The efficacy and safety of tacrolimus in treating refractory IgA vasculitis nephritis: a single-center retrospective study on 16 cases.

Background: This study aimed to observe the efficacy and safety of tacrolimus in the treatment of refractory immunoglobulin A vasculitis nephritis (IgAVN). Methods: Sixteen patients with IgAVN who had been previously treated with cyclophosphamide shock therapy at least five times, some of whom had also received mycophenolate but still had persistent proteinuria, were enrolled. The clinical and pathological data were collected and analysed. Results: The average (mean ± standard deviation) age at the initial assessment for the group of 16 patients was 10 ± 2.7 years. Finally, at the end of their respective follow-up time point, 6 of the 16 patients achieved complete remission (37.5%), 5 achieved partial remission (31.2%), and 5 had no remission (31.2%). A significant difference was found in the median proteinuria before and after a 6-month course of tacrolimus treatment [19.2 (11.2, 31.9) vs 7.8 (4.3, 13.9) mg/kg/day] (P < .05). During the first 6 months of tacrolimus treatment, all patients' estimated glomerular filtration rate levels remained normal. The mean tacrolimus blood concentration was 6.0 ± 2.6 ng/mL. The median prednisone dosage was decreased from 10 mg/day to 5 mg/day, and prednisone was eventually stopped in three individuals. No drug-related adverse effects were observed during treatment. Conclusions: Tacrolimus has demonstrated efficacy in increasing remission rates, significantly lowering urinary protein levels, and reducing steroid use in children with refractory IgAVN. Further research is required to investigate its optimal blood concentrations, long-term effects and renoprotective properties.

Comparison of different genetic testing modalities applied in paediatric patients with steroid-resistant nephrotic syndrome.

BACKGROUND: Steroid-resistant nephrotic syndrome (SRNS) are monogenic in some cases, however, there are still no clear guidelines on genetic testing in the clinical practice of SRNS in children. METHODS: Three hundred thirty-two children were diagnosed with SRNS, and all children underwent genetic testing, including gene panels and/or whole-exome/genome sequencing (WES/WGS), during treatment. We analysed the relationship between clinical manifestation and genotype, and compared different genetic testing methods' detection rates and prices. RESULTS: In this study, 30.12% (100/332) of children diagnosed with SRNS had monogenic causes of the disease. With 33.7% (122/332) of children achieving complete remission, 88.5% (108/122) received steroids combined with tacrolimus (TAC). In detectability, WES increased by 8.69% (4/46) on gene panel testing, while WGS increased by 4.27% (5/117) on WES, and WES was approximately 1/7 of the price of WGS for every further 1% increase in pathogenicity. CONCLUSIONS: We verified that steroids combined with TAC were the most effective option in paediatric SRNS. In detection efficiency, we found that WGS was the highest, followed by WES. The panel was the lowest, but the most cost-effective method when considering the economic-benefit ratio, and thus it should be recommended first in SRNS.

A genomic association study revealing subphenotypes of childhood steroid-sensitive nephrotic syndrome in a larger genomic sequencing cohort.

Dissecting the genetic components that contribute to the two main subphenotypes of steroid-sensitive nephrotic syndrome (SSNS) using genome-wide association studies (GWAS) strategy is important for understanding the disease. We conducted a multicenter cohort study (360 patients and 1835 controls) combined with a GWAS strategy to identify susceptibility variants associated with the following two subphenotypes of SSNS: steroid-sensitive nephrotic syndrome without relapse (SSNSWR, 181 patients) and steroid-dependent/frequent relapse nephrotic syndrome (SDNS/FRNS, 179 patients). The distribution of two single-nucleotide polymorphisms (SNPs) in ANKRD36 and ALPG was significant between SSNSWR and healthy controls, and that of two SNPs in GAD1 and HLA-DQA1 was significant between SDNS/FRNS and healthy controls. Interestingly, rs1047989 in HLA-DQA1 was a candidate locus for SDNS/FRNS but not for SSNSWR. No significant SNPs were observed between SSNSWR and SDNS/FRNS. Meanwhile, chromosome 2:171713702 in GAD1 was associated with a greater steroid dose (>0.75 mg/kg/d) upon relapse to first remission in patients with SDNS/FRNS (odds ratio = 3.14; 95% confidence interval, 0.97-9.87; P = 0.034). rs117014418 in APOL4 was significantly associated with a decrease in eGFR of greater than 20% compared with the baseline in SDNS/FRNS patients (P = 0.0001). Protein-protein intersection network construction suggested that HLA-DQA1 and HLA-DQB1 function together through GSDMA. Thus, SSNSWR belongs to non-HLA region-dependent nephropathy, and the HLA-DQA/DQB region is likely strongly associated with disease relapse, especially in SDNS/FRNS. The study provides a novel approach for the GWAS strategy of SSNS and contributes to our understanding of the pathological mechanisms of SSNSWR and SDNS/FRNS.

Desulfurization and upgrade of pyrolytic oil and gas during waste tires pyrolysis: The role of metal oxides.

Pyrolysis can effectively convert waste tires into high-value products. However, the sulfur-containing compounds in pyrolysis oil and gas would significantly reduce the environmental and economic feasibility of this technology. Here, the desulfurization and upgrade of waste tire pyrolysis oil and gas were performed by adding different metal oxides (Fe2O3, CuO, and CaO). Results showed that Fe2O3 exhibited the highest removal efficiency of 87.7 % for the sulfur-containing gas at 600 °C with an outstanding removal efficiency of 99.5 % for H2S. CuO and CaO were slightly inferior to Fe2O3, with desulfurization efficiencies of 75.9 % and 45.2 % in the gas when added at 5 %. Fe2O3 also demonstrated a notable efficacy in eliminating benzothiophene, the most abundant sulfur compound in pyrolysis oil, with a removal efficiency of 78.1 %. Molecular dynamics simulations and experiments showed that the desulfurization mechanism of Fe2O3 involved the bonding of Fe-S, the breakage of C-S, dehydrogenation and oxygen migration process, which promoted the conversion of Fe2O3 to FeO, FeS and Fe2(SO4)3. Meanwhile, Fe2O3 enhanced the cyclization and dehydrogenation reaction, facilitating the upgrade of oil and gas (monocyclic aromatics to 57.4 % and H2 to 22.3 %). This study may be helpful for the clean and high-value conversion of waste tires.

Characterization of glomerular basement membrane components within pediatric glomerular diseases.

Background: Disruptions in gene expression associated with the glomerular basement membrane (GBM) could precipitate glomerular dysfunction. Nevertheless, a comprehensive understanding of the characterization of GBM components within pediatric glomerular diseases and their potential association with glomerular function necessitates further systematic investigation. Methods: We conducted a systematic analysis focusing on the pathological transformations and molecular attributes of key constituents within the GBM, specifically Collagen IV α3α4α5, Laminin α5ß2γ1, and Integrin α3ß1, across prevalent pediatric glomerular diseases. Results: We observed upregulation of linear expression levels of COL4A3/4/5 and Laminin 5α proteins, along with a partial reduction in the linear structural expression of Podocin in idiopathic nephrotic syndrome (INS), encompassing minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS), but showing a reduction in IgA nephropathy (IgAN), IgA vasculitis nephritis (IgAVN) and lupus nephritis (LN). Furthermore, our study revealed reductions in Laminin ß2γ1 and Integrin α3ß1 in both primary and secondary childhood glomerular diseases. Conclusion: In INS, notably MCD and FSGS, there is a notable increase in the linear expression levels of COL4A3/4/5 and Laminin 5α proteins. In contrast, in IgAN, IgAVN, and LN, there is a consistent reduction in the expression of these markers. Furthermore, the persistent reduction of Laminin ß2γ1 and Integrin α3ß1 in both primary and secondary childhood glomerular diseases suggests a shared characteristic of structural alterations within the GBM across these conditions.

Clinical relevance of distolingual roots and periodontal status in mandibular first molars: a cross-sectional study employing CBCT analysis. / ä¸‹é¢Œç¬¬ä¸€ç£¨ç‰™è¿œèˆŒæ ¹çš„å­˜åœ¨ä¸Žç‰™å‘¨çŠ¶æ€çš„ä¸´åºŠç›¸å ³æ€§åˆ†æžï¼šä¸€é¡¹é‡‡ç”¨é”¥å½¢å°„æŸç”µè„‘æ–­å±‚æ‰«æåˆ†æžçš„æ¨ªæ–­é¢ç ”ç©¶.

OBJECTIVES: Distolingual root of the permanent mandibular first molar (PMFM-DLR) has been frequently reported, which may complicate the treatment of periodontitis. This study aimed to assess the morphological features of PMFM-DLR and investigate the correlation between the morphological features of PMFM-DLR and periodontal status in patients with Eastern Chinese ethnic background. MATERIALS AND METHODS: A total of 836 cone beam computed tomography (CBCT) images with 1497 mandibular first molars were analyzed to observe the prevalence of PMFM-DLR at the patients and tooth levels in Eastern China. Among them, complete periodontal charts were available for 69 Chinese patients with 103 teeth. Correlation and regression analyses were used to evaluate the correlation between the morphological features of DLR, bone loss, and periodontal clinical parameters, including clinical attachment loss (CAL), probing pocket depth (PPD), gingival recession (GR), and furcation involvement (FI). RESULTS: The patient-level prevalence and tooth-level prevalence of DLR in mandibular first molars were 29.4% and 26.3%, respectively. Multiple linear regression analysis suggested that bone loss at the lingual site and CAL were negatively affected by the angle of separation between distolingual and mesial roots in the transverse section, while they were significantly influenced by age and the angle of separation between distobuccal and mesial roots in the coronal section. CONCLUSIONS: The prevalence of PMFM-DLR in Eastern China was relatively high in our cohort. The morphological features of DLR were correlated with the periodontal status of mandibular first molars. This study provides critical information on the morphological features of DLR for improved diagnosis and treatment options of mandibular molars with DLR.

Coupling dechlorination and catalytic pyrolysis to produce carbon nanotubes from mixed polyvinyl chloride and polyethylene.

The presence of chlorine in polyvinyl chloride (PVC) presents a major challenge for realizing the high-value utilization of real waste plastics. The objective of this research was to develop a chlorine-resistant process for the preparation of carbon nanotubes (CNTs) from mixed plastics containing PVC. This study investigates the influence of PVC content and various dechlorinating agents (CaO, Na2CO3, red mud (RM), ZSM-5, Fe-Al2O3, Fe(OH)3) on CNTs formation. The results showed that PVC content exceeding 5 % significantly inhibits CNTs formation. Employing dechlorinating agents in the pyrolysis process results in a substantial yield of CNTs from mixed plastics containing 10 % PVC. Among the dechlorinating agents, RM proves to be the most effective, leading to the highest carbon yield (at 30 wt%) and superior CNTs quality. Other dechlorinating agents, except for ZSM-5, yield comparable results, although there were some obvious variations of volatiles. Further investigation of the role of dechlorinating agents from the perspective of volatiles evolution was conducted via Py-GC/MS, and found that the dechlorination agent efficiently absorbs the HCl from mixed plastics pyrolysis, while also exhibiting catalytic and regulatory influence on volatile components. These findings offer valuable insights for the development of a chlorine-resistant process in the preparation of CNTs from mixed plastics that contain PVC.

Cucurbit[8]uril-Based Supramolecular Probe for the Detection of 3-Nitrotyrosine in Human Serum and Plasma.

The biomarker 3-nitrotyrosine (3-NT) is widely recognized as an indicator of renal oxidative stress injury, making its detection crucial for the early identification of renal insufficiency. This study presents the design and synthesis of a tetraphenylstyrene imidazole derivative (TIPE-MI), which is utilized to create a supramolecular probe in conjunction with cucurbit[8]uril (Q[8]) through host-guest interactions. The resulting supramolecular self-assembly exhibits excellent optical properties and has been employed for the specific detection of 3-NT through fluorescence quenching. The introduction of 3-NT resulted in a decreased fluorescence intensity of the yellow fluorescent probe, which gradually transitioned from bright yellow to light yellow and then became colorless as the 3-NT concentration was increased. A portable detection platform was devised to augment the efficiency of detection. In order to facilitate biological applications, we have substantiated the probe's exceptional precision in detecting 3-NT in biological samples, encompassing human serum and plasma. The probe also exhibited negligible cytotoxicity. The accumulation of the probe in renal cells elicited a fluorescence signal, thereby indicating the prospective viability of this system for visual detection with renal cytocompatibility.

Molecular characteristics of circulating B cells and kidney cells at the single-cell level in special types of primary membranous nephropathy.

Background: Although primary membranous nephropathy (pMN) associated with podocyte autoantibodies (POS) is becoming well-known, the molecular characteristics of the specific type of pMN that is negative for podocyte autoantibodies (NEG) is still unclear. Methods: We performed single-cell transcriptome sequencing and single-cell B cell receptor sequencing on circulating CD19+ cells and kidney cells of a NEG paediatric patient with pMN. The single-cell datasets of POS patients and healthy control individuals were included for integrative analysis. Results: The gene expression characteristics and clonal expansion of naïve and memory B cells in the NEG patient changed significantly. We found that a group of CD38+ naïve B cells expanded in the NEG patient, which had the functional characteristics of cell activation. In addition, the conversion between immunoglobulin M (IgM)/IgD and IgG1 in the NEG patient was increased. Parietal epithelial cells (PECs) and podocytes shared similar signature genes (WT1, CLIC5), and new candidate marker genes for PECs, such as NID2, CAV1 and THY1, might contribute to the definition of cell subsets. PECs might have undergone significant changes in the disease, mainly manifested by changes in the expression of CCN2, PLAAT4 and SEPTIN2. The scores of gene sets related to extracellular matrix, cell adhesion and calcium channel in podocytes of the NEG patient was significantly increased. The gene expression of sodium transporter in a group of proximal tubule cells in the disease was significantly increased, especially SLC5A12, which might be related to the oedema of patients. Conclusions: Our research demonstrated the cell type-specific molecular features in the circulation and kidney of the NEG pMN patient.

Cell-type-specific molecular characterization of cells from circulation and kidney in IgA nephropathy with nephrotic syndrome.

Nephrotic syndrome (NS) is a relatively rare and serious presentation of IgA nephropathy (IgAN) (NS-IgAN). Previous research has suggested that the pathogenesis of NS-IgAN may involve circulating immune imbalance and kidney injury; however, this has yet to be fully elucidated. To investigate the cellular and molecular status of NS-IgAN, we performed single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) and kidney cells from pediatric patients diagnosed with NS-IgAN by renal biopsy. Consistently, the proportion of intermediate monocytes (IMs) in NS-IgAN patients was higher than in healthy controls. Furthermore, flow cytometry confirmed that IMs were significantly increased in pediatric patients with NS. The characteristic expression of VSIG4 and MHC class II molecules and an increase in oxidative phosphorylation may be important features of IMs in NS-IgAN. Notably, we found that the expression level of CCR2 was significantly increased in the CMs, IMs, and NCMs of patients with NS-IgAN. This may be related to kidney injury. Regulatory T cells (Tregs) are classified into two subsets of cells: Treg1 (CCR7 high, TCF7 high, and HLA-DR low) and Treg2 (CCR7 low, TCF7 low, and HLA-DR high). We found that the levels of Treg2 cells expressed significant levels of CCR4 and GATA3, which may be related to the recovery of kidney injury. The state of NS in patients was closely related to podocyte injury. The expression levels of CCL2, PRSS23, and genes related to epithelial-mesenchymal transition were significantly increased in podocytes from NS-IgAN patients. These represent key features of podocyte injury. Our analysis suggests that PTGDS is significantly downregulated following injury and may represent a new marker for podocytes. In this study, we systematically analyzed molecular events in the circulatory system and kidney tissue of pediatric patients with NS-IgAN, which provides new insights for targeted therapy in the future.

Collision Kidney Tumor Consisting of Clear Cell Renal Cell Carcinoma and Primary Renal Mantle Cell Lymphoma: A Case Report.

BACKGROUND: Non-Hodgkin's lymphoma (NHL) seldom involves the kidney, and it is even more uncommon for the kidney to be the primary renal non-Hodgkin's lymphoma (PRNHL). Due to its rarity, PRNHL is often confused with renal cell carcinoma (RCC). Tumor collision refers to the simultaneous development of two histologically distinct malignancies in the same organ or space. Collision kidney tumors have already been described but only in a few cases. Here, we report an extremely unusual case involving a collision tumor between PRNHL and RCC. CASE PRESENTATION: During a routine physical examination, a 61-year-old male was diagnosed with a tumor in his left kidney. The patient underwent a laparoscopic left partial nephrectomy. A 3.2 cm renal mass was seen on gross examination of the nephrectomy specimen, and the final pathology showed two different tumor types. The first type was a typical clear cell renal cell carcinoma (ccRCC), which made up the majority of the overall tumor. The second was composed of small- to medium-sized lymphoid monomorphic cells with uneven nuclei. Immunohistochemistry confirmed the diagnosis of a collision tumor consisting of PRNHC and ccRCC. After surgery, the patient received five courses of cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) therapy. With the gradual deterioration of all aspects of his physical function, the patient finally died of respiratory failure 15 months later. CONCLUSIONS: We present a rare case of a collision tumor consisting of renal cell carcinoma and primary renal non-Hodgkin's lymphoma. Despite their rarity, it is essential to report such cases to further understand the behavior of these tumors and develop evidence-based treatment strategies.

Circulating IL-17 reduces the risk of cisplatin-induced hearing loss in children: a bidirectional two-sample Mendelian randomization study.

Studies have reported that cytokines and their related signaling pathways play a role in inner ear diseases. In clinical practice, approximately 50% of pediatric cancer patients experience irreversible hearing loss after cisplatin treatment. However, currently, there is a lack of systematic research on the causal relationship between circulating cytokines and cisplatin-induced hearing loss in children. Genetic variant data for 41 circulating cytokines were obtained from a meta-analysis of genome-wide association studies (GWAS) among 8293 individuals of Finnish descent. The GWAS data for Cisplatin-induced hearing loss in children were derived from a multicenter cohort of European pediatric cancer patients and survivors (N = 390), including both cases with hearing loss after cisplatin chemotherapy and controls without hearing loss. Multiple methods were employed for bidirectional Mendelian randomization (MR) estimation. Bonferroni correction was applied to adjust the original P-values, followed by a series of sensitivity analyses. In the directional Mendelian randomization (MR) analysis, it was found that IL-17 was significantly associated with a reduced risk of Cisplatin-induced hearing loss in children (OR: 0.18, CI: 0.06-0.48, P < 0.001, FDR = 0.041). In the reverse MR analysis, there were some nominal causal relationships of Cisplatin-induced hearing loss in children with certain cytokines [M-CSF: (OR: 1.04, CI: 1.01-1.08, P = 0.010, FDR = 0.41); IL-2RA: (OR: 1.03, CI: 1.00-1.05, P = 0.044, FDR = 0.447); MIP-1ß: (OR: 1.02, CI: 1.00-1.04, P = 0.041, FDR = 0.447)]. leave-one-out analysis demonstrated that only M-CSF exhibited stability. These findings reveal a causal relationship between IL-17 and cisplatin-induced hearing loss in children. Further research is needed to determine the potential protective mechanisms of IL-17 in cisplatin-induced ototoxicity.

A fast permutation entropy for pulse rate variability online analysis with one-sample recursion.

Pulse rate variability (PRV) signals are extracted from pulsation signal can be effectively used for cardiovascular disease monitoring in wearable devices. Permutation entropy (PE) algorithm is an effective index for the analysis of PRV signals. However, PE is computationally intensive and impractical for online PRV processing on wearable devices. Therefore, to overcome this challenge, a fast permutation entropy (FPE) algorithm is proposed based on the microprocessor data updating process in this paper, which can analyze PRV signals with single-sample recursive. The simulation data and PRV signals extracted from pulse signals in "Fantasia database" were utilized to verify the performance and accuracy of the improved methods. The results show that the speed of FPE is 211 times faster than PE and maintain the accuracy of algorithm (Root Mean Squared Error = 0) for simulation data with a length of 10,000 samples and embedded dimension m = 5, time delay τ = 5, buffer length Lw = 512. For the RRV signals with 3000∼5000 samples, the result show that the consumption of FPE is less than 0.2 s, which is 175 times faster than PE. This indicates that FPE has better application performance than PE. Furthermore, a low-cost wearable signal detection system is developed to verify the proposed method, the result show that the proposed method can calculate the FPE of PRV signal online with single-sample recursive calculation. Subsequently, entropy-based features are used to explore the performance of decision trees in identifying life-threatening arrhythmias, and the method resulted in a classification accuracy of 85.43%. It can therefore be inferred that the proposed method has great potential in cardiovascular disease.

Klotho inhibits renal ox-LDL deposition via IGF-1R/RAC1/OLR1 signaling to ameliorate podocyte injury in diabetic kidney disease.

OBJECTIVE: Diabetic kidney disease (DKD) is characterized by the abnormal deposition of oxidized low-density lipoprotein (ox-LDL), which contributes to podocyte damage. Klotho, an aging suppressor that plays a critical role in protecting podocytes in DKD, is mainly expressed in kidney tubular epithelium and secreted in the blood. However, it has not been established whether Klotho can alleviate podocyte injury by inhibiting renal ox-LDL deposition, and the potential molecular mechanisms require further investigation. METHODS: We conducted a comprehensive analysis of serum and kidney biopsy samples obtained from patients diagnosed with DKD. Additionally, to explore the underlying mechanism of Klotho in the deposition of ox-LDL in the kidneys, we employed a mouse model of DKD with the Klotho genotype induced by streptozotocin (STZ). Furthermore, we conducted meticulous in vitro experiments on podocytes to gain further insights into the specific role of Klotho in the deposition of ox-LDL within the kidney. RESULTS: Our groundbreaking study unveiled the remarkable ability of the soluble form of Klotho to effectively inhibit high glucose-induced ox-LDL deposition in podocytes affected by DKD. Subsequent investigations elucidated that Klotho achieved this inhibition by reducing the expression of the insulin/insulin-like growth factor 1 receptor (IGF-1R), consequently leading to a decrease in the expression of Ras-related C3 botulinum toxin substrate 1 (RAC1) and an enhancement of mitochondrial function. Ultimately, this series of events culminated in a significant reduction in the expression of the oxidized low-density lipoprotein receptor (OLR1), thereby resulting in a notable decrease in renal ox-LDL deposition in DKD. CONCLUSION: Our findings suggested that Klotho had the potential to mitigate podocyte injury and reduced high glucose-induced ox-LDL deposition in glomerulus by modulating the IGF-1R/RAC1/OLR1 signaling. These results provided valuable insights that could inform the development of novel strategies for diagnosing and treating DKD.

Application of the International System for Reporting Serous Fluid Cytopathology (ISRSFC) in reporting serous effusion: A retrospective study.

In order to develop uniform diagnostic standards and reporting terminology, the International Academy of Cytology and the American Society of Cytopathology have recommended the establishment of the International System for Reporting Serous Fluid Cytopathology (ISRSFC). ISRSFC has 5 diagnostic categories: non-diagnostic (ND), negative for malignancy (NFM), atypia of unknown significance (AUS), suspicious for malignancy (SFM), and malignant (MAL). So far, very few studies have evaluated the risk of malignancy (ROM) and performance characteristics (sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy) of different categories. The purpose of this study was to reclassify serous effusions based on the ISRSFC and to assess their ROM and performance characteristics. All serous effusions from January 2017 to December 2022 were categorized according to the ISRSFC. Using histopathological diagnosis as the gold standard, the ROM and performance characteristics were calculated for each group. Finally, a total of 2103 serous effusion specimens were analyzed. After reclassification, 9 (0.4%) cases were classified as ND, 547 (26%) as NFM, 94 (4.5%) as AUS, 386 (18.4%) as SFM, and 1067 (50.7%) as MAL. The ROMs for ND, NFM, AUS, SFM and MAL were calculated to be 50%, 24.9%, 36.8%, 89.0%, and 100%, respectively. As an easy-to-grasp reporting system, ISRSFC provides a consistent standard for better communication between physicians and pathologists.

Collision Kidney Tumor Consisting of Clear Cell Renal Cell Carcinoma and Primary Renal Mantle Cell Lymphoma: A Case Report

Background: Non-Hodgkin’s lymphoma (NHL) seldom involves the kidney, and it is even more uncommon for the kidney to be the primary renal non-Hodgkin’s lymphoma (PRNHL). Due to its rarity, PRNHL is often confused with renal cell carcinoma (RCC). Tumor collision refers to the simultaneous development of two histologically distinct malignancies in the same organ or space. Collision kidney tumors have already been described but only in a few cases. Here, we report an extremely unusual case involving a collision tumor between PRNHL and RCC. Case Presentation: During a routine physical examination, a 61-year-old male was diagnosed with a tumor in his left kidney. The patient underwent a laparoscopic left partial nephrectomy. A 3.2 cm renal mass was seen on gross examination of the nephrectomy specimen, and the final pathology showed two different tumor types. The first type was a typical clear cell renal cell carcinoma (ccRCC), which made up the majority of the overall tumor. The second was composed of small- to medium-sized lymphoid monomorphic cells with uneven nuclei. Immunohistochemistry confirmed the diagnosis of a collision tumor consisting of PRNHC and ccRCC. After surgery, the patient received five courses of cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) therapy. With the gradual deterioration of all aspects of his physical function, the patient finally died of respiratory failure 15 months later. Conclusions: We present a rare case of a collision tumor consisting of renal cell carcinoma and primary renal non-Hodgkin’s lymphoma. Despite their rarity, it is essential to report such cases to further understand the behavior of these tumors and develop evidence-based treatment strategies (AU)

The nitrogen and carbon footprints of ammonia synthesis in China based on life cycle assessment.

The global nitrogen (N) cycle has emerged as an earth system process with more serious artificial disruption than climate change. Artificially synthesized reactive nitrogen (Nr) already accounts for nearly 50% of the total Nr in the earth system. The massive anthropogenic conversion of inert nitrogen (N2) to Nr is a major driver of imbalance and disruption of the earth's N cycle, where the artificial ammonia (NH3) synthesis process is the main trigger. Existing studies on life cycle environmental impacts of ammonia synthesis mainly focused on the greenhouse effect but lacked or underestimated the interference with the nitrogen cycle due to currently incomplete nitrogen footprint frameworks. In addition, the comprehensive evaluation of the nexus between nitrogen and carbon footprint of NH3 synthesis systems is also insufficient. Attempting to solve the above-mentioned problems, life cycle assessment models of seven ammonia synthesis systems were established considering different raw material pathways and production technologies under China's context, assisted by the Brightway2 platform. The general framework of nitrogen footprint accounting (GFNFA) that was established by the authors previously was employed to assess the ammonia synthesis on nitrogen footprint covered all ecosphere. The performance and hotspots of the system nitrogen footprint, carbon footprint (CF) and nitrogen-carbon nexus were then systematically quantified and analyzed. Results indicated that electrolysis-based ammonia powered by renewable and nuclear energy had the lowest Nr emission (0.499-1.148 kg Nr/t NH3) and carbon emission (592.822-1045.494 kg CO2-eq/t NH3). Among the seven ammonia synthesis systems investigated, biomass-based ammonia had the largest Nr emission and system nitrogen accumulation, and it converts the most N2 to Nr per ton ammonia produced, due to the extensive resources consumption and emissions during straw growth and direct Nr emission in gasification process. Thus, it caused the most significant disturbance to the earth's nitrogen cycle. The nexus between nitrogen and carbon footprints was revealed that the system's energy consumption was found to be a common driver through hotspots and contribution analysis. NH3 synthesis efficiency was the most determining factor in the system's Nr and carbon emissions. With a 15% increase in synthesis efficiency, nitrogen and carbon footprints can be reduced by more than 12.5%. This study can help researchers better understand the life cycle impacts of ammonia synthesis systems on earth's nitrogen and carbon cycle from multidisciplinary ecological origins.

Molecular basis of inherited protein C deficiency results from genetic variations in the signal peptide and propeptide regions.

BACKGROUND: Inherited protein C deficiency (PCD) caused by mutations in protein C (PC) gene (PROC) increases the risk of thrombosis. Missense mutations in PC's signal peptide and propeptide have been reported in patients with PCD, but their pathogenic mechanisms, except mutations in R42 residue, remain unclear. OBJECTIVES: To investigate the pathogenic mechanisms of inherited PCD caused by 11 naturally occurring missense mutations in PC's signal peptide and propeptide. METHODS: Using cell-based assays, we evaluated the impact of these mutations on various aspects such as activities and antigens of secreted PC, intracellular PC expression, subcellular localization of a reporter protein, and propeptide cleavage. Additionally, we investigated their effect on pre-messenger RNA (pre-mRNA) splicing using a minigene splicing assay. RESULTS: Our data revealed that certain missense mutations (L9P, R32C, R40C, R38W, and R42C) disrupted PC secretion by impeding cotranslational translocation to the endoplasmic reticulum or causing endoplasmic reticulum retention. Additionally, some mutations (R38W and R42L/H/S) resulted in abnormal propeptide cleavage. However, a few missense mutations (Q3P, W14G, and V26M) did not account for PCD. Using a minigene splicing assay, we observed that several variations (c.8A>C, c.76G>A, c.94C>T, and c.112C>T) increased the incidence of aberrant pre-mRNA splicing. CONCLUSION: Our findings suggest that variations in PC's signal peptide and propeptide have varying effects on the biological process of PC, including posttranscriptional pre-mRNA splicing, translation, and posttranslational processing. Additionally, a variation could affect the biological process of PC at multiple levels. Except for W14G, our results provide a clear understanding of the relationship between PROC genotype and inherited PCD.

Preparation of carbon nanotubes by catalytic pyrolysis of dechlorinated PVC.

Plastic waste is attracting growing interest for its utilization potential as a valuable resource. However, conventional thermochemical methods can hardly achieve high-value utilization of certain plastics, such as polyvinyl chloride (PVC) characterized with high chlorine content. Here, a low-temperature aerobic pretreatment method was introduced to realize high-efficiency dechlorination of PVC, and then the dechlorinated PVC was used to prepare carbon nanotubes (CNTs) by a catalytic pyrolysis. The results demonstrate that oxygen can significantly promote the HCl release in a pretty low-temperature range (260-340 °C). Chlorine was almost completely eliminated at 280 °C under 20 % oxygen concentration. Compared to untreated PVC, using the dechlorinated PVC as raw material, higher carbon deposition was obtained and over 60 % CNTs could be collected from the carbon deposition. This study provides a high-value utilization way for the production of CNTs from waste PVC.