Several factors exist that limit the efficacy of lung cancer treatment. These may be tumor-specific delivery of therapeutics, airway geometry, humidity, clearance mechanisms, presence of lung diseases, and therapy against tumor cell resistance. Advancements in drug delivery using nanotechnology based multifunctional nanocarriers, have emerged as a viable method for treating lung cancer with more efficacy and fewer adverse effects. This review does a thorough and critical examination of effective nano-enabled approaches for lung cancer treatment, such as nano-assisted drug delivery systems. In addition, to therapeutic effectiveness, researchers have been working to determine several strategies to produce nanotherapeutics by adjusting the size, drug loading, transport, and retention. Personalized lung tumor therapies using sophisticated nano modalities have the potential to provide great therapeutic advantages based on individual unique genetic markers and disease profiles. Overall, this review provides comprehensive information on newer nanotechnological prospects for improving the management of apoptosis in lung cancer.
The decoction of the whole plant of Enhydra fluctuans is used ethno medicinally by various tribes for the treatment of kidney stones and urinary problems. However, no scientific studies were carried out to delineate its influence on urinary stone formation and crystallisation. Hence, the present study is proposed to investigate the effect of the aqueous extract of Enhydra fluctuans extract on in vitro crystallisation of calcium oxalate. The present study also evaluated. in silico studies of the metabolites with the target proteins present in the renal calcium oxalate stone matrix. The plant material was subjected to decoction to obtain an aqueous extract. The effect of the extract on calcium oxalate crystallization was evaluated by in vitro nucleation and aggregation assays. Further, the metabolites present in E. fluctuans were mined from the existing literature and their number was found to be 35. The selected 35 metabolites of E. fluctuans were subjected to molecular docking with the 5 proteins which are known to be responsible for calcium oxalate crystal growth. Results of in vitro studies indicated that the extract (50, 100, and 200 μg/mL) and standard drug cystone (1,000 μg/mL) exhibited an inhibitory role in the nucleation process where the percentage inhibitions were 52.69, 43.47, 21.98, and 31.67 μg/mL respectively. The results of molecular docking studies revealed that 2 out of 35 metabolites i.e. Baicalein-7-O-diglucoside and 4',5,6,7-Tetrahydroxy-8-methoxy isoflavone-7-O-beta-D- galactopyranosyl-(1→3)-O-beta-D-xylopyranosyl-(1→4)- O-alpha-L-rhamnopyranoside showed modulatory effects on the four renal stone matrix-associated protein (Human CTP: Phosphoethanolamine Cytidylyltransferase (Protein Data Bank ID: 3ELB), UDP glucose: glycoprotein glucosyltransferase 2 (Gene: UGGT2) (AlphaFold) and RIMS-binding protein 3A (Gene: RIMBP3) (AlphaFold), and Ras GTPase activating-like protein (PDB: 3FAY) based on their docking scores which indicates that they may inhibit the crystallization process. Findings from this study show that Enhydra fluctuans may be effective in the prevention of the crystallization of calcium oxalate. However, further, in vivo studies as well as molecular studies are needed to be conducted to confirm and strengthen its anti-urolithiatic activity and to elucidate the possible mechanism of action involved therein.
Environmental problems with chemical and biological water pollution have become a major concern for society. Providing people with safe and affordable water is a grand challenge of the 21st century. The study investigates the photocatalytic degradation capabilities of hydrothermally prepared pure and Cu-doped ZnO nanoparticles (NPs) for the elimination of dye pollutants. A simple, cost-effective hydrothermal process is employed to synthesize the Cu-doped ZnO NPs. The photocatalytic dye degradation activity of the synthesized Cu-doped ZnO NPs is tested by using methylene blue (MB) dye. In addition, the parameters that affect photodegradation efficiency, such as catalyst concentration, starting potential of hydrogen (pH), and dye concentration, were also assessed. The dye degradation is found to be directly proportional to the irradiation time, as 94% of the MB dye is degraded in 2 hrs. Similarly, the dye degradation shows an inverse relation to the MB dye concentration, as the degradation reduced from 94% to 20% when the MB concentration increases from 5 ppm to 80 ppm. The synthesized cost-effective and environmentally friendly Cu-doped ZnO NPs exhibit improved photocatalytic activity against MB dye and can therefore be employed in wastewater treatment materials.
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.
The first measurements of diboson production cross sections in proton-proton interactions at a center-of-mass energy of 5.02 TeV are reported. They are based on data collected with the CMS detector at the LHC, corresponding to an integrated luminosity of 302 pb^{-1}. Events with two, three, or four charged light leptons (electrons or muons) in the final state are analyzed. The WW, WZ, and ZZ total cross sections are measured as σ_{WW}=37.0_{-5.2}^{+5.5}(stat)_{-2.6}^{+2.7}(syst) pb, σ_{WZ}=6.4_{-2.1}^{+2.5}(stat)_{-0.3}^{+0.5}(syst) pb, and σ_{ZZ}=5.3_{-2.1}^{+2.5}(stat)_{-0.4}^{+0.5}(syst) pb. All measurements are in good agreement with theoretical calculations at combined next-to-next-to-leading order quantum chromodynamics and next-to-leading order electroweak accuracy.
The coronavirus disease 2019 (COVID-19) pandemic is an issue of global significance that has taken the lives of many across the world. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible for its pathogenesis. The pulmonary manifestations of COVID-19 have been well described in the literature. Initially, it was thought to be limited to the respiratory system; however, we now recognize that COVID-19 also affects several other organs, including the nervous system. Two similar human coronaviruses (CoV) that cause severe acute respiratory syndrome (SARS-CoV-1) and Middle East respiratory syndrome (MERS-CoV) are also known to cause disease in the nervous system. The neurological manifestations of SARS-CoV-2 infection are growing rapidly, as evidenced by several reports. There are several mechanisms responsible for such manifestations in the nervous system. For instance, post-infectious immune-mediated processes, direct virus infection of the central nervous system (CNS), and virus-induced hyperinflammatory and hypercoagulable states are commonly involved. Guillain-Barré syndrome (GBS) and its variants, dysfunction of taste and smell, and muscle injury are numerous examples of COVID-19 PNS (peripheral nervous system) disease. Likewise, hemorrhagic and ischemic stroke, encephalitis, meningitis, encephalopathy acute disseminated encephalomyelitis, endothelialitis, and venous sinus thrombosis are some instances of COVID-19 CNS disease. Due to multifactorial and complicated pathogenic mechanisms, COVID-19 poses a large-scale threat to the whole nervous system. A complete understanding of SARS-CoV-2 neurological impairments is still lacking, but our knowledge base is rapidly expanding. Therefore, we anticipate that this comprehensive review will provide valuable insights and facilitate the work of neuroscientists in unfolding different neurological dimensions of COVID-19 and other CoV associated abnormalities.
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.
The first measurement of the dependence of γγ→μ^{+}μ^{-} production on the multiplicity of neutrons emitted very close to the beam direction in ultraperipheral heavy ion collisions is reported. Data for lead-lead interactions at sqrt[s_{NN}]=5.02 TeV, with an integrated luminosity of approximately 1.5 nb^{-1}, are collected using the CMS detector at the LHC. The azimuthal correlations between the two muons in the invariant mass region 88.3. The back-to-back correlation structure from leading-order photon-photon scattering is found to be significantly broader for events with a larger number of emitted neutrons from each nucleus, corresponding to interactions with a smaller impact parameter. This observation provides a data-driven demonstration that the average transverse momentum of photons emitted from relativistic heavy ions has an impact parameter dependence. These results provide new constraints on models of photon-induced interactions in ultraperipheral collisions. They also provide a baseline to search for possible final-state effects on lepton pairs caused by traversing a quark-gluon plasma produced in hadronic heavy ion collisions.
The CMS experiment at the LHC has measured the differential cross sections of Z bosons decaying to pairs of leptons, as functions of transverse momentum and rapidity, in lead-lead collisions at a nucleon-nucleon center-of-mass energy of 5.02 TeV. The measured Z boson elliptic azimuthal anisotropy coefficient is compatible with zero, showing that Z bosons do not experience significant final-state interactions in the medium produced in the collision. Yields of Z bosons are compared to Glauber model predictions and are found to deviate from these expectations in peripheral collisions, indicating the presence of initial collision geometry and centrality selection effects. The precision of the measurement allows, for the first time, for a data-driven determination of the nucleon-nucleon integrated luminosity as a function of lead-lead centrality, thereby eliminating the need for its estimation based on a Glauber model.
The increasing burden of respiratory diseases caused by microbial infections poses an immense threat to global health. This review focuses on the various types of biofilms that affect the respiratory system and cause pulmonary infections, specifically bacterial biofilms. The article also sheds light on the current strategies employed for the treatment of such pulmonary infection-causing biofilms. The potential of nanocarriers as an effective treatment modality for pulmonary infections is discussed, along with the challenges faced during treatment and the measures that may be implemented to overcome these. Understanding the primary approaches of treatment against biofilm infection and applications of drug-delivery systems that employ nanoparticle-based approaches in the disruption of biofilms are of utmost interest which may guide scientists to explore the vistas of biofilm research while determining suitable treatment modalities for pulmonary respiratory infections.
Aim: This study was aimed at evaluating the anticancer potential of curcumin-loaded poly(lactic-co-glycolic acid) (PLGA) based nanoparticles (NPs) in MDA-MB231 human breast cancer cells. Methods: Curcumin-loaded PLGA NPs were developed using a modified solvent evaporation technique. Physical characterization was performed on the formulated NPs. Furthermore, in vitro experiments were conducted to study the biological activity of the curcumin-loaded NPs. Results: Curcumin-loaded PLGA NPs demonstrated high encapsulation efficiency and sustained payload release. Moreover, the NPs exhibited a significant reduction in cell viability, cell migration and cell invasion in the MDA-MB231 cells. Conclusion: The study revealed that the formulated curcumin-loaded PLGA NPs possessed significant anti-metastatic properties. The findings showcased the possible potential of curcumin-loaded NPs in the management of debilitating conditions such as cancer. In addition, this study could form the basis for further research and advancements in this area.
The contagiosity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has startled mankind and has brought our lives to a standstill. The treatment focused mainly on repurposed immunomodulatory and antiviral agents along with the availability of a few vaccines for prophylaxis to vanquish COVID-19. This seemingly mandates a deeper understanding of the disease pathogenesis. This necessitates a plausible extrapolation of cell-based therapy to COVID-19 and is regarded equivalently significant. Recently, correlative pieces of clinical evidence reported a robust decline in lymphocyte count in severe COVID-19 patients that suggest dysregulated immune responses as a key element contributing to the pathophysiological alterations. The large granular lymphocytes also known as natural killer (NK) cells play a heterogeneous role in biological functioning wherein their frontline action defends the body against a wide array of infections and tumors. They prominently play a critical role in viral clearance and executing immuno-modulatory activities. Accumulated clinical evidence demonstrate a decrease in the number of NK cells in circulation with or without phenotypical exhaustion. These plausibly contribute to the progression of pulmonary inflammation in COVID-19 pneumonia and result in acute lung injury. In this review, we have outlined the present understanding of the immunological response of NK cells in COVID-19 infection. We have also discussed the possible use of these powerful biological cells as a therapeutic agent in view of preventing immunological harms of SARS-CoV-2 and the current challenges in advocating NK cell therapy for the same.
The Ξ_{b}^{-}π^{+}π^{-} invariant mass spectrum is investigated with an event sample of proton-proton collisions at sqrt[s]=13 TeV, collected by the CMS experiment at the LHC in 2016-2018 and corresponding to an integrated luminosity of 140 fb^{-1}. The ground state Ξ_{b}^{-} is reconstructed via its decays to J/ψΞ^{-} and J/ψΛK^{-}. A narrow resonance, labeled Ξ_{b}(6100)^{-}, is observed at a Ξ_{b}^{-}π^{+}π^{-} invariant mass of 6100.3±0.2(stat)±0.1(syst)±0.6(Ξ_{b}^{-}) MeV, where the last uncertainty reflects the precision of the Ξ_{b}^{-} baryon mass. The upper limit on the Ξ_{b}(6100)^{-} natural width is determined to be 1.9 MeV at 95% confidence level. The low Ξ_{b}(6100)^{-} signal yield observed in data does not allow a measurement of the quantum numbers of the new state. However, following analogies with the established excited Ξ_{c} baryon states, the new Ξ_{b}(6100)^{-} resonance and its decay sequence are consistent with the orbitally excited Ξ_{b}^{-} baryon, with spin and parity quantum numbers J^{P}=3/2^{-}.
A fiducial cross section for Wγ production in proton-proton collisions is measured at a center-of-mass energy of 13 TeV in 137 fb^{-1} of data collected using the CMS detector at the LHC. The W→eν and μν decay modes are used in a maximum-likelihood fit to the lepton-photon invariant mass distribution to extract the combined cross section. The measured cross section is compared with theoretical expectations at next-to-leading order in quantum chromodynamics. In addition, 95% confidence level intervals are reported for anomalous triple-gauge couplings within the framework of effective field theory.
Middle East respiratory syndrome (MERS) is a lethal respiratory disease with its first case reported back in 2012 (Jeddah, Saudi Arabia). It is a novel, single-stranded, positive-sense RNA beta coronavirus (MERS-CoV) that was isolated from a patient who died from a severe respiratory illness. Later, it was found that this patient was infected with MERS. MERS is endemic to countries in the Middle East regions, such as Saudi Arabia, Jordan, Qatar, Oman, Kuwait and the United Arab Emirates. It has been reported that the MERS virus originated from bats and dromedary camels, the natural hosts of MERS-CoV. The transmission of the virus to humans has been thought to be either direct or indirect. Few camel-to-human transmissions were reported earlier. However, the mode of transmission of how the virus affects humans remains unanswered. Moreover, outbreaks in either family-based or hospital-based settings were observed with high mortality rates, especially in individuals who did not receive proper management or those with underlying comorbidities, such as diabetes and renal failure. Since then, there have been numerous reports hypothesising complications in fatal cases of MERS. Over the years, various diagnostic methods, treatment strategies and preventive measures have been strategised in containing the MERS infection. Evidence from multiple sources implicated that no treatment options and vaccines have been developed in specific, for the direct management of MERS-CoV infection. Nevertheless, there are supportive measures outlined in response to symptom-related management. Health authorities should stress more on infection and prevention control measures, to ensure that MERS remains as a low-level threat to public health.
Artemisia and its allied species have been employed for conventional medicine in the Northern temperate regions of North America, Europe, and Asia for the treatments of digestive problems, morning sickness, irregular menstrual cycle, typhoid, epilepsy, renal problems, bronchitis malaria, etc. The multidisciplinary use of artemisia species has various other health benefits that are related to its traditional and modern pharmaceutical perspectives. The main objective of this review is to evaluate the traditional, modern, biological as well as pharmacological use of the essential oil and herbal extracts of Artemisia nilagirica, Artemisia parviflora, and other allied species of Artemisia. It also discusses the botanical circulation and its phytochemical constituents viz disaccharides, polysaccharides, glycosides, saponins, terpenoids, flavonoids, and carotenoids. The plants have different biological importance like antiparasitic, antimalarial, antihyperlipidemic, antiasthmatic, antiepileptic, antitubercular, antihypertensive, antidiabetic, anxiolytic, antiemetic, antidepressant, anticancer, hepatoprotective, gastroprotective, insecticidal, antiviral activities, and also against COVID-19. Toxicological studies showed that the plants at a low dose and short duration are non or low-toxic. In contrast, a high dose at 3 g/kg and for a longer duration can cause toxicity like rapid respiration, neurotoxicity, reproductive toxicity, etc. However, further in-depth studies are needed to determine the medicinal uses, clinical efficacy and safety are crucial next steps.
In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
Large numbers of bioactive peptides with potential applications in protecting against human diseases have been identified from plant sources. In this review, we summarized recent progress in the research of plant-derived bioactive peptides, encompassing their production, biological effects, and mechanisms. This review focuses on antioxidant, antimicrobial, antidiabetic, and anticancer peptides, giving special attention to evidence derived from cellular and animal models. Studies investigating peptides with known sequences and well-characterized peptidic fractions or protein hydrolysates will be discussed. The use of molecular docking tools to elucidate inter-molecular interactions between bioactive peptides and target proteins is highlighted. In conclusion, the accumulating evidence from in silico, in vitro and in vivo studies to date supports the envisioned applications of plant peptides as natural antioxidants as well as health-promoting agents. Notwithstanding, much work is still required before the envisioned applications of plant peptides can be realized. To this end, future researches for addressing current gaps were proposed.
This paper presents new sets of parameters ("tunes") for the underlying-event model of the H E R W I G 7 event generator. These parameters control the description of multiple-parton interactions (MPI) and colour reconnection in H E R W I G 7 , and are obtained from a fit to minimum-bias data collected by the CMS experiment at s = 0.9 , 7, and 13 Te . The tunes are based on the NNPDF 3.1 next-to-next-to-leading-order parton distribution function (PDF) set for the parton shower, and either a leading-order or next-to-next-to-leading-order PDF set for the simulation of MPI and the beam remnants. Predictions utilizing the tunes are produced for event shape observables in electron-positron collisions, and for minimum-bias, inclusive jet, top quark pair, and Z and W boson events in proton-proton collisions, and are compared with data. Each of the new tunes describes the data at a reasonable level, and the tunes using a leading-order PDF for the simulation of MPI provide the best description of the data.
Results of the Model Unspecific Search in CMS (MUSiC), using proton-proton collision data recorded at the LHC at a centre-of-mass energy of 13 TeV , corresponding to an integrated luminosity of 35.9 fb - 1 , are presented. The MUSiC analysis searches for anomalies that could be signatures of physics beyond the standard model. The analysis is based on the comparison of observed data with the standard model prediction, as determined from simulation, in several hundred final states and multiple kinematic distributions. Events containing at least one electron or muon are classified based on their final state topology, and an automated search algorithm surveys the observed data for deviations from the prediction. The sensitivity of the search is validated using multiple methods. No significant deviations from the predictions have been observed. For a wide range of final state topologies, agreement is found between the data and the standard model simulation. This analysis complements dedicated search analyses by significantly expanding the range of final states covered using a model independent approach with the largest data set to date to probe phase space regions beyond the reach of previous general searches.