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This paper proposes a novel multi-band textile monopole antenna for patient tracking applications. The designed antenna has compact footprints (0.13λ02) and works in the narrow band-internet of things (NB-IoT) 1.8 GHz, radio frequency identification (RFID), and industrial, scientific, and medical (ISM) 2.45 GHz and 5.8 GHz bands. The impedance bandwidths and gain of the antenna at 1.8 GHz, 2.45 GHz, and 5.8 GHz are 310 MHz, 960 MHz, and 1140 MHz; 3.7 dBi, 5.3 dBi, and 9.6 dBi, respectively. Also, the antenna's behavior is checked on different body parts of the human body in various bending scenarios. As per the evaluated link budget, the designed antenna can easily communicate up to 100 m of distance. The specific absorption rate values of the designed antenna are also within acceptable limits as per the (FCC/ICNIRP) standards at the reported frequency bands. Unlike traditional rigid antennas, the proposed textile antenna is non-intrusive, enhancing user safety and comfort. The denim material makes it comfortable for extended wear, reducing the risk of skin irritation. It can also withstand regular wear and tear, including stretching and bending. The presented denim-based antenna can be seamlessly integrated into clothing and accessories, making it less obtrusive and more aesthetically pleasing.
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Internet das Coisas , Dispositivo de Identificação por Radiofrequência , Têxteis , Dispositivos Eletrônicos Vestíveis , Humanos , Dispositivo de Identificação por Radiofrequência/métodos , Tecnologia sem Fio/instrumentação , Desenho de EquipamentoRESUMO
Delivering nucleic acid therapeutics across cell membranes is a significant challenge. Cell-penetrating peptides (CPPs) containing arginine (R), tryptophan (W), and histidine (H) show promise for siRNA delivery. To improve siRNA delivery and silence a model STAT3 gene, we hypothesized that oleyl acylation to CPPs, specifically (WRH)n, would enhance STAT3 silencing efficiency in breast and ovarian cancer cells. Using Fmoc/tBu solid-phase peptide chemistry, we synthesized, purified, and characterized the oleyl-conjugated (WRH)n (n = 1-4) peptides. The peptide/siRNA complexes were non-cytotoxic at N/P 40 (~20 µM) against MDA-MB-231, MCF-7, SK-OV-3, and HEK-293 cells after 72 h incubation. All peptide/siRNA complexes showed serum stability at N/P ≥ 40. The synthesized conjugates, with a diameter of <100 nm, formed nano-complexes with siRNA and exhibited a stable range of zeta potential values (13-18 mV at N/P = 40). Confocal microscopy and flow cytometry analysis provided qualitative and quantitative evidence of a successful cellular internalization of siRNA. The peptides oleyl-(WRH)3 and oleyl-(WRH)4 showed ~60% and ~75% cellular uptake of siRNA, respectively, in both MDA-MB-231 and SK-OV-3 cells. Western blot analysis of oleyl-(WRH)4 demonstrated effective silencing of the STAT-3 gene, with ~75% silencing in MDA-MB-231 cells and ~45% in SK-OV-3 cells.
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In this paper, we present the design of a millimeter-wave 1 × 4 linear MIMO array antenna that operates across multiple resonance frequency bands: 26.28-27.36 GHz, 27.94-28.62 GHz, 32.33-33.08 GHz, and 37.59-39.47 GHz, for mm-wave wearable biomedical telemetry application. The antenna is printed on a flexible substrate with dimensions of 11.0 × 44.0 mm2. Each MIMO antenna element features a modified slot-loaded triangular patch, incorporating 'cross'-shaped slots in the ground plane to improve impedance matching. The MIMO antenna demonstrates peak gains of 6.12, 8.06, 5.58, and 8.58 dBi at the four resonance frequencies, along with a total radiation efficiency exceeding 75%. The proposed antenna demonstrates excellent diversity metrics, with an ECC < 0.02, DG > 9.97 dB, and CCL below 0.31 bits/sec/Hz, indicating high performance for mm-wave applications. To verify its properties under flexible conditions, a bending analysis was conducted, showing stable S-parameter results with deformation radii of 40 mm (Rx) and 25 mm (Ry). SAR values for the MIMO antenna are calculated at 28.0/38.0 GHz. The average SAR values for 1 gm/10 gm of tissues at 28.0 GHz are found to be 0.0125/0.0079 W/Kg, whereas, at 38.0 GHz, average SAR values are 0.0189/0.0094 W/Kg, respectively. Additionally, to demonstrate the telemetry range of biomedical applications, a link budget analysis at both 28.0 GHz and 38.0 GHz frequencies indicated strong signal strength of 33.69 dB up to 70 m. The fabricated linear MIMO antenna effectively covers the mm-wave 5G spectrum and is suitable for wearable and biomedical applications due to its flexible characteristics.
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Telemetria , Dispositivos Eletrônicos Vestíveis , Telemetria/instrumentação , Telemetria/métodos , Humanos , Tecnologia sem Fio/instrumentação , Desenho de EquipamentoRESUMO
In this paper, a compact low-profile dual-band wearable textile antenna is proposed for on-body and off-body communications. The presented antenna works efficiently in the 5G n79 frequency band (4.4 - 5 GHz) and the ISM band (5.725 - 5.875 GHz). The designed antenna has an ultra-wide impedance bandwidth of 2.01 GHz and peak realized gains of 10.5 dBi and 12 dBi at 4.5 GHz and 5.8 GHz, respectively. The antenna has a small footprint (π × 0.3λ02), which is inspired by circular fractal geometry. The performance of the presented wearable antenna is evaluated at various body parts, including the arm, wrist, and chest. The link margin is evaluated in the on-body and off-body communication scenarios, i.e., communication with the implantable antenna and the outside-body antenna, which is 80 dB and 65 dB at 4.5 GHz and 5.8 GHz, respectively. The 1 gm/10 gm specific absorption rate values at 4.5 GHz and 5.8 GHz are 0.12/0.098 and 0.11/0.082, respectively, which are significantly lower than the standard values, making the proposed antenna suitable for modern wearable applications.
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This paper presents a novel, dual-band, four-port multi-input-multi-output (MIMO) antenna for 28/38 GHz millimeter wave 5G wearable applications. In the proposed work, we have used a novel design approach to get the dual-band behavior from a MIMO design with a small footprint of 18 × 8.5 × 0.25 mm3. For this purpose, each MIMO element is designed as a composite form of a circular and elliptical structure connected with a narrow strip and fed by a tapered feedline. The peak realized gains and total efficiencies of the antenna, evaluated in free space, are 4.15 dBi, 7.73 dBi and 80.13%, 85.44% at 28 GHz and 38 GHz frequencies, respectively. To appraise the thorough behavior of the MIMO antenna, we have evaluated all the parameters of the antenna: Envelope Correlation Coefficient (ECC), Diversity Gain (DG), Mean Effective Gain (MEG), Channel Capacity Loss (CCL), and Total Active Reflection Coefficient (TARC), and found them satisfactory. Channel capacity of the antenna at SNR = 20 dB is found to be 21.61 bps/Hz. For wearable applications, the proposed 4-port MIMO antenna is designed on a flexible Rogers 3003 substrate, and the performance is checked by evaluating bending analysis. The safety of the antenna is verified by analyzing the 1 g/10 g SAR at 28/38 GHz and the corresponding average SAR values are 0.11/0.08 W/kg and 0.05/0.04 W/kg, respectively. All the average SAR values for the proposed MIMO antenna are within the acceptable limits according to FCC/ICNIRP standards.
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Antimicrobial peptides (AMPs) are being explored as a potential strategy to combat antibiotic resistance due to their ability to reduce susceptibility to antibiotics. This study explored whether the [R4W4] peptide mode of action is bacteriostatic or bactericidal using modified two-fold serial dilution and evaluating the synergism between gentamicin and [R4W4] against Escherichia coli (E. coli) and methicillin-resistant Staphylococcus aureus (MRSA) by a checkered board assay. [R4W4] exhibited bactericidal activity against bacterial isolates (MBC/MIC ≤ 4), with a synergistic effect with gentamicin against E. coli (FICI = 0.3) but not against MRSA (FICI = 0.75). Moreover, we investigated the mechanism of action of [R4W4] against MRSA by applying biophysical assays to evaluate zeta potential, cytoplasmic membrane depolarization, and lipoteichoic acid (LTA) binding affinity. [R4W4] at a 16 mg/mL concentration stabilized the zeta potential of MRSA -31 ± 0.88 mV to -8.37 mV. Also, [R4W4] at 2 × MIC and 16 × MIC revealed a membrane perturbation process associated with concentration-dependent effects. Lastly, in the presence of BODIPY-TR-cadaverine (BC) fluorescence dyes, [R4W4] exhibited binding affinity to LTA comparable with melittin, the positive control. In addition, the antibacterial activity of [R4W4] against MRSA remained unchanged in the absence and presence of LTA, with an MIC of 8 µg/mL. Therefore, the [R4W4] mechanism of action is deemed bactericidal, involving interaction with bacterial cell membranes, causing concentration-dependent membrane perturbation. Additionally, after 30 serial passages, there was a modest increment of MRSA strains resistant to [R4W4] and a change in antibacterial effectiveness MIC [R4W4] and vancomycin by 8 and 4 folds with a slight change in Levofloxacin MIC 1 to 2 µg/mL. These data suggest that [R4W4] warrants further consideration as a potential AMP.
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[This corrects the article DOI: 10.1371/journal.pone.0261696.].
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The emergence of multidrug-resistant (MDR) strains causes severe problems in the treatment of microbial infections owing to limited treatment options. Antimicrobial peptides (AMPs) are drawing considerable attention as promising antibiotic alternative candidates to combat MDR bacterial and fungal infections. Herein, we present a series of small amphiphilic membrane-active cyclic peptides composed, in part, of various nongenetically encoded hydrophilic and hydrophobic amino acids. Notably, lead cyclic peptides 3b and 4b showed broad-spectrum activity against drug-resistant Gram-positive (MIC = 1.5-6.2 µg/mL) and Gram-negative (MIC = 12.5-25 µg/mL) bacteria, and fungi (MIC = 3.1-12.5 µg/mL). Furthermore, lead peptides displayed substantial antibiofilm action comparable to standard antibiotics. Hemolysis (HC50 = 230 µg/mL) and cytotoxicity (>70 % cell viability against four different mammalian cells at 100 µg/mL) assay results demonstrated the selective lethal action of 3b against microbes over mammalian cells. A calcein dye leakage experiment substantiated the membranolytic effect of 3b and 4b, which was further confirmed by scanning electron microscopy. The behavior of 3b and 4b in aqueous solution and interaction with phospholipid bilayers were assessed by employing nuclear magnetic resonance (NMR) spectroscopy in conjunction with molecular dynamics (MD) simulations, providing a solid structural basis for understanding their membranolytic action. Moreover, 3b exhibited stability in human blood plasma (t1/2 = 13 h) and demonstrated no signs of resistance development against antibiotic-resistant S. aureus and E. coli. These findings underscore the potential of these newly designed amphiphilic cyclic peptides as promising anti-infective agents, especially against Gram-positive bacteria.
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Biofilmes , Farmacorresistência Bacteriana Múltipla , Hemólise , Testes de Sensibilidade Microbiana , Humanos , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Hemólise/efeitos dos fármacos , Peptídeos Cíclicos/farmacologia , Peptídeos Cíclicos/química , Antibacterianos/farmacologia , Antibacterianos/química , Peptídeos Catiônicos Antimicrobianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/química , Animais , Fungos/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Antifúngicos/farmacologia , Antifúngicos/química , Bactérias Gram-Negativas/efeitos dos fármacosRESUMO
Introduction: The flavivirus NS5, a non-structural protein of Japanese Encephalitis Virus (JEV), a serious deadly human pathogen responsible for epidemics in South East Asia, consists of N-terminal methyl transferase (MTase) domain and RNA-dependent RNA polymerase (RdRp) is known for unique viral genome replication and cap formation activity. S-adenosyl executes a crucial function in these viral activities. S-adenosyl derivatives are chosen as potential binders with the MTase domain of NS5 based on MM and docking studies. Methods: MM GBSA (Generalized Born Surface Area) simulation were performed to evaluate the binding energy, following the 100 nanosecond (ns) production MD simulation in the periodic boundary condition (PBC) for the selected docked ligands with NS5. Quasi-harmonic entropy of the ligands was also calculated with semi-empirical calculations at the PM3/PM6 level supporting docking and MM-GBSA results. Results and discussion: The residue-wise decomposition energy reveals that the key hydrophobic residues Gly 81, Phe 133, and Ile 147 in the RdRp-MTase interface, indicate the biological relevance. These residues act as the key residue stabilizer, binding vigorously with S-Adenosyl derivatives in the vicinity of the interface between the MTase domain and RdRp. This paves the way for the other potential drug as an inhibitor for the enzymatic activity of the NS5.
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Effective communication is the cornerstone of efficient patient care. It is vital to obtain a thorough history, build the patient's trust, and ensure compliance to treatment. Image-based communication (IBC) using comic-like strips is better than the conventional verbal and written modes, as it is inexpensive, less human resource dependent, and diversity agnostic. Strips based on local and socioculturally relevant issues and characters grab readers' attention, are relatable and entertaining, and utilize a storyline that invigorates thinking. The medical advice delivered by an ideal IBC strip is easy to comprehend, has a better recall, and promotes patient adherence. With an idea that IBC strips can serve as a vital supportive tool in underserved and overburdened clinics, we have described the nuances of adapting them into the existing physician-patient experience. We utilize a prototype IBC of an elderly woman helping a family whose child developed acute fever, possibly malaria. Various elements of an IBC strip, namely, panels, gutters, background, characters, bubbles, captions, and visual effects, are illustrated, and their variations are described later. Once designed, an IBC strip must be critically evaluated for the accuracy of the educational message, and errors, if any, must be corrected. The images are then subjected to a series of local field tests to ensure that they serve their purpose and have the desired cultural competence. Once ready, IBC strips can be posted in public spaces and outside clinics or distributed to healthcare workers or patients. Here, they serve as educational and health literacy tools. The strips can significantly reduce caregiver-patient interaction time and improve the quality of communication, especially when patients are illiterate or understand a different language. It is easier to develop rapport and partnership with a patient when the communication is presented through a pictorial tool. An IBC strip can be used to train grassroot workers, who subsequently train patients, thereby serving a dual purpose. To obtain tangible clinical and epidemiologic benefits from IBC strips, rigorous evidence building and standardization are a crucial long-term goal.
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Mycobacterium avium (M. avium), a type of nontuberculous mycobacteria (NTM), poses a risk for pulmonary infections and disseminated infections in immunocompromised individuals. Conventional treatment consists of a 12-month regimen of the first-line antibiotics rifampicin and azithromycin. However, the treatment duration and low antibiotic tolerability present challenges in the treatment of M. avium infection. Furthermore, the emergence of multidrug-resistant mycobacterium strains prompts a need for novel treatments against M. avium infection. This study aims to test the efficacy of a novel antimicrobial peptide, cyclic [R4W4], alongside the first-line antibiotics azithromycin and rifampicin in reducing M. avium survival. Colony-forming unit (CFU) counts were assessed after treating M. avium cultures with varying concentrations of cyclic [R4W4] alone or in conjunction with azithromycin or rifampicin 3 h and 4 days post-treatment. M. avium growth was significantly reduced 4 days after cyclic [R4W4] single treatment. Additionally, cyclic [R4W4]-azithromycin and cyclic [R4W4]-rifampicin combination treatments at specific concentrations significantly reduced M. avium survival 3 h and 4 days post-treatment compared with single antibiotic treatment alone. These findings demonstrate cyclic [R4W4] as a potent treatment method against M. avium and provide insight into novel therapeutic approaches against mycobacterium infections.
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Alzheimer's disease (AD) is a progressive neurodegenerative disease with a few FDA-approved drugs that provide modest symptomatic benefits and only two FDA-approved disease-modifying treatments for AD. The advancements in understanding the causative genes and non-coding sequences at the molecular level of the pathophysiology of AD have resulted in several exciting research papers that employed small interfering RNA (siRNA)-based therapy. Although siRNA is being sought by academia and biopharma industries, several challenges still need to be addressed. We comprehensively report the latest advances in AD pathophysiology, druggable targets, ongoing clinical trials, and the siRNA-based approaches across the blood-brain barrier for addressing AD. This review describes the latest delivery systems employed to address this barrier. Critical insights and future perspectives on siRNA therapy for AD are also provided.
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Doença de Alzheimer , Doenças Neurodegenerativas , Humanos , Barreira Hematoencefálica , Doença de Alzheimer/tratamento farmacológico , RNA Interferente Pequeno , Doenças Neurodegenerativas/tratamento farmacológico , Sistemas de Liberação de Medicamentos/métodosRESUMO
The biological significance of benzopyran-4-ones as cytotoxic agents against multi-drug resistant cancer cell lines and isoxazoles as anti-inflammatory agents in cellular assays prompted us to design and synthesize their hybrid compounds and explore their antiproliferative activity against a panel of six cancer cell lines and two normal cell lines. Compounds 5a-d displayed significant antiproliferative activities against all the cancer cell lines tested, and IC50 values were in the range of 5.2-22.2 µM against MDA-MB-231 cancer cells, while they were minimally cytotoxic to the HEK-293 and LLC-PK1 normal cell lines. The IC50 values of 5a-d against normal HEK-293 cells were in the range of 102.4-293.2 µM. Compound 5a was screened for kinase inhibitory activity, proteolytic human serum stability, and apoptotic activity. The compound was found inactive towards different kinases, while it completely degraded after 2 h of incubation with human serum. At 5 µM concentration, it induced apoptosis in MDA-MB-231 by 50.8%. Overall, these findings suggest that new benzopyran-4-one-isoxazole hybrid compounds, particularly 5a-d, are selective anticancer agents, potentially safe for human cells, and could be synthesized at low cost. Additionally, Compound 5a exhibits potential anticancer activity mediated via inhibition of cancer cell proliferation and induction of apoptosis.
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Antineoplásicos , Resistência a Múltiplos Medicamentos , Humanos , Células HEK293 , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Ensaios de Seleção de Medicamentos Antitumorais , Benzopiranos/farmacologia , Antineoplásicos/farmacologia , Proliferação de Células , Relação Estrutura-Atividade , Estrutura Molecular , Relação Dose-Resposta a DrogaRESUMO
Fibroblast growth factor receptors 1 (FGFR1) is an emerging target for the development of anticancer drugs. Uncontrolled expression of FGFR1 is strongly associated with a number of different types of cancers. Apart from a few FGFR inhibitors, the FGFR family members have not been thoroughly studied to produce clinically effective anticancer drugs. The application of proper computational techniques may aid in understanding the mechanism of protein-ligand complex formation, which may provide a better notion for developing potent FGFR1 inhibitors. In this study, a variety of computational techniques, including 3D-QSAR, flexible docking and MD simulation followed by MMGB/PBSA, H-bonds and distance analysis, have been performed to systematically explore the binding mechanism of pyrrolo-pyrimidine derivatives against FGFR1. The 3D-QSAR model was generated to deduce the structural determinants of FGFR1 inhibition. The high q2 and r2 values for the CoMFA and CoMSIA models indicated that the created 3D-QSAR models could reliably predict the bioactivities of FGFR1 inhibitors. The computed binding free energies (MMGB/PBSA) for the selected compounds were consistent with the ranking of their experimental binding affinities against FGFR1. Furthermore, per-residue energy decomposition analysis revealed that the residues Lys514 in catalytic region, Asn568, Glu571 in solvent accessible portion and Asp641 in DFG motif exhibited a strong tendency to mediate ligand-protein interactions through the hydrogen bonding and Van Der Waals interactions. These findings may benefit researchers in gaining better knowledge of FGFR1 inhibition and may serve as a guideline for the development of novel and highly effective FGFR1 inhibitors.Communicated by Ramaswamy H. Sarma.
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Antineoplásicos , Simulação de Dinâmica Molecular , Simulação de Acoplamento Molecular , Ligantes , Inibidores de Proteínas Quinases/farmacologia , Pirimidinas/farmacologia , Antineoplásicos/farmacologia , Relação Quantitativa Estrutura-AtividadeRESUMO
The entry of proteins through the cell membrane is challenging, thus limiting their use as potential therapeutics. Seven cell-penetrating peptides, designed in our laboratory, were evaluated for the delivery of proteins. Fmoc solid-phase peptide synthesis was utilized for the synthesis of seven cyclic or hybrid cyclic-linear amphiphilic peptides composed of hydrophobic (tryptophan (W) or 3,3-diphenylalanine (Dip) and positively-charged arginine (R) residues, such as [WR]4, [WR]9, [WWRR]4, [WWRR]5, [(RW)5K](RW)5, [R5K]W7, and [DipR]5. Confocal microscopy was used to screen the peptides as a protein delivery system of model cargo proteins, green and red fluorescein proteins (GFP and RFP). Based on the confocal microscopy results, [WR]9 and [DipR]5 were found to be more efficient among all the peptides and were selected for further studies. [WR]9 (1-10 µM) + protein (GFP and RFP) physical mixture did not show high cytotoxicity (>90% viability) in triple-negative breast cancer cells (MDA-MB-231) after 24 h, while [DipR]5 (1-10 µM) physical mixture with GFP exhibited more than 81% cell viability. Confocal microscopy images revealed internalization of GFP and RFP in MDA-MB-231 cells using [WR]9 (2-10 µM) and [DipR]5 (1-10 µM). Fluorescence-activated cell sorting (FACS) analysis indicated that the cellular uptake of GFP was concentration-dependent in the presence of [WR]9 in MDA-MB-231 cells after 3 h of incubation at 37 °C. The concentration-dependent uptake of GFP and RFP was also observed in the presence of [DipR5] in SK-OV-3 and MDA-MB-231 cells after 3 h of incubation at 37 °C. FACS analysis indicated that the cellular uptake of GFP in the presence of [WR]9 was partially decreased by methyl-ß-cyclodextrin and nystatin as endocytosis inhibitors after 3 h of incubation in MDA-MB-231 cells, whereas nystatin and chlorpromazine as endocytosis inhibitors slightly reduced the uptake of GFP in the presence of [DipR]5 after 3 h of incubation in MDA-MB-231. [WR]9 was able to deliver therapeutically relevant proteins (Histone H2A) at different concentrations. These results provide insight into the use of amphiphilic cyclic peptides in the delivery of protein-related therapeutics.
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RNA interference (RNAi) has drawn enormous attention as a powerful tool because of its capability to interfere with mRNA and protein production. However, designing a safe and efficient delivery system in RNAi therapeutics remains challenging. Herein, we have designed and synthesized several linear peptides containing tryptophan (W) and arginine (R) residues separated by the ß-alanine (ßA) spacer and attached to a lipophilic fatty acyl chain, cholesterol, or PEG. The peptide backbone sequences were: Ac-C-ßA-ßA-W4-ßA-ßA-R4-CO-NH2 and Ac-K-ßA-ßA-W4-ßA-ßA-R4-CO-NH2, with only a difference in N-terminal amino acid. The cysteine side chain in the first sequence was used for the conjugation with PEG2000 and PEG550. Alternatively, the side chain of lysine in the second sequence was used for conjugation with cholesterol or oleic acid. We hypothesized that amphiphilic peptides and optimum fatty acyl chain or PEG could function as an effective siRNA carrier by complementing each structural component's self-assembly and membrane internalization properties. None of the designed peptides showed cytotoxicity up to 10 µM. Serum stability studies suggested that the newly designed peptides efficiently protected siRNA against early degradation by nucleases. Flow cytometry analysis indicated 50-90% cellular uptake of siRNA using the newly developed modified linear peptides (MLPs). Western blot results revealed more than 90% protein downregulation after targeting STAT3 in MDA-MB-231 and SKOV-3 cell lines. In summary, a new peptide class was developed to safely and efficiently deliver siRNA.
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The present study examined the equivalent black carbon (eBC) mass concentrations measured over 10.5 years (September 2005-March 2016) using a 7-wavelength Aethalometer (AE-31) at Mukteshwar, a high-altitude and regional background site in the foothills of Indian central Himalayas. The total spectral absorption coefficient (babs) was divided into three categories: black carbon (BC) and brown carbon (BrC); fossil fuels (FF) and wood/biomass burning (WB/BB); and primary and secondary sources. At the wavelength of 370 nm, a significant BrC contribution (25 %) to the total babs is identified, characterized by a pronounced seasonal variation with winter (December-January-February) maxima (31 %) and post-monsoon (October and November) minima (20 %); whereas, at 660 nm, the contribution of BrC is dramatically less (9 %). Climatologically, the estimated BCFF at 880 nm ranges from 0.25 ± 0.19 µg m-3 in July to 1.17 ± 0.80 µg m-3 in May with the annual average of 0.67 ± 0.63 µg m-3, accounting for 79 % of the BC mass. The maximum BCFF/BC fraction reaches its peak value during the monsoon (July and August, 85 %), indicating the dominance of local traffic emissions due to tourism activities. Further, the highest BCWB concentration observed during pre-monsoon (March-May) suggests the influence of local forest fires along with long-range transported aerosols from the low-altitude plains. The increased contribution of BrC (26 % at 370 nm) and WB absorption (61 % at 370 nm) to the total absorption at the shorter wavelengths suggests that wood burning is one of the major sources of BrC emissions. Secondary BrC absorption accounts for 24 % [91 %] of the total absorption [BrC absorption] at 370 nm, implying the dominance of secondary sources in BrC formation. A trend analysis for the measured BC concentration shows a statistically significant increasing trend with a slope of 0.02 µgm-3/year with a total increase of about 22 % over the study period. A back trajectory-based receptor model, potential source contribution function (PSCF), was used to identify the potential regional source region of BC. The main source regions of BC are the northwest states of India in the IGP region and the northeast Pakistan region.
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Cell-impermeable and negatively charged compounds' cellular uptake across the cell membranes remains challenging. Herein, the synthesis of four linear [(WWRR)2, (WWRR)3, (WWRR)4, and (WWRR)5] and four cyclic ([WWRR]2, [WWRR]3, [WWRR]4, and [WWRR]5) peptides containing alternate two tryptophan (WW) and two arginine (RR) residues and their biological evaluation as molecular transporters are reported. The peptides did not show any significant cytotoxicity in different cell lines (MDA-MB-23, SK-OV-3, and HEK 293) at a concentration of 5 µM and after 3 h of incubation time. The uptake of fluorescence-labeled cargo molecules (F'-GpYEEI, F'-siRNA, and F'-3TC) in the presence of the peptides was monitored in different cell lines (SK-OV-3 and MDA-MB-231) with fluorescence-activated cell sorting. Among all the peptides, [WWRR]5 (C4) showed the highest cellular uptake of cargo molecules, indicating it can act as effective molecular transporter. Confocal microscopy in MDA-MB-231 cells showed the cellular uptake of F'-GpYEEI in the presence of C4 and the intracellular localization of fluorescence-labeled C4 (F'-C4) in the cytosol. The F'-C4 cellular uptake was found to be concentration- and time-dependent, as shown by flow cytometry in MDA-MB-231 cells. Confocal microscopy and flow cytometry of F'-C4 in MDA-MB-231 cells were examined alone and in the presence of different endocytosis inhibitors (chlorpromazine, methyl-ß-cyclodextrin, chloroquine, and nystatin). The data showed that the cellular uptake of F'-C4 in the presence of chlorpromazine, chloroquine, and methyl-ß-cyclodextrin was reduced but not completely eliminated, indicating that both energy-independent and energy-dependent pathways contributed to the cellular uptake of F'-C4. Similar results were obtained using the confocal microscopy of C4 and F'-GpYEEI in the presence of endocytosis inhibitors (chlorpromazine, methyl-ß-cyclodextrin, chloroquine, and nystatin). These data indicate that C4 has the potential to be used as a cell-penetrating peptide and cargo transporter.
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Peptídeos Penetradores de Células , Peptídeos Cíclicos , Humanos , Peptídeos Cíclicos/química , Clorpromazina , Células HEK293 , Nistatina , Linhagem Celular Tumoral , EndocitoseRESUMO
We designed a library of 24 cyclic peptides containing arginine (R) and tryptophan (W) residues in a sequential manner [RnWn] (n = 2-7) to study the impact of the hydrophilic/hydrophobic ratio, charge, and ring size on the antibacterial activity against Gram-positive and Gram-negative strains. Among peptides, 5a and 6a demonstrated the highest antimicrobial activity. In combination with 11 commercially available antibiotics, 5a and 6a showed remarkable synergism against a large panel of resistant pathogens. Hemolysis (HC50 = 340 µg/mL) and cell viability against mammalian cells demonstrated the selective lethal action of 5a against bacteria over mammalian cells. Calcein dye leakage and scanning electron microscopy studies revealed the membranolytic effect of 5a. Moreover, the stability in human plasma (t1/2 = 3 h) and the negligible ability of pathogens to develop resistance further reflect the potential of 5a for further development as a peptide-based antibiotic.
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Antibacterianos , Peptídeos Cíclicos , Humanos , Peptídeos Cíclicos/farmacologia , Antibacterianos/farmacologiaRESUMO
The excessive use of digital platforms with rapidly increasing users in the wireless domain enforces communication systems to provide information with high data rates, high reliability and strong transmission connection quality. Wireless systems with single antenna elements are not able to accomplish the desired needs. Therefore, multiple-input multiple-output (MIMO) antennas are getting more attention in modern high-speed communication systems and play an essential part in the current generation of wireless technology. However, along with their ability to significantly increase channel capacity, it is a challenge to achieve an optimal isolation in a compact size for fifth-generation (5G) terminals. Portable devices, automobiles, handheld gadgets, smart phones, wireless sensors, radio frequency identification and other applications use MIMO antenna systems. In this review paper, the fundamentals of MIMO antennas, the performance parameters of MIMO antennas, and different design approaches and methodologies are discussed to realize the three most commonly used MIMO antennas, i.e., ultra-wideband (UWB), dual-band and circularly polarized antennas. The recent MIMO antenna design approaches with UWB, dual band and circularly polarized characteristics are compared in terms of their isolation techniques, gain, efficiency, envelope correlation coefficient (ECC) and channel capacity loss (CCL). This paper is very helpful to design suitable MIMO antennas applicable in UWB systems, satellite communication systems, GSM, Bluetooth, WiMAX, WLAN and many more. The issues with MIMO antenna systems in the indoor environment along with possible solutions to improve their performance are discussed. The paper also focuses on the applications of MIMO characteristics for future sixth-generation (6G) technology.