Regioselective and Enantioselective Nickel-Catalyzed Intermolecular Reductive Coupling of Aliphatic Alkenes with Imines.

Unactivated aliphatic alkenes are particularly desirable as starting materials because they are readily accessible in large quantities, but the enantioselective intermolecular reductive coupling of unactivated alkenes with imines is challenging. In this paper, we report a method for nickel-catalyzed intermolecular reductive coupling reactions between aliphatic alkenes and imines to yield chiral amines with excellent enantioselectivities and good linear selectivities. The reaction conditions are compatible with a broad range of aliphatic alkenes, including those derived from bioactive molecules. The success of this method can be attributed to the use of newly developed monodentate chiral spiro phosphine ligands.

Improved charge extraction in inverted perovskite solar cells with dual-site-binding ligands.

Inverted (pin) perovskite solar cells (PSCs) afford improved operating stability in comparison to their nip counterparts but have lagged in power conversion efficiency (PCE). The energetic losses responsible for this PCE deficit in pin PSCs occur primarily at the interfaces between the perovskite and the charge-transport layers. Additive and surface treatments that use passivating ligands usually bind to a single active binding site: This dense packing of electrically resistive passivants perpendicular to the surface may limit the fill factor in pin PSCs. We identified ligands that bind two neighboring lead(II) ion (Pb2+) defect sites in a planar ligand orientation on the perovskite. We fabricated pin PSCs and report a certified quasi-steady state PCE of 26.15 and 24.74% for 0.05- and 1.04-square centimeter illuminated areas, respectively. The devices retain 95% of their initial PCE after 1200 hours of continuous 1 sun maximum power point operation at 65°C.

Surface heterojunction based on n-type low-dimensional perovskite film for highly efficient perovskite tandem solar cells.

Enhancing the quality of junctions is crucial for optimizing carrier extraction and suppressing recombination in semiconductor devices. In recent years, metal halide perovskite has emerged as the most promising next-generation material for optoelectronic devices. However, the construction of high-quality perovskite junctions, as well as characterization and understanding of their carrier polarity and density, remains a challenge. In this study, using combined electrical and spectroscopic characterization techniques, we investigate the doping characteristics of perovskite films by remote molecules, which is corroborated by our theoretical simulations indicating Schottky defects consisting of double ions as effective charge dopants. Through a post-treatment process involving a combination of biammonium and monoammonium molecules, we create a surface layer of n-type low-dimensional perovskite. This surface layer forms a heterojunction with the underlying 3D perovskite film, resulting in a favorable doping profile that enhances carrier extraction. The fabricated device exhibits an outstanding open-circuit voltage (VOC) up to 1.34 V and achieves a certified efficiency of 19.31% for single-junction wide-bandgap (1.77 eV) perovskite solar cells, together with significantly enhanced operational stability, thanks to the improved separation of carriers. Furthermore, we demonstrate the potential of this wide-bandgap device by achieving a certified efficiency of 27.04% and a VOC of 2.12 V in a perovskite/perovskite tandem solar cell configuration.

Triple-junction solar cells with cyanate in ultrawide-bandgap perovskites.

Perovskite bandgap tuning without quality loss makes perovskites unique among solar absorbers, offering promising avenues for tandem solar cells1,2. However, minimizing the voltage loss when their bandgap is increased to above 1.90 eV for triple-junction tandem use is challenging3-5. Here we present a previously unknown pseudohalide, cyanate (OCN-), with a comparable effective ionic radius (1.97 Å) to bromide (1.95 Å) as a bromide substitute. Electron microscopy and X-ray scattering confirm OCN incorporation into the perovskite lattice. This contributes to notable lattice distortion, ranging from 90.5° to 96.6°, a uniform iodide-bromide distribution and consistent microstrain. Owing to these effects, OCN-based perovskite exhibits enhanced defect formation energy and substantially decreased non-radiative recombination. We achieved an inverted perovskite (1.93 eV) single-junction device with an open-circuit voltage (VOC) of 1.422 V, a VOC × FF (fill factor) product exceeding 80% of the Shockley-Queisser limit and stable performance under maximum power point tracking, culminating in a 27.62% efficiency (27.10% certified efficiency) perovskite-perovskite-silicon triple-junction solar cell with 1 cm2 aperture area.

An effective electricity worker identification approach based on Yolov3-Arcface.

To address the issues of low efficiency and high complexity of detection models for electric power workers in distribution rooms, the electric power worker identification approach is proposed. The ArcFace loss function is used as the coordinate regression loss of the target box. According to the score, the template box with the highest score is selected for prediction, which speeds up the rate of convergence. Dimensional clustering is used to set template boxes for bounding box prediction. The experimental results show that the improved YOLOv3 is a high-performance and lightweight model. The electric power worker identification approach proposed in this paper has a high-speed recognition process, accurate recognition results. The effectiveness of the approach is verified with better detection performance and robustness.

Construction of Ge-Stereogenic Center by Desymmetric Carbene Insertion of Dihydrogermanes.

We developed a method for the enantioselective synthesis of germanium-stereogenic compounds by the desymmetric carbene insertion of dihydrogermanes. A chiral rhodium phosphate catalyst decomposes diaryldiazo-methanes to generate rhodium carbenes that insert enantioselectively into one of the two Ge-H bonds of dihydrogermanes to form germanium-stereogenic compounds under mild reaction conditions. By this method, a variety of chiral germanes with germanium-stereogenic centers were synthesized in high yields and excellent enantioselectivities. Kinetic studies of the reaction showed that the diazo decomposition process was the rate-determining step. The remaining Ge-H bond of the chiral germane products provides a possibility for preparing chiral tetra-substituted germanium-stereogenic compounds.

Multimodal non-invasive evaluation in MRI-negative epilepsy patients.

Presurgical evaluation is still challenging for MRI-negative epilepsy patients. As non-invasive modalities are the easiest acceptable and economic methods in determining the epileptogenic zone, we analyzed the localization value of common non-invasive methods in MRI-negative epilepsy patients. In this study, we included epilepsy patients undergoing presurgical evaluation with presurgical negative MRI. MRI post-processing was performed using a Morphometric Analysis Program (MAP) on T1-weighted volumetric MRI. The relationship between MAP, magnetoencephalography (MEG), scalp electroencephalogram (EEG), and seizure outcomes was analyzed to figure out the localization value of different non-invasive methods. Eighty-six patients were included in this study. Complete resection of the MAP-positive regions or the MEG-positive regions was positively associated with seizure freedom (p = 0.028 and 0.007, respectively). When an area is co-localized by MAP and MEG, the resection of the area was significantly associated with seizure freedom (p = 0.006). However, neither the EEG lateralization nor the EEG localization showed statistical association with the surgical outcome (p = 0.683 and 0.505, respectively). In conclusion, scalp EEG had a limited role in presurgical localization and predicting seizure outcome, combining MAP and MEG results can significantly improve the localization of epileptogenic lesions and have a positive association with seizure-free outcome. PLAIN LANGUAGE SUMMARY: Due to the lack of obvious structure abnormalities on neuroimaging examinations, the identification of epilepsy lesions in MRI-negative epilepsy patients can be difficult. In this study, we intended to use non-invasive examinations to explore the potential epileptic lesions in MRI-negative epilepsy patients and to determine the results accuracy by comparing the neuroimaging results with the epilepsy surgery outcomes. A total of 86 epilepsy patients without obvious structure lesions on MRI were included, and we found that the combinations of different non-invasive examinations and neuroimaging post-processing methods are significantly associated with the seizure freedom results of epilepsy surgery.

Ligand-Controlled Regiodivergent Nickel-Catalyzed Hydroaminoalkylation of Unactivated Alkenes.

Ligand modulation of transition-metal catalysts to achieve optimal reactivity and selectivity in alkene hydrofunctionalization is a fundamental challenge in synthetic organic chemistry. Hydroaminoalkylation, an atom-economical approach for alkylating amines using alkenes, is particularly significant for amine synthesis in the pharmaceutical, agrochemical, and fine chemical industries. However, the existing methods usually require specific substrate combinations to achieve precise regio- and stereoselectivity, which limits their practical utility. Protocols allowing for regiodivergent hydroaminoalkylation from the same starting materials, controlling both regiochemical and stereochemical outcomes, are currently absent. Herein, we report a ligand-controlled, regiodivergent nickel-catalyzed hydroaminoalkylation of unactivated alkenes with N-sulfonyl amines. The reaction initiates with amine dehydrogenation and involves aza-nickelacycle intermediates. Tritert-butylphosphine promotes branched regioselectivity and syn diastereoselectivity, whereas ethyldiphenylphosphine enables linear selectivity, yielding regioisomers with inverse orientation. Systematic evaluation of diverse monodentate phosphine ligands reveals distinct regioselectivity cliffs, and % Vbur (min), a ligand steric descriptor, was established as a predictive parameter correlating ligand structure to regioselectivity. Computational investigations supported experimental findings, offering mechanistic insights into the origins of regioselectivity. Our method provides an efficient and predictable route for amine synthesis, demonstrating broad substrate scope, excellent tolerance toward various functional groups, and practical advantages. These include the use of readily available starting materials and cost-effective nickel(II) salts as precatalysts.

miRNA profiling of granulosa cell-derived exosomes reveals their role in promoting follicle development.

To explore whether granulosa cell (GC)-derived exosomes (GC-Exos) and follicular fluid-derived exosomes (FF-Exos) have functional similarities in follicle development and to establish relevant experiments to validate whether GC-Exos could serve as a potential substitute for follicular fluid-derived exosomes to improve folliculogenesis. GC-Exos were characterized. MicroRNA (miRNA) profiles of exosomes from human GCs and follicular fluid were analyzed in depth. The signature was associated with folliculogenesis, such as phosphatidylinositol 3 kinases-protein kinase B signal pathway, mammalian target of rapamycin signal pathway, mitogen-activated protein kinase signal pathway, Wnt signal pathway, and cyclic adenosine monophosphate signal pathway. A total of five prominent miRNAs were found to regulate the above five signaling pathways. These miRNAs include miRNA-486-5p, miRNA-10b-5p, miRNA-100-5p, miRNA-99a-5p, and miRNA-21-5p. The exosomes from GCs and follicular fluid were investigated to explore the effect on folliculogenesis by injecting exosomes into older mice. The proportion of follicles at each stage is counted to help us understand folliculogenesis. Exosomes derived from GCs were isolated successfully. miRNA profiles demonstrated a remarkable overlap between the miRNA profiles of FF-Exos and GC-Exos. The shared miRNA signature exhibited a positive influence on follicle development and activation. Furthermore, exosomes derived from GCs and follicular fluid promoted folliculogenesis in older female mice. Exosomes derived from GCs had similar miRNA profiles and follicle-promoting functions as follicular fluid exosomes. Consequently, GC-Exos are promising for replacing FF-Exos and developing new commercial reagents to improve female fertility.

Asymmetric Synthesis of Cyclopamine, a Hedgehog (Hh) Signaling Pathway Inhibitor.

Cyclopamine is a teratogenic steroidal alkaloid, which inhibits the Hedgehog (Hh) signaling pathway by targeting the Smoothened (Smo) receptor. Suppression of Hh signaling with synthetic small molecules has been pursued as a therapeutic approach for the treatment of cancer. We report herein the asymmetric synthesis of cyclopamine based on a two-stage relay strategy. Stage-I: total synthesis of veratramine through a convergent approach, wherein a crucial photoinduced excited-state Nazarov reaction was applied to construct the basic [6-6-5-6] skeleton of C-nor-D-homo-steroid. Stage-II: conversion of veratramine to cyclopamine was achieved through a sequence of chemo-selective redox manipulations.

Illumination of Hydroxyl Radical in Kidney Injury and High-Throughput Screening of Natural Protectants Using a Fluorescent/Photoacoustic Probe.

The hydroxyl radical (•OH) is shown to play a crucial role in the occurrence and progression of acute kidney injury (AKI). Therefore, the development of a robust •OH probe holds great promise for the early diagnosis of AKI, high-throughput screening (HTS) of natural protectants, and elucidating the molecular mechanism of intervention in AKI. Herein, the design and synthesis of an activatable fluorescent/photoacoustic (PA) probe (CDIA) for sensitive and selective imaging of •OH in AKI is reported. CDIA has near-infrared fluorescence/PA channels and fast activation kinetics, enabling the detection of the onset of •OH in an AKI model. The positive detection time of 12 h using this probe is superior to the 48-hour detection time for typical clinical assays, such as blood urea nitrogen and serum creatinine detection. Furthermore, a method is established using CDIA for HTS of natural •OH inhibitors from herbal medicines. Puerarin is screened out by activating the Sirt1/Nrf2/Keap1 signaling pathway to protect renal cells in AKI. Overall, this work provides a versatile and dual-mode tool for illuminating the •OH-related pathological process in AKI and screening additional compounds to prevent and treat AKI.

A Mid-Infrared Multifunctional Optical Device Based on Fiber Integrated Metasurfaces.

A metasurface is a two-dimensional structure with a subwavelength thickness that can be used to control electromagnetic waves. The integration of optical fibers and metasurfaces has received much attention in recent years. This integrated device has high flexibility and versatility. We propose an optical device based on fiber-integrated metasurfaces in the mid-infrared, which uses a hollow core anti-resonant fiber (HC-ARF) to confine light transmission in an air core. The integrated bilayer metasurfaces at the fiber end face can achieve transmissive modulation of the optical field emitted from the HC-ARF, and the Fano resonance excited by the metasurface can also be used to achieve refractive index (RI) sensing with high sensitivity and high figure of merit (FOM) in the mid-infrared band. In addition, we introduce a polydimethylsiloxane (PDMS) layer between the two metasurfaces; thus, we can achieve tunable function through temperature. This provides an integrated fiber multifunctional optical device in the mid-infrared band, which is expected to play an important role in the fields of high-power mid-infrared lasers, mid-infrared laser biomedicine, and gas trace detection.

Practical synthesis of allylic amines via nickel-catalysed multicomponent coupling of alkenes, aldehydes, and amides.

Molecules with an allylic amine motif provide access to important building blocks and versatile applications of biologically relevant chemical space. The need for diverse allylic amines requires the development of increasingly general and modular multicomponent reactions for allylic amine synthesis. Herein, we report an efficient catalytic multicomponent coupling reaction of simple alkenes, aldehydes, and amides by combining nickel catalysis and Lewis acid catalysis, thus providing a practical, environmentally friendly, and modular protocol to build architecturally complex and functionally diverse allylic amines in a single step. The method is remarkably simple, shows broad functional-group tolerance, and facilitates the synthesis of drug-like allylic amines that are not readily accessible by other methods. The utilization of accessible starting materials and inexpensive Ni(ii) salt as the alternative precatalyst offers a significant practical advantage. In addition, the practicality of the process was also demonstrated in an efficient, gram-scale preparation of the prostaglandin agonist.

Enantioselective Synthesis of Chiral Amides by a Phosphoric Acid Catalyzed Asymmetric Wolff Rearrangement.

The enantioselective addition of potent nucleophiles to ketenes poses challenges due to competing background reactions and poor stereocontrol. Herein, we present a method for enantioselective phosphoric acid catalyzed amination of ketenes generated from α-aryl-α-diazoketones. Upon exposure to visible light, the diazoketones undergo Wolff rearrangement to generate ketenes. The phosphoric acid not only accelerates ketene capture by amines to form a single configuration of aminoenol intermediates but also promotes an enantioselective proton-transfer reaction of the intermediates to yield the products. Mechanistic studies elucidated the reaction pathway and explained how the catalyst expedited the transformation and controlled the enantioselectivity.

Diastereodivergent and Enantioselective Synthesis of Homoallylic Alcohols via Nickel-Catalyzed Borylative Coupling of 1,3-Dienes with Aldehydes.

We present the first enantioselective nickel-catalyzed borylative coupling of 1,3-dienes with aldehydes, providing an efficient route to highly valuable homoallylic alcohols in a single step. The reaction involves the 1,4-carboboration of dienes, leading to the formation of C-C and C-B bonds accompanied by the construction of two continuous stereogenic centers. Enabled by a chiral spiro phosphine-oxazoline nickel complex, this transformation yields products with exceptional diastereoselectivity, E-selectivity, and enantioselectivity. The diastereoselectivity of the reaction can be controlled by employing either (Z)-1,3-dienes or (E)-1,3-dienes.

SUMO2/3 promotes the progression and oxaliplatin resistance of colorectal cancer through facilitating the SUMOylation at Ku80-K307.

Colorectal cancer (CRC) is one of the most prevalent cancers worldwide and is typically treated with the FOLFOX regimen (folinic acid, 5-fluorouracil, and oxaliplatin). However, oxaliplatin resistance remains a serious clinical problem. In the present study, we found that SUMO2/3 was overexpressed in CRC tissues and exogenous overexpression of SUMO2/3 promoted CRC cell proliferation, extension, and invasion and positively regulated the cell cycle. In contrast, SUMO2/3 gene knockdowns inhibited migration and repressed cell viability in vitro and in vivo. In addition, we found that SUMO2/3 was recruited to the cell nucleus and suppressed oxaliplatin-induced apoptosis of CRC cells. Moreover, Ku80, a DNA-binding protein essential for the repair of DNA double-strand breaks, was confirmed to bind with SUMO2/3. Notably, Ku80 undergoes SUMOylation at K307 by SUMO2/3 and this correlated with apoptosis in CRC cells suffering oxaliplatin stress. Collectively, we found that SUMO2/3 plays a specific role in CRC tumorigenesis and acts through Ku80 SUMOylation which is linked with the development of CRC-oxaliplatin resistance.

Ketone α-alkylation at the more-hindered site.

Control of the regioselectivity of α-alkylation of carbonyl compounds is a longstanding topic of research in organic chemistry. By using stoichiometric bulky strong bases and carefully adjusting the reaction conditions, selective alkylation of unsymmetrical ketones at less-hindered α-sites has been achieved. In contrast, selective alkylation of such ketones at more-hindered α-sites remains a persistent challenge. Here we report a nickel-catalysed alkylation of unsymmetrical ketones at the more-hindered α-sites with allylic alcohols. Our results indicate that the space-constrained nickel catalyst bearing a bulky biphenyl diphosphine ligand enables the preferential alkylation of the more-substituted enolate over the less-substituted enolate and reverses the conventional regioselectivity of ketone α-alkylation. The reactions proceed under neutral conditions in the absence of additives, and water is the only byproduct. The method has a broad substrate scope and permits late-stage modification of ketone-containing natural products and bioactive compounds.

ELFN1-AS1 promotes GDF15-mediated immune escape of colorectal cancer from NK cells by facilitating GCN5 and SND1 association.

The ability of colorectal cancer (CRC) cells to escape from natural killer (NK) cell immune surveillance leads to anti-tumor treatment failure. The long non-coding RNA (lncRNA) ELFN1-AS1 is aberrantly expressed in multiple tumors suggesting a role as an oncogene in cancer development. However, whether ELFN1-AS1 regulates immune surveillance in CRC is unclear. Here, we determined that ELFN1-AS1 enhanced the ability of CRC cells to escape from NK cell surveillance in vitro and in vivo. In addition, we confirmed that ELFN1-AS1 in CRC cells attenuated the activity of NK cell by down-regulating NKG2D and GZMB via the GDF15/JNK pathway. Furthermore, mechanistic investigations demonstrated that ELFN1-AS1 enhanced the interaction between the GCN5 and SND1 protein and this influenced H3k9ac enrichment at the GDF15 promotor to stimulate GDF15 production in CRC cells. Taken together, our findings indicate that ELFN1-AS1 in CRC cells suppresses NK cell cytotoxicity and ELFN1-AS1 is a potential therapeutic target for CRC.

Preparation, Physicochemical Properties, and Structural Characterization of Resistant Starch-Aspirin-Loaded Microspheres.

BACKGROUND Resistant starch is a novel type of dietary fiber that can be considered as a natural polymer carrier with potential development prospects in the field of oral colonic release preparations since it can be degraded by bacteria in the large intestine. MATERIAL AND METHODS In this study, oral resistant starch-drug-loaded microspheres were prepared by spraydrying, and the response surface method was used to optimize the process based on the encapsulation efficiency. RESULTS The optimal preparation process conditions for the resistant starch-aspirin-loaded microspheres were as follows: core material: wall material ratio of 1: 1.98, chitosan solution concentration of 1.98%, and spray drying air inlet temperature of 130.45°C resulted in a reliable entrapment efficiency of 68.96%. Infrared spectroscopy analysis indicated that the encapsulated aspirin-starch microspheres did not differ significantly from the original resistant starch material. The ultrastructure of the drug-loaded microspheres was evenly wrapped with the capsule core and appeared as smooth spheres. The combination of resistant starch, aspirin, and chitosan resulted in a cross-linking reaction that reduced the overall gelatinization temperature compared with the original starch material alone. The light transmittance of the drug-loaded microspheres was slightly higher than that of the original resistant starch, while digestibility was similar to that of the resistant starch, indicating that the release would exist in the environment of the large intestine. CONCLUSIONS This study provides pivotal insights into the development of resistant starch in the field of colonic release preparations.

Intermolecular Enantioselective Benzylic C(sp3 )-H Amination by Cationic Copper Catalysis.

Chiral benzylic amines are privileged motifs in pharmacologically active molecules. Intramolecular enantioselective radical C(sp3 )-H functionalization by hydrogen-atom transfer has emerged as a straightforward, powerful tool for the synthesis of chiral amines, but methods for intermolecular enantioselective C(sp3 )-H amination remain elusive. Herein, we report a cationic copper catalytic system for intermolecular enantioselective benzylic C(sp3 )-H amination with peroxide as an oxidant. This mild, straightforward method can be used to transform an array of feedstock alkylarenes and amides into chiral amines with high enantioselectivities, and it has good functional group tolerance and broad substrate scope. More importantly, it can be used to synthesize bioactive molecules, including chiral drugs. Preliminary mechanistic studies indicate that the amination reaction involves benzylic radicals generated by hydrogen-atom transfer.