Small noncoding vault RNA2-1 disrupts gut epithelial barrier function via interaction with HuR.

Vault RNAs (vtRNAs) are small noncoding RNAs and highly expressed in many eukaryotes. Here, we identified vtRNA2-1 as a novel regulator of the intestinal barrier via interaction with RNA-binding protein HuR. Intestinal mucosal tissues from patients with inflammatory bowel diseases and from mice with colitis or sepsis express increased levels of vtRNAs relative to controls. Ectopically expressed vtRNA2-1 decreases the levels of intercellular junction (IJ) proteins claudin 1, occludin, and E-cadherin and causes intestinal epithelial barrier dysfunction in vitro, whereas vtRNA2-1 silencing promotes barrier function. Increased vtRNA2-1 also decreases IJs in intestinal organoid, inhibits epithelial renewal, and causes Paneth cell defects ex vivo. Elevating the levels of tissue vtRNA2-1 in the intestinal mucosa increases the vulnerability of the gut barrier to septic stress in mice. vtRNA2-1 interacts with HuR and prevents HuR binding to claudin 1 and occludin mRNAs, thus decreasing their translation. These results indicate that vtRNA2-1 impairs intestinal barrier function by repressing HuR-facilitated translation of claudin 1 and occludin.

Object detection: A novel AI technology for the diagnosis of hepatocyte ballooning.

Metabolic dysfunction-associated fatty liver disease (MAFLD) has reached epidemic proportions worldwide and is the most frequent cause of chronic liver disease in developed countries. Within the spectrum of liver disease in MAFLD, steatohepatitis is a progressive form of liver disease and hepatocyte ballooning (HB) is a cardinal pathological feature of steatohepatitis. The accurate and reproducible diagnosis of HB is therefore critical for the early detection and treatment of steatohepatitis. Currently, a diagnosis of HB relies on pathological examination by expert pathologists, which may be a time-consuming and subjective process. Hence, there has been interest in developing automated methods for diagnosing HB. This narrative review briefly discusses the development of artificial intelligence (AI) technology for diagnosing fatty liver disease pathology over the last 30 years and provides an overview of the current research status of AI algorithms for the identification of HB, including published articles on traditional machine learning algorithms and deep learning algorithms. This narrative review also provides a summary of object detection algorithms, including the principles, historical developments, and applications in the medical image analysis. The potential benefits of object detection algorithms for HB diagnosis (specifically those combined with a transformer architecture) are discussed, along with the future directions of object detection algorithms in HB diagnosis and the potential applications of generative AI on transformer architecture in this field. In conclusion, object detection algorithms have huge potential for the identification of HB and could make the diagnosis of MAFLD more accurate and efficient in the near future.

Universal Image Restoration with Text Prompt Diffusion.

Universal image restoration (UIR) aims to accurately restore images with a variety of unknown degradation types and levels. Existing methods, including both learning-based and prior-based approaches, heavily rely on low-quality image features. However, it is challenging to extract degradation information from diverse low-quality images, which limits model performance. Furthermore, UIR necessitates the recovery of images with diverse and complex types of degradation. Inaccurate estimations further decrease restoration performance, resulting in suboptimal recovery outcomes. To enhance UIR performance, a viable approach is to introduce additional priors. The current UIR methods have problems such as poor enhancement effect and low universality. To address this issue, we propose an effective framework based on a diffusion model (DM) for universal image restoration, dubbed ETDiffIR. Inspired by the remarkable performance of text prompts in the field of image generation, we employ text prompts to improve the restoration of degraded images. This framework utilizes a text prompt corresponding to the low-quality image to assist the diffusion model in restoring the image. Specifically, a novel text-image fusion block is proposed by combining the CLIP text encoder and the DA-CLIP image controller, which integrates text prompt encoding and degradation type encoding into time step encoding. Moreover, to reduce the computational cost of the denoising UNet in the diffusion model, we develop an efficient restoration U-shaped network (ERUNet) to achieve favorable noise prediction performance via depthwise convolution and pointwise convolution. We evaluate the proposed method on image dehazing, deraining, and denoising tasks. The experimental results indicate the superiority of our proposed algorithm.

[A new cucurbitane glycoside from Picrorhiza scrophulariiflora].

Chemical constituents from the ethanol extract of Picrorhiza scrophulariiflora were isolated and purified by column chromatography. Their structures were identified by HR-MS, 1D and 2D-NMR, and their cytotoxicity was assessed by CCK-8 assay. Four compounds were isolated and identified as follows: 2ß-D-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosterol-5,25-diene-22-one(1), 2ß-D-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosta-5,24-diene-22-one(2), 25-acetoxy-2ß-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosta-5-ene-22-one(3) and 25-acetoxy-2ß-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosta-5,23-(E)-diene-22-one(4). Compound 1 represents a new cucurbitane glycoside. The half inhibitory concentrations of the 4 compounds exceeded 100 µmol·L~(-1) against four tumor cell lines, indicating no significant cytotoxicity.

[Serum folate and vitamin B12 levels and their association with neurodevelopmental features in preschool children with autism spectrum disorder]. / å­¦é¾„å‰å­¤ç‹¬ç—‡è°±ç³»éšœç¢å„¿ç«¥è¡€æ¸ å¶é ¸ã€ç»´ç”Ÿç´ B12æ°´å¹³åŠå ¶ä¸Žç¥žç»å‘è‚²ç‰¹å¾çš„å ³è”.

OBJECTIVES: To investigate the levels of serum folate and vitamin B12 (VB12) and their association with the level of neurodevelopment in preschool children with autism spectrum disorder (ASD). METHODS: A total of 324 ASD children aged 2-6 years and 318 healthy children aged 2-6 years were recruited. Serum levels of folate and VB12 were measured using chemiluminescent immunoassay. The Social Responsiveness Scale and the Childhood Autism Rating Scale were used to assess the core symptoms of ASD children, and the Gesell Developmental Schedule was employed to evaluate the level of neurodevelopment. RESULTS: The levels of serum folate and VB12 in ASD children were significantly lower than those in healthy children (P<0.05). Serum folate levels in ASD children were positively correlated with gross and fine motor developmental quotients (P<0.05), and serum VB12 levels were positively correlated with adaptive behavior, fine motor, and language developmental quotients (P<0.05). In ASD children aged 2 to <4 years, serum folate levels were positively correlated with developmental quotients in all domains (P<0.05), and serum VB12 levels were positively correlated with language developmental quotient (P<0.05). In male ASD children, serum VB12 levels were positively correlated with language and personal-social developmental quotients (P<0.05). CONCLUSIONS: Serum folate and VB12 levels in preschool ASD children are lower than those in healthy children and are associated with neurodevelopmental levels, especially in ASD children under 4 years of age. Therefore, maintaining normal serum folate and VB12 levels may be beneficial for the neurodevelopment of ASD children, especially in ASD children under 4 years of age.

Enhancement of phytoextraction efficiency coupling Pteris vittata with low-dose biochar in arsenic-contaminated soil.

Phytoremediation of arsenic (As) by Pteris vittata (P. vittata) is a cost-effective and environmentally friendly method for restoring As-contaminated sites. However, the phytoextraction efficiency is low in some cases, such as clay soil, thus biochar was applied to enhance the efficiency of As extraction. The paper investigated the effect of biochar on soil characteristic, As mobility, and As uptake in P. vittata with a 90-day greenhouse experiment. Biochar derived from rice straw was added at rates of 0.5, 1.5, and 4% (w/w). The results showed that, under biochar amendment, soil pH raised from 5.24 to 6.03 and 4.91 to 5.85, soil dissolved organic carbon (DOC) increased 11.1-46.1% and 2.8-11.2%, respectively, in rhizosphere and bulk soils. Biochar also increased soil catalase (CAT) activity significantly, especially for the rhizosphere soil. Besides, biochar increased the labile As in the soils and transfer coefficient from roots to aboveground, thereby enhancing As accumulation by P. vittata tissues. The accumulation of As in fronds of P. vittata was up to 350 mg kg-1 in 1.5% biochar, which was more than twice the control and far beyond other biochar treatments. The results indicate that biochar addition is favorable to improve phytoremediation of P. vittata in As-contaminated soil and 1.5% (w/w) biochar may be a reasonable application ratio, thus providing an effective solution to enhance the efficiency of As phytoextraction.

Biochar increased soil catalase activity in the rhizosphere of P. vittata.Biochar increased the labile concentration of arsenic in soil and arsenic accumulation in P. vittata significantly.Combining biochar and P. vittata reduced arsenic in soil.Biochar amendment was favorable for phytoremediation of P. vittata in arsenic-contaminated soil.

Circular RNA CircHIPK3 Promotes Homeostasis of the Intestinal Epithelium by Reducing MicroRNA 29b Function.

BACKGROUND & AIMS: Circular RNAs (circRNAs) are a class of endogenous noncoding RNAs that form covalently closed circles. Although circRNAs influence many biological processes, little is known about their role in intestinal epithelium homeostasis. We surveyed circRNAs required to maintain intestinal epithelial integrity and identified circular homeodomain-interacting protein kinase 3 (circHIPK3) as a major regulator of intestinal epithelial repair after acute injury. METHODS: Intestinal mucosal tissues were collected from mice exposed to cecal ligation and puncture for 48 hours and patients with inflammatory bowel diseases and sepsis. We isolated primary enterocytes from the small intestine of mice and derived intestinal organoids. The levels of circHIPK3 were silenced in intestinal epithelial cells (IECs) by transfection with small interfering RNAs targeting the circularization junction of circHIPK3 or elevated using a plasmid vector that overexpressed circHIPK3. Intestinal epithelial repair was examined in an in vitro injury model by removing part of the monolayer. The association of circHIPK3 with microRNA 29b (miR-29b) was determined by biotinylated RNA pull-down assays. RESULTS: Genome-wide profile analyses identified ∼300 circRNAs, including circHIPK3, differentially expressed in the intestinal mucosa of mice after cecal ligation and puncture relative to sham mice. Intestinal mucosa from patients with inflammatory bowel diseases and sepsis had reduced levels of circHIPK3. Increasing the levels of circHIPK3 enhanced intestinal epithelium repair after wounding, whereas circHIPK3 silencing repressed epithelial recovery. CircHIPK3 silencing also inhibited growth of IECs and intestinal organoids, and circHIPK3 overexpression promoted intestinal epithelium renewal in mice. Mechanistic studies revealed that circHIPK3 directly bound to miR-29b and inhibited miR-29 activity, thus increasing expression of Rac1, Cdc42, and cyclin B1 in IECs after wounding. CONCLUSIONS: In studies of mice, IECs, and human tissues, our results indicate that circHIPK3 improves repair of the intestinal epithelium at least in part by reducing miR-29b availability.

Boosting Electrocatalytic Activity of Single Atom Catalysts Supported on Nitrogen-Doped Carbon through N Coordination Environment Engineering.

Nonprecious group metal (NPGM)-based single atom catalysts (SACs) hold a great potential in electrocatalysis and dopant engineering has been extensively exploited to boost their catalytic activity, while the coordination environment of dopant, which also significantly affects the electronic structure of SACs, and consequently their electrocatalytic performance, have been largely ignored. Here, by adopting a precursor modulation strategy, the authors successfully synthesize single cobalt atom catalysts embedded in nitrogen-doped carbon, Co-N/C, with similar overall Co and N concentrations but different N types, that is, pyridinic N (NP ), graphitic N (NG ), and pyrrolic N (NPY ). Co-N/C with the Co-N4 moieties coordinated with NG displays far superior activity for oxygen reduction (ORR) and evolution reactions, and superior activity and stability in both zinc-air batteries and proton exchange membrane fuel cells. Density functional theory calculation indicates that coordinated N species in particular NG functions as electron donors to the Co core of Co-N4 active sites, leading to the downshift of d-band center of Co-N4 and weakening the binding energies of the intermediates on Co-N4 sites, thus, significantly promoting catalytic kinetics and thermodynamics for ORR in a full pH range condition.

Multimodal treatment combining cold atmospheric plasma and acidic fibroblast growth factor for multi-tissue regeneration.

Cold atmospheric plasma (CAP) is an emerging technology for biomedical applications, exemplified by its antimicrobial and antineoplastic potentials. On the contrary, acidic fibroblast growth factor (aFGF) has been a long-standing potent mitogen for cells from various origins. In this study, we are the first to develop a multimodal treatment combining the aforementioned physicochemical and pharmacological treatments and investigated their individual and combined effects on wound healing, angiogenesis, neurogenesis, and osteogenesis. This work was performed at the tissue, cellular, protein, and gene levels, using histochemical staining, flow cytometry, ELISA, and PCR, respectively. Depending on the type of target tissue, various combinations of aforementioned methods were used. The results showed that the enhancement on would healing and angiogenesis by CAP and aFGF were synergistic. The former was manifested by increased murine fibroblast proliferation and reduced cutaneous tissue inflammation, whereas the latter by upregulated proangiogenic markers in vivo, for example, CD31, VEGF, and TGF-ß, and downregulated antiangiogenic proteins in vitro, for example, angiostatin and angiopoietin-2, respectively. In addition, aFGF outperformed CAP during neurogenesis, which was evidenced by superior neurite outgrowth, while CAP exceeded aFGF in osteogenesis which was demonstrated by more substantial bone nodule formation. These novel findings not only support the fact that CAP and aFGF are both multipotent agents during tissue regeneration, but also highlight the potential of our multimodal treatment combining the individual advantages of CAP and aFGF. The versatile administration route, that is, topical and/or systemic, might further broaden its applications.

Genomic and transcriptomic investigations of the evolutionary transition from oviparity to viviparity.

Viviparous (live-bearing) vertebrates have evolved repeatedly within otherwise oviparous (egg-laying) clades. Over two-thirds of these changes in vertebrate reproductive parity mode happened in squamate reptiles, where the transition has happened between 98 and 129 times. The transition from oviparity to viviparity requires numerous physiological, morphological, and immunological changes to the female reproductive tract, including eggshell reduction, delayed oviposition, placental development for supply of water and nutrition to the embryo by the mother, enhanced gas exchange, and suppression of maternal immune rejection of the embryo. We performed genomic and transcriptomic analyses of a closely related oviparous-viviparous pair of lizards (Phrynocephalus przewalskii and Phrynocephalus vlangalii) to examine these transitions. Expression patterns of maternal oviduct through reproductive development of the egg and embryo differ markedly between the two species. We found changes in expression patterns of appropriate genes that account for each of the major aspects of the oviparity to viviparity transition. In addition, we compared the gene sequences in transcriptomes of four oviparous-viviparous pairs of lizards in different genera (Phrynocephalus, Eremias, Scincella, and Sphenomorphus) to look for possible gene convergence at the sequence level. We discovered low levels of convergence in both amino acid replacement and evolutionary rate shift. This suggests that most of the changes that produce the oviparity-viviparity transition are changes in gene expression, so occasional reversals to oviparity from viviparity may not be as difficult to achieve as has been previously suggested.

EmhR is an indole-sensing transcriptional regulator responsible for the indole-induced antibiotic tolerance in Pseudomonas fluorescens.

Indole is well known as an interspecies signalling molecule to modulate bacterial physiology; however, it is not clear how the indole signal is perceived and responded to by plant growth promoting rhizobacteria (PGPR) in the rhizosphere. Here, we demonstrated that indole enhanced the antibiotic tolerance of Pseudomonas fluorescens 2P24, a PGPR well known for its biocontrol capacity. Proteomic analysis revealed that indole influenced the expression of multiple genes including the emhABC operon encoding a major multidrug efflux pump. The expression of emhABC was regulated by a TetR-family transcription factor EmhR, which was demonstrated to be an indole-responsive regulator. Molecular dynamics simulation showed that indole allosterically affected the distance between the two DNA-recognizing helices within the EmhR dimer, leading to diminished EmhR-DNA interaction. It was further revealed the EmhR ortholog in Pseudomonas syringae was also responsible for indole-induced antibiotic tolerance, suggesting this EmhR-dependent, indole-induced antibiotic tolerance is likely to be conserved among Pseudomonas species. Taken together, our results elucidated the molecular mechanism of indole-induced antibiotic tolerance in Pseudomonas species and had important implications on how rhizobacteria sense and respond to indole in the rhizosphere.

Causal effects of plasma lipids on the risk of atrial fibrillation: A multivariable mendelian randomization study.

BACKGROUND AND AIMS: Observational studies have suggested that plasma lipids contribute substantially to cardiovascular disease, but "cholesterol paradox" in atrial fibrillation (AF) remains. We sought to investigate the causal effects of lipid profiles on the risk of AF. METHODS AND RESULTS: Two-sample Mendelian randomization (MR) framework was implemented to examine the causality of association. Summary estimations of genetic variants associated with low density lipoprotein (LDL)-cholesterol, high density lipoprotein (HDL)-cholesterol, total cholesterol, triglycerides, lipoprotein-a [Lp(a)], apolipoprotein A1 (ApoA 1), and apolipoprotein B (ApoB) were 81, 99, 96, 61, 30, 10, and 23 single nucleotide polymorphisms, respectively. Genetic association with AF were retrieved from a genome-wide association study that included 1,030,836 individuals. The complications for AF were predefined as cardioembolic stroke (CES) and heart failure (HF). In the multivariable MR, the odds ratios for AF per standard deviation (SD) increase were 1.030 (95% confidence interval (CI) 0.979-1.083; P = 0.257) for LDL-cholesterol, 0.986 (95% CI 0.931-1.044; P = 0.622) for HDL-cholesterol, 0.965 (95% CI 0.896-1.041; P = 0.359) for triglycerides, 1.001 (95% CI 1.000-1.003; P = 0.023) for Lp(a), 1.017 (95% CI 0.966-1.070; P = 0.518) for ApoA1, and 1.002 (95% CI 0.963-1.043; P = 0.923) for ApoB. There was no evidence that other lipid components were causally associated with AF, CES, or HF, other than for a marginal association between triglycerides and HF. CONCLUSIONS: This MR study provides robust evidence that high Lp(a) increases the risk of AF, suggesting that interventions targeting Lp(a) may contribute to the primary prevention of AF.

Study on different pathogenic factors in different disease stages of patients with Wilson disease.

OBJECTIVE: To investigate in different stages of patients with Wilson disease (WD), there are different pathogenic factors such as metal deposition, oxidative stress, and inflammatory response in the brain. METHODS: A total of 32 untreated WD patients and 10 normal controls were enrolled in the study. The neurological symptoms were evaluated using the modified Young scale. Liver function, metal metabolism, susceptibility-weighted imaging (SWI), diffusion tensor imaging (DTI), and magnetic resonance spectroscopy (MRS) examination were done. The clinical disease stages were divided into metal deposition period, fiber damage period, and neuronal necrosis period according to the imaging results. The content of 24-h urine copper, serum copper, and serum iron; and the levels of catalase (CAT), glutathione peroxidase (GSH-PX), malondialdehyde (MDA), nitric oxide (NO), nitric oxide synthase (NOS), superoxide dismutase (SOD), interleukin (IL-1), and tumor necrosis factor alpha (TNF-α) were detected. RESULTS: The contents of urinary copper in WD patients at neuronal necrosis stage were lower than those in patients at the metal deposition stage (P = 0.011) and fiber injury stage (P = 0.023). The contents of NOS (P = 0.039) and NO (P = 0.047) in WD patients at the stage of fiber injury were higher than those of the normal control, while GSH-PX (P = 0.025) and CAT (P = 0.041) were lower in the neuronal necrosis stage. In the stage of neuronal necrosis, the levels of IL-1 (P = 0.030) and TNF-α were higher than those of the normal control (P = 0.042). The neurological symptom scores in patients with fiber injury (P = 0.013) and neuron injury were higher than those with metal deposition (P = 0.026). CONCLUSION: There are different pathogenic factors in different stages of WD. At the neuronal necrosis stage, copper deposition was decreased in WD patients. In the stage of fiber injury and neuronal necrosis, there is oxidative stress injury in WD patients. In the neuronal necrosis phase, WD patients have an inflammatory response.

Three-Dimensional Computed Tomography of the Detoured Facial Artery: Variations and Implications for Nasojugal Groove Correction.

BACKGROUND: When performing filler injection procedures to the nasojugal groove, there is the risk of iatrogenic damage to the detoured facial artery. OBJECTIVE: To determine the 3-dimensional location of the detoured facial artery. MATERIALS AND METHODS: The branches of the facial arteries from 118 cadaveric hemifaces were scanned using computed tomography and reconstructed using the Mimics software program. RESULTS: Detoured facial arteries were found in 47 of the 118 hemifaces (39.8%). Two main arterial patterns were identified: in Type I (29 of 47 cases), there were both detoured and nasolabial trunks where the facial artery originated, whereas in Type II (18 of 47 cases), there was only a detoured trunk. The detoured trunk originated 32.0 ± 5.3 mm from the midsagittal line, 5.0 ± 2.8 mm from the occlusion plane, and 5.9 ± 3.5 mm below the skin layer; the inflection of the detoured trunk was located 30.0 ± 5.6 mm laterally, 26.2 ± 4.4 mm superiorly, and 5.7 ± 2.6 mm deep. The meeting point with the inferior orbital rim plane was located 17.1 ± 3.4 mm laterally, 43.4 ± 3.1 mm superiorly, and 2.8 ± 1.7 mm deep. CONCLUSION: The 3-dimensional location of the detoured facial artery as reported here will help clinicians to avoid iatrogenic damage when they are performing filler injection procedures.

Deployment of the Ophthalmic and Facial Angiosomes in the Upper Nose Overlaying the Nasal Bones.

BACKGROUND: Nasal filler placement is associated with a high risk of blindness. The arterial supply to the upper nose overlaying the nasal bones is poorly understood. OBJECTIVES: The aim of this study was to visualize and analyze the deployment of the ophthalmic and facial angiosomes in the upper nose to help prevent blindness following nasal filler injections. METHODS: The arterial systems of 62 cadaveric heads were filled with lead oxide contrast agent, and computed tomography (CT) images were acquired and reconstructed in 3 dimensions. RESULTS: Twenty-six of the cadaveric noses examined demonstrated clear CT images of the facial and ophthalmic angiosomes in the upper nose. The Type 1 upper nose (15.4%) is supplied by 2 independent ophthalmic angiosomes that communicate indirectly through a choke anastomosis. The Type 2 upper nose (38.5%) is supplied by 2 ophthalmic angiosomes with a true anastomosis between them. The Type 3 upper nose (46.1%) is supplied by both ophthalmic and facial angiosomes with true anastomoses across the dorsal midline. These true anastomoses are mediated by the radix arcade in 46% of the noses and involve the dorsal nasal artery in 65% of the cases. The anastomoses all cross the upper dorsal midline and are directly linked to the ophthalmic angiosome. CONCLUSIONS: The deployment and anastomosis of the facial and ophthalmic angiosomes in the upper nose fall into 3 major patterns. About 85% of the noses have true anastomotic arteries that cross the upper dorsal midline and are directly linked to the ophthalmic circulation. Dorsum filler injection poses a significant risk of blindness.

Three-Dimensional Computed Tomography Scanning of Temporal Vessels to Assess the Safety of Filler Injections.

BACKGROUND: Temple filler injection is one of the most common minimally invasive cosmetic procedures involving the face; however, vascular complications are not uncommon. OBJECTIVES: This study aimed to investigate the anatomy of the temporal vessels and provide a more accurate protocol for temple filler injection. METHODS: Computed tomography (CT) scans of 56 cadaveric heads injected with lead oxide were obtained. We then used Mimics software to construct 3-dimensional (3D) images of the temporal vessels described by a coordinate system based on the bilateral tragus and right lateral canthus. RESULTS: In the XOY plane, the superficial temporal artery (STA), middle temporal artery (MTA), zygomatico-orbital artery (ZOA), posterior branch of the deep temporal artery (PDTA), and lateral margin of the orbital rim divide the temple into 4 parts (A, B, C, and D). The probabilities of the STA, MTA, ZOA, and PDTA appearing in parts A, B, C, and D were 30.73%, 37.06%, 39.48%, and 77.18%, respectively. In 3D images, these vessels together compose an arterial network that is anastomosed with other vessels, such as the external carotid, facial, and ocular arteries. CONCLUSIONS: 3D CT images can digitally elucidate the exact positions of temporal vessels in a coordinate system, improving the safety of temple filler injections in a clinical setting.

RNA-binding protein HuR regulates translation of vitamin D receptor modulating rapid epithelial restitution after wounding.

Homeostasis of the intestinal epithelium is tightly regulated by numerous extracellular and intracellular factors including vitamin D and the vitamin D receptor (VDR). VDR is highly expressed in the intestinal epithelium and is implicated in many aspects of gut mucosal pathophysiology, but the exact mechanism that controls VDR expression remains largely unknown. The RNA-binding protein human antigen R (HuR) regulates the stability and translation of target mRNAs and thus modulates various cellular processes and functions. Here we report a novel role of HuR in the posttranscriptional control of VDR expression in the intestinal epithelium. The levels of VDR in the intestinal mucosa decreased significantly in mice with ablated HuR, compared with control mice. HuR silencing in cultured intestinal epithelial cells (IECs) also reduced VDR levels, whereas HuR overexpression increased VDR abundance; neither intervention changed cellular Vdr mRNA content. Mechanistically, HuR bound to Vdr mRNA via its 3'-untranslated region (UTR) and enhanced VDR translation in IECs. Moreover, VDR silencing not only inhibited IEC migration over the wounded area in control cells but also prevented the increased migration in cells overexpressing HuR, although it did not alter IEC proliferation in vitro and growth of intestinal organoids ex vivo. The human intestinal mucosa from patients with inflammatory bowel diseases exhibited decreased levels of both HuR and VDR. These results indicate that HuR enhances VDR translation by directly interacting with its mRNA via 3'-UTR and that induced VDR by HuR is crucial for rapid intestinal epithelial restitution after wounding.

Tojapride prevents CaSR-mediated NLRP3 inflammasome activation in oesophageal epithelium irritated by acidic bile salts.

Impairment of the oesophageal epithelium in patients with reflux oesophagitis (RE) is a cytokine-mediated injury rather than a chemical burn. The present study was conducted to explore CaSR/NLRP3 inflammasome pathway activation and cytokines IL-1ß and IL-18 release in oesophageal epithelia injured by refluxates and the effects of Tojapride on that signal regulation. Using a modified RE rat model with Tojapride administration and Tojapride-pretreated SV40-immortalized human oesophageal epithelial cells (HET-1A) exposed to acidic bile salts pretreated with Tojapride, we evaluated the therapeutic effects of Tojapride on oesophageal epithelial barrier function, the expression of CaSR/NLRP3 inflammasome pathway-related proteins and the release of downstream cytokines in response to acidic bile salt irritation. In vivo, Tojapride treatment ameliorated the general condition and pathological lesions of the oesophageal epithelium in modified RE rats. In addition, Tojapride effectively blocked the CaSR-mediated NLRP3 inflammasome activation in modified RE rats. In vitro, Tojapride treatment can reverse the harmful effect of acidic bile salts, which reduced transepithelial electrical resistance (TEER), up-regulated the CaSR-mediated NLRP3 inflammasome pathway and increased caspase-1 activity, LDH release and cytokines secretion. Taken together, these data show that Tojapride can prevent CaSR-mediated NLRP3 inflammasome activation and alleviate oesophageal epithelial injury induced by acidic bile salt exposure.

An intriguing case of regular RR and QRS alternans during idiopathic left posterior fascicle ventricular tachycardia.

This study represents a case of idiopathic left posterior fascicle ventricular tachycardia (LPF-VT), which is intriguing due to regular alternation of short-long RR intervals and QRS morphology. Transthoracic echocardiogram analysis did not detect any structural heart disease. A baseline electrophysiological study was performed. Intracardiac recording during tachycardia showed V-A dissociation, confirming the final diagnosis of idiopathic LPF-VT. No regularity in the monomorphic VT was recorded. Previous relevant studies suggested that a single focus with two exits in distal branches of the left posterior fascicle or two different foci localized in the Purkinje-myocardial network of the left posterior fascicle can clarify the mechanisms. Our team proposed an additional explanation that combines the physiological refractory period with the Ashman phenomenon in individual reentrant LPF-VT circuit.

Three-Dimensional Computed Tomographic Study on the Periorbital Branches of the Ophthalmic Artery: Arterial Variations and Clinical Relevance.

BACKGROUND: Filler injection is a popular cosmetic procedure, but it can entail vascular complications. Periorbital injections have the highest risk within the entire injection area. OBJECTIVES: The authors sought to systematically screen for periorbital arterial variations prior to treatment. METHODS: The external carotid arteries of 10 cadaveric heads were infused with adequate lead oxide contrast. The facial and superficial temporal arteries of another 11 cadaveric heads were injected with the contrast in sequential order. Computed tomography (CT) scanning was performed after injection of contrast, and 3-dimensional (3D) CT scans were reconstructed using validated algorithms. RESULTS: Three types of periorbital blood vessels were found to derive from the ophthalmic artery, including 30% directly originating from the ophthalmic artery, 65% originating from its trochlear branch, and 5% originating from its supraorbital branch. In the forehead, the ophthalmic artery, originating from the internal carotid arteries, formed anastomoses between the frontal branch of the superficial temporal artery, originating from the external carotid artery, with the deep and superficial branches of the supratrochlear and supraorbital arteries, respectively. The lateral orbit and malar plexus can be classified into 4 types based on the trunk artery: the zygomatic orbital artery (27%), the transverse facial artery (23%), the premasseteric branch of the facial artery (19%), and all 3 contributing equally (31%). CONCLUSIONS: Postmortem 3D CT can map periorbital arterial variations. The branching pattern of the ophthalmic artery, the ophthalmic angiosome in the forehead, and the distribution of the lateral orbit and malar plexus were identified at high resolution to guide clinical practice.