The role of reactive oxygen species in regulation of the plasma membrane H+-ATPase activity in Masson pine (Pinus massoniana Lamb.) roots responding to acid stress.

To understand the role of reactive oxygen species (ROS) in regulation of the plasma membrane (PM) H+-ATPase in acid-stressed Masson pine roots, different acidity (pH 6.6 as the control, pH 5.6 and pH 4.6) of simulated acid rain (SAR) added with and without external chemicals (H2O2, enzyme inhibitors and ROS scavenger) was prepared. After 30 days of SAR exposure, the plant morphological phenotype attributes, levels of cellular ROS and lipid peroxidation, enzymatic activities of antioxidants, PM nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and PM H+-ATPase activity in pine seedlings were measured. Compared with the control, the growth of pine seedlings exposed to SAR in the presence or absence of H2O2 was well-maintained, but the application of Na3VO4, 1,3-dimethyl-2-thiourea, N, N-dimethylthiourea (DMTU) and diphenyleneiodonium chloride (DPI) caused a substantial growth inhibition. In addition, SAR exposure, SAR with H2O2 treatment, and SAR with Na3VO4 treatment increased the cellular H2O2 content, O2- content and malondialdehyde (MDA) content, while the use of DMTU and DPI lead to relatively low levels. Similarly, the enzymatic activities of antioxidants, PM NADPH oxidase and PM H+-ATPase in acid stressed pine seedlings elevated with the increasing acidity. A significant stimulation of these enzymatic activities obtained from SAR with H2O2 treatment was observed, whereas which decreased obviously with the addition of Na3VO4, DMTU and DPI (P < 0.05). Moreover, a positive correlation was found between plant morphological attributes and the PM H+-ATPase activity (P < 0.05). Besides, the PM H+-ATPase activity positively correlated with the cellular ROS contents and the enzymatic activities of antioxidants and PM NADPH oxidase (P < 0.05). Therefore, the PM H+-ATPase is instrumental in the growth of pine seedlings resisting to acid stress by enhancing its activity. The process involves the signaling transduction of cellular ROS and coordination with PM NADPH oxidase.

c-Cbl induced podocin ubiquitination contributes to the podocytes injury in diabetic nephropathy.

The ubiquitination function in diabetic nephropathy (DN) has attracted much attention, but there is a lack of information on its ubiquitylome profile. To examine the differences in protein content and ubiquitination in the kidney between db/db mice and db/m mice, we deployed liquid chromatography-mass spectrometry (LC-MS/MS) to conduct analysis. We determined 145 sites in 86 upregulated modified proteins and 66 sites in 49 downregulated modified proteins at the ubiquitinated level. Moreover, 347 sites among the 319 modified proteins were present only in the db/db mouse kidneys, while 213 sites among the 199 modified proteins were present only in the db/m mouse kidneys. The subcellular localization study indicated that the cytoplasm had the highest proportion of ubiquitinated proteins (31.87%), followed by the nucleus (30.24%) and the plasma membrane (20.33%). The enrichment analysis revealed that the ubiquitinated proteins are mostly linked to tight junctions, oxidative phosphorylation, and thermogenesis. Podocin, as a typical protein of slit diaphragm, whose loss is a crucial cause of proteinuria in DN. Consistent with the results of ubiquitination omics, the K261R mutant of podocin induced the weakest ubiquitination compared with the K301R and K370R mutants. As an E3 ligase, c-Cbl binds to podocin, and the regulation of c-Cbl can impact the ubiquitination of podocin. In conclusion, in DN, podocin ubiquitination contributes to podocyte injury, and K261R is the most significant site. c-Cbl participates in podocin ubiquitination and may be a direct target for preserving the integrity of the slit diaphragm structure, hence reducing proteinuria in DN.

Identification of urinary extracellular vesicles differentially expressed RNAs in diabetic nephropathy via whole-transcriptome integrated analysis.

BACKGROUND: Diabetic nephropathy (DN) is a common systemic microvascular complication of diabetes and a leading cause of chronic kidney disease worldwide. Urinary extracellular vesicles (uEVs), which are natural nanoscale vesicles that protect RNA from degradation, have the potential to serve as an invasive diagnostic biomarker for DN. METHODS: We enrolled 24 participants, including twelve with renal biopsy-proven T2DN and twelve with T2DM, and isolated uEVs using ultracentrifugation. We performed microarrays for mRNAs, lncRNAs, and circRNAs in parallel, and Next-Generation Sequencing for miRNAs. Differentially expressed RNAs (DE-RNAs) were subjected to CIBERSORTx, ssGSEA analysis, GO enrichment, PPI network analysis, and construction of the lncRNA/circRNA-miRNA-mRNA regulatory network. Candidate genes and potential biomarker RNAs were validated using databases and machine learning models. RESULTS: A total of 1684 mRNAs, 126 lncRNAs, 123 circRNAs and 66 miRNAs were found in uEVs in T2DN samples compared with T2DM. CIBERSORTx revealed the involvement of uEVs in immune activity and ssGSEA explored possible cell or tissue sources of uEVs. A ceRNA co-expression and regulation relationship network was constructed. Candidate genes MYO1C and SP100 mRNA were confirmed to be expressed in the kidney using Nephroseq database, scRNA-seq dataset, and Human Protein Atlas database. We further selected 2 circRNAs, 2 miRNAs, and 2 lncRNAs from WGCNAs and ceRNAs and demonstrated their efficacy as potential diagnostic biomarkers for T2DN using machine learning algorithms. CONCLUSIONS: This study reported, for the first time, the whole-transcriptome genetic resources found in urine extracellular vesicles of T2DN patients. The results provide additional support for the possible interactions, and regulators between RNAs from uEVs themselves and as potential biomarkers in DN.

Anticancer effect of Dihydroartemisinin via dual control of ROS-induced apoptosis and protective autophagy in prostate cancer 22Rv1 cells.

BACKGROUND: Dihydroartemisinin (DHA), a natural agent, exhibits potent anticancer activity. However, its biological activity on prostate cancer (PCa) 22Rv1 cells has not been previously investigated. OBJECTIVE: In this study, we demonstrate that DHA induces anticancer effects through the induction of apoptosis and autophagy. METHODS: Cell viability and proliferation rate were assessed using the CCK-8 assay and cell clone formation assay. The generation of reactive oxygen species (ROS) was detected by flow cytometry. The molecular mechanism of DHA-induced apoptosis and autophagy was examined using Western blot and RT-qPCR. The formation of autophagosomes and the changes in autophagy flux were observed using transmission electron microscopy (TEM) and confocal microscopy. The effect of DHA combined with Chloroquine (CQ) was assessed using the EdU assay and flow cytometry. The expressions of ROS/AMPK/mTOR-related proteins were detected using Western blot. The interaction between Beclin-1 and Bcl-2 was examined using Co-IP. RESULTS: DHA inhibited 22Rv1 cell proliferation and induced apoptosis. DHA exerted its anti-prostate cancer effects by increasing ROS levels. DHA promoted autophagy progression in 22Rv1 cells. Inhibition of autophagy enhanced the pro-apoptotic effect of DHA. DHA-induced autophagy initiation depended on the ROS/AMPK/mTOR pathway. After DHA treatment, the impact of Beclin-1 on Bcl-2 was weakened, and its binding with Vps34 was enhanced. CONCLUSION: DHA induces apoptosis and autophagy in 22Rv1 cells. The underlying mechanism may involve the regulation of ROS/AMPK/mTOR signaling pathways and the interaction between Beclin-1 and Bcl-2 proteins. Additionally, the combination of DHA and CQ may enhance the efficacy of DHA in inhibiting tumor cell activity.

High-performance thermoplastic starch/poly(butylene adipate-co-terephthalate) blends through synergistic plasticization of epoxidized soybean oil and glycerol.

Utilizing starch, an abundant polysaccharide, as the renewable filler to blend with poly(butylene adipate-co-terephthalate) (PBAT) is a feasible tactic to construct cost-effective and high-performance biodegradable materials. It's worth noting that the thermal processing properties of starch can be manipulated by its plasticized behavior. Herein, epoxidized soybean oil (ESO) and glycerol were used as the plasticizer for native corn starch and the plasticized starch was integrated with PBAT to manufacture starch-based biodegradable blend films. ESO breaks the hydrogen bonds between starch chains through the fatty chains grafting reaction and increases the distance between starch molecular chains due to the large molecular weight of ESO. Meanwhile, glycerol molecules are incorporated into the starch molecular chains, and fatty chains grafted starch chains, effectively reducing the intermolecular forces of molecular chains. On account of the synergistic plasticization of ESO and glycerol which possess good compatibility with PBAT, the PSG20E10 blend film achieved a tensile strength, an elongation at break of 16.11 MPa and 612.09 %, and the balanced water and oxygen permeability properties.

Novel Insight into Ferroptosis in Kidney Diseases.

BACKGROUND: Various kidney diseases such as acute kidney injury, chronic kidney disease, polycystic kidney disease, renal cancer, and kidney stones, are an important part of the global burden, bringing a huge economic burden to people around the world. Ferroptosis is a type of nonapoptotic iron-dependent cell death caused by the excess of iron-dependent lipid peroxides and accompanied by abnormal iron metabolism and oxidative stress. Over the past few decades, several studies have shown that ferroptosis is associated with many types of kidney diseases. Studying the mechanism of ferroptosis and related agonists and inhibitors may provide new ideas and directions for the treatment of various kidney diseases. SUMMARY: In this review, we discuss the differences between ferroptosis and other types of cell death such as apoptosis, necroptosis, pyroptosis, cuprotosis, pathophysiological features of the kidney, and ferroptosis-induced kidney injury. We also provide an overview of the molecular mechanisms involved in ferroptosis and events that lead to ferroptosis. Furthermore, we summarize the possible clinical applications of this mechanism among various kidney diseases. KEY MESSAGE: The current research suggests that future therapeutic efforts to treat kidney ailments would benefit from a focus on ferroptosis.

Decorating hexahistidine-metal assemblies with tyrosine enhances the ability of proteins to pass through corneal biobarriers.

In recent decades, the use of protein drugs has increased dramatically for almost every clinical indication, including autoimmunity and cancer infection, given their high specificity and limited side effects. However, their easy deactivation by the surrounding microenvironment and limited ability to pass through biological barriers pose large challenges to the use of these agents for therapeutic effects; these deficits could be greatly improved by nanodelivery using platforms with suitable physicochemical properties. Here, to assess the effect of the hydrophobicity of nanoparticles on their ability to penetrate biological barriers, the hydrophobic amino acid tyrosine (Y) was decorated onto hexahistidine peptide, and two nanosized YHmA and HmA particles were generated, in which Avastin (Ava, a protein drug) was encapsulated by a coassembly strategy. In vitro and in vivo tests demonstrated that these nanoparticles effectively retained the bioactivity of Ava and protected Ava from proteinase K hydrolysis. Importantly, YHmA displayed a considerably higher affinity to the ocular surface than HmA, and YHmA also exhibited the ability to transfer proteins across the barriers of the anterior segment, which greatly improved the bioavailability of the encapsulated Ava and produced surprisingly good therapeutic outcomes in a model of corneal neovascularization. STATEMENT OF SIGNIFICANCE: Improving the ability to penetrate tissue barriers and averting inactivation caused by surrounding environments, are the keys to broaden the application of protein drugs. By decorating hydrophobic amino acid, tyrosine (Y), on hexahistidine peptide, YHmA encapsulated protein drug Ava with high efficiency by co-assembly strategy. YHmA displayed promising ability to maintain bioactivity of Ava during encapsulation and delivery, and protected Ava from proteinase K hydrolysis. Importantly, YHmA transferred Ava across the corneal epithelial barrier and greatly improved its bioavailability, producing surprisingly good therapeutic outcomes in a model of corneal neovascularization. Our results contributed to not only the strategy to overcome shortcomings of protein drugs, but also suggestion on hydrophobicity as a nonnegligible factor in nanodrug penetration through biobarriers.

Inhibition of the glycogen synthase kinase 3ß-hypoxia-inducible factor 1α pathway alleviates NLRP3-mediated pyroptosis induced by high glucose in renal tubular epithelial cells.

NEW FINDINGS: What is the central question of this study? Activation of the glycogen synthase kinase 3 ß (GSK-3ß)-hypoxia-inducible factor 1 α (HIF-1α) pathway results in stimulation of pyroptosis under high glucose, and exerts actions in a number renal diseases: does this pathway have a role in renal tubular epithelial cells? What is the main finding and its importance? Down-regulation of GSK-3ß can inhibit pyroptosis of renal tubular epithelial cells induced by high glucose and this may be related to down-regulation of HIF-1α. This role of the GSK-3ß-HIF-1α pathway has not previously been reported and identifies a potential new therapeutic target in diabetic nephropathy. ABSTRACT: Diabetic nephropathy (DN) is not only one of the main complications of diabetes, but also has a high incidence rate and a high mortality rate. Glycogen synthase kinase 3 ß (GSK-3ß) and hypoxia-inducible factor 1 α (HIF-1α) have been demonstrated to influence DN by regulating pyroptosis. This study aimed to investigate the effect of the GSK-3ß-HIF-1α pathway on pyroptosis of high-glucose (HG)-induced renal tubular cells. Mouse renal proximal tubular epithelial cells (TKPT cells) were induced by HG to simulate DN cell and we transfected TKPT cells with GSK-3ß knockdown lentivirus. Western blot analysis confirmed the transfection effects and detected the expression of GSK-3ß, HIF-1α, Nod-like receptor protein 3 (NLRP3), cleaved-caspase-1, pro-caspase-1, gasdermin D (GSDMD) and GSDMD-N. The expression of GSDMD-N and HIF-1α were also verified by immunofluorescence. The levels of interleukin (IL)-1ß and IL-18 were measured by enzyme linked immunosorbent assay. Flow cytometric analysis determined the apoptosis rate. Results showed that HIF-1α expression was increased in HG-induced TKPT cells, and GSK-3ß knockdown could decrease the levels of NLRP3, cleaved-caspase-1, GSDMD-N and HIF-1α, verified by immunofluorescence. Moreover, GSK-3ß knockdown suppressed the expression of IL-1ß and IL-18, and reduced the apoptosis rate. Lithium chloride (LiCl) interference could cause the same changes as GSK-3ß knockdown for HG-induced TKPT cells, and dimethyloxallyl glycine could reverse the effect of GSK-3ß-knockdown interference. Our studies definitively demonstrate that the GSK-3ß-HIF-1α signalling pathway mediates HG-stimulated pyroptosis in renal tubular epithelial cells and that down-regulation of GSK-3ß inhibited HG-induced pyroptosis by inhibiting the expression of HIF-1α. These findings suggest a new potential target for the treatment of DN.

Down-regulation of Risa improves podocyte injury by enhancing autophagy in diabetic nephropathy.

BACKGROUND: LncRNA AK044604 (regulator of insulin sensitivity and autophagy, Risa) and autophagy-related factors Sirt1 and GSK3ß play important roles in diabetic nephropathy (DN). In this study, we sought to explore the effect of Risa on Sirt1/GSK3ß-induced podocyte injury. METHODS: Diabetic db/db mice received Risa-inhibition adeno-associated virus (AAV) via tail vein injection, and intraperitoneal injection of lithium chloride (LiCl). Blood, urine, and kidney tissue samples were collected and analyzed at different time points. Immortalized mouse podocyte cells (MPCs) were cultured and treated with Risa-inhibition lentivirus (LV), EX-527, and LiCl. MPCs were collected under different stimulations as noted. The effects of Risa on podocyte autophagy were examined by qRT-PCR, Western blotting analysis, transmission electron microscopy, Periodic Acid-Schiff staining, and immunofluorescence staining. RESULTS: Risa and activated GSK3ß were overexpressed, but Sirt1 was downregulated in DN mice and high glucose-treated MPCs (P < 0.001, db/m vs. db/db, NG or HM vs. HG), which was correlated with poor prognosis. Risa overexpression attenuated Sirt1-mediated downstream autophagy levels and aggravated podocyte injury by inhibiting the expression of Sirt1 (P < 0.001, db/m vs. db/db, NG or HM vs. HG). In contrast, Risa suppression enhanced Sirt1-induced autophagy and attenuated podocyte injury, which could be abrogated by EX-527 (P < 0.001, db/db + Risa-AAV vs. db/db, HG + Risa-LV vs. HG). Furthermore, LiCl treatment could restore GSK3ß-mediated autophagy of podocytes (P < 0.001, db/db + LiCl vs. db/db, HG + LiCl vs. HG), suggesting that Risa overexpression aggravated podocyte injury by decreasing autophagy. CONCLUSION: Risa could inhibit autophagy by regulating the Sirt1/GSK3ß axis, thereby aggravating podocyte injury in DN. Risa may serve as a therapeutic target for the treatment of DN.

Modification of plasma membrane H+-ATPase in Masson pine (Pinus massoniana Lamb.) seedling roots adapting to acid deposition.

To understand the regulation of roots plasma membrane H+-ATPase in Masson pine responding to acid deposition, the changes in biomass, plant morphology, intracellular H+, enzyme activity and H+-ATPase genes expression in Masson pine seedlings exposed to simulated acid rain (SAR, pH 5.6 and 4.6) with and without vanadate were studied. Simulated acid rain exposure for 60 days increased the intracellular H+ in pine roots whether added with 0.1 mM Na3VO4 or not. The growth of seedlings treated with SAR was maintained well, even the primary lateral root length, root dry weight and number of root tips in seedlings exposed to SAR at pH 4.6 were higher than that of the control (pH 6.6). However, the addition of vanadate resulted in severe growth inhibition and obvious decline in morphological parameters. Similarly, ATP hydrolytic activity and H+ transport activity of roots plasma membrane H+-ATPase, both were stimulated by SAR whereas they were inhibited by vanadate, and the highest activity stimulation was observed in pine roots subjected to SAR at pH 4.6. In addition, SAR also induced the expression of the investigated H+-ATPase subunits (atpB, atpE, atpF, atpH and atpI). Therefore, the roots plasma membrane H+-ATPase is instrumental in the growth of Masson pine seedlings adapting to acid rain by a manner of pumping more protons across the membrane through enhancing its activity, and which involves the upregulated gene expression of roots H+-ATPase subunits at transcriptional level.

Determining the influence of high glucose on exosomal lncRNAs, mRNAs, circRNAs and miRNAs derived from human renal tubular epithelial cells.

Diabetic nephropathy is a lethal disease that can lead to chronic kidney disease and end-stage kidney disease. Exosomes, which are nanosized extracellular vesicles, are closely involved in intercellular communication. Most importantly, exosomes play critical roles in disease occurrence and development. However, the function of exosomes in diabetic nephropathy progression has not been fully elucidated. In the present study, we determined the expression profiles and differences of lncRNAs, mRNAs, circRNAs and miRNAs in exosomes derived from human renal tubular epithelial cells with or without high glucose (HG) treatment. A total of 169 lncRNAs, 885 mRNAs, 3 circRNAs and 152 miRNAs were differentially expressed in exosomes secreted by HG-challenged HK-2 cells (HG group) compared with controls (NC group). The functions of differentially expressed mRNAs, mRNAs colocalized or coexpressed with differentially expressed lncRNAs (DElncRNAs), potential target genes of miRNAs and source genes of circRNAs were investigated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. According to these differentially expressed RNAs, we established an integrated circRNA-lncRNA-miRNA-mRNA regulatory network. In conclusion, our study suggested that exosomal lncRNAs, mRNAs, circRNAs and miRNAs participate in the progression of diabetic nephropathy and may be possible biomarkers and therapeutic targets in diabetic nephropathy.

Enhanced proliferation and angiogenic phenotype of endothelial cells via negatively-charged alginate and chondroitin sulfate microsphere hydrogels.

Sodium alginate-based hydrogel was the one of the most used polymers for cell delivery. However, the adsorption of extracellular matrix and proteins was inhibited due to the formation of a hydrated surface layer of these hydrogels. In this study, a novel cell delivery system, negatively-charged alginate and chondroitin sulfate microsphere hydrogel (nCACSMH), was fabricated with excellent permeability and biocompatibility in the action of a high voltage direct-current electric field. Negative charge was introduced to the surface of nCACSMH to obtain the expanded network and enhanced permeability. Additionally, the increasing content of chondroitin sulfate in nCACSMH could give rise to the charge density and its asymmetric structure, thus the uneven, plicate and expanded surface of nCACSMH which was favorable to cell proliferation was developed. Moreover, chondroitin sulfate was released with the degradation of nCACSMH, which played a crucial role in maintaining the normal physiological functions of cells. Thus the proliferation of human umbilical vein endothelial cells (HUVECs) was further accelerated and the angiogenesis related genes expression in endothelial cells was continuously and dramatically up-regulated. After 4 d, the proliferation and viability of HUVECs were significantly improved, the cells were distributed evenly in nCACSMH. The novel nCACSMH has the potential to be used as cell delivery, three-dimensional (3D) cell cultures for cell therapy, 3D bioprinting, high-throughput screening for drugs, and disease model for regeneration and constructing of tissue engineering.

Integrated Analysis of a Risk Score System Predicting Prognosis and a ceRNA Network for Differentially Expressed lncRNAs in Multiple Myeloma.

Long non-coding RNAs (lncRNAs) are non-protein-coding RNAs longer than 200 nucleotides. Accumulating evidence demonstrates that lncRNA is a potential biomarker for cancer diagnosis and prognosis. However, there are no prognostic biomarkers and lncRNA models for multiple myeloma (MM). Hence, it is necessary to screen novel lncRNA that can potentially participate in the initiation and progression of MM and consequently construct a risk score system for the disease. Raw microarray datasets were obtained from the Gene Expression Omnibus website. Weighted gene co-expression network analysis and principal component analysis identified 12 lncRNAs of interest. Then, univariate, least absolute shrinkage and selection operator Cox regression and multivariate Cox hazard regression analysis identified two lncRNAs (LINC00996 and LINC00525) that were formulated to construct a risk score system to predict survival. Receiver operating characteristic analysis certificated the superior performance in predicting 3-year overall survival (area under the curve = 0.829). The similar prognostic values of the two-lncRNA signature were also observed in the tested The Cancer Genome Atlas dataset. Furthermore, two other lncRNAs (LINC00324 and LINC01128) were differentially expressed between CD138+ plasma cells from normal donors and MM patients and were verified to be associated with cancer stage in the Gene Expression Omnibus dataset. A lncRNA-mediated competing endogenous RNA network, including 2 lncRNAs, 12 mitochondrial RNAs, and 103 target messenger RNAs, was constructed. In conclusion, we developed a two-lncRNA expression signature to predict the prognosis of MM and constructed a key lncRNA-based competing endogenous RNA network in MM. These lncRNAs were associated with survival and are probably involved in the occurrence and progression of MM.

Expression Profile Analysis of m6A RNA Methylation Regulators Indicates They Are Immune Signature Associated and Can Predict Survival in Kidney Renal Cell Carcinoma.

N6-Methyladenosine (m6A) refers to the methylation modification occurring at the nitrogen-6 position of adenosine. Many human physiological processes such as modulation of spermatogenesis are caused by m6A RNA modifications. However, the relationship between m6A RNA methylation regulators and kidney renal clear cell carcinoma (KIRC) remains rarely investigated. This work aimed to explore the influence of m6A RNA methylation regulators in KIRC. We examined abnormally expressed m6A RNA methylation regulators among different clinicopathological features of KIRC. We recognized three subgroups (KIRC1, KIRC2, and KIRC3) with significant differences in overall survival through consensus clustering of m6A RNA methylation regulators. Surprisingly, KIRC2 displayed elevated immune activity, but high proportions of immune-inhibitory cells (Tregs and myeloid-derived suppressor cell) based on single-sample gene set enrichment analysis (ssGSEA) and CIBERSORT analysis. Moreover, the KIRC2 subgroup had the lowest tumor mutation burden levels and the highest expression levels of 80% (12/15) of co-inhibitory molecules. Next, correlation analysis indicated that RBM15B expression was negatively correlated with multiple immune signatures, which was verified by ssGSEA and CIBERSORT analyses. Multiple immune-related and cancer-related pathways were enriched in the group with high RBM15B expression. Furthermore, a four-m6A RNA methylation regulator-based risk signature was constructed based on an ArrayExpress (E-MTAB-3267) dataset and confirmed in the The Cancer Genome Atlas (TCGA) testing cohort. In conclusion, our study successfully classified TCGA samples into three subgroups with different immune signatures, and suggested that the worse prognosis of KIRC2 is probably mediated by immune evasion. These findings will facilitate personalized immunotherapy in patients with KIRC. In addition, the risk score system was revealed as an independent prognostic marker that can predict survival in KIRC patients.

Effects of surgical septal myectomy on survival in patients with hypertrophic obstructive cardiomyopathy.

OBJECTIVE: The purpose of this study was to determine the effects of surgical resection of muscle layer on the long-term survival of patients with hypertrophic obstructive cardiomyopathy (HOCM). METHODS: The original study cohort consisted of 552 patients with hypertrophic cardiomyopathy (HCM), including 380 patients with HOCM and 172 patients with nonobstructive HCM. All these patients had a definite diagnosis in our center from October 1, 2009, to December 31, 2012. They were divided into three groups, viz., HOCM with myectomy group (n=194), nonoperated HOCM group (n=186), and nonobstructive HCM group (n=172). Median follow-up duration was 57.57±13.71 months, and the primary end point was a combination of mortality from all causes. RESULTS: In this survival study, we compared the prognoses of patients with HOCM after myectomy, patients with nonoperated HOCM, and patients with nonobstructive HCM. Among the three groups, the myectomy group showed a lower rate of reaching the all-cause mortality with statistically indistinguishable overall survival compared with patients with nonobstructive HCM (p=0.514). Among patients with left ventricular outflow tract (LVOT) obstruction, the overall survival in the myectomy group was noticeably better than that in the nonoperated HOCM group (log-rank p<0.001). Parameters that showed a significant univariate correlation with survival included age, previous atrial fibrillation (AF), NT-proBNP, Cr, myectomy, and LV ejection fraction. When these variables were entered in the multivariate model, the only independent predictors of survival were myotomy [hazard ratio (HR): 0.109; 95% CI: 0.013-0.877, p<0.037], age (HR: 1.047; 95% CI: 1.007-1.088, p=0.021), and previous AF (HR: 2.659; 95% CI: 1.022-6.919, p=0.021). CONCLUSION: Patients with HOCM undergoing myectomy appeared to suffer from a lower risk of reaching the all-cause mortality and demonstrated statistically indistinguishable overall survival compared with patients with nonobstructive HCM. Multivariate analysis clearly demonstrated myectomy as a powerful, independent factor of survival, confirming that the differences in long-term survival recorded in this study may be due to surgical improvement in the LVOT gradient.

Juncus effusus fiber-based cellulose cigarette filter with 3D hierarchically porous structure for removal of PAHs from mainstream smoke.

Polycyclic aromatic hydrocarbons (PAHs) from cigarettes are one of the main pollutants affecting public health. Herein, a cellulose cigarette filter with three-dimensional (3D) hierarchically porous structure was fabricated using a natural cellulose Juncus effusus (JE) fiber, whose pore size was well controlled by biocompatible polyvinylpyrrolidone (PVP) using a simple dip-dry method. The adsorption capacity and mechanism of the PVP-JE filter tips (PJF) against PAHs were investigated in detail. Compared with conventional cellulose acetate filter tips (CAF), the cellulose PJF were superior at filtering and adsorbing of PAHs from mainstream smoke with the removal efficiency of 61.79 %, which was 22.57 % higher than that of CAF (39.22 %). The ternary structures including polymer filter membrane, 3D network, and interconnected channels were demonstrated as the main roles for highly effective removal of PAHs. The JE-based cellulose cigarette filter can be a promising candidature to broaden the application range of polysaccharide in pollutant elimination.

Electrospun zirconium oxide embedded in graphene-like nanofiber for aptamer-based impedimetric bioassay toward osteopontin determination.

An impedimetric bioassay was constructed based on a nanohybrid of zirconium oxide nanoparticles and graphene-like nanofiber (denoted by ZrO2@GNF) for the determination of osteopontin (OPN). A series of ZrO2@GNF nanohybrids with different morphologies and nanostructures were derived from zirconium-based metal-organic frameworks (UiO-66) entrapped within the electric spun polyacrylonitrile (PAN) fiber (represented by UiO-66@PAN) by calcination at different temperatures. The basic characterizations revealed that the UiO-66@PAN nanofibers were collapsed into short nanorods. As such, homogeneously distributed ZrO2 nanoparticles were found to be embedded within the GNF nanostructure. This transition in the chemical structure and nanostructure not only can greatly enhance the electrochemical conductivity of the nanohybrid but also can strengthen the adsorbed bioaffinity toward OPN aptamer strands. As compared with bioassays based on ZrO2@GNF calcined at 500 °C and 900 °C, the ZrO2@GNF nanohybrid obtained at 700 °C (ZrO2@GNF700) demonstrated superior sensing performance, showing a determination limit of 4.76 fg mL-1 within a OPN concentration ranging 0.01 pg mL-1 to 2.0 ng mL-1. It also displayed high selectivity, accompanied by  good reproducibility and stability, acceptable applicability, and excellent repeatability. Graphical abstractSchematic representation of an impedimetric aptasensor based on nanohybrids of zirconium oxide nanoparticles and graphene-like nanofiber (ZrO2@CNF) was constructed for osteopontin detection. The ZrO2@CNF700 nanohybrid-based aptasensor demonstrated superior sensing performances, providing a promising tool for detecting cancer markers in biomedical diagnosis.

Midterm Results of Transaxillary Occluder Device Closure of Perimembranous Ventricular Septal Defect Guided Solely by Transesophageal Echocardiography.

BACKGROUND: Perimembranous ventricular septal defect (pmVSD) is a common congenital heart disease. Transaxillary occluder device closure of the pmVSD has been proved effective and an alternative to surgical closure. The study aimed to evaluate the immediate operation outcomes and the early and midterm follow-up outcomes of transaxillary occluder device closure. METHODS: From January 2014 to December 2017, we retrospectively analyzed the patients who underwent transaxillary device closure of the pmVSD. All patients underwent transthoracic echocardiography (TTE), chest x-ray, and electrocardiogram (ECG) before and after the procedure (before discharging). Follow-up evaluation was completed at the time of 3, 6, 12 months and yearly thereafter in outpatient setting with TTE and ECG. RESULTS: A total of 428 patients (216 male, 212 female) underwent transaxillary occluder device closure of the pmVSD under the guidance of transesophageal echocardiography (TEE). The mean age at the operation time was 2.2 ± 1.5 year (range 0.5-16.2 year). The mean weight was 8.5 ± 4.1 kg (range 6-61 kg). The mean size of the occluder implanted in the operation was 5.3 ± 1.4 (range 4-8 mm), matching the mean defect size of 4.2 ± 1.1 (range 3-6 mm). The device closure operation was successfully achieved in 422 pmVSD patients (98.6%), and 6 patients failed in occluding and were converted to open surgery because of a great residual shunt and obvious device-related aortic regurgitation . Immediate complete closure was detected by postoperative TEE in all, but 3 patients had trivial residual shunting. Total early adverse events emerged in 47 patients (11.1%). New mild tricuspid and aortic regurgitation occurred in 17 and 3 patients and disappeared in follow-up. Abnormal atrioventricular conduction events emerged in 23 patients, including left anterior block, complete right bundle branch block (CRBBB), incomplete right bundle branch block (IRBBB), administrated with close follow-up. Pericardial effusion occurred in 2 other patients, managed with puncture drainage. During a median follow-up period of 26.8 months (range 6-48 months), no serious adverse event and later-on complete atrioventricular block were encountered. CONCLUSION: In our experience, transaxillary device closure was performed via right infra-axillary mini-incision (invisible) guided by TEE, with low incidence of postoperative adverse events, confirming that transaxillary device closure of the pmVSD under the guidance of TEE is an effective alternative to surgical closure in well-selected pmVSD patients.

Three-dimensional printing enhances preparation for repair of double outlet right ventricular surgery.

OBJECTIVE: To assess the clinical value of three-dimensional (3D) printing technology for treatment strategies for complex double outlet right ventricle (DORV). METHODS: Twenty-five patients with complex double outlet right ventricle were enrolled in this study. The patients were divided into two groups: 3D printing group (eight patients) and a non-3-D printing control group (17 patients). The cardiac images of patients in the 3D printing group were transformed to Digital Imaging and Communications and were segmented and reconstructed to create a heart model. No cardiac models were created in the control group. A Pearson coefficient analysis was used to assess the correlation between measurements of 3D printed models and computed tomography angiography (CTA) data. Pre-operative assessment and planning were performed with 3D printed models, and then operative time and recovery time were compared between the two groups. RESULTS: There was good correlation (r = 0.977) between 3D printed models and CTA data. Patients in the 3D printing group had shorter aortic cross-clamp time (102.88 vs 127.76 min, P = 0.094) and cardiopulmonary bypass time (151.63 vs 184.24 min; P = 0.152) than patients in the control group. Patients with 3D printed models had significantly lower mechanical ventilation time (56.43 vs 96.76 h, P = 0.040) and significantly shorter intensive care unit time (99.04 vs 166.94 h, P = 0.008) than patients in the control group. CONCLUSIONS: 3D printed models can accurately demonstrate anatomic structures and are useful for pre-operative treatment strategies in DORV.

A Fully-Automatic Multiparametric Radiomics Model: Towards Reproducible and Prognostic Imaging Signature for Prediction of Overall Survival in Glioblastoma Multiforme.

In fully-automatic radiomics model for predicting overall survival (OS) of glioblastoma multiforme (GBM) patients, the effect of image standardization parameters such as voxel size, quantization method and gray level on model reproducibility and prognostic performance are still unclear. In this study, 45792 multiregional radiomics features were automatically extracted from multi-modality MR images with different voxel sizes, quantization methods, and gray levels. The feature reproducibility and prognostic performance were assessed. Multiparametric and fixed-parameter radiomics signatures were constructed based on a training cohort (60 patients). In an independent validation cohort (32 patients), the multiparametric signature achieved better performance for OS prediction (C-Index = 0.705, 95% CI: 0.672, 0.738) and significant stratification of patients into high- and low-risk groups (P = 0.0040, HR = 3.29, 95% CI: 1.40, 7.70), which outperformed the fixed-parameter signatures and conventional factors such as age, Karnofsky Performance Score and tumor volume. This study demonstrated that voxel size, quantization method and gray level had influence on reproducibility and prognosis of radiomics features for GBM OS prediction. An automatic method to determine the optimal parameter settings was provided. It indicated that multiparametric radiomics signature had the potential of offering better prognostic performance than fixed-parameter signatures.