Background and purpose: Necroptosis amplifies inflammation and plays an important role in atherosclerosis progression. However, the role of necroptosis of vascular smooth muscle cell (VSMC)-derived foam cells in atherosclerosis remains unknown. In the present study, we evaluated the effect of oxidized low-density lipoprotein (ox-LDL) on VSMC-derived foam cell necroptosis. Furthermore, we determined whether and how C1q/TNF-related protein 9 (CTRP9), a cardiovascular protective adipokine, protects against ox-LDL-induced cell dysfunction and atherosclerosis. Experimental approach: The VSMC-derived foam cell were established followed by incubation with ox-LDL and Tempol, CTRP9 and Compound C for 24 h. Cell death was detected by the mtROS levels and ΔΨm, and the cellular inflammation was tested by the expression of inflammatory factors. Transmission electron microscopy and flow cytometry were used to confirm the occurrence of Necroptosis. Western blotting was used to detect the expression of necroptosis-related proteins and antioxidant enzymes. In vivo, adeno-associated virus (AAV) was used to construct an animal model of CTRP9 overexpression. Then the stability and necroptosis of aortic sinus plaque were detected. Key Results: Our results revealed that ox-LDL potently induced VSMC-derived foam cell necroptosis and promoted the expression of pro-atherosclerotic factors via an oxidative stress-related mechanism. CTRP9 significantly reversed ox-LDL-induced cell damage and the related dysfunction through the AMPK pathway-mediated expression of antioxidant enzymes. CTRP9 overexpression reduced atherosclerotic lesion size in the aortic sinus and enhanced features of plaque stability. Conclusions & Implications: Overall, our findings suggest that CTRP9 is a potential drug target to suppress atherosclerosis and stabilize plaques.

Human prion protein and prion-like protein misfolding are widely recognized as playing a causal role in a large and growing number of neurodegenerative diseases. Here we summarize the compelling evidence that the spike protein of SARS-CoV-2 contains extended amino acid sequences previously established as characteristic of a prion-like protein. This suggests that vaccine-induced spike protein production is synonymous with production of a prion-like protein, and we trace some of the various pathways through which these proteins should be expected to traverse and distribute throughout the body. We describe some of the highly concerning biological consequences that would be expected to occur with increased frequency as a consequence. Specifically, we describe spike-protein contribution, via its prion-like properties, to neuroinflammation and neurodegenera-tive diseases; to clotting disorders within the vasculature; to suppressed prion protein regulation in the context of widely prevalent insulin resistance; and other health complications it could be expected to induce. We explain why these prion-like characteristics are more relevant to vaccine-related mRNA-induced spike proteins than natural infection with SARS-CoV-2. We conclude with some potentially ominous public health implications and recommendations for investigations of these possibilities.

Cardiovascular diseases (CVDs) cause massive morbidity and mortality. In recent years, natural small-molecule therapeutics have attracted much attention for their significant efficacy. Articles have been published to study the intervention of natural drugs (including monomers, compounds, compound and neo-combinations) on one type of cardiovascular disease, but the number and variety of natural drugs included are small and insufficient, and there are no articles detailing the protective effects of different types of natural small molecule drugs on multiple cardiovascular diseases. Natural small molecule drugs have high biological activity and structural diversity, and are more likely to enter the body to exert their effects. In this article, we describe the efficacy of such drugs for anti-atherosclerosis, cardiomyocyte repair, and antagonism of ventricular remodeling, heart failure, and arrhythmias to provide an experimental basis for clinical research and identification of new therapeutic approaches.

Background and Purpose Belonging to the family Anacardiaceae, Spondias mombin Linn (SM) has been used in ethnomedicines in the treatment of diseases including viral diseases. This study aims to identify anti-viral volatiles from Geraniin and alcoholic leaf extracts of Spondias mombin Linn as potential anti-Filoviral agent against the Marburg virus (MARV VP35) by the use Gas Chromatographic–Mass Spectrometry (GC-MS) and computer-aided techniques. Experimental Approach We used phytochemical processes and computer aided drug design in the identification (by GC-MS) of anti-viral phytochemical compounds from leaf extracts of S. mombin, constituents of Geraniin and anti-filoviral activity through molecular docking and molecular simulation respectively. Key Results Geranyl benzoate including four (4) antiviral compounds, D-Limonene, p-Cymene, Thymol, L-.alpha.- Terpineol and 1,2-Benzenedicarboxylic acid, butyl -2- methylpropyl ester (1,2BAB-2-MPE) were obtained from fractions of alcoholic SM leaf extracts and 98% pure Geraniin respectively. In silico analysis identified 1,2BAB-2-MPE as the most favourable potential binders MARV VP35 binder characterised by high-affinity interactions binding site residues which favour pocket stability. Conclusions and Implications Our findings, identified Geranyl benzoate compound reported for the first time in ethanolic leaf extracts of SM and 1,2BAB-2-MPE as potential anti-filoviral candidate against Marburg viruses VP35. Our study may provide insights further developed 1,2BAB-2-MPE and /or SM leaf extracts as a therapeutic agent against Marburg viruses

The catastrophe of hypoxia in complex aortic surgery

Measuring the particle mixing parameters at multi positions in three-dimensional fluidized beds continuously remains a challenging task. A novel measurement method for the mixing and segregation of particles inside three-dimensional fluidized beds is developed based on capacitance probe. The measurement error is generally below 7%. The particle mixing parameters and dispersion coefficients at multi-positions of the three-dimensional fluidized bed are acquired. The effect of convection and diffusion mechanism on particle mixing is discussed. Results show that the governing mechanism of particle mixing at center and top of the bed is convection; meanwhile the governing mechanism for particle mixing at bottom and near the wall is diffusion. The radial dispersion coefficient at half-radius of the bed is mainly between 0.0038 and 0.026 m2/s, which is about 1.5 times that near the wall. The axial dispersion coefficient is mainly between 0.004-0.056 m2/s, which is about 2.3 times that in radial direction.

A rapid and convenient strategy to monitor the productivity of biomanufacturing is essential for the research in optimizing relevant bioprocesses. In this work, we have developed a fluorescein-derived probe (FL-DT) that reacts rapidly with thiol groups via 1, 4-Micheal addition reaction of the sulfhydryl to unsaturated ketone and releases fluorescence. FL-DT specifically forms fluorescent adduct with two adjacent thiols in a protein of interest (POI), making the probe a reliable tool for protein quantification. The production of xylanase fused with a short di-Cys tag was then successfully monitored and quantified with FL-DT in E. coli system under different protein expression conditions, providing useful information for optimizing the bioprocess. Our work provides a convenient and efficient strategy for POI labeling and monitoring bioproduction.

Background While open surgical repair continues to be the mainstay option for aortic arch reconstruction, the associated mortality, morbidity, and high turn-down rates have led to a need for the development of minimally invasive options for aortic arch repair. Though RELAY™ Branched (Terumo Aortic, Inchinnan, UK) represents a promising option for complex endovascular aortic arch repair, neurological complications remain a pertinent risk. Herein we seek to present multi-centre data from Europe documenting the neurological outcomes associated with RELAY™ Branched. Methods Prospective data collected between January 2019 and January 2022 associated with patients treated with RELAY™ single-, double-, and triple-branched endoprostheses from centres across Europe was retrospectively analysed with descriptive and distributive analysis. Follow up data from 30 days and 6-, 12-, and 24 months postoperatively was included. Patients follow up was evaluated for the onset of disabling stroke (DS) and non-disabling stroke (NDS). Results Technical success was achieved in 147 (99.3%) cases. Over 24 months period, in total, 6 (4.1%) patients suffered DS and 8 (5.4%) patients suffered NDS after undergoing aortic arch repair with RELAY™. All patients that developed postoperative DS had been treated with the double-branched RELAY™ endoprosthesis. Discussion The data presented herein demonstrates that RELAY™ Branched is associated with favourable neurological outcomes and excellent technical success rates. Key design features of the endoprosthesis and good perioperative management can contribute greatly to mitigating neurological complications following endovascular aortic arch repair.

Parkinson’s psychosis refers to psychotic symptoms such as illusions, hallucinations, and delusions that are frequently referred to as ‘positive,’ meaning a benefit. Quetiapine was the most commonly used initial atypical antipsychotic medicine for therapy, followed by Risperidone, Olanzapine, Aripiprazole, and other atypical antipsychotics. According to new research, Pimavanserin may surpass other therapy for older people with Parkinson’s disease (PD) psychosis. Pimavanserin is a powerful inverse agonist with a preference for 5-HT2A receptors over 5-HT2C receptors and no functional activity at a number of G-Protein coupled receptors GPRCs such as dopaminergic, muscarinic, adrenergic, and histaminergic receptors. Pimavanserin had a relative protective effect in 85 percent of the study group of PD patients living in the community.

Fluoroelastomer has received increasing attention for energetic materials application due to its high fluorine contents. Different contents of poly(VDF-ter-HFP- ter- TFE) terpolymer are added into Al/MnO2 nanothermite. The peak exothermic temperature of thermite reaction for Al/MnO2 system is about 554 oC with 1070 Jg-1 heat release. After adding terpolymer, it mainly exists in the gap among Al nanoparticles and MnO2 nanorods, and can react with Al and MnO2 at the range of 350 oC to 540 oC before the occurrence of thermite reaction. 10wt% terpolymer has relatively little effect on the thermite reaction, and for the samples with higher terpolymer content, more nanothermite components reacts with terpolymer at early stage. Ignition and combustion performance show terpolymer can reduce ignition energy threshold by up to 9.82% and increase combustion duration time at least several times. The potential reasons for above results are analyzed. This work can shed light on application of fluoroelastomer in energetic-materials.

Mapping the distribution of ticks and tick-borne pathogens linked to their molecular information from previously unexplored geographic areas provide valuable information about the cryptic tick fauna and their associated pathogens of zoonotic and veterinary importance. The present research was designed to investigate the epidemiologic and phylogenetic aspects of ticks and tick-borne pathogens infesting goats and sheep in the north and north-western territories of Pakistan. A total of 1587 ixodid ticks were collected from goat and sheep herds (n = 600). The collected ticks were taxonomically classified using morphological keys and the molecular markers 16S rRNA and COI. The presence of tick-borne pathogens in collected ticks was assessed by PCR targeting the genetic markers 16S rRNA and gltA for bacterial pathogens, and 18S rRNA for Apicomplexan parasites. The morpho-molecular characterization of hard ticks revealed three ixodid tick genera ( Hyalomma, Haemaphysalis, and Rhipicephalus) which included 11 tick species viz. Hy. anatolicum (5.9%) , Hy. dromedarii (9.1%), Hy. excavatum (2.8%), Hy. isacci (5.1%) , Hy. scupense (7.7%), Hae. montgomeryi (18.3%) , Hae. sulcata (6.5%), Rh. decoloratus (4.4%) , Rh. haemaphysaloides (13.2%) , Rh. microplus (10.8%) , and Rh. turanicus (16.2%). Amplified tick 16S rRNA and COI nucleotide sequences shared 99.74-100% similarity and clustered phylogenetically with similar tick species reported previously in China, India, Iran, Saudi Arabia, Sri Lanka, South Africa, Turkey, and Pakistan. The 16S rRNA , 18S rRNA and gltA nucleotide sequences of detected tick-borne pathogens, including R. massiliae (24.5%) followed by T. ovis (16.4%), A. capra (9.1%), T. luwenshuni (6.4%), A. ovis (5.9%), R. hoogstraalii, (5.0%), Anaplasma spp. (4.5%), Ehrlichia spp. (4.5%), Rickettsia spp. (4.5%), T. annulata (4.1%) and A. marginale (3.6%), shared 99.48-100% similarity and grouped with sequences previously reported in South Asia, middle east Africa and USA. This study showed for the first time the presence of two tick ( Hae. montgomeryi and R. decoloratus) and one tick-borne pathogen species ( R. hoogstraali) in Pakistan. Our results are the first available reports documenting important ticks and tick-borne pathogens of veterinary and public health concern from previously neglected parts of Pakistan. These results could be used as a baseline to facilitate future large-scale epidemiological and molecular studies about ticks and tick-borne pathogens of small ruminants at the local and global levels.

This study analyzed global data and provides insights how economic conditions in various countries associate with epidemic control measures during different epidemic periods by mutant strains. In this study, the elasticity coefficient is estimated through a log-log model, which represents the percent change of the confirmed case number with respect to a percent change of the total number of screening tests in a country for epidemic control. The elasticity estimate was used to show the effectiveness of epidemic control by community screening. The 7-day rolling data of screening tests and confirmed cases from the Our World in Data (OWID) database for the pandemic periods of Alpha strain in 2020, Delta strain in 2021, and Omicron strain in 2022, suggests that the magnitude of the elasticity was associated with the economic condition of a country. Compared with the result s during either Alpha - or Delta- pandemic period, the Omicron pandemic has a much higher estimated elasticity coefficient of 1.317 (Alpha: 0.827 and Delta: 0.885). Further comparison of economic conditions that were classified by quartile ranges, the result reveals the elasticity in countries with GDP per capita between $11,354 and $26,651 or GDP per capita above $26,651 is statistically significantly lower than that in countries having GDP per capita below $3,335. The findings of this study imply that the performance of epidemic control in a country is not only dependent on epidemiological measures applied, but is also influenced by the economic condition of a country.

One of greatest common main cancerous tumor of the brain in adults is glioblastoma, which is fatal without treatment. For individuals diagnosed having glioblastoma, typical gold level treatment consists of surgical removal of the tumor supported by radiation treatment plus concurrent chemotherapy drugs. Despite this, overall, prognostic level is still dismal; approximately 12-to 15-month life expectancy is typical. Cell signaling, angiogenesis, Gene mutation have all been highlighted as promising areas to explore in the lookout for potential treatments, thanks to years of study. The pathophysiology of glioblastoma is now much more complicated due to new discoveries of extrachromosomal DNA (ecDNA). Numerous oncogenes found within those ecDNAs, which seem to be important driving therapeutic resistance, faster tumor progression and intra-tumoral heterogeneity, are also found in cancer cells nucleus, where their genome size is noticeably larger. Existing knowledge regarding therapy significance, tumor growth and ecDNA synthesis in glioblastoma will indeed be reviewed in this article.

Competition and indirect ELISAs are currently being used to monitor rabbit hemorrhagic disease viruses (RHDV1 and RHDV2) in rabbits worldwide. Temporal changes in the sensitivity (Se) and specificity (Sp) of assays were investigated using Bayesian Latent Class models (BCLM) in the Australian wild rabbit population where both viruses circulate simultaneously and a long-term serological dataset exists. When cELISA1 was compared to IgG1 ELISA, the Se of cELISA1 improved while the Sp of IgG1 ELISA declined over the 2011-2021. This corresponded with a decline in the true RHDV1 prevalence in 2018-21, suggesting that a large proportion of RHDV1 exposed rabbits survived the introduction and dominance of RHDV2 up to approximately 2017/2018, after which they died and were not replaced. The Se and Sp estimates for 2014-15 for both cELISA1 and IgG1 ELISA, and the true prevalence when analysing all three tests together were similar to those obtained from the analysis of cELISA1/IgG1. The same was also true for the Se and Sp of cELISA2 and IgG1 estimates from 2018 onwards. This suggests that RHDV1 was the dominant infection status in 2014-15, but RHDV2 was the dominant infection status in 2018-2021. Further, the increase in Se of cELISA2 and the low Sp of IgG1 ELISA in the cELISA2/IgG1 ELISA analysis, compared to the Se of cELISA2 and Sp of IgG1 ELISA when analysing all three tests together suggests that the underlying infection status was more influenced by RHDV2 and that the higher Se of IgG1 ELISA is due to cross-reaction of RHDV2 antibodies on IgG1 ELISA. The true prevalence data suggests that RHDV2 exposure peaked in 2017. Our findings show that test characteristics changed in response to the changing virus prevalences over time. IgG1 ELISA currently has a high Se, should be used to monitor both viruses and will perform better than both cELISAs.

Many of the microorganisms that compose the microbiome of human are favorable or even helpful to the host's health, and this group play a crucial part in the body's physiological functioning. A number of microorganisms, meanwhile, have been related with cancer and other disorders defined mostly by abnormal inflammation and are thus thought to be harmful to human welfare. Cancer is only one of several diseases that may develop as a result of dysbiosis, a microbiological disequilibrium in which hazardous bacteria species compete effectively harmless bacteria. The skin microbiome, the urogenital microbiome and the gut microbiome, are especially clearly defined, although the microbial diversity differs between body locations. Nevertheless, there is little knowledge about the human microbiome and about the way, it relates to both healthy and diseased breasts. According to a variety of research, breast tissue has a unique microbiome, with certain types being elevated in the tissue alone; along with in the gut and nipple aspirate microorganism of the breast cancer patients. In addition, the breast microbiome and its surroundings can influence the treatment reaction and function as conceivable biomarkers in the detection and evaluation of breast cancer at any stage.

14-years old asymptomatic boy with holosystolic murmur heard over the lower left sternal border. Zoomed apical 5 chamber view revealed a perimembranous ventricular septal defect (VSD) which was closed by an aneurysmal leaflet of the tricuspid valve (TV) (Figure A) .Color Doppler across the defect showed left to right shunt (Figure B) Short axis view at the level of the aortic valve showed that VSD was extending from 10 to 11 o’clock . (Figure C). Injection of bubbles showed negative contrast inside the right ventricle indicating incomplete defect closure. (Figure D) 3D Transesophageal Echocardiography (TOE) with zoomed mode showed the entry point from the left ventricular side and exit point from the right ventricular side.(Figure E) En-face viewing of the TV from the right ventricular perspective showed an aneurysm-like pouch formed by the anterior leaflet (Figure F) The left atrial and ventricular size was normal and the shunt ratio was 1.3 so he was treated conservatively. Ventricular septal defect is the most common congenital anomaly.The incidence of spontaneous closure is still undetermined .Different mechanisms for anatomical closure have been proposed such as the adherence of the septal leaflet and/or the anterior leaflet of the tricuspid valve to the margins of the defect forming an aneurysm-like pouch that maybe mistaken for an aneurysm of the membranous septum. Echocardiography is the gold standard for evaluation of the site , size and type of VSD and its relation to the tricuspid valve. Recently, transcatheter closure is feasible and efficacious in properly selected patients.

Background: Coronary artery fistula (CAF) is a congenital connection between a coronary artery and cardiac chambers, or a vessel bypassing a capillary system. The clinical presentation of congenital CAF varies, depending on its size and the draining chamber. Case presentation: A 23-year-old patient without a prior medical history consulted to cardiology clinic with a referral diagnosis of interatrial septal aneurysm and defect. Transthoracic echocardiography revealed a dilated right coronary artery to a sac into the right atrium with dilated right side of the heart. Transesophageal echocardiography provided the calculation of the narrowest part of the fistula where the closure device was planned to be deployed, and two sequential sacs of the fistula on its way to the right atrium. Cardiac computed tomography demonstrated the aneurysmatic dilatation of the proximal portion of the right coronary artery (CA) was 14*20 mm and the narrowest exit of the CAF as 8*8.3 mm width. transcatheter closure of an isolated enormous CAF was decided and surgery left to be reserved for CAF with failed percutaneous closure. Conclusion: Multi-modality imaging take part in the diagnosis and follow-up of the CAFs for identifying the anatomy/physiology, guiding the intervention, supplementary hemodynamic information, assessing the anatomical relationship and ischemia.

Abernethy malformation, also known as congenital extrahepatic shunt, is a rare anomaly characterized by partial or complete diversion of the portal blood into the systemic venous circulation. The clinical manifestations of Abernethy malformation during childhood include neonatal cholestasis, failure to thrive, mental retardation, and other congenital defects. We report a case of Abernethy malformation Type Ⅱ in a 9-year-old boy whose left ventricle was slightly enlarged because of several major aortopulmonary collateral arteries but normal laboratory examinations five years earlier. The characteristics of congenital heart disease in patients with Abernethy malformation are discussed. We propose that enlargement of the left ventricular with systemic-pulmonary collateral circulation should raise the suspicion of Abernethy malformation.

Physical parameters representing the energy components of the cardiac pump related to inertance, resistance, and compliance are developed. The martingale optimality principle and the Malliavin calculus are used to estimate these time-varying parameters. The methods are applied to the ejection phase of the cardiac cycle, using pressure and flow measured at the root of the aorta for the left ventricle. We find the compliance parameter to be in general agreement with data reported by others, but our resistive parameter differs considerably and has a value commensurate with the expected efficiency of the cardiac pump. The inertance parameter, not represented in models reported by others, is shown to be of significance and may contribute to differences in values of the other parameters.

Increases in critical land in the Bengawan Solo River Basin contribute to floods and severe damage to infrastructures along the river channel. Additionally, the occurrence of excessive erosion is a source of sediment materials, especially at meandering sections. Riverbank erosion destabilises dykes and sediment deposition decrease capacity, thereby resulting in floods (especially during rainy seasons). Although both phenomena can be evaluated by observing flow velocity and sediment concentration, there is a paucity of field investigations on parameters that affect erosion under dry and rainy seasons. This study investigates the aforementioned parameters and contrasts circumstances during dry and rainy seasons by presenting relevant information on sediment quantity and flow velocity. The results indicate that sediment concentration at the outer banks of the flow path significantly exceeds that at the inner banks, thereby indicating significant occurrence of erosion. Further examination of riverbed material suggests that the interaction between sediment concentration and flow velocity, especially in meandering segments, can provide an estimate of the erosion rate and the change in the morphology of the alluvial river. Sediment concentration is correlated with seasonal conditions such that sediment concentration during the rainy season is approximately five times that in the dry season. This clarifies that more significant river morphology changes occur during peak seasons. Further, the results of the study can be used in river dynamic process prediction, especially in alluvial streams or in soft soil with properties similar to that of alluvial streams.

In this paper, the differentiability on time and continuity on fractional order of solutions for a class of Caputo fractional evolution equations are studied. Under appropriate assumptions, the existence and differentiability on time of solutions for linear as well as semilinear Caputo fractional evolution equations are analyzed, the continuity of solutions on fractional order for linear and semilinear Caputo fractional evolution equations are discussed. In addition, if the fractional order converges to $1$, then the solutions of the Caputo fractional differential equations become the solutions of classic evolution equations. The continuity of solutions on fractional order for some fractional systems is numerically studied, and the results are basically consistent with the theoretical results.

Distributed order fractional differential equations are efficient in describing physical phenomena because of the differential order distribution. In this paper, the distributed order time-fractional reaction-diffusion equation is considered in the sense of Caputo fractional derivative. A hybrid method is developed based on the Moving Kriging (MK) interpolation and finite difference method for solving this distributed order equation. First, the distributed integral is discretized by the $M$-point Gauss Legendre quadrature rule. Then, the $L2-1_{\sigma}$ method is applied to approximate the solution of the fractional derivative discretization. Also, the unconditionally stability and rate of convergence $O(\tau^{2})$ of the time-discrete technique are illustrated. Furthermore, the MK interpolation is applied in the space variables discretization. Finally, some examples are presented to indicate the efficiency of this method and endorsement the theoretical results.

In this paper, Rational Bernstein polynomials on the semi-infinite interval are adapted to solve a Magnetohydrodynamic (MHD) problem. Also, the derivative, product, convert, and Galerkin Exact Operational Matrices (EOMs) of these polynomials are produced. Using the spectral Galerkin method and the Exact Operational Matrices (EOMs) of Rational Bernstein polynomials, we solve the problem with high accuracy and speed. The problem is the flow of MHD micropolar over a moving plate with suction and injection boundary conditions. Comparing the results of the Rational Bernstein Galerkin method with operational matrices and without operational matrices shows that the present method is faster than another method. Also, comparing the results of the Rational Bernstein Galerkin method and Rational Gegenbauer Tau method shows that the present method is more accurate than another method.

The most common pediatric extragonadal pelvic cancers include germ cell tumors, sacrococcygeal teratomas, and rhabdomyosarcomas (arising from the urinary bladder, prostate, paratesticular tissues, vagina, uterus, and perineum). This manuscript describes the radiological and nuclear medicine features of these entities and provides consensus-based recommendations for the assessment at diagnosis, during and after treatment.