SARS-CoV-2 nucleocapsid protein enhances the level of mitochondrial reactive oxygen species.

Coronavirus disease 2019 (COVID-19) pathogenesis is influenced by reactive oxygen species (ROS). Nevertheless, the precise mechanisms implicated remain poorly understood. The nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the main driver for this condition, is a structural protein indispensable for viral replication and assembly, and its role in ROS production has not been reported. This study shows that SARS-CoV-2 N protein expression enhances mitochondrial ROS level. Bulk RNA-sequencing suggests of aberrant redox state of the electron transport chain. Accordingly, this protein hinders ATP production but simultaneously augments the activity of complexes I and III, and most mitochondrially encoded complex I and III proteins are upregulated by it. Mechanistically, N protein of SARS-CoV-2 shows significant mitochondrial localization. It interacts with mitochondrial transcription components and stabilizes them. Moreover, it also impairs the activity of antioxidant enzymes with or without detectable interaction.

Association of bone turnover markers and cognitive function in Chinese chronic schizophrenia patients with or without vitamin D insufficiency.

BACKGROUND: Increasing evidence shows that bone turnover markers (BTMs) and vitamin D can affect human cognitive function. However, there are few studies that have investigated the association between BTMs and cognitive function in chronic schizophrenia patients. The aim of this study was to investigate the relationship between BTMs and cognitive function in chronic schizophrenia patients with or without vitamin D insufficiency (VDI). METHODS: In all, 118 chronic schizophrenia patients were enrolled in this cross-sectional study. Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was applied to evaluate the cognitive function of the subjects. Blood analysis included bone turnover markers, vitamin D levels, and glycolipid levels. RESULTS: Relative to 72 vitamin D-sufficient (VDS) patients, 46 VDI patients had higher bone resorption markers levels and lower bone formation markers levels. Regression analysis showed that, in the total sample, CTX and language function exhibited independent positive correlation (p = 0.027, R2 change = 0.042), and in the VDS group, procollagen type I N-terminal propeptide (PINP) was independently negatively correlated with language function (p = 0.031, R2 change = 0.065), while the positive correlation between osteopontin (OPN) and delayed memory remained in the VDI group (p = 0.036, R2 change = 0.083). CONCLUSION: Our study showed an association between the levels of BTMs and cognitive function among chronic schizophrenia patients. This correlation may have different mechanisms of action at different vitamin D levels.

Use of urinary balloon catheter to prevent postoperative bleeding after ultrasound-guided vacuum-assisted breast biopsy.

Postoperative bleeding is the most frequent serious complications after vacuum-assisted breast biopsy (VABB). The aim of this study was to evaluate the clinical effect of using urinary balloon catheter to prevent postoperative bleeding after ultrasound-guided VABB. From May 2016 to June 2018, 324 patients who underwent ultrasound-guided VABB were randomized into the study group and control group. In the study group, an urinary balloon catheter was inserted into the excision cavity to prevent bleeding and hematoma. In the control group, compression with thorax pressure bandage was used for hemostasis. Postoperative subcutaneous ecchymosis and hematoma were recorded and compared between the two groups. The rates of postoperative ecchymosis and hematoma in the study group were significantly lower than that in the control group (5.6% vs 13.0%, P < .05; 8.0% vs 20.4%, P < .05). Among patients with lesions ≤1.5 cm, the rates of postoperative ecchymosis and hematoma were 2.9% and 4.3% in the study group, 6.5% and 11.7% in the control group, but there was no statistically significant difference between the two groups (P > .05). Among patients with lesions >1.5 cm, the rates of postoperative ecchymosis and hematoma in the study group were significantly lower than that in the control group (7.6% vs 18.8%, P < .05; 10.9% vs 28.2%, P < .05). Hemostasis with balloon urinary catheter is a safe and effective method to prevent postoperative bleeding after VABB.

A nomogram based on mammary ductoscopic indicators for evaluating the risk of breast cancer in intraductal neoplasms with nipple discharge.

Mammary ductoscopy (MD) is commonly used to detect intraductal lesions associated with nipple discharge. This study investigated the relationships between ductoscopic image-based indicators and breast cancer risk, and developed a nomogram for evaluating breast cancer risk in intraductal neoplasms with nipple discharge. A total of 879 consecutive inpatients (916 breasts) with nipple discharge who underwent selective duct excision for intraductal neoplasms detected by MD from June 2008 to April 2014 were analyzed retrospectively. A nomogram was developed using a multivariate logistic regression model based on data from a training set (687 cases) and validated in an independent validation set (229 cases). A Youden-derived cut-off value was assigned to the nomogram for the diagnosis of breast cancer. Color of discharge, location, appearance, and surface of neoplasm, and morphology of ductal wall were independent predictors for breast cancer in multivariate logistic regression analysis. A nomogram based on these predictors performed well. The P value of the Hosmer-Lemeshow test for the prediction model was 0.36. Area under the curve values of 0.812 (95 % confidence interval (CI) 0.763-0.860) and 0.738 (95 % CI 0.635-0.841) was obtained in the training and validation sets, respectively. The accuracies of the nomogram for breast cancer diagnosis were 71.2 % in the training set and 75.5 % in the validation set. We developed a nomogram for evaluating breast cancer risk in intraductal neoplasms with nipple discharge based on MD image findings. This model may aid individual risk assessment and guide treatment in clinical practice.

Clinical characteristics and long-term prognosis in patients with chronic heart failure and reduced ejection fraction in China.

AIMS: Chronic heart failure with reduced ejection fraction (CHF-REF) remains a major public health problem with high morbidity and mortality, but the data on current treatment status and long-term prognosis in China were still missing. METHODS: Among prospectively recruited 2368 patients with CHF-REF in 10 hospitals, 2154 patients provided complete followed data. Two aetiology subgroups (dilated cardiomyopathy, DCM and ischaemic cardiomyopathy, ICM) were classified. Clinical data and long-term prognosis were analysed. RESULTS: After a median follow-up of 52 months, 850 (39.46%) patients died, of whom 302 (35.53%) were sudden cardiac death (SCD). Unadjusted rates of all-cause mortality and SCD were higher in DCM than those in ICM (p<0.001 for both modes of death), but mortalities were comparable after adjustment for co-variables (p=0.387 and p=0.483 respectively). ACEIs/ARBs, aldosterone receptor antagonists, ß-blockers and diuretics were dominant prescribed drugs with the prescription rates of 65.97%, 74.61%, 68.29% and 74.37% respectively. Multivariable analysis identified co-morbidities (eg, hypertension), NHYA class, ventricular tachycardia/fibrillation (VT/VF), QRS duration, left ventricular EF and creatinine as independent predictors of mortalities, whereas ACEIs/ARB, ß-blockers and statins were associated with better prognosis. Survived from sustained VT/VF episodes had the highest predictive value for SCD (HR, 4.230; 95% CI, 2.500-7.157; p<0.001). The predictors for mortalities in DCM and ICM were different. CONCLUSIONS: Patients with CHF-REF had a poor prognosis in China despite being under current standard therapies, especially patients with DCM. Predictors for all-cause mortality and SCD might be identified for evaluating the prognosis of these patients.

Knockdown of LCN2 Attenuates Brain Injury After Intracerebral Hemorrhage via Suppressing Pyroptosis.

Objective: The aims of this study are to screen novel differentially expressed genes (DEGs) for intracerebral hemorrhage (ICH) and reveal the role of Lipocalin-2 (LCN2) in ICH. Methods: We constructed the ICH model by injection of autologous whole blood into the right basal ganglia in rats. RNA-sequencing and bioinformatics analyses were performed to identify the DEGs between ICH and sham rats, and some important ones were confirmed using quantitative real-time PCR (qRT-PCR). LCN shRNA was used to knockdown of LCN2 in ICH rats. Pathological examination was carried out using 2,3,5-triphenyltetrazolium chloride (TTC) staining and Hematoxylin-eosin (HE) staining. Immunohistochemistry detected Caspase-3, and co-staining of Terminal dUTP nick end labeling (TUNEL) and NEUN staining were performed for neuron apoptosis assessment. Western blot analysis was performed to quantify pyroptosis-related proteins. Enzyme-linked immunosorbent assay (ELISA) was used to measure inflammatory cytokine levels. Results: ICH rats exhibited significant hematomas, higher brain water content, obvious interstitial edema, and inflammatory infiltration, as well as more apoptotic cells in brain tissues. RNA-seq analysis identified 103 upregulated and 81 downregulated DEGs. The expression of LCN2, HSPB1, CXCL10, and MEF2B were upregulated in ICH rats. ICH triggered the release of interleukin (IL)-1ß, tumor necrosis factor-α (TNF-α), and IL-18, and promoted the expression of pyroptosis-related proteins Caspase-1, GSDMD, NLRP3, and ASC. LCN2 knockdown attenuated the pathological characteristics of ICH, and also reduced pyroptosis in brain tissues. Conclusion: Inhibition of LCN2 attenuates brain injury after ICH via suppressing pyroptosis, which provide guidance for ICH management.

The role of SARS-CoV-2 nucleocapsid protein in antiviral immunity and vaccine development.

ABSTRACTThe coronavirus disease 2019 (COVID-19) has caused enormous health risks and global economic disruption. This disease is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The SARS-CoV-2 nucleocapsid protein is a structural protein involved in viral replication and assembly. There is accumulating evidence indicating that the nucleocapsid protein is multi-functional, playing a key role in the pathogenesis of COVID-19 and antiviral immunity against SARS-CoV-2. Here, we summarize its potential application in the prevention of COVID-19, which is based on its role in inflammation, cell death, antiviral innate immunity, and antiviral adaptive immunity.

A Lightweight Low-dose PET Image Super-resolution Reconstruction Method based on Convolutional Neural Network.

BACKGROUND: PET imaging is one of the most widely used neurological disease screening and diagnosis techniques. AIMS: Since PET involves the radiation and tolerance of different people, the improvement that has always been focused on is to cut down radiation, in the meantime, ensuring that the generated images with low-dose tracer and generated images with standard-dose tracer have the same details of images. METHODS: We propose a lightweight low-dose PET super-resolution network (SRPET-Net) based on a convolutional neural network. In this research, We propose a method for accurately recovering highresolution (HR) PET images from low-resolution (LR) PET images. The network learns the details and structure of the image between low-dose PET images and standard-dose PET images and, afterward, reconstructs the PET image by the trained network model. RESULTS: The experiments indicate that the SRPET-Net can achieve a superior peak signal-to-noise ratio (PSNR) and structural similarity index measurement (SSIM) values. Moreover, our method has less memory consumption and lower computational cost. CONCLUSION: In our follow-up work, the technology can be applied to medical imaging in many different directions.

Cross-cultural adaptation and construct validity of the Chinese Version of Visual Vertigo Analogue Scale by using structural equation modeling.

BACKGROUND: Visual vertigo (VV) is a disease characterized by various visual signal-induced discomforts, including dizziness, unsteady balance, activity avoiding, and so forth. Distinguishing it from other kinds of dizziness is important because it needs the combination of visual training and vestibular rehabilitation together. However, there is no appropriate tool to diagnose VV in China, thus we would like to introduce an effective tool to China. OBJECTIVE: The aim of this study was to establish the reliability and validity of the Chinese version of visual vertigo analogue scale (VVAS-CH) and to achieve its crosscultural adaptation in order to promote its further usage in China. METHODS: A total of 1681 patients complaining of vertigo or dizziness were enrolled and they were asked to complete the VVAS-CH. The cross-cultural adaptation, reliability and construct validity of the VVAS-CH were determined. RESULTS: Split-half reliability was 0.939, showing a good reliability. Factor analysis identified only one common factor for the nine items that explained 64.83% of the total variance. Most fit indices reached acceptable levels, proving the good fit of the VVAS-CH model. CONCLUSIONS: The VVAS-CH validated in this study can be used as an effective tool for diagnosing and evaluating VV in patients whose native language is Chinese.

[Central reactive oxygen species mediate cardiovascular effects of urotensin II in spontaneously hypertensive rats].

Central urotensin II (UII) may participate in the regulation of cardiovascular functions by stimulating sympathy pathway. However, the central mechanism remained unknown. Recent studies have shown that brain reactive oxygen species (ROS) mediate the sympatho-excitatory effects. In the present study, we tested the hypothesis that ROS mediate central cardiovascular effects of UII. Experiments were conducted in Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). Immunocytochemistry, intracerebroventricular (icv) infusion and lucigenin-enhanced chemiluminescence assay were employed to detect UII receptor expression and ROS level, respectively. The following results were obtained: (1) Expressions of UII receptors of rostral ventrolateral medulla (RVLM) and nucleus tractus solitarii (NTS) were increased in SHR rats compared with WKY rats (P < 0.05). (2) UII (icv) significantly increased mean arterial pressure (MAP) (P < 0.05), and the effect of UII was significantly more pronounced in SHR rats than that in WKY rats (P < 0.05); (3) Tempol (a superoxide dismutase mimic) or Urantide (an antagonist of UII receptor) pretreatments eliminated the pressor effect of UII (P < 0.05) in SHR rats; (4) Brain superoxide level was increased in UII-treated SHR rats compared with that in cerebrospinal fluid (CSF)-treated SHR rats (P < 0.05). These results indicate that ROS mediate central cardiovascular effects of UII in SHR rats and provide evidence for a novel relationship between UII and ROS.

Metastatic low-grade endometrial stromal sarcoma with variable morphologies in the ovaries and mesentery: A case report.

BACKGROUND: Low-grade endometrial stromal sarcoma (LGESS) classically exhibits a proliferative morphology. However, morphological variation of extrauterine tumors presents a diagnostic challenge. CASE SUMMARY: We report the case of a 76-year-old female patient with extensive extrauterine and abdominal neoplastic lesions. Computed tomography showed massive pleural and ascitic fluid, and there was an increase in serum cancer antigen 125. She underwent bilateral adnexectomy and tumor resection. The right ovary had been replaced by a multinodular mass that was 8.5 cm × 4.5 cm × 3.5 cm in size. In addition, there was a 24 cm × 15 cm × 13 cm mesenteric mass, which was also multinodular, with local invasion of the intestinal serosa and underlying muscle. Under the microscope, the tumors in different places exhibited two different patterns, thus presenting great challenges to diagnosis and treatment. Thorough pathological assessment eliminated all differential diagnoses in favor of metastatic LGESS derived from a 20-year-old primary tumor initially misdiagnosed as leiomyosarcoma. CONCLUSION: LGESS morphology varies according to tumor location. Accurate diagnosis is critical for appropriate treatment and improved prognosis and patient care.

The Study of Mechanical Behaviors of Caprinae Horn Sheath under Pendulum Impact.

As a light-weight natural keratin biocomposite, Bovidae horn exhibits high mechanical properties and energy absorption. Different to the widely studied horn from subfamily Bovinae and Antilocapridae, few studies have focused on the horn sheath of subfamily Caprinae. In this work, three Caprinae horn sheathes from Cashmere goat, White goat and Black sheep were selected. Charpy pendulum impact tests were performed, and the fracture characteristics were evaluated. It was demonstrated that water plays an important role in acquiring balanced dynamic mechanical properties in all Caprinae horn sheaths. The hydrated keratin provides large plastic deformation capacity and further gives rise to a gradual generation of micro-cracks. Multi-scale structure including wavy-shaped interface, scattered voids and hierarchical micro-fibre were observed. Such a structure induced complex fracture mechanisms, such as delamination, 90° crack deflection and fibre pull-out, which were probably influenced by interfacial strength. The results are expected to endow the research and thinking of Bovidae horn.

A Deep-Learning-Based Artificial Intelligence System for the Pathology Diagnosis of Uterine Smooth Muscle Tumor.

We aimed to develop an artificial intelligence (AI) diagnosis system for uterine smooth muscle tumors (UMTs) by using deep learning. We analyzed the morphological features of UMTs on whole-slide images (233, 108, and 30 digital slides of leiomyosarcomas, leiomyomas, and smooth muscle tumors of uncertain malignant potential stained with hematoxylin and eosin, respectively). Aperio ImageScope software randomly selected ≥10 areas of the total field of view. Pathologists randomly selected a marked region in each section that was no smaller than the total area of 10 high-power fields in which necrotic, vascular, collagenous, and mitotic areas were labeled. We constructed an automatic identification algorithm for cytological atypia and necrosis by using ResNet and constructed an automatic detection algorithm for mitosis by using YOLOv5. A logical evaluation algorithm was then designed to obtain an automatic UMT diagnostic aid that can "study and synthesize" a pathologist's experience. The precision, recall, and F1 index reached more than 0.920. The detection network could accurately detect the mitoses (0.913 precision, 0.893 recall). For the prediction ability, the AI system had a precision of 0.90. An AI-assisted system for diagnosing UMTs in routine practice scenarios is feasible and can improve the accuracy and efficiency of diagnosis.

Composition and spatial distribution of elements and isotopes of a giant human bladder stone and environmental implications.

The composition and spatial distribution of minerals, trace elements, as well as carbon and nitrogen isotopes from the outer crust to inner nucleus of a 20-year old giant human bladder stone comprising thirteen layers were intensively investigated. Calcium oxalate monohydrate (COM) was found to concentrate in the inner and middle layers, struvite was concentrated in middle and outer layers, and fluorapatite occurred in almost all layers. The spatial distribution of minerals has the potential to provide preliminary knowledge regarding the long-term urine composition, or even the physiological condition of the patient. The stable carbon isotope ratio (δ13C) and stable nitrogen isotope ratio (δ15N) were measured in each layer and significant correlation was found between δ13C with calcium oxalate monohydrate content and between δ15N and struvite content. Nearly constant values of -23.2‰ and 7.1‰ for δ13C and δ15N, respectively, were found in the organic components of the stone. Both isotope ratios indicate a long-term fixed diet consisting mainly of C3 plants, such as rice and wheat, for the 20-year time period of the stone formation. In addition, eighteen elements (Ca, P, Mg, K, Na, Al, Fe, Zn, Pb, Cu, Sr, Ba, Ti, V, Cr, Ni, Mn and Co) were measured in all the layers. The trace elements Al, Fe, Cu, Zn, Pb, Sr, Ba and Ti showed a similar spatial distribution pattern from the outer crust to the inner core. Although there were complex correlations between elements and minerals, Factor Analysis suggests that the occurrence of these elements in stones may be mainly the result of environmental exposure to metals during the formation of the stone, indicating that urinary stones may serve as potential long-term biomonitors. In particular, Ni and Cr showed a distinct distribution pattern in the stone, which may relate to human metabolic activities.

Stop codons and the +4 nucleotide may influence the efficiency of G418 in rescuing nonsense mutations of the HERG gene.

The importance of the local sequence context in determining how efficiently aminoglycosides rescue nonsense mutations has been established previously in disease models. Different stop codons appear to facilitate the termination process with differing efficiencies. Furthermore, the efficiency with which termination is suppressed may also be influenced by the local sequence context surrounding the stop codon. The strongest bias has usually been identified with the nucleotide base that immediately follows the stop codon in the majority of experiments. However, how the sequence context influences the efficiency of aminoglycosides in rescuing the human ether­a­go­go­related (HERG) protein in mammalian cells remains to be fully elucidated. Therefore, the present study was devised to examine the susceptibility of different termination codons on the HERG gene and the +4 nucleotide immediately following them to be suppressed by aminoglycosides in 293 cells. The 293 cells were transiently transfected with the wild­type or mutant genes. The read­through effect was subsequently examined by adding aminoglycoside G418 into the culture medium, followed by incubation of the cells for 24 h. An immunofluorescence method was then used to observe the protein expression of HERG prior to and following drug treatment. Patch clamping was performed to evaluate the function of the HERG protein. These experiments revealed that stop codons TGA and TAA in the R1014X mutant were more susceptible to treatment with the drug G418. Similar results were observed with the W927X­TGA and W927X­TAA mutants. Subsequently, R1014X­TGAC, R1014X­TGAG and R1014X­TGAA mutants were constructed based on the R1014X­TGAT mutant. The level of red fluorescence was observed prior to and following the administration of G418 using antibodies targeting the N­ or C­terminus of the HERG protein. However, the tail current density was found only to increase with the R1014X­TGAT mutant following G418 treatment. Taken together, the results of the present study suggest that the type of premature stop codon and the context of the nucleotide immediately following at the +4 position, may determine the pharmacological rescue efficiency of the HERG gene.

One-step preparation of single-crystalline beta-MnO2 nanotubes.

Single-crystal beta-MnO(2) nanotubes with diameters in the range 200-500 nm and lengths up to several micrometers were successfully prepared by a simple hydrothermal method through oxidizing MnSO(4) with NaClO(3) in the presence of poly(vinyl pyrrolidone) (PVP). It was found that the formation process of beta-MnO(2) nanotubes included two primary evolution stages over time: (1) the MnOOH nanoparticles initially formed in the hydrothermal system and anisotropic growth to nanorods and nanorod aggregates, and (2) the MnOOH nanorods transformed into beta-MnO(2) tubular structure and grown into beta-MnO(2) nanotubes due to continuous growth through a dissolution-recrystallization process eventually. Based on a series of experimental analysis, the formation mechanism of these nanostructures was discussed briefly. The present study has enlarged the family of nanotubes available and offers a possible new, general route to one-dimensional single-crystalline nanotubes of other materials.

Single-crystalline CuO nanobelts fabricated by a convenient route.

A reverse micelle-assisted route for preparing CuO nanobelts from precursor Cu(OH)2- 4 is reported. The reverse micelles were used as microreactors, which led to anisotropic growth crystals during a simple solvothermal process. The formation conditions of the CuO nanobelts were also studied.

Common Variants in TRDN and CALM1 Are Associated with Risk of Sudden Cardiac Death in Chronic Heart Failure Patients in Chinese Han Population.

BACKGROUND: Recent studies suggest that variants in two calcium handling genes (RyR2 and CASQ2) associated with sudden cardiac death (SCD) and non-sudden cardiac death (NSCD) in subjects with heart failure and coronary artery disease, respectively. The purpose of this study was to identify other calcium handling genes associated with SCD in the long-term of chronic heart failure (CHF) in Chinese Han population. METHODS AND RESULTS: We investigated 20 SNPs representing 10 genes that regulated calcium handling in 1429 patients with CHF, and the genetic association with SCD and all-cause death was analysed. During a median follow-up period of 63 months, 538 patients (37.65%) died from CHF, of whom 185 (34.38%) had SCD and the others were NSCD. SNPs that pass a P value cut-off of 0.0025 were considered as significant. We found that patients carrying the CC genotype of rs3814843 on CALM1 gene had greater risks of SCD (HR 5.542, 95% CI 2.054-14.948, P = .001) and all cause death (HR 3.484, 95% CI 1.651-7.350, P = .001). After adjusting for other risk factors, significant associations remained. Moreover, patients carrying G allele of rs361508 on TRDN gene also had increased risk of SCD. CONCLUSIONS: Common variants in TRDN and CALM1 are associated with increased risk of SCD in patients with CHF. These findings provide further evidence for association of variants in calcium handling regulating proteins and SCD in chronic heart failure.