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Dysregulated T cell activation underpins the immunopathology of rheumatoid arthritis (RA), yet the machineries that orchestrate T cell effector program remain incompletely understood. Herein, we leveraged bulk and single-cell RNA sequencing data from RA patients and validated protein disulfide isomerase family A member 3 (PDIA3) as a potential therapeutic target. PDIA3 is remarkably upregulated in pathogenic CD4 T cells derived from RA patients and positively correlates with C-reactive protein level and disease activity score 28. Pharmacological inhibition or genetic ablation of PDIA3 alleviates RA-associated articular pathology and autoimmune responses. Mechanistically, T cell receptor signaling triggers intracellular calcium flux to activate NFAT1, a process that is further potentiated by Wnt5a under RA settings. Activated NFAT1 then directly binds to the Pdia3 promoter to enhance the expression of PDIA3, which complexes with STAT1 or PKM2 to facilitate their nuclear import for transcribing T helper 1 (Th1) and Th17 lineage-related genes, respectively. This non-canonical regulatory mechanism likely occurs under pathological conditions, as PDIA3 could only be highly induced following aberrant external stimuli. Together, our data support that targeting PDIA3 is a vital strategy to mitigate autoimmune diseases, such as RA, in clinical settings., Competing Interests: Declaration of interests The authors declare that they have no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Osteonecrosis of the femoral head (ONFH) is a destructive condition most commonly affecting young and middle-aged patients. The leading consequence of ONFH is often a significant articular disability. Effective joint-preserving surgical treatments are urgently needed for patients with early stage ONFH when outcomes of treatment are in general better than the advanced stage disease., Aim: To introduce a new surgery procedure called percutaneous expanded core decompression and mixed bone graft technique, which is a new way of joint-preserving surgical treatments., Methods: The clinical data of 6 patients with ONFH diagnosed and treated with the procedure called percutaneous expanded core decompression and mixed bone graft technique at The First Hospital of Qiqihar from March 2013 to August 2019 were retrospectively analyzed; the follow-up ended in December 2019., Results: There were 6 male patients with an average age of 43 years in our study. Gratifying results have been obtained from the comparison of Harris hip score, visual analogue scale, and imaging examination before and after operation., Conclusion: This new modified technique is simple, safe, and reliable. No serious perioperative complications were observed in our cases. Advantages of the single blade expandable reamer are obvious. The adjuvant substance is inexpensive and easy to obtain. Thus, this technique is an effective joint-preserving surgical treatment for patients with early stage of ONFH., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflicts of interest., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

In prior work, congenic strains carrying the DBA/2Igb (D2) region of chromosome 2 (Chr2) for alcohol preference were bred onto a C57BL/6Ibg (B6) background and as predicted were found to reduce voluntary consumption. Subsequently, interval-specific congenic recombinant strains (ISCRS) were generated and also tested. These ISCRS strains reduced the quantitative trait loci (QTL) interval to a comparatively small 3.4 Mb region. Here, we have exploited an integrative approach using both murine and human populations to critically evaluate candidate genes within this region. First, we used bioinformatics tools to search for genes relevant to alcohol preference within the QTL region. Second, we searched for single nucleotide polymorphisms (SNPs) within exons of every gene in this region. Third, we conducted follow-up microarray analyses to identify differentially expressed genes between the B6 and ISCRS strains in mice from each group. Fourth, we analyzed correlations between the expression level of candidate genes and phenotypes of alcohol preference in a large family of BXD recombinant inbred strains derived from B6 and D2. Finally, we evaluated SNP segregation in both BXD mouse strains and in humans who were heavy alcohol drinkers or non-drinkers. Among several potential candidate genes in this region, we identified activating transcription factor 2 (Atf2) as the most plausible gene that would influence alcohol preference. However, the candidacy of Atf2 was only weakly supported when we used a genetic network approach and by focused reanalysis of genome-wide association study data from European-American and African-American populations. Thus, we cannot conclude that Atf2 plays a role in the regulation of the QTL of mouse Chr2.

The mitochondrial ATP synthase, subunit c, isoform 3 gene (Atp5g3) encodes subunit 9, the subunit of the multisubunit enzyme that catalyzes ATP synthesis during oxidative phosphorylation in mitochondria. According to the Ensembl database, Atp5g3 in mice is located on chromosome 2 between 73746504 and 73749383 bp, within the genomic regions of two sets of quantitative trait loci - alcohol preference and body weight. Both of those traits are more influenced by epigenetic factors than many other traits are. Using currently available phenotype and gene expression profiles from the GeneNetwork database, we obtained correlations between Atp5g3 and alcoholism- and obesity-relevant phenotypes. The correlation in expression levels between Atp5g3 and each of its 12 partner genes in the molecular interaction are different in various tissues and genes. Transcriptome mapping indicated that Atp5g3 is differentially regulated in the hippocampus, cerebellum, and liver. Owing to a lack of known polymorphisms of Atp5g3 among three relevant mouse strains, C57BL/6J (B6), DBA/2J (D2), and BALB/ cJ, the molecular mechanism for the connection between Atp5g3 and alcoholism and body weight requires further investigation.

Background and Purpose: MicroRNAs have recently been shown to regulate the downstream bioprocesses of intracerebral hemorrhage. The aim of this study was to investigate whether miRNAs can be used as biomarkers to predict secondary hematoma enlargement (HE) in patients with ICH., Methods: Consecutively, 79 ICH patients admitted within 6 h of symptom onset and 30 healthy individuals were enrolled in this study. Whole-genome miRNA expression profiles were generated in 32 patients (HE/non-HE: 14/18). Representative differentially expressed miRNAs were measured in all cases (HE/non-HE: 30/49) and normal controls (n = 30) by real-time PCR., Results: Thirty miRNAs showed differential expressions in the plasma samples from patients with HE as compared with the non-HE controls. Compared to the hierarchical cluster analysis with all probes on microarray, all patients were separated into two main branches with only four exceptions by 30 differentially expressed miRNAs, improving the overall accuracy from 47.62 to 77.78% in the HE and 72.73 to 100% in the non-HE group. Further support vector machine (SVM) test can discriminate the two groups with 100% accuracy with 10 differentially expressed miRNAs., Conclusions: We demonstrated that multiple miRNAs are differentially expressed in the plasma of ICH patients with or without HE and may serve as circulating biomarkers for predicting HE after ICH., (© 2012 Blackwell Publishing Ltd.)

Background and Purpose: Elevated plasma C-reactive protein (CRP) has been suggested as a risk factor for ischemic stroke (IS) and coronary ischemic disease. Evidence has shown that high-sensitivity CRP (hs-CRP) is related to a worsening prognosis after IS, but hs-CRP was rare in a large-sample study in a Chinese population. We investigated the associations between hs-CRP and outcome of Chinese patients after acute IS., Methods: Seven hundred and forty-one consecutive acute IS patients (74.9% male, mean age 60.9 years), with baseline characteristics and hs-CRP measured within 24 h after hospitalization, were admitted in this study. We also prospectively followed up for clinical outcome and death 3 months after disease onset. hs-CRP was divided into two categories: hs-CRP >3 mg/L and hs-CRP ≤3 mg/L. Survival analysis using multivariable Cox regression was performed to analyze the association between hs-CRP and stroke outcomes after adjusting for potential confounding factors., Results: Compared with low hs-CRP, patients with high hs-CRP (>3 mg/L) had a significantly higher rate of all-cause death (0.71% vs. 10.00%; P < 0.001) at 3 months after stroke onset. High hs-CRP was an independent risk factor for all-cause death (HR, 6.48; 95% CI, 1.41 to 29.8; P= 0.016), as well as history of atrial fibrillation (HR, 5.24; 95% CI, 1.83 to 15.0; P= 0.002), no statin therapy during hospitalization (HR, 4.56; 95% CI, 2.18 to 9.55; P < 0.001), high homocysteine (>15.1 mmol/L) (HR, 2.66; 95% CI, 1.26 to 5.60; P= 0.01); fasting glucose (>6.1 mmol/L) (HR, 9.14; 95% CI, 3.34 to 25.0; P < 0.001), NIHSS at admission (HR, 2.35; 95% CI, 1.35 to 4.09; P= 0.003) and history of coronary heart disease (CHD) (HR, 2.34; 95% CI, 1.06 to 5.17; P= 0.035). Kaplan-Meier survival curves showed a higher risk of death for patients with hs-CRP >3 mg/L (P= 0.016)., Conclusion: Elevated plasma hs-CRP independently predicted risk of all-cause death within 3 months after acute IS in Chinese patients., (© 2012 Blackwell Publishing Ltd.)

This article makes a pilot study on the key points of the quality management system of in-vitro diagnostic reagents by analyzing the technical characteristics and production methods of these products as well as the status in quo, and problems the in-vitro diagnostic reagent industry in China is facing nowadays. It can serve as a reference to the supervision departments and the manufacturers in this field which are establishing and running the quality management system.

This article introduces the definition, classification, premarket admission and other administering specialities about In-Vitro Diagnostic Reagents in the U.S.A. and China. And by analyzing manufacture and administration of In-Vitro Diagnostic Reagents in our country, It is pointed out that a suitable administering model in accordance with the characteristics of In-Vitro Diagnostic Reagents should be adopted to perfect the administration.

Unique correct correspondence cannot be obtained only by use of gray correlation technique, which describes gray similar degree of feature points between the left and right images too unilaterally. The gray correlation technique is adopted to extract gray correlation peaks as a coarse matching set called multi-peak set. The disparity gradient limited constraint is utilized to optimize the multi-peak set. Unique match will be obtained by calculating the correlation of hybrid matrices consisting of reference differences and disparities from the multi-peak set. Two of the known corresponding points in the left and right images, respectively, are set as a pair of reference points to determine search direction and search scope at first. After the unique correspondence is obtained by calculating the correlation of the hybrid matrices from the multi-peak set, the obtained match is regarded as a new reference point till all feature points in the left (or right) image have been processed. Experimental results proved that the proposed algorithm was feasible and accurate.

The linear multi-baseline stereo system introduced by the CMU-RI group has been proven to be a very effective and robust stereovision system. However, most traditional stereo rectification algorithms are all designed for binocular stereovision system, and so, cannot be applied to a linear multi-baseline system. This paper presents a simple and intuitional method that can simultaneously rectify all the cameras in a linear multi-baseline system. Instead of using the general 8-parameter homography transform, a two-step virtual rotation method is applied for rectification, which results in a more specific transform that has only 3 parameters, and more stability. Experimental results for real stereo images showed the presented method is efficient.

One QTL and genes and phenotypes have been localized in the region between 92 cM and 95cM of mouse chromosome 1. The QTL locus contributes to approximately 40% of the variation of the peak bone density between C57BL/6J (B6) and CAST/EiJ (CAST) strains. Other loci located in this chromosomal region include a neural tube defect mutant loop-tail (Lp), a lymphocyte-stimulating determinant (Lsd), and the Transgelin 2 (Tagln 2). The human chromosome region homologous to this region is 1q21-23, which also contains a QTL locus for high bone mineral density (BMD). Furthermore, it has been reported that this region may have duplicated several times in the mouse genome. Therefore, genomic sequencing of this region will provide important information for mouse genome structure, for positional cloning of mouse genes, and for the study of human homologous genes. In order to provide a suitable template for genomic sequencing by the NIH-sponsored genomic centers, we have constructed a BAC contig of this region using the RPCI-23 library. We have also identified the currently available mouse genomic sequences localized in our BAC contig. Further analysis of these sequences and BAC clones indicated a high frequency of repetitive sequences within this chromosomal area. This region also contains L1 retrotransposon sequences, providing a potential mechanism for the repetitive sequences described in the literature.

A three-dimensional biomechanical model was used to calculate the mechanical response of the foot to a load of 683 Newtons with the subtalar joint in the neutral position, at five degrees of pronation, and at five degrees of supination. Pronation causes the forefoot to evert, increasing the load borne by the first metatarsal. This results in a 47% increase in the moment about the talonavicular joint and a 58% increase in the moment about the navicular-medial cuneiform joint. Subtalar joint supination causes the forefoot to invert and results in a 55% increase in the moment about the calcaneal-cuboid joint.

A simple, PCR-based method has been developed for the rapid genotyping of large numbers of samples. The method involves a alkaline extraction of DNA from plant tissue using a slight modification of the procedure of Wang et al. (Nucleic Acids Res 21:4153-4154, 1993). Template DNA is amplified using allelespecific associated primers (ASAPs) which, at stringent annealing temperatures, generate only a single DNA fragment and only in those individuals possessing the appropriate allele. This approach eliminates the need to separate amplified DNA fragments by electrophoresis. Instead, samples processing the appropriate allele are identified by direct staining of DNA with ethidium bromide. Total technician time required for extraction, amplification and detection of 96 samples is about 4 h, and this time requirement can be reduced by automation. Excluding labor, cost per sample is less than $0.40. The method is tested using the codominant isozyme marker, alcohol dehydrogenase (Adh-1) gene in pea (Pisum sativum), and applied to the screening of photoperiod genes in common bean (Phaseolus vulgaris L.).

To extract line drawings with positional information from perspective veiws of three-dimensional objects is essential in image analysis and understanding. A new heuristic-search algorithm driven by a priori knowledge contained in a world model is presented which extracts a connected line drawing from a perspective view of a polyhedron. A main feature of our algorithm is that the search is concentrated on local areas centered at corners found with a corner finder. Therefore, the search time is significantly reduced and so are the positional errors in the extracted line drawing. An iterative process removes the false corners and lines and thus guarantees that our algorithm will work stably and reliably even in a noisy environment. Experimental results are presented.

We present a novel approach for finding corresponding points between two line drawings extracted from perspective views of a moving object whose surface is composed of planar polygons. In our approach, each circuit of the drawings is encoded with a boundary shape code which we call the RLCC code (run length code of convex and concave strings), then a clustering technique is used to obtain the matching result recursively. A series of measures are taken to make the algorithm tolerate considerable dissimilarities which may exist between the two drawings, such as missing lines, scale differences, rotation, perspective shape distortions, etc. Experimental results are presented.