The role of the extension region on the structural and physicochemical characteristics of the α-subunit of ß-conglycinin: implications of pH value and ionic strength.

BACKGROUND: To clarify the role of the extension region on the structure-functional relationship of the α-subunit of ß-conglycinin, α-subunit and its segment of the core region (αc-subunit) were expressed via an Escherichia coli system. Their physicochemical properties were compared under acid, neutral or alkaline conditions (pH 4.0, 7.0, and 8.0) and high or low ionic strength (µ = 0.05 and 0.5), respectively. RESULTS: The results showed that the extension region contributed to increasing thermal stability, especially at low ionic strength under acidic and neutral conditions. The extension region stabilized the α-subunit with high solubility, low turbidity, and small particle size under neutral and alkaline conditions, whereas these impacts were suppressed at a high ionic strength and acidic conditions. Surface hydrophobicity of the α-subunit decreased under acidic and alkaline conditions without being interfered with by ionic strength. CONCLUSION: It can be concluded that the extension region played different roles under different pH and ionic strength conditions. These factors should be specified carefully and speculated individually to explore the more detailed and profound nature of ß-conglycinin at the submolecular level. The results could benefit a better understanding of the relationship between domain structure and functions of soybean protein. © 2022 Society of Chemical Industry.

The landscape of gene co-expression modules correlating with prognostic genetic abnormalities in AML.

BACKGROUND: The heterogenous cytogenetic and molecular variations were harbored by AML patients, some of which are related with AML pathogenesis and clinical outcomes. We aimed to uncover the intrinsic expression profiles correlating with prognostic genetic abnormalities by WGCNA. METHODS: We downloaded the clinical and expression dataset from BeatAML, TCGA and GEO database. Using R (version 4.0.2) and 'WGCNA' package, the co-expression modules correlating with the ELN2017 prognostic markers were identified (R2 ≥ 0.4, p < 0.01). ORA detected the enriched pathways for the key co-expression modules. The patients in TCGA cohort were randomly assigned into the training set (50%) and testing set (50%). The LASSO penalized regression analysis was employed to build the prediction model, fitting OS to the expression level of hub genes by 'glmnet' package. Then the testing and 2 independent validation sets (GSE12417 and GSE37642) were used to validate the diagnostic utility and accuracy of the model. RESULTS: A total of 37 gene co-expression modules and 973 hub genes were identified for the BeatAML cohort. We found that 3 modules were significantly correlated with genetic markers (the 'lightyellow' module for NPM1 mutation, the 'saddlebrown' module for RUNX1 mutation, the 'lightgreen' module for TP53 mutation). ORA revealed that the 'lightyellow' module was mainly enriched in DNA-binding transcription factor activity and activation of HOX genes. The 'saddlebrown' module was enriched in immune response process. And the 'lightgreen' module was predominantly enriched in mitosis cell cycle process. The LASSO- regression analysis identified 6 genes (NFKB2, NEK9, HOXA7, APRC5L, FAM30A and LOC105371592) with non-zero coefficients. The risk score generated from the 6-gene model, was associated with ELN2017 risk stratification, relapsed disease, and prior MDS history. The 5-year AUC for the model was 0.822 and 0.824 in the training and testing sets, respectively. Moreover, the diagnostic utility of the model was robust when it was employed in 2 validation sets (5-year AUC 0.743-0.79). CONCLUSIONS: We established the co-expression network signature correlated with the ELN2017 recommended prognostic genetic abnormalities in AML. The 6-gene prediction model for AML survival was developed and validated by multiple datasets.

HELQ and EGR3 expression correlate with IGHV mutation status and prognosis in chronic lymphocytic leukemia.

BACKGROUND: IGHV mutation status is a crucial prognostic biomarker for CLL. In the present study, we investigated the transcriptomic signatures associating with IGHV mutation status and CLL prognosis. METHODS: The co-expression modules and hub genes correlating with IGHV status, were identified using the GSE28654, by 'WGCNA' package and R software (version 4.0.2). The over-representation analysis was performed to reveal enriched cell pathways for genes of correlating modules. Then 9 external cohorts were used to validate the correlation of hub genes expression with IGHV status or clinical features (treatment response, transformation to Richter syndrome, etc.). Moreover, to elucidate the significance of hub genes on disease course and prognosis of CLL patients, the Kaplan-Meier analysis for the OS and TTFT of were performed between subgroups dichotomized by the median expression value of individual hub genes. RESULTS: 2 co-expression modules and 9 hub genes ((FCRL1/FCRL2/HELQ/EGR3LPL/LDOC1/ZNF667/SOWAHC/SEPTIN10) correlating with IGHV status were identified by WGCNA, and validated by external datasets. The modules were found to be enriched in NF-kappaB, HIF-1 and other important pathways, involving cell proliferation and apoptosis. The expression of hub genes was revealed to be significantly different, not only between CLL and normal B cell, but also between various types of lymphoid neoplasms. HELQ expression was found to be related with response of immunochemotherapy treatment significantly (p = 0.0413), while HELQ and ZNF667 were expressed differently between stable CLL and Richter syndrome patients (p < 0.0001 and p = 0.0278, respectively). By survival analysis of subgroups, EGR3 expression was indicated to be significantly associated with TTFT by 2 independent cohorts (GSE39671, p = 0.0311; GSE22762, p = 0.0135). While the expression of HELQ and EGR3 was found to be associated with OS (p = 0.0291 and 0.0114 respectively).The Kras, Hedgehog and IL6-JAK-STAT3 pathways were found to be associating with the expression of hub genes, resulting from GSEA. CONCLUSIONS: The expression of HELQ and EGR3 were correlated with IGHV mutation status in CLL patients. Additionally, the expression of HELQ/EGR3 were prognostic markers for CLL associating with targetable cell signaling pathways.

MAPK14 over-expression is a transcriptomic feature of polycythemia vera and correlates with adverse clinical outcomes.

BACKGROUND: The transcriptomic signature has not been fully elucidated in PV, as well as mRNA markers for clinical variables (thrombosis, leukemic transformation, survival, etc.). We attempted to reveal and validate crucial co-expression modules and marker mRNAs correlating with polycythemia vera (PV) by weighted gene co-expression network analysis (WGCNA). MATERIAL AND METHODS: The GSE57793/26014/61629 datasets were downloaded from Gene Expression Omnibus (GEO) database and integrated into one fused dataset. By R software and 'WGCNA' package, the PV-specific co-expression module was identified, the pathway enrichment profile of which was obtained by over-representation analysis (ORA). Protein-protein interaction (PPI) network and hub gene analysis identified MAPK14 as our target gene. Then the distribution of MAPK14 expression in different disease/mutation types, were depicted based on external independent datasets. Genome-scale correlation analysis revealed the association of MAPK14 and JAK/STAT family genes. Then gene set enrichment analysis (GSEA) was performed to detect the activated and suppressed pathways associating with MAPK14 expression. Moreover, GSE47018 dataset was utilized to compare clinical variables (thrombosis, leukemic transformation, survival, etc.) between MAPK14-high and MAPK14-low groups. RESULTS: An integrated dataset including 177 samples (83 PV, 35 ET, 17 PMF and 42 normal donors) were inputted into WGCNA. The 'tan' module was identified as the PV-specific module (R2 = 0.56, p = 8e-16), the genes of which were dominantly enriched in pro-inflammatory pathways (Toll-like receptor (TLR)/TNF signaling, etc.). MAPK14 is identified as the top hub gene in PV-related PPI network with the highest betweenness. External datasets validated that the MAPK14 expression was significantly higher in PV than that of essential thrombocytosis (ET)/primary myelofibrosis (PMF) patients and normal donors. JAK2 homozygous mutation carriers have higher level of MAPK14 than that of other mutation types. The expression of JAK/STAT family genes significantly correlated with MAPK14, which also contributed to the activation of oxidated phosphorylation, interferon-alpha (IFNα) response and PI3K-Akt-mTOR signaling, etc. Moreover, MAPK14-high group have more adverse clinical outcomes (splenectomy, thrombosis, disease aggressiveness) and inferior survival than MAPK14-low group. CONCLUSION: MAPK14 over-expression was identified as a transcriptomic feature of PV, which was also related to inferior clinical outcomes. The results provided novel insights for biomarkers and therapeutic targets for PV.

Overexpression of HOXA10 is associated with unfavorable prognosis of acute myeloid leukemia.

BACKGROUND: HOXA family genes were crucial transcription factors involving cell proliferation and apoptosis. While few studies have focused on HOXA10 in AML. We aimed to investigate the prognostic significance of HOXA10. METHODS: We downloaded datasets from GEO and BeatAML database, to compare HOXA expression level between AML patients and controls. Kaplan-Meier curves were used to estimate the impact of HOXA10 expression on AML survival. The differentially expressed genes, miRNAs, lncRNAs and methylated regions between HOXA10-high and -low groups were obtained using R (version 3.6.0). Accordingly, the gene set enrichment analysis (GSEA) was accomplished using MSigDB database. Moreover, the regulatory TFs/microRNAs/lncRNAs of HOXA10 were identified. A LASSO-Cox model fitted OS to clinical and HOXA10-associated genetic variables by glmnet package. RESULTS: HOXA10 was overexpressed in AML patients than that in controls. The HOXA10-high group is significantly associated with shorter OS and DFS. A total of 1219 DEGs, 131 DEmiRs, 282 DElncRs were identified to be associated with HOXA10. GSEA revealed that 12 suppressed and 3 activated pathways in HOXA10-high group. Furthermore, the integrated regulatory network targeting HOXA10 was established. The LASSO-Cox model fitted OS to AML-survival risk scores, which included age, race, molecular risk, expression of IKZF2/LINC00649/LINC00839/FENDRR and has-miR-424-5p. The time dependent ROC indicated a satisfying AUC (1-year AUC 0.839, 3-year AUC 0.871 and 5-year AUC 0.813). CONCLUSIONS: Our study identified HOXA10 overexpression as an adverse prognostic factor for AML. The LASSO-COX regression analysis revealed novel prediction model of OS with superior diagnostic utility.

LINC00649 underexpression is an adverse prognostic marker in acute myeloid leukemia.

BACKGROUND: Long noncoding RNAs (lncRNA) play a role in leukemogenesis, maintenance, development, and therapeutic resistance of AML. While few studies have focused on the prognostic significance of LINC00649 in AML, which we aim to investigate in this present study. METHODS: We compared the expression level of LINC00649 between AML patients and healthy controls. The Kaplan-Meier curves of AML patients expressing high versus low level of LINC00649 was performed. The LINC00649 correlated genes/miRNAs/lncRNAs and methylation CpG sites were screened by Pearson correlation analysis with R (version 3.6.0), using TCGA-LAML database. The LINC00649 associated ceRNA network was established using lncBase 2.0 and miRWalk 2.0 online tools, combining results from correlation analysis. Finally, a prediction model was constructed using LASSO-Cox regression. RESULTS: LINC00649 was underexpressed in bone marrow of AML group than that in healthy control group. The patients of LINC00649-low group have significantly inferior PFS and OS. A total of 154 mRNAs, 31 miRNAs, 28 lncRNAs and 1590 methylated CpG sites were identified to be significantly correlated with LINC00649. Furthermore, the network of ceRNA was established with 6 miRNAs and 122 mRNAs. The Lasso-Cox model fitted OS/PFS to novel prediction models, which integrated clinical factors, ELN risk stratification, mRNA/miRNA expression and methylation profiles. The analysis of time-dependent ROC for our model showed a superior AUC (AUC = 0.916 at 1 year, AUC = 0.916 at 3 years, and AUC = 0.891 at 5 years). CONCLUSIONS: Low expression of LINC00649 is a potential unfavorable prognostic marker for AML patients, which requires the further validation. The analysis by LASSO-COX regression identified a novel comprehensive model with a superior diagnostic utility, which integrated clinical and genetic variables.

Different binding properties of two general-odorant binding proteins in Athetis lepigone with sex pheromones, host plant volatiles and insecticides.

Athetis lepigone (Alep) is a polyphagous pest native to Europe and Asia that has experienced major outbreaks in the summer maize area of China since 2011 and has shown evidence of resistance to some insecticides. Insect olfaction is crucial for recognition of sex pheromones, host plant volatiles and even insecticides, in which two general-odorant binding proteins (GOBPs) play important roles. To elucidate the functions of GOBPs in A. lepigone, we first expressed the two AlepGOBP proteins in the E. coli expression system. Then, the results of fluorescence competitive binding assays demonstrated that the high binding affinity of AlepGOBP2 with sex pheromones [(Z)-7-dodecenyl acetate (Z7-12:Ac), Ki = 0.65 µM; (Z)-9-tetradecenyl acetate (Z9-14:Ac), Ki = 0.83 µM], two maize plant volatiles [Ocimene, Ki = 9.63 µM; (E)-ß-Farnesene, Ki = 4.76 µM] and two insecticides (Chlorpyrifos Ki =5.61 µM; Phoxim, Ki = 4.38 µM). However, AlepGOBP1 could only bind Ocimene (Ki = 13.0 µM) and two insecticides (Chlorpyrifos Ki =4.46 µM; Phoxim, Ki = 3.27 µM). These results clearly suggest that AlepGOBP1 and AlepGOBP2 differentiate among odorants and other ligands. The molecular docking results further revealed different key residues involved in the ligand binding of AlepGOBPs. In summary, this study provides a foundation for exploring the olfactory mechanism of A. lepigone and identified two potential target genes for the development of highly effective insecticides in the future.

Plant Volatiles Increase Sex Pheromone Attraction of Holotrichia parallela (Coleoptera: Scarabaeoidea).

Holotrichia parallela (Coleoptera: Scarabaeoidea) is a notorious pest of many crops. To improve the effectiveness of its female-produced sex pheromone (L-isoleucine methyl ester:(R)-(-)-linalool = 6:1), 14 plant volatiles, including dodecanoic acid, dodecanal, farnesol, α-farnesene, (Z)-3-hexen-1-ol, (E)-2-hexen-1-ol, (Z)-3-hexenyl acetate, (E)-2-hexenyl acetate, (R)-(+)-limonene, α-phellandrene, α-pinene, ocimene, methyl benzoate, and benzaldehyde, were individually evaluated using electroantennography and olfactometer assays. (E)-2-Hexenyl acetate and (Z)-3-hexenyl acetate were found to elicit the strongest responses in both males and females. Further testing of these two compounds in mixtures with the sex pheromone indicated that (E)-2-hexenyl acetate had a stronger synergistic effect than (Z)-3-hexenyl acetate. Field evaluations showed that mixtures of (E)-2-hexenyl acetate and the sex pheromone resulted in significantly higher catches than the sex pheromone alone. Using a 5:1 mixture of the sex pheromone and (E)-2-hexenyl acetate, the maximum number of females per trap per day was 14, showing a synergistic effect of a factor of four. For males, a 3:1 mixture of the sex pheromone and (E)-2-hexenyl acetate yielded a maximum number of 310 individuals per trap per day, equivalent to a synergistic effect of 175%. These results may provide the basis for the development of efficient pest management systems against H. parallela using plant volatiles and insect sex pheromones.

Transcriptome and tissue-specific expression analysis of Obp and Csp genes in the dark black chafer.

The dark black chafer, Holotrichia parallela, is an economically important pest in China and worldwide. Traps based on chemical communication are being developed as an alternative control measure to pesticides for this pest, and studies to reveal chemical communication mechanisms in this pest are highly desirable. To systematically analyze genes potentially involved in chemical communication in this pest, we generated a comprehensive transcriptome with combined samples derived from multiple tissues and developmental stages. A total of 43,967 nonredundant sequences (unigenes) with average length of 806 bp were obtained. These unigenes were annotated into different pathways using gene ontology analysis and cluster analysis of orthologous groups of proteins, and kyoto encyclopedia of genes and genomes. In total, 25 transcripts encoding odorant-binding proteins (OBPs) and 16 transcripts encoding chemosensory proteins (CSPs) were identified based on homology searches. Tissue-specific expression profile indicates that OBP17 and CSP7 are likely responsible for male sex pheromone recognition, whereas OBP1-4, OBP9, OBP13-14, OBP17-18, OBP20, OBP22, OBP25, CSP1-7, CSP11, and CSP12-15 are likely responsible for chemical communication between the beetle and environments. Our data shall provide a foundation for further research on the molecular aspects of chemical communication of this insect, and for comparative genomic studies with other species.

Development of plant-based whole egg analogs using emulsion technology.

RuBisCO is a plant protein that can be derived from abundant and sustainable natural resources (such as duckweed), which can be used as both an emulsifying and gelling agent. Consequently, it has the potential to formulate emulsion gels that can be used for the development of plant-based replacements of whole eggs. In this study, we investigated the ability of RuBisCO-based emulsion gels to mimic the desirable properties of whole eggs. The emulsion gels contained 12.5 wt% RuBisCO and 10 wt% corn oil to mimic the macronutrient composition of real whole eggs. Initially, an oil-in-water emulsion was formed, which was then heated to convert it into an emulsion gel. The impact of oil droplet diameter (∼15, 1, and 0.2 µm) on the physicochemical properties of the emulsion gels was investigated. The lightness and hardness of the emulsion gels increased as the droplet size decreased, which meant that their appearance and texture could be modified by controlling droplet size. Different concentrations of curcumin (3, 6, and 9 mg/g oil) were incorporated into the emulsions using a pH-driven approach. The curcumin was used as a natural dual functional ingredient (colorant and nutraceutical). The yellow-orange color of curcumin allowed us to match the appearance of raw and cooked whole eggs. This study shows that whole egg analogs can be formulated using plant-based emulsion gels containing natural pigments.

Impact of lipid droplet characteristics on the rheology of plant protein emulsion gels: Droplet size, concentration, and interfacial properties.

Plant-based meat analogs are being developed to address environmental, sustainability, health, and animal welfare concerns associated with real meat products. However, it is challenging to mimic the desirable physicochemical, functional, and sensory properties of real meat products using plant-based ingredients. Emulsion gels consisting of lipid droplets embedded in biopolymer matrices are commonly used to create products with appearances, textures, and sensory attributes like meat products. In this study, the impact of soybean oil droplet characteristics (concentration, size, and charge) on the physicochemical properties of potato protein gels was studied. The oil droplets were either coated by a non-ionic surfactant (Tween 20) or a plant protein (patatin) to obtain different surface properties. The introduction of the oil droplets caused the protein gels to change from mauve to off-white, which was attributed to increased light scattering. Increasing the oil droplet concentration in the emulsion gels decreased their shear modulus and Young's modulus, which was mainly attributed to the fact that the oil droplets were less rigid than the surrounding protein network. Moreover, increasing the oil droplet size made this effect more pronounced, which was attributed to their greater deformability. Competitive adsorption of proteins and surfactants at the oi-water interface in the Tween emulsion promoted emulsion instability. This research highlights the complexity of the interactions between oil droplets and protein networks in emulsion gels. These insights are important for the utilization of emulsion gels in the formulation of plant-based foods with improved quality attributes.

Heat-induced aggregation of subunits/polypeptides of soybean protein: Structural and physicochemical properties.

To reveal the nature of thermal aggregation of soybean protein at subunit level, structure and physicochemical properties of αα'- and ß-subunits isolated from ß-conglycinin, acidic polypeptide, and basic polypeptide from glycinin, as well as ß-conglycinin and glycinin, were characterized before and after heat treatment. The transmission electron microscopy (TEM) images showed that ß-conglycinin, αα'-subunits and acidic polypeptide formed regular thermal aggregates, which exhibited high solubility, high ζ-potential value, and small particle size. While glycinin, ß-subunit, and basic polypeptide aggregated to insoluble clusters with large particle size distribution. The results of size exclusion chromatography and non-reducing electrophoresis showed that the disulfide bond was the important force in stabilizing the protein conformation of thermal aggregates in ß-conglycinin, glycinin, and their isolated subunits/polypeptides but ß-subunit. The results of surface hydrophobicity and intrinsic fluorescence spectra showed that the thermal aggregations of ß-subunit and basic polypeptide were mainly driven by hydrophobic interactions.

Phytic acid-modified manganese dioxide nanoparticles oligomer for magnetic resonance imaging and targeting therapy of osteosarcoma.

Osteosarcoma is the most common malignant tumor in the skeletal system with high mortality. Phytic acid (PA) is a natural compound extracted from plant seeds, which shows certain antitumor activity and good bone targeting ability. To develop a novel theranostics for magnetic resonance imaging (MRI) and targeting therapy of osteosarcoma, we employed PA to modify manganese dioxide nanoparticles (MnO2@PA NPs) for osteosarcoma treatment. The MnO2 NPs oligomer was formed by PA modification with uniformed size distribution and negative zeta potential. Fourier-transform infrared spectroscopy, X-ray diffraction, energy dispersive spectroscopy, X-ray photoelectron spectroscopy, and thermogravimetric analysis demonstrated that PA has been successfully modified on MnO2 NPs, and the structure of MnO2@PA NPs is amorphous. In vitro experiments demonstrated that MnO2@PA NPs oligomer can be efficiently internalized by tumor cell, and the internalized NPs can react with H2O2 under acid microenvironment to produce Mn2+ and O2. In vivo experiments demonstrated that MnO2@PA NPs oligomer can passively accumulate in tumor tissue, and the accumulated NPs can produce Mn2+ and O2 for MRI and targeting therapy of osteosarcoma. In conclusion, we prepared a novel bone-targeting nano theranostics for MRI and therapy of osteosarcoma.

Influence of pH and ionic strength on the physicochemical and structural properties of soybean ß-conglycinin subunits in aqueous dispersions.

Understanding the impact of pH and ionic strength on the physicochemical and structural properties of soy proteins at subunit level is essential for design and fabrication of many plant-based foods. In this study, soybean ß-conglycinin and its subunit fractions αα' and ß were dispersed in solutions with different pH values (3.7, 7.6, and 9.0) at low (5 mM NaCl) and high (400 mM NaCl) ionic strengths, respectively. The solubility, rheology, particle size, zeta potential, microstructure, secondary structure, and tertiary structure of the different dispersions were analyzed using a range of analytical methods. The ß-conglycinin, αα'- and ß-subunits aggregated near the isoelectric point (pH 3.7). Increasing the ionic strength led to the assembly of more homogeneous units. An increase in ionic strength at pH 7.6 and pH 9.0 led to electrostatic screening, which promoted dissociation of the aggregates. The ß-subunit showed a greater sensitivity to pH and ionic strength than the αα'-subunits. Based on the evidence from a range of analytical methods, the highly hydrophilic extension region of the αα'-subunits played an important role in determining the stability of the ß-conglycinin dispersions under different environmental conditions. Moreover, the N-linked glycans appeared to impact the conformation and aggregation state of the ß-conglycinin.

Human anti-EGFL7 recombinant full-length antibodies selected from a mammalian cell-based antibody display library.

Epidermal growth factor-like domain 7 (EGFL7) has been implicated in promoting solid tumor growth and metastasis via stimulating tumor-associated angiogenesis. The advent of antibody display technology (phage, bacteria, and yeast) led to an enormous revival in the use of antibodies as diagnostic and therapeutic tools for fighting cancer. However, problems with protein folding, posttranslational modification, and codon usage still limit the number of improved antibodies that can be obtained. We describe here the isolation of an EGFL7-specific antibody from a mammalian cell-based full-length antibody display library generated from peripheral blood mononuclear cells of patients with hepatocellular carcinoma. Using a novel vector, contained glycosylphosphatidylinositol anchor and restriction enzyme sites NheI and ClaI, antibody libraries are displayed as whole IgG molecules on the cell surface and screened for specific antigen binding by a combination of magnetic beads and measured by cell ELISA. Anti-EGFL7 antibody was successfully isolated from the library. The mammalian cell-based full-length antibody display library is a great potential application for rapid identification and cloning of human mAbs of targeting hepatocellular carcinoma.

Molecular and biochemical characterization of two odorant-binding proteins from dark black chafer, Holotrichia parallela.

The dark black chafer, Holotrichia parallela Motschulsky, is an economically important pest worldwide. Odorant-based lures and traps are being developed as a key kind of alternative control measures for this pest, and studies to reveal the mechanisms for chemotaxis in this pest are necessary. Two full-length cDNAs encoding different odorant-binding proteins (OBPs) were cloned. The predicted proteins were found to have the functional domains characteristic of typical OBPs and share a high degree of sequence similarity with OBP1 and OBP2 from other insects and were therefore designated as H. parallela OBP-1 and H. parallela OBP-2 (HparOBP-1 and HparOBP-2, respectively). These two OBPs were specifically expressed in antennae. The binding affinity of two purified proteins indicated that HparOBP-1 and HparOBP-2 could selectively interact with various volatiles emitted from host plants and pheromone components. Among the 10 chemicals tested, HparOBP-1 could bind to six of the tested compounds with a dissociation concentration (Ki) less than 20, and HparOBP-2 could bind to three of the compounds. The two OBPs are probably involved in chemotaxis of the dark black chafer. This discovery should accelerate research on chemical communications of this pest, which could potentially lead to the improvement of control measures based on lures and traps.

[Evaluation of papillary muscle function of patients with chronic ischemic mitral regurgitation using two-dimensional speckle tracking imaging].

OBJECTIVE: To evaluate the papillary muscle function of patients with chronic ischemic mitral regurgitation (IMR) using two-dimensional speckle tracking imaging. METHODS: 119 patients with chronic IMR and 94 normal controls were enrolled in this study. The peak systolic strain (PSS) and peak systolic strain rate (PSSR) of the papillary muscle were assessed with two-dimensional strain software. The PSS and PSSR were compared between the patients with anterior myocardial infarct (AMI) and those with inferior myocardial infarct (IMI). The correlation between the degree of IMR and the position of MI was analysed. RESULTS: The patients with chronic IMR had significantly lower PSS and PSSR than the normal controls. The IMI patients had significantly lower PSS and PSSR than the AMI patients. The IMI patients had significantly higher degree of MR than the AMI patients. CONCLUSION: Two-dimensional speckle tracking imaging is a reliable method for assessing papillary muscle function.

[Visualization of right atrial flow patterns and quantification of pulmonary to systemic flow ratio in patients with atrial septal defect by vector flow mapping].

OBJECTIVE: To evaluate the ability of vector flow mapping (VFM) in visualizing right atrial flow and quantifying pulmonary to systemic flow ratio in patients with atrial septal defect (ASD). METHODS: VFM was performed on 30 patients with ASD and 50 healthy volunteers. The pulmonary to systemic flow ratio (Qp/Qs) was calculated using VFM and spectral doppler compared with that obtained through oximetric data derived from cardiac catheterization. RESULTS: Blood streams from superior and inferior caval veins did not collide but turned forward, contributing to a forward clockwise vortex during systole on the subcostal bi-atrial plane in the healthy volunteers. The vortex was disrupted continuously by a left to right shunt in the patients with ASD during the hole cardiac cycle. The Qp/Qs measured by VFM was less angle-dependent in all the cases than the other methods. The mean value of Qp/Qs of the healthy volunteers calculated by apical three-chamber view and apical five-chamber view ranged from 0.84:1 to 1.15:1, which is consistent with the theoretical value 1 of no left to right shunts. The values of Qp/Qs of patients with ASD measured by VFM and spectral doppler showed no significant differences with those obtained through oximetric data [(2.18 +/- 0.48) vs. (2.29 +/- 0.76), P = 0.29; (2.30 +/- 0.91) vs. (2.29 +/- 0.76), P = 0.86]. However, the Qp/Qs value measured by VFM had a better correlation with the oximetric data than that measured by spectral doppler (r = 0.71, P < 0.001 vs. r = 0.38, P < 0.05). The inter-observer and intraobserver variability of Qp/Qs measured by VFM was 9.84% and 9.86% respectively. CONCLUSION: VFM can visualize right atrial flow field in patients with ASD and quantify Qp/Qs in a more accurate way than spectral dopler.

Association of HER-2/CEP17 Ratio and HER-2 Copy Number With pCR Rate in HER-2-Positive Breast Cancer After Dual-Target Neoadjuvant Therapy With Trastuzumab and Pertuzumab.

Objective: To explore the correlation between HER-2 status and pathological complete response (pCR) in HER-2-positive breast cancer after dual anti-HER-2 neoadjuvant therapy with trastuzumab and pertuzumab. Methods: A total of 57 HER-2-positive breast cancer patients admitted to the Second Affiliated Hospital of Anhui Medical University and Xijing Hospital Affiliated to Air Force Military Medical University, between January 1, 2019 and September 30, 2020, were enrolled in this multicenter retrospective study. HER-2 status, including HER-2/CEP17 ratio and HER-2/cell number ratio, was detected by FISH. The correlation between HER-2 status/clinicopathological data and pCR was analyzed. The ROC curve was drawn to determine the cutoff value. Results: IHC assessment revealed 40 (70.18%) patients with IHC 3+ and 17 (29.82%) with IHC 2+. 41/57 (71.93%) patients achieved pCR. FISH revealed that the ratio of HER-2/chromosome 17 centromere (HER-2/CEP17) (p<0.001) and the ratio of HER-2/cell number (p<0.001) was significantly correlated with the pCR rate. ROC analysis showed that patients with an HER-2/CEP17 ratio ≥4.495 or HER-2/cell number ≥11.650 have a high pCR rate after dual anti-HER-2 neoadjuvant therapy, suggesting its predictive significance. Conclusion: The response to dual-targeted neoadjuvant therapy with trastuzumab and pertuzumab was adequate in hormone receptor-negative, HER-2-positive breast cancer patients. HER-2/CEP17 ratio and HER-2/cell number ratio were crucial for predicting efficacy.

FIGNL1 is a potential biomarker of cisplatin resistance in non-small cell lung cancer.

BACKGROUND: Fidgetin-like 1 (FIGNL1) participates in tumor resistance by playing the function of homologous recombination repair(HRR). However, the role of FIGNL1 in non-small cell lung cancer (NSCLC) is still unclear. This study aims to understand the expression of FIGNL1 in NSCLC and preliminarily explore its relationship with cisplatin resistance. METHODS: FIGNL1 messenger RNA (mRNA) was analyzed in 1018 NSCLC tissues and 111 adjacent tissues using The Cancer Genome Atlas program. FIGNL1mRNA in cisplatin-resistant and cisplatin-sensitive cell lines was analyzed by the Gene Expression Omnibus project. FIGNL1 protein was detected in 58 NSCLC tissues and 58 adjacent tissues by immunohistochemistry. The relationship between FIGNL1, clinical pathological characteristics and disease-free survival was retrospectively analyzed. Gene ontology was used to analyze the biological process mainly involving FIGNL1, and STRING online constructed its protein interaction network and screened the key genes (hub genes). RESULTS: The Cancer Genome Atlas showed that FIGNL1mRNA was higher in 1018 NSCLC tissues than in 111 adjacent tissues (P < 0.05). In the dataset "GSE157692," FIGNL1mRNA was higher in cisplatin-resistant cell lines (P = 3.80e-05). The hub genes in FIGNL1 and HRR directions are RAD51 and CCDC36. Immunohistochemistry showed that the FIGNL1 protein in 58 NSCLC tissues was higher than that in 58 adjacent tissues (P < 0.01). FIGNL1 is associated with gender, histopathological type, and nerve invasion in NSCLC. The disease-free survival in NSCLC patients with high FIGNL1 expression was shorter (P = 0.032). CONCLUSION: FIGNL1 is associated with poor prognosis in NSCLC, and cisplatin resistance may be involved. These observations provide a clinical basis for exploring FIGNL1 as a potential biomarker for cisplatin resistance in NSCLC.