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Non-Hermiticity has emerged as a new paradigm for controlling coupled-mode systems in ways that cannot be achieved with conventional techniques. One aspect of this control that has received considerable attention recently is the encircling of exceptional points (EPs). To date, most work has focused on systems consisting of two modes that are tuned by two control parameters and have isolated EPs. While these systems exhibit exotic features related to EP encircling, it has been shown that richer behavior occurs in systems with more than two modes. Such systems can be tuned by more than two control parameters, and contain EPs that form a knot-like structure. Control loops that encircle this structure cause the system’s eigenvalues to trace out non-commutative braids. Here we consider a hybrid scenario: a three-mode system with just two control parameters. We describe the relationship between control loops and their topology in the full and two-dimensional parameter space. We demonstrate this relationship experimentally using a three-mode mechanical system in which the control parameters are provided by optomechanical interaction with a high-finesse optical cavity. When multiple oscillators are tuned, degeneracies occur on a knot-shaped region in the space of tuning parameters. This knot influences how such systems can be tuned. Here, the authors reconcile two common means for visualizing this influence.

Water is a vital and widely spread component required for sustaining the life. Groundwater is vastly valuable source and it is extremely beneficial for the human beings. But, the toxic elements release from sources such as industries, landfills as well as non-point causes of pollution such as pesticides and fertilizer from the past year showed high levels of pollution in ground water, hence this is very crucial for evaluating the water quality not only for it’s existing usage, but also a its capacity to develop as a sustainable source of water for human utilization. In rural areas of India, Groundwater is a significant water-drinking source. In Bhokardan area of Jalna District, quality of ground water is great significance, because it is a key alternative source of domestic supply along with drinking water and peoples residing there facing several water quality issues for drinking purpose. In this current research work, an endeavor has been developed to investigate the quality of groundwater as well as spatial distribution by utilizing Remote Sensing along with GIS approaches. Water quality analysis was performed for developing the quality index of water, by utilizing 12 quality parameters of water like Alkalinity, pH, Electrical Conductivity, Fluoride, Chloride, Nitrate, Sulphate, Potassium, Total Hardness, E. coli, Turbidity and Total Dissolved Solids measured at 35 different selected locations in this research work. Spatial distribution map showed that each region of research area falls under category of “Poor water” and “Very poor water” except some sites at Northern regions of the area which falls under “Good water” category during pre-monsoon, whereas most of the sites from Northern and Southern part of the region shifted category from poor to good water along with very poor to poor water during post-monsoon season. The quality index data of water of the current research disclosed that, the high WQI “Water Quality Index” values in the samples of groundwater were principally due to the occurrence of higher values of turbidity and E. Coli. The higher level of water quality parameters like TH, EC, alkalinity, potassium, TDS, chloride and fluoride were also accountable for high values of WQI in this research work. None of the location falls under excellent quality for water during pre-monsoon as well as post-monsoon season.

Plants possess an array of photoreceptors, such as UVR8, cryptochromes, and phytochromes, that perceive the spectral quality of light and regulate plant morphology, growth, and physiology. The use of light-emitting diodes enables the application of targeted light spectra to elicit specific plant responses during cultivation. However, there is a lack of comparative studies evaluating the effects of different spectral regions within the same crop. We comprehensively quantified how various light spectra, ranging from ultraviolet-B to red, affect plant growth and the accumulation of beneficial phytochemicals, including anthocyanins, phenolics, and ascorbic acid, in red leaf lettuce ( Lactuca sativa ) cv. Red Salad Bowl and Rouxai. Plants were grown under a background white LED light of 200 µmol m -2 s -1 for 16 hours per day (control), and supplemented with red (peak at 659 nm), blue (444 nm), violet (404 nm), ultraviolet-A (UVA; 368 nm) radiation at 60 µmol m -2 s -1 , or ultraviolet-B (UVB; 309 nm) radiation at 3 µmol m -2 s -1 during the last 7 days of a 28-day production period (end-of-production stage, EOP). For both lettuce cultivars, red, blue and UVB treatments significantly enhanced leaf anthocyanin content compared to the control, with UVB being the most effective despite its low application dosage, followed by the blue and red light treatments. UVB radiation significantly increased total phenolic content in both cultivars (by 80%–99.1% compared to the control), while blue light treatment increased total phenolics by 31.4% in ‘Red Salad Bowl’ only. However, supplemental UVB radiation did not affect total ascorbic acid in either cultivar; the other EOP treatments (red to UVA) increased total ascorbic acid by 19%–35% in ‘Red Salad Bowl’ but had no significant effects in ‘Rouxai’. Notably, crop yield under the UVB treatment was the lowest in both cultivars, with 8.9%–49% lower shoot fresh weight compared to other treatments. In contrast, the violet light treatment resulted in the highest leaf area and shoot biomass in both lettuce cultivars, although it was not effective in enhancing anthocyanins and total phenolics. Our result indicated that there is often a tradeoff between nutritional quality and crop yield, and specific light spectra can be strategically used to enhance nutritional quality or biomass. Low-intensity UVB was the most effective at maximizing anthocyanins and total phenolics, followed by blue light, while supplemental violet light most significantly enhanced lettuce leaf expansion and biomass compared to other light spectra.

The use of an appropriate delivery system capable of protecting, translocating, and selectively releasing therapeutic moieties to desired sites can promote the efficacy of an active compound. In this work, we have developed a nanoformulation which preserves its magnetization to load a model anticancerous drug and to explore the controlled release of the drug in a cancerous environment. For the preparation of the nanoformulation, self-assembled magnetic nanospheres (MNS) made of superparamagnetic iron oxide nanoparticles were grafted with a monolayer of (3-aminopropyl)triethoxysilane (APTES). A direct functionalization strategy was used to avoid the loss of the MNS magnetization. The successful preparation of the nanoformulation was validated by structural, microstructural, and magnetic investigations. X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR) were used to establish the presence of APTES on the MNS surface. The amine content quantified by a ninhydrin assay revealed the monolayer coverage of APTES over MNS. The monolayer coverage of APTES reduced only negligibly the saturation magnetization from 77 emu/g (for MNS) to 74 emu/g (for MNS-APTES). Detailed investigations of the thermoremanent magnetization were carried out to assess the superparamagnetism in the MNS. To make the nanoformulation pH-responsive, the anticancerous drug Nintedanib (NTD) was conjugated with MNS-APTES through the acid liable imine bond. At pH 5.5, which mimics a cancerous environment, a controlled release of 85% in 48 h was observed. On the other hand, prolonged release of NTD was found at physiological conditions ( i.e. , pH 7.4). In vitro cytotoxicity study showed dose-dependent activity of MNS-APTES-NTD for human lung cancer cells L-132. About 75% reduction in cellular viability for a 100 μg/mL concentration of nanoformulation was observed. The nanoformulation designed using MNS and monolayer coverage of APTES has potential in cancer therapy as well as in other nanobiological applications.

Theobroma cacao L. is a commercially important food/beverage and is used as traditional medicine worldwide against a variety of ailments. In the present study, computational biology approaches were implemented to elucidate the possible role of cocoa in cancer therapy. Bioactives of cocoa were retrieved from the PubChem database and queried for targets involved in cancer pathogenesis using BindingDB (similarity index ≥0.7). Later, the protein-protein interactions network was investigated using STRING and compound-protein via Cytoscape. In addition, intermolecular interactions were investigated via molecular docking. Also, the stability of the representative complex Hirsutrin-epidermal growth factor receptor (EGFR) complex was explored using molecular dynamics simulations. Crude extract metabolite profile was carried out by LC-MS. Further, anti-oxidant and cytotoxicity studies were performed in Chinese hamster ovary (normal) and Ehrlich ascites carcinoma (cancer) cell lines. Herein, the gene set enrichment and network analysis revealed 34 bioactives in cocoa targeting 50 proteins regulating 21 pathways involved in cancer and oxidative stress in humans. EGFR scored the highest edge count amongst 50 targets modulating 21 key pathways. Hence, it was selected as a promising anticancer target in this study. Structural refinement of EGFR was performed via all-atom molecular dynamics simulations in explicit solvent. A complex EGFR-Hirsutrin showed the least binding energy (-7.2 kcal/mol) and conserved non-bonded contacts with binding pocket residues. A stable complex formation of EGFR-Hirsutrin was observed during 100 ns MD simulation. In vitro studies corroborated antioxidant activity for cocoa extract and showed a significantly higher cytotoxic effect on cancer cells compared to normal cells. Our study virtually predicts anti-cancer activity for cocoa affected by hirsutrin inhibiting EGFR. Further wet-lab studies are needed to establish cocoa extract against cancer and oxidative stress.

Targeted inhibition of the PD-L1–PD-1 pathway might be further amplified through combination of PD-1 or PD-L1 inhibitors with novel anti-TIGIT inhibitory immune checkpoint agents, such as tiragolumab. In the CITYSCAPE trial, we aimed to assess the preliminary efficacy and safety of tiragolumab plus atezolizumab (anti-PD-L1) therapy as first-line treatment for non-small-cell lung cancer (NSCLC). CITYSCAPE is a phase 2, randomised, double-blind, placebo-controlled trial. Patients with chemotherapy-naive, PD-L1-positive (defined as a tumour proportion score of ≥1% by 22C3 immunohistochemistry pharmDx assay; Dako, Agilent Technologies, Santa Clara, CA, USA) recurrent or metastatic NSCLC with measurable disease, Eastern Cooperative Oncology Group performance status of 0 or 1, and no EGFR or ALK alterations were enrolled from 41 clinics in Europe, Asia, and the USA. Patients were randomly assigned (1:1), via an interactive voice or web-based response system, to receive tiragolumab (600 mg) plus atezolizumab (1200 mg) or placebo plus atezolizumab intravenously once every 3 weeks. Investigators and patients were masked to treatment assignment. The co-primary endpoints were investigator-assessed objective response rate and progression-free survival as per Response Evaluation Criteria in Solid Tumors version 1.1 in the intention-to-treat population, analysed after approximately 80 progression-free survival events had been observed in the primary population. Safety was assessed in all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT03563716, and is ongoing. Patients were enrolled between Aug 10, 2018, and March 20, 2019. At data cutoff for the primary analysis (June 30, 2019), 135 of 275 patients assessed for eligibility were randomly assigned to receive tiragolumab plus atezolizumab (67 [50%]) or placebo plus atezolizumab (68 [50%]). In this primary analysis, after a median follow-up of 5·9 months (4·6–7·6, in the intention-to-treat population, 21 patients (31·3% [95% CI 19·5–43·2]) in the tiragolumab plus atezolizumab group versus 11 patients (16·2% [6·7–25·7]) in the placebo plus atezolizumab group had an objective response (p=0·031). Median progression-free survival was 5·4 months (95% CI 4·2–not estimable) in the tiragolumab plus atezolizumab group versus 3·6 months (2·7–4·4) in the placebo plus atezolizumab group (stratified hazard ratio 0·57 [95% CI 0·37–0·90], p=0·015). 14 (21%) patients receiving tiragolumab plus atezolizumab and 12 (18%) patients receiving placebo plus atezolizumab had serious treatment-related adverse events. The most frequently reported grade 3 or worse treatment-related adverse event was lipase increase (in six [9%] patients in the tiragolumab plus atezolizumab group vs two [3%] in the placebo plus atezolizumab group). Two treatment-related deaths (of pyrexia and infection) occurred in the tiragolumab plus atezolizumab group. Tiragolumab plus atezolizumab showed a clinically meaningful improvement in objective response rate and progression-free survival compared with placebo plus atezolizumab in patients with chemotherapy-naive, PD-L1-positive, recurrent or metastatic NSCLC. Tiragolumab plus atezolizumab was well tolerated, with a safety profile generally similar to that of atezolizumab alone. These findings demonstrate that tiragolumab plus atezolizumab is a promising immunotherapy combination for the treatment of previously untreated, locally advanced unresectable or metastatic NSCLC. F Hoffmann-La Roche and Genentech.

Over the years, the use of pesticides has risen significantly, primarily to combat undesirable organisms that threaten crucial crops. A variety of pesticides are available, each designed to protect crops from specific threats like fungi, bacteria, and other pests. Other than crop protection, pesticides are also used in controlling insect vector-borne diseases like malaria and Lyme disease in humans. However, the application of these pesticides must be carefully measured and managed to prevent adverse effects on humans, non-target animals, and the environment. This review delves into the detailed classification of pesticides, exploring their mechanisms of action, applications, benefits, and potential side effects. Understanding the different categories of pesticides, such as herbicides, insecticides, fungicides, rodenticides, and biopesticides, helps us comprehend how each function to control pests. Additionally, we discuss the advantages of pesticide use, including increased crop yields and the prevention of crop diseases, which contribute to food security and agricultural productivity. This review also addresses the significant concerns related to pesticide usage, such as the development of pest resistance, health risks to humans through exposure and residues in food, as well as the impact on biodiversity and ecosystems. The review emphasizes the importance of using pesticides responsibly and implementing integrated pest management strategies to mitigate this risk of exposure. By providing a comprehensive overview of pesticide classification, mechanisms of action, and implications, this review aims to inform and guide us to the safe and effective use of pesticides for daily agricultural practices.

Background Exposure to environmental tobacco smoke (ETS) is arguably the most ubiquitous and hazardous, even at very low levels, starting in early life. The objective of this study was to describe the state of research and future trends on ETS exposure and Children’s Health (CH) topics with bibliometrics and altmetrics. Methods An electronic search was performed in Scopus database on January 31, 2023. Consensus was arrived on 100 most-cited articles by two reviewers. These papers were then cross matched with citations harvested from Web of Science (WoS) and Google Scholar. Altmetric Attention Score (AAS) and Dimension counts were also collected. Analysis and network visualization of authors, countries, and keywords were generated using VOSviewer software. Results Among a total of 1107 articles published on ETS and CH, the 100 top-cited articles appeared in 54 journals, with Pediatrics (n = 12) contributing a maximum number of articles. The time period between 2000 and 2009 accounted for 44% of all publications. With respect to the research design employed across these studies, cross-sectional design took precedence over others accounting for approximately 40%. Predominantly, articles focused on childhood asthma; however, current research trends have shifted towards emerging fields such as children’s oral health and DNA methylation. Twitter, policy documents, and news outlets were the main platforms where outputs were discussed. The AAS was not associated with journal impact factor or access type. Weak correlations were observed between AAS and citation count in Scopus, WoS, and Google Scholar (r = 0.17 to 0.27) while a positive association existed between dimension count and the number of citations across all three databases (r = 0.84 to 0.98). Conclusion This study demonstrates the evolution, digital dissemination and research hotspots in the field of ETS and CH, predicting the possible future research directions. High-quality studies with more specific exposure classification are warranted to better understand the relationship between ETS and CH.

Global trends show that the rapid increase in maize production is associated more with the expansion of maize growing areas than with rapid increases in yield. This is possible through achieving possible higher productivity through maize production practices intensification to meet the sustainable production. Therefore, a field experiment on “Ecological intensification of climate-resilient maize–chickpea cropping system” was conducted during consecutive three years from 2017–2018 to 2019–2020 at Main Agricultural Research Station, Dharwad, Karnataka, India. Results of three years pooled data revealed that ecological intensification (EI) treatment which comprises of all best management practices resulted in higher grain yield (7560 kg/ha) and stover yield compared to farmers’ practice (FP) and all other treatments which were deficit in one or other crop management practices. Similarly, in the succeeding winter season, significantly higher chickpea yield (797 kg/ha) was recorded in EI. Further EI practice recorded significant amount of soil organic carbon, available nitrogen, phosphorus, potassium, zinc, and iron after completion of third cycle of experimentation (0.60%, 235.3 kg/ha,21.0 kg/ha,363.2 kg/ha,0.52 ppm and 5.2 ppm respectively). Soil enzymatic activity was also improved in EI practice over the years and improvement in each year was significant. Lower input energy use was in FP (17,855.2 MJ/ha). Whereas total output energy produced was the highest in EI practice (220,590 MJ ha −1 ) and lower output energy was recorded in EI–integrated nutrient management (INM) (149,255 MJ/ha). Lower energy productivity was noticed in EI-INM. Lower specific energy was recorded in FP and was followed by EI practice. Whereas higher specific energy was noticed is EI–INM. Each individual year and pooled data showed that EI practice recorded higher net return and benefit–cost ratio. The lower net returns were obtained in EI-integrated weed management (Rs. 51354.7/ha), EI-recommended irrigation management (Rs. 56,015.3/ha), integrated pest management (Rs. 59,569.7/ha) and farmers’ practice (Rs. 67,357.7/ha) which were on par with others.

Modulation of initial burst and long term release from electrospun fibrous mats can be achieved by sandwiching the drug loaded mats between hydrophobic layers of fibrous polycaprolactone (PCL). Ibuprofen (IBU) loaded PCL fibrous mats (12% PCL-IBU) were sandwiched between fibrous polycaprolactone layers during the process of electrospinning, by varying the polymer concentrations (10% (w/v), 12% (w/v)) and volume of coat (1 ml, 2 ml) in flanking layers. Consequently, 12% PCL-IBU (without sandwich layer) showed burst release of 66.43% on day 1 and cumulative release (%) of 86.08% at the end of 62 days. Whereas, sandwich groups, especially 12% PCLSW-1 & 2 (sandwich layers—1 ml and 2 ml of 12% PCL) showed controlled initial burst and cumulative (%) release compared to 12% PCL-IBU. Moreover, crystallinity (%) and hydrophobicity of the sandwich models imparted control on ibuprofen release from fibrous mats. Further, assay for cytotoxicity and scanning electron microscopic images of cell seeded mats after 5 days showed the mats were not cytotoxic. Nuclear Magnetic Resonance spectroscopic analysis revealed weak interaction between ibuprofen and PCL in nanofibers which favors the release of ibuprofen. These data imply that concentration and volume of coat in flanking layer imparts tighter control on initial burst and long term release of ibuprofen.