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Jiong Zhang - Top 30 Publications

Scalable Convex Multiple Sequence Alignment via Entropy-Regularized Dual Decomposition.

Multiple Sequence Alignment (MSA) is one of the fundamental tasks in biological sequence analysis that underlies applications such as phylogenetic trees, profiles, and structure prediction. The task, however, is NP-hard, and the current practice resorts to heuristic and local-search methods. Recently, a convex optimization approach for MSA was proposed based on the concept of atomic norm [23], which demonstrates significant improvement over existing methods in the quality of alignments. However, the convex program is challenging to solve due to the constraint given by the intersection of two atomic-norm balls, for which the existing algorithm can only handle sequences of length up to 50, with an iteration complexity subject to constants of unknown relation to the natural parameters of MSA. In this work, we propose an accelerated dual decomposition algorithm that exploits entropy regularization to induce closed-form solutions for each atomic-norm-constrained subproblem, giving a single-loop algorithm of iteration complexity linear to the problem size (total length of all sequences). The proposed algorithm gives significantly better alignments than existing methods on sequences of length up to hundreds, where the existing convex programming method fails to converge in one day.

Therapeutic Mechanism of Glucocorticoids on Cellular Crescent Formation in Patients With Antiglomerular Basement Membrane Disease.

This study aimed to explore the therapeutic mechanism of glucocorticoids (GCs) in antiglomerular basement membrane disease.

Substitution urethroplasty for anterior urethral stricture repair: comparison between lingual mucosa graft and pedicled skin flap.

The aim of this study was to compare the effectiveness and outcomes of lingual mucosa graft (LMG) urethroplasty versus pedicled skin flap (PSF) urethroplasty in the repair of anterior urethral strictures.

Connexin43, but not connexin30, contributes to adult neurogenesis in the dentate gyrus.

The subgranular zone of the dentate gyrus represents a niche in which radial glia (RG)-like cells generate new neurons throughout postnatal life in the mammalian brain. Previous data showed that RG-like cells are coupled through gap junction channels, primarily formed by connexin43 (Cx43) and Cx30, and that the expression of these proteins is required for adult neurogenesis in the hippocampus. However, their individual function and underlying mechanisms remain unclear. Here we demonstrate that Cx43, but not Cx30, is crucial for adult neurogenesis. To assess whether Cx43-dependent intercellular coupling between RG-like cells or rather channel-independent interactions of the protein regulate neurogenesis, mice bearing a Cx43 point mutation (Cx43G138R) in RG-like cells and protoplasmic astrocytes cells were employed, which was expected to cause channel closure without affecting the trafficking of the protein to the membrane. We confirmed the disruption of coupling between RG-like cells and astrocytes in the hippocampus of Cx43G138R mice. Proliferative activity and neurogenesis in the DG were significantly decreased in the mutant mouse line, indicating that functional Cx43 channels are essential for proper adult neurogenesis. The fate of proliferating cells in the DG was not affected by Cx43 mutation as revealed by 5-bromo-2-deoxyuridine (BrdU) incorporation assays. Together, these findings suggest that adult neurogenesis in the hippocampus does not require Cx30 but channel-dependent functions of Cx43.

New Interleukins in Psoriasis and Psoriatic Arthritis Patients: The Possible Roles of Interleukin-33 to Interleukin-38 in Disease Activities and Bone Erosions.

New interleukins (ILs), especially members of IL-1 and IL-12 families, have recently been reported to be involved in the development and regulation of autoimmune and inflammatory diseases. In this study, we aimed to explore the impact of these new ILs in psoriasis (Ps) and psoriatic arthritis (PsA).

Retrieving challenging vessel connections in retinal images by line co-occurrence statistics.

Natural images contain often curvilinear structures, which might be disconnected, or partly occluded. Recovering the missing connection of disconnected structures is an open issue and needs appropriate geometric reasoning. We propose to find line co-occurrence statistics from the centerlines of blood vessels in retinal images and show its remarkable similarity to a well-known probabilistic model for the connectivity pattern in the primary visual cortex. Furthermore, the probabilistic model is trained from the data via statistics and used for automated grouping of interrupted vessels in a spectral clustering based approach. Several challenging image patches are investigated around junction points, where successful results indicate the perfect match of the trained model to the profiles of blood vessels in retinal images. Also, comparisons among several statistical models obtained from different datasets reveal their high similarity, i.e., they are independent of the dataset. On top of that the best approximation of the statistical model with the symmetrized extension of the probabilistic model on the projective line bundle is found with a least square error smaller than [Formula: see text]. Apparently, the direction process on the projective line bundle is a good continuation model for vessels in retinal images.

Intermediate-Term Outcomes and Complications of Long Segment Urethroplasty with Lingual Mucosa Grafts.

We evaluated outcomes and donor site complications in male patients with complex urethral strictures who underwent urethroplasty using with long strip oral mucosal grafts. We also analyzed whether a lingual mucosa graft is a good substitute for repairing long segment urethral strictures.

Facile Synthesis for Benzo-1,4-Oxazepine Derivatives by Tandem Transformation of C-N Coupling/C-H Carbonylation.

A tandem transformation of C-N coupling/C-H carbonylation has been developed for the synthesis of benzo-1,4-oxazepine pharmaceutically derivatives. Notably, this reaction was accomplished by various phenylamine with ally halides under carbon dioxide atmosphere employing 2-(2-dimethylamino-vinyl)-1H-inden-1-olcatalyzed. Furthermore, under the optimized conditions, various benzo-1,4-oxazepine derivatives were obtained in good yields. Finally, a plausible Cu(I)/Cu(III) mechanism of C-N coupling/C-H carbonylation transformation was proposed.

Interleukin 37 limits monosodium urate crystal-induced innate immune responses in human and murine models of gout.

Interleukin (IL)-37 has emerged as a fundamental inhibitor of innate immunity. Acute gout is a self-limiting inflammatory response to monosodium urate (MSU) crystals. In the current study, we assessed the preventive and therapeutic effect of recombinant human IL-37 (rhIL-37) in human and murine gout models.

HMGB1-TLR4 signaling participates in renal ischemia reperfusion injury and could be attenuated by dexamethasone-mediated inhibition of the ERK/NF-κB pathway.

Studies have shown that the HMGB1-TLR4 (High-mobility group protein B1, toll-like receptor 4) pathway participates in renal ischemic reperfusion injury (IRI) and that dexamethasone (DEX) could protect the kidney against IRI. This study aims to examine the protective effects of DEX on renal IRI and further explore the possible mechanism of action. During mouse renal IRI, HMGB1-TLR4 signals changed markedly including HMGB1 translocation and TLR4 up-regulation, resulting in histological damage and an increase in MPO expression. Treatment with DEX markedly decreased the damage to renal function (serum Cr and BUN; kidney KIM-1 expression) and the histological pathology of the kidney after renal IRI. The activation of GR by DEX did not suppress p38 and JNK activity but inhibited ERK phosphorylation. Treatment with DEX also attenuated IκB-α phosphorylation and further reduced NF-κB expression in the nucleus by decreasing acetylation of the p65 subunit. Furthermore, the HMGB1-TLR4 inflammatory pathway was inhibited via the attenuated translocation of HMGB1 from the nucleus to the cytoplasm and the down-regulation of TLR4 expression through DEX treatment. The inhibition of HMGB1 translocation may interact with acetyltransferase and attenuate HMGB1 acetylation. As a result, the levels of cytokines (TNF-α, IL-6, and IL-1β) were down-regulated and inflammatory cell infiltration after renal IRI was attenuated by treatment with DEX. This study demonstrated that the HMGB1-TLR4 pathway may play a critical role in renal IRI. DEX may attenuate renal IRI by suppressing ERK and NF-κB activation, followed by attenuating the HMGB1-TLR4 pathway through inhibiting acetyltransferases.

Reliability of Using Retinal Vascular Fractal Dimension as a Biomarker in the Diabetic Retinopathy Detection.

The retinal fractal dimension (FD) is a measure of vasculature branching pattern complexity. FD has been considered as a potential biomarker for the detection of several diseases like diabetes and hypertension. However, conflicting findings were found in the reported literature regarding the association between this biomarker and diseases. In this paper, we examine the stability of the FD measurement with respect to (1) different vessel annotations obtained from human observers, (2) automatic segmentation methods, (3) various regions of interest, (4) accuracy of vessel segmentation methods, and (5) different imaging modalities. Our results demonstrate that the relative errors for the measurement of FD are significant and FD varies considerably according to the image quality, modality, and the technique used for measuring it. Automated and semiautomated methods for the measurement of FD are not stable enough, which makes FD a deceptive biomarker in quantitative clinical applications.

Differential expression of miR-184 in temporal lobe epilepsy patients with and without hippocampal sclerosis - Influence on microglial function.

Epilepsy is one of the most common neurological disorders characterized by recurrent seizures due to neuronal hyperexcitability. Here we compared miRNA expression patterns in mesial temporal lobe epilepsy with and without hippocampal sclerosis (mTLE + HS and mTLE -HS) to investigate the regulatory mechanisms differentiating both patient groups. Whole genome miRNA sequencing in surgically resected hippocampi did not reveal obvious differences in expression profiles between the two groups of patients. However, one microRNA (miR-184) was significantly dysregulated, which was confirmed by qPCR. We observed that overexpression of miR-184 inhibited cytokine release after LPS stimulation in primary microglial cells, while it did not affect the viability of murine primary neurons and primary astrocytes. Pathway analysis revealed that miR-184 is potentially involved in the regulation of inflammatory signal transduction and apoptosis. Dysregulation of some the potential miR-184 target genes was confirmed by qPCR and 3'UTR luciferase reporter assay. The reduced expression of miR-184 observed in patients with mTLE + HS together with its anti-inflammatory effects indicate that miR-184 might be involved in the modulation of inflammatory processes associated with hippocampal sclerosis which warrants further studies elucidating the role of miR-184 in the pathophysiology of mTLE.

HLA-DR, and not PLA2R, is expressed on the podocytes in kidney allografts in de novo membranous nephropathy.

Idiopathic membranous nephropathy (IMN) is known to be associated with antibodies acting on the M-type phospholipase A2 receptor (PLA2R) of the podocyte. However, the mechanism underlying de novo membranous nephropathy (dn MN) posttransplantation remains unclear. In this study, we aimed to elucidate the mechanism underlying dn MN.We selected 8 cases with dn MN and compared them to 20 IMN cases. Fifteen cases of stable grafts were selected as controls.Several differences between the dn MN group and the IMN group were detected. IgG4 showed negligible positive staining in patients with dn MN, while it was predominant in the IMN group (1/8 vs 20/20, P < 0.001). Serum anti-PLA2R antibodies and anti-PLA2R antibodies of the podocyte were very few in the dn MN patients; however, these antibodies were detected in most of the IMN patients (serum anti-PLA2R antibodies: 1/8 vs 16/20, P = 0.002, anti-PLA2R antibodies of the podocyte: 0/8 vs 17/20, P < 0.001). The dn MN patients also showed higher ratio of interstitial inflammation, peritubular capillaritis, and peritubular capillary C4d deposition. Importantly, human leukocyte antigens (HLA)-DR expression was detected on the podocytes in most of the dn MN patients, but none of the IMN patients and stable graft patients showed HLA-DR expression.These data suggested that the PLA2R pathway, which is known to play a role in IMN, was not involved in the mechanism underlying dn MN. On the contrary, dn MN might be associated with the alloimmune response directed against the podocyte.

A Convex Atomic-Norm Approach to Multiple Sequence Alignment and Motif Discovery.

Multiple Sequence Alignment and Motif Discovery, known as NP-hard problems, are two fundamental tasks in Bioinformatics. Existing approaches to these two problems are based on either local search methods such as Expectation Maximization (EM), Gibbs Sampling or greedy heuristic methods. In this work, we develop a convex relaxation approach to both problems based on the recent concept of atomic norm and develop a new algorithm, termed Greedy Direction Method of Multiplier, for solving the convex relaxation with two convex atomic constraints. Experiments show that our convex relaxation approach produces solutions of higher quality than those standard tools widely-used in Bioinformatics community on the Multiple Sequence Alignment and Motif Discovery problems.

Robust Retinal Vessel Segmentation via Locally Adaptive Derivative Frames in Orientation Scores.

This paper presents a robust and fully automatic filter-based approach for retinal vessel segmentation. We propose new filters based on 3D rotating frames in so-called orientation scores, which are functions on the Lie-group domain of positions and orientations [Formula: see text]. By means of a wavelet-type transform, a 2D image is lifted to a 3D orientation score, where elongated structures are disentangled into their corresponding orientation planes. In the lifted domain [Formula: see text], vessels are enhanced by means of multi-scale second-order Gaussian derivatives perpendicular to the line structures. More precisely, we use a left-invariant rotating derivative (LID) frame, and a locally adaptive derivative (LAD) frame. The LAD is adaptive to the local line structures and is found by eigensystem analysis of the left-invariant Hessian matrix (computed with the LID). After multi-scale filtering via the LID or LAD in the orientation score domain, the results are projected back to the 2D image plane giving us the enhanced vessels. Then a binary segmentation is obtained through thresholding. The proposed methods are validated on six retinal image datasets with different image types, on which competitive segmentation performances are achieved. In particular, the proposed algorithm of applying the LAD filter on orientation scores (LAD-OS) outperforms most of the state-of-the-art methods. The LAD-OS is capable of dealing with typically difficult cases like crossings, central arterial reflex, closely parallel and tiny vessels. The high computational speed of the proposed methods allows processing of large datasets in a screening setting.

Etiology and Management of Male Iatrogenic Urethral Stricture: Retrospective Analysis of 172 Cases in a Single Medical Center.

To investigate the etiology and management of male iatrogenic urethral stricture in China.

Poor performance of Enduron polyethylene liner in total hip arthroplasty: a minimum ten-year follow up and ultra-morphological analysis of wear particles.

The aim of the present study was to investigate the long-term outcome and the wear characteristics of two distinct types of ultra-high molecular weight polyethylene (UHMWPE) liners in total hip arthroplasty (THA).

The Selection of Procedures in One-stage Urethroplasty for Treatment of Coexisting Urethral Strictures in Anterior and Posterior Urethra.

To explore selection of the procedures in one-stage urethroplasty for treatment of coexisting urethral strictures in the anterior and posterior urethra.

Cytomegalovirus Pneumonia in Patients with Rheumatic Diseases After Immunosuppressive Therapy: A Single Center Study in China.

Rheumatic diseases involve multiple organs that are affected by immunological mechanisms. Treatment with corticosteroids and immunosuppressive agents may also increase the frequency of infection. Cytomegalovirus (CMV) is a widespread herpes virus and a well-recognized pathogen, which causes an opportunistic and potentially fatal infection in immunocompromised patients. This retrospective study aimed to investigate the clinical and laboratory characteristics of CMV pneumonia in patients with rheumatic diseases after immunosuppressive therapy in a single center in Shanghai, China.

Anterior Urethra Reconstruction With Lateral Lingual Mucosa Harvesting Technique.

To describe a new technique for harvesting the long lingual mucosal graft (LMG) to repair the long-segment urethral strictures.

Chalcone-benzoxaborole hybrids as novel anticancer agents.

In this study, we report the synthesis of a series of chalcone-benzoxaborole hybrid molecules and the evaluation of their anticancer activity. Their anticancer potency and toxicity were tested on three human cancer cell lines and two normal cell lines. The 4-fluoro compound 15 was found to be the most potent compound with an IC50 value of 1.4μM on SKOV3 cells. The 4-iodo compound 18 and 3-methyloxy-4-amino compound 47 showed good potency on SKOV3 cells while exhibiting low toxicity on normal cells. This work extended the application of benzoxaboroles to the field of anticancer research.

The peroxisome proliferator-activated receptor γ agonist pioglitazone prevents NF-κB activation in cisplatin nephrotoxicity through the reduction of p65 acetylation via the AMPK-SIRT1/p300 pathway.

The thiazolidinedione pioglitazone, which is also a PPAR-γ agonist, now is widely used in patients with hypercholesterolemia and hypertriglyceridemia. NF-κB is a ubiquitously expressed transcription factor controlling the expression of numerous genes involved in inflammation. The aim of the present study was to evaluate whether the activation of PPAR-γ attenuates the cisplatin-induced NF-κB activation in cisplatin nephrotoxicity. The results showed that the PPAR-γ agonist pioglitazone decreased the expression of NF-κB p65 transcription target genes (e.g., IL-6, IL-1β, and TNF-α) and inhibited histological injury and inflammatory cells infiltration in cisplatin nephrotoxicity. The suppression of NF-κB activity following pioglitazone treatment inhibited the cisplatin-induced IκB-α degredation and NF-κB p65 subunit translocation. Translocation of the NF-κB p65 subunit depends on p65 acetylation, which primarily regulated by SIRT1 or p300. Notably, AMP kinase (AMPK) activation not only decreased the phosphorylation, activation and p65 interaction of p300 but also increased SIRT1 expression, activation and p65 binding, thus leading to a significant reduction in p65 acetylation. Interestingly, the reduction of IL-6, TNF-α and IL-1β, the inhibition of histological injury and the inflammatory cells infiltration following pioglitazone treatment in cisplatin nephrotoxicity were attenuated after treatment with the PPAR-γ antagonist GW9662. These results suggest that the PPAR-γ agonist pioglitazone prevents NF-κB activation in cisplatin nephrotoxicity through a reduction in p65 acetylation via the AMPK-SIRT1/p300 pathway.

One-stage dorsal lingual mucosal graft urethroplasty for the treatment of failed hypospadias repair.

The aim of this study was to retrospectively investigate the outcomes of patients who underwent one-stage onlay or inlay urethroplasty using a lingual mucosal graft (LMG) after failed hypospadias repairs. Inclusion criteria included a history of failed hypospadias repair, insufficiency of the local skin that made a reoperation with skin flaps difficult, and necessity of an oral mucosal graft urethroplasty. Patients were excluded if they had undergone a failed hypospadias repair using the foreskin or a multistage repair urethroplasty. Between January 2008 and December 2012, 110 patients with failed hypospadias repairs were treated in our center. Of these patients, 56 underwent a one-stage onlay or inlay urethroplasty using LMG. The median age was 21.8 years (range: 4-45 years). Of the 56 patients, one-stage onlay LMG urethroplasty was performed in 42 patients (group 1), and a modified Snodgrass technique using one-stage inlay LMG urethroplasty was performed in 14 (group 2). The median LMG urethroplasty length was 5.6 ± 1.6 cm (range: 4-13 cm). The mean follow-up was 34.7 months (range: 10-58 months), and complications developed in 12 of 56 patients (21.4%), including urethrocutaneous fistulas in 7 (6 in group 1, 1 in group 2) and neourethral strictures in 5 (4 in group 1, 1 in group 2). The total success rate was 78.6%. Our survey suggests that one-stage onlay or inlay urethroplasty with LMG may be an effective option to treat the patients with less available skin after failed hypospadias repairs; LMG harvesting is easy and safe, irrespective of the patient's age.

Selective refinement and selection of near-native models in protein structure prediction.

In recent years in silico protein structure prediction reached a level where fully automated servers can generate large pools of near-native structures. However, the identification and further refinement of the best structures from the pool of models remain problematic. To address these issues, we have developed (i) a target-specific selective refinement (SR) protocol; and (ii) molecular dynamics (MD) simulation based ranking (SMDR) method. In SR the all-atom refinement of structures is accomplished via the Rosetta Relax protocol, subject to specific constraints determined by the size and complexity of the target. The best-refined models are selected with SMDR by testing their relative stability against gradual heating through all-atom MD simulations. Through extensive testing we have found that Mufold-MD, our fully automated protein structure prediction server updated with the SR and SMDR modules consistently outperformed its previous versions.

Factors that influence the outcome of open urethroplasty for pelvis fracture urethral defect (PFUD): an observational study from a single high-volume tertiary care center.

To report the clinical features of pelvic fracture urethral injury (PFUI) and assess the real effect of factors that are believed to have adverse effects on delayed urethroplasty.

Erythropoietin pretreatment ameliorates renal ischaemia-reperfusion injury by activating PI3K/Akt signalling.

Renal ischaemia-reperfusion (I/R) injury, a primary cause of acute renal failure, can induce high morbidity and mortality. This study aimed to explore the effect of erythropoietin on renal I/R injury and its underlying mechanism.

Complete androgen insensitivity syndrome in juveniles and adults with female phenotypes.

To report on six cases of the diagnosis and treatment of patients with complete androgen insensitivity syndrome (CAIS) and a review of the relevant published work.

The effect of CXCL9 on the invasion ability of hepatocellular carcinoma through up-regulation of PREX2.

Elevated expression of CXCL9 has been shown to involve in the infiltration of inflammatory cells and liver damage after Hepatitis B virus (HBV) infection. However, whether and by what underlying mechanism does CXCL9 play a role in HBV infection associated hepatocellular carcinoma (HCC) invasion ability remain unclear. In this study, human HCC as well as adjacent noncancerous tissues, together with three kinds of liver cancer cell lines were investigated to clarify the possible involvement of CXCL9 in the regulation of HCC invasion and metastasis. Invasion ability of liver cancer cells were evaluated by transwell assays and it is enhanced after co-cultured with recombined human CXCL9 (rhCXCL9). As a trigger of Rac GTPase signaling after G protein-coupled receptors (GPCR) activated by CXCL9, Phosphatidylinositol-3, 4, 5-trisphosphate RAC Exchanger 2 (PREX2) mRNA expression of the liver cancer cell lines was elevated after co-cultured with rhCXCL9. Moreover, the mRNA level of PREX2 in HCC tissues was significantly higher than those in adjacent noncancerous tissues. Besides, the mRNA levels of PREX2 were positively correlated with the poor differentiation, portal vein invasion, metastasis and qualitative HbsAg results in 45 pairs of HCC specimens. Similarly, PREX2 mRNA was higher in three liver cancer cell lines when compared with the normal liver cell line whereas knocked down of PREX2 by small interference RNA (PREX2-siRNA) reduced the invasion ability of liver cancer cells in transwell assays. Overall, our results suggested CXCL9 was involved in the invasion ability of HCC possibly through up-regulation of its potential effector PREX2.

ACE-inhibition increases podocyte number in experimental glomerular disease independent of proliferation.

The objective of this article is to test the effects of angiotensin-converting enzyme (ACE)-inhibition on glomerular epithelial cell number in an inducible experimental model of focal segmental glomerulosclerosis (FSGS).

Glucocorticoid receptor agonist dexamethasone attenuates renal ischemia/reperfusion injury by up-regulating eNOS/iNOS.

The aim of this study was to determine the effect of dexamethasone (DEX) on renal ischemia/reperfusion injury (IRI). C57BL/6 mice were randomly divided into Sham group, IRI group and DEX group. The mice in IRI and DEX groups subjected to renal ischemia for 60 min, were treated with saline or DEX (4 mg/kg, i.p.) 60 min prior to I/R. After 24 h of reperfusion, the renal function, renal pathological changes, activation of extracellular signal-regulated kinase (ERK) and glucocorticoid receptor (GR), and the levels of iNOS and eNOS were detected. The results showed DEX significantly decreased the damage to renal function and pathological changes after renal IRI. Pre-treatment with DEX reduced ERK activation and down-regulated the level of iNOS, whereas up-regulated the level of eNOS after renal IRI. DEX could further promote the activation of GR. These findings indicated GR activation confers preconditioning-like protection against acute IRI partially by up-regulating the ratio of eNOS/iNOS.