In this task, you're given a paragraph and title from the research paper. Your task is to classify whether the given title is suitable or not for the research paper based on the given paragraph. Return "True" if title is proper according to paragraph else "False".
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Question: Paragraph: was first discovered in 2012. MERS-CoV can infect multiple host species and cause severe diseases in human. We conducted a series of phylogenetic and bioinformatic analyses to study the evolution dynamics of MERS-CoV among different host species with genomic data. Our analyses show: 1) 28 potential recombinant sequences were detected and they can be classified into seven potential recombinant types; 2) The spike (S) protein of MERS-CoV was under strong positive selection when Middle East Respiratory Syndrome coronavirus (MERS-CoV) is a novel beta-coronavirus with high pathogenicity, which imposes a serious threat to human health 1 . Substantial evidence has showed that MERS-CoVs have existed in central and east Africa for decades 2,3 , and have many natural hosts including two species of bats (Neoromicia capensis and Vespertilio superans), dromedary camel (Camelus dromedarius), and European hedgehog (Erinaceus europaeus) 4-7 . Yet it seemed that human MERS-CoV first isolated in Saudi Arabian in 2012, and then spread among humans worldwide 8 . Studies of prototype human MERS-CoV also suggested that the tMRCA (the time of most recent common ancestor) of human MERS-CoV can be traced back to about 2011 9 . Because the genome sequence of bat MERS-CoV is highly identical to that of human MERS-CoV, it has been indicated that human MERS-CoV might have a bat origin 10 , while there is also some evidence of camel-to-human MERS-CoV transmission 11,12 . Together, these studies proposed that zoonotic event may play a nontrivial part in MERS-CoV evolution and transmission. Previous studies showed that recombination was common among the members of beta-coronavirus 13,14 . By joining the previously unlinked DNA, recombination event can create new viral strains which may be capable of infecting new hosts and evading host's immuno-responses. The phylogenetic analysis showed that there were two main MERS-CoV clades-clade A and B, and clade B can be further divided into five phylogenetic groups 15 . There is evidence that recombination event had happened between group III and group V 15 . However, whether there was potential recombination event happened between the other groups or among multiple phylogenetic groups remains unclear. The genome of MERS-CoV is over 30,000 nucleotides (nt) in length, which contains seven predicted open reading frames (ORFs) and four structural genes-spike (S), envelope (E), membrane (M), and nucleocapsid (N) 16 (supplementary Fig. 1c ). The surface located spike (S) protein of beta-coronaviruses is one of the major determinants in their cross-species transmission because it mediates the virus-receptor recognition and thereby activates viral infection process 17 . Additionally, the receptor binding domain (RBD) on S protein's N-terminal is the key element for beta-coronavirus entering into host cells and the mutations in coronavirus's RBD affects its infection and cross-species capability 18, 19 . For example, the study of the spike protein from severe acute respiratory syndrome coronavirus (SARS-CoV), another beta-coronavirus with high pathogenicity, revealed four amino 
 Title: Evolutionary Dynamics of MERS- CoV: Potential Recombination, Positive Selection and Transmission OPEN

Answer: False


Question: Paragraph: Apelin is an inotropic and cardioprotective peptide that exhibits beneficial effects through activation of the APJ receptor in the pathology of cardiovascular diseases. Apelin induces the expression of angiotensin-converting enzyme 2 (ACE2) in failing hearts, thereby improving heart function in an angiotensin 1-7-dependent manner. Whether apelin antagonizes the over-activation of the renin-angiotensin system in the heart remains elusive. In this study we show that the detrimental effects of angiotensin II (Ang II) were exacerbated in the hearts of aged apelin-gene-deficient mice. Ang II-mediated cardiac dysfunction and hypertrophy were augmented in apelin knockout mice. The loss of apelin increased the ratio of angiotensin-converting enzyme (ACE) to ACE2 expression in the Ang II-stressed hearts, and Ang II-induced cardiac fibrosis was markedly enhanced in apelin knockout mice. mRNA expression of pro-fibrotic genes, such as transforming growth-factor beta (TGF-β) signaling, were significantly upregulated in apelin knockout hearts. Consistently, treatment with the ACE-inhibitor Captopril decreased cardiac contractility in apelin knockout mice. In vitro, apelin ameliorated Ang II-induced TGF-β expression in primary cardiomyocytes, accompanied with reduced hypertrophy. These results provide direct evidence that endogenous apelin plays a crucial role in suppressing Ang II-induced cardiac dysfunction and pathological remodeling. Int. J. Mol. Sci. 2019, 20, 239 2 of 12 dysfunctions [8, 10, 11] . By contrast, APJ was identified as a dual receptor to mediate cardiac hypertrophy [12, 13] via β-arrestin signaling [14, 15] . Thus, the precise role of endogenous apelin signaling in heart function remains elusive. Cardiac hypertrophy is an adaptive response to maintain cardiac function in the event of an increased workload, although prolonged cardiac hypertrophy can lead to heart failure via the ischemia of cardiomyocytes [16, 17] . In addition, cardiac fibrosis adversely increases tissue stiffness and impairs ventricular function. Consistently, cardiac hypertrophy and the development of fibrosis correlate with the deterioration of myocardial function in heart failure [18] [19] [20] . Thus, cardiac hypertrophy and fibrosis are key features of heart failure, and apelin's inotropic and protective roles in the heart are attractive as a potential therapeutic candidate for treating heart failure. Apelin has also been identified as a substrate for angiotensin-converting enzyme 2 (ACE2), which cleaves apelin with similar efficiency as its primary substrate angiotensin II (Ang II) [21] [22] [23] . ACE2 is a negative regulator of the renin-angiotensin system (RAS) that inactivates Ang II by converting it to angiotensin 1-7 (Ang 1-7) [21] [22] [23] , whereas angiotensin-converting enzyme 1 (or ACE1) activates RAS by converting Ang I to Ang II. ACE2 was also identified as a regulator of heart failure [24-26], diabetic nephropathy [27, 28] , acute lung failure [29, 30] , and the SARS (severe acute respiratory syndrome) coronavirus receptor [31, 32] . Apelin-APJ signaling has been shown to counteract the effects of Ang II on AT1R in defined physiological and pathophysiological settings. For instance, in hypertensive rat models, the continuous infusion of Ang II downregulates apelin and APJ expression [33] . We have shown that Apelin upregulates ACE2 expression. Apelin-induced ACE2 downregulates Ang II signaling while enhancing Ang 1-7-Mas receptor signaling in aged or failing hearts [34] . On the other hand, it has been suggested that the counter-balancing effects of the apelin-APJ axis on Ang II-AT1R signaling are mediated by receptor dimerization. The APJ receptor physically interacts with AT1 receptors, and exogenous apelin negatively regulates Ang II-AT1R signaling in in vitro cell culture systems and in an in vivo atherosclerosis model [35] . However, whether endogenous apelin counteracts the over-activation of RAS in the heart remains unexplored. In this study, we aimed to determine the effects of endogenous apelin on Ang II-induced pathology in the heart. We showed that Ang II-mediated cardiac dysfunction, hypertrophy, and fibrosis were augmented in apelin knockout (Apelin KO) mice. 
 Title: Loss of Apelin Augments Angiotensin II-Induced Cardiac Dysfunction and Pathological Remodeling

Answer: True


Question: Paragraph: this work presents a simple one-pot protocol to achieve core-doped shell nanohybrids comprising silver nanoparticles, curcumin and thermoresponsive polymeric shell taking advantage of the reducing properties of phenolic curcumin substance and its ability to decorate metallic surfaces. Silver nanoparticles were synthesized, via sodium citrate and silver nitrate addition into a boiling aqueous solution of curcumin, monomers and surfactant. curcumin and sodium citrate promoted silver nucleation, acting as reducing and stabilizing agents. these curcumin-capped Agnps enabled, after adding the radical polymerization initiator, the assembling of the growing polymer chains around the hydrophobic Agnp surface. the resultant core-doped shell nanohybrids exhibit plasmonic, luminescent and volume thermoresponsive properties, with improved possibilities to be used as successful therapeutic platforms. In fact, the possibility to nanoconfine the synergistic antioxidant, antiviral, antibacterial features of silver and curcumin in one bioavailable hybrid paves the way to promising applications in the biomedical field. The exciting electronic, optical, catalytic and antimicrobial properties of metal NPs can be stymied by their tendency to aggregate. To overcome this issue and provide metallic nanoparticles with additional features, the hybridization with polymeric materials is a successful strategy. In this regard, polymer micro/nanogels exhibit high colloidal stability, great versatility in their chemical and topological composition, drug loading and functionalization capabilities 1 that make them unique vehicles and reservoirs for metal nanoparticles 2,3 . Additionally, the permeability of the gel-system coating allows a controlled loading and release of bioactive molecules and drugs. Furthermore, polymer microgels are frequently used as nanoreactors for the in situ synthesis of metallic NPs 4 , and small particles decorating the microgel are successfully formed 5 . However, the control over the metallic NP structure and distribution is rather difficult. Core-shell hybrid nanogels usually face metal@polymer nanohybrid synthesis from a different point of view; and the most reported protocols are based on the polymer self-assembling around a preformed metal NP. The ligand exchange using polymers with functional groups able to attach the metal NP is a successful approach to attain thin polymer shells 6 . However to achieve polymer coating with tunable thickness, polymerization in heterogeneous media, as free radical precipitation polymerization (FRPP) is the most widely choice 7,8 . Since this technique relies on the precipitation of water insoluble growing polymer chain, a previous surface preparation of metal NP is required. Note that the organic polymer is not compatible with the anionic citrate ligand, commonly used to synthesize metal NPs, in aqueous medium 9,10 . Therefore a variety of strategies can be found in the literature, mainly for gold 7, 8, [11] [12] [13] [14] [15] , whereas works focused on achieving silver@polymer core-shell nanogels are scarce; despite the reliable properties of silver NPs in applications as ultrasensitive analysis of molecules through Surface Enhanced Raman Spectroscopy (SERS) 2,16 , catalysis 17 , cancer cell imaging 16,18 and other applications related to their antimicrobial properties 19 . Recently, we developed one-step protocol supporting core-shell hybrid nanogel synthesis, regardless of the monomer polarity. The strategy was based on the use of hydrophobic thiolated methacrylate monomer as compatible bridge between the as-synthesized Au@citrate surface and the growing polymer chains 14 . The modification of the metal surface with the hydrophobic compound led to effective polymer self-assembling around the inorganic core. Thus, we envisioned, in this work, that hydrophobic molecules as curcumin (Fig. 1A) , having a two-fold function, as reducing agent in silver NP synthesis as well as diminishing the interfacial energy between the growing polymer chain and the metallic surface, might trigger the core-shell hybrid NP assembly. Previous backgrounds evidenced the curcumin ability to reduce Ag + and Au 3+ ions to silver 20-22 and gold 23 nanoparticles, without any other additional reductant or in the presence of citrate and CTBA to modulate NP shape 24 . Thus, Kundu and Nithiyanantham 20 , in a pioneer work, were able to synthesize different shapes of AgNP (spheres, nanowires and anisotropic nanoflakes) by tuning the molar ratio of curcumin to AgNO 3 . Nevertheless, even though the reductant ability of curcumin has been already reported, it should be noted that, as far as we know, none has postulated that hydrophobic curcumin presence nearby metal surface may facilitate polymer self-assembling during post-crosslinking polymerization. In addition, by considering the antioxidant properties of this natural phenolic compound, our curcumin-promoted Ag@nanogel hybrid system will state a double benefit arising from the biomedical properties of curcumin itself, as antibacterial, self-healing 25,26 , antiviral 27 and anti-inflammatory 28 ; and from the antibacterial 19 synergistic effect and remarkable antiviral 29 activity of particles comprising silver nanoparticles and curcumin in one hybrid. Moreover, encapsulation of curcumin in the hydrophobic polymer shell will increase curcumin bioavailability protecting curcumin from hydrolytic degradation 30 , since this is the main limitation for its therapeutic applications. experimental Materials. The monomer 2-(2-methoxyethoxy)ethyl methacrylate (MEO 2 MA) (Aldrich 95%) was purified by passing through a neutral alumina column. Tetraethylene glycol dimethacrylate (TEGDMA) (≥90%), trisodium citrate dihydrate (≥98%) and silver nitrate (AgNO 3 ) (99.99%) were purchased from Aldrich. Sodium dodecyl sulfate (SDS) (≥97%) and ammonium persulfate (APS) (>98%), were purchased from Fluka. Curcumin (≥98%) was obtained from Acros Organics. All chemical reagents were employed as received. The solvents used, ethanol and water, were analytical and Milli-Q grade, respectively. 
 Title: curcumin to promote the Synthesis of Silver nps and their Self- Assembly with a thermoresponsive polymer in core-Shell nanohybrids

Answer:
True