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Oxidation of styrene is a key reaction in the synthesis of pharmaceuticals and fine chemicals, and therefore oxidizing styrene with selective, efficient, and recyclable heterogeneous catalysts is significant from an environmental and economic standpoint. In this study, we report the transition Cr-based metal-organic framework [NH 2 -MIL-101(Cr)] as a heterogeneous photocatalyst, which efficiently promotes styrene epoxidation using H 2 O 2 as a green oxidant, achieving high conversion efficiency (98%) and excellent selectivity (82%) under ambient conditions. Radical detection and quenching experiments reveal that the superoxide radical anion (O 2 ˙ - ) acts as an active oxygen species, selectively promoting the oxidation of styrene to its oxidized form. This work provides insight into the development of a sustainable and cost-effective method for producing styrene oxide.

Limited by the strong oxidation environment and sluggish reconstruction process in oxygen evolution reaction (OER), designing rapid self-reconstruction with high activity and stability electrocatalysts is crucial to promoting anion exchange membrane (AEM) water electrolyzer. Herein, trace Fe/S-modified Ni oxyhydroxide (Fe/S-NiOOH/NF) nanowires are constructed via a simple in situ electrochemical oxidation strategy based on precipitation-dissolution equilibrium. In situ characterization techniques reveal that the successful introduction of Fe and S leads to lattice disorder and boosts favorable hydroxyl capture, accelerating the formation of highly active γ-NiOOH. The Density Functional Theory (DFT) calculations have also verified that the incorporation of Fe and S optimizes the electrons redistribution and the d-band center, decreasing the energy barrier of the rate-determining step ( * O→ * OOH). Benefited from the unique electronic structure and intermediate adsorption, the Fe/S-NiOOH/NF catalyst only requires the overpotential of 345 mV to reach the industrial current density of 1000 mA cm -2 for 120 h. Meanwhile, assembled AEM water electrolyzer (Fe/S-NiOOH//Pt/C-60 °C) can deliver 1000 mA cm -2 at a cell voltage of 2.24 V, operating at the average energy efficiency of 71% for 100 h. In summary, this work presents a rapid self-reconstruction strategy for high-performance AEM electrocatalysts for future hydrogen economy., (© 2024 Wiley‐VCH GmbH.)

The poor conductivities and instabilities of accessible nickel oxyhydroxides hinder their use as oxygen evolution reaction (OER) electrocatalysts. Herein, we constructed Fe-NiOOH-O V -600, an Fe-doped nickel oxide hydroxide with abundant oxygen vacancies supported on nickel foam (NF), using a hydrothermal method and an electrochemical activation strategy involving 600 cycles of cyclic voltammetry, assisted by the precipitation/dissolution equilibrium of ferrous sulfide (FeS) in the electrolyte. This two-step method endows the catalyst with abundant Fe-containing active sites while maintaining the ordered structure of nickel oxide hydroxide (NiOOH). Characterization and density functional theory (DFT) calculations revealed that synergy between trace amounts of the Fe dopant and the oxygen vacancies not only promotes the generation of reconstructed active layers but also optimizes the electronic structure and adsorption capacity of the active sites. Consequently, the as-prepared Fe-NiOOH-O V -600 delivered large current densities of 100 and 1000 mA cm -2 for the OER at overpotentials of only 253 and 333 mV in 1 mol/L KOH. Moreover, the catalyst is stable for at least 100 h at 500 mA cm -2 . This work provides insight into the design of efficient transition-metal-based electrocatalysts for the OER., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Metal organic framework (MOF) is currently-one of the key catalysts for oxygen evolution reaction (OER), but its catalytic performance is severely limited by electronic configuration. In this study, cobalt oxide (CoO) on nickel foam (NF) was first prepared, which then wrapped it with FeBTC synthesized by ligating isophthalic acid (BTC) with iron ions by electrodeposition to obtain CoO@FeBTC/NF p-n heterojunction structure. The catalyst requires only 255 mV overpotential to reach a current density of 100 mA cm -2 , and can maintain 100 h long time stability at 500 mA cm -2 high current density. The catalytic properties are mainly related to the strong induced modulation of electrons in FeBTC by holes in the p-type CoO, which results in stronger bonding and faster electron transfer between FeBTC and hydroxide. At the same time, the uncoordinated BTC at the solid-liquid interface ionizes acidic radicals which form hydrogen bonds with the hydroxyl radicals in solution, capturing them onto the catalyst surface for the catalytic reaction. In addition, CoO@FeBTC/NF also has strong application prospects in alkaline electrolyzers, which only needs 1.78 V to reach a current density of 1 A cm -2 , and it can maintain long-term stability for 12 h at this current. This study provides a new convenient and efficient approach for the control design of the electronic structure of MOF, leading to a more efficient electrocatalytic process., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

The enantioconvergent C(sp 3 )-N cross-coupling of racemic alkyl halides with (hetero)aromatic amines represents an ideal means to afford enantioenriched N -alkyl (hetero)aromatic amines yet has remained unexplored due to the catalyst poisoning specifically for strong-coordinating heteroaromatic amines. Here, we demonstrate a copper-catalyzed enantioconvergent radical C(sp 3 )-N cross-coupling of activated racemic alkyl halides with (hetero)aromatic amines under ambient conditions. The key to success is the judicious selection of appropriate multidentate anionic ligands through readily fine-tuning both electronic and steric properties for the formation of a stable and rigid chelating Cu complex. Thus, this kind of ligand could not only enhance the reducing capability of a copper catalyst to provide an enantioconvergent radical pathway but also avoid the coordination with other coordinating heteroatoms, thereby overcoming catalyst poisoning and/or chiral ligand displacement. This protocol covers a wide range of coupling partners (89 examples for activated racemic secondary/tertiary alkyl bromides/chlorides and (hetero)aromatic amines) with high functional group compatibility. When allied with follow-up transformations, it provides a highly flexible platform to access synthetically useful enantioenriched amine building blocks.

Chiral amines are commonly used in the pharmaceutical and agrochemical industries 1 . The strong demand for unnatural chiral amines has driven the development of catalytic asymmetric methods 1,2 . Although the N-alkylation of aliphatic amines with alkyl halides has been widely adopted for over 100 years, catalyst poisoning and unfettered reactivity have been preventing the development of a catalyst-controlled enantioselective version 3-5 . Here we report the use of chiral tridentate anionic ligands to enable the copper-catalysed chemoselective and enantioconvergent N-alkylation of aliphatic amines with α-carbonyl alkyl chlorides. This method can directly convert feedstock chemicals, including ammonia and pharmaceutically relevant amines, into unnatural chiral α-amino amides under mild and robust conditions. Excellent enantioselectivity and functional-group tolerance were observed. The power of the method is demonstrated in a number of complex settings, including late-stage functionalization and in the expedited synthesis of diverse amine drug molecules. The current method indicates that multidentate anionic ligands are a general solution for overcoming transition-metal-catalyst poisoning., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

The copper-catalyzed enantioconvergent radical C(sp 3 )-C(sp 2 ) cross-coupling of tertiary α-bromo-β-lactams with organoboronate esters could provide the synthetically valuable α-quaternary β-lactams. The challenge arises mainly from the construction of sterically congested quaternary stereocenters between the tertiary alkyl radicals and chiral copper(II) species. Herein, we describe our success in achieving such transformations through the utilization of a copper/hemilabile N,N,N-ligand catalyst to forge the sterically congested chiral C(sp 3 )-C(sp 2 ) bond via a single-electron reduction/transmetalation/bond formation catalytic cycle. The synthetic potential of this approach is shown in the straightforward conversion of the corresponding products into many valuable building blocks. We hope that the developed catalytic cycle would open up new vistas for more enantioconvergent cross-coupling reactions., (© 2022 Wiley-VCH GmbH.)

In contrast with the well-established enantioconvergent radical C(sp 3 )-C cross-coupling of racemic secondary alkyl electrophiles, the corresponding coupling of tertiary electrophiles to forge all-carbon quaternary stereocentres remains underexplored. The major challenge arises from the steric hindrance and the difficult enantio-differentiation of three distinct carbon substituents of prochiral tertiary radicals. Here we demonstrate a general copper-catalysed enantioconvergent C(sp 3 )-C(sp) cross-coupling of diverse racemic tertiary alkyl halides with terminal alkynes (87 examples). Key to the success is the rational design of chiral anionic N,N,N-ligands tailor-made for the computationally predicted outer-sphere radical group transfer pathway. This protocol provides a practical platform for the construction of chiral C(sp 3 )-C(sp/sp 2 /sp 3 ) bonds, allowing for expedient access to an array of synthetically challenging quaternary carbon building blocks of interest in organic synthesis and related areas., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

When the structures of 1342 molecules are optimized by 30 methods and 7 basis sets, there appear 289 (21.54%) problematic molecules and 112 (8.35%) failed ones. When 278 problematic molecules are compared, the best methods are BHandH and LC-wPBE, while B97D, BP86, HFS, VSXC, and HCTH are very unreliable. When 179 problematic molecules are computed with larger basis sets, the smallest mean absolute deviation (MAD) of bond angle (2.3°) is shown by QCISD(T)/cc-pVTZ, while the smallest MAD of bond length (0.021 Å), the best SUM1 (4.9 unit), and the best SUM2 (2.4 unit) are shown by DSDPBEP86(Full), DSDPBEP86, PBE1PBE-D3, MP2, and MP2(Full) in combination with aug-cc-pVQZ, cc-pVQZ, Def2QZVP, Def2TZVPP, and/or 6-311++G(3df,3pd). Very large basis sets, for example, larger than cc-pVTZ usually have to be used to obtain very good structures and the performances of many density-functional theory methods are encouraging. The best results may be the limit of modern computational chemistry., (© 2022 Wiley Periodicals LLC.)

α-Chiral alkyl primary amines are virtually universal synthetic precursors for all other α-chiral N-containing compounds ubiquitous in biological, pharmaceutical, and material sciences. The enantioselective amination of common alkyl halides with ammonia is appealing for potential rapid access to α-chiral primary amines, but has hitherto remained rare due to the multifaceted difficulties in using ammonia and the underdeveloped C(sp 3 )-N coupling. Here we demonstrate sulfoximines as excellent ammonia surrogates for enantioconvergent radical C-N coupling with diverse racemic secondary alkyl halides (>60 examples) by copper catalysis under mild thermal conditions. The reaction efficiently provides highly enantioenriched N -alkyl sulfoximines (up to 99% yield and >99% ee) featuring secondary benzyl, propargyl, α-carbonyl alkyl, and α-cyano alkyl stereocenters. In addition, we have converted the masked α-chiral primary amines thus obtained to various synthetic building blocks, ligands, and drugs possessing α-chiral N-functionalities, such as carbamate, carboxylamide, secondary and tertiary amine, and oxazoline, with commonly seen α-substitution patterns. These results shine light on the potential of enantioconvergent radical cross-coupling as a general chiral carbon-heteroatom formation strategy.

The oriented distribution and strong bonding of Fe active sites in multiple metal hydroxides are crucial to modulate activity and stability for efficient oxygen evolution reaction (OER). However, the dispersion and inevitable dissolution of Fe species still need to be addressed through deliberate design. Here, trace amounts of Fe chelated with tannic acid (TA) are precisely anchored to ultrathin Co hydroxides (TF@Co(OH) 2 -t) through a new anodic interfacial coordination assembly strategy: firstly, the ZIF-67@Co(OH) 2 precursor with ultrathin Co(OH) 2 nanosheets vertically grown on the shell, provides abundant active sites and sufficient anchoring regions for subsequent TA-Fe coating; secondly, the TA-Fe ligand network quickly and robustly coats the surface of the Co(OH) 2 via positive potential-driven chronopotentiometry, yielding TF@Co(OH) 2 -t with good dispersion and controllable Fe species. The TA-Fe network efficiently activates Co species and prevents the dissolution of Fe ions. Physical characterization and DFT simulations reveal that the optimized OER activity with 317 mV at 10 mA cm -2 for TF@Co(OH) 2 -500 can be attributed to the accelerated electron transfer, increased active sites, and the moderate fall in d-band center levels due to Fe integration. Moreover, prolonged stability is realized benefiting from the robust TA-Fe coating protecting the actives sites.

Promoting the reconstruction of electrocatalysts during the oxygen evolution reaction (OER) is generally regarded as a promising strategy for enhanced activity. F anions with strong electronegativity are predicted to enhance this transformation. Herein, a fluorine-anion doping route is proposed to convert the well-latticed NiMoO 4 @MNF to amorphous F-NiMoO 4 @MNF by a facile and versatile molten salt strategy. The well-defined nanorod arrays guarantee abundant exposed active sites, rapid mass transfer, and fast gas bubble release. Moreover, the emerged loose amorphous structure is conducive to the dynamic migration of F species and effective penetration of the electrolyte; therefore, the resulting exchange between F and hydroxide anions induces the formation of an active oxy(hydroxide) layer, thus finally optimizing the electronic structure and absorption/desorption energy on the surface of F-NiMoO 4 @MNF. The boosted OER performance of reconstructed F-NiMoO 4 @MNF is reliably confirmed by a low overpotential of 188 mV at 50 mA cm -2 , a small Tafel slope of 33.8 mV dec -1 , and favorable long-term stability. In addition, accelerated hydrogen evolution is observed, which is ascribed to the finely tuned electron distribution. This work would provide a new reconstruction route assisted by F-anion doping to the development of high-performance catalysts.

There is still a lack of competing risk analysis of patients with papillary renal cell carcinoma (pRCC) following surgery. We performed the cumulative incidence function (CIF) to estimate the absolute risks of cancer-specific mortality (CSM) and other-cause mortality (OCM) of pRCC over time, and constructed a nomogram predicting the probability of 2-, 3- and 5-year CSM based on competing risk regression. A total of 5993 pRCC patients who underwent nephrectomy between 2010 and 2016 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. The 2-, 3-, 5-year CSM rates were 3.2%, 4.4% and 6.5%, respectively, and that of OCM were 3.2%, 5.0% and 9.3%, respectively. The estimates of 5-year cumulative mortality were most pronounced among patients aged > 75 years in OCM (17.0%). On multivariable analyses, age, tumor grade, T stage, N stage, and with or without bone, liver and lung metastases were identified as independent predictors of CSM following surgery and were integrated to generate the nomogram. The nomogram achieved a satisfactory discrimination with the AUC t of 0.730 at 5-year, and the calibration curves presented impressive agreements. Taken together, age-related OCM is a significant portion of all-cause mortality in elderly patients and our nomogram can be used for decision-making and patient counselling.

All-optical switch and multiple logic gates have been demonstrated using a hybrid-cavity semiconductor laser composed of a square microcavity and a Fabry-Perot cavity experimentally. In this paper, two-section tri-mode rate equations with optical injection terms are proposed and applied to study all-optical logic gates of NOT, NOR, and NAND operations utilizing the hybrid-cavity laser. Steady-state and dynamical characteristics of all-optical multiple logic gates are simulated, taking into account the influence of mode frequency detuning, gain suppression coefficients, mode Q factor, injection energy, and biasing current. All-optical logic NOT, NOR, and NAND gates up to 20, 15, and 20 Gbit/s are obtained numerically with dynamic extinction ratios of over 20, 20, and 10 dB, respectively, which are potential response speeds of the all-optical logic gates based on the hybrid-cavity semiconductor lasers.

FeOOH on the real catalytic interface for the oxygen evolution reaction (OER) is chemically unstable to dissolve in alkaline media. Herein, based on the perspective of the dynamically stable interface, we purposely design the well-dispersed nanorod arrays of CoMoO 4 as a host on activated iron foam (IF) to realize the optimal redeposition of FeOOH, constructing a self-sacrificial template rich in the FeOOH surface. Notably, at long-time oxidation potential, the precatalyst FeOOH-CoMoO 4 can realize MoO 4 2- dissolution and redeposition of Co oxyhydroxides on FeOOH host simultaneously, constructing a dynamically stable Fe(Co)OOH interface. The introduction of CoOOH improves conductivity and provides synergistic effect with FeOOH to lower the energy barrier for OER and maintain long-time stability, eventually exhibiting a low overpotential of 298 mV to reach the current density of 100 mA cm -2 and high stability over 60 h. This work demonstrates the feasibility of manipulating metal dissolution-redeposition process for a dynamically stable interface.

The development of enantioconvergent cross-coupling of racemic alkyl halides directly with heteroarene C(sp 2 )-H bonds has been impeded by the use of a base at elevated temperature that leads to racemization. We herein report a copper(I)/cinchona-alkaloid-derived N,N,P-ligand catalytic system that enables oxidative addition with racemic alkyl bromides under mild conditions. Thus, coupling with azole C(sp 2 )-H bonds has been achieved in high enantioselectivity, affording a number of potentially useful α-chiral alkylated azoles, such as 1,3,4-oxadiazoles, oxazoles, and benzo[d]oxazoles as well as 1,3,4-triazoles, for drug discovery. Mechanistic experiments indicated facile deprotonation of an azole C(sp 2 )-H bond and the involvement of alkyl radical species under the reaction conditions., (© 2020 Wiley-VCH GmbH.)

The roles played by several inflammatory factors in screening for prostate cancer (PCa) among gray area patients, namely those with serum prostate-specific antigen (PSA) levels between 4 and 10 ng/ml, have not been completely identified, and few effective diagnostic nomograms have been developed exclusively for these patients. We aimed to investigate new independent predictors of positive biopsy (PB) results and develop a novel diagnostic nomogram for this group of patients. The independent predictors of PB results were identified, and a nomogram was constructed using multivariate logistic regression analysis based on a cohort comprising 401 Gy area patients diagnosed at Xijing Hospital (Xi'an, China) between January 2016 and December 2019. The predictive accuracy of the nomogram was assessed using the receiver operating characteristic curve, and the nomogram was calibrated by comparing the prediction with the observation. The performance of the nomogram was further validated using an independent cohort. Finally, lymphocyte-to-monocyte ratio (LMR) > 4.11 and red blood cell distribution width (RDW)-standard deviation (SD) > 42.9 fl were identified as independent protective predictors of PB results, whereas PSA density (PSAD) > 0.141 was identified as an independent risk predictor. The nomogram established using PSAD, LMR, and RDW-SD was perfectly calibrated, and its predictive accuracy was superior to that of PSAD in both internal and external validations (0.827 vs 0.769 and 0.765 vs 0.713, respectively). This study is the first to report the importance of LMR and RDW-SD in screening for PCa among gray area patients and to construct an exclusive nomogram to predict the individual risk of positive 13-core biopsy results in this group of patients. With superior performance over PSAD, our nomogram will help increase the accuracy of PCa screening, thereby avoiding unnecessary biopsy.

A copper-catalyzed intermolecular three-component asymmetric radical 1,2-carboalkynylation of alkenes has been developed, providing straightforward access to diverse chiral alkynes from readily available alkyl halides and terminal alkynes. The utilization of a cinchona alkaloid-derived multidentate N,N,P-ligand is crucial for the efficient radical generation from mildly oxidative precursors by copper and the effective inhibition of the undesired Glaser coupling side reaction. The substrate scope is broad, covering (hetero)aryl-, alkynyl-, and aminocarbonyl-substituted alkenes, (hetero)aryl and alkyl as well as silyl alkynes, and tertiary to primary alkyl radical precursors with excellent functional group compatibility. Facile transformations of the obtained chiral alkynes have also been demonstrated, highlighting the excellent complementarity of this protocol to direct 1,2-dicarbofunctionalization reactions with C( sp 2 / sp 3 )-based reagents.

Continued development of the Sonogashira coupling has made it a well established and versatile reaction for the straightforward formation of C-C bonds, forging the carbon skeletons of broadly useful functionalized molecules. However, asymmetric Sonogashira coupling, particularly for C(sp 3 )-C(sp) bond formation, has remained largely unexplored. Here we demonstrate a general stereoconvergent Sonogashira C(sp 3 )-C(sp) cross-coupling of a broad range of terminal alkynes and racemic alkyl halides (>120 examples) that are enabled by copper-catalysed radical-involved alkynylation using a chiral cinchona alkaloid-based P,N-ligand. Industrially relevant acetylene and propyne are successfully incorporated, laying the foundation for scalable and economic synthetic applications. The potential utility of this method is demonstrated in the facile synthesis of stereoenriched bioactive or functional molecule derivatives, medicinal compounds and natural products that feature a range of chiral C(sp 3 )-C(sp/sp 2 /sp 3 ) bonds. This work emphasizes the importance of radical species for developing enantioconvergent transformations.

Osteosarcoma is an aggressive bone tumor characterized by a high level of genetic instability and recurring DNA deletions and amplifications. This study aims to investigate how microRNA-496 (miR-496) affects proliferation, invasion, and migration of human osteosarcoma (OS) cells and in vivo tumorigenicity by targeting eukaryotic translation initiation factor 4E (eIF4E). Microarray-based gene expression profiling involving OS was used in order to identify differentially expressed genes. After that, the interaction between miR-496 expression and OS patients' survival rate was determined. The expression pattern of miR-496 and eIF4E was determined in OS tissues and cells, and their potential relationship was further analyzed by using the dual luciferase reporter gene assay. With the purpose of identifying the functional role miR-496 in OS, cell proliferation, migration, and invasion were measured in cells treated with miR-496 mimic or inhibitor. A nude mouse model was constructed in order to investigate the regulatory effects of miR-496 on tumor growth in vivo by regulating eIF4E. OS cells exhibited a down-regulated expression of miR-496 and an up-regulated expression of eIF4E. miR-496 expression was positively correlated to OS patients' survival rate. Bioinformatics analysis suggested eIF4E would be a direct target of miR-496, and the expression of eIF4E was inhibited by overexpression of miR-496. miR-496 elevation was found to exert suppressive effects on OS cell proliferation, migration and invasion in vitro and tumor growth in vivo, with the effects being reversed using miR-496 depletion. Altogether, the above findings support a conclusion that miR-496 could work as a tumor suppressor in OS through down-regulation of eIF4E. This study may provide a novel target for treatment of OS., (Copyright © 2019. Published by Elsevier B.V.)

We propose and demonstrate an optoelectronic oscillator with a directly modulated AlGaInAs/InP integrated twin-square microlaser for generating wideband frequency-tunable microwave signals with low phase noise. Apart from the relaxation oscillation peak, the modulation response of the twin-square microlaser working at the mutual optical injection state exhibits a significant enhancement around the beating frequency of the lasing modes in the two square cavities owing to the photon-photon resonance. A self-sustaining oscillation can be generated around the modulation response peak with the lowest loop loss occurring at the relaxation oscillation frequency or the beating frequency, depending on the practical state of the twin-square microlaser. High-quality tunable microwave signals ranging from 2.22 to 19.52 GHz are generated with single sideband phase noises below -110 dBc/Hz at the 10 kHz offset frequency and side-mode suppression ratios of approximately 40 dB by tuning the injection currents of the twin-square microlaser.

An effective method for millimeter-wave (mmW) carrier generation from a dual-transverse-mode microsquare laser is experimentally demonstrated. By directly modulating the dual-mode microsquare laser at 6.7 GHz, multiple sidebands are generated due to enhanced modulation nonlinearity, and the lasing modes with an interval of 40 GHz are phase-locked. MmW carriers up to 47 GHz, corresponding to seven times that of the modulation frequency, are achieved with a linewidth below 10 Hz. The single-sideband phase noises of the signals keep the same level after transmission over 2.5 km of optical fiber.

AlGaInAs/InP waveguide-coupled deformed hexagonal resonator microlasers with enhanced mode quality (Q)-factors are demonstrated for realizing single-transverse-mode operation. A circular hole is introduced to the center of the hexagonal resonators with rounded corners to enhance the mode Q-factors and suppress high-order transverse modes simultaneously. Single-mode lasing with side-mode suppression ratios up to 40 dB is obtained for the 10-μm-sidelength hexagonal microlasers with a center hole. All the lasing spectra demonstrate pure single-transverse-mode properties within the whole tuning range of injection current, and mode hopping with one, two, and three longitudinal-mode intervals is observed due to the mode Q-factor modification by the center holes. To further reduce the device size and threshold current, the deformed hexagonal resonator microlasers with the flat sides replaced by circular arcs are analyzed and demonstrated experimentally. The Q-factors of the fundamental transverse modes can be enhanced by two orders of magnitude due to the convergence effect of the circular sides by optimizing the deformation amplitude, while the single-transverse-mode property is still maintained. A threshold current of 2.4 mA is realized for a circular-side hexagonal microlaser with the side length of 8.5 μm and the deformation amplitude of 0.55 μm.

Dendritic cell (DC) can be stimulated by both exogenous pathogen-associated molecular patterns (PAMPs) such as lipopolysaccharide (LPS) and endogenous damage-associated molecular patterns (DAMPs) such as high mobility group box-1 protein (HMGB1). MicroRNAs (miRNAs) act as post-transcriptional fine tuners of mRNA. Studies have focused mostly on the potential role of miRNAs in DCs maturation triggered by PAMPs, especially LPS, however, little is known about the regulatory mechanism underlying the effects of miRNAs in DC maturation mediated by DAMPs, including HMGB1. Here, we first profiled a miRNA microarray of DCs stimulated by HMGB1 and determined that the up-regulated miRNA miR-181a-5p may act as a regulatory miRNA in these cells. Computational algorithms predicted TNF-α 3'UTR to be targeted by miR-181a-5p, which was confirmed by the experiments involving luciferase reporters. In addition, we found that TNF-α mRNA was down-regulated by miR-181a-5p mimic, and significantly up-regulated by miR-181a-5p inhibitor. Taken together, we identified miR-181a-5p a negative regulator in HMGB1-induced immune responses by targeting TNF-α mRNA in DCs. Moreover, we suggested that miR-181a-5p may play a role in regulating DC responses to HMGB1 and serve as evidence indicating that novel therapies targeting miRNAs may be useful for treating immune dysfunction in the setting of sepsis.

A compact, simple, and bistable hybrid square-rectangular laser is experimentally demonstrated as an all-optical flip-flop memory. Controllable bistability is induced by two-mode competition, together with the saturable absorption at the square microcavity section. The all-optical set and reset operations are realized by injecting signal pulses at two-mode wavelengths, with the response times of 165 and 60 ps at the triggering pulse width of 100 ps and switching energies of 2.7 and 14.2 fJ, respectively. The robust hybrid-cavity design has an active area of 660  μm 2 and permits efficient unidirectional single-mode lasing, low-power flip-flop operation, and superior fabrication tolerance for monolithic photonic integration.

A novel difunctionalization-type (hetero)arylation of unactivated alkenes has been developed via remote 1,4(5)-(hetero)aryl migration triggered by radical alkene azidation, trifluoromethylation, or phosphonylation. The overall process serves as an unusual and reliable approach for straightforward access to diversely substituted ketones with broad functional group compatibility from readily available substrates and reagents.

Although great success has been achieved in asymmetric fluoroalkylation reactions via nucleophilic or electrophilic processes, the development of asymmetric radical versions of this type of reactions remains a formidable challenge because of the involvement of highly reactive radical species. Here we report a catalytic asymmetric radical aminoperfluoroalkylation and aminodifluoromethylation of alkenes with commercially available fluoroalkylsulfonyl chlorides as the radical sources, providing a versatile platform to access four types of enantioenriched α-tertiary pyrrolidines bearing β-perfluorobutanyl, trifluoromethyl, difluoroacetyl and even difluoromethyl groups in excellent yields and with excellent enantioselectivity. The key to success is not only the introduction of the CuBr/chiral phosphoric acid dual-catalytic system but also the use of silver carbonate to suppress strong background and side hydroamination reactions caused by a stoichiometric amount of the in situ generated HCl. Broad substrate scope, excellent functional group tolerance and versatile functionalization of the products make this approach very practical and attractive.

Background: Epilepsy is a chronic disorder characterized by recurrent seizures and has significant psychological and social consequence for everyday living. Epilepsy affects various aspects of ones' social life. The present study aimed to investigate the influence of marital status on the quality of life of adult Chinese patients with epilepsy., Methods: This study surveyed 805 Chinese adults who have been clinically diagnosed with epilepsy for longer than 1 year in 11 hospitals in Beijing. In this survey, 532 (66.1%) participants were married. All of them completed the case report form with enquiries on demographic data, social factors, and illness. The marriage status of adult epileptic quality of life was the dependent variable, and demographic data and clinical data were independent variables, analyzed through the multiple linear regression analysis methods. The patients' quality of life was assessed using the Quality of Life in patients with Epilepsy-31 items (QOLIE-31) questionnaire, the Patient Health Questionnaire-9 items (PHQ-9), and the Generalized Anxiety Disorder-7 items (GAD-7)., Results: The PHQ-9 and GAD-7 scores in the unmarried group (PHQ-9 = 6.0 and GAD-7 = 5.0) were significantly higher than that of the married group (PHQ-9 = 4.0 and GAD-7 =3.0). The scores of married adult patients with epilepsy on QOLIE (61.8 ± 15.3) and social function (70.9 ± 22.7) were higher than the scores of the unmarried patients aged between 20 and 44 years. The scores of married adult epileptics on the QOLIE (58.4 ± 14.6) and the energy/fatigue (62.1 ± 20.4) were higher than the scores of the unmarried patients (QOLIE = 58.4 ± 14.6 and the energy/fatigue = 62.1 ± 20.4) aged between 45 and 59 years. For the adult epilepsy patients, depression, anxiety, seizures within the last year, disease course, medical expense category, and marriage* age are negatively correlated with the quality of life. Occupation, educational level, and average monthly income are closely related to the quality of life., Conclusions: Married adult epileptic patients have better quality of life than that of unmarried adult patients in young and middle-aged age groups. Unmarried adult patients with epilepsy are more anxious and depressed than married adult patients., Competing Interests: There are no conflicts of interest.

Medium-sized and medium-bridged rings are attractive structural motifs in natural products and therapeutic agents. Due to the unfavourable entropic and/or enthalpic factors with these ring systems, their efficient construction remains a formidable challenge. To address this problem, we herein disclose a radical-based approach for diversity-oriented synthesis of various benzannulated carbon- and heteroatom-containing 8-11(14)-membered ketone libraries. This strategy involves 1,4- or 1,5-aryl migration triggered by radical azidation, trifluoromethylation, phosphonylation, sulfonylation, or perfluoroalkylation of unactivated alkenes followed by intramolecular ring expansion. Demonstration of this method as a highly flexible tool for the construction of 37 synthetically challenging medium-sized and macrocyclic ring scaffolds including bridged rings with diverse functionalities and skeletons is highlighted. Some of these products showed potent inhibitory activity against the cancer cell or derivative of human embryonic kidney line in preliminary biological studies. The mechanism of this novel strategy is investigated by control experiments and DFT calculations.

Background: The detection of solitary pulmonary nodules (SPNs) that may potentially develop into a malignant lesion is essential for early clinical interventions. However, grading classification based on computed tomography (CT) imaging results remains a significant challenge. The 2-[18F]-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography (PET)/CT imaging produces both false-positive and false-negative findings for the diagnosis of SPNs. In this study, we compared 18F-FDG and 3-deoxy-3-[18F]-fluorothymidine (18F-FLT) in lung cancer PET/CT imaging., Methods: The binding ratios of the two tracers to A549 lung cancer cells were calculated. The mouse lung cancer model was established (n = 12), and micro-PET/CT analysis using the two tracers was performed. Images using the two tracers were collected from 55 lung cancer patients with SPNs. The correlation among the cell-tracer binding ratios, standardized uptake values (SUVs), and Ki-67 proliferation marker expression were investigated., Results: The cell-tracer binding ratio for the A549 cells using the 18F-FDG was greater than the ratio using 18F-FLT (P < 0.05). The Ki-67 expression showed a significant positive correlation with the 18F-FLT binding ratio (r = 0.824, P< 0.01). The tumor-to-nontumor uptake ratio of 18F-FDG imaging in xenografts was higher than that of 18F-FLT imaging. The diagnostic sensitivity, specificity, and the accuracy of 18F-FDG for lung cancer were 89%, 67%, and 73%, respectively. Moreover, the diagnostic sensitivity, specificity, and the accuracy of 18F-FLT for lung cancer were 71%, 79%, and 76%, respectively. There was an obvious positive correlation between the lung cancer Ki-67 expression and the mean maximum SUV of 18F-FDG and 18F-FLT (r = 0.658, P< 0.05 and r = 0.724, P< 0.01, respectively)., Conclusions: The 18F-FDG uptake ratio is higher than that of 18F-FLT in A549 cells at the cellular level. 18F-FLT imaging might be superior for the quantitative diagnosis of lung tumor tissue and could distinguish lung cancer nodules from other SPNs., Competing Interests: There are no conflicts of interest.

An effective method for multicoherence wavelength generation is experimentally demonstrated using an integrated twin-microdisk laser as a seeding source. Dual-wavelength lasing with variable wavelength spacing is achieved by adjusting injection currents independently. Using the integrated laser as a pump seed, we obtain multicoherence wavelength in a nonlinear optical fiber, which has a tunable frequency interval from 50 to 300 GHz. Ten waves with optical signal to noise ratio from 28 to 10 dB are produced at the frequency interval of 200 GHz and a pulse width of 1.2 ps. The high extinction ratio of the pulse trace indicates the high coherence in the mode-locked multiwavelength light source.

Background: Epilepsy is one of the most common serious neurological disorders. The present study aimed to investigate the influence of occupational status on the quality of life of Chinese adult patients with epilepsy., Methods: This study surveyed 819 subjects clinically diagnosed with epilepsy for more than 1 year in 11 hospitals in Beijing; 586 were employed (71.55%). All subjects completed the case report form with inquiries on demographic data, social factors, and illness. The patients' quality of life was assessed using the quality of life in patients with epilepsy-31 items (QOLIE-31) questionnaire., Results: The QOLIE-31 score in the employed group was significantly higher than that in the unemployed group. Furthermore, the scores in all the sections (overall quality of life, energy/fatigue, emotional well-being, seizure worry, cognition, social function, and medication effects) of the employed group were higher than those of the unemployed group. Both the employed and unemployed groups achieved the highest difference in social function. The QOLIE-31 score of students was higher than those of farmers and workers. Both the students and workers scored higher in the quality of life compared with the adult peasants living with epilepsy. The students and farmers showed significant differences in QOLIE-31 score, cognition, emotional well-being, overall quality of life, energy/fatigue, and social function. In contrast, no significant difference was noted in seizure worry and medication effects across the three different kinds of occupation., Conclusion: Occupational status might affect the quality of life of Chinese adult patients with epilepsy, and social function is the most important contributing factor.

Background: We analyzed the expression of heme oxygenase-1 (HO-1) in patients undergoing radical nephrectomy for advanced clear cell renal cell carcinoma (CC-RCC) and evaluated the effects of the targeted therapies treated with sorafenib and sunitinib., Methods: Expression of HO-1 in cancer tissue from 66 patients was measured by immunohis-tochemical staining. The patients received either oral sorafenib (n=40) or oral sunitinib (n=26) within 4 weeks after nephrectomy and were followed up long term to determine the tumor response and prognosis., Results: Our current study revealed a high HO-1 expression level in 57.6% (38/66) of patients and a low HO-1 expression level in 42.4% (28/66) of patients with CC-RCC. The study also revealed that patients with high HO-1 expression did not have a higher objective response rate (2.6% versus 53.6%, P<0.01), clinical benefit rate (47.4% versus 92.9%, P<0.01), longer progression-free survival (4.4 versus 42 months, P=0.022), or overall survival (χ (2)=4.775, P=0.029) than patients with low HO-1 expression. In the low HO-1 level group, a higher tumor response rate and a longer survival time was achieved in patients who received sorafenib or sunitinib. Multivariate analysis showed that HO-1 expression was an independent prognostic factor for tumor response and overall survival., Conclusion: High expression of HO-1 was associated with a lower tumor response rate and a shorter overall survival time when compared with low expression of HO-1. Overall, HO-1 expression might be a useful biomarker for predicting the response to sunitinib and sorafenib for patients with metastatic CC-RCC.

Purpose: To compare the treatment outcomes of concurrent involved-field radiotherapy and XELOX (oxaliplatin and capecitabine) versus XELOX chemotherapy alone in gastric adenocarcinoma patients with locoregional recurrence., Materials and Methods: From 2004 to 2008, 79 patients with recurrent locoregional gastric cancer after curative resection of gastric tumor were enrolled. Among them, 41 patients received involved-field radiotherapy (median dose 50 Gy) by a 3-dimensional conformal radiotherapy technique and concurrent XELOX chemotherapy, and 38 patients were treated with XELOX chemotherapy alone (oxaliplatin 130 mg/m, capecitabine 1000 mg/m, twice daily, 3 wk each cycle)., Results: The concurrent radiochemotherapy group showed better overall response (including complete response and partial response) when compared with the chemotherapy group (87.8% vs. 63.0%, P=0.01). The control rates for pain, bleeding, and dysphagia/obstruction were 89.5% (17/19), 81.8% (9/11), and 80% (8/10), respectively, in the radiochemotherapy group and 58.8% (10/17), 50% (5/10), and 57.1% (4/7), respectively, in the chemotherapy group. The concurrent radiochemotherapy group showed better overall symptom-control rate when compared with the chemotherapy group (55.9% vs. 85%, P=0.006). Patients receiving concurrent radiochemotherapy trended toward a better median overall survival when compared with those receiving chemotherapy alone (13.4 vs. 5.4 mo, P=0.06). In addition, there were no significant differences in the rates of toxicity or adverse reactions between the 2 groups., Conclusions: Concurrent involved-field radiotherapy and XELOX showed better responses and overall symptom-control rates compared with XELOX chemotherapy alone in gastric cancer patients with postoperative locoregional recurrence. A trend of survival benefit from radiochemotherapy was also observed but needs to be further explored.

Increased expression of CARMA3 has been reported to be involved in tumorigenesis and tumor progression of several cancer types. The aim of our study is to investigate the prognostic role of CARMA3 expression in patients with renal cell carcinoma (RCC). Real-time quantitative PCR was performed to detect CARMA3 mRNA expression level in 31 paired samples of RCC and adjacent noncancerous renal tissues. Subsequently, extensive immunohistochemistry was performed to detect CARMA3 protein expression in 114 RCC cases. Clinicopathological data for these patients were evaluated. The prognostic significance was assessed using the Kaplan-Meier survival estimates and log-rank tests. CARMA3 mRNA expression was significantly higher in RCC tissues compared with adjacent noncancerous renal tissues (3.525 ± 1.233 vs. 1.512 ± 0.784, P < 0.001). In addition, high CARMA3 expression in RCC tissues was significantly associated with tumor size (P = 0.026), histological differentiation (P = 0.039), tumor stage (P = 0.006), and the presence of metastasis (P < 0.001). Moreover, Kaplan-Meier analysis showed that patients with high CARMA3 expression also had a significantly poorer prognosis than those with low CARMA3 expression (log-rank test, P < 0.001). Furthermore, multivariate analysis illustrated that CARMA3 overexpression might be an independent prognostic indicator for the survival of patients with RCC. In conclusion, this work shows that CARMA3 may serve as a novel and prognostic marker for RCC and play a role during the development and progression of the disease.

The fluorescent components and their distribution and variation of dissolved organic matter (DOM) were examined using excitation emission matrix fluorescence spectroscopy-parallel factor analysis technique (EEMs-PARAFAC) for samples collected during June, 2008 from Minjiang River, a typical subtropical reservoir-type river ecosystem. Three separate fluorescent components were identified by PARAFAC, including two dominant humic-like components (C1: < 250, 325/424 nm; C2: 270, 395/482 nm) and one protein-like component (C3: < 250, 280/358 nm), of which humic-like components were dominant. Fluorescence analysis provided a 'fingerprint' technique to trace the mixing of DOM between three tributaries in the upstream of Minjiang River. The nearly constant concentration and composition in the main stream of Minjiang River reflected the effect of dam construction Correlation and principal component analysis (PCA) revealed that humic-like components were principally derived from flushing of watershed soils, while protein-like component was formed from in-situ production which could be used as a proxy of the concentration of total dissolved nitrogen (TDN). Multi-linear regression of fluorescent components C2 and C3 can be used to trace the variation of dissolved organic carbon (DOC) concentration. This study demonstrates that Minjiang is a typical subtropical reservoir-type river which still keeps relatively 'unpolluted' aquatic environment.

Aim: To study the clinical significance of early diagnosis and differential diagnosis of IL-18 by observing its changes in renal allograft recipients with infection, acute rejection and CsA-induced nephrotoxicity., Methods: The sequential monitoring of serum IL-18 in 90 patients was conducted by ELISA technique before and after renal transplantation with 30 healthy people as control., Results: The levels of serum IL-18 levels in the patients for renal transplantation was significantly higher than that in control before operation(P<0.01). The level of serum IL-18 increased on the first day after transplantation, decreased and stabilized after 10 days. However, it maintained the high levels in acute rejection. The level of IL-18 rapidly decreased with effective methylpredmisolone impaction therapy, but persisted at high level when the therapy did not work. IL-18 also increased in infection, but compared with that in CsA-induced nephrotoxicity, there was no significant difference., Conclusion: The sequential monitoring of serum IL-18 in renal allograft recipients is a useful method to make early and differential diagnosis of acute renal rejection.

Dendritic cells (DCs) are highly potent initiators of the immune response, but DC effector functions are often inhibited by immunosuppressants such as transforming growth factor beta (TGF-beta). The present study was conducted to develop a treatment strategy for prostate cancer using a TGF-beta-insensitive DC vaccine. Tumor lysate-pulsed DCs were rendered TGF-beta insensitive by dominant-negative TGF-beta type II receptor (TbetaRIIDN), leading to the blockade of TGF-beta signals to members of the Smad family, which are the principal cytoplasmic intermediates involved in the transduction of signals from TGF-beta receptors to the nucleus. Expression of TbetaRIIDN did not affect the phenotype of transduced DCs. Phosphorylated Smad-2 was undetectable and expression of surface co-stimulatory molecules (CD80/CD86) were upregulated in TbetaRIIDN DCs after antigen and TGF-beta1 stimulation. Vaccination of C57BL/6 tumor-bearing mice with the TbetaRIIDN DC vaccine induced potent tumor-specific cytotoxic T lymphocyte responses against TRAMP-C2 tumors, increased serum IFN-gamma and IL-12 level, inhibited tumor growth and increased mouse survival. Furthermore, complete tumor regression occurred in two vaccinated mice. These results demonstrate that blocking TGF-beta signals in DC enhances the efficacy of DC-based vaccines.

Aim: To investigate the clinical significance of basic fibroblast growth factor (b-FGF) in human benign prostatic hyperplasia (BPH) and prostatic carcinoma (Pca)., Methods: b-FGF expressions were examined by RNA dot blot hybridization and immunohistochemical staining in prostate tissues from 40 normal cases (NP), 38 BPH and 36 Pca., Results: The expressions of b-FGF in BPH and Pca tissues were significantly higher than those in normal prostate tissues (P < 0.01). There was no significant correlation between the increased expression of b-FGF and the graduation of BPH, pathologic grading as well as clinical stages of Pca., Conclusion: b-FGF may be secreted from BPH and Pca tissues themselves, which is closely involved in the genesis and development of BPH and Pca.

Objective: Coronary heart disease (CHD) is one of the most common causes of death in the world. Some studies suggested that CHD begins in childhood. Obesity and dyslipidemia are important risk factors of coronary heart disease. Apolipoprotein (apo)E gene associated with dyslipidemia and coronary heart disease. The present study was designed to investigate the expression status of apoE gene in peripheral blood monocyte and association of apoE gene expression with lipids in children with obesity., Methods: Among 32 children with obesity and 32 healthy children without obesity or overweight, ApoE gene expressions were determined by competitive reverse transcription-polymerase chain reaction in peripheral blood monocyte. The concentrations of plasma triglyceride, total cholesterol, low density lipoprotein-cholesterol, high density lipoprotein-cholesterol, lipoprotein(a), apoA I, apoB(100) and apoE were measured., Results: Expression of apoE gene was detected in peripheral blood monocyte. Expression of apoE gene was significantly reduced in children with obesity as compared with control group (0.29 +/- 0.14 moles/mole GAPDH mRNA vs. 0.36 +/- 0.10 moles/mole GAPDH mRNA, t = 2.15, P < 0.05). The more severe was the degree of obesity, the more significantly reduced the expression of apoE gene; the degree of obesity was negatively correlated with the levels of expression of apoE gene (correlation coefficient = -0.40, P < 0.05). Compared with control group, the levels of triglyceride, total cholesterol, low density lipoprotein-cholesterol, and apoB(100) were higher, and those of high density lipoprotein-cholesterol, apoA I and apoE were lower in children with obesity [(1.68 +/- 0.50) mmol/L vs. (0.99 +/- 0.54) mmol/L, (4.47 +/- 0.91) mmol/L vs. (3.33 +/- 0.90) mmol/L, (2.23 +/- 0.71) mmol/L vs. (1.13 +/- 0.96) mmol/L, (94.48 +/- 9.97) mg/dl vs. (83.81 +/- 15.64) mg/dl, (1.47 +/- 0.39) mmol/L vs. (1.73 +/- 0.36) mmol/L, (112.71 +/- 27.86) mg/dl vs. (134.80 +/- 45.36) mg/dl, (24.50 +/- 10.92) mg/L vs.(35.07 +/- 9.79) mg/L, respectively, P < 0.05]. ApoE gene expression was associated with plasma lipids metabolism in children with obesity. The quantity of apoE gene expression was inversely associated with low density lipoprotein-cholesterol, positively correlated with apoE (correlation coefficient = -0.33, 0.35, respectively, P < 0.05). The quantity of apoE gene expression was not associated with total cholesterol, triglyceride, high density lipoprotein-cholesterol, lipoprotein(a), apoA I, and apoB(100) (correlation coefficient = -0.19, -0.11, 0.16, 0.09, 0.18, 0.22, P > 0.05)., Conclusion: Expression of apoE gene was significantly reduced in peripheral blood monocyte in children with obesity. The quantity of apoE gene expression was associated with degree of obesity and abnormality of blood lipids.

The reactions between HSA and acidic phenolsulfonphthaleins, including phenol red, cresol red, chlorophenol red, bromocresol purple and m-cresol purple, have been investigated by fluorescence spectrometry. The experiments showed that all of the selected acidic phenolsulfonphthaleins strongly quenched the fluorescence produced by HSA, and this fluorescence quenching could be interpreted in terms of statistic quenching. From the calculation results of binding constants K for these dyes at various temperatures, it could be found that the increase in the functional groups numbers of dyes molecules resulted in an increase in K, while the increase in reaction temperature led to a decrease in K. The interactions between dyes and HSA were attributed to static-electricity gravitation, which was confirmed by the calculation results of enthalpy and entropy for these reactions. According to the non-radiation energy transfer theory, the distances and energy transfer efficiencies between dyes and protein at various temperatures were obtained. These results further supported the conclusion that these reactions belonged to the single static quenching caused by the energy transfer.

On the basis of the difference between the absorption spectra of free and bound BPB, the interaction of bamphenol blue (BPB) with bovine serum albumin (BSA) in acidic solution was investigated by a spectrophotometric method. Solutions containing 5.0 x 10(-6) mol.L-1 of dye concentration and various BSA concentrations from 0.5 x 10(-6) to 3.8 x 10(-6) mol.L-1 were prepared in pH 2.79 Britton-robinson buffer, and the absorbances were measured at 605 nm. The result calculated from the above experiments show that the ratio between the average number of dye molecules bound per protein molecule and the concentration of free BPB is approximately constant. So the interaction of BSA and BPB in the experimental conditions selected in this paper can be regarded as a kind of phase distribution. A simple double reciprocal equation for the estimation of apparent binding constant and the maximum binding number was easily derived. The linear regression between the reciprocal of the observed absorbance change at 605 nm due to the addition of BSA to a fixed quantity of BPB (delta A-1) and the reciprocal of the concentration of BSA (CP-1) was made. All of the regression coefficients for the lines of delta A-1 versus CP-1 obtained from various pH values, BPB concentrations and ion strengths were better than 0.99. Through the ratio of intercept and slop, both the apparent binding constants and the maximum binding numbers were calculated for various experimental conditions.