Search

Patulin (PAT) is one of mycotoxins that usually contaminates apple juice, and it is not easily detoxified by cysteine (CYS) at room temperature due to the highly acidic conditions based on the Michael addition reaction. However, it could be effectively degraded by a heating treatment at 120 °C for 30 min in the presence of cysteine. In our study, a total of eight degradation products (DP A–H) were characterized and identified via liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS) in a negative ion mode, and their structures and formulas were proposed based on their accurate mass data. The fragmentation patterns of PAT and its degradation products were obtained from the MS/MS analysis. Meanwhile, the possible reaction mechanisms involved in the degradation of PAT were established and explained for the first time. According to the relation between the structure and toxicity of PAT, it could be deduced that the toxic effects of PAT degradation products were potentially much less than those of PAT-self.

The stability and wide temperature performance range of solid electrolytes are the keys to the development of high-energy density all-solid-state lithium-ion batteries. In this work, a PVDF-HFP-LiClO4-Li6.4La3Zr1.4Ta0.6O12 (LLZTO) composite solid electrolyte was prepared using the solution pouring method. The PVDF-HFP-LiClO4-LLZTO composite solid electrolyte shows excellent electrochemical performance in the temperature range of 30 to 60 °C. By assembling this electrolyte into the battery, the LiFePO4/PVDF-HFP-LiClO4-LLZTO/Li battery shows outstanding electrochemical performance in the temperature range of 30 to 60 °C. The ionic conductivity of the composite electrolyte membrane at 30 °C and 60 °C is 5.5 × 10−5 S cm−1 and 1.0 × 10−5 S cm−1, respectively. At a current density of 0.2 C, the LiFePO4/PVDF-HFP-LiClO4-LLZTO/Li battery shows a high initial specific discharge capacity of 133.3 and 167.2 mAh g−1 at 30 °C and 60 °C, respectively. After 50 cycles, the reversible electrochemical capacity of the battery is 121.5 and 154.6 mAh g−1 at 30 °C and 60 °C; the corresponding capacity retention rates are 91.2% and 92.5%, respectively. Therefore, this work provides an effective strategy for the design and preparation of solid-state lithium-ion batteries.

Hypoxia-inducible factor 1α (HIF-1α) plays pivotal roles in maintaining pluripotency, and the developmental potential of pluripotent stem cells (PSCs). However, the mechanisms underlying HIF-1α regulation of neural stem cell (NSC) differentiation of human induced pluripotent stem cells (hiPSCs) remains unclear. In this study, we demonstrated that HIF-1α knockdown significantly inhibits the pluripotency and self-renewal potential of hiPSCs. We further uncovered that the disruption of HIF-1α promotes the NSC differentiation and development potential in vitro and in vivo. Mechanistically, HIF-1α knockdown significantly enhances mitofusin2 (MFN2)-mediated Wnt/β-catenin signaling, and excessive mitochondrial fusion could also promote the NSC differentiation potential of hiPSCs via activating the β-catenin signaling. Additionally, MFN2 significantly reverses the effects of HIF-1α overexpression on the NSC differentiation potential and β-catenin activity of hiPSCs. Furthermore, Wnt/β-catenin signaling inhibition could also reverse the effects of HIF-1α knockdown on the NSC differentiation potential of hiPSCs. This study provided a novel strategy for improving the directed differentiation efficiency of functional NSCs. These findings are important for the development of potential clinical interventions for neurological diseases caused by metabolic disorders.

PurposeThe prognosis for small cell lung cancer (SCLC) patients receiving later-line treatment is very poor and there is still no standard treatments after the second-line setting. Analyzing the susceptibility of chemotherapeutic drugs with circulating tumor cells (CTCs) cultured in vitro may contribute to optimize the therapeutic regimen. However, so far CTCs have been barely used for studying their chemosensitivity due to the lack of technology to obtain wholly intact and viable CTCs.MethodsBased on a retrospective study of the therapeutic response of 99 patients with unresectable SCLC, the CTC count in 14 SCLC patients was detected before and after chemotherapy to evaluate its role as a potential marker of response. Furthermore, the drug susceptibility of CTCs cultured in vitro obtained from ClearCell FX® System was tested and the therapy response was evaluated.ResultsAll of the 99 patients received the first-line chemotherapy and the objective response rate (ORR) was 74.7%. A total of 36 patients received the second-line therapy and the average duration was 2.6 months, and only 11 cases out of them received the third-line therapy but no one responded. The change of CTC counts was identified to be correlated with therapy response. However all the five SCLC patients who were administered with the drugs according to the drug susceptibility test of CTCs for two cycles underwent progression of disease.ConclusionThe results showed that the responses of chemotherapy are very poor in later lines and the drug susceptibility test using CTCs primary cultured in vitro may not benefit the improvement of therapeutic regimen of SCLC patients.

Summary: There is an urgent need for antivirals to treat the newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To identify new candidates, we screen a repurposing library of ∼3,000 drugs. Screening in Vero cells finds few antivirals, while screening in human Huh7.5 cells validates 23 diverse antiviral drugs. Extending our studies to lung epithelial cells, we find that there are major differences in drug sensitivity and entry pathways used by SARS-CoV-2 in these cells. Entry in lung epithelial Calu-3 cells is pH independent and requires TMPRSS2, while entry in Vero and Huh7.5 cells requires low pH and triggering by acid-dependent endosomal proteases. Moreover, we find nine drugs are antiviral in respiratory cells, seven of which have been used in humans, and three are US Food and Drug Administration (FDA) approved, including cyclosporine. We find that the antiviral activity of cyclosporine is targeting Cyclophilin rather than calcineurin, revealing essential host targets that have the potential for rapid clinical implementation.

Abstract Coronavirus disease 2019 (COVID‐19) is a global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). The models that can accurately resemble human‐relevant responses to viral infection are lacking. Here, a biomimetic human disease model on chip that allows to recapitulate lung injury and immune responses induced by SARS‐CoV‐2 in vitro at organ level is created. This human alveolar chip reproduce the key features of alveolar‐capillary barrier by coculture of human alveolar epithelium, microvascular endothelium, and circulating immune cells under fluidic flow in normal and disease. Upon SARS‐CoV‐2 infection, the epithelium exhibits higher susceptibility to virus than endothelium. Transcriptional analyses show activated innate immune responses in epithelium and cytokine‐dependent pathways in endothelium at day 3 post‐infection, revealing the distinctive responses in different cell types. Notably, viral infection causes the immune cell recruitment, endothelium detachment, and increased inflammatory cytokines release, suggesting the crucial role of immune cells involved in alveolar barrier injury and exacerbated inflammation. Treatment with remdesivir can inhibit viral replication and alleviate barrier disruption on chip. This organ chip model can closely mirror human‐relevant responses to SARS‐CoV‐2 infection, which is difficult to be achieved by in vitro models, providing a unique platform for COVID‐19 research and drug development.

Magnolia officinalis Rehd. et Wils. and Magnolia officinalis Rehd. et Wils. var. biloba Rehd. et Wils, as the legal botanical origins of Magnoliae Officinalis Cortex, are almost impossible to distinguish according to their appearance traits with respect to medicinal bark. The application of AFLP molecular markers for differentiating the two origins has not yet been successful. In this study, a combination of e-nose measurements, e-tongue measurements, and chemical analyses coupled with multiple-source data fusion was used to differentiate the two origins. Linear discriminant analysis (LDA) and quadratic discriminant analysis (QDA) were applied to compare the discrimination results. It was shown that the e-nose system presented a good discriminant ability with a low classification error for both LDA and QDA compared with e-tongue measurements and chemical analyses. In addition, the discriminating capacity of LDA for low-level fusion with original data, similar to a combined system, was superior or equal to that acquired individually with the three approaches. For mid-level fusion, the combination of different principals extracted by PCA and variables obtained on the basis of PLS-VIP exhibited an analogous discrimination ability for LDA (classification error 0.0%) and was significantly superior to QDA (classification error 1.67–3.33%). As a result, the combined e-nose, e-tongue, and chemical analysis approach proved to be a powerful tool for differentiating the two origins of Magnoliae Officinalis Cortex.

Pancreatic cancer (PC) is an aggressive and fatal disease with high incidences of metastasis and recurrence. However, there are no effective treatment options for the majority of PC patients, especially for those with locally advanced tumors and metastatic diseases. Therefore, it is urgently needed to develop safe and effective anti-PC therapeutic agents. We have recently identified a novel marine-derived natural product terphenyllin with potent anti-PC activity. The present study was designed to investigate the efficacy and mechanisms of action of terphenyllin in several human PC cell lines and an orthotopic PC mouse model. The results showed that terphenyllin significantly inhibited the viability of all PC cell lines with minimal effects on a normal human pancreatic cell line (HPNE). We next demonstrated the effects of terphenyllin on colony formation, apoptosis, migration, and invasion in both Panc1 and HPAC cell lines in a concentration-dependent manner. Terphenyllin also suppressed the tumor growth and metastasis in the Panc1 orthotopic mouse model. We further showed the profound effects of terphenyllin on the expression of apoptosis-associated proteins, including Bax, Bad, Puma, BimL, Bcl-2, phos-Bcl-2 (Ser70), Bcl-xL, caspase 7, and PARP, which contributed to its anti-PC activity. In summary, terphenyllin suppressed the PC cell growth and metastasis in vitro and in vivo and may be developed as an anti-PC therapeutic agent in the future.

In this paper, a dual-polarization weather radar echo signal simulation method is proposed for the evaluation of the performance enhancement of dual-polarization weather radar systems, the optimization of signal processing algorithms and the improvement of scanning strategies. The actual weather radar base data are used in the simulation as the reference weather scene, which avoids using a complex algorithm for weather modeling. Moreover, based on radar weather equations, the radar system parameters are added into the radar echo signal modeling to establish the relationship between the simulated echo signal and radar system. As a result, the final simulated echo signal not only shows both the time and frequency domain characteristics of the weather target, but also includes the effects of the important performance of the dual-polarization weather radar system. In addition, to evaluate the performance of range ambiguity mitigation using phase coding and batch working modes, two different simulation methods for the radar signal are established on the method above; one is for batch working mode with long-PRT (pulse repetition time) and short-PRT transmission and receiving, and the other is for phase-coded mode with phase-coded transmission and phase-uncoded receiving. Under the same weather scene, the observation of these two different methods of range ambiguity mitigation are simulated and compared. Results show that the performance of the phase coding mode for mitigating range ambiguity is better than that of the batch mode. Obviously, the simulation method can be used to directly show the observation of different algorithms for mitigation range ambiguity under the same weather process, and quickly compare and evaluate the algorithm’s performance, which is not possible for real radars.

The emerging spintronics applications are hampered by low current-induced torque efficiency in, for example, inversion-symmetry-breaking ferromagnetic heterostructures. Here the authors demonstrate an orbital Rashba-Edelstein effect which can enhance the torque efficiency in Pt/Co/SiO2/Pt films due to the intrinsic Co 3d orbital anisotropy.

Betatron radiation from laser wakefield accelerated electrons and X-rays scattered off a counter-propagating relativistic electron bunch are collimated and hold the potential to extend the energy range to hard X-ray or gamma ray band. The peak brightness of these incoherent radiations could reach the level of the brightest synchrotron light sources in the world due to their femtosecond pulse duration and source size down to a few micrometers. In this article, the principle and properties of these radiation sources are briefly reviewed and compared. Then we present our recent progress in betatron radiation enhancement in the perspective of both photon energy and photon number. The enhancement is triggered by using a clustering gas target, arousing a second injection of a fiercely oscillating electron bunch with large charge or stimulating a resonantly enhanced oscillation of the ionization injected electrons. By adopting these methods, bright photon source with energy over 100 keV is generated which would greatly impact applications such as nuclear physics, diagnostic radiology, laboratory astrophysics and high-energy density science.

ABSTRACT: Purpose: The present study aimed to assess the associations of expansive remodeling of carotid arteries with ischemic symptoms and the degree of stenosis.Materials and Methods: A total of 41 symptomatic patients with vulnerable plaques and 25 asymptomatic individuals with stable plaques were included. All patients underwent 3.0T high-resolution MRI of the carotid artery (CA) for measuring the expansive remodeling (ER) ratio and assessing plaque stability. The ER ratio was calculated by dividing the maximum distance between the lumen and the outer border of the plaque in the internal CA by the lumen diameter within 1 centimeter of the plaque at the distal ipsilateral internal CA. ER ratios were compared between the symptomatic and asymptomatic groups. The 41 symptomatic patients were further divided into 4 groups according to stenosis rate (CA stenosis 90%), and the correlation between the ER ratio and the rate of stenosis was evaluated.Results: There was a significant difference in ER ratio between the symptomatic and asymptomatic groups (p

Kudzu is cosmopolitan and low-cost as a source of fiber, food, medicine, and fuel. However, it is not well utilized as a kind of fiber due to the degumming problem. In order to take full advantage of the kudzu resource in the world and expand the application field of kudzu fiber, this study deals with preparation of kudzu fiber by combined steam explosion and chemical degumming. Kudzu fibers are characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, and X-ray diffraction. It is found that kudzu fiber after combined degumming has a clean surface with most nonfibrous composition removed and fibers dispersed; the cellulose I structure of kudzu cellulose did not change after treatment but its crystallinity increased. These results suggest this combined degumming is feasible for preparing kudzu fiber. It will probably provide theoretical basis for subsequent utilization of kudzu fibers.

Abstract To evaluate the relationship between wall shear stress (WSS) magnitude and cerebral aneurysm rupture and provide new insight into the disparate computational fluid dynamics (CFD) findings concerning the role of WSS in intracranial aneurysm (IA) rupture. A systematic electronic database (PubMed, Medline, Springer, and EBSCO) search was conducted for all accessible published articles up to July 1, 2016, with no restriction on the publication year. Abstracts, full-text manuscripts, and the reference lists of retrieved articles were analyzed. Random effects meta-analysis was used to pool the complication rates across studies. Twenty-two studies containing CFD data on 1257 patients with aneurysms were included in the analysis. A significantly higher rate of low WSS (0–1.5 Pa) was found in ruptured aneurysms (odds ratio [OR] 2.17; 95% confidence interval [CI], 1.73–2.62). The pooled analyses across 14 studies with low WSS showed significantly lower mean WSS (0.64 vs. 1.4 Pa) (p = 0.037) in the ruptured group. This meta-analysis provides evidence that decreased local WSS may be an important predictive parameter of IA rupture.

Pedestrian simulation modeling has become an important means to study the dynamic characters of dense populations. In the continuous pedestrian simulation model for complex simulation scenario with obstacles, the pedestrian path planning algorithm is an indispensable component, which is used for the calculation of pedestrian macro path and microscopic movement desired direction. However, there is less efficiency and poor robustness in the existing pedestrian path planning algorithm. To address this issue, we propose a new pedestrian path planning algorithm to solve these problems in this article. In our algorithm, we have two steps to determine pedestrian movement path, that is, the discrete potential fields are first generated by the flood fill algorithm and then the pedestrian desired speeds are determined along the negative gradient direction in the discrete potential field. Combined with the social force model, the proposed algorithm is applied in a corridor, a simple scene, and a complex scene, respectively, to verify its effectiveness and efficiency. The results demonstrate that the proposed pedestrian path planning algorithm in this article can greatly improve the computational efficiency of the continuous pedestrian simulation model, strengthen the robustness of application in complex scenes.

Aims: Metformin is commonly used to treat type 2 diabetes mellitus; however, in recent years, it was found to play a potential role in the protection of myocardial injury. In this study, we intended to investigate whether metformin had protective effects on bacterial myocarditis. Methods and Results: We stimulated rat cardiac myoblast H9c2 cells with lipopolysaccharide (LPS) and administrated with metformin. The results showed that cell viability after LPS stimulation was greatly reduced. The expression levels of phosphorylated p38 mitogen-activated protein kinases (MAPK) and c-Jun N-terminal kinases (JNK), nuclear factor (NF)-κB (NF-κB), BAX, and cleaved Caspase3 were significantly increased, while the expression of antiapoptotic protein Bcl-2 showed a prominent decrease compared to control. Nevertheless, the cells activity increased remarkably after metformin administration, and the expression levels of intracellular related proteins showed the opposite trend to that of the LPS group. Conclusion: We demonstrate that LPS stimulation may activate intracellular MAPK/JNK and NF-κB signaling pathways and thus induce cell apoptosis. In contrast, metformin reduced apoptosis by inhibiting this signaling pathway and increasing the expression level of Bcl-2. Moreover, it was found that metformin could enhance the ability of cells to antagonize redox damage by regulating the activities of superoxide dismutase and lactate dehydrogenase and subsequently promote the recovery of cardiomyocyte function.

Aims: Metformin has been shown to play a protective role in diabetes. However, we found that metformin could mediate myocardial protection. Given that protein kinase C eplison (PKCε) and interferon regulatory factor 4 (IRF4) are critical for cardioprotection signaling. And measurement of fluorescence resonance energy transfer (FRET) efficiency can be used to determine whether 2 fluorophores are within a certain distance of each other. So we sought to determine whether metformin promotes PKCε/IRF4 activation by FRET. Methods and Results: The study built a mouse septic myocarditis model by intraperitoneal injection of Escherichia coli ; thus, it provides valuable experimental data for the diagnosis and treatment of septic myocarditis. And cellular model of cardiomyocyte damage from adult rat cardiacmyocytes or H9c2 cells was induced by lipopolysaccharide employed to examine PKCε by molecular, biochemical, and cellular imaging analysis. Life span of septic myocarditis mouse was significantly prolonged by metformin. Metformin also decreased transforming growth factor β level and increased interleukin-10 productions. The FRET analysis in H9c2 cells suggested that there is prominent FRET signal for PKCε along in mitochondrial by metformin. Conclusion: We demonstrate that metformin promotes rapid association of PKCε with IRF4 at mitochondrial microdomain of cardiac myocytes and PKCε via direct molecular interaction with IRF4. This regulatory mechanism may play an important role in cardioprotection.

Cellulosic fibers from the bast of Pueraria lobata (P. lobata) vine were separated using a “green” and efficient method that combined steam explosion (SE) and a laccase mediator system (LMS). The chemical components, structure, and thermal alterations in the fibers were evaluated. The SE performed at 180 °C for 10 min did not change the chemical composition of P. lobata; however, SE did alter the fiber structure and rendered its surface more accessible to the laccase enzyme. Treated and untreated samples were characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffractometry (XRD), thermogravimetric analysis (TGA), and chemical methods. The cellulose content of the processed fibers was approximately 68.2%, and the lignin content was 11.8%, which was much lower than the 22.98% lignin content of the raw material. The cellulose fibers exhibited higher cellulose crystallinity and thermal stability compared with the untreated samples. This combined treatment approach may be useful for the isolation of cellulose fibers for composites, textiles, and other industrial applications.

The chemical and structural properties of kenaf fibers that were treated at different steam pressures during the steam explosion process were investigated. With increased steam pressure, a higher percentage of cellulose and acid-insoluble lignin and a lower content of hemicellulose and pectin were obtained. This result was further confirmed by Fourier transform infrared (FTIR) spectroscopy. X-ray diffraction (XRD) studies revealed that the steam-exploded kenaf fibers were more crystalline than the raw kenaf fibers, and that excessive steam pressure above 3 MPa damaged the cellulose crystalline structure. Scanning electron microscopy (SEM) analysis showed a change in the surface morphology of the treated kenaf fibers. The lower content of gums and the effective defibrillation of steam-exploded kenaf fibers demonstrated the potential of steam explosion treatment in applications of kenaf fibers.

Almost 90% of patients undergoing hematopoietic stem cell transplantation (HSCT) experience diarrheal episodes, which represent a severe, often life-threatening complication for these patients. Although fecal microbiota transplantation (FMT) represents an alternative treatment option for infection-related diarrhea, the application of FMT in HSCT patients is greatly restricted for safety reasons. Furthermore, the therapeutic outcomes of FMT as a diarrhea treatment are somewhat related to the choice of the FMT donor. Here, we comprehensively profiled the dynamic changes in the intestinal microbiota after FMT from two donors with different feeding patterns and the same severely diarrheal recipient undergoing HSCT via a 45-day clinical observation. Importantly, no adverse events attributed to FMT were observed. The stool volume and frequency of the patient were reduced when we used feces from donor #1 (mixed feeding), but these changes were not observed after FMT from donor #2 (exclusive breastfeeding). Interestingly, no obvious differences in overall diversity (Shannon) or richness (Chao1) between the two donors were observed. Additionally, Bifidobacterium accounted for 29.9% and 18.1% of OTUs in the stools of donors #1 and #2, respectively. Lactobacillus accounted for 16.3% and 2.9% of the stools of donors #1 and #2, respectively. Furthermore, through longitudinal monitoring of the patient, we identified 6 OTUs that were particularly sensitive to the different FMT complements. Together, we present a case report suggesting that the overall diversity of the intestinal microbiota may not be the only important element in the selection of an effective FMT donor.

In this work, Ta/M/CoFeB/MgO/Ta multilayers were designed to investigate the effect of M insertion on the anomalous Hall effect (AHE) and perpendicular magnetic anisotropy (PMA). Once inserted, Bi did not remain at the interface of Ta and CoFeB; it migrated to the surface of the films, which was not beneficial to PMA. X-ray photoelectron spectroscopic analyses revealed that the segregation of Ta was partly suppressed by the insertion of an Mo, Hf or Pt layer. However, the formation of a CoPt (or FePt) alloy decreased the PMA in the case of a Pt layer. The sample with Hf and Mo still exhibited a clear PMA after annealing at a 350 and 500 °C, respectively.

The interferon-induced transmembrane (IFITM) proteins have been recently shown to restrict HIV-1 and other viruses. Here, we provide evidence that IFITM proteins, particularly IFITM2 and IFITM3, specifically antagonize the HIV-1 envelope glycoprotein (Env), thereby inhibiting viral infection. IFITM proteins interact with HIV-1 Env in viral producer cells, leading to impaired Env processing and virion incorporation. Notably, the level of IFITM incorporation into HIV-1 virions does not strictly correlate with the extent of inhibition. Prolonged passage of HIV-1 in IFITM-expressing T lymphocytes leads to emergence of Env mutants that overcome IFITM restriction. The ability of IFITMs to inhibit cell-to-cell infection can be extended to HIV-1 primary isolates, HIV-2 and SIVs; however, the extent of inhibition appears to be virus-strain dependent. Overall, our study uncovers a mechanism by which IFITM proteins specifically antagonize HIV-1 Env to restrict HIV-1 infection and provides insight into the specialized role of IFITMs in HIV infection.

PURPOSE:Diets high in saturated fat acids (SFA) have been linked with cardio-metabolic disease risk. The purpose of this study was to determine whether only 1-2 weeks of a high SFA diet could impact disease risk factors in overweight adults who normally eat a relatively low proportion of SFA (i.e.,

This paper presents a design of a high performance and low power consumption triple-track magnetic sensor chip which was fabricated in TSMC 0.35 μm CMOS process. This chip is able to simultaneously sense, decode and read out the information stored in triple-track magnetic cards. A reference voltage generating circuit, a low-cost filter circuit, a power-on reset circuit, an RC oscillator, and a pre-decoding circuit are utilized as the basic modules. The triple-track magnetic sensor chip has four states, i.e., reset, sleep, swiping card and data read-out. In sleep state, the internal RC oscillator is closed, which means that the digital part does not operate to optimize energy consumption. In order to improve decoding accuracy and expand the sensing range of the signal, two kinds of circuit are put forward, naming offset correction circuit, and tracking circuit. With these two circuits, the sensing function of this chip can be more efficiently and accurately. We simulated these circuit modules with TSMC technology library. The results showed that these modules worked well within wide range input signal. Based on these results, the layout and tape-out were carried out. The measurement results showed that the chip do function well within a wide swipe speed range, which achieved the design target.

The aim of this study was to investigate the extent of the crack of a cracked tooth on an artificial simulation model with Periapical Radiography (PR) and cone beam computed tomography (CBCT) in vitro, providing the basis for early diagnosis and an appropriate treatment plan.Forty-four teeth with different extents of artificial cracks, created by exposure to liquid nitrogen after hot water at 100°C, were collected. They were subjected to PR and CBCT. Micro-computed tomography (micro-CT) examination, regarded as a relatively more accurate measurement than others, was used to measure and record the crack depth. Three observers, an endodontic graduate student, an experienced endodontist, and an experienced radiologist, examined the PR and CBCT results independently, and the presence or absence of cracks with PR and CBCT were respectively recorded. The external consistency ICC with 95% confidence interval (95% CI) was used to analyze the consistency among the graduate student, endodontist, and radiologist; ROC curves were used for the analysis of diagnostic performance of both radiographic modalities for tooth cracks with crack depth.For the interpretation of the PR results, there were statistically significant differences among the three different observers (P < 0.001), and the interpretation of the CBCT results (P < 0.001). In the group of results read by the graduate student, the sensitivity of diagnosis with CBCT and PR was 77.27% and 22.73%, respectively (P < 0.001). In the group of results read by the endodontist, the sensitivity of diagnosis with CBCT and PR was 81.81% and 8.19%, respectively (P < 0.001). In the group of results read by the radiologist, the sensitivity of diagnosis with CBCT and PR was 88.64% and 11.36%, respectively (P < 0.001). As for CBCT diagnosis, the critical value for the graduate, endodontist, and radiologist was 3.20 mm, 2.06 mm, and 1.24 mm, respectively. For the PR diagnosis, the critical value for the graduate, endodontist, and radiologist was 6.12 mm, 6.94 mm, and 6.94 mm, respectively.Within the limitations of this study, on an artificial simulation model of cracked teeth for early diagnosis, we recommend that it would be better for a cracked tooth to be diagnosed by a radiologist with CBCT than PR, CBCT with a minimum depth of 1.24 mm.

The nonclassical androgen signaling pathway translates signals into alterations in cellular function within minutes, and this action is proposed to be mediated by an androgen receptor (AR) localized to the plasma membrane. This study was designed to determine the mechanism underlying the membrane association of androgen receptor in TM4 cells, a mouse Sertoli cell line. Western blot analysis indicated testosterone-induced AR translocation to the cell membrane. Data from coimmunoprecipitation indicated that AR is associated with caveolin-1, and testosterone enhanced this association. Knockdown of caveolin-1 by shRNA decreased the amount of AR localized to membrane fraction and prevented AR membrane trafficking after being exposed to testosterone at physiological concentration. The palmitoylation inhibitor 2-bromopalmitate decreased AR membrane localization in basal condition and completely blocked testosterone-induced AR translocation to membrane fraction. These data suggested that AR localized to membrane fraction by binding with caveolin-1 through palmitoylation of the cysteine residue. This study provided a new evidence for AR membrane localization and its application for clarifying the nonclassical signaling pathway of androgens.

The current Japanese encephalitis (JE) vaccine derived from G3 JE virus (JEV) can induce protective immunity against G1-G4 JEV genotypes. However, protective efficacy against the emerging G5 genotype has not been reported.Using in vitro and in vivo tests, biological phenotype and cross-immunoreactions were compared between G3 JEV and G5 JEV (wild strains). The PRNT90 method was used to detect neutralizing antibodies against different genotypes of JEV in JE vaccine-immunized subjects and JE patients. In JE vaccine-immunized mice, the lethal challenge protection rates against G3 and G5 JEV wild strains were 100% and 50%, respectively. The seroconversion rates (SCRs) of virus antibodies against G3 and G5 JEV among vaccinated healthy subjects were 100% and 35%, respectively. All clinically identified JE patients showed high levels of G3 JEV neutralizing antibodies (≥1:10-1280) with positive serum geometric mean titers (GMTs) of 43.2, while for G5 JEV, neutralizing antibody conversion rates were only 64% with positive serum GMTs of 11.14. Moreover, the positive rate of JEV neutralizing antibodies against G5 JEV in pediatric patients was lower than in adults.Low levels of neutralizing/protective antibodies induced by the current JE vaccine, based on the G3 genotype, were observed against the emerging G5 JEV genotype. Our results demonstrate the need for more detailed studies to reevaluate whether or not the apparent emergence of G5 JEV can be attributed to failure of the current vaccine to induce appropriate immune protectivity against this genotype of JEV.

Japanese encephalitis (JE) is very prevalent in China, but the incidence of JE among children has been greatly reduced by extensive promotion of vaccinations. The incidence of JE among adults, however, has increased in some parts of China.Data on JE in mainland China, in terms of incidence, gender, and age, were collected between 2004 and 2014. We conducted spatial and temporal analyses on data from different age groups. Generally, children aged 0-15 years still represent the major population of JE cases in China, despite the gradual decrease in incidence over years. However, the incidence of JE among adults in several provinces is notably higher than the national average, especially during the epidemic waves in 2006, 2009, and 2013. The JE cases in the 0-15-year-old group are distributed mainly in the area south of the Yangtze River, with peak incidence occurring from July to September. In the adult group, especially for those over 40 years old, the JE cases are concentrated mainly in the area north of the Yangtze River. JE incidence in the adult group in September and October is significantly greater compared to the other groups. Further analysis using Local Indicators of Spatial Association (LISA) reveals that the distribution of adult JE cases in the six provinces north of the Yangtze River, between north 30-35° latitude and east 110-130° longitude, is a hotspot for adult JE cases.The rate of JE case increase for adults is much greater than for children and has become a public health issue. Therefore, studies on the necessity and feasibility of vaccinating adults who live in JE-endemic areas, but have never been vaccinated for JE, should become a new focus of JE prevention in the future.

We studied the thermal stability of perpendicular magnetic anisotropy (PMA) in Ta/Mo/CoFeB/MgO/Ta films with and without inserted Mo layers. In the absence of a Mo layer, the films show PMA at annealing temperatures below 300 °C. On the other hand, the insertion of a Mo layer preserves PMA at annealing temperatures of up to 500 °C; however, a higher annealing temperature leads to the collapse of PMA. X-ray photoelectron spectroscopy (XPS) and high-resolution transmission electron microscopy (HRTEM) were used to study the microstructure of the films to understand the deterioration of PMA. The XPS results show that the segregation of Ta is partly suppressed by inserting a Mo layer. Once inserted, Mo does not remain at the interface of Ta and CoFeB but migrates to the surface of the films. The HRTEM results show that the crystallization of the MgO (001) texture is improved owing to the higher annealing temperature of the Mo inserted sample. A smooth and clear CoFeB/MgO interface is evident. The inserted Mo layer not only helps to obtain sharper and smoother interfaces but also contributes to the crystallization after the higher annealing temperature of films.

We have investigated the influence of ultrathin Pt insertion layers on the perpendicular magnetic anisotropy (PMA) and annealing stability of Ta/Pt/(Co/Ni)×3/Co/Pt/Ta multilayered films. When the Pt layers were inserted at the Co/Ni interfaces, the PMA of the multilayered films decreased monotonically as the thickness of the Pt insertion layer (tPt) was increased. However, when the Pt layers were inserted at the Ni/Co interfaces, the PMA increased from 1.39 × 106 to 3.5 × 106 erg/cm3 as tPt increased from 0 to 10 Å. Moreover, the multilayered film containing 6-Å-thick Pt insertion layers that inserted at the Ni/Co interfaces exhibited the highest annealing stability for PMA, which was up to temperature of 480 °C. We hypothesize that the introduced Pt/Co interfaces, due to the Pt insertion layers, are responsible for the enhanced PMA and high annealing stability. This study is particularly important for perpendicularly magnetized spintronic devices that require high PMA and high annealing stability.

Japanese encephalitis (JE) is arguably one of the most serious viral encephalitis diseases worldwide. China has a long history of high prevalence of Japanese encephalitis, with thousands of cases reported annually and incidence rates often exceeding 15/100,000. In global terms, the scale of outbreaks and high incidence of these pandemics has almost been unique, placing a heavy burden on the Chinese health authorities. However, the introduction of vaccines, developed in China, combined with an intensive vaccination program initiated during the 1970s, as well as other public health interventions, has dramatically decreased the incidence from 20.92/100,000 in 1971, to 0.12/100,000 in 2011. Moreover, in less readily accessible areas of China, changes to agricultural practices designed to reduce chances of mosquito bites as well as mosquito population densities have also been proven effective in reducing local JE incidence. This unprecedented public health achievement has saved many lives and provided valuable experience that could be directly applicable to the control of vector-borne diseases around the world. Here, we review and discuss strategies for promotion and expansion of vaccination programs to reduce the incidence of JE even further, for the benefit of health authorities throughout Asia and, potentially, worldwide.

The monitoring of pancreatic ductal adenocarcinoma (PDAC) in high-risk populations is essential. Cathepsin E (CTSE) is specifically and highly expressed in PDAC and pancreatic intraepithelial neoplasias (PanINs), and its expression gradually increases along with disease progression. In this study, we first established an in situ 7,12-dimethyl-1,2-benzanthracene (DMBA)-induced rat model for PanINs and PDAC and then confirmed that tumorigenesis properties in this model were consistent with those of human PDAC in that CTSE expression gradually increased with tumor development using histology and immunohistochemistry. Then, using in vivo imaging of heterotopically implanted tumors generated from CTSE- overexpressing cells (PANC-1-CTSE) in nude mice and in vitro imaging of PanINs and PDAC in DMBA-induced rats, the specificity of the synthesized CTSE-activatable probe was verified. Quantitative determination identified that the fluorescence signal ratio of pancreatic tumor to normal pancreas gradually increased in association with progressive pathological grades, with the exception of no significant difference between PanIN-II and PanIN-III grades. Finally, we monitored pancreatic carcinogenesis in vivo using confocal laser endomicroscopy (CLE) in combination with the CTSE-activatable probe. A prospective double-blind control study was performed to evaluate the accuracy of this method in diagnosing PDAC and PanINs of all grades (>82.7%). This allowed us to establish effective diagnostic criteria for CLE in PDAC and PanINs to facilitate the monitoring of PDAC in high-risk populations.

BACKGROUND: The genus Orbivirus includes a number of important pathogenic viruses, including Bluetongue virus (BTV), African horse sickness virus (AHSV), and Epizootic hemorrhagic disease virus (EHDV). In this study we describe the isolation and characterization of an Orbivirus strain isolated from Anopheles maculatus mosquitoes collected in Tibet, China. METHODS AND RESULTS: Initial viral screening identified a viral strain (XZ0906) that caused significant cytopathic effect (CPE) in BHK-21 cells, including rounding, cell rupture, and floating. Although CPE was not observed in insect cells (C6/36), these cells supported viral replication. Polyacrylamide gel analysis revealed a genome consisting of 10 segments of double-stranded RNA (dsRNA), with a distribution pattern of 3-3-3-1. 454 high throughput sequencing of culture supernatant was used for viral identification. Complete genome sequencing was performed by Sanger sequencing in combination with 5'-RACE and 3'-RACE. Sequence analysis demonstrated that all 5'- and 3'- untranslated regions (UTRs) for each of the 10 genome segments contained a series of six highly conserved nucleotides. In addition, homology analysis and phylogenetic analysis based on amino acid sequence was completed, and all results show that virus XZ0906 was not a member of any known species or serotype of Orbivirus, indicating it to be a new species within the genus Orbivirus. CONCLUSIONS: The isolated Orbivirus strain was designated Tibet Orbivirus, TIBOV to denote the location from which it was isolated. TIBOV is a novel orbivirus species which is isolated from Anopheles maculatus mosquitoes collected in Tibet, China.

In this work we prepared double-layer antireflection coatings (DARC) by using the SiO2/SiNx:H heterostructure design. SiO2 thin films were deposited by electron-beam evaporation on the conventional solar cell with SiNx:H single-layer antireflection coatings (SARC), while to avoid the coverage of SiO2 on the front side busbars, a steel mask was utilized as the shelter. The thickness of the SiNx:H as bottom layer was fixed at 80 nm, and the varied thicknesses of the SiO2 as top layer were 105 nm and 122 nm. The results show that the SiO2/SiNx:H DARC have a much lower reflectance and higher external quantum efficiency (EQE) in short wavelengths compared with the SiNx:H SARC. A higher energy conversion efficiency of 17.80% was obtained for solar cells with SiO2 (105 nm)/SiNx:H (80 nm) DARC, an absolute conversion efficiency increase of 0.32% compared with the conventional single SiNx:H-coated cells.

Biodegradation of decabrominated diphenyl ether (BDE-209) in soil by white rot fungi under various experimental conditions was investigated in this study. It was found that BDE-209 in soil could be rapidly and efficiently degraded by white rot fungi, and the biodegradation fits the pseudo-first-order kinetics during a 15-day incubation period. The residues of BDE-209 in soil decreased with the increased amount of white rot fungi addition. It can be seen from the results that white rot fungi have a good degradation ability with one-step and two-step addition method. In native soil, the degradation of BDE-209 reached 52.65%, which was higher than that in sterilized soil. About 37.76–53.74% of BDE-209 degradation was observed in different soil types after 15 days. In addition, it was confirmed in this study that the presence of Cu2+, Cd2+ could enhance the remediation of soil contaminated with BDE-209, and the residues decreased by 69.20% and 54.65% for Cu2+ and Cd2+ treatment, respectively. However, the superior ability of white rot fungi to degrade BDE-209 was not obvious at low pollution level (

We apply different polarization imaging techniques for cancerous liver tissues, and compare the relative contrasts for difference polarization imaging (DPI), degree of polarization imaging (DOPI) and rotating linear polarization imaging (RLPI). Experimental results show that a number of polarization imaging parameters are capable of differentiating cancerous cells in isotropic liver tissues. To analyze the contrast mechanism of the cancer-sensitive polarization imaging parameters, we propose a scattering model containing two types of spherical scatterers and carry on Monte Carlo simulations based on this bi-component model. Both the experimental and Monte Carlo simulated results show that the RLPI technique can provide a good imaging contrast of cancerous tissues. The bi-component scattering model provides a useful tool to analyze the contrast mechanism of polarization imaging of cancerous tissues.

The interferon-inducible transmembrane (IFITM) protein family represents a new class of cellular restriction factors that block early stages of viral replication; the underlying mechanism is currently not known. Here we provide evidence that IFITM proteins restrict membrane fusion induced by representatives of all three classes of viral membrane fusion proteins. IFITM1 profoundly suppressed syncytia formation and cell-cell fusion induced by almost all viral fusion proteins examined; IFITM2 and IFITM3 also strongly inhibited their fusion, with efficiency somewhat dependent on cell types. Furthermore, treatment of cells with IFN also markedly inhibited viral membrane fusion and entry. By using the Jaagsiekte sheep retrovirus envelope and influenza A virus hemagglutinin as models for study, we showed that IFITM-mediated restriction on membrane fusion is not at the steps of receptor- and/or low pH-mediated triggering; instead, the creation of hemifusion was essentially blocked by IFITMs. Chlorpromazine (CPZ), a chemical known to promote the transition from hemifusion to full fusion, was unable to rescue the IFITM-mediated restriction on fusion. In contrast, oleic acid (OA), a lipid analog that generates negative spontaneous curvature and thereby promotes hemifusion, virtually overcame the restriction. To explore the possible effect of IFITM proteins on membrane molecular order and fluidity, we performed fluorescence labeling with Laurdan, in conjunction with two-photon laser scanning and fluorescence-lifetime imaging microscopy (FLIM). We observed that the generalized polarizations (GPs) and fluorescence lifetimes of cell membranes expressing IFITM proteins were greatly enhanced, indicating higher molecularly ordered and less fluidized membranes. Collectively, our data demonstrated that IFITM proteins suppress viral membrane fusion before the creation of hemifusion, and suggested that they may do so by reducing membrane fluidity and conferring a positive spontaneous curvature in the outer leaflets of cell membranes. Our study provides novel insight into the understanding of how IFITM protein family restricts viral membrane fusion and infection.

miRNAs regulate gene expression and are key mediators of tumourigenesis. miR-129 has diverse effects in tumours, but its role in laryngeal squamous cell carcinoma (LSCC) remains unknown. This article focuses on the role of miR-129-5p in LSCC. We show miR-129-5p is upregulated in primary LSCC tumours and correlated with advanced disease. Down-regulating miR-129-5p suppressed cell proliferation and migration, and caused cell cycle arrest in Hep-2 cell lines. Downregulation of miR-129-5p alone is sufficient to induce apoptosis both in vivo and in vitro. Moreover, the growth of LSCC xenograft exposed to miR-129-5p antisense oligonucleotides (ASO) in BALB/c mice was markedly inhibited. In addition, we found that miR-129-5p targeted adenomatous polyposis coli (APC) to release inhibition of Wnt signalling causing cell growth and tumourigenesis. Our results suggest miR-129-5p functions as an oncogene in LSCC by repressing APC and is a potential therapeutic target for LSCC.

We presented a method to use SiO2/SiNx:H double layer antireflection coatings (DARC) on acid textures to fabricate colored multicrystalline silicon (mc-Si) solar cells. Firstly, we modeled the perceived colors and short-circuit current density (Jsc) as a function of SiNx:H thickness for single layer SiNx:H, and as a function of SiO2 thickness for the case of SiO2/SiNx:H (DARC) with fixed SiNx:H (refractive index n=2.1 at 633 nm, and thickness = 80 nm). The simulation results show that it is possible to achieve various colors by adjusting the thickness of SiO2 to avoid significant optical losses. Therefore, we carried out the experiments by using electron beam (e-beam) evaporation to deposit a layer of SiO2 over the standard SiNx:H for 156×156 mm2 mc-Si solar cells which were fabricated by a conventional process. Semisphere reflectivity over 300 nm to 1100 nm and I-V measurements were performed for grey yellow, purple, deep blue, and green cells. The efficiency of colored SiO2/SiNx:H DARC cells is comparable to that of standard SiNx:H light blue cells, which shows the potential of colored cells in industrial applications.

This paper uses data from the National Survey of America's Families (1997–2002) to explore the links between eligibility for the State Children's Health Insurance Program (SCHIP), health insurance coverage, medical care utilization, and health outcomes. We find that SCHIP significantly increased health insurance coverage rates for American children between 1997 and 2002, with most of the gains in coverage for older children. Higher coverage rates translated into increased utilization of the types of medical care that would be expected to improve children's health, such as well-child doctor visits. The effects of SCHIP eligibility expansions on health outcomes, however, are relatively small.

The hippocampal CA3 region plays an important role in learning and memory. CA3 pyramidal neurons (PNs) receive two prominent excitatory inputs-mossy fibers (MFs) from dentate gyrus (DG) and recurrent collaterals (RCs) from CA3 PNs-that play opposing roles in pattern separation and pattern completion, respectively. Although the dorsoventral heterogeneity of the hippocampal anatomy, physiology, and behavior has been well established, nothing is known about the dorsoventral heterogeneity of synaptic connectivity in CA3 PNs. In this study, we performed Timm’s sulfide silver staining, dendritic and spine morphological analyses, and ex vivo electrophysiology in mice of both sexes to investigate the heterogeneity of MF and RC pathways along the CA3 dorsoventral axis. Our morphological analyses demonstrate that ventral CA3 (vCA3) PNs possess greater dendritic lengths and more complex dendritic arborization, compared with dorsal CA3 (dCA3) PNs. Moreover, using ChannelRhodopsin2 (ChR2)-assisted patch-clamp recording, we found that the ratio of the RC-to-MF excitatory drive onto CA3 PNs increases substantially from dCA3 to vCA3, with vCA3 PNs receiving significantly weaker MFs, but stronger RCs, excitation than dCA3 PNs. Given the distinct roles of MF versus RC inputs in pattern separation versus completion, our findings of the significant dorsoventral variations of MF and RC excitation in CA3 PNs may have important functional implications for the contribution of CA3 circuit to the dorsoventral difference in hippocampal function [ABSTRACT FROM AUTHOR]

The level-set subdifferential error bound (LSEB) is weaker than the Kurdyka-Łojasiewicz (KL) property and can replace it to establish linear convergence for various first-order algorithms. In this paper, we mainly study the behaviour of the level-set subdifferential error bound via Moreau envelopes under suitable assumptions. We provide an example that the Moreau envelope does not have the KL property but has the LSEB when the original function does not satisfy the KL property but only the LSEB. [ABSTRACT FROM AUTHOR]