Epstein-Barr virus gp42 antibodies reveal sites of vulnerability for receptor binding and fusion to B cells.

Epstein-Barr virus (EBV) causes infectious mononucleosis and is associated with B cell lymphomas. EBV glycoprotein 42 (gp42) binds HLA class II and activates membrane fusion with B cells. We isolated gp42-specific monoclonal antibodies (mAbs), A10 and 4C12, which use distinct mechanisms to neutralize virus infection. mAb A10 was more potent than the only known neutralizing gp42 mAb, F-2-1, in neutralizing EBV infection and blocking binding to HLA class II. mAb 4C12 was similar to mAb A10 in inhibiting glycoprotein-mediated B cell fusion but did not block receptor binding, and it was less effective in neutralizing infection. Crystallographic structures of gH/gL/gp42/A10 and gp42/4C12 complexes revealed two distinct sites of vulnerability on gp42 for receptor binding and B cell fusion. Passive transfer of mAb A10 into humanized mice conferred nearly 100% protection from viremia and EBV lymphomas after EBV challenge. These findings identify vulnerable sites on EBV that may facilitate therapeutics and vaccines.

Epstein-Barr virus gH/gL has multiple sites of vulnerability for virus neutralization and fusion inhibition.

Epstein-Barr virus (EBV) is nearly ubiquitous in adults. EBV causes infectious mononucleosis and is associated with B cell lymphomas, epithelial cell malignancies, and multiple sclerosis. The EBV gH/gL glycoprotein complex facilitates fusion of virus membrane with host cells and is a target of neutralizing antibodies. Here, we examined the sites of vulnerability for virus neutralization and fusion inhibition within EBV gH/gL. We developed a panel of human monoclonal antibodies (mAbs) that targeted five distinct antigenic sites on EBV gH/gL and prevented infection of epithelial and B cells. Structural analyses using X-ray crystallography and electron microscopy revealed multiple sites of vulnerability and defined the antigenic landscape of EBV gH/gL. One mAb provided near-complete protection against viremia and lymphoma in a humanized mouse EBV challenge model. Our findings provide structural and antigenic knowledge of the viral fusion machinery, yield a potential therapeutic antibody to prevent EBV disease, and emphasize gH/gL as a target for herpesvirus vaccines and therapeutics.

Cognitive Reappraisal and Expressive Suppression Evoke Distinct Neural Connections during Interpersonal Emotion Regulation.

Interpersonal emotion regulation is the dynamic process where the regulator aims to change the target's emotional state, which is presumed to engage three neural systems: cognitive control (i.e., dorsal and ventral lateral PFC, etc.), empathy/social cognition (i.e., dorsal premotor regions, temporal-parietal junction, etc.), and affective response (i.e., insula, amygdala, etc.). This study aimed to identify the underlying neural correlate (especially the interpersonal one), of interpersonal emotion regulation based on two typical strategies (cognitive appraisal, expressive suppression). Thirty-four female dyads (friends) were randomly assigned into two strategy groups, with one assigned as the target and the other as the regulator to downregulate the target's negative emotions using two strategies. A functional near-infrared spectroscopy system was used to simultaneously measure participants' neural activity. Results showed that these two strategies could successfully downregulate the targets' negative emotions. Both strategies evoked intrapersonal and interpersonal neural couplings between the cognitive control, social cognition, and mirror neuron systems (e.g., PFC, temporal-parietal junction, premotor cortex, etc.), whereas cognitive reappraisal (vs expressive suppression) evoked a broader pattern. Further, cognitive reappraisal involved increased interpersonal brain synchronization between the prefrontal and temporal areas at the sharing stage, whereas expressive suppression evoked increased interpersonal brain synchronization associated with the PFC at the regulation stage. These findings indicate that intrapersonal and interpersonal neural couplings associated with regions within the abovementioned systems, possibly involving mental processes, such as cognitive control, mentalizing, and observing, underlie interpersonal emotion regulation based on cognitive reappraisal or expressive suppression.SIGNIFICANCE STATEMENT As significant as intrapersonal emotion regulation, interpersonal emotion regulation subserves parent-child, couple, and leader-follower relationships. Despite enormous growth in research on intrapersonal emotion regulation, the field lacks insight into the neural correlates underpinning interpersonal emotion regulation. This study aimed to probe the underlying neural correlates of interpersonal emotion regulation using a multibrain neuroimaging (i.e., hyperscanning) based on functional near-infrared spectroscopy. Results showed that both cognitive reappraisal and expressive suppression strategies successfully downregulated the target's negative emotions. More importantly, they evoked intrapersonal and interpersonal neural couplings associated with regions within the cognitive control, social cognition, and mirror neuron systems, possibly involving mental processes, such as cognitive control, mentalizing, and observing. These findings deepen our understanding of the neural correlates underpinning interpersonal emotion regulation.

Transcranial Direct Current Stimulation (tDCS) over the left dorsolateral prefrontal cortex reduced attentional bias toward natural emotional sounds.

Previous research has indicated that the left dorsolateral prefrontal cortex (DLPFC) exerts an influence on attentional bias toward visual emotional information. However, it remains unclear whether the left DLPFC also play an important role in attentional bias toward natural emotional sounds. The current research employed the emotional spatial cueing paradigm, incorporating natural emotional sounds of considerable ecological validity as auditory cues. Additionally, high-definition transcranial direct current stimulation (HD-tDCS) was utilized to examine the impact of left dorsolateral prefrontal cortex (DLPFC) on attentional bias and its subcomponents, namely attentional engagement and attentional disengagement. The results showed that (1) compared to sham condition, anodal HD-tDCS over the left DLPFC reduced the attentional bias toward positive and negative sounds; (2) anodal HD-tDCS over the left DLPFC reduced the attentional engagement toward positive and negative sounds, whereas it did not affect attentional disengagement away from natural emotional sounds. Taken together, the present study has shown that left DLPFC, which was closely related with the top-down attention regulatory function, plays an important role in auditory emotional attentional bias.

Ultrafast restricted intramolecular rotation in molecules with aggregation induced emission.

In this work, the ultrafast intramolecular rotation behavior of 1,1,2,3,4,5-hexaphenylsilole has been investigated in several solutions with different viscosities using femtosecond transient absorption spectroscopy combined with density functional theory and time-dependent density functional theory calculations. It is demonstrated that the nonradiative process, which competes with radiative decay, involves two main stages, namely the restricted intramolecular rotation and internal conversion processes. The intramolecular rotation depends on viscosity and presents a significant restriction. The restricted rotational rate is determined to be dozens of picoseconds. The following nonradiative process is strongly dominated by intramolecular rotation. The nonradiative decay rate will decrease with the increase in viscosity, leading to a rise in the radiative probability and photoluminous yield. These results have borne out the mechanism of ultrafast restricted intramolecular rotation of aggregation induced emission and provided a detailed photophysical picture of nonradiative processes.

Interpersonal emotion regulation and physiological synchrony: cognitive reappraisal versus expressive suppression.

The present study aimed to explore the effectiveness of two typical intrapersonal strategies (cognitive reappraisal, CR; expressive suppression, ES) on interpersonal emotion regulation (IER), and uncover the physiological synchrony pattern underlying this. A sample of 90 friend dyads (N = 180) was randomly assigned to the CR, the ES, or the control group. In each dyad, the target underwent a negative emotional task (induce sadness by recalling a negative event), and the regulator was assigned to implement the CR strategy, the ES strategy, or no action to down-regulate the targets' negative emotions. Self-reported results showed that compared to the control group, both CR and ES strategies decreased the targets' negative emotions, and increased the targets' positive emotions, indicating a successful IER effect. And the ECG results revealed that relative to the control condition, both CR and ES strategies evoked stronger physiological synchrony (heart rate synchrony and heart rate variation synchrony) during the emotion regulation stage of IER. Overall, these findings demonstrated the similar efficacy of reappraisal and suppression strategies implemented by the regulators to improve the targets' negative emotions, and suggested that the physiological synchrony might have an important relational meaning during the IER process.

[Clinical and genetic characteristics of four children with Kabuki syndrome due to de novo variants of KMT2D gene].

OBJECTIVE: To explore the clinical and genetic characteristics of four children with Kabuki syndrome (KS) due to variants of KMT2D gene. METHODS: Four children with KS diagnosed at the Children's Hospital of Shanxi Province between January 2020 and December 2022 were selected as the study subjects. Whole exome sequencing was carried out for the children and their family members. Candidate variants were verified by Sanger sequencing and pathogenicity analysis. RESULTS: The KS phenotype scores for the four children were 7, 8, 6, and 6, respectively. Child 2 also presented with a rare solitary kidney malformation. Genetic testing revealed that all children had harbored novel de novo variants of the KMT2D gene, including c.16472_16473del, c.858dup, c.11899C>T, and c.12844C>T, respectively. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), all of the variants were classified as pathogenic. CONCLUSION: For children showing phenotypes such as distinctive facial features, intellectual disability, developmental delay, cardiac abnormalities, and urinary system anomalies, KS should be considered. Early diagnosis and intervention can be achieved through genetic testing, especially in the presence of KMT2D gene mutations.

AMPK/mTOR/p70S6K axis prevents apoptosis of Porphyromonas gingivalis-infected gingival epithelial cells via BadSer136 phosphorylation.

Epithelial disruption is the initiation of most infectious disease. Regulation of epithelium apoptosis may play a key role in balance the survival competition between resident bacteria and host cells. The role of the mTOR/p70S6K pathway in preventing apoptosis of human gingival epithelial cells (hGECs) infected with Porphyromonas gingivalis (Pg) was investigated in order to further understand the survival strategy of the epithelial cells in during Pg infecting. hGECs was challenged with Pg for 4, 12, and 24 h. Additionally, hGECs was pretreated with LY294002 (PI3K signaling inhibitor) or Compound C (AMPK inhibitor) for 12 h and exposed them to Pg for 24 h. Subsequently, apoptosis was detected using flow cytometry, and expression and activity of Bcl-2, Bad, Bax, PI3K, AKT, AMPK, mTOR, and p70S6K proteins were analyzed using western blotting. Pg-infecting did not increase apoptosis of hGECs; but the expression ratio of Bad to Bcl-2 was increased after infecting. In contrast, BadSer136 phosphorylation was promoted, accompanied by a significant reduction of mTOR/p70S6K and PI3K/AKT signaling, along with the upregulation of AMPKThr172 signaling. Morrover, the PI3K inhibitor LY294002 promoted Pg-mediated reduction of mTOR/p70S6K expression, and the increase of AMPK signaling and BadSer136 phosphorylation rate, eventually decreasing apoptosis. While Compound C inhibited Pg-mediated activation of AMPK and downregulation of mTOR/p70S6K signaling, significantly reduced the BadSer136 phosphorylation rate, thereby increasing apoptosis. Thus, hGECs prevent apoptosis via an inherent cellular-homeostasis, pro-survival mechanism during Pg infection, the AMPK/mTOR/p70S6K pathway helps prevent apoptosis in hGECs infected with Pg by regulating BadSer136 phosphorylation.

Chlorogenic acid, rutin, and quercetin from Lysimachia christinae alleviate triptolide-induced multi-organ injury in vivo by modulating immunity and AKT/mTOR signal pathway to inhibit ferroptosis and apoptosis.

Drug-induced organ injury is one of the key factors causing organ failure and death in the global public. Triptolide (TP) is the main immunosuppressive component of Tripterygium wilfordii Hook. f. (Leigongteng, LGT) for the first-line management of autoimmune conditions, but it can cause serious multi-organ injury. Lysimachia christinae (Jinqiancao, JQC) is a detoxifying Chinese medicine and could suppress LGT's toxicity. It contains many immune enhancement and organ protection components including chlorogenic acid (CA), rutin (Rut), and quercetin (Que). This study aimed to explore the protection of combined treatments of these organ-protective ingredients of JQC on TP-induced liver, kidney, and heart injury and initially explore the mechanisms. Molecular docking showed that CA, Rut, and Que bounded protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) pathway-related molecules intimately and might competitively antagonize TP. Corresponding in vivo results showed that the combination activated TP-inhibited protein of AKT/mTOR pathway, and reversed TP-induced excessive ferroptosis (excessive Fe 2+ and lipid peroxidation malondialdehyde accumulation, decreased levels of antioxidant enzymes catalase, glutathione peroxidase, glutathione-s transferase, reduced glutathione, and superoxide dismutase, and down-regulated P62/nuclear factor erythroid-2-related factor 2/heme oxygenase-1 pathway), and apoptosis (activated apoptotic factor Fas and Bax and inhibited Bcl-2) in the organ of mice to varying degrees. In conclusion, the combined treatments of CA, Rut, and Que from JQC inhibited TP-induced multi-organ injury in vivo, and the mechanism may largely involve immunomodulation and activation of the AKT/mTOR pathway-mediated cell death reduction including ferroptosis and apoptosis inhibition.

Microglia-neuron interactions promote chronic itch via the NLRP3-IL-1ß-GRPR axis.

BACKGROUND: Spinal astrocytes contribute to chronic itch via sensitization of itch-specific neurons expressing gastrin-releasing peptide receptor (GRPR). However, whether microglia-neuron interactions contribute to itch remains unclear. In this study, we aimed to explore how microglia interact with GRPR+ neurons and promote chronic itch. METHODS: RNA sequencing, quantitative real-time PCR, western blot, immunohistochemistry, RNAscope ISH, pharmacologic and genetic approaches were performed to examine the roles of spinal NLRP3 (The NOD-like receptor family, pyrin-containing domain 3) inflammasome activation and IL-1ß-IL1R1 signaling in chronic itch. Grpr-eGFP and Grpr KO mice were used to investigate microglia-GRPR+ neuron interactions. RESULTS: We observed NLRP3 inflammasome activation and IL-1ß production in spinal microglia under chronic itch conditions. Blockade of microglial activation and the NLRP3/caspase-1/IL-1ß axis attenuated chronic itch and neuronal activation. Type 1 IL-1 receptor (IL-1R1) was expressed in GRPR+ neurons, which are essential for the development of chronic itch. Our studies also find that IL-1ß+ microglia are localized in close proximity to GRPR+ neurons. Consistently, intrathecal injection of IL1R1 antagonist or exogenous IL-1ß indicate that the IL-1ß-IL-1R1 signaling pathway enhanced the activation of GRPR+ neurons. Furthermore, our results demonstrate that the microglial NLRP3/caspase-1/IL-1ß axis contributes to several different chronic itches triggered by small molecules and protein allergens from the environment and drugs. CONCLUSION: Our findings reveal a previously unknown mechanism in which microglia enhances the activation of GRPR+ neurons through the NLRP3/caspase-1/IL-1ß/IL1R1 axis. These results will provide new insights into the pathophysiology of pruritus and novel therapeutic strategies for patients with chronic itch.

Diagnostic efficiency of [68 Ga]Ga-DOTA-FAPI-04 in differentiating periprosthetic hip joint infection and aseptic failure.

PURPOSE: To assess the efficiency of [68 Ga]Ga-DOTA-FAPI-04 in diagnosing periprosthetic hip joint infection and establish a diagnostic standard of clinical significance based on uptake pattern. METHODS: [68 Ga]Ga-DOTA-FAPI-04 PET/CT was performed in patients with symptomatic hip arthroplasty from December 2019 to July 2022. The reference standard was based on the 2018 Evidence-Based and Validation Criteria. Two diagnostic criteria, SUVmax and uptake pattern, were used to diagnose PJI. Meanwhile, original data were imported into IKT-snap to draw the view of interest, A.K. was used to extract features of clinical cases, and unsupervised clustering analysis was applied according to the groups. RESULTS: A total of 103 patients were included, 28 of whom had PJI. The area under the curve of SUVmax was 0.898, which was better than that of all of the serological tests. The cutoff value of SUVmax was 7.53, and the sensitivity and specificity were 100 and 72%, respectively. The sensitivity, specificity and accuracy of the uptake pattern were 100, 93.1 and 95%, respectively. In radiomics analysis, the features of PJI were significantly different from those of aseptic failure. CONCLUSION: The efficiency of [68 Ga]Ga-DOTA-FAPI-04 PET/CT in diagnosing PJI showed promising results, and the diagnostic criteria of the uptake pattern were more clinically instructive. Radiomics also showed certain application prospects in the field of PJI. TRIAL REGISTRATION NUMBER: Trial registration: ChiCTR2000041204. Registered 24 September 2019.

Predicting pathological complete response of neoadjuvant radiotherapy and targeted therapy for soft tissue sarcoma by whole-tumor texture analysis of multisequence MRI imaging.

OBJECTIVES: To construct effective prediction models for neoadjuvant radiotherapy (RT) and targeted therapy based on whole-tumor texture analysis of multisequence MRI for soft tissue sarcoma (STS) patients. METHODS: Thirty patients with STS of the extremities or trunk from a prospective phase II trial were enrolled for this analysis. All patients underwent pre- and post-neoadjuvant RT MRI examinations from which whole-tumor texture features were extracted, including T1-weighted with fat saturation and contrast enhancement (T1FSGd), T2-weighted with fat saturation (T2FS), and diffusion-weighted imaging (DWI) sequences and their corresponding apparent diffusion coefficient (ADC) maps. According to the postoperative pathological results, the patients were divided into pathological complete response (pCR) and non-pCR (N-pCR) groups. pCR was defined as less than 5% of residual tumor cells by postoperative pathology. Delta features were defined as the percentage change in a texture feature from pre- to post-neoadjuvant RT MRI. After data reduction and feature selection, logistic regression was used to build prediction models. ROC analysis was performed to assess the diagnostic performance. RESULTS: Five of 30 patients (16.7%) achieved pCR. The Delta_Model (AUC 0.92) had a better predictive ability than the Pre_Model (AUC 0.78) and Post_Model (AUC 0.76) and was better than AJCC staging (AUC 0.52) and RECIST 1.1 criteria (AUC 0.52). The Combined_Model (pre, post, and delta features) had the best predictive performance (AUC 0.95). CONCLUSION: Whole-tumor texture analysis of multisequence MRI can well predict pCR status after neoadjuvant RT and targeted therapy in STS patients, with better performance than RECIST 1.1 and AJCC staging. KEY POINTS: • MRI multisequence texture analysis could predict the efficacy of neoadjuvant RT and targeted therapy for STS patients. • Texture features showed incremental value beyond routine clinical factors. • The Combined_Model with features at multiple time points showed the best performance.

A CT-based deep learning radiomics nomogram outperforms the existing prognostic models for outcome prediction in clear cell renal cell carcinoma: a multicenter study.

OBJECTIVES: To develop and validate a CT-based deep learning radiomics nomogram (DLRN) for outcome prediction in clear cell renal cell carcinoma (ccRCC), and its performance was compared with the Stage, Size, Grade, and Necrosis (SSIGN) score, the University of California, Los Angeles, Integrated Staging System (UISS), the Memorial Sloan-Kettering Cancer Center (MSKCC), and the International Metastatic Renal Cell Database Consortium (IMDC). METHODS: A multicenter of 799 localized (training/ test cohort, 558/241) and 45 metastatic ccRCC patients were studied. A DLRN was developed for predicting recurrence-free survival (RFS) in localized ccRCC patients, and another DLRN was developed for predicting overall survival (OS) in metastatic ccRCC patients. The performance of the two DLRNs was compared with that of the SSIGN, UISS, MSKCC, and IMDC. Model performance was assessed with Kaplan-Meier curves, time-dependent area under the curve (time-AUC), Harrell's concordance index (C-index), and decision curve analysis (DCA). RESULTS: In the test cohort, the DLRN achieved higher time-AUCs (0.921, 0.911, and 0.900 for 1, 3, and 5 years, respectively), C-index (0.883), and net benefit than SSIGN and UISS in predicting RFS for localized ccRCC patients. The DLRN provided higher time-AUCs (0.594, 0.649, and 0.754 for 1, 3, and 5 years, respectively) than MSKCC and IMDC in predicting OS for metastatic ccRCC patients. CONCLUSIONS: The DLRN can accurately predict outcomes and outperformed the existing prognostic models in ccRCC patients. CLINICAL RELEVANCE STATEMENT: This deep learning radiomics nomogram may facilitate individualized treatment, surveillance, and adjuvant trial design for patients with clear cell renal cell carcinoma. KEY POINTS: • SSIGN, UISS, MSKCC, and IMDC may be insufficient for outcome prediction in ccRCC patients. • Radiomics and deep learning allow for the characterization of tumor heterogeneity. • The CT-based deep learning radiomics nomogram outperforms the existing prognostic models in ccRCC outcome prediction.

Current evidence for J147 as a potential therapeutic agent in nervous system disease: a narrative review.

Curcumin has anti-inflammatory, antioxidant, and anticancer effects and is used to treat diseases such as dermatological diseases, infection, stress, depression, and anxiety. J147, an analogue of curcumin, is designed and synthesized with better stability and bioavailability. Accumulating evidence demonstrates the potential role of J147 in the prevention and treatment of Alzheimer's disease, diabetic neuropathy, ischemic stroke, depression, anxiety, and fatty liver disease. In this narrative review, we summarized the background and biochemical properties of J147 and discussed the role and mechanism of J147 in different diseases. Overall, the mechanical attributes of J147 connote it as a potential target for the prevention and treatment of neurological diseases.

Channel Competition and Control of Relaxation Pathways in S1 State of Acrolein: Role of Conical Intersection and Surface Crossing.

Channel competition and further photochemical control of relaxation pathways in excited molecules are of primary importance in photochemistry and related areas. Acrolein, as the simplest and most typical α,ß-enone, is suitable to provide a model for understanding the photochemistry and photophysics of α,ß-enones. Here, the ultrafast dynamics in acrolein following S1(nπ*) excitation has been studied by time-resolved photoelectron imaging (TRPEI) and mass spectroscopy. The competition between intersystem crossing (ISC) and internal conversion (IC) is investigated. The key factor influencing the decay pathways and the relative contributions are revealed to be the position of the excitation relative to the energy of the S1/S0 conical intersection (CI), which is obtained to be 3.65-3.76 eV experimentally. If the excitation is above the CI, IC is superior to ISC and most excited molecules go back to the ground. Otherwise, ISC will dominate the relaxation and lead the triplet products formation. These results show the potential of affecting the dynamics and governing the fate of excited molecules by adjusting the excitation conditions from the point of view of chemical control.

Rydberg state dynamics and fragmentation mechanism of N,N,N',N'-tetramethylmethylenediamine.

The non-adiabatic relaxation processes and the fragmentation dynamics of Rydberg-excited N,N,N',N'-tetramethylmethylenediamine (TMMDA) are investigated using femtosecond time-resolved photoelectron imaging and time-resolved mass spectroscopy. Excitation at 208 nm populates TMMDA in a charge-localized 3p state. Rapid internal conversion (IC) to 3s produces two charge-delocalized conformers with independent time constants and distinct population ratios. As the system explores the 3s potential surface, the structural evolution continues on a 1.55 ps timescale, followed by a slower (12.1 ps) relaxation to the ground state. A thorough comparison of the time-dependent mass and photoelectron spectra suggests that ionization out of the 3p state ends up with the parent ion, the vibrational energy of which is insufficient for the bond cleavage. On the contrary, by virtue of the additional energy acquired by IC from 3p, the internal energy deposited in 3s is available to break the C-N bond, leading to the fragment ion. The fragmentation is found to occur on the ion surface instead of the Rydberg surface.

Deep learning model for automatic image quality assessment in PET.

BACKGROUND: A variety of external factors might seriously degrade PET image quality and lead to inconsistent results. The aim of this study is to explore a potential PET image quality assessment (QA) method with deep learning (DL). METHODS: A total of 89 PET images were acquired from Peking Union Medical College Hospital (PUMCH) in China in this study. Ground-truth quality for images was assessed by two senior radiologists and classified into five grades (grade 1, grade 2, grade 3, grade 4, and grade 5). Grade 5 is the best image quality. After preprocessing, the Dense Convolutional Network (DenseNet) was trained to automatically recognize optimal- and poor-quality PET images. Accuracy (ACC), sensitivity, specificity, receiver operating characteristic curve (ROC), and area under the ROC Curve (AUC) were used to evaluate the diagnostic properties of all models. All indicators of models were assessed using fivefold cross-validation. An image quality QA tool was developed based on our deep learning model. A PET QA report can be automatically obtained after inputting PET images. RESULTS: Four tasks were generated. Task2 showed worst performance in AUC,ACC, specificity and sensitivity among 4 tasks, and task1 showed unstable performance between training and testing and task3 showed low specificity in both training and testing. Task 4 showed the best diagnostic properties and discriminative performance between poor image quality (grade 1, grade 2) and good quality (grade 3, grade 4, grade 5) images. The automated quality assessment of task 4 showed ACC = 0.77, specificity = 0.71, and sensitivity = 0.83, in the train set; ACC = 0.85, specificity = 0.79, and sensitivity = 0.91, in the test set, respectively. The ROC measuring performance of task 4 had an AUC of 0.86 in the train set and 0.91 in the test set. The image QA tool could output basic information of images, scan and reconstruction parameters, typical instances of PET images, and deep learning score. CONCLUSIONS: This study highlights the feasibility of the assessment of image quality in PET images using a deep learning model, which may assist with accelerating clinical research by reliably assessing image quality.

Establishment and evaluation of nomogram for predicting intraventricular hemorrhage in neonatal acute respiratory distress syndrome.

BACKGROUND: Intraventricular hemorrhage (IVH) is the most common type of brain injury in newborns, especially in newborns with Neonatal acute respiratory distress syndrome (ARDS). IVH can cause brain parenchyma damage and long-term neurological sequelae in children. Early identification and prevention of sequelae are essential. This study aims to establish a predictive nomogram for the early prediction of IVH in newborns with ARDS. METHODS: From 2019 to 2021, we collected data from 222 infants diagnosed with ARDS in the Department of Neonatology, First Affiliated Hospital of Xinjiang Medical University. Infants have been randomly assigned to the training set (n = 161) or the validation set (n = 61) at a ratio of 7:3. Variables were screened using the Least Absolute Contract and Selection Operator (LASSO) regression to create a risk model for IVH in infants with ARDS. The variables chosen in the LASSO regression model were used to establish the prediction model using multivariate logistic regression analysis. RESULTS: We recognized 4 variables as independent risk factors for IVH in newborns with ARDS via LASSO analysis, consisting of premature rupture of membranes (PROM), pulmonary surfactant (PS) dosage, PH1 and Arterial partial pressure of oxygen (PaO21). The C-Index for this dataset is 0.868 (95% CI: 0.837-0.940) and the C index in bootstrap verification is 0.852 respectively. The analysis of the decision curve shows that the model can significantly improve clinical efficiency in predicting IVH. We also provide a website based on the model and open it to users for free, so that the model can be better applied to clinical practice. CONCLUSION: In conclusion, the nomogram based on 4 factors shows good identification, calibration and clinical practicability. Our nomographs can help clinicians make clinical decisions, screen high-risk ARDS newborns, and facilitate early identification and management of IVH patients.

RNF20/RNF40 ameliorates streptozotocin-induced type 1 diabetes by activating vitamin D receptors in vivo.

BACKGROUND: Type 1 diabetes is one of the chronic autoimmune diseases. Its features include the immune-triggered pancreatic beta-cells destruction. Ubiquitin ligases RNF20 and RNF40 have been discovered to participate into beta cells gene expression, insulin secretion, and expression of vitamin D receptors (VDRs). However, no reports about the role of RNF20/RNF40 in type 1 diabetes are known till now. The aim of this study was to clarify the role of RNF20/RNF40 in type 1 diabetes and explore the mechanism. METHODS: In this study, streptozotocin (STZ)-induced mice type 1 diabetes model was used. The protein expressions of genes were examined through Western blot analysis. Fasting blood glucose was detected through glucose meter. The plasma insulin was tested through the commercial kit. Hematoxylin and eosin staining was utilized to observe pathological changes of pancreatic tissues. Immunofluorescence assay was performed to evaluate the level of insulin. The levels of pro-inflammatory cytokines in serum were assessed by enzyme-linked-immunosorbent serologic assay. The cell apoptosis was measured through terminal deoxynucleotidyl transferase dUTP nick end labelling assay. RESULTS: STZ was used to stimulate mice model for type 1 diabetes. At first, both RNF20 and RNF40 expressions were down-regulated in STZ-mediated type 1 diabetes. Additionally, RNF20/RNF40 improved hyperglycemia in STZ-stimulated mice. Moreover, RNF20/RNF40 relieved pancreatic tissue injury in STZ-induced mice. Further experiments found that RNF20/RNF40 rescued the strengthened inflammation mediated by STZ treatment. The cell apoptosis was enhanced in the pancreatic tissues of STZ-triggered mice, but this effect was weakened by overexpression of RNF20/RNF40. Besides, the VDR expression was positively regulated by RNF20/RNF40. Finally, VDR knockdown reversed improved hyperglycemia, inflammation, and cell apoptosis stimulated by overexpression of RNF20/RNF40. CONCLUSION: Our findings proved that RNF20/RNF40 activated VDR to relieve type 1 diabetes. This work might highlight the functioning of RNF20/RNF40 in the treatment of type 1 diabetes.

Retraction.

The article "The circRNA-MYLK plays oncogenic roles in the Hep-2 cell line by sponging microRNA-145-5p" by Yao Chen, Yanmei Wang, Congcong Li, Xuechang Li, Tiejun Yuan, Shuqin Yang and Xiaoyan Sun, published in Gen. Physiol. Biophys. 39(3), 2020, pp. 229-237 (doi: 10.4149/gpb_2019060) has been retracted by agreement between the author(s) and journal's Editor in Chief, Prof. Dr. Lubica Lacinova, and AEPresss, s.r.o.. The corresponding author Xiaoyan Sun asked to retract this manuscript as there were some substantial problems in it, which needed more time and research to solve and can more fully re-examine and revise his research results.The authors were not available for a final confirmation of the retraction.