In this research, we characterized the histopathological impact of dengue virus (serotype DENV-2) infection in livers of BALB/c mice. The mice were infected with different doses of DENV-2 via intraperitoneal injection and liver tissues were processed for histological analyses and variation was documented. In the BALB/c mouse model, typical liver tissues showed regular hepatocyte architecture, with normal endothelial cells surrounding sinusoid capillary. Based on histopathological observations, the liver sections of BALB/c mice infected by DENV-2 exhibited a loss of cell integrity, with a widening of the sinusoidal spaces. There were marked increases in the infiltration of mononuclear cells. The areas of hemorrhage and micro- and macrovesicular steatosis were noted. Necrosis and apoptosis were abundantly present. The hallmark of viral infection, i.e., cytopathic effects, included intracellular edema and vacuole formation, cumulatively led to sinusoidal and lobular collapse in the liver. The histopathological studies on autopsy specimens of fatal human DENV cases are important to shed light on tissue damage for preventive and treatment modalities, in order to manage future DENV infections. In this framework, the method present here on BALB/c mouse model may be used to study not only the effects of infections by other DENV serotypes, but also to investigate the effects of novel drugs, such as recently developed nano-formulations, and the relative recovery ability with intact immune functions of host.
A main challenge in parasitology is the development of reliable tools to prevent or treat mosquito-borne diseases. We investigated the toxicity of magnetic nanoparticles (MNP) produced by Magnetospirillum gryphiswaldense (strain MSR-1) on chloroquine-resistant (CQ-r) and sensitive (CQ-s) Plasmodium falciparum, dengue virus (DEN-2), and two of their main vectors, Anopheles stephensi and Aedes aegypti, respectively. MNP were studied by Fourier-transform infrared spectroscopy and transmission electron microscopy. They were toxic to larvae and pupae of An. stephensi, LC50 ranged from 2.563 ppm (1st instar larva) to 6.430 ppm (pupa), and Ae. aegypti, LC50 ranged from 3.231 ppm (1st instar larva) to 7.545 ppm (pupa). MNP IC50 on P. falciparum were 83.32 μg ml(-1) (CQ-s) and 87.47 μg ml(-1) (CQ-r). However, the in vivo efficacy of MNP on Plasmodium berghei was low if compared to CQ-based treatments. Moderate cytotoxicity was detected on Vero cells post-treatment with MNP doses lower than 4 μg ml(-1). MNP evaluated at 2-8 μg ml(-1) inhibited DEN-2 replication inhibiting the expression of the envelope (E) protein. In conclusion, our findings represent the first report about the use of MNP in medical and veterinary entomology, proposing them as suitable materials to develop reliable tools to combat mosquito-borne diseases.
Human adipose-derived stem cells (hADSCs) are easily isolated from fat tissue without ethical concerns, but differ in purity, pluripotency, differentiation ability, and stem cell marker expression, depending on the isolation method. We isolated hADSCs from a primary fat tissue solution using: (1) conventional culture, (2) a membrane filtration method, (3) a membrane migration method where the primary cell solution was permeated through membranes, adhered hADSCs were cultured, and hADSCs migrated out from the membranes. Expression of mesenchymal stem cell markers and pluripotency genes, and osteogenic differentiation were compared for hADSCs isolated by different methods using nylon mesh filter membranes with pore sizes ranging from 11 to 80 μm. hADSCs isolated by the membrane migration method had the highest MSC surface marker expression and efficient differentiation into osteoblasts. Osteogenic differentiation ability of hADSCs and MSC surface marker expression were correlated, but osteogenic differentiation ability and pluripotent gene expression were not.
Camptothecin (CPT) is an anti-cancer drug that effectively treats various cancers, including colon cancer. However, poor solubility and other drawbacks have restricted its chemotherapeutic potential. To overcome these restrictions, CPT was encapsulated in CEF (cyclodextrin-EDTA-FE3O4), a composite nanoparticle of magnetic iron oxide (Fe3O4), and β-cyclodextrin was cross-linked with ethylenediaminetetraacetic acid (EDTA). This formulation improved CPT's solubility and bioavailability for cancer cells. The use of magnetically responsive anti-cancer formulation is highly advantageous in cancer chemotherapy. The chemical characterisation of CPT-CEF was studied here. The ability of this nano-compound to induce apoptosis in HT29 colon cancer cells and A549 lung cancer cells was evaluated. The dose-dependent cytotoxicity of CPT-CEF was shown using MTT. Propidium iodide and Annexin V staining, mitochondrial membrane depolarisation (JC-1 dye), and caspase-3 activity were assayed to detect apoptosis in CPT-CEF-treated cancer cells. Cell cycle analysis also showed G1 phase arrest, which indicated possible synergistic effects of the nano-carrier. These study results show that CPT-CEF causes a dose-dependent cell viability reduction in HT29 and A549 cells and induces apoptosis in colon cancer cells via caspase-3 activation. These data strongly suggest that CPT could be used as a major nanocarrier for CPT to effectively treat colon cancer.
Leptospirosis is a widespread zoonotic disease caused by pathogenic Leptospira species (Leptospiraceae). LipL32 is an abundant lipoprotein from the outer membrane proteins (OMPs) group, highly conserved among pathogenic and intermediate Leptospira species. Several studies used LipL32 as a specific gene to identify the presence of leptospires. This research was aimed to study the characteristics of LipL32 protein gene code, to fill the knowledge gap concerning the most appropriate gene that can be used as antigen to detect the Leptospira. Here, we investigated the features of LipL32 in fourteen Leptospira pathogenic strains based on comparative analyses of their primary, secondary structures and 3D modeling using a bioinformatics approach. Furthermore, the physicochemical properties of LipL32 in different strains were studied, shedding light on the identity of signal peptides, as well as on the secondary and tertiary structure of the LipL32 protein, supported by 3D modelling assays. The results showed that the LipL32 gene was present in all the fourteen pathogenic Leptospira strains used in this study, with limited diversity in terms of sequence conservation, hydrophobic group, hydrophilic group and number of turns (random coil). Overall, these results add basic knowledge to the characteristics of LipL32 protein, contributing to the identification of potential antigen candidates in future research, in order to ensure prompt and reliable detection of pathogenic Leptospira species.
Mosquito-borne diseases represent a deadly threat for millions of people worldwide. However, the use of synthetic insecticides to control Culicidae may lead to high operational costs and adverse non-target effects. Plant-borne compounds have been proposed for rapid extracellular synthesis of mosquitocidal nanoparticles. Their impact against biological control agents of mosquito larval populations has been poorly studied. We synthesized silver nanoparticles (AgNP) using the aqueous leaf extract of Mimusops elengi as a reducing and stabilizing agent. The formation of AgNP was studied using different biophysical methods, including UV-vis spectrophotometry, TEM, XRD, EDX and FTIR. Low doses of AgNP showed larvicidal and pupicidal toxicity against the malaria vector Anopheles stephensi and the arbovirus vector Aedes albopictus. AgNP LC50 against A. stephensi ranged from 12.53 (I instar larvae) to 23.55 ppm (pupae); LC50 against A. albopictus ranged from 11.72 ppm (I) to 21.46 ppm (pupae). In the field, the application of M. elengi extract and AgNP (10 × LC50) led to 100 % larval reduction after 72 h. In adulticidal experiments, AgNP showed LC50 of 13.7 ppm for A. stephensi and 14.7 ppm for A. albopictus. The predation efficiency of Gambusia affinis against A. stephensi and A. albopictus III instar larvae was 86.2 and 81.7 %, respectively. In AgNP-contaminated environments, predation was 93.7 and 88.6 %, respectively. This research demonstrates that M. elengi-synthesized AgNP may be employed at ultra-low doses to reduce larval populations of malaria and arbovirus vectors, without detrimental effects on predation rates of mosquito natural enemies, such as larvivorous fishes.
A search for new long-lived particles decaying to leptons is presented using proton-proton collisions produced by the LHC at √[s]=8 TeV. Data used for the analysis were collected by the CMS detector and correspond to an integrated luminosity of 19.7 fb(-1). Events are selected with an electron and muon with opposite charges that both have transverse impact parameter values between 0.02 and 2 cm. The search has been designed to be sensitive to a wide range of models with nonprompt e-μ final states. Limits are set on the "displaced supersymmetry" model, with pair production of top squarks decaying into an e-μ final state via R-parity-violating interactions. The results are the most restrictive to date on this model, with the most stringent limit being obtained for a top squark lifetime corresponding to cτ=2 cm, excluding masses below 790 GeV at 95% confidence level.
A study of vector boson scattering in pp collisions at a center-of-mass energy of 8 TeV is presented. The data sample corresponds to an integrated luminosity of 19.4 fb(-1) collected with the CMS detector. Candidate events are selected with exactly two leptons of the same charge, two jets with large rapidity separation and high dijet mass, and moderate missing transverse energy. The signal region is expected to be dominated by electroweak same-sign W-boson pair production. The observation agrees with the standard model prediction. The observed significance is 2.0 standard deviations, where a significance of 3.1 standard deviations is expected based on the standard model. Cross section measurements for W(±)W(±) and WZ processes in the fiducial region are reported. Bounds on the structure of quartic vector-boson interactions are given in the framework of dimension-eight effective field theory operators, as well as limits on the production of doubly charged Higgs bosons.
Results are presented of a search for a "natural" supersymmetry scenario with gauge mediated symmetry breaking. It is assumed that only the supersymmetric partners of the top quark (the top squark) and the Higgs boson (Higgsino) are accessible. Events are examined in which there are two photons forming a Higgs boson candidate, and at least two b-quark jets. In 19.7 fb-1 of proton-proton collision data at s=8 TeV, recorded in the CMS experiment, no evidence of a signal is found and lower limits at the 95% confidence level are set, excluding the top squark mass below 360 to 410 GeV, depending on the Higgsino mass.
Searches for the direct electroweak production of supersymmetric charginos, neutralinos, and sleptons in a variety of signatures with leptons and [Formula: see text], [Formula: see text], and Higgs bosons are presented. Results are based on a sample of proton-proton collision data collected at center-of-mass energy [Formula: see text] with the CMS detector in 2012, corresponding to an integrated luminosity of 19.5 [Formula: see text]. The observed event rates are in agreement with expectations from the standard model. These results probe charginos and neutralinos with masses up to 720 [Formula: see text], and sleptons up to 260 [Formula: see text], depending on the model details.
A search for narrow resonances in proton-proton collisions at sqrt[s]=13 TeV is presented. The invariant mass distribution of the two leading jets is measured with the CMS detector using a data set corresponding to an integrated luminosity of 2.4 fb^{-1}. The highest observed dijet mass is 6.1 TeV. The distribution is smooth and no evidence for resonant particles is observed. Upper limits at 95% confidence level are set on the production cross section for narrow resonances with masses above 1.5 TeV. When interpreted in the context of specific models, the limits exclude string resonances with masses below 7.0 TeV, scalar diquarks below 6.0 TeV, axigluons and colorons below 5.1 TeV, excited quarks below 5.0 TeV, color-octet scalars below 3.1 TeV, and W^{'} bosons below 2.6 TeV. These results significantly extend previously published limits.
The production cross sections of the B^{+}, B^{0}, and B_{s}^{0} mesons, and of their charge conjugates, are measured via exclusive hadronic decays in p+Pb collisions at the center-of-mass energy sqrt[s_{NN}]=5.02 TeV with the CMS detector at the CERN LHC. The data set used for this analysis corresponds to an integrated luminosity of 34.6 nb^{-1}. The production cross sections are measured in the transverse momentum range between 10 and 60 GeV/c. No significant modification is observed compared to proton-proton perturbative QCD calculations scaled by the number of incoherent nucleon-nucleon collisions. These results provide a baseline for the study of in-medium b quark energy loss in Pb+Pb collisions.
Results are presented from a search for new decaying massive particles whose presence is inferred from an imbalance in transverse momentum and which are produced in association with a single top quark that decays into a bottom quark and two light quarks. The measurement is performed using 19.7 fb^{-1} of data from proton-proton collisions at a center-of-mass energy of 8 TeV, collected with the CMS detector at the CERN LHC. No deviations from the standard model predictions are observed and lower limits are set on the masses of new invisible bosons. In particular, scalar and vector particles, with masses below 330 and 650 GeV, respectively, are excluded at 95% confidence level, thereby substantially extending a previous limit published by the CDF Collaboration.
The relative yields of ϒ mesons produced in pp and Pb-Pb collisions at sqrt[s_{NN}]=5.02 TeV and reconstructed via the dimuon decay channel are measured using data collected by the CMS experiment. Double ratios are formed by comparing the yields of the excited states, ϒ(2S) and ϒ(3S), to the ground state, ϒ(1S), in both Pb-Pb and pp collisions at the same center-of-mass energy. The double ratios, [ϒ(nS)/ϒ(1S)]_{Pb-Pb}/[ϒ(nS)/ϒ(1S)]_{pp}, are measured to be 0.308±0.055(stat)±0.019(syst) for the ϒ(2S) and less than 0.26 at 95% confidence level for the ϒ(3S). No significant ϒ(3S) signal is found in the Pb-Pb data. The double ratios are studied as a function of collision centrality, as well as ϒ transverse momentum and rapidity. No significant dependencies are observed.
The first study of charm quark diffusion with respect to the jet axis in heavy ion collisions is presented. The measurement is performed using jets with p_{T}^{jet}>60 GeV/c and D^{0} mesons with p_{T}^{D}>4 GeV/c in lead-lead (Pb-Pb) and proton-proton (pp) collisions at a nucleon-nucleon center-of-mass energy of sqrt[s_{NN}]=5.02 TeV, recorded by the CMS detector at the LHC. The radial distribution of D^{0} mesons with respect to the jet axis is sensitive to the production mechanisms of the meson, as well as to the energy loss and diffusion processes undergone by its parent parton inside the strongly interacting medium produced in Pb-Pb collisions. When compared to Monte Carlo event generators, the radial distribution in pp collisions is found to be well described by pythia, while the slope of the distribution predicted by sherpa is steeper than that of the data. In Pb-Pb collisions, compared to the pp results, the D^{0} meson distribution for 4
Using a data sample of proton-proton collisions at sqrt[s]=13 TeV, corresponding to an integrated luminosity of 140 fb^{-1} collected by the CMS experiment in 2016-2018, the B_{s}^{0}→X(3872)ϕ decay is observed. Decays into J/ψπ^{+}π^{-} and K^{+}K^{-} are used to reconstruct, respectively, the X(3872) and ϕ. The ratio of the product of branching fractions B[B_{s}^{0}→X(3872)ϕ]B[X(3872)→J/ψπ^{+}π^{-}] to the product B[B_{s}^{0}→ψ(2S)ϕ]B[ψ(2S)→J/ψπ^{+}π^{-}] is measured to be [2.21±0.29(stat)±0.17(syst)]%. The ratio B[B_{s}^{0}→X(3872)ϕ]/B[B^{0}→X(3872)K^{0}] is found to be consistent with one, while the ratio B[B_{s}^{0}→X(3872)ϕ]/B[B^{+}→X(3872)K^{+}] is two times smaller. This suggests a difference in the production dynamics of the X(3872) in B^{0} and B_{s}^{0} meson decays compared to B^{+}. The reported observation may shed new light on the nature of the X(3872) particle.
A search for resonancelike structures in the B_{s}^{0}π^{±} invariant mass spectrum is performed using proton-proton collision data collected by the CMS experiment at the LHC at sqrt[s]=8 TeV, corresponding to an integrated luminosity of 19.7 fb^{-1}. The B_{s}^{0} mesons are reconstructed in the decay chain B_{s}^{0}→J/ψϕ, with J/ψ→μ^{+}μ^{-} and ϕ→K^{+}K^{-}. The B_{s}^{0}π^{±} invariant mass distribution shows no statistically significant peaks for different selection requirements on the reconstructed B_{s}^{0} and π^{±} candidates. Upper limits are set on the relative production rates of the X(5568) and B_{s}^{0} states times the branching fraction of the decay X(5568)^{±}→B_{s}^{0}π^{±}. In addition, upper limits are obtained as a function of the mass and the natural width of possible exotic states decaying into B_{s}^{0}π^{±}.
A search for narrow resonances decaying to bottom quark-antiquark pairs is presented, using a data sample of proton-proton collisions at sqrt[s]=8 TeV corresponding to an integrated luminosity of 19.7 fb^{-1}. The search is extended to masses lower than those reached in typical searches for resonances decaying into jet pairs at the LHC, by taking advantage of triggers that identify jets originating from bottom quarks. No significant excess of events is observed above the background predictions. Limits are set on the product of cross section and branching fraction to bottom quarks for spin 0, 1, and 2 resonances in the mass range of 325-1200 GeV. These results improve on the limits for resonances decaying into jet pairs in the 325-500 GeV mass range.
The prompt D^{0} meson azimuthal anisotropy coefficients, v_{2} and v_{3}, are measured at midrapidity (|y|<1.0) in Pb-Pb collisions at a center-of-mass energy sqrt[s_{NN}]=5.02 TeV per nucleon pair with data collected by the CMS experiment. The measurement is performed in the transverse momentum (p_{T}) range of 1 to 40 GeV/c, for central and midcentral collisions. The v_{2} coefficient is found to be positive throughout the p_{T} range studied. The first measurement of the prompt D^{0} meson v_{3} coefficient is performed, and values up to 0.07 are observed for p_{T} around 4 GeV/c. Compared to measurements of charged particles, a similar p_{T} dependence, but smaller magnitude for p_{T}<6 GeV/c, is found for prompt D^{0} meson v_{2} and v_{3} coefficients. The results are consistent with the presence of collective motion of charm quarks at low p_{T} and a path length dependence of charm quark energy loss at high p_{T}, thereby providing new constraints on the theoretical description of the interactions between charm quarks and the quark-gluon plasma.
Three of the most significant measured deviations from standard model predictions, the enhanced decay rate for B→D^{(*)}τν, hints of lepton universality violation in B→K^{(*)}ℓℓ decays, and the anomalous magnetic moment of the muon, can be explained by the existence of leptoquarks (LQs) with large couplings to third-generation quarks and masses at the TeV scale. The existence of these states can be probed at the LHC in high energy proton-proton collisions. A novel search is presented for pair production of LQs coupled to a top quark and a muon using data at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 35.9 fb^{-1}, recorded by the CMS experiment. No deviation from the standard model prediction has been observed and scalar LQs decaying exclusively into tμ are excluded up to masses of 1420 GeV. The results of this search are combined with those from previous searches for LQ decays into tτ and bν, which excluded scalar LQs below masses of 900 and 1080 GeV. Vector LQs are excluded up to masses of 1190 GeV for all possible combinations of branching fractions to tμ, tτ and bν. With this analysis, all relevant couplings of LQs with an electric charge of -1/3 to third-generation quarks are probed for the first time.