Glycolysis in Peritubular Endothelial Cells and Microvascular Rarefaction in CKD.

BACKGROUND: Peritubular endothelial cell dropout leading to microvascular rarefaction is a common manifestation of chronic kidney disease (CKD). The role of metabolism reprogramming in peritubular endothelial cell loss in CKD is undetermined. METHODS: Single-cell sequencing and metabolic analysis were used to characterize metabolic profile of peritubular endothelial cells from CKD patients and from CKD mouse models. In vivo and in vitro models demonstrated metabolic reprogramming in peritubular endothelial cells in conditions of CKD and its contribution to microvascular rarefaction. RESULTS: Here, we identified glycolysis as a top dysregulated metabolic pathway in peritubular endothelial cells from CKD patients. Specifically, CKD peritubular endothelial cells were hypoglycolytic while displaying an anti-angiogenic response with decreased proliferation and increased apoptosis. The hypoglycolytic phenotype of peritubular endothelial cells was recapitulated in CKD mouse models and in peritubular endothelial cells stimulated by hydrogen peroxide (H2O2). Mechanically, oxidative stress, through activating a redox sensor kruppel-like transcription factor 9, downregulated the glycolytic activator 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase (PFKFB3) expression, thereby reprogramming peritubular endothelial cells towards a hypoglycolytic phenotype. PFKFB3 overexpression in peritubular endothelial cells restored H2O2-induced reduction in glycolysis and cellular ATP levels, and enhanced the G1/S cell cycle transition, enabling peritubular endothelial cells to improve proliferation and reduce apoptosis. Consistently, restoration of peritubular endothelial cell glycolysis in CKD mice, via overexpressing endothelial Pfkfb3, reversed the anti-angiogenic response in peritubular endothelial cells and protected the kidney from microvascular rarefaction and fibrosis. In contrast, suppression of glycolysis by endothelial Pfkfb3 deletion exacerbated microvascular rarefaction and fibrosis in CKD mice. CONCLUSIONS: Our study revealed a disrupted regulation of glycolysis in peritubular endothelial cells as an initiator of microvascular rarefaction in CKD. Restoration of peritubular endothelial cell glycolysis in CKD kidney improved microvascular rarefaction and ameliorated fibrotic lesions.

Dynamically visualizing profibrotic maladaptive repair after acute kidney injury by fibroblast activation protein imaging.

A major challenge in prevention and early treatment of organ fibrosis is the lack of valuable tools to assess the evolving profibrotic maladaptive repair after injury in vivo in a non-invasive way. Here, using acute kidney injury (AKI) as an example, we tested the utility of fibroblast activation protein (FAP) imaging for dynamic assessment of maladaptive repair after injury. The temporospatial pattern of kidney FAP expression after injury was first characterized. Single-cell RNA sequencing and immunostaining analysis of patient biopsies were combined to show that FAP was specifically upregulated in kidney fibroblasts after AKI and was associated with fibroblast activation and chronic kidney disease (CKD) progression. This was corroborated in AKI mouse models, where a sustained and exaggerated kidney FAP upregulation was coupled to persistent fibroblast activation and a fibrotic outcome, linking kidney FAP level to post-insult maladaptive repair. Furthermore, using positron emission tomography (PET)/CT scanning with FAP-inhibitor tracers ([18F]FAPI-42, [18F]FAPT) targeting FAP, we demonstrated the feasibility of non-invasively tracking of maladaptive repair evolution toward kidney fibrosis. Importantly, a sustained increase in kidney [18F]FAPT (less hepatobiliary metabolized than [18F]FAPI-42) uptake reflected persistent kidney upregulation of FAP and characterized maladaptive repair after AKI. Kidney [18F]FAPT uptake at hour 2-day 7 correlated with kidney fibrosis 14 days after AKI. Similar changes in [18F]FAPI-42 PET/CT imaging were observed in patients with AKI and CKD progression. Thus, persistent kidney FAP upregulation after AKI was associated with maladaptive repair and a fibrotic outcome. Hence, FAP-specific PET/CT imaging enables dynamic visualization of maladaptive repair after AKI and prediction of kidney fibrosis within a clinically actionable window.

Maize auxin response factor ZmARF1 confers multiple abiotic stresses resistances in transgenic Arabidopsis.

Prolonged exposure to abiotic stresses causes oxidative stress, which affects plant development and survival. In this research, the overexpression of ZmARF1 improved tolerance to low Pi, drought and salinity stresses. The transgenic plants manifested tolerance to low Pi by their superior root phenotypic traits: root length, root tips, root surface area, and root volume, compared to wide-type (WT) plants. Moreover, the transgenic plants exhibited higher root and leaf Pi content and upregulated the high affinity Pi transporters PHT1;2 and phosphorus starvation inducing (PSI) genes PHO2 and PHR1 under low Pi conditions. Transgenic Arabidopsis displayed tolerance to drought and salt stress by maintaining higher chlorophyll content and chlorophyll fluorescence, lower water loss rates, and ion leakage, which contributed to the survival of overexpression lines compared to the WT. Transcriptome profiling identified a peroxidase gene, POX, whose transcript was upregulated by these abiotic stresses. Furthermore, we confirmed that ZmARF1 bound to the auxin response element (AuxRE) in the promoter of POX and enhanced its transcription to mediate tolerance to oxidative stress imposed by low Pi, drought and salt stress in the transgenic seedlings. These results demonstrate that ZmARF1 has significant potential for improving the tolerance of crops to multiple abiotic stresses.

Hyperglycolysis in endothelial cells drives endothelial injury and microvascular alterations in peritoneal dialysis.

BACKGROUND: Endothelial cell (EC) dysfunction leading to microvascular alterations is a hallmark of technique failure in peritoneal dialysis (PD). However, the mechanisms underlying EC dysfunction in PD are poorly defined. METHODS: We combined RNA sequencing with metabolite set analysis to characterize the metabolic profile of peritoneal ECs from a mouse model of PD. This was combined with EC-selective blockade of glycolysis by genetic or pharmacological inhibition of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) in vivo and in vitro. We also investigated the association between peritoneal EC glycolysis and microvascular alterations in human peritoneal samples from patients with end-stage kidney disease (ESKD). RESULTS: In a mouse model of PD, peritoneal ECs had a hyperglycolytic metabolism that shunts intermediates into nucleotide synthesis. Hyperglycolytic mouse peritoneal ECs displayed a unique active phenotype with increased proliferation, permeability and inflammation. The active phenotype of mouse peritoneal ECs can be recapitulated in human umbilical venous ECs and primary human peritoneal ECs by vascular endothelial growth factor that was released from high glucose-treated mesothelial cells. Importantly, reduction of peritoneal EC glycolysis, via endothelial deficiency of the glycolytic activator PFKFB3, inhibited PD fluid-induced increases in peritoneal capillary density, vascular permeability and monocyte extravasation, thereby protecting the peritoneum from the development of structural and functional damages. Mechanistically, endothelial PFKFB3 deficiency induced the protective effects in part by inhibiting cell proliferation, VE-cadherin endocytosis and monocyte-adhesion molecule expression. Pharmacological PFKFB3 blockade induced a similar therapeutic benefit in this PD model. Human peritoneal tissue from patients with ESKD also demonstrated evidence of increased EC PFKFB3 expression associated with microvascular alterations and peritoneal dysfunction. CONCLUSIONS: These findings reveal a critical role of glycolysis in ECs in mediating the deterioration of peritoneal function and suggest that strategies targeting glycolysis in peritoneal ECs may be of therapeutic benefit for patients undergoing PD.

Restoration of CPT1A-mediated fatty acid oxidation in mesothelial cells protects against peritoneal fibrosis.

Background: Peritoneal dialysis (PD) is limited by gradual fibrotic remodeling in the peritoneum, a process involving profibrotic response of mesothelial cells. However, the role of fatty acid oxidation (FAO) and carnitine palmitoyltransferase 1A (CPT1A) in this process remains unexplored. Methods: FAO and CPT1A expression were characterized in mesothelial cells from patients on long-term PD and from a mouse model of PD using multiple experimental methods, including single-cell sequencing, seahorse assay, real-time quantitative PCR, Western blot, and immunofluorescence staining. Overexpression of CPT1A was achieved in a human mesothelial cell line and in primary mouse mesothelial cells. Finally, genetic and pharmacological manipulations of CPT1A were performed in a mouse model of PD. Results: Herein, FAO and CPT1A expression were reduced in mesothelial cells from patients on long-term PD, which negatively correlated with expression of fibrogenic markers in these cells. This was corroborated in PD mice, as well as in mouse and human mesothelial cells incubated with transforming growth factor (TGF) ß1. CPT1A overexpression in mesothelial cells, which prevented TGFß1-induced suppression of mitochondrial respiration, restored cellular ATP levels and downregulated the expression of fibrogenic markers. Furthermore, restoration of FAO by overexpressing CPT1A in PD mice reversed profibrotic phenotype in mesothelial cells and reduced fibrotic lesions in the peritoneum. Treatment with the CPT1A activator C75 induced similar therapeutic benefit in PD mice. In contrast, inhibition of FAO with a CPT1 inhibitor caused more severe fibrosis in PD mice. Conclusions: A defective FAO is responsible for the profibrotic response of mesothelial cells and thus the peritoneal fibrogenesis. This aberrant metabolic state could be improved by modulating CPT1A in mesothelial cells, suggesting FAO enhancement in mesothelial cells is a potential treatment of peritoneal fibrosis.

Overexpression of Rice Histone H1 Gene Reduces Tolerance to Cold and Heat Stress.

Temperature stresses, including low- and high-temperature stresses, are the main abiotic stresses affecting rice yield. Due to global climate change, the impact of temperature pressure on rice yield is gradually increasing, which is also a major concern for researchers. In this study, an H1 histone in Oryza sativa (OsHis1.1, LOC_Os04g18090) was cloned, and its role in rice's response to temperature stresses was functionally characterized. The GUS staining analysis of OsHis1.1 promoter-GUS transgenic rice showed that OsHis1.1 was widely expressed in various rice tissues. Transient expression demonstrated that OsHis1.1 was localized in the nucleus. The overexpression of OsHis1.1 reduces the tolerance to temperature stress in rice by inhibiting the expression of genes that are responsive to heat and cold stress. Under stress conditions, the POD activity and chlorophyll and proline contents of OsHis1.1-overexpression rice lines were significantly lower than those of the wild type, while the malondialdehyde content was higher than that of the wild type. Compared with Nip, OsHis1.1-overexpression rice suffered more serious oxidative stress and cell damage under temperature stress. Furthermore, OsHis1.1-overexpression rice showed changes in agronomic traits.

Overexpression of OsHAD3, a Member of HAD Superfamily, Decreases Drought Tolerance of Rice.

Haloacid dehalogenase-like hydrolase (HAD) superfamily have been shown to get involved in plant growth and abiotic stress response. Although the various functions and regulatory mechanism of HAD superfamily have been well demonstrated, we know little about the function of this family in conferring abiotic stress tolerance to rice. Here, we report OsHAD3, a HAD superfamily member, could affect drought tolerance of rice. Under drought stress, overexpression of OsHAD3 increases the accumulation of reactive oxygen species and malondialdehyde than wild type. OsHAD3-overexpression lines decreased but antisense-expression lines increased the roots length under drought stress and the transcription levels of many well-known stress-related genes were also changed in plants with different genotypes. Furthermore, overexpression of OsHAD3 also decreases the oxidative tolerance. Our results suggest that overexpression of OsHAD3 could decrease the drought tolerance of rice and provide a new strategy for improving drought tolerance in rice.

Antifungal mechanisms of the antagonistic bacterium Bacillus mojavensis UTF-33 and its potential as a new biopesticide.

Biological control has gradually become the dominant means of controlling fungal disease over recent years. In this study, an endophytic strain of UTF-33 was isolated from acid mold (Rumex acetosa L.) leaves. Based on 16S rDNA gene sequence comparison, and biochemical and physiological characteristics, this strain was formally identified as Bacillus mojavensis. Bacillus mojavensis UTF-33 was sensitive to most of the antibiotics tested except neomycin. Moreover, the filtrate fermentation solution of Bacillus mojavensis UTF-33 had a significant inhibitory effect on the growth of rice blast and was used in field evaluation tests, which reduced the infestation of rice blast effectively. Rice treated with filtrate fermentation broth exhibited multiple defense mechanisms in response, including the enhanced expression of disease process-related genes and transcription factor genes, and significantly upregulated the gene expression of titin, salicylic acid pathway-related genes, and H2O2 accumulation, in plants; this may directly or indirectly act as an antagonist to pathogenic infestation. Further analysis revealed that the n-butanol crude extract of Bacillus mojavensis UTF-33 could retard or even inhibit conidial germination and prevent the formation of adherent cells both in vitro and in vivo. In addition, the amplification of functional genes for biocontrol using specific primers showed that Bacillus mojavensis UTF-33 expresses genes that can direct the synthesis of bioA, bmyB, fenB, ituD, srfAA and other substances; this information can help us to determine the extraction direction and purification method for inhibitory substances at a later stage. In conclusion, this is the first study to identify Bacillus mojavensis as a potential agent for the control of rice diseases; this strain, and its bioactive substances, have the potential to be developed as biopesticides.

Isolation of Bacillus siamensis B-612, a Strain That Is Resistant to Rice Blast Disease and an Investigation of the Mechanisms Responsible for Suppressing Rice Blast Fungus.

Rice yield can be significantly impacted by rice blast disease. In this investigation, an endophytic strain of Bacillus siamensis that exhibited a potent inhibitory effect on the growth of rice blast was isolated from healthy cauliflower leaves. 16S rDNA gene sequence analysis showed that it belongs to the genus Bacillus siamensis. Using the rice OsActin gene as an internal control, we analyzed the expression levels of genes related to the defense response of rice. Analysis showed that the expression levels of genes related to the defense response in rice were significantly upregulated 48 h after treatment. In addition, peroxidase (POD) activity gradually increased after treatment with B-612 fermentation solution and peaked 48 h after inoculation. These findings clearly demonstrated that the 1-butanol crude extract of B-612 retarded and inhibited conidial germination as well as the development of appressorium. The results of field experiments showed that treatment with B-612 fermentation solution and B-612 bacterial solution significantly reduced the severity of the disease before the seedling stage of Lijiangxintuan (LTH) was infected with rice blast. Future studies will focus on exploring whether Bacillus siamensis B-612 produces new lipopeptides and will apply proteomic and transcriptomic approaches to investigate the signaling pathways involved in its antimicrobial effects.

Neural and central mechanisms of kidney fibrosis after relief of ureteral obstruction.

Obstructive uropathy from nephrolithiasis remains a leading cause of end-stage kidney disease. Mechanisms of kidney fibrosis after relief of ureteral obstruction represent opportunities for therapeutic intervention. Here, in mouse models of ureteral obstruction, we have combined methods of virus tracing and optogenetic techniques to identify an overactive central pathway in the paraventricular nucleus (PVN)-rostral ventrolateral medulla (RVLM) that determines the fibrotic fate of kidney after relief of the obstruction. The overactive pathway is driven by kidney afferent nerves that activate angiotensin II signaling in RVLM-projecting PVN neurons to drive sympathetic discharge back to the kidney. This causes the kidney to undergo fibrosis with loss of function. Blockade of sympathetic traffic or deletion of AT1a in PVN preserves the structure of the post-obstructed kidney. Human post-obstructed kidneys also demonstrate evidence of increased sympathetic nerve activity associated with a fibrotic outcome. Manipulating these neural elements is a potential treatment strategy.

Inhibition of calpain9 attenuates peritoneal dialysis-related peritoneal fibrosis.

Aim: Peritoneal dialysis is a common renal replacement method for end-stage renal disease. Long-term peritoneal dialysis leads to peritoneal dialysis-related peritoneal fibrosis, which leads to a cessation of treatment. Calpain is a protein belonging to calcium-dependent endopeptidase family and plays an important role in extracellular matrix remodeling. Here, we evaluated the effect of calpain in peritoneal dialysis-related peritoneal fibrosis. Methods: We established two animal models of peritoneal fibrosis and inhibited the activity of Calpain, and then collected peritoneal tissue to evaluate the progress of fibrosis and the changes of Calpain and ß-catenin. We obtained Rat peritoneal mesothelial cells and Human peritoneal mesothelial cell line and stimulated with TGF-ß to produce extracellular matrix. Next we inhibited Calpain activity or reduced Calpain9 expression, and then assessed changes in extracellular matrix and ß-catenin. Results: Inhibition of calpain activity attenuated chlorhexidine glucose and peritoneal dialysis-induced peritoneal thickening and ß-catenin expression in mice. In addition, compared with the control group, when primary rat peritoneal mesothelial cells or human peritoneal mesothelial cells were treated with transforming growth factor beta, down-regulation of calpain activity inhibited the expression of Fibronectin and Collagen I, and increased the expression of E-cadherin. These changes could be adjusted after silencing calpain9. Finally, calpain9 deficiency was associated with down-regulation of Fibronectin and ß-catenin in human peritoneal mesothelial cells. Conclusion: Our results suggest that calpain9 may be a key molecule in mediating peritoneal dialysis-related peritoneal fibrosis.

Dietary choline, via gut microbe- generated trimethylamine-N- oxide, aggravates chronic kidney disease-induced cardiac dysfunction by inhibiting hypoxia-induced factor 1α.

Chronic kidney disease (CKD) is a global public health problem that shortens lifespan primarily by increasing the risk of cardiovascular diseases. Trimethylamine-N-oxide (TMAO), a gut microbiota-derived toxin produced by metabolizing high-choline or carnitine foods, is associated with cardiovascular events in patients with CKD. Although the deleterious effect of TMAO on CKD-induced cardiac injury has been confirmed by various researches, the mechanisms remain unclear. Here, we tested the hypothesis that TMAO aggravates CKD-induced cardiac injury and explores the potential mechanism. CD1 mice underwent 5/6 nephrectomy to induce CKD, and then fed with a diet supplemented with choline (1.2% total) for 8 weeks. Serum TMAO levels were elevated in CKD mice compared with SHAM group, and higher TMAO levels were found in choline-supplemented CKD mice compared with CKD group. Dietary choline aggravated CKD-induced cardiac dysfunction, and reducing TMAO levels via medicinal charcoal tablets improved cardiac dysfunction. RNA-seq analysis revealed that dietary choline affected cardiac angiogenesis in CKD mice. Reduced cardiac capillary density and expressions of angiogenesis-related genes were observed in choline-treated CKD mice. Furthermore, dietary choline inhibited cardiac Hif-1α protein level in CKD mice, and Hif-1α stabilizer FG-4592 could improve cardiac angiogenesis and dysfunction in CKD mice on a high-choline diet. In conclusion, these data indicate that dietary choline, via gut microbe-generated TMAO, inhibits cardiac angiogenesis by reducing Hif-1α protein level, ultimately aggravates cardiac dysfunction in CKD mice.

Circular RNA circBNC2 inhibits epithelial cell G2-M arrest to prevent fibrotic maladaptive repair.

The mechanisms underlying fibrogenic responses after injury are not well understood. Epithelial cell cycle arrest in G2/M after injury is a key checkpoint for determining wound-healing leading to either normal cell proliferation or fibrosis. Here, we identify a kidney- and liver-enriched circular RNA, circBNC2, which is abundantly expressed in normal renal tubular cells and hepatocytes but significantly downregulated after acute ischemic or toxic insult. Loss of circBNC2 is at least partially mediated by upregulation of DHX9. Gain- and loss-of-function studies, both in vitro and in vivo, demonstrate that circBNC2 acts as a negative regulator of cell G2/M arrest by encoding a protein that promotes formation of CDK1/cyclin B1 complexes. Restoring circBNC2 in experimentally-induced male mouse models of fibrotic kidney and liver, decreases G2/M arrested cell numbers with secretion of fibrotic factors, thereby mitigating extracellular matrix deposition and fibrosis. Decreased expression of circBNC2 and increased G2/M arrest of epithelial cells are recapitulated in human ischemic reperfusion injury (IRI)-induced chronic kidney disease and inflammation-induced liver fibrosis, highlighting the clinical relevance. These findings suggest that restoring circBNC2 might represent a potential strategy for therapeutic intervention in epithelial organ fibrosis.

Corrigendum: Orange-derived and dexamethasone-encapsulated extracellular vesicles reduced proteinuria and alleviated pathological lesions in IgA nephropathy by targeting intestinal lymphocytes.

[This corrects the article DOI: 10.3389/fimmu.2022.900963.].

Orange-derived and dexamethasone-encapsulated extracellular vesicles reduced proteinuria and alleviated pathological lesions in IgA nephropathy by targeting intestinal lymphocytes.

Current evidence highlights the critical role of the gut-kidney axis in the pathogenesis of IgA nephropathy (IgAN). However, few attempts have been made to explore targeted intestinal immunity therapy. This research aims to develop an oral intestine targeting medication based on extracellular vesicles (EVs) and investigate its therapeutic efficacy in IgAN. EVs were isolated from orange juice and electroporated with dexamethasone sodium phosphate (DexP). After oral administration, EVs-DexP was picked up by lymphocytes in the submucosal area of ileocecum. EVs-DexP outperformed DexP not only in suppressing lymphocyte stimulation in vitro but also in alleviating renal pathological lesions in the IgAN mouse model. Clinical improvement was accompanied by a reducing IgA secreted by the intestine and a decreasing IgA + B220 + lymphocytes in Peyer's patches. The present study develops a cost-effective, biofriendly EVs-based glucocorticoid strategy for IgAN.

OsMLP423 Is a Positive Regulator of Tolerance to Drought and Salt Stresses in Rice.

Rice (Oryza sativa L.) is one of the main food crops for human survival, and its yield is often restricted by abiotic stresses. Drought and soil salinity are among the most damaging abiotic stresses affecting today's agriculture. Given the importance of abscisic acid (ABA) in plant growth and abiotic stress responses, it is very important to identify new genes involved in ABA signal transduction. We screened a drought-inducing gene containing about 158 amino acid residues from the transcriptome library of rice exposed to drought treatment, and we found ABA-related cis-acting elements and multiple drought-stress-related cis-acting elements in its promoter sequence. The results of real-time PCR showed that OsMLP423 was strongly induced by drought and salt stresses. The physiological and biochemical phenotype analysis of transgenic plants confirmed that overexpression of OsMLP423 enhanced the tolerance to drought and salt stresses in rice. The expression of OsMLP423-GFP fusion protein indicated that OsMLP423 was located in both the cell membrane system and nucleus. Compared with the wild type, the overexpressed OsMLP423 showed enhanced sensitivity to ABA. Physiological analyses showed that the overexpression of OsMLP423 may regulate the water loss efficiency and ABA-responsive gene expression of rice plants under drought and salt stresses, and it reduces membrane damage and the accumulation of reactive oxygen species. These results indicate that OsMLP423 is a positive regulator of drought and salinity tolerance in rice, governing the tolerance of rice to abiotic stresses through an ABA-dependent pathway. Therefore, this study provides a new insight into the physiological and molecular mechanisms of OsMLP423-mediated ABA signal transduction participating in drought and salt stresses.

Magnetic Resonance Imaging Features on Deep Learning Algorithm for the Diagnosis of Nasopharyngeal Carcinoma.

The objective of this research was to investigate the application values of magnetic resonance imaging (MRI) features of the deep learning-based image super-resolution reconstruction algorithm optimized convolutional neural network (OPCNN) algorithm in nasopharyngeal carcinoma (NPC) lesion diagnosis. A total of 54 patients with NPC were selected as research objects. Based on the traditional CNN structure, OPCNN was proposed. Besides, MRI processed by the traditional CNN model and the U-net network model was introduced to be analyzed and compared with its algorithm. The used assessment parameters included volume transfer constant (K trans), rate constant (K ep), volume fraction (V e), and apparent diffusion coefficient (ADC). The results showed that the values of Dice coefficient, peak signal-to-noise ratio (PSNR), and structural similarity (SSIM) of the OPCNN algorithm were significantly higher than those of the traditional CNN model and the U-net network model. Meanwhile, the difference was statistically significant (P < 0.05). K trans, K ep, and V e in tumor lesions were significantly higher than those in the healthy side, while the ADC was significantly lower than that in the healthy side (P < 0.05). The sensitivity, specificity, and accuracy of dynamic contrast-enhancement magnetic resonance imaging (DCE-MRI) in the diagnosis of nasopharyngeal carcinoma staging were slightly higher than those in T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI). The diagnostic sensitivity of DCE-MRI was more than 85%, its diagnostic specificity was more than 75%, and its diagnostic accuracy was more than 90%. The AUC area of NPC diagnosed by combination of the three was significantly different from that diagnosed by single T2WI, DWI, and DCE-MRI (P < 0.05). The diagnostic accuracy of MRI based on the OPCNN algorithm for nasopharyngeal carcinoma (93.2%) was significantly higher than that of single MRI (76.4%). In summary, the OPCNN algorithm proposed in this study could improve the quality of MRI images, and the effect was better than the traditional deep learning model, which had the value of clinical promotion. The application value of DCE-MRI in the diagnosis of pathogenic lesions of nasopharyngeal carcinoma was better than conventional MRI. The combined application of T2WI, DWI, and DCE-MRI in the screening of nasopharyngeal carcinoma lesions could greatly improve the diagnostic accuracy of nasopharyngeal carcinoma.

OsSCL30 overexpression reduces the tolerance of rice seedlings to low temperature, drought and salt.

Rice is one of the main food crops for the world population. Various abiotic stresses, such as low temperature, drought, and high salinity, affect rice during the entire growth period, determining its yield and quality, and even leading to plant death. In this study, by constructing overexpression vectors D-163 + 1300:OsSCL30 and D-163 + 1300-AcGFP:OsSCL30-GFP, the mechanism of action of OsSCL30 in various abiotic stresses was explored. Bioinformatics analysis showed that OsSCL30 was located on the chromosome 12 of rice Nipponbare, belonging to the plant-specific SCL subfamily of the SR protein family. The 1500 bp section upstream of the open reading frame start site contains stress-related cis-acting elements such as ABRE, MYC, and MYB. Under normal conditions, the expression of OsSCL30 was higher in leaves and leaf sheaths. The results of reverse transcription polymerase chain reaction showed that the expression of OsSCL30 decreased after low temperature, drought and salt treatment. In root cells OsSCL30 was localized in the nuclei. The results of the rice seedling tolerance and recovery tests showed that overexpression of OsSCL30 diminished the resistance to low temperature, drought and salt stresses in transgenic rice and resulted in larger accumulation of reactive oxygen species. This study is of great significance for exploring the response mechanisms of SR proteins under abiotic stresses.

Clinicopathological Characteristics and Outcomes of PLA2R-Associated Membranous Nephropathy in Seropositive Patients Without PLA2R Staining on Kidney Biopsy.

RATIONALE & OBJECTIVE: Phospholipase A2 receptor (PLA2R)-associated membranous nephropathy (MN) with circulating serum autoantibodies to PLA2R (SAb+) but no deposits of PLA2R antigen in glomerular tissue by immunofluorescence (GAg-) has been reported. However, little is known about the clinicopathological characteristics or prognosis of this subtype of MN. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: 130 SAb+ patients in China with biopsy-proven MN who had follow-up data and received immunosuppressive therapy. The median follow-up was 16 (IQR, 9-25) months. PREDICTOR: PLA2R antigen detection by immunofluorescence staining of kidney biopsy specimens. OUTCOMES: Complete remission (CR) was defined as proteinuria levels <0.3 g/d and a >50% decrease compared with a previously established baseline. Partial remission (PR) was defined as proteinuria levels <3.5 g/d and a >50% decrease compared with a previously established baseline. The kidney function outcome was defined as a >40% decrease in estimated glomerular filtration rate (eGFR) at the end of the study compared with baseline. ANALYTICAL APPROACH: Kaplan-Meier analysis of PR and CR comparing SAb+/GAg+ and SAb+/GAg- patients. Cox proportional hazards models to examine these associations were adjusted for confounders. RESULTS: Among 130 SAb+ patients with PLA2R-associated MN, 18 were GAg-. Compared with SAb+/GAg+ patients, those who were SAb+/GAg- presented with more severe kidney injury as evidenced by higher SAb titer, greater proteinuria, lower serum albumin concentrations, lower eGFR (all P < 0.05), and more severe disease with higher chronicity scores (P < 0.001) on kidney biopsies. SAb+/GAg- patients exhibited a significantly lower probability of PR (P < 0.001) and CR (P = 0.03) and were more likely to experience a >40% decrease in eGFR (P = 0.008) than patients who were SAb+/GAg+. After adjusting for clinical and pathologic variables available at the time of biopsy, compared with SAb+/GAg+ patients, SAb+/GAg- patients had a lower rate of experiencing remission (hazard ratio, 0.32 [95% CI, 0.15-0.68]; P = 0.003) and a higher rate of the >40% eGFR decrease outcome (hazard ratio, 7.66 [95% CI, 1.54-38.08]; P = 0.01). LIMITATIONS: Retrospective study, small sample size, and lack of a uniform approach to treatment. CONCLUSIONS: Seropositive PLA2R-associated MN without PLA2R staining on kidney biopsy may represent a distinct clinical subtype with more severe disease and a worse prognosis. GAg- is independently associated with poor response to treatment and >40% eGFR decrease in seropositive PLA2R-associated MN.