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Transition metal-catalyzed enantioselective Sonogashira-type oxidative C( sp 3 )—C( sp ) coupling of unactivated C( sp 3 )−H bonds with terminal alkynes has remained a prominent challenge. The difficulties mainly stem from the regiocontrol in unactivated C( sp 3 )—H bond functionalization and the inhibition of readily occurring Glaser homocoupling of terminal alkynes. Here, we report a copper/chiral cinchona alkaloid-based N,N,P -ligand catalyst for asymmetric oxidative cross-coupling of unactivated C( sp 3 )—H bonds with terminal alkynes in a highly regio-, chemo-, and enantioselective manner. The use of N -fluoroamide as a mild oxidant is essential to site-selectively generate alkyl radical species while efficiently avoiding Glaser homocoupling. This reaction accommodates a range of (hetero)aryl and alkyl alkynes; (hetero)benzylic and propargylic C( sp 3 )−H bonds are all applicable. This process allows expedient access to chiral alkynyl amides/aldehydes. More importantly, it also provides a versatile tool for the construction of chiral C( sp 3 )—C( sp ), C( sp 3 )—C( sp 2 ), and C( sp 3 )—C( sp 3 ) bonds when allied with follow-up transformations. Enantioselective oxidative cross-coupling of unactivated C( sp 3 )−H bonds and terminal alkynes is challenging. Here, the authors developed a copper/cinchona alkaloid catalyst for the asymmetric Sonogashira-type alkynylation of C( sp 3 )-H bonds via radical intermediates.

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. Asymmetric Sonogashira C( sp 3 )–C( sp ) couplings provide complementary approaches to established C( sp 3 )–C( sp 2 / sp 3 ) couplings for chiral C–C bond formation; however, relatively few reactions have been developed. Now, a versatile, enantioconvergent Sonogashira coupling via a radical intermediate has been developed. The approach uses a copper catalyst featuring a multidentate electron-rich cinchona alkaloid-derived ligand.

Immunotherapy has become the breakthrough strategies for treatment of cancer in recent years. The application of messenger RNA in cancer immunotherapy is gaining tremendous popularity as mRNA can function as an effective vector for the delivery of therapeutic antibodies on immune targets. The high efficacy, decreased toxicity, rapid manufacturing and safe administration of mRNA vaccines have great advantages over conventional vaccines. The unprecedent success of mRNA vaccines against infection has proved its effectiveness. However, the instability and inefficient delivery of mRNA has cast a shadow on the wide application of this approach. In the past decades, modifications on mRNA structure and delivery methods have been made to solve these questions. This review summarizes recent advancements of mRNA vaccines in cancer immunotherapy and the existing challenges for its clinical application, providing insights on the future optimization of mRNA vaccines for the successful treatment of cancer.

Aims To compare the performance of logistic regression and machine learning methods in predicting postoperative delirium (POD) in elderly patients. Method This was a retrospective study of perioperative medical data from patients undergoing non‐cardiac and non‐neurology surgery over 65 years old from January 2014 to August 2019. Forty‐six perioperative variables were used to predict POD. A traditional logistic regression and five machine learning models (Random Forest, GBM, AdaBoost, XGBoost, and a stacking ensemble model) were compared by the area under the receiver operating characteristic curve (AUC‐ROC), sensitivity, specificity, and precision. Results In total, 29,756 patients were enrolled, and the incidence of POD was 3.22% after variable screening. AUCs were 0.783 (0.765–0.8) for the logistic regression method, 0.78 for random forest, 0.76 for GBM, 0.74 for AdaBoost, 0.73 for XGBoost, and 0.77 for the stacking ensemble model. The respective sensitivities for the 6 aforementioned models were 74.2%, 72.2%, 76.8%, 63.6%, 71.6%, and 67.4%. The respective specificities for the 6 aforementioned models were 70.7%, 99.8%, 96.5%, 98.8%, 96.5%, and 96.1%. The respective precision values for the 6 aforementioned models were 7.8%, 52.3%, 55.6%, 57%, 54.5%, and 56.4%. Conclusions The optimal application of the logistic regression model could provide quick and convenient POD risk identification to help improve the perioperative management of surgical patients because of its better sensitivity, fewer variables, and easier interpretability than the machine learning model. Six prediction models were constructed for POD using logistic regression, RF, AdaBoost, XGBoost, GBM, and stacking ensemble learning based on retrospective analysis of a large sample dataset. The logistic regression model had the same AUC(0.78) with the RF, and performed better than the machine learning models because of its better sensitivity, fewer variables, and easier interpretability.

In this study, the nonlinear vibrations of an axially moving beam are investigated by considering the coupling of the longitudinal and transversal motion. The Galerkin method is used to truncate the governing partial differential equations into a set of coupled nonlinear ordinary differential equations. By detuning the axially velocity, the exact parameters with which the system may turn to internal resonance are detected. The method of multiple scales is applied to the governing equations to study the nonlinear dynamics of the steady-state response caused by the internal–external resonance. The saturation and jump phenomena of such system have been reported by investigating the nonlinear amplitude–response curves with respect to external excitation, internal, and external detuning parameters. The longitudinal external excitation may trigger only longitudinal response when excitation amplitude is weak. However, beyond the critical excitation amplitude, the response energy will be transferred from the longitudinal motion to the transversal motion even the excitation is employed on the longitudinal direction. Such energy transfer due to saturation has the potential to be used in the vibration suppression.

Widespread deployment of NH 3 -adsorbing MOF materials remains challenging due to the significant energy-penalty of regeneration. In this work, we address this limitation by integrating photothermal technologies into a bipyridinium-functionalized MOF matrix, enabling effective NH 3 desorption in a more eco-friendly and sustainable manner. This MOF adsorbent exhibits selective NH 3 capture via specific hydrogen bonding interactions, rendering it suitable for purifying effluent gases in industrial NH 3 synthesis. The NH 3 adsorption process is accompanied by an obvious color change due to the formation of bipyridinium radicals through an electron transfer reaction between NH 3 molecules and bipyridinium ligands. This distinctive property endows the MOF with favorable NH 3 detection capabilities. Furthermore, the colored MOF matrix functions as an exceptional photothermal medium under 808 nm laser irradiation, effectively facilitating the release of captured NH 3 molecules through light-triggered localized heating. Importantly, the synthesis of this MOF material can be scaled up to gram-level with minimal complexity using a straightforward one-pot reflux method, significantly enhancing its practical applicability. An eco-friendly and sustainable NH 3 desorption process has been successfully realized in a bipyridinium-bearing MOF adsorbent via free radical-dominated photothermal conversion for localized heating.

Hepatocellular carcinoma (HCC) is one of the most common human malignancies worldwide with very poor prognosis. Resistance to targeted therapeutic drugs such as sorafenib remains one of the major challenges in clinical treatment. In the present study, PARP1 was found to be highly expressed in human embryonic stem cells, but progressively decreased upon specified hepatic differentiation. Reactivation of PARP1 expression was also detected in HCC residual tumors after sorafenib treatment in xenograft mouse model, indicating the potential important roles of PARP1 in stem cell pluripotency and HCC sorafenib treatment resistance. Overexpression of PARP1 was frequently observed in HCC patients, and closely associated with poor clinical outcome. Treatment of Sorafenib induced activation of DNA damage repair signaling, which is highly active and essential for maintenance of stem cell pluripotency in HCC residual tumors. PARP inhibitor Olaparib extensively suppressed the DNA damage repair signaling, and significantly inhibited the global pluripotent transcriptional network. The repression of key pluripotent transcriptional factors and DNA damage repair signaling by Olaparib was mainly through CHD1L-mediated condensation of the chromatin structure at their promotor regions. The global reshaping of the pluripotent transcriptome by Olaparib might reinforce Sorafenib in eliminating HCC residual tumors and enhance therapeutic efficiency.

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. Methods for the asymmetric introduction of organofluorine groups are often limited by the lack of variability in the starting materials. Here the authors report an asymmetric radical process for the introduction of fluoroalkyl groups using readily available fluoroalkylated sulfonyl chlorides.

As a one of the focuses of ecological research, understanding the regulation of plant diversity on community stability is helpful to reveal the adaption of plant to environmental changes. However, the relationship between plant diversity and community stability is still controversial due to the scale effect of its influencing factors. In this study, we compared the changes in community stability and different plant diversity (i.e., species, functional, and phylogenetic diversities) between three communities (i.e., riparian forest, ecotone community, and desert shrubs), and across three spatial scales (i.e., 100, 400, and 2500 m 2 ), and then quantified the contribution of soil properties and plant diversity to community stability by using structural equation model (SEM) in the Ebinur Lake Basin Nature Reserve of the Xinjiang Uygur Autonomous Region in the NW China. The results showed that: (1) community stability differed among three communities (ecotone community > desert shrubs > riparian forest). The stability of three communities all decreased with the increase of spatial scale (2) species diversity, phylogenetic richness and the mean pairwise phylogenetic distance were higher in ecotone community than that in desert shrubs and riparian forest, while the mean nearest taxa distance showed as riparian forest > ecotone community > desert shrubs. (3) Soil ammonium nitrogen and total phosphorus had the significant direct negative and positive effects on the community stability, respectively. Soil ammonium nitrogen and total phosphorus also indirectly affected community stability by adjusting plant diversity. The interaction among species, functional and phylogenetic diversities also regulated the variation of community stability across the spatial scales. Our results suggested that the effect of plant diversities on community stability were greater than that of soil factors. The asynchronous effect caused by the changes in species composition and functional traits among communities had a positive impact on the stability. Our study provided a theoretical support for the conservation and management of biodiversity and community functions in desert areas.

Flat bands have empowered novel phenomena such as robust canalization with strong localization, high-collimation and low-loss propagation. However, the spatial symmetry protection in photonic or acoustic lattices naturally forces flat bands to manifest in pairs aligned at an inherently specific angle, resulting in a fixed bidirectional canalization. Here, we report an acoustic flat-band metasurface, allowing not only unidirectional canalization at all in-plane angles but also robust tunability in band alignment. The twist, tilt, and skew angles of the bilayer metasurface can be flexibly controlled to break both in-plane and out-of-plane spatial symmetries. These features can thereby turn arbitrary twist angles between bilayers into ‘magic angles’, while maintaining all unidirectional canalization and band alignment tunability. This work may significantly contribute to pushing twisted moiré physics into higher dimensions and facilitate the application of advanced acoustic or optical devices. Flat bands have empowered novel phenomena such as canalization, high-collimation and low-loss propagation. Here, the authors propose the concept of symmetry broken moiré systems, which overcomes the limitations of fixed flat bands, enabling multiple and unidirectional canalizations.