Phosphine-catalyzed 1,2-cis-diboration of 1,3-butadiynes.

Trialkyl phosphines PMe3 and PEt3 catalyze the 1,2-cis-diboration of 1,3-butadiynes to give 1,2-diboryl enynes. The products were utilized to synthesize 1,1,2,4-tetraaryl enynes using a Suzuki-Miyaura protocol and can readily undergo proto-deborylation.

Enantioselective Construction of Quaternary Stereocenters via Cooperative Photoredox/Fe/Chiral Primary Amine Triple Catalysis.

The catalytic and enantioselective construction of quaternary (all-carbon substituents) stereocenters poses a formidable challenge in organic synthesis due to the hindrance caused by steric factors. One conceptually viable and potentially versatile approach is the coupling of a C-C bond through an outer-sphere mechanism, accompanied by the realization of enantiocontrol through cooperative catalysis; however, examples of such processes are yet to be identified. Herein, we present such a method for creating different compounds with quaternary stereocenters by photoredox/Fe/chiral primary amine triple catalysis. This approach facilitates the connection of an unactivated alkyl source with a tertiary alkyl moiety, which is also rare. The scalable process exhibits mild conditions, does not necessitate the use of a base, and possesses a good functional-group tolerance. Preliminary investigations into the underlying mechanisms have provided valuable insights into the reaction pathway.

Device for Measuring Contact Reaction Forces during Animal Adhesion Landing/Takeoff from Leaf-like Compliant Substrates.

A precise measurement of animal behavior and reaction forces from their surroundings can help elucidate the fundamental principle of animal locomotion, such as landing and takeoff. Compared with stiff substrates, compliant substrates, like leaves, readily yield to loads, presenting grand challenges in measuring the reaction forces on the substrates involving compliance. To gain insight into the kinematic mechanisms and structural-functional evolution associated with arboreal animal locomotion, this study introduces an innovative device that facilitates the quantification of the reaction forces on compliant substrates, like leaves. By utilizing the stiffness-damping characteristics of servomotors and the adjustable length of a cantilever structure, the substrate compliance of the device can be accurately controlled. The substrate was further connected to a force sensor and an acceleration sensor. With the cooperation of these sensors, the measured interaction force between the animal and the compliant substrate prevented the effects of inertial force coupling. The device was calibrated under preset conditions, and its force measurement accuracy was validated, with the error between the actual measured and theoretical values being no greater than 10%. Force curves were measured, and frictional adhesion coefficients were calculated from comparative experiments on the landing/takeoff of adherent animals (tree frogs and geckos) on this device. Analysis revealed that the adhesion force limits were significantly lower than previously reported values (0.2~0.4 times those estimated in previous research). This apparatus provides mechanical evidence for elucidating structural-functional relationships exhibited by animals during locomotion and can serve as an experimental platform for optimizing the locomotion of bioinspired robots on compliant substrates.

Quality of life, household income, and dietary habits are associated with the risk of sarcopenia among the Chinese elderly.

BACKGROUND: Health-related quality of life (HRQoL), which can be influenced by various aspects, especially socioeconomic status and lifestyle, has been identified as an important predictor of the prognosis of older adults. Dietary habit, a major part of lifestyle, can affect the nutritional status, which is closely correlated with the development of geriatric syndromes in the elderly. AIMS: The aim of the study was to examine the association of HRQoL, socioeconomic status, and lifestyle with the risk and severity of sarcopenia, a geriatric syndrome characterized by progressive loss of skeletal muscle mass, strength and function. METHODS: A cross-sectional retrospective study with 2877 participants aged ≥65 years was performed. HRQoL was assessed using EuroQoL Five Dimensions questionnaire. Socioeconomic status was assessed by the educational attainment, occupation, and household income. Lifestyle was assessed using 12 items closely related to Chinese living habits. The information of daily dietary habits including tea, alcohol, type of diet, and volume of drinking water were collected. The associations of HRQoL, socioeconomic status, and lifestyle with the risk of sarcopenia were examined by multivariate regression logistical analysis. The potential causal role of age, body mass index, and waist circumference in the effect of HRQoL on sarcopenia risk was analyzed by causal mediation analysis. RESULTS: High HRQoL [adjusted odds ratio (OR) =0.85, 95% confidence interval (CI) =0.69-0.95, P=0.034] and household income levels (adjusted OR =0.74, 95% CI =0.57-0.95, P=0.019) were inversely associated with the risk of sarcopenia. Meanwhile, more consumption of spicy food (adjusted OR =1.34, 95% CI =1.09-1.81, P =0.037) and occasionally drinking (adjusted OR =1.46, 95% CI =1.07-2.00, P =0.016, as compared to those never drinking) were associated with higher risk of sarcopenia, while skipping breakfast occasionally (adjusted OR =0.37, 95% CI =0.21-0.64, P <0.001, as compared to those eating breakfast every day) and less consumption of salt (adjusted OR =0.71, 95% CI =0.52-0.96, P =0.026, as compared to those consuming high amount of salt) were associated with lower risk of sarcopenia. Further causal mediation analysis aimed to explore how much age, body mass index, and waist circumference might explain the effect of HRQoL on the risk of sarcopenia showed that the estimated proportion that mediated the effect of HRQoL on the risk of sarcopenia by age was 28.0%. CONCLUSIONS: In summary, our findings demonstrate that low levels of HRQoL and household income, more intake of salt and spicy food, and occasional intake of alcohol are correlated with higher risk of sarcopenia, while skipping breakfast occasionally is associated with lower risk of sarcopenia in a Chinese population of older adults.

Photo-Responsive Ascorbic Acid-Modified Ag2S-ZnS Heteronanostructure Dropping pH to Trigger Synergistic Antibacterial and Bohr Effects for Accelerating Infected Wound Healing.

Nonantibiotic approaches must be developed to kill pathogenic bacteria and ensure that clinicians have a means to treat wounds that are infected by multidrug-resistant bacteria. This study prepared matchstick-like Ag2S-ZnS heteronanostructures (HNSs). Their hydrophobic surfactants were then replaced with hydrophilic poly(ethylene glycol) (PEG) and thioglycolic acid (TGA) through the ligand exchange method, and this was followed by ascorbic acid (AA) conjugation with TGA through esterification, yielding well-dispersed PEGylated Ag2S-ZnS@TGA-AA HNSs. The ZnS component of the HNSs has innate semiconductivity, enabling the generation of electron-hole pairs upon irradiation with a light of wavelength 320 nm. These separate charges can react with oxygen and water around the HNSs to produce reactive oxygen species. Moreover, some holes can oxidize the surface-grafted AA to produce protons, decreasing the local pH and resulting in the corrosion of Ag2S, which releases silver ions. In evaluation tests, the PEGylated Ag2S-ZnS@TGA-AA had synergistic antibacterial ability and inhibited Gram-negative Escherichia coli and Gram-positive methicillin-resistant Staphylococcus aureus (MRSA). Additionally, MRSA-infected wounds treated with a single dose of PEGylated Ag2S-ZnS@TGA-AA HNSs under light exposure healed significantly more quickly than those not treated, a result attributable to the HNSs' excellent antibacterial and Bohr effects.

Gold-Manganese Bimetallic Redox Coupling with Light.

The classical Au(I)/Au(III) redox couple chemistry has been limited to constructing C-C and C-X bonds, and thus, the exploration of the elementary reaction of gold redox coupling is very significant to enrich its organometallic features. Herein, we report the first visible-light-mediated, external oxidant-free Au(I)/Au(III) redox couple using commercially available Mn2(CO)10 to generate Mn-Au(III)-Mn intermediates for bimetallic redox coupling. A wide range of structurally diverse heterodinuclear and polynuclear L-Au(I)-Mn-L' complexes (19 examples, up to >99% yields) are readily constructed, providing a robust strategy for the concise construction of Au-Mn complexes under mild reaction conditions. The mechanistic studies together with DFT calculations support the radical oxidative addition of •Mn(CO)5 to gold and bimetallic reductive elimination mechanisms from highly active Mn-Au(III)-Mn species, representing an important step toward an elementary reaction in gold chemistry research. Furthermore, the resulting Au-Mn complexes exhibit unique catalytic activity, with which divergent reductive coupling of nitroarenes can readily afford azoxybenzenes, azobenzenes, and hydrazobenzenes in moderate to good yields.

Spatial-temporal pattern of change in production-living-ecological space of Nanchong City from 2000 to 2020 and underlying factors.

This study analyzed the spatial-temporal change pattern and underlying factors in production-living-ecological space (PLES) of Nanchong City, China, over the past 20 years using historical land use data (2000, 2010, 2020). A land use transfer matrix was calculated from the historical land use maps, and spatial analysis was conducted to analyze changes in the land use dynamics degree, standard deviation ellipse, and center of gravity. The results showed that there was a rapid spatial evolution of the PLES in Nanchong from 2000 to 2010, followed by a stabilization in the second decade. The transfer of ecological-production space occurred mainly in the Jialing and Yilong River basins, while the reduction of production space and the increase of living space were most prominent in the intersection of three districts (Shunqing, Jialing, and Gaoping districts). The return of production-ecological space was observed in the south and northeast of Yingshan, and there was little notable transfer of other types. The distribution of production space in Nanchong evolved in a north-south to east-west trend, with the center of gravity moving from Yilong to Peng'an County. The living space and production space expanded in a north-south direction, and the center of gravity position was in Nanbu, indicating a more balanced growth or decrease in the last 20 years. The changes in the spatial-temporal pattern of PLES in Nanchong were attributed to the intertwined factors of national policies, economic development, population growth, and the natural environment. This study introduced a novel approach towards rational planning of land resources in Nanchong, which may facilitate more sustainable urban planning and development.

Dinuclear Gold-Catalyzed para-Selective C-H Arylation of Undirected Arenes by Noncovalent Interactions.

The regioselectivity of C-H functionalization is commonly achieved by directing groups, electronic factors, or steric hindrance, which facilitate the identification of reaction sites. However, such strategies are less effective for reactants such as simple monofluoroarenes due to their relatively low reactivity and the modest steric demands of the fluorine atom. Herein, we present an undirected gold-catalyzed para-C-H arylation of a wide array of monofluoroarenes using air-stable aryl silanes and germanes at room temperature. A high para-regioselectivity (up to 98 : 2) can be realized by utilizing a dinuclear dppm(AuOTs)2 (dppm=bis(diphenylphosphino)methane) as the catalyst and hexafluorobenzene as the solvent. This provides a general and practical protocol for the concise construction of structurally diverse para-arylated monofluoroarenes through C-H activation manner. It features excellent functional group tolerance and a broad substrate scope (>80 examples). Besides, this strategy is also robust for other simple monosubstituted arenes and heteroarenes. Our mechanistic studies and theoretical calculations suggest that para-C-H selectivity arises from highly electrophilic and structurally flexible dinuclear Ar-Au(III)-Au(I) species, coupled with noncovalent interaction induced by hexafluorobenzene.

[Screening and obataining of aptamers for the blood group antigen-binding adhesin (BabA) to block Helicobacter pylori (H.pylori) colonization in the stomach of mice].

Objective To explore the aptamer specific binding blood group antigen-binding adhesin (BabA) of Helicobacter pylori (H.pylori) for blocking of H.pylori adhering host cell. Methods H.pylori strain was cultured and its genome was extracted as templates to amplify the BabA gene by PCR with designed primers. The BabA gene obtained was cloned and constructed into prokaryotic expression plasmid, which was induced by isopropyl beta-D-galactoside (IPTG) and purified as target. The single stranded DNA (ssDNA) aptamers that specifically bind to BabA were screened by SELEX. Enzyme-linked oligonucleotide assay (ELONA) was used to detect and evaluate the characteristics of candidate aptamers. The blocking effect of ssDNA aptamers on H.pylori adhesion was subsequently verified by flow cytometry and colony counting at the cell level in vitro and in mouse model of infection, respectively. Meanwhile, the levels of cytokines, interleukin 6 (IL-6), IL-8, tumor necrosis factor α (TNF-α), IL-10 and IL-4 in the homogenate of mouse gastric mucosa cells were detected by ELISA. Results The genome of H.pylori ATCC 43504 strains was extracted and the recombinant plasmid pET32a-BabA was constructed. After induction and purification, the relative molecular mass (Mr) of the recombinant BabA protein was about 39 000. The amino acid sequence of recombinent protein was consistent with BabA protein by peptide mass fingerprint (PMF). Five candidate aptamers were selected to bind to the above recombinent BabA protein by SELEX. The aptamers A10, A30 and A42 identified the same site, while A3, A16 and the above three aptamers identified different sites respectively. The aptamer significantly blocked the adhesion of H.pylori in vitro. Animal model experiments showed that the aptamers can block the colonization of H.pylori in gastric mucosa by intragastric injection and reduce the inflammatory response. The levels of IL-4, IL-6, IL-8 and TNF-α in gastric mucosal homogenates in the model group with aptamer treatment were lower than that of model group without treatment. Conclusion Aptamers can reduce the colonization of H.pylori in gastric mucosa via binding BabA to block the adhesion between H.pylori and gastric mucosal epithelial cells.

Merging Manganese and Iminium Catalysis: Selective Hydroalkenylation of Unsaturated Aldehydes and Ketones.

The use of synergistic catalytic strategy can usually circumvent the intrinsic limitations of one catalytic system. In this communication, we disclose a cooperative catalysis strategy of manganese and iminium catalysis to realize selective hydroalkenylation of unsaturated aldehydes and ketones. Its success stems from the LUMO activation of unsaturated carbonyl compounds with secondary amines as the organocatalyst and the synergistic HOMO activation of alkenylboronic acids with Mn2 (CO)8 Br2 . This protocol exhibits several synthetic advances, e.g., simple operation, good functional group compatibility and good regioselectivity. The theoretical calculation indicates the migratory insertion followed by demetallation-isomerization process is kinetically more favorable than Michael-like nucleophilic addition. The use of proline-derived organocatalyst can deliver the desired products in moderate enantioselectivity.

Prussian blue analog with separated active sites to catalyze water driven enhanced catalytic treatments.

Chemodynamic therapy (CDT) uses the Fenton or Fenton-like reaction to yield toxic ‧OH following H2O2 → ‧OH for tumoral therapy. Unfortunately, H2O2 is often taken from the limited endogenous supply of H2O2 in cancer cells. A water oxidation CoFe Prussian blue (CFPB) nanoframes is presented to provide sustained, external energy-free self-supply of ‧OH from H2O to process CDT and/or photothermal therapy (PTT). Unexpectedly, the as-prepared CFPB nanocubes with no near-infrared (NIR) absorption is transformed into CFPB nanoframes with NIR absorption due to the increased Fe3+-N ≡ C-Fe2+ composition through the proposed proton-induced metal replacement reactions. Surprisingly, both the CFPB nanocubes and nanoframes provide for the self-supply of O2, H2O2, and ‧OH from H2O, with the nanoframe outperforming in the production of ‧OH. Simulation analysis indicates separated active sites in catalyzation of water oxidation, oxygen reduction, and Fenton-like reactions from CFPB. The liposome-covered CFPB nanoframes prepared for controllable water-driven CDT for male tumoral mice treatments.

Electroactive membrane fusion-liposome for increased electron transfer to enhance radiodynamic therapy.

Dynamic therapies have potential in cancer treatments but have limitations in efficiency and penetration depth. Here a membrane-integrated liposome (MIL) is created to coat titanium dioxide (TiO2) nanoparticles to enhance electron transfer and increase radical production under low-dose X-ray irradiation. The exoelectrogenic Shewanella oneidensis MR-1 microorganism presents an innate capability for extracellular electron transfer (EET). An EET-mimicking photocatalytic system is created by coating the TiO2 nanoparticles with the MIL, which significantly enhances superoxide anions generation under low-dose (1 Gy) X-ray activation. The c-type cytochromes-constructed electron channel in the membrane mimics electron transfer to surrounding oxygen. Moreover, the hole transport in the valence band is also observed for water oxidation to produce hydroxyl radicals. The TiO2@MIL system is demonstrated against orthotopic liver tumours in vivo.

IRAK-M Ablation Promotes Status Epilepticus-Induced Neuroinflammation via Activating M1 Microglia and Impairing Excitatory Synaptic Function.

Epilepsy is one of the most common neurological disorders. The pro-epileptic and antiepileptic roles of microglia have recently garnered significant attention. Interleukin-1 receptor-associated kinase (IRAK)-M, an important kinase in the innate immune response, is mainly expressed in microglia and acts as a negative regulator of the TLR4 signaling pathway that mediates the anti-inflammatory effect. However, whether IRAK-M exerts a protective role in epileptogenesis as well as the molecular and cellular mechanisms underlying these processes are yet to be elucidated. An epilepsy mouse model induced by pilocarpine was used in this study. Real-time quantitative polymerase chain reaction and western blot analysis were used to analyze mRNA and protein expression levels, respectively. Whole-cell voltage-clamp recordings were employed to evaluate the glutamatergic synaptic transmission in hippocampal neurons. Immunofluorescence was utilized to show the glial cell activation and neuronal loss. Furthermore, the proportion of microglia was analyzed using flow cytometry. Seizure dynamics influenced the expression of IRAK-M. Its knockout dramatically exacerbated the seizures and the pathology in epilepsy and increased the N-methyl-d-aspartate receptor (NMDAR) expression, thereby enhancing glutamatergic synaptic transmission in hippocampal CA1 pyramidal neurons in mice. Furthermore, IRAK-M deficiency augmented hippocampal neuronal loss via a possible mechanism of NMDAR-mediated excitotoxicity. IRAK-M deletion promotes microglia toward the M1 phenotype, which resulted in high levels of proinflammatory cytokines and was accompanied by a visible increase in the expressions of key microglial polarization-related proteins, including p-STAT1, TRAF6, and SOCS1. The findings demonstrate that IRAK-M dysfunction contributes to the progression of epilepsy by increasing M1 microglial polarization and glutamatergic synaptic transmission. This is possibly related to NMDARs, particularly Grin2A and Grin2B, which suggests that IRAK-M could serve as a novel therapeutic target for the direct alleviation of epilepsy.

Dinuclear-gold-catalyzed cyclization of 1,7-enynes with alkyl bromides.

Dinuclear-gold-catalyzed radical difunctionalization of alkyl bromides with 1,7-enynes has been established via dehalogenation and 1,5-HAT processes. This protocol was used to construct, in a facile and efficient manner, a wide range of cyclopenta[c]quinolines bearing two quaternary carbon centers with good yields (28 examples, up to 84% yield). The good functional group compatibility and gram-scale preparation ability of the reaction proved its synthetic robustness.

Site-Selective Arylation of Carboxamides from Unprotected Peptides.

The amidated peptides are an important class of biologically active compounds due to their unique biological properties and wide applications as potential peptide drugs and biomarkers. Despite the abundance of free amide motifs (Asn, Gln, and C-terminal amide) in native peptides, late-stage modification of the amide unit in naturally occurring peptides remains very rare because of the intrinsically weak nucleophilicity of amides and the interference of multiple competing nucleophilic residues, which generally lead to undesired side reactions. Herein, chemoselective arylation of amides in unprotected polypeptides has been developed under an air atmosphere to afford the N-aryl amide peptides bearing various functional motifs. Its success relies on the combination of gold catalysis and silver salt to differentiate the relative inert amide among a collection of reactive nucleophilic amino acid residues (e.g., -NH2, -OH, and -COOH), favoring the C-N bond coupling toward amides over other more nucleophilic groups. Experimental and DFT studies reveal a crucial role of the silver cation, which serves as a transient coordination mask of the more reactive reaction sites, overcoming the inherently low reactivity of amides. The excellent biocompatibility of this strategy has been applied to functionalize a wide range of peptide drugs and complex peptides. The application could be further extended to peptide labeling and peptide stapling.

Gold-catalyzed four-component multifunctionalization of alkynes.

The alkyne unit is a versatile building block in organic synthesis and the development of selective multifunctionalization of alkynes is an important object of research in this field. Herein, we report an interesting gold-catalyzed, four-component reaction that achieves the oxo-arylfluorination or oxo-arylalkenylation of internal aromatic or aliphatic alkynes, efficiently breaking a carbon-carbon triple bond and forming four new chemical bonds. The reaction divergence can be controlled by site-directing functional groups in the alkynes; the presence of a phosphonate unit favors the oxo-arylfluorination, while the carboxylate motif benefits oxo-arylalkenylation. This reaction is enabled by an Au(I)/Au(III) redox coupling process using Selectfluor as both an oxidant and a fluorinating reagent. A wide range of structurally diverse α,α-disubstituted ketones, and tri- or tetra-substituted unsaturated ketones have been prepared in synthetically valuable yields and with excellent chemo-, regio- and stereoselectivity. The gram-scale preparation and late-stage application of complex alkynes have further enhanced their synthetic value.

Trinuclear Gold-Catalyzed 1,2-Difunctionalization of Alkenes.

Activated alkyl halides have been extensively explored to generate alkyl radicals with Ru- and Ir- photocatalysts for 1,2-difunctionalization of alkenes, but unactivated alkyl bromides remain challenging substrates due to their strong reduction potential. Here we report a three-component 1,2-difunctionalization reaction of alkenes, unactivated alkyl bromides and nucleophiles (e.g., amines and indoles) using a trinuclear gold catalyst [Au3 (tppm)2 ](OTf)3 . It can achieve the 1,2-aminoalkylation and 1,2-alkylarylation readily. This protocol has a broad reaction scope and excellent functional group compatibility (>100 examples with up to 96 % yield). It also affords a robust formal [2+2+1] cyclization strategy for the concise construction of pyrrolidine skeletons under mild reaction conditions. Mechanistic studies support an inner-sphere single electron transfer pathway for the successful cleavage of inert C-Br bonds.

Unlocking Migratory Insertion in Gold Redox Catalysis.

Exploration of elementary reactions in organometallic catalysis is an important method with which to discover new reactions. In this article, we report a gold(I)-catalyzed iodo-alkynylation of benzyne involving the merging of challenging migratory insertion and an oxidative addition process in gold catalytic cycle. A wide range of structurally diverse alkynyl iodides are good coupling partners in this iodo-alkynylation transformation. Both aliphatic and aromatic alkynyl iodides can react with benzynes smoothly to afford highly functionalized 1,2-disubstituted aromatics in moderate to good yields. Its good functional group compatibility and late-stage application of complex molecules demonstrate its synthetic robustness. Studies of the mechanism reveals the feasibility of oxidative addition and the DFT calculations demonstrate the possible migratory insertion of benzyne into AuIII -carbon bonds in the AuI /AuIII redox catalytic cycle, representing an important step towards an elementary reaction in gold chemistry research.

PT-Symmetric Feedback Induced Linewidth Narrowing.

Narrow linewidth is a long-pursued goal in precision measurement and sensing. We propose a parity-time symmetric (PT-symmetric) feedback method to narrow the linewidths of resonance systems. By using a quadrature measurement-feedback loop, we transform a dissipative resonance system into a PT-symmetric system. Unlike the conventional PT-symmetric systems that typically require two or more modes, here the PT-symmetric feedback system contains only a single resonance mode, which greatly extends the scope of applications. The method enables remarkable linewidth narrowing and enhancement of measurement sensitivity. We illustrate the concept in a thermal ensemble of atoms, achieving a 48-fold narrowing of the magnetic resonance linewidth. By applying the method in magnetometry, we realize a 22-times improvement of the measurement sensitivity. This work opens the avenue for studying non-Hermitian physics and high-precision measurements in resonance systems with feedback.

Constraints on Spin-Spin Velocity-Dependent Interactions.

The existence of exotic spin-dependent forces may shine light on new physics beyond the standard model. We utilize two iron shielded SmCo_{5} electron-spin sources and two optically pumped magnetometers to search for exotic long-range spin-spin velocity-dependent force. The orientations of spin sources and magnetometers are optimized such that the exotic force is enhanced and common-mode noise is effectively subtracted. We set direct limit on proton-electron interaction in the force range from 1 cm to 1 km. Our experiment represents more than 10 orders of magnitude improvement than previous works.