Green fabrication of high-performance silver nanoparticles/reduced Ti3C2TxMXene nanocomposite catalyst for 4-nitrophenol reduction.

The outstanding electrical conductivity of transition metal carbides Ti3C2Tx(MXene) makes it as an excellent electron transfer medium for fabrication of efficient catalysts. However, the poor stability of MXene may restrict its application. Herein, a novel silver nanoparticles/reduced MXene nanocomposite (AgNPs/rMXene) catalyst was prepared by using L-arginine (L-Arg) as a green reducing agent. In the AgNPs/rMXene catalyst, the silver nanoparticles (AgNPs) and reduced MXene (rMXene) acted as catalytic active species and electron transfer medium, respectively. The composite catalyst exhibited superior catalytic activity in the conversion of 4-nitrophenol (4-NP) to 4-aminophenol (4-AP), and the conversion frequency (TOF) was high up to 1109.4 h-1. Notably, the composite catalyst also showed high stability due to the reduction of L-Arg (i.e. the repair of defect groups on MXene surface). The conversion efficiency for 4-NP reduction by AgNPs/rMXene was high up to 90% after five recycles. This present study offers a simple and green approach for the design and development of efficient MXene-based catalysts.

Regorafenib-induced renal-limited thrombotic microangiopathy: a case report and review of literatures.

BACKGROUND: Regorafenib belongs to a sub-group of small-molecule multi-targeted tyrosine kinase inhibitors(TKIs). In various studies with respect to the side-effect of regorafenib, drug-associated proteinuria standardly qualified to be defined as nephrotic syndrome was rarely reported as well as the relation of regorafenib with the occurrence and development of thrombotic microangiopathy (TMA). CASE PRESENTATION: In this case report and literature review, we presented a 62-year-old patient receiving regorafenib for metastatic colon cancer, manifesting abundant proteinuria, in which TMA was also diagnosed through renal biopsy. As far as we were concerned, this was the first reported in terms of regorafenib-induced TMA confirmed by renal biopsy. CONCLUSION: This case indicates that regorafenib, a kind of TKIs may result in TMA, which is a rare but life-threatening complication of cancer treatment drug. Insights from this case might help physicians diagnose rare forms of TMA and adjust treatment for patients in a timely manner.

Lipoprotein glomerulopathy induced by ApoE Kyoto mutation in ApoE-deficient mice.

BACKGROUND: Lipoprotein glomerulopathy (LPG) is a rare autosomal dominant kidney disease that is most commonly caused by mutations in ApoE Kyoto (p.R43C) and ApoE Sendai (p.R163P). Differences in phenotype among the various ApoE mutations have been suggested, but the pathogenic role of ApoE Kyoto has not been validated in an animal model. This study intended to establish an ApoE Kyoto murine model and to further compare the pathologic differences between ApoE Kyoto and ApoE Sendai. METHOD: Male ApoE-deficient mice, 3 months of age, were divided into five groups, including the AD-ApoE Sendai, AD-ApoE Kyoto, AD-ApoE3, AD-eGFP, and ApoE (-/-) groups. The first four groups received recombinant adenovirus that contained the entire coding regions of the human ApoE Sendai and ApoE Kyoto, apoE3, and eGFP genes, respectively. Fasting blood and urine samples were collected at multiple time points. Lipid profiles and urine albumin-creatinine ratio were measured. Renal and aortic histopathologic alterations were analyzed. RESULTS: After virus injection, plasma human ApoE was detected and rapidly reached the maximum level at 4-6 days in the AD-ApoE Kyoto and AD-ApoE Sendai groups (17.4 ± 3.1 µg/mL vs.: 22.2 ± 4.5 µg/mL, respectively) and at 2 days in the AD-ApoE3 group (38.4 µg/mL). The serum total cholesterol decreased by 63%, 65%, and 73% in the AD-ApoE Kyoto, AD-ApoE Sendai and AD-ApoE3 groups, respectively. There were no significant changes in serum triglyceride and urinary albumin-creatinine ratio among the five groups. Typical lipoprotein thrombi with positive ApoE staining were detected in the AD-ApoE Kyoto and AD-ApoE Sendai groups. The Oil-red O-positive glomerular area tended to be higher in the AD-ApoE Kyoto group (9.2%) than in the AD-ApoE Sendai (3.9%), AD-ApoE3 (4.8%), AD-eGFP (2.9%), and ApoE (-/-) (3.6%) groups. The atherosclerotic plaque area in the aorta was lower in the group injected with various ApoE mutations than in the group without injection of ApoE mutation. CONCLUSIONS: In this animal study, we first established an ApoE Kyoto mutation murine model and confirmed its pathogenic role in LPG. Our results suggested that LPG may be more severe with the ApoE Kyoto than with the ApoE Sendai.

Resolution of huge thrombi in bilateral ventricles caused by severe lupus cardiomyopathy.

Ventricular thrombus is an uncommon, severe condition with high morbidity and mortality. Simultaneous left and right ventricular thrombi caused by lupus myocardiopathy have not been previously reported in the literature. This case presents a 42-year-old woman who has bilateral ventricular thrombi with reduced left ventricular ejection fraction (35.4%) and acute kidney injury. Pro-brain natriuretic peptide was >35000 pg/mL. Systemic lupus erythematosus was confirmed based on multiorgan injuries including malar rash, anemia, renal injury, positive antinuclear, anti-Smith antibodies, and decreased complements. Renal biopsy revealed lupus nephritis class III + V. Low molecular weight heparin, steroids, and mycophenolate mofetil were initiated, after which the patient experienced transient numbness in the right limbs and hemoptysis. She then recovered quickly and improved significantly with recovery of left ventricular systolic function (left ventricular ejection fraction 46%) and the eventual disappearance of thrombi. Simultaneous left and right ventricular thrombi are rare but life-threatening condition, prompting consideration of myocardiopathy caused by autoimmune diseases such as lupus. Timely treatment with immunosuppressants and anticoagulants may resolve the thrombi and improve cardiac function.

Atypical anti-glomerular basement membrane disease with anti-GBM antibody negativity and ANCA positivity: a case report.

BACKGROUND: Anti-glomerular basement membrane (anti-GBM) disease is an organ-specific autoimmune disease that involves the lung and kidneys and leads to rapid glomerulonephritis progression, with or without diffuse alveolar hemorrhage, and even respiratory failure. Classic cases of anti-GBM disease are diagnosed based on the presence of the anti-GBM antibody in serum samples and kidney or lung biopsy tissue samples. However, atypical cases of anti-GBM disease are also seen in clinical practice. CASE PRESENTATION: We herein report the rare case of a patient with atypical anti-GBM disease whose serum was negative for the anti-GBM antibody but positive for the myeloperoxidase (MPO) anti-neutrophil cytoplasmic antibody (p-ANCA) and another atypical ANCA. Laboratory test results showed severe renal insufficiency with a creatinine level of 385 µmol/L. Renal biopsy specimen analysis revealed 100% glomeruli with crescents; immunofluorescence showed immunoglobulin G (IgG) linearly deposited alongside the GBM. Finally, the patient was discharged successfully after treatment with plasmapheresis, methylprednisolone and prednisone. CONCLUSION: This patient, whose serum was negative for the anti-GBM antibody but positive for p-ANCA and another atypical ANCA, had a rare case of anti-GBM disease. Insights from this unusual case might help physicians diagnose rare forms of glomerulonephritis and treat affected patients in a timely manner.

Associations of noise kurtosis, genetic variations in NOX3 and lifestyle factors with noise-induced hearing loss.

BACKGROUND: Noise-induced hearing loss (NIHL) is a complex disease caused by environmental and genetic risk factors. This study was to explore the association of noise kurtosis, triphosphopyridine nucleotide oxidase 3 (NOX3) and lifestyles with NIHL. METHODS: This case-control study included 307 patients with NIHL and 307 matched control individuals from Zhejiang province of China. General characteristics, noise exposure data, the exfoliated cells of the oral mucosa, and lifestyle details of individuals were collected. The kompetitive allele specific polymerase chain reaction (KASP) method was used to analyze the genotypes of three single nucleotide polymorphisms (SNPs) of NOX3. RESULTS: People who exposed to complex noise had a higher risk of NIHL than those exposed to steady noise (adjusted: OR = 1.806, P = 0.002). The GT genotype of additive model and TT + GT genotype of dominant model in NOX3 rs12195525 decreased the risk of NIHL (adjusted: OR = 0.618, P = 0.043; OR = 0.622, P = 0.036). Smoking and exposure to high video volume increased the risk of NIHL (adjusted: OR = 1.486, P = 0.038; OR = 1.611, P = 0.014). Oppositely, regular physical exercise decreased the risk of NIHL (adjusted: OR = 0.598, P = 0.004). A positive interaction was found between complex noise and lifestyles including high video volume exposure and no physical exercise in the additive models (RERI = 1.088, P < 0.001; RERI = 1.054, P = 0.024). A positive interaction was also found between NOX3 rs12195525 GG genotype and lifestyles including smoking and high video volume exposure in the additive models (RERI = 1.042, P = 0.005; RERI = 0.774, P = 0.044). CONCLUSIONS: Noise temporal structure, NOX3 rs12195525 polymorphism, and the three lifestyles of smoking, video volume, and physical exercise were related to the NIHL. There were the interactions between noise temporal structure and the lifestyle of video volume or physical exercise, as well as between NOX3 and the lifestyle of smoking or video volume. These results provide a theoretical basis for the prevention and genetic testing of NIHL.

Stat3-Efemp2a modulates the fibrillar matrix for cohesive movement of prechordal plate progenitors.

Recently, emerging evidence has shown that Stat3 controls tumor cell migration and invasion. However, the molecular mechanisms by which Stat3 controls the cell movement remain largely unknown. Embryonic gastrula progenitors display coordinated and orientated migration, called collective cell migration. Collective cell migration is the simultaneous movement of multiple cells and is universally involved in physiological and pathological programs. Stat3 activity is required for the migration of gastrula progenitors, but it does not affect cell specification, thus suggesting that gastrula movements are an excellent model to provide insight into Stat3 control of cell migration in vivo. In this study, we reveal a novel mechanism by which Stat3 modulates extracellular matrix (ECM) assembly to control the coherence of collective migration of prechordal plate progenitors during zebrafish embryonic gastrulation. We show that Stat3 regulates the expression of Efemp2a in the prechordal plate progenitors that migrate anteriorly during gastrulation. Alteration of Stat3-Efemp2a signaling activity disrupted the configuration of fibronectin (FN) and laminin (LM) matrices, resulting in defective coherence of prechordal plate progenitor movements in zebrafish embryos. We demonstrate that Efemp2a acts as a downstream effector of Stat3 to promote ECM configuration for coherent collective cell migrations in vivo.

A dosimetric comparison of ultra-hypofractionated passively scattered proton radiotherapy and stereotactic body radiotherapy (SBRT) in the definitive treatment of localized prostate cancer.

BACKGROUND: We compared target and normal tissue dosimetric indices between ultra-hypofractionated passively scattered proton radiotherapy and stereotactic body radiotherapy (SBRT) in the definitive treatment of localized prostate cancer. MATERIAL AND METHODS: Ten patients were treated definitively for localized prostate cancer with SBRT to a dose of 36.25 Gy in 5 fractions prescribed to a volume encompassing the prostate only. Dose-volume constraints were applied to the rectum, bladder, penile bulb, femoral heads, and prostatic and membranous urethra. Three-field passively scattered proton plans were retrospectively generated using target volumes from the same patients. Dosimetric indices were compared between the SBRT and proton plans using the Wilcoxon signed rank test. RESULTS: All dose constraints were achieved using both ultra-hypofractionated passively scattered proton and SBRT planning. Proton plans demonstrated significant improvement over SBRT in mean dose delivered to the penile bulb (5.2 CGE vs. 11.4 Gy; p=0.002), rectum (6.7 CGE vs. 10.6 Gy; p=0.002), and membranous urethra (32.2 CGE vs. 34.4 Gy; p=0.006) with improved target homogeneity resulting in a significant reduction in hot spots and volumes of tissue exposed to low doses of radiation. Compared to proton planning, SBRT planning resulted in significant improvement in target conformality with a mean index of 1.17 versus 1.72 (p=0.002), resulting in a dose reduction to the volume of bladder receiving more than 90% of the PD (V32.6, 7.5% vs. 15.9%; p=0.01) and mean dose to the left (7.1 Gy vs. 10.4 CGE; p=0.004) and right (4.0 Gy vs. 10.9 CGE; p=0.01) femoral heads. CONCLUSION: Target and normal tissue dose constraints for ultra-hypofractionated definitive radiotherapy of localized prostate cancer are readily achieved using both CK SBRT and passively scattered proton-based therapy suggesting feasibility of either modality.

Osteogenic differentiation of amniotic epithelial cells: synergism of pulsed electromagnetic field and biochemical stimuli.

BACKGROUND: Pulsed electromagnetic field (PEMF) is a non-invasive physical therapy used in the treatment of fracture nonunion or delayed healing. PEMF can facilitate the osteogenic differentiation of bone marrow mesenchymal stem cells in vitro. Amniotic epithelial cells (AECs) have been proposed as a potential source of stem cells for cell therapy. However, whether PEMF could modulate the osteogenic differentiation of AECs is unknown. In the present study, the effects of PEMF on the osteogenic differentiation of AECs were investigated. METHODS: AECs were isolated from amniotic membrane of human placenta by trypsin digestion and were induced by PEMF and/or osteo-induction medium. After 21 days we used real time RT-PCR and immunocytochemistry to study the expression of osteoblast markers. The signal transduction of osteogenesis was further investigated. RESULTS: The PEMF stimulation, or osteo-induction medium alone could induce osteogenic differentiation of AECs, as shown by expression of osteoblast specific genes and proteins including alkaline phosphatase and osteocalcin. Furthermore, a combination of PEMF and osteo-induction medium had synergy effects on osteogenic differentiation. In our study, the gene expression of BMP-2, Runx2, ß-catenin, Nrf2, Keap1 and integrinß1 were up-regulated in the osteogenic differentiation of AECs induced by PEMF and/or osteo-induction medium. CONCLUSIONS: Combined application of PEMF and osteo-induction medium is synergistic for the osteogenic differentiation of AECs. It might be a novel approach in the bone regenerative medicine.

Production of lactulose from lactose using a novel cellobiose 2-epimerase from Clostridium disporicum.

Lactulose is a semisynthetic nondigestive sugar derived from lactose, with wide applications in the food and pharmaceutical industries. Its biological production routes which use cellobiose 2-epimerase (C2E) as the key enzyme have attracted widespread attention. In this study, a set of C2Es from different sources were overexpressed in Escherichia coli to produce lactulose. We obtained a novel and highly efficient C2E from Clostridium disporicum (CDC2E) to synthesize lactulose from lactose. The effects of different heat treatment conditions, reaction pH, reaction temperature, and substrate concentrations were investigated. Under the optimum biotransformation conditions, the final concentration of lactulose was up to 1.45 M (496.3 g/L), with a lactose conversion rate of 72.5 %. This study provides a novel C2E for the biosynthesis of lactulose from low-cost lactose.

Drug Repositioning Based on Deep Sparse Autoencoder and Drug-Disease Similarity.

Drug repositioning is critical to drug development. Previous drug repositioning methods mainly constructed drug-disease heterogeneous networks to extract drug-disease features. However, these methods faced difficulty when we are using structurally simple models to deal with complex heterogeneous networks. Therefore, in this study, the researchers introduced a drug repositioning method named DRDSA. The method utilizes a deep sparse autoencoder and integrates drug-disease similarities. First, the researchers constructed a drug-disease feature network by incorporating information from drug chemical structure, disease semantic data, and existing known drug-disease associations. Then, we learned the low-dimensional representation of the feature network using a deep sparse autoencoder. Finally, we utilized a deep neural network to make predictions on new drug-disease associations based on the feature representation. The experimental results show that our proposed method has achieved optimal results on all four benchmark datasets, especially on the CTD dataset where AUC and AUPR reached 0.9619 and 0.9676, respectively, outperforming other baseline methods. In the case study, the researchers predicted the top ten antiviral drugs for COVID-19. Remarkably, six out of these predictions were subsequently validated by other literature sources.

Demographic distribution analysis of different glomerular diseases in Southwest China from 2008 to 2022.

BACKGROUND: Environmental and lifestyle factors play an etiological role in the pathogenesis of different glomerular diseases. Thus, exploring the epidemic characteristics of renal disease in different nationalities and regions is important. MATERIALS AND METHODS: Patients who underwent renal biopsy from October 2008 to October 2022 were included. The proportion and change tendency of glomerular diseases and the differences between the sexes and different ages and races were analyzed. RESULTS: There were 15,146 cases of glomerular diseases (98.5%), involving 7538 males (49.8%) and 7608 females (50.2%). The mean age was 37.0 years (range 0-80 years). The proportion of membranous nephropathy (MN) and diabetic nephropathy (DN) showed an increased trend. The most common primary glomerulonephritis (PGN) was IgA nephropathy (IgAN, 44.6%), followed by minimal-change disease (MCD, 24.3%) and MN (15.4%). Lupus nephritis (LN, 30%) accounted for the largest proportion of SGNs, followed by Henoch-Schonlein purpura nephritis (HSPN, 20.9%) and DN (19.8%). Compared with adults aged 18-60 years old, MCD and HSPN were more common in children and MN and DN in elderly individuals, statistically significant differences. Additionally, the sex and age distribution of PGN and SGN between the Tibetan and Han populations differed significantly, whereby LN was higher in the Han population and HSPN in the Tibetan population. CONCLUSION: The distribution of glomerular diseases showed age, sex and race differences. This research will be beneficial for providing epidemiological evidence for clinical diagnosis, disease prevention and public health decision-making.

The role of kurtosis and kurtosis-adjusted energy metric in occupational noise-induced hearing loss among metal manufacturing workers.

Background: Noise energy has been well-established to increase the risk of occupational noise-induced hearing loss (NIHL). However, the role of noise temporal structure (expressed by kurtosis) or its combination with energy metrics (e.g., kurtosis-adjusted cumulative noise exposure, adj-CNE) in occupational NIHL was still unclear. Methods: A cross-sectional survey of 867 Chinese workers, including 678 metal manufacturing workers and 189 workers exposed to Gaussian noise, was conducted. Noise energy metrics, including LAeq,8h and CNE, kurtosis (ß), and adj-CNE were used to quantify noise exposure levels. Noise-induced permanent threshold shift at frequencies 3, 4, and 6 kHz (NIPTS346) and the prevalence of high-frequency NIHL (HFNIHL%) were calculated for each participant. The dose-response relationship between kurtosis or adj-CNE and occupational NIHL was observed. Results: Among 867 workers, different types of work had specific and independent noise energy and kurtosis values (p > 0.05). HFNIHL% increased with an increase in exposure duration (ED), LAeq,8h, CNE, or kurtosis (p < 0.01), and there were strong linear relationships between HFNIHL% and ED (coefficient of determination [R2] = 0.963), CNE (R2 = 0.976), or kurtosis (R2 = 0.938, when CNE < 100 dB(A)∙year). The "V" shape notching extent in NIPTS became deeper with increasing kurtosis when CNE < 100 dB(A)∙year and reached the notching bottom at the frequency of 4 or 6 kHz. The workers exposed to complex noise (ß ≥ 10) had a higher risk of NIHL than those exposed to Gaussian noise (ß < 10) at the frequencies of 3, 4, 6, and 8 kHz (OR > 2, p < 0.01). Moreover, HFNIHL% increased with adj-CNE (p < 0.001). There were strong linear relationships between NIHL and adj-CNE or CNE when ß ≥ 10 (R2adj-CNE > R2CNE). After CNE was adjusted by kurtosis, average differences in NIPTS346 or HFNIHL% between the complex and Gaussian noise group were significantly reduced (p < 0.05). Conclusion: Kurtosis was a key factor influencing occupational NIHL among metal manufacturing workers, and its combination with energy metrics could assess the risk of NIHL more effectively than CNE alone.

Loss-of-Function Homozygous Variant in LPL Causes Type I Hyperlipoproteinemia and Renal Lipidosis.

Introduction: Lipoprotein lipase (LPL) is an important enzyme in lipid metabolism, individuals with LPL gene variants could present type I hyperlipoproteinemia, lipemia retinalis, hepatosplenomegaly, and pancreatitis. To date, there are no reports of renal lipidosis induced by type I hyperlipoproteinemia due to LPL mutation. Methods: Renal biopsy was conducted to confirm the etiological factor of nephrotic syndrome in a 44-year-old Chinese man. Lipoprotein electrophoresis, apoE genotype detection, and whole-exome sequencing were performed to confirm the dyslipidemia type and genetic factor. Analysis of the 3-dimensional protein structure and in vitro functional study were conducted to verify variant pathogenicity. Results: Renal biopsy revealed numerous CD68 positive foam cells infiltrated in the glomeruli; immunoglobulin and complement staining were negative; and electron microscopy revealed numerous lipid droplets and cholesterol clefts in the cytoplasm of foam cells. Lipoprotein electrophoresis revealed that the patient fulfilled the diagnostic criteria of type I hyperlipoproteinemia. The apoE genotype of the patient was the ε3/ε3 genotype. Whole-exome sequencing revealed an LPL (c.292G > A, p.A98T) homozygous variant with α-helix instability and reduced post-heparin LPL activity but normal lipid uptake capability compared to the wild-type variant. Conclusion: LPL (c.292G > A, p.A98T) is a pathogenic variant that causes renal lipidosis associated with type I hyperlipoproteinemia. This study provides adequate evidence of the causal relationship between dyslipidemia and renal lesions. However, further research is needed to better understand the pathogenetic mechanism of LPL variant-related renal lesions.

[Pathological changes after periocular injection of triamcinolone and hyaluronidase in guinea pigs].

OBJECTIVE: To analyze the pathological change after periocular injection of triamcinolone and hyaluronidase in guinea pigs. METHODS: Twenty guinea pigs of clean grade were used in this study. The animals were randomly divided into 4 groups (n = 5 each). The right eye was used as intervention side, while the left eye was used as control side. Group A received periocular injection of saline water 0.2 mL at right eyes, Group B received periocular injection of triamcinolone 2 mg (0.2 mL), Group C received periocular injection of hyaluronidase 80 IU (0.2 mL), Group D received periocular injection of triamcinolone 2 mg (0.1 mL) + hyaluronidase 80 IU (0.1 mL). The injection was performed once a week for totally 4 times. One animal from each group was sacrificed at day 3, 7, 14, 28 and 35 after the first injection. The specimens of periocular tissue were obtained for microscopic examination and transmission electron microscopic examination to observe the pathological changes. The expressions of transforming growth factor-beta1 (TGF-beta1) in the granulomas were detected by immunohistochemistry stain method. RESULTS: Compared with the control side, group A presented no obvious change. Group C presented looser intercellular space than the control group. Foreign-body granulomas was seen in 2nd-5th pathological section of group B and in the third and fifth pathological sections of group D. The size of the granulomas was smaller and the density of fibroblast was lower in group D than those in group B. The immunohistochemistry stain of TGF-beta1 showed strong positive reaction in group B, while weakly positive reaction in group D. The positive staining cells in group D were fewer than those in group B, and the difference was statistically significant (P < 0.05). Most of the fibroblasts in group B presented as pyknic type with oval nucleus, amounts of cytoplasm and cell organs under electron microscope. Comparatively, the fibroblasts in group C and D remain inactive with spindle nucleus, less cytoplasm and cell organs. CONCLUSION: Repeated periocular injection of triamcinolone may cause the formation of foreign-body granulomas around the injection site, leading to fibrosis and adhesion at later period. The injection combined with hyaluronidase can enhance the diffusion and absorption of triamcinolone, relieving the possible fibrosis.

Drug repositioning based on heterogeneous networks and variational graph autoencoders.

Predicting new therapeutic effects (drug repositioning) of existing drugs plays an important role in drug development. However, traditional wet experimental prediction methods are usually time-consuming and costly. The emergence of more and more artificial intelligence-based drug repositioning methods in the past 2 years has facilitated drug development. In this study we propose a drug repositioning method, VGAEDR, based on a heterogeneous network of multiple drug attributes and a variational graph autoencoder. First, a drug-disease heterogeneous network is established based on three drug attributes, disease semantic information, and known drug-disease associations. Second, low-dimensional feature representations for heterogeneous networks are learned through a variational graph autoencoder module and a multi-layer convolutional module. Finally, the feature representation is fed to a fully connected layer and a Softmax layer to predict new drug-disease associations. Comparative experiments with other baseline methods on three datasets demonstrate the excellent performance of VGAEDR. In the case study, we predicted the top 10 possible anti-COVID-19 drugs on the existing drug and disease data, and six of them were verified by other literatures.

Experimental and Numerical Analyses of Stud Shear Connectors in Steel-SFRCC Composite Beams.

To investigate the shear performance and failure mechanism of stud shear connectors in steel fiber-reinforced cementitious composite (SFRCC) beams, six steel-SFRCC and six steel-normal strength concrete (NC) push-out specimens with two heights (80 mm, 120 mm) and three diameters (14 mm, 18 mm, 22 mm) of stud connectors were prepared. The experimental results revealed that the stud shearing failure was the main failure mode of all push-out specimens. In comparison to the steel-NC specimens, the development of cracks in the SFRCC beams was efficiently restrained due to the existence of high-strength steel fibers added to the normal concrete. The shear resistance and stiffness of studs in the steel-SFRCC beams were, respectively, 22.3% and 15.1% greater than those in the steel-NC specimens; however, their ductility was reduced, and the stud shear connectors failed in advance. The finite element (FE) model was developed and verified by push-out test results. FE analysis results indicated that the shear resistance of stud shear connectors was significantly improved with the increase in the concrete compressive strength, the stud diameter and tensile strength, whereas the aspect ratio of studs had a small impact on the ultimate resistance of stud shear connectors. Based on the as-obtained push-out experiment and FE analysis results, empirical formulas were presented to predict the load-slip curves and ultimate shear resistance of stud shear connectors in the steel-SFRCC specimens, and higher accuracy and a wider application range were obtained than with previous formulas.

Experimental Study on Seismic Performance of Precast Columns Repaired with CFRP Fabrics.

Earthquakes worldwide highlight the seismic vulnerability of reinforced concrete (RC) bridge columns. RC bridges are likely to collapse or lose service function due to damage to the bridge columns from strong earthquakes. Rapid repair of RC bridge columns is of great significance for maintaining traffic lines for emergency rescue work after earthquakes. In this study, an improved rapid repair method was developed to restore the bearing capacity of a damaged precast column after earthquake damage. A cyclic loading test was performed to simulate the seismic loading. The original column and the repaired column were both tested. The test results showed that the bearing capacity of the repaired columns was increased by 8%, and the energy dissipation capacity was 53% higher than that of the original column. The ductility decreased because the test for the repaired specimen ended in advance. The initial stiffness of the repaired columns was reduced, but the stiffness was significantly developed in the later loading stage. The rapid repair method proposed in this study exhibited an excellent effect on restoring the seismic resistance of the damaged columns.

Abnormal decrement on high-frequency repetitive nerve stimulation in congenital myasthenic syndrome with GFPT1 mutations and review of literature.

Objectives: Congenital myasthenic syndrome (CMS) is a clinically and genetically heterogeneous group of inherited disorders characterized by neuromuscular junction defects. Mutations in GFPT1 have been shown to underlie CMS. An increasing number of patients with CMS due to mutations in GFPT1 have been reported. However, a comprehensive review of clinical and genetic analyses of GFPT-related CMS worldwide is lacking, especially, given that the common or hotspot mutations in GFPT1 have not been reported. Here, we described the clinical and genetic findings of three patients with GFPT1 mutations from southwestern China and reviewed the clinical and genetic features of patients with GFPT1-related CMS worldwide. Methods: Clinical, laboratory, electrophysiological, myopathological, and genetic analyses of three patients with GFPT1-related CMS from southwestern China were conducted, and a review of previously published or reported cases about congenital myasthenic syndrome with GFPT1 mutations in the PubMed database was made. Results: The clinical, laboratory, electrophysiological, and myopathological features by muscle biopsy of three patients with GFPT1-related CMS were consistent with those of previously reported patients with GFPT1 mutations. Additionally, an abnormal decrement in high-frequency RNS was found. Two different homozygous missense mutations (c.331C>T, p.R111C; c.44C>T, p.T15M) were detected by whole-exome sequencing (WES) or targeted neuromuscular disorder gene panels. Conclusion: A distinct decremental response to high-frequency RNS was found in three patients with GFPT1-related CMS from southwestern China, which has never been reported thus far. In addition, the location and degree of tubular aggregates (TAs) seemed to be associated with the severity of clinical symptoms and serum creatine kinase levels, further expanding the phenotypic spectrum of GFPT1-related CMS. Lastly, some potential hotspot mutations in GFPT1 have been found in GFPT1-CMS worldwide.

Experimental and Numerical Evaluation on the Performance of Perfobond Leiste Shear Connectors in Steel-SFRCC Composite Beams.

The difference between the shear performances of Perfobond Leiste (PBL) shear connectors embedded in steel fiber-reinforced cementitious composite (SFRCC) structure and normal strength concrete (NC) structure was investigated by push-out tests and finite element (FE) simulations. Push-out tests were carried out on nine steel-SFRCC specimens and nine steel-NC specimens. The mechanical behavior of the PBL shear connector was examined according to the failure modes, load-slip curves, and strain distribution laws of the push-out specimens. Experimental results revealed that the extension of cracks in SFRCC was hindered by steel fibers, and the number and width of cracks in SFRCC were smaller than those in NC. The failure mode of the steel-SFRCC specimens and the single-hole steel-NC specimens was the shear failure of the penetrating reinforcement, whereas that of the multi-hole NC specimens was concrete slab cracking. The ultimate shear bearing capacity of PBL shear connectors in the steel-SFRCC specimens was 47.8% greater than that in the steel-NC specimens. Furthermore, an FE model verified by the test results was established to conduct parametric analyses. It was found that the hole diameter and thickness of the steel plate and the yield strength of the penetrating rebar greatly affected the shear bearing capacity of PBL shear connectors. Finally, based on the experimental and FE simulation results, an expression for calculating the ultimate shear bearing capacity of PBL shear connectors in the steel-SFRCC composite structure was developed by considering the bearing effects of concrete dowels, penetrating rebars, and end parts.