A Unified Synthetic Approach to the Pleurotin Natural Products.

The asymmetric total syntheses of four pleurotin natural products, namely, (-)-pleurotin, (+)-leucopleurotin, (+)-leucopleurotinic acid, and (+)-dihydropleurotinic acid, were described in a concise manner. Key transformations feature a Johnson-Claisen rearrangement, a diastereo-controlled sequential hydroboration-oxidation, a SOMO/photoredox activated aldehyde α-alkylation, and oxidative cyclizations.

Cationic Ir(III) Complexes with 4-Fluoro-4'-pyrazolyl-(1,1'-biphenyl)-2-carbonitrile as the Cyclometalating Ligand: Synthesis, Characterizations, and Application to Ultrahigh-Efficiency Light-Emitting Electrochemical Cells.

Light-emitting electrochemical cells (LECs) promise low-cost, large-area luminescence applications with air-stabilized electrodes and a versatile fabrication that enables the use of solution processes. Nevertheless, the commercialization of LECs is still encountering many obstacles, such as low electroluminescence (EL) efficiencies of the ionic materials. In this paper, we propose five blue to yellow ionic Ir complexes possessing 4-fluoro-4'-pyrazolyl-(1,1'-biphenyl)-2-carbonitrile (ppfn) as a novel cyclometalating ligand and use them in LECs. In particular, the device within di[4-fluoro-4'-pyrazolyl-(1,1'-biphenyl)-2-carbonitrile]-4,4'-di-tert-butyl-2,2'-bipyridyl iridium(III) hexafluorophosphate (DTBP) shows a remarkable photoluminescence quantum yield (PLQY) of 70%, and by adjusting the emissive-layer thickness, the maximal external quantum efficiency (EQE) reaches 22.15% at 532 nm under the thickness of 0.51 µm, showing the state-of-the-art value for the reported blue-green LECs.

Multiple-cycle photochemical cascade reactions.

Cascade reactions represent an efficient and economical synthetic approach, enabling the rapid synthesis of a wide array of structurally complex organic compounds. These compounds, previously inaccessible, can now be synthesized in a remarkably limited number of steps. Concurrently, the photochemical reactions of organic molecules have gained prominence as a potent strategy for accessing a diverse range of radical species and intermediates. This is achieved in a controlled manner under mild conditions. Owing to the relentless endeavors of chemists, significant strides have been made in the realm of photochemical cascade reactions. These advancements have facilitated the synthesis of novel molecular structures with high complexity, structures that are typically challenging to generate under thermal conditions. In this review, we comprehensively summarize and underscore the recent pivotal advancements in visible-light-induced cascade reactions. Our focus is on the elucidation of multiple photochemical catalytic cycles, emphasizing the catalytic activation modes and the types of reactions involved.

Identification of hub genes and key pathways in spinal cord injury via bioinformatics analysis.

This study aimed to explore the hub genes and related key pathways in Spinal Cord Injury (SCI) based on the bioinformatics analysis. Two microarray datasets (GSE45006, GSE45550) were obtained from the GEO database and were merged and batch-corrected. The differentially expressed genes (DEGs) in SCI were explored with the Limma, and the weighted gene co-expression network analysis (WGCNA) was conducted to explore the module genes. Functional enrichment analysis and Gene set variation analysis (GSVA) were used to investigate the biological functions and key pathways of the key genes related to SCI. Then the protein-protein interaction (PPI) network was generated using the STING online tool, and the hub genes in SCI were identified. Receiver operating characteristic (ROC) curves were applied to assess the diagnostic value of the selected hub genes. We identified 554 DEGs in SCI, and 1236 key genes in SCI were selected via WGCNA. Totally 111 key genes related to SCI were discovered. Furthermore, the functional enrichment analysis showed that these key mRNAs were primarily enriched in the extracellular matrix (ECM)-related pathways and processes associated with wound healing and cell growth. The PPI network further filtered six hub genes (Cd44, Timp1, Loxl1, Col6a1, Col3a1, Col5a1) ranked by the degree, and the diagnostic value of the six hub genes was confirmed by the ROC curves. Six hub genes including Cd44, Timp1, Loxl1, Col6a1, Col3a1, and Col5a1 were identified in SCI, with differential expression and excellent diagnostic value, which might provide insight into the targeted therapy of SCI.

Cytokine analysis of aqueous humor in patients with cytomegalovirus corneal endotheliitis.

PURPOSE: To evaluate cytokine levels of aqueous humor in patients with cytomegalovirus (CMV) corneal endotheliitis and their relationships with CMV DNA load. METHODS: 44 aqueous humor samples were obtained from 26 patients with CMV corneal endotheliitis at various stages of treatment. 33 samples obtained from cataract patients during the same period were selected as a control group. Each sample was used to measure the concentration of the CMV DNA load using real-time quantitative polymerase chain reaction, and to examine the levels of IL-6, IL-8, IL-10, MCP-1, VCAM-1, VEGF, IP-10, G-CSF, ICAM-1 and IFN-γ using a cytometric bead array. RESULTS: All 10 cytokines were found to have statistically significant differences between the CMV endotheliitis and cataract groups. The Spearman correlation test showed that the concentration of CMV DNA load was significantly associated with the levels of IL-6 (P = 0.005, r = 0.417), IL-8 (P < 0.001, r = 0.514), IL-10 (P < 0.001, r = 0.700), MCP-1 (P = 0.001, r = 0.487), VEGF (P < 0.001, r = 0.690), IP-10 (P = 0.001, r = 0.469), G-CSF (P < 0.001, r = 0.554) and ICAM-1 (P < 0.001, r = 0.635), but not significantly associated with VCAM-1 (P = 0.056) and IFN-γ (P = 0.219). CONCLUSIONS: There was a combined innate and adaptive immune response in aqueous humor in patients with CMV endotheliitis. Levels of multiple cytokines were significantly correlated with viral particle. Cytokines are potential indicators to help diagnose CMV endotheliitis, evaluate disease activity and assess treatment response.

Chlorogenic acid alleviates renal fibrosis by reducing lipid accumulation in diabetic kidney disease through suppressing the Notch1 and Stat3 signaling pathway.

AIMS: Abnormal renal lipid metabolism causes renal lipid deposition, which leads to the development of renal fibrosis in diabetic kidney disease (DKD). The aim of this study was to investigate the effect and mechanism of chlorogenic acid (CA) on reducing renal lipid accumulation and improving DKD renal fibrosis. METHODS: This study evaluated the effects of CA on renal fibrosis, lipid deposition and lipid metabolism by constructing in vitro and in vivo models of DKD, and detected the improvement of Notch1 and Stat3 signaling pathways. Molecular docking was used to predict the binding between CA and the extracellular domain NRR1 of Notch1 protein. RESULTS: In vitro studies have shown that CA decreased the expression of Fibronectin, α-smooth muscle actin (α-SMA), p-smad3/smad3, alleviated lipid deposition, promoted the expression of carnitine palmitoyl transferase 1 A (CPT1A), and inhibited the expression of cholesterol regulatory element binding protein 1c (SREBP1c). The expression of Notch1, Cleaved Notch1, Hes1, and p-stat3/stat3 were inhibited. These results suggested that CA might reduce intercellular lipid deposition in human kidney cells (HK2) by inhibiting Notch1 and stat3 signaling pathways, thereby improving fibrosis. Further, in vivo studies demonstrated that CA improved renal fibrosis and renal lipid deposition in DKD mice by inhibiting Notch1 and stat3 signaling pathways. Finally, molecular docking experiments showed that the binding energy of CA and NRR1 was -6.6 kcal/mol, which preliminarily predicted the possible action of CA on Notch1 extracellular domain NRR1. CONCLUSION: CA reduces renal lipid accumulation and improves DKD renal fibrosis by inhibiting Notch1 and stat3 signaling pathways.

Obesity, Glycemic Traits, Lifestyle Factors, and Risk of Facial Aging: A Mendelian Randomization Study in 423,999 Participants.

BACKGROUND: Several recent observational studies have associated obesity, lifestyle factors (smoking, sleep duration, and alcohol drinking), and glycemic traits with facial aging. However, whether this relationship is causal due to confounding and reverse causation is yet to be substantiated. AIMS: We aimed to assess these relationships using Mendelian randomization (MR). METHODS: For the instrumental variables, this paper selected independent single nucleotide polymorphisms (SNPs) linked to the exposures at a genome-wide state (P < 5 × 10-8) in equivalent genome-wide association studies (GWAS). Using the UK Biobank, we obtained summary-level data for facial aging on 423,999 individuals. The primary assessments were performed through the combination of complementing techniques (simple method approaches, weighted model, MR-Egger, and weighted median) and the inverse-variance-weighted method. Along with that, we examined the heterogeneity and horizontal pleiotropy through different types of sensitivity analyses. RESULTS: The correlations were (a) facial aging for body mass index (BMI, OR = 1.054, 95% CI 1.044-1.64), (b) waist/hip ratio (OR = 1.056, 95% CI 1.023-1.091), and (c) smoking (OR = 1.023, 95% CI 1.007-1.039). Equally important, the correlations for waist/hip ratio remained robust after adjusting for the genetically predicted BMI (OR = 1.028, 95% CI 1.003-1.054). However, no causal effects of alcoholic drinking, glycemic traits, and sleep duration on facial aging were observed. CONCLUSIONS: The outcomes shed light on the potential correlation of obesity and cigarette smoking with facial aging while putting forward a more comprehensive and credible foundation for the optimization of facial aging strategies. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

One-Pot Synthesis of Diverse 1,4-[60]Fullerephenols via Three-Component Umpolung Cascade Coupling of Phenols, C60 , and Nucleophiles.

A three-component umpolung cascade coupling reaction of phenols, C60 , and different nucleophiles which includes H2 O, alcohols, triphenylamines and carbazoles was developed. Furthermore, one-pot 1,4-bisphenol coupling on C60 has been realized by this method. This practical protocol features high chemo- and regioselectivity, wide substrate range, easy operation and low cost, thus providing a robust method for the one-pot synthesis of various unsymmetrical 1,4-[60]fullerephenols.

White Light-Emitting Electrochemical Cells Employing Phosphor-Sensitized Thermally Activated Delayed Fluorescence to Approach All-Phosphorescent Device Efficiencies.

Solid-state light-emitting electrochemical cells (LECs) show promising advantages of simple device architecture, low operation voltage, and insensitivity to the electrode work functions such that they have high potential in low-cost display and lighting applications. In this work, novel white LECs based on phosphor-sensitized thermally activated delayed fluorescence (TADF) are proposed. The emissive layer of these white LECs is composed of a blue-green phosphorescent host doped with a deep-red TADF guest. Efficient singlet-to-triplet intersystem crossing (ISC) on the phosphorescent host and the subsequent Förster energy transfer from the host triplet excitons to guest singlet excitons can make use of both singlet and triplet excitons on the host. With the good spectral overlap between the host emission and the guest absorption, 0.075 wt.% guest doping is sufficient to cause substantial energy transfer efficiency (ca. 40 %). In addition, such a low guest concentration also reduces the self-quenching effect and a high photoluminescence quantum yield of up to 84 % ensures high device efficiency. The phosphor-sensitized TADF white LECs indeed show a high external quantum efficiency of 9.6 %, which is comparable with all-phosphorescent white LECs. By employing diffusive substrates to extract the light trapped in the substrate, the device efficiency can be further improved by ca. 50 %. In the meantime, the intrinsic EL spectrum and device lifetime of the white LECs recover since the microcavity effect is destroyed. This work successfully demonstrates that the phosphor-sensitized TADF white LECs are potential candidates for efficient white light-emitting devices.

KOtBu-Promoted, Three-Component Domino Reaction of Arenes(indoles/phenols), C60, and (Per/poly)fluoroarenes: Achieving Direct C-C Cross-Coupling of Fullerene with (Per/poly)fluoroarenes.

A KOtBu-promoted, three-component cross-coupling of arenes(indoles/phenols), C60, and (per/poly)fluoroarenes has been established for the one-pot efficient synthesis of various 1,4-arene-bridged bis(polyfluoroaryl)-functionalized [60]fullerenes. This developed reaction system demonstrates good functional group compatibilities with broad substrate scope, which exhibits high regio- and chemoselectivities. Further control experiment succeeded in providing a one-pot protocol for the synthesis of various 1,2-N-(per/poly)fluoroarene-substituted 1,2-(3-indole)(hydro)fullerenes.

Synthesis of spiro[indolenine]-methanofullerenes via Deoxofluor promoted deoxygenative cyclopropanation of 1,2-(3-indole)-fullerenols.

Deoxofluor-promoted intramolecular cyclopropanation of 1,2-(3-indole)fullerenols has been developed as a straightforward and efficient protocol for the synthesis of various spiro[indolenine]-methanofullerenes. This approach exhibits low cost, operational simplicity, and convenient conditions, and thus has potential application value.

Azoxy Compounds-From Synthesis to Reagents for Azoxy Group Transfer Reactions.

The azoxy functional group is an important structural motif and represents the formally oxidized counterpart of the azo group. Azoxy compounds find numerous applications ranging from pharmaceuticals to functional materials, yet their synthesis remains underdeveloped with a main focus on the formation symmetric azoxy compounds. To overcome challenges in the synthesis of such unsymmetric azoxy compounds, we designed a process employing readily accessible nitroso compounds and iminoiodinanes. This method builds on the use of visible light irradiation to generate a triplet nitrene from iminoiodinanes, which is trapped by nitroso arenes to give access to sulfonyl-protected azoxy compounds with a good substrate scope and functional group tolerance. We further describe two applications of these sulfonyl-protected azoxy compounds as radical precursors in synthesis, where the whole azoxy group can be transferred and employed in C(sp3 )-H functionalization of ethers or 1,2-difunctionalization of vinyl ethers. All of the reactions occurred at room temperature under visible light irradiation without the addition of any photoredox catalysts and additives. Control experiments, mechanism investigations, and DFT studies well explained the observed reactivity.

Practical synthesis of isocoumarins via Rh(III)-catalyzed C-H activation/annulation cascade.

Herein, we report an unprecedented Rh(III)-catalyzed C-H activation/annulation cascade of readily available enaminones with iodonium ylides towards the convenient synthesis of isocoumarins. This coupling system proceeds in useful chemical yields (up to 93%) via a cascade C-H activation, Rh-carbenoid migratory insertion and acid-promoted intramolecular annulation. The success of gram-scale reaction and diverse functionalization of isocoumarins demonstrated the synthetic utility of this protocol.

Ligand Modification of Au25 Nanoclusters for Near-Infrared Photocatalytic Oxidative Functionalization.

The inorganic-organic interface between metal catalysts and their substrates greatly influences reaction processes, but few studies of this interface have been conducted for a detailed understanding of its structure. Herein, we describe the synthesis and structural determination of an arylthiolated Au25(F-Ph)18- nanocluster and characterize in detail the key roles of its ligands in photocatalyzed oxidative functionalization reactions. The most significant findings are that (i) interactions are established between ligands to avoid distortion of the geometric structure, limit the Jahn-Teller effect, and protect the nanocluster from oxidization and (ii) the low energy gap (HOMO-LUMO) of the synthetic clusters enables three types of photocatalytic oxidative functionalization reactions by near-infrared light (850 nm).

ezGeno: an automatic model selection package for genomic data analysis.

MOTIVATION: To facilitate the process of tailor-making a deep neural network for exploring the dynamics of genomic DNA, we have developed a hands-on package called ezGeno. ezGeno automates the search process of various parameters and network structures and can be applied to any kind of 1D genomic data. Combinations of multiple abovementioned 1D features are also applicable. RESULTS: For the task of predicting TF binding using genomic sequences as the input, ezGeno can consistently return the best performing set of parameters and network structure, as well as highlight the important segments within the original sequences. For the task of predicting tissue-specific enhancer activity using both sequence and DNase feature data as the input, ezGeno also regularly outperforms the hand-designed models. Furthermore, we demonstrate that ezGeno is superior in efficiency and accuracy compared to the one-layer DeepBind model and AutoKeras, an open-source AutoML package. AVAILABILITY AND IMPLEMENTATION: The ezGeno package can be freely accessed at https://github.com/ailabstw/ezGeno. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Transition-Metal-Free Domino Reaction of [60]Fullerene, Indole, and DMSO/HCl: One-Pot Access to Diverse N-Substituted [60]Fulleroindole Derivatives.

An unprecedented multicomponent domino reaction of [60]fullerene, indole, and DMSO/HCl has been developed for the one-pot efficient synthesis of diverse N-substituted [60]fulleroindole derivatives. This methodology features simple operation, low cost, and transition-metal-circumvented and good functional group tolerance in indole.

Discovery of EGFR-Targeted Environment-Sensitive fluorescent probes for cell imaging and efficient tumor detection.

Overexpression of human epidermal growth factor receptor (EGFR) plays an important role in several signaling pathways inside and outside the cell, especially in the processes of cell proliferation, differentiation, and death in various cancers. Due to the complexity of the structure and function of EGFR, research on the fluorescence visualization of EGFR protein visualization has proved challenging. One possible strategy for designing a receptor-targeting fluorescent probe with a switching mechanism is to introduce an environment-sensitive fluorophore into the drug ligand. Based on this strategic molecular design, we introduced two environment-sensitive small molecular fluorophores, dansyl chloride (DNS) and nitrobenzoxadiazole (NBD), to replace the morpholine group of gefitinib, achieving a series of fluorescent molecular probes bearing a switching mechanism. The GN probes exhibited prominent environment sensitivity, suggesting good performance as turn-on EGFR-targeting fluorescent ligands. The representative probe GN3 specifically responded to tumor cells overexpressing EGFR, which was validated with live-cell fluorescence imaging and in vivo xenograft tumor imaging. Ligand-induced EGFR phosphorylation in A431 cells was considerably inhibited by probe GN3, demonstrating that this probe still functions as an EGFR inhibitor. Owing to the turn-on response of GN3 to EGFR in tumor cells, and the competitive replacement behavior to the EGFR inhibitor gefitinib, these probes have the potential to be used for fluorescence imaging of cells overexpressing EGFR.

Lasers and Intense Pulsed Light for the Treatment of Pathological Scars: A Network Meta-Analysis.

BACKGROUND: Laser and intense pulsed light (IPL) therapies have shown promising effects on pathological scars, but the comparative effectiveness of laser and IPL therapies has not yet been studied. OBJECTIVES: The aim of this study was to compare and rank the efficacy of laser and IPL therapies to determine the most effective treatment method for pathological scars. METHODS: Relevant studies published up to February 2022 were identified by searching PubMed, Web of Science, Cochrane Library, CNKI, and Wanfang databases. We defined Vancouver Scar Scale score as the primary outcome. Both frequentist and Bayesian approaches were used to perform a network meta-analysis. RESULTS: We included 25 trials with a total of 1688 participants. The rankings based on the surface under the cumulative ranking curve for the Vancouver Scar Scale score based on the Bayesian approach suggested IPL + CO2 (96.43%) > pulsed dye laser (PDL) + 1064-nm Nd:YAG (yttrium aluminum garnet) laser (86.21%) > PDL + CO2 (82.15%) > CO2 (58.97%) > 1064-nm Nd:YAG (57.03%) > PDL (52%) > 532-nm Nd:YAG (33.28%) > Er:YAG + IPL (28.38%) > Er:YAG (26.56%) > IPL (15.03%) > control (13.97%). The ranking results based on the frequentist approach were basically consistent with those based on the Bayesian approach. CONCLUSIONS: The results of the network meta-analysis showed that the combination of IPL and CO2 laser has the highest probability of being the most effective intervention. However, our conclusions must be interpreted with caution due to the relatively few evaluation indicators included in our study. Future well-designed randomized controlled trials with large sample sizes are required to confirm our conclusions.

Chemical Investigations of Differentially Oxidized Polycylic Pyrroles from Bipolaris Fungi: Synthetic Entry Into the Bipolamine Alkaloids.

indolizidine alkaloids of unusual biosynthetic origin have recently been characterized from several species of fungi within the Pleosporaceae family. Possessing distinct polycyclic architectures with two embedded electron-rich pyrroles as well as reported antibacterial activity against gram positive and negative pathogens, these natural products represent attractive targets for total synthesis. Herein we survey the differential functionalization of a chemically sensitive bispyrrole framework resulting in the preparation of multiple bipolamine alkaloids, work which sheds light on their innate chemical reactivity and potential biosynthetic relationships.

Evolution of a Synthetic Strategy for Complex Polypyrrole Alkaloids: Total Syntheses of Curvulamine and Curindolizine.

Structurally unprecedented antibacterial alkaloids containing multiple electron-rich pyrrole units have recently been isolated from Curvularia sp. and Bipolaris maydis fungi. This article documents the evolution of a synthetic program aimed at accessing the flagship metabolites curvulamine and curindolizine which are presumably a dimer and trimer of a C10N biosynthetic building block, respectively. Starting with curvulamine, we detail several strategies to merge two simple, bioinspired fragments, which while ultimately unsuccessful, led us toward a pyrroloazepinone building block-based strategy and an improved synthesis of this 10π-aromatic heterocycle. A two-step annulation process was then designed to forge a conserved tetracyclic bis-pyrrole architecture and advanced into a variety of late-stage intermediates; unfortunately, however, a failed decarboxylation thwarted the total synthesis of curvulamine. By tailoring our annulation precursors, success was ultimately found through the use of a cyanohydrin nucleophile which enabled a 10-step total synthesis of curvulamine. Attempts were then made to realize a biomimetic coupling of curvulamine with an additional C10N fragment to arrive at curindolizine, the most complex family member. Although unproductive, we developed a 14-step total synthesis of this alkaloid through an abiotic coupling approach. Throughout this work, effort was made to harness and exploit the innate reactivity of the pyrrole nucleus, an objective which has uncovered many interesting findings in the chemistry of this reactive heterocycle.