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Self-driven recycling of sulfur-containing wastewater and hydrogen production is a novel concept that integrates environmental protection and new energy development. In this study, we designed for the first time a Zn-air battery self-driven coupling system for the hydrogen evolution reaction (HER), sulfur oxidation reaction (SOR) and developed a trifunctional catalyst suitable for this system capable of HER, SOR, and oxygen reduction reaction (ORR). By synthesizing cobalt sulfide (Co 3 S 4) in situ on nickel foam (NF), we obtained Co 3 S 4 /NF monolithic catalyst. It only requires 0.312 V and 0.244 V in SOR and HER, respectively, at 100 mA cm−2. Based on this achievement, the SOR||HER coupled electrolysis system was assembled, which achieved 0.69 V at 100 mA cm−2. Furthermore, the Zn-air battery (using Co 3 S 4 as ORR catalyst) could spontaneously drive the SOR||HER system to achieve high-rate hydrogen production. These findings provide promising opportunities for zero-energy consumption H 2 production and recycling of sulfur-containing wastewater. [Display omitted] • The self-driven SOR||HER hybrid electrolysis system was successfully designed. • Co 3 S 4 electrocatalysts were grown on Ni foam as three-dimensional catalyst for HER, SOR and ORR. • The electrolysis can be realized without energy consumption. • The sulfur-containing waste water can be recycled and H 2 generation occurs spontaneously. [ABSTRACT FROM AUTHOR]

• Atmospheric degradation performance of passive coating on tinplate is studied by EIS. • Two models for passive coating failure have been proposed based on EIS data fitting. • The proposed failure models correspond well to findings by SIMS characterizations. • EIS measurement has a great potential in degradation evaluation of passive coatings. Understanding the atmospheric exposure induced degradation of passive coating is of substantial importance in gaining information regarding degradation behavior of the coating itself and its protection effect to underlying substrate. In this work, the structural evolution of a pre-engineered passive Cr 2 O 3 coating on tinplate under atmospheric exposure conditions has been interpretated based on EIS responses to structural evolution of the passive coating. Results indicate that the EIS data interpretation by graphical method can accurately provide parameters of coating thickness δ and CPE parameter n that are associated with structural evolution and corrosion resistance of the passive coating. Following the evolutions in δ and n , two degradation patterns be determined. The first relates an initial degradation in outer layer under high humidity condition and then the failure of inner layer. The second relates an initially moderate but then an excessive growth in the inner layer under high temperature condition, which results in a structural heterogeneity in the inner layer and thus the degradation in corrosion resistance. Such evolutions correspond well to the result by SIMS characterizations. Therefore, EIS measurement can provide an accurate and detailed evaluation on degradation behavior of a passive coating under atmospheric exposure conditions, and it is believed to have a great potential in industrial practice. [ABSTRACT FROM AUTHOR]

Epigenetic alterations relate to various human diseases, and developing inhibitors of Kme regulatory proteins is considered to be a new frontier for drug discovery. We were inspired by the known multicyclic ligands, UNC669 and UNC926 , which are the first reported small molecule ligands for a methyl-lysine binding domain. We hypothesized that reducing the conformational flexibility of the key amine moiety of UNC669 would result in a unique set of ligands. Twenty-five novel compounds containing a fused bi- or tricyclic amine or a spirocyclic amine were designed and synthesized. To gauge the potential of these amine-containing compounds to interact with Kme regulatory proteins, the compounds were screened against a panel of 24 protein methyltransferases. Compound 13 was discovered as a novel scaffold that interacts with SETD8 and could serve as a starting point for the future development of PKMT inhibitors. [ABSTRACT FROM AUTHOR]

Biochar (BC) has been widely used for soil remediation and pollutant removal from environmental water. The pollutant-adsorbing BC often exerts different cytotoxicity from pollutant-free BC. However, how adsorption of multiple pollutants alters the cytotoxicity of BC and how to modulate such toxicity are still unclear. By preparing BCs from two different materials (Banana peel (BP) and corn stalk (CS)) at two pyrolysis temperatures (300 °C and 500 °C, namely BP300-BC, BP500-BC, CS300-BC, and CS500-BC, respectively), we systemically investigated factors that affect the combined cytotoxicity of pollutant-adsorbing BC in Human normal rectal mucosal cells (FHC). The reduction of Cr(VI) to Cr(III) occurred on BC, in particular on BC prepared at 300 °C, in which larger amount of organic matters were left. The presence of Cu(II) promoted the release of Cr from BC once entering cells, which was more obvious for BC prepared at 500 °C. The changes in valence states and release rates of Cr adsorbed on BC prepared at different pyrolysis temperatures together caused reduced cytotoxicity of BP300-BC-Cr-Cu but enhanced cytotoxicity of BP500-BC-Cr-Cu, compared to the same amount of mixture of Cr(VI)–Cu(II). Our findings offer insight understanding of how pyrolysis temperature and the adsorbed multiple pollutants affect the combined cytotoxicity of BC-pollutant complex, allowing for safe applications of BC in future. [Display omitted] • Biochars (BCs) were prepared from different raw materials and at different pyrolysis temperatures. • Cr(VI) and Cu(II) were selected to investigate the combined cytotoxicity of BC-pollutant complex in human FHC cells. • The combined cytotoxicity of singal pollutant- and multiple pollutants-adsorbing BC was investigated. • The changes in valence states and release rates of Cr together caused distinct cytotoxicity of BC-pollutant complexes. [ABSTRACT FROM AUTHOR]

Abstract: Why the cysteine dioxygenase (CDO) cannot catalyze the oxidation of selenocysteine (Sec) but that of cysteine (Cys) is still an open question. In order to solve this question, the CDO model complex, the active site of CDO, and their selenium-substituted complexes have been selected as the computational models in this work. The stepwise donation of electron density during the first two reaction steps has been explored. In the first step, the electron density-donor ability of Se to donate to Fe is stronger than that of S; in the second step, S has the better electron density-donor ability to donate to O(2) than Se. Under the influence, in the Cys-bound complexes, the change of the oxidation state for the Fe center is II→III→II, while the Fe center in the Sec-bound complexes remains in the II oxidation state throughout. Considering that the ferric-superoxo species is an active oxidant and exhibits high reactivity in such reaction, it is speculated that the valence change of the Fe center makes the Cys-bound complexes effectively catalyze the oxidation of Cys, while the Sec-bound complexes cannot catalyze the oxidation of Sec. The competition for donation of electron density determines the valence change and the reaction ability. [Copyright &y& Elsevier]

Abstract: The isolation and characterization of the process related impurities and degradation products of larotaxel drug substance were described. Forced degradation of larotaxel was carried out under acidic, basic, oxidation, light and thermal conditions to assess the nature of the impurities. The pure impurities were obtained by semi-preparative LC isolation and analyzed by NMR and MS. The structures of impurities were confirmed as 7,8-cyclopropyl baccatin III, 10-deacetyl larotaxel, 10-deacetyl-7, 8-cyclopropyl baccatin III, 7-acetyl-8-methyl larotaxel and 2′,13-bissidechain larotaxel. [Copyright &y& Elsevier]

Abstract: In this paper, a novel glucose biosensor was developed based on immobilizing glucose oxidase (GOD) on Prussian blue–multiwall carbon nanotubes (PB@MWNTs) composite and hollow PtCo (H-PtCo) nanochains modified electrode. The PB@MWNTs/H-PtCo membrane showed good biocompatibility, large surface-to-volume ratio and excellent electron-conductive ability. The successful fabrication of the PB@MWNTs composite synthesized with MWNTs as a template and Fe(III)-reducer were characterized by UV–vis absorption spectroscopy, Fourier transform infrared (FTIR) spectrometry and transmission electron microscopy (TEM). The hollow PtCo nanochains were also characterized by TEM and X-ray photoelectron spectroscopy (XPS). The response of the biosensor towards glucose under the optimized conditions, as investigated by chronoamperometry, is linear from 3.0μM to 3.6mM, with a low detection limit of 0.85μM (S/N=3) and a high sensitivity 21mAM−1 cm−2. Moreover, the biosensor exhibits strong anti-interferent ability, good reproducibility and excellent stability. [Copyright &y& Elsevier]

Abstract: The mechanism of the cycloaddition reaction of forming germanic bis-heterocyclic compound between singlet germylene carbene and acetone has been investigated with MP2/6-31G* method, including geometry optimization and vibrational analysis for the involved stationary points on the potential energy surface. The energies of the different conformations are calculated by CCSD (T)//MP2/6-31G* method. From the potential energy profile, it can be predicted that the dominant reaction pathway of the cycloadditional reaction of forming germanic bis-heterocyclic compound consists of three steps: (1) the two reactants firstly form an intermediate INT4 through a barrier-free exothermic reaction of 181.4kJ/mol; (2) INT4 further reacts with acetone (R2) to form an intermediate (INT5), which is also a barrier-free exothermic reaction of 148.9kJ/mol; (3) INT5 then isomerizes to a germanic bis-heterocyclic product P5 via a transition state TS5 with an energy barrier of 53.3kJ/mol. [Copyright &y& Elsevier]

Abstract: Novel pyrimidine-fused 5,6-dihydrobenzodiazepines were prepared via a Pictet–Spengler-like cyclization. It was based on the intramolecular electrophilic substitution of the phenyl ring of 5-amino-6-chloro-4-(N-methylanilino)pyrimidine 1 by the iminium intermediate formed with an aldehyde in one pot. The products may be further transformed by subsequent nucleophilic substitution of the chloro atom. This strategy may provide an efficient method to access a library of compounds based on privileged substructures that are of interest in drug discovery. [Copyright &y& Elsevier]

• The peak time delay was an independent predictor of good collaterals in AIS patients. • The peak time delay was an independent predictor of good outcomes in AIS patients. • Tissue fate were moderately positively correlated with peak density decrease. Collateral status is a pivotal determinant of clinical outcomes in acute ischemic stroke (AIS); however, its evaluation can be challenging. We investigated the predictive value of CT perfusion (CTP) derived time and density alterations versus CTP for collateral status prediction in AIS. Consecutive patients with anterior circulation occlusion within 24 h were retrospectively included. Time-density curves of the CTP specified ischemic core, penumbra, and the corresponding contralateral unaffected brain were obtained. The collateral status was dichotomised into robust (4–5 scores) and poor (0–3 scores) using multiphase collateral scoring, as described by Menon et al.. Receiver operating characteristic curves and multivariable regression analysis were performed to assess the predictive ability of CTP-designated tissue time and density alterations, CTP for robust collaterals, and favourable outcomes (mRS score of 0–2 at 90 days). One-hundred patients (median age, 68 years; interquartile range, 57–80 years; 61 men) were included. A smaller ischemic core, shorter peak time delay, lower peak density decrease, lower cerebral blood volume ratio, and cerebral blood flow ratio in the CTP specified ischemic core were significantly associated with robust collaterals (P FDR ≤ 0.004). The peak time delay demonstrated the highest diagnostic value (AUC, 0.74; P < 0.001) with 66.7 % sensitivity and 73.7 % specificity. Furthermore, the peak time delay of less than 8.5 s was an independent predictor of robust collaterals and favourable clinical outcomes. Robust collateral status was significantly associated with the peak time delay in the ischemic core. It is a promising image marker for predicting collateral status and functional outcomes in AIS. [ABSTRACT FROM AUTHOR]

Abstract: Nanostructured lipid carriers (NLC)-based gel was developed as potential topical system for flurbiprofen (FP) topical delivery. The characterizations of the prepared semisolid formulation for topical application on skin were assessed by means of particle size distribution, zeta potential analysis, X-ray analysis, in vitro percutaneous penetration, rheological study, skin irritation test, in vivo pharmacodynamic evaluation and in vivo pharmacokinetic study. The NLC remained within the colloidal range and it was uniformly dispersed after suitably gelled by carbopol preparation. It was indicated in vitro permeation studies through rat skin that FP-NLC-gel had a more pronounced permeation profile compared with that of FP-loaded common gel. Pseudoplastic flows with thixotropy were obtained for all NLC-gels after storage at three different temperatures. No oedema and erythema were observed after administration of FP-NLC-gel on the rabbit skin, and the ovalbumin induced rat paw edema could be inhibited by the gel. The maximum concentration in plasma was 29.44μg/ml and 2.49μg/ml after oral and topical administration, respectively. While the amount of drug accumulated in skin after topical application was much higher than oral application. In conclusion, NLC-based gel could be a promising vehicle for topical delivery of FP. [Copyright &y& Elsevier]

Abstract: Although various drugs for the treatment of rheumatoid arthritis (RA) have been used in clinics, RA is not completely curable to date. Thus, to seek new drugs for the treatment of RA has been a hotspot. Hydroxynaphthoquinones are the major anti-inflammatory active constituents in Arnebia euchroma (Royle) Johnst. The present study aims to evaluate the anti-arthritic activity of a hydroxynaphthoquinone mixture (HM) of A. euchroma (Royle) Johnst, including its anti-inflammatory and analgesic effects. The anti-arthritic efficacy of HM was examined using complete Freund''s adjuvant- and bovine type II collagen-induced arthritic models. The paw edema, polyarthritis index and histopathological change were evaluated. The analgesic effect was assessed using the chemical and thermal models of nociception. Results found that HM administered prophylactically and curatively showed marked anti-arthritic activity by suppressing the paw swelling and development of inflammation, lowering the levels of TNF-α and IL-1β and protecting cartilage and bone from damage. The protection of HM was superior to that of reference drugs such as prednisone acetate or etanercept, and showed no direct deleterious effect. Similarly, HM showed significant analgesic effects. In summary, HM possessed potent anti-arthritic activity. It could relieve inflammatory symptoms and protect against joint destruction. These findings indicate that HM would be a potential therapeutic agent for arthritic disease, which provide pharmacological evidence for its clinical application. [Copyright &y& Elsevier]

[Display omitted] • Astragaloside core–shell nanofibers with dual release properties were constructed by coaxial electrospinning. • Coaxial astragaloside/PVP/PLA nanofiber functional dressing had excellent hydrophilicity, antioxidant properties and mechanical strength. • Coaxial astragaloside/PVP/PLA nanofiber functional dressing had excellent biocompatibility and promotes cell proliferation, adhesion and migration. • Coaxial astragaloside/PVP/PLA nanofiber functional dressing achieved dual release of astragaloside through the core–shell structure, thereby accelerating wound healing. Diabetic wound is often a chronic wound with complex healing process and long healing time. It is evident that conventional dressings are inadequate in promoting the healing of diabetic wounds. In this study, a novel nanofiber dressing, produced through coaxial electrostatic spinning technology, was created to facilitate the healing of diabetic chronic wounds. This dressing was composed of Astragaloside (AS), polyvinylpyrrolidone (PVP) and polylactic acid (PLA). The morphology of the nanofiber dressing was characterized by scanning electron microscopy (SEM). Confirmation of the core–shell structure was done with the help of transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD). A pharmacodynamic study was conducted both in vivo and in vitro. It was shown that the nanofibers were approximately 604.83 ± 127.96 nm and with a core–shell structure. Additionally, in vitro drug release experiments revealed that the coaxial AS/PVP/PLA nanofiber functional dressings had a first rapid and then slow release property. Antioxidant activity experiment showed that the free radical scavenging rate of Astragaloside-loaded nanofibers reached 61 %. Mechanical tests also indicated that the nanofibers had an elastic modulus of 38.37 ± 1.81 MPa. Coaxial AS/PVP/PLA nanofiber functional dressings had good antimicrobial activity, and its diameter of the circle of inhibition against Staphylococcus aureus was 17.17 ± 2.04 mm, and its diameter of the circle of inhibition against Escherichia coli was 6.80 ± 0.78 mm. In addition, the findings of in vitro cellular tests showed that coaxial AS/PVP/PLA nanofiber functional dressings could promote the multiplication, adhesion and the migration ability of L929 fibroblasts with better biocompatibility. Finally, the wound healing rate of diabetic rats in the coaxial AS/PVP/PLA nanofiber functional dressing group was 96.54 ± 0.29 % on day 14. Consequently, the coaxial AS/PVP/PLA nanofiber functional dressings prepared by coaxial electrostatic spinning technique had satisfactory morphology, met the requirements of performance, and had the potential to be developed as a dressing for improving diabetic chronic wound healing. [ABSTRACT FROM AUTHOR]

The periosteum plays a crucial role in both bone development and the healing process of bone fractures. However, few studies have focused on developing artificial periosteum due to the complexity of its construction and the biological risks for clinical practice. To address this issue, we proposed a strategy for the fabrication of a photocrosslinkable natural hydrogel nanofibrous membrane (SFMA-Lap@AcBP) based on methacrylated silk fibroin (SFMA), photoinitiator (Lap), acrylate bisphosphonate (AcBP) through combining electrospinning technology with hydrogel, mimicking the structure and function of periosteum to promote bone regeneration. AcBP were covalently attached to the SFMA hydrogel nanofibrous membrane via conjugation. With the degradation of SFMA-Lap@AcBP hydrogel nanofibrous membrane, the released BP-grafted derivates could promote bone regeneration. Moreover, SFMA-Lap@AcBP hydrogel membranes were found to be able to trap metal ions such as Mg2+ and Ca2+ in vivo , which might play a synergistic role in inducing complete bone regeneration. Furthermore, the hydrogel membranes had excellent cytocompatibility. They could imitate the microenvironment of the extracellular matrix, thereby offering structural and biochemical cues for the adhesion, proliferation, and differentiation of cells, without the need of exogenous cells or inductive growth factors, resulting in a facilitated osteogenesis. After implanting membranes into a cranial periosteal and bone defect in rats, both the amount and quality of new bone in the SFMA-Lap@AcBP group were found to be higher than those in the other groups. Therefore, the hydrogel membrane bionic periosteum was efficient and versatile in inducing bone regeneration, providing a potential strategy to address clinical issues. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract The nonuniformity of infrared focal plane array (IRFPA) seriously affects the image quality and the measurement accuracy of the infrared detector system. Long-wave infrared (LWIR) detector has highly sensitivity and image unstable factors, and the nonuniformity tends to drift slowly with the change of the environment. In this paper, we propose a new nonuniformity correction (NUC) algorithm based on gradient sky scene. Firstly, we obtain the two-point calibration images at two different pitch angles in the pure sky without any cloud. And then, the gain and offset coefficients are calculated from the standard two-point NUC. Finally, the local weighted filter based denoising algorithm is employed to eliminate a few residual isolated noise. Computational result shows that the SNR gain of the proposed method is increased 2.50 dB compared to the standard two-point method based on uniform blackbody. Results indicate that the proposed algorithm exhibits a superior correction effect and has the advantage of low complexity which meets the real-time requirements. [ABSTRACT FROM AUTHOR]

Human kidney-type glutaminase (KGA) is an important target that is often over expressed in many cancer cells but very few effective inhibitors of this enzyme have yet reached clinical trials. Caudatan A and caudatan B, two undescribed tetracyclic flavans with an unusual ether bond between the C-4 and C-2′ were isolated from the roots of Ohwia caudata (Thunb.) H.Ohashi. Caudatan A exhibited stronger inhibitory activity and caudatan B showed moderate effect from the results of inhibitory activities evaluations on KGA. The molecular docking and primary structure-activity relationship analysis revealed that the less steric hindrance at ring A was necessary to the effect. Therefore, combined its better solubility than that of bis-2-(5-phenylacetimido-1,2,4-thiadiazol-2-yl)ethyl sulfide (BPTES), caudatan A might be the potential candidate as the inhibitor of KGA for further studies. [ABSTRACT FROM AUTHOR]

In order to increase the solubility of poorly water-soluble natural product, xanthoceraside, an effective anti-AD compound from Xanthoceras sorbifolia Bunge , and maintain its natural property, the xanthoceraside hollow gold nanoparticles were successively prepared by green ultrasonic method with silica spheres as templates and HF solution as selective etching solvent. Hollow gold nanoparticles and drug-loaded hollow gold nanoparticles were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD) and differential scanning calorimetry (DSC). The solubilities of xanthoceraside loaded on hollow gold nanoparticles were increased obviously from 3.0 μg/ml and 2.5 μg/ml to 12.7 μg/ml and 10.7 μg/ml at 25 °C and 37 °C, respectively. The results of XRD and DSC indicated that the reason for this increase was mainly due to the amorphous state of xanthoceraside loaded on the hollow gold nanoparticles. In summary, the method of loading xanthoceraside onto hollow gold nanoparticles was a green and useful strategy to improve the solubility and dissolution of poorly water-soluble natural products and worth to applying to other natural products. [ABSTRACT FROM AUTHOR]

With more production and application of ion-exchange fibers ( IEFs), it becomes necessary to understand the interaction between IEFs and amine compounds, an important group of organic drugs and structural components of large organic molecules in biological systems. However, so far few experimental studies have been conducted to systematically investigate the exchanging mechanism of amine compounds to IEFs. Therefore, 15 amine drugs were selected to investigate the effect of amine type on the loading and release of them from the related IEFs. Loading affinity of these drugs by IEFs decreased in the order of secondary, tertiary, and primary. The following items: basicity, aromaticity, molar volume, rotatability, and so on, were emphatically discussed to address the underlying mechanism of drug loading and releasing extent and rate of IEFs. It was evident that strong alkaline drugs strengthened the ionic bond between the amine groups and IEFs, and thus the loading affinity. These results will advance the understanding of the exchanging behavior of IEFs in the drug delivery system. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:1095-1103, 2014 [ABSTRACT FROM AUTHOR]

Abstract: Based on the blend of styrene-isoprene-styrene (SIS) thermoplastic elastomer and acrylic resin Eudragit® EPO, amphiphilic hot-melt pressure sensitive adhesives (HMPSAs) were fabricated. Compatibility and micromorphology of SIS/EPO blends (SEBs) were analyzed with differential scanning calorimetry (DSC), atomic force microscopy (AFM) and scanning electron microscopy (SEM). The results showed that when the mass ratio of SIS to EPO was 1:1~1:2, bicontinuous structure was formed. Following the addition of an appropriate amount of polyethylene glycol (PEG), mineral oil and C5 resin, the amphiphilic HMPSAs were prepared. Because of the compatibility between SIS and EPO, as well as the hydrogen bond interaction between EPO and PEG, amphiphilic HMPSAs showed good thermostability. The adhesive performance of HMPSAs was measured with 180° peeling strength and holding power. Geniposide and oleanolic acid were used as model drugs to investigate drug release behavior. When the mass ratio of PEG to SEB was 13:30~16:30, the HMPSAs could maintain good adhesion performance and achieve continual release of both hydrophilic and lipophilic drugs. In weakly acidic conditions, the HMPSAs exhibited good hygroscopicity and release profile, it was shown that pH sensitive amphiphilic HMPSAs were more suitable for transdermal drug delivery system (TDDS). [Copyright &y& Elsevier]

Biased agonism refers to the ability of compounds to drive preferred signaling pathways and avoid adverse signaling pathways in a ligand-dependent manner for some G-protein–coupled receptors. It is thought that the separation of therapeutic efficacy (e.g., analgesia) from adverse effects (e.g., respiration depression) can be achieved through the design of biased MOR agonists and one example is the recently approved MOR biased agonist oliceridine (TRV130). However, oliceridine only demonstrates modest beneficial effects as compared to other opioids in terms of therapeutic/adverse effect balance. One possibility attributable to the modest success of oliceridine is its limited bias, and as such developing MOR ligands with a more biased agonism profile could in theory further improve the beneficial effects of the ligands. Here, we rationally designed and synthesized a series of derivatives as potent highly biased MOR agonists (19a-v) through the modification and structure-activity relationship study of TRV130. This novel synthetic molecule, LPM3480392 (19m), demonstrated improved in vitro biased agonism (EC 50 = 0.35 nM, Emax = 91.4%) with no measured β-arrestin recruitment (EC 50 > 30000 nM, Emax = 1.6%), good brain penetration (B/P ratio = 4.61, 0.25 h post-IV dosing 2.0 mg/kg), a favorable pharmacokinetic profile (distribution volume = 10766 mL/kg, t 1/2 = 1.9 h) and produced potent antinociceptive effect with reduced respiratory suppression (sO 2 (%) = 92.17, 0.32 mg/kg, SC) as compared to TRV130. LPM3480392 has completed preclinical studies and is currently under clinical development (CTR20210370) as an analgesic for the treatment of moderate to severe pain. [Display omitted] • A novel class of μ-opioid receptor (MOR) ligands were designed and synthesized. • The effects on MOR cAMP potency and β-arrestin recruitment of all compounds were evaluated. • 19 m demonstrated potent antinociceptive effect in vivo with reduced respiratory suppression as compared to TRV130. • 19 m is currently undergoing phase I clinical trials (CTR20210370) for managing moderate to severe pain. [ABSTRACT FROM AUTHOR]

Abstract: A novel gastro-mucoadhesive delivery system based on ion-exchange fiber has been developed. Rriboflavin-5′-phosphate sodium salt (RF5P), which is site-specifically absorbed from the upper gastrointestinal tract, was used as model drug. A modified dissolution system, which can also be called ‘flow through diffusion cell’ (FTDC), was used to study the drug release from the drug fibers. Gastrointestinal transit studies of the RF5P fiber complexes in rats and gamma imaging study in volunteer was carried out to evaluate the gastro-retentive behavior of the fiber. The pharmacokinetic profile and parameters of riboflavin via analysis of urinary excretion of riboflavin on man were measured. Study on rat and man provide evidence for the validity of the hypothesis that the drug fiber provided good mucoadhesive properties in vivo and should therefore be of considerable interest for the development of future mucoadhesive oral drug delivery dosage forms. [Copyright &y& Elsevier]

A direct electroreductive dimerization of electron-deficient vinylarenes for the synthesis of 1,4-diarylbutane has been developed using a simple undivided cell with inexpensive carbon electrodes at room temperature. The control and deuterium-labeling experiments of electroreductive dimerization suggest that the hydrogen source comes from the solvent CH 3 CN. This protocol provides a mild and efficient route for the construction of C–C bond in moderate to good yields with high regioselectivity and broad substrate scope. A highly regioselective linear dimerization of electron-deficient vinylarenes under mild electrochemical conditions is introduced, which could provide direct access to a diverse set of 1,4-diarylbutanes. [Display omitted] [ABSTRACT FROM AUTHOR]