Associations of PD-1 and PD-L1 gene polymorphisms with cancer risk: a meta-analysis based on 50 studies.

Programmed death-1 and its ligand-1 (PD-1/PD-L1), immune checkpoints proteins, play a crucial role in anti-tumor responses. A large number of studies have evaluated the relationships of PD-1/PD-L1 polymorphisms with risk of cancer, but evidence for the associations remains inconsistent. Therefore, we performed a meta-analysis to examine the associations between PD-1/PD-L1 single nucleotide polymorphisms (SNPs) and cancer predisposition. Results showed that PD-1.3 and PD-L1 rs17718883 were significantly correlated with overall cancer risk. PD-1.5 was prominently linked with cervical cancer (CC), non-small cell lung cancer (NSCLC), TC (thyroid cancer), brain tumor, AML (acute myelocytic leukemia) and UCC (urothelial cell carcinoma) risk, PD-1.9 with breast cancer (BC), AML, esophageal cancer (EC) and ovarian cancer (OC) risk, and PD-1.3 with colorectal cancer (CRC) and BCC (basal cell carcinoma) risk. PD-1.1 polymorphism slightly elevated BC and OC susceptibility, whereas the rs4143815 variant notably decreased the risk of gastric cancer (GC), hepatocellular carcinoma (HCC) and OC, but increased the risk of BC. PD-1.6 was closely linked with AML risk, PD-L1 rs2890658 with NSCLC, HCC and BC risk, rs17718883 with HCC and GC risk, rs10815225 with GC risk, and rs2297136 with NSCLC and HCC risk. Interestingly, the rs7421861, rs10815225, and rs10815225 markedly reduced cancer susceptibility among Asians. The rs7421861 polymrophism decreased cancer risk among Caucasians, rather than the rs10815225 elevated cancer risk. Our results supported that PD-1 and PD-L1 SNPs were dramatically correlated with cancer risk.

Cellular nucleic acid binding protein facilitates cardiac repair after myocardial infarction by activating ß-catenin signaling.

The regenerative capacity of the adult mammalian heart is limited, while the neonatal heart is an organ with regenerative and proliferative ability. Activating adult cardiomyocytes (CMs) to re-enter the cell cycle is an effective therapeutic method for ischemic heart disease such as myocardial infarction (MI) and heart failure. Here, we aimed to reveal the role and potential mechanisms of cellular nucleic acid binding protein (CNBP) in cardiac regeneration and repair after heart injury. CNBP is highly expressed within 7 days post-birth while decreases significantly with the loss of regenerative ability. In vitro, overexpression of CNBP promoted CM proliferation and survival, whereas knockdown of CNBP inhibited these processes. In vivo, knockdown of CNBP in CMs robustly hindered myocardial regeneration after apical resection in neonatal mice. In adult MI mice, CM-specific CNBP overexpression in the infarct border zone ameliorated myocardial injury in acute stage and facilitated CM proliferation and functional recovery in the long term. Quantitative proteomic analysis with TMT labeling showed that CNBP overexpression promoted the DNA replication, cell cycle progression, and cell division. Mechanically, CNBP overexpression increased the expression of ß-catenin and its downstream target genes CCND1 and c-myc; Furthermore, Luciferase reporter and Chromatin immunoprecipitation (ChIP) assays showed that CNBP could directly bind to the ß-catenin promoter and promote its transcription. CNBP also upregulated the expression of G1/S-related cell cycle genes CCNE1, CDK2, and CDK4. Collectively, our study reveals the positive role of CNBP in promoting cardiac repair after injury, providing a new therapeutic option for the treatment of MI.

Sesamin alleviates lipid accumulation induced by oleic acid via PINK1/Parkin-mediated mitophagy in HepG2 cells.

Sesamin, a special compound present in sesame and sesame oil, has been reported a role in regulating lipid metabolism, while the underlying mechanisms remain unclear. Autophagy has been reported associated with lipid metabolism and regarded as a key modulator in liver steatosis. The present work aimed to investigate whether sesamin could exert its protective effects against lipid accumulation via modulating autophagy in HepG2 cells stimulated with oleic acid (OA). Cell viability was evaluated using the CCK-8 method, and triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein, cholesterol (LDL-C), alanine aminotransferase (ALT), along with aspartate aminotransferase (AST) were assessed by oil red O staining, transmission electron microscopy (TEM), and biochemical kits to investigate the lipid-lowering effects of sesamin. Differentially expressed genes were screened by RNA sequencing and validated using real-time quantitative PCR and Western blot. Autophagy and mitophagy related molecules were analyzed employing TEM, Western blot, and immunofluorescence. The data shows that in HepG2 cells stimulated by OA, sesamin reduces levels of TG, TC, LDL-C, ALT, and AST while elevating HDL-C, alleviates the lipid accumulation and improves fatty acid metabolism through modulating the levels of fat metabolism related genes including PCSK9, FABP1, CD36, and SOX4. Sesamin restores the suppressed autophagy in HepG2 cells caused by OA, which could be blocked by autophagy inhibitors. This indicates that sesamin improves fatty acid metabolism by enhancing autophagy levels, thereby mitigating the intracellular lipid accumulation. Furthermore, sesamin significantly enhances the mitophagy and improves mitochondrial homeostasis via activating the PINK/Parkin pathway. These data suggest that sesamin alleviates the excessive lipid accumulation in HepG2 caused by OA by restoring the impaired mitophagy via the PINK1/Parkin pathway, probably playing a preventive or therapeutic role in hepatic steatosis.

Eukaryotic translation elongation factor 1 alpha (eEF1A) inhibits Siniperca chuatsi rhabdovirus (SCRV) infection through two distinct mechanisms.

IMPORTANCE: Although a virus can regulate many cellular responses to facilitate its replication by interacting with host proteins, the host can also restrict virus infection through these interactions. In the present study, we showed that the host eukaryotic translation elongation factor 1 alpha (eEF1A), an essential protein in the translation machinery, interacted with two proteins of a fish rhabdovirus, Siniperca chuatsi rhabdovirus (SCRV), and inhibited virus infection via two different mechanisms: (i) inhibiting the formation of crucial viral protein complexes required for virus transcription and replication and (ii) promoting the ubiquitin-proteasome degradation of viral protein. We also revealed the functional regions of eEF1A that are involved in the two processes. Such a host protein inhibiting a rhabdovirus infection in two ways is rarely reported. These findings provided new information for the interactions between host and fish rhabdovirus.

SIRT3-dependent mitochondrial redox homeostasis mitigates CHK1 inhibition combined with gemcitabine treatment induced cardiotoxicity in hiPSC-CMs and mice.

Administration of CHK1-targeted anticancer therapies is associated with an increased cumulative risk of cardiac complications, which is further amplified when combined with gemcitabine. However, the underlying mechanisms remain elusive. In this study, we generated hiPSC-CMs and murine models to elucidate the mechanisms underlying CHK1 inhibition combined with gemcitabine-induced cardiotoxicity and identify potential targets for cardioprotection. Mice were intraperitoneally injected with 25 mg/kg CHK1 inhibitor AZD7762 and 20 mg/kg gemcitabine for 3 weeks. hiPSC-CMs and NMCMs were incubated with 0.5 uM AZD7762 and 0.1 uM gemcitabine for 24 h. Both pharmacological inhibition or genetic deletion of CHK1 and administration of gemcitabine induced mtROS overproduction and pyroptosis in cardiomyocytes by disrupting mitochondrial respiration, ultimately causing heart atrophy and cardiac dysfunction in mice. These toxic effects were further exacerbated with combination administration. Using mitochondria-targeting sequence-directed vectors to overexpress CHK1 in cardiomyocyte (CM) mitochondria, we identified the localization of CHK1 in CM mitochondria and its crucial role in maintaining mitochondrial redox homeostasis for the first time. Mitochondrial CHK1 function loss mediated the cardiotoxicity induced by AZD7762 and CHK1-knockout. Mechanistically, mitochondrial CHK1 directly phosphorylates SIRT3 and promotes its expression within mitochondria. On the contrary, both AZD7762 or CHK1-knockout and gemcitabine decreased mitochondrial SIRT3 abundance, thus resulting in respiration dysfunction. Further hiPSC-CMs and mice experiments demonstrated that SIRT3 overexpression maintained mitochondrial function while alleviating CM pyroptosis, and thereby improving mice cardiac function. In summary, our results suggest that targeting SIRT3 could represent a novel therapeutic approach for clinical prevention and treatment of cardiotoxicity induced by CHK1 inhibition and gemcitabine.

Fusing a TurboID tag with the Andrias davidianus ranavirus 2L reduced virus adsorption efficiency.

Andrias davidianus ranavirus (ADRV) is a member of the genus ranavirus (family Iridoviridae). ADRV 2L is an envelope protein that could be essential in viral infection. In the present study, the function of ADRV 2L was investigated by fusion with the biotin ligase TurboID tag. A recombinant ADRV with a V5-TurboID tag fused in the N-terminal of 2L (ADRVT-2L) and a recombinant ADRV expressing V5-TurboID (ADRVT) were constructed, respectively. Infection of the recombinant viruses and wild-type ADRV (ADRVWT) in the Chinese giant salamander thymus cell line (GSTC) showed that ADRVT-2L had reduced cytopathic effect and lower virus titers than the other two viruses, indicating the fusion of a big tag affected ADRV infection. Analysis of the temporal expression profile showed that the expression of V5-TurboID-2L was delayed than wild-type 2L. However, electron microscopy found that the virion morphogenesis was not affected in ADRVT-2L-infected cells. Furthermore, the virus binding assay revealed that the adsorption efficiency of ADRVT-2L was considerably decreased compared to the other two viruses. Therefore, these data showed that linking the TurboID tag to ADRV 2L affected virus adsorption to the cell membrane, which suggested an important role of 2L in virus entry into cells.

Identification of citrus APX gene family and their response to CYVCV infection.

Ascorbate peroxidase (APX) is one of the most important antioxidant enzymes in the reactive oxygen metabolic pathway of plants. The role of APX under biotic and abiotic stress conditions has been explored, but the response pattern of APX under biotic stresses is relatively less known. In this study, seven CsAPXs gene family members were identified based on the sweet orange (Citrus sinensis) genome and subjected to evolutionary and structural analysis using bioinformatics software. The APX genes of lemon (ClAPXs) were cloned and showed a high conservation to CsAPXs by sequences alignment. In citrus yellow vein clearing virus (CYVCV)-infected Eureka lemons (C. limon) at 30th day post inoculation, APX activity and accumulation of hydrogen peroxide (H2O2) and malondialdehyde were measured to be 3.63, 2.29, and 1.73 times to that of the healthy control. The expression levels of 7 ClAPX genes in different periods of CYVCV-infected Eureka lemon were analyzed. Notably, ClAPX1, ClAPX5, and ClAPX7 showed higher expression levels compared to healthy plants, while ClAPX2, ClAPX3, and ClAPX4 showed lower expression levels. Functional identification of ClAPX1 in Nicotiana benthamiana showed that increasing the expression of ClAPX1 could significantly reduce the accumulation of H2O2, and it was verified that ClAPX1 is located in the plasma membrane of the cell. The present study provided information on the evolution and function of citrus APXs and revealed for the first time their response pattern to CYVCV infection.

Transcriptome analysis of Citrus limon infected with Citrus yellow vein clearing virus.

BACKGROUND: Citrus yellow vein clearing virus (CYVCV) is the causative agent of citrus yellow vein clearing disease, and poses a serious threat to the lemon industry in Asia. The common symptoms of CYVCV-infected lemon plants are leaf crinkling, leaf chlorotic mottling, and yellow vein clearing. However, the molecular mechanisms underlying CYVCV-citrus interaction that responsible for symptom occurrence is still unclarified. In this study, RNA-seq was performed to analyze the gene expression patterns of 'Eureka' lemon (Citrus limon Burm. f.) plants in response to CYVCV infection. RESULTS: There were 3691 differentially expressed genes (DEGs) identified by comparison between mock and CYVCV-infected lemon plants through RNA-seq. Bioinformatics analyses revealed that these DEGs were components of different pathways involved in phenylpropanoid biosynthesis, brassinosteroid biosynthesis, flavonoid biosynthesis and photosynthesis. Among these, the DEGs related to phytohormone metabolism and photosynthesis pathways were further enriched and analyzed. This study showed that different phytohormone-related genes had different responses toward CYVCV infection, however almost all of the photosynthesis-related DEGs were down-regulated in the CYVCV-infected lemon plants. The obtained RNA-seq data were validated by RT-qPCR using 12 randomly chosen genes, and the results of mRNA expression analysis were consistent with those of RNA-seq. CONCLUSIONS: The phytohormone biosynthesis, signaling and photosynthesis-related genes of lemon plants were probably involved in systemic infection and symptom occurrence of CYVCV. Notably, CYVCV infection had regulatory effects on the biosynthesis and signaling of phytohormone, which likely improve systemic infection of CYVCV. Additionally, CYVCV infection could cause structural changes in chloroplast and inhibition of photosynthesis pathway, which probably contribute to the appearance of leaf chlorotic mottling and yellow vein clearing in CYVCV-infected lemon plants. This study illustrates the dynamic nature of the citrus-CYVCV interaction at the transcriptome level and provides new insights into the molecular mechanism underlying the pathogenesis of CYVCV in lemon plants.

Construction of Full-Length Infectious cDNA Clones of Citrus Mosaic Virus RNA1 and RNA2 and Infection of Citrus Seedlings by Agrobacterium-Mediated Vacuum-Infiltration.

The development of full-length infectious cDNA clones for plant RNA viruses is important for studying their molecular biological characteristics, functional genomics, pathogenesis, and vectorization applications. Citrus mosaic virus (CiMV), a member of the genus Sadwavirus, is of economic importance to the citrus industry and comprises a bipartite, positive-sense, single-stranded RNA genome encapsidated in icosahedral virions. In the present study, full-length cDNA clones of CiMV RNA1 and RNA2 were constructed based on a ternary yeast-Escherichia coli-Agrobacterium tumefaciens shuttle vector, pTY, using transformation-associated recombination (TAR) strategy. Infectivity of cDNA clones of CiMV RNA1 and RNA2 was examined in multiple citrus varieties via Agrobacterium-mediated vacuum-infiltration (AVI) through symptom observation, RT-PCR, and virion detection with an electron microscope. Furthermore, the genome-sized RT-PCR fragments of RNA1 and RNA2 were obtained from symptomatic Jinchengyou (Citrus grandis) plants infected by the cloned virus (CiMV211). In addition, CiMV211 produced typical symptoms of wild-type CiMV in cowpea (Vigna angularis) plants inoculated by Agrobacterium-mediated injection. This is the first report of infectious cDNA clones of CiMV, which may lay the foundation for research on the pathogenesis and vectorization of the virus.

Mediation Effect of Body Mass Index on the Association of Urinary Nickel Exposure with Serum Lipid Profiles.

The objective of this study was to determine the relationship of urinary nickel (U-Ni) exposure to serum lipid profiles and the mediation effect of body mass index (BMI) in a US general population. We analyzed the cross-sectional data from 3517 participants in the National Health and Nutrition Examination Survey (NHANES) (2017-March 2020). Multivariable linear regression and restricted cubic spline (RCS) regression were conducted to explore the association of U-Ni with four serum lipids and four lipids-derived indicators. Mediation analysis was performed to examine the effect of BMI on the relationship between U-Ni levels and serum lipid profiles. Compared with the lowest quartile, the ß with 95% confidence intervals (CIs) in the highest quartile were - 12.83 (- 19.42, - 6.25) for total cholesterol (TC) (P for trend < 0.001), - 12.76 (- 19.78, - 5.74) for non-high-density lipoprotein cholesterol (non-HDL-C) (P for trend = 0.001) and - 0.29 (- 0.51, - 0.07) for TC/HDL-C (P for trend = 0.007) in the fully adjusted model. RCS plots showed the linear association of log2-transformed U-Ni levels with TC, non-HDL-C and TC/HDL-C (P for nonlinearity = 0.294, 0.152, and 0.087, respectively). Besides, BMI decreased monotonically in correlation with increasing U-Ni levels (P for trend < 0.001). Mediation analysis revealed that BMI significantly mediated the relationship of U-Ni to TC, non-HDL-C and TC/HDL-C with mediated proportions of 11.17%, 22.20% and 36.44%, respectively. In summary, our findings suggest that BMI mediates the negative association of U-Ni with TC, non-HDL-C, and TC/HDL-C in the US general population.

Integrated transcriptomic and proteomic analysis reveals potential targets for heart regeneration.

Research on the regenerative capacity of the neonatal heart could open new avenues for the treatment of myocardial infarction (MI). However, the mechanism of cardiac regeneration remains unclear. In the present study, we constructed a mouse model of heart regeneration and then performed transcriptomic and proteomic analyses on them. Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and Gene Set Enrichment Analysis (GSEA) of differentially expressed genes (DEGs) were conducted. Western blot (WB) and qPCR analyses were used to validate the hub genes expression. As a result, gene expression at the mRNA level and protein level is not the same. We identified 3186 DEGs and 42 differentially expressed proteins (DEPs). Through functional analysis of DEGs and DEPs, we speculate that biological processes such as ubiquitination, cell cycle, and oxygen metabolism are involved in heart regeneration. Integrated transcriptomic and proteomic analysis identified 19 hub genes and Ankrd1, Gpx3, and Trim72 were screened out as potential regulators of cardiac regeneration through further expression verification. In conclusion, we combined transcriptomic and proteomic analyses to characterize the molecular features during heart regeneration in neonatal mice. Finally, Ankrd1, Gpx3, and Trim72 were identified as potential targets for heart regeneration therapy.

Application of Intravoxel Incoherent Motion in the Evaluation of Hepatocellular Carcinoma after Transarterial Chemoembolization.

(1) Background: To assess the efficacy of the quantitative parameters of intravoxel incoherent motion (IVIM) diffusion-weighted imaging for hepatocellular carcinoma (HCC) diagnosis after transarterial chemoembolization (TACE). (2) Methods: Fifty HCC patients after TACE were included and underwent MRI. All of the patients were scanned with the IVIM-DWI sequence and underwent TACE retreatment within 1 week. Referring to digital subtraction angiography (DSA) and MR enhanced images, two readers measured the f, D, and D* values of the tumor active area (TAA), tumor necrotic area (TNA), and adjacent normal hepatic parenchyma (ANHP). Then, the distinctions of the TAA, TNA, and ANHP were compared and we analyzed the differential diagnosis of the parameters in three tissues. (3) Results: For values of f and D, there were significant differences between any of the TAA, TNA, and ANHP (p < 0.05). The values of f and D were the best indicators for identifying the TAA and TNA, with AUC values of 0.959 and 0.955, respectively. The values of f and D performed well for distinguishing TAA from ANHP, with AUC values of 0.835 and 0.753, respectively. (4) Conclusions: Quantitative IVIM-DWI was effective for evaluating tumor viability in HCC patients treated with TACE and may be helpful for non-invasive monitoring of the tumor viability.

Association of glycated albumin to hemoglobin A1c ratio with all-cause and cardiovascular mortality among US adults: A population-based cohort study.

AIMS: To investigate the association of glycated albumin to hemoglobin A1c (GA/HbA1c) ratio, an indicator of blood glucose fluctuations, with all-cause and cardiovascular mortality among US adults. METHODS: This cohort study used data from the National Health and Nutrition Examination Survey 1999-2004. Participants were linked to National Death Index mortality data through December 31, 2015. Cox proportional hazards model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs), and restricted cubic spline (RCS) regression was conducted. RESULTS: A total of 11,508 US adults (weighted mean age, 43.9 years; 5748 males [weighted, 48.9 %]) were included. During a median follow­up of 13.6 years, 1963 total deaths occurred, including 383 cardiovascular deaths. After multivariable adjustments, a higher GA/HbA1c ratio was associated with a higher risk of all-cause (tertiles: P for trend < 0.001; continuous: HR 1.49 [95 % CI 1.32-1.69]) and cardiovascular (tertiles: P for trend = 0.048; continuous: HR 1.65 [95 % CI 1.27-2.14]) mortality. RCS revealed a linear relationship of GA/HbA1c ratio to mortality. CONCLUSIONS: In the nationally representative cohort of US adults, GA/HbA1c ratio was significantly associated with the risk of all-cause and cardiovascular mortality. These findings suggest that GA/HbA1c ratio may serve as an effective indicator for identifying high-risk individuals.

CDK9 binds and activates SGK3 to promote cardiac repair after injury via the GSK-3ß/ß-catenin pathway.

The mammalian heart possesses entire regeneration capacity after birth, which is lost in adulthood. The role of the kinase network in myocardial regeneration remains largely elusive. SGK3 (threonine-protein kinase 3) is a functional kinase we identified previously with the capacity to promote cardiomyocyte proliferation and cardiac repair after myocardial infarction. However, the upstream signals regulating SGK3 are still unknown. Based on the quantitative phosphoproteomics data and pulldown assay, we identified cyclin-dependent kinase 9 (CDK9) as a novel therapeutic target in regeneration therapy. The direct combination between CDK9 and SGK3 was further confirmed by co-immunoprecipitation (Co-IP). CDK9 is highly expressed in the newborn period and rarely detected in the adult myocardium. In vitro, the proliferation ratio of primary cardiomyocytes was significantly elevated by CDK9 overexpression while inhibited by CDK9 knockdown. In vivo, inhibition of CDK9 shortened the time window of cardiac regeneration after apical resection (AR) in neonatal mice, while overexpression of CDK9 significantly promoted mature cardiomyocytes (CMs) to re-enter the cell cycle and cardiac repair after myocardial infarction (MI) in adult mice. Mechanistically, CDK9 promoted cardiac repair by directly activating SGK3 and downstream GSK-3ß/ß-catenin pathway. Consequently, our study indicated that CDK9 might be a novel target for MI therapy by stimulating myocardial regeneration.

Protein Kinase C Inhibitors Reduce SARS-CoV-2 Replication in Cultured Cells.

Infection by severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) has posed a severe threat to global public health. The current study revealed that several inhibitors of protein kinases C (PKCs) possess protective activity against SARS-CoV-2 infection. Four pan-PKC inhibitors, Go 6983, bisindolylmaleimide I, enzastaurin, and sotrastaurin, reduced the replication of a SARS-CoV-2 replicon in both BHK-21 and Huh7 cells. A PKCδ-specific inhibitor, rottlerin, was also effective in reducing viral infection. The PKC inhibitors acted at an early step of SARS-CoV-2 infection. Finally, PKC inhibitors blocked the replication of wild-type SARS-CoV-2 in ACE2-expressing A549 cells. Our work highlights the importance of the PKC signaling pathway in infection by SARS-CoV-2 and provides evidence that PKC-specific inhibitors are potential therapeutic agents against SARS-CoV-2. IMPORTANCE There is an urgent need for effective therapeutic drugs to control the pandemic caused by severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2). We found that several inhibitors of protein kinases C (PKCs) dramatically decrease the replication of SARS-CoV-2 in cultured cells. These PKC inhibitors interfere with an early step of viral infection. Therefore, the rapid and prominent antiviral effect of PKC inhibitors underscores that they are promising antiviral agents and suggests that PKCs are important host factors involved in infection by SARS-CoV-2.

Association of hemoglobin glycation index and glycation gap with cardiovascular disease among US adults.

AIMS: To investigate the association of hemoglobin glycation index (HGI) and glycation gap (GGap), reflecting mismatches between HbA1c and other measures of glycemia, with cardiovascular disease (CVD) in the general population. METHODS: 5966 US adult (age ≥ 20 years) participants were included from the National Health and Nutrition Examination Survey (NHANES) (1999-2004). In this cross-sectional study, predicted HbA1c was calculated based on fasting plasma glucose (FPG) and glycated albumin (GA), respectively. Multivariable binary logistic regression analysis was performed to explore the association of HGI and GGap with CVD prevalence. RESULTS: Compared to the lowest tertile, the ORs with 95% CIs for CVD across the tertiles were 1.41 (1.01, 1.96) and 0.87 (0.58, 1.31) for HGI (P for trend = 0.535) and 1.06 (0.77, 1.47) and 1.60 (1.18, 2.17) for GGap (P for trend = 0.002) in the fully-adjusted model. Besides, the discordantly high GGap/low HbA1c group was associated with higher CVD prevalence compared with the low GGap/high HbA1c group (OR = 1.50, 95% CI, 1.04-2.16, P = 0.030). CONCLUSIONS: GGap derived from GA is associated with CVD independent of traditional risk factors, even HbA1c, in US general adults. Considering the potential limitations of HbA1c, the introduction of GGap is warranted.

Leverage knowledge graph and GCN for fine-grained-level clickbait detection.

Clickbait is the use of an enticing title as bait to deceive users to click. However, the corresponding content is often disappointing, infuriating or even deceitful. This practice has brought serious damage to our social trust, especially to online media, which is one of the most important channels for information acquisition in our daily life. Currently, clickbait is spreading on the internet and causing serious damage to society. However, research on clickbait detection has not yet been well performed. Almost all existing research treats clickbait detection as a binary classification task and only uses the title as the input. This shallow usage of information and detection technology not only suffers from low performance in real detection (e.g., it is easy to bypass) but is also difficult to use in further research (e.g., potential empirical studies). In this work, we proposed a novel clickbait detection model that incorporated a knowledge graph, a graph convolutional network and a graph attention network to conduct fine-grained-level clickbait detection. According to experiments using a real dataset, our novel proposed model outperformed classical and state-of-the-art baselines. In addition, certain explainability can also be achieved in our model through the graph attention network. Our fine-grained-level results can provide a measurement foundation for future empirical study. To the best of our knowledge, this is the first attempt to incorporate a knowledge graph and deep learning technique to detect clickbait and achieve explainability.

The Titer of Citrus Yellow Vein Clearing Virus Is Positively Associated with the Severity of Symptoms in Infected Citrus Seedlings.

Citrus yellow vein clearing virus (CYVCV), a new member of the genus Mandarivirus in the family Alphaflexiviridae, is the causal agent of citrus yellow vein clearing disease. CYVCV is transmitted to citrus by Dialeurodes citri, grafting, and contaminated knife blades, threatening citrus production. In this study, four infectious full-length complementary DNA clones of CYVCV (namely AY112, AY132, AY212, and AY221) derived from CYVCV isolate AY were obtained through yeast homologous recombination and inoculated to 'Eureka' lemon (Citrus limon Burm. f.) by Agrobacterium-mediated vacuum infiltration. Pathogenicity analysis indicated that the clones AY212 and AY221 caused more severe symptoms than AY112 and AY132. Northern blot and quantitative reverse transcription PCR analyses showed that the titers of virulent clones (AY212 and AY221) were significantly higher than those of attenuated clones (AY112 and AY132) in the infected 'Eureka' lemon seedlings. Subsequent comparative studies of viral infectivity, accumulation, and symptoms induced by AY221 in nine citrus cultivars indicated that the infectivity of AY221 varied from 25 to 100% between cultivars; 'Oota' ponkan (C. reticulata L.) showed the lowest infection rate, with mild symptoms, which might be a useful resource for CYVCY-resistance genes; and CYVCV titer was positively associated with the symptom development in infected citrus seedlings. In general, this report revealed the biological properties of CYVCV, thus laying a foundation for further investigation of pathogenic mechanisms in this virus.

Quantitative dual-energy CT for evaluating hepatocellular carcinoma after transarterial chemoembolization.

We aimed to investigate the role of the quantitative parameters of dual-energy computed tomography (DECT) in evaluating patients with hepatocellular carcinoma (HCC) treated by transarterial chemoembolization (TACE). We retrospectively identified 80 HCC patients (mean age, 56 years; 61 men) treated by TACE who received contrast-enhanced DECT and were retreated by TACE within 7 days between November 2018 and December 2019. Taking digital subtraction angiography (DSA) and CT images as reference standard, two readers measured and calculated the values of normalized iodine concentration at arterial phase (NICAP), normalized iodine concentration at portal venous phase (NICPP), iodine concentration difference (ICD), arterial iodine fraction (AIF) and slope of the spectral Hounsfield unit curve (λHu) by placing matched regions of interests (ROIs) within the tumor active area (TAA), adjacent normal hepatic parenchyma (ANHP) and tumor necrotic area (TNA). Differences between the parameters were analyzed by the Kruskal-Wallis H test. Receiver operating characteristic analysis of the parameters performance in differentiating the three tissues types was performed. AIF exhibited a good performance in distinguishing TAA (0.93 ± 0.31) and ANHP (0.18 ± 0.14), the areas under the receiver operating characteristic curve (AUC) was 0.989, while the λHu exhibited an excellent performance in distinguishing TAA (3.32 ± 1.24) and TNA (0.29 ± 0.27), with an AUC of 1.000. In conclusion, quantitative DECT can be effectively used to evaluate the tumor viability in HCC patients treated by TACE.

Scientific publications in laboratory medicine from mainland China, Hong Kong and Taiwan: A ten-year survey of the literature.

BACKGROUND: We investigated scientific publications in laboratory medicine originating from mainland China, Hong Kong and Taiwan over the past 10 years. METHODS: The information about articles published in the included journals were determined by computer-searching on PubMed and data were extracted independently and analyzed in relation to the number of articles. RESULTS: From 2000 to 2009 there were 1166 articles published in laboratory medicine journals from the major Chinese regions (mainland China, Hong Kong and Taiwan). This exceeded Japan, Germany, the United Kingdom and France from 2005 onwards. Also, the number of articles from mainland China exceeded those from Hong Kong and Taiwan from 2004 onwards. The average impact factor (IF) from Hong Kong ranked the first, followed by mainland China, and then Taiwan. Clinica Chimica Acta seems to be the most popular laboratory medicine journal among Chinese authors. CONCLUSION: Over the past 10 years, Chinese authors have been more and more active in the field of laboratory medicine. Mainland China seems to have caught up to Hong Kong and Taiwan regarding publication of papers in this field.