57 µM) and H1299 cells (IC 50 , 8.46 µM). DAPI staining revealed decreased cell numbers, and most H1299 cells became round after treatment with 20 µM saikosaponin D. As saikosaponin D concentration increased, the proportions of cells in G0/G1 phase, and cells undergoing apoptosis, increased. Levels of phosphorylated p44/42 and signal transducer and activator of transcription (STAT)3 were significantly downregulated in both cell lines, while total STAT3 levels were not significantly affected. The cleaved form of caspase 3 was significantly upregulated. Conclusions Saikosaponin D inhibits proliferation, inducing cell cycle arrest and apoptosis, in lung cancer cells in a dose-dependent manner, possibly through inhibition of STAT3 phosphorylation and activation of caspase 3.

Acetaminophen (APAP) overdose induces hepatocyte necrosis and causes liver hepatotoxicity. Currently, the role of galactosyltransferase in APAP-induced liver injury is still unclear. This study assessed the contribution of the GLT25D2 gene, a kind of collagen galactosyltransferase, to the development of APAP-induced liver injury. This study found that the expression of GLT25D2 markedly increased first and then decreased in the liver of mice treated with APAP, however, it downregulated in the liver of APAP overdose-patients compared with normal controls. Knockout of GLT25D2 significantly ameliorated the liver injury, meanwhile, it downregulated the proinflammatory cytokines (IL-6, TNF-α) and chemokines (CXCL-10, MIG and CXCL-1) levels, however, and upregulated the anti-inflammatory cytokines (IL-22, IL-10) levels. Mechanistic explorations showed that (1) GLT25D2 knockout promoted autophagy pathway; and (2) the GLT25D2 knockout-induced autophagy selected to clear damaged mitochondria in APAP-induced liver injury by mitophagy; and (3) the autophagy intervention by Atg 7 siRNA cancelled liver protection by knockout of GLT25D2 through regulating liver inflammation. In conclusion, our study proves that the upregulated expression of GLT25D2 decreased autophagy contributing to APAP-induced hepatotoxicity by mediating the inflammatory immune regulatory mechanism.

Recent studies have revealed that natural plants-derived polysaccharides exhibit potent anti-tumor activity. Our earlier studies suggest that dandelion polysaccharide (DP) inhibits hepatocellular carcinoma (HCC) cell proliferation in vitro and in vivo. Here, we investigated the effects of DP on the angiogenesis of HCC and the potential molecular mechanisms by which DP regulates angiogenesis. Wound-healing and transwell invasion assays revealed that DP inhibited HUVECs migration and invasion in vitro, respectively. Tube formation assay, chick chorioallantoic membrane (CAM) assay, and immunohistochemistry (IHC) demonstrated that DP suppressed vasculogenesis in vitro and in vivo. Moreover, Western blot and immunofluorescence staining verified that DP treatment decreased the protein levels of some key factors involved in angiogenesis of HCC, such as hypoxia-inducible factor 1α (HIF-1α), vascular endothelial growth factor (VEGF), p-PI3K, and p-AKT. However, activation of PI3K/AKT pathway with insulin-like growth factor 1 (IGF-1) treatment attenuated the effect of DP on angiogenesis via lowering the expression of HIF-1α and VEGF. In summary, we found that DP treatment inhibited angiogenesis in vivo and in vitro through suppressing expression of VEGF and HIF-1a. Furthermore, we showed that the expression of VEGF and HIF1-α was modulated by PI3K/AKT signaling. Collectively, our study suggests that DP is a promising anti-cancer drug candidate for treating HCC.

The purpose of this study was to investigate the variations of arch index from static standing to dynamic walking and running; furthermore, the interlimb symmetry was checked in the two populations. A total of eighty male participants were recruited for this study, with forty habitually barefoot and forty habitually shod males, respectively. Arch index (AI) was calculated following the previously established “gold standard” measurement via contact areas recorded from EMED. Repeated measure analysis of variance (ANOVA) was employed to compare the difference between static and dynamic walking and running arch index. Paired-samples t-test and symmetry index (SI) were used to investigate the symmetry of the left foot arch index and right foot arch index. It was found that the dynamic arch index was significantly higher than the static arch index in barefoot and shod males, showing an increase from static weight-bearing standing to dynamic walking and running. However, interlimb (right-left) symmetry in the foot arch index was observed in the two populations. Dynamic changes of the arch index may provide implications that need to be considered while designing shoe lasts or insoles. Knowledge of the healthy arch index range reported from this study could also be used as a standard baseline to probe into foot and arch disorders.

Research on ecological total-factor energy efficiency (ETFEE) is conducive to energy conservation, emission reduction, and ecological protection. This paper focuses on the measurement and decomposition of the ETFEE in the Beijing-Tianjin-Hebei (BTH) region in China. In order to measure the ETFEE values, the window technology is combined with a nonradial and nonoriented SBM-undesirable model considering undesirable outputs to overcome the defect of insufficient data of research objects and ensure the calculation process to be implemented. The findings show that Beijing and Tianjin are DEA-efficient, while Hebei is not. The technological progress rates of Beijing and Tianjin reach up to 11.92% and 14.96%, while that of Hebei retrogresses by 4.47%. The scale efficiencies of Beijing, Tianjin, and Hebei are 97.75%, 86.60%, and 93.81%, respectively, which means that there are potentials for further optimization in the energy structures. The impulse response results between the energy structure and the ETFEE show that the proportions of coal and petroleum have negative effects on the ETFEE, while that of natural gas has a positive effect. The research results can provide reference for decision makers to formulate regional development plans.

Abstract Background Growing evidence suggests that MiRNAs play essential roles in the initiation and progression of colorectal cancer (CRC). The aberrant expression of miR-384 has been reported in some cancers. However, the role and mechanism of miR-384 in CRC proliferation remains unknown. Methods The expression of miR-384 was detected in CRC and their paired normal tissues by real-time PCR. In vivo and in vitro assays were conducted to confirm the role of miR-384 in the proliferation of CRC. Bioinformatics analysis, luciferase reporter assays, western blot and in vitro assays were used to confirm that AKT3 was the target gene of miR-384. Finally, Spearman’s correlation analyses was carried out to analyze the relationship between miR-384 expression and AKT3 expression in CRC. Results MiR-384 was down‑regulated in CRC tissues. The in vivo and vitro functional assays verified that the ectopic upregulation of miR-384 inhibited the proliferation of CRC and the inhibition of miR-384 promoted the proliferation of CRC. Bioinformatics analysis, luciferase reporter assays, western blot and in vitro functional assays confirmed AKT3 as the target gene of miR-384. The expression of miR-384 was negatively correlated with the expressions of AKT3. Conclusion Our study verified that miR-384 could significantly suppress the proliferation of CRC by directing targeting AKT3.

Abstract Background Crizotinib is a multi-target inhibitor approved for the treatment of advanced non-small-cell lung cancer patients with a ROS1 rearrangement. However, interstitial lung disease is a rare but severe and fatal side effect of crizotinib that should lead to immediate discontinuation of the drug. Unfortunately, the pathophysiology, molecular mechanism and risk factors for crizotinib-induced interstitial lung disease remain poorly understood. Case presentation We first identified and reported interstitial lung disease induced de novo by crizotinib in a 47-year-old female patient who was diagnosed with advanced lung adenocarcinoma with a ROS1 rearrangement in a malignant pleural effusion. Subsequent next-generation sequencing analysis revealed both ROS1 rearrangement and an EGFR exon 19 deletion mutation in lung biopsy specimens, which were histologically confirmed to be interstitial lung disease. Although crizotinib treatment was ceased immediately and a shock treatment with high-dose methylprednisolone as well as other necessary treatment procedures was applied to reverse the interstitial lung disease process, the patient died. Conclusions The present case indicates that while treating non-small-cell lung cancer patients with crizotinib, it is important to constantly monitor any newly emerging respiratory symptoms and unexplained imaging changes, which may suggest an adverse effect related to drug-induced interstitial lung disease or even lethality. Histopathology and molecular pathological examination of lung biopsy specimens may help clinicians understand the development mechanism and exclude other causes.

Background/Aims: Iron plays a fundamental role in cell biology and its concentration must be precisely regulated. It is well documented that excess iron burden contributes to the occurrence and progression of cancer. Hepcidin secreted by liver plays an essential role in orchestrating iron metabolism. In the present study, we aimed to investigate the ability of angelica sinensis polysaccharide (ASP) to decrease iron burden in tumor-bearing mice and the mechanism of ASP regulation hepcidin expression. Methods: Western blot, RT-PCR, immunohistochemistry (IHC), and enzyme-linked immunosorbent assay (ELISA) were used to detect the regulation of hepcidin and related cytokines by ASP. The role of ASP in tumor proliferation was investigated using in vivo assays. Iron depositions and iron concentrations in organs were determined by hematoxylin-eosin (H&E) staining and atomic absorption spectrophotometer. Results: We found that ASP could inhibit tumor growth in mice xenografted with 4T1 and H22 cancer cells. In vivo experiments also showed that ASP could potently regulate hepcidin expression in liver and serum and decrease iron burden in liver, spleen and grafted tumors in mouse model. Treatment with ASP in hepatic cell lines reproduced comparable results in decreasing hepcidin as in mouse liver. Furthermore, we found that ASP markedly suppressed the expression of interleukin-6 (IL-6), JAK2, p-STAT3, and p-SMAD1/5/8 in liver, suggesting that JAK/STAT and BMP-SMAD pathways were involved in the regulation of hepcidin expression by ASP. We also found down-regulation of iron-related cytokines in ASP treated mice. Conclusion: The present study provides new evidence that ASP decreases hepcidin expression, which can reduce iron burden and inhibit tumor proliferation. These findings might aid ASP developed as a potential candidate for cancer treatment in patients with iron overload.

Abstract We report on the embedded silver (Ag) nanoparticles fabricated by Ag+ ion implantation into the Bi4Ge3O12 (BGO) crystal. Localized surface plasmon resonance (LSPR) phenomenon has been observed by linear optical absorption spectrum, which is accordance with the expectation based on Mie theory calculation. Further proofs are given by SRIM, TEM and SAED analysis, which explain the slight difference between experiment and calculation. Based on the z-scan system, it is found that the nonlinear optical response is converted from two-photon absorption to three-photon absorption under the 515 nm femtosecond pulse excitation within the LSPR band. The nonlinear absorption coefficient is measured to be ~3.1 × 10−9 cm/W (two-photon absorption coefficient) and ~8.9 × 10−14cm3/W2 (three-photon absorption coefficient) for pure BGO crystal and the sample embedded with Ag nanoparticles (Ag:BGO), respectively. Finally, we have proposed a model to explain the asymmetric nonlinear transmittance, which is in good agreement with the experimental results.

Developing high-performance tungsten plasma-facing materials for fusion reactors is an urgent task. In this paper, novel nanochannel structural W films prepared by magnetron sputtering deposition were irradiated using a high-power pulsed electron beam or ion beam to study their edge-localized modes, such as transient thermal shock resistance. Under electron beam irradiation, a 1 μm thick nanochannel W film with 150 watt power showed a higher absorbed power density related cracking threshold (0.28–0.43 GW/m2) than the commercial bulk W (0.16–0.28 GW/m2) at room temperature. With ion beam irradiation with an energy density of 1 J/cm2 for different pulses, the bulk W displayed many large cracks with the increase of pulse number, while only micro-crack networks with a width of tens of nanometers were found in the nanochannel W film. For the mechanism of the high resistance of nanochannel W films to transient thermal shock, a residual stress analysis was made by Grazing-incidence X-ray diffraction (GIXRD), and the results showed that the irradiated nanochannel W films had a much lower stress than that of the irradiated bulk W, which indicates that the nanochannel structure can release more stress, due to its special nanochannel structure and ability for the annihilation of irradiation induced defects.

A series of novel Li+ doped Bi3.46Ho0.04Yb0.5Ti3O12 (BHYTO: xLi, 0 ≤ x ≤ 0.15) upconversion phosphors were prepared through a sol-gel-sintering method. There exist three emission bands centered at 545 nm, 658 nm, and 756 nm in the upconversion emission spectra at 980 nm excitation, corresponding to energy transitions of 5F4/5S2 → 5I8, 5F5 → 5I8 and 5F4/5S2 → 5I7 of Ho3+, and the upconversion emission intensity of BHYTO: 0.05Li is about 2.2 times stronger than that of BHYTO samples. The luminescent lifetime of the strongest emission (545 nm) is in the range of 45.25 to 65.99 μs for the different BHYTO: xLi phosphors. The energy transfers during the upconversion pumping process from Yb3+ to Ho3+ are mainly responsible for all the emissions, each belonging to a double-photon process. Li+ mainly entered into the interspace sites or occupied Bi3+ sites in Bi4Ti3O12 host during the fabrication process according to its dosage, and the possibility is very low for Li+ to take part in the energy transfer process directly due to its lack of matching levels with 4f of Ho3+ and Yb3+. However, Li+ doping can not only increase the size of crystal grains to improve crystallinity through XRD analysis, but also reduced oxygen vacancies to decrease the number of quenching centers through XPS analysis. The improved crystallinity and reduced quenching centers are proposed to be the main causes for the enhanced upconversion luminescence of the Li+ doped BHYTO phosphor.

Acute-on-chronic liver failure (ACLF) carries a significant burden on critical care services and health care resources. However, the exact pathogenesis of ACLF remains to be elucidated, and novel treatments are desperately required. In our previous work, we utilized mice subjected to acute insult in the context of hepatic fibrosis to simulate the development of ACLF and documented the favorable hepatoprotection conferred by M2-like macrophages in vivo and in vitro . In the present study, we focused on the phenotypic switch of human and mouse macrophages and assessed the effects of this switch on apoptosis resistance in hepatocytes. For this purpose, human and mouse macrophages were isolated and polarized into M0, M(IFN-γ), M(IFN-γ→IL-4), M(IL-4) or M(IL-4→IFN-γ) subsets. Conditioned media (CM) from these subsets were applied to human and mouse hepatocytes followed by apoptosis induction. Cell apoptosis was evaluated by immunostaining for cleaved caspase-3. As a result, M(IFN-γ) or M(IL-4) macrophages switched their phenotype into M(IFN-γ→IL-4) or M(IL-4→IFN-γ) through reprogramming with IL-4 or IFN-γ, respectively. Importantly, hepatocytes pre-treated with M(IFN-γ→IL-4) CMs exhibited much weaker expression of cleaved caspase-3, compared to those pre-treated with M(IFN-γ) CM, and vice versa . Together, phenotypic switch of macrophages toward M(IL-4) phenotype confers hepatocytes enhanced resistance to apoptosis.

This study was aimed to analyze the foot posture index and plantar pressure characteristics of fifteen badminton players and fifteen controls. The hypothesis was that people with the habit of playing badminton would be significantly different with nonplaying people in foot posture index, 3D foot surface data, and plantar pressure distribution. Nine regions of plantar pressure were measured by using the EMED force platform, and badminton players showed significantly higher peak pressure in the hallux (p=0.003), medial heel (p=0.016), and lateral heel (p=0.021) and force-time integral in the hallux (p=0.002), medial heel (p=0.026), and lateral heel (p=0.015). There is no asymmetrical plantar pressure distribution between the left foot and the right foot of players. The mean foot posture index values of male and female badminton players are 5.2 ± 1.95 and 5.7 ± 1.15, respectively, and comparatively, those values of male and female controls are 1.5 ± 1.73 and 1.7 ± 4.16, respectively. This study shows that significant differences in morphology between people with the habit of playing badminton and people without that habit could be taken as a factor for a future study in locomotion biomechanics characteristics and foot shape of badminton players and in a footwear design in order to reduce injury risks.

Background and Purpose: Although trastuzumab has shown considerable activity in the treatment of HER2-positive breast and gastric cancers, a significant proportion of patients do not respond to trastuzumab. Recent studies revealed that osthole, an active coumarin isolated from Cnidium monnieri (L.) Cusson possesses potent anti-tumor activity. Here, we for the first time investigated the anti-tumor activity of trastuzumab in combination with osthole in HER2-overexpressing cancers.Materials and Methods: N87 and SK-BR-3 cell lines, which were HER2-overexpressing cancer cells were used in our study. Cell Counting Kit-8 (CCK-8) assay was utilized to test the inhibitory effects of trastuzumab plus osthole. Combination index (CI) values were calculated using the Chou-Talalay method. Fluorescence-Activated Cell Sorter (FACS) assay was used to examine the cell cycle change and apoptosis upon combinatorial treatment. N87 tumor xenografts were established to evaluate in vivo effects of trastuzumab plus osthole. In addition, molecular mechanisms were analyzed by Western blot in vitro and in vivo.Results: As shown in our study, osthole alone exhibited effective anti-tumor activity against HER2-overexpressed N87 gastric cancer cells and SK-BR-3 breast cancer cells, which may be attributed to cell cycle arrest on G2/M phase and apoptosis. More importantly, our data demonstrated that trastuzumab plus osthole was much more potent than either agent alone in inhibiting the growth of N87 cancer cells in vitro and in vivo, which may be partly explained by the enhanced apoptosis upon the combinatorial treatment. Besides these, we also observed a significant decrease on the phosphorylation of AKT and MAPK in N87 cells when treated with trastuzumab plus osthole compared to either agent alone. Further data from N87 tumor xenografts revealed that trastuzumab plus osthole exerted their synergistic effects mainly on AKT signaling pathway.Conclusion: Collectively, these results support the clinical development of combination osthole with trastuzumab for the treatment of HER2-overexpressed gastric cancer.

Peroxisome proliferator-activated receptor α (PPARα) is a key regulator to ameliorate liver injury in cases of acute liver failure (ALF). However, its regulatory mechanisms remain largely undetermined. Endoplasmic reticulum stress (ER stress) plays an important role in a number of liver diseases. This study aimed to investigate whether PPARα activation inhibits ER stress-induced hepatocyte apoptosis, thereby protecting against ALF. In a murine model of D-galactosamine (D-GalN)- and lipopolysaccharide (LPS)-induced ALF, Wy-14643 was administered to activate PPARα, and 4-phenylbutyric acid (4-PBA) was administered to attenuate ER stress. PPARα activation ameliorated liver injury, because pre-administration of its specific inducer, Wy-14643, reduced the serum aminotransferase levels and preserved liver architecture compared with that of controls. The protective effect of PPARα activation resulted from the suppression of ER stress-induced hepatocyte apoptosis. Indeed, (1) PPARα activation decreased the expression of glucose-regulated protein 78 (Grp78), Grp94 and C/EBP-homologous protein (CHOP) in vivo; (2) the liver protection by 4-PBA resulted from the induction of PPARα expression, as 4-PBA pre-treatment promoted upregulation of PPARα, and inhibition of PPARα by small interfering RNA (siRNA) treatment reversed liver protection and increased hepatocyte apoptosis; (3) in vitro PPARα activation by Wy-14643 decreased hepatocyte apoptosis induced by severe ER stress, and PPARα inhibition by siRNA treatment decreased the hepatocyte survival induced by mild ER stress. Here, we demonstrate that PPARα activation contributes to liver protection and decreases hepatocyte apoptosis in ALF, particularly through regulating ER stress. Therefore, targeting PPARα could be a potential therapeutic strategy to ameliorate ALF.

Cancer cells under stress use acetate to maintain the acetyl-CoA pool and fuel lipid biosynthesis. Here, the authors show that acetate also promotes de novo lipid synthesis by increasing histone acetylation at the promoters of lipogenic enzymes ACACA and FASN, thus inducing their expression.

In order to meet the requirements of high-frequency vacuum electronic devices with small size, high current density, and low working temperature, a kind of porous tungsten scandate cathode with micro-blade-type arrays was developed. The micro-blade-type arrays were fabricated by laser engraving technology. Subsequently, the cathode was prepared by a vacuum copper removal process and impregnated with active substances at high temperature. Experimental results show that the cathode exhibits excellent low-temperature electron emission performance and that the maximum pulse electron emission current density reaches 81.18 A/cm2 at 800 °C. The cathode also shows apparent combined thermal-field emission characteristics. Further analysis shows that a high electric field strength plays an important role in the electron emission of the scandate cathode. By virtue of the electric field enhancement effect formed by the fabricated micro-blade-type arrays on the cathode surface, the prepared cathode achieves high electron emission capacity.

Previously, we developed a novel EGFR-targeted antibody (denoted as Pan), which has superior antitumor activity against EGFR-overexpressed tumors. However, it shows marginal effect on the growth of esophageal cancers. Therefore, the variable region of Pan was fused to a fragment of Pseudomonas exotoxin A (PE38) to create the immunotoxin, denoted as Ptoxin (PT). Results indicated that PT shows more effective antitumor activity as compared with Pan both on EGFR-overexpressed KYSE-450 and KYSE-150 esophageal cancer cells, especially on KYSE-450 cells. Moreover, treatment of PT induces regression of KYSE-450 tumor xenografts in nude mice. Furthermore, we investigated the potential mechanism involved in the enhanced antitumor effects of PT. Data showed that PT was more potent in reducing the phosphorylation of EGFR and ERK1/2. More importantly, we for the first time found that PT was more effective than Pan in inducing ROS accumulation by suppression of the Nrf2-Keap1 antioxidant pathway, and then induced apoptosis in KYSE-450 esophageal cancer cells, which may partly explain the more sensitive response of KYSE-450 to PT treatment. To conclude, our study provides a promising therapeutic approach for immunotoxin-based esophageal cancer treatment.

Objective: To explore the relation between serum sphingolipids and hepatic injury in chronic HBV infection. Methods: A cohort of participants including 48 healthy persons, 103 chronic HBV-infected patients containing chronic hepatitis B (CHB) and HBV-related cirrhosis were included. High performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) was performed to detect serum sphingolipids. The serological indicators were detected and quantified. The valid liver biopsy specimens were acquired from twenty five CHB. Results: Twenty four serum sphingolipids were detected. There were eighteen sphingolipids showing significant differences between the healthy control and chronic HBV infection groups. In patients with chronic HBV infection, fourteen sphingolipids differed significantly between CHB and HBV-related cirrhosis. Among sphingolipids with a significant difference in both HBV infection vs healthy control and CHB vs cirrhosis, seven sphingolipids were independently related to the presence of cirrhosis. SM(d18:1/24:0), a sphingomyelin (SM) compound, was found to have a negative correlation with model for end-stage liver disease (MELD) score. Additionally, SM(d18:1/24:0) was demonstrated to have a correlation with inflammation grades by liver biopsy in CHB patients. Conclusions: Serum sphingolipids have close relation with hepatic injury in chronic HBV infection, especially that SM(d18:1/24:0) might be a potential serum biomarker.

Objectives: To evaluate the progression of fibrosis and factors influencing this in interferon (IFN) treatment-naive Chinese plasma donors infected with hepatitis C virus (HCV) for approximately 20 years. Methods: From July 2010 to June 2011, we investigated 122 IFN treatment-naive chronic hepatitis C (CHC) patients infected by plasma donation in 1992–1995. Liver fibrosis stage and inflammation grade were evaluated by Metavir and Scheuer scoring systems, respectively. Results: One hundred and twenty patients underwent liver biopsy. Liver biopsy was not performed in one patient with cirrhosis due to ascites, and another patient was excluded because of an invalid biopsy specimen. Cirrhosis was observed in three patients (fibrosis stage F4 in two patients revealed by biopsy, and one patient with ascites confirmed by physical and Doppler ultrasound examination). Fibrosis stages F1 and F2 were present in 55 and 50 patients, respectively. The severity of liver inflammation was independently related to moderate to severe fibrosis (F ≥2). Older age and male sex showed an increasing tendency for more severe fibrosis (F3/F4) in the present cohort. Conclusions: Based on histopathology results, the progression of fibrosis in patients with CHC infected by repeated plasma donation is slow after HCV infection of approximately 20 years. Liver inflammation is closely related to the development of moderate to severe liver fibrosis.

The knee and ankle are the two most injured joints associated with the sport of badminton. This study evaluates biomechanical factors between professional and amateur badminton players using an injury mechanism model. The aim of this study was to investigate the kinematic motion and kinetic loading differences of the right knee and ankle while performing a maximal right lunge. Amateur players exhibited greater ankle range of motion (p

Seed oil content is an important agronomic trait in oilseed rape. However, the molecular mechanism of oil accumulation in rapeseeds is unclear so far. In this report, RNA sequencing technique (RNA-Seq) was performed to explore differentially expressed genes in siliques of two Brassica napus lines (HFA and LFA which contain high and low oil contents in seeds, respectively) at 15 and 25 days after pollination (DAP). The RNA-Seq results showed that 65746 and 66033 genes were detected in siliques of low oil content line at 15 and 25 DAP, and 65236 and 65211 genes were detected in siliques of high oil content line at 15 and 25 DAP, respectively. By comparative analysis, the differentially expressed genes (DEGs) were identified in siliques of these lines. The DEGs were involved in multiple pathways, including metabolic pathways, biosynthesis of secondary metabolic, photosynthesis, pyruvate metabolism, fatty metabolism, glycophospholipid metabolism, and DNA binding. Also, DEGs were related to photosynthesis, starch and sugar metabolism, pyruvate metabolism, and lipid metabolism at different developmental stage, resulting in the differential oil accumulation in seeds. Furthermore, RNA-Seq and qRT-PCR data revealed that some transcription factors positively regulate seed oil content. Thus, our data provide the valuable information for further exploring the molecular mechanism of lipid biosynthesis and oil accumulation in B. nupus.