Miracle-dz/UniFAR-FTUs huggingface dataset:
Critical role of E6 oncoprotein in cervical cancer: involved in cell proliferation, angiogenesis and apoptosis

Cervical cancer represents one of the most common malignancies in women worldwide and predominantly affects women of poor socioeconomic status. Persistent infection with high-risk human papilloma virus (HPV) is an essential factor for development of cervical cancer. The advent of functional genomics and proteomics has provided hope of discovering novel biological markers for use in the screening, early diagnosis, prognostication and prediction of response to therapy. E6 and E7 oncoproteins of HPV have been known to play major roles in malignant transformation of cervical cells. Accumulating evidences have suggested that E6 oncoprotein may also contribute to cervical carcinogenesis through modulating cellular signaling pathways. Multiple mechanisms, including activation of EGFR or inflammatory cell signaling pathway, have been implicated in malignant transformation by HPV. Therefore, targeting E6 may be a rational approach for chemoprevention and treatment of cervical cancer, and understanding its oncogenic processes may help us to design novel therapeutic strategies. In this review, we discussed the roles of E6 oncoprotein in cervical carcinogenesis, altering several cellular signaling pathways involved in cell proliferation, angiogenesis and apoptosis.
Role of P-glycoprotein in region-specific gastrointestinal absorption of talinolol in rats

P-glycoprotein (PGP) is non-uniformly distributed along the gastro-intestinal (GI) tract; however, the data regarding regional differences in PGP function in the intestine are controversial. The aim of this work is to investigate the role of PGP efflux in region-specific absorption of talinolol from the GI tract in rats. Plasma talinolol concentrations were measured following several modes of administration, including high (40 mg/kg) and low (4 mg/kg) dose levels, to different segments of the GI tract (stomach vs. colon), and co-dosing with PGP inhibitors (verapamil or cyclosporine A). The bioavailability (F) of talinolol following high dose administration to the stomach was significantly greater than that achieved by the low dose (about 18% vs. 2%). Co-administration of low dose talinolol with cyclosporine increased F by about 5-fold (p<0.01). For the high dose, co-dosing with PGP inhibitors did not increase the extent of absorption. Talinolol demonstrated poor colonic absorption that was significantly increased by co-administration with cyclosporine (F = 0.76% vs. 8.1%). Oral verapamil significantly increased systemic clearance and the steady state volume of distribution of intravenous talinolol. A semi-physiological model was developed that successfully captured the pharmacokinetic profiles of talinolol following various modes of administration. PGP-mediated efflux appears to be a major factor responsible for GI region-specific absorption of talinolol in rats and gastro-retentive dosage forms may provide an advantage in the delivery of talinolol and PGP substrate drugs. groups were conducted using the two tailed t-test. A p-value of less than 0.05 was considered statistically significant. Data are presented as mean±SEM, unless stated otherwise.
Silencing of Ago-2 Interacting Protein SERBP1 Relieves KCC2 Repression by miR-92 in Neurons

RNA-binding proteins (RBPs) play important roles in modulating miRNA-mediated mRNA target repression. Argonaute2 (Ago2) is an essential component of the RNA-induced silencing complex (RISC) that plays a central role in silencing mechanisms via small non-coding RNA molecules known as siRNAs and miRNAs. Small RNAs loaded into Argonaute proteins catalyze endoribonucleolytic cleavage of target RNAs or recruit factors responsible for translational silencing and mRNA target destabilization. In previous studies we have shown that KCC2, a neuronal Cl (−) extruding K (+) Cl (−) co-transporter 2, is regulated by miR-92 in neuronal cells. Searching for Ago2 partners by immunoprecipitation and LC-MS/MS analysis, we isolated among other proteins the Serpine mRNA binding protein 1 (SERBP1) from SH-SY5Y neuroblastoma cells. Exploring the role of SERBP1 in miRNA-mediated gene silencing in SH-SY5Y cells and primary hippocampal neurons, we demonstrated that SERBP1 silencing regulates KCC2 expression through the 3′ untranslated region (UTR). In addition, we found that SERBP1 as well as Ago2/miR-92 complex bind to KCC2 3′UTR. Finally, we demonstrated the attenuation of miR-92-mediated repression of KCC2 3′UTR by SERBP1 silencing. These findings advance our knowledge regarding the miR-92-mediated modulation of KCC2 translation in neuronal cells and highlight SERBP1 as a key component of this gene regulation.
Combination of daratumumab and doxorubicin loaded polycaprolactone nanoparticles in the treatment of diffuse large B-cell lymphoma

Aim: The purpose of this study is to evaluate the activity of daratumumab in combination with polycaprolactone (PCL) nanoparticles (NPs) for decreasing toxicity and enhancing the anticancer efficiency of doxorubicin (Dox) for diffuse large B-cell lymphoma (DLBCL). Material and Methods: Polycaprolactone nanoparticles were developed using double emulsion technique. For characterization of blank and doxorubicin loaded PCL nanoparticles; particle size, polydispersity index and surface charge were determined. Cell culture study was realized to conclude the cytotoxicity of Dox-loaded PCL NPs alone or combination with Daratumumab. Results: Blank and Dox-loaded PCL nanoparticles remained within 235 nm and 250 nm, respectively. Zeta potential values were -3.9 and -13.3 mV for blank and Dox-loaded PCL nanoparticles, respectively. In cell culture study, whole formulations showed a timedependent model; the cytotoxicity enhanced with the increase of incubation time. Blank nanoparticles have no toxicity; cell viability was above 85%. Dox-loaded nanoparticles showed more toxicity to A20 cells than Dox solution. Dox-loaded NPs in combination Daratumumab exhibited higher cell toxicity than Dox-loaded NPs and mAb solution, respectively (P < 0.05). Conclusion: Dox-loaded PCL nanoparticles in combination with antibody-targeted chemotherapy could be a considered as promising synergistic strategy for controlling tumor growth by increasing the antitumor efficacy while minimizing toxicity.
SPRR 3 , a novel miR ‐ 338 ‐ 3 p target , regulates the malignant progression of clear cell renal cell carcinoma in vitro via the PI 3 K / Akt signaling pathway

Clear cell renal cell carcinoma (ccRCC) is the most common type of renal cell carcinoma and has a poor prognosis. However, its underlying mechanisms remain unclear. The present study aimed to evaluate the role of small proline‐rich repeat protein 3 (SPRR3) in the proliferation, migration and invasion of ccRCC cells and to investigate its upstream and downstream regulatory mechanisms. Survival analysis was performed using the UALCAN website based on the The Cancer Genome Atlas database. Normal renal cell line HK‐2 and ccRCC cell lines (786‐O, CaKi‐1 and UMRC‐2) were used. Reverse transcription‐quantitative PCR (RT‐qPCR) was used to detect mRNA and microRNA (miRNA) levels. Western blotting was used to detect protein levels. Cell Counting Kit‐8 and colony formation assays, a wound healing assay and a Transwell invasion assay were used to assess the prolif‐ eration, migration and invasion of ccRCC cells, respectively. Transfection of overexpression plasmids and small interfering RNAs were used to upregulate and knockdown SPRR3 expres‐ sion, respectively. Transfection of miRNA‐mimics was used to overexpress miR‐338‐3p. A luciferase reporter gene assay was used to verify the predicted binding relationship between SPRR3 mRNA and miR‐338‐3p. The results indicated the following: i) SPRR3 was a risk factor for the survival of patients with ccRCC, and was upregulated in ccRCC cell lines; ii) SPRR3 promoted the proliferation, migration and invasion of ccRCC cells; iii) SPRR3 regulated the tumor phenotypes of ccRCC cells via the PI3K/Akt pathway; iv) miR‐338‐3p directly targeted SPRR3 mRNA and negatively regulated SPRR3 expression; and v) miR‐338‐3p inhibited the PI3K/Akt pathway and the tumor phenotypes of ccRCC cells by down‐ regulating SPRR3. In conclusion, SPRR3, as a novel target of miR‐338‐3p, regulated the proliferation, migration and inva‐ sion of ccRCC cells via the PI3K/Akt pathway; this finding not only enriches our understanding of the mechanism underlying ccRCC development, but also demonstrates a potential novel therapeutic target for this disease.
Learning From the von Kármán Vortex Street

With the recent success of deep learning algorithms, there has been a re-emergence of applying deep learning techniques to partial differential equations (PDEs). Much of the recent work has been focused on learning solutions to PDEs given training data and the general form of the PDE. One largely unexplored area is learning the parameterization of PDEs when provided information about their solutions. In this work, data from simulations of Navier-Stokes fluid flow equations are used to infer the Reynolds number that would parameterize the PDE. Fluid flow around a cylinder creates a wake, known as the von Kármán vortex street, in which different structures form depending on the Reynolds number. Using multi-layer perceptrons and convolutional neural networks these structures are used to determine the Reynolds number governing the fluid flow system. Additionally, the structures found in the von Kármán vortex street are used to determine the location of objects in the fluid flow. In this case, two cylinders are placed in different locations upstream of an observer in an area unseen by the deep learning methods. The deep learning methods take solution data from the area downstream of these objects and use the information to infer an (x,y) coordinate for each object with respect to a global coordinate system. This thesis shows that deep learning algorithms can successfully learn the parameterization of the Navier-Stokes equations from the von Kármán vortex street and predict object locations with a high accuracy.
Antitumor activity of the dual PI3K/mTOR

The phosphatidylinositol 3‐kinase/mammalian target of rapamycin (PI3K/mTOR) signaling pathway is a therapeutic target for various types of human tumors, and dual PI3K/mTOR inhibitors demonstrate antitumor activities in both preclinical and clinical studies. However, resistance mechanisms limit their abilities. As the molecular mechanisms involved in the cellular resistance are not clear in any canine tumors, an understanding of resistance mechanisms would support the potential use of dual PI3K/mTOR inhibitors in canine tumors. The antitumor activity of gedatolisib on cell viability, protein phosphorylation, and cell cycle distribution was assessed using 12 canine tumor cell lines from 6 types of tumors. In addition, the molecular deter‐ minants involved in the cellular sensitivity to gedatolisib were explored by investigating the involvement of serum‐and‐gluco‐ corticoid‐induced kinase 1 (SGK1), PIK3CA, and ATP‐binding cassette, subfamily B, member 1 (ABCB1). The results demon‐ strated that gedatolisib decreased cell viability in all cell lines, with IC50 values <1 μM in 10 of the 12 lines. Gedatolisib inhib‐ ited Akt and mTOR complex 1 substrate phosphorylation and induced G0/G1 cell cycle arrest. However, certain cell lines with higher IC50 values were more resistant to these effects. These cell lines exhibited higher ABCB1 activity and the ABCB1 inhibitor cyclosporin A enhanced the decrease of cell viability caused by gedatolisib. SGK1 overexpression did not confer resistance to gedatolisib. The mutations of E545K and H1047R in PIK3CA were not observed. The present results indicated that gedatolisib decreased cell viability in canine tumor cell lines and ABCB1 played an important role in gedatolisib resistance, supporting the potential use of gedatolisib for canine tumors.
Coagulopathy and Fibrinolytic Pathophysiology in COVID-19 and SARS-CoV-2 Vaccination

Coronavirus Disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is frequently complicated by thrombosis. In some cases of severe COVID-19, fibrinolysis may be markedly enhanced within a few days, resulting in fatal bleeding. In the treatment of COVID-19, attention should be paid to both coagulation activation and fibrinolytic activation. Various thromboses are known to occur after vaccination with SARS-CoV-2 vaccines. Vaccine-induced immune thrombotic thrombocytopenia (VITT) can occur after adenovirus-vectored vaccination, and is characterized by the detection of anti-platelet factor 4 antibodies by enzyme-linked immunosorbent assay and thrombosis in unusual locations such as cerebral venous sinuses and visceral veins. Treatment comprises high-dose immunoglobulin, argatroban, and fondaparinux. Some VITT cases show marked decreases in fibrinogen and platelets and marked increases in D-dimer, suggesting the presence of enhanced-fibrinolytic-type disseminated intravascular coagulation with a high risk of bleeding. In the treatment of VITT, evaluation of both coagulation activation and fibrinolytic activation is important, adjusting treatments accordingly to improve outcomes.
Reproduction of small ruminants in extreme environments

Small ruminants are undemanding species and highly adaptable to various environmental conditions. For this reason, they are widely distributed around the world, finding herds from sea level to 5000 meters of altitude, in hot and cold climates, as well as in semi-desert or rainy regions. Despite its adaptive capacity, exposure to extreme environments such as high altitudes and the sub-Antarctic cold climate, negatively influence its reproductive efficiency. In this article we review the most important effects of these extreme conditions on various reproductive variables in small domestic ruminants, analyzing some mechanisms that mediate these effects, as well as an alternative approach aimed to improving reproductive efficiency under these environments.
Self-Propelled Pre-Biased Synchronous Charge Extraction Circuit for Triboelectric Nanogenerator

Triboelectric nanogenerators (TENGs) are suitable for harvesting ambient mechanical energy to increase the battery life of the Internet of Things (IoT) devices. Energy extraction circuits (EECs) are required as an interface between TENG and the onboard battery load to rectify and improve the energy transfer efficiency. Here, for the first time, a novel “self-propelled pre-biased synchronous charge extraction (spSCE)” EEC is presented with theoretical analysis as well as experimental results. The proposed EEC offers a universal plug-and-play solution for any TENG operating under any ambient vibration, due to its self-propelled switching feature. In addition, its inbuilt pre-biasing (precharging of TENG capacitor at the operation extremes) action enhances the net transduced energy from the mechanical source beyond the per-cycle energy limit for any non-pre-biasing EEC set by the existing synchronous charge extraction (SCE) circuit. Accounting for the energy costs of spSCE actions, our experiments validated 119.7% (resp., 163.7%) energy gain over the SCE circuit at a load of 5 V (resp., 15 V).
Is there an optimum internal diameter for subway tunnels in terms of economic and technical viewpoints?

Subways, one of the most popular modes of the rapid transit systems, play an important role in maintaining the sustainability of transportation in large metropolitan areas. This study focuses on the optimum dimension of the internal diameter of subway tunnels that creates a space for train passage that is large enough to preventing collisions with electromechanical and wayside facilities and emergency walkways and is small enough to minimize costs. The discussion hinges around how a train in the worst-case situation of a super-elevated track with a minimum curve radius can pass through a tunnel equipped with wayside facilities without any accidents while satisfying all the economic aspects of the project. Limiting the speed of a train in response to the confined area between a train’s dynamic envelope and emergency walkways leads to extended travel times, excess wear on the wheel and rail and even changes in the amount of electricity consumed by the train. All the mentioned factors result in an operational cost and the total cost is achieved by summing up this cost and the construction costs for different tunnel diameters. An economic analysis is performed by comparing the costs of construction and operation for different tunnels against the benefits of passenger revenues. Generating net-present-value diagrams for tunnels with different internal diameters as a function of time shows that a double-tracked single-tube tunnel with an 8.40-m internal diameter is the optimum from both an economic point of view and being able to match technical specifications.
Pharmacological Inhibition of Glutaminase 1 Attenuates Alkali-Induced Corneal Neovascularization by Modulating Macrophages

Corneal neovascularization (CoNV) in response to chemical burns is a leading cause of vision impairment. Although glutamine metabolism plays a crucial role in macrophage polarization, its regulatory effect on macrophages involved in chemical burn-induced corneal injury is not known. Here, we elucidated the connection between the reprogramming of glutamine metabolism in macrophages and the development of alkali burn-induced CoNV. Glutaminase 1 (GLS1) expression was upregulated in the mouse corneas damaged with alkali burns and was primarily located in F4/80-positive macrophages. Treatment with a selective oral GLS1 inhibitor, CB-839 (telaglenastat), significantly decreased the distribution of polarized M2 macrophages in the alkali-injured corneas and suppressed the development of CoNV. In vitro studies further demonstrated that glutamine deprivation or CB-839 treatment inhibited the proliferation, adhesion, and M2 polarization of bone marrow-derived macrophages (BMDMs) from C57BL/6J mice. CB-839 treatment markedly attenuated the secretion of proangiogenic factors, including vascular endothelial growth factor-A (VEGF-A) and platelet-derived growth factor-BB (PDGF-BB) from interleukin-4- (IL-4-) regulated M2 macrophages. Our findings revealed that GLS1 inhibition or glutamine deprivation prevented alkali-induced CoNV by inhibiting the infiltration and M2 polarization of macrophages. This work suggests that pharmacological GLS1 inhibition is a feasible and effective treatment strategy for chemical burn-related CoNV in humans.
Some numerical radius inequality for several semi-Hilbert space operators

The paper deals with the generalized numerical radius of linear operators acting on a complex Hilbert space , which are bounded with respect to the seminorm induced by a positive operator A on . Here A is not assumed to be invertible. Mainly, if we denote by and the generalized and the classical numerical radii respectively, we prove that for every A-bounded operator T we have where is the Moore-Penrose inverse of . In addition, several new inequalities involving for single and several operators are established. In particular, by using new techniques, we cover and improve some recent results due to Najafi [Linear Algebra Appl. 2020;588:489–496].
Formulation of Entomopathogenic Nematode, Steinernema kushidai, their Survival and Infectivity

The commercialization and large-scale use of EPNs are limited by their short shelf life in formulations and in storage, thus leading to poor quality and reduced efficacy against insects in the field. This study explored the effects of some formulations on survival and infectivity of infective juveniles (IJs) of entomopathogenic nematodes , Steinernema kushidai at 5 and 25°C for 6 weeks. In the formulations, the survival and virulence rate differed at different temperature with decrease over the period of time. The alginate retained most of the IJs and can be stored for a longer time at 5°C followed by sawdust formulation . From the economic point of view sawdust formulation shows better results.
The Economics of Non-Fungible Tokens

We construct a comprehensive dataset on a near universe of non-fungible token (NFT) transactions, create indices for the NFT market and its components, and analyze their properties. The NFT market return is significantly exposed to the cryptocurrency market return, but the majority of the NFT market variations remain unexplained. NFT market returns have low exposures to other cryptocurrency factors and factors from traditional asset markets. In the time-series, volatility and the NFT valuation ratio significantly predict NFT market returns. In the cross-section, NFT returns exhibit size and return reversal effects. *Nicola Borri is with LUISS University, Rome. Yukun Liu is with the Univeristy of Rochester, Simon Business School. Aleh Tsyvinski is with Yale University and NES. We thank Stefano Giglio, Giuseppe Moscarini, and Wei Xiong for helpful comments. Disclosure Statement: Nicola Borri I have nothing to disclose. Disclosure Statement: Yukun Liu I have nothing to disclose. Disclosure Statement: Aleh Tsyvinski I have nothing to disclose.
Increased Attack Rates and Decreased Incubation Periods in Raccoons with Chronic Wasting Disease Passaged through Meadow Voles

Chronic wasting disease (CWD) is a naturally-occurring neurodegenerative disease of cervids. Raccoons (Procyon lotor) and meadow voles (Microtus pennsylvanicus) have previously been shown to be susceptible to the CWD agent. To investigate the potential for transmission of the agent of CWD from white-tailed deer to voles and subsequently to raccoons, we intracranially inoculated raccoons with brain homogenate from a CWD-affected white-tailed deer (CWDWtd) or derivatives of this isolate after it had been passaged through voles 1 or 5 times. We found that passage of the CWDWtd isolate through voles led to a change in the biologic behavior of the CWD agent, including increased attack rates and decreased incubation periods in raccoons. A better understanding of the dynamics of cross-species transmission of CWD prions can provide insights into how these infectious proteins evolve in new hosts.