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.

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.

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.

Statin initiation and risk of incident kidney disease in patients with diabetes.

BACKGROUND: The role of statin therapy in the development of kidney disease in patients with type 2 diabetes mellitus (DM) remains uncertain. We aimed to determine the relationships between statin initiation and kidney outcomes in patients with type 2 DM. METHODS: Through a new-user design, we conducted a multicentre retrospective cohort study using the China Renal Data System database (which includes inpatient and outpatient data from 19 urban academic centres across China). We included patients with type 2 DM who were aged 40 years or older and admitted to hospital between Jan. 1, 2000, and May 26, 2021, and excluded those with pre-existing chronic kidney disease and those who were already on statins or without follow-up at an affiliated outpatient clinic within 90 days after discharge. The primary exposure was initiation of a statin. The primary outcome was the development of diabetic kidney disease (DKD), defined as a composite of the occurrence of kidney dysfunction (estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m2 and > 25% decline from baseline) and proteinuria (a urinary albumin-to-creatinine ratio ≥ 30 mg/g and > 50% increase from baseline), sustained for at least 90 days; secondary outcomes included development of kidney function decline (a sustained > 40% decline in eGFR). We used Cox proportional hazards regression to evaluate the relationships between statin initiation and kidney outcomes, as well as to conduct subgroup analyses according to patient characteristics, presence or absence of dyslipidemia, and pattern of dyslipidemia. For statin initiators, we explored the association between different levels of lipid control and outcomes. We conducted analyses using propensity overlap weighting to balance the participant characteristics. RESULTS: Among 7272 statin initiators and 12 586 noninitiators in the weighted cohort, statin initiation was associated with lower risks of incident DKD (hazard ratio [HR] 0.72, 95% confidence interval [CI] 0.62-0.83) and kidney function decline (HR 0.60, 95% CI 0.44-0.81). We obtained similar results to the primary analyses for participants with differing patterns of dyslipidemia, those prescribed different statins, and after stratification according to participant characteristics. Among statin initiators, those with intensive control of high-density lipoprotein cholesterol (LDL-C) (< 1.8 mmol/L) had a lower risk of incident DKD (HR 0.51, 95% CI 0.32-0.81) than those with inadequate lipid control (LDL-C ≥ 3.4 mmol/L). INTERPRETATION: For patients with type 2 DM admitted to and followed up in academic centres, statin initiation was associated with a lower risk of kidney disease development, particularly in those with intensive control of LDL-C. These findings suggest that statin initiation may be an effective and reasonable approach for preventing kidney disease in patients with type 2 DM.

Association between dialysis effluent leukocyte count after initial antibiotic treatment and outcomes of patients with peritoneal dialysis-associated peritonitis: a retrospective study.

BACKGROUND: Among patients with peritoneal dialysis-associated peritonitis (PDAP), It has been regarded as an indicator of deterioration of clinical condition that peritoneal dialysis effluent leukocyte count (PDELC) cannot be restored to normal after initial antibiotic therapy. However, the precise relationship between PDELC on day 5 and the clinical outcomes of PDAP episodes remains uncertain. AIMS: To explore the association between PDELC on day 5 and clinical outcomes of PDAP episodes. METHODS: This retrospective study was based on the medical chart database of the Affiliated Hospital of Guangdong Medical University. Multivariable regressions were used to evaluate the association between PDELC on day 5 and 60-day mortality, half-year mortality, treatment failure, and the length of stay in hospital with adjustment for confounding factors. RESULTS: A total of 549 PDAP episodes in 309 patients were enrolled. The total 60-day mortality, half-year mortality, and rate of treatment failure was 6.0%, 9.8%, and 14.2%, respectively. Compared with patients with normal PDELC, those with PDELC ≥2000 × 106/L on day 5 had significantly higher 60-day mortality (31.1% vs 2.7%), half-year mortality (35.6% vs 5.6%), and treatment failure (46.7% vs 5.7%). In multivariate adjusted regression, the ORs (95%CI) were 6.99 (2.33, 20.92; p = 0.001), 4.97(1.93, 12.77; p = 0.001), and 5.77 (2.07, 16.11; p = 0.001), respectively. Patients with PDELC were 100-2000 × 106/L on day 5 had a higher rate of treatment failure than those with normal PDELC (26.9% vs 5.7%) (OR = 3.03, 95%CI 1.42, 6.46; p = 0.004). After sensitivity analysis, the results remained robust. CONCLUSIONS: Among patients with PDAP, increased PDELC on day 5 was associated with a greater risk of 60-day mortality, half-year mortality, and treatment failure.

Role of Transcription Factor EB in Mitochondrial Dysfunction of Cisplatin-Induced Acute Kidney Injury.

Cisplatin, a widely used anticancer agent, can cause nephrotoxicity, including both acute kidney injury (AKI) and chronic kidney diseases, by accumulating in renal tubular epithelial cells (TECs). Mitochondrial pathology plays an important role in the pathogenesis of AKI. Based on the regulatory role of transcription factor EB (TFEB) in mitochondria, we investigated whether TFEB is involved in cisplatin-induced TEC damage. The results show that the expression of TFEB decreased in a concentration-dependent manner in both mouse kidney tissue and HK-2 cells when treated with cisplatin. A knockdown of TFEB aggravated cisplatin-induced renal TEC injury, which was partially reversed by TFEB overexpression in HK-2 cells. It was further observed that the TFEB knockdown also exacerbated cisplatin-induced mitochondrial damage in vitro, and included the depolarization of membrane potential, mitochondrial fragmentation and swelling, and the production of reactive oxygen species. In contrast, TFEB overexpression alleviated cisplatin-induced mitochondrial damage in TECs. These findings suggest that decreased TFEB expression may be a key mechanism of mitochondrial dysfunction in cisplatin-induced AKI, and that upregulation of TFEB has the potential to act as a therapeutic target to alleviate mitochondrial dysfunction and cisplatin-induced TEC injury. This study is important for developing therapeutic strategies to manipulate mitochondria through TFEB to delay AKI progression.

Cellular Protein Aggregates: Formation, Biological Effects, and Ways of Elimination.

The accumulation of protein aggregates is the hallmark of many neurodegenerative diseases. The dysregulation of protein homeostasis (or proteostasis) caused by acute proteotoxic stresses or chronic expression of mutant proteins can lead to protein aggregation. Protein aggregates can interfere with a variety of cellular biological processes and consume factors essential for maintaining proteostasis, leading to a further imbalance of proteostasis and further accumulation of protein aggregates, creating a vicious cycle that ultimately leads to aging and the progression of age-related neurodegenerative diseases. Over the long course of evolution, eukaryotic cells have evolved a variety of mechanisms to rescue or eliminate aggregated proteins. Here, we will briefly review the composition and causes of protein aggregation in mammalian cells, systematically summarize the role of protein aggregates in the organisms, and further highlight some of the clearance mechanisms of protein aggregates. Finally, we will discuss potential therapeutic strategies that target protein aggregates in the treatment of aging and age-related neurodegenerative diseases.

Effect of Lacking ZKSCAN3 on Autophagy, Lysosomal Biogenesis and Senescence.

Transcription factors can affect autophagy activity by promoting or inhibiting the expression of autophagic and lysosomal genes. As a member of the zinc finger family DNA-binding proteins, ZKSCAN3 has been reported to function as a transcriptional repressor of autophagy, silencing of which can induce autophagy and promote lysosomal biogenesis in cancer cells. However, studies in Zkscan3 knockout mice showed that the deficiency of ZKSCAN3 did not induce autophagy or increase lysosomal biogenesis. In order to further explore the role of ZKSCAN3 in the transcriptional regulation of autophagic genes in human cancer and non-cancer cells, we generated ZKSCAN3 knockout HK-2 (non-cancer) and Hela (cancer) cells via the CRISPR/Cas9 system and analyzed the differences in gene expression between ZKSCAN3 deleted cells and non-deleted cells through fluorescence quantitative PCR, western blot and transcriptome sequencing, with special attention to the differences in expression of autophagic and lysosomal genes. We found that ZKSCAN3 may be a cancer-related gene involved in cancer progression, but not an essential transcriptional repressor of autophagic or lysosomal genes, as the lacking of ZKSCAN3 cannot significantly promote the expression of autophagic and lysosomal genes.

Blip up-down acquisition for spin- and gradient-echo imaging (BUDA-SAGE) with self-supervised denoising enables efficient T2 , T2 *, para- and dia-magnetic susceptibility mapping.

PURPOSE: To rapidly obtain high resolution T2 , T2 *, and quantitative susceptibility mapping (QSM) source separation maps with whole-brain coverage and high geometric fidelity. METHODS: We propose Blip Up-Down Acquisition for Spin And Gradient Echo imaging (BUDA-SAGE), an efficient EPI sequence for quantitative mapping. The acquisition includes multiple T2 *-, T2 '-, and T2 -weighted contrasts. We alternate the phase-encoding polarities across the interleaved shots in this multi-shot navigator-free acquisition. A field map estimated from interim reconstructions was incorporated into the joint multi-shot EPI reconstruction with a structured low rank constraint to eliminate distortion. A self-supervised neural network (NN), MR-Self2Self (MR-S2S), was used to perform denoising to boost SNR. Using Slider encoding allowed us to reach 1 mm isotropic resolution by performing super-resolution reconstruction on volumes acquired with 2 mm slice thickness. Quantitative T2 (=1/R2 ) and T2 * (=1/R2 *) maps were obtained using Bloch dictionary matching on the reconstructed echoes. QSM was estimated using nonlinear dipole inversion on the gradient echoes. Starting from the estimated R2 /R2 * maps, R2 ' information was derived and used in source separation QSM reconstruction, which provided additional para- and dia-magnetic susceptibility maps. RESULTS: In vivo results demonstrate the ability of BUDA-SAGE to provide whole-brain, distortion-free, high-resolution, multi-contrast images and quantitative T2 /T2 * maps, as well as yielding para- and dia-magnetic susceptibility maps. Estimated quantitative maps showed comparable values to conventional mapping methods in phantom and in vivo measurements. CONCLUSION: BUDA-SAGE acquisition with self-supervised denoising and Slider encoding enables rapid, distortion-free, whole-brain T2 /T2 * mapping at 1 mm isotropic resolution under 90 s.

2.4 ng/√Hz low-noise fiber-optic MEMS seismic accelerometer.

This paper introduces a fiber-optic microelectromechanical system (MEMS) seismic-grade accelerometer that is fabricated by bulk silicon processing using photoresist/silicon dioxide composite masking technology. The proposed sensor is a silicon flexure accelerometer whose displacement transduction system employs a light intensity detection method based on Fabry-Perot interference (FPI). The FPI cavity is formed between the end surface of the cleaved optical fiber and the gold-surfaced sidewall of the proof mass. The proposed MEMS accelerometer is fabricated by one-step silicon deep reactive ion etching with different depths using the composite mask, among which photoresist is used as the etching-defining mask for patterning the etching area while silicon dioxide is used as the depth-defining mask. Noise evaluation experiment results reveal that the overall noise floor of the fiber-optic MEMS accelerometer is 2.4 ng/H z at 10 Hz with a sensitivity of 3165 V/g, which is lower than that of most reported micromachined optical accelerometers, and the displacement noise floor of the optical displacement transduction system is 208 fm/H z at 10 Hz. Therefore, the proposed MEMS accelerometer is promising for use in high-performance seismic exploration applications.

Mechanism and restoration strategy of lysosomal abnormalities induced by urinary protein overload in proximal tubule epithelial cells.

BACKGROUND: Persistent elevated concentrations of urinary protein can destroy proximal tubule epithelial cells (PTECs) by inducing lysosomal abnormalities, thereby aggravating PTEC damage and renal fibrosis. However, the specific mechanisms of these serial biochemical events and methods for treating or preventing PTEC damage upon proteinuria need further investigation. RESULTS: In this study, electron microscopy and dual-labeled immunofluorescence analysis for identifying lysosome type revealed inadequate primary lysosome biogenesis and secondary lysosome accumulation in the PTECs of patients with minimal change nephrotic syndrome or membranous nephropathy who suffered from proteinuria. In vitro studies on HK-2 cells indicated that this abnormality was associated with decreased expression of transcription factor EB (TFEB). In contrast, TFEB overexpressing HK-2 cells under urinary protein overload exhibited significantly reduced accumulation of secondary lysosomes and increased proportion and quantity of primary lysosomes as indicated by dual-labeled immunofluorescence. Further, these cells could upregulate lysosomal degradation functions, as determined using Cathepsin L activity assays and flow cytometry for dye quenched-albumin. CONCLUSIONS: These results indicate that abnormal TFEB expression is a key mechanism of lysosomal dyshomeostasis caused by protein overload in PTECs. TFEB is thus a potential therapeutic target for the treatment of urinary protein-related kidney disease.

Cyclosporine A blocks autophagic flux in tubular epithelial cells by impairing TFEB-mediated lysosomal function.

Cyclosporine A (CsA) is an immunosuppressor widely used for the prevention of acute rejection during solid organ transplantation. However, severe nephrotoxicity has substantially limited its long-term usage. Recently, an impaired autophagy pathway was suggested to be involved in the pathogenesis of chronic CsA nephrotoxicity. However, the underlying mechanisms of CsA-induced autophagy blockade in tubular cells remain unclear. In the present study, we observed that CsA suppressed the activation and expression of transcription factor EB (TFEB) by increasing the activation of mTOR, in turn promoting lysosomal dysfunction and autophagy flux blockade in tubular epithelial cells (TECs) in vivo and in vitro. Restoration of TFEB activation by Torin1-mediated mTOR inhibition significantly improved lysosomal function and rescued autophagy pathway activity, suppressing TEC injury. In summary, targeting TFEB-mediated autophagy flux represents a potential therapeutic strategy for CsA-induced nephrotoxicity.

Lansoprazole promotes cisplatin-induced acute kidney injury via enhancing tubular necroptosis.

Acute kidney injury (AKI) is the main obstacle that limits the use of cisplatin in cancer treatment. Proton pump inhibitors (PPIs), the most commonly used class of medications for gastrointestinal complications in cancer patients, have been reported to cause adverse renal events. However, the effect of PPIs on cisplatin-induced AKI remains unclear. Herein, the effect and mechanism of lansoprazole (LPZ), one of the most frequently prescribed PPIs, on cisplatin-induced AKI were investigated in vivo and in vitro. C57BL/6 mice received a single intraperitoneal (i.p.) injection of cisplatin (18 mg/kg) to induce AKI, and LPZ (12.5 or 25 mg/kg) was administered 2 hours prior to cisplatin administration and then once daily for another 2 days via i.p. injection. The results showed that LPZ significantly aggravated the tubular damage and further increased the elevated levels of serum creatinine and blood urea nitrogen induced by cisplatin. However, LPZ did not enhance cisplatin-induced tubular apoptosis, as evidenced by a lack of significant change in mRNA and protein expression of Bax/Bcl-2 ratio and TUNEL staining. Notably, LPZ increased the number of necrotic renal tubular cells compared to that by cisplatin treatment alone, which was further confirmed by the elevated necroptosis-associated protein expression of RIPK1, p-RIPK3 and p-MLKL. Furthermore, LPZ deteriorated cisplatin-induced inflammation, as revealed by the increased mRNA expression of pro-inflammatory factors including, NLRP3, IL-1ß, TNF-α and caspase 1, as well as neutrophil infiltration. Consistently, in in vitro study, LPZ increased HK-2 cell death and enhanced inflammation, compared with cisplatin treatment alone. Collectively, our results demonstrate that LPZ aggravates cisplatin-induced AKI, and necroptosis may be involved in the exacerbation of kidney damage.

Rapid high-quality PET Patlak parametric image generation based on direct reconstruction and temporal nonlocal neural network.

Parametric imaging based on dynamic positron emission tomography (PET) has wide applications in neurology. Compared to indirect methods, direct reconstruction methods, which reconstruct parametric images directly from the raw PET data, have superior image quality due to better noise modeling and richer information extracted from the PET raw data. For low-dose scenarios, the advantages of direct methods are more obvious. However, the wide adoption of direct reconstruction is inevitably impeded by the excessive computational demand and deficiency of the accessible raw data. In addition, motion modeling inside dynamic PET image reconstruction raises more computational challenges for direct reconstruction methods. In this work, we focused on the 18F-FDG Patlak model, and proposed a data-driven approach which can estimate the motion corrected full-dose direct Patlak images from the dynamic PET reconstruction series, based on a proposed novel temporal non-local convolutional neural network. During network training, direct reconstruction with motion correction based on full-dose dynamic PET sinograms was performed to obtain the training labels. The reconstructed full-dose /low-dose dynamic PET images were supplied as the network input. In addition, a temporal non-local block based on the dynamic PET images was proposed to better recover the structural information and reduce the image noise. During testing, the proposed network can directly output high-quality Patlak parametric images from the full-dose /low-dose dynamic PET images in seconds. Experiments based on 15 full-dose and 15 low-dose 18F-FDG brain datasets were conducted and analyzed to validate the feasibility of the proposed framework. Results show that the proposed framework can generate better image quality than reference methods.

Efficient T2 mapping with blip-up/down EPI and gSlider-SMS (T2 -BUDA-gSlider).

PURPOSE: To rapidly obtain high isotropic-resolution T2 maps with whole-brain coverage and high geometric fidelity. METHODS: A T2 blip-up/down EPI acquisition with generalized slice-dithered enhanced resolution (T2 -BUDA-gSlider) is proposed. A RF-encoded multi-slab spin-echo (SE) EPI acquisition with multiple TEs was developed to obtain high SNR efficiency with reduced TR. This was combined with an interleaved 2-shot EPI acquisition using blip-up/down phase encoding. An estimated field map was incorporated into the joint multi-shot EPI reconstruction with a structured low rank constraint to achieve distortion-free and robust reconstruction for each slab without navigation. A Bloch simulated subspace model was integrated into gSlider reconstruction and used for T2 quantification. RESULTS: In vivo results demonstrated that the T2 values estimated by the proposed method were consistent with gold standard spin-echo acquisition. Compared to the reference 3D fast spin echo (FSE) images, distortion caused by off-resonance and eddy current effects were effectively mitigated. CONCLUSION: BUDA-gSlider SE-EPI acquisition and gSlider-subspace joint reconstruction enabled distortion-free whole-brain T2 mapping in 2 min at ~1 mm3 isotropic resolution, which could bring significant benefits to related clinical and neuroscience applications.

The miR172/IDS1 signaling module confers salt tolerance through maintaining ROS homeostasis in cereal crops.

Salt stress triggers the overdose accumulation of reactive oxygen species (ROS) in crop plants, leading to severe oxidative damage to living tissues. MicroRNAs (miRNAs) act as master regulators orchestrating the stress responsive regulatory networks as well as salt tolerance. However, the fundamental roles of miRNAs in modulating salt tolerance in cereal crops, especially in salt-triggered ROS scavenging remain largely unknown. Through small RNA sequencing, a salt-responsive miRNA, miR172 was identified in rice. Further, by generating the miR172-overexpression or MIR172 gene loss-of-function mutant lines, the biological significance of miR172 and its downstream signaling pathways related to salt tolerance were defined. We demonstrated that miR172 is a positive regulator of salt tolerance in both rice and wheat. More interestingly, miR172a and miR172b, but not miR172c or miR172d are involved in salt stress response, emphasizing the functional differentiation within miR172 family members. Further evidence uncovers a novel miR172/IDS1 regulatory module that functions as a crucial molecular rheostat in maintaining ROS homeostasis during salt stress, mainly through balancing the expression of a group of ROS-scavenging genes. Our findings establish a direct molecular link between miRNAs and detoxification response in cereal crops for improving salt tolerance.