Protein phosphorylation and ADP-ribosylation (ADPr), as two types of post-translational modifications (PTM), are the process of adding phosphate group and ADP-ribose moieties to proteins, respectively. Although both PTM types can occur on many amino acid types, serine is the most common. Serine phosphorylation (pS), serine ADPr (SADPr), and their in situ crosstalks (pSADPr) play essential roles in biological processes. Although in silico classifiers have been developed for predicting pS and SADPr sites, the classifier for predicting pSADPr sites is unavailable. In this study, we developed classifiers to predict pSADPr sites. Specifically, we collected 3250 human pSADPr, 7520 SADPr, 151,227 pS and 80,096 unmodified serine sites. Based on them, we investigated the characteristics of pSADPr sites and constructed three classifiers to predict pSADPr sites from the pS dataset, the SADPr dataset and the protein sequences separately. We built and evaluated five deep-learning classifiers in ten-fold cross-validation and independent test datasets. Three of them (e.g. Convolutional Neural Network with the One-Hot encoding, dubbed CNNOH) performed better than the rest two. For instance, CNNOH had the AUC values of 0.700, 0.914 and 0.954 for recognizing pSADPr sites from the SADPr, pS and unmodified serine sites.Therefore, it is challenging to distinguish pSADPr sites from SADPr sites compared to the other two. It is consistent with our observation that pSADPr's characteristics are more similar to those of SADPr than the rest. Furthermore, we used the classifiers as base classifiers to develop a few stacking-based ensemble classifiers to improve performance. However, none of the ensemble classifiers showed better performances, suggesting that the base classifiers have good enough performances. Finally, we developed an online tool for extensively predicting human pSADPr sites based on the CNNOH classifier, dubbed EdeepSADPr. It is freely available through http://edeepsadpr.bioinfogo.org/.

Slow growth of calcite in confinement is abundant in Nature and man made materials. There is ample evidence that such confined growth may create forces that fracture solids. The thermodynamic limits are well known but since confined crystal growth is transport limited and difficult to control in experiment we have almost no information on the mechanisms or limits of these processes. We present a novel approach to in situ study of confined crystal growth using microfluidics for accurate control of the saturation state of the fluid and interferometric measurement of the topography of the growing confined crystal surface. We observe and explain the diffusion limited confined growth structures observed and can measure the crystal "floating" on a fluid film of 10-40~nm thickness due to the disjoining pressure. We find that there are two end member behaviours: smooth or intermittent growth in the contact region, the latter being faster than the former.

Background: Progression of metabolic dysfunction associated steatotic liver disease (MASLD) to steatohepatitis (MASH) is driven by stress-inducing lipids that promote liver inflammation and fibrosis. MASH can lead to cirrhosis and hepatocellular carcinoma. We showed coordinated defenses regulated by transcription factors, nuclear factor erythroid 2 related factor-1 (Nrf1) and -2 (Nrf2), protect against hepatic lipid stress. Here, we investigated protective effects of hepatocyte Nrf1 and Nrf2 against MASLD-induced liver fibrosis and tumorigenesis. Methods: Using mice fed MASH diet for 24-52 weeks, we examined MASLD in mice with hepatocyte specific Nrf1, Nrf2, or combined deletion, and compared this to control. In a separate study, mice received weekly injections of carbon tetrachloride to induce liver fibrosis. From week 16-24, mice were treated with Nrf2 activating drug bardoxolone, hepatocyte overexpression of human NRF1 (hNRF1), or both, and groups were compared to control. Results: Hepatocyte Nrf2 deficiency had no effect. Hepatocyte Nrf1 and combined deficiency caused MASH but only hepatocyte Nrf1 deficiency in male mice increased tumor number. Bardoxolone reduced liver steatosis, fibrosis, inflammation, and proliferation, and this effect when combined with hNRF1 was greater than bardoxolone alone. Conclusion: Physiologic Nrf1 delays MASLD progression, Nrf2-induction alleviates MASH, and combined enhancement synergistically protects against steatosis.

Background: Hepatocellular carcinoma (HCC) is one of the most prevalent cancers in human populations worldwide. Conversely, Huanglian Decoction is one of the most important Chinese medicine formulas, with the potential to treat cancer. Methods: To identify differentially expressed genes (DEG), we herein downloaded gene expression profile data from the TCGA (TCGA-LIHC) and GEO (GSE45436) databases. We obtained phytochemicals of the four constituent herbs of Huanglian Decoction from the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP). We also established a regulatory network of DEG and their drug target genes and subsequently analyzed key genes using bioinformatic approaches. Furthermore, we explored the effect of Huanglian Decoction by conducting in vitro experiments so as to verify the prediction. In particular, the CCNB1 gene was knockdown to verify the primary target of this Decoction. Results: Based on the results of network pharmacological analysis, we revealed that there are 5 bioactive compounds in Huanglian Decoction acting on HCC. In addition, our findings confirmed that CCNB1 was the primary key gene, which can be highly expressed in tumors and was significantly associated with a worse prognosis (P = 0.002) according to PPI network analysis of the target genes of these five compounds, as well as expression and prognosis analyses in tumors. We also noted that CCNB1 can be used as an independent prognostic indicator of HCC (P < 0.01). Moreover, in vitro experimental results demonstrate that Huanglian Decoction can significantly inhibit the growth, migration, and invasion of HCC cells. Finally, further analysis showed that this Decoction may inhibit the growth of HCC cells by down-regulating the expression level of CCNB1.

Smart Internet of Vehicles (IoVs) combined with Artificial Intelligence (AI) will contribute to vehicle decision-making in the Intelligent Transportation System (ITS). Multi-Vehicle Pursuit games (MVP), a multi-vehicle cooperative ability to capture mobile targets, is becoming a hot research topic gradually. Although there are some achievements in the field of MVP in the open space environment, the urban area brings complicated road structures and restricted moving spaces as challenges to the resolution of MVP games. We define an Observation-constrained MVP (OMVP) problem in this paper and propose a Transformer-based Time and Team Reinforcement Learning scheme (T3OMVP) to address the problem. First, a new multi-vehicle pursuit model is constructed based on decentralized partially observed Markov decision processes (Dec-POMDP) to instantiate this problem. Second, by introducing and modifying the transformer-based observation sequence, QMIX is redefined to adapt to the complicated road structure, restricted moving spaces and constrained observations, so as to control vehicles to pursue the target combining the vehicle’s observations. Third, a multi-intersection urban environment is built to verify the proposed scheme. Extensive experimental results demonstrate that the proposed T3OMVP scheme achieves significant improvements relative to state-of-the-art QMIX approaches by 9.66%~106.25%. Code is available at https://github.com/pipihaiziguai/T3OMVP.

Background: primary sclerosing cholangitis (PSC) is a chronic cholestatic disease characterized by inflammation and fibrosis of the bile ducts. Cholestasis may lead to hepatic inflammation and fibrosis, and amelioration of cholestasis may allow recovery from inflammatory and fibrotic pathological damage. Prevotella copri (P. copri) intervention have been reported could significantly improve cholestasis and liver fibrosis in DDC-induced PSC mice model. Despite alone P. copri treatment could not recover DDC-induced inflammation, it increased the abundance of Lactobacillus murinus (L. murinus) compared to DDC treatment, which has been reported to have anti-inflammatory effects. The abundance of L. murinus still not recover to normal level may underlie hepatic inflammation in P. copri+DDC mice. Method: alone or in combination interventions of P. copri and L. murinus were used to investigate the molecular mechanism of improvement of PSC inflammation and fibrosis. Results: P. copri and L. murinus significantly reduced the hepatic inflammatory cell aggregation and inflammatory factor expression, as well as the hepatic collagen content and fibrin factor expression in PSC mice. Further analysis of phosphorylation and dephosphorylation levels revealed that P. copri and L. murinus combined intervention in PSC mice inhibited the activity of DDC-activated TGF-β1/Smad pathway, thereby reducing liver inflammation and fibrosis. Conclusion: combination of P. copri and L. murinus inhibits the TGF-β1/Smad pathway and reduces inflammation and fibrosis in PSC.

A sensitive electrochemical sensor based on AuPtPd trimetallic nanoparticles functionalized multi-walled carbon nanotubes coupled with chitosan modified glassy carbon electrode (GCE/CS/MWCNTs-AuPtPd) for the rapid detection of bisphenol A (BPA) was proposed. AuPtPd trimetallic nanoparticles were first assembled on MWCNTs to obtain MWCNTs-AuPtPd nanocomposite. Then the MWCNTs-AuPtPd was further dispersed on the surface of chitosan modified electrode surface to fabricate the GCE/CS/MWCNTs-AuPtPd sensor. Due to the superior catalytic properties of MWCNTs-AuPtPd and the good film formation of chitosan, the constructed sensor displayed good performances for BPA detection. The structural morphology of CS/MWCNTs-AuPtPd was characterized by many methods, such as SEM, UV-vis and TEM. Under the optimal conditions, the designed sensor showed a linear range from 0.05 to 100 µM for BPA detecting with a low detection limit of 1.4 nM. The designed sensor was further used to realize the determination of BPA in real samples and the recoveries ranged from 94.4% to 103.6%. The results demonstrated that the electrochemical sensor designed by CS/MWCNTs-AuPtPd nanocomposites was reliable and could be a useful tool for the monitoring of food safety.

The nucleon-pair shell model (NPSM) with broken symmetry basis is studied. The results demonstrate the validity of NPSM with symmetry broken basis, which leads to a significant reduction in the dimensionality of the multi-pair configuration space. We have observed that the axial-deformed basis provides a satisfactory description of the low-lying spectrum, even without the need for the projection procedure. In the case of the triaxial-deformed basis, we have investigated the variation after angular momentum projection, indicating the potential for NPSM to find exact solutions in the half-closed system.

Using the techniques of computer-aided drug design, the docking of Survivin and known active small molecules was simulated and then the key amino acid residue fragment of the target protein was analyzed. It led to the discovery of active groups capable of binding to the critical sites. Through the use of the natural product, Oleanolic Acid, as a lead compound, the introduction of the active groups onto the A-ring, and the modification of the carboxyl group at the C-28 position using esterification or amidation, twenty new Oleanolic acid derivatives had been designed and synthesized.A549 and SGC-7901 cells were used to screen the antitumor activity in vitro through the standard MTT method. The compounds, II₃, III₅ and Ⅳ_4, exhibited more potent cytotoxicity than positive drugs.

(1) Background: Information overload challenges decision-making in the Industry 4.0 era. While Natural Language Processing (NLP), especially Automatic Text Summarization (ATS), offers solutions, issues with factual accuracy persist. This research bridges cognitive neuroscience and NLP, aiming to improve model interpretability. (2) Methods: This research examined four fact extraction techniques: dependency relation, named entity recognition, part-of-speech tagging, and TF-IDF, in order to explore their correlation with human EEG signals. Representational Similarity Analysis (RSA) was applied to gauge the relationship between language models and brain activity. (3) Results: Named entity recognition showed the highest sensitivity to EEG signals, marking the most significant differentiation between factual and non-factual words with a score of -0.99. The dependency relation followed with -0.90, while part-of-speech tagging and TF-IDF resulted in 0.07 and -0.52, respectively. Deep language models such as GloVe, BERT, and GPT-2 exhibited noticeable influences on RSA scores, highlighting the nuanced interplay between brain activity and these models. (4) Conclusions: Our findings emphasize the crucial role of named entity recognition and dependency relations in fact extraction and demonstrate the independent effects of different models and TOIs on RSA scores. These insights aim to refine algorithms to reflect human text processing better, thereby enhancing ATS models’ factual integrity.

Gaze tracking of high-speed moving targets is a novel application mode for low Earth orbit microsatellites. In this mode, small satellites are equipped with high-resolution narrow-field-of-view video cameras for stable gaze-tracking imaging of high-speed moving targets. This paper proposes a high-precision attitude adaptive integral sliding mode control method with a feedforward compensation disturbance observer to enhance the capability of a microsatellite attitude control system for gaze tracking of high-speed moving targets. Specifically, first, we present the attitude control system model for microsatellites and the calculation method for the desired attitude of target tracking based on image feedback. Then, an adaptive integral sliding mode attitude control algorithm with a feedforward compensation disturbance observer, which meets the requirements of high-precision tracking control, is designed. The developed algorithm utilizes the disturbance observer to observe the friction torque of the flywheel and compensates for it through feedforward control. It also employs the adaptive integral sliding mode control algorithm to reduce the impact of uncertain disturbances, decrease the steady-state error of the system, and enhance the attitude control precision. Simulation experiments demonstrated that the designed disturbance observer can successfully observe the frictional disturbance torque of the flywheel. The attitude Euler angle control precision for high-speed moving target tracking reached 0.009°, and the angular velocity control precision reached 0.005°/s, validating the effectiveness of the proposed approach.

High salinity in soil affects the normal growth and development of crop. MicroRNA171 (miR171) plays a momentous role in plant resistance to adversity stress. The functions of Sly-miR171d and Sly-miR171e on growth of tomato and fruit nutritional quality under salt stress were studied. The results showed that the seed germination and seedling growth of tomato that silencing of Sly-miR171d/e by short tandem target mimic (STTM) were better than those of wild-type (WT). Silencing of Sly-miR171d/e seeds maintained a high germination rate, while WT tomato seeds barely germinated under 50 mM NaCl stress. Under 100 mM NaCl stress, silencing of Sly-miR171d/e increased the expression of their target gene SlGRAS24 with increasing duration of salt stress, while they enhanced the antioxidant activity, reduced reactive oxygen species (ROS) accumulation, and enhanced the salt tolerance of tomato plant by regulating gibberellin (GA) level. Moreover, the preharvest and postharvest fruit nutritional quality under salt stress was also studied, and the results showed that silencing of Sly-miR171d/e increased soluble solids, lycopene, total carotenoids, Vitamin C, organic acids and phenolic substances in tomato fruit. The present study demonstrated that silencing of Sly-miR171d/e enhanced plant salt tolerance through the GA pathway, and improved fruit nutritional quality under salt stress.

The application of artificial intelligence to point-of-care testing (POCT) disease detection has become a hot research field, in which breath detection which detects the patient's exhaled VOCs combined with sensor arrays of Convolutional Neural Network (CNN) algorithms as a new lung cancer detection is attracting more researchers' attention. However, due to low accuracy, high complexity computation and large number of parameters make the CNN algorithms difficult transplant to the embedded system of POCT devices. A lightweight neural network (LTNet) in this work is proposed to deal with this problem, and meanwhile, achieve high-precision classification of acetone and ethanol gases, which are respiratory markers for lung cancer patients. Compared to currently popular lightweight CNN models such as EfficientNet, LTNet has fewer parameters (32K) and its training weight size is only 0.155 MB. LTNet achieved an overall classification accuracy of 99.06% and 99.14% in the own mixed gas dataset and the University of California (UCI) dataset, which are both higher than that of the five existing models’, and it also offers the shortest training (844.38s and 584.67s) and inference time (23s and 14s) in the same validation set. Compared to the existing CNN models, LTNet is more suitable for resource-limited POCT devices.

A fluorescent probe, N'-((3-methyl-5-oxo-1-phenyl-4, 5-dihydro-1H-pyrazol-4-yl) methylene)-2-oxo-2H-chromene-3-carbohydrazide (MPMC), was synthesized and characterized. Characterizations of the synthetic MPMC were conducted by proton nuclear magnetic resonance (1HNMR) spectroscopy and carbon-13 nuclear magnetic resonance spectroscopy (13C NMR). The fluorescence emission behaviors of probe MPMC towards diverse metal ions were detected and the probe exhibited high sensitivity and selectivity towards Cu2+ over other metal ions via quenching of its fluorescence. Furthermore, the existence of other metal actions made no difference on the fluorescence intensity of the MPMC-Cu2+ system apparently, that is, MPMC displayed a good anti-interference ability. Job’s plot of MPMC and copper ions indicated the detection limit was 15.16 nM (R2=0.9612) for the assayed actions, with a stoichiometric ratio of 1:1 for MPMC and Cu2+. Additionally, the color of MPMC probe solution changed from nearly colorless to yellow in the presence of Cu2+ in visible light, which the color change could be observed by the naked eye. Similarly, the color resolved bright yellow into blue in ultraviolet light. Also reusability studies indicated that MPMC probe was reusable. The pH effect of probe MPMC to Cu2+ had a broad range of pH detection 4.0 to 11.0. The response time of MPMC probe for determining Cu2+ was within 1 min. The recognition of Cu2+ by MPMC performed on pre-treated paper under sunlight and UV light both had a distinct colour change. Thus, the solid-state method for detecting Cu2+ with the naked-eye, was both economical and convenient.

Studies have shown that stress such as hypoxia, chemotherapy, radiotherapy can lead to polyploidization of tumor cells, which play an important role in tumor heterogeneity and malignant phenotype. Paclitaxel (PTX) treatment promoted polyploid cancer cells (PCCs) formation, and miR-378d is sharply reduced in PCCs of esophageal squamous cell carcinomas (ESCC) cells, but miR-378d participation PCCs formation and the impact on the biological behavior of ESCC remains unclear. We analyzed the PCCs formation and biological behavior of ESCC cells in vivo and in vitro, and the related proteins regulated by miR-378d. Results showed that miR-378d expression was associated with good prognosis in ESCC patients. miR-378d inhibition promoted PCCs formation, heterogenicity, chemo-resistance, monoclonal formation, EMT, migration, invasion, stemness and metastasis of ESCC cells. miR-378d can target downregulated AKT1, and inactivating the AKT-β-catenin signaling pathway, miR-378d and AKT can also regulated RhoA expression. AKT and RhoA regulated polyploidization and depolyploidization. Therefore, miR-378d expression is a good prognostic factor of ESCC patients and regulates polyploidization and malignant phenotype of tumor cells through AKT and RhoA.