circRNADisease v2.0: an updated resource for high-quality experimentally supported circRNA-disease associations.

circRNADisease v2.0 is an enhanced and reliable database that offers experimentally verified relationships between circular RNAs (circRNAs) and various diseases. It is accessible at http://cgga.org.cn/circRNADisease/ or http://cgga.org.cn:9091/circRNADisease/. The database currently includes 6998 circRNA-disease entries across multiple species, representing a remarkable 19.77-fold increase compared to the previous version. This expansion consists of a substantial rise in the number of circRNAs (from 330 to 4246), types of diseases (from 48 to 330) and covered species (from human only to 12 species). Furthermore, a new section has been introduced in the database, which collects information on circRNA-associated factors (genes, proteins and microRNAs), molecular mechanisms (molecular pathways), biological functions (proliferation, migration, invasion, etc.), tumor and/or cell line and/or patient-derived xenograft (PDX) details, and prognostic evidence in diseases. In addition, we identified 7 159 865 relationships between mutations and circRNAs among 30 TCGA cancer types. Due to notable enhancements and extensive data expansions, the circRNADisease 2.0 database has become an invaluable asset for both clinical practice and fundamental research. It enables researchers to develop a more comprehensive understanding of how circRNAs impact complex diseases.

Boosting Monolayer Transition Metal Dichalcogenides Growth by Hydrogen-Free Ramping during Chemical Vapor Deposition.

The controlled vapor-phase synthesis of two-dimensional (2D) transition metal dichalcogenides (TMDs) is essential for functional applications. While chemical vapor deposition (CVD) techniques have been successful for transition metal sulfides, extending these methods to selenides and tellurides often faces challenges due to uncertain roles of hydrogen (H2) in their synthesis. Using CVD growth of MoSe2 as an example, this study illustrates the role of a H2-free environment during temperature ramping in suppressing the reduction of MoO3, which promotes effective vaporization and selenization of the Mo precursor to form MoSe2 monolayers with excellent crystal quality. As-synthesized MoSe2 monolayer-based field-effect transistors show excellent carrier mobility of up to 20.9 cm2/(V·s) with an on-off ratio of 7 × 107. This approach can be extended to other TMDs, such as WSe2, MoTe2, and MoSe2/WSe2 in-plane heterostructures. Our work provides a rational and facile approach to reproducibly synthesize high-quality TMD monolayers, facilitating their translation from laboratory to manufacturing.

Genotype-phenotype correlations and clinical outcomes of patients with von Hippel-Lindau disease with large deletions.

BACKGROUND: Approximately 20%-40% of patients with von Hippel-Lindau (VHL) disease, an autosomal dominant hereditary disease, exhibit large deletions (LDs). Few studies have focused on this population. Hence, we aimed to elucidate the genotype-phenotype correlations and clinical outcomes in VHL patients with LDs. METHODS: In this retrospective study, we included 119 patients with VHL disease from 50 unrelated families in whom LDs were detected using traditional and next-generation sequencing methods. Other germline mutations were confirmed by Sanger sequencing. Genotype-phenotype correlations and survival were analysed in different groups using Kaplan-Meier and Cox regression. We also evaluated therapeutic response to tyrosine kinase inhibitor (TKI) therapy. RESULTS: The overall penetrance of patients aged <60 was 95.2%. Two VHL patients with LDs also carried CHEK2 and FLCN germline mutations. An earlier age of onset of retinal haemangioblastoma was observed in the next generation. Patients with exon 2 deletion of VHL had an earlier onset age of renal cell carcinoma and pancreatic lesions. The risk of renal cell carcinoma was lower in VHL patients with LDs and a BRK1 deletion. The group with earlier age of onset received poorer prognosis. Four of eight (50%) patients showed partial response to TKI therapy. CONCLUSION: The number of generations and the status of exon 2 could affect age of onset of VHL-related manifestations. Onset age was an independent risk factor for overall survival. TKI therapy was effective in VHL patients with LDs. Our findings would further support clinical surveillance and decision-making processes.

Imaging segmentation mechanism for rectal tumors using improved U-Net.

OBJECTIVE: In radiation therapy, cancerous region segmentation in magnetic resonance images (MRI) is a critical step. For rectal cancer, the automatic segmentation of rectal tumors from an MRI is a great challenge. There are two main shortcomings in existing deep learning-based methods that lead to incorrect segmentation: 1) there are many organs surrounding the rectum, and the shape of some organs is similar to that of rectal tumors; 2) high-level features extracted by conventional neural networks often do not contain enough high-resolution information. Therefore, an improved U-Net segmentation network based on attention mechanisms is proposed to replace the traditional U-Net network. METHODS: The overall framework of the proposed method is based on traditional U-Net. A ResNeSt module was added to extract the overall features, and a shape module was added after the encoder layer. We then combined the outputs of the shape module and the decoder to obtain the results. Moreover, the model used different types of attention mechanisms, so that the network learned information to improve segmentation accuracy. RESULTS: We validated the effectiveness of the proposed method using 3773 2D MRI datasets from 304 patients. The results showed that the proposed method achieved 0.987, 0.946, 0.897, and 0.899 for Dice, MPA, MioU, and FWIoU, respectively; these values are significantly better than those of other existing methods. CONCLUSION: Due to time savings, the proposed method can help radiologists segment rectal tumors effectively and enable them to focus on patients whose cancerous regions are difficult for the network to segment. SIGNIFICANCE: The proposed method can help doctors segment rectal tumors, thereby ensuring good diagnostic quality and accuracy.

In Situ Defect Engineering of Controllable Carrier Types in WSe2 for Homomaterial Inverters and Self-Powered Photodetectors.

WSe2 has a high mobility of electrons and holes, which is an ideal choice as active channels of electronics in extensive fields. However, carrier-type tunability of WSe2 still has enormous challenges, which are essential to overcome for practical applications. In this work, the direct growth of n-doped few-layer WSe2 is realized via in situ defect engineering. The n-doping of WSe2 is attributed to Se vacancies induced by the H2 flow purged in the cooling process. The electrical measurements based on field effect transistors demonstrate that the carrier type of WSe2 synthesized is successfully transferred from the conventional p-type to the rarely reported n-type. The electron carrier concentration is efficiently modulated by the concentration of H2 during the cooling process. Furthermore, homomaterial inverters and self-powered photodetectors are fabricated based on the doping-type-tunable WSe2. This work reveals a significant way to realize the controllable carrier type of two-dimensional (2D) materials, exhibiting great potential in future 2D electronics engineering.

Low-Temperature Vapor-Phase Growth of 2D Metal Chalcogenides.

2D metal chalcogenides (MCs) have garnered significant attention from both scientific and industrial communities due to their potential in developing next-generation functional devices. Vapor-phase deposition methods have proven highly effective in fabricating high-quality 2D MCs. Nevertheless, the conventionally high thermal budgets required for synthesizing 2D MCs pose limitations, particularly in the integration of multiple components and in specialized applications (such as flexible electronics). To overcome these challenges, it is desirable to reduce the thermal energy requirements, thus facilitating the growth of various 2D MCs at lower temperatures. Numerous endeavors have been undertaken to develop low-temperature vapor-phase growth techniques for 2D MCs, and this review aims to provide an overview of the latest advances in low-temperature vapor-phase growth of 2D MCs. Initially, the review highlights the latest progress in achieving high-quality 2D MCs through various low-temperature vapor-phase techniques, including chemical vapor deposition (CVD), metal-organic CVD, plasma-enhanced CVD, atomic layer deposition (ALD), etc. The strengths and current limitations of these methods are also evaluated. Subsequently, the review consolidates the diverse applications of 2D MCs grown at low temperatures, covering fields such as electronics, optoelectronics, flexible devices, and catalysis. Finally, current challenges and future research directions are briefly discussed, considering the most recent progress in the field.

Molecular and clinical characterization of PTRF in glioma via 1,022 samples.

Polymerase I and transcript release factor (PTRF) plays a role in the regulation of gene expression and the release of RNA transcripts during transcription, which have been associated with various human diseases. However, the role of PTRF in glioma remains unclear. In this study, RNA sequencing (RNA-seq) data (n = 1022 cases) and whole-exome sequencing (WES) data (n = 286 cases) were used to characterize the PTRF expression features. Gene ontology (GO) functional enrichment analysis was used to assess the biological implication of changes in PTRF expression. As a result, the expression of PTRF was associated with malignant progression in gliomas. Meanwhile, somatic mutational profiles and copy number variations (CNV) revealed the glioma subtypes classified by PTRF expression showed distinct genomic alteration. Furthermore, GO functional enrichment analysis suggested that PTRF expression was associated with cell migration and angiogenesis, particularly during an immune response. Survival analysis confirmed that a high expression of PTRF is associated with a poor prognosis. In summary, PTRF may be a valuable factor for the diagnosis and treatment target of glioma.

Decision system for extent of resection in WHO grade 3 gliomas: a Chinese Glioma Genome Atlas database analysis.

BACKGROUND: Extensive surgical resection has been found to be associated with longer survival in patients with gliomas, but the interactive prognostic value of molecular pathology of the surgical resection is unclear. This study evaluated the impact of molecular pathology and clinical characteristics on the surgical benefit in WHO grade 3 IDH-mutant gliomas. METHODS: Clinical and pathological information of 246 patients with WHO grade 3 IDH-mutant gliomas were collected from the Chinese Glioma Genome Atlas database (2006-2020). The role of the extent of resection on overall survival, stratified by molecular pathology and clinical characteristics, was investigated. We then assessed prognostic factors using a univariate log-rank test and multivariate Cox proportional hazards model in the subgroups. RESULTS: The extent of resection was an independent prognostic factor in the entire cohort, even when adjusted for molecular pathology. Gross total resection was found to be associated with longer survival in all patients and in the astrocytoma group but not in the oligodendroglioma group. Compared with subtotal resections, gross total resections resulted in a longer survival time for astrocytoma patients aged ≤ 45 years. However, there was no survival benefit from total resection in patients with astrocytoma aged > 45 years. CONCLUSIONS: Extensive resection benefits only a proportion of patients with WHO grade 3 IDH-mutant gliomas. Younger patients with astrocytomas had survival benefits from extensive resection. In addition to clinical characteristics (especially age), molecular pathology impacted prognosis in patients with gliomas. Our findings provide guiding information to neurosurgeons while planning surgeries.

Clinical characteristics and risk factors for survival in affected offspring of von Hippel-Lindau disease patients.

BACKGROUND: Von Hippel-Lindau (VHL) disease is an autosomal dominant genetic tumour syndrome with poor prognosis. The clinical manifestation was found to be more serious in affected offspring of patients with VHL disease, but the risk factors and survival for them have never been reported before. We aimed to explore how these patients were influenced by genetic and clinical factors. METHODS: In this retrospective study, we collected 372 affected offspring of VHL patients from 118 unrelated VHL families. Patients were stratified into different groups based on sets of variables. The age-related risk, overall survival and central nervous systemhaemangioblastoma (CHB)-specific survival were analysed between different groups using Kaplan-Meier survival analysis and Cox regression analysis. RESULTS: The estimated median life expectancy and median age of onset for affected offspring of VHL patients were 66 years and 28 years, respectively. The later generation and patients with mutations in exon 3 had an earlier onset age. The first presenting symptom was the only independent risk factor influencing overall survival and CHB-specific survival. Patients that the first presenting symptom is central nervous system (CNS) significantly had a lower life expectancy both in overall survival and CHB-specific survival analysis than abdominal lesions group. CONCLUSION: This study indicated that affected offspring of VHL patients with CNS as the first presenting symptom was an independent risk factor for overall survival and CHB-specific survival. Generation and mutation region only had an effect on the onset age, which is helpful to clinical decision-making and generate a more precise surveillance protocol.

Changes in nutrient consumption patterns of Lactobacillus fermentum mediated by sodium lactate.

BACKGROUND: During high-cell-density culture of Lactobacillus fermentum, the optimal pH is often maintained by adding NaOH. During cultivation at controlled pH, L. fermentum experiences osmotic stress due to the continuous accumulation of sodium lactate as a neutralizer product, affecting its survival in subsequent processing. The purpose of this study was to evaluate the nutrient consumption patterns of L. fermentum ATCC 14931 under sodium lactate stress and to screen nutrients that help it resist osmotic stress. RESULTS: The consumption and consumption rates of amino acids, purines, pyrimidines, vitamins, and metal ions were analyzed in chemically defined media containing 0.13, 0.31, or 0.62 mm L-1 sodium lactate. The highest consumption rates were found for arginine, guanine, folic acid, and Mn2+ , and the most consumed nutrients were glutamate + glutamine, guanine, ascorbic acid, and Na+ . Arginine 2.58 mm L-1 , guanine 0.23 mm L-1 , and Mn2+ 0.25 mm L-1 were added to the medium at sodium lactate concentrations of 0.13 and 0.62 mm L-1 , and arginine 2.58 mm L-1 , guanine 0.26 mm L-1 , and Mn2+ 0.25 mm L-1 at a sodium lactate concentration of 0.31 mm L-1 . The viable cell counts of L. fermentum ATCC 14931 were approximately 1.02-fold (P < 0.05) of the counts observed in control medium at all three concentrations of sodium lactate. CONCLUSION: The present results suggest that certain nutrients accelerate the growth of L. fermentum under sodium lactate stress and enhance its resistance to this adverse condition. © 2022 Society of Chemical Industry.

Band Alignment Engineering by Twist Angle and Composition Modulation for Heterobilayer.

Atomically thin monolayer semiconducting transition metal dichalcogenides (TMDs), exhibiting direct band gap and strong light-matter interaction, are promising for optoelectronic devices. However, an efficient band alignment engineering method is required to further broaden their practical applications as versatile optoelectronics. In this work, the band alignment of two vertically stacked monolayer TMDs using the chemical vapor deposition (CVD) method is effectively tuned by two strategies: 1) formulating the compositions of MoS2(1-x) Se2x alloys, and 2) varying the twist angles of the stacked heterobilayer structures. Photoluminescence (PL) results combined with density functional theory (DFT) calculation show that by changing the alloy composition, a continuously tunable band alignment and a transition of type II-type I-type II band alignment of TMD heterobilayer is achieved. Moreover, only at moderate (10°-50°) twist angles, a PL enhancement of 28%-110% caused by the type I alignment is observed, indicating that the twist angle is coupled with the global band structure of heterobilayer. A heterojunction device made with MoS0.76 Se1.24 /WS2 of 14° displays a significantly high photoresponsivity (55.9 A W-1 ), large detectivity (1.07 × 1010 Jones), and high external quantum efficiency (135%). These findings provide engineering tools for heterostructure design for their application in optoelectronic devices.

Electrical control of spatial resolution in mixed-dimensional heterostructured photodetectors.

Low-dimensional nanomaterials, such as one-dimensional (1D) nanomaterials and layered 2D materials, have exhibited significance for their respective unique electronic and optoelectronic properties. Here we show that a mixed-dimensional heterostructure with building blocks from multiple dimensions will present a synergistic effect on photodetection. A carbon nanotube (CNT)-[Formula: see text]-graphene photodetector is representative on this issue. Its spatial resolution can be electrically switched between high-resolution mode (HRM) and low-resolution mode (LRM) revealed by scanning photocurrent microscopy (SPCM). The reconfigurable spatial resolution can be attributed to the asymmetric geometry and the gate-tunable Fermi levels of these low-dimensional materials. Significantly, an interference fringe with 334 nm in period was successfully discriminated by the device working at HRM, confirming the efficient electrical control. Electrical control of spatial resolution in CNT-[Formula: see text]-graphene devices reveals the potential of the mixed-dimensional architectures in future nanoelectronics and nano-optoelectronics.

Plasminogen Activator Urokinase Receptor Implies Immunosuppressive Features and Acts as an Unfavorable Prognostic Biomarker in Glioma.

BACKGROUND: Clinical outcomes of patients with glioma are still poor, even after standard treatments, including surgery combined with radiotherapy and chemotherapy. New therapeutic strategies and targets for glioma are urgently needed. Plasminogen activator urokinase receptor (PLAUR), a highly glycosylated integral membrane protein, is reported to modulate plasminogen activation and extracellular matrix degradation in many malignant cancers, but its role in gliomas remains unclear. METHODS: Glioma samples with mRNA sequencing data and clinical information from the Chinese Glioma Genome Atlas (n = 310) data set and The Cancer Genome Atlas (n = 611) data set were collected for this study. Analyses using Kaplan-Meier plots, time-dependent receiver operating characteristic curves, Cox regression, and nomograms were conducted to evaluate the prognostic performance of PLAUR expression. Analyses using Metascape, ESTIMATE, EPIC, and immunohistochemical staining were performed to reveal the potential biological mechanism. The statistical analysis and graphical work were completed using SPSS, R language, and GraphPad Prism. RESULTS: PLAUR was highly expressed in phenotypes associated with glioma malignancy and could serve as an independent prognostic indicator. Functional analysis revealed the correlation between PLAUR and immune response. Further studies found that samples with higher PLAUR expression were infiltrated with fewer CD8 T cells and many more M2 macrophages. Strong positive correlation was demonstrated between PLAUR expression and some immunosuppressive markers, including immune checkpoints and cytokines. These findings were also confirmed in patient samples. CONCLUSION: Our results elucidated the clinical significance and immunosuppressive effect of PLAUR in gliomas, which might provide some clues in glioma immunotherapy. IMPLICATIONS FOR PRACTICE: Although the efficacy of immunotherapy has been verified in other tumors, its application in glioma is impeded because of the unique microenvironment. Tumor-associated macrophages, which are particularly abundant in a glioma mass, contribute much to the immunosuppressive microenvironment and offer new opportunities in glioma immunotherapy. The results of this study identified plasminogen activator urokinase receptor (PLAUR) expression as a potential marker to predict the infiltration of macrophages and the status of immune microenvironment in patients with glioma, suggesting that treatment decisions could be based on PLAUR level when administering immunotherapeutics. The soluble PLAUR in blood and other body fluids would make this approach easy to implement in the clinic.

Novel genetic characterisation and phenotype correlation in von Hippel-Lindau (VHL) disease based on the Elongin C binding site: a large retrospective study.

BACKGROUND: Von Hippel-Lindau (VHL) disease is an autosomal dominant genetic tumour syndrome resulting from mutations in the VHL gene lineage, and its prognosis is generally poor. This study aimed to provide a more valuable genotype-phenotype correlation based on the Elongin C binding site in VHL disease. METHODS: This study included 553 patients (194 families) who were diagnosed with VHL disease in our centre from September 2010 to February 2019. According to the type of gene mutation, the patients were divided into the Elongin C binding site missense mutation (EM) group, the non-Elongin C binding site missense mutation (nEM) group and the truncation mutation (TR) group. We analysed and compared the age-related tumour risk and prognosis of the three groups. RESULTS: A total of 14 new intragenic mutations were found in this cohort. The age-related risk of central nervous system haemangioblastoma (CHB) and pancreatic tumour in the EM group was lower than in the combined nEM-TR group, while the corresponding risk of pheochromocytoma (PHEO) was higher. Additionally, the prognoses of EM and nEM-TR were analysed. The median survival period in the EM group was longer than that in the nEM-TR group, and both the total survival and the CHB-specific survival of the EM group were better than those of the nEM-TR group. CONCLUSION: In conclusion, our study demonstrated that the EM was an independent risk factor for PHEO. The EM is also an independent protective factor for CHB age-related risk, overall survival and CHB-specific survival in VHL disease. This modified genotype-phenotype correlation integrates gene mutation, the Elongin B binding site, and phenotypic diversity and provides a reference for clinical diagnosis.

Quasicrystalline 30° twisted bilayer graphene as an incommensurate superlattice with strong interlayer coupling.

The interlayer coupling can be used to engineer the electronic structure of van der Waals heterostructures (superlattices) to obtain properties that are not possible in a single material. So far research in heterostructures has been focused on commensurate superlattices with a long-ranged Moiré period. Incommensurate heterostructures with rotational symmetry but not translational symmetry (in analogy to quasicrystals) are not only rare in nature, but also the interlayer interaction has often been assumed to be negligible due to the lack of phase coherence. Here we report the successful growth of quasicrystalline 30° twisted bilayer graphene (30°-tBLG), which is stabilized by the Pt(111) substrate, and reveal its electronic structure. The 30°-tBLG is confirmed by low energy electron diffraction and the intervalley double-resonance Raman mode at 1383 cm-1 Moreover, the emergence of mirrored Dirac cones inside the Brillouin zone of each graphene layer and a gap opening at the zone boundary suggest that these two graphene layers are coupled via a generalized Umklapp scattering mechanism-that is, scattering of a Dirac cone in one graphene layer by the reciprocal lattice vector of the other graphene layer. Our work highlights the important role of interlayer coupling in incommensurate quasicrystalline superlattices, thereby extending band structure engineering to incommensurate superstructures.

Identification of an ATP metabolism-related signature associated with prognosis and immune microenvironment in gliomas.

As the core element of material and energy metabolism pathways, the biological functions and prognostic significance of ATP metabolism in diffuse gliomas have so far remained unclear. Based on comprehensive analysis of ATP metabolism-related gene expression profiles, we constructed an ATP metabolism-related risk signature to determine the role of ATP metabolism. We found that this ATP metabolism-related gene expression profile could divide patients into 2 robust groups with distinct clinical characteristics and prognosis. Patients in the high-risk group tended to be predicted as malignant entities, indicating that the activation of ATP metabolism may promote the malignant progress of diffuse gliomas. Cox regression and Kaplan-Meier analyses suggested that this risk signature was an independent predictor for prognosis. Furthermore, we constructed an individualized prognosis prediction model through nomogram and time-dependent receiver operating characteristic (ROC) curve analyses. Functional analysis suggested that, in addition to material and energy metabolism, ATP metabolism also played an essential role in the regulation of the tumor immune microenvironment. In brief, the ATP metabolism-related signature was tightly associated with regulation of the tumor immune microenvironment and could serve as an independent prognostic biomarker in diffuse gliomas.

AB- Versus AA+BB-Suzuki Polycondensation: A Palladium/Tris(tert-butyl)phosphine Catalyst Can Outperform Conventional Catalysts.

A Pd/Pt-Bu3 catalyst having bulky, electron-rich ligands significantly outperforms conventional "step-growth catalysts" Pd(PPh3 )4 and Pd(Po-Tol3 )3 in the Suzuki polycondensation of the AB-type arylene-based monomers, such as some of the substituted fluorenes, carbazoles, and phenylenes. In the AA+BB polycondensation, Pd/Pt-Bu3 also performs better under homogeneous reaction conditions, in combination with the organic base Et4 NOH. The superior performance of Pd/Pt-Bu3 is discussed in terms of its higher reactivity in the oxidative addition step and inherent advantages of the intramolecular catalyst transfer, which is a key step joining catalytic cycles of the AB-polycondensation. These findings are applied to the synthesis of a carbazole-based copolymer designed for the use as a hole conductor in solution-processed organic light-emitting diodes.

Elastic Properties and Fracture Behaviors of Biaxially Deformed, Polymorphic MoTe2.

Biaxial deformation of suspended membranes widely exists and is used in nanoindentation to probe elastic properties of structurally isotropic two-dimensional (2D) materials. However, the elastic properties and, in particular, the fracture behaviors of anisotropic 2D materials remain largely unclarified in the case of biaxial deformation. MoTe2 is a polymorphic 2D material with both isotropic (2H) and anisotropic (1T' and Td) phases and, therefore, an ideal system of single-stoichiometric materials with which to study these critical issues. Here, we report the elastic properties and fracture behaviors of biaxially deformed, polymorphic MoTe2 by combining temperature-variant nanoindentation and first-principles calculations. It is found that due to similar atomic bonding, the effective moduli of the three phases deviate by less than 15%. However, the breaking strengths of distorted 1T' and Td phases are only half the value of 2H phase due to their uneven distribution of bonding strengths. Fractures of both isotropic 2H and anisotropic 1T' phases obey the theorem of minimum energy, forming triangular and linear fracture patterns, respectively, along the orientations parallel to Mo-Mo zigzag chains. Our findings not only provide a reference database for the elastic behaviors of versatile MoTe2 phases but also illuminate a general strategy for the mechanical investigation of any isotropic and anisotropic 2D materials.

[Effect of Sijunzi Decoction on regulation of Aß-related proteins across blood-brain barrier].

According to traditional Chinese medicine, "spleen transport" is closely related to the metabolism of substance and energy. Studies have shown that Alzheimer's disease(AD) is a disease related to glucose and lipid metabolism and energy metabolism. The traditional Chinese medicine Jiangpi Recipe can improve the learning ability and memory of AD animal model. Sijunzi Decoction originated from Taiping Huimin Hefang Prescription is the basic prescription for strengthening and nourishing the spleen, with the effects of nourishing Qi and strengthening the spleen. In this experiment, human brain microvascular endothelial cells(HBMEC) and Sijunzi Decoction water extract(0.25, 0.5, 1 mg·L~(-1)) were pre-incubated for 2 h, and then Aß_(25-35) oligomers(final concentration 40 µmol·L~(-1)) was added for co-culture for 22 hours. The effect of Sijunzi Decoction on the activity of Aß_(25-35) oligomer injured cells and the expression of related proteins were investigated. Q-TOF-LC-MS was used first for principal component analysis of Sijunzi Decoction water extract. Then MTT assay was used to investigate the effect of Sijunzi Decoction water extract on the proliferation of HBMEC cells. Real-time fluorescence quantitative PCR(RT-qPCR) was employed to detect the mRNA expression of GLUT1, RAGE, and LRP1. The expression of Aß-related proteins across blood-brain barrier(RAGE, LRP1) was detected by Western blot. The results showed that 40 µmol·L~(-1) Aß_(25-35) oligomers could induce endothelial cell damage, reduce cell survival, increase expression of RAGE mRNA and RAGE protein, and reduce expression of GLUT1 mRNA, LRP1 mRNA, and LRP1 protein. Sijunzi Decoction water extract could reduce the Aß_(25-35) oligomer-induced cytotoxicity of HBMEC, decrease the expression of RAGE mRNA and RAGE protein, and increase the expression of GLUT1 mRNA, LRP1 mRNA and LRP1 protein. The results indicated that Sijunzi Decoction could reduce the injury of HBMEC cells induced by Aß_(25-35) oligomer, and regulate the transport-related proteins GLUT1, RAGE and LRP1, which might be the mechanism of regulating Aß_(25-35) transport across the blood-brain barrier.

Enantioselective Synthesis of Isoxazolines Enabled by Palladium-Catalyzed Carboetherification of Alkenyl Oximes.

Reported here is a highly efficient Pd/Xiang-Phos catalyzed enantioselective carboetherification of alkenyl oximes with either aryl or alkenyl halides, delivering various chiral 3,5-disubstituted and 3,5,5-trisubstituted isoxazolines in good yields with up to 97 % ee. The sterically bulky and electron-rich (S,Rs)-NMe-X2 ligand is responsible for the excellent reactivities and enantioselectivities. The salient features of this transformation include mild reaction conditions, general substrate scope, good functional-group tolerance, good yields, high enantioselectivities, easy scale-up, and application in the late-stage modification of bioactive compounds. The obtained products can be readily transformed into useful chiral 1,3-aminoalcohols.