Dual-ligand quasi-2D perovskites with chiral-induced spin selectivity for room temperature spin-LEDs.

Spin-LEDs have been a central topic in semiconductor spintronics research and represent a promising avenue for advanced optoelectronic devices and applications. The future advancements of spin-LEDs will undoubtedly hinge on the generation and manipulation of spin-polarized population at room temperature. In this research, we elucidate the development of room-temperature spin-LEDs using quasi-2D perovskites, based on the chiral-induced spin selectivity (CISS) effect. During the carrier transfer from the chiral n2 phase to the randomly oriented high-n phase caused by the bandgap gradient distribution, CISS works to generate non-equilibrium spin population, leading to room-temperature spin-polarized fluorescence. A spin-polarization of ∼93% is observed for the films. Finally, we realize spin-LEDs at room temperature, exhibiting a |gCP-EL| value of 0.05 and an EQE of 3.8%. This work highlights the potential of integrating dual ligands to optimize the phase distribution and crystalline orientation in quasi-2D films to achieve efficient CISS for spin-LED applications.

Achieving High Proton Conductivity in MIL-91(Al) Aerogel.

The processability and sustainability of proton conductors are two important indicators of their application. Here, MIL-91(Al) with an intrinsic proton conduction framework originating from protonated phosphonate groups was cross-linked with poly(vinyl alcohol) (PVA) to obtain MIL-91(Al) aerogel through freeze-drying. This simple and inexpensive strategy not only facilitated the processing of MIL-91(Al) powder but also resulted in a molded MIL-91(Al) aerogel having a high proton conductivity of 1.02 × 10-2 S cm-1 at 70 °C and 100% relative humidity. Furthermore, MIL-91(Al) aerogel was recyclable and reusable, in line with the principles of environmental protection and sustainability. To the best of our knowledge, this is the first example of using a metal-organic framework aerogel as a proton conductor, which may develop a new model system in this field.

In situ synergistic halogen passivation of semiconducting PbS quantum dot inks for efficient photovoltaics.

Lead sulfide colloidal quantum dots (PbS CQDs) show great potential in next-generation photovoltaics. However, their high specific surface area and complex surface crystallography lead to a high surface trap density, which normally requires more than one type of capping ion or ligand to achieve effective surface passivation. In this study, we performed in situ mixed halogen passivation (MHP) during the direct synthesis of semiconducting PbS CQD inks by using different lead halogens. The different halogens can bind with the surface of the CQD throughout the nucleation/growth process, resulting in optimal surface configuration. As a result, the MHP CQD exhibited superior surface passivation compared to the conventionally iodine-capped CQDs. Finally, we achieved a substantial improvement in efficiency from 10.64% to 12.58% after the MHP treatment. Our work demonstrates the advantages of exploring efficient passivation in the directly synthesized CQD inks.

Effect of fat concentration on protein digestibility of Chinese sausage.

Chinese sausage is a popular traditional Chinese meat product, but its high-fat content makes consumers hesitant. The purpose of this study is to compare the nutritional differences of Chinese sausages with different fermentation times (0, 10, 20, 30 d) and fat content (the initial content was 11.59% and 20.14%) during digestion. The comparison of digestion degree, protein structure, and peptide composition between different sausages were studied through in vitro simulated digestion. Chinese sausages with high-fat content had higher α-helix, ß-turn, and random coil, making them easier to digest. The fermentation process made this phenomenon more pronounced. The high-fat sausage fermented for 10 d showed the highest release of primary amino acids (about 9.5%), which was about 3.5% higher than the low-fat sausage under the same conditions. The results of peptidomics confirmed the relevant conclusions. After gastric digestion, the types of peptides in the digestive fluid of high-fat sausages were generally more than those in low-fat sausages, while after intestinal digestion, the opposite results were observed. The type of peptide reached its peak after fermentation for 20 d. These findings are of obvious significance for selecting the appropriate fermentation time and fat content of Chinese sausages.

PLANET: A Multi-objective Graph Neural Network Model for Protein-Ligand Binding Affinity Prediction.

Predicting protein-ligand binding affinity is a central issue in drug design. Various deep learning models have been published in recent years, where many of them rely on 3D protein-ligand complex structures as input and tend to focus on the single task of reproducing binding affinity. In this study, we have developed a graph neural network model called PLANET (Protein-Ligand Affinity prediction NETwork). This model takes the graph-represented 3D structure of the binding pocket on the target protein and the 2D chemical structure of the ligand molecule as input. It was trained through a multi-objective process with three related tasks, including deriving the protein-ligand binding affinity, protein-ligand contact map, and ligand distance matrix. Besides the protein-ligand complexes with known binding affinity data retrieved from the PDBbind database, a large number of non-binder decoys were also added to the training data for deriving the final model of PLANET. When tested on the CASF-2016 benchmark, PLANET exhibited a scoring power comparable to the best result yielded by other deep learning models as well as a reasonable ranking power and docking power. In virtual screening trials conducted on the DUD-E benchmark, PLANET's performance was notably better than several deep learning and machine learning models. As on the LIT-PCBA benchmark, PLANET achieved comparable accuracy as the conventional docking program Glide, but it only spent less than 1% of Glide's computation time to finish the same job because PLANET did not need exhaustive conformational sampling. Considering the decent accuracy and efficiency of PLANET in binding affinity prediction, it may become a useful tool for conducting large-scale virtual screening.

Cirsiliol induces autophagy and mitochondrial apoptosis through the AKT/FOXO1 axis and influences methotrexate resistance in osteosarcoma.

BACKGROUND: Osteosarcoma (OS) is the most common primary malignant bone tumor in children and adolescents, with poor outcomes for patients with metastatic disease or chemotherapy resistance. Cirsiliol is a recently found flavonoid with anti-tumor effects in various tumors. However, the effects of cirsiliol in the regulation of aggressive behaviors of OS remain unknown. METHODS: The effect of cirsiliol on the proliferation of OS cells was detected using a cell counting kit-8 (CCK-8) assay and 5-ethynyl-2'-deoxyuridine (EdU) staining, while cell apoptosis was detected using flow cytometry. Immunofluorescence was applied to visualize the expression level of the mitochondria, lysosomes and microtubule-associated protein light chain 3 (LC3). A computational molecular docking technique was used to predict the interaction between cirsiliol and the AKT protein. The impact of cirsiliol on resistance was investigated by comparing it between a methotrexate (MTX)-sensitive OS cell line, U2OS, and a MTX-resistant OS cell line, U2OS/MTX. Finally, in situ xenogeneic tumor models were used to validate the anti-tumor effect of cirsiliol in OS. RESULTS: Cirsiliol inhibited cell proliferation and induced apoptosis in both U2OS and U2OS/MTX300 OS cells. In addition, treatment with cirsiliol resulted in G2 phase arrest in U2OS/MTX300 and U2OS cells. Cell fluorescence probe staining results showed impaired mitochondria and increased autophagy in OS cells after treatment with cirsiliol. Mechanistically, it was found that cirsiliol targeted AKT by reducing the phosphorylation of AKT, which further activated the transcriptional activity of forkhead Box O transcription factor 1 (FOXO1), ultimately affecting the function of OS cells. Moreover, in situ tumorigenesis experiments showed that cirsiliol inhibited the tumorigenesis and progression of OS in vivo. CONCLUSIONS: Cirsiliol inhibits OS cell growth and induces cell apoptosis by reducing AKT phosphorylation and further promotes FOXO1 expression. These phenomena indicate that cirsiliol is a promising treatment option for OS.

Controlled Synthesis of α-CF2H or α-CF2Cl Styrenes from the Same Precursors: Dehydrazinative Hydrogenation or Chlorination of 3,3-Difluoroallyl Hydrazines.

By carefully choosing the reaction conditions, we have developed the controllable FeCl3- or CuCl2-mediated dehydrazinative hydrogenation or chlorination of 3,3-difluoroallyl hydrazines to access α-CF2H or α-CF2Cl styrenes. The current reaction provides for the first time a facile method for the direct and selective synthesis of α-CF2H and α-CF2Cl styrenes starting from the same precursors, which is easy to scale up and displays a broad substrate scope and good functional group tolerance. Moreover, product derivatization experiments demonstrated that the resulting α-CF2Cl styrenes are practical and versatile building blocks for the diversified synthesis of fluorinated molecules.

Neuroprotective effect of aloe emodin against Huntington's disease-like symptoms in R6/1 transgenic mice.

Aloe emodin is a natural anthraquinone derived from aloe or rhubarb, showing anti-renal fibrosis, anti-atherosclerosis and anti-cancer effects. Aloe emodin also shows neuroprotective effects in ischemic stroke rats. Naturally, anthraquinone derivatives generally have the effect of inhibiting the transforming growth factor-ß1 (TGF-ß1) pathway. There is an increase in the calcium/calmodulin-dependent protein kinase II (CaMKII) and TGF-ß1 levels in both Huntington's disease (HD) patients' brains and HD transgenic mice. Thus, we hypothesized that aloe emodin may inhibit the phosphorylation of CaMKII (p-CaMKII) and TGF-ß1/sma- and mad-related protein (Smad) signaling in the brain, further preventing motor and cognitive dysfunction. Aloe emodin was orally administered to 10- to 20-week-old HD R6/1 transgenic mice. Aloe emodin improved the motor coordination of R6/1 transgenic mice in the rotarod test and attenuated visual recognition impairment in the novel object recognition test. Aloe emodin downregulated levels of the mutant huntingtin protein, p-CaMKII and TGF-ß1, but not the TGF-ß2 or TGF-ß3 levels, in the brains of R6/1 mice. Aloe emodin could also inhibit neuronal apoptosis in the hippocampus of R6/1 mice. Altogether, these results indicated that aloe emodin prevents several HD-like symptoms through the inhibition of CaMKII/Smad and TGF-ß1/Smad signaling in mice.

Flavor evolution of normal- and low-fat Chinese sausage during natural fermentation.

This work compared the flavor evolution of normal-fat (NF) with that of low-fat (LF) Chinese sausage during natural fermentation. Higher degree of lipid oxidation occurred in NF sausages, resulting in its faster formation of stable volatile profiles. Faster formation of esters occurred in NF sausage in the initial 10 days, whereas prolonged fermentation reduced the level of ethyl lactate-M, ethyl heptanoate, ethyl hexanoate-D and ethyl pentanoate-D. Gradual reduction of alcohols was observed in both groups, and surge in aldehydes occurred in LF samples during day 20-30 period. Faster formation of taste characteristics and larger amount of 2-methylfuran as well as 2,3-dimethylpyrazine were found in LF sausages, since more free amino acids were liberated in LF sausages. Umami and aftertaste tastes formed in the first 20 days, whereas prolonged fermentation reduced these favorable taste. These results highlight that the choice of proper fermentation duration should largely depend on the fat content in Chinese sausages.

A-to-I RNA Editing in Klebsiella pneumoniae Regulates Quorum Sensing and Affects Cell Growth and Virulence.

Millions of adenosine (A) to inosine (I) RNA editing events are reported and well-studied in eukaryotes; however, many features and functions remain unclear in prokaryotes. By combining PacBio Sequel, Illumina whole-genome sequencing, and RNA Sequencing data of two Klebsiella pneumoniae strains with different virulence, a total of 13 RNA editing events are identified. The RNA editing event of badR is focused, which shows a significant difference in editing levels in the two K. pneumoniae strains and is predicted to be a transcription factor. A hard-coded Cys is mutated on DNA to simulate the effect of complete editing of badR. Transcriptome analysis identifies the cellular quorum sensing (QS) pathway as the most dramatic change, demonstrating the dynamic regulation of RNA editing on badR related to coordinated collective behavior. Indeed, a significant difference in autoinducer 2 activity and cell growth is detected when the cells reach the stationary phase. Additionally, the mutant strain shows significantly lower virulence than the WT strain in the Galleria mellonella infection model. Furthermore, RNA editing regulation of badR is highly conserved across K. pneumoniae strains. Overall, this work provides new insights into posttranscriptional regulation in bacteria.

Design, Synthesis, and Biological Evaluation of Sulfonamide Methoxypyridine Derivatives as Novel PI3K/mTOR Dual Inhibitors.

Phosphatidylinositol 3-kinase (PI3K) plays an important role in cell proliferation, survival, migration, and metabolism, and has become an effective target for cancer treatment. Meanwhile, inhibiting both PI3K and mammalian rapamycin receptor (mTOR) can simultaneously improve the efficiency of anti-tumor therapy. Herein, a series of 36 sulfonamide methoxypyridine derivatives with three different aromatic skeletons were synthesized as novel potent PI3K/mTOR dual inhibitors based on a scaffold hopping strategy. Enzyme inhibition assay and cell anti-proliferation assay were employed to assess all derivatives. Then, the effects of the most potent inhibitor on cell cycle and apoptosis were performed. Furthermore, the phosphorylation level of AKT, an important downstream effector of PI3K, was evaluated by Western blot assay. Finally, molecular docking was used to confirm the binding mode with PI3Kα and mTOR. Among them, 22c with the quinoline core showed strong PI3Kα kinase inhibitory activity (IC50 = 0.22 nM) and mTOR kinase inhibitory activity (IC50 = 23 nM). 22c also showed a strong proliferation inhibitory activity, both in MCF-7 cells (IC50 = 130 nM) and HCT-116 cells (IC50 = 20 nM). 22c could effectively cause cell cycle arrest in G0/G1 phase and induce apoptosis of HCT-116 cells. Western blot assay showed that 22c could decrease the phosphorylation of AKT at a low concentration. The results of the modeling docking study also confirmed the binding mode of 22c with PI3Kα and mTOR. Hence, 22c is a promising PI3K/mTOR dual inhibitor, which is worthy of further research in the area.

Antimicrobial susceptibility to polymyxin B and other comparators against Gram-negative bacteria isolated from bloodstream infections in China: Results from CARVIS-NET program.

Objective: To investigate the bacterial distribution and antimicrobial resistance profile of clinical isolates from Gram-negative bacteria bloodstream infections (GNBSI) in China. Methods: The clinical bacterial strains isolated from blood culture were collected during April 2019 to December 2021 in 21 member hospitals of China Bloodstream Gram-negative Pathogens Antimicrobial Resistance and Virulence Surveillance Network (CARVIS-NET). Antibiotic susceptibility test was conducted by broth microdilution method recommended by Clinical and Laboratory Standards Institute (CLSI, United States). WHONET 2021 and SPSS 22.0 were used to analyze data. Results: During the study period, 1939 Gram-negative bacteria were collected from 21 hospitals, among which 1,724 (88.9%) were Enterobacteriaceae, 207 (10.7%) were non-fermenting Gram-negative bacteria and 8 (0.4%) were others. The top five bacterial species were Escherichia coli (46.2%), Klebsiella pneumoniae (31.6%), Pseudomonas aeruginosa (4.9%), Acinetobacter baumannii (4.2%) and Enterobacter cloacae (3.0%). For K. pneumoniae, antibiotic resistance was mainly prevalent in hospital-associated bloodstream infections, while for A. baumannii, antibiotic resistance was mainly prevalent in community-associated bloodstream infections. It is worth mentioning that 94.1% of the 1939 Gram-negative isolates were susceptible to polymyxin B. The sensitivity of the strains involved in our investigation to polymyxin B is highly correlated with their sensitivity to colistin. Conclusion: The surveillance results in CARVIS-NET-2021 showed that the main pathogens of GNBSI in China were Enterobacteriaceae, while E. coli was the most common pathogen. The resistance rates of K. pneumonia, P. aeruginosa, A. baumannii, and E. cloacae to multiple antibiotics kept on a high level. In many cases, polymyxin B and colistin has become the last-resort agents to combat bloodstream infections caused by multidrug-resistant (MDR) Gram-negative bacteria.

An electrochemical chiral sensor for amino acids based on cyclodextrin modified thiophene-based copolymer.

Two series of thiophene-based copolymers with cyclodextrins (CDs) grafted on side chain (OH-ß-CD-P3HT and Ph-ß-CD-P3HT) were synthesized via click reaction, in which the pendant CDs and the polythiophenes (PTs) main chain afford stereo-selective interactions and high conductivity respectively. The copolymers have been employed to construct an electrochemical sensor to achieve efficient enantio-recognition for amino acids. The OH-ß-CD-P3HT and Ph-ß-CD-P3HT shows reverse interaction preference for D- and L-isomer due to the different interaction mode of native and substituted CDs with chiral guest. It is found that, higher content of block with CD in the copolymer favors lower LOD because of the specific inclusion abilities of CD, while lower content of block with CD is beneficial to chiral selectivity related to the higher structural flexibility of the polymer. The electrochemical sensor was also proven to be capable of determining the relative content of L- or D-isomer in an enantiomer pair.

Silibinin Ameliorates Formaldehyde-Induced Cognitive Impairment by Inhibiting Oxidative Stress.

Silibinin is a flavonoid extracted from the medicinal plant Silybum marianum (milk thistle), traditionally used to treat liver disease. Recent studies have shown that the antioxidative stress and anti-inflammatory effects of milk thistle are used in the treatment of neurological diseases. Silibinin has antioxidative stress and antiapoptotic effects and reduces cognitive impairment in models of Alzheimer's disease (AD). However, the underlying mechanism of silibinin related to improvement of cognition remains poorly understood. In this study, we used the model of lateral ventricle injection of formaldehyde to examine the related mechanism of silibinin in improving cognitive impairment disorders. Oral administration of silibinin for three weeks significantly attenuated the cognitive deficits of formaldehyde-induced mice in a Y-maze test and Morris water maze test. Y-maze results show that silibinin increases the rate of spontaneous response alternation in FA-induced mice. Silibinin increases the target quadrant spending time and decreases escape latency in the Morris water maze test. We examined the effect of silibinin on the NRF2 signaling pathway, and silibinin promoted the nuclear transfer of NRF2 and increased the expression of HO-1 but did not significantly increase the protein expression of NRF2 in the hippocampus. Well, silibinin reduces the content of DHE and decreases the levels of apoptosis of mature neuron cells. We investigated the effect of silibinin on the content of formaldehyde degrading enzymes; biochemical analyses revealed that silibinin increased GSH and ALDH2 in formaldehyde-induced mice. In addition, as one of the pathological changes of AD, TAU protein is also hyperphosphorylated in FA model mice. Silibinin inhibits the expression of GSK-3ß in model mice, thereby reducing the phosphorylation of TAU proteins ser396 and ser404 mediated by GSK3ß. Based on our findings, we verified that the mechanism of silibinin improving cognitive impairment may be antioxidative stress, and silibinin is one of the potentially promising drugs to prevent formaldehyde-induced cognitive impairment.