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Abstract This paper presents a biodegradation study conducted for 90 days under standardized controlled composting conditions of poly (lactic acid) (PLA) filled with functionalized anatase-titania nanofiller (PLA/TiO2 nanocomposites). The surface morphology, thermal properties, percentage of biodegradation, and molecular weight changes at different incubation times were evaluated via visual inspection, scanning electron microscopy (SEM), X-ray diffraction (XRD), differential scanning calorimetry (DSC), and gel permeation chromatography (GPC) by taking degraded samples from compost at the end of target biodegradation time interval. The rapid increase of crystallinity indicated that the PLA and PLA/TiO2 nanocomposites had heterogeneous degradation mechanisms under controlled composting conditions. The biodegradation rate of PLA/TiO2 nanocomposites was higher than that of pure PLA because water molecules easily penetrated the nanocomposites. The dispersion of the nanoparticles in the PLA/TiO2 nanocomposites affected the biodegradation rate of PLA. Moreover, the biodegradation of PLA could be controlled by adding an amount of dispersed TiO2 nanofillers under controlled composting conditions.

In order to solve the problem of safe transmission of telemedicine information in complex field environment, a new communication protocol of wireless sensor network (WSN) is designed in this paper. After the design of the communication protocol, the typical field environment is selected for testing. Based on the propagation characteristics of the wireless channel, the propagation model and attenuation law of WSN radio frequency signal in complex field environment are studied under the premise of fixed communication rate, antenna gain, communication distance, and other parameters. The errors in the actual test are corrected in time to guide the deployment of WSN. The experimental data are fitted by the least square method and linear regression analysis. The experimental results show that the channel models of telemedicine information wireless signals in complex field environment are quite different in different altitudes and a different climate space.

The theoretical analysis of breakdown model for a deep trench superjunction (DT-SJ) SiC VDMOS is presented in this paper. The vertical electric field distribution is derived by the electric field decomposition. Then, a fitting dependence of the critical electric field on the doping concentration for the device is obtained, based on which, the model of breakdown voltage is given for the DT-SJ SiC VDMOS. Analytical results are compared with simulative results with the same thicknesses of drift region from 8 μm to 16 μm and the doping concentrations from 4 × 1016 cm-3 to 8 × 1016 cm-3. It is numerically demonstrated that the errors between model and simulation are less than 3% when N pillar and P pillar have the same width of 1μm.

The location of an acute ischemic stroke is associated with its prognosis. The widely used Gaussian model-based parameter, apparent diffusion coefficient (ADC), cannot reveal microstructural changes in different locations or the degree of infarction. This prospective observational study was reviewed and approved by the Institutional Review Board of Xiamen Second Hospital, China (approval No. 2014002).Diffusion kurtosis imaging (DKI) was used to detect 199 lesions in 156 patients with acute ischemic stroke (61 males and 95 females), mean age 63.15 ± 12.34 years. A total of 199 lesions were located in the periventricular white matter (n = 52), corpus callosum (n = 14), cerebellum (n = 29), basal ganglia and thalamus (n = 21), brainstem (n = 21) and gray-white matter junctions (n = 62). Percentage changes of apparent diffusion coefficient (ΔADC) and DKI-derived indices (fractional anisotropy [ΔFA], mean diffusivity [ΔMD], axial diffusivity [ΔDa], radial diffusivity ΔDr, mean kurtosis [ΔMK], axial kurtosis [ΔKa], and radial kurtosis [ΔKr]) of each lesion were computed relative to the normal contralateral region. The results showed that (1) there was no significant difference in ΔADC, ΔMD, ΔDa or ΔDr among almost all locations. (2) There was significant difference in ΔMK among almost all locations (except basal ganglia and thalamus vs. brain stem; basal ganglia and thalamus vs. gray-white matter junctions; and brainstem vs. gray-white matter junctions. (3) The degree of change in diffusional kurtosis in descending order was as follows: corpus callosum > periventricular white matter > brainstem > gray-white matter junctions > basal ganglia and thalamus > cerebellum. In conclusion, DKI could reveal the differences in microstructure changes among various locations affected by acute ischemic stroke, and performed better than diffusivity among all groups.

In order to enhance the feed’s nutritive value and utilisation efficiency of local straws in Tibet, hulless-barley straw was conserved as silage by mixing with tall fescue and adding the tested additives and their combination. In experiment 1, hulless-barley straw was ensiled with four levels of tall fescue (0, 20, 40 or 60 of fresh weight, FW) in laboratory silos (1 L) for 60 days. The results suggested that 40% hulless-barley straw inclusion of 60% tall fescue was proper for further study. In experiment 2, a mixture of hulless-barley straw and tall fescue (40/60) were treated with (1) no additive (control), (2) fibrolytic enzymes (E, 0.1% FW), (3) molasses (M, 4% FW), (4) Lactobacillus plantarum MTD-1 (Lp, 106 cfu g−1 FW), (5) E + Lp and (6) M + Lp, respectively. Silos were opened after 7, 24, 45 and 60 days of ensiling respectively. The fermentation quality and structural carbohydrates were analysed. After 60 days of ensiling, all the additives except fibrolytic enzymes increased the lactic acid contents, and decreased the pH, ammonia nitrogen and butyric acid contents. All the treated silages had lower neutral detergent fibre, acid detergent fibre, hemicellulose and cellulose contents than that of control, especially in E + Lp and M + Lp treated silages. In conclusion, application of L. plantarum together with fibrolytic enzymes or molasses could further improve the fermentation quality and structural carbohydrate compositions in comparison with using each of the three additives alone.Highlights Enhancing the utilisation efficiency of local straws by mixed silage. Improving the feed’s nutritive value by reducing the crude fibre contents.

This work was aimed to develop levodopa (L-dopa) nasal powder to achieve controllable drug release and high nasal deposition efficiency. A series of uniform microparticles, composed of amorphous L-dopa and excipients of hydroxypropyl methyl cellulose (HPMC), polyvinylpyrrolidone (PVP), or hydroxypropyl-β-cyclodextrin (CD), were fabricated by a self-designed micro-fluidic spray dryer. The effects of excipient type and drug/excipient mass ratio on the particle size, morphology, density, and crystal property, as well as the in vitro performance of drug release, mucoadhesion, and nasal deposition, were investigated. Increased amounts of added excipient, regardless of its type, could accelerate the L-dopa release to different extent. The addition of CD showed the most obvious effect, i.e., ~83% of L-dopa released in 60 min for SD-L1CD2, compared to 37% for raw L-dopa. HPMC could more apparently improve the particle mucoadhesion than PVP and CD, with respective adhesive forces of ~269, 111, and 26 nN for SD-L1H2, -L1P2, and -L1CD2. Nevertheless, the deposition fractions in the olfactory region for such samples were almost the same (~14%), probably ascribable to their quite similar particle aerodynamic diameter (~30 μm). This work demonstrates a feasible methodology for the development of nasal powder.

BackgroundTo compare perioperative, functional and oncological outcomes between transperitoneal robotic partial nephrectomy (TRPN) and retroperitoneal robotic partial nephrectomy (RRPN).MethodsA literature searching of Pubmed, Embase, Cochrane Library and Web of Science was performed in August, 2020. Pooled odds ratios (ORs) or weighted mean differences (WMDs) with 95% confidence intervals (CIs) were estimated using fixed-effect or random-effect model. Publication bias was evaluated with funnel plots. Only comparative studies with matched design or similar baseline characteristics were included.ResultsEleven studies embracing 2,984 patients were included. There was no significant difference between the two groups regarding conversion to open (P = 0.44) or radical (P = 0.31) surgery, all complications (P = 0.06), major complications (P = 0.07), warm ischemia time (P = 0.73), positive surgical margin (P = 0.87), decline in eGFR (P = 0.42), CKD upstaging (P = 0.72), and total recurrence (P = 0.66). Patients undergoing TRPN had a significant higher minor complications (P = 0.04; OR: 1.39; 95% CI, 1.01–1.91), longer operative time (P < 0.001; WMD: 21.68; 95% CI, 11.61 to 31.76), more estimated blood loss (EBL, P = 0.002; WMD: 40.94; 95% CI, 14.87 to 67.01), longer length of hospital stay (LOS, P < 0.001; WMD: 0.86; 95% CI, 0.35 to 1.37). No obvious publication bias was identified.ConclusionRRPN is more favorable than TRPN in terms of less minor complications, shorter operative time, less EBL, and shorter LOS. Methodological limitations of the included studies should be considered while interpreting these results.

BackgroundTo evaluate the efficacy and safety of everolimus, a mTOR inhibitor, on invasive malignant renal epithelioid angiomyolipoma (EAML).Materials and MethodsFrom Oct 2014 to May 2019, we collected data from seven patients with a definite (clinical and pathological) diagnosis of EAML received everolimus in our hospital. Targeted sequence capture array technique with next-generation of high throughput sequencing (NGS) were performed to detect mutations of TSC1/2 genes. All patients had received surgery and everolimus. The clinical efficacy and safety of the therapy were evaluated.ResultsMutations of TSC1 and TSC2 were detected in two and three patients though targeted sequence capture array technique with NGS, respectively. Among seven patients, three had missense mutations, one had nonsense mutation, and one had the large fragment deletion mutation. Five patients accompanied with tuberous sclerosis complex (TSC) were identified. All patients were administered 10mg everolimus once daily, the treatment duration lasted for 3 to 28 months. The objective response was assessed 3 months later, five partial response, two stable disease (SD), the mean greatest tumor diameter of all patients decreased from 9.6 to 5.2cm. Six patients stayed SD and one patient died during follow up. Patients accompanying with TSC had better responses to everolimus compared with non-TSC.ConclusionThe mTOR inhibitor can be an effective treatment for patients with invasive malignant renal EAML. Patients with TSC may benefit more from the therapy.

Alveolar echinococcosis (AE) is a life-threatening disease in humans caused by the larval stage of Echinococcus multilocularis. The tapeworm is transmitted between small mammals and dogs/foxes in the Northern Hemisphere. In this study 286 AE cases were reported from eight counties and one city in Yili Prefecture, Xinjiang Autonomous Region, the People's Republic of China from 1989 to 2015 with an annual incidence (AI) of 0.41/100,000. Among the patients, 73.08% were diagnosed in the last 11 years. Four counties in the high mountainous areas showed higher AI (0.51-1.22 cases/100,000 residents) than the four counties in low level areas (0.19-0.29/100,000 residents). The AI of AE in Mongolian (2.06/100,000 residents) and Kazak (0.93/100,000 residents) ethnic groups was higher than the incidence in other ethnic groups indicating sheep-farming is a risk for infection given this activity is mainly practiced by these two groups in the prefecture. A total of 1411 small mammals were captured with 9.14% infected with E. multilocularis metacestodes. Microtus obscurus was the dominant species in the mountain pasture areas with 15.01% of the voles infected, whereas Mus musculus and Apodemus sylvaticus were the dominant small mammals in the low altitude areas. Only 0.40% of A. sylvaticus were infected with E. multilocularis. PCR amplification and sequencing analysis of the mitochondrial cox1 gene showed that E. multilocularis DNA sequences from the small mammals were identical to isolates of local human AE cases. The overall results show that Yili Prefecture is a highly endemic area for AE and that the high-altitude pasture areas favorable for M. obscurus may play an important role in its transmission in this region.

Double silicon drift layers are used to reduce the specific on-resistance (Ron,sp) for a trench-gate-integrated lateral double-diffused MOSFET (DDL TG LDMOS) based on SOI technology in this paper. A trench-gate is incorporated into the oxide trench, a n-type drift layer with a high doping concentration is introduced on the topside of the original drift layer around the oxide trench, and a p-type pillar layer with a high doping concentration is inserted between the dual drift layers. First, the incorporated trench-gate constitutes dual current conduction channels, which decreases the Ron,sp. Second, the whole electric fields on the device surface and around the oxide trench are modulated on the basis of RESURF condition, leading to a higher breakdown voltage (BV) at off-state. Finally, the doping concentration of the drift layers is increased by an assistant depletion effect from the p-pillar, which not only improves the BV but also reduces the Ron,sp. Consequently, compared with those of the conventional trench SOI LDMOS on the same drift region of 18 μm and top silicon layer of 25 μm, a higher BV of 477 V and a lower Ron,sp of 32.1 mΩ∙cm2 are obtained for the DDL TG SOI LDMOS, while BV is improved by 33.5% and Ron,sp is reduced by 92.9%, respectively.

Multi-modal and controllable shape-morphing constitutes the cornerstone of the functionalization of soft actuators/robots. Involving heterogeneity through material layout is a widely used strategy to generate internal mismatches in active morphing structures. Once triggered by external stimuli, the entire structure undergoes cooperative deformation by minimizing the potential energy. However, the intrinsic limitation of soft materials emerges when it comes to applications such as soft actuators or load-bearing structures that require fast response and large output force. Many researchers have explored the use of the structural principle of snap-through bistability as the morphing mechanisms. Bistable or multi-stable mechanical systems possess more than one local energy minimum and are capable of resting in any of these equilibrium states without external forces. The snap-through motion could overcome energy barriers to switch among these stable or metastable states with dramatically distinct geometries. Attributed to the energy storage and release mechanism, such snap-through transition is quite highly efficient, accompanied by fast response speed, large displacement magnitude, high manipulation strength, and moderate driving force. For example, the shape-morphing timescale of conventional hydrogel systems is usually tens of minutes, while the activation time of hydrogel actuators using the elastic snapping instability strategy can be reduced to below 1 s. By rationally embedding stimuli-responsive inclusions to offer the required trigger energy, various controllable snap-through actuations could be achieved. This review summarizes the current shape-morphing programming strategies based on mismatch strain induced by material heterogeneity, with emphasis on how to leverage snap-through bistability to broaden the applications of the shape-morphing structures in soft robotics and mechanical metamaterials.

With the development of intelligent automotive human-machine systems, driver emotion detection and recognition has become an emerging research topic. Facial expression-based emotion recognition approaches have achieved outstanding results on laboratory-controlled data. However, these studies cannot represent the environment of real driving situations. In order to address this, this paper proposes a facial expression-based on-road driver emotion recognition network called FERDERnet. This method divides the on-road driver facial expression recognition task into three modules: a face detection module that detects the driver’s face, an augmentation-based resampling module that performs data augmentation and resampling, and an emotion recognition module that adopts a deep convolutional neural network pre-trained on FER and CK+ datasets and then fine-tuned as a backbone for driver emotion recognition. This method adopts five different backbone networks as well as an ensemble method. Furthermore, to evaluate the proposed method, this paper collected an on-road driver facial expression dataset, which contains various road scenarios and the corresponding driver’s facial expression during the driving task. Experiments were performed on the on-road driver facial expression dataset that this paper collected. Based on efficiency and accuracy, the proposed FERDERnet with Xception backbone was effective in identifying on-road driver facial expressions and obtained superior performance compared to the baseline networks and some state-of-the-art networks.

To reduce specific on-resistance (Ron,sp) of power devices, a novel SOI (silicon-on-insulator) trench gate LDMOS with heavily doping L-shaped P/N pillars and vertical dual-trench-gates is proposed in this paper, and its physical mechanism and electrical performance are investigated by numerical simulation. The L-shaped P-pillar raises the optimal doping impurity concentration of the drift region (Nd) remarkably from 1.7 × 1015 cm−3 to 1.25 × 1016 cm−3 by causing assistant depletion effect for drift region, hence a lower specific on-resistance (Ron,sp) with a 3.6 mΩ·cm2 is achieved. Meanwhile, the voltage capacity of the new structure is improved resulting from two new electric-field peaks produced by L-shaped P/N pillars. Consequently, a much lower Ron,sp and a higher breakdown voltage (BV) are achieved by the proposed structure. Simulated results show that the Ron,sp, BV, and Baliga’s figure of merit (FOM, FOM = BV2/Ron,sp) for the new structure are improved by 84.3%, 31.4%, and 991%, respectively, in comparison with the conventional trench LDMOS.

Targeting cancer antigens by T cell-engaging bispecific antibody (BiAb) or chimeric antigen receptor T cell therapy has achieved successes in hematological cancers, but attempts to use it to fight solid cancers have been disappointing, in part due to antigen escape. MEK inhibitor had limited activity as a single agent, but enhanced antitumor activity when combined with other therapies, such as targeted drugs or immunotherapy agents. This study aimed to analyze the expression of B7-H3 in non-small-cell lung cancer (NSCLC) and bladder cancer (BC) and to evaluate the combinatorial antitumor effect of B7-H3 × CD3 BiAb with MEK inhibitor trametinib. We found B7-H3 was highly expressed in NSCLC and BC compared with normal samples and its increased expression was associated with poor prognosis. Treatment with trametinib alone could induce apoptosis in tumor cell, while has no effect on T cell proliferation, and a noticeable elevation of B7-H3 expression in tumor cells was also observed following treatment. B7-H3 × CD3 BiAb specifically and efficiently redirected their cytotoxicity against B7-H3 overexpressing tumor cells both in vitro and in xenograft mouse models. While trametinib treatment alone affected tumor growth, the combined therapy increased T cell infiltration and significantly suppressed tumor growth. Together, these data suggest that combination therapy with B7-H3 × CD3 BiAb and MEK inhibitor may serve as a new therapeutic strategy in the future clinical practice for the treatment of NSCLC and BC.

The effect of 3 MeV proton irradiation on interface traps under a Schottky contact in an AlGaN/GaN heterostructure has been investigated in this work. Utilizing the frequency-dependent conductance technique, the detailed information about interface traps under different proton doses has been evaluated. When the proton irradiation dose is increased to 5 × 1014 H+/cm2, it is observed that the deepest energy level of interface traps changes from 0.375 eV to 0.346 eV and the shallowest energy level changes from 0.284 eV to 0.238 eV. The corresponding energy range expands from 0.091 eV to 0.108 eV. Especially, the trap density at the deepest energy level and that at the shallowest energy level are reduced by 65% and 93%, respectively. Transmission electron microscopy and energy dispersive x-ray spectroscopy are also used to assess the Schottky contact interface, and no element inter-diffusion is observed after proton irradiation. The reverse gate leakage current decreases with an increase in the proton irradiation dose, which agrees with the reduction in interface trap density.

Extranodal nasal natural killer (NK)/T cell lymphoma (ENKTCL) is a rare but highly aggressive subtype of non-Hodgkin lymphoma (NHL). Nevertheless, despite extensive research, the estimated 5-year overall survival of affected patients remains low. Therefore, new treatment strategies are needed urgently. Recent advances in immunotherapy have the potential to broaden the applications of chimeric antigen receptor-modified T (CAR-T) cells and the bispecific T-cell engaging (BiTE) antibody. Here, we screened a panel of biomarkers including the B7-H3, CD70, TIM-3, VISTA, ICAM-1, and PD-1 in NKTCL cell lines. As a result, we found for the first time that B7-H3 was highly and homogeneously expressed in these cells. Consequently, we constructed a novel anti-B7-H3/CD3 BiTE antibody and B7-H3-redirected CAR-T cells, and evaluated their efficacy against NKTCL cel lines both in vitro and in vivo. Notably, we found that both anti-B7-H3/CD3 BiTE and B7-H3-redirected CAR-T cells effectively targeted and killed NKTCL cells in vitro, and suppressed the growth of NKTCL tumors in NSG mouse models. Thus, B7-H3 might be a promising therapeutic target for treating patients with NKTCL tumors.

BackgroundCystic echinococcosis is a life-threatening disease caused by the larval stages of the dog tapeworm Echinococcus granulosus. Protoscoleces (PSCs) of this worm have the ability of bi-directional development to either larval cysts or strobilar adult worms. However, the molecular mechanisms underlying this development process are unknown.ResultsRNA and small RNAs sequencing was employed to characterize the gene and miRNA expression at 0–24 h and 7–14 days in the bi-directional development of PSCs. A total of 963 genes and 31 miRNAs were differentially expressed in the early development of PSCs to adult worms whereas 972 genes and 27 miRNAs were differentially expressed in the early development of PSCs to cysts. Pairwise comparison between the two developmental patterns showed that 172 genes and 15 miRNAs were differentially expressed at three time-points. Most of these genes were temporally changed at 24 h or 7 days. GO enrichment analysis revealed that the differentially expressed genes in early adult worm development are associated with nervous system development and carbohydrate metabolic process; whereas, the differentially expressed genes in early cystic development are associated with transmembrane transporter activity and nucleoside triphosphatase activity. In addition, miR-71 and miR-219 regulated genes are likely involved in oxidation reduction in adult worm development.ConclusionThe early stages of bi-directional development in E. granulosus PSCs are controlled by miRNAs and genes likely associated with nervous system development and carbohydrate metabolic process. ATP-dependent transporter genes are associated with cystic development. These results may be important for exploring the mechanisms underlying early development in E. granulosus providing novel information that can be used to discover new therapeutics for controlling cystic echinococcosis.

Background: Cystic echinococcosis (CE), a condition caused by the larval stage of the dog tapeworm Echinococcus granulosus sensu stricto, is a globally distributed zoonotic disease. Current treatment options for CE are limited, and an effective and safe anti-echinococcal drug is urgently required. Methods: Drug repurposing strategy was employed to identify new therapeutic agents against echinococcal cysts. An in vitro protoscolicidal assay along with in vivo murine models was applied in the drug screening. A microinjection procedure was employed to mimic the clinical PAIR (puncture, aspiration, injection and reaspiration) technique to evaluate the potential application of the candidate drug in clinical practice. Findings: We repurposed pyronaridine, an approved antimalarial drug, for the treatment of CE. Following a three-dose intraperitoneal regimen (57 mg/kg, q.d. for 3 days), pyronaridine caused 100% cyst mortality. Oral administration of pyronaridine at 57 mg/kg, q.d. for 30 days significantly reduced the parasitic burden in the pre-infected mice compared with albendazole group (p < 0.001). Using a microinjection of drug into cysts, pyronaridine (200 μM) showed highly effective in term of inhibition of cyst growth (p < 0.05, compared with saline group). Pharmacokinetic analysis revealed that pyronaridine was highly distributed in the liver and lungs, the most affected organs of CE. Function analysis showed that pyronaridine inhibited the activity of topoisomerase I (IC50 = 209.7 ± 1.1 μM). In addition, classical apoptotic hallmarks, including DNA fragmentation and caspase activation, were triggered. Interpretation: Given its approved clinical safety, the repurposing of pyronaridine offers a rapidly translational option for treating CE including PAIR. Fund: National Natural Science Foundation of China and International Cooperation Project of the Qinghai Science and Technology Department. Keywords: Echinococcus granulosus sensu stricto, Pyronaridine, Cystic echinococcosis, Drug repurposing, Topoisomerase I

In recent years, the incidence of hepatitis B (HB) in Guangxi is higher than that of the national level; it has been increasing, so it is urgent to do a good predictive research of HB incidence, which can help analyze the early warning of hepatitis B in Guangxi, China. In the study, the feasibility of predicting HB incidence in Guangxi by autoregressive integrated moving average (ARIMA) model method and Elman neural network (ElmanNN) method was discussed respectively, and the prediction accuracy of the two models was compared. Finally, we established the ARIMA (0, 1, 1) model and ElmanNN with 8 neurons. Both ARIMA (0, 1, 1) model and ElmanNN model had good performance, and their prediction accuracy were high. The fitting and prediction root-mean-square error (RMSE) and mean absolute error (MAE) of ElmanNN were smaller than those of ARIMA (0, 1, 1) model, which indicated that ElmanNN was superior to ARIMA (0, 1, 1) model in predicting the incidence of hepatitis B in Guangxi. Based on the ElmanNN, the HB incidence from September 2019 to December 2020 in Guangxi was predicted, the predicted results showed that the incidence of HB in 2020 was slightly higher than that in 2019 and the change trend was similar to that in 2019, for 2021 and beyond, the ElmanNN model could be used to continue the predictive analysis.

Abstract Objective We conducted a first‐in‐human study to evaluate the bioactivity and safety of B7‐H3‐targeted chimeric antigen receptor (CAR) autologous T cells for treating recurrent anaplastic meningioma. Methods Tumor tissues from a patient with recurrent anaplastic meningioma were evaluated for B7‐H3 expression. B7‐H3‐targeted CAR‐T cells were delivered into the intracranial tumor resection cavity using an Ommaya device at a maximum dose of 1.5 × 107 cells. Magnetic resonance imaging (MRI) screening and multiple serum indexes were regularly monitored. The patient received surgical intervention after three‐cycle infusions, allowing analysis for CAR‐T‐cell infiltration and target antigen expression in post‐CAR‐T therapy tumor tissues. Results Immunochemical analysis demonstrated high and homogeneous B7‐H3 expression in tumor samples. MRI results indicated that the tumor near the delivery device was relatively stable compared with the rapid progression of tumors distant from the device. We found CAR‐T‐cell trafficking to regions of B7‐H3+ tumor tissues near the device, but not to tumor tissues distant from the device. Decreased B7‐H3 expression was observed near the region of CAR‐T‐cell infiltration after therapy. The intracavitary delivery of B7‐H3‐targeted CAR‐T cells was well‐tolerated and not associated with any toxic effects of grade 3 or higher. Conclusion Our results suggested that although intracavitary administration of B7‐H3‐targeted CAR‐T cells was safe and resulted in local bioactivity, addressing antigen loss and CAR‐T‐cell trafficking may further enhance the applications of B7‐H3‐targeted CAR‐T‐cell therapy.

Pregnancy-induced hypertension (PIH) remains the main cause of maternal and fatal mortality. Insulin resistance (IR) and autonomic nervous system (ANS) imbalance are two principal drivers of PIH development. Few previous researches investigated the association between IR and ANS imbalance in Chinese PIH patients. 120 pregnant women were enrolled in our study, sixty healthy pregnant women (control group), fourty one gestational hypertension (GH group) and nineteen preeclampsia patients (PE group). The homeostasis model assessment of IR (HOMA-IR) and markers of ANS (plasma biomarkers and heart rate variability (HRV) components) were collected. Body mass index (BMI), Ln(HOMA-IR), noradrenaline level, LnTP (total power), Ln SDNN (standard deviation of the normal-to-normal interval), LnLF (low frequency), LnLF/LnHF (low frequency/high frequency) were different in the GH and PE groups compared with the controls. Significant correlations were observed between Ln (HOMA-IR) and gestational duration (r = 0.237, P = 0.031), BMI（r = 0.314, P = 0.002), systolic blood pressure (r = 0.108, P = 0.016), noradrenaline (r = 0.451, P = 0.009), LnTP (r = −0.269, P = 0.015) and LnLF/HF (r = 0.183, P = 0.026) in those PIH patients. Furthermore, BMI, noradrenaline and LnTP were independent determinants of Ln(HOMA-IR) in PIH patients by multiple regression analysis. Our finding verified both IR and ANS imbalance were more severe in PIH patients than healthy pregnant women. Moreover, IR had a close association with ANS parameters in PIH patients, suggesting that they probably had contributory effects on the occurrence and development of PIH. We propose that these parameters could be added to the traditional indexes for individualized treatment of PIH patients in the future.

To master theoretical calculation for dust removal efficiency of high pressure atomization in an underground coal mine, the corresponding atomization characteristics and dust removal efficiency were both comprehensively studied in theory by virtue of related theories of hydromechanics and aerosol. According to actual measurements of flow coefficients and atomization angles of X-type swirl nozzle, computational formula was derived for atomized particle sizes of such a nozzle in conjunction with relevant empirical equation. Moreover, a mathematical model for applying high pressure atomization to dust removal in underground coal mine was also established to deduce theoretical computation formula of fractional efficiency. Then, Matlab was adopted to portray the relation curve between fractional efficiency and influence factors. In addition, a theoretical formula was also set up for removal efficiency of respirable dust and total coal dust based on dust size and frequency distribution equations. In the end, impacts of dust characteristic parameters on various dust removal efficiencies were analyzed. Keywords: Underground coal mine, High pressure atomization, Atomization characteristics, Dust removal efficiency

Abstract Background Dogs play a pivotal role in the transmission of cystic echinococcosis (CE), a zoonosis caused by the tapeworm Echinococcus granulosus. We showed previously that dogs vaccinated with two E. granulosus adult-worm specific proteins, EgM9 and EgM123, emulsified with Freund’s adjuvants induced significant protective efficacy in terms of reduction in worm burden and egg production after 45 days post-infection. It was not known whether this protection can be sustained using adjuvants suitable for use in dogs. Methods Recombinant EgM9 and EgM123 were mixed with Quil A or ISCOMs for vaccinating dogs. After three vaccine injections, all the dogs were orally challenge-infected with 200 000 protoscoleces of E. granulosus. After 45 days of infection, all the dogs were euthanized and necropsied for collecting and counting E. granulosus worms. Immunoglobins, including the IgG subclasses IgG1 and IgG2, were detected in the sera of vaccinated dogs by ELISA. To determine whether the protection efficacy could be maintained after 45 days post-infection, we implemented a longevity trial to count eggs in dog faeces for 170 days after infection. Results The dogs vaccinated with EgM9 and EgM123 mixed with Quil A and ISCOMs showed similar protective efficacy as the proteins emulsified with Freund’s adjuvants in our previous study in terms of reduction of worms and eggs at 45 days post-infection. The longevity trial showed that EgM9 protein-vaccinated group released lower number of eggs per gram compared with the egg counts in the control dogs during the dog trial study. Conclusion EgM9 and EgM123 are thus suitable vaccine candidates against E. granulosus infection in dogs.

Abstract Background Multi-contrast images in magnetic resonance imaging (MRI) provide abundant contrast information reflecting the characteristics of the internal tissues of human bodies, and thus have been widely utilized in clinical diagnosis. However, long acquisition time limits the application of multi-contrast MRI. One efficient way to accelerate data acquisition is to under-sample the k-space data and then reconstruct images with sparsity constraint. However, images are compromised at high acceleration factor if images are reconstructed individually. We aim to improve the images with a jointly sparse reconstruction and Graph-based redundant wavelet transform (GBRWT). Methods First, a sparsifying transform, GBRWT, is trained to reflect the similarity of tissue structures in multi-contrast images. Second, joint multi-contrast image reconstruction is formulated as a ℓ2, 1 norm optimization problem under GBRWT representations. Third, the optimization problem is numerically solved using a derived alternating direction method. Results Experimental results in synthetic and in vivo MRI data demonstrate that the proposed joint reconstruction method can achieve lower reconstruction errors and better preserve image structures than the compared joint reconstruction methods. Besides, the proposed method outperforms single image reconstruction with joint sparsity constraint of multi-contrast images. Conclusions The proposed method explores the joint sparsity of multi-contrast MRI images under graph-based redundant wavelet transform and realizes joint sparse reconstruction of multi-contrast images. Experiment demonstrate that the proposed method outperforms the compared joint reconstruction methods as well as individual reconstructions. With this high quality image reconstruction method, it is possible to achieve the high acceleration factors by exploring the complementary information provided by multi-contrast MRI.

Hyperhomocysteinemia is an independent risk factor for cardiovascular impairment in hypertension. Oxidative stress is important in the molecular mechanisms associated with hypertension, but there are few studies focusing on the comparison of oxidative stress biomarkers in hypertensive patients with or without hyperhomocysteinemia. The study included 50 newly diagnosed hypertensive patients with hyperhomocysteinemia, 50 newly diagnosed hypertensive patients without hyperhomocysteinemia, and 50 age-matched healthy controls. Serum levels of malondialdehyde, nitric oxide, 8-isoprostane-F2ɑ, superoxide dismutase, catalase, and glutathione peroxides were compared. Levels of malondialdehyde and 8-isoprostane-F2ɑ were higher in both hypertensive groups than in the control group (8.3 ± 1.8 μmol/L vs. 6.5 ± 1.3 μmol/L vs. 4.3 ± 1.2 μmol/L, P

Abstract By using new Schrödinger type inequalities appearing in Jiang and Usó (J. Inequal. Appl. 2016:233, 2016), we study the existence of weak solutions of stochastic delay differential systems with Schrödinger–Brownian motions.

Objective The impact of forage feeding strategy on growth performance, ruminal fermentation and nutrient digestibility in post-weaning calves was investigated. Methods Forty-five female Holstein calves (body weight [BW] = 79.79±0.38 kg) were enrolled in the 35-d study at one week after weaning and randomly assigned to one of three dietary treatments. All diets were fed as total mixed ration containing 60% (dry matter [DM] basis) of basal starter feed and 40% (DM basis) of forage, but varied in composition of forage source including i) alfalfa (40% DM, AH); ii) alfalfa hay (26.7% DM)+oat hay (13.3% DM; OH); iii) alfalfa hay (26.7% DM)+corn silage (13.3% DM; WS). Results Dry matter intake was not different among treatment groups (p>0.05). However, BW (p

Abstract Background Porcine reproductive and respiratory syndrome virus (PRRSV) causes porcine reproductive and respiratory syndrome (PRRS), which is currently insufficiently controlled. From a previous small-scale screen we identified an effective DNA-based short antisense oligonucleotide (AS-ON) targeting viral NSP9, which could inhibit PRRSV replication in both Marc-145 cells and pulmonary alveolar macrophages (PAMs). The objective of this study was to explore the strategy of incorporating locked nucleic acids (LNAs) to achieve better inhibition of PRRSV replication in vitro. Methods The effective DNA-based AS-ON (YN8) was modified with LNAs at both ends as gap-mer (LNA-YN8-A) or as mix-mer (LNA-YN8-B). Marc-145 cells or PAMs were infected with PRRSV and subsequently transfected. Results Compared with the DNA-based YN8 control, the two AS-ONs modified with LNAs were found to be significantly more effective in decreasing the cytopathic effect (CPE) induced by PRRSV and thus in maintaining cell viability. LNA modifications conferred longer lifetimes to the AS-ON in the cell culture model. Viral ORF7 levels were more significantly reduced at both RNA and protein levels as shown by quantitative PCR, western blot and indirect immunofluorescence staining. Moreover, transfection with LNA modified AS-ON reduced the PRRSV titer by 10-fold compared with the YN8 control. Conclusion Taken together, incorporation of LNA into AS-ON technology holds higher therapeutic promise for PRRS control.

Background/Aims: Multiple exposures to anesthesia in children may increase the risk of developing cognitive impairment. Sevoflurane is an anesthetic that is commonly used in children during surgery. Cyclin-dependent kinase (CDK) 5 is involved in the regulation of sevoflurane-induced cognitive dysfunction, but the mechanistic details remain unclear. The present study evaluated the mechanism by which CDK5 mediates sevoflurane-induced cognitive dysfunction in mice. Methods: Hippocampal neurons were isolated from postnatal day 0 C57BL/6 mouse pups. Six-day-old wild-type mice were exposed to sevoflurane and then treated with the CDK5 inhibitor roscovitine. The effects on cognitive function were evaluated with the Morris water maze and neuronal damage in the hippocampus was assessed by immunohistochemical analysis. Results: CDK5 activation increased neuronal damage by inducing Tau/glycogen synthase kinase (GSK) 3β and suppressing extracellular signal-regulated kinase (ERK)/peroxisome proliferator-activated receptor (PPAR)γ/cyclic AMP response element-binding protein (CREB) signaling following exposure to sevoflurane. CDK5 inhibition by roscovitine administration alleviated sevoflurane-induced neuronal damage and cognitive impairment. Conclusions: Inhibiting CDK5 with roscovitine has neuroprotective effects against neuronal injury and cognitive dysfunction caused by sevoflurane anesthesia that are exerted via modulation of Tau/GSK3β and ERK/PPARγ/CREB signaling.

This study was conducted to evaluate the potential of hydrolysable tannin (chestnut tannin, CHT) without or with condensed tannin (quebracho tannin, QT) for modulating alfalfa silage fermentation characteristics and in vitro ruminal methane (CH4) production, fermentation profile, and microbiota. Alfalfa (235 g/kg fresh weight) was ensiled with no tannins (control), 2% CHT (CHT2), 5% CHT (CHT5), the combination of CHT and QT at 1% each (CHQ2), and CHT and QT at 2.5% each (CHQ5) of forage dry matter (DM). The CHQ2 treatment was more effective in reducing DM losses, pH, and ammonia–nitrogen to total nitrogen ratios of alfalfa silage than CHT2 and CHT5 treatments. All tannin treatments decreased ruminal CH4 production, and the magnitude of the decrease was greater for the combinations than the individual ones. Total volatile fatty acid (VFA) concentrations and DM degradation decreased by tannin treatments, but microbial protein (MCP) synthesis increased. The total VFA concentrations and DM degradation were lower with CHQ2 treatment than with CHT5 and CHQ5 treatments, but the MCP concentrations were comparable among these treatments. Tannin inclusion decreased the abundance of the anaerobic fungi Ruminococcus albus and Ruminococcus flavefaciens, but enhanced Fibrobacter succinogenes. The combination of CHT and QT alleviated the inhibition of CHT supply alone in Butyrivibrio fibrisolvens, Ruminobacer amylophilus, and Prevotella ruminicola as well as protease. The results revealed that a combination of HT from CHT and CT from QT at a low level can reduce proteolysis and CH4 production of alfalfa silage without impairing ruminal fermentation and microbiota.

BRAF-V600E (1799T > A) is one of the most frequently reported driver mutations in multiple types of cancers, and patients with such mutations could benefit from selectively inactivating the mutant allele. Near this mutation site, there are two TTTN and one NGG protospacer-adjacent motifs (PAMs) for Cpf1 and Cas9 CRISPR nucleases, respectively. The 1799T > A substitution also leads to the occurrence of a novel NGNG PAM for the EQR variant of Cas9. We examined the editing efficacy and selectivity of Cpf1, Cas9, and EQR variant to this mutation site. Only Cpf1 demonstrated robust activity to induce specific disruption of only mutant BRAF, not wild-type sequence. Cas9 recognized and cut both normal and mutant alleles, and no obvious gene editing events were observed using EQR variant. Our results support the potential applicability of Cpf1 in precision medicine through highly specific inactivation of many other gain-of-function mutations. Keywords: Cpf1, targeted therapy, BRAF V600E

Abstract Background The objective of the present study was to estimate (co)variance components of female fertility traits in Chinese Holsteins, considering fertility traits in different parities as different traits. Data on 88,647 females with 215,632 records (parities) were collected during 2000 to 2014 from 32 herds in the Sanyuan Lvhe Dairy Cattle Center, Beijing, China. The analyzed female fertility traits included interval from calving to first insemination, interval from first to last insemination, days open, conception rate at first insemination, number of inseminations per conception and non-return rates within 56 days after first insemination. Results The descriptive statistics showed that the average fertility of heifers was superior to that of cows. Moreover, the genetic correlations between the performances of a trait in heifers and in cows were all moderate to high but far from one, which suggested that the performances of a trait in heifers and cows should be considered as different but genetically correlated traits in genetic evaluations. On the other hand, genetic correlations between performances of a trait in different parities of cows were greater than 0.87, with only a few exceptions, but variances were not homogeneous across parities for some traits. The estimated heritabilities of female fertility traits were low; all were below 0.049 (except for interval from calving to first insemination). Additionally, the heritabilities of the heifer interval traits were lower than those of the corresponding cow interval traits. Moreover, the heritabilities of the interval traits were higher than those of the threshold traits when measuring similar fertility functions. In general, estimated genetic correlations between traits were highly consistent with the biological categories of the female fertility traits. Conclusions Interval from calving to first insemination, interval from first to last insemination and non-return rates within 56 days after first insemination are recommended to be included in the selection index of the Chinese Holstein population. The parameters estimated in the present study will facilitate the development of a genetic evaluation system for female fertility traits to improve the reproduction efficiency of Chinese Holsteins.

Abstract Fibroblastic reticular cells (FRCs) in the T cell zone of lymph nodes (LNs) are pivotal for T cell survival, mobility, and peripheral tolerance. Here, we demonstrate that during homeostasis, FRCs also suppress T cell activation via producing high level of prostaglandin E2 (PGE2) due to their thousands-fold higher cyclooxygenase-2 (COX-2) expression than immune cells. This hyperactive COX-2/PGE2-induced suppression is evident during antigen-specific and non-antigen-specific activations. It is implicated as suppressed TCR-signaling cascades, reduced alterations in activation markers, and inhibited cytokine production of freshly isolated T cells or T cells co-cultured with FRCs compared with those cultured without FRCs. Different from T cell dysfunction, this FRC-mediated suppression is surmountable by enhancing the strength of stimulation and is reversible by COX-2 inhibitors. Furthermore, T cells in the FRC environment where Cox-2 is genetic inactivated are more sensitive and rapidly activated upon stimulations than those in WT environment. Significantly, FRCs of human lymphoid organs manifest similar COX-2/PGE2 hyperactivity and T cell suppression. Together, this study identifies a previously unappreciated intrinsic mechanism of FRCs shared between mice and humans for suppressing T cell sensitivity to activation via PGE2, underscoring the importance of FRCs in shaping the suppressive milieu of lymphoid organs during homeostasis.

Objective Four lactic acid bacteria (LAB) strains isolated from common vetch, tall fescue and perennial ryegrass on the Tibetan Plateau were characterized, and their effects on the fermentation quality of Italian ryegrass (Lolium multiflorum Lam.) silage were studied. Methods The four isolated strains and one commercial inoculant (G, Lactobacillus plantarum MTD-1) were evaluated using the acid production ability test, morphological observation, Gram staining, physiological, biochemical and acid tolerance tests. The five LAB strains were added to Italian ryegrass for ensiling at three different temperatures (10°C, 15°C, and 25°C). Results All isolated strains (LCG3, LTG7, I5, and LI3) could grow at 5°C to 20°C, pH 3.0 to 8.0 and NaCl (3.0%, 6.5%). Strains LCG3, LTG7, I5, and LI3 were identified as Lactobacillus plantarum, Pediococcus acidilactici, Lactobacillus paraplantarum, and Lactobacillus casei by sequencing 16S rDNA, respectively. All LAB inoculants significantly (p

Abstract Pulmonary fibrosis is a kind of devastating interstitial lung disease due to the limited therapeutic strategies. Traditional Chinese medicine (TCM) practices have put forth Shenks as a promising treatment approach. Here, we performed in vivo study and in vitro study to delineate the anti-fibrotic mechanisms behind Shenks treatment for pulmonary fibrosis. We found that regardless of the prophylactic or therapeutic treatment, Shenks was able to attenuate BLM-induced-fibrosis in mice, down regulate extracellular matrix genes expression, and reduce collagen production. The aberrantly high Smad3 phosphorylation levels and SBE activity in TGF-β-induced fibroblasts were dramatically decreased as a result of Shenks treatment. At the same time, Shenks was able to increase the expression of antioxidant-related genes, including Gclc and Ec-sod, while reduce the transcription levels of oxidative-related genes, such as Rac1 and Nox4 demonstrated by both in vivo and in vitro studies. Further investigations found that Shenks could decrease the oxidative productions of protein (3-nitrotyrosine) and lipid (malondialdehyde) and increase GSH content both in bleomycin treated mouse lungs and TGF-β stimulated fibroblasts, as well as inhibit the production of ROS stimulated by TGF-β to fight against oxidative stress. Overall, Shenks inhibited fibrosis by blocking TGF-β pathway and modulating the oxidant/antioxidant balance.

Abstracts Stress, including both psychological and physical stimulation, can cause changes in the microbiota and mucosal function of the gastrointestinal system. There are few research studies available about the faecal microbiota changes after stress, such as water immersion restraint stress (WIRS). Therefore, in this study, we focused on analysing the composition changes of faecal microbiota in WIRS mice. The WIRS model, in which Blab/c mice were immersed in 21 ± 2 °C water for 4 h each day for 14 days, was established. Behavioural changes, the serum levels of corticosterone, IFN-γ and IL-17 and gastric mucosal injury were also assessed. Ten faecal microbiota samples were detected by Illumina Miseq sequencing of the 16S rRNA genes from 367205 characterised sequences. Finally, we find significant differences in the faecal microbiota composition between the control and the WIRS groups. There was an obvious increase in Lachnospiraceae in the WIRS mice (p = 0.0286, p

This experiment was conducted to study the effect of molasses on the fermentation characteristics of mixed silage ensiled rice straw and vegetable by-products with alfalfa. Mixture (202 g kg−1 dry matter (DM)) consisting of rice straw, broccoli residue and alfalfa at the ratio of 5:4:1 was ensiled with three experimental treatments: (1) no additives (control); (2) molasses at 2.5% (M1); (3) molasses at 5% (M2) on a fresh matter basis of mixture, respectively. All treatments were packed into laboratory-scale silos, and three silos per treatment were sampled on days 1, 3, 5, 14 and 30. The result showed that the pH value of all mixed silages decreased gradually with the time of ensiling except for the control silage, in which a significant increase (P

Dexamethasone acetate (DA) produces neuroprotective effects by inhibiting lipid peroxidation and inflammation by reducing cytokine release and expression. However, its clinical application is limited by its hydrophobicity, low biocompatibility and numerous side effects when using large dosage. Therefore, improving DA’s water solubility, biocompatibility and reducing its side effects are important goals that will improve its clinical utility. The objective of this study is to use a biodegradable polymer as the delivery vehicle for DA to achieve the synergism between inhibiting lipid peroxidation and inflammation effects of the hydrophobic-loaded drugs and the amphipathic delivery vehicle. We successfully prepared DA-loaded polymeric micelles (DA/MPEG-PCL micelles) with monodispersed and approximately 25 nm in diameter, and released DA over an extended period in vitro. Additionally, in the hemisection spinal cord injury (SCI) model, DA micelles were more effective in promoting hindlimb functional recover, reducing glial scar and cyst formation in injured site, decreasing neuron lose and promoting axon regeneration. Therefore, our data suggest that DA/MPEG-PCL micelles have the potential to be applied clinically in SCI therapy.

Inflammaging is well understood in the study of humans; however, it is rarely reported for dairy cows. To understand the changing pattern of the gut microbiota, inflammatory status and milk production performance during the aging process in cows, we grouped 180 cows according to their lactation period: L1 (n = 60, 1st lactation), L3 (n = 60, 3rd lactation), and L5+ (n = 60, at least 5th lactation) and analyzed their milk components and daily milk yields to evaluate the changing pattern of milk production. The microbiota was analyzed using high-throughput sequencing of amplicons of 16S rRNA, which also allowed us to predict the functions of microbes and then study the changing pattern of the ruminal and fecal microbiota. Serum cytokines, including TNF-α, IL-6, IL-10, and TGF-β were measured to study the progress of inflammaging in the cows. We found that old cows (L5+) suffered from a long-term and low-level chronic inflammation, as indicated by significantly higher levels of inflammatory cytokines IL-10, TNF-α, and TGF-β in the L5+ group (p < 0.001). We also observed a significant decrease in daily milk yield and milk lactose, as well as a significant increase in somatic cell score, among the cows in the L5+ group. For the gut microbiota, most of the genera belonging to Prevotellaceae and Lachnospiraceae, which had a higher abundance among cows of both the L1 and L3 groups (LEfSe, LDA > 2), showed a similar change pattern during the aging process, both in the rumen and in feces, and across the six farms. Beneficial bacteria, like Bacteroidaceae, Eubacterium, and Bifidobacterium, displayed lower abundance in the feces of the L5+ group (LEfSe, LDA > 2). Reconstruction of the fecal bacteria community indicated transformation of the fermenting pattern of older cows’ (L5+) feces microbiota, with increased functions related the protein metabolism and fewer functions related to carbohydrate and lipid metabolism compared with those in L1 (p < 0.05). Finally, the connections among these changing patterns were revealed using redundancy analysis and network analysis. The results support the hypothesis of prolonging a cows’ productive life and improve dairy cow milk productive performances by manipulating the gut microbiota.

Schizophrenic subject is thought as a self-disorder patient related with abnormal brain functional network. It has been hypothesized that self-disorder is associated with the deficient functional integration of multisensory body signals in schizophrenic subjects. To further verify this assumption, 53 chronic schizophrenic subjects and 67 healthy subjects were included in this study and underwent resting-state functional magnetic resonance imaging. The data-driven methods, whole-brain temporal variability of fractional amplitude of low-frequency fluctuations and regional homogeneity (ReHo), were used to investigate dynamic local functional connectivity and dynamic local functional activity changes in schizophrenic subjects. Patients with schizophrenia exhibited increased temporal variability ReHo and fractional amplitude of low-frequency fluctuations across time windows within sensory and perception network (such as occipital gyrus, precentral and postcentral gyri, superior temporal gyrus, and thalamus). Critically, the increased dynamic ReHo of thalamus is significantly correlated with positive and total symptom of schizophrenic subjects. Our findings revealed that deficit in sensory and perception functional networks might contribute to neural physiopathology of self-disorder in schizophrenic subjects.

Neonatal-streptozotocin (n-STZ)-induced diabetes mimics most of the clinicopathological symptoms of type 2 diabetes mellitus (T2DM) peripheral neuropathy. Berberine, a plant alkaloid, is reported to have antidiabetic, antioxidant, anti-inflammatory, and neuroprotective potential. The aim of the present study was to investigate the potential of berberine against n-STZ-induced painful diabetic peripheral polyneuropathy by assessing various biochemical, electrophysiological, morphological, and ultrastructural studies. Type 2 diabetes mellitus was produced neonatal at the age of 2 days (10-12 g) by STZ (90 mg/kg intraperitoneal). After confirmation of neuropathy at 6 weeks, rats were treated with berberine (10, 20, and 40 mg/kg). Administration of n-STZ resulted in T2DM-induced neuropathic pain reflected by a significant alterations ( P < .05) in hyperalgesia, allodynia, and motor as well as sensory nerve conduction velocities whereas berberine (20 and 40 mg/kg) treatment significantly attenuated ( P < .05) these alterations. Berberine treatment significantly inhibited ( P < .05) STZ-induced alterations in aldose reductase, glycated hemoglobin, serum insulin, hepatic cholesterol, and triglyceride levels. The elevated oxido-nitrosative stress and decreased Na-K-ATPase and pulse Ox levels were significantly attenuated ( P < .05) by berberine. It also significantly downregulated ( P < .05) neural tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6 messenger RNA (mRNA), and protein expressions both. Streptozotocin-induced downregulated mRNA expressions of brain-derived neurotrophic factor (BDNF), insulin-like growth factor (IGF-1), and peroxisome proliferator-activated receptors-γ (PPAR-γ) in sciatic nerve were significantly upregulated ( P < .05) by berberine. Western blot analysis revealed that STZ-induced alterations in adenosine monophosphate protein kinase (AMPK; Thr-172) and protein phosphatase 2C-α protein expressions in dorsal root ganglia were inhibited by berberine. It also attenuated histological and ultrastructural alterations induced in sciatic nerve by STZ. In conclusion, berberine exerts its neuroprotective effect against n-STZ-induced diabetic peripheral neuropathy via modulation of pro-inflammatory cytokines (TNF α, IL-1β, and IL-6), oxido-nitrosative stress, BDNF, IGF-1, PPAR-γ, and AMPK expression to ameliorate impaired allodynia, hyperalgesia, and nerve conduction velocity during T2DM.

A rising amount of evidences show that gut microbiota is an important factor in mediating the growth of ulcerative colitis (UC), the major product of colon bacteria fermentation butyrate as mediator have effects on the mucosal immune system by expanding regulatory T cells (Treg) in the colon. Turkish galls, an insect gall parasitized on the tree branches of Quercus infectoria Oliv., exhibiting the promising prospect in treating the remedy of UC by regulating the bacteria, whereas its mechanism remains unclear. Here, this work found that three types of gut bacteria collaborating to improve DSS-induced UC in mice after Turkish galls intervention, including putative SCFAs-producing bacteria (PCPB), anti-inflammatory bacteria and harmful bacteria. The Helicobacter, Bilophila, Acinetobacter and Odoribacter, which belong to the harmful bacteria were dramatically increased in UC group, whereas the harmful bacteria were reduced after treatment with Turkish galls. The Allobaculum, Bacteriodes, Blautia, Butyricimonas, belonging to PCPB, were significantly increased after Turkish galls and butyrate intervention, and we also observed that the concentration of butyrate increased with the grows of PCPB. The Bifidobacterium, Lactococcus, which belong to the anti-inflammatory bacteria, were also significantly increased after Turkish galls intervention. Meanwhile, rectal administration of Turkish galls and butyrate could increase mucosa inflammation and diarrhea. The expression of cytokines in the colon was improved by butyrate and Turkish galls treatment group. The percentage of Treg out of CD4+ population was evaluated by flow cytometry after Turkish galls and butyrate intervention. The results suggested that Turkish galls alleviated UC by modulating three types of the gut microbiota, and butyrate may be used to relieve inflammatory. This study may help us to understand the mechanism of Turkish galls in treating UC from the perspective of intestinal flora and also offered a mechanism reference for UC treatment using an insect gall in rich of polyphenolic compounds.

Head and neck squamous cell carcinomas (HNSCCs) are highly aggressive, multi-factorial tumors in the upper aerodigestive tract affecting more than half a million patients worldwide each year. Alcohol, tobacco, and human papillomavirus (HPV) infection are well known causative factors for HNSCCs. Current treatment options for HNSCCs are surgery, radiotherapy, chemotherapy, or combinatorial remedies. Over the past decade, despite the marked improvement in clinical outcome of many tumor types, the overall 5-year survival rate of HNSCCs remained ∼40–50% largely due to poor availability of effective therapeutic options for HNSCC patients with recurrent disease. Therefore, there is an urgent and unmet need for the identification of specific molecular signatures that better predict the clinical outcomes and markers that serve as better therapeutic targets. With recent technological advances in genomic and epigenetic analyses, our knowledge of HNSCC molecular characteristics and classification has been greatly enriched. Clinical and genomic meta-analysis of multicohort HNSCC gene expression profile has clearly demonstrated that HPV+ and HPV- HNSCCs are not only derived from tissues of different anatomical regions, but also present with different mutation profiles, molecular characteristics, immune landscapes, and clinical prognosis. Here, we briefly review our current understanding of the biology, molecular profile, and immunological landscape of the HPV+ and HPV- HNSCCs with an emphasis on the diversity and heterogeneity of HNSCC clinicopathology and therapeutic responses. After a review of recent advances and specific challenges for effective immunotherapy of HNSCCs, we then conclude with a discussion on the need to further enhance our understanding of the unique characteristics of HNSCC heterogeneity and the plasticity of immune landscape. Increased knowledge regarding the immunological characteristics of HPV+ and HPV- HNSCCs would improve therapeutic targeting and immunotherapy strategies for different subtypes of HNSCCs.

Cystic echinococcosis (CE) is a chronic infectious disease caused by Echinococcus granulosus. To confirm whether the infection impacts on the gut microbiota, we established a mouse model of E. granulosus infection in this study whereby BALB/c mice were infected with micro-cysts of E. granulosus. After 4 months of infection, fecal samples were collected for high-throughput sequencing of the hypervariable regions of the 16S rRNA gene. Sequence analysis revealed a total of 13,353 operational taxonomic units (OTUs) with only 40.6% of the OTUs having genera reference information and 101 of the OTUs were significantly increased in infected mice. Bioinformatics analysis showed that the common core microbiota were not significantly changed at family level. However, two genera (Eisenbergiella and Parabacteroides) were enriched in the infected mice (PAMOV A < 0.05) at genus level. Functional analysis indicated that seven pathways were altered in the E. granulosus Infection Group compared with the Uninfected Group. Spearman correlation analysis showed strong correlations of IgG, IgG1 and IgG2a with nine major genera. E. granulosus cyst infection may change the gut microbiota which may be associated with metabolic pathways.

Mild cognitive impairment (MCI) is the prodromal stage of Alzheimer’s disease (AD). Identifying MCI subjects who are at high risk of converting to AD is crucial for effective treatments. In this study, a deep learning approach based on convolutional neural networks (CNN), is designed to accurately predict MCI-to-AD conversion with magnetic resonance imaging (MRI) data. First, MRI images are prepared with age-correction and other processing. Second, local patches, which are assembled into 2.5 dimensions, are extracted from these images. Then, the patches from AD and normal controls (NC) are used to train a CNN to identify deep learning features of MCI subjects. After that, structural brain image features are mined with FreeSurfer to assist CNN. Finally, both types of features are fed into an extreme learning machine classifier to predict the AD conversion. The proposed approach is validated on the standardized MRI datasets from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) project. This approach achieves an accuracy of 79.9% and an area under the receiver operating characteristic curve (AUC) of 86.1% in leave-one-out cross validations. Compared with other state-of-the-art methods, the proposed one outperforms others with higher accuracy and AUC, while keeping a good balance between the sensitivity and specificity. Results demonstrate great potentials of the proposed CNN-based approach for the prediction of MCI-to-AD conversion with solely MRI data. Age correction and assisted structural brain image features can boost the prediction performance of CNN.

Antimicrobial peptides (AMPs), which are evolutionarily conserved components of the innate immune response, contribute to the first line of defense against microbes in the skin and at mucosal surfaces. Here, we report the identification of a human peptide, encoded by the chromosome 5 open reading frame 46 (C5orf46) gene, as a type of AMP, which we termed antimicrobial peptide with 64 amino acid residues (AP-64). AP-64 is an anionic amphiphilic peptide lacking cysteines (MW = 7.2, PI = 4.54). AP-64 exhibited significant antibacterial activity against Gram-negative bacteria, including Escherichia coli DH5α, Escherichia coli O157:H7, Vibrio cholerae, and Pseudomonas aeruginosa. Moreover, AP-64 was efficient in combating Escherichia coli O157:H7 infections in a mouse model and exhibited cytotoxic effects against human T-cell lymphoma Jurkat and B-cell lymphoma Raji cells. We also observed that Gm94, encoded by mouse C5orf46 homologous gene, closely resembles AP-64 in its antibacterial properties. Compared with other human AMPs, AP-64 has distinct characteristics, including a longer sequence length, absence of cysteine residues, a highly anionic character, and cell toxicity. Together, this study identified that AP-64 is an AMP worthy of further investigation.

The use of conceptual scheme evaluation is a key step in the development of new products. In this paper, a multi-dimensional evaluation method that involves subjective evaluation, eye-tracking, and product image evaluation is established. In this study, subjective evaluation is used to test customers’ initial reactions to conceptual schemes, and eye- tracking is used to highlight the features of conceptual schemes that are most attractive to customers. With the help of Kansei engineering, the most attractive features of a particular product are described and clarified from the product image evaluation. This multi- dimensional method can be applied not only in screening conceptual schemes, but also in exploring the reasons and suggestions for product improvement. The method was assessed in this study through a case study evaluation of conceptual design schemes for a mobile phone.

Objective To analyze the effect of intensive lipid regulation treatment with atorvastatin on the blood lipid levels and carotid artery plaques in patients with atherosclerotic cerebral infarction. Methods Ninety-two patients with atherosclerotic cerebral infarction were randomly divided into two groups: observation group (treated by atorvastatin calcium with the dosage of 20 mg/d, N = 46) and control group (treated by diet without lipid-rich food, N=46). Besides, other drugs given to the patients in two groups were the same. The blood lipid levels and the changes of carotid artery plaques in two groups were analyzed and compared before treatment and 3 months after treatment. Results After treatment, the concentrations of total cholesterol [TC, (4.23 ± 0.92) mmol/L vs (5.24 ± 0.68) mmol/L], triglyceride [TG, (2.46 ± 0.28) mmol/L vs (3.33 ± 0.47) mmol/L], low-density lipoprotein cholesterol [LDL-C, (2.52 ± 0.38) mmol/L vs (4.78 ± 0.86) mmol/L] in the patients of observation group were all decreased and significantly lower than those in the control group (P = 0.000, for all), and the concentration of high-density lipoprotein cholesterol [HDL-C, (1.13 ± 0.41) mmol/L vs (0.85 ± 0.32) mmol/L] in the patients of observation group was increased and significantly than that in the control group (P = 0.003). The carotid artery plaque size [(20.25 ± 0.32) mm2 vs (24.42 ± 10.33) mm2] and thickness [(0.59 ± 0.13) mm vs (1.93 ± 0.23) mm] of carotid artery plaques and intima?media thickness [IMT, (1.32 ± 0.67) mm vs (1.63 ± 0.56) mm] of common carotid artery (CCA) in the patients of observation group were all significantly lower than those in patients in the control group (P = 0.000, 0.000, 0.010, respectively). Comparing serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatine kinase (CK) and creatinine (Cr) levels after treatment with before treatment, there was no significant difference between 2 groups (P > 0.05, for all). Conclusions Atorvastatin can effectively improve the abnormal blood lipids and soften or even lessen the carotid artery plaques in patients with atherosclerotic cerebral infarction, therefore it is helpful to the second prevention of cerebral infarction with no obvious adverse reactions. DOI: 10.3969/j.issn.1672-6731.2015.11.014

Remote sensing is an important method for monitoring marine oil-spill accidents. However, methods for measuring oil-film thickness remain insufficient. Due to the stable differences in the surface emissivity and temperature of oil and water, the oil film can be detected using thermal infrared. This study measured emissivity of seven different oil-film thicknesses and seven different American Petroleum Institute (API) densities, and analyzed the spectral characteristics. Results show an optimal wavelength position for oil-film thickness and fuel API density monitoring is 12.55 μm. Principal component analysis and continuum removal methods were used for data processing. Stepwise multiple linear regression was used to establish relationships between emissivity and oil slick thicknesses and API densities. Oil-film thickness and fuel API density data were analyzed by principal component analysis and continuum removal before regression analysis. The spectral emissivity data was convolved into Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) and Advanced Very High Resolution Radiometer (AVHRR) thermal bands to determine potential of the sensor in oil-film detection. The result shows that neither could be used to estimate thickness. The AVHRR-4 band and band 12 and 13 of the ASTER could be used to separate oils from water and have potential to distinguish different oil types.