Manipulating the processing window of directed self-assembly in contact hole shrinking with binary block copolymer/homopolymer blending.

Directed self-assembly (DSA) lithography has demonstrated significant potential in fabricating integrated circuits. However, DSA encounters limited processing windows due to the requirement for precise matching between the period of block copolymers (BCPs) and graphoepitaxy templates. We propose a binary BCP/homopolymer blending strategy to manipulate the self-assembly behavior and the processing window of graphoepitaxy DSA in contact hole shrinking. By carefully tailoring the blending rates of poly(methyl methacrylate) (PMMA) with different molecular weights in cylindrical polystyrene-b-poly(methyl methacrylate) (PS-b-PMMA), we manipulate the period and morphology of BCP/homopolymer self-assembly. Specifically, we employ BCP/homopolymer blending to fine-tune the critical dimension (CD) of contact holes with PS-affined topographical templates. Subsequent pattern transferring is achieved by selectively etching defect-free shrinkable cylinders as hard masks. Furthermore, self-consistent field theory (SCFT) simulation was employed to explore the self-assembly of BCP/homopolymer blending in confined cylindrical space and the results were in good consistency with the experimental results.

The Effect of Dietary Protein Hydrolysate from Black Soldier Fly Larvae and Schizochytrium on Palatability, Nutrient Metabolites and Health Status in Beagle Dogs.

Protein hydrolysate from black soldier fly larvae (BSFP) has garnered great attention with its lower allergenicity, high amount of essential amino acids, and small bioactive peptides. Schizochytrium is a promising alternative source of n-3 FUFA because it has enriched docosahexaenoic acid (DHA, C22: 6). The aim of this study was to assess palatability, the presence of diarrhea, plasma biochemistry panels, anti-oxidative and anti-inflammatory effects, and immune function in beagle dogs when supplementing a mixture of protein hydrolysate from black soldier fly larvae and schizochytrium (BSFPs) into their diets. Experiment I: 24 young beagle dogs (16 males and 8 females; 4-5 months; BW: 6.40 ± 0.15 kg) were randomly divided into four groups: (1) control (CON), (2) 5% BSFPs, (3) 10% BSFPs, (4) 15% BSFPs. Their body weights and fecal scores were recorded, and blood samples were collected for analysis. Experiment II: three diets containing 5%, 10%, and 15% BSFPs were evaluated by comparing them with a basal diet (CON) to evaluate palatability. These results suggested that a lower presence of diarrhea existed in the BSFP diet than the CON diet (p < 0.05). Three treatment groups remarkably increased their total protein (TP) and albumin (ALB) contents and decreased their concentrations of triglyceride (TG) and total cholesterol (TC) in plasma (p < 0.05). Moreover, the 5% and 15% BSFPs groups had a higher calcium (CA) content in plasma, and the activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and contents of creatinine (CREA) and urea nitrogen (BUN) were significantly reduced by supplementing BSFP in their diets (p < 0.05). Their anti-oxidative enzyme activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) were dramatically enhanced, and their malondialdehyde (MDA) concentrations were remarkably reduced (p < 0.05). Immunoglobulin A and G (IgA and IgG) concentrations in the plasma in the 10% and 15% BSFPs groups were significantly increased (p < 0.05). Furthermore, lower interleukin-8 (IL-8) contents were shown in the BSFP diets than the CON diet (p < 0.05). Similarly, the diets supplemented with BSFPs exhibited a positive effect on palatability (p < 0.05). To sum up, the diets supplemented with BSFPs significantly enhanced palatability, immune function, and anti-oxidative and anti-inflammatory capacity to alleviate diarrhea and improve the general health of the beagle dogs.

Influence of a Mixture of Protein Hydrolysate from Black Soldier Fly Larvae and Schizochytrium on Palatability, Plasma Biochemistry, and Antioxidative and Anti-Inflammatory Capacity in Cat Diets.

The objective of this research was to evaluate palatability, plasma biochemistry, antioxidative and anti-inflammatory capacity, and immune levels in cats by feeding supplementing inclusion of different levels of a mixture of protein hydrolysate from black soldier fly larvae and schizochytrium (BSFPs) in diets. In the feed experiment, a total of 24 adult cats (12 females and 12 males; BW: 3.02 ± 0.06 kg) were randomly divided into four groups: (1) diet with chicken and fish meal as primary protein resource (CON); (2) diet with 5% BSFPs replacing chicken meal, fish meal, chicken oil, and fish oil (5% BSFPs); (3) 10% BSFPs; and (4) 15% BSFPs. The body weight and feed intake were recorded, and a blood sample was collected for analysis. In the palatability experiment, three diets containing 5%, 10%, and 15% BSFPs were evaluated by comparing with CON. These results suggested that different levels of BSFPs could improve palatability in cat diets by enhancing the first sniff, the first bite, and feed intake (p < 0.05). However, no significant influence existed in body weight and average daily feed intake (p > 0.05). In comparison to the CON group, 5% and 15% BSFPs significantly increased the total protein content, and all treatment groups decreased the triglyceride content and enhanced the calcium concentration in plasma; in addition, the activity of aspartate aminotransferase and alanine aminotransferase and the content of creatinine and urea nitrogen were significantly reduced by the supplementation inclusion of BSFPs in the diets (p < 0.05). The enzyme activity of glutathione peroxidase was dramatically enhanced by the supplementation of 10% and 15% BSFPs in diets compared with the CON diet, and the activity of superoxide dismutase was increased and the malondialdehyde concentration was remarkably reduced in all three treatments (p < 0.05). Compared with the CON group, different levels of BSFPs in the diets significantly increased the immunoglobulin A content in plasma; similarly, the immunoglobulin G concentration was significantly enhanced by the supplementation of 10% and 15% BSFPs in the diets (p < 0.05). Furthermore, the interleukin-1ß content was significantly reduced in the inclusion of 10% and 15% BSFPs in the diets, and 15% BSFPs remarkably decreased the content of interleukin-8 in plasma compared with the CON diet (p < 0.05). To sum up, the supplementation of different levels of BSFPs exhibited a positive effect on palatability and enhanced the antioxidant, anti-inflammatory, and immune capacity. Particularly, the addition levels of 10% and 15% BSFPs were more effective in antioxidation, anti-inflammation, and immunity.

GINv2.0: a comprehensive topological network integrating molecular interactions from multiple knowledge bases.

Knowledge bases have been instrumental in advancing biological research, facilitating pathway analysis and data visualization, which are now widely employed in the scientific community. Despite the establishment of several prominent knowledge bases focusing on signaling, metabolic networks, or both, integrating these networks into a unified topological network has proven to be challenging. The intricacy of molecular interactions and the diverse formats employed to store and display them contribute to the complexity of this task. In a prior study, we addressed this challenge by introducing a "meta-pathway" structure that integrated the advantages of the Simple Interaction Format (SIF) while accommodating reaction information. Nevertheless, the earlier Global Integrative Network (GIN) was limited to reliance on KEGG alone. Here, we present GIN version 2.0, which incorporates human molecular interaction data from ten distinct knowledge bases, including KEGG, Reactome, and HumanCyc, among others. We standardized the data structure, gene IDs, and chemical IDs, and conducted a comprehensive analysis of the consistency among the ten knowledge bases before combining all unified interactions into GINv2.0. Utilizing GINv2.0, we investigated the glycolysis process and its regulatory proteins, revealing coordinated regulations on glycolysis and autophagy, particularly under glucose starvation. The expanded scope and enhanced capabilities of GINv2.0 provide a valuable resource for comprehensive systems-level analyses in the field of biological research. GINv2.0 can be accessed at: https://github.com/BIGchix/GINv2.0 .

High-Density Packing of Spherical Microdomains from A(AB3)3 Dendron-like Miktoarm Star Copolymer.

An A(AB3)3 dendron-like miktoarm star copolymer consisting of polystyrene (PS, A) and poly(2-vinylpyridine) (P2VP, B) was synthesized using a series of anionic polymerization, atom-transfer radical polymerization (ATRP), and click reaction. The morphology of A(AB3)3 changed greatly depending on the volume fraction of A and the chain asymmetry. Interestingly, a body-centered cubic spherical phase was found even at fA = 0.51 because the chain architecture of A(AB3)3 stabilizes the large interfacial curvature toward A domains. On the other hand, when the length difference between the end and middle A blocks decreased, a hexagonally packed cylindrical phase was formed at fA = 0.50. This is attributed to the fact that the middle A chains are arranged in a more relaxed way, resulting in a milder interfacial curvature toward A domains. The experimental observations are well-consistent with the predictions based on self-consistent-field theory.

Autotrophic denitrification based on sulfur-iron minerals: advanced wastewater treatment technology with simultaneous nitrogen and phosphorus removal.

Autotrophic denitrification technology has many advantages, including no external carbon source addition, low sludge production, high operating cost efficiency, prevention of secondary sewage pollution, and stable treatment efficiency. At present, the main research on autotrophic denitrification electron donors mainly includes sulfur, iron, and hydrogen. In these autotrophic denitrification systems, pyrite has received attention due to its advantages of easy availability of raw materials, low cost, and pH stability. When pyrite is used as a substrate for autotropic denitrification, sulfide (S2-) and ferrous ion (Fe2+) in the substrate will provide electrons to convert nitrate (NO3-) in sewage first to nitrite (NO2-), then to nitrogen (N2), and finally to discharge the system. At the same time, sulfide (S2-) loses electrons to sulfate (SO42-) and ferrous ion (Fe2+) loses electrons to ferric iron (Fe3+). Phosphates (PO43-) in wastewater are chemically combined with ferric iron (Fe3+) to form ferric phosphate (FePO4) precipitate. This paper aims to provide a detailed and comprehensive overview of the dynamic changes of nitrogen (N), phosphorus (P), and other substances in the process of sulfur autotrophic denitrification using iron sulfide, and to summarize the factors that affect wastewater treatment in the system. This work will provide a relevant research direction and theoretical basis for the field of sulfur autotrophic denitrification, especially for the related experiments of the reaction conversion of various substances in the system.

SnS2/MoS2 van der Waals Heterostructure Photodetector with Ultrahigh Responsivity Realized by a Photogating Effect.

Photoresponsivity is a fundamental parameter used to quantify the ability of photoelectric conversion of a photodetector device. High-responsivity photodetectors are essential for numerous optoelectronic applications. Due to the strong light-matter interactions and the high carrier mobility, two-dimensional (2D) materials are promising candidates for the next-generation photodetectors. However, poor light absorption, lack of photoconductive gain, and the interfacial recombination lead to the relatively low responsivity of 2D photodetectors. The photogating effect, which extends the lifetime of photoexcited carriers, provides a simple approach to enhance responsivity in photodetector devices. Here, the O2 plasma treatment introduced surface traps on the SnS2 surface, leading to a gate-tunable photogating effect in SnS2/MoS2 heterojunctions. The heterojunction device exhibits an ultrahigh responsibility of up to 28 A/W. Moreover, the photodetector possesses a wide spectral photoresponse spanning from 300 to 1100 nm and a high specific detectivity (D*) of 4 × 1011 Jones under a 532 nm laser at VDS = 1 V. These results demonstrate that O2 plasma treatment is an efficient and simple avenue to achieve photogating effects, which can be employed to enhance the performance of van der Waals heterostructure photodetector devices and make them suitable for future integration into advanced electronic and optoelectronic systems.

Flow-driven translocation of comb-like copolymer micelles through a nanochannel.

Using hybrid lattice-Boltzmann molecular dynamics simulations, we investigate the flow-driven translocation of comb-like copolymer micelles through a nanochannel, in particular, making a detailed comparison with micelles formed by the corresponding diblock copolymers. Our results demonstrate that the critical flow flux of micelles formed by the comb-like copolymers is higher than that of micelles formed by the corresponding diblock copolymers, which is more pronounced with increasing side chain lengths or grafting densities, as evidenced by the free energy computed by self-consistent field theory. Our work indicates that the impact of chain topology on the stability of micelles, especially with the same size, can be well characterized using the critical flow fluxes, which provides a theoretical basis for designing self-assembling micelles for various applications.

Zinc finger transcription factor Egf1 promotes non-alcoholic fatty liver disease.

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) contributes to the global epidemic of metabolic syndrome and is considered a prelude to end-stage liver diseases such as cirrhosis and hepatocellular carcinoma. During NAFLD pathogenesis, hepatic parenchymal cells (hepatocytes) undergo both morphological and functional changes owing to a rewired transcriptome. The underlying mechanism is not entirely clear. In the present study, we investigated the involvement of early growth response 1 (Egr1) in NAFLD. Methods: Quantitative PCR, Western blotting, and histochemical staining were used to assess gene expression levels. Chromatin immunoprecipitation was used to evaluate protein binding to DNA. NAFLD was evaluated in leptin receptor-deficient (db/db) mice. Results: We report here that Egr1 was upregulated by pro-NAFLD stimuli in vitro and in vivo. Further analysis revealed that serum response factor (SRF) was recruited to the Egr1 promoter and mediated Egr1 transactivation. Importantly, Egr1 depletion markedly mitigated NAFLD in db/db mice. RNA sequencing revealed that Egr1 knockdown in hepatocytes, on the one hand, boosted fatty acid oxidation (FAO) and, on the other hand, suppressed the synthesis of chemoattractants. Mechanistically, Egr1 interacted with peroxisome proliferator-activated receptor α (PPARα) to repress PPARα-dependent transcription of FAO genes by recruiting its co-repressor NGFI-A binding protein 1 (Nab1), which potentially led to promoter deacetylation of FAO genes. Conclusions: Our data identify Egr1 as a novel modulator of NAFLD and a potential target for NAFLD intervention. Impact and Implications: Non-alcoholic fatty liver disease (NAFLD) precedes cirrhosis and hepatocellular carcinoma. In this paper, we describe a novel mechanism whereby early growth response 1 (Egr1), a transcription factor, contributes to NAFLD pathogenesis by regulating fatty acid oxidation. Our data provide novel insights and translational potential for NAFLD intervention.

Nickel-Catalyzed C-I-Selective C(sp2 )-C(sp3 ) Cross-Electrophile Coupling of Bromo(iodo)arenes with Alkyl Bromides.

Despite several methodologies established for C(sp2 )-I selective C(sp2 )-C(sp3 ) bond formations, achieving arene-flanked quaternary carbons by cross-coupling of tertiary alkyl precursors with bromo(iodo)arenes in a C(sp2 )-I selective manner is rare. Here we report a general Ni-catalyzed C(sp2 )-I selective cross-electrophile coupling (XEC) reaction, in which, beyond 3° alkyl bromides (for constructing arene-flanked quaternary carbons), 2° and 1° alkyl bromides are also demonstrated to be viable coupling partners. Moreover, this mild XEC displays excellent C(sp2 )-I selectivity and functional group compatibility. The practicality of this XEC is demonstrated in simplifying the routes to several medicinally relevant and synthetically challenging compounds. Extensive experiments show that the terpyridine-ligated NiI halide can exclusively activate alkyl bromides, forming a NiI -alkyl complex through a Zn reduction. Attendant density functional theory (DFT) calculations reveal two different pathways for the oxidative addition of the NiI -alkyl complex to the C(sp2 )-I bond of bromo(iodo)arenes, explaining both the high C(sp2 )-I selectivity and generality of our XEC.

CT-derived radiomic analysis for predicting the survival rate of patients with non-small cell lung cancer receiving radiotherapy.

BACKGROUND: Radiomics provides an opportunity to minimize adverse effects and optimize the efficacy of treatments noninvasively. This study aims to develop a computed tomography (CT) derived radiomic signature to predict radiological response for the patients with non-small cell lung cancer (NSCLC) receiving radiotherapy. METHODS: Total 815 NSCLC patients receiving radiotherapy were sourced from public datasets. Using CT images of 281 NSCLC patients, we adopted genetic algorithm to establish a predictive radiomic signature for radiotherapy that had optimal C-index value by Cox model. Survival analysis and receiver operating characteristic curve were performed to estimate the predictive performance of the radiomic signature. Furthermore, radiogenomics analysis was performed in a dataset with matched images and transcriptome data. RESULTS: Radiomic signature consisting of three features was established and then validated in the validation dataset (log-rank P = 0.0047) including 140 patient, and showed a significant predictive power in two independent datasets totaling 395 NSCLC patients with binary 2-year survival endpoint. Furthermore, the novel proposed radiomic nomogram significantly improved the prognostic performance (concordance index) of clinicopathological factors. Radiogenomics analysis linked our signature with important tumor biological processes (e.g. Mismatch repair, Cell adhesion molecules and DNA replication) associated with clinical outcomes. CONCLUSIONS: The radiomic signature, reflecting tumor biological processes, could noninvasively predict therapeutic efficacy of NSCLC patients receiving radiotherapy and demonstrate unique advantage for clinical application.

Diagnosis, treatment and genetic analysis of a case of hypoglycemia caused by glucokinase gene mutation.

Congenital hyperinsulinemia (CHI) is a disease phenotype characterized by persistent or recurrent hypoglycemia due to abnormal secretion of insulin by ß cells of the pancreas. CHI induced by activation mutation of a single allele of glucokinase (GCK) is the rarest type. In this paper, the clinical data of a patient with hypoglycemia of unknown cause were collected without obvious clinical symptoms. And a heterozygous missense mutation (c.295T> C:p.W99R) was detected in exon 3 of the GCK gene. The mutation was found in both the son and daughter of the proband, and the blood glucose level was low, while the others were normal. By summarizing and analyzing the characteristics of this case and the genetic pedigree of the family, the possibility of congenital hyperinsulinemia caused by a single gene mutation should be considered for hypoglycemia whose etiology is difficult to be determined clinically. This case also provides new clinical data for subsequent genetic studies of the disease.

Anti-Inflammatory and Repairing Effects of Mesoporous Silica-Loaded Metronidazole Composite Hydrogel on Human Dental Pulp Cells.

In order to test an effective biopolymer scaffold in promoting the growth of human dental pulp stem cells (HDPSCs), mesoporous silica @ hydrogel (MSN@Gel) nanocomposites are invented as a new type of biopolymer scaffold for HDPSCs proliferation in this paper. The expression levels of alkaline phosphatase (ALP), dentin matrix protein 1 (DMP1), and dentin sialophosphoprotein (DSPP) are significantly increased in the MSN@Gel group so as to better repair damaged dentin. In order to inhibit the proliferation of bacteria in the dental pulp, metronidazole (MTR) is loaded into MSN. The study found that MSN could effectively prolong the half-life of MTR by 1.75 times, and the viability of HDPSCs could be better maintained in the MSN-MTR@Gel group so as to better promote its proliferation to repair pulpitis. However, with the increase of the MTR concentration, its proliferation effect on HDPSCs decreased gradually, and the proliferation effect is the best in 10 µmol/L. Therefore, the MSN-MTR@Gel scaffold is expected to become an effective method for pulpitis therapy in the future.

Chemoselective and Diastereoselective Synthesis of C-Aryl Nucleoside Analogues by Nickel-Catalyzed Cross-Coupling of Furanosyl Acetates with Aryl Iodides.

Canonical nucleosides are vulnerable to enzymatic and chemical degradation, yet their stable mimics-C-aryl nucleosides-have demonstrated potential utility in medicinal chemistry, chemical biology, and synthetic biology, although current synthetic methods remain limited in terms of scope and selectivity. Herein, we report a cross-electrophile coupling to prepare C-aryl nucleoside analogues from readily available furanosyl acetates and aryl iodides. This nickel-catalyzed modular approach is characterized by mild reaction conditions, broad substrate scope, excellent ß-selectivity, and high functional-group compatibility. The exclusive chemoselectivity with respect to the aryl iodide enables efficient preparation of a variety of C-aryl halide furanosides suitable for various downstream transformations. The practicality of this transformation is demonstrated through the synthesis of a potent analogue of a naturally occurring NF-κB activator.

HES5-mediated repression of LIGHT transcription may contribute to apoptosis in hepatocytes.

Non-alcoholic fatty liver disease (NAFLD) is prototypical form of metabolic syndrome and has become a global pandemic. Hepatocytes undergo apoptosis in the pathogenesis of NAFLD. We report that the lymphokine LIGHT/TNFSF14 was upregulated in the murine NAFLD livers and in hepatocytes treated with free fatty acids (palmitate, PA). LIGHT knockdown or neutralization attenuated PA-induced apoptosis of hepatocytes. Similarly, knockdown or blockade of LTßR, the receptor for LIGHT, ameliorated apoptosis in hepatocytes exposed to PA. Ingenuity pathway analysis (IPA) revealed several Notch-related transcription factors as upstream regulators of LIGHT, of which HES5 expression was downregulated paralleling LIGHT induction in the pathogenesis of NAFLD. HES5 knockdown enhanced whereas HES5 over-expression weakened LIGHT induction in hepatocytes. HES5 was found to directly bind to the LIGHT promoter and repress LIGHT transcription. Mechanistically, HES5 interacted with SIRT1 to deacetylate histone H3/H4 on the LIGHT promoter to repress LIGHT transcription. SIRT1 knockdown or inhibition offset the effect of HES5 over-expression on LIGHT transcription and hepatocyte apoptosis. In conclusion, our data unveil a novel mechanism that might contribute to excessive apoptosis in hepatocyte exposed to free fatty acids.

DDIT4 S-Nitrosylation Aids p38-MAPK Signaling Complex Assembly to Promote Hepatic Reactive Oxygen Species Production.

Mitogen-activated protein kinase (MAPK) signaling plays a significant role in reactive oxygen species (ROS) production. The authors have previously shown that Brahma-related gene 1 (BRG1), a chromatin remodeling protein, contributes to hepatic ROS accumulation in multiple animal and cellular models of liver injury. Here it is reported that DNA damage-induced transcript 4 (DDIT4) is identified as a direct transcriptional target for BRG1. DDIT4 overexpression overcomes BRG1 deficiency to restore ROS production whereas DDIT4 knockdown phenocopies BRG1 deficiency in suppressing ROS production in vitro and in vivo. Mechanistically, DDIT4 coordinates the assembly of the p38-MAPK signaling complex to drive ROS production in an S-nitrosylation dependent manner. Molecular docking identifies several bioactive DDIT4-inteacting compounds including imatinib, nilotinib, and nateglinide, all of which are confirmed to attenuate hepatic ROS production, dampen p38-MAPK signaling, and ameliorate liver injury by influencing DDIT4 S-nitrosylation. Importantly, positive correlation between ROS levels and BRG1/DDIT4/S-nitrosylated DDIT4 levels is detected in human liver biopsy specimens. In conclusion, the data reveal a transcription-based signaling cascade that contributes to ROS production in liver injury.

Efficacy and safety of Lianhuaqingwen for mild or moderate coronavirus disease 2019: A meta-analysis of randomized controlled trials.

BACKGROUND: : Coronavirus disease 2019 (COVID-19) is an emerging and rapidly evolving disease, with no recommended effective anti-coronavirus treatments. Traditional Chinese Medicine (TCM) has been widely used to treat COVID-19 in China, and the most used one is Lianhuaqingwen (LH). This study aimed to assess the efficacy and safety of LH combined with usual treatment vs usual treatment alone in treating mild or moderate COVID-19 by a meta-analysis of randomized controlled trials (RCTs). METHODS AND ANALYSIS: : We systematically searched the Medline (OVID), Embase, the Cochrane Library, and 4 Chinese databases from inception to July 2020 to include the RCTs that evaluated the efficacy and safety of LH in combination with usual treatment vs usual treatment for mild or moderate COVID-19. A meta-analysis was performed to calculate the risk ratio (RR) and 95% confidence interval (CI) for binary outcomes and mean difference (MD) for continuous outcomes. RESULTS: : A total of 5 RCTs with 824 individuals with mild or moderate COVID 19 were included. Compared with the usual treatment alone, LH in combination with usual treatment significantly improved the overall clinical efficacy (RR = 2.39, 95% CI 1.61-3.55), increased the rate of recovery of chest computed tomographic manifestations (RR = 1.80, 95% CI 1.08-3.01), reduced the rate of conversion to severe cases (RR = 0.47, 95% CI 0.29-0.74), shorten the duration of fever (MD = -1.00, 95% CI -1.17 to -0.84). Moreover, LH in combination with usual treatment did not increase the occurrence of the adverse event compared to usual treatment alone. CONCLUSION: : Our meta-analysis of RCTs indicated that LH in combination with usual treatment may improve the clinical efficacy in patients with mild or moderate COVID-19 without increasing adverse events. However, given the limitations and poor quality of included trials in this study, further large-sample RCTs or high-quality real-world studies are needed to confirm our conclusions.

Electrochemically Enabled, Nickel-Catalyzed Dehydroxylative Cross-Coupling of Alcohols with Aryl Halides.

As alcohols are ubiquitous throughout chemical science, this functional group represents a highly attractive starting material for forging new C-C bonds. Here, we demonstrate that the combination of anodic preparation of the alkoxy triphenylphosphonium ion and nickel-catalyzed cathodic reductive cross-coupling provides an efficient method to construct C(sp2)-C(sp3) bonds, in which free alcohols and aryl bromides-both readily available chemicals-can be directly used as coupling partners. This nickel-catalyzed paired electrolysis reaction features a broad substrate scope bearing a wide gamut of functionalities, which was illustrated by the late-stage arylation of several structurally complex natural products and pharmaceuticals.

Total Synthesis of (-)-Daphnezomines A and B.

Daphnezomines A and B are structurally unusual Daphniphyllum alkaloids that contain a unique aza-adamantane core skeleton. Herein, a modular approach to these alkaloids is presented that exploits a diverse array of reaction strategies. Commencing from a chiral pool terpene-(S)-carvone, the azabicyclo[3.3.1]nonane backbone, which occurs widely in Daphniphyllum alkaloids, was easily accessed through a Sharpless allylic amination and a palladium-catalyzed oxidative cyclization. A protecting group enabled a stereoselective B-alkyl Suzuki-Miyaura coupling sequence and an Fe-mediated hydrogen atom transfer (HAT)-based radical cyclization were then applied to construct C6 and C8 stereocenters. A final epimer locking strategy enabled the assembly of the highly congested aza-adamantane core, thereby achieving the first total synthesis of (-)-daphnezomines A and B in 14 steps.

Brahma related gene 1 (Brg1) contributes to liver regeneration by epigenetically activating the Wnt/ß-catenin pathway in mice.

Liver regeneration is a complicated pathophysiologic process that is regulated by a myriad of signaling pathways and transcription factors. The interaction among these pathways and factors, either cooperatively or antagonistically, may ultimately lead to recovery and restoration of liver function or permanent loss of liver function and liver failure. In the present study, we investigated the mechanism whereby the chromatin remodeling protein brahma related gene 1 (Brg1) regulates liver regeneration in mice. The Smarca4-Flox strain of mice was crossbred with the Alb-Cre strain to generate hepatocyte-specific Brg1 knockout mice. Liver injury was induced by partial hepatectomy (PHx). We report that Brg1 deletion in hepatocyte compromised liver regeneration and dampened survival after PHx in mice. Brg1 interacted with ß-catenin to potentiate Wnt signaling and promote hepatocyte proliferation. Mechanistically, Brg1 recruited lysine demethylase 4 (KDM4) to activate ß-catenin target genes. Our data suggest that Brg1 might play an essential role maintaining hepatic homeostasis and contributing to liver repair.-Li, N., Kong, M., Zeng, S., Hao, C., Li, M., Li, L., Xu, Z., Zhu, M., Xu, Y. Brahma related gene 1 (Brg1) contributes to liver regeneration by epigenetically activating the Wnt/ß-catenin pathway in mice.