Programmed cell death 10 can be used as a potential biomarker for ankylosing spondylitis diagnosis and treatment.

STUDY DESIGN: Diagnostic study. OBJECTIVE: Programmed cell death 10 (PDCD10) is a new versatile molecule involved in signal transduction regulation in angiogenesis and tumors. The potential of using it as a biomarker for the diagnosis of ankylosing spondylitis (AS) is still unknown. SETTING: University laboratory in Gannan Medical University, China. METHODS: Expression of PDCD10 was analyzed using clinical samples of patients with AS and Gene Expression Omnibus (GEO) data GDS5231. To explore its function, PDCD10 was upregulated and downregulated in synovial cells. Spearman analysis was used to study the association between PDCD10 and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). The Receiver operating characteristic (ROC) curve was applied to evaluate the sensitivity and specificity of PDCD10. RESULTS: Expression of PDCD10 was upregulated in patients with AS and it is capable of promoting the calcification of synovial cells. A positive association between PDCD10 and the BASDAI and the mSASSS was observed. The area under the ROC curve (AUC) of PDCD10 was 82% with a 95% confidence interval of [0.772, 0.868]. CONCLUSIONS: PDCD10 is upregulated in patients with AS and it can promote the calcification of synovial cells in vitro. PDCD10 is positively associated with outcome parameters of AS. ROC analysis of PDCD10 suggests that it can be used as a biomarker for the diagnosis and treatment of AS.

CAD Modeling method of the electrospun membrane under multifractal dimension optimization control.

Based on an analysis of large sample data, this paper improves the calculation method of the fractal dimension in an electrospun membrane and proposes a method to generate a computer-aided design (CAD) model of an electrospun membrane under the control of fractal dimension. Fifteen electrospun membrane samples of PMMA and PMMA/poly(vinylidene fluoride) (PVDF) materials were prepared under similar concentrations and voltage parameters, and 525 SEM images of the surface morphology with a resolution of 2560 × 1920 were taken as a dataset. The feature parameters, such as fiber diameter and direction, are extracted from the image. Second, based on the minimum value of the power law behavior, the pore perimeter data were preprocessed to calculate the fractal dimensions. A 2D model was reconstructed randomly based on the inverse transformation of the characteristic parameters. The genetic optimization algorithm adjusts the fiber arrangement to realize the control of characteristic parameters, such as the fractal dimension. Based on the 2D model, a long fiber network layer with a thickness consistent with the depth of the SEM shooting is generated in ABAQUS software. Finally, a solid CAD model of the electrospun membrane with realistic thickness was constructed by combining multiple fiber layers. The result shows that the improved fractal dimension exhibits multifractal characteristics and distinct sample differences, which are more similar to the experimental results. The proposed 2D modeling method of the long fiber network can allow the control of various characteristic parameters, including the fractal dimension, and can generate the required model quickly.

Pseudolycorine chloride ameliorates Th17 cell-mediated central nervous system autoimmunity by restraining myeloid-derived suppressor cell expansion.

CONTEXT: The alkaloids of Narcissus tazetta L. var. Chinensis Roem (Amaryllidaceae) have antitumor and antiviral activities. However, the immunopharmacological effects of one of its constituents, pseudolycorine chloride (PLY), have not been reported yet. OBJECTIVE: We evaluated the effect of PLY on myeloid-derived suppressor cells (MDSCs) expansion and differentiation into monocyte-like MDSCs (M-MDSCs) and examined whether PLY alleviates Th17 cell-mediated experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS). MATERIALS AND METHODS: In vitro, MDSCs were treated with PLY (0.67, 2 and 6 µM) or solcitinib (10 µM, positive control) for 48 or 96 h, and their proliferation, expansion, and differentiation into M-MDSCs were examined by flow cytometry. Myelin oligodendrocyte glycoprotein (MOG35-55) was used to induce EAE in female C57BL/6 mice, and the mice were treated with 40 mg/kg/d PLY or 1 mg/kg/d FK-506 (tacrolimus, positive control) for 21 days. Inflammatory infiltration, spinal cord demyelination, and MDSCs and Th17 cells infiltration into the spinal cord were examined using haematoxylin and eosin staining, Luxol fast blue staining, and immunofluorescence, respectively. RESULTS: In vitro, PLY (IC50/24 h = 6.18 µM) significantly inhibited IL-6 and GM-CSF-induced MDSCs proliferation, expansion and differentiation into M-MDSCs at all concentrations used. However, these concentrations did not show cytotoxicity. In mice, PLY (40 mg/kg) treatment alleviated EAE and inhibited inflammatory infiltration, demyelination, and MDSCs and Th17 cells infiltration into the spinal cord. DISCUSSION AND CONCLUSIONS: PLY may be an excellent candidate for the treatment of MS and other autoimmune diseases.

Down-regulated miR-495 can target programmed cell death 10 in ankylosing spondylitis.

BACKGROUND: MicroRNAs (miRNAs) play crucial roles in regulating eukaryotic gene expression. Recent studies indicated that aberrantly expressed miRNAs are involved in the pathogenesis of ankylosing spondylitis (AS). Indeed, hsa-miR-495-3p (miR-495) has been reported as an anti-oncogene in different cancers. However, the role of miR-495 in AS is still unknown. METHODS: In this study, quantitative real-time polymerase chain reaction (PCR) was used to detect the expression of miR-495 in the peripheral blood mononuclear cells (PBMCs), whole blood, and serum of patients with AS. Bisulfite-specific PCR sequencing and methylated DNA immunoprecipitation were used to detect the methylation in the promoter region of miR-495. To determine the influence of miR-495 expression on the target gene, programmed cell death 10 (PDCD10), dual luciferase reporter assays together with an adenoviral vector containing the miR-495 locus were used. Receiver operating characteristic (ROC) curves were used to evaluate the efficacy of miR-495 as a diagnostic biomarker of AS. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway analysis, and western blotting were used to explore the potential role of miR-495 in AS pathogenesis and the mechanism by which it facilitates AS pathogenesis. RESULTS: miR-495 is down-regulated and the promoter region of miR-495 is highly methylated in AS. The expression of miR-495 is negatively associated with PDCD10 expression in both patients with AS and healthy controls. Further experiments showed that PDCD10 can be targeted by miR-495. The ROC curves of miR-495 suggested that it is a very specific and sensitive biomarker for AS diagnosis. Bioinformatics analysis and signal pathway studies indicated that miR-495 can down-regulate ß-catenin and transforming growth factor-ß1. CONCLUSIONS: Our studies indicated that down-regulation of miR-495 can be used as a potential molecular marker for the diagnosis and treatment of AS, thus providing new insights into the role of miRNAs in AS pathology.

Transcriptome analysis of ovarian maturation in a chondrostei Chinese sturgeon Acipenser sinensis.

Chinese sturgeon (Acipenser sinensis) with an evolutionary history of over 200 million years, has a long lifespan, and an extremely late and asynchronous sexual maturation (8-18 years for males and 14-26 years for females), resulting in the difficulty of mature adult culture. However, little is known about the regulatory mechanisms of the transition among ovarian maturation stages in the Chinese sturgeon. We performed de novo transcriptome sequencing of the Chinese sturgeon at different ovarian maturation stages (FII, FIII, and FIV). The number of differentially expressed genes (DEGs) between FII and FIII/FIV (33,517/34,217) was more than that between FIII and FIV (22,123), suggesting that the transition from FII to FIII/FIV is more important than that from FIII to FIV for ovarian maturation. The number of upregulated genes was more than that of the downregulated genes, suggesting that increased gene expression was involved in the transition from FII to FIII/FIV. The representative pathways of DEGs were steroid biosynthesis, fatty acid biosynthesis, fatty acid elongation, glycerolipid metabolism, biosynthesis of unsaturated fatty acid, and α-linolenic acid metabolism. The differential expressions from the transcriptome sequencing were validated with real-time reverse-transcription polymerase chain reaction. We also found 13 genes in sexual development, female sex determination, gonadal development, ovarian maturation, ovarian follicle development, and oocyte development pathways, which were differently expressed among fish at FII, FIII, and FIV. We suggest that enhanced synthesis of steroid, unsaturated fatty acid, and α-linolenic acid may contribute to ovarian maturation of the Chinese sturgeon. These potential determinants provide a glimpse of the molecular architecture of ovary development in sturgeons.

[The Effects of PKCι on Anti-tumor Activity of Cytokine-induced Killer Cells Against Pancreatic Cancer Cells and the Possible Underlying Mechanisms].

OBJECTIVE: To study the impact of atypical protein kinase Cι (PKCι) isoform PKC on the pancreatic cancer cells towards the tumoricidal effect of cytokine-induced killer (CIK) cells and explore its mechanisms. METHODS: CIK cells were prepared by inducing mononuclear cells isolated from the peripheral blood of healthy people with interleukin-2 (IL-2), interferon (IFN) and CD3 mAb and subsequently co-cultured with pancreatic epithelial cell HPDE6-C7, pancreatic cancer cells MiaPaCa and PANC-1 with or without PKC inhibitor named sodium thiomalate (ATM). All cells were divided into control group, ATM group, co-culture group with CIK and co-culture group with CIK+ATM. Cell count was used to detect the growth of each group from 1 to 8 d. Flow cytometry was used to detect the death rate of the cell lines after 48 h cell culture in each group. The small hairpin RNA (shRNA) was used for PKCι knockdown and the recombinant plasmid transfection was for PKCι overexpression in pancreatic cancer cells. Western blot and real-time fluorescent quantitative PCR (qRT-PCR) were utilized to determine the expression of PKCι protein and the impact on gene expression of transforming growth factor-ß (TGF-ß), a downstream effector modulated by PKC. Different mass concentrations of TGF-ß (1, 10, 20 ng/mL) were added into the co-culture of MiaPaCa and PANC-1 with CIK. The cell death rate was detected by flow cytometry 48 h later, so as to explore the possible mechanisms of the impact of PKCι on the tumoricidal effects of CIK cells. RESULTS: ATM and CIK were shown to suppress the growth and induce apoptosis or death of pancreatic cancer cells, meanwhile, ATM can enhance the tumoricidal effect of CIK on pancreatic cancer cells. Moreover, we found that PKCι knockdown in pancreatic cancer cells can down-regulate the gene expression of TGF-ß. In return, PKCι overexpression in pancreatic cancer cells can increase the gene expression of TGF-ß. The death rate of cancer cells with 10, 20 ng/mL TGF-ß was lower compared with the control group (P < 0.05). CONCLUSIONS: PKCι knockdown in pancreatic cancer cells can not only inhibit the growth of pancreatic cancer cells, but also enhance the tumoricidal effects of CIK on cancer cells. The possible mechanism of PKCι is to affect the immune escape of tumor cells by regulating the expression of TGF-ß.

K313, a novel benzoxazole derivative, exhibits anti-inflammatory properties via inhibiting GSK3ß activity in LPS-induced RAW264.7 macrophages.

Benzoxazole and its derivatives have been widely studied in recent years due to their various biological properties. A previous study has demonstrated that K313 (1H-indole-2,3-dione 3-(1,3-benzoxazol-2-ylhydrazone)), a novel benzoxazole derivative, inhibits T cell proliferation to yield immunosuppressive effects. However, there are no related reports about its anti-inflammatory effects. In the present study, we investigated the anti-inflammatory properties and the underlying molecular mechanism of K313 in lipopolysaccharide (LPS)-induced RAW264.7 macrophages. K313 dose-dependently (5, 10, and 20 µM) inhibited LPS-stimulated nitric oxide (NO), interleukin (IL)-6, tumor necrosis factor (TNF)-α, and 3-nitrotyrosine (3-NT) production and significantly decreased the gene transcription levels of inducible nitric oxide (iNOS), IL-6, and TNF-α. In addition, the results showed that the inflammatory cytokines suppressed by K313 were not regulated by p65 NF-κB, ERK1/2, AKT, or p38 MAPK. Instead, K313 increased phosphorylation of glycogen synthase kinase-3 beta (GSK-3ß) (Ser9) resulting in GSK-3ß deactivation. Moreover, in LPS-stimulated RAW264.7 macrophages, K313 and lithium chloride (LiCl) had a synergistic effect on the anti-inflammatory response. These results indicated that K313 exhibited anti-inflammatory properties and revealed the potential mechanism. K313 can increase GSK-3ß (Ser9) phosphorylation to decrease GSK-3ß activation in LPS-induced RAW264.7 macrophages.

Noncoding RNAs in Calcific Aortic Valve Disease: A Review of Recent Studies.

Calcific aortic valve disease (CAVD) is the most common heart valve disorder in human populations. Nevertheless, there are presently no effective means for its prevention and treatment. It is therefore critical to comprehensively define key mechanisms of the disease. A major focus of cardiovascular research has been characterization of how regulation of gene expression maintains healthy physiologic status of the component tissues of the system and how derangements of gene regulation may become pathological. Recently, substantial evidence has emerged that noncoding RNAs, which are an enormous and versatile class of regulatory elements, such as microRNAs and long noncoding RNAs, have roles in onset and prognosis of CAVD. Authors of the present report have therefore here provided a summary of the current understanding of contributions made by noncoding RNAs major features of CAVD. It is anticipated that this article will serve as a valuable guide to research strategy in this field and may additionally provide both researchers and clinicians with an expanded range of CAVD-associated biomarkers.

Cardioprotective effects of rutin in rats exposed to pirarubicin toxicity.

We established both an acute and chronic cardiac toxicity rat model, which showed pretreatment with rutin attenuated pirarubicin-induced myocardial histopathological injury, electrocardiogram abnormalities, and cardiac dysfunction. Rutin also significantly reduced serum levels of MDA, BNP, CK-MB, CTnT, and LDH and increased serum SOD levels. Treatment with rutin and dexrazoxane resulted in an increase in Bcl-2/Bax ratio (p < 0.05) and reduction in JNK and Caspase-3 protein levels, compared to the pirarubicin group (all p < 0.05). Furthermore, rutin at a dose of 50 mg/kg significantly attenuated the above-mentioned alterations. Our study suggests the antioxidant and anti-apoptotic properties of rutin may be responsible for the cardioprotective effects observed.

Tolerogenic dendritic cells induced by BD750 ameliorate proinflammatory T cell responses and experimental autoimmune encephalitis in mice.

BD750, a novel JAK3/STAT5 inhibitor, can inhibit T cell proliferation. This study aims to evaluate whether BD750 can induce tolerogenic dendritic cells (tolDC) and their function in experimental autoimmune encephalitis (EAE) in mice. Following BD750 treatment, LPS-induced maturation of DC, allogeneic T cell proliferation, Th1 and Th17 cell functional differentiation, the STAT5 and AKT activation were determined. The effect of tolDC loaded with antigen peptide on the development and severity of EAE and their splenic Th1 and Th17 cell responses were determined. In comparison with LPS-induced mature DC (mDC), BD750 treatment induced tolDC with lower expression levels of costimulatory molecules and pro-inflammatory cytokines and lower levels of STAT5 phosphorylation. TolDC inhibited allogeneic T cell proliferation and reduced Th1 and Th17 responses. Adoptive transfer of tolDC loaded with MOG35-55 inhibited the development and severity of EAE in mice, accompanied by reduced numbers of inflammatory infiltrates and decreased levels of demyelination in the spinal cord tissues of mice. In addition, treatment with tolDC loaded with antigen peptide also significantly reduced the frequency of splenic Th1 and Th17 cells in EAE mice. The effects of tolDC were similar to that of the JAK/STAT inhibitor, CP690550-treated DC. In conclusion, treatment with BD750 induced tolDC that inhibited pro-inflammatory T cell immunity in vitro and in vivo. BD750 and tolDC may be valuable for development of new therapies for EAE and other autoimmune diseases.

Good outcome of severe lupus patients with high-dose immunosuppressive therapy and autologous peripheral blood stem cell transplantation: a 10-year follow-up study.

OBJECTIVES: This study aimed to examine the long-term efficacy, remission and survival of patients with severe systemic lupus erythematosus (SLE) after the combination treatment with high-dose immunosuppressive therapy (HDIT) and autologous peripheral blood stem cell transplantation (APBSCT). METHODS: Chinese patients with severe SLE receiving combination therapy with HDIT and APBSCT in Peking Union Medical College Hospital were enrolled from July 1999 to October 2005. Disease activity, treatment, and adverse effects of these patients were evaluated. The 10-year overall survival and 10-year remission survival were also analysed. RESULTS: Among the 27 patients, one patient failed to collect enough CD34+ cells and data was missing for two patients. In the end, 24 patients were included in the final analysis. After APBSCT, one patient died, two patients achieved partial remission and 21 (87.5%) achieved remission at 6 months. The median follow-up duration of the 23 patients was 120 months. Fourteen patients had completed a ten-year follow-up. The median proteinuria level of the 14 patients with LN with ten years of follow-up significantly decreased from 4.00 g/24 hours at pre-treatment to 0.00g/24 hours at year 5 and 0.00 g/24 hours at year 10 (both p=0.001). The 10-year overall survival rate and 10-year remission survival rate were both 86.0% (95% CI: 71.1-100.9%). After a median follow-up for 120 months, 16 patients (66.7%) remained in remission, 4 patients were lost to follow-up, 2 patients died and 1 patient remained active. CONCLUSIONS: The combination of HDIT and APBSCT may be an option to improve the survival of severe lupus patients.

Identification and characterization of lymph organ microRNAs in red swamp crayfish, Procambarus clarkii infected with white spot syndrome virus.

MicroRNAs (miRNAs) were important post-transcriptional regulators and played vital roles in innate immunity system of invertebrates, especially in the aspect of antivirus. In this study, using high-throughput small RNAs Illumina sequencing system, differentially expressed miRNAs (DEMs) from lymph organs in red swamp crayfish, Procambarus clarkii, infected with white spot syndrome virus, were identified. As a result, 32 known miRNAs and 7 novel miRNAs were identified in crayfish lymph organ small RNAs library of NG and WG. Among them, 7 differentially expressed miRNAs (DEMs) were predicted to be involved in the lymph organ antiviral innate immunity of P. clarkii. Besides, the results showed that putative target genes of these DEMs were related with tight junction, RNA transport, regulation of actin cytoskeleton, focal adhesion, vascular smooth muscle contraction, mRNA surveillance pathway, NOD-like receptor signaling pathway, leukocyte transendothelial migration, and protein processing in endoplasmic reticulum. These results might provide the guiding theoretical foundation for future studies about crustaceans' antiviral innate immunity.

Congenital microcornea-cataract syndrome-causing mutation X253R increases ßB1-crystallin hydrophobicity to promote aggregate formation.

The high solubility and lifelong stability of crystallins are crucial to the maintenance of lens transparency and optical properties. Numerous crystallin mutations have been linked to congenital cataract, which is one of the leading causes of newborn blindness. Besides cataract, several crystallin mutations have also been linked to syndromes such as congenital microcornea-cataract syndrome (CMCC). However, the molecular mechanism of CMCC caused by crystallin mutations remains elusive. In the present study, we investigated the mechanism of CMCC caused by the X253R mutation in ßB1-crystallin. The exogenously expressed X253R proteins were prone to form p62-negative aggregates in HeLa cells, strongly inhibited cell proliferation and induced cell apoptosis. The intracellular X253R aggregates could be successfully redissolved by lanosterol but not cholesterol. The extra 26 residues at the C-terminus of ßB1-crystallin introduced by the X253R mutation had little impact on ßB1-crystallin structure and stability, but increased ßB1-crystallin hydrophobicity and decreased its solubility. Interestingly, the X253R mutant fully abolished the aggregatory propensity of ßB1- and ßA3/ßB1-crystallins at high temperatures, suggesting that X253R was an aggregation-inhibition mutation of ß-crystallin homomers and heteromers in dilute solutions. Our results suggest that an increase in hydrophobicity and a decrease in solubility might be responsible for cataractogenesis induced by the X253R mutation, while the cytotoxic effect of X253R aggregates might contribute to the defects in ocular development. Our results also highlight that, at least in some cases, the aggregatory propensity in dilute solutions could not fully mimic the behaviours of mutated proteins in the crowded cytoplasm of the cells.

Conservation and divergence of transcriptional coregulations between box C/D snoRNA and ribosomal protein genes in Ascomycota.

Coordinated assembly of the ribosome is essential for proper translational activity in eukaryotic cells. It is therefore critical to coordinate the expression of components of ribosomal programs with the cell's nutritional status. However, coordinating expression of these components is poorly understood. Here, by combining experimental and computational approaches, we systematically identified box C/D snoRNAs in four fission yeasts and found that the expression of box C/D snoRNA and ribosomal protein (RP) genes were orchestrated by a common Homol-D box, thereby ensuring a constant balance of these two genetic components. Interestingly, such transcriptional coregulations could be observed in most Ascomycota species and were mediated by different cis-regulatory elements. Via the reservation of cis elements, changes in spatial configuration, the substitution of cis elements, and gain or loss of cis elements, the regulatory networks of box C/D snoRNAs evolved to correspond with those of the RP genes, maintaining transcriptional coregulation between box C/D snoRNAs and RP genes. Our results indicate that coregulation via common cis elements is an important mechanism to coordinate expression of the RP and snoRNA genes, which ensures a constant balance of these two components.

[Study on the Synergistic Antioxidant Mechanism of Chlorogenic Acids (CQAs) with Electrochemical and Spectroscopy Property].

The synergistic antioxidant mechanism of chlorogenic acids (CQAs) was studied in this paper through cyclic voltammograms (CV), oil-water partition coefficient (P), FT-IR, XRD and circular dichroism (CD). The antioxidant capability of CQAs isomers and their mixture was determined by using ABTS free radical quenching ability assay. The results showed that the bigger the antioxidant activity disparity between the CQAs molecules was, the higher the content of high antioxidant activity CQAs was, the better the synergistic effect of the CQAs combination mixture became; The oxidation potential (Epa) of CQAs combination mixture kept constant in the synergistic experiments, which indicted the oxidative coupling interaction don't exist between the CQAs; The charge transferred (Q) and antioxidant activity exhibited high correlation (0.92); the practical Q was higher than the theoretical Q in the synergistic process and this confirmed that the CQAs (dicaffeoylquinic acids) regeneration of high antioxidant activity happened; the CQAs mixture with the absolute difference value of oil-water partition coefficient of 0.13 gave the good interface effect and high synergistic degree; the interaction and the regular arrangement between the CQAs combination were not discovered through FT-IR, XRD and CD. Therefore, the regeneration mechanism of CQAs molecules and the interface effect of reaction system were the main cause of the phenomenon of the synergistic antioxidant of CQAs.

The importance of the last strand at the C-terminus in ßB2-crystallin stability and assembly.

Congenital cataract is the leading cause of childhood blindness worldwide. Investigations of the effects of inherited mutations on protein structure and function not only help us to understand the molecular mechanisms underlying congenital hereditary cataract, but also facilitate the study of complicated cataract and non-lens abnormities caused by lens-specific genes. In this research, we studied the effects of the V187M, V187E and R188H mutations on ßB2-crystallin structure and stability using a combination of biophysical, cellular and molecular dynamic simulation analysis. Both V187 and R188 are located at the last strand of ßB2-crystallin Greek-key motif 4. All of the three mutations promoted ßB2-crystallin aggregation in vitro and at the cellular level. These three mutations affected ßB2-crystallin quite differentially: V187M influenced the hydrophobic core of the C-terminal domain, V187E was a Greek-key motif breaker with the disruption of the backbone H-bonding network, while R188H perturbed the dynamic oligomeric equilibrium by dissociating the dimer and stabilizing the tetramer. Our results highlighted the importance of the last strand in the structural integrity, folding, assembly and stability of ß-crystallins. More importantly, we proposed that the perturbation of the dynamic equilibrium between ß-crystallin oligomers was an important mechanism of congenital hereditary cataract. The selective stabilization of one specific high-order oligomer by mutations might also be deleterious to the stability and folding of the ß-crystalllin homomers and heteromers. The long-term structural stability and functional maintenance of ß-crystallins are achieved by the precisely regulated oligomeric equilibrium.

Three-dimensional transesophageal echocardiographic study of aortic-mitral valve coupling after coronary artery bypass grafting.

AIMS: To observe the geometric changes in aortic-mitral valve coupling (AMC) on three-dimensional transesophageal echocardiography and the factors leading to decreased mitral regurgitation (MR) after coronary artery bypass grafting (CABG). METHODS AND RESULTS: This study included 23 patients undergoing CABG for coronary artery disease. Fifteen patients with moderate to severe MR were separately analyzed to determine whether the severity of MR influences the geometric change in AMC. Echocardiographic examinations were performed pre- and post-CABG, and the studied parameters were obtained using Siemens Auto Valve Analysis software. The effective mitral regurgitant orifice area, left ventricular ejection fraction (LVEF), end-diastolic volume (EDV), and end-systolic volume (ESV) were measured pre- and post-CABG using Philips QLAB software. Ischemic MR, EDV, and ESV significantly decreased (all P < 0.05) and LVEF significantly improved (P < 0.05) after CABG. There were no significant differences between the pre- and post-CABG mitral valve (MV) parameters, aortic valve parameters, aortic-mitral annular angle, or centroid distance (all P > 0.05). Patients with moderate to severe MR exhibited the same results. CONCLUSION: The results of this study show that CABG does not cause an acute change in the geometry of AMC. Improved left ventricular function might increase the closing force of the MV, leading to decreased MR after CABG alone. MR significantly improved after CABG alone without MV treatment in the present study. This result may help to guide surgeons in choosing the optimal surgical methods for individual patients.

The N-terminal extension of ßB1-crystallin chaperones ß-crystallin folding and cooperates with αA-crystallin.

ß/γ-Crystallins are the major structural proteins in mammalian lens. The N-terminal truncation of ßB1-crystallin has been associated with the regulation of ß-crystallin size distributions in human lens. Herein we studied the roles of ßB1 N-terminal extension in protein structure and folding by constructing five N-terminal truncated forms. The truncations did not affect the secondary and tertiary structures of the main body as well as stability against denaturation. Truncations with more than 28 residues off the N-terminus promoted the dissociation of the dimeric ßB1 into monomers in diluted solutions. Interestingly, the N-terminal extension facilitated ßB1 to adopt the correct folding pathway, while truncated proteins were prone to undergo the misfolding/aggregation pathway during kinetic refolding. The N-terminal extension of ßB1 acted as an intramolecular chaperone (IMC) to regulate the kinetic partitioning between folding and misfolding. The IMC function of the N-terminal extension was also critical to the correct refolding of ß-crystallin heteromer and the action of the lens-specific molecular chaperone αA-crystallin. The cooperation between IMC and molecular chaperones produced a much stronger chaperoning effect than if they acted separately. To our knowledge, this is the first report showing the cooperation between IMC and molecular chaperones.

The ribosomal protein rpl26 promoter is required for its 3' sense terminus ncRNA transcription in Schizosaccharomyces pombe, implicating a new transcriptional mechanism for ncRNAs.

Transcriptome studies have revealed that many non-coding RNAs (ncRNAs) are located near the 3' sense terminus of protein-coding genes. However, the transcription and function of these RNAs remain elusive. Here, we identify a 3' sense termini-associated sRNA (TASR) downstream of rpl26 in Schizosaccharomyces pombe (S. pombe). Structure and function assays indicate that the TASR is an H/ACA box snoRNA required for 18S rRNA pseudouridylation at U121 and U305 sites and is therefore a cognate of snR49 from the budding yeast. Transcriptional studies show that pre-snR49 overlaps most of the coding sequence (CDS) of rpl26. Using scanning deletion analysis within promoter region, we show that the rpl26 promoter is required for the 3' TASR transcription. Interestingly, chromosomal synteny of rpl26-snR49 is found in the Schizosaccharomyces groups. Taken together, we have revealed a new transcriptional mechanism for 3' sense TASRs, which are transcribed by the same promoter as their upstream protein genes. These results further suggest that the origin and function of 3' sense ncRNAs are associated with upstream genes in higher eukaryotes.

Differences and Correlations of Morphological and Hemodynamic Parameters between Anterior Circulation Bifurcation and Side-wall Aneurysms.

OBJECTIVE: The objective of this research was to explore the difference and correlation of the morphological and hemodynamic features between sidewall and bifurcation aneurysms in anterior circulation arteries, utilizing computational fluid dynamics as a tool for analysis. METHODS: In line with the designated inclusion criteria, this study covered 160 aneurysms identified in 131 patients who received treatment at Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, China, from January 2021 to September 2022. Utilizing follow-up digital subtraction angiography (DSA) data, these cases were classified into two distinct groups: the sidewall aneurysm group and the bifurcation aneurysm group. Morphological and hemodynamic parameters in the immediate preoperative period were meticulously calculated and examined in both groups using a three-dimensional DSA reconstruction model. RESULTS: No significant differences were found in the morphological or hemodynamic parameters of bifurcation aneurysms at varied locations within the anterior circulation. However, pronounced differences were identified between sidewall and bifurcation aneurysms in terms of morphological parameters such as the diameter of the parent vessel (Dvessel), inflow angle (θF), and size ratio (SR), as well as the hemodynamic parameter of inflow concentration index (ICI) (P<0.001). Notably, only the SR exhibited a significant correlation with multiple hemodynamic parameters (P<0.001), while the ICI was closely related to several morphological parameters (R>0.5, P<0.001). CONCLUSIONS: The significant differences in certain morphological and hemodynamic parameters between sidewall and bifurcation aneurysms emphasize the importance to contemplate variances in threshold values for these parameters when evaluating the risk of rupture in anterior circulation aneurysms. Whether it is a bifurcation or sidewall aneurysm, these disparities should be considered. The morphological parameter SR has the potential to be a valuable clinical tool for promptly distinguishing the distinct rupture risks associated with sidewall and bifurcation aneurysms.