Incorporating the image formation process into deep learning improves network performance.

We present Richardson-Lucy network (RLN), a fast and lightweight deep learning method for three-dimensional fluorescence microscopy deconvolution. RLN combines the traditional Richardson-Lucy iteration with a fully convolutional network structure, establishing a connection to the image formation process and thereby improving network performance. Containing only roughly 16,000 parameters, RLN enables four- to 50-fold faster processing than purely data-driven networks with many more parameters. By visual and quantitative analysis, we show that RLN provides better deconvolution, better generalizability and fewer artifacts than other networks, especially along the axial dimension. RLN outperforms classic Richardson-Lucy deconvolution on volumes contaminated with severe out of focus fluorescence or noise and provides four- to sixfold faster reconstructions of large, cleared-tissue datasets than classic multi-view pipelines. We demonstrate RLN's performance on cells, tissues and embryos imaged with widefield-, light-sheet-, confocal- and super-resolution microscopy.

Inhibition of TFEB deacetylation in proximal tubular epithelial cells (TECs) promotes TFEB activation and alleviates TEC damage in diabetic kidney disease.

The inhibition of the autophagolysosomal pathway mediated by transcription factor EB (TFEB) inactivation in proximal tubular epithelial cells (TECs) is a key mechanism of TEC injury in diabetic kidney disease (DKD). Acetylation is a novel mechanism that regulates TFEB activity. However, there are currently no studies on whether the adjustment of the acetylation level of TFEB can reduce the damage of diabetic TECs. In this study, we investigated the effect of Trichostatin A (TSA), a typical deacetylase inhibitor, on TFEB activity and damage to TECs in both in vivo and in vitro models of DKD. Here, we show that TSA treatment can alleviate the pathological damage of glomeruli and renal tubules and delay the DKD progression in db/db mice, which is associated with the increased expression of TFEB and its downstream genes. In vitro studies further confirmed that TSA treatment can upregulate the acetylation level of TFEB, promote its nuclear translocation, and activate the expression of its downstream genes, thereby reducing the apoptosis level of TECs. TFEB deletion or HDAC6 knockdown in TECs can counteract the activation effect of TSA on autophagolysosomal pathway. We also found that TFEB enhances the transcription of Tfeb through binding to its promoter and promotes its own expression. Our results, thus, provide a novel therapeutic mechanism for DKD that the alleviation of TEC damage by activating the autophagic lysosomal pathway through upregulating TFEB acetylation can, thus, delay DKD progression.

ZmC2H2-149 negatively regulates drought tolerance by repressing ZmHSD1 in maize.

Drought is a major abiotic stress that limits maize production worldwide. Therefore, it is of great importance to improve drought tolerance in crop plants for sustainable agriculture. In this study, we examined the roles of Cys2 /His2 zinc-finger-proteins (C2H2-ZFPs) in maize's drought tolerance as C2H2-ZFPs have been implicated for plant stress tolerance. By subjecting 150 Ac/Ds mutant lines to drought stress, we successfully identified a Ds-insertion mutant, zmc2h2-149, which shows increased tolerance to drought stress. Overexpression of ZmC2H2-149 in maize led to a decrease in both drought tolerance and crop yield. DAP-Seq, RNA-Seq, Y1H and LUC assays additionally showed that ZmC2H2-149 directly suppresses the expression of a positive drought tolerance regulator, ZmHSD1 (hydroxysteroid dehydrogenase 1). Consistently, the zmhsd1 mutants exhibited decreased drought tolerance and grain yield under water deficit conditions compared to their respective wild-type plants. Our findings thus demonstrated that ZmC2H2-149 can regulate ZmHSD1 for drought stress tolerance in maize, offering valuable theoretical and genetic resources for maize breeding programmes that aim for improving drought tolerance.

IE-CycleGAN: improved cycle consistent adversarial network for unpaired PET image enhancement.

PURPOSE: Technological advances in instruments have greatly promoted the development of positron emission tomography (PET) scanners. State-of-the-art PET scanners such as uEXPLORER can collect PET images of significantly higher quality. However, these scanners are not currently available in most local hospitals due to the high cost of manufacturing and maintenance. Our study aims to convert low-quality PET images acquired by common PET scanners into images of comparable quality to those obtained by state-of-the-art scanners without the need for paired low- and high-quality PET images. METHODS: In this paper, we proposed an improved CycleGAN (IE-CycleGAN) model for unpaired PET image enhancement. The proposed method is based on CycleGAN, and the correlation coefficient loss and patient-specific prior loss were added to constrain the structure of the generated images. Furthermore, we defined a normalX-to-advanced training strategy to enhance the generalization ability of the network. The proposed method was validated on unpaired uEXPLORER datasets and Biograph Vision local hospital datasets. RESULTS: For the uEXPLORER dataset, the proposed method achieved better results than non-local mean filtering (NLM), block-matching and 3D filtering (BM3D), and deep image prior (DIP), which are comparable to Unet (supervised) and CycleGAN (supervised). For the Biograph Vision local hospital datasets, the proposed method achieved higher contrast-to-noise ratios (CNR) and tumor-to-background SUVmax ratios (TBR) than NLM, BM3D, and DIP. In addition, the proposed method showed higher contrast, SUVmax, and TBR than Unet (supervised) and CycleGAN (supervised) when applied to images from different scanners. CONCLUSION: The proposed unpaired PET image enhancement method outperforms NLM, BM3D, and DIP. Moreover, it performs better than the Unet (supervised) and CycleGAN (supervised) when implemented on local hospital datasets, which demonstrates its excellent generalization ability.

Selenium nanoparticles alleviate renal ischemia/reperfusion injury by inhibiting ferritinophagy via the XBP1/NCOA4 pathway.

Acute kidney injury (AKI) is closely related to lysosomal dysfunction and ferroptosis in renal tubular epithelial cells (TECs), for which effective treatments are urgently needed. Although selenium nanoparticles (SeNPs) have emerged as promising candidates for AKI therapy, their underlying mechanisms have not been fully elucidated. Here, we investigated the effect of SeNPs on hypoxia/reoxygenation (H/R)-induced ferroptosis and lysosomal dysfunction in TECs in vitro and evaluated their efficacy in a murine model of ischemia/reperfusion (I/R)-AKI. We observed that H/R-induced ferroptosis was accompanied by lysosomal Fe2+ accumulation and dysfunction in TECs, which was ameliorated by SeNPs administration. Furthermore, SeNPs protected C57BL/6 mice against I/R-induced inflammation and ferroptosis. Mechanistically, we found that lysosomal Fe2+ accumulation and ferroptosis were associated with the excessive activation of NCOA4-mediated ferritinophagy, a process mitigated by SeNPs through the upregulation of X-box binding protein 1 (XBP1). Downregulation of XBP1 promoted ferritinophagy and partially counteracted the protective effects of SeNPs on ferroptosis inhibition in TECs. Overall, our findings revealed a novel role for SeNPs in modulating ferritinophagy, thereby improving lysosomal function and attenuating ferroptosis of TECs in I/R-AKI. These results provide evidence for the potential application of SeNPs as therapeutic agents for the prevention and treatment of AKI.

Intravenous methylprednisolone for nephrotic syndrome with minimal change lesions in adults: a randomized controlled trial.

BACKGROUND AND HYPOTHESIS: Patients with minimal change nephrotic syndrome (MCNS) usually experienced severe edema which can affect the absorption of oral corticosteroid during the first 2 weeks. We conducted a randomized controlled trial to compare the efficacy of intravenous isovalent methylprednisolone induction followed by oral prednisone therapy with conventional oral prednisone therapy in highly edematous MCNS patients, aiming to provide a better therapy for MCNS patients. METHODS: A single-center, open-label, parallel-arm randomized controlled trial was performed in the Nephrology Department of the Affiliated Hospital of Guangdong Medical University. Patients who met the inclusion were enrolled in our study from May 2015 to October 2020, and were randomized to receive conventional oral steroid or 2 weeks intravenous methylprednisolone followed by oral prednisone. RESULTS: 117 patients were enrolled and randomly assigned to either the sequential group (N = 57) or the oral group (N = 60). Total remission rate in the sequential group was higher than the oral group after treatment for 2 weeks and 4 weeks (P = 0.032, P = 0.027). Complete remission rate was higher in the sequential group than in the oral group (63.3% vs. 41.5%, P = 0.031) after treatment for 2 weeks. The time to achieve CR is shorter in the sequential group than the oral group, with a statistically significant difference (14.0 days, 95% CI [13.5 to 14.5] vs. 16.0 days, 95% CI [12.7 to 19.3], P = 0.024). There were no significant difference in relapse rate (24.5% vs 28.3%, P = 0.823) and time to relapse (155 ± 103 days vs 150.7 ± 103.7 days, P = 0.916) between two groups. CONCLUSION: This study suggested that highly edematous MCNS patients received intravenously isovalent methylprednisolone induction therapy follow by oral prednisone achieved earlier remission than the conventional oral prednisone regimen without differences in relapse rates or adverse effects. Short-term intravenous methylprednisolone followed by oral prednisone may be a better choice for MCNS patients with highly edema.

Incidence, risk factors and outcome of postoperative acute kidney injury in China.

BACKGROUND: Postoperative acute kidney injury (AKI) is a common condition after surgery, however, the available data about nationwide epidemiology of postoperative AKI in China from large and high-quality studies are limited. This study aimed to determine the incidence, risk factors and outcomes of postoperative AKI among patients undergoing surgery in China. METHODS: This was a large, multicentre, retrospective study performed in 16 tertiary medical centres in China. Adult patients (≥18 years of age) who underwent surgical procedures from 1 January 2013 to 31 December 2019 were included. Postoperative AKI was defined by the Kidney Disease: Improving Global Outcomes creatinine criteria. The associations of AKI and in-hospital outcomes were investigated using logistic regression models adjusted for potential confounders. RESULTS: Among 520 707 patients included in our study, 25 830 (5.0%) patients developed postoperative AKI. The incidence of postoperative AKI varied by surgery type, which was highest in cardiac (34.6%), urologic (8.7%) and general (4.2%) surgeries. A total of 89.2% of postoperative AKI cases were detected in the first 2 postoperative days. However, only 584 (2.3%) patients with postoperative AKI were diagnosed with AKI on discharge. Risk factors for postoperative AKI included older age, male sex, lower baseline kidney function, pre-surgery hospital stay ≤3 days or >7 days, hypertension, diabetes mellitus and use of proton pump inhibitors or diuretics. The risk of in-hospital death increased with the stage of AKI. In addition, patients with postoperative AKI had longer lengths of hospital stay (12 versus 19 days) and were more likely to require intensive care unit care (13.1% versus 45.0%) and renal replacement therapy (0.4% versus 7.7%). CONCLUSIONS: Postoperative AKI was common across surgery type in China, particularly for patients undergoing cardiac surgery. Implementation and evaluation of an alarm system is important for the battle against postoperative AKI.

Enhanced intersubject similarity in functional connectivity by long-term abacus training.

The individual difference of intrinsic functional connectivity is increasingly acknowledged to be biologically informative and behaviorally relevant. However, such valuable information is still discounted as a stochastic variation in previous studies of cognitive training. Here, we explored the plasticity of intersubject similarity in functional connectivity (ISFC), induced by long-term abacus-based mental calculation (AMC) training. Using a longitudinal dataset (AMC: n = 40, 5-year training; Control: n = 43), we found robust training effect of enhanced ISFC, after accounting for the factor of development. Notably, the enhancement focused on selective subsets of FCs, or the "critical FCs," which predominantly impacted the default-mode and visual networks. Using a cross-sectional dataset with a larger sample (AMC: n = 93, 1/3/5-year training; Control: n = 110), we observed that the "critical FCs" and its intersubject similarity could predict mental calculation ability and its intersubject similarity, respectively, in the AMC group. However, such predictions cannot be generalized to the control group, suggesting that long-term training may be a prerequisite for establishing such brain-behavior relationships. Jointly, our findings implicated that the enhanced ISFC with profound impact on the default-mode network could be a plastic change that is associated with behavioral gains of training.

Detecting Neonatal AKI by Serum Cystatin C.

SIGNIFICANCE STATEMENT: Serum creatinine is not a sensitive biomarker for neonatal AKI because it is confounded by maternal creatinine level, gestational age, and neonatal muscle mass. In this multicenter cohort study of 52,333 hospitalized Chinese neonates, the authors proposed serum cystatin C-related criteria (CyNA) for neonatal AKI. They found that cystatin C (Cys-C) is a robust and sensitive biomarker for identifying AKI in neonates who are at an elevated risk of in-hospital mortality and that CyNA detects 6.5 times as many cases as the modified Kidney Disease Improving Global Outcomes creatinine criteria. They also show that AKI can be detected using a single test of Cys-C. These findings suggest that CyNA shows promise as a powerful and easily applicable tool for detecting AKI in neonates. BACKGROUND: Serum creatinine is not a sensitive biomarker for AKI in neonates. A better biomarker-based criterion for neonatal AKI is needed. METHODS: In this large multicenter cohort study, we estimated the upper normal limit (UNL) and reference change value (RCV) of serum cystatin C (Cys-C) in neonates and proposed cystatin C-based criteria (CyNA) for detecting neonatal AKI using these values as the cutoffs. We assessed the association of CyNA-detected AKI with the risk of in-hospital death and compared CyNA performance versus performance of modified Kidney Disease Improving Global Outcomes (KDIGO) creatinine criteria. RESULTS: In this study of 52,333 hospitalized neonates in China, Cys-C level did not vary with gestational age and birth weight and remained relatively stable during the neonatal period. CyNA criteria define AKI by a serum Cys-C of ≥2.2 mg/L (UNL) or an increase in Cys-C of ≥25% (RCV) during the neonatal period. Among 45,839 neonates with measurements of both Cys-C and creatinine, 4513 (9.8%) had AKI detected by CyNA only, 373 (0.8%) by KDIGO only, and 381 (0.8%) by both criteria. Compared with neonates without AKI by both criteria, neonates with AKI detected by CyNA alone had an increased risk of in-hospital mortality (hazard ratio [HR], 2.86; 95% confidence interval [95% CI], 2.02 to 4.04). Neonates with AKI detected by both criteria had an even higher risk of in-hospital mortality (HR, 4.86; 95% CI, 2.84 to 8.29). CONCLUSIONS: Serum Cys-C is a robust and sensitive biomarker for detecting neonatal AKI. Compared with modified KDIGO creatinine criteria, CyNA is 6.5 times more sensitive in identifying neonates at elevated risk of in-hospital mortality.

Thermally activated delayed fluorescence (TADF) organic molecules for efficient X-ray scintillation and imaging.

X-ray detection, which plays an important role in medical and industrial fields, usually relies on inorganic scintillators to convert X-rays to visible photons; although several high-quantum-yield fluorescent molecules have been tested as scintillators, they are generally less efficient. High-energy radiation can ionize molecules and create secondary electrons and ions. As a result, a high fraction of triplet states is generated, which act as scintillation loss channels. Here we found that X-ray-induced triplet excitons can be exploited for emission through very rapid, thermally activated up-conversion. We report scintillators based on three thermally activated delayed fluorescence molecules with different emission bands, which showed significantly higher efficiency than conventional anthracene-based scintillators. X-ray imaging with 16.6 line pairs mm-1 resolution was also demonstrated. These results highlight the importance of efficient and prompt harvesting of triplet excitons for efficient X-ray scintillation and radiation detection.