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The direct C-H activation without directing groups can realize the para-selectivity, which is a powerful and concise approach for functionalization of arenes. Utilizing the strategy, a C5-olefination of methyleneindolinones has been successfully developed by palladium-catalyzed direct C-H activation, which provides an expeditious access to 5-vinylindolin-2-ones with high regioselectivity. The protocol is distinguished by a mild reaction system avoiding ligand and high temperature. The kinetic isotope experiments indicate that the C-H bond cleavage is the rate-limiting step.

Although post-functionalization is extensively used to introduce diverse functional groups into supramolecular polymers (SPs) in solution, post-functionalization of SPs on surfaces still remains unexplored. Here we achieved the on-surface post-functionalization of two SPs derived from 5,10,15-tri-(4-pyridyl)-20-bromophenyl porphyrin (Br-TPyP) via cross-coupling reactions on Au(111). The ladder-shaped, Cu-coordinated SPs preformed from Br-TPyP were functionalized through Heck reaction with 4-vinyl-1,1'-biphenyl. In the absence of Cu, Br-TPyP formed chiral SPs as two enantiomers via self-assembly, which were functionalized via divergent cross-coupling reaction with 4-isocyano-1,1'-biphenyl (ICBP). Surprisingly, this reaction was discovered as an enantioselective on-surface reaction induced by the chirality of SPs. Mechanistic analysis and DFT calculations indicated that after debromination of Br-TPyP and the first addition of ICBP, only one attack direction of ICBP to the chiral SP intermediate is permissive in the second addition step due to the steric hindrance, which guaranteed the high enantioselectivity of the reaction.

Vinylethylene carbonates have been extensively used to trigger [3 + n] or [5 + n] cycloaddition via the formation of η3-allylic intermediates, while the important [4 + n] cycloaddition has not been explored yet. Here, we report a new strategy to convert vinylethylene carbonates into 4-(trimethylsilyl)but-2-en-1-ols, which can readily undergo [4 + 2] cycloaddition by in situ formation of 1,3-dienes. This novel reaction involves [PdII]-catalyzed decarboxylative silylation, [FeIII]-catalyzed vinylogous Peterson elimination, and subsequent [4 + 2] cycloaddition to afford a multisubstituted cyclohexa-1,4-diene skeleton.

Molecular adsorption conformations and arrangement configurations on surfaces are important structural aspects of surface stereochemistry, but their roles in steering the structures of metal-organic networks (MONs) remain vague and unexplored. In this study, we constructed MONs by the coordination self-assembly of isocyanides on Cu(111) and Ag(111) surfaces and demonstrated that the MON structures can be steered by surface stereochemistry, including the adsorption conformations of the isocyanide molecules and the arrangement configurations of the coordination nodes and subunits. The coordination self-assembly of 1,4-phenylene diisocyanobenzene afforded a honeycomb MON consisting of 3-fold (isocyano)3-Cu motifs on a Cu(111) surface. In contrast, geometrically different chevron-shaped 1,3-phenylene diisocyanobenzene (m-DICB) failed to generate a MON, which is ascribable to its standing conformation on the Cu(111) surface. However, m-DICB was adsorbed in a flat conformation on a Ag(111) surface, which has a larger lattice constant than a Cu(111) surface, and smoothly underwent coordination self-assembly to form a MON consisting of (isocyano)3-Ag motifs. Interestingly, only C3-Ag nodes with heterotactic configurations could grow into larger subunits; those subunits with heterotactic configurations further grew into Sierpinski triangle fractals (up to fourth order), while subunits with homotactic configurations afforded a triangular MON.

Ladder phenylenes (LPs) composed of alternating fused benzene and cyclobutadiene rings have been synthesized in solution with a maximum length no longer than five units. Longer polymeric LPs have not been obtained so far because of their poor stability and insolubility. Here, we report the synthesis of linear LP chains on the Au(111) surface via dehalogenative [2+2] cycloaddition, in which the steric hindrance of the methyl groups in the 1,2,4,5-tetrabromo-3,6-dimethylbenzene precursor improves the chemoselectivity as well as the orientation orderliness. By combining scanning tunneling microscopy and noncontact atomic force microscopy, we determined the atomic structure and the electronic properties of the LP chains on the metallic substrate and NaCl/Au(111). The tunneling spectroscopy measurements revealed the charged state of chains on the NaCl layer, and this finding is supported by density functional theory calculations, which predict an indirect bandgap and antiferromagnetism in the polymeric LP chains.

Background/aims Visfatin is known to act as a mediator in several metabolic disorders, such as obesity, diabetes, and cardiovascular diseases. This study aimed to investigate the effect of visfatin on the adhesion of THP-1 monocytes to human vascular endothelial cells and the underlying mechanism. Methods Monocytes adhesion to endothelial cells was determined by using fluorescence-labeled monocytes. ICAM-1 and VCAM-1 expression in endothelial cells were measured by western blotting. Production of reactive oxygen species (ROS) was measured by using a fluorescent dye. The amounts of nuclear factor-kappa B (NF-κB) and phosphorylation of inhibitory factor of NF-κB (IκB) were determined by using western blot analysis. The translocation of NF-κB from the cytoplasm to the nucleus was determined by using immunofluorescence. Results Here we showed that visfatin significantly caused the upregulation of intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in endothelial cells, as well as enhanced monocyte adhesion to endothelial cells. Moreover, we found that inhibition of PI3K, Akt, and p38 MAPK activation significantly prevented visfatin-enhanced expression of ICAM-1 and VCAM-1 and monocyte adhesion to endothelial cells. Visfatin enhanced ROS production and IKK/NF-кB activation and then led to upregulation of ICAM-1 and VCAM-1 and enhanced monocyte adhesion to endothelial cells. These effects were also p38/PI3K/Akt-dependent. Conclusion These results demonstrated that visfatin promoted monocyte-endothelial cell adhesion by increasing ICAM-1 and VCAM-1 expression via the activation of p38/PI3K/Akt signaling and downstream ROS production and IKK/NF-кB activation.

Purpose γ-Cyclodextrin glycosyltransferase (γ-CGTase) catalyzes the biotransformation of low-cost starch into valuable γ-cyclodextrin (γ-CD), which is widely applied in biotechnology, food, and pharmaceutical industries. However, the low specificity and activity of soluble γ-CGTase increase the production cost of γ-CD, thereby limiting its applications. Therefore, the present study aimed at optimizing an economical medium for high production of γ-CGTase by the recombinant Escherichia coli (E. coli) BL21 (DE3) and evaluating its enzymatic properties and product specificity. Methods The γ-CGTase production was optimized using the combination of Plackett-Burman experimental design (PBD) and Box-Behnken design-response surface methodology (BBD-RSM). The hydrolysis and cyclization properties of γ-CGTase were detected under the standard assay conditions with buffers of various pHs and different reaction temperatures. The product specificity of γ-CGTase was investigated by high-performance liquid chromatography (HPLC) analysis of three CDs (α-, β-, γ-CD) in the biotransformation product of cassava starch. Results The γ-CGTase activity achieved 53992.10 U mL−1 under the optimum conditions with the significant factors (yeast extract 38.51 g L−1, MgSO4 4.19 mmol L−1, NiSO4 0.90 mmol L−1) optimized by the combination of PBD and BBD-RSM. The recombinant γ-CGTase exhibited favorable stability in a wide pH and temperature range and maintained both the hydrolysis and cyclization activity under the pH 9.0 and 50 °C. Further analysis of the products from cassava starch catalyzed by the γ-CGTase reported that the majority (90.44%) of product CDs was the γ form, which was nearly 11% higher than the wild enzyme. Cyclododecanone added to the transformation system could enhance the γ-CD purity to 98.72%, which is the highest purity value during the transformation process reported so far. Conclusion The yield of γ-CGTase activity obtained from the optimized medium was 2.83-fold greater than the unoptimized medium, and the recombinant γ-CGTase exhibited a favorable thermal and pH stability, and higher γ-cyclization specificity. These results will provide a fundamental basis for the high productivity and purity of γ-CD in the industrial scale.

Bing Yuan,1,* Feng Liao,1,* Zhi-Zhou Shi,2 Yuan Ren,1 Xiao-Li Deng,1 Ting-Ting Yang,1 Deng-Yuan Li,1 Ru-Fang Li,1 Dan-Dan Pu,1 Yu-Jue Wang,1 Yan Tan,1 Zhen Yang,1 Yun-Hui Zhang1 1Department of Pulmonary and Critical Care Medicine, The First People’s Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, People’s Republic of China; 2Medical School, Kunming University of Science and Technology, Kunming, Yunnan, People’s Republic of China*These authors contributed equally to this work.Correspondence: Zhen YangDepartment of Pulmonary and Critical Care Medicine, The First People’s Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, People’s Republic of ChinaEmail 49387127@qq.comYun-Hui ZhangDepartment of Pulmonary and Critical Care Medicine, The First People’s Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, People’s Republic of ChinaEmail yunhuizhang3188@126.comObjective: Lung cancer is the first leading cause of cancer-related deaths both worldwide and in China and threatens human health and quality of life. New drugs and therapeutic methods are urgently needed. Our study evaluated the roles of dihydroartemisinin (DHA) in lung cancer and further explored its underlying mechanisms.Methods: CCK-8, colony formation and trypan blue exclusion assays were used to detect the cell viability, colony formation ability and cell death. qRT-PCR and Western blotting assays were applied to analyze the expressions of key molecules.Results: DHA inhibited the proliferation and colony formation abilities and enhanced the cell death and induced ferroptosis of lung NCI-H23 and XWLC-05 cancer cells. DHA reduced PRIM2 expression and silencing PRIM2 mimicked the inhibitory roles on proliferation and colony formation and promotive roles on cell death and ferroptosis of DHA in lung NCI-H23 and XWLC-05 cancer cells. We further found that DHA treatment and loss of PRIM2 reduced the GSH level and increased the cellular lipid ROS and mitochondrial MDA levels, and further downregulated the expressions of SLC7A11 and β-catenin in lung cancer cells, respectively. Exogenetic overexpression of PRIM2 recovered the inhibitory effects of DHA on proliferation and colony formation in lung NCI-H23 cancer cells, meanwhile loss of PRIM2 sensitizes NCI-H23 cells to DHA therapy. In vivo experiment further showed that DHA treatment significantly suppressed the tumor growth and downregulated PRIM2 and SLC7A11.Conclusion: Our study suggested that DHA inhibited the proliferation, colony formation and enhanced cell death and induced ferroptosis of lung cancer cells by inactivating PRIM2/SLC7A11 axis. Loss of PRIM2 induced ferroptosis might developed to be a novel therapeutic method in lung cancer therapy.Keywords: dihydroartemisinin, lung cancer, proliferation, ferroptosis, PRIM2, SLC7A11

A transition-metal-free double addition/double rearrangement domino reaction affording CF3-substituted pyrimidines was developed, which enables the one-pot construction of five new bonds, namely three C-C bonds and two C-N bonds. The keys to achieve this highly efficient reaction include the delicate design of the bis-nucleophiles in situ generated from the dimerization of alkyl nitriles and the use of trifluoroacetimidoyl nitriles containing C[double bond, length as m-dash]N, C[triple bond, length as m-dash]N, and CF3 groups as the reactant. The mechanistic studies by the experiments and DFT calculations reveal that the transformation involves two addition and two unprecedented rearrangement processes.

A novel copper-catalyzed radical cyanotrifluoromethylation has been achieved through a multicomponent reaction of isocyanides, Togni's reagent, and trimethylsilyl cyanides, affording trifluoroacetimidoyl nitriles in good yields. This reaction demonstrates a unique feature of merging two valuable functional groups-trifluoromethyl (CF3) and cyan (CN)-onto the same C atom. The transformation proceeds by the initial addition of the CF3 radical to isocyanide and the subsequent intermolecular C-CN formation. The products can be successfully transformed to a series of CF3-containing amines and imines that may serve in the synthesis of valuable pharmaceuticals and agrochemicals.

Gold nanostars (AuNSs), with unique physicochemical properties, are thought to be a promising agent for photothermal therapy (PTT). In this study, we prepared PEGylated gold nanostars (pAuNSs) using the HEPES-reduction method. The high photothermal conversion efficiency (∼80%) and photothermal stability of pAuNSs were demonstrated in vitro and in vivo. 111In-DTPA-pAuNSs were prepared as a radioactive surrogate for the biodistribution studies of pAuNSs. In both microSPECT/CT images and the biodistribution study, the tumor-to-muscle (T/M) ratio reached a maximum at 24 h post intravenous injection of 111In-DTPA-pAuNSs. The high linear correlation between the 111In radioactivity and the gold content in the tumors (R2 0.86-0.99) indicated that 111In-DTPA-pAuNSs were appropriate for noninvasively tracking pAuNSs in vivo after systemic administration. Histological examination after silver enhancement staining clearly illustrated that the accumulated pAuNSs in the tumors were mainly located on the luminal surface of vessels. The mice bearing a SKOV-3 xenograft exhibited remarkable therapeutic efficacy with negligible organ damage after receiving pAuNS-mediated photothermal therapy. Our findings suggested that pAuNSs, together with their radioactive surrogate 111In-DTPA-pAuNSs, are promising for applications in image-guided photothermal therapy.

A new nucleic acid-based fluorescence sensor is reported for simultaneous detection of Pb2+, Ag+, and Hg2+ based on the specific catalytic activity of Pb2+ for a particular DNAzyme, specific regulation of Ag+ on “C-Ag+-C” complex, and stable complex formed by Hg2+ and rhodamine B isothiocyanate (RBITC). Three fluorescence dyes, aminomethylcoumarin acetic acid (AMCA), 5-carboxyfluorescein (FAM), and RBITC, were modified on the probes and served as fluorescent donors. Upon DNA interaction with these metal ions and AuNP fluorescence quenching effect on the fluorescence dyes,the fluorescencerecovery of RBITC and the fluorescencequenching of AMCA and FAM were monitored to detect Hg2+, Pb2+, and Ag+, separately, without the need of using any masking reagents. This sensor exhibited high sensitivity and selectivity. The limit of detection (LOD) is 0.48 nM for Pb2+, 0.23 nM for Ag+, and 0.17 nM for Hg2+. Finally, this sensor was successfully applied for simultaneous detection of Pb2+, Ag+, and Hg2+ in real sample.

A cascade C–H arylation/amination protocol using homoallylic primary amines as the starting materials in the presence of a palladium catalyst produces 2-aryl-1-pyrrolines with excellent regioselectivity and in good yields. Mechanistic studies indicate that this transformation proceeds via palladium-catalyzed Heck coupling, C–H amination, and tautomerization. As an unprecedented example of aryl iodide acting as an arylation reagent and a cocatalyst, the key role of aryl iodide as a cocatalyst is to generate the active bivalent aryl palladium catalyst to promote C–N formation during the C–H amination step.

The heterobicyclic core retained hydroarylation of oxa/azabenzonorbornadienes with quinoline N-oxides has been achieved under rhodium catalysis, giving quinoline N-oxide substituted heterobicyclic structures with excellent regioselectivity and in good yields. As the first example of the direct introduction of quinoline N-oxides onto heterobicyclic structures, the strained heterobicyclic core was well retained in the reaction. The products could be successfully transformed into a series of useful compounds, including epibatidine analogues.

The reaction of aryl chloride and porphyrin macrocycles, which are merged into a single precursor, has been achieved on Cu(111). Scanning tunneling microscopy analysis of the oligomer products showed that the adjacent porphyrin moieties linked mainly by the phenyl group with the porphyrin macrocycle.

The existence of hydroxyl and carboxyl groups makes the photothermal stability of cellulose nanofibers (CNFs) poor and thus limits its scale application. This problem could be solved by doping layered double hydroxides (LDHs) nanopowders with opposite charge on the surface of CNFs. This work mainly focused on investigation of the influence of the crystal morphology of the inorganic ultraviolet shielding agent (i.e. ZnAl-LDHs) on the thermal stability of CNFs/ZnAl-LDHs composited films. The results showed that the morphology of LDHs was positively correlated with the photothermal stability of CNFs-based films. Specially, the ZnAl-LDHs with uniform crystal morphology could be prepared by controlling the molar ratio of Zn/Al at 3:1 and thus enhance the photothermal stability of CNFs-based films without any serious light transmittance deteriorating after doping. This work provided a practical and effective way for preparation of photothermal-stable CNFs-based transparent films for industrial application in the fields of photonics and electronics.

A copper-catalyzed cascade reaction of alkynols and 2-azidobenzaldehydes has been achieved, giving 6H-isochromeno[4,3-c]quinoline in yields of 40-81%. This reaction provides a novel, concise strategy for rapidly constructing compounds with fused N- and O-containing heterocycles. In contrast to previously reported reactions of alkynols in which the first step is intramolecular cycloisomerization, the first step in this novel reaction of alkynols is entropically unfavorable intermolecular addition. The resulting hemiacetal intermediate then undergoes intramolecular cyclization and aromatization to afford the product.

A cascade reaction of homopropargyl azides in the presence of a Cu catalyst was achieved, affording 3-(trifluoromethyl)but-3-enenitriles with good yields and excellent regioselectivity. This reaction appears to be the first direct conversion of homopropargyl azides into trifluoromethylated nitriles. Mechanistic studies indicate that the transformation proceeds by addition of a CF3 radical to the alkyne, C–C cleavage by 1,4-aryl radical migration, and nitrile formation. This protocol provides a novel strategy for transforming azides into nitriles via C–C cleavage derived from radical migration.

Radical cascade difluoroacetamidation of N-(arylsulfonyl)acrylamides with α,α-difluoro-α-(TMS)-acetamides has been achieved for the first time. This CuBr-mediated transformation is easy to perform, generates high yields and shows a good substrate scope. This cascade reaction proceeds via difluoroacetamidation, aryl migration and desulfonylation. The products can be readily transformed into synthetically useful compounds such as difluorofunctionalized esters and alcohols in excellent yields.

A novel cascade reaction of internal alkynols with 1-(2-aminophenyl)prop-2-ynols has been developed to form a new N,O-containing fused 5,5,6-tricyclic skeleton. Mechanistic studies indicate that this reaction proceeds via alkynol cycloisomerization, intermolecular substitution with 1-(2-aminophenyl)prop-2-ynols, and intermolecular addition with alkynols and consequent cyclizations. In this way, two C-C bonds, one C-O bond and one C-N bond form to give a tricyclic skeleton in a single reaction.

Obesity is a risk factor that promotes progressive kidney disease. Studies have shown that an adipocytokine imbalance contributes to impaired renal function in humans and animals, but the underlying interplay between adipocytokines and renal injury remains to be elucidated. We aimed to investigate the mechanisms linking obesity to chronic kidney disease. We assessed renal function in high-fat (HF) diet-fed and normal diet-fed rats, and the effects of preadipocyte- and adipocyte-conditioned medium on cultured podocytes. HF diet-fed and normal diet-fed Sprague Dawley rats were used to analyze the changes in plasma BUN, creatinine, urine protein and renal histology. Additionally, podocytes were incubated with preadipocyte- or adipocyte-conditioned medium to investigate the effects on podocyte morphology and protein expression. In the HF diet group, 24 h urinary protein excretion (357.5 ± 64.2 mg/day vs 115.9 ± 12.4 mg/day, P P P P P

Dendrimers are homostructural and highly branched macromolecules with unique dendritic effects and extensive use in multidisciplinary fields. Although thousands of dendrimers have been synthesized in solution, the on-surface synthetic protocol for planar dendrimers has never been explored, limiting the elucidation of the mechanism of dendritic effects at the single-molecule level. Herein, we describe an on-surface synthetic approach to planar dendrimers, in which exogenous palladium is used as a catalyst to address the divergent cross-coupling of aryl bromides with isocyanides. This reaction enables one aryl bromide to react with two isocyanides in sequential steps to generate the divergently grown product composed of a core and two branches with high selectivity and reactivity. Then, a dendron with four branches and dendrimers with eight or twelve branches in the outermost shell are synthesized on Au(111). This work opens the door for the on-surface synthesis of various planar dendrimers and relevant macromolecular systems., Although many strategies exist to synthesize dendrimers in solution, the synthesis of planar dendrimers on a surface has proven challenging. Here, the authors produce planar dendrimers through a divergent on-surface cross-coupling reaction between one aryl bromide and two isocyanides, which enables the growth of branches from a single reactive site.

A highly efficient palladium-catalyzed cascade annulation of 2-vinylbenzaldehydes with indoles has been achieved to afford 6-(3-indolyl)benzo[b]carbazoles under mild conditions in good yield and with excellent regioselectivity. Mechanistic investigations reveal that the reaction proceeds via double addition of indoles, unexpected intramolecular 1,4-aryl and 1,2-hydrogen migrations, and oxidative aromatization.

Colorectal cancer is one of the major causes of cancer-related death in Taiwan and worldwide. Patients with peritoneal metastasis from colorectal cancer have reduced overall survival and poor prognosis. Hybrid protein-inorganic nanoparticle systems have displayed multifunctional applications in solid cancer theranostics. In this study, a gold nanocore-encapsulated human serum albumin nanoparticle (Au@HSANP), which is a hybrid protein-inorganic nanoparticle, and its radioactive surrogate 111In-labeled Au@HSANP (111In-Au@HSANP), were developed and their biological behaviors were investigated in a tumor/ascites mouse model. 111In-Au@HSANP was injected either intravenously (iv) or intraperitoneally (ip) in CT-26 tumor/ascites-bearing mice. After ip injection, a remarkable and sustained radioactivity retention in the abdomen was noticed, based on microSPECT images. After iv injection, however, most of the radioactivity was accumulated in the mononuclear phagocyte system. The results of biodistribution indicated that ip administration was significantly more effective in increasing intraperitoneal concentration and tumor accumulation than iv administration. The ratios of area under the curve (AUC) of the ascites and tumors in the ip-injected group to those in the iv-injected group was 93 and 20, respectively. This study demonstrated that the ip injection route would be a better approach than iv injections for applying gold-albumin nanoparticle in peritoneal metastasis treatment.

As the first cascade C–H activation directed by a transient group, reaction of alkynols and 7-oxabenzonorbornadienes has been achieved via synergistic rhodium and scandium catalysis to afford spirocyclic dihydrobenzo[a]fluorenefurans. This transformation proceeds by a transient hemiketal group directed C–H activation, dehydrative naphthylation, and intramolecular Prins-type cyclization. Mechanistic studies and density functional theory calculations indicate that the rate-determining step is C–H bond cleavage and both the transient hemiketal group and synergistic RhIII/ScIII catalysis play key roles.

A convenient palladium-catalyzed tandem reaction of aryl iodides and salicyl N-tosylhydrazones has been achieved to afford a series of compounds containing the novel spiro[benzofuran-3,2′-chromene] scaffold in moderate to good yields. This efficient catalytic reaction, which tolerates various functional groups, combines alkyne-based 5-exo-dig cyclization, palladium(II) carbene migratory insertion and intramolecular cyclization, generating three new bonds in one reaction.

Obesity is a risk factor of insulin resistance and metabolic disorders. Studies demonstrated that adipose tissue dysfunction may cause insulin resistance in obese individuals. Several pieces of evidence suggested that adipose tissues of obese individuals were in a low-oxygen status compared with the lean control. Other studies demonstrated that exercise re-arranged tissue blood flow, disposing cells to low oxygen concentration and increasing insulin sensitivity. According to the above findings, regulation of hypoxia on insulin sensitivity is still controversial. The purpose of the present study was to investigate the regulatory mechanism of hypoxia on adipogenesis and insulin sensitivity in 3T3-L1 dipocytes. To explore the effect of hypoxia on adipogenesis, 3T3-L1 preadipocytes were incubated in hypoxia status for 6 h in initial adipocyte differentiation. Differentiation efficiency was determined by intracellular triglyceride content measurement, oil red O staining of oil droplets, and expression of adipocyte lipidbinding protein (ALBP/aP2). Expressions of key transcriptional regulators, including those of preadipocyte factor-1 (pref-1), CCAAT/enhancer binding protein α (C/EBPα), and peroxisome proliferator-activated receptor-γ (PPARγ), were measured by immunoblotting. To investigate the effect of hypoxia on insulin sensitivity, differentiated 3T3-L1 adipocytes were preincubated in hypoxia status for 6 h, and then insulin-stimulated phosphorylation of insulin signaling pathways and glucose uptake were measured. To further elucidate the underlying mechanism, we clarify the involvement of hypoxia inducible factor-1α (HIF-1α) on hypoxia-regulated adipogenesis and insulin sensitivity by using HIF-1α inhibitor. Our results showed that hypoxia significantly decreased lipid accumulation and aP2 expression compared with normoxia control. Inhibitory effects of hypoxia on adipocyte differentiation were associated with increased pref-1 expression and decreased PPARγ expression. Hypoxia treatment increased insulinstimulated insulin receptor autophosphorylation and Akt phosphorylation and glucose uptake in 3T3-L1 adipocytes compared with normoxia control. Both hypoxia-inhibited adipogenesis and hypoxia-enhanced insulin sensitivity could be prevented by pretreatment with HIF-1α inhibitor, YC-1. In conclusion, short-term hypoxia suppressed adipogenesis and enhanced insulin sensitivity through HIF- 1α-dependent pathway in 3T3-L1 adipocytes.

On-surface Ullmann coupling reaction of aryl chlorides has been achieved on Cu(111), Ag(111), and Au(111), and the mechanism has been investigated on the single molecule level using scanning tunneling microscopy and density functional theory. The different reactivity of the aryl halides was utilized to design a stepwise on-surface synthesis, which affords a zigzag template and then converts to 2D porous networks.

Objective The aim of this study was to investigate the regulatory mechanism of endothelin-1 (ET-1), an endothelium-derived vasoconstrictor, on adipogenesis in vitro and in vivo. Methods 3T3-L1 preadipocytes were used to explore the mechanisms mediating ET-1 actions on preadipocyte proliferation and adipocyte differentiation. To investigate the in vivo effect of ET-1, male Sprague-Dawley rats were infused with ET-1 or saline for 4 weeks via intraperitoneally implanted osmotic pumps, and the fat pad weight and adipocyte size of adipose tissues were measured. Results ET-1 stimulated preadipocyte proliferation and increased the cell number at the mitotic clonal expansion stage of adipocyte differentiation via the endothelin A receptor (ETAR) and activation of the protein kinase C (PKC) pathway. ET-1, via ETAR, inhibited adipocyte differentiation partially through an ERK-dependent pathway. Furthermore, no significant difference in the body weight and fat pad weight was observed in either ET-1- or saline-infused rats. Compared with saline-infused rats, the adipocyte cell number was significantly increased but the adipocyte size was significantly decreased in ET-1-infused rats. Conclusions Chronic ET-1 infusion increased the number of small adipocytes without the change of white adipose tissue mass in rats, which were associated with ET-1-stimulated preadipocyte proliferation, but not ET-1-suppressed adipocyte differentiation.

Two tunable cascade reactions of alkynols and alkynes have been developed by combining Sc(OTf)3 and rhodium catalysis. In the absence of H2O, an endo-cycloisomerization/C-H activation cascade reaction provided 2,3-dihydronaphtho[1,2-b]furans in good to high yields. In the presence of H2O, the product of alkynol hydration underwent an addition/C-H activation cascade reaction with an alkyne, which led to the formation of 4,5-dihydro-3H-spiro[furan-2,1'-isochromene] derivatives in good yields under mild reaction conditions. Mechanistic studies of the cascade reactions indicated that the rate-determining step involves C-H bond cleavage and that the hydration of the alkynol plays a key role in switching between the two reaction pathways.

Background The understanding for the impact of petrochemical pollutants exposure on renal functions is limited. Objectives Our study examined the associations between renal functions and pollutants exposure in adult residents living in the vicinity of a petrochemical industry. Methods We recruited 2069 adult residents near a big petrochemical complex in Taiwan in 2009–2012, and they were categorized into high exposure (HE) and low exposure (LE) groups based on their address to source by 10 km radius. Study subjects were measured the urinary levels of arsenic, cadmium, mercury, thallium, and 1-hydroxypyrene (1-OHP). The estimated glomerular filtration rate (eGFR) was calculated using the Taiwanese Chronic Kidney Disease Epidemiology Collaboration equation, and the chronic kidney disease (CKD) prevalence and risks were defined according to KDIGO 2012 guidelines. Adjusted generalized linear and logistic regression models were applied to evaluate the associations between petrochemical exposure and renal functions. Results Subjects in the HE areas had significantly lower eGFR, higher CKD prevalence, and higher levels of urinary arsenic, cadmium, mercury, thallium and 1-OHP. The closer to complex and high exposure group of study subjects were significantly associated with the decrease in eGFR, higher ORs for CKD and high-intermediate risk of CKD. In addition, the study subjects who had two-fold urinary arsenic and 1-OHP levels were significantly with decreased 0.68 and 0.49 ml/min/1.73 m2 of eGFR, respectively. Conclusions Residing closer and higher arsenic and polycyclic aromatic hydrocarbon exposure were associated with the renal impairment and risks of CKD among the residential population near the petrochemical industry.

Cross-coupling is of great importance in organic synthesis. Here it is demonstrated that cross-coupling of aryl-bromide and porphyrin-bromide takes place on aA u(111 )s urface in vacuo. The products are oligomers consisting of porphyrin moieties linked by p-phenylene at porphyrin's meso-positions. The ratio of the cross-coupled versus homocoupled bonds can be regulated by the reac- tant concentrations. Kinetic Monte Carlo simulations were applied to determine the activatio nb arrier .I ti se xpected that this reaction can be employed in other aryl-bromide precursors for designing alternating co-polymers incorpo- rating porphyrin and other functional moieties.

A convenient potassium tert -butoxide catalyzed addition–elimination reaction has been achieved using exo -cyclic enol ethers and aryl aldehydes as the starting materials. The transition-metal free reaction proceeded smoothly to afford 1,3-dihydroisobenzofuran derivatives with good to excellent yields. More importantly, the resulting products were discovered as novel fluorophores with good fluorescence properties and remarkable Stokes shifts. Changing the nature of the substituents in 1,3-dihydroisobenzofurans derivatives allowed the maximum emission wavelengths to be tuned between 438 and 597 nm and the Stokes shifts varied between 63 and 166 nm. In particular, derivative C27 containing a piperidyl and a cyano group showed the maximum emission wavelength of 597 nm and a Stokes shift of 166 nm.

We employed three metal-coordination structures as templates to control the Sonogashira cross-coupling reactions on a Au(111) surface catalyzed by loaded Pd. We used scanning tunnelling microscopy to resolve the products formed at the successive reaction steps and identified three vital characteristics for an efficient template: high accessibility of reaction sites, structural rigidity and thermal stability.

Potassium tert -butoxide ( t -BuOK) was found to be an effective catalyst for the cyclization of aromatic alkynols and alkynylamines. In the presence of 10 mol % t -BuOK, a range of alkynols were converted to the corresponding exo -cyclic enol ethers as pure Z -stereoisomers with 100% selectivity and moderate to excellent yields. Moreover, the cyclization of alkynylamines was also achieved to afford indoles and isoindolin-1-ones in good yields.

Intermolecular benzylic methylene functionalization of exo-cyclic enol ethers has been achieved using imines as reagents and potassium tert-butoxide as the catalyst. Depending on the solvent used, the reaction proceeds by two pathways. In THF, an addition/elimination reaction of exo-cyclic enol ethers with imines provides dihydroisobenzofuran derivatives in good yield. In DMSO, an addition/ring-opening/cyclization cascade reaction occurs with unexpected cleavage of C-O and C-C bonds, affording isoquinolin-1(2H)-one products in high yield under ambient reaction conditions.

A convenient palladium-catalyzed tandem reaction of aryl iodides and salicyl N-tosylhydrazones has been achieved to afford a series of compounds containing the novel spiro[benzofuran-3,2′-chromene] scaffold in moderate to good yields. This efficient catalytic reaction, which tolerates various functional groups, combines alkyne-based 5-exo-dig cyclization, palladium(II) carbene migratory insertion and intramolecular cyclization, generating three new bonds in one reaction.

The efficiency of Ullmann reaction of aryl chlorides on an Au(111) surface has been substantially increased by using dosed Cu as a catalyst. The different reactivity of aryl bromides and aryl chlorides has been exploited to design a programmed, on-surface synthesis to form 2D covalent organic frameworks.

Two tunable cascade reactions of alkynols and alkynes have been developed by combining Sc(OTf)3 and rhodium catalysis. In the absence of H2O, an endo-cycloisomerization/C-H activation cascade reaction provided 2,3-dihydronaphtho[1,2-b]furans in good to high yields. In the presence of H2O, the product of alkynol hydration underwent an addition/C-H activation cascade reaction with an alkyne, which led to the formation of 4,5-dihydro-3H-spiro[furan-2,1'-isochromene] derivatives in good yields under mild reaction conditions. Mechanistic studies of the cascade reactions indicated that the rate-determining step involves C-H bond cleavage and that the hydration of the alkynol plays a key role in switching between the two reaction pathways.

Bismuth telluride thin films with layered nanostructure have been fabricated by radio frequency (RF) mag- netron sputtering. Thin films were deposited at various substrate temperatures and durations with a single Bi2Te3 target. The microstructures and chemical compositions of these films were characterized by X-ray diffraction (XRD), scan- ning electron microscope (SEM) and energy dispersive spectroscope (EDS). Electrical transport property and Seebeck coefficient were measured on these thin films. The results show that substrate temperature is a key factor on the micro- structure and transport property of bismuth telluride thin films. High temperature is beneficial for the formation of lay- ered nanostructure and the enhancement of power factor. The highest power factor was obtained on the thin film de- posited at 400℃. However, Te deficiency was observed in these thin films. Thus thermoelectric property would be further enhanced by optimizing composition of these thin films.

Radial ZnO clusters have been synthesized in a large-scale by a simple microemulsion method using sulfonate-polystyrene (S-PS) as a template. The clusters are formed by the radial growth of ZnO hexagonal nanorods. The product is characterized by using XRD, SEM, TEM, FT-IR, and photoluminescence spectra (PL). Furthermore, the SEM images indicate that the radial ZnO structures possess hexagonal prisms structures. On the meanwhile, FT-IR spectrum reveals that S-PS is present in the radial ZnO nanostructures, and the PL spectrum shows a sharp UV emission. As a result, the formation mechanism of the radial ZnO nanostructures has been proposed.

A tetradentate nitrogen-phosphorus ligand is used for the ruthenium-catalyzed title reaction with high exo-selectivity.

Potassium tert -butoxide ( t -BuOK) was found to be an effective catalyst for the cyclization of aromatic alkynols and alkynylamines. In the presence of 10 mol % t -BuOK, a range of alkynols were converted to the corresponding exo -cyclic enol ethers as pure Z -stereoisomers with 100% selectivity and moderate to excellent yields. Moreover, the cyclization of alkynylamines was also achieved to afford indoles and isoindolin-1-ones in good yields.

The result of the title cascade reaction of alkynols with imines depends on the solvent used (DMSO or THF).

Rhodium-catalyzed addition-cyclization of hydrazines with alkynes has been achieved to afford highly substituted pyrazoles under mild conditions. The cascade reaction involves two transformations: addition of the C-N bond of hydrazines to alkynes via unexpected C-N bond cleavage and intramolecular dehydration cyclization.