A chalcone derivative reactivates latent HIV-1 transcription through activating P-TEFb and promoting Tat-SEC interaction on viral promoter.

The principal barrier to the eradication of HIV/AIDS is the existence of latent viral reservoirs. One strategy to overcome this barrier is to use latency-reversing agents (LRAs) to reactivate the latent proviruses, which can then be eliminated by effective anti-retroviral therapy. Although a number of LRAs have been found to reactivate latent HIV, they have not been used clinically due to high toxicity and poor efficacy. In this study, we report the identification of a chalcone analogue called Amt-87 that can significantly reactivate the transcription of latent HIV provirses and act synergistically with known LRAs such as prostratin and JQ1 to reverse latency. Amt-87 works by activating the human transcriptional elongation factor P-TEFb, a CDK9-cyclin T1 heterodimer that is part of the super elongation complex (SEC) used by the viral encoded Tat protein to activate HIV transcription. Amt-87 does so by promoting the phosphorylation of CDK9 at the T-loop, liberating P-TEFb from the inactive 7SK snRNP, and inducing the formation of the Tat-SEC complex at the viral promoter. Together, our data reveal chalcones as a promising category of compounds that should be further explored to identify effective LRAs for targeted reversal of HIV latency

Multilevel leapfrogging initialization for quantum approximate optimization algorithm

The quantum approximate optimization algorithm (QAOA) is a prospective hybrid quantum-classical algorithm widely used to solve combinatorial optimization problems. However, the external parameter optimization required in QAOA tends to consume extensive resources to find the optimal parameters of the parameterized quantum circuit, which may be the bottleneck of QAOA. To meet this challenge, we first propose multilevel leapfrogging learning (M-Leap) that can be extended to quantum reinforcement learning, quantum circuit design, and other domains. M-Leap incrementally increases the circuit depth during optimization and predicts the initial parameters at level $p+r$ ($r>1$) based on the optimized parameters at level $p$, cutting down the optimization rounds. Then, we propose a multilevel leapfrogging-interpolation strategy (MLI) for initializing optimizations by combining M-Leap with the interpolation technique. We benchmark its performance on the Maxcut problem. Compared with the Interpolation-based strategy (INTERP), MLI cuts down at least half the number of rounds of optimization for the classical outer learning loop. Remarkably, the simulation results demonstrate that the running time of MLI is 1/3 of INTERP when MLI gets quasi-optimal solutions. In addition, we present the greedy-MLI strategy by introducing multi-start, which is an extension of MLI. The simulation results show that greedy-MLI can get a higher average performance than the remaining two methods. With their efficiency to find the quasi-optima in a fraction of costs, our methods may shed light in other quantum algorithms

Identification of Antioxidant Proteins With Deep Learning From Sequence Information

Antioxidant proteins have been found closely linked to disease control for its ability to eliminate excess free radicals. Because of its medicinal value, the study of identifying antioxidant proteins is on the upsurge. Many machine-learning classifiers have performed poorly owing to the nonlinear and unbalanced nature of biological data. Recently, deep learning techniques showed advantages over many state-of-the-art machine learning methods in various fields. In this study, a deep learning based classifier was proposed to identify antioxidant proteins based on mixed g-gap dipeptide composition feature vector. The classifier employed deep autoencoder to extract nonlinear representation from raw input. The t-Distributed Stochastic Neighbor Embedding (t-SNE) was used for dimensionality reduction. Support vector machine was finally performed for classification. The classifier achieved F1 score of 0.8842 and MCC of 0.7409 in 10-fold cross validation. Experimental results show that our proposed method outperformed the traditional machine learning methods and could be a promising tool for antioxidant protein identification. For the convenience of others' scientific research, we have developed a user-friendly web server called IDAod for antioxidant protein identification, which can be accessed freely at http://bigroup.uestc.edu.cn/IDAod/

Selection of Pru p 3 hypoallergenic peach and nectarine varieties

To the Editor, Peach is an important fruit consumed worldwide. However, it is also one of the most frequently reported allergenic fruits.1 Component diagnosis of peach allergy indicates Pru p 1, Pru p 2, Pru p 3, Pru p 4, Pru p 7, and Pru p 9 are involved.2, 3 Pru p 3 is the dominant allergen responsible for severe allergic reaction,4 and it is considered to be the primary sensitizer to other LTPs in Mediterranean and Central Europe.5 The levels of Pru p 3 differ between varieties.6 To date, measurement of Pru p 3 in a limited number of peach and nectarines from Spain, United States, and Italy has been reported.7 Significant variation of allergen concentration in processed foods containing peach has also been observed.8 The content of Pru p 3 of peach/nectarine determines the potential risk for peach allergic patients. China is the origin of peach with representative genetic diversity to be explored for hypoallergenic varieties.9 A core collection of 103 varieties cultivated in Jiaxing, Zhejiang Province were selected to represent this diversity, including 23 nectarines and 80 peach varieties (with fruit hair, round or flat, 77 cultivated, three wild) (Table S1). The soluble solid content (SSC), ripening date, and peach aroma intensity were recorded. Specific methods are detailed in the Supporting Information. Pru p 3 was quantified by ELISA based on our previous research.6info:eu-repo/semantics/publishedVersio

A STUDY ON THE INHIBITORY EFFECT OF RADIX SEMIAQUILEGIAE EXTRACT ON HUMAN HEPATOMA HEPG-2 AND SMMC-7721 CELLS

The main objective of this paper was to investigate the extraction process of ethanol extract of Radix Semiaquilegiae, as well as its inhibitory activity on human hepatoma HepG-2 and SMMC-7721 cells, and to compare the inhibitory effects of different concentrations of ethanol extracts against these two hepatoma cells. Ethanol reflux extraction and ultrasound-assisted extraction with ethanol at room temperature were used in the extraction process, and MTT assay was mainly used in the activity experiment to perform in-vitro anti HepG-2 and SMMC-7721 cell activity screening of ethanol extract, and to calculate the cell inhibition rates of the extracts. The results showed that among the two types of extracts, ethanol reflux extract had more superior antitumour activity to that of the ultrasonic extract, but all of the extracts obtained had certain anti-cancer activities, and the anti-proliferative activity increased with the increase of concentration

Elevated atmospheric CO2 concentration triggers redistribution of nitrogen to promote tillering in rice

Elevated atmospheric CO2 concentration (eCO2) often reduces nitrogen (N) content in rice plants and stimulates tillering. However, there is a general consensus that reduced N would constrain rice tillering. To resolve this contradiction, we investigated N distribution and transcriptomic changes in different rice plant organs after subjecting them to eCO2 and different N application rates. Our results showed that eCO2 significantly promoted rice tillers (by 0.6, 1.1, 1.7, and 2.1 tillers/plant at 0, 75, 150, and 225 kg N ha−1 N application rates, respectively) and more tillers were produced under higher N application rates, confirming that N availability constrained tillering in the early stages of growth. Although N content declined in the leaves (−11.0 to −20.7 mg g−1) and sheaths (−9.8 to −28.8 mg g−1) of rice plants exposed to eCO2, the N content of newly emerged tillers on plants exposed to eCO2 equaled or exceeded the N content of tillers produced under ambient CO2 conditions. Apparently, the redistribution of N within the plant per se was a critical adaptation strategy to the eCO2 condition. Transcriptomic analysis revealed that eCO2 induced less extensive alteration of gene expression than did N application. Most importantly, the expression levels of multiple N-related transporters and receptors such as nitrate transporter NRT2.3a/b and NRT1.1a/b were differentially regulated in leaf and shoot apical meristem, suggesting that multiple genes were involved in sensing the N signal and transporting N metabolites to adapt to eCO2. The redistribution of N in different organs could be a universal adaptation strategy of terrestrial plants to eCO2

Enhanced antitumor immunity by targeting dendritic cells with tumor cell lysate-loaded chitosan nanoparticles vaccine

Whole tumor cell lysates (TCL) have been implemented as tumor antigens for cancer vaccine development, although clinical outcomes of TCL-based antitumor immunotherapy remain unsatisfactory. In order to improve the efficacy of TCL-based vaccines, biomaterials have been employed to enhance antigen delivery and presentation. Here, we have developed chitosan nanoparticles (CTS NPs) with surface mannose (Man) moieties for specific dendritic cells (DCs) targeting (Man-CTS NPs). The Man-CTS NPs were then loaded with TCL generated from B16 melanoma cells (Man-CTS-TCL NPs) for in vitro and in vivo assessment. Potency of the Man-CTS-TCL NPs as cancer vaccine was also assessed in vivo by immunization of mice with Man-CTS-TCL NPs followed by re-challenge with B16 melanoma cell inoculation. We have shown here that Man-CTS-TCL NPs promote bone marrow-derived dendritic cells (BMDCs) maturation and antigen presentation in vitro. In vivo evaluation further demonstrated that the Man-CTS-TCL NPs were readily taken up by endogenous DCs within the draining lymph node (DLN) following subcutaneous administration accompanied by increasing in serum IFN-γ and IL-4 levels. Tumor growth was also significantly delayed in mice primed with Man-CTS-TCL NPs vaccine, attributable at least in part to cytotoxic T lymphocytes response. Moreover, Man-CTS-TCL NPs vaccine also exhibited therapeutic effects in mice with melanoma. Thus, we report here the Man-CTS-TCL NPs as effective anti-tumor vaccine for cancer immunotherapy