Simulation research on aerodynamic noise characteristics of a compressor under different working conditions.

The shear stress transport turbulence model is employed to conduct a detailed study of flow characteristics at the highest efficiency point and near-stall point in a full-channel 1.5-stage compressor in this paper. The simulation results for the compressor's total pressure ratio and efficiency exhibit good agreement with experimental data. Emphasis is placed on examining the internal flow structure in the tip area of the compressor rotor under near-stall conditions. The results reveal that significant differences in flow structure primarily occur in the tip area as the compressor approaches stall. Specifically, a reduction in turbulent kinetic energy is observed in a region spanning approximately 20%-60% of the chord length on the rotor suction face near-stall conditions. Two additional peak frequencies, at 0.8 and 1.6 times the blade passage frequency, are observed, and the intricate flow phenomena are elaborated at the near-stall point. The near-stall point exhibits greater noise levels than the highest efficiency point, where the intensity of the surface source increases by more than 10 dB, peaking at 20 dB. This additional peak serves as a significant supplementary noise source near the stall point, leading to a maximum increase of 33.3 dB in the free radiated sound power. The acoustic response within the duct indicates that the compressor operating at the near-stall point continues to produce substantial noise on the actual test bench, showing an average increase of 6 dB in noise levels, and the distribution of the additional peak single-tone noise at the entrance significantly differs from that observed at the highest efficiency point.

Reactive oxygen species (ROS) modulate nitrogen signaling using temporal transcriptome analysis in foxtail millet.

Reactive oxygen species (ROS) is a chemically reactive chemical substance containing oxygen and a natural by-product of normal oxygen metabolism. Excessive ROS affect the growth process of crops, which will lead to the decrease of yield. Nitrogen, as a critical nutrient element in plants and plays a vital role in plant growth and crop production. Nitrate is the primary nitrogen source available to plants in agricultural soil and various natural environments. However, the molecular mechanism of ROS-nitrate crosstalk is still unclear. In this study, we used the foxtail millet (Setaria italica L.) as the material to figure it out. Here, we show that excessive NaCl inhibits nitrate-promoted plant growth and nitrogen use efficiency (NUE). NaCl induces ROS accumulation in roots, and ROS inhibits nitrate-induced gene expression in a short time. Surprisingly, low concentration ROS slight promotes and high concentration of ROS inhibits foxtail millet growth under long-term H2O2 treatment. These results may open a new perspective for further exploration of ROS-nitrate signaling pathway in plants.

Mobile phone addiction and academic burnout: the mediating role of technology conflict and the protective role of mindfulness.

With the rapid development of Internet technology, more and more college students are facing the threat of mobile phone addiction. However, the relationship and underlying mechanism between mobile phone addiction and academic burnout haven't been explored in depth. This study proves the mediating role of technology conflict and the moderating role of mindfulness in the relation between mobile phone addiction and academic burnout. 752 college students were recruited to complete the questionnaire of mobile phone addiction, technology conflict, mindfulness and academic burnout. Results showed that mobile phone addiction was significantly and positively associated with academic burnout, and this relationship could be mediated by technology conflict. Besides, the direct effect of mobile phone addiction on academic burnout and the indirect effect of technology conflict in this link were moderated by mindfulness. Both these two effects are stronger for college students with lower level of mindfulness. Our findings enrich our understanding of how and when mobile phone addiction was related to academic burnout. Educational professionals and parents should take timely measure to the academic burnout of college students suffering from mobile phone addiction, particularly for those with lower level of mindfulness.

Amorphous/crystalline RhFeP metallene for hydrazine-assisted water splitting.

Replacing the slow oxygen evolution reaction with favorable hydrazine oxidation reaction (HzOR) is a green and efficient way to produce hydrogen. In this work, we synthesize amorphous/crystalline RhFeP metallene via phase engineering and heteroatom doping. RhFeP metallene has good catalytic activity and stability for HER and HzOR, and only an ultralow voltage of 18 mV is required to achieve 10 mA cm-2in a two-electrode hydrazine-assisted water splitting system. The superior result is mainly ascribed to the co-doping of Fe and P and the formation of amorphous/crystalline RhFeP metallene with abundant phase boundaries, thereby adjusting electronic structure and increasing active sites.

Structural insights into the Oryza sativa cation transporters HKTs in salt tolerance.

The high-affinity potassium transporters (HKTs), selectively permeable to either Na+ alone or Na+/K+, play pivotal roles in maintaining plant Na+/K+ homeostasis. Although their involvement in salt tolerance is widely reported, the molecular underpinnings of Oryza sativa HKTs remain elusive. In this study, we elucidate the structures of OsHKT1;1 and OsHKT2;1, representing two distinct classes of rice HKTs. The dimeric assembled OsHKTs can be structurally divided into four domains. At the dimer interface, a half-helix or a loop in the third domain is coordinated by the C-terminal region of the opposite subunit. Additionally, we present the structures of OsHKT1;5 salt-tolerant and salt-sensitive variants, a key quantitative trait locus associated with salt tolerance. The salt-tolerant variant of OsHKT1;5 exhibits enhanced Na+ transport capability and displays a more flexible conformation. These findings shed light on the molecular basis of rice HKTs and provide insights into their role in salt tolerance.

Interstitial Boron-Modulated Porous Pd Nanotubes for Ammonia Electrosynthesis.

Electrochemical conversion of nitrogen into ammonia at ambient conditions as a sustainable approach has gained significant attention, but it is still extremely challenging to simultaneously obtain a high faradaic efficiency (FE) and NH3 yield. In this work, the interstitial boron-doped porous Pd nanotubes (B-Pd PNTs) are constructed by combining the self-template reduction method with boron doping. Benefiting from distinctive one-dimensional porous nanotube architectonics and the incorporation of the interstitial B atoms, the resulting B-Pd PNTs exhibit high NH3 yield (18.36 µg h-1 mgcat.-1) and FE (21.95%) in neutral conditions, outperforming the Pd/PdO PNTs (10.4 µg h-1 mgcat.-1 and 8.47%). The present study provides an attractive method to enhance the efficiency of the electroreduction of nitrogen into ammonia by incorporating interstitial boron into porous Pd-based catalysts.

Degradation and translation of maternal mRNA for embryogenesis.

Maternal mRNAs accumulate during egg growth and must be judiciously degraded or translated to ensure successful development of mammalian embryos. In this review we integrate recent investigations into pathways controlling rapid degradation of maternal mRNAs during the maternal-to-zygotic transition. Degradation is not indiscriminate, and some mRNAs are selectively protected and rapidly translated after fertilization for reprogramming the zygotic genome during early embryogenesis. Oocyte specific cofactors and pathways have been illustrated to control different futures of maternal mRNAs. We discuss mechanisms that control the fate of maternal mRNAs during late oogenesis and after fertilization. Issues to be resolved in current maternal mRNA research are described, and future research directions are proposed.

Comparison of the effects of different artificial discs on hybrid surgery: A finite element analysis.

In recent years, artificial cervical discs have been used in intervertebral disc replacement surgery and hybrid surgery (HS). The advantages and disadvantages of different artificial cervical discs in artificial cervical disc replacement surgery have been compared. However, few scholars have studied the biomechanical effects of various artificial disc prostheses on the human cervical spine in HS which include the Anterior Cervical Discectomy and Fusion (ACDF) and Cervical Disc Arthroplasty (CDA). This study compared the biomechanical behavior of Mobi-C and Prestige LP in the operative and adjacent segments during two-level hybrid surgery. A three-dimensional finite element model of C2-C7 was first established and validated. Subsequently, clinical surgery was then simulated to establish a surgical model of anterior cervical fusion at the C4-C5 level. Mobi-C and Prestige-LP artificial disc prostheses were implanted at the C5-C6 level to create two hybrid models. All finite element models were fixed on the lower endplate of the C7 vertebra and subjected to a load of 73.6 N and different directions of 1 Nm torque on the odontoid process of the C2 vertebra to simulate human flexion, extension, lateral bending, and axial rotation. This paper compares the ROM, intervertebral pressure, and facet joint force after hybrid surgery with the intact model. The results show that compared with Prestige LP, Mobi-C can improve ROM of the replacement segment and compensate for the intervertebral pressure of the adjacent segment more effectively, but the facet joint pressure of the replacement segment may be higher.

Paternally imprinted LATE-FLOWERING2 transcription factor contributes to paternal-excess interploidy hybridization barriers in wheat.

Interploidy hybridization between hexaploid and tetraploid genotypes occurred repeatedly during genomic introgression events throughout wheat evolution, and is commonly employed in wheat breeding programs. Hexaploid wheat usually serves as maternal parent because the reciprocal cross generates progeny with severe defects and poor seed germination, but the underlying mechanism is poorly understood. Here, we performed detailed analysis of phenotypic variation in endosperm between two interploidy reciprocal crosses arising from tetraploid (Triticum durum, AABB) and hexaploid wheat (Triticum aestivum, AABBDD). In the paternal- versus the maternal-excess cross, the timing of endosperm cellularization was delayed and starch granule accumulation in the endosperm was repressed, causing reduced germination percentage. The expression profiles of genes involved in nutrient metabolism differed strongly between these endosperm types. Furthermore, expression patterns of parental alleles were dramatically disturbed in interploidy versus intraploidy crosses, leading to increased number of imprinted genes. The endosperm-specific TaLFL2 showed a paternally imprinted expression pattern in interploidy crosses partially due to allele-specific DNA methylation. Paternal TaLFL2 binds to and represses a nutrient accumulation regulator TaNAC019, leading to reduced storage protein and starch accumulation during endosperm development in paternal-excess cross, as confirmed by interploidy crosses between tetraploid wild-type and clustered regularly interspaced palindromic repeats (CRISPR) - CRISPR-associated protein 9 generated hexaploid mutants. These findings reveal a contribution of genomic imprinting to paternal-excess interploidy hybridization barriers during wheat evolution history and explains why experienced breeders preferentially exploit maternal-excess interploidy crosses in wheat breeding programs.

Structural basis for the activity regulation of Salt Overly Sensitive 1 in Arabidopsis salt tolerance.

The plasma membrane Na+/H+ exchanger Salt Overly Sensitive 1 (SOS1) is crucial for plant salt tolerance. Unlike typical sodium/proton exchangers, SOS1 contains a large cytoplasmic domain (CPD) that regulates Na+/H+ exchange activity. However, the underlying modulation mechanism remains unclear. Here we report the structures of SOS1 from Arabidopsis thaliana in two conformations, primarily differing in CPD flexibility. The CPD comprises an interfacial domain, a cyclic nucleotide-binding domain-like domain (CNBD-like domain) and an autoinhibition domain. Through yeast cell-based Na+ tolerance test, we reveal the regulatory role of the interfacial domain and the activation role of the CNBD-like domain. The CPD forms a negatively charged cavity that is connected to the ion binding site. The transport of Na+ may be coupled with the conformational change of CPD. These findings provide structural and functional insight into SOS1 activity regulation.

Effects of nitrogen addition on species composition and diversity of early spring herbs in a Korean pine plantation.

Under the background of global nitrogen deposition, temperate forest ecosystems are suffering increasing threats, and species diversity is gradually decreasing. In this study, nitrogen addition experiments were conducted on Korean pine (Pinus koraiensis) plantations in Northeast China to explore the effect of long-term nitrogen addition on herb species diversity to test the following hypothesis: long-term nitrogen addition further reduced plant species diversity by affecting plant growth, which may be due to soil acidification caused by excessive nitrogen addition. Experimental nitrogen addition was conducted from 2014 to 2021, and the nitrogen treatment levels were as follows: N0 (control treatment, 0/(kg N ha-1 year-1)), N20 (low nitrogen treatment, 20/(kg N ha-1 year-1)), N40 (medium nitrogen treatment, 40/(kg N ha-1 year-1)) and N80 (high nitrogen treatment, 80/(kg N ha-1 year-1)). A herb community survey was conducted in the region from 2015 to 2021. The results showed that long-term nitrogen addition decreased soil pH, changed the species and composition of herbaceous plants, and decreased the species diversity of understory herbaceous plants. With the increase in nitrogen application years, middle- and high-nitrogen treatments significantly reduced the diversity of early-spring flowering herbs and early-spring foliating herbs, and their diversity decreased with the decrease in soil pH, indicating that soil acidification caused by long-term nitrogen addition may lead to the decrease of plant diversity. However, for early-spring growing herbs, adequate nitrogen addition may promote their growth. Our results show that plants have evolved different life-history strategies based on their adaptation mechanisms to the environment, and different life-history strategies have different responses to long-term nitrogen addition. However, for most plants, long-term nitrogen application will have a negative impact on the growth and diversity of herbs in temperate forests.

Factorial structure and measurement invariance of the Chinese version of the Oral Health Impact Profile-14 among clinical populations and non-clinical populations: an evidence for public oral investigations.

OBJECTIVE: Oral health-related quality of life (OHRQoL) is a multidimensional concept that is commonly used to examine the impact of oral health status on quality of life. The purpose of this study was to examine the optimal factor model of the Chinese version of the Oral Health Impact Profile (OHIP-14) questionnaire in clinical populations, measurement invariance across clinical status and gender cohorts. This would ensure equal validity of the Chinese version of OHIP-14 in different populations and further support public oral investigations. METHODS: The Chinese version of OHIP-14 was used to investigate 490 dental patients and 919 college students. Confirmatory factor analysis (CFA), item analysis and reliability, measurement invariance, and the t-test were used for data analyses. RESULTS: We found that the 7-factor structure had the best-fit index in the sample (CFI = 0.970, TLI = 0.952; SRMR = 0.029, RMSEA = 0.052(0.040,0.063)). The reliability of the scales was satisfactory (Cronbach's α = 0.942). The error variance invariance fitted the data adequately in measurement invariance, indicating that measurement invariance is acceptable both across the clinical and non-clinical populations (∆CFI=-0.017, ∆RMSEA = 0.010) and across genders in the clinical population (∆CFI = 0.000, ∆RMSEA=-0.003). T-test for scores showed that the clinical populations scored significantly higher than the non-clinical populations, as did the overall score (t = 7.046, p < 0.001, d = 0.396), in terms of functional limitation (t = 2.178, p = 0.030, d = 0.125), physical pain (t = 7.880, p < 0.001,d = 0.436), psychological discomfort (t = 8.993, p < 0.001, d = 0.514), physical disability (t = 6.343, p < 0.001, d = 0.358), psychological disability (t = 5.592, p < 0.001, d = 0.315), social disability (t = 5.301, p < 0.001,d = 0.304), social handicap (t = 4.452, p < 0.001, d = 0.253), and that in the non-clinical populations, females scored significantly higher than males, as did in terms of physical pain (t = 3.055, p = 0.002, d = 0.280), psychological discomfort (t = 2.478, p = 0.014, d = 0.222), and psychological disability (t = 2.067, p = 0.039, d = 0.188). CONCLUSION: This study found that the Chinese version of OHIP-14 has measurement invariance between the clinical and non-clinical populations and across genders in the clinical populations, and can be widely used in OHRQoL assessment for public oral investigations.

Analysis of heart displacement during thoracic radiotherapy based on electrocardiograph-gated 4-dimensional magnetic resonance imaging.

Background: Periodic cardiac movement may expose the heart to radiation field induced damage, leading to radiation-induced heart disease (RIHD). Studies have proven that delineation of the heart based on planning CT fails to show the real margin of the substructures and a compensatory margin should be applied. The purpose of this study was to quantify the dynamic changes and the compensatory extension range by breath-hold and electrocardiogram gated 4-dimensional magnetic resonance imaging (4D-MRI), which had the advantage of discriminating soft tissues. Methods: Eventually, 15 patients with oesophageal or lung cancers were enrolled, including one female and nine males aged from 59 to 77 years from December 10th, 2018, to March 4th, 2020. The displacement of the heart and its substructures was measured through a fusion volume and the compensatory expansion range was calculated by expending the boundary on the planning CT to that of the fusion volume. The differences were tested through the Kruskal-Wallis H test and were considered significant at a two-side P<0.05. Results: The extent of movement of heart and its substructures during one cardiac cycle were approximately 4.0-26.1 millimetre (mm) in anterior-posterior (AP), left-right (LR), and cranial-caudal (CC) axes, and the compensatory margins should be applied to planning CT by extending the margins by 1.7, 3.6, 1.8, 3.0, 2.1, and 2.9 centimetres (cm) for pericardium; 1.2, 2.5, 1.0, 2.8, 1.8, and 3.3 cm for heart; 3.8, 3.4, 3.1, 2.8, 0.9, and 2.0 cm for interatrial septum; 3.3, 4.9, 2.0, 4.1, 1.1, and 2.9 cm for interventricular septum; 2.2, 3.0, 1.1, 5.3, 1.8, and 2.4 cm for left ventricular muscle (LVM); 5.9, 3.4, 2.1, 6.1, 5.4, and 3.6 cm for antero-lateral papillary muscle (ALPM); and 6.6, 2.9, 2.6, 6.6, 3.9, and 4.8 cm for postero-medial papillary muscle (PMPM) in anterior, posterior, left, right, cranial, and caudal directions, respectively. Conclusions: Periodic cardiac activity causes obvious displacement of the heart and its substructures, and the motion amplitude of substructures differs. Extending a certain margin as the compensatory extension to represent the organs at risk (OAR) and then limiting the dose-volume parameters could be performed in clinical practice.

Numerical study of granular flow in a slit funnel with a novel structure to avoid particle clogging.

To solve the problem of particle clogging in slit funnels and to obtain a stable discharge flow rate, we proposed a new funnel structure, namely the slit baffle funnel. We conducted a systematic investigation using the discrete element method (DEM) to study the effects of funnel half-angle θ, outlet width W, and baffle height H on flow rate and flow pattern. We found that the proposed structure could effectively avoid particle clogging and guarantee a continuous and stable flow rate with small outlet width. Under the condition of H >3 d, a bigger flow rate was obtained at a smaller funnel half-angle. This new funnel structure could be applied to solve clogging problems associated with granular matter in the slit geometry in mining, agriculture, food, and pharmaceuticals.

Efficient diagnosis of hematologic malignancies using bone marrow microscopic images: A method based on MultiPathGAN and MobileViTv2.

BACKGROUND AND OBJECTIVES: Hematologic malignancies, including the associated multiple subtypes, are critically threatening to human health. The timely detection of malignancies is crucial for their effective treatment. In this regard, the examination of bone marrow smears constitutes a crucial step. Nonetheless, the conventional approach to cell identification and enumeration is laborious and time-intensive. Therefore, the present study aimed to develop a method for the efficient diagnosis of these malignancies directly from bone marrow microscopic images. METHODS: A deep learning-based framework was developed to facilitate the diagnosis of common hematologic malignancies. First, a total of 2033 microscopic images of bone marrow analysis, including the images for 6 disease types and 1 healthy control, were collected from two Chinese medical websites. Next, the collected images were classified into the training, validation, and test datasets in the ratio of 7:1:2. Subsequently, a method of stain normalization to multi-domains (stain domain augmentation) based on the MultiPathGAN model was developed to equalize the stain styles and expand the image datasets. Afterward, a lightweight hybrid model named MobileViTv2, which integrates the strengths of both CNNs and ViTs, was developed for disease classification. The resulting model was trained and utilized to diagnose patients based on multiple microscopic images of their bone marrow smears, obtained from a cohort of 61 individuals. RESULTS: MobileViTv2 exhibited an average accuracy of 94.28% when applied to the test set, with multiple myeloma, acute lymphocytic leukemia, and lymphoma revealed as the three diseases diagnosed with the highest accuracy values of 98%, 96%, and 96%, respectively. Regarding patient-level prediction, the average accuracy of MobileViTv2 was 96.72%. This model outperformed both CNN and ViT models in terms of accuracy, despite utilizing only 9.8 million parameters. When applied to two public datasets, MobileViTv2 exhibited accuracy values of 99.75% and 99.72%, respectively, and outperformed previous methods. CONCLUSIONS: The proposed framework could be applied directly to bone marrow microscopic images with different stain styles to efficiently establish the diagnosis of common hematologic malignancies.

Ethyl Gallate Inhibits Bovine Viral Diarrhea Virus by Promoting IFITM3 Expression, Lysosomal Acidification and Protease Activity.

Bovine viral diarrhea virus (BVDV) is a highly contagious viral disease which causes economic losses to the cattle industry. Ethyl gallate (EG) is a phenolic acid derivative which has various potentials to modulate the host response to pathogens, such as via antioxidant activity, antibacterial activity, inhibition of the production of cell adhesion factors, and so on. This study aimed to evaluate if EG influences BVDV infection in Madin-Darby Bovine Kidney (MDBK) cells, and to understand the antiviral mechanism. Data indicated that EG effectively inhibited BVDV infection by co-treatment and post-treatment in MDBK cells with noncytotoxic doses. In addition, EG suppressed BVDV infection at an early stage of the viral life cycle by blocking entry and replication steps but not viral attachment and release. Moreover, EG strongly inhibited BVDV infection by promoting interferon-induced transmembrane protein 3 (IFITM3) expression, which localized to the cytoplasm. The protein level of cathepsin B was significantly reduced by BVDV infection, whereas with treatment with EG, it was significantly enhanced. The fluorescence intensities of acridine orange (AO) staining were significantly decreased in BVDV-infected cells but increased in EG-treated cells. Finally, Western blot and immunofluorescence analyses demonstrated that EG treatment significantly enhanced the protein levels of autophagy markers LC3 and p62. Chloroquine (CQ) significantly increased IFITM3 expression, and Rapamycin significantly decreased it. Thus, EG may regulate IFITM3 expression through autophagy. Our results showed that EG could have a solid antiviral activity on BVDV replication in MDBK cells via increased IFITM3 expression, lysosomal acidification, protease activity, and regulated autophagy. EG might have value for further development as an antiviral agent.

Germ cell-specific eIF4E1b regulates maternal mRNA translation to ensure zygotic genome activation.

Translation of maternal mRNAs is detected before transcription of zygotic genes and is essential for mammalian embryo development. How certain maternal mRNAs are selected for translation instead of degradation and how this burst of translation affects zygotic genome activation remain unknown. Using gene-edited mice, we document that the oocyte-specific eukaryotic translation initiation factor 4E family member 1b (eIF4E1b) is the regulator of maternal mRNA expression that ensures subsequent reprogramming of the zygotic genome. In oocytes, eIF4E1b binds to transcripts encoding translation machinery proteins, chromatin remodelers, and reprogramming factors to promote their translation in zygotes and protect them from degradation. The protein products are thought to establish an open chromatin landscape in one-cell zygotes to enable transcription of genes required for cleavage stage development. Our results define a program for rapid resetting of the zygotic epigenome that is regulated by maternal mRNA expression and provide new insights into the mammalian maternal-to-zygotic transition.

Effects of Spatial Expression of Activating Transcription Factor 4 on the Pathogenicity of Two Phenotypes of Bovine Viral Diarrhea Virus by Regulating the Endoplasmic Reticulum-Mediated Autophagy Process.

The endoplasmic reticulum (ER) stress response is a highly conserved stress-defense mechanism and activates the adaptive unfolded protein response (UPR) to mitigate imbalance. The ER stress-activated signaling pathways can also trigger autophagy to facilitate cellular repair. Bovine viral diarrhea virus (BVDV) utilizes the host cellular ER as the primary site of the life cycle. However, the interplay between cellular ER stress and BVDV replication remains unclear. This report reveals that cytopathic (cp) and noncytopathic (ncp) BVDV have distinct strategies to regulate UPR mechanisms and ER stress-mediated autophagy for their own benefit. Immunoblot analysis revealed that cp and ncp BVDV differentially regulated the abundance of ER chaperone GRP78 for viral replication, while the protein kinase RNA-like ER kinase (PERK)-eukaryotic translation initiation factor 2 subunit α (eIF2α)-activating transcription factor 4 (ATF4) pathway of the UPR was switched on at different stages of infection. Pretreatment with ER stress inducer promoted virion replication, but RNA interference (RNAi) knockdown of ATF4 in BVDV-infected cells significantly attenuated BVDV infectivity titers. More importantly, the effector ATF4 activated by cp BVDV infection translocated into the nucleus to mediate autophagy, but ATF4 was retained in the cytoplasm during ncp BVDV infection. In addition, we found that cp BVDV core protein was localized in the ER to induce ER stress-mediated autophagy. Overall, the potential therapeutic target ATF4 may contribute to the global eradication campaign of BVDV. IMPORTANCE The ER-tropic viruses hijack the host cellular ER as the replication platform of the life cycle, which can lead to strong ER stress. The UPR and related transcriptional cascades triggered by ER stress play a crucial role in viral replication and pathogenesis, but little is known about these underlying mechanisms. Here, we report that cytopathic and noncytopathic BVDV use different strategies to reprogram the cellular UPR and ER stress-mediated autophagy for their own advantage. The cytopathic BVDV unconventionally downregulated the expression level of GRP78, creating perfect conditions for self-replication via the UPR, and the noncytopathic BVDV retained ATF4 in the cytoplasm to provide an advantage for its persistent infection. Our findings provide new insights into exploring how BVDV and other ER-tropic viruses reprogram the UPR signaling pathway in the host cells for replication and reveal the attractive host target ATF4 for new antiviral agents.

Transformer-based deep learning method for optimizing ADMET properties of lead compounds.

A successful drug needs to exhibit both effective pharmacodynamics (PD) and safe pharmacokinetics (PK). However, the coordinated optimization of PD and PK properties in molecule generation tasks remains a great challenge for most existing methods, especially when they focus on the pursuit of affinity and selectivity for the lead compound. Thus, molecular optimization for PK properties is a critical step in the drug discovery pipeline, in which absorption, distribution, metabolism, excretion and toxicity (ADMET) property predictive models play an increasingly important role by providing an effective method to assess multiple PK properties of compounds. Here, we proposed a Graph Bert-based ADMET prediction model that achieves state-of-the-art performance on the public dataset Therapeutics Data Commons (TDC) by combining molecular graph features and descriptor features, with 11 tasks ranked first and 20 tasks ranked in the top 3. Based on this prediction model, we trained a Transformer model with multiple properties as constraints for learning the structural transformations involved in MMP and the accompanying property changes. The experimental results show that the trained Constraints-Transformer can implement targeted modifications to the starting molecule, while preserving the core scaffold. Moreover, molecular docking and binding mode analysis demonstrate that the optimized molecules still retain the activity and selectivity for biological targets. Therefore, the proposed method accounts for biological activity and ADMET properties simultaneously. Finally, a webserver containing ADMET property prediction and molecular optimization functions is provided, enabling chemists to improve the properties of starting molecules individually.