Recent Advancements in Continuous-Flow Suzuki-Miyaura Coupling Utilizing Immobilized Molecular Palladium Complexes.

Immobilized Pd-catalyzed Suzuki-Miyaura coupling under continuous-flow conditions using a packed-bed reactor, representing an efficient, automated, practical, and safe technology compared to conventional batch-type reactions. The core objective of this study is the development of an active and durable catalyst. In contrast to supported Pd nanoparticles, the attachment of Pd complexes onto solid supports through well-defined coordination sites is considered a favorable approach for preparing highly dispersed and stabilized Pd species. These species can be directly employed in various flow reactions without the need for pre-treatment. This concept paper explores recent achievements involving the application of immobilized Pd complexes as precatalysts for continuous-flow Suzuki-Miyaura coupling. Our focus is to elucidate the significance of the designed catalyst structures in relation to their catalytic performance under flow conditions. Additionally, we highlight various reaction systems and catalyst packing methods, emphasizing their crucial roles in establishing a practical synthesis process.

Prognostic value of radiological T category using conventional MRI in patients with oral tongue cancer: comparison with pathological T category.

PURPOSE: This study aimed to compare the radiological tumor (T)-category using multiparametric MRI with the pathological T category in patients with oral tongue squamous cell carcinoma (OTSCC) and to examine which is a better predictor of prognosis. METHODS: This retrospective study included 110 consecutive patients with surgically resected primary OTSCC who underwent preoperative contrast-enhanced MRI. T categories determined by maximum diameter and depth of invasion were retrospectively assessed based on the pathological specimen and multiparametric MRI. The MRI assessment included the axial and coronal T1-weighted image (T1WI), axial T2-weighted image (T2WI), coronal fat-suppressed T2WI, and axial and coronal fat-suppressed contrast-enhanced T1WI (CET1WI). Axial and coronal CET1WI measurements were divided into two groups: measurements excluding peritumoral enhancement (MEP) and measurements including peritumoral enhancement. The prognostic values for recurrence and disease-specific survival after radiological and pathological T categorization of cases into T1/T2 and T3/T4 groups were compared. RESULTS: The T category of MEP on coronal CET1WI was the most relevant prognostic factor for recurrence [hazard ratio (HR) = 3.30, p = 0.001] and the HR was higher than the HR for pathological assessment (HR = 2.26, p = 0.026). The T category determined by MEP on coronal CET1WI was also the most relevant prognostic factor for disease-specific survival (HR = 3.12, p = 0.03), and the HR was higher than the HR for pathological assessment (HR = 2.02, p = 0.20). CONCLUSION: The T category determined by MEP on the coronal CET1WI was the best prognostic factor among all radiological and pathological T category measurements.

Synthesis of Butterfly-Like Shaped Gold Nanomaterial: For the Regulation of Liquid-Liquid Phase-Separated Biomacromolecule Droplets.

Nanotechnology is a critical tool to manipulate the sophisticated behavior of biological structures and has provided new research fields. Liquid-liquid phase-separated (LLPS) droplets gather attention as basic reaction fields in a living cell. Droplets play critical roles in regulating protein behavior, including enzyme compartmentalization, stress response, and disease pathogenesis. The dynamic manipulation of LLPS droplet formation/deformation has become a crucial target in nanobiotechnology. However, the development of nanodevices specifically designed for this purpose remains a challenge. Therefore, this study presents butterfly-shaped gold nanobutterflies (GNBs) as novel nanodevices for manipulating LLPS droplet dynamics. The growth process of the GNBs is analyzed via time-lapse electroscopic imaging, time-lapse spectroscopy, and additives assays. Interestingly, GNBs demonstrate the ability to induce LLPS droplet formation in systems such as adenosine triphosphate/poly-l-lysine and human immunoglobulin G, whereas spherical and rod-shaped gold nanoparticles exhibit no such capability. This indicates that the GNB concave surface interacts with the droplet precursors facilitating the LLPS droplet formation. Near-infrared-laser irradiation applied to GNBs enables on-demand deformation of the droplets through localized heat effects. GNB regulates the enzymatic reaction of lysozymes. The innovative design of GNBs presents a promising strategy for manipulating LLPS dynamics and offers exciting prospects for future research.

Continuous-Flow Suzuki-Miyaura Coupling in Water and Organic Solvents Promoted by Blends of Stabilized Convoluted Polymeric Palladium Catalysts and Polymeric Auxiliary Materials.

Given that heterogeneous palladium-catalyzed C-C bond formation reactions under continuous-flow conditions are well suited for the efficient and safe production of pharmaceuticals and functional materials, the development of active and durable catalysts for this purpose is a matter of high practical significance. Here, a previously established molecular convolution methodology was used to synthesize catalysts for Suzuki-Miyaura coupling under flow conditions by blending convoluted polymeric palladium catalysts (prepared from copolymers of 4-vinylpyridine and 4-tert-butylstyrene) and crosslinked polymeric auxiliary materials (prepared from copolymers of divinylbenzene and 4-tert-butylstyrene). The optimal catalyst exhibited high performance and durability and allowed numerous biaryl products such as liquid-crystalline materials, organic electroluminescent materials, and pharmaceuticals to be continuously synthesized with turnover frequencies of up to 238 h-1 . In a demonstration of practical utility, the developed catalytic system was used for the continuous synthesis of two pharmaceuticals (felbinac and fenbufen) in water as the sole solvent.

Zuo1, a ribosome-associated J protein, is involved in glucose repression in Saccharomyces cerevisiae.

In Saccharomyces cerevisiae, the J-protein Zuo1 and the nonconventional Hsp70 homologue Ssz1 stimulate the ATPase activity of the chaperone proteins Ssb1 and Ssb2 (Ssb1/2), which are associated with the ribosomes. The dephosphorylation of sucrose nonfermenting 1 (Snf1) on Thr210 is required for glucose repression. The Ssb1/2 and 14-3-3 proteins Bmh1 and Bmh2 appear to be responsible for the dephosphorylation of Snf1 on Thr210 and glucose repression. Here, we investigated the role of Zuo1 in glucose repression. The zuo1∆ strain as well as the ssb1∆ssb2∆ strain exhibited a glucose-specific growth defect during logarithmic growth on glucose. Many of the respiratory chain genes examined were statistically significantly upregulated, but less than 2-fold, in the zuo1∆ strain as well as in the ssb1∆ssb2∆ strain on glucose. In addition, excessive phosphorylation of Snf1 on Thr210 was observed in the zuo1∆ strain as well as in the ssb1∆ssb2∆ strain in the presence of glucose. The mRNA levels of SSB1/2 and BMH1 were statistically significantly reduced by approximately 0.5- to 0.8-fold relative to the wild-type level in the zuo1∆ strain on glucose. These results suggest that Zuo1 is responsible for glucose repression, possibly by increasing the mRNA levels of SSB1/2 and BMH1 during growth on glucose.

Catalyst Design and Feature Engineering to Improve Selectivity and Reactivity in Two Simultaneous Cross-Coupling Reactions.

Highly active catalysts are required in numerous industrial fields; therefore, to minimize costs and development time, catalyst design using machine learning has attracted significant attention. This study focused on a reaction system where two types of cross-coupling reactions, namely, Buchwald-Hartwig type cross-coupling (BHCC) and Suzuki-Miyaura type cross-coupling (SMCC) reactions, occur simultaneously. Constructing a machine-learning model that considers all experimental conditions is essential to accurately predict the product yield for both the BHCC and the SMCC reactions. The objective of this study was to establish explanatory variables x that considered all experimental conditions within the reaction system involving simultaneous cross-couplings and to design catalysts that achieve the target yield and the development of novel reactions. To accomplish this, Bayesian optimization was combined with established variables x to design new catalysts and enhance reaction selectivity. Moreover, the catalyst design in this study successfully pioneered new reactions involving Cu, Rh, and Pt catalysts in a reaction system that did not previously react with transition metals other than Ni or Pd.

Superatom Molecular Orbitals of Endohedral C82.

Understanding superatom molecular orbital (SAMO) states in fullerene derivatives has been in the limelight ever since the first discovery of SAMOs owing to the fundamental interest in this topic as well as to the possible applications in molecular switches and other organic electronics. Nevertheless, very few reports have been published on SAMO states of larger fullerenes so far. Using density functional theory, we attempt to partially remedy this situation by presenting a study on SAMO states in C82 and its Ca and Sc endohedrally doped derivatives, comparing results with previous relevant findings for C60. We find that C82 possesses higher SAMO energies compared to C60, as associated with the symmetry of the molecule, and that endohedral doping leads to energetically favorable side positions of Ca and Sc inside the C82 cage. Among the two, Sc@C82 has more stable SAMO states compared to Ca@C82 as reflected by the shift in the density of states, while the charge states are found to be similar. In the case of the monolayer form, the pz- and 2s-SAMO orbitals overlap with the nearest neighbors, causing parabolic band dispersion with the formation of near free electron states and that the SAMO state energies move closer to the Fermi energy compared to the related molecules. These findings provide promising information about the distribution of SAMO states in C82 fullerene, which can be further relevant in studies of SAMO states of higher fullerenes and for coming applications of these systems.

CO2 reduction driven by a pH gradient.

All life on Earth is built of organic molecules, so the primordial sources of reduced carbon remain a major open question in studies of the origin of life. A variant of the alkaline-hydrothermal-vent theory for life's emergence suggests that organics could have been produced by the reduction of CO2 via H2 oxidation, facilitated by geologically sustained pH gradients. The process would be an abiotic analog-and proposed evolutionary predecessor-of the Wood-Ljungdahl acetyl-CoA pathway of modern archaea and bacteria. The first energetic bottleneck of the pathway involves the endergonic reduction of CO2 with H2 to formate (HCOO-), which has proven elusive in mild abiotic settings. Here we show the reduction of CO2 with H2 at room temperature under moderate pressures (1.5 bar), driven by microfluidic pH gradients across inorganic Fe(Ni)S precipitates. Isotopic labeling with 13C confirmed formate production. Separately, deuterium (2H) labeling indicated that electron transfer to CO2 does not occur via direct hydrogenation with H2 but instead, freshly deposited Fe(Ni)S precipitates appear to facilitate electron transfer in an electrochemical-cell mechanism with two distinct half-reactions. Decreasing the pH gradient significantly, removing H2, or eliminating the precipitate yielded no detectable product. Our work demonstrates the feasibility of spatially separated yet electrically coupled geochemical reactions as drivers of otherwise endergonic processes. Beyond corroborating the ability of early-Earth alkaline hydrothermal systems to couple carbon reduction to hydrogen oxidation through biologically relevant mechanisms, these results may also be of significance for industrial and environmental applications, where other redox reactions could be facilitated using similarly mild approaches.

RPD3 and UME6 are involved in the activation of PDR5 transcription and pleiotropic drug resistance in ρ0 cells of Saccharomyces cerevisiae.

BACKGROUND: In Saccharomyces cerevisiae, the retrograde signalling pathway is activated in ρ0/- cells, which lack mitochondrial DNA. Within this pathway, the activation of the transcription factor Pdr3 induces transcription of the ATP-binding cassette (ABC) transporter gene, PDR5, and causes pleiotropic drug resistance (PDR). Although a histone deacetylase, Rpd3, is also required for cycloheximide resistance in ρ0/- cells, it is currently unknown whether Rpd3 and its DNA binding partners, Ume6 and Ash1, are involved in the activation of PDR5 transcription and PDR in ρ0/- cells. This study investigated the roles of RPD3, UME6, and ASH1 in the activation of PDR5 transcription and PDR by retrograde signalling in ρ0 cells. RESULTS: ρ0 cells in the rpd3∆ and ume6∆ strains, with the exception of the ash1∆ strain, were sensitive to fluconazole and cycloheximide. The PDR5 mRNA levels in ρ0 cells of the rpd3∆ and ume6∆ strains were significantly reduced compared to the wild-type and ash1∆ strain. Transcriptional expression of PDR5 was reduced in cycloheximide-exposed and unexposed ρ0 cells of the ume6∆ strain; the transcriptional positive response of PDR5 to cycloheximide exposure was also impaired in this strain. CONCLUSIONS: RPD3 and UME6 are responsible for enhanced PDR5 mRNA levels and PDR by retrograde signalling in ρ0 cells of S. cerevisiae.

Triflimide-Promoted Nucleophilic C-Arylation of Halopurines to Access N7-Substituted Purine Biaryls.

Functionalized nucleobases are utilized in a wide range of fields; therefore, the development of new synthesis methods is essential for their continued application. With respect to the C6-arylation of halopurines, which possess a substituent at the N7-position, only a small number of successful cases have been reported, which is predominately a result of large steric hinderance effects. Herein, we report efficient and metal-free C6-arylations and SNAr reactions of N7-substituted chloropurines in aromatic and heteroatom nucleophiles promoted by triflimide (Tf2NH) in fluoroalcohol.

Beyond 53% internal quantum efficiency in a AlGaN quantum well at 326 nm UVA emission and single-peak operation of UVA LED: publisher's note.

This publisher's note contains corrections to Opt. Lett.45, 495 (2020)OPLEDP0146-959210.1364/OL.376894.

Synthesis, Structure, and Complexation of an S-Shaped Double Azahelicene with Inner-Edge Nitrogen Atoms.

Invited for the cover of this issue is Ken Kamikawa and co-workers at Osaka Prefecture University and RIKEN Center for Sustainable Resource Science. The image depicts an S-shaped double azahelicene capturing the palladium in a trans-chelating fashion. Read the full text of the article at 10.1002/chem.202002405.

Synthesis, Structure, and Complexation of an S-Shaped Double Azahelicene with Inner-Edge Nitrogen Atoms.

An S-shaped double azahelicene (1) was synthesized in excellent yield by a palladium-catalyzed double dehydrogenative C-H coupling reaction. The stereochemistry of 1 was confirmed to be dl by single-crystal X-ray diffraction analysis. Selective formation of dl-1 was attributed to the isomerization of the kinetically controlled product (meso-1) into the more thermodynamically stable dl-1 under the applied reaction conditions. dl-1 can coordinate to palladium(II) in a bidentate trans-chelating fashion, which was confirmed by X-ray absorption fine structure (XAFS) as well as by X-ray photoelectron spectroscopy (XPS), diffuse reflectance (DR) UV/Vis, and far-infrared (FIR) absorption spectroscopy. Theoretical calculations of palladium complex 16 revealed a weak attractive interaction between palladium and carbon atoms on the central dimethoxynaphthalene core, which could facilitate a disproportionation between a trans-chelating (dl-1)⋅PdCl2 complex and PdCl2 to form 16.

Recent Advances in Continuous-Flow Enantioselective Catalysis.

The increased demand for more efficient, safe, and green production in fine chemical and pharmaceutical industry calls for the development of continuous-flow manufacturing, and for chiral chemicals in particular, enantioselective catalytic processes. In recent years, this emerging direction has received considerable attention and has seen rapid progress. In most cases, catalytic enantioselective flow processes using homogeneous, heterogeneous, or enzymatic catalysts have shown significant advantages over the conventional batch mode, such as shortened reaction times, lower catalysts loadings, and higher selectivities in addition to the normal merits of non-enantioselective flow operations. In this Minireview, the advancements, key strategies, methods, and technologies developed the last six years as well as remaining challenges are summarized.

Diagnostic Cytokines and Comparative Analysis Secreted from Exfoliated Deciduous Teeth, Dental Pulp, and Bone Marrow Derived Mesenchymal Stem Cells for Functional Cell-Based Therapy.

The aim of the study was to clarify the distinctive features of stem cells for effective cell-based therapy strategies in regenerative medicine. The expression levels of cytokines secreted from stem cells from exfoliated deciduous teeth (SHED), dental pulp stem cells (DPSCs), and bone marrow derived mesenchymal stem cells (BMMSCs) were examined to identify the details of their characteristics. A total of 174 cytokines were analyzed using cytokine antibody array, and their expression levels were confirmed by an enzyme-linked immunosorbent assay. These results indicated that 11 cytokines that were related to tissue regeneration, including growth factors, chemokines, and inflammatory cytokines, were identical in SHED, DPSCs, and BMMSCs. The comparative analyses between SHED and BMMSCs revealed that hepatocyte growth factor (HGF), matrix metalloproteinase-3, and stromal cell derived factor 1 (SDF-1) were expressed 6.7-, 2.5-, and 2.1-fold higher, respectively, in SHEDs. HGF was also expressed 3.4-fold higher in DPSCs than BMMSCs. Monocyte chemoattractant protein-1, and-3 were expressed more strongly in BMMSCs. SHED contained significantly higher SDF-1 levels than DPSCs. The distinct cytokine secretion indicated that they had different character besides basic MSC features. This knowledge of diagnostic cytokines analysis secreted from SHED, DPSCs, and BMMSCs extends our understanding, and can provide a novel therapeutic paradigm shift for functional cell-based therapy.

Clinical Potential and Current Progress of Dental Pulp Stem Cells for Various Systemic Diseases in Regenerative Medicine: A Concise Review.

Dental pulp stem cells (DPSCs) are mesenchymal stem cells (MSCs) that have multipotent differentiation and a self-renewal ability. They have been useful not only for dental diseases, but also for systemic diseases. Extensive studies have suggested that DPSCs are effective for various diseases, such as spinal cord injuries, Parkinson's disease, Alzheimer's disease, cerebral ischemia, myocardial infarction, muscular dystrophy, diabetes, liver diseases, eye diseases, immune diseases, and oral diseases. DPSCs have the potential for use in a cell-therapeutic paradigm shift to treat these diseases. It has also been reported that DPSCs have higher regenerative potential than the bone marrow-derived mesenchymal stem cells known as representative MSCs. Therefore, DPSCs have recently gathered much attention. In this review, the therapeutic potential of DPSCs, the latest progress in the pre-clinical study for treatment of these various systemic diseases, and the clinical applications of DPSCs in regenerative medicine, are all summarized. Although challenges, including mechanisms of the effects and establishment of cell processing and transplantation methods for clinical use, still remain, DPSCs could be promising stem cells sources for various clinical applications, because of their easy isolation by a noninvasive procedure without ethical concerns.

Synthesis of Uracil-Iodonium(III) Salts for Practical Utilization as Nucleobase Synthetic Modules.

Iodonium(III) salts bearing uracil moieties have recently appeared in the literature, but their structural scope and utilization are limited because of their hygroscopic characteristics. In this study, we describe our detailed investigations for synthesizing a series of uracil iodonium(III) salts derived with various structural motifs and counterions. These new compounds have been utilized as attractive synthetic modules in constructing functionalized nucleobase and nucleosides.

Development of Batch and Flow Immobilized Catalytic Systems with High Catalytic Activity and Reusability.

My mission in catalysis research is to develop highly active and reusable supported catalytic systems in terms of fundamental chemistry and industrial application. For this purpose, I developed three types of highly active and reusable supported catalytic systems. The first type involves polymeric base-supported metal catalysts: Novel polymeric imidazole-Pd and Cu complexes were developed that worked at the mol ppm level for a variety of organic transformations. The second involves catalytic membrane-installed microflow reactors: Membranous polymeric palladium and copper complex/nanoparticle catalysts were installed at the center of a microtube to produce novel catalytic membrane-immobilized flow microreactor devices. These catalytic devices mediated a variety of organic transformations to afford the corresponding products in high yield within 1-38 s. The third is a silicon nanowire array-immobilized palladium nanoparticle catalyst. This device promoted a variety of organic transformations as a heterogeneous catalyst. The Mizoroki-Heck reaction proceeded with 280 mol ppb (0.000028 mol%) of the catalyst, affording the corresponding products in high yield.

Supramolecular Scaffold for Tailoring the Two-Dimensional Assembly of Functional Molecular Units into Organic Thin Films.

Tailoring structurally anisotropic molecular assemblies while controlling their orientation on solid substrates is an important subject for advanced technologies that use organic thin films. Here we report a supramolecular scaffold based on tripodal triptycene assemblies, which enables functional molecular units to assemble into a highly oriented, multilayered two-dimensional (2D) structure on solid substrates. The triptycene building block carries an ethynyl group and three flexible side chains at the 10- and 1,8,13-positions, respectively. These bridgehead-substituted tripodal triptycenes self-assembled on solid substrates to form a well-defined "2D hexagonal + 1D lamellar" structure, which developed parallel to the surface of the substrates. Remarkably, the assembling properties of the triptycene building blocks, particularly for a derivative with tri(oxyethylene)-containing side chains, were not impaired when the alkyne terminal was functionalized with a large molecular unit such as C60, which is comparable in diameter to the triptycene framework. Consequently, thin films with a multilayered 2D assembly of the C60 unit were obtained. Flash-photolysis time-resolved microwave conductivity (FP-TRMC) measurements revealed that the C60 film exhibits highly anisotropic charge-transport properties. Bridgehead-substituted tripodal triptycenes may provide a versatile supramolecular scaffold for tailoring the 2D assembly of molecular units into a highly oriented thin film, and in turn for exploiting the full potential of anisotropic molecular functions.

Protective and therapeutic effects of fucoxanthin against sunburn caused by UV irradiation.

Mild exposure to ultraviolet (UV) radiation is also harmful and hazardous to the skin and often causes a photosensitivity disorder accompanied by sunburn. To understand the action of UV on the skin we performed a microarray analysis to isolate UV-sensitive genes. We show here that UV irradiation promoted sunburn and downregulated filaggrin (Flg); fucoxanthin (FX) exerted a protective effect. In vitro analysis showed that UV irradiation of human dermal fibroblasts caused production of intracellular reactive oxygen species (ROS) without cellular toxicity. ROS production was diminished by N-acetylcysteine (NAC) or FX, but not by retinoic acid (RA). In vivo analysis showed that UV irradiation caused sunburn and Flg downregulation, and that FX, but not NAC, RA or clobetasol, exerted a protective effect. FX stimulated Flg promoter activity in a concentration-dependent manner. Flg promoter deletion and chromatin immunoprecipitation analysis showed that caudal type homeo box transcription factor 1 (Cdx1) was a key factor for Flg induction. Cdx1 was also downregulated in UV-exposed skin. Therefore, our data suggested that the protective effects of FX against UV-induced sunburn might be exerted by promotion of skin barrier formation through induction of Flg, unrelated to quenching of ROS or an RA-like action.