A computational framework of routine test data for the cost-effective chronic disease prediction.

Chronic diseases, because of insidious onset and long latent period, have become the major global disease burden. However, the current chronic disease diagnosis methods based on genetic markers or imaging analysis are challenging to promote completely due to high costs and cannot reach universality and popularization. This study analyzed massive data from routine blood and biochemical test of 32 448 patients and developed a novel framework for cost-effective chronic disease prediction with high accuracy (AUC 87.32%). Based on the best-performing XGBoost algorithm, 20 classification models were further constructed for 17 types of chronic diseases, including 9 types of cancers, 5 types of cardiovascular diseases and 3 types of mental illness. The highest accuracy of the model was 90.13% for cardia cancer, and the lowest was 76.38% for rectal cancer. The model interpretation with the SHAP algorithm showed that CREA, R-CV, GLU and NEUT% might be important indices to identify the most chronic diseases. PDW and R-CV are also discovered to be crucial indices in classifying the three types of chronic diseases (cardiovascular disease, cancer and mental illness). In addition, R-CV has a higher specificity for cancer, ALP for cardiovascular disease and GLU for mental illness. The association between chronic diseases was further revealed. At last, we build a user-friendly explainable machine-learning-based clinical decision support system (DisPioneer: http://bioinfor.imu.edu.cn/dispioneer) to assist in predicting, classifying and treating chronic diseases. This cost-effective work with simple blood tests will benefit more people and motivate clinical implementation and further investigation of chronic diseases prevention and surveillance program.

Exploiting Molecular Orders at the Interface of Microdroplets for Intelligent Materials.

ConspectusThe intrinsic molecular order of liquid crystals (LCs) and liquid crystalline elastomers (LCEs) is the origin of their stimuli-responsive properties. The programmable responsiveness and functionality, such as shape morphing and color change under external stimuli, are the key features that attract interest in designing LC- and LCE-based intelligent material platforms. Methods such as mechanical stretching and shearing, surface alignment, and field-assisted alignment have been exploited to program the order of LC molecules for the desired responsiveness. However, the huge size mismatch between the nanometer-sized LC mesogens and the targeted macroscopic objects calls for questions about how to delicately control molecular order for desired performance. Microparticles that can be synthesized with intrinsic molecular order precisely controlled to micrometer size can be used as building blocks for bulk materials, thus offering opportunities to bridge the gap and transcend molecular orders across scales. By taking advantage of the interfacial anchoring effects, we can control and engineer the molecular orders inside the microdroplets, allowing for the realization of various responsive behaviors. Furthermore, designer LC microparticles with multiple responsiveness can be assembled and confined within a matrix, opening a new pathway to engineering LC-enabled intelligent materials.In this Account, we present our recent work on exploiting the molecular order inside microdroplets for the construction of intelligent materials. We briefly introduce the typical chemicals used in the synthesis and the methods developed to control LC molecular alignment within a microdroplets. We then present examples of microparticles synthesized from microdroplets that can transform into complex morphologies upon cooling from the isotropic to nematic phase or due to phase separation within the droplets coupled with the segregation of LC oligomers (LCOs) with polydisperse chain lengths. Furthermore, we show the synthesis of elliptical LCE microparticles and exploit their thermal and magnetic responsiveness to program shape-morphing behaviors and microarrays with switchable optical polarization. By mixing magnetic nanoparticles in cholesteric liquid crystals (CLCs) and silicone oils, we created Janus microparticles capable of color switching for camouflage and information encryption. Moreover, we can engineer complex molecular orders in LCE microparticles by mixing different surfactants, yielding microparticles of diverse anisotropic, temperature-responsive shapes after photopolymerization and extraction of the template LC molecules with different solvents. We conclude the Account with an outlook on the design of intelligent material systems via the design of unprecedented molecular ordering within the microparticles and their coupling with bulk materials.

Safety and efficacy of radiotherapy combined with chemotherapy for recurrent metastatic renal pelvic and ureteral carcinoma.

PURPOSE: To retrospectively investigate the safety and efficacy of radiotherapy combined with chemotherapy for recurrent metastatic renal pelvic and ureteral carcinoma. METHODS: 109 patients were enrolled in this study, including 44 patients in the radiochemotherapy group and 65 patients in the chemotherapy group. Propensity score matching (PSM) was used to balance the baseline characteristics of the two groups by 1:1 matching. Kaplan-Meier method was used to calculate PFS and OS. Cox regression model was used for multivariate analysis. The side effects were evaluated by CTCAE v5.0 RESULTS: The median follow-up time was 14.5 months. Multivariate analysis showed that radiotherapy was a good independent prognostic factor for OS (HR: 0.327, 95% CI 0.157-0.680, P = 0.003). After matching, there were 40 patients in both groups, and the median PFS and OS in the radiochemotherapy group were longer than those in the chemotherapy group (PFS: 10.4 vs. 6.7 months, P = 0.035; OS: 43.5 vs. 18.8 months, P < 0.001). In addition, in the radiochemotherapy group, patients treated with radiotherapy before first-line chemotherapy failure had a longer PFS than those treated with radiotherapy after chemotherapy failure (median PFS: 15.7 vs. 6 months, P = 0.003). There was no significant difference in the incidence of grade 3-4 toxicities between the two groups (52.3% vs. 50.8%, P = 0.878). CONCLUSION: For patients with recurrent metastatic renal pelvic and ureteral carcinoma, radiotherapy combined with chemotherapy is well tolerable and expected to bring long-term survival benefits, and the benefits of early interventional radiotherapy may be more obvious.

Phenotypic characteristics and immune response of Procypris merus following challenge with aquatic isolate of Klebsiella pneumoniae.

Currently, aquaculture is a relatively mature industry; however, disease problems are continuously threatening the industry and hindering its development to a certain extent. Klebsiella pneumoniae is one of the zoonotic bacteria widely present in different hosts and has caused some degree of harm to the aquaculture industry, posing a potential threat to the water environment and indirectly also affecting human food safety issues. In this study, K. pneumoniae was isolated from the aquaculture environment, named as ELD, and subjected to pathogenic and immunological related studies. The results of the study showed that the strain carries at least four virulence-related genes, magA, wabG, ureA and uge, and has developed resistance to at least seven antibacterial drugs, such as amoxicillin, doxycycline, rifampicin, and so on. Moreover, the strain is highly pathogenic and is capable of causing systemic clinical foci in Procypris merus. In addition, after infection with K. pneumoniae, the expression of IL-1ß, IL-8, HSP70 and C2 was upregulated in P. merus as a whole, whereas the expression of TNF-α did not change significantly in any of the tissues, which might be a kind of immune response of P. merus against K. pneumoniae infection. This study provides an important theoretical basis for the in-depth exploration of the pathogenic mechanism of K. pneumoniae in fish and the immune response that occurs after the disease is contracted in fish, as well as theoretical support for the development of effective preventive and therapeutic strategies against K. pneumoniae-infected aquatic animals in the future.

Synthesis of Microparticles with Diverse Thermally Responsive Shapes Originated from the Same Janus Liquid Crystalline Microdroplets.

Liquid crystalline elastomer (LCE)-based microparticles that can change shapes in response to external stimuli are of great interest for potential applications such as artificial cells, micro-actuators, micro-valves, and smart drug carriers. Here, the synthesis of LCE microparticles with diverse temperature-dependent anisotropic shapes originated from the same Janus microdroplets is reported. The Janus microdroplets, suspended in an aqueous solution of surfactants, are transformed from microdroplets consisting of a mixture of liquid crystal (LC) monomers, oligomers, silicone oil, and an organic solvent, after the removal of the organic solvent. The molecular alignment of the LC part at the interface, whether planar, homeotropic, or hybrid, is dependent on the choice of the surfactants but not affected by the silicone oil. After polymerization and solvent extraction of the unreacted components, LCE microparticles of various shapes are obtained depending on the concentration and composition of the surfactants, the weight ratio of the LC part to the silicone oil part, and the choice of the extraction solvent. The microparticles that undergo different synthetic pathways show distinct thermally responsive shapes, much like how stem cells differentiate in different environmental conditions.

Identification of ISG15 in golden pompano, Trachinotus ovatus, and its role in virus and bacteria infections.

Interferon (IFN)-stimulated gene product 15 (ISG15) is a ubiquitin-like protein critical for the control of microbial infections. Golden pompano, Trachinotus ovatus is one of the precious marine economic fish in the southern coast of China, always suffering from viruses, bacteria, and parasite infections. To date, the roles of golden pompano genes involved in viral and bacterial infections, especially IFN-related genes remained largely unknown. To identify the interferon system genes of golden pompano and explore their function, in this study, the ISG15 homolog (ToISG15) was cloned from golden pompano, and its role in response to grouper iridovirus (SGIV), nervous necrosis virus (NNV), and Aeromonas hydrophila infection was investigated. The whole ORF of ToISG15 was composed of 465 bp and encoded a polypeptide of 154 amino acids with different identity with the known ISG15 homologs from other fish species. Two conserved ubiquitin-like (UBL) domains and an Ub-conjugation domain (LRGG) were found in ToISG15 sequence. Expression analysis showed that ToISG15 was located mainly in the cytoplasm of golden pompano cells, and dramatically induced following SGIV, Aeromonas hydrophila, or poly I:C treatment, but little change was observed when NNV infection. Overexpression of ToISG15 in vitro significantly inhibited the replication of SGIV and NNV. Interestingly, ToISG15 possessed the ability to restrain the growth of Aeromonas hydrophila. Furthermore, To-ISG15 overexpression enhanced the expression of IFNc, IFNh, IRF3, IRF7, and viperin genes as well as, to a lesser extent, the IL-6 gene. Taken together, our results demonstrated the antiviral and antibacterial effect of To-ISG15, shedding light on the evolutionary conservation of ISG15 in the immune response to microbial infection.

Molecular and functional characterization of viperin in golden pompano, Trachinotus ovatus.

The radical S-adenosyl methionine domain-containing protein 2 (RSAD2), also known as viperin, plays a momentous and multifaceted role in antiviral immunity. However, the function of viperin is uninvestigated in golden pompano, Trachinotus ovatus. In the present study, a viperin homolog, named To-viperin, was cloned and characterized from golden pompano, and its role in response to grouper iridovirus (SGIV) and nervous necrosis virus (NNV) infection was investigated. The whole open reading frame (ORF) of To-viperin was composed of 1050 bp and encoded a polypeptide of 349 amino acids with 70.66%-83.51% identity with the known viperin homologs from other fish species. A variable N-terminal domain, a highly conserved C-terminal domain, and a conserved middle radical SAM domain (aa 61-271) with the three-cysteine motif CxxCxxC was found in To-viperin sequence. Expression analysis showed that To-viperin was constitutively expressed in all tested organs and was located mainly in the ER of golden pompano cells. Treatments with SGIV, poly I: C, or NNV could induce the up-regulation of viperin to varying degrees. The ectopic expression of To-viperin in vitro significantly reduced the viral titer of SGIV and NNV. Furthermore, To-viperin overexpression enhanced the expression of IFNc, IRF3, and ISG15 genes as well as, to a lesser extent, the IL-6 gene. In summary, our results suggested that the function of viperin is likely to be conserved in fish specise, as observed in other vertebrates, shedding light on the evolutionary conservation of viperin.

A Comparative Study on the Oxidation Mechanisms of Substituted Phenolic Pollutants by Ferrate(VI) through Experiments and Density Functional Theory Calculations.

In this work, the oxidation of five phenolic contaminants by ferrate(VI) was comparatively investigated to explore the possible reaction mechanisms by combined experimental results and theoretical calculations. The second-order rate constants were positively correlated with the energy of the highest occupied molecular orbital. Considering electronic effects of different substituents, the easy oxidation of phenols by ferrate(VI) could be ranked as the electron-donating group (-R) > weak electron-withdrawing group (-X) > strong electron-withdrawing group (-(C═O)-). The contributions of reactive species (Fe(VI), Fe(V)/(IV), and •OH) were determined, and Fe(VI) was found to dominate the reaction process. Four main reaction mechanisms including single-oxygen transfer (SOT), double-oxygen transfer (DOT), •OH attack, and electron-transfer-mediated coupling reaction were proposed for the ferrate(VI) oxidation process. According to density functional theory calculation results, the presence of -(C═O)- was more conducive for the occurrence of DOT and •OH attack reactions than -R and -X, while the tendency of SOT for different substituents was -R > -(C═O)- > -X and that of e--transfer reaction was -R > -X > -(C═O)-. Moreover, the DOT pathway was found in the oxidation of all four substituted phenols, indicating that it may be a common reaction mechanism during the ferrate(VI) oxidation of phenolic compounds.

Promoting Effect of Silver Oxide Nanoparticles on the Oxidation of Bisphenol B by Ferrate(VI).

Bisphenol B (BPB, 2,2-bis(4-hydroxyphenyl) butane), as a substitute for bisphenol A, has been widely detected in the environment and become a potential threat to environmental health. This work found that silver oxide nanoparticles (Ag2O) could greatly promote the removal of BPB by ferrate (Fe(VI)). With the presence of 463 mg/L Ag2O, the amount of Fe(VI) required for the complete removal of 10 µM BPB will be reduced by 70%. Meanwhile, the recyclability and stability of Ag2O have been verified by recycling experiments. The characterization results and in situ electrochemical analyses showed that Ag(II) was produced from Ag(I) in the Fe(VI)-Ag2O system, which has a higher electrode potential to oxidize BPB to enhance its removal. A total of 13 intermediates were identified by high-resolution mass spectrometry, and three main reaction pathways were proposed, including oxygen transfer, bond breaking, and polymerization. Based on the toxicity assessment through the ECOSAR program, it is considered that the presence of Ag2O reduced the toxicity of BPB oxidation intermediates to aquatic organisms. These results would deepen our understanding of the interaction between Fe(VI) and Ag2O, which may provide an efficient and environmentally friendly method for water and wastewater treatment.

DFT Study on the Oxidation Mechanism of Common Cyclic Carbonates in the Presence of BF4- Anions.

Oxidative decomposition reactions of common cyclic carbonates in the presence of BF4- anions were investigated using density functional theory. A polarized continuum model was utilized to model solvent effects in the oxidation of ethylene carbonate (EC) and propylene carbonate (PC) clusters. We have found that the presence of BF4- significantly reduces EC and PC oxidation stability, from 7.11 to 6.17 and from 7.10 to 6.06 V (vs Li+/Li), respectively. The sequence of EC and PC oxidative decomposition paths and the oxidative products were affected by the BF4- anion. The decomposition products of the oxidized EC-BF4- contained CO2, vinyl alcohol, and acetaldehyde, while the decomposition products of the oxidized PC-BF4- contained CO2, acetone, and propanal, in agreement with the previous experimental studies. The oxidative decomposition reactions for PC-BF4- are compared with those for the isolated PC, PC2, PC-ClO4-, and PC-PF6-.

The regulatory roles of DDIT4 in TDCIPP-induced autophagy and apoptosis in PC12 cells.

Tris (1,3-dichloro-2-propyl) phosphate (TDCIPP) is a commonly used organophosphate-based flame retardant and can bio-accumulate in human tissues and organs. As its structure is similar to that of neurotoxic organophosphate pesticides, the neurotoxicity of TDCIPP has raised widespread concerns. TDCIPP can increase neuronal apoptosis and induce autophagy. However, its regulatory mechanism remains unclear. In this study, we found that the expression upregulation of the DNA Damage-Inducible Transcript 4 (DDIT4) protein, which might play essential roles in TDCIPP-induced neuronal autophagy and apoptosis, was observed in TDCIPP-treated differentiated rat PC12 cells. Furthermore, we determined the protective effect of the DDIT4 suppression on the autophagy and apoptosis induced by TDCIPP using Western blot (WB) and Flow cytometry (FACS) analysis. We observed that TDCIPP treatment increased the DDIT4, the autophagy marker Beclin-1, and the microtubule-associated protein light chain 3-II (LC3II) expressions and decreased the mTOR phosphorylation levels. Conversely, the suppression of DDIT4 expression increased the p-mTOR expression and decreased cell autophagy and apoptosis. Collectively, our results revealed the function of DDIT4 in cell death mechanisms triggered by TDCIPP through the mTOR signaling axis in differentiated PC12 cells. Thus, this study provided vital evidence necessary to explain the mechanism of TDCIPP-induced neurotoxicity in differentiated PC12 cells.

Supramolecularly Engineered Reporters with Superoxide Anion-Triggered Chemiluminescence for Early Diagnosis and Efficient Amelioration of Acute Kidney Injury.

We report the "water-in-oil-in-water" preparation of kidney injury molecule-1-targeting supramolecular chemiluminescence (CL) reporters (PCCS), consisting of L-serine-modified poly(lactic-co-glycolic) acid (PLGA)-encapsulated peroxyoxalate (CPPO), chlorin e6 (Ce6) and superoxide dismutase (SOD), for early diagnosis and amelioration of acute kidney injury (AKI). In this system, O2 ⋅- , a biomarker of AKI, triggers the oxidation of CPPO to 1,2-dioxetanedione and subsequent CL emission via CL resonance energy transfer to Ce6. The L-serine-modified PLGA stabilizes CPPO and Ce6 via noncovalent interactions, promoting long-lived CL (half-lives: ≈1000 s). Transcriptomics analysis shows that PCCS reporters reduce the inflammatory response through glutathione metabolism and inhibition of the tumor necrosis factor signaling pathway. The reporters are able to non-invasively detect AKI at least 12 h earlier than current assays, and their antioxidant properties allow simultaneous treatment of AKI.

Glycolysis addiction compensating for a defective pentose phosphate pathway confers gemcitabine sensitivity in SETD2-deficient pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy driven by genetic mutations and/or epigenetic dysregulation. Gemcitabine chemotherapy is the first-line regimen for pancreatic cancer but has limited efficacy. Our previous study revealed the role of SETD2-H3K36me3 loss in the initiation and metastasis of PDAC, but little is known about its role in tumor metabolism. Here, we found that SETD2-deficient PDAC enhanced glycolysis addiction via upregulation of glucose transporter 1 (GLUT1) to meet its large demand for glucose in progression. Moreover, SETD2 deficiency impaired nucleoside synthesis by directly downregulating the transcriptional level of transketolase (TKT) in the pentose phosphate pathway. The metabolic changes confer SETD2-deficient PDAC cells with increased sensitivity to gemcitabine under glycolysis restriction conditions. Collectively, our study provides mechanistic insights into how SETD2 deficiency reprograms glycolytic metabolism to compensate for insufficient nucleoside synthesis, suggesting that glycolysis restriction combined with gemcitabine might be a potential therapeutic strategy for PDAC patients with SETD2 deficiency.

Research on the indirect antiviral function of medicinal plant ingredient quercetin against grouper iridovirus infection.

Grouper iridovirus is a devastating pathogen that belongs to the genus Ranavirus. Based on the previous results that natural ingredient quercetin isolated from Illicium verum Hook. f. could effectively inhibit Singapore grouper iridovirus (SGIV) replication, suggesting that quercetin could serve as potential antiviral agent against grouper iridovirus. To know about whether quercetin has indirect antiviral activity against SGIV, this study made the investigation in vitro and in vivo, and the potential mechanism was also explored. Pretreating the cells with quercetin (12.5 µg/mL) significantly inhibited the replication of SGIV, similar results were also confirmed in vivo. Importantly, quercetin pretreatment could induce the expression of genes involved in type I interferon (IFN) system (IFN, STAT1, PKR, MxI and ISG15) and TLR9. It suggested that quercetin exerted the indirect antiviral activity against SGIV infection through promoting the recognition of SGIV and activating the IFN pathway to establish the antiviral status of host cell. Taken together, our results shedded light on the indirect antiviral function of natural ingredient quercetin, and clearly demonstrated that natural ingredient quercetin will be an excellent potential agent against SGIV infection in grouper aquaculture.

Metabolic characterization of hemolymph in Bombyx mori varieties after Bombyx mori nucleopolyhedrovirus infection by GC-MS-based metabolite profiling.

The "Huakang 2" silkworm variety, bred by the Sericulture Research Institute of the Chinese Academy of Agricultural Sciences, is highly resistant to Bombyx mori nucleopolyhedrovirus (BmNPV) and effectively solves the issue of frequent Bombyx mori nuclear polyhedrosis in sericultural production. The molecular mechanism of its resistance to BmNPV, however, is still unknown. The purpose of the present study was therefore to identify these anti-BmNPV mechanisms by using metabolomics in combination with transcriptomics after subcutaneous injection of budded virus (BV) with high concentrations of BmNPV from specimens of the Baiyu N variety (which is highly resistant to BmNPV) and the Baiyu variety (which is sensitive to BmNPV). A total of 375 differential metabolites were identified, which mainly included sugars, acids, amines, alcohols, glycosides, and other small molecules. KEGG enrichment analysis and functional clustering of differential metabolites identified possible metabolic pathways, including tyrosine metabolism, oxidative phosphorylation, and alanine, aspartate, and glutamate metabolism. The differentially expressed genes (DEGs) identified by transcriptome analysis were annotated in KEGG. Association analysis showed that the metabolic pathways of different silkworm varieties are affected differently by BmNPV infection, triggering a series of complex physiological and biochemical changes in the organism. In particular, oxidative phosphorylation might be an essential pathway involved in regulation of disease resistance.

Detection of ochratoxin A by fluorescence sensing based on mesoporous materials.

We developed a new ochratoxin A (OTA) aptamer biosensor to promptly detect OTA in food. Mesoporous silica nanoparticles were used as carriers, and aptamers were used as recognition probes and gating molecules. The fluorescent dye rhodamine 6G was loaded into mesoporous silica, and through electrostatic contact, the OTA aptamer was adsorbed on amino-modified mesoporous silica. The fluorescent dye released from the mesopore in the presence of OTA because of the conformational change induced in the aptamer by the target. The amount of ochratoxin was determined by measuring the fluorescence intensity. Our findings revealed a positive relationship between the fluorescence intensity and OTA concentration, with a limit of detection of 0.28 ng mL-1, and the detection range was 0.05-200 ng mL-1. The recovery rate was 80.7%-110.8% in real samples. The proposed approach is suitable for the quantification of other toxins.

Impact of early term and late preterm birth on infants' neurodevelopment: evidence from a cohort study in Wuhan, China.

BACKGROUND: The incidences of early term and late preterm birth have increased worldwide during recent years. However, there is a lack of prospective study about the influence of early term and late preterm birth on infants' neurodevelopment, especially at the early stage. Therefore, we conducted this cohort study to investigate the impact of early term and late preterm birth on infants' neurodevelopment within 6 months. METHODS: This cohort study was conducted in Wuhan, China, between October 2012 and September 2013. A total of 4243 singleton infants born within 34-41 weeks of gestation at Wuhan Children's Hospital were included. The Gesell Developmental Scale (GDS) was utilized to evaluate the neurodevelopment of infants. RESULTS: Among the 4243 included participants, 155 (3.65%) were late preterm infants, 1288 (30.36%) were early term infants, and 2800 (65.99%) were full term infants. After adjusted for potential confounders, significant negative relationship was shown between late preterm birth and development quotient (DQ) in all domains of neurodevelopment: gross motor (ß = - 17.42, 95% CI: - 21.15 to - 13.69), fine motor (ß = - 23.61, 95% CI: - 28.52 to - 18.69), adaptability (ß = - 10.10, 95% CI: - 13.82 to - 6.38), language (ß = - 6.28, 95% CI: - 9.82 to - 2.74) and social behavior (ß = - 5.99, 95% CI: - 9.59 to - 2.39). There was a significant negative trend for early term birth in DQ of fine motor (ß = - 2.01, 95% CI: - 3.93 to - 0.09). Late preterm infants had a significantly elevated risk of neurodevelopmental delay in domains of gross motor (adjusted OR = 3.82, 95% CI: 2.67 to 5.46), fine motor (adjusted OR = 3.51, 95% CI: 2.47 to 5.01), and adaptability (adjusted OR = 1.60, 95% CI: 1.12 to 2.29), whereas early term birth was significantly associated with neurodevelopmental delay of fine motor (adjusted OR = 1.22, 95% CI: 1.05 to 1.42). CONCLUSIONS: This study suggested that late preterm birth mainly elevated the risk of neurodevelopmental delay of gross motor, fine motor, and adaptability, whereas early term birth was associated with the developmental delay of fine motor within 6 months. Further research is needed to determine the effectiveness and necessity of the interventions at the early stage for early term and late preterm infants who had suspected neurodevelopmental delay.

Study on aptamer based high throughput approach identifies natural ingredients against RGNNV.

Nervous necrosis virus (NNV) is one of the most destructive pathogens in marine fish aquaculture and is capable of infecting more than 50 fish species worldwide, which resulted in great economic losses. Effective drugs for managing NNV infection are urgently required. Medicinal plants have been known for thousands of years and benefit of medicinal plants against pathogens in aquaculture have emerged. Nowadays, the most commonly used method for detecting virus infection and assessing antiviral drugs efficacy is reverse transcription-quantitative real-time PCR. However, the application is limited on account of high reagent costs, complex time-consuming operations and long detection time. Aptamers have been widely applied in application of pathogens or diseases diagnosis and treatments because of high specificity, strong affinity, good stability, easy synthesized and low costs. This study aimed to establish an aptamer (GBN34)-based high-throughput screening (GBN34-AHTS) model for efficient selection and evaluation of natural ingredients against NNV infection. GBN34-AHTS is an expeditious rapid method for selecting natural ingredients against NNV, which is characterized with high-speed, dram, sensitive and accurate. AHTS strategy could reduce work intensity and experimental costs and shorten the whole screening cycle of effective ingredients. AHTS should be suitable for rapid selection of effective ingredients against other viruses, which is important for improving the prevention and controlling of aquatic diseases.

Millisecond-Range Time-Resolved Bioimaging Enabled through Ultralong Aqueous Phosphorescence Probes.

Probes featuring room-temperature phosphorescence (RTP) are promising tools for time-resolved imaging. It is worth noting that the time scale of time-resolved bioimaging generally ranges around the microsecond level, because of the short-lived emission. Herein, the first example of millisecond-range time-resolved bioimaging is illustrated, which is enabled through a kind of ultralong aqueous phosphorescence probes (i.e., cyclo-(Arg-Gly-AspD-Tyr-Cys)-conjugated zinc-doped silica nanospheres), with a RTP emission lasting for ≈5 s and a lifetime as long as 743.7 ms. We demonstrate that live cells and deep tumor tissue in mice can be specifically targeted through immune-phosphorescence imaging, with a high signal-to-background ratio (SBR) value of ≈69 for in vitro imaging, and ≈627 for in vivo imaging, respectively. We further show that, compared to that of fluorescence imaging, the SBR enhancement of millisecond-range time-resolved in vivo bioimaging is up to 105 times.

PTPN2 regulates the activation of KRAS and plays a critical role in proliferation and survival of KRAS-driven cancer cells.

RAS genes are the most commonly mutated in human cancers and play critical roles in tumor initiation, progression, and drug resistance. Identification of targets that block RAS signaling is pivotal to develop therapies for RAS-related cancer. As RAS translocation to the plasma membrane (PM) is essential for its effective signal transduction, we devised a high-content screening assay to search for genes regulating KRAS membrane association. We found that the tyrosine phosphatase PTPN2 regulates the plasma membrane localization of KRAS. Knockdown of PTPN2 reduced the proliferation and promoted apoptosis in KRAS-dependent cancer cells, but not in KRAS-independent cells. Mechanistically, PTPN2 negatively regulates tyrosine phosphorylation of KRAS, which, in turn, affects the activation KRAS and its downstream signaling. Consistently, analysis of the TCGA database demonstrates that high expression of PTPN2 is significantly associated with poor prognosis of patients with KRAS-mutant pancreatic adenocarcinoma. These results indicate that PTPN2 is a key regulator of KRAS and may serve as a new target for therapy of KRAS-driven cancer.