Effect of nerve injury on the number of dorsal root ganglion neurons and autotomy behavior in adult Bax-deficient mice

Background: The proapoptotic molecule BAX, plays an important role in mitochondrial apoptotic pathway. Dorsal root ganglion (DRG) neurons depend on neurotrophic factors for survival at early developmental stages. Withdrawal of neurotrophic factors will induce apoptosis in DRG neurons, but this type of cell death can be delayed or prevented in neonatal Bax knockout (KO) mice. In adult animals, evidence also shows that DRG neurons are less dependent upon neurotrophic factors for survival. However, little is known about the effect of Bax deletion on the survival of normal and denervated DRG neurons in adult mice. Methods: A unilateral sciatic nerve transection was performed in adult Bax KO mice and wild-type (WT) littermates. Stereological method was employed to quantify the number of lumbar-5 DRG neurons 1 month post-surgery. Nerve injury-induced autotomy behavior was also examined on days 1, 3, and 7 post-surgery. Results: There were significantly more neurons in contralateral DRGs of KO mice as compared with WT mice. The number of neurons was reduced in ipsilateral DRGs in both KO and WT mice. No changes in size distributions of DRG neuron profiles were detected before or after nerve injury. Injury-induced autotomy behavior developed much earlier and was more serious in KO mice. Conclusion: Although postnatal death or loss of DRG neurons is partially prevented by Bax deletion, this effect cannot interfere with long-term nerve injury-induced neuronal loss. The exaggerated self-amputation behavior observed in the mutant mice indicates that Bax deficiency may enhance the development of spontaneous pain following nerve injury.publishedVersio

G Protein-Gated Inwardly Rectifying Potassium Channel Subunit 3 Is Upregulated in Rat DRGs and Spinal Cord After Peripheral Nerve Injury

Background: G protein-gated inwardly rectifying potassium (GIRK) channels are involved in the regulation of neuronal excitability. Four GIRK subunits (GIRK1-4) are expressed in rat dorsal root ganglia (DRGs). Recently, we have characterized the expression of GIRK1 and − 2, and both are downregulated in rat DRGs and spinal cord after a complete sciatic nerve transection (axotomy). Here, we aimed to study the neurochemical characteristics of GIRK3, and its regulation in rat DRGs and spinal cord induced by nerve injury. Methods: A sciatic nerve axotomy was performed to study the influences of injury on GIRK3 expression in DRGs and spinal cord. A dorsal root rhizotomy and a sciatic nerve crush were employed to study the axonal transport of GIRK3 protein, respectively. Immunohistochemistry analysis was employed for investigating the neurochemical characteristics of GIRK3. Results: In control DRGs, ∼ 18% of neuron profiles (NPs) were GIRK3-positive (+), and ∼ 41%, ∼ 48% and ∼ 45% of GIRK3+ NPs were CGRP+, IB4+ and NF200+, respectively. GIRK3-like immunoreactivity was observed in glabrous skin of hind paws and axons originating from DRG neurons. Fourteen days after axotomy, more than one-third of DRG NPs were GIRK3+, and among these ∼ 51% and ∼ 56% coexpressed galanin and neuropeptide Y, respectively. In control animals, a small group of interneurons found in the dorsal horn was GIRK3+. In addition, GIRK3+ processes could be observed in superficial laminae of spinal dorsal horn. After nerve injury, the intensity of GIRK3-like immunoreactivity in the superficial layers was increased. Evidence based on rhizotomy and sciatic nerve crush indicated both anterograde and retrograde transport of GIRK3. Conclusion: Our study demonstrates that GIRK3 is expressed in sensory neurons and spinal cord. GIRK3 has both anterograde and retrograde axonal transport. GIRK3 expression can be regulated by peripheral nerve injury.publishedVersio

Rainbow Kaposi's Sarcoma-Associated Herpesvirus Revealed Heterogenic Replication with Dynamic Gene Expression.

Molecular mechanisms of Kaposi's sarcoma-associated herpesvirus (KSHV) reactivation have been studied primarily by measuring the total or average activity of an infected cell population, which often consists of a mixture of both nonresponding and reactivating cells that in turn contain KSHVs at various stages of replication. Studies on KSHV gene regulation at the individual cell level would allow us to better understand the basis for this heterogeneity, and new preventive measures could be developed based on findings from nonresponding cells exposed to reactivation stimuli. Here, we generated a recombinant reporter virus, which we named "Rainbow-KSHV," that encodes three fluorescence-tagged KSHV proteins (mBFP2-ORF6, mCardinal-ORF52, and mCherry-LANA). Rainbow-KSHV replicated similarly to a prototype reporter-KSHV, KSHVr.219, and wild-type BAC16 virus. Live imaging revealed unsynchronized initiation of reactivation and KSHV replication with diverse kinetics between individual cells. Cell fractionation revealed temporal gene regulation, in which early lytic gene expression was terminated in late protein-expressing cells. Finally, isolation of fluorescence-positive cells from nonresponders increased dynamic ranges of downstream experiments 10-fold. Thus, this study demonstrates a tool to examine heterogenic responses of KSHV reactivation for a deeper understanding of KSHV replication.IMPORTANCE Sensitivity and resolution of molecular analysis are often compromised by the use of techniques that measure the ensemble average of large cell populations. Having a research tool to nondestructively identify the KSHV replication stage in an infected cell would not only allow us to effectively isolate cells of interest from cell populations but also enable more precise sample selection for advanced single-cell analysis. We prepared a recombinant KSHV that can report on its replication stage in host cells by differential fluorescence emission. Consistent with previous host gene expression studies, our experiments reveal the highly heterogenic nature of KSHV replication/gene expression at individual cell levels. The utilization of a newly developed reporter-KSHV and initial characterization of KSHV replication in single cells are presented

Privileged Prior Information Distillation for Image Matting

Performance of trimap-free image matting methods is limited when trying to decouple the deterministic and undetermined regions, especially in the scenes where foregrounds are semantically ambiguous, chromaless, or high transmittance. In this paper, we propose a novel framework named Privileged Prior Information Distillation for Image Matting (PPID-IM) that can effectively transfer privileged prior environment-aware information to improve the performance of students in solving hard foregrounds. The prior information of trimap regulates only the teacher model during the training stage, while not being fed into the student network during actual inference. In order to achieve effective privileged cross-modality (i.e. trimap and RGB) information distillation, we introduce a Cross-Level Semantic Distillation (CLSD) module that reinforces the trimap-free students with more knowledgeable semantic representations and environment-aware information. We also propose an Attention-Guided Local Distillation module that efficiently transfers privileged local attributes from the trimap-based teacher to trimap-free students for the guidance of local-region optimization. Extensive experiments demonstrate the effectiveness and superiority of our PPID framework on the task of image matting. In addition, our trimap-free IndexNet-PPID surpasses the other competing state-of-the-art methods by a large margin, especially in scenarios with chromaless, weak texture, or irregular objects.Comment: 15 pages, 7 figure

Translating Radiology Reports into Plain Language using ChatGPT and GPT-4 with Prompt Learning: Promising Results, Limitations, and Potential

The large language model called ChatGPT has drawn extensively attention because of its human-like expression and reasoning abilities. In this study, we investigate the feasibility of using ChatGPT in experiments on using ChatGPT to translate radiology reports into plain language for patients and healthcare providers so that they are educated for improved healthcare. Radiology reports from 62 low-dose chest CT lung cancer screening scans and 76 brain MRI metastases screening scans were collected in the first half of February for this study. According to the evaluation by radiologists, ChatGPT can successfully translate radiology reports into plain language with an average score of 4.27 in the five-point system with 0.08 places of information missing and 0.07 places of misinformation. In terms of the suggestions provided by ChatGPT, they are general relevant such as keeping following-up with doctors and closely monitoring any symptoms, and for about 37% of 138 cases in total ChatGPT offers specific suggestions based on findings in the report. ChatGPT also presents some randomness in its responses with occasionally over-simplified or neglected information, which can be mitigated using a more detailed prompt. Furthermore, ChatGPT results are compared with a newly released large model GPT-4, showing that GPT-4 can significantly improve the quality of translated reports. Our results show that it is feasible to utilize large language models in clinical education, and further efforts are needed to address limitations and maximize their potential

Head-Neck Dual-energy CT Contrast Media Reduction Using Diffusion Models

Iodinated contrast media is essential for dual-energy computed tomography (DECT) angiography. Previous studies show that iodinated contrast media may cause side effects, and the interruption of the supply chain in 2022 led to a severe contrast media shortage in the US. Both factors justify the necessity of contrast media reduction in relevant clinical applications. In this study, we propose a diffusion model-based deep learning framework to address this challenge. First, we simulate different levels of low contrast dosage DECT scans from the standard normal contrast dosage DECT scans using material decomposition. Conditional denoising diffusion probabilistic models are then trained to enhance the contrast media and create contrast-enhanced images. Our results demonstrate that the proposed methods can generate high-quality contrast-enhanced results even for images obtained with as low as 12.5% of the normal contrast dosage. Furthermore, our method outperforms selected competing methods in a human reader study

CHADS 2

Vascular events are one of the major causes of death in case of Cushing’s syndrome (CS). However, due to the relative low frequency of CS, it is hard to perform a risk assessment for these events. As represented congestive heart failure (C), hypertension (H), age (A), diabetes (D), and stroke (S), the CHADS2 score is now accepted to classify the risk of major adverse cardiovascular events (MACEs) in patients with atrial fibrillation. In this study, participants were enrolled from the National Health Research Institute Database (NHIRD) of Taiwan, and we reviewed 551 patients with their sequential clinically diagnosed CS data between 2002 and 2009 in relation to MACEs risk using CHADS2 score. Good correlation could be identified between the CS and CHADS2 score (AUC=0.795). Our results show that patients with CS show significantly higher risk of vascular events and the CHADS2 score could be applied for MACEs evaluation. Adequate lifestyle modifications and aggressive cardiovascular risks treatment are suggested for CS patients with higher CHADS2 score

Improving the onset potential and Tafel slope determination of earth-abundant water oxidation electrocatalysts

To date, a plethora of electrocatalysts for the Oxygen Evolution Reaction (OER) have been proposed. For evaluating their electrocatalytic behavior the determination of the onset potential in each studied electrolyte is a key parameter. Nevertheless, this evaluation becomes particularly problematic for first- transition metal catalysts as well as by the use of electroactive collectors ( e.g. Ni foams) whose redox peaks overlap the onset potential. A usual solution to detect the onset potential requires the availabil- ity of in-situ mass spectrometric determination of the generated oxygen. In this work, we present fast and easier available cyclic voltammetry and coulovoltammetric responses to determine the onset poten- tials of three benchmark electrocatalysts: a layered double hydroxide, a Prussian blue analogue and a β-Layered hydroxide. Cyclic coulovoltammetric responses allow, as we demonstrate here, a quantitative separation in the same potential range of the charge consumed by reversible (redox) reactions and the charge consumed by the irreversible reaction: the oxygen release. Quantifying the irreversible charges (that correspond to the OER) for different anodic potential limits permits the unambiguous determina- tion of both, the onset potential and the Tafel slope values without the catalyst redox contributions. As far as we know, this is the first time that this fast, available and cheap methodology has been applied for the OER determination. Thus, coulovoltammetry arises as a friendly and powerful tool for the investigation of electrocatalytic performances.To date, a plethora of electrocatalysts for the Oxygen Evolution Reaction (OER) have been proposed. For evaluating their electrocatalytic behavior the determination of the onset potential in each studied electrolyte is a key parameter. Nevertheless, this evaluation becomes particularly problematic for first- transition metal catalysts as well as by the use of electroactive collectors ( e.g. Ni foams) whose redox peaks overlap the onset potential. A usual solution to detect the onset potential requires the availabil- ity of in-situ mass spectrometric determination of the generated oxygen. In this work, we present fast and easier available cyclic voltammetry and coulovoltammetric responses to determine the onset poten- tials of three benchmark electrocatalysts: a layered double hydroxide, a Prussian blue analogue and a β-Layered hydroxide. Cyclic coulovoltammetric responses allow, as we demonstrate here, a quantitative separation in the same potential range of the charge consumed by reversible (redox) reactions and the charge consumed by the irreversible reaction: the oxygen release. Quantifying the irreversible charges (that correspond to the OER) for different anodic potential limits permits the unambiguous determina- tion of both, the onset potential and the Tafel slope values without the catalyst redox contributions. As far as we know, this is the first time that this fast, available and cheap methodology has been applied for the OER determination. Thus, coulovoltammetry arises as a friendly and powerful tool for the investigation of electrocatalytic performances

Identification of Gene Networks and Pathways Associated with Guillain-Barré Syndrome

BACKGROUND: The underlying change of gene network expression of Guillain-Barré syndrome (GBS) remains elusive. We sought to identify GBS-associated gene networks and signaling pathways by analyzing the transcriptional profile of leukocytes in the patients with GBS. METHODS AND FINDINGS: Quantitative global gene expression microarray analysis of peripheral blood leukocytes was performed on 7 patients with GBS and 7 healthy controls. Gene expression profiles were compared between patients and controls after standardization. The set of genes that significantly correlated with GBS was further analyzed by Ingenuity Pathways Analyses. 256 genes and 18 gene networks were significantly associated with GBS (fold change ≥2, P<0.05). FOS, PTGS2, HMGB2 and MMP9 are the top four of 246 significantly up-regulated genes. The most significant disease and altered biological function genes associated with GBS were those involved in inflammatory response, infectious disease, and respiratory disease. Cell death, cellular development and cellular movement were the top significant molecular and cellular functions involved in GBS. Hematological system development and function, immune cell trafficking and organismal survival were the most significant GBS-associated function in physiological development and system category. Several hub genes, such as MMP9, PTGS2 and CREB1 were identified in the associated gene networks. Canonical pathway analysis showed that GnRH, corticotrophin-releasing hormone and ERK/MAPK signaling were the most significant pathways in the up-regulated gene set in GBS. CONCLUSIONS: This study reveals the gene networks and canonical pathways associated with GBS. These data provide not only networks between the genes for understanding the pathogenic properties of GBS but also map significant pathways for the future development of novel therapeutic strategies