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When viewing omnidirectional images (ODIs), viewers can access different viewports via head movement (HM), which sequentially forms head trajectories in spatial-temporal domain. Thus, head trajectories play a key role in modeling human attention on ODIs. In this paper, we establish a large-scale dataset collecting 21,600 head trajectories on 1,080 ODIs. By mining our dataset, we find two important factors influencing head trajectories, i.e., temporal dependency and subject-specific variance. Accordingly, we propose a novel approach integrating hierarchical Bayesian inference into long short-term memory (LSTM) network for head trajectory prediction on ODIs, which is called HiBayes-LSTM. In HiBayes-LSTM, we develop a mechanism of Future Intention Estimation (FIE), which captures the temporal correlations from previous, current and estimated future information, for predicting viewport transition. Additionally, a training scheme called Hierarchical Bayesian inference (HBI) is developed for modeling inter-subject uncertainty in HiBayes-LSTM. For HBI, we introduce a joint Gaussian distribution in a hierarchy, to approximate the posterior distribution over network weights. By sampling subject-specific weights from the approximated posterior distribution, our HiBayes-LSTM approach can yield diverse viewport transition among different subjects and obtain multiple head trajectories. Extensive experiments validate that our HiBayes-LSTM approach significantly outperforms 9 state-of-the-art approaches for trajectory prediction on ODIs, and then it is successfully applied to predict saliency on ODIs.

Chronic, progressive retinal diseases, such as age-related macular degeneration (AMD), diabetic retinopathy, and retinitis pigmentosa, arise from genetic and environmental perturbations of cellular and tissue homeostasis. These disruptions accumulate with repeated exposures to stress over time, leading to progressive visual impairment and, in many cases, legal blindness. Despite decades of research, therapeutic options for the millions of patients suffering from these disorders remain severely limited, especially for treating earlier stages of pathogenesis when the opportunity to preserve the retinal structure and visual function is greatest. To address this urgent, unmet medical need, we employed a systems pharmacology platform for therapeutic development. Through integrative single-cell transcriptomics, proteomics, and phosphoproteomics, we identified universal molecular mechanisms across distinct models of age-related and inherited retinal degenerations, characterized by impaired physiological resilience to stress. Here, we report that selective, targeted pharmacological inhibition of cyclic nucleotide phosphodiesterases (PDEs), which serve as critical regulatory nodes that modulate intracellular second messenger signaling pathways, stabilized the transcriptome, proteome, and phosphoproteome through downstream activation of protective mechanisms coupled with synergistic inhibition of degenerative processes. This therapeutic intervention enhanced resilience to acute and chronic forms of stress in the degenerating retina, thus preserving tissue structure and function across various models of age-related and inherited retinal disease. Taken together, these findings exemplify a systems pharmacology approach to drug discovery and development, revealing a new class of therapeutics with potential clinical utility in the treatment or prevention of the most common causes of blindness.

Sweetpotato (Ipomoea batatas) is an important root crop that is infected by Fusarium solani in both seedling and root stages, causing irregular black or brown disease spots and root rot and canker. This study aims to use RNA sequencing technology to investigate the dynamic changes in root transcriptome profiles between control check and roots at 6 h, 24 h, 3 days, and 5 days post-inoculation (hpi/dpi) with F. solani. The results showed that the defense reaction of sweetpotato could be divided into an early step (6 and 24 hpi) without symptoms and a late step to respond to F. solani infection (3 and 5 dpi). The differentially expressed genes (DEGs) in response to F. solani infection were enriched in the cellular component, biological process, and molecular function, with more DEGs in the biological process and molecular function than in the cellular component. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the main pathways were metabolic pathways, the biosynthesis of secondary metabolites, and carbon metabolism. More downregulated genes were identified than upregulated genes in the plant–pathogen interaction and transcription factors, which might be related to the degree of host resistance to F. solani. The findings of this study provide an important basis to further characterize the complex mechanisms of sweetpotato resistance against biotic stress and identify new candidate genes for increasing the resistance of sweetpotato.

Background. Acute-on-chronic liver failure (ACLF) is a clinical syndrome characterized by acute deterioration of liver function and high short-term mortality. Clusterin, with biological functions similar to small heat shock proteins, can protect cells from apoptosis induced by various stressors. The aim of this study was to detect the level of serum clusterin in hepatitis B virus- (HBV-) related ACLF and to assess the predictive value of clusterin for the short-term prognosis of HBV-ACLF. Methods. We detected serum clusterin by ELISA in 108 HBV-ACLF patients, 63 HBV-non-ACLF patients, and 44 normal controls. Results. Serum clusterin was markedly lower in HBV-ACLF patients (median, 51.09 μg/mL) than in HBV-non-ACLF patients (median, 188.56 μg/mL) and normal controls (median, 213.45 μg/mL; allP<0.05). Nonsurviving HBV-ACLF patients who died within 90 days had much lower clusterin levels than did surviving patients, especially those who died within 28 days (nonsurvival group vs. survival group:39.82±19.34vs.72.26±43.52,P<0.001; survivaltime≤28vs. survivaltime>28: median 28.39 vs. 43.22,P=0.013). The results showed that for identifying HBV-ACLF, the sensitivity of clusterin (93.7%) was similar to the sensitivities of the international normalized ratio (INR; 94.4%) and total bilirubin (TBIL; 94.8%), but its specificity (90.7%) was higher than that of prothrombin activity (PTA; 65.8%) and TBIL (69.8%) and was similar to INR (88.9%). As the concentration of clusterin increased, the mortality of HBV-ACLF patients decreased significantly from 59.3% to 7.0%. Clusterin had better ability for predicting the prognosis of HBV-ACLF patients than did the model for end-stage liver disease (MELD) score and the chronic liver failure consortium (CLIF-C) ACLF score (MELD vs. clusterin:P=0.012; CLIF-C ACLF vs. clusterin:P=0.031). Conclusion. Serum clusterin is a potential biomarker for HBV-ACLF which can be used to assess clinical severity and the short-term prognosis of patients with this disease and may help clinicians identify HBV-ACLF with greater specificity and improved prognostic accuracy than existing prognostic markers.

Tomato is a major cultivated vegetable species of great economic importance throughout the world, but its fruit yield is severely impaired by drought stress. PopW, a harpin protein from Ralstonia solanacearum ZJ3721, plays vital roles in various plant defence responses and growth. In this study, we observed that the foliar application of PopW increased tomato drought tolerance. Our results showed that compared with water-treated plants, PopW-treated plants presented a significantly higher recovery rate and leaf relative water content under drought-stress conditions. PopW decreased the malondialdehyde content and relative electrical conductivity by 40.2% and 21%, respectively. Drought disrupts redox homeostasis through the excessive accumulation of reactive oxygen species (ROS). PopW-treated plants displayed an obvious reduction in ROS accumulation due to enhanced activities of the antioxidant enzyme catalase, superoxide dismutase and peroxidase. Moreover, PopW promoted early stomatal closure, thereby minimizing the water loss rate of plants under drought stress. Further investigation revealed that endogenous abscisic acid (ABA) levels and the transcript levels of drought-responsive genes involved in ABA signal transduction pathways increased in response to PopW. These results confirm that PopW increases drought tolerance through multiple mechanisms involving an enhanced water-retention capacity, balanced redox homeostasis, increased osmotic adjustment, reduced membrane damage and decreased stomatal aperture, suggesting that the application of exogenous PopW may be a potential method to enhance tomato drought tolerance.

Background. To compare the efficacies of transcatheter arterial chemoembolization (TACE) with radiofrequency ablation (RFA) (TACE + RFA) and TACE alone in patients with hepatocellular carcinoma (HCC) and macrovascular invasion (MVI). Methods. In total, 664 patients having HCC with MVI were included. Of these patients, 141 were treated with TACE + RFA, 254 with TACE alone, and 269 with supportive therapy (control group). The overall survival (OS) was compared among these groups. Propensity score matching (PSM) was performed for balancing the characteristics of the three groups. Results. After one-to-one PSM, the 12-month OS rates were higher in the TACE and TACE + RFA groups than in the control group (p=0.0009 and p=0.0017, respectively). Furthermore, higher 12-month OS rates were observed in the TACE + RFA group than in the TACE group (p=0.0192). The 12-month OS rates of patients were remarkably higher in α-fetoprotein (AFP) p=0.0122, p=0.0090, p=0112, and p=0.0071, respectively). Conclusions. TACE + RFA provides a superior survival outcome than TACE alone in HCC patients, especially in AFP

Convolutional dictionary learning has become increasingly popular in signal and image processing for its ability to overcome the limitations of traditional patch-based dictionary learning. Although most studies on convolutional dictionary learning mainly focus on the unimodal case, real-world image processing tasks usually involve images from multiple modalities, e.g., visible and near-infrared (NIR) images. Thus, it is necessary to explore convolutional dictionary learning across different modalities. In this paper, we propose a novel multi-modal convolutional dictionary learning algorithm, which efficiently correlates different image modalities and fully considers neighborhood information at the image level. In this model, each modality is represented by two convolutional dictionaries, in which one dictionary is for common feature representation and the other is for unique feature representation. The model is constrained by the requirement that the convolutional sparse representations (CSRs) for the common features should be the same across different modalities, considering that these images are captured from the same scene. We propose a new training method based on the alternating direction method of multipliers (ADMM) to alternatively learn the common and unique dictionaries in the discrete Fourier transform (DFT) domain. We show that our model converges in less than 20 iterations between the convolutional dictionary updating and the CSRs calculation. The effectiveness of the proposed dictionary learning algorithm is demonstrated on various multimodal image processing tasks, achieves better performance than both dictionary learning methods and deep learning based methods with limited training data.

Angelica dahurica is a famous functional food and herb. To guarantee quality of A. dahurica, a strategy “Q-markers targeted screening” was successfully developed by sufficient extraction of compounds and the targeted screening of qualitative and quantitative markers calculated through chemometric methods based fingerprints. Accelerated solvent extraction was selected due to its prominent advantages exhibiting the maximum extraction yields and varieties of compounds and especially excellent reproducibility (RSD

Background The current definitions and etiologies of acute-on-chronic liver failure (ACLF) are clearly very different between East and West. Aims This study aimed to develop an effective prognostic nomogram for acute-on-chronic hepatitis B liver failure (ACHBLF) as defined by the Asia Pacific Association for the Study of the Liver (APASL). Methods The nomogram was based on a retrospective study of 573 patients with ACHBLF, defined according to the APASL, at the Beijing Ditan Hospital. The results were validated using a bootstrapped approach to correct for bias in two external cohorts, including an APASL ACHBLF cohort (10 hospitals, N = 329) and an EASL-CLIF ACHBLF cohort (Renji Hospital, N = 300). Results Multivariate analysis of the derivation cohort for survival analysis helped identify the independent factors as age, total bilirubin, albumin, international normalized ratio, and hepatic encephalopathy, which were included in the nomogram. The predictive value of nomogram was the strongest compared with CLIF-C ACLF, MELD and MELD-Na and similar to COSSH-ACLF in both the derivation and prospective validation cohorts with APASL ACHBLF, but the CLIF-C ACLF was better in the EASL-CLIF ACHBLF cohort. Conclusions The proposed nomogram could accurately estimate individualized risk for the short-term mortality of patients with ACHBLF as defined by APASL.

Nanopore is used as a single-molecule detector for proteins, peptides and amino acids identification of biomedical importance. We, on the first try, extended its profiling application for peptidome encoded by the insect-resistance gene in rice. Taking brown planthopper (Bph) for example, we previously cloned and verified Bph32 gene, which encodes SCR ("Bph32") protein as direct executor against this injurious insect. However, the homology protein expressed in susceptible line doesn't have this antibiosis resistance. Hence, profiling the structural modulars (peptide domains) of Bph32 proteins may provide essential basis to understand rice in response to insects. Herein, we combined approaches of bioinformatics, biochemistry and nanopore analysis to profile the rice peptides with diverse properties. Bph32 proteins were theoretically modeled into 24 functional peptide domains using Swiss-Model workspace. Next, 22 water-soluble peptides were identified by biuret-chemistry amplified nanopore current modulations. Among those, 16 ones were distinguished at one amino acid resolution via reading the current modulation spectrum, consequently providing the peptidome fingerprints. In addition, the current modulations were evidenced as quadratic function of peptide's molecular masses. These findings suggest that nanopore may work as a new generation of mass detector for more omics analysis, especially in agricultural field where demands strongly.

The retinal pigment epithelium-photoreceptor interphase is renewed each day in a stunning display of cellular interdependence. While photoreceptors use photosensitive pigments to convert light into electrical signals, the RPE supports photoreceptors in their function by phagocytizing shed photoreceptor tips, regulating the blood retina barrier, and modulating inflammatory responses, as well as regenerating the 11-cis-retinal chromophore via the classical visual cycle. These processes involve multiple protein complexes, tightly regulated ligand-receptors interactions, and a plethora of lipids and protein-lipids interactions. The role of lipids in maintaining a healthy interplay between the RPE and photoreceptors has not been fully delineated. In recent years, novel technologies have resulted in major advancements in understanding several facets of this interplay, including the involvement of lipids in phagocytosis and phagolysosome function, nutrient recycling, and the metabolic dependence between the two cell types. In this review, we aim to integrate the complex role of lipids in photoreceptor and RPE function, emphasizing the dynamic exchange between the cells as well as discuss how these processes are affected in aging and retinal diseases.

Sander et al. have parsed the lipid composition of native-source photoreceptor disks and found large differences in fatty acid unsaturation and chain length between the center and rim regions. They selectively copurified membrane proteins and lipids from each region in SMALPs using nanobodies and antibodies., Photoreceptors rely on distinct membrane compartments to support their specialized function. Unlike protein localization, identification of critical differences in membrane content has not yet been expanded to lipids, due to the difficulty of isolating domain-specific samples. We have overcome this by using SMA to coimmunopurify membrane proteins and their native lipids from two regions of photoreceptor ROS disks. Each sample's copurified lipids were subjected to untargeted lipidomic and fatty acid analysis. Extensive differences between center (rhodopsin) and rim (ABCA4 and PRPH2/ROM1) samples included a lower PC to PE ratio and increased LC- and VLC-PUFAs in the center relative to the rim region, which was enriched in shorter, saturated FAs. The comparatively few differences between the two rim samples likely reflect specific protein–lipid interactions. High-resolution profiling of the ROS disk lipid composition gives new insights into how intricate membrane structure and protein activity are balanced within the ROS, and provides a model for future studies of other complex cellular structures.

Gardeniae Fructus (Zhizi in Chinese, ZZ in brief), a commonly used herbal medicine, has aroused wide concern for hepatotoxicity, but the mechanism remains to be investigated. This study was aimed at investigating the mechanism of ZZ-induced liver injury in vivo and in vitro based on metabolomics and evaluating the hepatotoxicity prediction ability of the in vitro model. SD rats were administered with extracted ZZ and HepG2 cells were treated with genipin, the major hepatotoxic metabolite of ZZ. Liver, plasma, intracellular and extracellular samples were obtained for metabolomics analysis. As a result, ZZ caused plasma biochemical and liver histopathological alterations in rats, and induced purine and amino acid metabolism disorder in the liver and pyrimidine, primary bile acids, amino acid metabolism and pantothenate and CoA biosynthesis disorder in the plasma. Pyrimidine, purine, amino acid metabolism and pantothenate and CoA biosynthesis were also found to be disturbed in the genipin-treated HepG2 cells, which exhibited similarity with the result in vivo. This study comprehensively illustrates the underlying mechanism involved in ZZ-related hepatotoxicity from the aspect of metabolome, and provides evidence that identifying hepatotoxicity can be achieved in cells, representing a non-animal alternative for systemic toxicology.

The yield heterosis of rice is sought by farmers and strong contributes to food safety, but the quality of hybrid rice may be reduced. Therefore, developing new varieties with both high yield and good quality is a heavily researched topic in hybrid rice breeding. However, the molecular mechanism governing yield heterosis and high rice quality has not been elucidated to date. In this study, a comparative transcriptomics and genomic analysis was performed on a hybrid rice variety, Chuanyou6203 (CY6203), and its parents to investigate the molecular mechanism and gene regulation network governing the formation of yield and quality stages. A total of 66,319 SNPs and InDels between CH3203 and C106B were detected in the 5′-UTR, exon, intronic, and 3′-UTR regions according to the reference genome annotation, which involved 7473 genes. A total of 436, 70, 551, 993, and 1216 common DEGs between CY6203 and both of its parents were identified at the same stage in panicles and flag leaves. Of the common DEGs, the numbers of upregulated DEGs between CY6203 and CH3203 were all greater than those of upregulated DEGs between CY6203 and C106B in panicles and flag leaves at the booting, flowering, and middle filling stages. Approximately 40.61% of mRNA editing ratios were between 0.4 and 0.6, and 1.68% of mRNA editing events (editing ratio ≥ 0.8) in CY6203 favored one of its parents at three stages or a particular stage, suggesting that the hypothetical heterosis mechanism of CY6203 might involve dominance or epistasis. Also 15,934 DEGs were classified into 19 distinct modules that were classified into three groups by the weighted gene coexpression network analysis. Through transcriptome analysis of panicles and flag leaves in the yield and quality stages, the DEGs in the green-yellow module primarily contributed to the increase in the source of CY6203 due to an in increase in photosynthetic efficiency and nitrogen utilization efficiency, and a small number of DEGs related to the grain number added spikelet number per panicle amplified its sink. The balanced expression of the major high-quality alleles of C106B and CH3203 in CY6203 contributed to the outstanding quality of CY6203. Our transcriptome and genome analyses offer a new data set that may help to elucidate the molecular mechanism governing the yield heterosis and high quality of a hybrid rice variety.

Mounting evidence indicates that long non-coding RNAs influence the progression of cervical cancer, but the precise function of LINC01503 in the pathogenesis of the disease remains unknown. Here, we found higher levels of LINC01503 in cervical cancer tissues. High LINC01503 expression was associated with enhanced progression of cervical cancer as indicated by advanced FIGO stage, increased metastasis of tumor cells to lymph nodes, and invasion into deeper cervical tissues. LINC01503 inhibition markedly suppressed the invasion and proliferative ability of tumor cells. Mechanistically, LINC01503 was demonstrated to negatively modulate the expression of miR-615-3p in cervical cancer. CCND1 was found to be a target of miR-615-3p. Rescue experiments indicated that LINC01503 inhibition suppressed the invasion and proliferative ability of the tumor cells, a phenomenon that was reversed following miR-615-3p inhibition or CCND1 overexpression. Collectively, these data indicate that LINC01503 enhances the progression of cervical cancer cells via interaction with miR-615-3p/CCND1 axis.

Background Probiotic therapy has been shown to be beneficial against some liver diseases. However, there is still uncertainty regarding the clinical efficacy of probiotics for the treatment of variceal rebleeding. This research explored the efficacy of probiotics in variceal rebleeding. Material/Methods This was a retrospective study of 704 consecutive patients with liver cirrhosis who recovered from esophagogastric variceal bleeding after endoscopic treatment. Patients were subdivided into a probiotics cohort (n=214) and a non-probiotics cohort (n=490) based on the cumulative defined daily dose (cDDD) of probiotics received during follow-up. Propensity score matching was utilized to obtain a relatively balanced cohort of 200 patients per group for the analysis. Patients were monitored for rebleeding during the one-year follow-up. Results Multivariate Cox regression analysis revealed that probiotic therapy (≥28cDDD) was an independent protector against rebleeding (AHR=0.623; 95% CI=0.488–0.795; P90 cDDD groups, respectively; P=0.011). The median rebleeding interval in the probiotics cohort (n=95) was significantly longer than that in the non-probiotics cohort (n=261) (147.0 vs. 91.0 days; P

Tomato is a major cultivated vegetable species of great economic importance throughout the world, but its fruit yield is severely impaired by drought stress. PopW, a harpin protein from Ralstonia solanacearum ZJ3721, plays vital roles in various plant defence responses and growth. In this study, we observed that the foliar application of PopW increased tomato drought tolerance. Our results showed that compared with water-treated plants, PopW-treated plants presented a significantly higher recovery rate and leaf relative water content under drought-stress conditions. PopW decreased the malondialdehyde content and relative electrical conductivity by 40.2% and 21%, respectively. Drought disrupts redox homeostasis through the excessive accumulation of reactive oxygen species (ROS). PopW-treated plants displayed an obvious reduction in ROS accumulation due to enhanced activities of the antioxidant enzyme catalase, superoxide dismutase and peroxidase. Moreover, PopW promoted early stomatal closure, thereby minimizing the water loss rate of plants under drought stress. Further investigation revealed that endogenous abscisic acid (ABA) levels and the transcript levels of drought-responsive genes involved in ABA signal transduction pathways increased in response to PopW. These results confirm that PopW increases drought tolerance through multiple mechanisms involving an enhanced water-retention capacity, balanced redox homeostasis, increased osmotic adjustment, reduced membrane damage and decreased stomatal aperture, suggesting that the application of exogenous PopW may be a potential method to enhance tomato drought tolerance.

Exosomes are cell-derived, phospholipid bilayer-enclosed vesicles that play important roles in intercellular interactions and regulate many biological processes. Accumulating evidence suggests that serum exosomes are potential biomarkers for the early diagnosis of cancer. To aid the downstream molecular analyses of tumour-secreted exosomes, purified exosomes are highly desirable. However, current techniques for exosome isolation are time-consuming and highly instrument-dependent, with limited specificity and recovery. Thus, rapid and efficient methods are strongly needed for both basic research and clinical applications. Here, we present a novel strategy for facile exosome isolation from human serum by taking advantage of the specific interaction of TiO2 with the phosphate groups on the lipid bilayer of exosomes. Due to their simplicity and highly affinitive binding, model exosomes can be reversibly isolated with a high recovery (93.4%). Downstream characterization and proteome profiling reveal that high-quality exosomes can be obtained from human serum by this TiO2-based isolation method in 5 min, which is a fraction of the time required for the commonly used ultracentrifugation method. We identified 59 significantly up-regulated proteins by comparing the serum exosomes of pancreatic cancer patients and healthy donors. In addition to the 30 proteins that were reported to be closely related to pancreatic cancer, we found an additional 29 proteins that had not previously been shown to be related to pancreatic cancer, indicating the potential of this novel method as a powerful tool for exosome isolation for health monitoring and disease diagnosis.

Background. Portal vein tumor thrombosis (PVTT) is one of the major predictive factors for patients with hepatocellular carcinoma (HCC). The objective of this study was to establish a prognostic nomogram for identifying individual survival outcomes in patients with HCC and PVTT on conservative treatment based on specific factors. Methods. Two hundred and ten patients with HCC and PVTT on conservative treatment in Beijing Ditan Hospital between June 2008 and May 2017 were studied retrospectively as a derivation cohort. We built a nomogram based on independent risk factors for survival prediction. The concordance index (c-index) and a calibration curve were used to evaluate the predictive accuracy. During the study, 102 patients were included at the Putuo Hospital and Third People’s Hospital of Changzhou as a validation cohort. Results. In the derivation cohort, the independent factors for overall survival were identified by multivariate analysis, namely, aspartate aminotransferase ≥119 IU/L, gamma-glutamyl transferase ≥115 IU/L, Child–Pugh class C liver function, creatinine ≥91 μmoI/L, α-fetoprotein ≥400 ng/ml, and largest tumor diameter ≥5 cm. The nomogram had a c-index of 0.737 (95% confidence interval, 0.692–0.782) and the calibration curves fitted well. The median survival time was 4.2 months in the derivation cohort, with an MST of 5 months for BCLC C stage and 1.8 months for BCLC D stage patients. Kaplan–Meier analysis showed significant statistical differences in the 6-month overall survival rates of the primary and validation cohorts after the total scores were divided into three quartiles (low risk: 0–85; intermediate risk: 86–210; high risk: ≥211; p<0.0001 in both cohorts). Conclusions. The nomogram can be a more accurate and individualized prediction for 6-month overall survival of patients with HCC and PVTT on conservative treatment, and it is possible to consider further active interventions for patients in the low-risk group (0–85 scores) to achieve the aim of prolonging survival.

Exosomes are vesicles secreted by many types of cells through exocytosis, and their sizes range from 30 to 200 nm. Exosomes consist of a lipid bilayer membrane, containing a number of bioactive molecules, e. g., proteins, ribose nucleic acid (RNA), and deoxyribo nucleic acid (DNA) derived from the cell of origin. As intercellular communication carriers, exosomes participate in many physiological and pathological processes. Because of the complexity of body fluids, as well as the small size and low density of exosomes, the isolation of exosomes is an essential and challenging step before subsequent analysis and functional studies. This review summarizes the advances in the analytical approaches, characterization methods, biological functions and clinical applications of exosomes, with particular emphasis on exosomes isolation techniques.

Cytochrome P450 (CYP450) and 5'-diphosphate glucuronosyltransferases (UGT) are the two major families of drug-metabolizing enzymes in the human liver microsome (HLM). As a result of their frequent abundance fluctuation among populations, the accurate quantification of these enzymes in different individuals is important for designing patient-specific dosage regimens in the framework of precision medicine. The preparation and quantification of internal standards is an essential step for the quantitative analysis of enzymes. However, the commonly employed stable isotope labeling-based strategy (QconCAT) suffers from requiring very expensive isotopic reagents, tedious experimental procedures, and long labeling times. Furthermore, arginine-to-proline conversion during metabolic isotopic labeling compromises the quantification accuracy. Therefore, we present a new strategy that replaces stable isotope-labeled amino acids with lanthanide labeling for the preparation and quantification of QconCAT internal standard peptides, which leads to a threefold reduction in the reagent costs and a fivefold reduction in the time consumed. The absolute amount of trypsin-digested QconCAT peptides can be obtained by lanthanide labeling and inductively coupled plasma-optical emission spectrometry (ICP-OES) analysis with a high quantification accuracy (%RE 20%). By taking advantage of the highly selective and facile ICP-OES procedure and multiplexed large-scale absolute target protein quantification using biological mass spectrometry, this strategy was successfully used for the absolute quantification of drug-metabolizing enzymes. We obtained good linearity (correlation coefficient 0.95) over concentrations spanning 2.5 orders of magnitude with improved sensitivity (limit of quantification = 2 fmol) in nine HLM samples, indicating the potential of this method for large-scale absolute target protein quantification in clinical samples. Graphical abstract.

Background Hepatocellular carcinoma (HCC) is a common malignant tumor with limited treatment options. Conventional antitumor therapy combined with traditional Chinese medicine (TCM) to limit tumor progression has gradually become the focus of complementary and alternative therapies for HCC treatment. The Fuzheng Jiedu Xiaoji formulation (FZJDXJ) alleviates the clinical symptoms of patients and inhibits tumor progression, but its curative effect still requires extensive clinical research and mechanistic analysis. Purpose To explore the effectiveness of FZJDXJ in HCC patients and investigate its biological function and mechanism underlying anticancer therapy. Methods This randomized controlled clinical trial enrolled 291 HCC patients receiving transcatheter arterial chemoembolization (TACE) therapy; patients received either FZJDXJ combined with standard treatment, or standard treatment alone, for 48 weeks. Statistical analyses were performed according to survival time at the end of the trial. The main constituents of the FZJDXJ extracts were identified and evaluated using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) and molecular docking. The antitumor effects of FZJDXJ and its specific biological mechanism of action were studied. Results After 48 weeks of treatment, one-year overall survival (OS) and progression-free survival (PFS) were significantly different between the two groups. Co-administration of FZJDXJ and TACE prolonged the OS of HCC patients, especially in BCLC A or B stage. FZJDXJ and TACE treatment effectively extended the PFS of patients, especially in the BCLC B stage. HPLC-MS/MS identified 1619 active constituents of FZJDXJ, including formononetin, chlorogenic acid (CGA), caffeic acid, luteolin, gallic acid, diosgenin, ergosterol endoperoxide, and lupeol, which may function through the AKT/CyclinD1/p21/p27 pathways. Through molecular docking, CGA and gallic acid could effectively combine with Thr308, an important phosphorylation site of AKT1. FZJDXJ inhibited tumor growth in nude mice. In vitro, FZJDXJ-mediated serum inhibited the proliferation, migration, and invasion of liver cancer cells, and promoted cell apoptosis. Conclusion Clinically, FZJDXJ combined with TACE therapy significantly prolonged OS and PFS and reduced the mortality rate of HCC patients. Mechanistically, FZJDXJ effectively inhibited the proliferation and migration of liver cancer cells through the modulation of the AKT/CyclinD1/p21/p27 pathways, and may be a promising TCM drug for anti-HCC therapy.

In “bottom-up” proteomics, proteins are first digested into peptides and then characterized by chromatographic separation and mass spectrometry analysis, in which proteolysis has an appreciable influence on the repeatability and reliability of analytical results. To improve recovery and enzymatic efficiency, proteins are often denatured and solubilized with chemical agents such as sodium dodecyl sulphate (SDS), urea (UA), etc. However, surfactant like SDS is difficult to remove from the reacting system and may interfere with protease activity, chromatographic separation of peptides and mass spectrometry analysis. To this end, we have prepared an immobilized surfactant which can preserve the solubilization and denaturation abilities of a surfactant and has the advantage of being easily separated from samples. The denaturation and solubilization capabilities of the newly developed immobilized surfactant were evaluated by comparing the enzymatic hydrolysis efficiencies in the pretreatment of protein samples treated with immobilized surfactant and other common methods. The results showed that the average protein sequence coverage was 42.1% (digested for 1 h), which was 76.89% higher than that of a control experiment (23.8%) in the digestion of a standard protein (BSA) and reached the same denaturation ability as that of heating at 95 °C. Moreover, the immobilized surfactant was further tested in the extraction and digestion of the total protein of HeLa cells. The number of identified proteins resulted in similar levels to those exploited with 0.1% SDS and 8 M UA, both of which are frequently used in lysis buffer, indicating that the immobilized surfactant had a good ability to denature and solubilize proteins. In brief, the immobilized surfactant avoids the shortcomings of UA and SDS and can be utilized in the pretreatment of complex biological samples.

Summary Flavodoxin (Fld) plays a pivotal role in photosynthetic microorganisms as an alternative electron carrier flavoprotein under adverse environmental conditions. Cyanobacterial Fld has been demonstrated to be able to substitute ferredoxin of higher plants in most electron transfer processes under stressful conditions. We have explored the potential of Fld for use in improving plant stress response in creeping bentgrass (Agrostis stolonifera L.). Overexpression of Fld altered plant growth and development. Most significantly, transgenic plants exhibited drastically enhanced performance under oxidative, drought and heat stress as well as nitrogen (N) starvation, which was associated with higher water retention and cell membrane integrity than wild‐type controls, modified expression of heat‐shock protein genes, production of more reduced thioredoxin, elevated N accumulation and total chlorophyll content as well as up‐regulated expression of nitrite reductase and N transporter genes. Further analysis revealed that the expression of other stress‐related genes was also impacted in Fld‐expressing transgenics. Our data establish a key role of Fld in modulating plant growth and development and plant response to multiple sources of adverse environmental conditions in crop species. This demonstrates the feasibility of manipulating Fld in crop species for genetic engineering of plant stress tolerance.

Grain appearance quality traits, measured as grain length (GL), grain width (GW), length to width ratio (LWR), grain thickness (GT) and the percentage of grain with chalkiness (PGWC), as well as 1 000-grain weight (TGW), are very important factors that contribute to rice grain quality and yield. To detect quantitative trait loci (QTLs) affecting these traits, we developed a set of recombinant inbred lines (RILs) derived from Gang46B (G46B) and K1075, a G46B introgression line with lower PGWC. Based on a linkage map containing 33 simple sequence repeat (SSR) markers, a total of 15 additive QTLs governing six measured traits were identified on 4 chromosomes across two environments. Of these, the five major QTLs which controlled GW, LWR, GT, PGWC, and TGW, each explaining up to 44.30, 55.29, 62.30, 30.94, and 28.78% of the variation, respectively, were found in the same interval of RM18004–RM18068 on chromosome 5. The G46B alleles contributed to the increase in GW, GT and PGWC at all loci, as well as the increase in TGW at its major QTL locus. Significant interactions between additive QTL and the environment were found at most loci, in which the largest, accounting for 15.06% of variation, was observed between qPGWC-5 and the environment. A total of 15 epistasis QTLs were detected for all the traits, and GL, GW and PGWC had significant epistasis QTLs based on environment interactions with minor effects. These results are valuable for future map-based cloning of the QTLs and the collaborative improvement of G46B in grain appearance quality and yield.

Behavioral Economics puts forward that the weakness of human decision-making is an important cause of the vulnerability of the poor. If the external environment of decision-making is bad, it is easy to fall into the trap of “phishing for fools” set by the economic subject, which causes economic loss or psychological burden and increases the risk of returning to poverty. This paper studies whether the low-income groups are more likely to fall into the trap of “phishing for fools” and make irrational decisions based on the fact that the excessive consumption of tobacco and alcohol is harmful to their health but the consumption is increasing year by year. Based on the data on the 2015 China Health and Retirement Longitudinal Study, this paper Constructs Logit model, linear regression model and ordered Probit model to empirically analyze the important factors influencing the smoking and drinking behavior of rural residents. The results showed that, under the control of individual characteristics and regional living habits, income level had a significant impact on low-income groups’ alcohol and tobacco consumption behavior.

Macroscopic vascular invasion cannot be properly predicted in advance in hepatocellular carcinoma patients based on clinical characteristics and imaging features. To develop a predictive scoring model of macroscopic vascular invasion in hepatocellular carcinoma patients after transcatheter arterial chemoembolization combined with radiofrequency ablation based on specific laboratory and tumor indicators. A predictive scoring model, which estimates the incidence of macroscopic vascular invasion at 1-year follow-up, was constructed based on a derivation cohort of 324 patients with hepatocellular carcinoma; a validation cohort of 120 patients was prospectively included. The prognostic value of the scoring model was determined by concordance index, time-dependent receiver operating characteristics, and calibration curves. Cox multivariate analysis of the derivation cohort identified prothrombin time, aspartate aminotransferase, and Barcelona clinic liver cancer (BCLC) staging as independent predictive factors of macroscopic vascular invasion. The areas under the receiver operating characteristic curves of the predictive scoring model were 0.832 and 0.785 in the derivation and validation cohorts, respectively, and the calibration curves fitted well. Kaplan–Meier analysis showed that the incidence of macroscopic vascular invasion was significantly higher in the high-risk group (score 0–2) than in the low-risk group (score 3–4) in both the derivation and validation cohorts (P

Exosomes can be efficiently isolated in a short period of time by the specific interaction of titanium dioxide with the phosphate groups on the surface of phospholipid bilayer., Exosomes are cell-derived, phospholipid bilayer-enclosed vesicles that play important roles in intercellular interactions and regulate many biological processes. Accumulating evidence suggests that serum exosomes are potential biomarkers for the early diagnosis of cancer. To aid the downstream molecular analyses of tumour-secreted exosomes, purified exosomes are highly desirable. However, current techniques for exosome isolation are time-consuming and highly instrument-dependent, with limited specificity and recovery. Thus, rapid and efficient methods are strongly needed for both basic research and clinical applications. Here, we present a novel strategy for facile exosome isolation from human serum by taking advantage of the specific interaction of TiO2 with the phosphate groups on the lipid bilayer of exosomes. Due to their simplicity and highly affinitive binding, model exosomes can be reversibly isolated with a high recovery (93.4%). Downstream characterization and proteome profiling reveal that high-quality exosomes can be obtained from human serum by this TiO2-based isolation method in 5 min, which is a fraction of the time required for the commonly used ultracentrifugation method. We identified 59 significantly up-regulated proteins by comparing the serum exosomes of pancreatic cancer patients and healthy donors. In addition to the 30 proteins that were reported to be closely related to pancreatic cancer, we found an additional 29 proteins that had not previously been shown to be related to pancreatic cancer, indicating the potential of this novel method as a powerful tool for exosome isolation for health monitoring and disease diagnosis.