[Retracted] KIF4A promotes the development of bladder cancer by transcriptionally activating the expression of CDCA3.

Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that certain of the tumour images in Fig. 3A and the immunohistochemistry data in Fig. 3C on p. 7, and colony formation assay data shown in Fig. 4F on p. 8 were strikingly similar to data that had already appeared in previous publications. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were under consideration for publication, prior to its submission to International Journal of Molecular Medicine, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they accepted the decision to retract this paper. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 47: 99, 2021; DOI: 10.3892/ijmm.2021.4932].

Polymerization of the backbone of the pectic polysaccharide rhamnogalacturonan I.

Rhamnogalacturonan I (RG-I) is a major plant cell wall pectic polysaccharide defined by its repeating disaccharide backbone structure of [4)-α-D-GalA-(1,2)-α-L-Rha-(1,]. A family of RG-I:Rhamnosyltransferases (RRT) has previously been identified, but synthesis of the RG-I backbone has not been demonstrated in vitro because the identity of Rhamnogalacturonan I:Galaturonosyltransferase (RG-I:GalAT) was unknown. Here a putative glycosyltransferase, At1g28240/MUCI70, is shown to be an RG-I:GalAT. The name RGGAT1 is proposed to reflect the catalytic activity of this enzyme. When incubated together with the rhamnosyltransferase RRT4, the combined activities of RGGAT1 and RRT4 result in elongation of RG-I acceptors in vitro into a polymeric product. RGGAT1 is a member of a new GT family categorized as GT116, which does not group into existing GT-A clades and is phylogenetically distinct from the GALACTURONOSYLTRANSFERASE (GAUT) family of GalA transferases that synthesize the backbone of the pectin homogalacturonan. RGGAT1 has a predicted GT-A fold structure but employs a metal-independent catalytic mechanism that is rare among glycosyltransferases with this fold type. The identification of RGGAT1 and the 8-member Arabidopsis GT116 family provides a new avenue for studying the mechanism of RG-I synthesis and the function of RG-I in plants.

KIF4A promotes the development of bladder cancer by transcriptionally activating the expression of CDCA3.

Bladder cancer (BC) is among the most common urinary system tumors with a high morbidity and mortality worldwide. Despite advancements being made in the diagnosis and treatment of bladder cancer, targeted therapy remains the most promising treatment, and novel therapeutic targets are urgently required in to improve the outcomes of patients with BC. Kinesin family member 4A (KIF4A) is a plus­end directed motor protein involved in the regulation of multiple cellular processes, such as mitosis and axon growth. Notably, KIF4A plays important roles in tumor growth and progression, and its expression is associated with the prognosis of several types of cancer. However, the potential role and molecular mechanisms of KIF4A in bladder cancer development remain unclear. The present study demonstrated that KIF4A was highly expressed in human BC tissues, and its expression was associated with patient clinicopathological characteristics, such as tumor stage (P=0.012) and with the prognosis of patients with BC. It was further found that KIF4A promoted the cell proliferation of bladder cancer both in vitro and in vivo. On the whole, the data presented herein provide evidence that KIF4A promotes the development of BC through the transcriptional activation of the expression of CDCA3. The present study indicates the involvement of KIF4A in the progression of BC and suggests that KIF4A may be a promising therapeutic target for the treatment of BC.

Author Correction: Temperature, Crystalline Phase and Influence of Substrate Properties in Intense Pulsed Light Sintering of Copper Sulfide Nanoparticle Thin Films.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Recombinant Sialyltransferase Infusion Mitigates Infection-Driven Acute Lung Inflammation.

Inappropriate inflammation exacerbates a vast array of chronic and acute conditions with severe health risks. In certain situations, such as acute sepsis, traditional therapies may be inadequate in preventing severe organ damage or death. We have previously shown cell surface glycan modification by the circulating sialyltransferase ST6Gal-1 regulates de novo inflammatory cell production via a novel extrinsic glycosylation pathway. Here, we show that therapeutic administration of recombinant, bioactive ST6Gal-1 (rST6G) mitigates acute inflammation in a murine model mimicking acute exacerbations experienced by patients with chronic obstructive pulmonary disease (COPD). In addition to suppressing proximal neutrophil recruitment at onset of infection-mediated inflammation, rST6G also muted local cytokine production. Histologically, exposure with NTHI, a bacterium associated with COPD exacerbations, in rST6G-treated animals revealed consistent and pronounced reduction of pulmonary inflammation, characterized by smaller inflammatory cuffs around bronchovascular bundles, and fewer inflammatory cells within alveolar walls, alveolar spaces, and on pleural surfaces. Taken together, the data advance the idea that manipulating circulatory ST6Gal-1 levels has potential in managing inflammatory conditions by leveraging the combined approaches of controlling new inflammatory cell production and dampening the inflammation mediator cascade.

Rapid Pulsed Light Sintering of Silver Nanowires on Woven Polyester for personal thermal management with enhanced performance, durability and cost-effectiveness.

Fabric-based personal heating patches have small geometric profiles and can be attached to selected areas of garments for personal thermal management to enable significant energy savings in built environments. Scalable fabrication of such patches with high thermal performance at low applied voltage, high durability and low materials cost is critical to the widespread implementation of these energy savings. This work investigates a scalable Intense Pulsed Light (IPL) sintering process for fabricating silver nanowire on woven polyester heating patches. Just 300 microseconds of IPL sintering results in 30% lesser electrical resistance, 70% higher thermal performance, greater durability (under bending up to 2 mm radius of curvature, washing, humidity and high temperature), with only 50% the added nanowire mass compared to state-of-the-art. Computational modeling combining electromagnetic and thermal simulations is performed to uncover the nanoscale temperature gradients during IPL sintering, and the underlying reason for greater durability of the nanowire-fabric after sintering. This large-area, high speed, and ambient-condition IPL sintering process represents an attractive strategy for scalably fabricating personal heating fabric-patches with greater thermal performance, higher durability and reduced costs.

Modeling nanoscale temperature gradients and conductivity evolution in pulsed light sintering of silver nanowire networks.

Sintering of metal nanowire (NW) networks on transparent polymers is an emerging approach for fabricating transparent conductive electrodes used in multiple devices. Pulsed light sintering is a scalable sintering process in which large-area, broad-spectrum xenon lamp light causes rapid NW fusion to increase network conductivity, while embedding the NWs in the polymer to increase mechanical robustness. This paper develops a multiphysical approach for predicting evolution of conductivity, NW fusion and nanoscale temperature gradients on the substrate during pulsed light sintering of silver NWs on polycarbonate. Model predictions are successfully validated against experimentally measured temperature and electrical resistance evolution. New insight is obtained into the diameter-dependent kinetics of NW fusion and nanoscale temperature gradients on the substrate, which are difficult to obtain experimentally. These observations also lead to the understanding that NW embedding in intense pulsed light sintering (IPL) can occur below the glass transition temperature of the polymer, and to a new differential thermal expansion-based mechanism of NW embedding during IPL. These insights, and the developed model, create a framework for physics-guided choice of NWs, substrate and process parameters to control conductivity and prevent substrate damage during the process.

Temperature, Crystalline Phase and Influence of Substrate Properties in Intense Pulsed Light Sintering of Copper Sulfide Nanoparticle Thin Films.

Intense Pulsed Light sintering (IPL) uses pulsed, visible light to sinter nanoparticles (NPs) into films used in functional devices. While IPL of chalcogenide NPs is demonstrated, there is limited work on prediction of crystalline phase of the film and the impact of optical properties of the substrate. Here we characterize and model the evolution of film temperature and crystalline phase during IPL of chalcogenide copper sulfide NP films on glass. Recrystallization of the film to crystalline covellite and digenite phases occurs at 126 °C and 155 °C respectively within 2-7 seconds. Post-IPL films exhibit p-type behavior, lower resistivity (~10-3-10-4 Ω-cm), similar visible transmission and lower near-infrared transmission as compared to the as-deposited film. A thermal model is experimentally validated, and extended by combining it with a thermodynamic approach for crystal phase prediction and via incorporating the influence of film transmittivity and optical properties of the substrate on heating during IPL. The model is used to show the need to a-priori control IPL parameters to concurrently account for both the thermal and optical properties of the film and substrate in order to obtain a desired crystalline phase during IPL of such thin films on paper and polycarbonate substrates.

Modulating Cell-Surface Receptor Signaling and Ion Channel Functions by In†Situ Glycan Editing.

Glycans anchored on cell-surface receptors are active modulators of receptor signaling. A strategy is presented that enforces transient changes to cell-surface glycosylation patterns to tune receptor signaling. This approach, termed in situ glycan editing, exploits recombinant glycosyltransferases to incorporate monosaccharides with linkage specificity onto receptors in situ. α2,3-linked sialic acid or α1,3-linked fucose added in situ suppresses signaling through epidermal growth factor receptor and fibroblast growth factor receptor. We also applied the same strategy to regulate the electrical signaling of a potassium ion channel-human ether-à-go-go-related gene channel. Compared to gene editing, no long-term perturbations are introduced to the treated cells. In situ glycan editing therefore offers a promising approach for studying the dynamic role of specific glycans in membrane receptor signaling and ion channel functions.

Expression system for structural and functional studies of human glycosylation enzymes.

Vertebrate glycoproteins and glycolipids are synthesized in complex biosynthetic pathways localized predominantly within membrane compartments of the secretory pathway. The enzymes that catalyze these reactions are exquisitely specific, yet few have been extensively characterized because of challenges associated with their recombinant expression as functional products. We used a modular approach to create an expression vector library encoding all known human glycosyltransferases, glycoside hydrolases, and sulfotransferases, as well as other glycan-modifying enzymes. We then expressed the enzymes as secreted catalytic domain fusion proteins in mammalian and insect cell hosts, purified and characterized a subset of the enzymes, and determined the structure of one enzyme, the sialyltransferase ST6GalNAcII. Many enzymes were produced at high yields and at similar levels in both hosts, but individual protein expression levels varied widely. This expression vector library will be a transformative resource for recombinant enzyme production, broadly enabling structure-function studies and expanding applications of these enzymes in glycochemistry and glycobiology.

Synthesis of asymmetrical multiantennary human milk oligosaccharides.

Despite mammalian glycans typically having highly complex asymmetrical multiantennary architectures, chemical and chemoenzymatic synthesis has almost exclusively focused on the preparation of simpler symmetrical structures. This deficiency hampers investigations into the biology of glycan-binding proteins, which in turn complicates the biomedical use of this class of biomolecules. Herein, we describe an enzymatic strategy, using a limited number of human glycosyltransferases, to access a collection of 60 asymmetric, multiantennary human milk oligosaccharides (HMOs), which were used to develop a glycan microarray. Probing the array with several glycan-binding proteins uncovered that not only terminal glycoepitopes but also complex architectures of glycans can influence binding selectivity in unanticipated manners. N- and O-linked glycans express structural elements of HMOs, and thus, the reported synthetic principles will find broad applicability.

Large-scale Generation of Patterned Bubble Arrays on Printed Bi-functional Boiling Surfaces.

Bubble nucleation control, growth and departure dynamics is important in understanding boiling phenomena and enhancing nucleate boiling heat transfer performance. We report a novel bi-functional heterogeneous surface structure that is capable of tuning bubble nucleation, growth and departure dynamics. For the fabrication of the surface, hydrophobic polymer dot arrays are first printed on a substrate, followed by hydrophilic ZnO nanostructure deposition via microreactor-assisted nanomaterial deposition (MAND) processing. Wettability contrast between the hydrophobic polymer dot arrays and aqueous ZnO solution allows for the fabrication of heterogeneous surfaces with distinct wettability regions. Heterogeneous surfaces with various configurations were fabricated and their bubble dynamics were examined at elevated heat flux, revealing various nucleate boiling phenomena. In particular, aligned and patterned bubbles with a tunable departure frequency and diameter were demonstrated in a boiling experiment for the first time. Taking advantage of our fabrication method, a 6 inch wafer size heterogeneous surface was prepared. Pool boiling experiments were also performed to demonstrate a heat flux enhancement up to 3X at the same surface superheat using bi-functional surfaces, compared to a bare stainless steel surface.

Selective Exo-Enzymatic Labeling Detects Increased Cell Surface Sialoglycoprotein Expression upon Megakaryocytic Differentiation.

Selective exo-enzymatic labeling (or SEEL) uses recombinant glycosyltransferases and nucleotide-sugar analogues to allow efficient labeling of cell surface glycans. SEEL can circumvent many of the possible issues associated with metabolic labeling, including low incorporation of sugar precursors, and allows for sugars to be added selectively to different types of glycans by virtue of the inherent specificity of the glycosyltransferases. Here we compare the labeling of sialoglycoproteins in undifferentiated and differentiated human erythroleukemia cells (HEL) using SEEL using the sialyltransferases ST6Gal1 and ST3Gal1, which label N- and O-glycans, respectively. Our results show that the profile of glycoproteins detected varies between undifferentiated HEL cells and those differentiated to megakaryocytes, with a shift to more N-linked sialoglycoproteins in the differentiated cells. The efficiency of SEEL for both sialyltransferases in HEL cells was greatly increased with prior neuraminidase treatment highlighting the necessity for the presence of available acceptors with this labeling method. Following metabolic labeling or SEEL, tagged glycoproteins were enriched by immunoprecipitation and identified using mass spectrometry. The proteomic findings demonstrated that the detection of many glycoproteins is markedly improved by SEEL labeling, and that unique glycoproteins can be identified using either ST6Gal1 or ST3Gal1. Furthermore, this analysis enabled the identification of increased surface expression of several sialylated cell adhesion molecules, including the known megakaryocytic markers integrinß3 and CD44, upon differentiation of HEL cells to adherent megakaryocytes.

[Efficacy of combination therapy of tamsulosin and solifenacin for mild and moderate benign prostatic hyperplasia with overactive bladder].

OBJECTIVE: To evaluate the efficacy and safety of the combination therapy of tamsulosin and solifenacin for mild and moderate benign prostatic hyperplasia (BPH) with overactive bladder (OAB). METHODS: We randomly divided 166 patients with BPH and concomitant OAB into a mild obstruction symptom group (n = 88) and a moderate obstruction symptom group (n =78), 48 of the former group treated with 0. 2 mg tamsulosin + 5 mg solifenacin and the other 40 with 0. 2 mg tamsulosin; 36 of the latter group treated with 0. 2 mg tamsulosin + 5 mg solifenacin and the other 42 with 0. 2 mg tamsulosin, all administered once daily for 12 weeks. We obtained the International Prostate Symptom Score (IPSS), urine storage period symptom score (USPSS), voiding symptom score (VSS), Qmax, residual urine volume, OAB symptom score (OABSS) and adverse reactions, and compared them among different RESULTS: Among the patients with mild obstruction symptoms, the combination of tamsulosin and solifenacin achieved remark-groups. able improvement in IPSS, USPSS, Qmax and OABSS as compared with the baseline (P < 0.05), but made no significant difference in the residual urine volume (P > 0. 05) , while tamsulosin improved IPSS only (P < 0.05). The combination therapy exhibited an obvious superiority over tamsulosin alone in improving IPSS (9.7 micro 3.0 vs 15.8 micro 3.3), USPSS (8. 1 micro 1.7 vs 12.3 micro 3.1), Qmax ([18.6 micro 2.3] ml/s vs [14.2 micro 2.3] ml/s ), and OABSS (5.3micro 1.3 vs 9.7 micro 2.7) (P < 0.05), but there were no obvious differences in residual urine, urine routine test results and adverse events between the two therapies ( P > 0. 05). In those with moderate obstruction symptoms, the combination therapy significantly improved IPSS, VSS, Qmax and OABSS (P < 0.05) but not the residual urine (P > 0. 05) in comparison with the baseline. The tamsulosin therapy achieved obvious improvement in IPSS, VSS, Qmax, OABSS and residual urine. The combination therapy showed a better effect than tamsulosin only in OABSS (4. 8 +/-1.5 vs 6.5 +/-2.5, P < 0.05), but no significant differences from the latter in IPSS, Qmax, VSS, routine urine test results, and adverse CONCLUSION: Combination therapy of tamsulosin and solifenacin is obviously safe and efficacious in the treatment (P > 0.05). events of both mild and moderate BPH with concomitant OAB, and it is superior to tamsulosin alone.

Enzymatic basis for N-glycan sialylation: structure of rat α2,6-sialyltransferase (ST6GAL1) reveals conserved and unique features for glycan sialylation.

Glycan structures on glycoproteins and glycolipids play critical roles in biological recognition, targeting, and modulation of functions in animal systems. Many classes of glycan structures are capped with terminal sialic acid residues, which contribute to biological functions by either forming or masking glycan recognition sites on the cell surface or secreted glycoconjugates. Sialylated glycans are synthesized in mammals by a single conserved family of sialyltransferases that have diverse linkage and acceptor specificities. We examined the enzymatic basis for glycan sialylation in animal systems by determining the crystal structures of rat ST6GAL1, an enzyme that creates terminal α2,6-sialic acid linkages on complex-type N-glycans, at 2.4 Å resolution. Crystals were obtained from enzyme preparations generated in mammalian cells. The resulting structure revealed an overall protein fold broadly resembling the previously determined structure of pig ST3GAL1, including a CMP-sialic acid-binding site assembled from conserved sialylmotif sequence elements. Significant differences in structure and disulfide bonding patterns were found outside the sialylmotif sequences, including differences in residues predicted to interact with the glycan acceptor. Computational substrate docking and molecular dynamics simulations were performed to predict and evaluate the CMP-sialic acid donor and glycan acceptor interactions, and the results were compared with kinetic analysis of active site mutants. Comparisons of the structure with pig ST3GAL1 and a bacterial sialyltransferase revealed a similar positioning of donor, acceptor, and catalytic residues that provide a common structural framework for catalysis by the mammalian and bacterial sialyltransferases.

Multiple renal arteries with renal cell carcinoma: preoperative evaluation using computed tomography angiography prior to laparoscopic nephrectomy.

OBJECTIVE: To investigate anatomical variations in the renal arteries of patients with renal cell carcinoma (RCC) using computed tomography angiography (CTA). METHODS: Patients diagnosed with RCC were evaluated using CTA prior to undergoing laparoscopic nephrectomy. Any anatomical variations of the renal arteries on the side affected by the RCC were recorded. The CTA results were compared with the observations made during surgery and those produced by conventional digital subtraction angiography. RESULTS: A total of 107 patients with RCC were enrolled in the study. Multiple renal arteries were found in 11 patients (10.3%). Accessory renal inferior polar arteries were the most common type of multiple renal arteries. Multiple renal arteries acting as the feeding arteries to the RCC were found in five patients (4.7%). CONCLUSION: CTA can be used as part of the preoperative evaluation prior to laparoscopic nephrectomy to provide anatomical information about the presence of multiple renal arteries in the affected kidney of patients with RCC. This could help with planning the surgery and reducing surgical complications.

Cucurbit[5]uril-metal complex-induced room-temperature phosphorescence of α-naphthol and ß-naphthol.

Similar to the larger members of the cucurbituril family, such as cucurbit[8]uril (Q[8]), the smallest member, cucurbit[5]uril (Q[5]), can also induce room-temperature phosphorescence (RTP) of α-naphthol (1) and ß-naphthol (2). The relationship between the RTP intensity of 1 and 2 and the concentration of Q[5] or Q[8] suggests that the mechanism underlying the Q[5] complex-induced RTP is different from that of the Q[8]-induced RTP for these luminophores. The crystal structures of 1-Q[5]-KI, 2-Q[5]-KI, 1-Q[5]-TlNO(3), and 2-Q[5]-TlNO(3) systems show that in each case Q[5] and the respective metal ions, K(+) or Tl(+), form infinite ···Q[5]-M(+)-Q[5]-M(+)··· chains that surround the luminophores. Although these tube- or wall-like structures are likely destroyed in solution, the key interaction between the convex-shaped outer walls of Q[5] and the plane of the aromatic naphthols, via π···π stacking and C-H···π interactions, is postulated to be essentially maintained leading to a microenvironment that holds the luminophore and the heavy atom perturber together; such a model is supported by the observed Q[5] complex-induced RTP of the above naphthols. With respect to this, a high Q[5]/luminophore concentration was employed in an endeavour to promote the formation of π···π stacking and C-H···π interactions similar to those observed in the crystal structures of the 1- or 2-Q[5]-K(+) and -Tl(+) systems. In keeping with the proposed model, the RTP of each system is quenched when Q[5] is replaced by the alkyl-substituted Q[5] derivatives, decamethylQ[5] and pentacyclohexanoQ[5]. This is in agreement with the substituent groups on the surface of the metal-bond Q[5] obstructing the naphthol molecule from accessing the convex glycouril backbone of Q[5].

Relationship between PTEN and Livin expression and malignancy of renal cell carcinomas.

OBJECTIVES: This study focused on PTEN and Livin expression and associations with malignancy in human renal clear cell carcinomas (RCCC). METHODS: PTEN and Livin expression was assessed in 100 RCCC tissue samples, 50 paracarcinoma cases, and 20 normal renal tissue samples using the immunohistochemical Streptavidin proxidase (SP) method. The relationships between binding and corresponding biological characteristics, such as histological grade, lymph node metastases, and clinical stages were analyzed. RESULTS: Positive PTEN expression in RCCC was significantly lower than in renal tissue adjacent to carcinoma tissue and normal renal tissue (P<0.01). Livin expression in the renal tissue adjacent to the carcinoma and normal renal tissues exhibited only low levels, whereas overall Livin expression in RCCC was statistically significant (P<0.01). In RCCC, PTEN expression rate gradually decreased with an increase in clinical stage, whereas that of Livin increased to statistically significant levels (P<0.01), PTEN and Livin levels being negatively correlated (r=-0.395, P<0.01). CONCLUSIONS: PTEN and Livin are important in RCCC development. The two factors combined are expected to provide indices for estimating RCCC malignancy and progression levels, as well as references for RCCC diagnosis and treatment.

NMR characterization of immunoglobulin G Fc glycan motion on enzymatic sialylation.

The terminal carbohydrate residues of the N-glycan on the immunoglobulin G (IgG) fragment crystallizable (Fc) determine whether IgG activates pro- or anti-inflammatory receptors. The IgG Fc alone becomes potently anti-inflammatory upon addition of α2-6-linked N-acetylneuraminic acid residues to the N-glycan, stimulating interest in use of this entity in novel therapies for autoimmune disease [Kaneko et al. (2006) Science313, 670-3]. Complete Fc sialylation has, however, been deemed challenging due to a combination of branch specificity and perceived protection by glycan-protein interactions. Here we report the preparation of high levels of disialylated Fc by using sufficient amounts of a highly active α2-6 sialyltransferase (ST6Gal1) preparation expressed in a transiently transformed human cell culture. Surprisingly, ST6Gal1 sialylated the two termini of the complex-type binantennary glycan in a manner remarkably similar to that observed for the free N-glycan, suggesting the Fc polypeptide does not greatly influence ST6Gal1 specificity. In addition, sialylation of either branch terminus does not appear to dramatically alter the motional behavior of the N-glycan as judged by solution NMR spectroscopy. Together these, data suggest the N-glycan occupies two distinct states: one with both glycan termini sequestered from enzymatic modification by an α1-6Man-branch interaction with the polypeptide surface and the other with both glycan termini exposed to the bulk solvent and free from glycan-polypeptide interactions. The results suggest new modes by which disialylated Fc can act as an anti-inflammatory effector.