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A steerable parametric array loudspeaker (PAL) aims to steer a highly directional audio beam without the need to mechanically rotate the source. The Gaussian beam expansion (GBE) method is often used to model PALs because it is a computationally efficient approach, however the method relies on a paraxial approximation that can result in significant inaccuracies at large steering angles. To address this limitation, a steerable non-paraxial GBE is proposed in this article, where the mainlobe of the steered ultrasonic beam is included in the calculation by rotating the coordinate system. A non-paraxial approximation is then used to improve the accuracy of the method when integrating the virtual audio sources. The numerical results obtained using the proposed method are compared against those using the conventional GBE, as well as an exact solution. For a typical configuration, it is shown that for a conventional GBE the prediction error can be more than 30 dB at large angles, whereas the proposed method reduces this to less than 1 dB. The advantage of the proposed method is more significant at large steering angles, low audio frequencies, and those locations outside of the paraxial region. This improvement in performance is achieved with a computational cost that remains the same as the conventional GBE. [ABSTRACT FROM AUTHOR]

This paper investigates the feasibility of remotely generating a quiet zone in an acoustic free field using multiple parametric array loudspeakers (PALs). A primary sound field is simulated using point monopoles located randomly in a two-dimensional plane, or three-dimensional (3D) space, whereas the secondary sound field is generated by multiple PALs uniformly distributed around the circumference of a circle sitting on the same plane as the primary sources, or on the surface of a sphere for 3D space. A quiet zone size is defined as the diameter of the maximal circular zone within which the noise reduction is greater than 10 dB. The size of this quiet zone is found to be proportional to 0.19λN for N secondary sources with a wavelength λ when the primary and secondary sources are in the same plane, whereas it is found to be 0.55λN1/2 for the 3D case. The size of the quiet zones generated by PALs is similar to that observed with traditional omnidirectional loudspeakers; however, the effects of using PALs on the sound field outside the target zone is much smaller due to their sharp radiation directivity and slow decay rate along the propagation distance. Experimental results are also presented to validate these numerical simulations. [ABSTRACT FROM AUTHOR]

Oxycodone is one of the most prescribed narcotic medications for the treatment of moderate to severe pain in clinical practice. During long-term stability studies of oxycodone hydrochloride for injection performed as per ICH Q1A (R2) guidelines, an unknown degradation product, impurity-I, increased over time and reached a level of 0.21% after 24 months, based on the results of HPLC analysis. The observed impurity was preliminarily characterized as an oxycodone aldol dimer by using two-dimensional (2D) liquid chromatography (LC) coupled with quadrupole time-of-flight mass spectrometry (QTOF MS/MS) analysis. Impurity-I was synthesized and its molecular structure confirmed based on detailed analysis of 1D-NMR (1H, 13C, and DEPT) and 2D-NMR (1H–1H COSY, HSQC, and HMBC) spectroscopy data. The plausible mechanism for the formation of impurity-I was an aldol condensation reaction under weakly acidic conditions. In addition, the potential toxicity of impurity-I was assessed by in silico toxicity predictions using the TOPKAT software. [ABSTRACT FROM AUTHOR]

Path tracing has been used for real‐time renderings, thanks to the powerful GPU device. Unfortunately, path tracing produces noisy rendered results, thus, filtering or denoising is often applied as a post‐process to remove the noise. Previous works produce high‐quality denoised results, by accumulating the temporal samples. However, they cannot handle the details from bidirectional reflectance distribution function (BRDF) maps (e.g. roughness map). In this paper, we introduce the BRDF pre‐integration factorization for denoising to better preserve the details from BRDF maps. More specifically, we reformulate the rendering equation into two components: the BRDF pre‐integration component and the weighted‐lighting component. The BRDF pre‐integration component is noise‐free, since it does not depend on the lighting. Another key observation is that the weighted‐lighting component tends to be smooth and low‐frequency, which indicates that it is more suitable for denoising than the final rendered image. Hence, the weighted‐lighting component is denoised individually. Our BRDF pre‐integration demodulation approach is flexible for many real‐time filtering methods. We have implemented it in spatio‐temporal variance‐guided filtering (SVGF), ReLAX and ReBLUR. Compared to the original methods, our method manages to better preserve the details from BRDF maps, while both the memory and time cost are negligible. [ABSTRACT FROM AUTHOR]

Over the last 20 years, university–industry–government collaborative innovation has received extensive attention in theory and practice. However, the question of how to integrate and understand collaborative innovation from a theoretical perspective has not been thoroughly studied. This study designed a regional collaborative innovation evaluation model based on the triple helix theory. The invention patent data of 31 provincial regions in China for the last 5 years are used to investigate the regional differences and dynamic evolution of the collaborative innovation and the interaction and coupling relationship between intraregional and interregional industries, universities, and governments empirically. This study found that the number of invention patents in China has rapidly grown yearly, indicating that industries are the most important source of invention patents. The difference in the regional distribution of China's collaborative innovation output is remarkable, showing a pattern of "strong east and weak west" in the total volume and "south fast north slow" in the growth rate. The bilateral synergistic effect of industry–university relations is strong considering two‐dimensional cooperation, and the relationship is close. Collaborative innovation is dominated by intraregional cooperation, whereas interregional cooperation shows a growing trend. The tripartite relationship between university, industry, and government shows a loose trend. Certain provinces with weak regional innovation capabilities, such as Gansu, Hainan, Xinjiang, and Qinghai, have a relatively close cooperation level, which is in the stage of government‐led innovation and development. However, Guangdong, Chongqing, Anhui, Jiangsu, and other provinces with outstanding regional innovation capability do not have close cooperation between universities, industries, and governments, which are in the stage of innovation and development led by industries. This paper discusses the policy implications for different regions based on the research conclusions. [ABSTRACT FROM AUTHOR]

By utilizing panel data of provinces in China from 2012 to 2018, this paper measured innovation efficiency of each regional innovation system and the triple helix relationship of the university‐industry‐government system, then, empirically investigated the influence of the triple helix relationship on regional innovation efficiency. It has been found that: (1) the regional innovation efficiency in China increases slightly year by year, the regional differences are obvious, and university–industry bilateral cooperation is the tightest; (2) cooperation between universities and industries is most beneficial to improve regional innovation efficiency, cooperation between universities and governments significantly promotes scale efficiency in the long run, cooperation between industries and governments significantly promotes regional innovation comprehensive efficiency and pure technical efficiency, meanwhile inhibits scale efficiency, coordinated relation among universities, industries, and governments is beneficial to improve regional innovation comprehensive efficiency and scale efficiency. The research results provide useful theoretical support and policy enlightenment for improving regional innovation efficiency. [ABSTRACT FROM AUTHOR]

Identifying acoustic sources with high spatial resolution and precision is significant for machinery noise control. Off-grid compressive beamforming is an effective method for creating acoustic maps with a high spatial resolution. In this study, a two-dimensional off-grid compressive beamforming method via weighted block ℓ 1 norm regularization (WBS-OCSBF) is proposed. The weighted ℓ 1 norm offers a more uniform sparsity penalty compared to the ℓ 1 norm. This method can enhance the performance of off-grid compressive beamforming. Additionally, it is easily implemented on mature linear programming solvers and converges with only a few iterations. Numerical simulations are conducted to analyze the effects of several major parameters on the performance of the proposed method. The simulation results demonstrate the superiority of the proposed method over some traditional methods. The proposed method is then validated using a loudspeaker noises localization experiment. A gearbox transmission system and a transformer are used as two specific objects to explore the industrial application value. The proposed method can effectively localize the gear meshing noise and transformer discharge faults with a high spatial resolution. • Compressive beamforming via weighted Block L1 Norm is proposed in this paper. It enhances the spatial sparsity of the reconstruction results. • Simulation and speaker positioning experiments verify the effectiveness of the method. • Two industrial application experiments proved the potential industrial application value of the method proposed in this paper. [ABSTRACT FROM AUTHOR]

Cardiac fibrosis is a major player in cardiovascular disease, both as a contributor to the development of disease and a post-injury response that drives progression to heart failure. Despite the identification of many mechanisms responsible for cardiovascular fibrosis, such as angiotensin II, TGF- β and endothelin-1, to date no treatments have emerged that have effectively reduced the excess deposition of extracellular matrix associated with fibrotic conditions. Matricellular CCN proteins spatiotemporally regulated nonstructural components of the extracellular matrix (ECM) and participated in many essential biological functions, including wound healing and fibrotic diseases. CCN5 exhibited the opposing effects of CCN2 on the development of cardiac hypertrophy and fibrosis, and overexpression of matricellular protein CCN5 in the heart by adenoviral deliver significantly improved cardiac fibrosis in severe heart failure. Future time- and cell-specific study of CCN5 effect and its domain-specific function on fibrotic development and progression will advance our understanding of cardiac fibrosis, and meanwhile provide opportunities for therapeutic intervention of heart failure. [ABSTRACT FROM AUTHOR]

Background: Pathological cardiac fibrosis and hypertrophy, the common features of left ventricular remodeling, often progress to heart failure. Forkhead box transcription factor P1 (Foxp1) in endothelial cells (ECs) has been shown to play an important role in heart development. However, the effect of EC-Foxp1 on pathological cardiac remodeling has not been well clarified. This study aims to determine the role of EC-Foxp1 in pathological cardiac remodeling and the underlying mechanisms.Methods: Foxp1 EC-specific loss-of-function and gain-of-function mice were generated, and an angiotensin II infusion or a transverse aortic constriction operation mouse model was used to study the cardiac remodeling mechanisms. Foxp1 downstream target gene transforming growth factor-β1 (TGF-β1) was confirmed by chromatin immunoprecipitation and luciferase assays. Finally, the effects of TGF-β1 blockade on EC-Foxp1 deletion-mediated profibrotic and prohypertrophic phenotypic changes were further confirmed by pharmacological inhibition, more specifically by RGD-peptide magnetic nanoparticle target delivery of TGF-β1-siRNA to ECs.Results: Foxp1 expression is significantly downregulated in cardiac ECs during angiotensin II-induced cardiac remodeling. EC-Foxp1 deletion results in severe cardiac remodeling, including more cardiac fibrosis with myofibroblast formation and extracellular matrix protein production, as well as decompensated cardiac hypertrophy and further exacerbation of cardiac dysfunction on angiotensin II infusion or transverse aortic constriction operation. In contrast, EC-Foxp1 gain of function protects against pathological cardiac remodeling and improves cardiac dysfunction. TGF-β1 signals are identified as Foxp1 direct target genes, and EC-Foxp1 deletion upregulates TGF-β1 signals to promote myofibroblast formation through fibroblast proliferation and transformation, resulting in severe cardiac fibrosis. Moreover, EC-Foxp1 deletion enhances TGF-β1-promoted endothelin-1 expression, which significantly increases cardiomyocyte size and reactivates cardiac fetal genes, leading to pathological cardiac hypertrophy. Correspondingly, these EC-Foxp1 deletion-mediated profibrotic and prohypertrophic phenotypic changes and cardiac dysfunction are normalized by the blockade of TGF-β1 signals through pharmacological inhibition and RGD-peptide magnetic nanoparticle target delivery of TGF-β1-siRNA to ECs.Conclusions: EC-Foxp1 regulates the TGF-β1-endothelin-1 pathway to control pathological cardiac fibrosis and hypertrophy, resulting in cardiac dysfunction. Therefore, targeting the EC-Foxp1-TGF-β1-endothelin-1 pathway might provide a future novel therapy for heart failure. [ABSTRACT FROM AUTHOR]

Halogenated biphenyls are worldwide persistent pollutants of great environmental concern. In particular, polychlorinated biphenyls and polybrominated biphenyls have been globally used for industrial purposes until they were found highly toxic, mutagenic and carcinogenic to humans. Therefore, ecological strategies to remove halogenated biphenyls, such as enzyme-catalyzed degradation, are needed. Here, we studied the effect of substitution of F, Cl, Br or I at the 4,4′-positions of 2,3-dihydro-2,3-dihydroxybiphenyl-2,3-dehydrogenase (BphB) on the degradation of halogenated biphenyls by quantum and molecular mechanics. Results show that Boltzmann-weighted average degradation barriers of substituted BphB are all lower than the unsubstituted biphenyl, except for chlorinated biphenyl. The roles of residues nearby the active site, e.g., isoleucine89, asparagine115, serine142, asparagine143, proline184, methionine187 and threonine189, were also investigated. [ABSTRACT FROM AUTHOR]

Abstract Polychlorinated dibenzo‑ p ‑dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) are highly toxic, carcinogenic and mutagenic to humans. As precursors of PCDD/Fs, dibenzofuran (DF) and dibenzo‑ p ‑dioxin (DD) have received considerable public and scientific attention. To reduce the emission of PCDD/Fs, it is critical to explore the formation mechanisms of DF and DD. The present study delineated the DF and DD formation mechanisms from anthracene partial oxidation with the aid of high-accuracy quantum chemistry calculations. The rate constants of crucial elementary steps were obtained utilizing canonical variational transition-state (CVT) theory with the small curvature tunneling (SCT) correction. The results indicate that anthracene could be important precursor of DF and DD, because of the potential barriers for all the major elementary reactions are lower than 33.54 kcal mol−1. This work also reveals that water molecule plays an important catalytic effect during the formation of both DF and DD by lowering the barriers of about 27.24 kcal mol−1. For the water-assisted formation pathway, DF is the dominate product of anthracene partial oxidation with the highest barrier of 30.45 kcal mol−1. For the non-water-assisted formation pathway, DD is the dominate product with the highest barrier of 33.54 kcal mol−1. Graphical abstract Unlabelled Image Highlights • The formation of DD and DF occurs via anthracene partial oxidation. • The water molecule plays an important catalytic effect on the formation of DD and DF. • Anthracene could be important precursor of DF and DD. • The rate constants of crucial elementary steps have been obtained. [ABSTRACT FROM AUTHOR]

Degradation of Chlorine-containing disinfection by-products(Cl-DBPs) on surface by electrocatalytic hydrodechlorination (EHDC) is considered a promising advanced water treatment method. Cl-DBPs have ecological toxicity and health risks so that it is urgent to degrade DBPs. We designed and verified the degradation performance of the EHDC of 18 kinds of DBPs (TAAs, TANs, TALs, TNMs, TAcAms, THMs) with different substituents led by the Ti 3 C 2 X 2 (X = O/OH) system by the first-principles. On the surface of Ti 3 C 2 (OH) 2 , DBPs react with atomic hydrogen (*H) by a direct-indirect continuous reduction mechanism to eliminate the Cl atom in turn. Dissociative adsorption of DBPs on the surface of Ti 3 C 2 (OH) 2 simultaneously realizes the first electron transfer step and forms H vacancy, which makes its electrocatalytic activity superior to that of Ti 3 C 2 O 2. Removing the six types of DBPs only needs to add −0.1 V of applied potential. In addition, we investigated the impact of substituents and chlorination degree on the reactivity of DBPs removal. The strong electron-withdrawing group is more conducive to the dechlorination reaction. Dehalogenation is much favorable in thermodynamics as the increase in chlorination degree. This study provides important insights and efficient catalysts for the degradation of DBPs and shows the potential of MXenes in eliminating chloride in water. [Display omitted] • The degradation performance of Ti 3 C 2 (OH) 2 is superior to Ti 3 C 2 O 2. • Cl atom was removed in Ti 3 C 2 (OH) 2 by direct-indirect continuous reaction. • The high activity results from H vacancy formation and synchronous first electron transfer. • Substituents effect and chlorination degree affect the reaction activity. [ABSTRACT FROM AUTHOR]

Abstract: Dendritic cells (DCs) are specialized antigen presenting cells specializing in antigen uptake and processing, and play an important role in the innate and adaptive immune response. A subset of bovine peripheral blood DCs was identified as CD172a+/CD11c+/MHC (major histocompatibility complex) class II+ cells. Although DCs are identified at 0.1%–0.7% of peripheral blood mononuclear cells (PBMC), the phenotype and function of DCs remain poorly understood with regard to maintaining tolerance during the pregnancy. All cattle used in this study were 1 month before parturition. We have established a novel method for the purification of DCs from PBMC using magnetic‐activated cell sorting, and purified the CD172a+/CD11c+ DCs, with high expression of MHC class II and CD40, at 84.8% purity. There were individual differences in the expressions of CD205 and co‐stimulatory molecules CD80 and CD86 on DCs. There were positive correlations between expression of cytokine and co‐stimulatory molecules in DCs, and the DCs maintained their immune tolerance, evidenced by their low expressions of the co‐stimulatory molecules and cytokine production. These results suggest that before parturition a half of DCs may be immature and tend to maintain tolerance based on the low cytokine production, and the other DCs with high co‐stimulatory molecules may already have the ability of modulating the T‐cell linage. [ABSTRACT FROM AUTHOR]

Eighteen China III and IV diesel vehicles, including light-duty diesel trucks (LDDTs), medium-duty diesel trucks (MDDTs), heavy-duty diesel trucks (HDDTs) and buses, were tested with real-world measurements using a portable emission measurement system (PEMS). The emission factors (EFs), chemical components and surface morphology of emitted particles from these vehicles were characterized. Measured features included organic carbon (OC), elemental carbon (EC), water soluble ions (WSIs) and trace elements of PM2.5. The modelling system MOtor Vehicle Emission Simulator (MOVES) was also employed to estimate the PM2.5 EFs from these vehicles. Carbonaceous content made up 35.8-110.8% of PM2.5, the largest contribution of all the determined chemical components; WSIs and elements accounted for less than 10%. The average PM2.5 EFs of MDDTs and HDDTs were 0.389 g·km−1 and 0.115 g·km−1, respectively, approximately one order of magnitude higher than that of LDDTs. The PM2.5 EFs of China III buses were much lower than those of China III MDDTs and HDDTs, indicating that the inspection maintenance program (I/M) system was carried out effectively on public diesel vehicles. Moreover, the chemical composition of 9.2-56.2% of the PM2.5 mass emitted from China IV diesel trucks could not be identified in the present study. It was possible this unidentified mass was particle bound water, but this hypothesis should be confirmed with further measurements. The SEM images of PM2.5 samples presented a loose floc structure. In addition, the trends of variation of estimated PM2.5 EFs derived from the MOVES simulation were essentially consistent with those of tested values. Copyright © 2018 American Association for Aerosol Research [ABSTRACT FROM AUTHOR]

Olanzapine is a marketed antipsychotic agent for treatment of both positive and negative symptoms of schizophrenia. The chemical synthesis of olanzapine drug substance involved the reaction of thienobenzodiazepine hydrochloride with N -methylpiperazine. During the manufacture of olanzapine, two unknown impurities were present in pilot batches in the range of 0.08–0.22% based upon HPLC analysis. These unknown impurities were enriched from the mother liquor of reaction by preparative HPLC, and characterized by UV, FT-IR, LC–MS/TOF, 1D-NMR ( 1 H, 13 C, DEPT), 2D-NMR ( 1 H- 1 H COSY, HSQC, HMBC, ROESY) and single-crystal X-ray diffraction analysis. Based on the complete spectral analysis and knowledge of the synthetic route of olanzapine, these two new impurities were identified as 2-methyl-4-(4-methyl piperazin-1-yl)-10-((methylthio)methyl)-thieno[2,3 -b ][1,5] benzodiazepine (impurity-I) and 10-(3-(1H-benzo[d]imidazol-2-yl)-5-methylthiophen-2-yl)-2-methyl-4-(4-methyl piperazin-1-yl)-thieno[2,3 -b ][1,5]benzodiazepine (impurity-II). Finally, prospects to the formation and controlling of impurity-I and II were discussed in detail. [ABSTRACT FROM AUTHOR]

Upland cotton is a leading natural fiber crop; and an important source of vegetable oil and protein. The protein content and fatty acid composition are important nutritional indicators of cottonseed. In order to establish rapid, high throughout, nondestructive and low-cost method for cottonseed nutrition evaluation, phenotypic data of seed kernel protein, oil and fatty acid content were combined with preprocessed near-infrared spectra of shell-intact cottonseed from 179 upland cotton genotypes to establish calibration models for these cottonseed nutrients. A total of 17 kinds of fatty acids were stably detected and quantitatively determined using Gas Chromatography-Mass Spectrometry (GC-MS) technology, including 7 kinds of fatty acids which were detected in cottonseed, to the best of our knowledge, for the first time. Finally, 19 NIR calibration models were established through partial least squares regression analysis, and evaluated by cross-validation and external verification. Results indicated that 16 models for seed protein, oil, and 14 fatty acids (capric acid, lauric acid, myristic acid, pentadecanoic acid, palmitic acid, heptadecanoic acid, linoleic acid, arachidic acid, cis-11-eicosenoic acid, linolenic acid, heneicosanoic acid, docosanoic acid, tridecanoic acid, and lignoceric acid) achieved acceptable or satisfactory prediction ability. Three calibration models for palmitoleic acid, stearic acid and oleic acid obtained moderate prediction ability with R 2 cal above 0.7 which could be used in rough screening. Nine fatty acids in cottonseed were modeled for the first time. These results broadened our understanding of the fatty acid profile of cottonseed oil and laid a foundation for fast, nondestructive evaluation of cottonseed nutrient quality for cotton breeding, processing and marketing. • 17 fatty acids, including 7 for the first time were stably detected in cottonseed. • NIR models for protein and oil content in cottonseed were established. • NIR calibration models for 17 fatty acids in cottonseed were constructed. • NIR models for 9 fatty acids were established for the first time. [ABSTRACT FROM AUTHOR]

To develop safer and potent analgesics, we designed, synthesized, and evaluated a new series of benzylaminofentanyl derivates as bifunctional μ opioid receptor (MOR) and σ 1 receptor (σ 1 R) ligands. Compound 68 (Tao-191) showed desirable MOR agonism (K i = 6.5 nΜ; EC 50 = 48.5 nΜ, E max = 66.3%) and σ 1 R antagonism (K i = 35.7 nM) in vitro , and exerted powerful analgesic effects in the abdominal constriction test (ED 50 = 0.32 mg/kg, in mice), formalin-induced pain test (phase II, ED 50 = 2.26 mg/kg, in rats), and paclitaxel-induced neuropathic pain model (ED 50 = 0.30 mg/kg, in mice). The contributions of MOR and σ 1 R to its antinociceptive effect were verified by combined administration with the MOR antagonist naloxone and the σ 1 R agonist PRE-084, respectively. At equianalgesic doses, compound 68 induced fewer MOR-related side effects—including physical and psychological dependence, respiratory depression, constipation, and acute hyperlocomotion—than fentanyl. The results provide a rationale for further exploration of the action and safety of dual MOR/σ 1 R ligands as a promising avenue for the development of potent and safe analgesics. [Display omitted] • A series of benzylaminofentanyl derivates were synthesized as bifunctional MOR/σ 1 R ligands to develop safer analgesics. • Compound 68 showed desirable MOR agonism (EC 50 = 48.5 nΜ, E max = 66.3%) and σ 1 R antagonism (K i = 35.7 nM) in vitro. • Compound 68 exerted powerful analgesic effects in abdominal constriction test and formalin-induced pain test in rodents. • At equianalgesic doses, compound 68 induced fewer MOR-related side effects than fentanyl in mice. [ABSTRACT FROM AUTHOR]

The full harvest of solar energy by semiconductors requires a material that simultaneously absorbs across the whole solar spectrum and collects photogenerated electrons and holes separately. The stepwise integration of three semiconducting sulfides, namely ZnS, CdS, and Cu2− xS, into a single nanocrystal, led to a unique ternary multi-node sheath ZnS-CdS-Cu2− xS heteronanorod for full-spectrum solar energy absorption. Localized surface plasmon resonance (LSPR) in the nonstoichiometric copper sulfide nanostructures enables effective NIR absorption. More significantly, the construction of pn heterojunctions between Cu2− xS and CdS leads to staggered gaps, as confirmed by first-principles simulations. This band alignment causes effective electron-hole separation in the ternary system and hence enables efficient solar energy conversion. [ABSTRACT FROM AUTHOR]

The full harvest of solar energy by semiconductors requires a material that simultaneously absorbs across the whole solar spectrum and collects photogenerated electrons and holes separately. The stepwise integration of three semiconducting sulfides, namely ZnS, CdS, and Cu2− xS, into a single nanocrystal, led to a unique ternary multi-node sheath ZnS-CdS-Cu2− xS heteronanorod for full-spectrum solar energy absorption. Localized surface plasmon resonance (LSPR) in the nonstoichiometric copper sulfide nanostructures enables effective NIR absorption. More significantly, the construction of pn heterojunctions between Cu2− xS and CdS leads to staggered gaps, as confirmed by first-principles simulations. This band alignment causes effective electron-hole separation in the ternary system and hence enables efficient solar energy conversion. [ABSTRACT FROM AUTHOR]

It has been a long-standing demand to design hetero-nanostructures for charge-flow steering in semiconductor systems. Multi-component nanocrystals exhibit multifunctional properties or synergistic performance, and are thus attractive materials for energy conversion, medical therapy, and photoelectric catalysis applications. Herein we report the design and synthesis of binary and ternary multi-node sheath hetero-nanorods in a sequential chemical transformation procedure. As verified by first-principles simulations, the conversion from type-I ZnS-CdS heterojunction into type-II ZnS-(CdS/metal) ensures well-steered collections of photo-generated electrons at the exposed ZnS nanorod stem and metal nanoparticles while holes at the CdS node sheaths, leading to substantially improved photocatalytic hydrogen-evolution performance. [ABSTRACT FROM AUTHOR]

It has been a long-standing demand to design hetero-nanostructures for charge-flow steering in semiconductor systems. Multi-component nanocrystals exhibit multifunctional properties or synergistic performance, and are thus attractive materials for energy conversion, medical therapy, and photoelectric catalysis applications. Herein we report the design and synthesis of binary and ternary multi-node sheath hetero-nanorods in a sequential chemical transformation procedure. As verified by first-principles simulations, the conversion from type-I ZnS-CdS heterojunction into type-II ZnS-(CdS/metal) ensures well-steered collections of photo-generated electrons at the exposed ZnS nanorod stem and metal nanoparticles while holes at the CdS node sheaths, leading to substantially improved photocatalytic hydrogen-evolution performance. [ABSTRACT FROM AUTHOR]

Phytochemical investigation of the whole plants of Saururus chinensis resulted in the isolation of two sesquiterpenes ( 1 and 2 ), five lignans ( 3-7 ), one alkaloid ( 8 ) and two steroids ( 9 and 10 ). Among them, compound 3 has not been reported as a natural product before. Compounds 1 , 2 , 8 and 10 were firstly reported from the family Saururaceae. The possible biosynthesis pathway for sauchinone-like neolignans ( 6 and 11 ) was also firstly proposed. Furthermore, the chemotaxonomic significance of these compounds was summarized. [ABSTRACT FROM AUTHOR]

Here, we describe the optimization, synthesis, and associated pharmacological analgesic activities of a new series of bifunctional piperidinamide derivatives as sigma-1 receptor (σ 1 R) antagonists and mu opioid receptor (MOR) agonists. The new compounds were evaluated in vitro in σ 1 R and MOR binding assays. The most promising compound 114 (also called HKC-126), showed superior affinities for σ 1 R and MOR and good selectivity to additional receptors related to pain. Compound 114 showed powerful dose-dependent analgesic effects in the acetic acid writhing test, formalin test, hot plate test, and chronic constriction injury (CCI) neuropathic pain model. In contrast to an equianalgesic dose of fentanyl, compound 114 produced fewer opioid-like side effects, such as reward liability, respiratory depression, physical dependence, and sedation. Lastly, the pharmacokinetic properties of this drug were also acceptable, and these results suggest that compound 114 , as a mixed σ 1 R/MOR ligand, has potential for treating neuropathic pain. [Display omitted] 1. A new series of bifunctional piperidinamide derivatives were synthesized and evaluated biological activity. 2. Compound 114 showed superior affinities for σ 1 R and MOR and good selectivity to additional receptors related to pain. 3. Compound 114 showed powerful dose-dependent analgesic effects in different models. 4. Compound 114 produced fewer opioid-like side effects, such as reward liability, respiratory depression, physical dependence and sedation than fentanyl at an equianalgesic dose. [ABSTRACT FROM AUTHOR]

Opioid analgesics are highly effective painkillers for the treatment of moderate or severe pain, but they are associated with a number of undesirable adverse effects, including the development of tolerance, addiction, constipation and life-threatening respiratory depression. The development of new and safer analgesics with innovative mechanisms of action, which can enhance the efficacy in comparison to available treatments and reduce their side effects, is urgently needed. The sigma-1 receptor (σ 1 R), a unique Ca2+-sensing chaperone protein, is expressed throughout pain-modulating tissues and affects neurotransmission by interacting with different protein partners, including molecular targets that participate in nociceptive signalling, such as the μ-opioid receptor (MOR), N -methyl- d - aspartate receptor (NMDAR) and cannabinoid 1 receptor (CB 1 R). Overwhelming pharmacological and genetic evidence indicates that σ 1 R antagonists induce anti-hypersensitive effects in sensitising pain conditions (e.g. chemically induced, inflammatory and neuropathic pain) and enhance opioid analgesia but not opioid-mediated detrimental effects. It has been suggested that balanced modulation of MORs and σ 1 Rs may improve both the therapeutic efficacy and safety of opioids. This review summarises the functional profiles of ligands with mixed MOR agonist and σ 1 R antagonist activities and highlights their therapeutic potentials for pain management. Dual MOR agonism/σ 1 R antagonism represents a promising avenue for the development of potent and safer analgesics. [Display omitted] • σ 1 R antagonists exhibit anti-hypersensitive effects in sensitising pain conditions. • σ 1 R antagonists enhance opioid analgesia but not opioid-mediated unwanted effects. • Bifunctional MOR and σ 1 R ligands possess wider therapeutic window with fewer adverse effects. • Representative ligands with MOR agonist and σ 1 R antagonist activities were summarised. • Dual MOR-agonism/σ 1 R-antagonism represents a promising avenue for the development of potent and safer analgesics. [ABSTRACT FROM AUTHOR]

Abstract: Well-dispersible poly-N-[5-(8-quinolinol)ylmethyl]aniline/nano-TiO2 composite was synthesized by the surface modification of nano-TiO2 particles using poly-N-[5-(8-quinolinol)ylmethyl] (PANQ), and it was characterized by Fourier-transform infrared spectroscopy, photoluminescence spectroscopy, thermogravimetric analysis and scanning electron microscope, as well as conductivity and cyclic voltammogram were given. The conductivity of this composite was 2.1×10−2 Scm−1 at 25°C, and showed good redox reversibility. It was easy to cast a transparent conducting film with photoluminescent property. [Copyright &y& Elsevier]

Abstract: Stabilizer-free polyaniline nanofiber aqueous colloids were obtained by the direct dispersing of polyaniline nanofiber prepared in the presence of β-cyclodextrin. The polyaniline nanofiber, the diameters of which are between 80 and 100 nm, can be steadily dispersed in near neuter (pH=6.5) aqueous solution for about 60 days without any steric or electrostatic stabilizer. [Copyright &y& Elsevier]

Unique kinked semiconductor–metal Au–Ag2S–ZnS and Au–Ag2S–ZnS–Au heteronanorods have been synthesized for the first time by a seed-mediated growth method. A plausible mechanism for the formation of kinked heteronanorods is proposed. The catalytic activity of such novel kinked semiconductor–metal heteronanorods with selective deposition and uniform morphology is also investigated via a model reaction based on the reduction of 4-nitrophenol by NaBH4. [ABSTRACT FROM AUTHOR]

In this study, we introduce a theoretical model designed to explore both the photochemical and photothermal behavior of arc plasma radiation-induced ablation in gassing materials. We employ time-dependent density functional theory to analyze the photochemical behavior, while reactive force field molecular dynamics are used to explore the photothermal behavior. The phenomena, behavior and consequences of valence shell electronic excitation are analyzed in terms of ultraviolet (UV) absorption, electron-hole distribution, and Mayer bond order. Based on the photochemical findings, we apply a periodic electric field that corresponds to the vibration frequency of the permanent dipole moment to simulate infrared radiation, and convert UV photon energy into atomic kinetic energy to analyze UV radiation. This atomic-scale insight into photothermal behavior enables us to identify the final composition of ablation gases, including H2, CO, H2O, NH3, as well as specific cyanides, amines, and hydrocarbons. The results of the theoretical model and physical properties indicate that the concentration of hydrogen-containing gases in the ablation gas significantly affects the arc extinguishing capabilities of different polymers. Finally, we propose modification schemes suitable for polymers in power circuit breakers, considering UV absorption and smoke black production. Additionally, we present the potential application of theoretical models for calculating the ablation rate, necessitating further in-depth re-search. [ABSTRACT FROM AUTHOR]

[Display omitted] • Isolation, identification and characterization of an unknown process-related impurity (impurity-I) in sugammadex sodium. • Structural elucidation of this new impurity has been confirmed by LC–MS/QTOF, 1D-NMR and 2D-NMR data. • Prospects to the formation and controlling of impurity-I have been discussed in detail. Sugammadex sodium is the first selective relaxant binding agent (SRBA) indicated for reversal of neuromuscular blockade induced by rocuronium or vecuronium during surgery. The chemical synthesis of sugammadex involved the nucleophilic substitution reaction between 6-per-deoxy-6-per-halo-γ-cyclodextrin and 3-mercaptopropionic acid under basic conditions. During the manufacture of sugammadex sodium, an unknown process-related impurity was observed in pilot batches in the range of 0.21–1.9 % based upon HPLC analysis. The same impurity was also detected in commercial Bridion® samples at the levels of more than 0.1 %. Thus this unknown impurity was enriched from the mother liquor of reaction by preparative HPLC and characterized by LC–MS/QTOF, 1D-NMR (1H, 13C, DEPTQ) and 2D-NMR (1H-1H COSY, TOCSY, HSQC, HMBC, NOESY) techniques. Based on spectroscopic analysis and the synthetic route of sugammadex sodium, this new impurity was identified as monocyanoethyl sugammadex (impurity-I). The prospects to the formation mechanism and control strategy of impurity-I were discussed in detail. Moreover, the toxicological properties of impurity-I were evaluated using ADMET Predictor® software. [ABSTRACT FROM AUTHOR]

To investigate the effects of carbon nanotubes (CNTs) on the performances of graphene (Gr)/trans-1,4-polyisoprene (TPI)/natural rubber (NR) composites, CNTs/Gr/TPI/NR vulcanizates were fabricated via the partial replacement of Gr with CNTs. The results displayed that partially substituting CB with Gr or hybrid in a Gr/CNTs ratio of 2 enabled the TPI/NR composites to embrace simultaneously improved wet-skid resistance, lowered rolling resistance as well as heat buildup (HBU), which is conducive to prepare energy efficient tire rubber. The hybrids of Gr with CNTs raised the crosslinking densities of TPI/NR vulcanizates, and elevated the tensile strength, tear strength, modulus at 300%, hardness, and wear resistance of TPI/NR composites more efficiently than Gr only. Besides, hybrids with higher Gr/CNTs ratio aided in retaining or lifting the resilience of TPI/NR vulcanizate, and raising the thermal conductivities of vulcanizates at 20 and 150℃. So, the partial substitution of CB with Gr/CNTs hybrids in proper ratio is supposed to upgrade the overall properties of TPI/NR vulcanizates. [ABSTRACT FROM AUTHOR]

Rh SAs/TpPa-1 was first fabricated by anchoring Rh SAs in TpPa-1 via Rh C 3 N bond, which showed an improved perfomance for photocatalytic H 2 production. [Display omitted] • Rh SAs/TpPa-1 was first fabricated by anchoring Rh SAs in TpPa-1 via Rh C 3 N bond. • The unique Rh C 3 N coordination optimized the local electronic environment at the atomic interface. • Rh SAs/TpPa-1 achieved an excellent hydrogen evolution activity (1836.81 μmol h−1 g−1). • DFT and in situ Raman confirmed the proton reduction sites and a decreased energy barrier for H* formation. Developing efficient and stable photocatalysts for solar hydrogen (H 2) energy conversion is meaningful but challenging. Herein, a novel photocatalyst with Rh single atoms (Rh SAs) anchoring in β-ketoimine-linked covalent organic frameworks (TpPa-1) via Rh C 3 N sites is proposed for achieving highly efficient H 2 production in phosphate buffer saline (PBS) solution with sodium ascorbate (SA) as sacrificial agent under visible light. TpPa-1 with abundant N and C-chelate sites provides a reliable basis for anchoring Rh single atoms. The optimized Rh SAs/TpPa-1 exhibits an outstanding hydrogen evolution activity (1836.81μmol h−1 g−1), 9.34 and 2.27 folds enhancement than that of pristine TpPa-1 and Rh NPs/TpPa-1. X-ray absorption fine structure (XAFS) combined with density functional theory (DFT) calculations reveal that the significant improvement in H 2 evolution performance on Rh SAs/TpPa-1 originates from the unique Rh C 3 N coordination environment, promoting the charge separation and migration at the atomic interface, and thus decreasing the energy barrier for H* formation. Notably, in situ Raman technique confirmed Rh SAs was the main active sites (Rh H) for proton reduction. [ABSTRACT FROM AUTHOR]

The immobilization of catalysts hinders the application of nanosized photocatalysts in wastewater treatment. In this study, a simple method for the preparation of flexible composite non-woven catalysts with a good spectral response is presented. Firstly, the porous g-C3N4 nanosheets containing nitrogen defects (DCN) and sodium alginate (SA) were blended to prepare the casting solution and then coated on the surface of polyester and viscose blend non-woven fabric (NW). Finally, the robust three-dimensional composite non-woven catalyst (DCN@SA/NW) was constructed by cross-linking with CaCl2. The as-prepared samples were characterized by different physicochemical techniques including SEM, EDS, FTIR, Raman, XRD, XPS, and TGA. The photocatalytic degradation of dyes and antibiotics and self-cleaning and antibacterial properties of the catalyst were investigated. The optimal DCN@SA/NW formulation was 2.0 wt.% DCN and 2.0 wt.% SA. The DCN@SA/NW composite efficiently degraded rhodamine (RhB) and tetracycline hydrochloride (TC). Moreover, the synthesized non-woven composite catalyst was easily recycled and remained stable, indicating its promising potential in wastewater treatment. The DCN@SA/NW also exhibited outstanding self-cleaning and antibacterial performance. This study provides an interesting idea for the research and development of immobilized photocatalysts and has great potential in future practical photocatalytic applications. [ABSTRACT FROM AUTHOR]

Mastitis is one of the most frequent and costly diseases affecting dairy cattle. Natural antibodies (immunoglobulins) and cyclophilin A (CyPA), the most abundant member of the family of peptidyl prolyl cis / trans isomerases, in milk may serve as indicators of mastitis resistance in dairy cattle. However, genetic information for CyPA is not available, and knowledge on the genetic and nongenetic relationships between these immune-related traits and somatic cell score (SCS) and milk yield in dairy cattle is sparse. Therefore, we aimed to comprehensively evaluate whether immune-related traits consisting of 5 Ig classes (IgG, IgG 1 , IgG 2 , IgA, and IgM) and CyPA in the test-day milk of Holstein cows can be used as genetic indicators of mastitis resistance by evaluating the genetic and nongenetic relationships with SCS in milk. The nongenetic factors affecting immune-related traits and the effects of these traits on SCS were evaluated. Furthermore, the genetic parameters of immune-related traits according to health status and genetic relationships under different SCS environments were estimated. All immune-related traits were significantly associated with SCS and directly proportional. Additionally, evaluation using a classification tree revealed that IgA, IgG 2 , and IgG were associated with SCS levels. Genetic factor analyses indicated that heritability estimates were low for CyPA (0.08) but moderate for IgG (0.37), IgA (0.44), and IgM (0.44), with positive genetic correlations among Ig (0.25–0.96). We also evaluated the differences in milk yield and SCS of cows between the low and high groups according to their sires' estimated breeding value for immune-related traits. In the high group, IgA had a significantly lower SCS in milk at 7 to 30 d compared with that in the low group. Furthermore, the Ig in milk had high positive genetic correlations between healthy and infected conditions (0.82–0.99), suggesting that Ig in milk under healthy conditions could interact with those under infected conditions, owing to the genetic ability based on the level of Ig in milk. Thus, Ig in milk are potential indicators for the genetic selection of mastitis resistance. However, because only the relationship between immune-related traits and SCS was investigated in this study, further study on the relationship between clinical mastitis and Ig in milk is needed before Ig can be used as an indicator of mastitis resistance. [ABSTRACT FROM AUTHOR]

Coralloid CoN/Ni/NiO electrocatalyst has been synthesized via a one-step urea nitriding-reduction strategy and exhibits excellent overall water splitting performance in alkaline. [Display omitted] • CoN/Ni/NiO is prepared by a unique one-step urea nitriding-reduction strategy. • CoN/Ni/NiO shows superior HER/OER activity (92/114 mV at 10 mA cm−2). • The ΔG H2O (0.088 eV) and ΔG H* (0.18 eV) in HER are optimized. • The ΔG OOH* of rate determining step (O*→OOH*) in OER is reduced to 1.4 eV. The introduction of nitride in Ni/NiO-based catalytic system for electrocatalystic water splitting via a skillful strategy remains a great challenge. Herein, we proposed a one-step urea nitriding-reduction strategy for the fabrication of novel CoN/Ni/NiO electrocatalyst on carbon cloth (CC). The combination of CoN and Ni/NiO could construct CoN/Ni interface and expose more active sites, thus exhibiting excellent hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) performance in alkaline media. Consequently, CoN/Ni/NiO catalyst exhibited remarkable HER/OER performance with an overpotential of 92 mV/114 mV at 10 mA cm−2 in 1.0 M KOH, along with a low cell voltage of 1.56 V to enhance overall water splitting. In addition, when CoN was introduced in Ni/NiO system, CoN/Ni/NiO displayed high conductivity, large active surface areas, high Faradic efficiency (FE) and remarkable stability. Density functional theory (DFT) calculations demonstrated that CoN/Ni/NiO possessed a decreased d-band center beneficial for optimizing the energy barrier of intermediates. Specifically, the ΔG H2O (0.088 eV) and ΔG H* (0.18 eV) in HER and the ΔG OOH* (1.4 eV) of rate determining step (O*→OOH*) in OER of CoN/Ni/NiO catalyst were optimized to achieve high water splitting activity. Simultaneously, for adsorbed H 2 O on CoN/Ni/NiO, the O H bond length extended from 0.975 to 1.110 Å, and the bond angle enlarged from 104.271 to 109.471°, thereby directly demonstrating the excellent HER/OER performance of CoN/Ni/NiO. [ABSTRACT FROM AUTHOR]

Ein ternäres halbleitendes Nanokomposit, ZnS‐CdS‐Cu2−xS, wurde von S. H. Yu, J. Jiang et al. in der Zuschrift auf S. 6506 ff. hergestellt. Diese Heteronanostäbe zeichnen sich durch effiziente Ladungstrennung aus und absorbieren über das gesamte Sonnenspektrum, was die effiziente Umwandlung von Solarenergie ermöglicht. [ABSTRACT FROM AUTHOR]

A ternary semiconductor nanosystem, ZnS–CdS–Cu2−xS, is described by S. H. Yu, J. Jiang, and co‐workers in their Communication on page 6396 ff. These hetero‐nanorods benefit from efficient charge separation and absorb across the full spectrum of solar radiation, which leads to superior solar energy conversion. [ABSTRACT FROM AUTHOR]

The article presents a general colloidal method for the construction of ultrathin 1D binary and ternary multi-node sheath hetero-nanorods. Researchers started with the ZnS-CdS hybrids. The heteronanostructures comprising ZnS and CdS show good absorption of ultraviolet light. The optical spectra of the synthesized ZnS nanorods, binary multinode sheath ZnS-CdS hetero-nanorods, and ternary ZnS-(CdS/Au) are characterized by UV/Vis-near infrared (NIR) absorption.

An image is presented of the segmented node sheaths of a ternary hetero-nanorod structure.

Review: 102 refs. [ABSTRACT FROM AUTHOR]

BACKGROUND Heat-induced composite gels were prepared with 20 g kg−1 (2%) myofibrillar protein (MP) sol and 100 g kg−1 (10%) olive oil pre-emulsified by MP or non-meat protein in 0.6 mol L−1 NaCl, at pH 6.2. The effect of different non-meat protein (soy protein isolate, egg-white protein isolate and sodium caseinate) pre-emulsions on the rheological properties and microstructure of MP gel was evaluated. RESULTS Adding emulsion enhanced the gel strength of MP gel except for the soy protein isolate (SPI) as emulsifier group, but all emulsion group markedly improved ( P < 0.05) the water-holding capacity and the storage modulus ( G′) of MP gels. SDS-PAGE show that some non-meat protein bands partially participated in the formation of MP composite gels with different kinds of emulsion added. Micrographs revealed that these emulsions made the gels become denser and more compact with subtle diverse effects. CONCLUSION Different meat or non-meat proteins as emulsifier have varied impacts on the rheology and microstructure of MP gels, indicating the potential and feasibility of these non-meat proteins as emulsifiers to modify the textural properties in comminuted meat products. © 2017 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

To meet the comprehensive demand for flexible microwave absorbing (MA) materials, a novel MA rubber containing homemade Polypyrrole nanotube (PPyNT) is produced based on the natural rubber (NR) and acrylonitrile-butadiene rubber (NBR) blends. To achieve the optimal MA performance in the X band, the PPyNT content and NR/NBR blend ratio are adjusted in detail. The 6 phr PPyNT filled NR/NBR (90/10) composite has the superior MA performance with the minimum reflection loss value of −56.67 dB and the corresponding effective bandwidth of 3.7 GHz at a thickness of 2.9 mm, which has the merits in virtue of achieving strong absorption and wide effective absorption band with low filler content and thickness compared to most reported microwave absorbing rubber materials over the same frequency. This work provides new insight into the development of flexible microwave-absorbing materials. [ABSTRACT FROM AUTHOR]

Rationale: Drug combinations are commonly used in pain management, which can produce potent analgesic effects with reduced dosage and adverse effects. Objective: This study was designed to evaluate the anti-nociceptive effects and adverse effects of new combinations of flupirtine (a Kv7 potassium channel opener) and antihistamines (promethazine, fexofenadine) on acute and chronic pain in mice, and the possible mechanisms behind the synergistic analgesic effects were preliminarily investigated. Methods: In acetic acid writhing test, carrageenan-induced inflammatory pain model, and paclitaxel-induced neuropathic pain model, the interaction indexes (γ) between flupirtine and antihistamines were determined by isobolographic analysis. Furthermore, the Kv7 channel blocker XE991 was used to determine whether the effects of single agents and drug combinations on paclitaxel- and carrageenan-induced mechanical allodynia were mediated by Kv7 channels. Finally, hepatotoxicity markers, liver histopathology, and the rotarod test were used to investigate the adverse effects of drugs in combination doses. Results: The interaction indexes of flupirtine-promethazine and flupirtine-fexofenadine in all the above three pain models were lower than 1. The analgesic effects of flupirtine (13 mg/kg), promethazine (5 mg/kg), fexofenadine (20 mg/kg), and their combinations were antagonized significantly by XE991 (3 mg/kg). And the adverse effects of flupirtine and antihistamines in combination doses were not significantly different from the vehicle group. Conclusions: Flupirtine and antihistamines produced synergistic analgesic effects in all the above pain models. The analgesic effects of antihistamines were partially mediated by Kv7/M channels, and the activation of Kv7/M channels may be partly responsible for the synergistic analgesic effects between flupirtine and antihistamines. [ABSTRACT FROM AUTHOR]

Furosemide is a widely used loop diuretic in the treatment of congestive heart failure and edema. During the preparation of furosemide, a new process-related impurity G in the levels ranging from 0.08% to 0.13% was detected in pilot batches by a new high performance liquid chromatography (HPLC) method. The new impurity was isolated and characterized by comprehensive analysis of FT-IR, Q-TOF/LC-MS, 1D-NMR (1H, 13C, and DEPT), and 2D-NMR (1H-1H-COSY, HSQC, and HMBC) spectroscopy data. The possible formation pathway of impurity G was also discussed in detail. Moreover, a novel HPLC method was developed and validated for the determination of impurity G and the other six known impurities registered in the European Pharmacopoeia as per ICH guidelines. The HPLC method was validated with respect to system suitability, linearity, the limit of quantitation, the limit of detection, precision, accuracy, and robustness. The characterization of impurity G and the validation of its quantitative HPLC method were reported for the first time in this paper. Finally, the toxicological properties of impurity G were predicted by the in silico webserver ProTox-II. [ABSTRACT FROM AUTHOR]

M1 macrophages are an important cell type related to tumor immunology and are known to phagocytose cancer cells. In previous studies, the organogermanium compound poly-trans-[(2-carboxyethyl)germasesquioxane] (Ge-132) and its hydrolysate, 3-(trihydroxygermyl) propanoic acid (THGP), have been reported to exert antitumor effects by activating NK cells and macrophages through the induction of IFN-γ activity in vivo. However, the detailed molecular mechanism has not been clarified. In this study, we found that macrophages differentiate into the M1 phenotype via NF-κB activation under long-term culture in the presence of THGP in vitro and in vivo. Furthermore, long-term culture with THGP increases the ability of RAW 264.7 cells to suppress B16 4A5 melanoma cell proliferation. These mechanisms indicate that THGP promotes the M1 polarization of macrophages and suppresses the expression of signal-regulatory protein alpha (SIRP-α) in macrophages and CD47 in cancers. Based on these results, THGP may be considered a new regulatory reagent that suppresses tumor immunity. [ABSTRACT FROM AUTHOR]

Pain is a common public health problem and remains as an unmet medical need. Currently available analgesics usually have limited efficacy or are accompanied by many adverse side effects. To achieve satisfactory pain relief by multimodal analgesia, new combinations of nefopam and gabapentinoids (pregabalin/gabapentin) were designed and assessed in inflammatory, osteoarthritis and neuropathic pain. Isobolographic analysis was performed to analyze the interactions between nefopam and gabapentinoids in carrageenan-induced inflammatory pain, mono-iodoacetate-induced osteoarthritis pain and paclitaxel-induced peripheral neuropathic pain in mice. The anti-inflammatory effect and motor performance of monotherapy or their combinations were evaluated in the carrageenan-induced inflammatory responses and rotarod test, respectively. Nefopam (1, 3, 5, 10, 30 mg/kg, p.o.), pregabalin (3, 6, 12, 24 mg/kg, p.o.) or gabapentin (25, 50, 75, 100 mg/kg, p.o.) dose-dependently reversed mechanical allodynia in three pain models. Isobolographic analysis indicated that the combinations of nefopam and gabapentinoids exerted synergistic anti-nociceptive effects in inflammatory, osteoarthritis, and neuropathic pain mouse models, as evidenced by the experimental ED 50 (median effective dose) falling below the predicted additive line. Moreover, the combination of nefopam–pregabalin/gabapentin alleviated carrageenan-induced inflammation and edema, and also prevented gabapentinoids-related sedation or ataxia by lowering their effective doses. Collectively, the co-administration of nefopam and gabapentinoids showed synergistic analgesic effects and may result in improved therapeutic benefits for treating pain. [Display omitted] • Our study indicated nefopam exerted significant anti-allodynic effects in osteoarthritis pain model for the first time. • Nefopam and gabapentinoids exerted synergistic anti-nociceptive effects in inflammatory, osteoarthritis and neuropathic pain. • Nefopam–gabapentinoids showed significantly improved anti-inflammatory effects than the equimolar dose of monotherapy. • Nefopam–gabapentinoids can alleviate gabapentinoids-induced sedation or ataxia by lowering their effective doses. [ABSTRACT FROM AUTHOR]

Background: Plants suffer from various abiotic stresses during their lifetime, of which drought and salt stresses are two main factors limiting crop yield and quality. Previous studies have shown that abscisic acid (ABA) responsive element binding protein (AREB)/ ABRE binding factors (ABFs) in bZIP transcription factors are involved in plant stress response in an ABA-dependent manner. However, little is known about the properties and functions of AREB/ABFs, especially ABF3, in cotton. Results: Here, we reported the cloning and characterization of GhABF3. Expression of GhABF3 was induced by drought,salt and ABA treatments. Silencing of GhABF3 sensitized cotton to drought and salt stress, which was manifested in decreased cellular antioxidant capacity and chlorophyll content. Overexpression of GhABF3 significantly improved the drought and salinity tolerance of Arabidopsis and cotton. Exogenous expression of GhABF3 resulted in longer root length and less leaf wilting under stress conditions in Arabidopsis thaliana. Overexpressing GhABF3 significantly improved salt tolerance of upland cotton by reducing the degree of cellular oxidation, and enhanced drought tolerance by decreasing leaf water loss rate. The increased expression of GhABF3 up-regulated the transcriptional abundance of downstream ABA-inducible genes under salt stress in Arabidopsis. Conclusion: In conclusion, our results demonstrated that GhABF3 plays an important role in plant drought and salt tolerance. Manipulation of GhABF3 by biotechnology might be an important strategy to alter the stress resistance of cotton. [ABSTRACT FROM AUTHOR]

Highlights: [•] Isl1 nuclear LacZ is expressed in a pattern that recapitulates its endogenous protein expression. [•] In some cases, Isl1nlacZ appears to be more readily detectable than Isl1 protein when expression level is low. [•] Isl1nlacZ may act as a lineage tracer, likely owing to perdurance of the nuclear bgal. [ABSTRACT FROM AUTHOR]

[Display omitted] As the monotherapy of available analgesics is usually accompanied by serious side effects or limited efficacy in the management of chronic pain, multimodal analgesia is widely used to achieve improved benefit-to-risk ratios in clinic. Drug-drug salts are extensively researched to optimize the physicochemical properties of active pharmaceutical ingredients (APIs) and achieve clinical benefits compared with individual APIs or their combination. New drug-drug salt crystals metformin-ibuprofen (MET-IBU) and metformin-naproxen (MET-NAP) were prepared from metformin (MET) and two poorly water-soluble anti-inflammatory drugs (IBU and NAP) by the solvent evaporation method. The structures of these crystals were confirmed by single crystal and powder X-ray diffraction, Hirshfeld surface, Fourier transform infrared spectroscopy and thermal analysis. Both MET-IBU and MET-NAP showed significantly improved solubility and intrinsic dissolution rate than the pure IBU or NAP. The stability test indicated that MET-IBU and MET-NAP have excellent physical stability under stressing test (10 days) and accelerated conditions (3 months). Moreover, isobolographic analysis suggested that MET-IBU and MET-NAP exerted potent and synergistic antinociceptive effects in λ-Carrageenan-induced inflammatory pain in mice, and both of them had an advantage in rapid pain relief. These results demonstrated the potential of MET-IBU and MET-NAP to achieve synergistic antinociceptive effects by developing drug-drug salt crystals. [ABSTRACT FROM AUTHOR]