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Additional file 1: Table S1. Upregulated transcripts in co-cultivated S. elongatus cscB+ compared with those under axenic conditions. Table S2. Downregulated transcripts in co-cultivated S. elongatus cscB+ compared with those under axenic conditions. Table S3. Fold change of transcriptomics and qRT-PCR analyses. Table S4. Selected differentially expressed proteins associated with cross-feeding and metabolite exchange in co-cultivated S. elongatus cscB+ compared with those under axenic conditions.

In this study, the conditions of extraction of loquat flowers polyphenolics were optimized through response surface methodology (RSM). Proper extraction conditions were: solid to liquid ratio 1 g per 50 mL and ethanol concentration 50% at 61°C for 9 min. Furthermore, the antioxidant and anti-polyphenol oxidase (PPO) activity of purified total polyphenolics (PTP) were investigated. PTP displayed strong antioxidant activity with IC50 values of 126.3 ± 8.9, 162.4 ± 6.3 and 94.97 mg ascorbic acid equivalent/g dry weight (mg AAE/d.w.) for ABTS, DPPH, and FRAP assays. In addition, PTP has a substantial inhibitory activity on PPO (IC50 = 115 ± 9.2 μg/mL). From the kinetics analysis, it was proved to be a reversible and mixed-type inhibitor of PPO with KI and KIS values of 76.77 μg/mL and 227.86 μg/mL, respectively. Further, the molecular mechanism underlying the inhibition of PPO by PTP was investigated by molecular docking techniques. The results showed that PTP units could form interaction with the catalytic pocket of PPO through the interaction with amino acid residues in the enzyme active center. The antioxidant activities of PTP together with its effect on PPO activity provide a strong starting point for their practical usage in the food industry., Graphical Abstract

Purpose: Retinoic acid α (RARα) is overexpressed in various tumors and facilitates cancer progression. Although RARα has been shown to facilitate colorectal cancer (CRC) progression, more efforts to characterize mechanisms of RARα in CRC are needed in order to develop better target-based drugs for tumor therapy. Methods: RARα expression in CRC was assessed by IHC. EdU, QPCR, Western blotting, dual-luciferase reporter assay and ChIP were performed to explore the role of RARα in CRC and the mechanism involoved. Results: Here, we show an overexpression of RARα in 73.5% (i.e., 25 of 34 human CRC specimens). RARα knockdown decreased cell proliferation, migration, and invasion. Such phenotypic manifestations can be correlated to lowered activation of Akt and expression of PCNA (proliferating cell nuclear antigen) as well as MMP2 (matrix metallopeptidase). Mechanistically, RARα facilitates CRC growth through Akt signaling activation to cause levels of PCNA to be upregulated. Furthermore, RARα promotes migration and invasion of CRC cells by directly recruiting the MMP2 promoter to enhance the expression of MMP2. Conclusions: These findings demonstrate that CRC carcinogenesis is promoted by RARα via an enhanced Akt signaling and by increasing MMP2 transcription. CRC therapy can examine the use of RARα as a prospective molecular target.

DNA methylation is one of the key epigenetic regulatory mechanisms in development and spermatogenesis. However, the dynamic regulatory mechanisms of genome-wide DNA methylation during testicular development remain largely unknown. Herein, we generated a single-base resolution DNA methylome and transcriptome atlas of precocious porcine testicular tissues across three developmental stages (1, 75, and 150 days old). The results showed that the dynamic methylation patterns were directly related to the expression of the DNMT3A gene. Conjoint analysis revealed a negative regulatory pattern between promoter methylation and the positive regulation of 3'-untranslated region (3'UTR) methylation. Mechanistically, the decrease in promoter methylation affected the upregulation of meiosis-related genes, such as HORMAD1, SPO11, and SYCE1. Demethylation in the 3'UTR induced the downregulation of the INHBA gene and knockdown of INHBA inhibited cell proliferation by reducing the synthesis of activin A. These findings contribute to exploring the regulatory mechanisms of DNA methylation in testicular development.

The Al–Al2O3–MgO composites with added aluminum contents of approximately 0wt%, 5wt%, and 10wt%, named as M1, M2, and M3, respectively, were prepared at 1700°C for 5 h under a flowing N2 atmosphere using the reaction sintering method. After sintering, the Al–Al2O3–MgO composites were characterized and analyzed by X-ray diffraction, scanning electron microscopy, and energy-dispersive X-ray spectroscopy. The results show that specimen M1 was composed of MgO and MgAl2O4. Compared with specimen M1, specimens M2 and M3 possessed MgAlON, and its production increased with increasing aluminum addition. Under an N2 atmosphere, MgO, Al2O3, and Al in the matrix of specimens M2 and M3 reacted to form MgAlON and AlN-polytypoids, which combined the particles and the matrix together and imparted the Al–Al2O3–MgO composites with a dense structure. The mechanism of MgAlON synthesis is described as follows. Under an N2 atmosphere, the partial pressure of oxygen is quite low; thus, when the Al–Al2O3–MgO composites were soaked at 580°C for an extended period, aluminum metal was transformed into AlN. With increasing temperature, Al2O3 diffused into AlN crystal lattices and formed AlN-polytypoids; however, MgO reacted with Al2O3 to form MgAl2O4. When the temperature was greater than (1640 ± 10)°C, AlN diffused into Al2O3 and formed spinel-structured AlON. In situ MgAlON was acquired through a solid-solution reaction between AlON and MgAl2O4 at high temperatures because of their similar spinel structures.

Zhongbao Zhou,1,2,* Shiqiang Song,3,* Zhenli Gao,2 Jitao Wu,2 Jiajia Ma,2 Yuanshan Cui2 1School of clinical medicine, Binzhou Medical University, Yantai, Shandong, China; 2Department of Urology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, China; 3Department of Urology, Qingdao Chengyang People’s Hospital, Qingdao, Shandong, China *These authors contributed equally to this work Aim: We performed a meta-analysis to evaluate the efficacy and safety of dutasteride and finasteride in treating men with androgenetic alopecia (AGA) during a 24-week treatment cycle.Methods: Randomized controlled trials of dutasteride and finasteride for treating AGA were searched using MEDLINE, EMBASE, and the Cochrane Controlled Trials Register. The data were calculated using Rev Man v5.3.0. The reference lists of retrieved studies were also investigated.Results: Three articles including 576 participants which compared dutasteride with finasteride were selected for our analysis. The mean change in total hair count (mean difference [MD], 28.57; 95% CI, 18.75–38.39; P

Chiral transition metal catalysts in which the chirality exclusively originates from a stereogenic metal center witness a more recent advance and their excellent catalytic performance has been demonstrated through applications into diverse enantioselective transformations, especially visible-light-activated photoredox reactions. This thesis deals with the synthesis of new chiral-at-metal rhodium Lewis acid catalysts and their applications in enantioselective photoredox chemistry. 1) Synthesis of a new member of the rhodium-based chiral Lewis acids family, named RhS, with exclusive octahedral centrochirality which features the Λ-configuration (left-handed propeller) and Δ-configuration (right-handed propeller) has been accomplished. Both enantiomers Λ-and Δ-RhS contain two cyclometalating 5-tert-butyl-2-phenylbenzothiazoles in addition to two exchange-labile acetonitriles with a hexafluorophosphate counterion, were synthesized conveniently through a chiral-auxiliary-mediated strategy. Compared with the previously developed Λ/Δ-RhO complexes bearing corresponding benzoxazoles, the Λ/Δ-RhS have been recognized as better chiral Lewis acid catalysts due to the higher steric congestion directed by the benzothiazole ligands, in which the longer C-S bonds over C-O bonds position the steric bulky tertiary butyl groups closer to the substrate coordination site (chapter 3.1). Subsequently, the newly developed chiral-at-rhodium Lewis acids were applied to visible-light-activated asymmetric photoredox catalysis as discussed in chapters 3.2-3.5. 2) The chiral Lewis acid Λ-RhS combined with the photoredox catalyst [Ru(bpy)3](PF 6) 2 enabled the visible-light-activated redox coupling of alpha-silyl alkyl amines with 2-acyl imidazoles to afford, after desilylation, 1,2-amino-alcohols in yields of 69–88% and with high enantioselectivities (54–99% ee). The reaction is proposed to proceed via single electron transfer (SET) between the alpha-silylamine (electron donor) and the rhodium-chelated 2-acyl imidazole (electron acceptor), followed by a stereocontrolled radical–radical recombination (chapter 3.2). 3) A new and simple commercially available photoredox mediator 4,4-difluorobenzil was developed to cooperate with the chiral-at-rhodium Lewis acids Λ/Δ-RhS. This synergistic catalytic system permits an enantioselective three-component photoreaction to provide the fluoroalky l-containing products under dual C bond formation with high enantioselectivities (up to 98% ee) and modest diastereoselectivities (up to 6:1 dr). Excellent diastereoselectivities (up to >38:1:1 dr) for natural chiral compound derivatives were observed. The photoexcited 4,4-difluorobenzil is VI proposed to enable the single electron oxidation of sodium perfluoroalkyl sulfonates under the generation of corresponding perfluoroalkyl radicals which are trapped by electron-rich vinyl ethers to deliver alpha-oxy carbon-centered radicals. These nucleophilic radical species are involved in a subsequent Rh-catalyzed radical conjugate addition with acceptor-substituted alkenes (chapter 3.3). 4) The single chiral-at-rhodium Lewis acids catalyzed radical conjugate addition of alpha-amino alkyl radicals with acceptor-substituted alkenes provided the C formation products in good yields (up to 89%) and with excellent enantioselectivities (up to 97% ee) under visible-light-activated photocatalyst-free conditions. The -amino alkyl radicals are generated from simple glycine derivatives upon single electron reduction triggered by the photoreductant Hantzsch ester. This methodology is recognizedas a practical and versatile avenue to access diverse pharmaceutically demanding chiral beta-substituted gamma-aminobutyric acid analogs, including previously unaccessible derivatives containing fluorinated quaternary stereocenters. Synthetically valuable applications are demonstrated by providing straightforward access to the pharmaceuticals or related bioactive compounds (S)-pregabalin, (R)-baclofen, (R)-rolipram and (S)-nebracetam (chapter 3.4). 5) Visible-light-activated enantioselective β-C(sp3)H functionalization of 2-acyl imidazoles and 2-acylpyridines with 1,2-dicarbonyl compounds catalyzed by a single chiral-at-rhodium Lewis acid Δ-RhS derivative was developed. The C bond formation products are obtained in high yields (up to 99%) and with excellent stereoselectivities (up to >20:1 drand up to >99% ee). Experimental and computational studies support a mechanism in which a photoactivated Rh-enolate intermediate, produced through the coordination of an acceptor-substituted ketone to the central rhodium in the presence of base, transfers a single electron to the 1,2-dicarbonyl compound followed by deprotonation at β position of initial ketone and a subsequent stereocontrolled radical-radical recombination. The chiral-at-rhodium Lewis acid is capable of serving a dual function as a chiral catalyst and a photoredox (pre)catalyst (chapter 3.5)., Chirale Übergangsmetallkatalysatoren, welche nur achirale Liganden koordinieren und bei denen die Chiralität des gesamten Komplexes auf ein stereogenes Metallzentrum zurückgeführt werden kann, bilden eine neuere Klasse von asymmetrischen Übergangsmetallkatalysatoren. Ihre ausgezeichneten katalytischen Fähigkeiten wurde durch die Anwendungen in verschiedenen enantioselektiven Umwandlungen demonstriert, insbesondere auch in lichtaktivierten Photoredoxreaktionen. Diese Arbeit beschäftigt sich mit der Synthese neuartiger Rhodium-basierter chiraler Lewissäurekatalysatoren mit ausschliesslich metallzentrierter Chiralität und deren Anwendungen in der enantioselektiven Photoredoxchemie. 1) Die Synthese eines neuen Mitglieds der Familie Rhodium-basierter chiraler Lewis-Säuren wurde entwickelt. Der neue Komplex wurde RhS genannt. Mit einer ausschliesslich oktaedrischen Zentrochiralität weist der racemische Komplex eine Λ-Konfiguration (linksdrehender Propeller) und Δ-Konfiguration (rechtsdrehender Propeller) auf. Die beiden Enantiomere, Λ- und Δ-RhS, enthalten zwei cyclometallierende 5-tert-Butyl-2-phenylbenzothiazole, zwei austauschlabilen Acetonitrile und ein Hexafluorophosphat-Gegenion. Sie wurden mit Hilfe einer Chirales-Auxiliar-vermittelten Strategie enantiomerenrein synthetisiert. Im Vergleich zu den zuvor entwickelten Λ/Δ-RhO-Komplexen, die entsprechende Benzoxazole tragen, wurden Λ/Δ-RhS als bessere chirale Lewis-Säure-Katalysatoren ermittelt. Dies kann mit einer höheren sterischen Abschirmung erklärt werden. Durch die im Vergleich zu den C-O-Bindungen im Benzoxazol längeren C-S-Bindungen der Benzothiazole befinden sich die tert-Butylgruppen von RhS näher am Reaktionszentrum (Kapitel 3.1). Anschließend wurden die neu entwickelten chiralen Rhodium-Lewissäuren auf die durch sichtbares Licht aktivierte asymmetrische Photoredoxkatalyse angewendet, wie es in den Kapiteln 3.2-3.5 beschrieben wurde. 2) Die mit dem Photoredoxkatalysator [Ru(bpy)3](PF6)2 kombinierte chirale Lewis-Säure Λ-RhS ermöglichte die durch sichtbares Licht aktivierte Redoxkupplung von alpha-Silylalkylaminen mit 2-Acylimidazolen. Nach der Desilylierung wurden 1,2-Aminoalkohole mit Ausbeuten von 69% bis 88% und mit hohen Enantioselektivitäten (54-99% ee) erhalten. Es wird vorgeschlagen, dass die Reaktion über einen Einzelelektronentransfer (SET) zwischen dem alpha-Silylalkylamin (Elektronendonor) und dem Rhodium-Chelat-2-Acylimidazol (Elektronenakzeptor) verläuft, gefolgt von einer stereokontrollierten Radikal-Radikal-Rekombination (Kapitel 3.2). 3) Ein neuer und kommerziell erhältlicher Photoredox-Vermittler 4,4'-Difluorbenzil wurde entwickelt. Dieser Vermittler kann mit den chiralen Rhodium-Lewis-Säuren Λ/Δ-RhS kooperieren. Dieses synergistische katalytische System ermöglichte eine enantioselektive Drei-Komponenten-Photoreaktion, um die fluoralkylhaltigen Produkte unter dualer C-C-Verknüpfung mit hohen Enantioselektivitäten (bis zu 98% ee) und moderaten Diastereoselektivitäten (bis zu 6: 1 dr) zu liefern. Ausgezeichnete Diastereoselektivitäten (bis zu > 38: 1: 1 dr) für natürliche chirale Verbindungsderivate wurden beobachtet. Es wird vorgeschlagen, dass das photoangeregte 4,4'-Difluorbenzil die Einzelelektronenoxidation von Natriumperfluoralkylsulfinaten unter Erzeugung von entsprechenden Perfluoralkylradikalen ermöglicht, die durch elektronenreiche Vinylether abgefangen werden, um alpha-Oxy-Kohlenstoff-zentrierte Radikale zu liefern. Diese nucleophilen Radikalspezies sind an einer anschließenden Rh-katalysierten radikalkonjugierten Addition mit Akzeptor-substituierten Alkenen beteiligt (Kapitel 3.3). 4) Unter durch sichtbares Licht aktivierten Photokatalysator-freien Bedingungen lieferte die durch chirale Rhodium-Lewis-Säuren katalysierte radikalische Addition von alpha-Aminoalkylresten mit Akzeptor-substituierten Alkenen die C-C-Bildungsprodukte in guten Ausbeuten (bis zu 89%) und mit ausgezeichneten Enantioselektivitäten (bis zu 97% ee). Die alpha-Aminoalkylreste wurden aus einfachen Glycinderivaten bei der durch den Photoreduktanten-Hantzsch-Ester ausgelösten Einzelelektronenreduktion erzeugt. Diese Methode wird als ein praktischer und vielseitiger Weg angesehen, um Zugang zu verschiedenen pharmazeutisch anspruchsvollen chiralen beta-substituierten gamma-Aminobuttersäure-Analoga zu erhalten, einschließlich bisher unerreichbarer Derivate, die fluorierte quartäre Stereozentren enthalten. Synthetisch wertvolle Anwendungen wurden durch einen einfachen Zugang zu den Pharmazeutika oder verwandten bioaktiven Verbindungen (S)-Pregabalin, (R)-Baclofen, (R)-Rolipram und (S)-Nebracetam (Kapitel 3.4) demonstriert. 5) Eine durch sichtbares Licht aktivierte enantioselektive β-C(sp3)-H-Funktionalisierung von 2-Acylimidazolen und 2-Acylpyridinen mit 1,2-Dicarbonylverbindungen wurde entwickelt, welche von einem einzigen chiralen Rhodium-Lewis-Säure-Δ-RhS-Derivat katalysiert wird. Die C-C-Bindungsbildungsprodukte wurden in hohen Ausbeuten (bis zu 99%) und mit ausgezeichneten Stereoselektivitäten (bis zu > 20: 1 dr und bis zu > 99% ee) erhalten. Experimentelle und theoretische Untersuchungen stützen den folgenden Mechanismus. Zuerst bildet sich ein Rh-Enolat-Intermediat in Gegenwart einer Base durch Koordination eines Akzeptor-substituierten Ketons an das zentrale Rhodium. Das photoaktivierte Rh-Enolat-Intermediat überträgt ein einzelnes Elektron auf die 1,2-Dicarbonylverbindung. Nach der Deprotonierung an β-Position des anfänglichen Ketons kommt es zu einer stereokontrollierten Rekombination der beiden Radikale. Die chirale Rhodium-Lewis-Säure ist in der Lage, eine doppelte Funktion als chiraler Katalysator und als Vorläuer des Photoredox-Katalysators zu erfüllen (Kapitel 3.5).