Chronic respiratory diseases have collectively become a major public health concern and have now taken form as one of the leading causes of mortality worldwide. Most chronic respiratory diseases primarily occur due to prolonged airway inflammation. In addition, critical environmental factors such as cigarette smoke, industrial pollutants, farm dust, and pollens may also exacerbate such diseases. Moreover, alterations in the genetic sequence of an individual, abnormalities in the chromosomes or immunosuppression resulting from bacterial, fungal, and viral infections may also play a key role in the pathogenesis of respiratory diseases. Over the years, multiple in vitro models have been employed as the basis of existing as well as emerging advancements in chronic respiratory disease research. These include cell lines, gene expression techniques, single cell RNA sequencing, cytometry, culture techniques, as well as serum/sputum biomarkers that can be used to elucidate the molecular mechanisms underlying these diseases, and to identify novel diagnostic and management options for these diseases. This review summarizes the current understanding of the pathogenesis of various chronic respiratory diseases derived through in vitro experimental models, where the knowledge obtained from these studies can greatly benefit researchers in the discovery and development of novel screening techniques and advanced therapeutic strategies that could be translated into clinical use in the future.
Parkinson's disease is the second most common neurodegenerative condition with its prevalence projected to 8.9 million individuals globally in the year 2019. Parkinson's disease affects both motor and certain non-motor functions of an individual. Numerous research has focused on the neuroprotective effect of the glial cell line-derived neurotrophic factor (GDNF) in Parkinson's disease. Discovered in 1993, GDNF is a neurotrophic factor identified from the glial cells which was found to have selective effects on promoting survival and regeneration of certain populations of neurons including the dopaminergic nigrostriatal pathway. Given this property, recent studies have focused on the exogenous administration of GDNF for relieving Parkinson's disease-related symptoms both at a pre-clinical and a clinical level. This review will focus on enumerating the molecular connection between Parkinson's disease and GDNF and shed light on all the available drug delivery approaches to facilitate the selective delivery of GDNF into the brain paving the way as a potential therapeutic candidate for Parkinson's disease in the future.
In the current scenario, alternative energy sources are the need of the hour. Organic wastes having a larger fraction of biodegradable constituents present a sustainable bioenergy source. It has been reported that the calorific value of biogas generated by anaerobic digestion (AD) is 21-25 MJ/m3 with the treatment which makes it an excellent replacement of natural gas and fossil fuels and can reduce more than 80% greenhouse gas emission to the surroundings. However, there are some limitations associated with the AD process for instance ammonia build-up at the first stage reduces the rate of hydrolysis of biomass, whereas, in the last stage it interferes with methane formation. Owing to special physicochemical properties such as high activity, high reactive surface area, and high specificity, tailor-made conductive nanoparticles can improve the performance of the AD process. In the AD process, H2 is used as an electron carrier, referred as mediated interspecies electron transfer (MIET). Due to the diffusion limitation of these electron carriers, the MIET efficiency is relatively low that limits the methanogenesis. Direct interspecies electron transfer (DIET), which enables direct cell-to-cell electron transport between bacteria and methanogen, has been considered an alternative efficient approach to MIET that creates metabolically favorable conditions and results in faster conversion of organic acids and alcohols into methane. This paper discusses in detail the application of conductive nanoparticles to enhance the AD process efficiency. Interaction between microbes in anaerobic conditions for electron transfer with the help of CNPs is discussed. Application of a variety of conductive nanomaterials as an additive is discussed with their potential biogas production and treatment enhancement in the anaerobic digestion process.
Tinospora crispa is a medicinal plant belonging to the botanical family Menispermiaceae. The plant is widely distributed in Southeast Asia and the northeastern region of India. A related species Tinospora cordifolia is used in Ayurveda for treating a large spectrum of diseases. Traditional healers of Thailand, Malaysia, Guyana, Bangladesh and the southern Indian province of Kerala use this plant in the treatment of diabetes. Many diterpenes, triterpenes, phytosteroids, alkaloids and their glycosides have been isolated from T. crispa. Cell culture and animal studies suggest that the herb stimulates secretion of insulin from β-cells. It also causes dose-dependent and time-dependent enhancement of glucose uptake in muscles. However, in view of the reported hepatotoxicity, this herb may be used with caution. This article reviews the animal studies and human clinical trials carried out using this herb. Areas of future research are also identified.
The extensive development in the strains of resistant bacteria is a potential hazard to public health worldwide. This necessitates the development of newer agents with the antibacterial property having new mechanisms of action. Mur enzymes catalyze the steps related to the biosynthesis of peptidoglycan, which constitutes a major part of the cell wall in bacteria. Peptidoglycan increases the stiffness of the cell wall, helping it to survive in unfavorable conditions. Therefore, the inhibition of Mur enzymes may lead to novel antibacterial agents that may help in controlling or overcoming bacterial resistance. Mur enzymes are classified into MurA, MurB, MurC, MurD, MurE, and MurF. Until-date, multiple inhibitors are reported for each class of the Mur enzymes. In this review, we have summarized the development of Mur enzyme inhibitors as antibacterial agents in the last few decades.
This paper focuses on examining the ‘cutting zone temperature’ while performing turning operation
on AZ91Mg alloy using cemented carbide tools. The regression model is developed by using the RSM
techniques based on experimental results. It is revealed that the cutting speed (v) is the most dominant
factor affecting cutting zone temperature. The developed models of cutting zone temperature sufficiently
map within the range of the turning conditions considered. The adequacy and accuracy of the regression
equation is justified through ANOVA. It is found that the optimal combinations of machining parameters
minimize the cutting temperature.
Diabetic retinopathy (DR) is a leading cause of blindness among working-age adults. Early diagnosis through effective screening programs is likely to improve vision outcomes. The ETDRS seven-standard-field 35-mm stereoscopic color retinal imaging (ETDRS) of the dilated eye is elaborate and requires mydriasis, and is unsuitable for screening. We evaluated an image analysis application for the automated diagnosis of DR from non-mydriatic single-field images. Patients suffering from diabetes for at least 5 years were included if they were 18 years or older. Patients already diagnosed with DR were excluded. Physiologic mydriasis was achieved by placing the subjects in a dark room. Images were captured using a Bosch Mobile Eye Care fundus camera. The images were analyzed by the Retinal Imaging Bosch DR Algorithm for the diagnosis of DR. All subjects also subsequently underwent pharmacological mydriasis and ETDRS imaging. Non-mydriatic and mydriatic images were read by ophthalmologists. The ETDRS readings were used as the gold standard for calculating the sensitivity and specificity for the software. 564 consecutive subjects (1128 eyes) were recruited from six centers in India. Each subject was evaluated at a single outpatient visit. Forty-four of 1128 images (3.9%) could not be read by the algorithm, and were categorized as inconclusive. In four subjects, neither eye provided an acceptable image: these four subjects were excluded from the analysis. This left 560 subjects for analysis (1084 eyes). The algorithm correctly diagnosed 531 of 560 cases. The sensitivity, specificity, and positive and negative predictive values were 91%, 97%, 94%, and 95% respectively. The Bosch DR Algorithm shows favorable sensitivity and specificity in diagnosing DR from non-mydriatic images, and can greatly simplify screening for DR. This also has major implications for telemedicine in the use of screening for retinopathy in patients with diabetes mellitus.
A search is presented for supersymmetric partners of the top quark (top squarks) in final states with two oppositely charged leptons (electrons or muons), jets identified as originating from b quarks, and missing transverse momentum. The search uses data from proton-proton collisions at s = 13 TeV collected with the CMS detector, corresponding to an integrated luminosity of 137 fb - 1 . Hypothetical signal events are efficiently separated from the dominant top quark pair production background with requirements on the significance of the missing transverse momentum and on transverse mass variables. No significant deviation is observed from the expected background. Exclusion limits are set in the context of simplified supersymmetric models with pair-produced lightest top squarks. For top squarks decaying exclusively to a top quark and a lightest neutralino, lower limits are placed at 95 % confidence level on the masses of the top squark and the neutralino up to 925 and 450 GeV , respectively. If the decay proceeds via an intermediate chargino, the corresponding lower limits on the mass of the lightest top squark are set up to 850 GeV for neutralino masses below 420 GeV . For top squarks undergoing a cascade decay through charginos and sleptons, the mass limits reach up to 1.4 TeV and 900 GeV respectively for the top squark and the lightest neutralino.
A search for dark matter particles is performed using events with a Z boson candidate and large missing transverse momentum. The analysis is based on proton-proton collision data at a center-of-mass energy of 13 Te , collected by the CMS experiment at the LHC in 2016-2018, corresponding to an integrated luminosity of 137 fb - 1 . The search uses the decay channels Z → e e and Z → μ μ . No significant excess of events is observed over the background expected from the standard model. Limits are set on dark matter particle production in the context of simplified models with vector, axial-vector, scalar, and pseudoscalar mediators, as well as on a two-Higgs-doublet model with an additional pseudoscalar mediator. In addition, limits are provided for spin-dependent and spin-independent scattering cross sections and are compared to those from direct-detection experiments. The results are also interpreted in the context of models of invisible Higgs boson decays, unparticles, and large extra dimensions.
A search for charged Higgs bosons produced in vector boson fusion processes and decaying into vector bosons, using proton-proton collisions at s = 13 TeV at the LHC, is reported. The data sample corresponds to an integrated luminosity of 137 fb - 1 collected with the CMS detector. Events are selected by requiring two or three electrons or muons, moderate missing transverse momentum, and two jets with a large rapidity separation and a large dijet mass. No excess of events with respect to the standard model background predictions is observed. Model independent upper limits at 95% confidence level are reported on the product of the cross section and branching fraction for vector boson fusion production of charged Higgs bosons as a function of mass, from 200 to 3000 GeV . The results are interpreted in the context of the Georgi-Machacek model.
A search is presented for a heavy vector resonance decaying into a Z boson and the standard model Higgs boson, where the Z boson is identified through its leptonic decays to electrons, muons, or neutrinos, and the Higgs boson is identified through its hadronic decays. The search is performed in a Lorentz-boosted regime and is based on data collected from 2016 to 2018 at the CERN LHC, corresponding to an integrated luminosity of 137 fb - 1 . Upper limits are derived on the production of a narrow heavy resonance Z ' , and a mass below 3.5 and 3.7 Te is excluded at 95% confidence level in models where the heavy vector boson couples predominantly to fermions and to bosons, respectively. These are the most stringent limits placed on the Heavy Vector Triplet Z ' model to date. If the heavy vector boson couples exclusively to standard model bosons, upper limits on the product of the cross section and branching fraction are set between 23 and 0.3 fb for a Z ' mass between 0.8 and 4.6 Te , respectively. This is the first limit set on a heavy vector boson coupling exclusively to standard model bosons in its production and decay.
The first search for scalar leptoquarks produced in τ-lepton-quark collisions is presented. It is based on a set of proton-proton collision data recorded with the CMS detector at the LHC at a center-of-mass energy of 13 TeV corresponding to an integrated luminosity of 138 fb^{-1}. The reconstructed final state consists of a jet, significant missing transverse momentum, and a τ lepton reconstructed through its hadronic or leptonic decays. Limits are set on the product of the leptoquark production cross section and branching fraction and interpreted as exclusions in the plane of the leptoquark mass and the leptoquark-τ-quark coupling strength.
A search for nonresonant Higgs boson (H) pair production via gluon and vector boson (V) fusion is performed in the four-bottom-quark final state, using proton-proton collision data at 13 TeV corresponding to 138 fb^{-1} collected by the CMS experiment at the LHC. The analysis targets Lorentz-boosted H pairs identified using a graph neural network. It constrains the strengths relative to the standard model of the H self-coupling and the quartic VVHH couplings, κ_{2V}, excluding κ_{2V}=0 for the first time, with a significance of 6.3 standard deviations when other H couplings are fixed to their standard model values.
A search for long-lived particles (LLPs) produced in decays of standard model (SM) Higgs bosons is presented. The data sample consists of 137 fb^{-1} of proton-proton collisions at sqrt[s]=13 TeV, recorded at the LHC in 2016-2018. A novel technique is employed to reconstruct decays of LLPs in the end cap muon detectors. The search is sensitive to a broad range of LLP decay modes and to masses as low as a few GeV. No excess of events above the SM background is observed. The most stringent limits to date on the branching fraction of the Higgs boson to LLPs subsequently decaying to quarks and τ^{+}τ^{-} are found for proper decay lengths greater than 6, 20, and 40 m, for LLP masses of 7, 15, and 40 GeV, respectively.
A search for dark matter in events with a displaced nonresonant muon pair and missing transverse momentum is presented. The analysis is performed using an integrated luminosity of 138 fb^{-1} of proton-proton (pp) collision data at a center-of-mass energy of 13 TeV produced by the LHC in 2016-2018. No significant excess over the predicted backgrounds is observed. Upper limits are set on the product of the inelastic dark matter production cross section σ(pp→A^{'}→χ_{1}χ_{2}) and the decay branching fraction B(χ_{2}→χ_{1}μ^{+}μ^{-}), where A^{'} is a dark photon and χ_{1} and χ_{2} are states in the dark sector with near mass degeneracy. This is the first dedicated collider search for inelastic dark matter.
A search for the standard model (SM) Higgs boson (H) produced with transverse momentum (p_{T}) greater than 450 GeV and decaying to a charm quark-antiquark (cc[over ¯]) pair is presented. The search is performed using proton-proton collision data collected at sqrt[s]=13 TeV by the CMS experiment at the LHC, corresponding to an integrated luminosity of 138 fb^{-1}. Boosted H→cc[over ¯] decay products are reconstructed as a single large-radius jet and identified using a deep neural network charm tagging technique. The method is validated by measuring the Z→cc[over ¯] decay process, which is observed in association with jets at high p_{T} for the first time with a signal strength of 1.00_{-0.14}^{+0.17}(syst)±0.08(theo)±0.06(stat), defined as the ratio of the observed process rate to the SM expectation. The observed (expected) upper limit on σ(H)B(H→cc[over ¯]) is set at 47 (39) times the SM prediction at 95% confidence level.
A search for the standard model Higgs boson decaying to a charm quark-antiquark pair, H→cc[over ¯], produced in association with a leptonically decaying V (W or Z) boson is presented. The search is performed with proton-proton collisions at sqrt[s]=13 TeV collected by the CMS experiment, corresponding to an integrated luminosity of 138 fb^{-1}. Novel charm jet identification and analysis methods using machine learning techniques are employed. The analysis is validated by searching for Z→cc[over ¯] in VZ events, leading to its first observation at a hadron collider with a significance of 5.7 standard deviations. The observed (expected) upper limit on σ(VH)B(H→cc[over ¯]) is 0.94 (0.50_{-0.15}^{+0.22})pb at 95% confidence level (C.L.), corresponding to 14 (7.6_{-2.3}^{+3.4}) times the standard model prediction. For the Higgs-charm Yukawa coupling modifier, κ_{c}, the observed (expected) 95% C.L. interval is 1.1
We present the first direct search for exotic Higgs boson decays H→AA, A→γγ in events with two photonlike objects. The hypothetical particle A is a low-mass spin-0 particle decaying promptly to a merged diphoton reconstructed as a single photonlike object. We analyze the data collected by the CMS experiment at sqrt[s]=13 TeV corresponding to an integrated luminosity of 136 fb^{-1}. No excess above the estimated background is found. We set upper limits on the branching fraction B(H→AA→4γ) of (0.9-3.3)×10^{-3} at 95% confidence level for masses of A in the range 0.1-1.2 GeV.
Breast cancer (BC) is one of the most challenging cancers to treat, accounting for many cancer-related deaths. Over some years, chemotherapy, hormone treatment, radiation, and surgeries have been used to treat cancer. Unfortunately, these treatment options are unsuccessful due to crucial adverse reactions and multidrug tolerance/resistance. Although it is clear that substances in the nutraceuticals category have a lot of anti-cancer activity, using a supplementary therapy strategy, in this case, could be very beneficial. Nutraceuticals are therapeutic agents, which are nutrients that have drug-like characteristics and can be used to treat diseases. Plant nutraceuticals categorized into polyphenols, terpenoids, vitamins, alkaloids, and flavonoids are part of health food products, that have great potential for combating BC. Nutraceuticals can reduce BC's severity, limit malignant cell growth, and modify cancer-related mechanisms. Nutraceuticals acting by attenuating Hedgehog, Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), Notch, and Wnt/β-catenin signaling are the main pathways in controlling the self-renewal of breast cancer stem cells (BCSCs). This article reviews some important nutraceuticals and their modes of action, which can be very powerful versus BC. PRACTICAL APPLICATIONS: Nutraceuticals' importance to the control and diagnosis of breast cancer is undeniable and cannot be overlooked. Natural dietary compounds have a wide range of uses and have been used in traditional medicine. In addition, these natural chemicals can enhance the effectiveness of other traditional medicines. They may also be used as a treatment process independently because of their capacity to affect several cancer pathways. This study highlights a variety of natural chemicals, and their mechanisms of action, routes, synergistic effects, and future potentials are all examined.
More than 10 million people worldwide have Alzheimer's disease (AD), a degenerative neurological illness and the most prevalent form of dementia. AD's progression in memory loss, cognitive deterioration, and behavioral changes are all symptoms. Amyloid-beta 42 (Aβ42), the hyperphosphorylated forms of microtubule-associated tau protein, and other cellular and systemic alterations are all factors that contribute to cognitive decline in AD. Rather than delivering a possible cure, present therapy strategies focus on reducing disease symptoms. It has long been suggested that various naturally occurring small molecules (plant extract products and microbiological isolates, for example) could be beneficial in preventing or treating disease. Small compounds, such as flavonoids, have attracted much interest recently due to their potential to alleviate cellular stress. Flavonoids have been proven helpful in various ways, including antioxidants, anti-inflammatory agents, and anti-apoptotic agents, but their mechanism remains unknown. The flavonoid therapy of Alzheimer's disease focuses on this review, which includes a comprehensive literature analysis.