Tea Polyphenol Epigallocatechin Gallate Protects Against Nonalcoholic Fatty Liver Disease and Associated Endotoxemia in Rats via Modulating Gut Microbiota Dysbiosis and Alleviating Intestinal Barrier Dysfunction and Related Inflammation.

Nonalcoholic fatty liver disease (NAFLD) is characterized by fat accumulation and inflammation. Epigallocatechin gallate (EGCG) has been proven to be effective against NAFLD, but its hepatoprotective mechanisms based on the "gut microbiota-barrier-liver axis" are still not fully understood. Herein, the results demonstrated that EGCG effectively ameliorated NAFLD phenotypes and metabolic disorders in rats fed a high-fat diet (HFD), and inhibited intestinal barrier dysfunction and inflammation, which is also supported in the experiment of Caco-2 cells. Moreover, EGCG could restore gut microbiota diversity and composition, particularly promoting beneficial microbes, including short-chain fatty acids (SCFAs) producers, such as Lactobacillus, and suppressing Gram-negative bacteria, such as Desulfovibrio. The microbial modulation raised SCFA levels, decreased lipopolysaccharide levels, inhibited the TLR4/NF-κB pathway, and strengthened intestinal barrier function via Nrf2 pathway activation, thereby alleviating liver steatosis and inflammation. Spearman's correlation analysis showed that 24 key OTUs, negatively or positively associated with NAFLD and metabolic disorders, were also reshaped by EGCG. Our results suggested that a combinative improvement of EGCG on gut microbiota dysbiosis, intestinal barrier dysfunction, and inflammation might be a potential therapeutic target for NAFLD.

PICALM as a Novel Prognostic Biomarker and Its Correlation with Immune Infiltration in Breast Cancer.

PICALM (phosphatidylinositol-binding clathrin assembly protein) mutations have been linked to a number of human disorders, including leukemia, Alzheimer's disease, and Parkinson's disease. Nevertheless, the effect of PICALM on cancer, particularly on prognosis and immune infiltration in individuals with BRCA, is unknown. We obtained the data of breast cancer patients from The Cancer Genome Atlas (TCGA) database, and analyzed the expression of PICALM in breast cancer, its impact on survival' and its role in tumor immune invasion. Finally, in vitro cellular experiments were performed to validate the results. Research has found that PICALM expression was shown to be downregulated in BRCA and to be substantially linked with clinical stage, histological type, PAM50, and age. PICALM downregulation was linked to a lower overall survival (OS) and disease-specific survival (DSS) in BRCA patients. A multivariate Cox analysis revealed that PICALM is an independent predictor of OS. The enriched pathways revealed by functional enrichment analysis included oxidative phosphorylation, angiogenesis, the TGF signaling pathway, and the IL-6/JAK/STAT3 signaling system. Furthermore, the amount of immune cell infiltration by B cells, eosinophils, mast cells, neutrophils, and T cells was positively linked with PICALM expression. Finally, we experimentally verified that low expression of PICALM can reduce proliferation, migration, and invasion in tumor cells. This evidence shows that PICALM expression impacts prognosis, immune infiltration, and pathway expression in breast cancer patients, and it might be a potential predictive biomarker for the disease.

Hypoxic Preconditioning Attenuates Neuroinflammation via Inhibiting NF-κB/NLRP3 Axis Mediated by p-MLKL after Transient Global Cerebral Ischemia.

Hypoxic preconditioning (HPC) has been reported to alleviate neuronal damage and microglial activation in hippocampal CA1 after transient global cerebral ischemia (tGCI). However, the molecular mechanism is unclear. Recent studies identified that nuclear factor-kappa-B (NF-κB)/oligomerization domain-like receptors protein (NLRP) 3 inflammasome pathway is mainly involved in the activation of microglia and that phosphorylated (p)-mixed lineage kinase domain-like (MLKL) is related to the regulation of NF-κB/NLRP3 axis. Hence, in this study, we set out to investigate whether HPC attenuates neuronal damage and microglial activation through inhibiting NF-κB/NLRP3 axis mediated by p-MLKL after tGCI in CA1 of male rats. We found that HPC decreased NLRP3 inflammasome in microglia and inhibited M1 polarization of microglia in CA1 after tGCI. Mechanistically, HPC inhibited the activation of NF-κB signaling pathway and reduced the mRNA and protein levels of NLRP3 inflammasome after tGCI. Additionally, the knockdown of p-MLKL by short hairpin RNA (shRNA) administration inhibited the activation of the NF-κB signaling pathway and reduced the formation of NLRP3 inflammasome, thus attenuating M1 polarization of microglia and decreasing the release of interleukin 1 beta (IL-1ß) and necrosis factor alpha (TNF-α) in CA1 post ischemia. We consider that p-MLKL in microglia may be derived from necroptotic neurons after tGCI. In conclusion, the new finding in this study is that HPC-induced neuroprotection against tGCI through inhibiting NF-κB/NLRP3 pathway mediated by p-MLKL.

Genome-Wide Association Study Unravels Quantitative Trait Loci and Genes Associated with Yield-Related Traits in Sugarcane.

Sugarcane, a major sugar and energy crop worldwide faces an increasing demand for higher yields. Identifying yield-related markers and candidate genes is valuable for breeding high-yield varieties using molecular techniques. In this work, seven yield-related traits were evaluated in a diversity panel of 159 genotypes, derived from Tripidium arundinaceum, Saccharum spontaneum, and modern sugarcane genotypes. All traits exhibited significant genetic variance with high heritability and high correlations. Genetic diversity analysis reveals a genomic decay of 23 kb and an average single nucleotide polymorphism (SNP) number of 25,429 per genotype. These 159 genotypes were divided into 4 subgroups. Genome-wide association analysis identified 47 SNPs associated with brix, spanning 36 quantitative trait loci (QTLs), and 138 SNPs for other traits across 104 QTLs, covering all 32 chromosomes. Interestingly, 12 stable QTLs associated with yield-related traits were identified, which contained 35 candidate genes. This work provides markers and candidate genes for marker-assisted breeding to improve sugarcane yields.

Iron/cobalt/nickel regulation for efficient photocatalytic carbon dioxide reduction over phthalocyanine covalent organic frameworks.

Using solar photocatalytic CO2 reduction to produce high-value-added products is a promising solution to environmental problems caused by greenhouse gases. Metal phthalocyanine COFs possess a suitable band structure and strong light absorption ability, making them a promising candidate for photocatalytic CO2 reduction. However, the relationship between the electronic structure of these materials and photocatalytic properties, as well as the mechanism of photocatalytic CO2 reduction, is still unclear. Herein, the electronic structure of three MPc-TFPN-COFs (M = Ni, Co, Fe) and the reaction process of CO2 reduction to CO, HCOOH, HCHO and CH3OH were studied using DFT calculations. The calculated results demonstrate that these COFs have a good photo response to visible light and are new potential photocatalytic materials. Three COFs show different reaction mechanisms and selectivity in generating CO2 reduction products. NiPc-TFPN-COFs obtain CO through the reaction pathway of CO2 → COOH → CO, and the energy barrier of the rate-determining step is 2.82 eV. NiPc-TFPN-COFs and FePc-TFPN-COFs generate HCHO through CO2 → COOH → CO → CHO → HCHO, and the energy barrier of the rate step is 2.82 eV and 2.37 eV, respectively. Higher energies are required to produce HCOOH and CH3OH. This work is helping in understanding the mechanism of photocatalytic reduction of CO2 in metallophthalocyanine COFs.

Exploring the Relationship between Self-Rated Health and Unmet Cancer Needs among Sexual and Gender Minority Adolescents and Young Adults with Cancer.

This study evaluates the unmet needs of sexual and gender minority (SGM) adolescent and young adult (AYA) cancer survivors by comparing SGM AYA self-rated health (SRH) scores to their non-SGM (i.e., cisgender/heterosexual) counterparts. The Cancer Needs Questionnaire-Young People (CNQ-YP) and self-rated health measures were used to assess unmet needs in AYAs aged 15-39 who had been diagnosed with cancer in the previous ten years (n = 342). Participants were recruited from a National Cancer Institute (NCI) Comprehensive Cancer Center registry using the modified Dillman's method. Self-reported sexual orientation and gender identity (SO/GI) data were collected. Independent t-tests were used to test between-group differences in unmet needs and Pearson's chi-square test was used to determine the difference in SRH scores between SGM and non-SGM AYA cancer survivors. SGM AYA cancer survivors reported greater mean needs than their non-SGM counterparts across all six domains and reported significantly greater needs in the domains of Feelings and Relationships, t(314) = -2.111, p = 0.036, Information and Activities, t(314) = -2.594, p = 0.009, and Education, t(207) = -3.289, p < 0.001. SGM versus non-SGM SRH scores were significantly different, indicating that a higher percentage of SGM AYAs reported poor/fair health compared to those who were non-SGM. Unmet life and activities needs were negatively associated with AYA cancer survivors' SRH, whereas unmet work needs were positively associated with AYA cancer survivors' SRH. An AYA's gender identity (SGM versus non-SGM) was not a moderator. SGM AYAs are an understudied group within an already vulnerable patient population. Unmet psychosocial needs related to one's feelings and relationships, and information and activity needs merit further research to develop tailored interventions that reflect the experiences of SGM AYAs.

Comparison of different therapeutic approaches for pulmonary cryptococcosis in kidney transplant recipients: a 15-year retrospective analysis.

Introduction: Organ transplant recipients are at increased risk of developing pulmonary cryptococcosis (PC) due to weakened cell-mediated immunity caused by immunosuppressors. However, the nonspecific symptoms associated with PC can often lead to misdiagnosis and inappropriate treatment. Methods: We conducted a retrospective analysis of data from 23 kidney transplant recipients with PC between April 2006 to January 2021. Results: The median time from transplantation to the diagnosis of pathology-proven PC 4.09 years. Seventeen patients presented respiratory symptoms, including sputum-producing cough and dyspnea. Additionally, three patients also developed central nervous system (CNS) infections. Chest CT scans frequently revealed nodule-shaped lesions, which can mimic lung carcinoma. Serological tests did not demonstrate any specific changes. Nine patients received surgical resection as treatment. Fourteen patients were treated with antifungal medication only. No recurrence was observed in all 23 patients. Conclusion: Our study suggests that fever and sputum-producing cough are common symptoms of PC, and cryptococcal meningitis should not be excluded if corresponding symptoms occur. Fluconazole is a common and effective antifungal agent. Surgical resection should be considered for patients who do not respond well to antifungal therapy. Clinicians should be aware of these findings when evaluating transplant recipients with respiratory symptoms.

The KRAS signaling pathway's impact on the characteristics of pancreatic cancer cells.

Pancreatic ductal adenocarcinoma (PDAC) is classified as a cancer with high metastasis so that its mortality rate is high and most of the patients could not survive longer than 5 years. RAS signaling participate in cellular processes, so it has a key role in PDAC.RAS activation is associated via three different signaling pathway including somatic oncogenic point mutations in KRAS, upstream signaling like EGFR, oncogenic activation of the downstream B-RAF molecule. Several targeted therapies have been developed against kinase effectors particularly those in the MAPK and PI3K (phosphoinositide 3-kinase)/mTOR signaling pathways and several inhibitors are undergoing clinical studies at the moment. However, because it is highly metastatic and frequently diagnosed at advanced disease stages, pancreatic cancer continues to be a challenging cancer to treat. This article will explore therapeutic approaches that focus on oncogenic KRAS signaling in pancreatic cancer and provide an updated synopsis of our knowledge of how mutant KRAS function in the illness.

First-Principles Study of Nitrogen Adsorption and Dissociation on ZrMnFe(110) Surface.

The adsorption, dissociation and penetration processes of N2 on the surface of ZrMnFe(110) were investigated using the first-principles calculation method in this paper. The results indicate that the vacancy Hollow 1 composed of 4Zr1Fe on the surface of ZrMnFe(110) is the best adsorption site for the N2 molecule and N atom, and the adsorption energies are 10.215 eV and 6.057 eV, respectively. Electron structure analysis indicates that the N2 molecule and N atoms adsorbed mainly interact with Zr atoms on the surface. The transition state calculation shows that the maximum energy barriers to be overcome for the N2 molecule and N atom on the ZrMnFe(110) surface were 1.129 eV and 0.766 eV, respectively. This study provides fundamental insight into the nitriding mechanism of nitrogen molecules in ZrMnFe.

The effect of okra (Abelmoschus esculentus l.) Powder Addition on Qualities of Gluten-free Chiffon Cake.

Rice flour (100%, 97.4%, 94.7%, 89.5% (w/w)) and okra powder (2.6%-10.5%) were used to replace wheat flour to make gluten-free chiffon cakes. The effects of okra powder addition on the physicochemical, color, texture, moisture content, total phenolic content, antioxidant, and sensory scores of cakes were evaluated. The batter viscosity, chewiness, ash, protein, fat, total phenolics, and antioxidant activities (1,1-diphenyl-z-picrylhydrazyl hydrate and reducing power) of cakes showed an increasing trend with okra powder addition. Gluten-free chiffon cake containing 5.3% okra powder showed significantly (p < 0.05) higher protein and ash contents as compared to their control and chiffon cake made with wheat flour. Nevertheless, center height, volume index, L*, a*, and b* values, and white index of gluten-free cake decreased with increased okra powder levels. The sensory characteristics of wheat and gluten-free chiffon cakes substituted with 2.6%-5.3% okra powder showed no difference (p > 0.05). Nevertheless, the sensory scores of the 5.3% okra powder addition cake obtained a higher preference than other gluten-free cakes. Although the overall acceptability of gluten-free chiffon cake supplemented with 10.5% okra flour had a lower (p < 0.05) overall acceptability (2.84) than all cake samples, it was still shown acceptable to consumers. Gluten-free rice chiffon cakes with high nutrient contents and antioxidant activities can be processed by the incorporation of okra powder of less than 10.5% to increase the diversification of gluten-free foods. Gluten-free cakes with high amounts of okra powder addition would produce cake having high water content, total phenol content, 1,1-diphenyl-z-picrylhydrazyl hydrate radical scavenging activity, reducing power, hardness, chewiness, cohesiveness, batter viscosity, ash, and crude protein content through principal component analysis.

Attenuation of Piwil2 induced by hypoxic postconditioning prevents cerebral ischemic injury by inhibiting CREB2 promoter methylation.

Epigenetic modification contributes to the pathogenesis of cerebral ischemia. Piwil2 belongs to the PIWI proteins subfamily and has a key role in the regulation of gene transcription through epigenetics. However, the roles of Piwil2 in cerebral ischemia have not been investigated. In this study, we aim to elucidate the roles and the underlying molecular mechanisms of Piwil2 in ischemic tolerance induced by hypoxic postconditioning (HPC) against transient global cerebral ischemia (tGCI). We found that the expression of Piwil2 in CA1 was downregulated by HPC after tGCI. Silencing Piwil2 with antisense oligodeoxynucleotide (AS-ODN) in CA1 after tGCI decreased the expression of apoptosis-related proteins and exerted neuroprotective effects. Opposite results were observed after overexpression of Piwil2 induced by administration of Piwil2-carried lentivirus. Furthermore, we revealed differentially expressed Piwil2-interacting piRNAs in CA1 between HPC and tGCI groups by RNA binding protein immunoprecipitation (RIP) assay. Moreover, downregulating Piwil2 induced by HPC or AS-ODN after tGCI caused a marked reduction of DNA methyltransferase 3A (DNMT3A), which in turn abolished the tGCI-induced increase in the DNA methylation of cyclic AMP response element-binding 2 (CREB2), thus increasing mRNA and protein of CREB2. Finally, downregulating Piwil2 restored dendritic complexity and length, prevented the loss of dentritic spines, thereby improving cognitive function after tGCI. These data firstly reveal that Piwil2 plays an important part in HPC-mediated neuroprotection against cerebral ischemia through epigenetic regulation of CREB2.

Is the diagnostic model based on convolutional neural network superior to pediatric radiologists in the ultrasonic diagnosis of biliary atresia?

Background: Many screening and diagnostic methods are currently available for biliary atresia (BA), but the early and accurate diagnosis of BA remains a challenge with existing methods. This study aimed to use deep learning algorithms to intelligently analyze the ultrasound image data, build a BA ultrasound intelligent diagnostic model based on the convolutional neural network, and realize an intelligent diagnosis of BA. Methods: A total of 4,887 gallbladder ultrasound images of infants with BA, non-BA hyperbilirubinemia, and healthy infants were collected. Two mask region convolutional neural network (Mask R-CNN) models based on different backbone feature extraction networks were constructed. The diagnostic performance between the two models was compared through good-quality images at the image level and the patient level. The diagnostic performance between the two models was compared through poor-quality images. The diagnostic performance of BA between the model and four pediatric radiologists was compared at the image level and the patient level. Results: The classification performance of BA in model 2 was slightly higher than that in model 1 in the test set, both at the image level and at the patient level, with a significant difference of p = 0.0365 and p = 0.0459, respectively. The classification accuracy of model 2 was slightly higher than that of model 1 in poor-quality images (88.3% vs. 86.4%), and the difference was not statistically significant (p = 0.560). The diagnostic performance of model 2 was similar to that of the two radiology experts at the image level, and the differences were not statistically significant. The diagnostic performance of model 2 in the test set was higher than that of the two radiology experts at the patient level (all p < 0.05). Conclusion: The performance of model 2 based on Mask R-CNN in the diagnosis of BA reached or even exceeded the level of pediatric radiology experts.

Cis-element amplified polymorphism (CEAP), a novel promoter- and gene-targeted molecular marker of plants.

In this study, we selected eight cis-elements: AAAG, ACGTG, CCGA, ACTCAT, GGTCA, TATCC, TGAC and GATAA, which are closely related to plant growth and development, signal transduction and stress response. The CEAP primers were 18 nucleotides long and consisted of a central cis-element nucleotide core flanked by a filler sequence at the 5' end and di- or tri-nucleotides at the 3' end. A total of two hundred and twenty-four primers were developed, and the PCR procedure consisted of 5 cycles of low-temperature annealing and 35 subsequent cycles of annealing at 50°C. The PCR products are electrophoretically separated by 1.8-2.3% agarose. The polymorphism of the CEAP marker was amplified in eight mango (Mangifera indica L.) species. The results showed that the CEAP primers could amplify clear, repeatable bands in mango and combine at least four cis-elements from which a large number of bands were amplified and six highly polymorphic primers for each cis-element can reach an accurate clustering result. The results of CEAP marker assays compared with ISSR, CBDP and iPBS marker assays showed that CEAP marker was better than the other three markers in the number of fragment bands, H and I indexes. In addition, we also tested the CEAP markers in rice, tomato, potato, wax gourd, citrus and longan and the results showed that the CEAP marker assay could amplify clear polymorphic bands in different species. Our results indicate that the CEAP markers could be universally used in different species for genetic diversity analysis, relationship analysis, and marker-assisted selection for breeding. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-022-01212-5.

A pyroptosis-related prognosis model to predict survival in colorectal cancer patients.

Pyroptosis is a recently-identified pathway of host cell death that is stimulated by a range of microbial infections. Emerging evidence indicates pyroptosis plays crucial roles in tumor growth, disease progression, and migration of different cancer cells. However, the clinical significance of pyroptosis in tumor behavior prognosis, as well as the underlying mechanism in different cancers remains elusive. Here, by evaluating the expression level of pyroptosis genes in colorectal cancer (CRC) patients from the TCGA cohort and GEO cohort (GSE39582), we identified pyroptosis-related DEGs and then built a 13-gene risk model by applying the LASSO Cox regression algorithm. Furthermore, functional analysis using GSEA and GSEV revealed that our prognostic model may function through regulating immune responses and tumor biogenesis pathways. Significant infiltration of activated immune cells (e.g. cytotoxic T cells) was observed in the low risk score group. The selected gene set was further validated in the GEO cohort. Time-dependent ROC curves confirmed that our risk score model is robust in predicting 1, 3 and 5-year overall survival in CRC patients. Overall, we have identified a pyroptosis-related gene signature that consists of 13 genes, which serves as a potent indicator of CRC prognosis. Thus, our model provides insights in how to make better clinical decision in the future.

Comprehensive Analysis of Gene Expression Profiles Identifies a P4HA1-Related Gene Panel as a Prognostic Model in Colorectal Cancer Patients.

Objective: Colorectal cancer (CRC) is the leading cause of mortality worldwide. Growing evidence suggests that the current pathological staging system is inadequate for efficient and accurate prognosis. In this study, we aim to build a prognosis model to predict the survival outcome of CRC patients by using gene expression profiles from The Cancer Genome Atlas (TCGA). Materials and Methods: Univariate and multivariate Cox regression analysis were used to assess the relationship between clinical factors and P4HA1 expression regarding the prognosis of patients with colon adenocarcinoma (COAD). The least absolute shrinkage and selection operator (LASSO) Cox regression model was used to select prognostic differential expression genes (DEGs) for the construction of prognostic risk score model. Kaplan-Meier and receiver operating characteristic (ROC) survival analysis were used to assess the performance of the model on both TCGA cohort and an independent dataset GSE39582. Results: Overexpression of P4HA1 was confirmed to be associated with poor clinical outcome of colon cancer patients in both TCGA and GSE39582 cohorts. Using the TCGA cohort, we identified 1528 DEGs related to elevated P4HA1 expression, and we established a 11-gene panel to construct the prognostic risk score model by LASSO Cox regression analysis based on their expression profiles. The 11-gene signature was further validated in the independent dataset GSE39582. Time-dependent ROC curves indicated good performance of our model in predicting 1, 2, and 3-years overall survival in COAD patients. Additionally, gene set enrichment analysis indicated that the 11-gene signature was related to pathways involved in tumor progression. Conclusions: Together, we have established a 11-gene signature significantly associated with prognosis in COAD patients, which could serve as a promising tool for clinical application in the future.

Atmospheric oxidation of fluoroalcohols initiated by ˙OH radicals in the presence of water and mineral dusts: mechanism, kinetics, and risk assessment.

The transport and formation of fluorinated compounds are greatly significant due to their possible environmental risks. In this work, the ˙OH-mediated degradation of CF3CF2CF2CH2OH and CF3CHFCF2CH2OH in the presence of O2/NO/NO2 was studied by using density functional theory and the direct kinetic method. The formation mechanisms of perfluorocarboxylic/hydroperfluorocarboxylic acids (PFCAs/H-PFCAs), which were produced from the reactions of α-hydroxyperoxy radicals with NO/NO2 and the ensuing oxidation of α-hydroxyalkoxy radicals, were clarified and discussed. The roles of water and silica particles in the rate constants and ˙OH reaction mechanism with fluoroalcohols were investigated theoretically. The results showed that water and silica particles do not alter the reaction mechanism but obviously change the kinetic properties. Water could retard fluoroalcohol degradation by decreasing the rate constants by 3-5 orders of magnitude. However, the heterogeneous ˙OH-rate coefficients on the silica particle surfaces, including H4SiO4, H6Si2O7, and H12Si6O18, are larger than that of the naked reaction by 1.20-24.50 times. This finding suggested that these heterogeneous reactions may be responsible for the atmospheric loss of fluoroalcohols and the burden of PFCAs. In addition, fluoroalcohols could be exothermically trapped by H12Si6O18, H6Si2O7, and H4SiO4, in which the chemisorption on H12Si6O18 is stronger than that on H6Si2O7 or H4SiO4. The global warming potentials and radiative forcing of CF3CF2CF2CH2OH/CF3CHFCF2CH2OH were calculated to assess their contributions to the greenhouse effect. The toxicities of individual species were also estimated via the ECOSAR program and experimental measurements. This work enhances the understanding of the environmental formation of PFCAs and the transformation of fluoroalcohols.

Single-Photon Emission Computed Tomography/Computed Tomography Image-Based Radiomics for Discriminating Vertebral Bone Metastases From Benign Bone Lesions in Patients With Tumors.

Purpose: The purpose of this study was to investigate the feasibility of Single-Photon Emission Computed Tomography/Computed Tomography (SPECT/CT) image-based radiomics in differentiating bone metastases from benign bone lesions in patients with tumors. Methods: A total of 192 lesions from 132 patients (134 in the training group, 58 in the validation group) diagnosed with vertebral bone metastases or benign bone lesions were enrolled. All images were evaluated and diagnosed independently by two physicians with more than 20 years of diagnostic experience for qualitative classification, the images were imported into MaZda software in Bitmap (BMP) format for feature extraction. All radiomics features were selected by least absolute shrinkage and selection operator (LASSO) regression and 10-fold cross-validation algorithms after the process of normalization and correlation analysis. Based on these selected features, two models were established: The CT model and SPECT model (radiomics features were derived from CT and SPECT images, respectively). In addition, a combination model (ComModel) combined CT and SPECT features was developed in order to better evaluate the predictive performance of radiomics models. Subsequently, the diagnostic performance between each model was separately evaluated by a confusion matrix. Results: There were 12, 13, and 18 features contained within the CT, SPECT, and ComModel, respectively. The constructed radiomics models based on SPECT/CT images to discriminate between bone metastases and benign bone lesions not only had high diagnostic efficacy in the training group (AUC of 0.894, 0.914, 0.951 for CT model, SPECT model, and ComModel, respectively), but also performed well in the validation group (AUC; 0.844, 0.871, 0.926). The AUC value of the human experts was 0.849 and 0.839 in the training and validation groups, respectively. Furthermore, both SPECT model and ComModel show higher classification performance than human experts in the training group (P = 0.021 and P = 0.001, respectively) and the validation group (P = 0.037 and P = 0.007, respectively). All models showed better diagnostic accuracy than human experts in the training group and the validation group. Conclusion: Radiomics derived from SPECT/CT images could effectively discriminate between bone metastases and benign bone lesions. This technique may be a new non-invasive way to help prevent unnecessary delays in diagnosis and a potential contribution in disease staging and treatment planning.

Genome-Wide Identification and Expression Analysis of Polygalacturonase Gene Family in Kiwifruit (Actinidia chinensis) during Fruit Softening.

Polygalacturonase (PG) is an essential hydrolytic enzyme responsible for pectin degradation and thus plays an important role in fruit softening and other cell separation processes. PG protein is encoded by a multigene family, however, the members of PG gene family in kiwifruit (Actinidia chinensis) have not been extensively identified. In this study, a total of 51 AcPG genes in kiwifruit genome were identified. They are phylogenetically clustered into seven clades, and of them AcPG4 and AcPG18 with other known PG genes involved in fruit softening from peach, pear, papaya and melon form a small cluster together. The members of kiwifruit PG gene family consist of three to nine exons and two to eight introns, and their exon/intron structures are generally conserved in all clades except the clade D and E. During fruit softening of kiwifruit 'Donghong' under ambient temperature, cell wall modifying enzymes, including PG, PL (pectate and pectin lyases), and PE (pectinesterase, also known as pectin methylesterase, PME) showed a different activity profile, and of them, PG and PE activities largely correlated with the change of pectin content and firmness. Moreover, only 11 AcPG genes were highly or moderately expressed in softening fruit, and of which three AcPG genes (AcPG4, AcPG18, and AcPG8, especially the former two) has been found to strongly correlate with the profile of PG activity and pectin content, as well as fruit firmness, suggesting that they maybe play an important role in fruit softening. Thus, our findings not only benefit the functional characterization of kiwifruit PG genes, but also provide a subset of potential PG candidate genes for further genetic manipulation.

Inhibitory Effects of Cyclopiazonic Acid on the Pacemaker Current in Sinoatrial Nodal Cells.

OBJECTIVE: The spontaneous action potential of isolated sinoatrial node (SAN) cells is regulated by a coupled-clock system of two clocks: the calcium clock and membrane clock. However, it remains unclear whether calcium clock inhibitors have a direct effect on the membrane clock. The purpose of this study was to investigate the direct effect of cyclopiazonic acid (CPA), a selective calcium clock inhibitor, on the function of the membrane clock of SAN cells. METHODS: at SAN cells were isolated by trypsinization and identified based on morphology and electrophysiology. If and HCN currents were recorded via patch clamp technique. The expression of the HCN channel protein was determined by Western blotting analysis. RESULTS: The diastolic depolarization rate of spontaneous action potentials and the current densities of If were reduced by exposure to 10 µM CPA. The inhibitory effect of CPA was concentration-dependent with an IC50 value of 16.3 µM and a Hill coefficient of 0.98. The effect of CPA on If current was also time-dependent, and the If current amplitude was partially restored after washout. Furthermore, the steady-state activation curve of the If current was shifted to a negative potential, indicating that channel activation slowed down. Finally, the protein expression of HCN4 in HEK293 cells was markedly downregulated by CPA. CONCLUSIONS: These results indicate that the direct inhibition effect of CPA on the If current in SAN cells is both concentration- and time-dependent. The underlying mechanisms may involve slowing down steady-state activation and the downregulation of pacemaker channel protein expression.