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.

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.

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.

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.

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.

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.

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.

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.

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.

NRN1 and CAT Gene Polymorphisms, Complex Noise, and Lifestyles interactively Affect the Risk of Noise-induced Hearing Loss.

OBJECTIVE: The effects of interactions between genetic and environmental factors on the noise-induced hearing loss (NIHL) are still unclear. This study aimed to assess interactions among gene polymorphisms, noise metrics, and lifestyles on the risk of NIHL. METHODS: A case-control study was conducted using 307 patients with NIHL and 307 matched healthy individuals from five manufacturing industries. General demographic data, lifestyle details, and noise exposure levels were recorded. The Kompetitive allele-specific polymerase chain reaction (KASP) was used to analyze the genotypes of 18 SNPs. RESULTS: GMDR model demonstrated a relevant interaction between NRN1 rs3805789 and CAT rs7943316 (P = 0.0107). Subjects with T allele of rs3805789 or T allele of rs7943316 had higher risks of NIHL than those with the SNP pair of rs3805789-CC and rs7943316-AA (P < 0.05). There was an interaction among rs3805789, rs7943316, and kurtosis (P = 0.0010). Subjects exposed to complex noise and carrying both rs3805789-CT and rs7943316-TT or rs3805789-CT/TT and rs7943316-AA had higher risks of NIHL than those exposed to steady noise and carrying both rs3805789-CC and rs7943316-AA (P < 0.05). The best six-locus model involving NRN1 rs3805789, CAT rs7943316, smoking, video volume, physical exercise, and working pressure for the risk of NIHL was found to be the interaction (P = 0.0010). An interaction was also found among smoking, video volume, physical exercise, working pressure, and kurtosis (P = 0.0107). CONCLUSION: Concurrence of NRN1 and CAT constitutes a genetic risk factor for NIHL. Complex noise exposure significantly increases the risk of NIHL in subjects with a high genetic risk score. Interactions between genes and lifestyles as well as noise metrics and lifestyles affect the risk of NIHL.

A metal-porphyrinic framework film as an efficient optical limiting layer in an electro-optical switchable device.

Herein we report a 2D surface-coordinated porphyrinic metal-organic framework film (SURMOF) CuTCPP prepared by a layer by layer method as an optical limiting layer in a polymer-dispersed liquid crystal (PDLC) device. The results show that the CuTCPP SURMOF/PDLC device has excellent switchable transparency and optical limiting performance, providing a new route to achieve mutilfunctional electro-optical applications.

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.

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.

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.

Stimulation of Sigma-1 Receptor Protects against Cardiac Fibrosis by Alleviating IRE1 Pathway and Autophagy Impairment.

Sigma-1 receptor (Sig1R), a chaperone in the endoplasmic reticulum (ER) membrane, has been implicated in cardiac hypertrophy; however, its role in cardiac fibroblast activation has not been established. This study investigated the possible association between Sig1R and this activation by subjecting mice to sham, transverse aortic constriction (TAC), and TAC plus fluvoxamine (an agonist of Sig1R) treatments. Cardiac function and fibrosis were evaluated four weeks later by echocardiography and histological staining. In an in vitro study, neonatal rat cardiac fibroblasts were treated with fluvoxamine or NE-100 (an antagonist of Sig1R) in the presence or absence of transforming growth factor beta1 (TGF-ß1). Fibrotic markers, ER stress pathways, and autophagy were then investigated by qPCR, western blotting, immunofluorescence, confocal microscopy, and transmission electron microscopy. Fluvoxamine treatment reduced cardiac fibrosis, preserved cardiac function, and attenuated cardiac fibroblast activation. Inhibition of the IRE1/XBP1 pathway, a branch of ER stress, by a specific inhibitor of IRE1 endonuclease activity, attenuated the pathological process. Fluvoxamine stimulation of Sig1R restored autophagic flux in cardiac fibroblasts, indicating that Sig1R appears to play a protective role in the activation of cardiac fibroblasts by inhibiting the IRE1 pathway and restoring autophagic flux. Sig1R may therefore represent a therapeutic target for cardiac fibrosis.