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Climate change seriously threatens global crop production. However, there are few reports on field crop yield and yield components based on long-term different climate conditions. The objectives of this study were to identify and compare the differences in crop yield and yield components in long-term tillage and straw returning under different climate regions. Conventional tillage (CT) and rotary tillage (RT) in combination with no straw return and whole straw return (S) were conducted under a wheat (Triticum aestivum L.)–maize (Zea mays L.) cropping system in cool-wet and warm-dry regions from 2010 to 2019. We hypothesized that long-term suitable tillage under warm-dry or cool-wet regions can increase the yield and components of wheat and maize, and temperature and precipitation had significant effects on crop yield and yield components. Conventional tillage with straw return (CTS) in the warm-dry region and rotary tillage with straw return (RTS) in the cool-wet region can increase the yield and yield components of wheat and maize, respectively, compared with CT. The yield stability of wheat was higher than that of maize under the two climate conditions. Compared with tillage practices, the effects of experimental sites and straw return on crop yield and yield components were more remarkable. The combination of mean temperature, annual precipitation, and yield components explained 75% and 100% of the variance in the wheat yield and maize yield, respectively. The thousand-kernel weight was the key factor in regulating wheat yield, and kernel number was the key factor in regulating maize yield. In conclusion, the combination of rotary tillage in cool-wet regions or conventional tillage in warm-dry regions with straw return is a good technique for increasing crop security. [ABSTRACT FROM AUTHOR]

Mass timber panel–concrete composite (MTPCC) floors combine timber and concrete through high-performance connections to create an efficient floor system with high stiffness, high strength, and low self-weight. Previous research on MTPCC floors focused on improving the composite efficiency of floors under static loadings by testing different types of shear connectors. The dynamic performances of MTPCC floors, which can govern the floor span and thickness, have not been well investigated. In this study, vibration tests were conducted on glued-laminated timber panels and notch-connected MTPCC floors with different spans, thicknesses, and connection layouts. The dynamic properties, including natural frequencies, damping ratios, and mode shapes, were obtained for floors under different supporting conditions. Test results showed that MTPCC floors with a 6-m span had fundamental natural frequencies generally higher than 8 Hz. The addition of the concrete layer to the bare timber panels improved the floor fundamental natural frequency and damping. Deflection tests and walking tests were performed on MTPCC floors to evaluate the floor vibration serviceability performance, and it was found that the existing design criteria predicted inconsistent results. The flexural stiffness of MTPCC floors determined from vibration and deflection tests was close to full composite, while only partial composite action in the composite floors was achieved under a higher load level in destructive bending tests. [ABSTRACT FROM AUTHOR]

Background: The ideal neural interface or scaffold for stem cell therapy shall have good biocompatibility promoting survival, maturation and integration of neural stem cells (NSCs) in targeted brain regions. The unique electrical, hydrophilic and surface-modifiable properties of Ti3C2Tx MXene make it an attractive substrate, but little is known about how it interacts with NSCs during development and maturation. Results: In this study, we cultured NSCs on Ti3C2Tx MXene and examined its effects on morphological and electrophysiological properties of NSC-derived neurons. With a combination of immunostaining and patch-clamp recording, we found that Ti3C2Tx MXene promotes NSCs differentiation and neurite growth, increases voltage-gated current of Ca2+ but not Na+ or K+ in matured neurons, boosts their spiking without changing their passive membrane properties, and enhances synaptic transmission between them. Conclusions: These results expand our understanding of interaction between Ti3C2Tx MXene and NSCs and provide a critical line of evidence for using Ti3C2Tx MXene in neural interface or scaffold in stem cell therapy. [ABSTRACT FROM AUTHOR]

With the rapid development of high-resolution synthetic aperture radar (SAR) systems, the technique that utilizes multiple two-dimensional (2-D) SAR images with different view angles to extract three-dimensional (3-D) coordinates of targets has gained wide concern in recent years. Unlike the traditional multi-channel SAR utilized for 3-D coordinate extraction, the single-channel curvilinear SAR (CLSAR) has the advantages of large variation of view angle, requiring fewer acquisition data, and lower device cost. However, due to the complex aerodynamic configuration and flight characteristics, important issues should be considered, including the mathematical model establishment, imaging geometry analysis, and high-precision extraction model design. In this paper, to address these challenges, a 3-D vector model of CLSAR was presented and the imaging geometries under different view angles were analyzed. Then, a novel 3-D coordinate extraction approach based on radargrammetry was proposed, in which the unique property of the SAR system, called cylindrical symmetry, was utilized to establish a novel extraction model. Compared with the conventional approach, the proposed one has fewer constraints on the trajectory of radar platform, requires fewer model parameters, and can obtain higher extraction accuracy without the assistance of extra ground control points (GCPs). Numerical results using simulated data demonstrated the effectiveness of the proposed approach. [ABSTRACT FROM AUTHOR]

The pathogenic variants in KCNQ4 cause DFNA2 nonsyndromic hearing loss. However, the understanding of genotype–phenotype correlations between KCNQ4 and hearing is limited. Here, we identified a novel KCNQ4 mutation p.G228D from a Chinese family, including heterozygotes characterized by high‐frequency hearing loss that is progressive across all frequencies and homozygotes with more severe hearing loss. We constructed a novel murine model with humanized homologous Kcnq4 mutation. The heterozygotes had mid‐frequency and high‐frequency hearing loss at 4 weeks, and moved toward all frequencies hearing loss at 12 weeks, while the homozygotes had severe‐to‐profound hearing loss at 8 weeks. The degeneration of outer hair cells (OHCs) was observed from basal to apical turn of cochlea. The reduced K+ currents and depolarized resting potentials were revealed in OHCs. Remarkably, we observed the loss of inner hair cells (IHCs) in the region corresponding to the frequency above 32 kHz at 8–12 weeks. The results suggest the degeneration of OHCs and IHCs may contribute to high‐frequency hearing loss in DFNA2 over time. Our findings broaden the variants of KCNQ4 and provide a novel mouse model of progressive hearing loss, which contributes to an understanding of pathogenic mechanism and eventually treatment of DFNA2 progressive hearing loss. [ABSTRACT FROM AUTHOR]

The effect of bismuth oxide addition on the sintering behavior and electrical properties of BaZr 0.3 Ce 0.5 Y 0.2 O 3−δ (BZCY) as an electrolyte for proton conducting solid oxide fuel cells (H-SOFCs) is studied. The introduction of Bi 2 O 3 is beneficial to improving sinterability of BZCY, resulting in high density. Meanwhile, the conductivity test indicates that BaZr 0.3 Ce 0.5 Y 0.2 O 3-δ – 2 mol% Bi 2 O 3 (BZCY-2) promises the highest conductivities. Further, single cells with BZCY-2 as the electrolyte are fabricated and evaluated. The cell with BZCY-2 presents excellent power densities, which reaches 0.67, 0.44, and 0.27 mW cm −2 at 700, 650, and 600 °C, respectively. The conductivities of BZCY-2 film are higher than BZCY in this work and other reported BZCY films. The encouraging results suggest that the addition of a small amount (2 mol%) of Bi 2 O 3 to BZCY can significantly promote sinterability and electrical conductivity for H-SOFCs. [ABSTRACT FROM AUTHOR]

The aim of the current study lies in the development of a reformative technique of image segmentation for Computed Tomography (CT) concrete images with the strength grades of C30 and C40. The results, through the comparison of the traditional threshold algorithms, indicate that three threshold algorithms and five edge detectors fail to meet the demand of segmentation for Computed Tomography concrete images. The paper proposes a new segmentation method, by combining multiscale noise suppression morphology edge detector with Otsu method, which is more appropriate for the segmentation of Computed Tomography concrete images with low contrast. This method cannot only locate the boundaries between objects and background with high accuracy, but also obtain a complete edge and eliminate noise. [ABSTRACT FROM AUTHOR]

Proliferation and migration disorders of vascular smooth muscle cells (VSMCs) contribute to the pathogenesis of proliferative cardiovascular diseases. Although, over the past two decades, a large panel of drugs has been developed for targeting VSMC proliferation, cardiovascular disease remains the leading cause of death worldwide. Thus, there is a compelling need to identify novel signaling pathways and molecules controlling VSMC proliferation and migration, to provide not only mechanistic insights but also safe and effective therapies for the treatment of cardiovascular diseases. Our recent studies have demonstrated that p55γ, a regulatory subunit of phosphoinositide 3-kinase, functions as an endogenous brake on VSMC proliferation. Here, we demonstrate that the small peptide N24, the first 24 amino acids of the NH terminus of p55γ, is a functional mimetic which negatively regulates VSMC proliferation and migration. Specifically, luminal delivery of adenovirus expressing N24 or local administration of Tat transactivator protein (TAT)-tagged N24 by pluronic gel alleviates neointimal formation following balloon injury in rat carotid arteries. Enforced expression of N24 suppresses the proliferation and migration of VSMCs induced by serum- or platelet-derived growth factor-BB. Mechanistically, N24 induces cell cycle arrest via activating the p53-p21 signal pathway, without triggering cell death. N24 interacts with and stabilizes p53 by blocking its ubiquitin-dependent degradation, subsequently promotes p21 transcription, and arrests cell cycle progression. Indeed, knockdown of p21 or p53 abrogates the N24-mediated cell growth arrest. Thus, N24 is a p55γ mimetic inhibiting VSMC proliferation as well as migration, thereby conferring important therapeutic implications for anti-proliferative treatment. Key message: [ABSTRACT FROM AUTHOR]

Traffic sensors serve as an important way to a number of intelligent transportation system applications which rely heavily on real-time data. However, traffic sensors are costly. Therefore, it is necessary to optimize sensor placement to maximize various benefits. Arterial street traffic is highly dynamic and the movement of vehicles is disturbed by signals and irregular vehicle maneuver. It is challenging to estimate the arterial street travel time with limited sensors. In order to solve the problem, the paper presents travel time estimation models that rely on speed data collected by sensor. The relationship between sensor position and vehicle trajectory in single link is investigated. A sensor location model in signalized arterial is proposed to find the optimal sensor placement with the minimum estimation error of arterial travel time. Numerical experiments are conducted in 3 conditions: synchronized traffic signals, green wave traffic signals, and vehicle-actuated signals. The results indicate that the sensors should not be placed in vehicle queuing area. Intersection stop line is an ideal sensor position. There is not any fixed sensor position that can cope with all traffic conditions. [ABSTRACT FROM AUTHOR]

• A multi-channel acoustic emission real-time efficient signal detection method and acquisition system. • A novel spatio-temporal complementary model (CNN-LSTM) for fusion of time-varying AE signal. • Dual circulation LSTM explains the decay mechanism of AE using temporal sampling points. • Stronger correlation between information from AE attenuation profile and surface quality. Laser shock peening (LSP) is one of the main anti-fatigue technologies in high-end manufacturing industries. However, guaranteeing its quality consistency is difficult due to its process complexity. Acoustic emission (AE) is a promising solution to accurately monitoring the surface quality of LSP, although, the large scale of monitoring data is still challenging for industrial applications. This paper studied the in-situ evaluation of surface residual compressive stress (SRCS) for 7075 aluminum alloy in LSP and the efficient sensing of AE based on deep learning methods. Firstly, a monitoring system of LSP with four types of AE sensors was developed in order to simultaneously acquire both the ultra-high and ultra-low amplitude of shock wave. The performance of those sensors is further quantitatively evaluated via long-short term memory (LSTM). Then, a new spatio-temporal parallel CNN-LSTM model for SRCS classification was proposed and experimentally validated to outperform CNN and LSTM after parameters optimization. Finally, aiming to efficient sensing of AE, the importance of different frames of AE signal was analyzed by means of the proposed dual circulation LSTM (DC-LSTM) model, which can accurately locate the key frame of time series signal. Besides, the effects of different frames of AE on classification performance was discussed. It was found that the broadband AE sensor without attenuator shows the highest classification accuracy, while the fast decay stage of AE signal has more contribution to the SRCS classification. This paper provides guidance for real-time non-destructive evaluation of residual stress via AE in laser manufacturing. [ABSTRACT FROM AUTHOR]

The study of divination remains of central relevance to anthropology for what it reveals about the relationship between intuitive and reflective cognition. What marks divination out is the reflective elaboration of the role granted to intuitive associations in arriving at verdicts, which produces two distinct forms of divinatory interpretation. Generative interpretation, exemplified by Cuban Ifá, relies on maximizing the opportunity for intuitive association to render divinatory results relevant to clients' circumstances. In contrast, reductive interpretation, exemplified by Chinese six lines prediction, minimizes the role of intuitive association by relying on highly formalized sets of fixed interpretive principles. Both approaches yield specific diagnoses but arrive at them by emphasizing different cognitive processes. A focus on the generative role of intuition has led some anthropologists of divination to argue that divinatory truth is properly understood as distinct from propositional or representational truth. Instead, anthropologists should take seriously diviners' claims to produce representational knowledge, demonstrating that claims for the "alterity" of divinatory truth stem from a lack of due acknowledgment of the role of reflection in moving from polyvalent divinatory results to specific verdicts or of the possibility of reductive interpretation as a key feature of certain divination systems. [ABSTRACT FROM AUTHOR]

Whether photosynthesis has improved with increasing yield in major crops remains controversial. Research in this area has often neglected to account for differences in light intensity experienced by cultivars released in different years. Light intensity is expected to be positively associated with photosynthetic capacity and the resistance of the photosynthetic apparatus to high light but negatively associated with light-utilization efficiency under low light. Here, we analyzed the light environment, photosynthetic activity, and protein components of leaves of 26 winter wheat cultivars released during the past 60 years in China. Over time, light levels on flag leaves significantly decreased due to architectural changes, but photosynthetic rates under high or low light and the resistance of the photosynthetic apparatus to high light remained steady, contrary to expectations. We propose that the difference between the actual and expected trends is due to breeding. Specifically, breeding has optimized photosynthetic performance under high light rather than low light. Moreover, breeding selectivity altered the stoichiometry of several proteins related to dynamic photosynthesis, canopy light distribution, and photoprotection. These results indicate that breeding has significantly altered the photosynthetic mechanism in wheat and its response to the light environment. These changes likely have helped increase wheat yields. [ABSTRACT FROM AUTHOR]

The mammalian target of rapamycin (mTOR) is dysregulated in diverse cancers and contributes to tumor progression and drug resistance. The first generation of mTOR inhibitors have failed to show clinical efficiency in treating pancreatic cancers due in part to the feedback relief of the insulin-like growth factor-1 receptor (IGF-1R)-AKT signaling pathway. The second generation of mTOR inhibitors, such as AZD8055, could inhibit AKT activation upon mTOR complex 2 (mTORC2) inhibition. However, whether this generation of mTOR inhibitors can obtain satisfactory activities in pancreatic cancer therapy remains unclear. In this study, we found AZD8055 did not show great improvement compared with everolimus, AZD8055 induced a temporal inhibition of AKT kinase activities and AKT was then rephosphorylated. Additionally, we found that AZD8055-induced transient AKT inhibition increased the expression and activation of epidermal growth factor receptor (EGFR) by releasing its transcriptional factors Fork-head box O 1/3a (FoxO1/3a), which might contribute to cell resistance to AZD8055. The in vitro and in vivo experiments further indicated the combination of AZD8055 and erlotinib synergistically inhibited the mTORC1/C2 signaling pathway, EGFR/AKT feedback activation, and cell growth, as well as suppressed the progression of pancreatic cancer in a xenograft model. This study provides a rationale and strategy for overcoming AZD8055 resistance by a combined treatment with the EGFR inhibitor erlotinib in pancreatic cancer therapy. [ABSTRACT FROM AUTHOR]

Objective: This study was performed to evaluate the clinical performance of APTIMA human papillomavirus (AHPV) assay and Hybrid Capture 2 (HC2) assay in screening for cervical disease, especially in women with atypical squamous cell of undetermined significance (ASC-US) and low-grade squamous intraepithelial lesion (LSIL). Methods: A total of 411 women diagnosed with ASC-US or LSIL were referred and further triaged by HC2 test. Prior to colposcopy, liquid-based cytology specimens were collected for the AHPV assay. Sensitivity and specificity were established based on the histological findings of cervical intraepithelial neoplasia (CIN). Results: In all 411 subjects, the positive detection rate of AHPV assay was 70.8% (95% confidence interval [CI], 66.4 to 75.2), which was significantly lower than the positive detection rate of 94.9% obtained using HC2 test (95% CI, 92.3 to 96.8). Only one CIN 3-positive case was detected among the 120 AHPV-negative women, which was then confirmed by Pap smear test to be LSIL. The sensitivities of AHPV and HC2 for CIN 3 were similar (94.1% and 100%, respectively). However, AHPV showed a significantly higher specificity than HC2 test (30.2% and 5.3%, respectively; p<0.001). Conclusion: AHPV assay is effective in identifying CIN 3-positive cases because of its high specificity and lower false-negative rate. The use of AHPV for the triage of ASC-US and LSIL might help to reduce the referral rate of colposcopy during cervical cancer screening. [ABSTRACT FROM AUTHOR]

A novel strategy has been developed to prepare hollow structured Nafion-modified-graphene/polyaniline (NGP) composites via interfacial assembly polymerization between an aqueous phase containing oxidant and an organic phase containing aniline monomers and Nafion-modified graphene. Fourier transform infrared (FTIR), Ultraviolet-visible (UV-vis) and X-ray diffraction (XRD) analyses confirmed the generation of polyaniline (PANI) on graphene during the interfacial polymerization. The morphological evolution of the product had been investigated by scanning electron microscopy (SEM) with respect to the reaction time, based on which a conceivable interpretation of the growth mechanism of the sphere architectures with composite component were given. The as-prepared hollow structured composites showed a good rate capability as electrode material for supercapacitor, and the as-designed interfacial assembly preparation strategy for such composites may provide a generic guideline in developing other graphene-base composite hollow spheres with different compositions. [ABSTRACT FROM AUTHOR]

To explore the mechanism of CircANKRD36 regulating cell heterogeneity and endothelial mesenchymal transition in aortic valve stromal cells by regulating miR-599 and TGF-β signaling pathway. Human tissue specimens were divided into Control group (n = 25) and CAVD group (n = 25). The mRNA expressions of CircANKRD36 and miR-599 in tissue samples were analyzed by qRT-PCR. Western blot was used to analyze the protein expression of osteogenic differentiation related factors induced by OM.The expressions of ALP, osteocalcin, osteopontin, Runx2 and Cadherin11 were detected by Western blot. The expression of CircANKRD36mRNA in CAVD tissue was lower than that in Control tissue (P < 0.05), and the expression of miR-599mRNA in CAVD tissue was higher than that in Control tissue (P < 0.05). CircANKRD36 was negatively correlated with ALP, osteocalcin, osteopontin, Runx2, Cadherin11 expression level after OM induced osteogenic differentiation. The expression level of miR-599 was positively correlated with ALP, osteocalcin, osteopontin, Runx2 and Cadherin11 after OM induced osteogenic differentiation.The expression of ALP, osteocalcin, osteopontin, Runx2 and Cadherin11 protein in circ+miR-599 group was lower than that in circ+miR-NC group (P < 0.05). Compared with Vector+miR-NC group, the protein expressions of TGF-β1, TGF-β2 and SMAD4 in circ+miR-NC group decreased (P < 0.05), while the protein expressions of TGF-β1, TGF-β2 and SMAD4 in circ+miR-599 group increased (P < 0.05). CircANKRD36 can inhibit the expression of miR-599 and the activation of TGF-β signaling pathway, thus inhibiting the expression of differentiation-related factors of VIC osteogenesis and the formation of calcified nodules. Therefore, circANKRD36-miR-599-TGF-β axis can be a new theoretical basis for treating CAVD. • CircANKRD36 can inhibit the expression of miR-599 and the activation of TGF-β signaling pathway • CircANKRD36 can inhibit the expression of differentiation-related factors of VIC osteogenesis • CircANKRD36 can inhibit the formation of calcified nodules • CircANKRD36-miR-599-TGF-β axis can be a new theoretical basis for treating CAVD. [ABSTRACT FROM AUTHOR]

Maize (Zea mays L.) is usually planted at high density, so most of its leaves grow in low light. Certain morphological and physiological traits improve leaf photosynthetic capacity under low light, but how light absorption, transmission, and transport respond at the proteomic level remains unclear. Here, we used tandem mass tag (TMT) quantitative proteomics to investigate maize photosynthesis-related proteins under low light due to dense planting, finding increased levels of proteins related to photosystem II (PSII), PSI, and cytochrome b6f. These increases likely promote intersystem electron transport and increased PSI end electron acceptor abundance. OJIP transient curves revealed increases in some fluorescence parameters under low light: quantum yield for electron transport (φEo), probability that an electron moves beyond the primary acceptor QA− (ψo), efficiency/probability of electron transfer from intersystem electron carriers to reduction end electron acceptors at the PSI acceptor side (δRo), quantum yield for reduction of end electron acceptors at the PSI acceptor side (φRo), and overall performance up to the PSI end electron acceptors (PItotal). Thus, densely planted maize shows elevated light utilization through increased electron transport efficiency, which promotes coordination between PSII and PSI, as reflected by higher apparent quantum efficiency (AQE), lower light compensation point (LCP), and lower dark respiration rate (Rd). [ABSTRACT FROM AUTHOR]

Chiral hybrid organic–inorganic metal halides (HOMHs) with intrinsic noncentrosymmetry have shown great promise for applications in second‐order nonlinear optics (NLO). However, established chiral HOMHs often suffer from their relatively small band gaps, which lead to negative impacts on transparent window and laser‐induced damage thresholds (LDT). Here, we have synthesized two chiral HOMHs based on CuI halides, namely (R‐/S‐MBA)CuBr2, which feature well‐balanced NLO performances with a highly efficient SHG response, outstanding optical transparency, and high LDT. The effective second‐order NLO coefficient of (R‐MBA)CuBr2 has been determined to be ≈24.7 pm V−1, which is two orders of magnitude higher than that of their CuII counterparts. This work shows the promising potential of CuI‐based chiral HOMHs for nonlinear photonic applications in wide wavelength regions. [ABSTRACT FROM AUTHOR]

Chiral hybrid organic–inorganic metal halides (HOMHs) with intrinsic noncentrosymmetry have shown great promise for applications in second‐order nonlinear optics (NLO). However, established chiral HOMHs often suffer from their relatively small band gaps, which lead to negative impacts on transparent window and laser‐induced damage thresholds (LDT). Here, we have synthesized two chiral HOMHs based on CuI halides, namely (R‐/S‐MBA)CuBr2, which feature well‐balanced NLO performances with a highly efficient SHG response, outstanding optical transparency, and high LDT. The effective second‐order NLO coefficient of (R‐MBA)CuBr2 has been determined to be ≈24.7 pm V−1, which is two orders of magnitude higher than that of their CuII counterparts. This work shows the promising potential of CuI‐based chiral HOMHs for nonlinear photonic applications in wide wavelength regions. [ABSTRACT FROM AUTHOR]

Autotrophic microorganisms in soil can increase soil carbon (C) sequestration by utilising chemical energy released from inorganic compounds to fix atmospheric CO 2. Therefore, the effects of tillage systems on soil C stocks and autotrophic microbial community deserves in-depth study. The effects of five tillage systems, including no tillage (NoTill), subsoiling (SubS), rotary tillage (RotTill, local general tillage), no tillage-subsoiling-no tillage (NoTill-SubS), and rotary tillage-subsoiling-rotary tillage (RotTill-SubS) were investigated within a 17-year field experiment. Their effects on soil aggregates, C content and enzyme activities were studied, and the impacts on C-fixing microbial communities were analysed using the C-fixing gene cbbL. The macroaggregate portion and RubisCO and ATPase activities were the highest under SubS, causing the aggregate-associated organic C (AOC) to be 93 % higher than that under RotTill. Under RotTill-SubS, SOC, AOC and aggregate-associated microbial biomass C (AMBC) were larger than those under RotTill. RotTill-SubS reduced the microaggregate portion, increased enzyme activities and the relative abundance of C-fixing bacteria, including Sphingomonadales, Burkholderiales, and Nitrosomonadales. The macroaggregate portion under NoTill-SubS and the relative abundance of Sphingomonadales and Burkholderiales was the highest. Correspondingly, the SOC content was the largest (29 % higher than that in RotTill), and the AOC and AMBC contents were 42 % and 31 % larger, respectively, than those in RotTill. Structural equation modelling reveals that increasing tillage or lowering AOC content can directly increase differences in autotrophic bacterial communities. The reduced aggregate stability decreases C content and increases ATPase and RubisCO activities can indirectly increase differences in bacterial community composition. Graphical abstract [Display omitted] • Tillage rotation increased macroaggregate, C concentration and enzyme activities. • Tillage increased community structure differences. • The microbial community structure of long-term rotary tillage soils is most unique. • Rhizobiales and Sphingomonadales increase C concentration, macroaggregate portion. [ABSTRACT FROM AUTHOR]

Background: Cell senescence is central to a large body of age related pathology, and accordingly, cardiomyocytes senescence is involved in many age related cardiovascular diseases. In consideration of that, delaying cardiomyocytes senescence is of great importance to control clinical cardiovascular diseases. Previous study indicated that bradykinin (BK) protected endothelial cells from senescence induced by oxidative stress. However, the effects of bradykinin on cardiomyocytes senescence remain to be elucidated. In this study, we investigated the effect of bradykinin on H2O2-induced H9C2 cells senescence. Methods and Results: Bradykinin pretreatment decreased the senescence induced by H2O2 in cultured H9C2 cells in a dose dependent manner. Interestingly, 1 nmol/L of BK almost completely inhibited the increase in senescent cell number and p21 expression induced by H2O2. Since H2O2 induces senescence through superoxide-induced DNA damage, we also observed the DNA damage by comet assay, and BK markedly reduced DNA damage induced by H2O2, and moreover, BK treatment significantly prevented reactive oxygen species (ROS) production in H9C2 cells treated with H2O2. Importantly, when co-incubated with bradykinin B2 receptor antagonist HOE-140 or eNOS inhibitor N-methyl-L-arginine acetate salt (L-NAME), the protective effects of bradykinin on H9C2 senescence were totally blocked. Furthermore, BK administration significantly prevented the increase in nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity characterized by increased ROS generation and gp91 expression and increased translocation of p47 and p67 to the membrane and the decrease in superoxide dismutase (SOD) activity and expression induced by H2O2 in H9C2 cells, which was dependent on BK B2 receptor mediated nitric oxide (NO) release. Conclusions: Bradykinin, acting through BK B2 receptor induced NO release, upregulated antioxidant Cu/Zn-SOD and Mn-SOD activity and expression while downregulating NADPH oxidase activity and subsequently inhibited ROS production, and finally protected against cardiomyocytes senescence induced by oxidative stress. [ABSTRACT FROM AUTHOR]

Idiopathic hypereosinophilic syndrome (HES) is a disease characterized by persistent hypereosinophilia (>1.5×109/L) for more than 6 months in the absence of other causes of reactive eosinophilia. Patients with HES presenting with multiorgan thromboses are rare. Herein we report a 57-year-old man with HES who presented with deep venous thrombosis of the lower extremities, portal thrombosis, pulmonary embolism, and mesenteric venous thrombosis, which led to intestinal obstruction. [ABSTRACT FROM AUTHOR]

Abstract: We report a novel and easy route to synthesize a mechanically strong hydrogel composed of graphene and poly (3,4-ethylenedioxythiophene) (PEDOT). 3,4-Ethylenedioxythiophene played the role of reducing agent to convert a highly oxidative graphite oxide (h-GO) to graphene and in situ polymerized itself synchronously on the active sites of the graphene to construct the hydrogel. The content of the carbonyl groups in h-GO was found to have a major impact on the generation of the hydrogel. Also the morphology and the quantity of PEDOT formed in the hydrogel were considered to be the key factors for improving the mechanical performance of the hydrogel. As-prepared enhanced graphene/PEDOT hydrogel displayed a compressive fracture stress as high as 29.6MPa, a storage modulus about 2.1MPa at 10rad/s, a good electrical conductivity of 0.73S/cm and a high specific capacitance of 174.4F/g, which make it a potential candidate for a number of technologies such as electrochemical sensor and supercapacitor. [Copyright &y& Elsevier]

Highlights: [•] We obtained comb-type polysiloxanes with carbonyl-functionalized side-chain. [•] We synthesized pseudo graft copolymers via hydrogen bonding interaction. [•] The sea urchin-like microspheres can be obtained. [•] The prepared films from DCAA displayed high conductivity of 20S/cm. [ABSTRACT FROM AUTHOR]

Current base editors (BEs) use DNA deaminases, including cytidine deaminase in cytidine BE (CBE) or adenine deaminase in adenine BE (ABE), to facilitate transition nucleotide substitutions. Combining CBE or ABE with glycosylase enzymes can induce limited transversion mutations. Nonetheless, a critical demand remains for BEs capable of generating alternative mutation types, such as T>G corrections. In this study, we leveraged pre-trained protein language models to optimize a uracil-N-glycosylase (UNG) variant with altered specificity for thymines (eTDG). Notably, after two rounds of testing fewer than 50 top-ranking variants, more than 50% exhibited over 1.5-fold enhancement in enzymatic activities. When eTDG was fused with nCas9, it induced programmable T-to-S (G/C) substitutions and corrected db/db diabetic mutation in mice (up to 55%). Our findings not only establish orthogonal strategies for developing novel BEs but also demonstrate the capacities of protein language models for optimizing enzymes without extensive task-specific training data. [Display omitted] • nCas9 with engineered UNGs enable transversion base editing without deamination • PLMs were used to predict enzymatic variant activities • Using the PLMs, an efficient T>S (G or C) base editor, TSBE3, was developed • TSBE3 effectively corrected a diabetic mutation (Lepr db ) in murine embryos He et al. utilized protein language models (PLMs) to engineer an enhanced UNG variant, eTDG, targeting thymine. Accurate predictions allowed the validation of over 80% of high-fitness variants. This enabled the development of TSBE3, a tool for efficient T>G or C substitutions in cell lines, T cells, and mouse embryos. [ABSTRACT FROM AUTHOR]

High sensitivity and low detection limit under visible light for glucose were obtained on CuO-TiO 2 NTs/Ti PEC photoelectrode due to the existence of CuO-TiO 2 heterojunction with 3D macroporous structure, 1D nanotubular structure of TiO 2 , and conductive substrate of titanium foil. Associated with chemometric tools, the accuracy of the sensor was further improved. [Display omitted] • 3D CuO-TiO 2 Heterojunction Nanotubes/Ti exhibit good PEC sensitivity for glucose. • PEC sensing mechanism of CuO-TiO 2 NTs/Ti for glucose was illuminated. • Combining with chemometric tools, sensitive and trustworthy PEC sensor was obtained. High sensitivity and low detection limit are important targets for biosensors. Using 3D hydrogen titanate nanotubes/Ti as precursor, CuO-TiO 2 heterojunction nanotubes/Ti (CuO-TiO 2 NTs/Ti) photoelectrode was prepared to fabricate photoelectrochemical (PEC) glucose sensor. The prominent Ti foil substrate, 3D mesoporous structure, and CuO-TiO 2 heterojunction of this PEC sensor can effectively improve the separation efficiency of charge carriers, facilitate electron transfer, and generate strong photoelectronic signals. Under visible light irradiation, the CuO-TiO 2 NTs/Ti electrode exhibited high sensitivity, low LOD, and good selectivity. Through density functional theory simulation, the enhanced electron-hole separation and improved PEC properties were illuminated in the CuO-TiO 2 heterojunction. Associated with chemometric tools, the accuracy of the sensitivity was significantly improved, which could enhance the practical application capability of PEC biosensors. [ABSTRACT FROM AUTHOR]

• The device proposes a segmented coupling solution for the first time. • The segmented design can separate the coupling process of mode multiplexing, thereby reducing the mode complexity. • By introducing a high refractive index ring structure into the central core, avoids serious crosstalk during mode conversion. • The designed dramatically improves fiber space utilization while achieving more higher-order mode conversion. In this paper, a segment-coupled six-mode multiplexer based on multi-core fiber (MCF) is proposed to achieve multiplexing of LP 01 , LP 11 , LP 21 , LP 02 , LP 31 and LP 12 modes according to the principle of mode coupling and phase matching. The mode multiplexer consists of a two-part fiber waveguide that supports six modes of transmission at 1.55 μm wavelength. The transmission performance is analyzed with the finite element method (FEM) and the beam propagation method (BPM). The simulation results show that the insertion loss (IL) of the mode multiplexer is less than 1 dB in the wavelength range of 1.5439–1.5558 μm, and the lowest IL is 0.1837 dB. The coupling efficiencies (CEs) of the six modes are 99.7 %, 92.0 %, 98.6 %, 98.3 %, 97.4 % and 86.6 %, respectively. The designed mode multiplexer dramatically improves fiber space utilization while achieving more higher-order mode conversion. The mode multiplexer can be applied to the mode division multiplexing (MDM) system to solve the problem of mode multiplexing and demultiplexing. [ABSTRACT FROM AUTHOR]

Androgenic alopecia (AGA) has a high incidence. Excess dihydrotestosterone in blood capillaries, which is converted from testosterone by 5α-reductase, is an AGA causative factor. We identified the inhibitory activity of four Polygonum multiflorum compounds against 5α-reductase via high-performance liquid chromatography, and the results showed that Physcion was a potent 5α-reductase inhibitor. Additionally, we found that through inhibiting 5α-reductase expression, Physcion could shorten the time of dorsal skin darkening and hair growth, improve hair follicle morphology, and significantly increase hair follicle count. Eventually, through molecular docking study, we found the binding energy and molecular interactions between Physcion and 5α-reductase type II. These results suggested that Physcion is a potent 5α-reductase inhibitor, as well as a new natural medicine for treating AGA. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effect of intravenous (IV) contrast on sensitivity, specificity, and accuracy of magnetic resonance (MR) neurography of the knee with attention to the common peroneal nerve (CPN) in identifying nerve lesions and active muscle denervation changes. Materials and methods: A retrospective search for contrast-enhanced MR neurography cases evaluating the CPN at the knee was performed. Patients with electrodiagnostic testing (EDX) within 3 months of imaging were included and those with relevant prior surgery were excluded. Two radiologists independently reviewed non-contrast sequences and then 4 weeks later evaluated non-contrast and contrast sequences. McNemar's tests were performed to detect a difference between non-contrast only and combined non-contrast and contrast sequences in identifying nerve lesions and active muscle denervation changes using EDX as the reference standard. Results: Forty-four exams in 42 patients (2 bilateral) were included. Twenty-eight cases had common peroneal neuropathy and 29, 21, and 9 cases had active denervation changes in the anterior, lateral, and posterior compartment/proximal muscles respectively on EDX. Sensitivity, specificity, and accuracy of non-contrast versus combined non-contrast and contrast sequences for common peroneal neuropathy were 50.0%, 56.2%, and 52.3% versus 50.0%, 56.2%, and 52.3% for reader 1 and 57.1%, 50.0%, and 54.5% versus 64.3%, 56.2%, and 61.4% for reader 2. Sensitivity, specificity, and accuracy of non-contrast and combined non-contrast and contrast sequences in identifying active denervation changes for anterior, lateral, and posterior compartment muscles were not significantly different. McNemar's tests were all negative. Conclusion: IV contrast does not improve the ability of MR neurography to detect CPN lesions or active muscle denervation changes. [ABSTRACT FROM AUTHOR]

In the hybrid AC/DC nano‐grid, the LLC‐type DC transformer (DCT) is widely utilized in the DC and AC bus connection system (BCS) with high frequency to improve the system power density. However, it always employs the simple open‐loop scheme for not increasing the control complexity of the nano‐grid system, which creates a big challenge on the inherent features of the DCT circuit for the energy efficiency and conversion ability. Therefore, a robust and low‐cost design approach of the LLC‐type DCT is put forward in this paper based on the specific requirements of hybrid AC/DC nano‐grid. First of all, the design challenges of the LLC‐type DCT are discussed by analyzing the functions of BCS in nano‐grid application. Then, the detailed parameter design approach is presented step‐by‐step to meet the energy efficiency and conversion requirements in the full power range. Finally, a 6 kW nano‐grid prototype is established to verify the effectiveness of the proposed design method. The results show that the designed DCT can enjoy good energy efficiency and conversion ability with simple control and hence accommodate the high‐frequency nano‐grid application. [ABSTRACT FROM AUTHOR]

This paper investigates the microstructure and mechanical properties of 1420 aluminum-lithium (Al-Li) alloy joints before and after heat treatment by CO laser-metal inter gas (MIG) hybrid welding. The 5-mm-thick 1420 Al-Li alloy plates were welded by CO laser-MIG hybrid welding. Full penetration joints without any defects were produced. Optic and scanning electron microscopy were used to study the microstructure and fractograph characteristics. The results show that the microstructures of the heat-affected zone (HAZ) and fusion zone exist as a predominantly discontinuous equiaxed dendritic structure and as a fine cellular dendritic structure, respectively. After heat treatment, the microstructures change from dendritic structure to a spheroidal crystal; the grain size of fusion zone is obviously larger than that of the base metal and the HAZ. Furthermore, the hardness recovers substantially to a level similar to that of the parent material. The tensile strengths of the joints in the as-welded condition and after heat treatment are 223 and 267 MPa, reaching up to 57 and 68 % of the parent materials' strength, respectively. The fractographs show that the joint as-welded condition exhibits the characteristics of dominated dimples and a small amount tear ridges, which are associated with the mixed ductile and brittle facture mechanisms. The fracture mode transforms from a transgranular to an intergranular after heat treatment; cleavage cracking coupled with an intergranular microvoid coalescence fracture mechanism occurs. [ABSTRACT FROM AUTHOR]

As an arsenical, realgar (AsS) is known as a poison and paradoxically as a therapeutic agent. However, a complete understanding of the precise biochemical alterations accompanying the toxicity and therapy effects of realgar is lacking. Using a combined ultrafast liquid chromatography (UFLC) coupled with ion trap time-of-flight mass spectrometry (IT-TOF/MS) and H NMR spectroscopy based metabolomics approach, we were able to delineate significantly altered metabolites in the urine samples of realgar-treated rats. The platform stability of the liquid chromatography LC/MS and NMR techniques was systematically investigated, and the data processing method was carefully optimized. Our results indicate significant perturbations in amino acid metabolism, citric acid cycle, choline metabolism, and porphyrin metabolism. Thirty-six metabolites were proposed as potential safety biomarkers related to disturbances caused by realgar, and glycine and serine are expected to serve as the central contacts in the metabolic pathways related to realgar-induced disturbance. The LC/MS and NMR based metabolomics approach established provided a systematic and holistic view of the biochemical effects of realgar on rats, and might be employed to investigate other drugs or xenobiotics in the future. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Abstract: Silicon is the most promising high capacity anode material to replace graphite for developing next generation high energy density Li-ion batteries. In this approach, patterned amorphous and microcrystalline Si thin film electrodes (a-Si and μc-Si) have been prepared by rf-sputtering and etched further by a reactive ion etching (RIE) system to form square-shape microcolumn electrodes with controllable size (5 × 5 μm width, 500 nm height, aspect ratio of width/height is 10:1) and array distance (5 μm). It has been found that the volume expansion and contraction of a-Si and μc-Si are anisotropic, about 180% along vertical direction and 40% along lateral direction. The total volume variation changes linearly with the increase of lithium insertion content up to ∼310% for a-Si and ∼300% for μc-Si. It occurs nearly reversibly. In addition, it is observed that the original square-shape Si column transforms into the dome-like appearance after lithium insertion and changes into bowl shape after lithium extraction gradually. Radial-like curved cracks are formed after 5−10 cycles and the neighboring Si columns tend to merge together when the distance of the columns is less than 1 μm. [Copyright &y& Elsevier]

A series of C,C-diacetylenic phosphaalkenes 1b—e has been prepared from 1 -chloropenta-1,2-dien-4-ynes 6b—e in a reaction with Mes*PCI2 (Mes* = 2,4,6(tBu)3Ph) in the presence of LDA. Under identical conditions, isomeric butadiyne-substituted phosphaalkenes 2c—f can be obtained from 3-chloropenta-1,4-diynes 5c—f. The title compounds represent rare examples of diethynylethenes in which a constituting methylene has been replaced by a phosphorus center. The formation of both isomers can be rationalized by a common pathway that involves isomeric allenyllithium species. Spectroscopic, electrochemical, and theoretical investigations show that the phosphorus heteroatoms are an intrinsic part of the compounds' π—systems and lead to decreased HOMO—LUMO gaps compared to those in all-carbon-based reference compounds. [ABSTRACT FROM AUTHOR]

Introduction. To date, no approved medication is available for the treatment of female sexual arousal disorder (FSAD). Aim. The purpose of this study was to evaluate the clinical efficacy and safety of a novel alprostadil topical cream for the treatment of FSAD. Methods. This was a multicenter, randomized, double blind, placebo-controlled, parallel design dose-ranging study. Four hundred female patients with FSAD (22–62 years of age), after a 4-week nontreatment baseline period, were provided with 10 blinded doses of 500, 700, or 900 mcg alprostadil or a placebo cream to be applied to the clitoris and the G-spot in the vagina prior to vaginal intercourse. Main Outcome Measures. The primary efficacy end point was the arousal success rate (equal number of the Yes responses to Question 3 of the Female Sexual Encounter Profile [FSEP] or number of the sexual encounters). Secondary endpoints included the Female Sexual Function Index (FSFI), Global Assessment Questionnaire, other FSEP question responses, and post-treatment changes in Female Sexual Distress Scale. Results. A total of 374 FSAD patients completed the study. Primary efficacy analysis of the intent-to-treat (ITT) population showed a significant increase in arousal success rates with dose. Arousal success rates at the end of the total evaluation period were 33.1%, 46.3% ( P = 0.0161), 43.5% ( P = 0.0400), and 53.9% ( P = 0.0002) in the placebo, 500, 700, and 900 mcg alprostadil groups, respectively. The changes of the FSFI score, relative to baseline were 14.7%, 20.7% ( P = 0.067), 21.7% ( P = 0.035), and 22.9% ( P = 0.002) for the placebo, 500, 700, and 900 mcg treatment groups, respectively. The other secondary efficacy end point values showed a consistent trend in support of the primary efficacy results. Conclusion. These results demonstrated that the application of topical alprostadil prior to vaginal intercourse significantly improved the sexual arousal rate of the subjects with FSAD. Liao Q, Zhang M, Geng Li, Wang X, Song X, Xia P, Lu T, Lu M, and Liu V. Efficacy and safety of alprostadil cream for the treatment of female sexual arousal disorder: A double-blind, placebo-controlled study in Chinese population. J Sex Med 2008;5:1923–1931. [ABSTRACT FROM AUTHOR]

Abstract: Adsorption of a weak acid dye, methyl orange (MO) by calcined layered double hydroxides (LDO) with Zn/Al molar ratio of 3:1 was investigated. In the light of so called “memory effect,” LDO was found to recover their original layered structure in the presence of appropriate anions, after adsorption part of MO− and CO2− 3 (come from air) intercalated into the interlayer of LDH which had been supported by XRD and ICP. The results of adsorption experiments indicate that the maximum capacity of MO at equilibrium () and percentage of adsorption (η%) with a fixed adsorbent dose of 0.5 g L−1 were found to be 181.9 mg g−1 and 90.95%, respectively, when MO concentration, temperature, pH and equilibrium time were 100 mg L−1, 298 K, 6.0 and 120 min, respectively. The isotherms showed that the adsorption of MO by Zn/Al-LDO was both consistent with Langmuir and Freundlich equations. The adsorption process was spontaneous and endothermic in nature and followed pseudo-second-order kinetic model. The calculated value of was found to be 77.1 kJ mol−1, which suggests that the process of adsorption of methyl orange is controlled by the rate of reaction rather than diffusion. The possible mechanism for MO adsorption has also been presumed. In addition, the competitive anions on adsorption and the regeneration of Zn/Al-LDO have also been investigated. [Copyright &y& Elsevier]

Abstract: Proton-density-weighted fMRI at low field (0.2 T) was carried out in the cervical spinal cord of healthy volunteers in this study to examine the feasibility of detecting proton density alteration accompanying activation in the spinal cord. Subjects were asked to grip both hands simultaneously, providing sensorimotor simulation for spinal fMRI. Over 70% subjects recruited had activation localized at C6–C7 spinal levels with discrete activation detected in both the anterior and posterior horns of the cervical spinal cord, and the average fractional signal change was 4.06%. The 0.2 T low magnetic field and the 24 ms short TE used in this study diminished the BOLD effect to a negligible level, thus the observed signal change was believed to be mainly attributable to proton density increase during neuronal stimulation. Our results suggested the existence of task-driven proton density change in the cervical spinal cord. [Copyright &y& Elsevier]

The KNAT1 gene is a member of the Class I KNOX homeobox gene family and is thought to play an important role in meristem development and leaf morphogenesis. Recent studies have demonstrated that KNAT1/BP regulates the architecture of the inflorescence by affecting pedicle development in Arabidopsis thaliana. Herein, we report the characterization of an Arabidopsis T-DNA insertion mutant that shares considerable phenotypic similarity to the previously identified mutant brevipedicle ( bp). Molecular and genetic analyses showed that the mutant is allelic to bp and that the T-DNA is located within the first helix of the KNAT1 homeodomain (HD). Although the mutation causes a typical abnormality of short pedicles, propendent siliques, and semidwarfism, no obvious defects are observed in the vegetative stage. A study on cell morphology showed that asymmetrical division and inhibition of cell elongation contribute to the downward-pointing and shorter pedicle phenotype. Loss of KNAT/BP function results in the abnormal development of abscission zones. Microarray analysis of gene expression profiling suggests that KNAT1/BP may regulate abscission zone development through hormone signaling and hormone metabolism in Arabidopsis. (Managing editor: Ping He) [ABSTRACT FROM AUTHOR]

4 contained some incorrectly incorporated data panels; specifically, the A-d, B-b and B-c panels did not display the correct data. (A) Results of the fundus examination using FA prior to drug intervention in the (a) normal, (b) DM, (c) Met, (d) TNTL-h, (e) TNTL-m and (f) TNTL-1 groups. (B) Results of the fundus examination using FA after the 18-week drug intervention in the (a) normal, (b) DM, (c) Met, (d) TNTL-h, (e) TNTL-m and (f) TNTL-1 groups. [Extracted from the article]

The phosphatidylinositol-specific phospholipase C (PI-PLC) activity is detected in purified Lilium pollen protoplasts. Two PI-PLC full length cDNAs, LdPLC1 and LdPLC2, were isolated from pollen of Lilium daviddi. The amino acid sequences for the two PI-PLCs deduced from the two cDNA sequences contain X, Y catalytic motifs and C2 domains. Blast analysis shows that LdPLCs have 60–65% identities to the PI-PLCs from other plant species. Both recombinant PI-PLCs proteins expressed in E. coli cells show the PIP2-hydrolyzing activity. The RT-PCR analysis shows that both of them are expressed in pollen grains, whereas expression level of LdPLC2 is induced in germinating pollen. The exogenous purified calmodulin (CaM) is able to stimulate the activity of the PI-PLC when it is added into the pollen protoplast medium, while anti-CaM antibody suppresses the stimulation effect caused by exogenous CaM. PI-PLC activity is enhanced by G protein agonist cholera toxin and decreased by G protein antagonist pertussis toxin. Increasing in PI-PLC activity caused by exogenous purified CaM is also inhibited by pertussis toxin. A PI-PLC inhibitor, U-73122, inhibited the stimulation of PI-PLC activity caused by cholera toxin and it also leads to the decrease of [Ca2+]cyt in pollen grains. Those results suggest that the PPI-PLC signaling pathway is present in Liliumdaviddi pollen, and PI-PLC activity might be regulated by a heterotrimeric G protein and extracellular CaM. [ABSTRACT FROM AUTHOR]

Here, we report our effort in generating an ORFeome collection for the Arabidopsis transcription factor (TF) genes. In total, ORFeome clones representing 1,282 Arabidopsis TF genes have been obtained in the Gateway high throughput cloning pENTR vector, including 411 genes whose annotation lack cDNA support. All the ORFeome inserts have also been mobilized into a yeast expression destination vector, with an estimated 85% rate of expressing the respective proteins. Sequence analysis of these clones revealed that 34 of them did not match with either the reported cDNAs or current predicted open-reading-frame sequences. Among those, novel alternative splicing of TF gene transcripts is responsible for the observed differences in at least five genes. However, those alternative splicing events do not appear to be differentially regulated among distinct Arabidopsis tissues examined. Lastly, expression of those TF genes in 17 distinct Arabidopsis organ types and the cultured cells was profiled using a 70-mer oligo microarray. [ABSTRACT FROM AUTHOR]

Crop diversity management is widely used to increase agricultural productivity and sustainability. Recent studies have demonstrated that maize root exudates can drive interspecific facilitation to enhance N2 fixation of bean in intercropping systems. However, the mechanisms of N2 fixation enhancement stimulated by root exudates in the intercropping systems remain unclear.Four experiments were designed to provide a progressively deeper understanding of how root exudates stimulate microbial‐mediated N2 fixation. First, the effects of faba bean/maize intercropping on yields and soil microbial communities were determined in a field experiment. Second, root‐derived interspecific facilitation was evaluated using a root partitioning approach. Third, the key microbial taxa in the faba bean rhizosphere were traced using 13C‐labelled maize root exudates. Fourth, the co‐driven mechanism of maize root exudates and micro‐organisms in the faba bean rhizosphere were explored.Faba bean/maize intercropping with maize residue return increased the yields of faba bean (26%), maize (27%) and broccoli (9.1%) compared to that under monocropping. Nodulin‐like 4 (NODL4), chalcone‐flavanone isomerase (CFI) and early nodulin‐like (ENODL2) gene expression in faba bean roots intercropped with maize increased by 1.5–2.3‐fold compared to that observed under monoculture. More than half of the N2 fixation of faba bean increase under intercropping was due to interactions with micro‐organisms. Nine key bacterial genera in the faba bean rhizosphere were identified by 13C‐DNA‐based stable isotope probing analysis. Among them Agromyces, Arthrobacter, Bacillus, Lysobacter and Paenibacillus directly fix N2, while Gemmatimonas, Heliobacillus, Natronocella and Sorangium increase the N2 fixation capacity of Azotobacter by providing additional carbon sources. These key bacteria triggered by maize root exudates played an important role in the rhizosphere facilitation of intercropping.Synthesis and applications. We demonstrated a novel root–root facilitation of N2 fixation and increased crop yields co‐driven by root exudates and rhizosphere bacteria under faba bean/maize intercropping, and nine key bacteria associated with this process were identified by 13C‐DNA‐based stable isotope probing. We recommend the adoption and optimization of intercropping systems with residue return to reduce the shortcomings of continuous cropping and to increase the sustainability of crop production. [ABSTRACT FROM AUTHOR]

In this study, a method using ultrahigh-performance liquid chromatography with photodiode array (UHPLC-PDA) was established and validated for the simultaneous quantification of 10 active components, including eight macamides and two glucosinolates, in Lepidium meyenii (maca). A gas chromatographic mass spectroscopy (GC-MS) method was used to determine the levels of three benzyl isothiocyanates and two sterols in maca. Liquid chromatographic separation was achieved on a Waters Acquity UHPLC HSS T3 column (2.1 mm × 100 mm, 1.8 μm) with gradient elution over 15 min. The mobile phase was (B) acetonitrile-(A) 10 mM aqueous ammonium phosphate, and the detection wavelength was 210 nm. The gas chromatographic separation was performed on an SH-Rxi-1 MS column, and the ionization mode was electron ionization (EI). Two methods were confirmed to have desirable precision (RSD < 1.58%), repeatability (RSD < 1.97%), stability (RSD < 1.76%), and good linearity (R2 ≥ 0.999) within the test range. The recoveries were in the range of 96.79–109.99%, with an RSD below 2.39%. We applied the established methods and successfully analyzed 15 compounds in maca processed under different drying conditions, providing a comprehensive reference for maca processing method of development. In summary, this study provided two rapid and effective methods for the quantification of 15 active components, which contributed to the in-depth maca quality control and provided a reference for the development of maca products. [ABSTRACT FROM AUTHOR]

Background. Inducible nitric oxide synthase (iNOS) plays a crucial role in neuroinflammation, especially microglial activity, and may potentially represent a useful biomarker of neuroinflammation. In this study, we carefully defined a strategic plan to develop iNOS-targeted molecular PET imaging using (4 ′ -amino-5 ′ ,8 ′ -difluoro-1 ′ H-spiro[piperidine-4,2 ′ -quinazolin]-1-yl)(4-fluorophenyl)methanone ([18F]FBAT) as a tracer in a mouse model of lipopolysaccharide- (LPS-) induced brain inflammation. Methods. An in vitro model, murine microglial BV2 cell line, was used to assess the uptake of [18F]FBAT in response to iNOS induction at the cellular level. In vivo whole-body dynamic PET/MR imaging was acquired in LPS-treated (5 mg/kg) and control mice. Standard uptake value (SUV), total volume of distribution ( V t ), and area under the curve (AUC) based on the [18F]FBAT PET signals were determined. The expression of iNOS was confirmed by immunohistochemistry (IHC) of brain tissues. Results. At the end of synthesis, the yield of [18F]FBAT was 2.2–3.1% (EOS), radiochemical purity was >99%, and molar radioactivity was 125–137 GBq/ μ mol. In vitro, [18F]FBAT rapidly and progressively accumulated in murine microglial BV2 cells exposed to LPS; however, [18F]FBAT accumulation was inhibited by aminoguanidine, a selective iNOS inhibitor. In vivo biodistribution studies of [18F]FBAT showed a significant increase in the liver and kidney on LPS-treated mice. At 3 h postinjection of LPS, in vivo, the [18F]FBAT accumulation ratios at 30 min post intravenous (i.v.) radiotracer injection for the whole brain, cortex, cerebellum, and brainstem were 2.16 ± 0.18 , 1.53 ± 0.25 , 1.41 ± 0.21 , and 1.90 ± 0.12 , respectively, compared to those of mice not injected with LPS. The mean area under the curve (AUC0-30min), total volume of distribution ( V t , mL/cm3), and K i (influx rate) of [18F]FBAT were 1.9 ± 0.21 - and 1.4 ± 0.22 -fold higher in the 3 h LPS group, respectively, than in the control group. In the pharmacokinetic two-compartment model, the whole brain K i of [18F]FBAT was significantly higher in mice injected with LPS compared to the control group. Aminoguanidine, selective iNOS inhibitor, pretreatment significantly reduced the AUC0-30min and V t values in LPS-induced mice. Quantitative analysis of immunohistochemically stained brain sections confirmed iNOS was preferentially upregulated in the cerebellum and cortex of mice injected with LPS. Conclusion. An automated robotic method was established for radiosynthesis of [18F]FBAT, and the preliminary in vitro and in vivo results demonstrated the feasibility of detecting iNOS activity/expression in LPS-treated neuroinflammation by noninvasive imaging with [18F]FBAT PET/MRI. [ABSTRACT FROM AUTHOR]

The serological analysis of antigens by recombinant expression cloning (SEREX) has been used by many laboratories to immunoscreen λ phage cDNA libraries produced from a range of tumour cell types. We and others have found it difficult to extract an optimal quality and quantity of mRNA for the preparation of cDNA libraries which represent the genes transcribed in haematological samples. The difficulty is believed to be due to residual haem groups in the isolated RNA sample which inhibit the activity of reverse transcriptase used in the later production of cDNA. During our preparation of a cDNA library for SEREX studies, we optimised the isolation of mRNA from samples from patients with haematological malignancies. We compared the efficacy of different methods of mRNA extraction using a range of haematological sample sizes and describe the most efficient techniques to maximise mRNA yield and quality for cDNA library production. The phage library we prepared contained a range of cDNA insert sizes, including high molecular weight sequences which, following immunoscreening with autologous patient sera, led to the isolation of 17 novel antigens. Using the methodology described, we have shown SEREX to be effective for the isolation of leukaemia-associated antigens, which may act as targets for immunotherapy. [Copyright &y& Elsevier]

Background. Inducible nitric oxide synthase (iNOS) plays a crucial role in neuroinflammation, especially microglial activity, and may potentially represent a useful biomarker of neuroinflammation. In this study, we carefully defined a strategic plan to develop iNOS-targeted molecular PET imaging using (4 ′ -amino-5 ′ ,8 ′ -difluoro-1 ′ H-spiro[piperidine-4,2 ′ -quinazolin]-1-yl)(4-fluorophenyl)methanone ([18F]FBAT) as a tracer in a mouse model of lipopolysaccharide- (LPS-) induced brain inflammation. Methods. An in vitro model, murine microglial BV2 cell line, was used to assess the uptake of [18F]FBAT in response to iNOS induction at the cellular level. In vivo whole-body dynamic PET/MR imaging was acquired in LPS-treated (5 mg/kg) and control mice. Standard uptake value (SUV), total volume of distribution ( V t ), and area under the curve (AUC) based on the [18F]FBAT PET signals were determined. The expression of iNOS was confirmed by immunohistochemistry (IHC) of brain tissues. Results. At the end of synthesis, the yield of [18F]FBAT was 2.2–3.1% (EOS), radiochemical purity was >99%, and molar radioactivity was 125–137 GBq/ μ mol. In vitro, [18F]FBAT rapidly and progressively accumulated in murine microglial BV2 cells exposed to LPS; however, [18F]FBAT accumulation was inhibited by aminoguanidine, a selective iNOS inhibitor. In vivo biodistribution studies of [18F]FBAT showed a significant increase in the liver and kidney on LPS-treated mice. At 3 h postinjection of LPS, in vivo, the [18F]FBAT accumulation ratios at 30 min post intravenous (i.v.) radiotracer injection for the whole brain, cortex, cerebellum, and brainstem were 2.16 ± 0.18 , 1.53 ± 0.25 , 1.41 ± 0.21 , and 1.90 ± 0.12 , respectively, compared to those of mice not injected with LPS. The mean area under the curve (AUC0-30min), total volume of distribution ( V t , mL/cm3), and K i (influx rate) of [18F]FBAT were 1.9 ± 0.21 - and 1.4 ± 0.22 -fold higher in the 3 h LPS group, respectively, than in the control group. In the pharmacokinetic two-compartment model, the whole brain K i of [18F]FBAT was significantly higher in mice injected with LPS compared to the control group. Aminoguanidine, selective iNOS inhibitor, pretreatment significantly reduced the AUC0-30min and V t values in LPS-induced mice. Quantitative analysis of immunohistochemically stained brain sections confirmed iNOS was preferentially upregulated in the cerebellum and cortex of mice injected with LPS. Conclusion. An automated robotic method was established for radiosynthesis of [18F]FBAT, and the preliminary in vitro and in vivo results demonstrated the feasibility of detecting iNOS activity/expression in LPS-treated neuroinflammation by noninvasive imaging with [18F]FBAT PET/MRI. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is a chronic metabolic disorder with multiple complications, patients who receive metformin may have a simultaneous intake of herbal medicine containing rutaecarpine due to cardiovascular protection and hypolipidemic effects of rutaecarpine. There might be drug interactions between metformin and rutaecarpine. This study aimed to investigate the effects of rutaecarpine on the pharmacodynamics and pharmacokinetics of metformin in diabetic rats. The diabetic rat model was induced with high-fat diet and low dose streptozotocin. Metformin with or without rutaecarpine was administered by oral gavage for 42 days. Pharmacodynamics and pharmacokinetics parameters were evaluated. The pharmacodynamics results revealed that co-administration of rutaecarpine with metformin resulted in a remarkable reduction of serum glucose and lipid profiles in diabetic rats compared to metformin treated alone. The pharmacokinetics results showed that co-treatments of rutaecarpine with metformin did not affect the systemic exposure and renal distribution of metformin, but increased metformin concentration in liver. Furthermore, rutaecarpine increased Oct1-mediated metformin uptake into hepatocytes by upregulation of Oct1 expression in the liver. The above data indicate that rutaecarpine enhanced the anti-diabetic effect of metformin, which may be associated with the increased hepatic distribution of metformin through up-regulation of Oct1 in response to rutaecarpine. [ABSTRACT FROM AUTHOR]

Lysine 2-hydroxyisobutyrylation (Khib) is a recently discovered post-translational modification (PTM) showing diverse biological functions and effects in living organisms. However, the study of Khib in plant species is still relatively limited. Wheat (Triticum aestivum L.) is a global important cereal plant. In this study, the systematic Khib analysis was performed in wheat leave tissues. A total of 3004 Khib sites in 1104 proteins were repeatedly identified. Structure characterization of these Khib peptides revealed 12 conserved sequence motifs. Function classification and enrichment analysis indicated these Khib proteins showed a wide function and pathway distribution, of which ribosome activity, protein biosynthesis and photosynthesis were the preferred biological processes. Subcellular location predication indicated chloroplast was the dominant subcellular compartment where Khib was distributed. There may be some crosstalks among Khib, lysine acetylation and lysine succinylation modification because some proteins and sites were modified by all these three acylations. The present study demonstrated the critical role of Khib in wheat biological and physiology, which has expanded the scope of Khib in plant species. Our study is an available resource and reference of Khib function demonstration and structure characterization in cereal plant, as well as in plant kingdom. [ABSTRACT FROM AUTHOR]