Regiodivergent Hydrosilylation of Polar Enynes to Synthesize Site-Specific Silyl-Substituted Dienes.

Herein, we present catalyst-regulated switchable site-selective hydrosilylation of enynes, which are suitable for a wide range of alkyl and aryl substituted polar enynes and exhibit excellent functional group compatibility. Under the optimized conditions, silyl groups can be precisely installed at various positions of 1,3-dienes. While α- and γ-silylation products were obtained under platinum-catalytic systems, ß-silylation products were delivered with [Cp*RuCl]4 as catalyst. This process lead to the formation of 1,3-dienoates with diverse substitutions, which would pose challenges with other methodologies.

Lipid-assisted PEG-b-PLA nanoparticles with ultrahigh SN38 loading capability for efficient cancer therapy.

The topoisomerase I inhibitor, 7-ethyl-10-hydroxycamptothecin (SN38), has demonstrated potent anticancer activity. However, its clinical application is hindered by its low solubility and high crystallization propensity, which further complicates its encapsulation into nanoparticles for systemic delivery. Herein, we explore the utilization of lipid-assisted poly(ethylene glycol)-block-poly(D,L-lactide) (PEG-b-PLA) nanoparticles to achieve ultrahigh loading capability for SN38. Through the introduction of cationic, anionic, or neutral lipids, the SN38 loading efficiency and loading capacity is elevated to >90% and >10% respectively. These lipids efficiently attenuate the intermolecular π-π stacking of SN38, thereby disrupting its crystalline structure. Moreover, we assess the therapeutic activity of SN38-loaded formulations in various tumor models and identify an anionic lipid 1,2-dioleoyl-sn-glycero-3-phospho-(1'-rac-glycerol) sodium salt (DOPG)-assisted formulation that exhibits the highest anticancer activity and has favorable biosafety. Overall, our findings present a simple and robust strategy to achieve ultrahigh loading efficiency of SN38 using commonly employed PEG-b-PLA nanoparticles, opening up a new avenue for the systemic delivery of SN38.

Regio- and enantioselective CuH-catalyzed 1,2- and 1,4-hydrosilylation of 1,3-enynes.

We report a copper-catalyzed ligand-controlled selective 1,2- and 1,4-hydrosilylation of 1,3-enynes, which furnishes enantiomerically enriched propargyl- and 1,2-allenylsilane products in high yields with excellent enantioselectivities (up to 99% ee). This reaction proceeds under mild conditions, shows broad substrate scope for both 1,3-enynes and trihydrosilanes, and displays excellent regioselectivities. Mechanistic studies based on deuterium-labeling reactions and density functional theory (DFT) calculations suggest that allenylcopper is the dominant reactive intermediate under both 1,2- and 1,4-hydrosilylation conditions, and it undergoes metathesis with silanes via selective four-membered or six-membered transition state, depending on the nature of the ligand. The weak interactions between the ligands and the reacting partners are found to be the key controlling factor for the observed regioselectivity switch. The origin of high enantiocontrol in the 1,4-hydrosilylation is also revealed by high level DLPNO-CCSD(T) calculations.

Copper-Catalyzed Enantioselective Desymmetric Protosilylation of Prochiral Diynes: Access to Optically Functionalized Tertiary Alcohols.

In this protocol, a copper-catalyzed desymmetric protosilylation of prochiral diynes was developed. The corresponding products were obtained in moderate to high yields and enantiomeric ratios. This approach provides a simple method for synthesizing functionalized chiral tertiary alcohols in the presence of a chiral pyridine-bisimidazoline (Pybim) ligand.

Copper-Catalyzed Borylation and Silylation of Dichlorocyclobutenones.

We report copper-catalyzed borylation and silylation of dichlorocyclobutenones, which furnish the boron-substituted and silicon-substituted polyfunctionalized cyclobutenones in high yields. The reactions proceed under mild reaction conditions, show broad substrate scope, and display high chemoselectivity. In addition, a series of transformations of the corresponding products has been realized.

USP18-mediated protein deISGylation and its role in tuberculosis and other infectious diseases.

The transcription of interferon-stimulated gene 15 (isg15) is induced by type I interferons. ISG15 can covalently modify target proteins through the sequential action of enzymesE1, E2, and E3, a process known as ISGylation. The ISGylation of host proteins is widely involved in immune responses, such as host antiviral defence. Ubiquitin-specific protease 18 (USP18), as a deubiquitinase (DUB), can remove ISG15 conjugated to target proteins and inhibit host immune responses by suppressing the type I interferon signaling. The dynamic balance between ISGylation and deISGylation mediated by ISG15 or USP18 respectively plays a significant role in the tuberculosis. Furthermore, similar to ISG15, USP18 is extensively involved in virus-host interaction. In this review, we summarize the roles of ISGylation and deISGylation in tuberculosis and other important diseases mediated by ISG15 and USP18 respectively, underlying regulator network. Further studies in this aspect will inspire new host-targeted strategies to control important diseases such as tuberculosis.

Copper-Catalyzed Markovnikov Selective 3,4-Hydrosilylation of 2-Substituted 1,3-Dienes.

A copper-catalyzed regioselective Markovnikov 3,4-hydrosilylation of 2-substituted 1,3-dienes has been accomplished. A wide range of 2-substituted 1,3-dienes and trihydrosilanes are compatible under the optimal conditions. The bisphosphine ligand with a rigid backbone provides the Markovnikov 3,4-hydrosilylation product in better yield and selectivity. Besides, the synthetic utilities of the allylsilanes also were demonstrated by their flexible derivatizations.

Copper-Catalyzed Enantioselective 1,4-Protosilylation of Alkynyl-substituted Enones to Synthesize the Highly Diastereomeric Chiral Homoallenylsilanes.

A copper-catalyzed 1,4-protosilylation of α-alkynyl-enones to form the functionalized chiral homoallenylsilanes was developed. In the presence of a chiral monopyridine oxazoline ligand, a variety of trisubstituted allene derivatives bearing a contiguous stereogenic center and axis were prepared in good yields with excellent enantioselectivities and diastereoselectivities.

[Distribution and Environmental Significance of Rare Earth Elements in Typical Protected Vegetable Soil, Northern China].

The concentrations of rare earth elements (REEs) in protected vegetable soils in Wuqing district of Tianjin City, Jinzhong district of Shanxi Province, Shenyang district of Liaoning Province, and Wulanchabu district of Inner Mongolia Autonomous Region in northern China were measured to analyze the change characteristics of soil REEs in the process of protected vegetable cultivation. Additionally, we sought to use the REEs parameters to trace the feasibility of characterizing the interference of human activities on the soil ecological environment. The results showed that the total content of REEs (REE) in the topsoil of protected vegetable fields ranged from 146.52 to 158.76 mg·kg-1, with an average of 152.34 mg·kg-1 in Shenyang; 92.16 to 137.69 mg·kg-1, with an average of 115.03 mg·kg-1in Wuqing; 91.38 to 118.84 mg·kg-1, with an average of 108.03 mg·kg-1 in Wulanchabu; and 97.62 to 111.27 mg·kg-1, with an average of 102.43 mg·kg-1in Jinzhong. The REEs distribution patterns in the soils of the four areas, standardized with chondrite, characterized by a right tilt, showed that light rare earth elements were obviously enriched in the soil, demonstrated by the ratios of LREE/HREE and (La/Yb) N, which were greater than 6 and 7, respectively. The values of (La/Sm)N in the soils were higher than 3, suggesting that there was an obvious fractionation between light rare earth elements, whereas the values of (Gd/Yb)N were between 1-2, and there was a weak fractionation between heavy rare earth elements. The values of δEu in the soils were between 0.56 and 0.61, showing that Eu had a negative abnormality. The values of δCe were between 0.89 and 1.11, showing that Ce had no abnormality or weak positive abnormality. The higher LREE/HREE and (La/Yb)N in protected vegetable soil than that in open-air vegetable soil indicated the increasing differentiation degree between light and heavy rare earth elements in protected vegetable soil. The lower (La/Sm)N in protected vegetable soils indicated the reduction in the differentiation among light rare earth elements in soil. Higher δCe values and lower δEu values suggested that Ce and Eu were relatively enriched and depleted, respectively, during vegetable planting. The REE, LREE, (La/Sm)N, and δEu in protective soil decreased with the number of cultivation years, whereas the (Gd/Yb)N and δCe increased, but the HREE values did not change significantly. There was a significant correlation between δCe, δEu, (La/Yb)N, (Gd/Yb)N, and soil bulk density, soil moisture content, and soil organic matter in Tianjin protected vegetable soils, showing preliminarily that rare earth elements can be used as tracer elements to characterize the interference intensity of human activities on soil.

Chelation-Controlled Stereospecific Cross-Coupling Reaction between Alkenes for Atroposelective Synthesis of Axially Chiral Conjugated Dienes.

In this protocol, an efficient palladium-catalyzed asymmetric synthesis of axially chiral conjugated dienes via alkenyl C-H olefination is reported. The corresponding atropisomeric styrenes containing a conjugated diene scaffold were obtained in good yields with good enantioselectivities. This synthetic strategy features an easy operation, mild reaction conditions, a wide functionality tolerance, and high efficiency.

Copper-Catalyzed Regiodivergent and Enantioselective Hydrosilylation of Allenes.

A copper-catalyzed regiodivergent hydrosilylation of a wide range of simple allenes is reported. Linear and branched allylsilanes were formed by judicious choice of solvents. Furthermore, branched allylsilanes were obtained with high enantioselectivity (up to 97% enantiomeric excess) with the aid of a C2-symmetric bisphosphine ligand in the unprecedented asymmetric allene hydrosilylation.

Synthesis of Structurally Diverse Allylsilanes via Copper-Catalyzed Regiodivergent Hydrosilylation of 1,3-Dienes.

Unprecedented copper-catalyzed regiodivergent hydrosilylation reactions of substituted 1,3-dienes with hydrosilanes have been developed. The 1,2- and 1,4-hydrosilylations of 1-(hetero)aryl-substituted 1,3-dienes were highly selectively controlled via variation of the catalytic systems. Meanwhile, the 1,4-hydrosilylation reaction of 2-aryl-substituted 1,3-dienes with diphenylsilane was also successfully realized for the first time. These methods provide convenient and efficient approaches for the synthesis of structurally diverse allylsilanes.

Copper-Catalyzed Chemoselective Silylative Cyclization of 2,2'-Diethynylbiaryl Derivatives.

In this protocol, copper-catalyzed diverse silylative carbocyclization reactions of 2,2'-diethynylbiaryl derivatives with silaboronate were reported. Three new and novel types of domino reactions for the copper-catalyzed transformation of silaboronate were discovered. The corresponding cyclobuta[l]phenanthrene, bis((silyl)methyl)phenanthrene, and silyl-substituted exocyclic diene products were chemoselectively formed with high efficiency.

Synthesis of Enynic and Allenic Orthoesters via Defluoromethoxylation of 2-Trifluoromethyl-1,3-enynes.

In this protocol, the chemoselective defluoromethoxylation reactions of 2-trifluoromethyl-1,3-enynes were developed. The enynic and allenic orthoesters were selectively produced in good to excellent yields via multiple substitution processes under mild reaction conditions, respectively. The enynic orthoester products were proved capable of acting as efficient "platform molecules" to access various functionalized allenyl compounds.

Copper-Catalyzed Anti-Markovnikov Hydrosilylation of Terminal Alkynes.

A copper-catalyzed anti-Markovnikov hydrosilylation of alkynes with PhSiH3 was reported. This reaction represents a notable and efficient example on copper-catalyzed hydrosilylatioin of alkynes, which shows excellent recognition between the terminal and internal triple bonds. Various (hetero)aromatic and aliphatic substituted terminal alkynes underwent this reaction to afford the (E)-vinylsilanes in high yields and with excellent regioselectivity.

Synthesis of Functionalized Vinylsilanes via Metal-Free Dehydrogenative Silylation of Enamides.

A novel method of metal-free dehydrogenative silylation of enamides has been developed. The desired functionalized vinylsilane products were obtained in moderate to good yield and with high stereoselectivities. This protocol displays good tolerance of various functionalities. Furthermore, the high chemoselectivity of this reaction enables us to introduce different unsaturated C-C moieties to the products. The ease of further derivatization of the products to other useful compounds also demonstrates the highly synthetic utility of the current methodology.

Ligand-Dependent-Controlled Copper-Catalyzed Regio- and Stereoselective Silaboration of Alkynes.

A copper-catalyzed highly regio- and stereoselective silaboration of alkynes was developed. In this work, direct cis-difunctionalization of alkynes was realized with silaboronate reagent and copper catalyst in aprotic solvents. The regiodivergent silaborations were controlled by tuning the copper catalysts and phosphine ligands used in reactions. This protocol provides an efficient and practical method to synthesize the multisubstituted functionalized alkenes with specific stereoselectivity.

Hsa-let-7c controls the committed differentiation of IGF-1-treated mesenchymal stem cells derived from dental pulps by targeting IGF-1R via the MAPK pathways.

The putative tumor suppressor microRNA let-7c is extensively associated with the biological properties of cancer cells. However, the potential involvement of let-7c in the differentiation of mesenchymal stem cells has not been fully explored. In this study, we investigated the influence of hsa-let-7c (let-7c) on the proliferation and differentiation of human dental pulp-derived mesenchymal stem cells (DPMSCs) treated with insulin-like growth factor 1 (IGF-1) via flow cytometry, CCK-8 assays, alizarin red staining, real-time RT-PCR, and western blotting. In general, the proliferative capabilities and cell viability of DPMSCs were not significantly affected by the overexpression or deletion of let-7c. However, overexpression of let-7c significantly inhibited the expression of IGF-1 receptor (IGF-1R) and downregulated the osteo/odontogenic differentiation of DPMSCs, as indicated by decreased levels of several osteo/odontogenic markers (osteocalcin, osterix, runt-related transcription factor 2, dentin sialophosphoprotein, dentin sialoprotein, alkaline phosphatase, type 1 collagen, and dentin matrix protein 1) in IGF-1-treated DPMSCs. Inversely, deletion of let-7c resulted in increased IGF-1R levels and enhanced osteo/odontogenic differentiation. Furthermore, the ERK, JNK, and P38 MAPK pathways were significantly inhibited following the overexpression of let-7c in DPMSCs. Deletion of let-7c promoted the activation of the JNK and P38 MAPK pathways. Our cumulative findings indicate that Let-7c can inhibit the osteo/odontogenic differentiation of IGF-1-treated DPMSCs by targeting IGF-1R via the JNK/P38 MAPK signaling pathways.

[Relationship Between Landscape Pattern and Spatial Variation of Heavy Metals in Aquatic Sediments in Headwaters Area of Yuqiao Reservoir].

Yuqiao Reservoir, an important adjusting reservoir in the project of diverting water from the Luanhe River to Tianjin City, is an important water resource for Tianjin City. Concentrations and spatial variation characteristics of Cd, As, Pb, Cu, Cr, and Zn from 33 sub watershed sampling sites of Yuqiao reservoir and the relationship to landscape pattern were discussed. The result showed that average concentrations of Cd, As, Cu, Cr in suspended particulate matter were higher than Chinese environmental quality standard Grade one for soils, and there were ecological risks for them because they could arrive at Yuqiao reservoir. The average concentrations of Cd, As, Pb, Cu, Cr, and Zn in surface sediments were 0.32 mg·kg-1, 30.39 mg·kg-1, 33.49 mg·kg-1, 58.20 mg·kg-1, 90.16 mg·kg-1 and 94.80 mg·kg-1 respectively. The average concentrations of Cd, As, Cu and the concentrations of Pb, Cr, Zn in partial samples exceeded Chinese environmental quality standard Grade one for soils. The average concentrations of Cd, Cr, Zn in surface sediments of three tributaries increased in the order of Linhe River >Shahe River >Lihe Rier, Cu decreased in the order of Linhe River < Shahe River < Lihe River, and As, Pb increased in the order of Shahe River >Linhe River >Lihe Ricer. Land use types in Yuqiao reservoir basin had some impact on the distribution of heavy metal concentrations in river surface sediments. Woodland and shrub grass land determined the natural distribution trend of heavy metals in surface sediments. Gardenland and industrial & mining land usage had impact on Cd, As, Pb, Cr distributions. Farmland and village & town land usage did not produce negative influence on heavy metal distribution.

Interleukin-1ß (3953/4) C→T polymorphism increases the risk of chronic periodontitis in Asians: evidence from a meta-analysis of 20 case-control studies.

INTRODUCTION: To investigate the association of the interleukin-1ß (IL-1ß) (3953/4) C→T polymorphism with chronic periodontitis (CP) in Asians. MATERIAL AND METHODS: Systematic searches of electronic databases and hand searching of references were performed, including PubMed, Embase, the Cochrane Library, and the Chinese National Knowledge Infrastructure (CNKI). Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the associations. Publication bias was tested by Egger's test. Sensitivity analysis was conducted by limiting the meta-analysis studies conforming to Hardy-Weinberg equilibrium (HWE). Data analyses were carried out using RevMan 6.0. RESULTS: A meta-analysis was performed on 20 published case-control studies, including 1,656 CP cases and 1,498 healthy controls. The pooled OR was 1.60 (95% CI = 1.02-2.52, p = 0.04) for the T allele carriers (TT + CT) compared with CC and 1.60 (95% CI = 1.06-2.42, p = 0.02) for T vs. C. Subgroup analysis by country revealed significant risks of CP among Indians carrying the T allele (TT vs. CC: OR = 3.88, 95% CI = 1.77-8.50, p = 0.0007). CONCLUSIONS: The analysis showed that IL-1ß (3953/4) C→T polymorphism probably increases the risk of CP in Asians, and the IL-1ß+3954 TT genotype may be associated with a strongly increased risk of CP in Indians, but not in Chinese.