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Fourteen eremophilane sesquiterpenoids (1-14), including nine new congeners, septoreremophilanes A-I (1-9), together with three known sesquiterpenes (15-17), two known tetralone derivatives (18, 19), and two known cholesterol analogues (20, 21), were isolated from the endophytic fungus Septoria rudbeckiae. Compounds 1-6 and 7a belong to the family of the highly oxygenated eremophilane sesquiterpenoids with a 6/6/5 tricyclic system and bearing a hemiacetal moiety. The inhibitions of all metabolites against eight bacteria were estimated in vitro, and nine new metabolites (1-9) were tested for antineuroinflammatory activity. Notably, the effects of 4 against Pseudomonas syringae pv. actinidae and 20 against Bacillus cereus displayed potent inhibitory, with the MIC values of 6.25 and 6.25 μM, respectively. Further, scanning electron microscopy analyses indicated that 4 and 20 were to change the outer configuration of bacterial cells, respectively, and the investigations demonstrated that 4 and 20 may act as potential structure templates for the development of the agrochemical bactericides. Additionally, compound 6 displayed potent inhibition of NO generation in lipopolysaccharide-induced BV-2 microglial cells (IC50 = 12.0 ± 0.32 μM), and the conceivable anti-inflammatory mechanisms implicated were also investigated by molecular docking. Thus, the bioactive metabolites of the strain S. rudbeckiae may serve as a novel resource to be developed.

In order to dispose of high level nuclear waste during the operation of underground geological repositories, the buffer/backfill performance of bentonite–based material might be affected by the combined influence of temperature field and infiltrating groundwater thereby leading to uncertainties in the safe operation of repositories. In order to address this issue, bentonite–sand mixtures (BSM) were prepared by mixing GMZ01 bentonite with sand using ratios of 70:30 and 30:70 by weight. One-dimensional deformation experiments were conducted on the prepared BSM in NaCl solutions of varying concentrations (0, 0.1, and 1.0 mol/L) at three different temperatures (25, 60, and 90 °C). The experimental results on the BSM in NaCl solutions indicated that the swelling deformation increased as temperature rises, because osmotic swelling is the dominant swelling type under the experimental conditions. The swelling deformation of BSM could be represented by fractal em–pe relation (em is the montmorillonite void ratio, pe is the effective stress incorporating osmotic suction). At each temperature interval, the swelling of BSM with high bentonite content in different NaCl solutions can be expressed as a unique em–pe relation; however, the swelling coefficient of montmorillonite in the em–pe relationship increases at higher temperature. When the effective stress pe exceeds a threshold, sand–particle skeletons will be formed in BSM with low bentonite content, thus resulting in deviations in the value of em from the em–pe curve. The em–pe relation offers a simple and efficacious method to estimate the deformation of BSM under combined thermal–salt effects.

Swelling deformation tests of GaoMiaoZi (GMZ01) bentonite were performed at 25, 40 60, and 90 °C in distilled water. Experimental results suggested that the maximum swelling strain of GMZ01 bentonite increased with temperature, due to the osmotic swelling dominated the swelling. The em − σv relation for compacted bentonite at a same temperature can be expressed as e m = K σ v D - 3 (em is montmorillonite void ratio, σv is vertical stress). The fractal dimension, D, of GMZ01 bentonite was unaffected by the temperature according to the results of N2 adsorption tests. Calculated by the diffuse double layer (DDL) model under the condition of osmotic swelling, a linearly relation was found between the montmorillonite swelling coefficient K and temperature Tc. Combing the fractal em − σv relation and linear K − Tc relation, a simple method for evaluating the swelling of GMZ01 bentonite affected by temperature was proposed.

The generalized gradient approximation (GGA) of density function theory (DFT) methods are employed to investigate the decomposition of TKX- -50 molecule on the Al(111) surface. The calculation employs an Al supercell slab model and periodic boundary conditions. Five kinds of adsorption configurations for TKX-50 on Al surface are studied. The TKX-50 is adsorbed on Al surface to form the N?Al, O?Al and OH?Al bonds. The adsorption energies are in the range from ?113.15 to ?1334.40 kJ/mol. The activation energies of all configurations are in the range of 100.34?354.10 kJ/mol. The N1-N2 ruptures in V1 and N2-N3 ruptures in V2 takes place easily. The activation energies of these two bonds rupture (100.34 and 108.06 kJ/mol, respectively) are less than that of pure TKX-50 (161.58 and 215.99 kJ/mol). Al atoms promote the breaking of the tetrazole ring of TKX-50. The quantities of electron transfer from Al atoms to TKX-50 are in range of 1.42?4.90 e.

Efficient production of lactide (LT) from highly concentrated lactic acid (LA) based on β zeolite catalysts is highly desired for an economically sustainable polylactic acid (PLA) industry. Like an...

In a high-level radioactive waste repository, bentonite may react with the alkaline solution produced by cement degradation. In this study, bentonite was mixed with alkaline solution in a closed system and reacted for 3–24 months. Furthermore, swelling tests were conducted on the alkaline-dissolved bentonite immersed in distilled water. The swelling deformation decreased significantly with increases in the concentration of NaOH solution and reaction time, and this was mainly due to montmorillonite dissolution. The fractal e–p relationship (e is the void ratio and p is the vertical pressure) with two calculation coefficients (the swelling coefficient and the fractal dimension) was employed to determine the swelling of alkaline-dissolved bentonite. The fractal dimension increased slightly with increasing reaction time or concentration of NaOH solution, as the dissolution traces caused by the alkaline solution favoured an increase in the irregularity and fractality of the bentonite surface. The swelling coefficient decreased linearly with decreasing montmorillonite content. In addition, the swelling coefficient and the fractal dimension were related exponentially to the reaction time in alkaline solution. A relationship between the swelling of alkaline-dissolved samples and the reaction time was proposed, which might be used to assess the swelling properties of bentonite barriers that would be affected by long-term dissolution of the alkaline solution in a closed repository.

Investigation of the effects of salinity concentration on shear strength of compressed bentonite and its sand mixture is desideratum to evaluate the safety of engineered barriers for disposal of highly radioactive nuclear waste. In this research study, the compacted bentonite–sand mixtures were first saturated using distilled water and NaCl solutions under a specified stress in oedometers. Then the specimens were subjected to shearing in a direct shear apparatus. The experimental results revealed that the shear strength increases at higher NaCl concentration and high sand content of mixture. By employing the modified effective stress (pe) containing the osmotic suction effect of porewater, the highest shear strength (τf), referred to as the peak shear strength (PSS) from hereon, of mixture in different NaCl concentrations can be represented by a unique line in the τf–pe plane. As per Mohr–Coulomb principle, the mixtures with a given bentonite content possess the same parameters of shear strength (effective angle of internal friction φ′ and effective cohesion c′), when they are placed and allowed to saturate in NaCl solution at various concentrations. On the contrary, the appearance of sand particles on the shearing surface offers more resilience to the movement of montmorillonite particles which increases the internal friction angle φ′ but poses negligible effects on the cohesion c′. When the effective stress approaches a threshold value, the skeleton of sand particles is formed in the mixture with high sand content bringing about a significant change in the shear strength of bentonite.

Funding Information: This work is supported by the National Natural Science Foundation of China under grant no. 6207030573 , the National Basic Research Program of China (973 Program) under grant no. 2012CB934200 , and the Specialized Research Fund for the Doctoral Program of Higher Education under grant no. 20130071110018 . Publisher Copyright: © 2021 Elsevier B.V. Copyright: Copyright 2021 Elsevier B.V., All rights reserved. The NO2 sensing performance of a special lateral photovoltaic self-powered gas sensor based on the N-hyperdoped microstructured silicon (N-Si) is systematically studied under the different light illumination. The dependence of sensing characteristics on light intensity and wavelength is obtained, respectively. Results show that the sensing properties can be changed effectively by the different intensities and wavelengths, suggesting that a multidimensional regulation/optimization for the sensing characteristics is possible by light. More interestingly, the light with wavelength of 940 nm and intensity of ∼18 μW/cm2 could bring a comprehensive optimization for gas sensing, under which the N-Si sensor exhibits the excellent overall performance with simultaneously the low light power needed, good gas response, high sensitivity, wide detectable range and short response time at room temperature.

Cold stress is a major threat to fish in both nature and aquaculture, and can induce oxidative stress in various fish. While the exact role of oxidative stress in cold-caused mortality is still unknown. The purpose of the present study was to evaluate the effects of oxidative stress on cold tolerance in fish and verify whether changing oxidative status could affect cold tolerance. We firstly demonstrated that acute cold exposure induced high oxidative stress in zebrafish liver, which may lead to mortality. Then we performed in vivo and in vitro experiments to determine the effects of the altered oxidative status on cold tolerance in zebrafish and zebrafish liver cell line (ZFL), respectively. In the in vivo study, the zebrafish which were fed with α-lipoic acid or reduced glutathione had lower cold-caused oxidative stress and tissues damage, and showed higher cold tolerance. In the experiment using zebrafish cells, increasing oxidative stress by H2O2 decreased the cellular cold tolerance, and the cold tolerance was partly recovered when oxidative stress was reduced by the addition of Vitamin C (VC). Taken together, we conclude that the reduction of oxidative stress increases cold tolerance in fish.

Fungal spoilage of bread remains an unsolved issue in bread making. This work aims to identify alternative strategies to conventional preservatives in order to prevent or delay fungal spoilage of bread. The minimum inhibitory concentration (MIC) of bacterial metabolites and chemical preservatives was evaluated in vitro, and compared to their in situ activity in baking trials. Calcium propionate, sorbic acid, 3-phenyllactic acid, ricinoleic acid, and acetic acid were tested both individually and in combination at their MIC values against Aspergillus niger and Penicillium roqueforti. The combination of acetic acid with propionate and sorbate displayed additive effects against the two fungi. For these reasons, we introduced sourdough fermentation with specific strains of lactobacilli, using wheat or flaxseed, in order to generate acetate in bread. A combination of Lactobacillus hammesii and propionate reduced propionate concentration required for shelf life extension of wheat bread 7-fold. Flaxseed sourdough bread fermented with L. hammesii, excluding any preservative, showed a shelf life 2 days longer than the control bread. The organic acid quantification indicated a higher production of acetic acid (33.8 ± 4.4 mM) when compared to other sourdough breads. Addition of 4% of sucrose to sourdough fermentation with L. brevis increased the mould free shelf-life of bread challenged with A. niger by 6 days. The combination of L. hammesii sourdough and the addition of ricinoleic acid (0.15% or 0.08%) prolonged the mould free shelf-life by 7–8 days for breads produced with wheat sourdoughs. In conclusion, the in vitro MIC of bacterial metabolites and preservatives matched the in situ antifungal effect. Of the different bacterial metabolites evaluated, acetic acid had the most prominent and consistent antifungal activity. The use of sourdough fermentation with selected strains able to produce acetic acid allowed reducing the use of chemical preservatives.

Three new pterocarpans, named abrusprecatins A-C (1–3), along with three known ones, namely medicarpin (4), maackiain (5), and 4-hydroxy-3-methoxy-8,9-methylenedioxypterocarpan (6) were isolated from the aerial parts of Abrus precatorius. The structures of these compounds were established by extensive analysis of mass spectrometric data, 1 D and 2 D NMR spectroscopic data. In addition, the absolute configurations were determined by a combination of single crystal X-ray diffraction analysis and circular dichroism spectroscopy.

A phytochemical investigation on the leaves of Callistemon viminalis resulted in the isolation of two unusual compounds, callistemonols A (1) and B (2). Callistemonol A (1) possesses a novel skeleton of a furan ring fusing both an α,β-triketone and a phloroglucinol unit, while callistemonol B (2) is an acylphloroglucinol derivative featuring two methyl substituents on a five-membered ring and an isovaleryl side chain. Their structures were fully characterized on the basis of extensive spectroscopic analysis, including 1D and 2D NMR parameters, as well as the IR and HRESIMS data. Callistemonol A (1) represents an example of a natural dibenzofuran with two phenyl moieties, and a plausible biogenetic pathway to generate this novel dibenzofuran through a C-C bond-forming radical SAM enzyme is proposed. Moreover, antimicrobial assays, in conjunction with time-killing and biophysical studies, revealed that 1 and 2 exert potent bactericidal activities against a panel of methicillin-resistant pathogenic microbes.

Human 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1) catalyses the last step in estrogen activation and is thus involved in estrogen-dependent diseases (EDDs). Unlike other 17β-HSD members, 17β-HSD1 undergoes a significant substrate-induced inhibition that we have previously reported. Here we solved the binary and ternary crystal structures of 17β-HSD1 in complex with estrone (E1) and cofactor analog NADP+ , demonstrating critical enzyme-substrate-cofactor interactions. These complexes revealed a reversely bound E1 in 17β-HSD1 that provides the basis of the substrate inhibition, never demonstrated in estradiol complexes. Structural analysis showed that His221 is the key residue responsible for the reorganization and stabilization of the reversely bound E1, leading to the formation of a dead-end complex, which exists widely in NADP(H)-preferred enzymes for the regulation of their enzymatic activity. Further, a new inhibitor is proposed that may inhibit 17β-HSD1 through the formation of a dead-end complex. This finding indicates a simple mechanism of enzyme regulation in the physiological background and introduces a pioneer inhibitor of 17β-HSD1 based on the dead-end inhibition model for efficiently targeting EDDs. DATABASES: Coordinates and structure factors of 17β-HSD1-E1 and 17β-HSD1-E1-NADP+ have been deposited in the Protein Data Bank with accession code 6MNC and 6MNE respectively. ENZYMES: 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1) EC 1.1.1.62.

Most tea plants (Camellia sinensis) are self-incompatible. Self-incompatibility is critical for preventing inbreeding depression and maintaining genetic diversity, but it can hinder breeding and genetic studies. Originally, the propose of this study was to identify fathers of 16 elite F1 individuals derived from open-pollinated seeds of an anthocyanin-rich tea cultivar ‘Ziyan’. In order to achieve this, 41 candidate parents and 16 F1 individuals were genotyped with 15 polymorphic SSR markers. Using exclusion and likelihood methods, fathers of 12 individuals were identified at 95% level of confidence. Surprisingly, the results showed that eight individuals were from self-crossing of ‘Ziyan’. Additional 36 SSR markers were used to further confirm selfing and the results were consistent, demonstrating that ‘Ziyan’ is self-compatible. As expected, the degrees of heterozygosity of the eight selfing individuals were significantly lower than ‘Ziyan’ and other tea accessions. This is the first report of a clonal cultivar of C. sinensis being self-compatible under open-pollination conditions and verified using DNA-based markers. Therefore, ‘Ziyan’ and its selfing offspring will be valuable materials for both genetic studies and breeding in C. sinensis.

The effect of the architecture of poly(ethylene glycol)/poly(L-lactide) (PEG/PLLA) block copolymers on the non-isothermal crystallization behaviors of PLLA blocks was investigated by differential scanning calorimetry (DSC) and wide angle X-ray diffraction (WAXD). 1-Arm MPEG-b-PLLA and 4-arm PEG-b-PLLA (4PEG-b-PLLA) were synthesized by the ring-opening polymerization of Llactide in the presence of poly(ethylene glycol) methyl ether (MPEG) and 4-arm poly(ethylene glycol) (4PEG). 4-Arm PLLA-b-MPEG (4PLLA-b-PEG) was synthesized by coupling 4-arm PLLA and MPEG. The WAXD results indicated that the crystalline structure of PLLA blocks did not alter due to the different chain architectures. The average values of Avrami index ( $$\bar{n}$$ ) were all above 4, which indicated that the nucleation mechanism of PLLA blocks was heterogeneous nucleation, regardless of the architectures. The overall crystallization rates were decreased markedly as following: MPEG-b-PLLA > 4PEG-b-PLLA > 4PLLA-b-PEG, ascribed to the different confinement by PEG blocks and to the steric hindrance of chain architectures. Therefore, the crystallization of PLLA blocks became more difficult and the crystallization activation energy of the PLLA blocks increased due to the confinement of chain architectures.

Most conventional high energetic molecules contain nitro group that endows them with high sensitivities. To overcome this disadvantage, 11 novel bistetrazole-diolated anions were designed by inserting different bridges into the dihydroxylammonium 5,5′-bistetrazole-1,1′-diolate (TKX-50) framework. Forty-two energetic salts were formulated from the bistetrazole-diolated anions and ammonium-based cations, which were paired according to their thermal stability. Their crystal densities, heats of formation (HOFs), energetic properties, and impact sensitivity were predicted using density functional theory (DFT) and volume-based thermodynamics calculations (VBT). It is found that the introduction of the tetrazole ring to the bridge of bistetrazole diolate is the most efficient to get high density, while the introduction of the tetrazine ring as a bridge is a good choice in order to obtain excellent HOFs. However, azo group is more helpful to obtain good detonation properties due to its better oxygen balance, and its corresponding dihydroxylammonium salt exhibits better detonation performance (D = 9.41 km s−1 and P = 41.27 GPa) than TKX-50 (A3, D = 9.25 km s−1 and P = 39.53 GPa). Therein, 18 energetic salts are endowed with better detonation properties and much lower sensitivity than the commonly used 1,3,5-trinitro-1,3,5-triazacyclohexane (RDX). The construction of the non-nitro energetic anions like bistetrazole diolate and oxygenated cation like hydroxylammonium is a potential efficient way for screening out the high energy density materials (HEDMs) with low sensitivity.

Human 17β-hydroxysteroid dehydrogenase type 7 (17β-HSD7), a special multifunctional enzyme, activates the estrogen estrone while inactivating the potent androgen dihydrotestosterone. Thus, this enzyme has become an ideal target for hormone-dependent breast cancer treatment, as its inhibition leads to estradiol reduction and dihydrotestosterone restoration. However, a particular concern has arisen related to an additional role in cholesterol biosynthesis, as inhibition of the enzyme may lead to undesirable side effects. Our findings demonstrate that the available enzyme inhibitors are non-competitive. Among these, many such as INH81, are specific toward sex-hormone conversion, whereas others represented by 4-bromo-ethynylestradiol, are more specific for zymosterone reduction occurring during cholesterol biosynthesis. The binding of non-competitive inhibitors does not affect the substrate binding on the enzyme. This is the first demonstration of non-competitive inhibitors acting selectively on different catalyses, thereby facilitating inhibitor uses for breast cancer treatment. We aim to quickly communicate the novel results.

To identify drugs that are potentially used for the treatment of COVID-19, the potency of 1403 FDA-approved drugs were evaluated using a robust pseudovirus assay and the candidates were further confirmed by authentic SARS-CoV-2 assay. Four compounds, Clomiphene (citrate), Vortioxetine, Vortioxetine (hydrobromide) and Asenapine (hydrochloride), showed potent inhibitory effects in both pseudovirus and authentic virus assay. The combination of Clomiphene (citrate), Vortioxetine and Asenapine (hydrochloride) is much more potent than used alone, with IC50 of 0.34 μM.

Eight natural biphenyl-type phytoalexins exhibiting antifungal effect were isolated from the leaves of Sorbus pohuashanensis, which invaded by Alternaria tenuissi, and their growth inhibition rate towards A. tenuissi were 50.3 %, 54.0 %, 66.4 %, 58.8 %, 48.5 %, 51.0 %, 33.3 %, and 37.0 %, respectively. In vivo activity assay verified the protective effect of these natural biphenyls on tobacco leaves. The observation of mycelial morphology revealed that these compounds possessed adverse effects on mycelial growth of A. tenuissi. Subsequently, the most potent active compounds, 3',4',5'-trimethoxy[1,1'-biphenyl]-4-ol (3) and 3,4,4',5-tetramethoxy-1,1'-biphenyl (4), were conducted to the further antifungal evaluation and showed significant activity against the other four crop pathogens, Fusarium graminearum, Helminthosporium maydis, Sclerotinia sclerotiorum, and Exserohilum turcicum. Further, the structure-activity relationships and biosynthesis of these compounds were speculated in this work.

A study on some morphological characteristics and the set and levels of phenolic compounds was performed for the first time on Spiraea hypericifolia L. (Rosaceae Juss.) growing under natural conditions in the Novosibirsk region (four sites). Two phenotypic varieties of S. hypericifolia were identified. Twenty-three phenolic compounds were found in aqueous-ethanol extracts from S. hypericifolia leaves by high-performance liquid chromatography. Chlorogenic, p-hydroxybenzoic, and p-coumaric acids and quercetin, hyperoside, isoquercitrin, avicularin, rutin, and astragalin were identified among them. Hyperoside (6.7–20.5 mg/g) is the main phenolic compound in S. hypericifolia leaves. Flavonoid aglycones were prepared from the leaves by hydrochloric-acid hydrolysis of the aqueous-ethanol extracts (1:1). Three flavonol aglycones (quercetin, kaempferol, and isorhamnetin) were identified in the extract hydrolysates from S. hypericifolia leaves by chromatographic analysis. Quercetin glycosides proved to be predominant phenolic compounds in all the extract hydrolysates. A comparative analysis was performed on the levels of phenolic compounds in leaves among S. hypericifolia from the different sites and between the two varieties of S. hypericifolia. It was revealed that an increase in plant size by approximately twofold correlates with a decrease in concentrations of the identified flavonoids and phenolcarboxylic acids in S. hypericifolia leaves.

An analytical method was developed to quantitatively determine residual monomers, namely, lactide (LA) and e-caprolactone (CL), in poly(lactide-co-e-caprolactone) (PLCL) using an internal-standard method of gas chromatography (GC). PLCL and diphenyl ether (DPE) as an internal standard were initially dissolved in dichloromethane (DCM), and then PLCL was precipitated in cyclohexane. The residual LA and CL monomers in PLCL, as well as DPE, were extracted into cyclohexane from the polymer solution. The resulting solution was directly injected into a GC system. This method was practical for measuring the residual LA and CL contents in PLCL. The relative standard deviation (RSD) (n = 5) denoting the repeatability of this method was less than 5.6% and 4.3% for the LA and CL measurements, respectively, indicating that the method was sufficiently precise. The recovery rate of standard addition was 96.5%-101.5% and 98.4%-104.2% for the determination of LA and CL in PLCL, respectively. The RSD of the recovery of standard addition (n = 5) was not more than 2.0%, indicating that the method was sufficiently accurate.

Background. Benvitimod cream, a novel synthetic small molecule, was effective in treating mild-to-moderate plaque psoriasis. We conducted a phase III clinical trial to assess the efficacy and safety of benvitimod cream in patients with mild-to-moderate plaque psoriasis. Methods. We randomly assigned 686 patients (2:1:1) to receive 1% benvitimod cream, 0.005% calcipotriol ointment or placebo twice a day for 12 weeks. The primary efficacy end points were the percentage of patients with a 75% or greater reduction from baseline in the psoriasis area and severity index (PASI 75) score and with a score of 0 or 1 in static physician's global assessment (sPGA) at week 12. Results. The results showed that 50.4% of patients in the benvitimod group achieved PASI 75, which was significantly higher than that in the calcipotriol (38.5%, P

Two novel secondary metabolites, including one thujopsene-type sesquiterpene designated thujasutchin N (1) and one norlignan named thujasutchin O (2) were obtained from the ethanolic extract of the stems and roots of Thuja sutchuenensis. Among them, thujasutchin O (2) represents the first example of lignan sharing a unique carbon-reduced skeleton with novel acetal functionality. Their structures were unambiguously determined by means of extensively spectroscopic analysis including UV, IR, HRESIMS, NMR, and single crystal X-ray diffraction. Both of the isolates were evaluated for their in vitro cytotoxic and antibacterial activities.

Pesticide carrier systems are highly desirable in achieving the effective utilization of pesticides and reduction of their loss. In order to increase utilization and enhance pesticide adhesion to harmful targets, adhesive and stimulus-responsive nanocomposites were prepared using graphene oxide (GO) and polydopamine (PDA). The results demonstrated that graphene oxide with a layer of PDA had a high hymexazol-loading capacity. The release curve of hymexazol from the nanocomposite showed that the release was NIR-laser-dependent and pH-dependent. The adhesion-performance investigation demonstrated that Hy-GO@PDA exhibited greater hymexazol persistence than a hymexazol solution after a simulated-rainwash experiment, and it also left more hymexazol residue than a hymexazol solution with a surfactant under high concentrations. Finally, the bioactivity of the prepared hymexazol-loaded nanocomposite was measured against Fusarium oxysporum f. sp. cucumebrium Owen, and it showed an inhibition activity similar to that of the hymexazol solution. All of these revealed that GO with a PDA layer could serve as pesticide carrier to solve low-utilization and wash-off problems, especially for water-soluble pesticides.

The microstructured and hyperdoped silicon as a superior photoelectric and photovoltaic material is first studied as a gas-sensing material. The material is prepared by femtosecond-laser irradiation on selenium-coated silicon and then fabricated as a conductive gas sensor, targeting ammonia. At room temperature, the sensitivity, response time, repeatability, distinguishability, selectivity, and natural aging effect of the sensor have been systematically studied. Results show that such black silicon has good potential for application as an ammonia-sensing material. On the basis of its unique optoelectronic properties, an additional optical drive is proposed for the formation of an optical and electric dual-driven sensor, which is achieved by asymmetric light illumination between the two electrode regions. In a certain range of applied voltage, the sensitivity is enhanced dramatically and even tends to be infinite. For the aged device with degraded sensitivity, a two-order increment is obtained for 500 ppm of NH

Site-selective phenol acylation mediated by thioacids with various phenols as acylation surrogates via visible light photoredox catalysis is described. This protocol provided facile access to an array of phenolic esters, with the exclusive acylation of a phenol hydroxyl group over an alcoholic one. The utility of this methodology was also demonstrated by the modification of biologically meaningful natural products.

Background and objectives: The main treatment goals for degenerative knee osteoarthritis are to relieve pain, restore knee function, improve quality of life, delay knee replacement, and reduce the number of revisions. Knee replacement is currently the most common treatment for degenerative knee osteoarthritis; however, the cost is high, and the procedure is often associated with prosthesis loosening and shedding and many adverse reactions. Therefore, we hypothesize that knee-preserving arthroscopic debridement for treatment of knee degenerative osteoarthritis in elderly patients is lower-cost, effective, safe, and reliable. >Design: Prospective, single-center, open-label, non-randomized controlled trial. Methods: In total, 212 elderly patients (knees) with degenerative knee osteoarthritis who receive treatment in the Second Hospital of Chaoyang (Liaoning Province, China) will be included in this study. These patients will be assigned to two groups according to each patient’s condition and wishes (n = 106/group). In the control group, intra-articular injection of sodium hyaluronate will be performed, followed by oral administration of nonsteroidal anti-inflammatory drugs, conventional physiotherapy, and quadriceps functional exercise. In the arthroscopic debridement group, arthroscopic debridement will be performed, followed by oral administration of nonsteroidal anti-inflammatory drugs, conventional physiotherapy, and quadriceps functional exercise. All patients will be followed up at 1 week, 1 month, 3 months, 6 months, 1 year, and 2 years. >Outcome measures: The primary outcome measure is the percentage of patients with a Hospital for Special Surgery (HSS) knee score of ≥ 85 points at 2 years after surgery, which will be used to evaluate knee function recovery. The secondary outcome measures are the percentage of patients with an HSS knee score of ≥ 85 points before surgery and at 1 week, 1 month, 3 months, 6 months, and 1 year after surgery; the HSS score, visual analog scale score, Western Ontario and McMaster Universities Osteoarthritis Index, knee range of motion, hospitalization costs, and knee X-ray morphology before surgery and 1 week, 1 month, 3 months, 6 months, 1 year, and 2 years after surgery; medical costs after 2 years of treatment; and incidence of adverse reactions at 1 week, 1 month, 3 months, 6 months, 1 year, and 2 years after surgery. Discussion: The findings from this study will reveal whether arthroscopic debridement for the treatment of degenerative knee osteoarthritis in elderly patients has the advantages of fewer adverse reactions and lower treatment costs with effective restoration of knee function. >Ethics and dissemination: This study was approved by Medical Ethics Committee of Second Hospital of Chaoyang of China (approval No. 2017-08-01). The study will be performed in accordance with the Declaration of Helsinki. Participants provided signed informed consent regarding the study protocol prior to participation in the study. This study was designed in June 2017. Patient recruitment and data collection will begin in June 2018. Patient recruitment will end in December 2018. Data analysis will be performed in June 2021. The study will be completed in August 2021. Results will be disseminated through presentations at scientific meetings and/or by publication in a peer-reviewed journal. Trial registration: This trial was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR1800015208). Protocol version (1.0).

This study addresses first the role of human 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1) in breast cancer (BC) cells. The enzyme has a high estrone-activating activity that is subject to strong substrate inhibition as shown by enzyme kinetics at the molecular level. We used BC cells to verify this phenomenon in living cells: estrone concentration increase did reduce the reaction with 0.025 to 4μM substrate. Moreover, 5α-dihydrotestosterone (DHT) demonstrated some inhibition of estrogen activation at both the molecular and cellular levels. The presence of DHT did not change the tendency toward substrate inhibition for estrone conversion, but shifted the inhibition toward higher substrate concentrations. Moreover, a binding study demonstrated that both DHT and dehydroepiandrosterone (DHEA) can be bound to the enzyme, thereby supporting the multi-specificity of 17β-HSD1. We then followed the concentrations of estradiol and performed q-RT-PCR measurements of reductive 17β-HSDs after 17β-HSD1 inhibition. The estradiol decrease by the 17β-HSD1 inhibition was demonstrated lending support to this observation. Knockdown and inhibition of 17β-HSD1 produced reduction in estradiol levels and the down-regulation of another reductive enzyme 17β-HSD7, thus "amplifying" the reduction of estradiol by the 17β-HSD1 modulation itself. The critical positioning of 17β-HSD7 in sex-hormone-regulation as well as the mutual regulation of steroid enzymes via estradiol in BC, are clearly demonstrated. Our study demonstrates that fundamental enzymological mechanisms are relevant in living cells. Moreover, further enzyme study in cells is merited to advance biological and medical research. We also demonstrated the central role of 17β-HSD7 in sex-hormone conversion and regulation, supporting it as a novel target for estrogen-dependent (ER+) BC.

Poly(lactide) stereocomplex (PLA SC) and poly(ethylene glycol) (PEG) crystallites were obtained in MPEG- b -PLLA/MPEG- b -PDLA (linear blend, 1/1) and 4PEG- b -PLLA/4PEG- b -PDLA (4-arm blend, 1/1) by solution-casting method. The molecular weights of PLLA and PDLA ( M n, PLA ) were similar in all the linear and 4-arm blends. Only PLA SC and PEG crystallites were observed, and PLA homocrystallites were absent in all blends. The different M n, PLA and chain architectures did not alter the crystalline structures of PLA SC and PEG, but greatly influenced their melting temperatures and crystallinities. As the average M n, PLA per arm of linear and 4-arm blends were similar, the melting temperatures and crystallinities of PLA SC and PEG in 4-arm blends were always lower than those of linear blends, which could be ascribed to the huge steric hindrance of 4-arm structures. This investigation on PEG- b -PLLA/PEG- b -PDLA blends with various structures could provide basic data for the applications of PLA stereocomplex.

One new ent-kaurane diterpene derivative (1), along with four known diterpenes, was isolated from the stems of Eurya chinensis R.Br. The structure of the new compound was established by extensive analysis of mass spectrometric and 1D and 2D NMR spectroscopic data. Compound 1 showed moderate anti-inflammatory activities with IC50 value of 8.12 μM. This is the first example of diterpenoids with 4-hydroxy-4-(2-hydroxyethyl)-1-hydroxyl-cyclohexanoyl substituent.

The metalloproteinase MP belongs to the serralysin family, which is involved in important functions such as nutrient acquisition and infection pathogenesis. Serralysin proteases in highly purified form are commonly used at the industrial level with several purposes. In this study, we set up an efficient and rapid purification protocol for MP using a p-aminobenzamidine-modified affinity chromatography. The affinity medium was synthesized by using p-aminobenzamidine as affinity ligand immobilized via cyanuric chloride spacer to Sepharose 6B sorbent carrier. According to the adsorption analysis, the dissociation constant Kd and theoretical maximum adsorption Qmax of this medium were 24.2 μg/mL and 24.1 mg/g wet sorbent, respectively. The purity of MP was assessed by a high-performance liquid chromatography on a TSK3000SW column and sodium dodecyl sulfate polyacrylamide gel electrophoresis, revealing values of 98.7 and ∼98%, respectively. The specific activity of purified MP was 95.6 U/mg, which is similar to values obtained through traditional purification protocols. In conclusion, our protocol could be easily employed for the rapid isolation of MP with high purity, and could be implemented for other serralysin family proteases.

Low melt strength and toughness of poly ( l -lactide) (PLLA) limited its large-scale application. In this work, a facile method was proposed and demonstrated to a feasible route to solve these problems. A series of PLLA-based block copolymers PLLA- block -poly (butylene succinate)- block -PLLA (PLLA- b -PBS- b -PLLA), and chain extender (PLLA- block -poly (glycidyl methacrylates)) 3 (PLLA- b -PGMA) 3 were synthesized and used for the improvement of the melt strength and toughness of PLLA by in situ reactive blending. The structure and composition of the copolymers were confirmed by nuclear magnetic resonance spectra, infrared spectra and gel permeation chromatography. The elongation at break increased from 4.2% for PLLA to 234% for the blend containing 40% block copolymer and 5% chain extender, and remarkably maintained their strength. Rheological analysis showed that the blends exhibited the strong strain-hardening behavior. Measurements of the linear viscoelastic properties of the melt blends suggested that the chain extender promoted the development of chain branching. DSC data showed that the crystallization was not perfect after addition of PLLA- b -PBS- b -PLLA and (PLLA- b -PGMA) 3 compared with neat PLLA. SEM measurements revealed the improved interface adhesion of the blends. The introduction of PLLA- b -PBS- b -PLLA and (PLLA- b -PGMA) 3 imparted both high toughness and high melt strength to the PLLA.

An analytical method to determine the residual lactide in polylactide (PLA) was proposed using an internal standard method of gas chromatography (GC). PLA samples and diphenyl ether (DPE) as an internal standard were dissolved in dichloromethane, then PLA was precipitated in anhydrous alcohol. The residual lactide and DPE were extracted to alcohol for GC analysis. At room temperature, lactide could react with alcohol and change into ethyl lactoyl lactate (ELL), but the relative response factor of lactide versus DPE could be obtained through a numerical analysis method. Therefore, the residual lactide content could be quantitatively calculated in PLA. The relative standard deviation (RSD) of the measurements is not more than 7.0%, indicating that the method is suitably precise.

Methicillin-resistant Staphylococcus aureus (MRSA) poses a serious threat to global public health, because it exhibits resistance to existing antibiotics and therefore high rates of morbidity and mortality. In this study, twenty-one natural product-based acylphloroglucinol congeners were synthesized, which possessed different side chains. Antibacterial screening against MRSA strains revealed that acyl moiety tailoring is a prerequisite for the antibacterial activity. Moreover, the lipophilicity, rather than the magnitude of the hydrophobic acyl tail dominates variability in activity potency. Compound 11j was identified as a promising lead for the generation of new anti-MRSA drug development. It was discovered by optimization of the side chain length in light of the potency, the breadth of the antibacterial spectrum, the rate of bactericidal action, as well as the membrane selectivity. Compound 11j exerted profound in vitro antibacterial activity against the MRSA strain (JCSC 2172), and its MIC was 3-4 orders of magnitude lower than that of vancomycin. A preliminary mode of action study of compound 11j at the biophysical and morphology levels disclosed that the mechanism underlying its anti-MRSA activity included membrane depolarization and, to a lesser extent, membrane disruption and cell lysis.

This work describes the isolation and characterization of twenty-nine compounds from the fruits of Rhus typhina L., including eleven flavonoids (1–11), eleven phenols (12–22), two pentacyclic triterpenes (23–24), two organic acids (25–26), one lumichrome (27), one courmarin (28) and one pyrimidine (29) on the basis of their spectroscopic data. Compounds apigenin (1), daidzein (4), orobol (5), 3′, 5, 5′, 7-tetrahydroxyflavanone (6), naringenin (7), butein (8), (-)-catechin (9), quercetin-3-O-α-L-(3″-O-galloyl)-rhamnoside (11), 2-hydroxybenzoic acid (13), 4-hydroxybenzaldehyde (14), vanillin (15), methyl 3,4-dihydroxybenzoate (16), 3,5-dihydroxybenzamide (18), tyrosol (19), caffeic acid (20), 3-(2,4,6-trihydroxyphenyl)-1-(4-hydroxyphenyl)-propan-1-one (21), phlorizin (22), friedelin (23), oleanolic acid (24), 4,4-dimethyl-heptanedioic acid (25), anthranilic acid (26), lumichrome (27), scoparone (28) and uracil (29) have not been recorded before in this plant. This is the first report on the occurrence of compounds 4–7, 9, 11, 13–14, 16, 18–21, 25–29 from the genus Rhus. Moreover, the chemotaxonomic significance of these isolated compounds was also summarized.

The first biomimetic total syntheses of three biologically meaningful acylphloroglucinols, watsonianones A and B and corymbone B, with potent antiplasmodial activity, were performed. Their total syntheses were carried out through a diversity-oriented synthetic strategy from congener 2,2,4,4-tetramethyl-6-(3-methylbutylidene)cyclohexane-1,3,5-trione with high step efficiency. The spontaneous enolization/air oxidation of the precursor 2,2,4,4-tetramethyl-6-(3-methylbutylidene)cyclohexane-1,3,5-trione through a singlet O2-induced Diels-Alder reaction pathway to assemble the key biosynthetic peroxide intermediate is also discussed.

Eight new sesquiterpenes with diverse skeletons involving four cuparenes, denominated thujasutchins F-I (1–4), one eudesmane and one cedrol, named thujasutchin J (5) and thujasutchin K (6), as well as two thujopsenes thujasutchins L-M (7–8) together with three known congener compounds (9–11) were isolated from EtOAc soluble fraction of ethanolic extract of the stems and roots of Thuja sutchuenensis. Their structures including absolute configurations were unambiguously established by extensive interpretation of the NMR and mass spectroscopic data, X-ray diffractions, and ECD measurements powered by molecular calculations. The biological assays disclosed that 5 and 9 displayed potent inhibitory effect against Staphylococcus. aureus (CMCC 26003), methicillin-resistant Staphylococcus aureus (JCSC 4744), Bacillus cereus (ATCC 10876), and Staphylococcus epidermidis (ATCC 12228) with MICs ranging from 6.25 to 25 μg/mL.

The fission yeast Schizosaccharomyces pombe uses a cAMP signaling pathway to link glucose-sensing to Protein Kinase A activity in order to regulate cell growth, sexual development, gluconeogenesis, and exit from stationary phase. We previously used a PKA-repressed fbp1-ura4 reporter to conduct high throughput screens (HTSs) for inhibitors of heterologously-expressed mammalian cyclic nucleotide phosphodiesterases (PDEs). Here, we describe the successful expression of all ten mammalian adenylyl cyclase (AC) genes, along with the human GNAS Gα(s) gene. By measuring expression of an fbp1-GFP reporter together with direct measurements of intracellular cAMP levels, we can detect both basal AC activity from all ten AC genes as well as GNAS-stimulated activity from eight of the nine transmembrane ACs (tmACs; AC2-AC9). The ability to use this platform to conduct HTS for novel chemical probes that reduce PKA activity was demonstrated by a pilot screen of the LOPAC®(1280) library, leading to the identification of diphenyleneiodonium chloride (DPI) as an inhibitor of basal AC activity. This screening technology could open the door to the development of therapeutic compounds that target GNAS or the ACs, an area in which there is significant unmet need.

Five new compounds including two stilbenes, designated thujasutchins A (1) and B (2), two phenolic compounds namely thujasutchins C (3) and D (4), as well as one sesquiterpene thujasutchin E (5), were isolated from the 95% ethanolic extract from the trunks and roots of Thuja sutchuenensis. Their structures were determined by means of extensively spectroscopic analysis including UV, IR, HRESIMS, 1H and 13C NMR (COSY, HSQC, HMBC). Moreover, compounds 1, 3-5 were evaluated for in vitro cytotoxic activities against SF-268, MCF-7, HepG-2, and A549 tumor cell lines.

Three new prenylated stilbenes, named as cajanusins A-C (1-3), and one new natural product cajanusin D (4), along with six known derivatives (5-10) were isolated from the leaves of Cajanus cajan. Their structures were fully elucidated by means of extensive spectroscopic methods and comparison with data in the reported literatures. The new compounds of 1 and 2 were evaluated for in vitro cytotoxic activities against a panel of human cancer cell lines.

Background Analysis of cell-free DNA (cfDNA) is promising for broad applications in clinical settings, but with significant bias towards late-stage cancers. Although recent studies have discussed the diverse and degraded nature of cfDNA molecules, little is known about its impact on the practice of cfDNA analysis. Methods We developed single-strand library preparation and hybrid-capture-based cfDNA sequencing (SLHC-seq) to analysis degraded cfDNA fragments. Next we used SLHC-seq to perform cfDNA profiling in 112 pancreatic cancer patients, and the results were compared with 13 previous reports. Extensive analysis was performed in terms of cfDNA fragments to explore the reasons for higher detection rate of KRAS mutations in the circulation of pancreatic cancers. Findings By applying the new approach, we achieved higher efficiency in analysis of mutations than previously reported using other detection assays. 791 cancer-specific mutations were detected in plasma of 88% patients with KRAS hotspots detected in 70% of all patients. Only 8 mutations were detected in 28 healthy controls without any known oncogenic or truncating alleles. cfDNA profiling by SLHC-seq was largely consistent with results of tissue-based sequencing. SLHC-seq rescued short or damaged cfDNA fragments along to increase the sensitivity and accuracy of circulating-tumour DNA detection. Interpretation We found that the small mutant fragments are prevalent in early-stage patients, which provides strong evidence for fragment size-based detection of pancreatic cancer. The new pipeline enhanced our understanding of cfDNA biology and provide new insights for liquid biopsy.

A general and excellent acylation reagent, diacyl disulfide, was uncovered for efficient ester formation enabled by DMAP (4-(N,N-dimethylamino)pyridine) catalysis. This protocol offered a promising synthetic platform on site-selective acylation of phenolic and primary aliphatic hydroxyl groups, which greatly expanded the realm of protecting group chemistry. The importance of the reagent was also reflected by its excellent moisture tolerance, high efficiency, and potential in synthetic chemistry and biologically meaningful natural product modification.

Aims To explore the potential of a dendrimer nanoprobe labeled with cyclic arginine-glycine-aspartic acid pentapeptide (cRGDyK) as a magnetic resonance imaging (MRI) tracer to non-invasively differentiate the extent of liver fibrosis. Methods Synthetic dendrimer nanoprobes were labeled with cRGDyK (Den-RGD) to form a formulation of hepatic stellate cell (HSC)-specific MRI tracer. An MRI modality was employed to visualize hepatic Den-RGD deposition in a mouse model of liver fibrosis caused by thioacetamide treatment. Results Den-RGD bound to activated HSCs via integrin αvβ3 receptors. The labeling of nanoprobes with cRGDyK increased their affinity to and accelerated their uptake by activated HSCs. Most of intravenously administrated Den-RGD nanoprobes deposited in the fibrotic areas, and the deposited amount was paralleled with the severity of liver fibrosis. Majority of cells taking-up Den-RGD was found to be activated HSCs in fibrotic livers. An MRI modality using Den-RGD as a tracer demonstrated that the relative hepatic T1-weighed MR signal value was increased in parallel with the severity of liver fibrosis. Conclusion The extent of Den-RGD deposition reflects integrin αvβ3 expression in activated HSCs, and Den-RGD appears to be a useful formulation of MRI tracer and may non-invasively and quantitatively assess the extent of liver fibrosis.

Following menopause virtually 100% of estrogens are synthesized in peripheral target tissues from precursor steroids of adrenal origin. These steroids are the unique source of sex steroids in these women. This positions some steroid metabolizing enzymes as primary targets for novel therapies for estrogen receptor-positive (ER+) breast cancer. However, previous research on the steroid-converting enzymes has been performed using their direct substrate as a hormone source, depending on the facility where studied and the robust signal obtained. These experiments may not always provide an accurate reflection of physiological and post-menopausal conditions. We suggest providing dehydroepiandrosterone (DHEA) as an intracrinological hormone source, and comparing the role of steroid-converting enzymes using DHEA and their direct substrates when an extensive mechanistic understanding is required. Here, we present a comparative study of these enzymes with the provision of DHEA and the direct substrates, estrone (E1) or dihydrotestosterone (DHT), or additional steroids as hormone sources, in breast cancer cells. Enzyme knockdown by respective specific siRNAs and observations on the resulting differences in biological function were carried out. Cell biology studies showed no difference in biological function for 17β-HSD1 and 17β-HSD7 when cultured with different steroid hormones: cell proliferation and estradiol levels decreased, whereas DHT accumulated; cyclinD1, PCNA, and pS2 were down-regulated after knocking down these two enzymes, although the quantitative results varied. However, culture medium supplementation was found to have a marked impact on the study of 3α-HSD3. We demonstrated that provision of different steroids as a substrate or hormone sources may promote modified biological effects: provision of DHEA is the preferred choice to mimic postmenopausal steroid metabolism in cell culture.

In this study, an efficient affinity purification protocol for an alkaline metalloprotease from marine bacterium was developed using immobilized metal affinity chromatography. After screening and optimization of the affinity ligands and spacer arm lengths, Cu-iminmodiacetic acid was chosen as the optimal affinity ligand, which was coupled to Sepharose 6B via a 14-atom spacer arm. The absorption analysis of this medium revealed a desorption constant Kd of 21.5 μg/mL and a theoretical maximum absorption Qmax of 24.9 mg/g. Thanks to this affinity medium, the enzyme could be purified by only one affinity purification step with a purity of approximately 95% pure when analyzed by high-performance liquid chromatography and reducing sodium dodecyl sulfate polyacrylamide gel electrophoresis. The recovery of the protease activity reached 74.6%, which is much higher than the value obtained by traditional protocols (8.9%). These results contribute to the industrial purifications and contribute a significant reference for the purification of other metalloproteases.

Modification of poly(l-lactide) (PLLA) via blending with two or more polymers is one of the effective approaches used to overcome the brittleness of PLLA, which often requires the addition of a compatibilizer and generate opaque materials. To solve this problem, multiarmed polycaprolactone-block-PLLA (PCL-b-PLLA) was synthesized by consecutive ring-opening polymerization of e-caprolactone and l-lactide using multihydroxyl alcohols as initiator. The structure and composition was confirmed by proton nuclear magnetic resonance and gel permeation chromatography. PLLA/multiarmed PCL-b-PLLA blends with various blend ratios were prepared via melt mixing. The presence of multiarmed PCL-b-PLLA (30%) in the PLLA matrix exhibited more than 80 times improvement in the elongation at break, as compared to unmodified PLLA. The addition of multiarmed PCL-b-PLLA in the PLLA contributed to the enhancement of the storage modulus in the low frequency, which was related to the entanglement of the PLLA and multiarmed PCL-b-PLLA. The blend interface had no obvious phase separation, and showed good adhesion between dispersed block copolymer phases within the continuous PLLA phase. The compatibilization mechanism and toughing mechanism were proposed. The resulting PLLA blends also showed good transparency. The current research opened a new route available to prepare transparent PLA-based resin with enhanced properties. POLYM. ENG. SCI., 2016. © 2016 Society of Plastics Engineers

A remarkable visible-light-promoted photoredox catalytic methodology involved with amines and eco-friendly potassium thioacids for amide formation was uncovered. This approach can mimic the natural coenzyme acetyl-CoA to selectively acylate amines without affecting other functional groups such as alcohols, phenols, esters, among others. The developed strategy may hold great potential for a comprehensive display of biologically interesting peptide synthesis and amino acid modification through a diacyl disulfide intermediate.

Tomentosenol A (1), along with a pair of epimers, 4S-focifolidione (2) and 4R-focifolidione (3), were isolated from the leaves of Rhodomyrtus tomentosa. 1 was the first example of a new meroterpenoid class with a unique skeleton that contained a free syncarpic acid coupled with a terpenoid unit, and showed excellent antimicrobial and cytotoxic activities. The absolute configuration of 1 was unambiguously determined by a chemical conversion between 1 and the predetermined 2. In contrast to the common hetero Diels–Alder cycloaddition embodied in previously reported meroterpenoid biosynthesis, an Alder-ene reaction was proposed as the key transformation to account for the biosynthesis of 1, which was confirmed by a biomimetic total synthesis.