Insights into renal damage in hyperuricemia: Focus on renal protection (Review).

The incidence of hyperuricemia has increased recently, posing a serious threat to public health. Hyperuricemia is associated with an increased risk of gout, chronic kidney disease (CKD), obesity, metabolic syndrome, type 2 diabetes mellitus, hypertension, hypertriglyceridaemia, metabolic dysfunction‑associated steatotic liver disease, acute kidney injury, coronary heart disease and cardiovascular disease (CVD). These diseases are commonly accompanied by varying degrees of kidney damage.

Prospective acceleration of whole-brain CEST imaging by golden-angle view ordering in Cartesian coordinates and joint k-space and image-space parallel imaging (KIPI).

Purpose: To prospectively accelerate whole-brain CEST acquisition by joint k-space and image-space parallel imaging (KIPI) with a proposed golden-angle view ordering technique (GAVOT) in Cartesian coordinates.

Theory And Methods: The T-decay effect will vary across frames with variable acceleration factors (AF) in the prospective acquisition using sequences with long echo trains. The GAVOT method uses a subset strategy to eliminate the T-decay inconsistency, where all frames use a subset of shots from the calibration frame to form their k-space view ordering.

Biomimetic Iron-Based Nanoparticles Remodel Immunosuppressive Tumor Microenvironment for Metabolic Immunotherapy.

Introduction: Immunotherapy has led to a paradigm shift in reinvigorating treatment of cancer. Nevertheless, tumor associated macrophages (TAMs) experience functional polarization on account of the generation of suppressive metabolites, contributing to impaired antitumor immune responses.

Methods: Hence, metabolic reprogramming of tumor microenvironment (TME) can synergistically improve the efficacy of anti-tumor immunotherapy.

A shape-independent analytical method for gear mesh stiffness with asymmetric spalling defects.

Spalling, a common failure mechanism of gear systems, greatly affects the dynamics of gears operation, which is reflected in the time-varying mesh stiffness (TVMS). Current TVMS models often overestimate the asymmetric spalling phenomenon and may lead to inaccuracy in identifying and predicting the spalling failure. To address this problem, in this paper, a new stiffness, namely torsional stiffness, is introduced to quantify the effect of asymmetric spalling defects, and an equivalent stiffness calculation method for different asymmetric shapes is proposed.

Targeted inhibition of transforming growth factor-β type I receptor by AZ12601011 improves paraquat poisoning-induced multiple organ fibrosis.

Paraquat (PQ) causes fatal poisoning that leads to systemic multiple organ fibrosis, and transforming growth factor (TGF)-β1 plays a critical role in this process. In this study, we aimed to investigate the effects of AZ12601011 (a small molecular inhibitor of TGFβRI) on PQ-induced multiple organ fibrosis. We established a mouse model of PQ in vivo and used PQ-treated lung epithelial cell (A549) and renal tubular epithelial cells (TECs) in vitro.

GRP/GRPR signaling pathway aggravates hyperuricemia-induced renal inflammation and fibrosis via ABCG2-dependent mechanisms.

The gastrin-releasing peptide receptor (GRPR) binds to ligands such as gastrin-releasing peptide (GRP) and plays a variety of biological roles. In this study, we investigated the therapeutic effect of a novel gastrin-releasing peptide receptor antagonist RH-1402 in hyperuricemia-induced kidney fibrosis and its underlying mechanisms. We conducted enzyme linked immunosorbent assay (ELISA) and immunohistochemical analyses and found that proGRP and GRPR expression levels were significantly increased in patients with hyperuricemic nephropathy (HN) and HN mice.

Accelerating CEST imaging using a model-based deep neural network with synthetic training data.

Purpose: To develop a model-based deep neural network for high-quality image reconstruction of undersampled multi-coil CEST data.

Theory And Methods: Inspired by the variational network (VN), the CEST image reconstruction equation is unrolled into a deep neural network (CEST-VN) with a k-space data-sharing block that takes advantage of the inherent redundancy in adjacent CEST frames and 3D spatial-frequential convolution kernels that exploit correlations in the x-ω domain. Additionally, a new pipeline based on multiple-pool Bloch-McConnell simulations is devised to synthesize multi-coil CEST data from publicly available anatomical MRI data.

Simultaneous determination of cyanide and thiocyanate in milk by GC-MS/MS using cetyltrimethylammonium bromide as both phase transfer catalyst and protein precipitant.

A method was developed for simultaneous determination of cyanide and thiocyanate in milk by gas chromatography-tandem quadrupole mass spectrometry (GC-MS/MS). Cyanide and thiocyanate were derivatized with pentafluorobenzyl bromide (PFBBr) as PFB-CN and PFB-SCN, respectively. Cetyltrimethylammonium bromide (CTAB) was employed both as a phase transfer catalyst and a protein precipitant in the sample pretreatment, which facilitates the separation of the organic and aqueous phases, and greatly simplifies the pretreatment procedures to achieve simultaneous and rapid determination of cyanide and thiocyanate.

3D diffusion MRI with twin navigator-based GRASE and comparison with 2D EPI for tractography in the human brain.

Purpose: 3D pulse sequences enable high-resolution acquisition with a high SNR and ideal slice profiles, which, however, is particularly difficult for diffusion MRI (dMRI) due to the additional phase errors from diffusion encoding.

Methods: We proposed a twin navigator-based 3D diffusion-weighted gradient spin-echo (GRASE) sequence to correct the phase errors between shots and between odd and even spin echoes for human whole-brain acquisition. We then compared the SNR of 3D GRASE and 2D simultaneous multi-slice EPI within the same acquisition time.

LINC00525 promotes tumour growth and epithelial-mesenchymal transition as an oncogene in oral squamous cell carcinoma.

Objective: Oral squamous cell carcinoma (OSCC) is the most common malignant tumour in the oral cavity. OSCC is aggressive and prone to metastasis; it is associated with high mortality and short survival. In this study, we investigated the function of the long non-coding RNA LINC00525 in OSCC progression and the molecular mechanisms through in vitro and in vivo experiments.

Joint K-space and Image-space Parallel Imaging (KIPI) for accelerated chemical exchange saturation transfer acquisition.

Purpose: To develop an auto-calibrated technique by joint K-space and Image-space Parallel Imaging (KIPI) for accelerated CEST acquisition.

Theory And Methods: The KIPI method selects a calibration frame with a low acceleration factor (AF) and auto-calibration signals (ACS) acquired, from which the coil sensitivity profiles and artifact correction maps are calculated after restoring the k-space by GRAPPA. Then the other frames with high AF and without ACS can be reconstructed by SENSE and artifact suppression.

Staufen Impairs Autophagy in Neurodegeneration.

Objective: The mechanistic target of rapamycin (mTOR) kinase is one of the master coordinators of cellular stress responses, regulating metabolism, autophagy, and apoptosis. We recently reported that staufen1 (STAU1), a stress granule (SG) protein, was overabundant in fibroblast cell lines from patients with spinocerebellar ataxia type 2 (SCA2), amyotrophic lateral sclerosis, frontotemporal degeneration, Huntington's, Alzheimer's, and Parkinson's diseases as well as animal models, and patient tissues. STAU1 overabundance is associated with mTOR hyperactivation and links SG formation with autophagy.

Comprehensive investigation of the content and the origin of matrine-type alkaloids in Chinese honeys.

A HPLC-MS/MS method for simultaneous determination of four matrine-type alkaloids (matrine, oxymatrine, sophocarpine and sophoridine) in honey was established and was applied to 567 Chinese honey samples. The overall detection rate was 61.0 % and all eight Sophora viciifolia Hance honey samples were detected with the average content of 1183.

Inversion-Recovery-Prepared Oscillating Gradient Sequence Improves Diffusion-Time Dependency Measurements in the Human Brain.

Background: Oscillating gradient diffusion MRI (dMRI) enables measurements at a short diffusion-time (t ), but it is challenging for clinical systems. Particularly, the low b-value and low resolution may give rise to cerebrospinal fluid (CSF) contamination.

Purpose: To assess the effect of CSF partial volume on t -dMRI measurements and efficacy of inversion-recovery (IR) prepared oscillating and pulsed gradient dMRI sequence to improve t -dMRI measurements in the human brain.

Gut Microbiome Signatures Are Predictive of Cognitive Impairment in Hypertension Patients-A Cohort Study.

Growing evidence has demonstrated that hypertension was associated with dysbiosis of intestinal flora. Since intestinal microbes could critically regulate neurofunction the intestinal-brain axis, the study aimed to reveal the role and prediction value of intestinal flora alteration in hypertension-associated cognitive impairment. A cohort of 97 participants included 63 hypertension patients and 34 healthy controls.

Acquisition sequences and reconstruction methods for fast chemical exchange saturation transfer imaging.

Chemical exchange saturation transfer (CEST) imaging is an emerging molecular magnetic resonance imaging (MRI) technique that has been developed and employed in numerous diseases. Based on the unique saturation transfer principle, a family of CEST-detectable biomolecules in vivo have been found capable of providing valuable diagnostic information. However, CEST MRI needs a relatively long scan time due to the common long saturation labeling module and typical acquisition of multiple frequency offsets and signal averages, limiting its widespread clinical applications.

CCG•CGG interruptions in high-penetrance SCA8 families increase RAN translation and protein toxicity.

Spinocerebellar ataxia type 8 (SCA8), a dominantly inherited neurodegenerative disorder caused by a CTG•CAG expansion, is unusual because most individuals that carry the mutation do not develop ataxia. To understand the variable penetrance of SCA8, we studied the molecular differences between highly penetrant families and more common sporadic cases (82%) using a large cohort of SCA8 families (n = 77). We show that repeat expansion mutations from individuals with multiple affected family members have CCG•CGG interruptions at a higher frequency than sporadic SCA8 cases and that the number of CCG•CGG interruptions correlates with age at onset.

Interference with long noncoding RNA SNHG3 alleviates cerebral ischemia-reperfusion injury by inhibiting microglial activation.

Neuroinflammation plays a strong part in cerebral ischemia-reperfusion injury, and microglial activation is regarded as a marker for neuroinflammation. Long noncoding RNA small nucleolar RNA host gene 3 (lncRNA SNHG3) is heavily expressed in cerebral ischemia-reperfusion models, but its mechanism is rarely studied. This study aims to explore whether SNHG3 is involved in cerebral ischemia-reperfusion injury by promoting microglial activation and inflammatory factor secretion.

The alternative initiation factor eIF2A plays key role in RAN translation of myotonic dystrophy type 2 CCUG•CAGG repeats.

Repeat-associated non-ATG (RAN) proteins have been reported in 11 microsatellite expansion disorders but the factors that allow RAN translation to occur and the effects of different repeat motifs and alternative AUG-like initiation codons are unclear. We studied the mechanisms of RAN translation across myotonic dystrophy type 2 (DM2) expansion transcripts with (CCUG) or without (CAGG) efficient alternative AUG-like codons. To better understand how DM2 LPAC and QAGR RAN proteins are expressed, we generated a series of CRISPR/Cas9-edited HEK293T cell lines.

ATF3 downmodulates its new targets IFI6 and IFI27 to suppress the growth and migration of tongue squamous cell carcinoma cells.

Activating transcription factor 3 (ATF3) is a key transcription factor involved in regulating cellular stress responses, with different expression levels and functions in different tissues. ATF3 has also been shown to play crucial roles in regulating tumor development and progression, however its potential role in oral squamous cell carcinomas has not been fully explored. In this study, we examined biopsies of tongue squamous cell carcinomas (TSCCs) and found that the nuclear expression level of ATF3 correlated negatively with the differentiation status of TSCCs, which was validated by analysis of the ATGC database.

Co-feeding glucose with either gluconate or galacturonate during clostridial fermentations provides metabolic fine-tuning capabilities.

Clostridium acetobutylicum ATCC 824 effectively utilizes a wide range of substrates to produce commodity chemicals. When grown on substrates of different oxidation states, the organism exhibits different recycling needs of reduced intracellular electron carrying co-factors. Ratios of substrates with different oxidation states were used to modulate the need to balance electron carriers and demonstrate fine-tuned control of metabolic output.

Repeat length increases disease penetrance and severity in C9orf72 ALS/FTD BAC transgenic mice.

C9orf72 ALS/FTD patients show remarkable clinical heterogeneity, but the complex biology of the repeat expansion mutation has limited our understanding of the disease. BAC transgenic mice were used to better understand the molecular mechanisms and repeat length effects of C9orf72 ALS/FTD. Genetic analyses of these mice demonstrate that the BAC transgene and not integration site effects cause ALS/FTD phenotypes.

ATF-3 expression inhibits melanoma growth by downregulating ERK and AKT pathways.

Activating transcription factor 3 (ATF-3), a cyclic AMP-dependent transcription factor, has been shown to play a regulatory role in melanoma, although its function during tumor progression remains unclear. Here, we demonstrate that ATF-3 exhibits tumor suppressive function in melanoma. Specifically, ATF-3 nuclear expression was significantly diminished with melanoma progression from nevi to primary to metastatic patient melanomas, correlating low expression with poor prognosis.

Survival and Motor Phenotypes in FVB C9-500 ALS/FTD BAC Transgenic Mice Reproduced by Multiple Labs.

Mordes et al. (2020) did not detect the survival or motor phenotypes in C9orf72 BAC transgenic mice originally described by Liu et al. (2016).

Ultra high-dimensional semiparametric longitudinal data analysis.

As ultra high-dimensional longitudinal data are becoming ever more apparent in fields such as public health and bioinformatics, developing flexible methods with a sparse model is of high interest. In this setting, the dimension of the covariates can potentially grow exponentially as with respect to the number of clusters n. We consider a flexible semiparametric approach, namely, partially linear single-index models, for ultra high-dimensional longitudinal data.