Direct Synthesis of α- and ß-2'-Deoxynucleosides with Stereodirecting Phosphine Oxide via Remote Participation.

2'-Deoxynucleosides and analogues play a vital role in drug development, but their preparation remains a significant challenge. Previous studies have focused on ß-2'-deoxynucleosides with the natural ß-configuration. In fact, their isomeric α-2'-deoxynucleosides also exhibit diverse bioactivities and even better metabolic stability. Herein, we report that both α- and ß-2'-deoxynucleosides can be prepared with high yields and stereoselectivity using a remote directing diphenylphosphinoyl (DPP) group. It is particularly efficient to prepare α-2'-deoxynucleosides with an easily accessible 3,5-di-ODPP donor. Instead of acting as a H-bond acceptor on a 2-(diphenylphosphinoyl)acetyl (DPPA) group in our previous studies for syn-facial O-glycosylation, the phosphine oxide moiety here acts as a remote participating group to enable highly antifacial N-glycosylation. This proposed remote participation mechanism is supported by our first characterization of an important 1,5-briged P-heterobicyclic intermediate via variable-temperature NMR spectroscopy. Interestingly, antiproliferative assays led to a α-2'-deoxynucleoside with IC50 values in the low micromole range against central nervous system tumor cell lines SH-SY5Y and LN229, whereas its ß-anomer exhibited no inhibition at 100 µM. Furthermore, the DPP group significantly enhanced the antitumor activities by 10 times.

Utilizing rubidium chloride as an effective and stable interface modification layer for high-efficiency solar cells.

The presence of interface defects between the perovskite layer and the underlying substrate has a significant impact on the power conversion efficiency (PCE) and stability of perovskite solar cells (PSCs). S n O 2 thin films are employed in PSCs as electron transport layers to achieve high PCE. However, the significant lattice mismatch between S n O 2 and the perovskite material leads to a large number of uncoordinated defects at the interface between perovskite and substrate, resulting in recombination losses at the interface. In this study, rubidium chloride (RbCl) was introduced as the interface modification layer between the perovskite layer and the S n O 2 electron transport layer to enhance the PCE of PSCs. The research showed that the RbCl interface modification layer effectively passivated the under-coordinated defects of Sn ions and optimized the energy level alignment between the perovskite layer and the S n O 2 film. Moreover, the fabricated PSCs exhibited an open-circuit voltage of 1.11 V and a power conversion efficiency of 21.64%. Furthermore, the device maintained 80% of initial efficiency after storage for 30 days in an inert gas environment and 60% of the value after storage for 30 days in ambient air.

Bis(benzonitrile) dichloroplatinum (II) interrupts PD-1/PD-L1 interaction by binding to PD-1.

Checkpoint inhibitors such as PD-1/PD-L1 antibody therapeutics are a promising option for the treatment of multiple cancers. Due to the inherent limitations of antibodies, great efforts have been devoted to developing small-molecule PD-1/PD-L1 signaling pathway inhibitors. In this study we established a high-throughput AlphaLISA assay to discover small molecules with new skeletons that could block PD-1/PD-L1 interaction. We screened a small-molecule library of 4169 compounds including natural products, FDA approved drugs and other synthetic compounds. Among the 8 potential hits, we found that cisplatin, a first-line chemotherapeutic drug, reduced AlphaLISA signal with an EC50 of 8.3 ± 2.2 µM. Furthermore, we showed that cisplatin-DMSO adduct, but not semplice cisplatin, inhibited PD-1/PD-L1 interaction. Thus, we assessed several commercial platinum (II) compounds, and found that bis(benzonitrile) dichloroplatinum (II) disturbed PD-1/PD-L1 interaction (EC50 = 13.2 ± 3.5 µM). Its inhibitory activity on PD-1/PD-L1 interaction was confirmed in co-immunoprecipitation and PD-1/PD-L1 signaling pathway blockade bioassays. Surface plasmon resonance assay revealed that bis(benzonitrile) dichloroplatinum (II) bound to PD-1 (KD = 2.08 µM) but not PD-L1. In immune-competent wild-type mice but not in immunodeficient nude mice, bis(benzonitrile) dichloroplatinum (II) (7.5 mg/kg, i.p., every 3 days) significantly suppressed the growth of MC38 colorectal cancer xenografts with increasing tumor-infiltrating T cells. These data highlight that platinum compounds are potential immune checkpoint inhibitors for the treatment of cancers.

Microscale gratings patterned in perovskite films to promote the electron-optical conversion efficiency of perovskite light-emitting diodes.

In this paper, we investigated an enhancement of luminance in a perovskite light-emitting diode (PeLED) by inserting periodic microscale gratings. Soft imprinting was employed to pattern the gratings onto the surface of perovskite film in the annealing process. It was found that the grain-refining effect deeply influenced the morphology and crystallinity of the perovskite film. The finite-element analysis was utilized to confirm the light extraction enhancement arising from the inserted microscale gratings. Additionally, the introduction of microscale gratings led to a 1.33 enhancement of the device's optoelectrical field intensity. Thus, the patterned PeLED obtained an enhancement of 2.96 and 2.1 of the luminance and external quantum efficiency, respectively.

Quantum routings for single photons with different frequencies.

Controllable single-photon routing takes the central roles in optical quantum networks for quantum information processing. Given that most of the schemes previously proposed are specifically designed for the photons with selected frequencies, here we investigate how to implement the routings of single photons with different frequencies. We show that the routing capabilities of the photons with different frequencies are manipulatable by properly designing the configuration of the scatters such as the cavity with embedded atoms and the channel boundaries. This is particularly important to implement the bandwidth routings of photons in future.

Synthesis of MeON-Glycoside Derivatives of Oleanolic Acid by Neoglycosylation and Evaluation of Their Cytotoxicity Against Selected Cancer Cell Lines.

A series of C-3 and C-28 MeON-neoglycosides of oleanolic acid were designed and synthesized by neoglycosylation as potential antiproliferative agents. Their cytotoxicity was evaluated in vitro against five human cancer cell lines: human non-small cell lung cancer cell line (A549), human melanoma cell line (A375), human colon cancer cell line (HCT116), human liver carcinoma cell line (HepG2), human breast adenocarcinoma cell line (MCF-7) by the Cell Counting Kit-8 (CCK-8) assay. Most of C-3 and C-28 MeON-neoglycosides of oleanolic acid exhibited notably inhibitory effects against the tested cancer cells and more sensitive to HepG2 cells than 5-Fluorouracil (5-FU). Structure-activities relationship (SAR) analysis revealed that sugar types and the d/l configuration of sugars would significantly affect their antiproliferative activities of neoglycosides. Among them, compound 8a (28-N-methoxyaminooleanane-ß-d-glucoside) exhibited the most potent antiproliferative activities against HepG2 cells with IC50 values of 2.1 µM. Further pharmacological experiments revealed that compound 8a could cause morphological changes and cell cycle arrest at G0/G1 phase and induce apoptosis in HepG2 cells. These results suggested that neoglycosylation could provide a rapid strategy for the discovery of potential antiproliferative agents and their possible pharmacological mechanisms need more further research.

One-sided device-independent quantum key distribution for two independent parties.

Remote distribution of secret keys is a challenging task in quantum cryptography. A significant step in this direction is the measurement-device independence quantum key distribution (MDI-QKD). For two remote (or independent) parties Alice and Bob who initially no share secret information, the MDI-QKD enables them to share a secret key by the measurement of an untrusted relay. Unfortunately, the MDI-QKD yields the assumption that the devices of both Alice and Bob have to be trusted. Here, we show that QKD between two independent parties can also be realized even if the device of either Alice or Bob is untrusted. We tackle the problem by resorting to the recently developed one-sided device-independent QKD protocol. We derive conditions on the extracted secret key to be unconditionally secure against arbitary attacks in the limit of asymptotic keys. In the presence of Gaussian states and measurements, we theoretically demonstrate our scheme is feasible, which could be an attractive candidate for long distance secret communication.

Biocatalytic allylic hydroxylation of unsaturated triterpenes and steroids by Bacillus megaterium CGMCC 1.1741.

In this study, we described the microbial catalyzed allylic oxidation by Bacillus megaterium CGMCC 1.1741 of three Δ12-pentacyclic triterpenes, erythrodiol (1), uvaol (2), hederagenin (3) and of four steroids including Δ5-steroids, diosgenin (4), pennogenin (5), 25(R,S)-ruscogenin (6) and Δ4-steroid, diosgenone (7). As a result, fourteen metabolites were generated with allyl hydroxyl moiety. Ten (1a-c, 2a, 2c, 3a, 5a-b, and 6a-b) of them were new natural products and their structures were determined on the basis of 1D/2D NMR and HR-MS data. Biocatalytic allylic oxidation by B. megaterium CGMCC 1.1741 is thus a potential non-toxic and efficient alternative method toward metal-mediated oxidation procedures in the synthesis of natural products and medicines.

Enhancing the electroluminescence of perovskite light-emitting diodes by optimizing the morphology of perovskite film to suppress leakage current.

Organic-inorganic hybrid perovskites have attracted much attention due to their high color purity, low material cost, ease of tuning of bandgap, and flexible manufacture. They are considered to be a new generation of promising light-emitting materials. In this paper, an appropriate doping of polyethylene oxide (PEO) into the perovskite precursor solution acquires the high quality and low defect density of perovskite film. In addition, the passivation of perovskite grain boundaries by PEO are investigated. The perovskite light-emitting diode (PeLED) is fabricated with a structure of ITO/PEDOT:PSS/MAPbBr3/TPBi/LiF/Ag. As the doping concentration of PEO is at 10 mg/ml, MAPbBr3-PEO-based PeLEDs exhibit a maximum luminance of 4665.1cdm-2, while their external quantum efficiency (EQE) and current efficiency (CE) are also maximized to be 1.355% and 5.556cdA-1, respectively.

Genome-wide identification, characterization, and expression patterns of the BZR transcription factor family in sugar beet (Beta vulgaris L.).

BACKGROUND: BRASSINAZOLE-RESISTANT (BZR) family genes encode plant-specific transcription factors (TFs) that participate in brassinosteroid signal transduction. BZR TFs have vital roles in plant growth, including cell elongation. However, little is known about BZR genes in sugar beet (Beta vulgaris L.). RESULTS: Therefore, we performed a genome-wide investigation of BvBZR genes in sugar beet. Through an analysis of the BES1_N conserved domain, six BvBZR gene family members were identified in the sugar beet genome, which clustered into three subgroups according to a phylogenetic analysis. Each clade was well defined by the conserved motifs, implying that close genetic relationships could be identified among the members of each subfamily. According to chromosomal distribution mapping, 2, 1, 1, 1, and 1 genes were located on chromosomes 1, 4, 5, 6, and 8, respectively. The cis-acting elements related to taproot growth were randomly distributed in the promoter sequences of the BvBZR genes. Tissue-specific expression analyses indicated that all BvBZR genes were expressed in all three major tissue types (roots, stems, and leaves), with significantly higher expression in leaves. Subcellular localization analysis revealed that Bv1_fxre and Bv6_nyuw are localized in the nuclei, consistent with the prediction of Wolf PSORT. CONCLUSION: These findings offer a basis to predict the functions of BZR genes in sugar beet, and lay a foundation for further research of the biological functions of BZR genes in sugar beet.

High-level expression of Proteinase K from Tritirachium album Limber in Pichia pastoris using multi-copy expression strains.

Proteinase K is widely used in scientific research and industries. This report was aimed to achieve high-level expression of proteinase K using Pichia pastoris GS115 as the host strain. The coding sequence of a variant of proteinase K that has higher activity than the wild type protein was chosen and optimized based on the codon usage preference of P. pastoris. The novel open reading frame was synthesized and a series of multi-copy expression vectors were constructed based on the pHBM905BDM plasmid, allowing for the tandem integration of multiple copies of the target gene into the genome of P. pastoris with a single recombination. These strains were used to study the correlation between the gene copy number and the expression level of proteinase K. The results of quantitative polymerase chain reaction (qPCR) indicated that the tandem expression cassettes were integrated into the host genome stably. Meanwhile, the results of qPCR and enzyme activity assays indicated that the mRNA and protein expression levels of the target gene increased as the gene copy number increased. Moreover, the effect of gene dosage on the expression level of the recombinant protein was more obvious using high-density fermentation. The maximum expression level and enzyme activity of proteinase K, which were obtained from the recombinant yeast strain bearing 5 copies of the target gene after an 84-h induction, were approximately 8.069 mg/mL and 108,295 U/mL, respectively. The recombinant proteinase was purified and characterized. The optimum pH and temperature for the activity of this protease were approximately pH 11 and 55 °C, respectively.

Anemarrhena asphodeloides Non-Steroidal Saponin Components Alter the Pharmacokinetic Profile of Its Steroidal Saponins in Rat.

A rapid, selective and sensitive UPLC-MS/MS assay was established to determine the plasma concentrations of four steroidal saponins. Sprague-Dawley rats were allocated to four groups which were orally administered Anemarrhena asphodeloides extracts (ASE), ASE combined with macromolecular fraction (ASE-MF), ASE combined with small molecule fraction (ASE-SF) and ASE combined with small molecule and macromolecular fraction (ASE-SF-MF) containing approximately the same dose of ASE. At different time points, the concentration of timosaponin BII, anemarsaponin BIII, timosaponin AIII and timosaponin E1 in rat plasma were determined and main pharmacokinetic parameters including Cmax, Tmax, T1/2, AUC were calculated using the DAS 3.2 software package. The statistical analysis was performed using the Student's t-test with p < 0.05 as the level of significance. MF had no effect on the pharmacokinetic behaviors and parameters of four steroidal saponins. It was found that Cmax and AUC of four steroidal saponins in group ASE-SF and ASE-SF-MF, were significantly increased compared with those in group ASE. These results indicate that SF in A. asphodeloides extracts could increase the absorption and improve the bioavailability of the steroidal saponins.

Simultaneous determination of five components in rat plasma by UPLC-MS/MS and its application to a comparative pharmacokinetic study in Baihe Zhimu Tang and Zhimu extract.

Baihe Zhimu Tang (BZT) is a famous traditional Chinese medicine recipe to treat dry coughing due to yin deficiency and for moisturizing the lungs. Zhimu is an essential ingredient in BZT used to treat inflammation, fever and diabetes. The most important active components in Zhimu are flavonoids such as neomangiferin, mangiferin, and steroid saponins (e.g., timosaponin BII, anemarsaponin BIII, timosaponin AIII). The aim of this study was to compare the pharmacokinetics of mangiferin, neomangiferin, timosaponin BII, anemarsaponin BIII and timosaponin AIII in rat plasma after oral administration of BZT and Zhimu extract (ZME). A sensitive, reliable and robust LC-MS/MS method to simultaneously determine steroid saponins and flavonoids in rat plasma was successfully validated. Significant differences (p < 0.05) were found in the pharmacokinetic parameters of timosaponin BII, anemarsaponin BIII and timosaponin AIII between BZT and ZME. It was surmised that formula compatibility could significantly influence the pharmacokinetics of BZT and our study is the first to study the administration of BZT based on pharmacokinetic studies.

The study of capacitive deionization behavior of a carbon nanotube electrode from the perspective of charge efficiency.

In this work, the capacitive deionization (CDI) performance of a single-walled carbon nanotube (CNT) electrode has been studied from the point view of charge efficiency theory. It is revealed here that the charge efficiency of a CNT electrode is strongly dependent upon the cell voltage and solution concentration. Either the high cell voltage or the low ionic strength results in a high charge efficiency, implying that CDI is expected to be a promising technique for an aqueous solution with low ionic strength. Additionally, it is found that the high decay constant and high electrical double-layer capacity are beneficial to enhance electrosorption performance.

[Quality Analysis and Evaluation of Anemarrhena asphodeloides Rhizome from Different Habitats].

UNLABELLED: tive: To compare and analyze the quality of Anemarrhena asphodeloides rhizome from different habitats. METHODS: Simultaneous determination of nine components in Anemarrhena asphodeloides rhizome by UPLC-TQ/MS was performed on a Phenomenex Kinetex XB-C18 (100 mm x 2.1 mm, 1.7 µm) column with the mobile phase consisted of 0.1% formic acid-acetonitrile (gradient elution) at the flow rate of 0.4 mL/min and thecolumn temperature at 35 degrees C. Multiple reaction mode detection (MRM) in mode was used in this assay. RESULTS: Nine components were separated totally within 15 min. Good correlation were found between the investigated compounds concentrations and their peak areas within the test ranges with the correlation coefficient from 0.9917 to 0.9992. The average recoveries were from 98.1% to 103.7%, and the RSD of precision was in the range of 1.7% - 4.7%. 0.074-3.620 mg/g for sarsasapogenin, 0.042-2.530 mg/g for timosaponin A III, 22.1- 50.4 mg/g for timosaponon B II, 0.10 -8.28 mg/g for officinalisinin II, 0.64 -7.29 mg/g for anemarsaponin B III, 3.28 -27.40 mg/g for mangiferin, 1.83 - 7.21 mg/g for isomangiferin, 0.36 -9.25 mg/g for neomangiferin and 4.72 x 10(-5) - 1.38 x 10(-3) mg/g for baohuoside I in Anemarrhena asphodeloides rhizome from different habitats were detected. CONCLUSION: The method is rapid, accurate and can be used for quality evaluation of Anemarrhena asphodeloides rhizome. The quality of Anemarrhena asphodeloides rhizome from different habitats are different. The saponins content of Anemarrhena asphodeloides rhizome in Hebei is higher than that of the others.

[Determination of lignans in schisandrae sphenantherae fructus from different regions].

With an objective to provide an experimental basis for scientific officinal of Schisandrae Sphenantherae Fructus, this research uses UPLC-TQ/MS method to analyze 7 different kinds of lignan in 70 batches of Schisandra sphenantherae Fructus samples from 9 regions. The results showed that in the area south of Qinling mountains, Schisandrae sphenantherae Fructus from Zhashui county and Shanyang county of Shangluo mainly contained schisantherin A and deoxyschizandrin. However, Schisandrae sphenantherae Fructus from Mei county of Baoji, Shiquan county and Ningshan county of Ankang, and Lueyang county of Hanzhong, mainly contained anwuligan. Samples from Ningshan county also consists relatively high level of deoxyschizandrin. In the central area of Qinling mountains and the Daba mountains, Schisandrae Sphenantherae Fructus from Nanzheng county of Hanzhong mainly contained schisanhenol and deoxyschizandrin. In conclusion, the kinds and level of lignan differ significantly in Schisandrae sphenantherae Fructus produced in different regions. In practical application, Schisandrae Sphenantherae Fructus produced in different regions should be distinguished and differently applied based on their main effective components corresponding to different diseases, which can lead to the best clinical use.

Isolation and microbial transformation of tea sapogenin from seed pomace of Camellia oleifera with anti-inflammatory effects.

In the current study, tea saponin, identified as the primary bioactive constituent in seed pomace of Camellia oleifera Abel., was meticulously extracted and hydrolyzed to yield five known sapogenins: 16-O-tiglogycamelliagnin B (a), camelliagnin A (b), 16-O-angeloybarringtogenol C (c), theasapogenol E (d), theasapogenol F (e). Subsequent biotransformation of compound a facilitated the isolation of six novel metabolites (a1-a6). The anti-inflammatory potential of these compounds was assessed using pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns molecules (DAMPs)-mediated cellular inflammation models. Notably, compounds b and a2 demonstrated significant inhibitory effects on both lipopolysaccharide (LPS) and high-mobility group box 1 (HMGB1)-induced inflammation, surpassing the efficacy of the standard anti-inflammatory agent, carbenoxolone. Conversely, compounds d, a3, and a6 selectivity targeted endogenous HMGB1-induced inflammation, showcasing a pronounced specificity. These results underscore the therapeutic promise of C. oleifera seed pomace-derived compounds as potent agents for the management of inflammatory diseases triggered by infections and tissue damage.

Novel MeON-glycosides of ursolic acid: Synthesis, antitumor evaluation, and mechanism studies.

Ursolic acid (UA) is a pentacyclic triterpenoid widely found in in medicinal plants, edible plants, fruits, and flowers. The great interest in this bioactive compound is related to the positive effects in human health. However, its limited solubility, moderate biological activity and poor bioavailability limit the potential and further applications of UA. Here, we explored the efficacy of MeON-Glycosides of UA in inhibiting tumor cell proliferation. A number of compounds showed significant antitumor activity against tested five cancer cell lines. Among them, compound 2a exhibited the most potent activity against HepG2 cells with IC50 values of 3.1 ± 0.5 µM. Especially, compound 2a could induce HepG2 cells apoptosis and reduce mitochondrial membrane potential. Western blot analysis showed that compound 2a up-regulated Bax, cleaved caspase-3/9, cleaved PARP levels and down-regulated Bcl-2 level of HepG2 cells. These results indicated that compound 2a could obviously induce the apoptosis of HepG2 cells. At the same time, compound 2a significantly decreased the expression of p-AKT and p-mTOR, which indicated that compound 2a might exert its cytotoxic effect by targeting PI3K/AKT/mTOR signaling pathway. Moreover, the in silico ADME predictions showed that compound 2a has improved water solubility and other properties. Thus, compound 2a may be a promising antitumor candidate, which may be potentially used to prevent or treat cancers.

BvCPD promotes parenchyma cell and vascular bundle development in sugar beet (Beta vulgaris L.) taproot.

Constitutive photomorpogenic dwarf (CPD) is a pivotal enzyme gene for brassinolide (BR) synthesis and plays an important role in plant growth, including increasing plant biomass and plant height, elongating cells, and promoting xylem differentiation. However, little is known about the function of the CPD gene in sugar beet. In the current study, we isolated CPD from Beta vulgaris L. (BvCPD), which encodes protein localized in the nucleus, cell membrane, and cell wall. BvCPD was strongly expressed in parenchyma cells and vascular bundles. The transgenic sugar beet overexpressing BvCPD exhibited larger diameter than that of the wild type (WT), which mainly owing to the increased number and size of parenchyma cells, the enlarged lumen and area of vessel in the xylem. Additionally, overexpression of BvCPD increased the synthesis of endogenous BR, causing changes in the content of endogenous auxin (IAA) and gibberellin (GA) and accumulation of cellulose and lignin in cambium 1-4 rings of the taproot. These results suggest that BvCPD can promote the biosynthesis of endogenous BR, improve cell wall components, promote the development of parenchyma cells and vascular bundle, thereby playing an important role in promoting the growth and development of sugar beet taproot.

Real-time wear monitoring of hob cutter based on statistical analysis.

Real-time wear monitoring of hob cutters is of great significance to the quality and efficiency of gear hobbing. To achieve this goal, a strategy based on statistical analysis is proposed in this paper. First, vibration signals during the entire life cycle of a hob cutter are collected. Then, a feature iterative integration method is proposed to integrate the initial features of vibration signals. The integrated features have obvious stages, reflecting the different wear status of hob cutters. Next, a probability tabular cumulative sum control chart method is established to monitor the wear status of hob cutters in real time. Finally, the verification results of two different data sets prove the effectiveness and transferability of the proposed methods.