Prediction of Human Microbe-Drug Association based on Layer Attention Graph Convolutional Network.

Human microbes are closely associated with a variety of complex diseases and have emerged as drug targets. Identification of microbe-related drugs is becoming a key issue in drug development and precision medicine. It can also provide guidance for solving the increasingly serious problem of drug resistance enhancement in viruses. METHODS: In this paper, we have proposed a novel model of layer attention graph convolutional network for microbe-drug association prediction. First, multiple biological data have been integrated into a heterogeneous network. Then, the heterogeneous network has been incorporated into a graph convolutional network to determine the embedded microbe and drug. Finally, the microbe-drug association scores have been obtained by decoding the embedding of microbe and drug based on the layer attention mechanism. RESULTS: To evaluate the performance of our proposed model, leave-one-out crossvalidation (LOOCV) and 5-fold cross-validation have been implemented on the two datasets of aBiofilm and MDAD. As a result, based on the aBiofilm dataset, our proposed model has attained areas under the curve (AUC) of 0.9178 and 0.9022 on global LOOCV and local LOOCV, respectively. Based on aBiofilm dataset, the proposed model has attained an AUC value of 0.9018 and 0.8902 on global LOOCV and local LOOCV, respectively. In addition, the average AUC and standard deviation of the proposed model for 5- fold cross-validation on the aBiofilm and MDAD datasets were 0.9141±6.8556e-04 and 0.8982±7.5868e-04, respectively. Also, two kinds of case studies have been further conducted to evaluate the proposed models. CONCLUSION: Traditional methods for microbe-drug association prediction are timeconsuming and laborious. Therefore, the computational model proposed was used to predict new microbe-drug associations. Several evaluation results have shown the proposed model to achieve satisfactory results and that it can play a role in drug development and precision medicine.

Clinical and neuroimaging features in neurological Wilson's disease with claustrum lesions.

According to early research, the incidence of claustrum lesions in patients with neurological Wilson's disease (WD) was inconsistent, ranging from 1.8 to 75% on magnetic resonance imaging (MRI). Our study aims to explore the incidence, clinical presentation features, iconography features, and possible pathological mechanisms in WD patients with claustrum lesions on magnetic resonance imaging (MRI), to characterize the clinical, and brain imaging findings and possible pathological mechanisms in the patients with WD. Retrospective cases meeting the inclusion criteria were studied for analyzing MRI characteristics and associated physicochemical examination data in neurological WD patients with claustrum lesions. 443 (66.3%) with brain MRI abnormalities were screened from 668 WD patients. The three (0.7%) patients with the claustrum lesions characteristics on MRI images were: (a) "bright claustrum" in T2-weighted and FLAIR sequences, (b) bilateral symmetrical, (c) non-isolated lesions, (d) occurred only in severe neurological manifestations. The claustrum lesions are not common in neurological WD and mainly appear in cases with severe neurological symptoms. On MRI, the "bright claustrum" signs may be a radiographic marker of neuroinflammation, the features of the lesions showed bilateral symmetry, and hyperintensity signals on T2-weighted, FLAIR, and DWI.

Radiopaque and Biocompatible PMMA Bone Cement Triggered by Nano Tantalum Carbide and Its Osteogenic Performance.

Poly(methyl methacrylate) (PMMA) bone cements have been widely used in orthopedics; thanks to their excellent mechanical properties, biocompatibility, and chemical stability. Barium sulfate and zirconia are usually added into PMMA bone cement to enhance the X-ray radiopacity, while the mechanical strength, radiopacity, and biocompatibility are not well improved. In this study, an insoluble and corrosion-resistant ceramic, tantalum carbide (TaC), was added into the PMMA bone cement as radiopacifies, significantly improving the mechanical, radiopaque, biocompatibility, and osteogenic performance of bone cement. The TaC-PMMA bone cement with varied TaC contents exhibits compressive strength over 100 MPa, higher than that of the commercial 30% BaSO4-PMMA bone cement. Intriguingly, when the TaC content reaches 20%, the radiopacity is equivalent to the commercial bone cement with 30% of BaSO4 in PMMA. The cytotoxicity and osteogenic performance indicate that the incorporation of TaC not only enhances the osteogenic properties of PMMA but also does not reduce cell viability. This study suggests that TaC could be a superior and multifunctional radio-pacifier for PMMA bone cement, offering a promising avenue for improving patient outcomes in orthopedic applications.

FUNDC1 alleviates doxorubicin-induced cardiotoxicity by restoring mitochondrial-endoplasmic reticulum contacts and blocked autophagic flux.

Rationale: Autophagy dysregulation is known to be a mechanism of doxorubicin (DOX)-induced cardiotoxicity (DIC). Mitochondrial-Endoplasmic Reticulum Contacts (MERCs) are where autophagy initiates and autophagosomes form. However, the role of MERCs in autophagy dysregulation in DIC remains elusive. FUNDC1 is a tethering protein of MERCs. We aim to investigate the effect of DOX on MERCs in cardiomyocytes and explore whether it is involved in the dysregulated autophagy in DIC. Methods: We employed confocal microscopy and transmission electron microscopy to assess MERCs structure. Autophagic flux was analyzed using the mCherry-EGFP-LC3B fluorescence assay and western blotting for LC3BII. Mitophagy was studied through the mCherry-EGFP-FIS1 fluorescence assay and colocalization analysis between LC3B and mitochondria. A total dose of 18 mg/kg of doxorubicin was administrated in mice to construct a DIC model in vivo. Additionally, we used adeno-associated virus (AAV) to cardiac-specifically overexpress FUNDC1. Cardiac function and remodeling were evaluated by echocardiography and Masson's trichrome staining, respectively. Results: DOX blocked autophagic flux by inhibiting autophagosome biogenesis, which could be attributed to the downregulation of FUNDC1 and disruption of MERCs structures. FUNDC1 overexpression restored the blocked autophagosome biogenesis by maintaining MERCs structure and facilitating ATG5-ATG12/ATG16L1 complex formation without altering mitophagy. Furthermore, FUNDC1 alleviated DOX-induced oxidative stress and cardiomyocytes deaths in an autophagy-dependent manner. Notably, cardiac-specific overexpression of FUNDC1 protected DOX-treated mice against adverse cardiac remodeling and improved cardiac function. Conclusions: In summary, our study identified that FUNDC1-meditated MERCs exerted a cardioprotective effect against DIC by restoring the blocked autophagosome biogenesis. Importantly, this research reveals a novel role of FUNDC1 in enhancing macroautophagy via restoring MERCs structure and autophagosome biogenesis in the DIC model, beyond its previously known regulatory role as an mitophagy receptor.

Detection of pathogens from venous or arterial blood of patients with left-sided infective endocarditis by metagenomic next-generation sequencing: A prospective study.

BACKGROUND: Infective endocarditis is a life-threatening uncommon infectious disease, and we aimed to explore the clinical utility of venous or arterial blood-based metagenomic next-generation sequencing (mNGS) approaches to diagnose left-sided infective endocarditis (LSIE). METHODS: We prospectively studied 79 LSIE patients who received valvular surgery in our hospital. Results of blood culture, valve culture, venous blood-based mNGS, arterial blood-based mNGS, venous blood-based mNGS plus blood culture, and arterial blood-based mNGS plus blood culture were evaluated and compared. RESULTS: Both venous blood- and arterial blood-based mNGS methods displayed significantly higher positive detection rates than blood culture and valve culture (43.0 %, 49.4 % vs. 32.9 %, 19.0 %; P < 0.001). Strikingly, when combining blood-based mNGS and blood culture, the positive rate could be further improved to more than 60 %. Moreover, we found mNGS LSIE detection was closely associated with preoperative leukocyte (P = 0.027), neutrophil value (P = 0.018), vegetation ≥ 14 mm (P = 0.043), and vegetations in aortic valve (P = 0.048). In addition, we discovered that blood-based mNGS had a superir capacity over blood culture to detect gram-negative bacteria, fungi, Bartonella Quintana, and mixed infections than blood culture. CONCLUSION: This study indicates that venous blood- and arterial blood-based mNGS displayed high positive rate in the rapid detection of pathogens in high-risk LSIE patients.

Protective mechanisms of quercetin in neonatal rat brain injury induced by hypoxic-ischemic brain damage (HIBD).

Neonatal hypoxic-ischemic brain damage (HIBD) is a leading cause of infant mortality worldwide. This study explored whether quercetin (Que) exerts neuroprotective effects in a rat model of HIBD. A total of 36 seven-day-old Sprague-Dawley rats were divided into control, Que, HI, and HI + Que groups. The Rice method was used to establish HIBD in HI and HI + Que rats, which were treated with hypoxia (oxygen concentration of 8%) for 2 h after ligation of the left common carotid artery. The rats in the HI + Que group were intraperitoneally injected with Que (30 mg/kg) 1 h before hypoxia, and the rats in the Que group were only injected with the same amount of Que. Brain tissues were harvested 24 h postoperation and assessed by hematoxylin and eosin staining, 2,3,5-triphenyltetrazolium chloride staining, and terminal deoxynucleotidyl transferase dUTP nick-end labeling assay; relative gene and protein levels were evaluated by RT-qPCR, IHC, or western blot (WB) assay. Brain tissue morphologies were characterized by transmission electron microscopy (TEM); LC3B protein levels were assessed by immunofluorescence staining. Escape latencies and platform crossing times were significantly improved (p < .05) in HI + Que groups; infarct volume significantly decreased (p < .001), whereas the numbers of autophagic bodies and apoptotic cells increased and decreased, respectively. Meanwhile, NLRX1, ATG7, and Beclin1 expressions were significantly upregulated, and mTOR and TIM23 expressions, LC3B protein level, and LC 3II/LC 3I ratio were significantly downregulated. Que exerted neuroprotective effects in a rat model of HIBD by regulating NLRX1 and autophagy.

Does the weekend effect exist for acute type A aortic dissection?-a retrospective case-control study.

Background: The weekend effect refers to the mortality difference for patients admitted/operated on weekends compared to those on weekdays. The study aimed to provide new evidence on the impact of the weekend effect on acute type A aortic dissection (ATAAD). Methods: Primary endpoints were operative mortality, stroke, paraplegia, and continuous renal replacement therapy (CRRT). A meta-analysis of current evidence on the weekend effect was first conducted. Analyses based on single-center data (retrospective, case-control study) were further performed. Results: A total of 18,462 individuals were included in the meta-analysis. The pooled results showed that mortality was not significantly higher for ATAAD on weekends compared to that on weekdays [odds ratio (OR): 1.16, 95% CI: 0.94-1.43]. The single-center cohort included 479 patients, which also showed no significant differences in primary and secondary outcomes between the two groups. The unadjusted OR for weekend group over weekday group was 0.90 (95% CI: 0.40-1.86, P=0.777). The adjusted OR for weekend group was 0.94 (95% CI: 0.41-2.02, P=0.880) controlling for significant preoperative factors, and 0.75 (95% CI: 0.30-1.74, P=0.24) controlling for significant preoperative and operative factors altogether. In PSM matched cohort, the operative mortality was still comparable between the weekend group [10 (7.2%)] and weekday group [9 (6.5%)] (P=1.000). No significant survival difference was observed between the two groups (P=0.970). Conclusions: The weekend effect was not found to be applicable to ATAAD. However, clinicians should be cautious of the weekend effect as it is disease-specific and may vary across healthcare systems.

Diffusion tensor imaging analysis of the corpus callosum in children with high-risk autism spectrum disorder.

BACKGROUND: Autism spectrum disorder (ASD) is a severe neurodevelopmental disorder that begins in early infancy and childhood and is characterized by impaired social communication and repetitive stereotyped behaviors. OBJECTIVE: The purpose of this study was to examine the development of the corpus callosum and its relationship to neurobehavior in young children with high-risk (HR) ASD using magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). METHODS: Twenty-one children with HR-ASD who visited Anhui Children's Hospital between January 2020 and December 2021 were selected as the study group, while 19 matched children with normal development during the same time were adopted as the control group. Cranial MRI+DTI were performed for all of the enrolled children and fractional anisotropy (FA) measurements were taken in each region of the corpus callosum. RESULTS: The FA values in all regions of the corpus callosum were higher in the study group than in the control group (0.417 ± 0.016 vs. 0.412 ± 0.02 in the corpus callosum knee, 0.439 ± 0.018 vs. 0.431 ± 0.023 in the corpus callosum body, and 0.446 ± 0.017 vs. 0.434 ± 0.019 in the splenium of corpus callosum [SCC]), where the difference in the FA in the SCC was statistically significant between the two groups (P< 0.05). There was a positive correlation between the FA in the corpus callosum knee and speech scores in the neuropsychological development of the study group (P< 0.05). CONCLUSION: There was a premature development tendency for corpus callosum myelination in young children with HR-ASD, and the developmental tendency was visible in the SCC. There was also a positive relationship between corpus callosum knee development and language function.

[Efficacy and mechanism of scalp acupuncture for spastic cerebral palsy].

OBJECTIVE: To observe the clinical efficacy of scalp acupuncture for spastic cerebral palsy (CP), and to explore its possible mechanism based on brain white matter fiber bundles, nerve growth related proteins and inflammatory cytokines. METHODS: A total of 90 children with spastic CP were randomly divided into a scalp acupuncture group and a sham scalp acupuncture group, 45 cases in each group. The children in the two groups were treated with conventional comprehensive rehabilitation treatment. The children in the scalp acupuncture group were treated with scalp acupuncture at the parietal temporal anterior oblique line, parietal temporal posterior oblique line on the affected side, and parietal midline. The children in the sham scalp acupuncture group were treated with scalp acupuncture at 1 cun next to the above point lines. The needles were kept for 30 min, once a day, 5 days a week, for 12 weeks. Before and after treatment, the diffusion tensor imaging (DTI) indexes of magnetic resonance (FA values of corticospinal tract [CST], anterior limb of internal capsule [ICAL], posterior limb of internal capsule [ICPL], genu of internal capsule [ICGL], genu of corpus callosum [GCC], body of corpus callosum [BCC] and splenium of corpus callosum [SCC]), serum levels of nerve growth related proteins (neuron-specific enolase [NSE], glial fibrillary acidic protein [GFAP], myelin basic protein [MBP], ubiquitin carboxy terminal hydrolase-L1 [UCH-L1]) and inflammatory cytokines (interleukin 33 [IL-33], tumor necrosis factor α [TNF-α]), cerebral hemodynamic indexes (mean blood flow velocity [Vm], systolic peak flow velocity [Vs] and resistance index [RI], pulsatility index [PI] of cerebral artery), surface electromyography (SEMG) signal indexes (root mean square [RMS] values of rectus femoris, hamstring muscles, gastrocnemius muscles, tibialis anterior muscles), gross motor function measure-88 (GMFM-88) score, modified Ashworth scale (MAS) score, ability of daily living (ADL) score were observed in the two groups. The clinical effect of the two groups was compared. RESULTS: After treatment, the FA value of each fiber bundle, Vm, Vs, GMFM-88 scores and ADL scores in the two groups were higher than those before treatment (P<0.05), and the above indexes in the scalp acupuncture group were higher than those in the sham scalp acupuncture group (P<0.05). After treatment, the serum levels of NSE, GFAP, MBP, UCH-L1, IL-33, TNF-α as well as RI, PI, MAS scores and RMS values of each muscle were lower than those before treatment (P<0.05), and the above indexes in the scalp acupuncture group were lower than those in the sham scalp acupuncture group (P<0.05). The total effective rate was 95.6% (43/45) in the scalp acupuncture group, which was higher than 82.2% (37/45) in the sham scalp acupuncture group (P<0.05). CONCLUSION: Scalp acupuncture could effectively treat spastic CP, improve the cerebral hemodynamics and gross motor function, reduce muscle tension and spasticity, and improve the ability of daily life. The mechanism may be related to repairing the white matter fiber bundles and regulating the levels of nerve growth related proteins and inflammatory cytokines.

Exendin-4 alleviates myocardial ischemia reperfusion injury by enhancing autophagy through promoting nuclear translocation of TFEB.

Ischemia-reperfusion (I/R) injury (IRI) is a common clinical consequence of myocardial infarction. Exendin-4 is a glucagon-like peptide-1 (GLP-1) analog that has been demonstrated to alleviate myocardial IRI. Autophagy, a lysosomal pathway balancing cell survival and cell death, is engaged in myocardial IRI. However, whether exendin-4 exerts a protective effect on myocardial IRI by modulating autophagy remains elusive. Herein, we investigated the effect of exendin-4 on autophagic flux and explored the underlying molecular mechanisms. Our data revealed that the autophagic flux was blocked in the human ventricular cardiomyocyte cell lines (AC16) subjected to oxygen glucose deprivation/reoxygenation (OGD/R) in vitro. Exendin-4 pre-treatment markedly restored the blocked autophagic flux induced by OGD/R through promoting nuclear translocation of TFEB and transcription of genes involving autophagy initiation, the effect of which was reversed by TFEB knockdown. The restoration of autophagic flux contributed to multiple beneficial effects of exendin-4 in cardiomyocytes, including reduction of oxidative stress, preservation of mitochondrial network as well as inhibition of cytochrome c leakage from mitochondrial permeability transition pore (MPTP) and the resulting apoptosis. Moreover, the administration of exendin-4 reduced infarct size and preserved cardiac function through its anti-apoptosis and antioxidative effects in vivo. These results shed some light on understanding the novel mechanism of exendin-4 as a protective agent against myocardial IRI.

Right axillary artery cannulation in acute type A aortic dissection with involvement of the right axillary artery.

OBJECTIVE: The right axillary artery is currently recommended for arterial cannulation in surgery for acute type A aortic dissection. However, the feasibility of cannulation on a dissected right axillary artery remains undetermined. The objective was to examine the feasibility of cannulation on a dissected right axillary artery. METHODS: From 2016 to 2020, 835 patients who underwent acute type A aortic dissection repair were included in this study. Cannulation strategy and perioperative outcomes of patients who did and did not have right axillary artery dissection were compared. Propensity score matching and logistic regression were applied. RESULTS: A total of 124 patients had right axillary artery dissection, and 711 patients did not. Direct right axillary artery cannulation was used for cardiopulmonary bypass in the majority of patients, but with a lower rate in patients with right axillary artery dissection (n = 88 [71.0%] vs n = 579 [81.4%], P = .007). Right axillary artery cannulation failure (n = 3 [2.4%] vs n = 5 [0.7%], P = .102) and related complications (n = 1 [0.8%] vs n = 6 [0.8%], P = 1.000) were rare in both groups. In-hospital mortality (n = 18 [14.5%] vs n = 59 [8.3%], P = .027) and stroke (n = 14 [11.3%] vs n = 42 [5.9%], P = .027) were significantly higher in the right axillary artery dissection group, but after propensity score matching, in-hospital outcomes were comparable. Right axillary artery dissection was not a risk factor for mortality, stroke, right axillary artery cannulation not performed, or right axillary artery cannulation failure. CONCLUSIONS: Direct right axillary artery cannulation is feasible for most patients with acute type A aortic dissection with right axillary artery dissection.

Surgical treatment strategies for patients with type A aortic dissection involving arch anomalies.

Objective: The aim of the study was to investigate surgical modalities and outcomes in patients with type A aortic dissection involving arch anomalies. Method: Patients with type A aortic dissection who underwent surgical treatment at our center between January 2017 and 31 December 2020 were selected for this retrospective analysis. Data including computed tomography (CT), surgical records, and cardiopulmonary bypass records were analyzed. Perioperatively survived patients were followed up, and long-term mortality and aortic re-interventions were recorded. Result: A total of 81 patients with arch anomalies were included, 35 with "bovine" anomalies, 23 with an aberrant right subclavian artery, 22 with an isolated left vertebral artery, and one with a right-sided arch + aberrant left subclavian artery. The strategies of arch management and cannulation differed according to the anatomic variation of the aortic arch. In total, seven patients (9%) died after surgery. Patients with "bovine" anomalies had a higher perioperative mortality rate (14%) and incidence of neurological complications (16%). Overall, four patients died during the follow-up period, with a 6-year survival rate of 94.6% (70/74). A total of four patients underwent aortic re-intervention during the follow-up period; before the re-intervention, three received the en bloc technique (13.6% 3/22) and one received hybrid therapy (11.1% 1/9). Conclusion: With complete preservation and reconstruction of the supra-arch vessels, patients with type A aortic dissection combining arch anomalies can achieve a favorable perioperative prognostic outcome. Patients who received the en bloc technique are more likely to require aortic re-intervention than patients who underwent total arch replacement with a four-branched graft vessel. Cannulation strategies should be tailored according to the variation of anatomy, but routine cannulation with the right axillary artery can still be performed in most patients with arch anomalies, even for patients with an aberrant right subclavian artery.

Chinese contribution to NEJM, Lancet, JAMA, and BMJ from 2011 to 2020: a 10-year bibliometric study.

Background: New England Journal of Medicine (NEJM), Lancet, Journal of the American Medical Association (JAMA), and British Medical Journal (BMJ) are collectively known as "the Top Four Medical Journals (TFMJ)" in China. Through the analysis of Chinese scholars' publications in the TFMJ in the recent 10 years, this study aimed to clarify the current situation of high-quality medical research conducted by Chinese scholars and institutions. Methods: Data were retrieved and downloaded manually from PubMed (2011-2020). Information on the publication year, journal, author, affiliation, and citation, etc. were extracted and analyzed using R software. Results: A total of 761 articles were involved in the final analysis. The number of articles published by Chinese scholars in the TFMJ was 135/29,942 (0.45%) in BMJ, 124/14,033 (0.88%) in JAMA, 314/16,117 (1.94%) in Lancet, and 188/15,242 (1.23%) in NEJM (P<0.001). Besides, the letter was the main research type, which was up to 44.54%, and the original research only accounted for 17.47%. The most popular subspecialty and subject were infectious diseases and COVID-19, respectively. The most productive researcher was Chen Wang, and Bin Cao was the most cited Chinese scholar. The most productive institute was Chinese Academy of Medical Sciences and Peking Union Medical College. The most cited study was "Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China". Conclusions: The presence of Chinese scholars in the TFMJ has grown, but there is still much room to improve. A Matthew effect in China's high-level scientific research was demonstrated.

[Relative molecular mass distribution and monosaccharide composition of polysaccharides in Polygonatum kingianum var.grandifolium].

Polygonatum kingianum var.grandifolium, different from most Polygonatum species in biological characteristics, sprouts and blooms in spring and autumn, respectively, and it is evergreen in winter.It is difficult to learn from the patterns of other Polygonatum plants because the chemical composition in P.kingianum var.grandifolium changes with phenology, which consequently restricts the production of high-quality medicinal and eatable substances.Samples of P.kingianum var.grandifolium in different months and ages collected from Xiushan, Chongqing were analyzed for polysaccharide content, polysaccharide relative molecular mass, and mono-saccharide composition by anthrone-sulfuric acid colorimetric assay, high-performance gel-permeation chromatography, and trimethylsilane(TMS) derivatization prior to GC-MS.The results showed that the polysaccharide content and composition in the rhizome of P.kingianum var.grandifolium were closely related to the growth period.New shoot sprouting promoted the accumulation of polysaccharides, and flowering and fruiting consumed polysaccharides.The highest polysaccharide content was found in April, reaching 134.04 mg·g~(-1).Polysaccharides in P.kingianum var.grandifolium were divided into five fractions according to the weight-average M_W, i.e., P1(2.02×10~7), P2(5.09×10~6), P3(1.37×10~6), P4(4.73×10~5), and P5(5.11×10~3), and P5 had the highest content.In terms of monosaccharide composition, polysaccharides were mainly composed of fructose, glucose, galactose, mannose, xylose, and arabinose with the average molar ratio of 1.31∶1.00∶0.90∶0.53∶0.22∶0.21.The results of the study provide a scientific basis for the precise harvesting and resource utilization of P.kingianum var.grandifolium.

Potential Threats to Human Health from Eurasian Avian-Like Swine Influenza A(H1N1) Virus and Its Reassortants.

During 2018-2020, we isolated 32 Eurasian avian-like swine influenza A(H1N1) viruses and their reassortant viruses from pigs in China. Genomic testing identified a novel reassortant H3N1 virus, which emerged in late 2020. Derived from G4 Eurasian H1N1 and H3N2 swine influenza viruses. This virus poses a risk for zoonotic infection.

cGAS Restricts PRRSV Replication by Sensing the mtDNA to Increase the cGAMP Activity.

Porcine reproductive and respiratory syndrome virus (PRRSV) is an RNA virus that causes great economic losses globally to the swine industry. Innate immune RNA receptors mainly sense it during infection. As a DNA sensor, cyclic GMP-AMP synthase (cGAS) plays an important role in sensing cytosolic DNA and activating innate immunity to induce IFN-I and establish an antiviral cellular state. In contrast, the role of innate immune DNA sensors during PRRSV infection has not been elucidated. In this study, we found that cGAS facilitates the production of IFN-ß during PRRSV infection. Western blot and virus titer assays suggested that cGAS overexpression suppressed the replication of multiple PRRSV strains, while knockout of cGAS increased viral titer and nucleocapsid protein expression. Besides, our results indicated that the mitochondria were damaged during PRRSV infection and leaked mitochondrial DNA (mtDNA) into the cytoplasm. The mtDNA in the cytoplasm co-localizes with the cGAS, and the cGAMP activity was increased when the cGAS was overexpressed during PRRSV infection. Furthermore, the cGAMP also possesses an anti-PRRSV effect. These results indicate for the first time that cGAS restricts PRRSV replication by sensing the mtDNA in the cytoplasm to increase cGAMP activity, which not only explains the molecular mechanism by which cGAS inhibits PRRSV replication but also provides research ideas for studying the role of the cGAS-STING signaling pathway in the process of RNA virus infection.

Expression of SH3 and Multiple Ankyrin Repeat Domains Protein 3 in Mouse Retina.

Synapse-associated gene mutations of SH3 and multiple ankyrin repeat domains protein 3 (SHANK3) may lead to autism spectrum disorder (ASD). In some ASD cases, patients may also have vision disorders. However, the effects of SHANK3 in the retina are barely mentioned in the literature. In this study, we used wild-type mice to systematically map the distribution of SHANK3 expression in entire mouse retinas. Using Western blot analysis and immunofluorescence double labeling, we identified a large number of prominent cells expressing high levels of SHANK3 in the inner retina, in particular, the ganglion cell layer (GCL) and inner nucleus layer. The inner plexiform layer and outer nucleus layer were also exhibited positive SHANK3 signals. In the inner layer, GABAergic amacrine cells (ACs) labeled by glutamate decarboxylase were colocalized with SHANK3-positive cells. Dopaminergic ACs (labeled by tyrosine hydroxylase) and cholinergic ACs (labeled by choline acetyltransferase) were also found to contain SHANK3-positive signals. Additionally, most GCs (labeled by Brn3a) were also found to be SHANK3 positive. In the outer retina, bipolar cells (labeled by homeobox protein ChX10) and horizontal cells (labeled by calbindin) were SHANK3 positive. In the outer nucleus layers, the somata of blue cones (labeled by S-opsin) were weekly co-labeled with SHANK3. The inner segments of blue cones and the outer segments of red/green cones (labeled by L/M-opsin) were partially colocalized with SHANK3 and the outer segments of rods (labeled by Rho4D2) were partially SHANK3 positive too. Moreover, SHANK3-positive labeling was also observed in Müller cells (labeled by cellular retinaldehyde-binding protein). These wide expression patterns indicate that SHANK3 may play an important role in the visual signaling pathway.

Aortic Balloon Occlusion Technique Does Not Improve Peri-Operative Outcomes for Acute Type A Acute Aortic Dissection Patients With Lower Body Malperfusion.

Background: The management of malperfusion is vital to improve the outcomes of surgery for acute type A acute aortic dissection (ATAAD). Open arch repair under hypothermic circulatory arrest with selective antegrade cerebral perfusion (HCA/sACP) is safe and efficient but associated with inevitable hypothermia and ischemia-reperfusion injury. The aortic balloon occlusion (ABO) technique is shown to be organ protective by allowing higher temperature and shorter circulatory arrest time. In this study, we aimed to evaluate the safety and efficacy of this new technique for ATAAD patients with lower body malperfusion. Methods: Between January 2013 and November 2020, 355 ATAAD patients with lower body malperfusion who underwent arch repair in our institute were enrolled. The patients were divided into 2 groups: ABO group (n = 85) and HCA/sACP group (n = 271). Propensity score matching was performed to correct baseline differences. Results: Using the propensity score matching, 85 pairs were generated. Circulatory arrest time was significantly lower in the ABO group compared with the HCA/sACP group (median, 8 vs. 22 min; p < 0.001). The incidence of in-hospital mortality (10.6 vs. 12.9%; p = 0.812), stroke (7.1 vs. 7.1%; p = 1.000), dialysis (25.9 vs. 32.9%; p = 0.183), hepatic dysfunction (52.9 vs. 57.6%; p = 0.537), tracheostomy (4.7 vs. 2.4%; p = 0.682), paraplegia (1.2 vs. 4.7%; p = 0.368) were comparable between ABO and HCA/sACP groups. Other outcomes and major adverse events were comparable. The multivariable logistic analysis did not recognize ABO technique protective against any major adverse outcomes. Conclusions: For ATAAD patients with lower body malperfusion, the ABO technique allows the performance of arch repair with frozen elephant trunk (FET) under higher temperature and shorter circulatory arrest time. However, ABO technique did not improve perioperative outcomes. Future studies are warranted to evaluate the efficacy of this technique.

Coronary Malperfusion Secondary to Acute Type A Aortic Dissection: Surgical Management Based on a Modified Neri Classification.

Background: Coronary malperfusion (CM) secondary to acute type A aortic dissection (ATAAD) is considered rare but has a high mortality rate. This study examined the incidence, management, and outcomes of patients with CM secondary to ATAAD and proposes a modified Neri classification. Methods: Between 2015 and 2020, out of 1018 patients who underwent surgical repair for ATAAD, 137 presented with CM, including 68 (49.6%), 43 (31.3%), and 15 (10.9%) with Neri types A, B, and C, respectively, and 11 (8.0%) with coronary orifice intimal tear (COIT), which we consider a novel category. Results: The occurrence rate of CM was 13.4%. CM was associated with higher in-hospital mortality (18.2% vs. 7.8%, p < 0.001). For Neri type A (98.5%) and most type B lesions (72.1%), coronary repair was adequate. Coronary artery bypass grafting (CABG) was necessary for type B patients unsuited for repair (23.2%) and for all type C patients (100%). Repair of COIT was possible (45.5%). The in-hospital mortality rates differed significantly among the four lesion groups (p = 0.006). Conclusions: The occurrence of CM secondary to ATAAD may be more frequent than previously reported. Surgical management based on lesion classification achieved acceptable outcomes. Repair was adequate for Neri type A and most type B lesions. Other type B and type C lesions could be treated by CABG. Coronary orifice intimal tear is a unique set of lesions, for which orifice repair was also possible.