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Genome re-sequencing and recombination analyses identified Capana06g000193 as a strong candidate for the minor male fertility restoration locus Rf2 in chili pepper G164 harboring two dominant male fertility restoration genes. Male fertility restoration genes of chili pepper restorer line G164 (Capsicum annuum L.) were studied using molecular marker genotypes of an F

Pharmaceutical salt formation is the most preferred and effective method to enhance the physicochemical properties of APIs. The aim of the study was to design and synthesize a series of new salts to improve the solubility of Imatinib (IM). Two stable salts with malonic acid (S1) and citric acid (S5), one metastable salt with fumaric acid (S2), two unstable salts with citric acid (S3, S4) were obtained for the first time. Single crystal and powder X-ray diffraction, Fourier transform infrared, differential scanning calorimetry, and thermogravimetric analysis were used to characterize the novel salts. The solubility and stability of the solid were also evaluated, and three salts (S1, S2, S5) had a more than 20 folds of solubility and a faster dissolution rate improved as compared to the pure drug in water and pH 6.8 buffer, respectively.

Solubility-driven optimization of the salts of nitro benzothiopyranone 1, which targets DprE1, led to an antimycobacterial preclinical candidate 2. Five pharmaceutically acceptable salts, including the maleate (2), fumarate (3), citrate (4, 5), and l-malate (6) of compound 1, were prepared via the salt formation reaction and evaluated for their physicochemical and pharmacokinetic properties. Compared with 1, all the target salts exhibited greatly increased aqueous solubility and improved oral bioavailability in mice. Maleate salt 2, which displayed higher chemical stability and lower log P, showed substantially improved bioavailability in rats and a much better in vivo effect compared with free base 1 at the same dose. The X-ray crystal structure of 2 revealed that the exposed hydrophilic piperazine-maleate moiety in the crystal structure cell may be critical in increasing the solubility of 2. Thus, this maleate salt 2 overcame the poor druggability of benzothiopyranone derivatives and was identified as a promising preclinical candidate for treating tuberculosis.

International audience; Pepper (Capsicum spp.) is an important vegetable crop that provides a unique pungent sensation when eaten. Through construction of a pepper variome map, we examined the main groups that emerged during domestication and breeding of C. annuum, their relationships and temporal succession, and the molecular events underlying the main transitions. The results showed that the initial differentiation in fruit shape and pungency, increase in fruit weight, and transition from erect to pendent fruits, as well as the recent appearance of large, blocky, sweet fruits (bell peppers), were accompanied by strong selection/fixation of key alleles and introgressions in two large genomic regions. Furthermore, we identified Up, which encodes a BIG GRAIN protein involved in auxin transport, as a key domestication gene that controls erect vs pendent fruit orientation. The up mutation gained increased expression especially in the fruit pedicel through a 579bp sequence deletion in its 5 0 upstream region, resulting in the phenotype of pendent fruit. The function of Up was confirmed by virus-induced gene silencing. Taken together, these findings constitute a cornerstone for understanding the domestication and differentiation of a key horticultural crop.

Objective. The objective is to explore the action and mechanism of circ_0109046 on the malignant phenotypes of ovarian cancer cells. Methods. Circ_0109046 and miR-338-3p expression were detected by quantitative real-time polymerase chain reaction (qRT-PCR). In vitro assays were conducted to investigate the action of circ_0109046 and miR-338-3p on ovarian cancer cell growth and metastasis. Western blotting was utilized to investigate the contents of apoptosis-related markers. The binding between circ_0109046 and miR-338-3p was validated using dual-luciferase reporter assay. Results. Circ_0109046 was increased, while miR-338-3p content was decreased in ovarian cancer tissues. Deficiency of circ_0109046 or the upregulation of miR-338-3p was observed to weaken cell proliferative, migratory, and invasive abilities and elevated cell apoptosis rate in ovarian cancer. Circ_0109046 targetedly suppressed miR-338-3p. Down-regulation of miR-338-3p was able to reverse the repressing impacts of circ_0109046 silencing on ovarian cancer growth and mobility. Conclusion. Circ_0109046 silencing impaired the proliferation, migration, and invasion of ovarian cancer cells through negatively regulating miR-338-3p in vitro, indicating the potential implication of circ_0109046 in ovarian cancer progression.

Donepezil has polymorphism. Different crystalline forms can exhibit different physicochemical properties and biological activities. Exploration of intermolecular interactions is essential to reveal the formation mechanism and differences in properties of polymorphs. This study explores the weak non-covalent intermolecular interactions of donepezil polymorphs through fully ab initio quantum mechanical methods, semi-empirical methods, and Hirshfeld surface analysis. The results show that the Hirshfeld surface analysis method can clearly and intuitively reveal the intermolecular interactions. Theoretical calculations using the atom-atom Coulomb-London-Pauli (AA-CLP) method were also performed to understand the interaction energies toward the total lattice energy. The value of the lattice energy was in accordance with the melting points of the donepezil polymorphs and brought to light the nature of thermal stability. In the specific energy distribution, the contribution of the dispersion force is the most prominent. Further interaction energy analysis found that within a distance of 3.8 Å from the center of the donepezil molecule, different crystalline forms of donepezil molecules have different interaction energies with surrounding molecules. The different interaction energies between polymorphs may lead to polymorphs with different physical-chemical properties.

Interphase in polymer composites plays a key role in enhancing their multi-functionality. Herein, an effective strategy is designed to optimize the interphase microstructure in graphene foam/PDMS (PDMS/GrF) using polypyrrole (PPy) nanowires (denoted as PDMS/GrF@PPy). The interfacial microenvironment of graphene foam is successfully modified by anchoring polypyrrole nanowires, showing strong interfacial strength with PDMS. The tensile strength, Young’s modulus, electrical conductivity, thermal conductivity, mechanical durability and electron-photo-thermal deicing efficiency of PDMS/GrF@PPy composites are simultaneously higher than that of PDMS/GrF composites. Molecular simulations further illustrated that the interfacial interaction energy increased from 100.4 to 280.2 kcal/mol after introducing PPy nanowires between GrF and PDMS. As a proof of concept for deicing application, PDMS/GrF@PPy composites displays excellent deicing efficiencies of 82.9% and 55.7% by Joule heat and NIR irradiation after 500th stretching cycles, respectively, which is obviously outperforming PPy@GrF composites (58.3% and 44.2%). Consequently, PPy nanowires not only optimizes the interfacial strength of polymer composites, but also endows them with multi-functionalities, providing promising candidates of deicing, strain sensor, thermal interface management, etc.

Crystallization of venlafaxine (VLF), a widely prescribed antidepressant, in the presence of 3,5-dinitrobenzoic acid (DA; C7H4N2O6) as a coformer led to the formation of a salt in a molar ratio of 1 : 1 and a salt cocrystal in a ratio of 1 : 2. The crystal structures were determined by single-crystal X-ray diffraction. One salt bond and one hydrogen bond form a R22(10) graph set in VLF–DA (1 : 1), and two salt bonds and two hydrogen bonds form an R44(20) graph set plus 2 extra hydrogen bonds in VLF–DA (1 : 2). VLF–DA (1 : 2) is a salt cocrystal, with a VLF–DA (1 : 1) salt in contact with a neutral DA molecule in the asymmetric unit. Both the salt and the salt cocrystal were differentiated from the pure components by powder X-ray diffraction, differential scanning calorimetry, thermogravimetry, Fourier transform infrared spectroscopy, and solid-state nuclear magnetic resonance. Stability measurements revealed that the salt and the salt cocrystal of VLF held superior phase stability against high temperature, high moisture, and illumination. Beyond our expectations, the VLF–DA (1 : 1) salt showed a significantly improved solubility over VLF free base, while the VLF–DA (1 : 2) salt cocrystal held a lower solubility which can be attributed to its crystal arrangements and molecular interactions.

Piperazine (PIP) is a pharmaceutically acceptable molecule and a good co-conformer in crystallographic engineering. Most of the non-steroidal anti-inflammatory drugs (NSAIDs) have poor aqueous solubility, which hinders their clinical application. The reports show that the solubility of many insoluble drugs can be significantly improved through salt formation with the PIP. In this work, we obtained a series of NSAIDs-PIP salts, such as ibuprofen-piperazine (IBU-0.5PIP) salt, indomethacin-piperazine (IND-0.5PIP) salt, sulindac-piperazine (SUL-0.5PIP) salt, phenylbutazone-piperazine (PBZ-0.5PIP) salt, ketoprofen-piperazine (KPF-0.5PIP) salt and flurbiprofen-piperazine (FLB-0.5PIP) salt. The spatial structure, arrangement, interaction and associations were expatiated by single crystal X-ray diffraction. Powder X-ray diffraction, Fourier transform infrared, differential scanning calorimetry, and thermogravimetric analysis were used to characterize the novel salts. The six new salts had more than 10 folds of solubility and a faster dissolution rate improved corresponding to the bulk drugs in pure water, and the significant improvement of solubility is closely related to the structure of salts.

Betulin (BE) can be obtained from many plants, such as those belonging Betulaceae family, and pharmacological investigations showed its notable biological properties and good potential for food and pharmaceutical development. We investigated the homogeneity, stability, purity, and uncertainty of a newly certified reference material (CRM) of BE. The certified purity value for the CRM of BE was 99.56% with an extended uncertainty of 0.07% (k = 2, P = 0.95), as determined by differential scanning calorimetry (DSC). In this study, DSC was used for the first time for purity determination of BE. Given its high accuracy, precision, and reproducibility, DSC can be used as an alternative technique for purity determination of CRMs in the pharmaceutical and food industry. Graphic abstract

Tuberculosis (TB) remains a serious public health challenge, and the research and development of new anti-TB drugs is an essential component of the global strategy to eradicate TB. In this work, we discovered a conformationally constrained oxazolidinone 19c with improved anti-TB activity and safety profile through a focused lead optimization effort. Compound 19c displayed superior in vivo efficacy in a mouse TB infection model compared to linezolid and sutezolid. The druggability of compound 19c was demonstrated in a panel of assays including microsomal stability, cytotoxicity, cytochrome P450 enzyme inhibition, and pharmacokinetics in animals. Compound 19c demonstrated an excellent safety profile in a battery of safety assays, including mitochondrial protein synthesis, hERG K+, hCav1.2, and Nav1.5 channels, monoamine oxidase, and genotoxicity. In a 4 week repeated dose toxicology study in rats, 19c appeared to have less bone marrow suppression than linezolid, which has been a major liability of the oxazolidinone class.

Abstract Mangiferin is a compound with many pharmacological activities and exists in many natural products. Anhydrous and hydrate of mangiferin have been reported separately in two literatures, but the polymorphism of this compound has not been realized until this paper. In this study, polymorph screening of mangiferin has been carried out and five forms have been obtained including three new forms never reported. Several solid state characterization methods, such as powder X-ray diffraction, differential scanning calorimetry and thermogravimetry, are used to identify and characterize all of mangiferin forms. The comparison of the crystallographic data and hirshfeld surface analysis were first reported for mangiferin anhydrous and hydrate. Furthermore, the studies on stability, transformation and solubility have been undertaken, the results prompt that form V can be used as the dominant polymorph for the development of innovative pharmaceuticals. Graphic Abstract

Salvianolic acid A (Sal A), a water-soluble ingredient in Danshen, has various biological activities. Sal A and its impurities have similar physical and chemical properties, as well as strong reducibility; therefore, they are difficult to prepare and purify. In this study, high-purity Sal A was obtained by purification of sephadex chromatography and preparative chromatography. Furthermore, HPLC–DAD tandem ECD and HPLC–DAD tandem MS methods were used for non-volatile organic impurity analysis, ICP-MS method was used for non-volatile inorganic impurities and mass balance method and quantitative nuclear magnetic resonance were employed to certify the product. The structures of Sal A and its relative impurities were validated by nuclear magnetic resonance spectroscopy and mass spectrometry, and their contents were quantified as well. Following the principles of ISO Guides 34:2009 and 35:2005, a Sal A reference material was certified, covering homogeneity studies, stability studies, characterization, and uncertainty estimations. Graphic Abstract Electronic supplementary material The online version of this article (10.1007/s13659-020-00236-2) contains supplementary material, which is available to authorized users.

Venlafaxine (VLF) is a widely prescribed antidepressant thought to have little effect on glucose metabolism, but some clinical reports showed that a VLF overdose may cause hypoglycemia. The raw mat...

Diffusion-enhancing holes (DEHs) have been used to mitigate the large density gradients that are formed in the thick-section ceramic matrix composites (CMCs) fabricated by chemical vapor infiltration (CVI). However, the densification characters of the thick-section CMCs with DEHs through vapor infiltration remain a concern. Here, the densifications of a10-mm-thick two dimensional (2D) C/SiC composite with or without DEHs are investigated by experiments and calculations. Results showed both the measured densities, the predicted final densities, and the density growth rates (DGRs) for the composite with DEHs (diameters of 2 or 4 mm) are higher than those of the counterpart without DEHs, due to the forming of dense rings (DRs) around DEHs and the increased infiltration in the large pores (diameter > 52 μm). In addition, the diffusion increase in infiltration with DEHs is attributed to the increase of Knudsen diffusion resulted from the reopening of the blocked/sealed pores by DEH-machining.

Amygdalin is an effective component of the traditional Chinese medicine bitter almond, peach kernel, and plum kernel. It has pharmacological effects, such as relieving cough and asthma. In a study of the crystallization process, we found a series of solvatomorphs of amygdalin (including hydrate). Interestingly, in the structures of these solvatomorphs, the same characteristic structural fragment is present, that is, amygdalin dihydrate. Multiple analytical techniques were used to characterize the solvatomorphs, such as X-ray diffraction and thermogravimetry-mass spectrometry. Void calculations of water and solvent were used to analyze the occupied volume in the unit cell of the corresponding solvatomorphs to explain the formation mechanism of the solvatomorphs from the perspective of space. To elucidate the formation mechanism of the solvatomorphs with this kind of characteristic structure from the perspective of energy, theoretical calculations based on density functional theory were applied, such as energy decomposition and molecular electrostatic potential surfaces. In addition, the transformation phenomenon between these solvatomorphs and amygdalin was identified, and the transformation pathways are described in detail.

Pepper (Capsicum spp.) is one of the earliest domesticated crops, providing a unique pungent sensation when eaten. Through the construction of the first pepper variome, we describe the main groups that emerged during domestication and breeding of C. annuum, their relations and temporal succession, and the molecular events underlying the main transitions. The initial differentiation in fruit shape and pungency, increase in fruit weight, and transition from erect to pendent fruits, and the recent appearance of blocky, large, sweet fruits (bell peppers), were accompanied by strong selection/fixation of key alleles and introgressions in two large genomic regions. Furthermore, we describe the identification of Up, a key domestication gene controlling erect vs pendent fruit orientation, encoding a BIG GRAIN protein involved in auxin transport, and Flip1 associated with capsaicinoid content, encoding a protein involved in phospholipid flipping. The function of Up was confirmed by virus-induced gene silencing. These findings constitute a cornerstone for understanding the domestication and differentiation of a key horticultural crop.

Fertility restoration of cytoplasmic male sterility (CMS) in Capsicum annuum is controlled by multiple alleles of Restorer-of-fertility (Rf) genes. The isolation of additional Rf genes should therefore enrich the knowledge of CMS/Rf systems and accelerate their exploitation in hybrid seed production. In this study, the fertility restorer gene CaRfm of ‘0601 M’, a non-pungent bell pepper, was genetically mapped to a 1.2-cM region flanked by KASP markers S761 and S183. CaRfm was then physically mapped to a 128.96-Kb interval predicted from 24 recombinants with two co-segregated markers, S423 and S424. CaPPR6 encoding a pentatricopeptide repeat (PPR) protein was suggested as the most likely candidate gene for the CaRfm locus on the basis of sequence alignment as well as genotyping of tightly linked markers. In addition, molecular markers S1597 and S1609, which are immediately adjacent to CaRfm at 15.7 and 57.8-Kb respectively, were developed and applied to marker-assisted selection. The results provided friendly markers for breeding pepper restorer lines and laid the foundation for elucidating the male fertility restoration mechanism. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12298-021-01109-9.

This study aimed to gain insight into cocrystal interactions through solid-state characterization and theoretical computation. We formulated four novel cocrystalline phases of antipyrine (AN) and a...

Background: Formononetin is a common soy isoflavonoid that can be found abundantly in many natural plants. Previous studies have shown that formononetin possesses a variety of activities which can be applied for various medicinal purposes. Certified Reference Materials (CRMs) play a fundamental role in the food, traditional medicine and dietary supplement fields, and can be used for method validation, uncertainty estimation, as well as quality control. Methods: The purity of formononetin was determined by Differential Scanning Calorimetry (DSC), Coulometric Titration (CT) and Mass Balance (MB) methods. Results: This paper reports the sample preparation methodology, homogeneity and stability studies, value assignment, and uncertainty estimation of a new certified reference material of formononetin. DSC, CT and MB methods proved to be sufficiently reliable and accurate for the certification purpose. The purity of the formononetin CRM was therefore found to be 99.40% ± 0.24 % (k = 2) based on the combined value assignments and the expanded uncertainty. Conclusion: This CRM will be a reliable standard for the validation of the analytical methods and for quality assurance/quality control of formononetin and formononetin-related traditional herbs, food products, dietary supplements and pharmaceutical formulations.

The concept of diffusion-assisting holes (DAHs) has been developed to increase matrix deposition in the middle layers of the thick-section ceramic matrix composites (CMCs) that are fabricated by chemical vapor infiltration (CVI). However, the effect of DAHs on the tensile properties of CMCs has not been studied. Here, the tensile properties and the state of matrix deposition of a 10-mm-thick two dimensional (2D) C/SiC with DAHs are investigated. Results showed, with DAHs, a zone of increased deposition with a radius of ca. 1.4 mm around a hole was introduced and the net-section strength of the 10-mm-thick 2D C/SiC was increased by 48.1%. In addition, the tensile load bearing capacity was also increased by 34.1%, although the load bearing section decreased with DAHs. The increased net-section strength and tensile load bearing capacity of the C/SiC are attributed to the increased matrix deposition in the middle layers of the thick-section composite.

Vertically-oriented graphene (VG) directly grown on carbon cloth serves as unique support for uniform growth of Zif-67 nanocrystals, and subsequent melamine-assisted pyrolysis results in the anchoring of multiwall carbon nanotubes (MWCNTs) encapsulated Co on VG. Systematic measurements indicate that pyridinic N and pyrrolitic N contents decreased from 600 to 900 °C, and the highest metallic Co contents, as well as well-defined MWCNTs were obtained at 800 °C. Taking advantage of the unique hierarchical nanostructures and adjusted compositions, the free-standing electrode shows excellent bifunctional oxygen evolution reaction (OER) and oxygen reduction reaction (ORR) activities. The presence of MWCNTs, metallic Co, active N species and Co-NxC sites, as well as in-situ formed Co oxides, will synergistically contribute to the electrocatalytic performance. Such free-standing film directly act as air-cathode to construct all solid-state Zn-air batteries (ZABs), showing comparable rechargeability to commercial Pt/C&Ir/C electrocatalysts, and also possessing unique flexibility. Present work opens a new avenue to improve the ORR and OER performance of Zif-67 derived nanomaterials via manipulating the hierarchical structure and chemical compositions, and sheds insights to the understanding of the electrocatalytic mechamism, also promotes the development of solid-state ZABs.

Inspired by bioinspired coating with nanostructures, a heterogeneous zirconia (ZrO2) ceramic membrane has been extensively aspired for changing its intrinsic surface properties. Hence, synthesizing specific nano-microscale architectures of ZrO2 has achieved great interest due to its novel surface properties and application. Here we reported a sol-gel strategy that involved the organic of P123, Brij@C10 and inorganic of Zr-precursor. Impressively, the heterogeneously growth demonstrated that an ultrathin buffer layer could be utilized as the rational mediation of thermal expansion mismatches between their heterogeneously interfaces. This work will raise the potential of bioinspired membrane for emerging applications in industrial processes, such as surface adhesion.

An imperative bottleneck of ceramic materials with weak dynamic response, associating with rigid covalent or ionic bonds, has restricted its extensively applications. Despite traditional reinforcements of carbon fibers or whiskers improved their dynamic response, it was still limited to a threshold owing to their heterogeneous dispersion and structural damage. Graphene has been regarded as an alternative reinforcement due to its excellent in-plane mechanical property. Here we developed a scalable process of chemical assembly to fabricate ZrB2-SiC/graphene composites. Graphene offered a shielding effect to arrest crack propagation, and ultimately restrained fracture and fragmentation of composites. Compared with pristine ZrB2-SiC composites, the dynamic strain of ZrB2-SiC/graphene composites (5.2 vol %) depicted a 138% increasing (from 0.095 to 0.226%), and their dynamic stress exhibited a 28% increasing (from 1.50 to 1.92 GPa). This work offers a paradigm for preparing graphene reinforced ceramic composites with strong dynamic response.

The silty clay in the lower reaches of the Yellow River is characterized by loose structure, low strength, and strong capillary effect. Based on the technology of ancient glutinous rice mortar and microbial-induced calcium carbonate precipitation (MICP), experiments on optimal mass ratio of cementitious liquid to bacterial liquid and optimal concentration of cementitious liquid for MICP and improved MICP technology were carried out by measuring the production of CaCO3, and direct shear test and unconfined compressive strength test of plain silt, glutinous mixing silt, and improved silt with MICP and modified MICP were conducted. The microstructure of the reaction products of MICP and improved MICP technology were also evaluated based on scanning electron microscopy (SEM). Research results showed that the mechanical properties of silt with glutinous rice slurry were effectively improved. With the increase in the concentration of glutinous rice slurry, the strength and internal friction angle of soil samples first increased and then decreased, and the cohesion presented a linear increasing trend. When the concentration of cementitious liquid was 0.5 M and the mass ratio of cementitious liquid to bacterial liquid was 2 : 1, the amount of CaCO3 formed was the most, and the conversion rate of Ca2+ was more than 80%. The improved MICP could increase the conversion rate of Ca2+ (93.44%). An improved MICP showed that glutinous rice slurry could improve bacterial activity, increase the urease content in the bacterial solution, and promote the production of CaCO3. Silt cohesion and internal friction angle of the silt were improved by the improved MICP technology, and the strengthening effect of mechanical properties of modified MICP-reinforced soil is better than that of the MICP-reinforced soil; conventional MICP technology could also improve the soil cohesion, but the improvement in the internal friction angle was not obvious. The SEM results indicated that compared with the reaction product of MICP technology, the structure of the product of improved MICP technology is more compact, resulting in a marked reinforcement of MICP performance with glutinous rice slurry. This study provides new insights into enhancing the mechanical behaviour of MICP-treated silt in the Yellow River Basin with glutinous rice slurry.

Additional file 1: Table S1. Sequences of the SSR, InDel, and KASPar markers used in this study to map AnRGO5 on chromosome 5. Table S2. Sequences of primers used to perform RT-qPCR experiments. Table S3. Sequences of primers used to clone candidate genes.