Unusual Kinetics Induced by Ligands in Rhodium(III)-Catalyzed Dehydrogenative Olefination Reactions.

In this study, we investigate the effects of ligands on C-H activation during rhodium(III)-catalyzed C-H bond olefination reactions using well-defined [CpXRhIII] catalytic systems with three representative CpX (Cp (η5-C5H5), CpCF3 (η5-C5Me4CF3), and Cp* (η5-C5Me5)) ligands. Our results demonstrate that C-H activation as the rate-limiting step is significantly influenced by the steric properties of the CpX ligands. Moreover, we observe a dramatic acceleration of the simple [CpRhIII]-catalyzed C-H olefination reaction with acid coproducts such as HOAc, implying an autocatalytic C-H activation process.

Unequal Perylene Diimide Twins in a Quadruple Assembly.

Natural light-harvesting (LH) systems can divide identical dyes into unequal aggregate states, thereby achieving intelligent "allocation of labor". From a synthetic point of view, the construction of such kinds of unequal and integrated systems without the help of proteinaceous scaffolding is challenging. Here, we show that four octatetrayne-bridged ortho-perylene diimide (PDI) dyads (POPs) self-assemble into a quadruple assembly (POP)4 both in solution and in the solid state. The two identical PDI units in each POP are compartmentalized into weakly coupled PDIs (P520) and closely stacked PDIs (P550) in (POP)4 . The two extreme pools of PDI chromophores were unambiguously confirmed by single-crystal X-ray crystallography and NMR spectroscopy. To interpret the formation of the discrete quadruple assembly, we also developed a two-step cooperative model. Quantum-chemical calculations indicate the existence of multiple couplings within and across P520 and P550, which can satisfactorily describe the photophysical properties of the unequal quadruple assembly. This finding is expected to help advance the rational design of dye stacks to emulate functions of natural LH systems.

Enhanced electrochemiluminescence of CdS quantum dots capped with mercaptopropionic acid activated by EDC for Zika virus detection.

Enhanced electrochemiluminescence (ECL) signals of CdS quantum dots capped with 3-mercaptopropionic acid (MPA@CdS QDs) have been observed after using N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide (EDC) to activate the carboxyl groups. The generated ECL signals are strong enough that their images can be captured using a Huawei mobile phone. A possible mechanism for the generation of enhanced ECL signals has been proposed. Then, a sandwich immunosensor platform for detecting Zika virus (ZIKV) was fabricated with silica microspheres as the carrier and MPA@CdS QDs as ECL signal labels. Due to the dual signal amplification of EDC activation and microsphere enrichment, good linearity from 1.0 fg mL-1 to 1.0 ng mL-1 was exhibited by the QD-based ECL immunosensor for ZIKV detection. The detection limit was 0.3 fg mL-1.

Naphthodithiophene Diimide Based Chiral π-Conjugated Nanopillar Molecules.

The synthesis, structures, and properties of [4]cyclonaphthodithiophene diimides ([4]C-NDTIs) are described. NDTIs as important n-type building blocks were catenated in the α-positions of thiophene rings via an unusual electrochemical-oxidation-promoted macrocyclization route. The thiophene-thiophene junction in [4]C-NDTIs results in an ideal pillar shape. This interesting topology, along with appealing electronic and optical properties inherited from the NDTI units, endows the [4]C-NDTIs with both near-infrared (NIR) light absorptions, strong excitonic coupling, and tight encapsulation of C60 . Stable orientations of the NDTI units in the nanopillars lead to stable inherent chirality, which enables detailed circular dichroism studies on the impact of isomeric structures on π-conjugation. Remarkably, the [4]C-NDTIs maintain the strong π-π stacking abilities of NDTI units and thus adopt two-dimensional (2D) lattice arrays at the molecular level. These nanopillar molecules have great potential to mimic natural photosynthetic systems for the development of multifunctional organic materials.

Supramolecular Alternating Donor-Acceptor Assembly toward Intercalated Covalent Organic Frameworks.

Conventionally, z-direction modulation of two-dimensional covalent organic frameworks (2D-COFs) is difficult to achieve because they rely on spontaneous π-π interactions to form 3D architectures. Herein, we report a facile construction of a novel intercalated covalent organic framework (Intercalated-COF) by synchronizing operations of supramolecular donor-acceptor (D-A) interactions (A unit: 2,5,8,11-tetra(p-formylphenyl)-perylene diimide (PDI) 1; D unit: perylene 3, as intercalator) in the vertical directions, with polymerizations (by only reacting 1 with p-phenylenediamine 2) in the lateral directions. In this Intercalated-COF, the PDI-based covalent 2D layers are uniformly separated by perylene guest layers. This supramolecular strategy opens the possibility for z-direction modulation of 2D-COFs through "intercalating" various guest molecules and thus may contribute to the exploration of advanced applications of these porous and crystalline frameworks.

Relationship between 25-Hydroxyvitamin D, bone density, and Parkinson's disease symptoms.

OBJECTIVES: Vitamin D deficiency is widespread in patients with Parkinson's disease (PD). Our aim was to determine whether serum vitamin D levels correlated with bone mineral density (BMD) and non-motor symptoms in patients with PD. MATERIALS & METHODS: A consecutive series of 182 patients with PD and 185 healthy controls were included. Serum 25-hydroxyvitamin D (25[OH]D) levels were measured by immunoassay, while BMD of the lumbar spine and femoral neck was measured by dual-energy X-ray absorptiometry. Associations between serum vitamin D levels and clinical data were evaluated using partial correlation analysis. RESULTS: Patients with PD had significantly lower serum 25(OH)D levels relative to healthy controls (49.75 ± 14.11 vs 43.40 ± 16.51, P < 0.001). Furthermore, PD patients with lower vitamin D levels had a significantly higher frequency of falls (P = 0.033) and insomnia (P = 0.015). They also had significantly higher scores for the Pittsburgh Sleep Quality Index (PSQI; P = 0.014), depression (P = 0.020), and anxiety (P = 0.009). Finally, patients with PD also had a significantly lower mean BMD of the lumbar spine (P = 0.011) and femoral neck (P < 0.001). After adjusting for age, sex, and body mass index, vitamin D levels significantly correlated with falls, insomnia, and scores for the PSQI, depression, and anxiety. CONCLUSIONS: In patients with PD, vitamin D levels significantly correlated with falls and some non-motor symptoms. However, no associations were found between BMD and the serum 25(OH)D levels in patients with PD. Thus, vitamin D supplementation is a potential therapeutic for non-motor PD symptoms.

Scalable Rhodium(III)-Catalyzed Aryl C-H Phosphorylation Enabled by Anodic Oxidation Induced Reductive Elimination.

Transition metal catalyzed C-H phosphorylation remains an unsolved challenge. Reported methods are generally limited in scope and require stoichiometric silver salts as oxidants. Reported here is an electrochemically driven RhIII -catalyzed aryl C-H phosphorylation reaction that proceeds through H2 evolution, obviating the need for stoichiometric metal oxidants. The method is compatible with a variety of aryl C-H and P-H coupling partners and particularly useful for synthesizing triarylphosphine oxides from diarylphosphine oxides, which are often difficult coupling partners for transition metal catalyzed C-H phosphorylation reactions. Experimental results suggest that the mechanism responsible for the C-P bond formation involves an oxidation-induced reductive elimination process.

Discrete π-Stacks from Self-Assembled Perylenediimide Analogues.

The formation of well-defined finite-sized aggregates represents an attractive goal in supramolecular chemistry. In particular, construction of discrete π-stacked dye assemblies remains a challenge. Reported here is the design and synthesis of a novel type of discrete π-stacked aggregate from two comparable perylenediimide (PDI) dyads (PEP and PBP). The criss-cross PEP-PBP dimers in solution and (PBP-PEP)-(PEP-PBP) tetramers in the solid state are well elucidated using single-crystal X-ray diffraction, dynamic light scattering, and diffusion-ordered NMR spectroscopy. Extensive π-π stacking between the PDI units of PEP and PBP as well as repulsive interactions of swallow-tailed alkyl substituents are responsible for the selective formation of discrete dimer and tetramer stacks. Our results reveal a new approach to preparing discrete π stacks that are appealing for making assemblies with well-defined optoelectronic properties.

Function and regulation of LAG3 on CD4+CD25- T cells in non-small cell lung cancer.

LAG3 is a surface molecule found on a subset of immune cells. The precise function of LAG3 appears to be context-dependent. In this study, we investigated the effect of LAG3 on CD4+CD25- T cells from non-small cell lung cancer (NSCLC) patients. We found that in the peripheral blood mononuclear cells of NSCLC patients, LAG3 was significantly increased in CD4+ T cells directly ex vivo and primarily in the CD4+CD25- fraction, which was regulated by prolonged TCR stimulation and the presence of IL-27. TCR stimulation also increased CD25 expression, but not Foxp3 expression, in LAG3-expressing CD4+CD25- cells Compared to LAG3-nonexpressing CD4+CD25- cells, LAG3-expressing CD4+CD25- cells presented significantly higher levels of PD1 and TIM3, two inhibitory receptors best described in exhausted CD8+ T effector cells. LAG3-expressing CD4+CD25- cells also presented impaired proliferation compared with LAG3-nonexpressing CD4+CD25- cells but could be partially rescued by inhibiting both PD1 and TIM3. Interestingly, CD8+ T cells co-incubated with LAG3-expressing CD4+CD25- cells at equal cell numbers demonstrated significantly lower proliferation than CD8+ T cells incubated alone. Co-culture with CD8+ T cell and LAG3-expressing CD4+CD25- T cell also upregulated soluble IL-10 level in the supernatant, of which the concentration was positively correlated with the number of LAG3-expressing CD4+CD25- T cells. In addition, we found that LAG3-expressing CD4+CD25- T cells infiltrated the resected tumors and were present at higher frequencies of in metastases than in primary tumors. Taken together, these data suggest that LAG3-expressing CD4+CD25- T cells represent another regulatory immune cell type with potential to interfere with anti-tumor immunity.

Pain Correlates with Sleep Disturbances in Parkinson's Disease Patients.

OBJECTIVES: Both sleep disorders and pain decrease quality of life in patients with Parkinson's disease (PD). However, little is known about the relationship between objective sleep disturbances and pain in patients with PD. This study aimed to (1) examine the clinical characteristics of pain in PD patients and (2) explore the correlation between pain and sleep disturbances in PD patients. METHODS: Parkinson's disease patients (N = 144) underwent extensive clinical evaluations of motor and nonmotor symptoms and characteristics of pain. Overnight video-polysomnography was also conducted. Clinical characteristics and sleep parameters were compared between PD patients with or without pain. RESULTS: Pain was reported by 75 patients (52.1%), with 49 (65.3%) reporting pain of at least moderate severity. PD patients with pain were older and had longer disease duration, more severe PD symptoms as assessed by Hoehn and Yahr stage and the Unified Parkinson's Disease Rating Scale, and higher L-dopa equivalent daily dose compared with PD patients without pain. PD patients with pain also showed significantly decreased sleep efficiency (57.06% ± 15.84% vs. 73.80% ± 12.00%, P < 0.001), increased nonrapid eye movement stage 1 (N1) sleep (33.38% ± 19.32% vs. 17.84% ± 8.48%, P < 0.001), and decreased rapid eye movement sleep (12.76% ± 8.24% vs. 16.06% ± 6.53%, P = 0.009). Binary logistic regression analysis revealed that poorer activities of daily living, depressed mood, higher percentage of N1 sleep, and lower sleep efficiency were independent predictors of pain in patients with PD. CONCLUSIONS: Musculoskeletal pain is the most common type of pain in patients with PD. Disrupted sleep continuity, altered sleep architecture, depressed mood, and compromised activities of daily living may be associated with pain in patients with PD.

Activation of caspase-12 at early stage contributes to cardiomyocyte apoptosis in trauma-induced secondary cardiac injury.

Trauma-induced secondary cardiac injury (TISCI) is associated with increased adverse cardiac events and death. We have previously reported that TISCI results in myocardial apoptosis and secondary cardiac dysfunction. However, the underlying mechanism is unclear. To identify the time course of trauma-induced cardiomyocyte apoptosis and possible apoptotic pathway, traumatic rat models were built with Noble-Collip drum. Meanwhile, normal rat cardiomyocytes were cultured with traumatic plasma (TP) for 48 h. Cardiomyocyte apoptosis, cardiac function and the apoptosis related enzymes, including caspase-3, -8, -9, and -12, were determined. The results showed that there was no direct injury of rat hearts immediately after trauma. However, compared with hearts from the sham rats, hearts isolated from traumatic rats exhibited reduced +dP/dTmax and -dP/dTmax 24 h after trauma. In traumatic rats, myocardial apoptotic index and caspase-3 activity obviously increased 6 h after trauma, and achieved the maximal value 12 h after trauma. The activity and expression of caspase-12, an endoplasmic reticulum (ER) stress-specific caspase, elevated markedly 3 h after trauma and reached its peak 6 h after trauma. Otherwise, caspase-8 (extrinsic apoptotic pathway) and caspase-9 (intrinsic apoptotic pathway) in the myocardial tissue of traumatic rats were activated 24 h after trauma. Meanwhile, incubation of normal rat cardiomyocytes with TP increased caspase-12 activity at 6 h, caspase-3 activity at 12 h, caspase-8 and -9 activities at 24 h, respectively. TP-induced cardiomyocyte apoptosis was virtually abolished by Z-ATAD-FMK (a caspase-12 specific inhibitor). In addition, there was a significant negative correlation between myocardial caspase-12 activity and trauma-induced secondary cardiac dysfunction. Our present study demonstrated that caspase-12 is firstly activated and plays an important role in TISCI rats. Inhibition of caspase-12 mediated apoptosis may be a novel strategy in ameliorating posttraumatic cardiomyocyte apoptosis and secondary cardiac injury.

Gene Polymorphisms Affect the Effectiveness of Atorvastatin in Treating Ischemic Stroke Patients.

BACKGROUND/AIMS: The aim of the present study is to investigate whether the single nucleotide polymorphism (SNP) in lipid metabolism related genes would affect the effectiveness of atorvastatin in both Han and Uighur populations. METHODS: 200 ischemic stroke patients were treated with atorvastatin. The differences of blood lipid level and their ratios were measured. Six lipid related genes, HMGCR, APOA5, LPL, CETP, LDLR and PCSK9 were selected as candidate genes. And nine SNP loci in these six genes were genotyped by SNaPshot technique. RESULTS: In all patients treated with atorvastatin, the SNP rs662799 significantly affected the ratio of x0394;LDL and x0394;LDL/LDL (p < 0.05); the SNP rs320 significantly affected the ratio of x0394;LDL/LDL and x0394;(LDL/HDL)/(LDL/HDL) (p < 0.01) and the SNP rs708272 significantly affected the ratio of x0394;LDL (p < 0.05). In Han population treated with atorvastatin, the SNP rs662799 significantly affected the ratio of x0394;TG (p < 0.05); the SNP rs320 significantly affected the ratio of x0394;LDL/LDL and x0394;(LDL/HDL)/(LDL/HDL) (p < 0.01). In Uighur population treated with atorvastatin, the SNP rs2266788 significantly affected the ratio of x0394;HDL (p < 0.05); the SNP rs662799 significantly affected the ratio of x0394;LDL/LDL (p < 0.05) and the SNP rs708272 significantly affected the ratio of x0394;LDL (p < 0.05). CONCLUSION: Polymorphisms of rs662799 and rs2266788 in APOA5 gene, rs320 in LPL gene and rs708272 in CETP gene had significant association with the effect of the lipid-lowering therapy via atorvastatin calcium on ischemic stroke patients.

Synthesis of α-Aminonaphthalenes via Copper-Catalyzed Aminobenzannulation of (o-Alkynyl)arylketones with Amines.

A copper-catalyzed aminobenzannulation of (o-alkynyl)arylketones with amines has been developed. This method features the use of a cheap copper catalyst, the facile annulation involving various amines, and the good functional group tolerance.

XRCC1 and XPD genetic polymorphisms and susceptibility to age-related cataract: a meta-analysis.

OBJECTIVE: This meta-analysis aimed to determine the relationships between XRCC1 Arg399Gln (rs25487 G>A) and XPD Lys751Gln (rs1052559 A>C) polymorphisms and susceptibility to age-related cataract. METHODS: Medline (1966-2013), the Cochrane Library Database (Issue 12, 2013), EMBASE (1980-2013), CINAHL (1982-2013), Web of Science (1945-2013) and the Chinese Biomedical Database (CBM; 1982-2013) were searched without language restrictions. Various combinations of the keywords and MeSH terms were used to screen for potentially relevant studies, specifically "genetic polymorphisms" or "SNPs" or "variation" or "single nucleotide polymorphism" or "polymorphism" or "mutation" or "variant"; "X-ray repair cross complementing protein 1" or "Xeroderma Pigmentosum Group D Protein" or "X-ray repair cross complementing protein 1" or "Xeroderma Pigmentosum Group D Protein" or "XPD" or "Xeroderma Pigmentosum Complementation Group D Protein" or "ERCC2" or "XRCC1" or "XRCC1 DNA repair protein"; and "Cataract" or " Membranous Cataract" or " Pseudoaphakia." Meta-analyses were conducted using Stata 12.0 software. Crude odds ratios (ORs) and their corresponding 95% confidence intervals (95% CI) were calculated. RESULTS: Six independent case-control studies were included in the meta-analysis. Our results indicated that the association between the genetic polymorphisms of XRCC1 Arg399Gln G>A and XPD Lys751Gln A>C and increased susceptibility to age-related cataracts was statistically significant (XRCC1 Arg399Gln: OR=1.30, 95% CI=1.17-1.44, p<0.001; XPD Lys751Gln: OR=1.25, 95% CI=1.12-1.40, p<0.001, respectively). Ethnicity-stratified analysis indicated that the XRCC1 Arg399Gln G>A polymorphism was correlated with the development and progression of age-related cataract in China, India, and Turkey in the allele model and the dominant model. For the XPD Lys751Gln A>C variant, the association with the pathogenesis of age-related cataract in China and Turkey in the allele model and the dominant model was investigated. CONCLUSIONS: The association of XRCC1 Arg399Gln and XPD Lys751Gln polymorphisms with age-related cataract susceptibility observed in our meta-analyses supports the view that XRCC1 and XPD may play important roles in susceptibility to age-related cataract.

Copper-Catalyzed Direct C2-Benzylation of Indoles with Alkylarenes.

The copper-catalyzed regioselective cross-dehydrogenative coupling of N-pyrimidylindoles with benzylic C(sp(3))-H bonds has been developed. Di-tert-butyl peroxide was employed as a mild oxidant, and benzaldehyde proved to be an effective additive. This reaction provides a direct and pratical route to a variety of 2-benzylindoles.

Rh(III)-Catalyzed Oxidative Coupling of Benzoic Acids with Geminal-Substituted Vinyl Acetates: Synthesis of 3-Substituted Isocoumarins.

The Rh(III)-catalyzed C-H activation initiated cyclization of benzoic acids with electron-rich geminal-substituted vinyl acetates was described. The reaction was employed to prepare a range of 3-aryl and 3-alkyl substituted isocoumarins selectively.

Photochemical intermolecular silylacylations of electron-deficient internal alkynes.

Light-induced Brook rearrangements of acylsilanes facilitate silylacylation reactions of electron-deficient internal alkynes. A wide range of aromatic substituents on the acylsilane aryl group are tolerated, affording a series of functionalized enonyl silanes. The presence of electron-withdrawing substituents on the alkyne is crucial for the success of the addition process.

Acylsilanes: valuable organosilicon reagents in organic synthesis.

Acylsilanes are a fascinating class of compounds that display a number of distinctive chemical and physical properties. The unique reactivity pattern of the acylsilane functional group [R-C(O)Si] makes them an increasingly attractive moiety in modern organic synthesis, and as such, they have been utilised in a diverse range of transformations. This review provides an overview of the recent advances in the synthesis and application of acylsilanes in organic chemistry, with a particular focus on the progress made in the last two decades.

Frustrated π-stacking.

The properties of functional materials based on organic π-conjugated systems are governed extensively by intermolecular interactions between π-molecules. To establish clear relationships between supramolecular structures and functional properties, it is essential to attain structurally well-defined π-stacks, particularly in solution, as this enables the collection of valuable spectroscopic data. However, precise control and fine-tuning of π-stacks pose significant challenges due to the weak and bidirectional nature of π-π stacking interactions. This article introduces the concept of "frustrated π-stacking," strategically balancing attractive (π-π interaction) and repulsive (steric hindrance) forces in self-assembly to exert control over the sizes, sequences of π-stacks, and slip-stacked structures. These research efforts contribute to a deeper understanding of the correlation between π-stacks and their properties, thereby providing useful insights for the development of molecular materials with the desired performance.

Two-dimensional radial-π-stacks in solution.

Highly organized π-aggregate architectures can strongly affect electronic couplings, leading to important photophysical behaviors. With the escalating interest in two-dimensional (2D) materials attributed to their exceptional electronic and optical characteristics, there is growing anticipation that 2D radial-π-stacks built upon radial π-conjugation nanorings, incorporating intra- and inter-ring electronic couplings within the confines of a 2D plane, will exhibit superior topological attributes and distinct properties. Despite their immense potential, the design and synthesis of 2D π-stacks have proven to be a formidable challenge due to the insufficient π-π interactions necessary for stable stacking. In this study, we present the successful preparation of single-layer 2D radial-π-stacks in a solution. Pillar-shaped radially π-conjugated [4]cyclo-naphthodithiophene diimide ([4]C-NDTIs) molecules were tetragonally arranged via in-plane intermolecular π-π interactions. These 2D π-stacks have a unique topology that differs from that of conventional 1D π-stacks and exhibit notable properties, such as acting as a 2D template capable of absorbing C60 guest molecules and facilitating the formation of 2D radial-π-stacks comprising [4]C-NDTI-C60 complexes, rapid exciton delocalization across the 2D plane, and efficient excitation energy funneling towards a trap.