Prediction of neoplastic gallbladder polyps in patients with different age level based on preoperative ultrasound: a multi-center retrospective real-world study.

BACKGROUND: The prevalence of neoplastic polyps in gallbladder polyps (GPs) increases sharply with age and is associated with gallbladder carcinoma (GBC). This study aims to predict neoplastic polyps and provide appropriate treatment strategies based on preoperative ultrasound features in patients with different age level. METHODS: According to the age classification of WHO, 1523 patients with GPs who underwent cholecystectomy from January 2015 to December 2019 at 11 tertiary hospitals in China were divided into young adults group (n=622), middle-aged group (n=665) and elderly group (n=236). Linear scoring models were established based on independent risk variables screened by the Logistic regression model in different age groups. The area under ROC (AUC) to evaluate the predictive ability of linear scoring models, long- and short- diameter of GPs. RESULTS: Independent risk factors for neoplastic polyps included the number of polyps, polyp size (long diameter), and fundus in the young adults and elderly groups, while the number of polyps, polyp size (long diameter), and polyp size (short diameter) in the middle-aged groups. In different age groups, the AUCs of its linear scoring model were higher than the AUCs of the long- and short- diameter of GPs for differentiating neoplastic and non-neoplastic polyps (all P<0.05), and Hosmer-Lemeshow goodness of fit test showed that the prediction accuracy of the linear scoring models was higher than the long- and short- diameter of GPs (all P>0.05). CONCLUSION: The linear scoring models of the young adults, middle-aged and elderly groups can effectively distinguish neoplastic polyps from non-neoplastic polyps based on preoperative ultrasound features.

Exercise Improves Heart Function after Myocardial Infarction: The Merits of AMPK.

BACKGROUND: AMPK is considered an important protein signaling pathway that has been shown to exert prominent cardioprotective effects on the pathophysiological mechanisms of numerous diseases. Following myocardial infarction, severe impairment of cardiac function occurs, leading to complications such as heart failure and arrhythmia. Therefore, protecting the heart and improving cardiac function are important therapeutic goals after myocardial infarction. Currently, there is substantial ongoing research on exercise-centered rehabilitation training, positioning exercise training as a significant nonpharmacological approach for preventing and treating numerous cardiovascular diseases. OBJECTIVE: Previous studies have reported that exercise can activate AMPK phosphorylation and upregulate the AMPK signaling pathway to play a cardioprotective role in coronary artery disease, but the specific mechanism involved remains to be elucidated. CONCLUSION: This review discusses the role and mechanism of the exercise-mediated AMPK pathway in improving postinfarction cardiac function through existing studies and describes the mechanism of exercise-induced myocardial repair of AMPK from multiple perspectives to formulate a reasonable and optimal exercise rehabilitation program for the prevention and treatment of myocardial infarction patients in the clinic.

Diagnosis and cardiac transplantation of a Carney syndrome-induced cardiac myxoma combined with dilated cardiomyopathy: a case report.

BACKGROUND: Carney syndrome is an uncommon autosomal disorder closely linked to mutations in the PRKAR1A gene. Skin lesions are the most pronounced feature of Carney syndrome, affecting over 80% of individuals with this condition. This syndrome is characterized by a triad of myxomas, skin pigmentation, and endocrine hyperfunction, featuring multiple endocrine neoplasms with skin and cardiac involvement. Dilated cardiomyopathy, a primary cardiomyopathy, is defined as the dilation and impaired systolic function of the left or both ventricles. Its clinical presentation varies from being asymptomatic to heart failure or sudden cardiac death, making it a leading global cause of heart failure. Currently, Dilated cardiomyopathy has an estimated prevalence of 1/2500-1/250 individuals, predominantly affecting those aged 30-40 years, with a male-to-female ratio of 3:1. This case report describes a heart failure patient with cardiac myxoma caused by Carney syndrome combined with dilated cardiomyopathy. The patient was successfully treated for heart failure by heart transplantation. CASE PRESENTATION: Herein, we report a case of heart failure due to Carney syndrome that resulted in cardiac myxoma combined with dilated cardiomyopathy. A 35-year-old male was admitted to the hospital three years ago because of sudden chest tightness and shortness of breath. Echocardiography indicated myxoma, and a combination of genetic screening and physical examination confirmed Carney syndrome with cardiac myxoma. Following symptomatic management, he was discharged. Surgical interventions were not considered at the time. However, the patient's chest tightness and shortness of breath symptoms worsened, and he returned to the hospital. A New York Heart Association grade IV heart function was confirmed, and echocardiography indicated the presence of dilated cardiomyopathy accompanied by cardiac myxoma. Ultimately, the patient's heart failure was successfully treated with heart transplantation. CONCLUSIONS: Cardiac myxoma caused by Carney syndrome combined with heart failure caused by dilated cardiomyopathy can be resolved by heart transplantation.

Radiomic features of gray matter in never-treated first-episode schizophrenia.

Alterations of radiomic features (RFs) in gray matter are observed in schizophrenia, of which the results may be limited by small study samples and confounding effects of drug therapies. We tested for RFs alterations of gray matter in never-treated first-episode schizophrenia (NT-FES) patients and examined their associations with known gene expression profiles. RFs were examined in the first sample with 197 NT-FES and 178 healthy controls (HCs) and validated in the second independent sample (90 NT-FES and 74 HCs). One-year follow-up data were available from 87 patients to determine whether RFs were associated with treatment outcomes. Associations between identified RFs in NT-FES and gene expression profiles were evaluated. NT-FES exhibited alterations of 30 RFs, with the greatest involvement of microstructural heterogeneity followed by measures of brain region shape. The identified RFs were mainly located in the central executive network, frontal-temporal network, and limbic system. Two baseline RFs with the involvement of microstructural heterogeneity predicted treatment response with moderate accuracy (78% for the first sample, 70% for the second sample). Exploratory analyses indicated that RF alterations were spatially related to the expression of schizophrenia risk genes. In summary, the present findings link brain abnormalities in schizophrenia with molecular features and treatment response.

Increased methylglyoxal formation in plasma and tissues during a glucose tolerance test is derived from exogenous glucose.

The dicarbonyl compound methylglyoxal (MGO) is a major precursor in the formation of advanced glycation endproducts (AGEs). MGO and AGEs are increased in subjects with diabetes and are associated with fatal and nonfatal cardiovascular disease. Previously, we have shown that plasma MGO concentrations rapidly increase in the postprandial phase, with a higher increase in individuals with type 2 diabetes. In current study, we investigated whether postprandial MGO formation in plasma and tissues originates from exogenous glucose and whether the increased plasma MGO concentration leads to a fast formation of MGO-derived AGEs. We performed a stable isotope-labelled oral glucose tolerance test (OGTT) in 12 healthy males with universally labelled D(+)13C glucose. Analysis of plasma-labelled 13C3 MGO and glucose levels at 11 time-points during the OGTT revealed that the newly formed MGO during OGTT is completely derived from exogenous glucose. Moreover, a fast formation of protein-bound MGO-derived AGEs during the OGTT was observed. In accordance, ex-vivo incubation of MGO with plasma or albumin showed a rapid decrease in MGO and a fast increase in MGO-derived AGEs. In an intraperitoneal glucose tolerance test in C57BL/6J mice, we confirmed that the formation of postprandial MGO is derived from exogenous glucose in plasma and also showed in tissues that MGO is increased and this is also from exogenous glucose. Collectively, increased formation of MGO during a glucose tolerance test arises from exogenous glucose both in plasma and in tissues, and this leads to a fast formation of MGO-derived AGEs.

Deep learning-assisted diagnosis of benign and malignant parotid tumors based on contrast-enhanced CT: a multicenter study.

OBJECTIVES: To develop deep learning-assisted diagnosis models based on CT images to facilitate radiologists in differentiating benign and malignant parotid tumors. METHODS: Data from 573 patients with histopathologically confirmed parotid tumors from center 1 (training set: n = 269; internal-testing set: n = 116) and center 2 (external-testing set: n = 188) were retrospectively collected. Six deep learning models (MobileNet V3, ShuffleNet V2, Inception V3, DenseNet 121, ResNet 50, and VGG 19) based on arterial-phase CT images, and a baseline support vector machine (SVM) model integrating clinical-radiological features with handcrafted radiomics signatures were constructed. The performance of senior and junior radiologists with and without optimal model assistance was compared. The net reclassification index (NRI) and integrated discrimination improvement (IDI) were calculated to evaluate the clinical benefit of using the optimal model. RESULTS: MobileNet V3 had the best predictive performance, with sensitivity increases of 0.111 and 0.207 (p < 0.05) in the internal- and external-testing sets, respectively, relative to the SVM model. Clinical benefit and overall efficiency of junior radiologist were significantly improved with model assistance; for the internal- and external-testing sets, respectively, the AUCs improved by 0.128 and 0.102 (p < 0.05), the sensitivity improved by 0.194 and 0.120 (p < 0.05), the NRIs were 0.257 and 0.205 (p < 0.001), and the IDIs were 0.316 and 0.252 (p < 0.001). CONCLUSIONS: The developed deep learning models can assist radiologists in achieving higher diagnostic performance and hopefully provide more valuable information for clinical decision-making in patients with parotid tumors. KEY POINTS: • The developed deep learning models outperformed the traditional SVM model in predicting benign and malignant parotid tumors. • Junior radiologist can obtain greater clinical benefits with assistance from the optimal deep learning model. • The clinical decision-making process can be accelerated in patients with parotid tumors using the established deep learning model.

Development of a CT radiomics nomogram for preoperative prediction of Ki-67 index in pancreatic ductal adenocarcinoma: a two-center retrospective study.

OBJECTIVES: To develop and validate a contrast-enhanced computed tomography (CECT)-based radiomics nomogram for the preoperative evaluation of Ki-67 proliferation status in pancreatic ductal adenocarcinoma (PDAC). METHODS: In this two-center retrospective study, a total of 181 patients (95 in the training cohort; 42 in the testing cohort, and 44 in the external validation cohort) with PDAC who underwent CECT examination were included. Radiomic features were extracted from portal venous phase images. The radiomics signatures were built by using two feature-selecting methods (relief and recursive feature elimination) and four classifiers (support vector machine, naive Bayes, linear discriminant analysis (LDA), and logistic regression (LR)). Multivariate LR was used to build a clinical model and radiomics-clinical nomogram. The predictive performances of the models were evaluated using area under receiver operating characteristic curve (AUC) and decision curve analysis (DCA). RESULTS: The relief selector and LDA classifier using twelve features built the optimal radiomics signature, with AUCs of 0.948, 0.927, and 0.824 in the training, testing, and external validation cohorts, respectively. The radiomics-clinical nomogram incorporating the optimal radiomics signature, CT-reported lymph node status, and CA19-9 showed better predictive performance with AUCs of 0.976, 0.955, and 0.882 in the training, testing, and external validation cohorts, respectively. The calibration curve and DCA demonstrated goodness-of-fit and improved benefits in clinical practice of the nomogram. CONCLUSIONS: The radiomics-clinical nomogram is an effective and non-invasive computer-aided tool to predict the Ki-67 expression status in patients with PDAC. CLINICAL RELEVANCE STATEMENT: The radiomics-clinical nomogram is an effective and non-invasive computer-aided tool to predict the Ki-67 expression status in patients with pancreatic ductal adenocarcinoma. KEY POINTS: The radiomics analysis could be helpful to predict Ki-67 expression status in patients with pancreatic ductal adenocarcinoma (PDAC). The radiomics-clinical nomogram integrated with the radiomics signature, clinical data, and CT radiological features could significantly improve the differential diagnosis of Ki-67 expression status. The radiomics-clinical nomogram showed satisfactory calibration and net benefit for discriminating high and low Ki-67 expression status in PDAC.

A Bayesian network prediction model for gallbladder polyps with malignant potential based on preoperative ultrasound.

BACKGROUND: It is important to identify gallbladder polyps (GPs) with malignant potential and avoid unnecessary cholecystectomy by constructing prediction model. The aim of the study is to develop a Bayesian network (BN) prediction model for GPs with malignant potential in a long diameter of 8-15 mm based on preoperative ultrasound. METHODS: The independent risk factors for GPs with malignant potential were screened by χ2 test and Logistic regression model. Prediction model was established and validated using data from 1296 patients with GPs who underwent cholecystectomy from January 2015 to December 2019 at 11 tertiary hospitals in China. A BN model was established based on the independent risk variables. RESULTS: Independent risk factors for GPs with malignant potential included age, number of polyps, polyp size (long diameter), polyp size (short diameter), and fundus. The BN prediction model identified relationships between polyp size (long diameter) and three other variables [polyp size (short diameter), fundus and number of polyps]. Each variable was assigned scores under different status and the probabilities of GPs with malignant potential were classified as [0-0.2), [0.2-0.5), [0.5-0.8) and [0.8-1] according to the total points of [- 337, - 234], [- 197, - 145], [- 123, - 108], and [- 62,500], respectively. The AUC was 77.38% and 75.13%, and the model accuracy was 75.58% and 80.47% for the BN model in the training set and testing set, respectively. CONCLUSION: A BN prediction model was accurate and practical for predicting GPs with malignant potential patients in a long diameter of 8-15 mm undergoing cholecystectomy based on preoperative ultrasound.

A Bayesian network model to predict neoplastic risk for patients with gallbladder polyps larger than 10 mm based on preoperative ultrasound features.

BACKGROUND: Polyp size of 10 mm is insufficient to discriminate neoplastic and non-neoplastic risk in patients with gallbladder polyps (GPs). The aim of the study is to develop a Bayesian network (BN) prediction model to identify neoplastic polyps and create more precise criteria for surgical indications in patients with GPs lager than 10 mm based on preoperative ultrasound features. METHODS: A BN prediction model was established and validated based on the independent risk variables using data from 759 patients with GPs who underwent cholecystectomy from January 2015 to August 2022 at 11 tertiary hospitals in China. The area under receiver operating characteristic curves (AUCs) were used to evaluate the predictive ability of the BN model and current guidelines, and Delong test was used to compare the AUCs. RESULTS: The mean values of polyp cross-sectional area (CSA), long, and short diameter of neoplastic polyps were higher than those of non-neoplastic polyps (P < 0.0001). Independent neoplastic risk factors for GPs included single polyp, polyp CSA ≥ 85 mm 2, fundus with broad base, and medium echogenicity. The accuracy of the BN model established based on the above independent variables was 81.88% and 82.35% in the training and testing sets, respectively. Delong test also showed that the AUCs of the BN model was better than that of JSHBPS, ESGAR, US-reported, and CCBS in training and testing sets, respectively (P < 0.05). CONCLUSION: A Bayesian network model was accurate and practical for predicting neoplastic risk in patients with gallbladder polyps larger than 10 mm based on preoperative ultrasound features.

Preoperative prediction of the lymphovascular tumor thrombus of colorectal cancer with the iodine concentrations from dual-energy spectral CT.

BACKGROUND: The aim of this study was to explore application value of iodine concentration from dual-energy spectral computed tomography (DESCT) in preoperative prediction of lymphovascular tumor thrombus in patients with colorectal cancer (CRC). METHODS: We finally retrospectively analyzed 50 patients with CRC who underwent abdominal DESCT before receiving any preoperative treatment and underwent surgery to obtain pathological specimens which were stained with hematoxylin-eosin (HE) staining. According to the presence of cancer cell nests in blood vessels and lymphatic vessels, the subjects were divided into the positive group and negative group of lymphovascular tumor thrombus. Two radiologists independently measured the normalized iodine concentration (NIC) values, effective atomic number (Zeff) and CT values of virtual monochromatic images (VMIs) at 40-90 keV of the primary tumors in the arterial phase (AP) and venous phase (VP). Used SPSS 17.0 to calculate the receiver operating characteristic (ROC) curve to evaluate diagnostic value. RESULTS: The patients were divided into lymphovascular tumor thrombus positive group(n = 16) and negative group(n = 34). The values of NIC-AP and NIC-VP in the positive group were 0.17 ± 0.09, 0.51 ± 0.13, respectively. And those in the negative group were 0.15 ± 0.06, 0.43 ± 0.12, respectively. There was significant difference in NIC-VP value between the two groups (p = 0.039), but there was no significant difference in NIC-AP value (p = 0.423). The optimal threshold value of NIC-VP value for diagnosis of lymphovascular tumor thrombus was 0.364. The sensitivity was 68.8% and the specificity was 67.6%. CONCLUSIONS: The NIC-VP value of DESCT can be used to predict the presence or absence of the lymphovascular tumor thrombus in CRC patients before operation, which is helpful to select the best treatment scheme and evaluate its prognosis.

Pentoxifylline inhibits phosgene-induced lung injury via improving hypoxia.

Inhalation of high concentrations of phosgene often causes pulmonary edema, which obstructs the airway and causes tissue hypoxia. There is currently no specific antidote. This study was performed to investigate the effect behind pentoxifylline (PTX) treatment for phosgene-induced lung injury in rat models. Rats were exposed to phosgene. The protein levels of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), and occludin proteins in lung tissue were determined. The effect of both prophylactic and therapeutic administration of PTX (50 mg/kg and 100 mg/kg) was evaluated. The lung permeability index and HIF-1α protein level increased, the arterial blood oxygenation index (PaO2/FIO2 ratio) and occludin protein level decreased significantly 6 h after phosgene exposure (P < 0.05). PTX exerted protective effects by HIF-1α-VEGF-occludin signaling pathway to some extent. Moreover, prophylactic, but not therapeutic administration of PTX (100 mg/kg), exhibited a significant protective effect. Pretreatment with PTX protected against phosgene-induced lung injury, possibly by inhibiting differential expression of HIF-1α, VEGF, and occludin.

A Retrospective Study of the No-Contact Technique to Obtain Radial Arteries for Coronary Artery Bypass Grafting.

BACKGROUND: To retrospectively study the experience with application of no-touch technique in radial artery (RA)-based coronary artery bypass grafting (CABG). METHODS: Clinical data of patients who underwent RA-based multi- (n = 45) or full-arterial CABG (n = 27) between January 2019 and June 2022 in the Affiliated Hospital of ZunYi Medical University were collected. The incidence of main cardiovascular events at 30-day follow-up, the antebrachial union condition and the vessel patency rate were analyzed. RESULTS: A total of 66 RAs were harvested and 70 RAs used as grafts. The number of RA used per patient was 1.46. Delayed antebrachial union occurred in 1 patient (1.45%). There was no death, cerebral infarction, myocardial infarction or revascularization at follow-up. Early coronary computed tomography (CT) after surgery revealed occlusion in 1 RA, with the patency rate being 98.57%. CONCLUSIONS: The No-touch RA harvesting technique, preservation and postoperative management applied in this study are effective and rational, and the application of RA as the graft in CABG is safe.

A Molybdenum Disulfide Nanozyme with Charge-Enhanced Activity for Ultrasound-Mediated Cascade-Catalytic Tumor Ferroptosis.

The deficient catalytic activity of nanozymes and insufficient endogenous H2 O2 in the tumor microenvironment (TME) are major obstacles for nanozyme-mediated catalytic tumor therapy. Since electron transfer is the basic essence of catalysis-mediated redox reactions, we explored the contributing factors of enzymatic activity based on positive and negative charges, which are experimentally and theoretically demonstrated to enhance the peroxidase (POD)-like activity of a MoS2 nanozyme. Hence, an acidic tumor microenvironment-responsive and ultrasound-mediated cascade nanocatalyst (BTO/MoS2 @CA) is presented that is made from few-layer MoS2 nanosheets grown on the surface of piezoelectric tetragonal barium titanate (T-BTO) and modified with pH-responsive cinnamaldehyde (CA). The integration of pH-responsive CA-mediated H2 O2 self-supply, ultrasound-mediated charge-enhanced enzymatic activity, and glutathione (GSH) depletion enables out-of-balance redox homeostasis, leading to effective tumor ferroptosis with minimal side effects.

Non-Invasive Thermal Therapy for Tissue Engineering and Regenerative Medicine.

Owing to the development of nanotechnology and noninvasive treatment, thermal therapy in combination with external stimuli has been applied for tissue engineering and regenerative medicine (TERM), which has attracted more and more attention in recent years. In this review, the recent progress of applying a variety of non-invasive thermal therapeutic modalities for TERM, including photothermal therapy, magnetic thermotherapy, and ultrasound thermotherapy, as well as other thermal therapeutics are discussed. The parameters and conditions that need to be considered and regulated to realize a well-controlled thermal therapy for tissue regeneration are also discussed. Afterwards, the current concerns and challenges of putting thermal therapy into clinical applications are pointed out. At last, perspectives are provided for the future development directions, aiming to providing opportunities and a novel pathway for TERM.

CircPrkcsh, a circular RNA, contributes to the polarization of microglia towards the M1 phenotype induced by spinal cord injury and acts via the JNK/p38 MAPK pathway.

Spinal cord injury (SCI) is a complex pathological change that includes primary SCI and gradually evolves into secondary SCI. Accumulating evidence demonstrates that circular RNAs (circRNAs) are involved in the pathology of a variety of neurological diseases and injuries. However, the characteristics and function of circRNAs in SCI have yet to be elucidated. Although previous research demonstrated that circPrkcsh induces astrocytes to produce inflammatory factors and chemokines, the precise function and mechanism of circPrkcsh in microglia after SCI remains unknown. In this study, we constructed a mouse model of SCI by applying a SCI impactor. Quantitative Real-time PCR and Fluorescence in situ hybridization analysis revealed that circPrkcsh was upregulated in the microglia of SCI mice when compared to sham-operated mice. Gain- or loss-of-function experiments and in vivo assays further indicated that circPrkcsh promotes microglia M1 polarization both in vivo and in vitro. Furthermore, bioinformatics analysis, dual-luciferase assays, and RNA immunoprecipitation assays, confirmed that circPrkcsh serves as a competing endogenous RNA (ceRNA) to promote the expression of MEKK1 mRNA by sponging miR-488. Double knockout rescue experiments further showed that circPrkcsh regulates the MEKK1/JNK/p38 MAPK pathway via miR-488. Our research provides a better understanding of the mechanism of circPrkcsh in SCI and demonstrates that the circPrkcsh/miR-488/Mekk1 axis is a promising regulatory method for the treatment of SCI.

Spinal microglia-derived TNF promotes the astrocytic JNK/CXCL1 pathway activation in a mouse model of burn pain.

Burn injury-induced pain (BIP) is an extremely complicated condition usually resistant to analgesic drugs, while its pathogenesis remains unknown. Considerable attention has been attracted to elucidate the glial mechanisms in chronic pain. In this study, we initiatively used a mouse model of second-degree BIP to investigate the underlying non-neuronal mechanisms at the spinal cord level. Our behavioral results showed that hind-paw burn injury caused persistent allodynia and hyperalgesia for 2 weeks in mice. Further studies revealed that both microglia and astrocytes activated in a spatially- and temporally-dependent manner in spinal cord after burn injury. In addition, the phosphorylated p38 mitogen-activated protein kinase (MAPK)-mediated tumor necrosis factor (TNF) release in spinal microglia is essentially attributed to the early stage of BIP, while the c-Jun N-terminal kinase (JNK) MAPK-dependent chemokine CXCL1 expression is mainly involved in the maintenance of pain hypersensitivity. Most strikingly, burn injury-induced pain symptoms and the activation of astrocytes were significantly suppressed by TNF inhibitor Thalidomide. On the contrary, intrathecal injection of TNF caused apparent pain hypersensitivity, accompanied by the activation of astrocytes and the upregulation of CXCL1 via the JNK MAPK signaling pathway, indicating that TNF is the key cytokine in the interaction between microglia and astrocytes at the spinal level. Moreover, treatment with the CXCR2 receptor antagonist SB225002 to block the biological activities of CXCL1 significantly attenuated the mechanical allodynia and thermal hyperalgesia in this BIP model. Taken together, this study indicates that intervention of glial pathways provides a new perspective in the management of BIP.

Rapid emergence of a PB2 D701N substitution during adaptation of an H9N2 avian influenza virus in mice.

H9N2 avian influenza viruses (AIVs) have been isolated frequently from multiple avian species and, occasionally, from humans. To explore the potential molecular basis of cross-species transmission of H9N2 AIVs, an H9N2 AIV (A/chicken/Zhejiang/221/2016) was serially passaged in mouse lung. The results showed that the mouse-adapted H9N2 virus exhibited higher virulence and replicated more efficiently in mouse lung and liver. Whole-genome sequencing showed an amino acid substitution, D701N, in the PB2 protein, which is likely associated with the increased replicative ability of H9N2 virus in mice. The rapid emergence of adaptive substitutions indicates the necessity of continuous monitoring of H9N2 virus in poultry.

Complete genome analysis of a nege-like virus in aphids (Astegopteryx formosana).

Negeviruses are a group of insect-specific viruses that have a wide geographic distribution and broad host range. In recent years, nege-like viruses have been discovered in aphids of various genera of the family Aphididae, including Aphis, Rhopalosiphum, Sitobion, and Indomegoura. Here, we report the complete genome sequence of a nege-like virus isolated from Astegopteryx formosana aphids collected in Guangdong, China, which we have designated as "Astegopteryx formosana nege-like virus" (AFNLV). AFNLV has a genome length of 10,107 nt (excluding the polyA tail) and possesses the typical conserved domains of negeviruses. These include a viral methyltransferase, an S-adenosylmethionine-dependent methyltransferase, a viral helicase, and an RNA-dependent RNA polymerase (RdRP) domain in open reading frame 1 (ORF1), a DiSB-ORF2_chro domain in ORF2, and a SP24 domain in ORF3. The genome of AFNLV shares the highest nucleotide sequence identity (74.89%) with Wuhan house centipede virus, identified in a mixture of barley aphids. As clearly revealed by RdRP-based phylogenetic analysis, AFNLV, together with other negeviruses and nege-like viruses discovered in aphids, formed a distinct "unclassified clade" closely related to members of the proposed genus "Sandewavirus" and the family Kitaviridae. In addition, small interfering RNAs (siRNAs) derived from AFNLV did not exhibit typical characteristics of virus-derived siRNAs processed by the host RNAi-based antiviral pathway. However, the extremely high abundance of viral transcripts (average read coverage 73,403X) strongly suggested that AFNLV might actively replicate in the aphid host. AFNLV described in this study is the first nege-like virus discovered in aphids of the genus Astegopteryx, which will contribute to future study of the co-evolution of nege/nege-like viruses and their host aphids.

Increased virulence of a novel reassortant H1N3 avian influenza virus in mice as a result of adaptive amino acid substitutions.

In this study, a novel multiple-gene reassortant H1N3 subtype avian influenza virus (AIV) (A/chicken/Zhejiang/81213/2017, CK81213) was isolated in Eastern China, whose genes were derived from H1 (H1N3), H7 (H7N3 and H7N9), and H10 (H10N3 and H10N8) AIVs. This AIV belongs to the avian Eurasian-lineage and exhibits low pathogenicity. Serial lung-to-lung passages of CK81213 in mice was performed to study the amino acid substitutions potentially related to the adaptation of H1 AIVs in mammals. And the mouse-adapted H1N3 virus showed greater virulence than wild-type H1N3 AIV in mice and the genomic analysis revealed a total of two amino acid substitutions in the PB2 (E627K) and HA (L67V) proteins. Additionally, the results of the animal study indicate that CK81213 could infect mice without prior adaption and become highly pathogenic to mice after continuous passage. Our findings show that routine surveillance of H1 AIVs is important for the prediction of influenza epidemics.

Autism-like behaviours and germline transmission in transgenic monkeys overexpressing MeCP2.

Methyl-CpG binding protein 2 (MeCP2) has crucial roles in transcriptional regulation and microRNA processing. Mutations in the MECP2 gene are found in 90% of patients with Rett syndrome, a severe developmental disorder with autistic phenotypes. Duplications of MECP2-containing genomic segments cause the MECP2 duplication syndrome, which shares core symptoms with autism spectrum disorders. Although Mecp2-null mice recapitulate most developmental and behavioural defects seen in patients with Rett syndrome, it has been difficult to identify autism-like behaviours in the mouse model of MeCP2 overexpression. Here we report that lentivirus-based transgenic cynomolgus monkeys (Macaca fascicularis) expressing human MeCP2 in the brain exhibit autism-like behaviours and show germline transmission of the transgene. Expression of the MECP2 transgene was confirmed by western blotting and immunostaining of brain tissues of transgenic monkeys. Genomic integration sites of the transgenes were characterized by a deep-sequencing-based method. As compared to wild-type monkeys, MECP2 transgenic monkeys exhibited a higher frequency of repetitive circular locomotion and increased stress responses, as measured by the threat-related anxiety and defensive test. The transgenic monkeys showed less interaction with wild-type monkeys within the same group, and also a reduced interaction time when paired with other transgenic monkeys in social interaction tests. The cognitive functions of the transgenic monkeys were largely normal in the Wisconsin general test apparatus, although some showed signs of stereotypic cognitive behaviours. Notably, we succeeded in generating five F1 offspring of MECP2 transgenic monkeys by intracytoplasmic sperm injection with sperm from one F0 transgenic monkey, showing germline transmission and Mendelian segregation of several MECP2 transgenes in the F1 progeny. Moreover, F1 transgenic monkeys also showed reduced social interactions when tested in pairs, as compared to wild-type monkeys of similar age. Together, these results indicate the feasibility and reliability of using genetically engineered non-human primates to study brain disorders.