The hospital Israelita Albert Einstein standards for constitutional sequence variants classification: version 2023.

BACKGROUND: Next-generation sequencing has had a significant impact on genetic disease diagnosis, but the interpretation of the vast amount of genomic data it generates can be challenging. To address this, the American College of Medical Genetics and Genomics and the Association for Molecular Pathology have established guidelines for standardized variant interpretation. In this manuscript, we present the updated Hospital Israelita Albert Einstein Standards for Constitutional Sequence Variants Classification, incorporating modifications from leading genetics societies and the ClinGen initiative. RESULTS: First, we standardized the scientific publications, documents, and other reliable sources for this document to ensure an evidence-based approach. Next, we defined the databases that would provide variant information for the classification process, established the terminology for molecular findings, set standards for disease-gene associations, and determined the nomenclature for classification criteria. Subsequently, we defined the general rules for variant classification and the Bayesian statistical reasoning principles to enhance this process. We also defined bioinformatics standards for automated classification. Our workgroup adhered to gene-specific rules and workflows curated by the ClinGen Variant Curation Expert Panels whenever available. Additionally, a distinct set of specifications for criteria modulation was created for cancer genes, recognizing their unique characteristics. CONCLUSIONS: The development of an internal consensus and standards for constitutional sequence variant classification, specifically adapted to the Brazilian population, further contributes to the continuous refinement of variant classification practices. The aim of these efforts from the workgroup is to enhance the reliability and uniformity of variant classification.

Establishment of a comprehensive diagnostic model for neuromyelitis optica spectrum disorders based on the analysis of laboratory indicators and clinical data.

BACKGROUND: To establish a comprehensive diagnostic model for neuromyelitis optica spectrum disorders (NMOSDs) based on laboratory indicators and clinical data. METHODS: A retrospective method was used to query the medical records of patients with NMOSD from January 2019 to December 2021. At the same time, clinical data of other neurological diseases were also collected for comparison. Clinical data of the NMOSD group and non-NMOSD group were analyzed, and the diagnostic model was established based on these data. In addition, the model was evaluated and verified by the receiver operating curve. RESULTS: A total of 73 patients with NMOSD were included, and the ratio of males to females was 1:3.06. The indicators that showed differences between the NMOSD group and non NMOSD group included neutrophils (P = 0.0438), PT (P = 0.0028), APTT (P < 0.0001), CK (P = 0.002), IBIL (P = 0.0181), DBIL (P < 0.0001), TG (P = 0.0078), TC (P = 0.0117), LDL-C (P = 0.0054), ApoA1 (P = 0.0123), ApoB (P = 0.0217), TPO antibody (P = 0.012), T3 (P = 0.0446), B lymphocyte subsets (P = 0.0437), urine sg (P = 0.0123), urine pH (P = 0.0462), anti-SS-A antibody (P = 0.0036), RO-52 (P = 0.0138), CSF simplex virus antibody I-IGG (P = 0.0103), anti-AQP4 antibody (P < 0.0001), and anti-MOG antibody (P = 0.0036). Logistic regression analysis showed that changes in ocular symptoms, anti-SSA antibody, anti-TPO antibody, B lymphocyte subsets, anti-AQP4 antibody, anti-MOG antibody, TG, LDL, ApoB, and APTT had a significant impact on diagnosis. The AUC of the combined analysis was 0.959. The AUC of the new ROC for AQP4- and MOG- antibody negative NMOSD was 0.862. CONCLUSIONS: A diagnostic model was successfully established, which can play an important role in differential diagnosis of NMOSD.

Morphological and biochemical studies of Salvia guaranitica St. Hil. under simulated deposition with different amounts of dust.

The collection of many environmental pollutants from road dust is harmful to living things and their surroundings. Previous studies have confirmed that road dust affects plant pigmentation, pollination, and biochemical properties. However, there are no comprehensive studies on multi-level dust pollution levels and multifaceted physiological properties of plants, and more importantly, there are no studies on atmospheric dust pollution monitors. In this experiment, the effect of road dust on the morphology and biochemistry of Salvia guaranitica St.Hil.was investigated by simulated deposition of different amounts of dust, and the changes of their physiological morphology under different pollution levels were also explored. A control group CK (0.00 g/plant), four experimental groups S1 (0.015 g/plant), S2 (0.030 g/plant), S3 (0.045 g/plant) and S4 (0.060 g/plant) were sprayed with the same dust samples every other day for 30 days. It was found that after 30 days of dust exposure, different degrees of morphological changes and damage occurred in Salvia. The different pollution levels also resulted in different degrees of biochemical characteristics of Salvia. With the increase of pollution, chlorophyll content, photosynthetic and evaporation rates decreased significantly, but the activity of SOD and the content of MDA increased significantly in different experimental groups. Especially, the experiments also revealed that severe road dust pollution caused damage and deformation to stomata, as well as a significant reduction in stomatal and glandular density. In addition, the regression curves of the different physiological responses of Salvia to road dust can be used as a preliminary basis for plant monitoring of dust pollution degrees, thus provided a scientific basis for the use of plant biomonitors in the field of pollution biology.

Combined analysis of mRNA and miRNA reveals the banana potassium absorption regulatory network and validation of miRNA160a.

Potassium (K) has an important effect on the growth and development of plants. Banana contains higher K content than many other fruits, and its plant requires more K nutrient in soil. However, the soil in the banana-producing areas in China is generally deficient in K. Therefore, understanding the mechanism of banana K absorption may assist in providing effective strategy to solve this problem. This study used two banana varieties with contrasting K tolerance, 'Guijiao No. 1' (low-K tolerant), and 'Brazilian banana' (low-K sensitive)to investigate K absorption mechanisms in response to low-K stress through miRNA and mRNA sequencing analysis. Under low-K condition, 'Guijiao No.1' showed higher plant height, dry weight, tissue K content and ATPase activity. Analysis of transcription factors showed that they were mainly in the types or classes of MYB, AP-EREBP, bHLH, etc. The sequencing results showed that 'Guijiao No. 1' had 776 differentially expressed genes (DEGs) and 27 differentially expressed miRNAs (DEMs), and 'Brazilian banana' had 71 DEGs and 14 DEMs between normal and low K treatments. RT-qPCR results showed that all miRNAs and mRNAs showed similar expression patterns with RNA-Seq and transcriptome. miRNA regulatory network was constructed by integrated analysis of miRNA-mRNA data. miR160a was screened out as a key miRNA, and preliminary functional validation was performed. Arabidopsis overexpressing miR160a showed reduced tolerance to low K, and inhibited phenotypic traits such as shorter root length, and reduced K accumulation. The overexpressed miR160a had a targeting relationship with ARF10 and ARF16 in Arabidopsis. These results indicate that miR160a may regulate K absorption in bananas through the auxin pathway. This study provides a theoretical basis for further study on the molecular mechanism of banana response to low potassium stress.

Establishment of SARS-CoV-2 Immunoglobulins (IgM, IgG) Reference Intervals for Elder Population in China based on 3,733 Samples.

BACKGROUND: Establishment of reference intervals (RIs) for different biomarkers is essential for clinical monitoring. The purpose of this study was to establish laboratory RIs of SARS-CoV-2 IgM and IgG for elder population. MATERIALS: Performance verification was conducted with reference to the Clinical and Laboratory Standards Institute (CLSI) guidelines, including linearity, imprecision, and allowable dilution ratio. Based on CLSI C28-A3 document, a total of 3,734 serum samples were collected, and 3,733 serum samples were used for the establishment of RIs for SARS-CoV-2 IgM and IgG. The subjects were grouped by gender and age. The age groups were as follows: 60 - 69 years, 70 - 79 years, 80 - 89 years, and 90 - 101 years. The RI was defined by nonparametric 95th percentile intervals. RESULTS: Percentage deviation of all the seven dilutions were all less than 12.5% during linearity evaluation. The inter-assay and intra-assay imprecision were all less than 5%. There is no significant difference between different gender and age groups for IgM (p = 0.0818, p = 0.7094), and there is significant difference between different gender and age groups for IgG (p = 0.0011, p = 0.0013). Harris-Boyd's test did not indicate partitioning for IgM and IgG. Cutoff values of RI for SARS-CoV-2 IgM and IgG were defined as 0.1523 S/CO and 0.2663 S/CO, respectively. CONCLUSIONS: RIs of SRAR-CoV-2 IgM and IgG were established for elder population, which can play an important role in the prevention and control of the epidemic.

Quality and Metabolomics Analysis of Houttuynia cordata Based on HS-SPME/GC-MS.

Houttuynia cordata is a medicinal and edible plant with a wide biological interest. Many parts were discarded due to various modes of consumption, resulting in resource waste. In this study, a comprehensive study was conducted on various edible indicators and medicinal components of Houttuynia cordata to understand its edible and medicinal value. The edible indexes of each root, stem, and leaf were determined, and the metabolites of different parts were investigated using the headspace solid-phase micro-extraction technique (HS-SPME-GC-MS). The differential metabolites were screened by orthogonal partial least squares discriminant analysis (OPLS-DA) and clustering analysis. The results of the study showed that the parts of Houttuynia cordata with high edibility values as a vegetable were mainly the roots and leaves, with the highest vitamin C content in the roots and the highest total flavonoids, soluble sugars, and total protein in the leaves. The nutrient content of all the stems of Houttuynia cordata was lower and significantly different from the roots and leaves (p < 0.05). In addition, 209 metabolites were isolated from Houttuynia cordata, 135 in the roots, 146 in the stems, 158 in the leaves, and 91 shared metabolites. The clustering analysis and OPLS-DA found that the parts of Houttuynia cordata can be mainly divided into above-ground parts (leaves and stems) and underground parts (roots). When comparing the differential metabolites between the above-ground parts and underground parts, it was found that the most important medicinal component of Houttuynia cordata, 2-undecanone, was mainly concentrated in the underground parts. The cluster analysis resulted in 28 metabolites with up-regulation and 17 metabolites with down-regulation in the underground parts. Most of the main components of the underground part have pharmacological effects such as anti-inflammatory, anti-bacterial and antiviral, which are more suitable for drug development. Furthermore, the above-ground part has more spice components and good antioxidant capacity, which is suitable for the extraction of edible flavors. Therefore, by comparing and analyzing the differences between the edible and medicinal uses of different parts of Houttuynia cordata as a medicinal and food plant, good insights can be obtained into food development, pharmaceutical applications, agricultural development, and the hygiene and cosmetic industries. This paper provides a scientific basis for quality control and clinical use.

Effect of Adjusted Antiplatelet Therapy on Preventing Ischemic Events After Stenting for Intracranial Aneurysms.

BACKGROUND AND PURPOSE: This study tests whether patients with unruptured intracranial aneurysm who underwent stent placement benefitted from platelet function monitoring-guided adjustment of antiplatelet therapy. METHODS: We conducted a randomized, open-label, parallel group, assessor-blinded trial. Patients with unruptured intracranial aneurysm who underwent stent placement were assigned in a 1:1 ratio to receive either drug adjustment (patients who had high on-treatment platelet reactivity to antiplatelet therapy on the basis of platelet function monitoring [monitoring group]) or conventional therapy (without monitoring and drug adjustment [conventional group]). The second monitoring was performed 14 days after randomization in patients with drug adjustment. The primary outcome was the composite frequency of ischemic stroke, transient ischemic attack, stent thrombosis, urgent revascularization, and cerebrovascular death within 7 days after stent implantation. The safety outcome was the composite frequency of major, minor, or minimal bleeding within 1 month after stent implantation. RESULTS: In total, 314 patients were included (n=157 per group). The primary combined outcome occurred in 19 patients (12.1%) in the conventional group and 8 patients (5.1%) in the monitoring group (hazard ratio, 0.39 [95% CI, 0.17-0.92]; P=0.03). Ischemic stroke occurred at a lower frequency in the monitoring group compared with that in the conventional group (4.5% versus 12.1%; hazard ratio, 0.34 [95% CI, 0.14-0.83]; P=0.01), which drove the overall primary combined outcome. The safety outcome occurred in the monitoring group (7.0%) and in the conventional group (1.9%; hazard ratio, 3.87 [95% CI, 1.06-14.14]; P=0.03). A significant difference was observed in the frequency of minor or minimal bleeding events between the two groups (monitoring group versus conventional group, 6.4% versus 1.3%; P=0.02) but not in the frequency of major bleeding events between the two groups. CONCLUSIONS: Platelet function monitoring-guided antiplatelet therapy reduces thromboembolic events in patients with unruptured intracranial aneurysm after stent placement, significantly enhancing minor or minimal bleeding events but not major bleeding events. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03989557.

Expression Analysis of MaTGA8 Transcription Factor in Banana and Its Defence Functional Analysis by Overexpression in Arabidopsis.

TGA transcription factor is a member of the D subfamily of the basic region-leucine zippers (bZIP) family. It is a type of transcription factor that was first identified in plants and is the main regulator in plant development and physiological processes, including morphogenesis and seed formation in response to abiotic and biotic stress and maintaining plant growth. The present study examined the sequence of the MaTGA8 transcription factor, the sequence of which belonged to subfamily D of the bZIP and had multiple cis-acting elements such as the G-box, TCA-element, TGACG-element, and P-box. Quantitative real time polymerase chain reaction (qRT-PCR) analyses showed that MaTGA8 was significantly down-regulated by the soil-borne fungus Fusarium oxysporum f. sp. cubense race 4 (Foc TR4). Under the induction of salicylic acid (SA), MaTGA8 was down-regulated, while different members of the MaNPR1 family responded significantly differently. Among them, MaNPR11 and MaNPR3 showed an overall upward trend, and the expression level of MaNPR4, MaNPR8, and MaNPR13 was higher than other members. MaTGA8 is a nuclear-localized transcription factor through strong interaction with MaNPR11 or weaker interaction with MaNPR4, and it is implied that the MaPR gene can be activated. In addition, the MaTGA8 transgenic Arabidopsis has obvious disease resistance and higher chlorophyll content than the wild-type Arabidopsis with the infection of Foc TR4. These results indicate that MaTGA8 may enhance the resistance of bananas to Foc TR4 by interacting with MaNPR11 or MaNPR4. This study provides a basis for further research on the application of banana TGA transcription factors in Foc TR4 stress and disease resistance and molecular breeding programs.

Diagnosis of Invasive Nonfunctional Pituitary Adenomas by Serum Extracellular Vesicles.

The invasiveness evaluation of nonfunctional pituitary adenoma (NFPAs) is crucial for the prediction of the malignant potential and for making surgical plans of NFPAs. Current invasiveness evaluation of NFPAs is based on neuroimaging, which can hardly predict the invasive potential and dynamically monitor disease progress. Here we used microbead-assisted flow cytometry to detect and analyze the serum extracellular vesicles (EVs) from 30 NFPAs patients (15 invasive and 15 noninvasive). Lower expressions of folate receptor 1 (FOLR1) and epithelial cell adhesion molecule (EpCAM) were found in serum EVs from the invasive NFPAs patients compared to the noninvasive ones [area under the curve (AUC) of 0.94 for FOLR1 and 0.88 for EpCAM]. Meanwhile, increased mRNA expression of vimentin and N-cadherin, two mesenchymal markers, was found in serum EVs from the invasive NFPAs patients compared to the noninvasive ones. Consistent results were observed in the tumor tissue that invasive NFPAs have lower expression of the epithelial markers while higher expression of the mesenchymal markers. These results suggested the possible role of epithelial-mesenchymal transition (EMT) in the invasiveness of NFPAs. Pituitary tumor transforming gene 1 (PTTG1) mRNA in serum EVs was also found to be an indicator for invasive NFPAs and is related with EMT. These results provide a method for the blood-based diagnosis and invasiveness evaluation of NFPAs and would be beneficial to the diagnosis, prognosis prediction, and surgical risk evaluation of NFPAs.

Synthesis of derivatives of cleistopholine and their anti-acetylcholinesterase and anti-ß-amyloid aggregation activity.

A series of 6- and 9-substituted cleistopholine derivatives has been designed, synthesized and investigated to inhibit the aggregation of acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and ß-myloid (A ß). Results showed that these synthetic compounds had excellent AChE inhibitory activity and a significant in vitro inhibitory potency toward the self-induced A ß aggregation. When SH-SY5Y cells were treated with these substituted cleistopholine derivatives during they overexpressed the Swedish mutant form of human ß -amyloid precursor protein (APPsw), A ß 42 secretion levels were significantly reduced. According to a parallel artificial membrane permeation assay for BBB, seven out of these sixteen synthetic compounds probably could cross the blood-brain barrier (BBB) to reach their targets in the central nervous system (CNS).

Deletion 21pterq22.11: Report of a Patient with Dysmorphic Features, Hypertonia, and Café-au-Lait Macules and Review of the Literature.

Partial monosomy 21 results in a great variability of clinical features that may be associated with the size and location of the deletion. In this study, we report a 22-month-old girl who showed a 45,XX,add(12)(p13)dn,-21 karyotype. The final cytogenomic result was 45,XX,der(12)t(12;21)(p13;q22.11) dn,-21.arr[hg19] 21q11.2q22.11(14824453_33868129)×1 revealing a deletion from 21pter to 21q22.11. Clinical manifestation of the patient included hypertonia, a long philtrum, epicanthic folds, low-set ears, and café-au-lait macules - a phenotype considered as mild despite the relatively large size of the deletion compared to patients from the literature.

Simultaneous quantitative determination of 20 active components in the traditional Chinese medicine formula Zhi-Zi-Da-Huang decoction by liquid chromatography coupled with mass spectrometry: application to study the chemical composition variations in different combinations.

Zhi-Zi-Da-Huang decoction (ZZDHD), a classical traditional Chinese medicine (TCM) prescription composed of four herbal medicines, has been widely used in treating various hepatobiliary disorders for a long time. The objective of this study was to develop a sensitive and efficient liquid chromatography coupled with mass spectrometry (LC-MS) method for quantitative determination of 20 active constituents, including three iridoid glycosides, 11 flavonoids, three anthraquinones and three tannins in ZZDHD. Separation was achieved on a phenomenex kinetex C18 column (150 × 4.6 mm, 2.6 µm) using gradient elution with a mobile phase consisting of acetonitrile and 0.1% formic acid in water. Detection was performed with electrospray ionization source in the negative ionization and selected ion monitoring mode. The established method was validated by determining the linearity (r(2) ≥ 0.9983), limit of quantification (0.16-300 ng/mL), precision (RSD ≤ 4.6%), average recovery (96.0-105.6%), repeatability (RSD ≤ 3.2%) and stability (RSD ≤ 4.5%). Then, the method was successfully applied to investigate the chemical composition variations owing to the interaction between the four component herbs of ZZDHD during the extraction process. It was found that different combinations of the herbs affect the extraction efficiency of chemical constituents in different ways. The validated LC-MS method provides a meaningful basis for quality control and further research on ZZDHD.

The Development of a Continuous Constitutive Model for Thin-Shell Components with A Sharp Change in the Property at Welded Joints.

Large-dimension complex integral thin-shell components are widely used in advanced transportation equipment. However, with the dimensional limitations of raw blanks and the manufacturing process, there are inhomogeneous geometric and mechanical properties at welded joints after welding, which have a significant effect on the subsequent forming process. Therefore, in this paper, the microstructure of welded joints with a sharp property change was accurately characterized by the proposed isothermal treatment method using the BR1500HS welded tube as an example. In addition, an accurate constitutive model of welded tubes was established to predict the deformation behavior. Firstly, the heat-treated specimens were subjected to uniaxial tensile tests and the stress-strain curves under different heat treatment conditions were obtained. Then, the continuous change in flow stress in the direction of the base metal zone, the heat-affected zone and the weld zone was described by the relationship between the microhardness, flow stress and center angle of the welded tube. Using such a method, a continuous constitutive model of welded tubes has been established. Finally, the constitutive model was compiled into finite-element software as a user material subroutine (VUHARD). The reliability of the established constitutive model was verified by simulating the free hydro-bulging process of welded tubes. The results indicated that the continuous constitutive model can well describe the deformation response during the free hydro-bulging process, and accurately predicted the equivalent strain distribution and thickness thinning rate. This study provides guidance in accurately predicting the plastic deformation behavior of welded tubes and its application in practice in hydroforming industries.

Association of TRPC1 gene polymorphisms with type 2 diabetes and diabetic nephropathy in Han Chinese population.

The recent genome-wide association studies reveal that chromosome 3q resides within the linkage region for diabetic nephropathy (DN) in type 1 and type 2 diabetes mellitus (T1D and T2D). The TRPC1 gene is on chromosome 3q22-24, and it has been demonstrated that TRPC1 expression is reduced in the kidney of diabetic animal models. Genetic association of TRPC1 polymorphism with T1D and DN has been reported in European Americans. However, there are no studies reporting the association of TRPC1 genetic polymorphism with T2D with and without DN in Chinese population. This study aimed to demonstrate the genetic role of TRPC1 in the development of T2D with and without DN in Chinese Han population. A genetic association study of TRPC1 was performed in T2D cases and in nondiabetic controls from Han population located in Northern Chinese areas. Six tag single nucleotide polymorphism (SNP) markers derived from HapMap data were genotyped. Among the six SNPs, only rs7638459 was suspected as risk factor of T2D without DN, fitting the log-additive model. The adjusted odds ratio (OR) for the CC genotyping was 2.39 (95% confidence interval (CI) = 1.00-5.68), compared with the TT genotyping. In addition, rs953239 was found to be a protective factor of getting DN in T2D, also fitting the log-additive model. When compared with the AA genotyping for SNP rs953239, the adjusted OR for CC genotyping was 0.63 (95% CI = 0.44-0.99). To summarize, this study shows that TRPC1 genetic polymorphisms are associated with T2D and DN in T2D in the Han Chinese population.

Cell-specific genome-scale metabolic modeling of SARS-CoV-2-infected lung to identify antiviral enzymes.

Computational systems biology plays a key role in the discovery of suitable antiviral targets. We designed a cell-specific, constraint-based modeling technique for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected lungs. We used the gene sequence of the alpha variant of SARS-CoV-2 to build a viral biomass reaction (VBR). We also used the mass proportion of lipids between the viral biomass and its host cell to estimate the stoichiometric coefficients of viral lipids in the reaction. We then integrated the VBR, the gene expression of the alpha variant of SARS-CoV-2, and the generic human metabolic network Recon3D to reconstruct a cell-specific genome-scale metabolic model. An antiviral target discovery (AVTD) platform was introduced using this model to identify therapeutic drug targets for combating COVID-19. The AVTD platform not only identified antiviral genes for eliminating viral replication but also predicted side effects of treatments. Our computational results revealed that knocking out dihydroorotate dehydrogenase (DHODH) might reduce the synthesis rate of cytidine-5'-triphosphate and uridine-5'-triphosphate, which terminate the viral building blocks of DNA and RNA for SARS-CoV-2 replication. Our results also indicated that DHODH is a promising antiviral target that causes minor side effects, which is consistent with the results of recent reports. Moreover, we discovered that the genes that participate in the de novo biosynthesis of glycerophospholipids and ceramides become unidentifiable if the VBR does not involve the stoichiometry of lipids.

Forming Limit Analysis of Thin-Walled Extruded Aluminum Alloy Tubes under Nonlinear Loading Paths Using an Improved M-K Model.

To meet the requirement of lighter weight and better performance in tube hydroforming, one of the most important tasks is to accurately predict the forming limit of thin-walled tubes under nonlinear loading paths. This work established the M-K+DF2012 model, a combination of the M-K model and the DF2012 ductile fracture criterion, for the forming limit prediction of thin-walled tubes under nonlinear loading paths. In this model, the failure of the groove is determined by the DF2012 criterion, and the corresponding strains in the uniform region are the limit strains. The limit strains of an AA6061 aluminum alloy tube under a set of linear loading paths and two typical nonlinear loading paths were tested. Parameter values of the M-K+DF2012 model for the tube were determined based on the experimental limit strains under linear loading paths, and the limit strains under the two nonlinear loading paths were predicted. Then the strain-based forming limit diagram (ε-FLD) and the polar effective plastic strain FLD (PEPS-FLD) of the tube under different pre-strains were predicted and discussed. The results show that the limit strains of the tube are obviously path-dependent, and the M-K+DF2012 model can reasonably capture the limit strains of the tube under both linear and nonlinear loading paths. The predicted ε-FLD shows a strong dependence on the pre-strain, while the predicted PEPS-FLD is weakly strain path-dependent and almost path-independent on the right-hand side for the AA6061 tube.

A Homogeneous Anisotropic Hardening Model in Plane Stress State for Sheet Metal under Nonlinear Loading Paths.

In sheet metal forming, the material is usually subjected to a complex nonlinear loading process, and the anisotropic hardening behavior of the material must be considered in order to accurately predict the deformation of the sheet. In recent years, the homogeneous anisotropic hardening (HAH) model has been applied in the simulation of sheet metal forming. However, the existing HAH model is established in the second-order stress deviator space, which makes the calculation complicated and costly, especially for a plane stress problem such as sheet metal forming. In an attempt to reduce the computational cost, an HAH model in plane stress state is proposed, and called the HAH-2d model in this paper. In the HAH-2d model, both the stress vector and microstructure vector contain only three in-plane components, so the calculation is significantly simplified. The characteristics of the model under typical nonlinear loading paths are analyzed. Additionally, the feasibility of the model is verified by the stress-strain responses of DP780 and EDDQ steel sheets under different two-step uniaxial tension tests. The results show that the HAH-2d model can reasonably reflect the Bauschinger effect and the permanent softening effect in reverse loading, and the latent hardening effect in cross loading, while the predictive accuracy for cross-loading softening remains to be improved. In the future, the HAH-2d model can be further modified to describe more anisotropic hardening behaviors and applied to numerical simulations.

Identification of Anisotropic Coefficients in the Non-Principal Axis Directions of Tubular Materials Using Hole Bulging Test.

We propose an experimental method to identify anisotropic coefficients in non-principal axis directions of thin-walled tubes. The method involves extracting specimens from the parent tubes and machining a hole in the axial center. The specimens are then inserted into a tube without a hole. The inner diameter of the specimen is theoretically equal to the outer diameter of the inner tube. The double-layer tube undergoes free bulging under internal pressure in our self-developed experimental equipment, with the hole on the specimen expanding simultaneously. The stress states around the hole are uniaxial, and the hole deformation can reflect the anisotropic plastic flow characteristics of the tube. Furthermore, based on the information obtained from the proposed experimental method, a hybrid numerical-experimental method was used to identify the anisotropic coefficients of tubes. Through FE simulations, the relationships between the thickness, stress, and strain states around the hole, the hole shape, and anisotropic coefficients of non-principal axis directions are revealed, and the factors that affect the hole deformation are analyzed. Finally, the hole bulging experiments and FE simulations of AA6061-O extruded tube were conducted, and modeled with Hill48 and calibrated by uniaxial tensile and hoop tensile tests. Its in-plane anisotropy coefficients in any direction are given for the first time which first increase and then decrease from 0° to 90°, reaching a maximum of 1.13 in 60° and a minimum of 0.69 in 0°. This work can provide the key experimental data for establishing an accurate anisotropic plastic constitutive model of thin-walled tubes.

Experiment for Measuring Mechanical Properties of High-Strength Steel Sheets under Cyclic Loading by V-Shaped Double-Shear-Zone Specimens.

The simple shear test shows significant advantages when measuring the hardening and shear properties of thin sheet metal at large strains. However, previous shear tests had an end effect caused by local stress concentration and a boundary effect caused by deformation overflow, resulting in non-uniform strain distribution in the shear zone. Therefore, a unique V-shaped double-shear-zone specimen is proposed to measure the Bauschinger effect under cyclic shear loading conditions in this paper. Simple shear experiments and three different types of cycle shear experiments are conducted to analyze the uniformity of deformation in the shear zone and the effect of pre-strain and the number of cyclic loads on the Bauschinger effect of Q890 high-strength steel sheets. The results indicate that the proposed V-shaped double-shear-zone specimen can still maintain uniform shear deformation in forward/reverse cyclic loading experiments, even at large strains. Q890 high-strength steel exhibits a significant Bauschinger effect, which is more pronounced with the increase in shear pre-strain and loading cycles. The results of this paper provide a new approach for studying the hardening characteristics under large strain and the mechanical properties under cyclic shear loading for metal sheets.

Inverse Problem Algorithm-Based Time-Resolved Imaging of Head and Neck Computed Tomography Angiography Contrast Kinetics with Clinical Testification.

This study mitigated the challenge of head and neck CT angiography by IPA-based time-resolved imaging of contrast kinetics. To this end, 627 cerebral hemorrhage patients with dizziness, brain aneurysm, stroke, or hemorrhagic stroke diagnosis were randomly categorized into three groups, namely, the original dataset (450), verification group (112), and in vivo testified group (65), in the Affiliated BenQ Hospital of Nanjing Medical University. In the first stage, seven risk factors were assigned: age, CTA tube voltage, body surface area, heart rate per minute, cardiac output blood per minute, the actual injected amount of contrast media, and CTA delayed trigger timing. The expectation value of the semi-empirical formula was the CTA number of the patient's left artery (LA). Accordingly, 29 items of the first-order nonlinear equation were calculated via the inverse problem analysis (IPA) technique run in the STATISTICA 7.0 program, yielding a loss function and variance of 3.1837 and 0.8892, respectively. A dimensionless AT was proposed to imply the coincidence, with a lower AT indicating a smaller deviation between theoretical and practical values. The derived formula was confirmed for the verification group of 112 patients, reaching high coincidence, with average ATavg and standard deviation values of 3.57% and 3.06%, respectively. In the second stage, the formula was refined to find the optimal amount of contrast media for the CTA number of LA approaching 400. Finally, the above procedure was applied to head and neck CTA images of the third group of 65 patients, reaching an average CTA number of LA of 407.8 ± 16.2 and finding no significant fluctuations.