Rationale and Design of a Phase 2, Double-blind, Placebo-Controlled, Randomized Trial Evaluating AMP Kinase-Activation by Metformin in Focal Segmental Glomerulosclerosis.

Introduction: Focal segmental glomerulosclerosis (FSGS), the most common primary glomerular disease leading to end-stage kidney disease (ESKD), is characterized by podocyte injury and depletion, whereas minimal change disease (MCD) has better outcomes despite podocyte injury. Identifying mechanisms capable of preventing podocytopenia during injury could transform FSGS to an "MCD-like" state. Preclinical data have reported conversion of an MCD-like injury to one with podocytopenia and FSGS by inhibition of AMP-kinase (AMPK) in podocytes. Conversely, in FSGS, AMPK-activation using metformin (MF) mitigated podocytopenia and azotemia. Observational studies also support beneficial effects of MF on proteinuria and chronic kidney disease (CKD) outcomes in diabetes. A randomized controlled trial (RCT) to test MF in podocyte injury with FSGS has not yet been conducted. Methods: We report the rationale and design of phase 2, double-blind, placebo-controlled RCT evaluating the efficacy and safety of MF as adjunctive therapy in FSGS. By randomizing 30 patients with biopsy-confirmed FSGS to MF or placebo (along with standard immunosuppression), we will study mechanistic biomarkers that correlate with podocyte injury or depletion and evaluate outcomes after 6 months. We specifically integrate novel urine, blood, and tissue markers as surrogates for FSGS progression along with unbiased profiling strategies. Results and Conclusion: Our phase 2 trial will provide insight into the potential efficacy and safety of MF as adjunctive therapy in FSGS-a crucial step to developing a larger phase 3 study. The mechanistic assays here will guide the design of other FSGS trials and contribute to understanding AMPK activation as a potential therapeutic target in FSGS. By repurposing an inexpensive agent, our results will have implications for FSGS treatment in resource-poor settings.

High amylopectin in waxy maize synergistically affects seed germination and seedling vigour over traditional maize genotypes.

Waxy maize grains rich in amylopectin have emerged as a popular food and industrial raw materials. Here, a set of waxy inbreds having recessive waxy1 (wx1) gene derived through marker-assisted selection (MAS), and their original versions were evaluated for germination, seed vigour index-I and vigour index-II, electrical conductivity (EC) and enzymatic activities viz., dehydrogenase (DH), esterase (EST), peroxidase (POX), superoxide dismutase (SOD) and α-amylase (AMY). Waxy inbreds under study possessed average 97.8% amylopectin compared to 72.4% in original inbreds. Waxy versions showed 15.2% more test weight, 4.3% increase in germination, 22.7% higher seed vigour index-I and 28.3% higher seed vigour index-II, respectively, over the original inbreds. Further, activity of DH, EST, POX, SOD and AMY of MAS-derived waxy inbreds was more than that of original inbreds, whereas EC was less in improved inbreds compared to originals. Amylopectin exhibited strong positive correlations (r = 0.69 to 0.97**) with seed germination, vigour index-I and -II, DH, SOD, POX, EST and AMY activity. However, amylopectin showed negative correlation of - 0.82** with EC. Seed germination and seed vigour indices were also positively correlated with all enzymatic activities (r = 0.58 to 0.92**). The analysis revealed that waxy inbreds possess better seed vigour and enzymatic activities over traditional inbreds. This is the first report of synergistic effects of wx1 gene on seed germination, vigour and enzymatic activities in maize endosperm.

A novel skin cancer detection model using modified finch deep CNN classifier model.

Skin cancer is one of the most life-threatening diseases caused by the abnormal growth of the skin cells, when exposed to ultraviolet radiation. Early detection seems to be more crucial for reducing aberrant cell proliferation because the mortality rate is rapidly rising. Although multiple researches are available based on the skin cancer detection, there still exists challenges in improving the accuracy, reducing the computational time and so on. In this research, a novel skin cancer detection is performed using a modified falcon finch deep Convolutional neural network classifier (Modified Falcon finch deep CNN) that efficiently detects the disease with higher efficiency. The usage of modified falcon finch deep CNN classifier effectively analyzed the information relevant to the skin cancer and the errors are also minimized. The inclusion of the falcon finch optimization in the deep CNN classifier is necessary for efficient parameter tuning. This tuning enhanced the robustness and boosted the convergence of the classifier that detects the skin cancer in less stipulated time. The modified falcon finch deep CNN classifier achieved accuracy, sensitivity, and specificity values of 93.59%, 92.14%, and 95.22% regarding k-fold and 96.52%, 96.69%, and 96.54% regarding training percentage, proving more effective than literary works.

Morpho-physiological studies of sandalwood-host interaction under individual and interactive water and salt stress.

To find out the possibilities of growing white sandalwood in sub-tropical regions of India where farmers facing the problem of water deficit and salinity stress, a RBD experiment was conducted. Sandalwood grown alone and with five selected hosts (Alternanthera sp., Neem, Shisham, Dek and Agarwood) on the basis of prior study under water deficit, salinity stress and combined water deficit and salinity stress. Sandalwood plants were harvested after 180 days of imposing stress treatments. Morphological traits (plant height, collar diameter, shoot fresh and dry biomass) showed significant reduction under water deficit and salinity stress, which were further aggravated under combined water deficit and salinity stress. Studied plant water traits, ionic balance and gas exchange attributes were also reduced by these stresses. While among studied host, Shisham and Dek identified as the best host species under water deficit, salinity and interactive stress by maintaining ion homeostasis, osmotic adjustments and plant water regulation. Results depicted that sandalwood plants cultivated alone were not able to survive under salinity and combined stress conditions and showed poor growth under water deficit and control conditions. Different indices were also calculated based on morpho-physiological and ionic traits and also indicated that sandalwood grown with Dalbergia sissoo and Melia dubia showed higher drought, salt and stress tolerance potential, which made sandalwood adaptable under these stresses. Therefore, the present study signifies the importance of host especially D. sissoo and M. dubia which might be excellent long-term host species for sandalwood cultivation under sub-tropical conditions to thrive under changing environments.

miRNAs in radiotherapy resistance of cancer; a comprehensive review.

While intensity-modulated radiation therapy-based comprehensive therapy increases outcomes, cancer patients still have a low five-year survival rate and a high recurrence rate. The primary factor contributing to cancer patients' poor prognoses is radiation resistance. A class of endogenous non-coding RNAs, known as microRNAs (miRNAs), controls various biological processes in eukaryotes. These miRNAs influence tumor cell growth, death, migration, invasion, and metastasis, which controls how human carcinoma develops and spreads. The correlation between the unbalanced expression of miRNAs and the prognosis and sensitivity to radiation therapy is well-established. MiRNAs have a significant impact on the regulation of DNA repair, the epithelial-to-mesenchymal transition (EMT), and stemness in the tumor radiation response. But because radio resistance is a complicated phenomena, further research is required to fully comprehend these mechanisms. Radiation response rates vary depending on the modality used, which includes the method of delivery, radiation dosage, tumor stage and grade, confounding medical co-morbidities, and intrinsic tumor microenvironment. Here, we summarize the possible mechanisms through which miRNAs contribute to human tumors' resistance to radiation.

From oncogenes to tumor suppressors: The dual role of ncRNAs in fibrosarcoma.

Fibrosarcoma is a challenging cancer originating from fibrous tissues, marked by aggressive growth and limited treatment options. The discovery of non-coding RNAs (ncRNAs), including long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and small interfering RNAs (siRNAs), has opened new pathways for understanding and treating this malignancy. These ncRNAs play crucial roles in gene regulation, cellular processes, and the tumor microenvironment. This review aims to explore the impact of ncRNAs on fibrosarcoma's pathogenesis, progression, and resistance to treatment, focusing on their mechanistic roles and therapeutic potential. A comprehensive review of literature from databases like PubMed and Google Scholar was conducted, focusing on the dysregulation of ncRNAs in fibrosarcoma, their contribution to tumor growth, metastasis, drug resistance, and their cellular pathway interactions. NcRNAs significantly influence fibrosarcoma, affecting cell proliferation, apoptosis, invasion, and angiogenesis. Their function as oncogenes or tumor suppressors makes them promising biomarkers and therapeutic targets. Understanding their interaction with the tumor microenvironment is essential for developing more effective treatments for fibrosarcoma. Targeting ncRNAs emerges as a promising strategy for fibrosarcoma therapy, offering hope to overcome the shortcomings of existing treatments. Further investigation is needed to clarify specific ncRNAs' roles in fibrosarcoma and to develop ncRNA-based therapies, highlighting the significance of ncRNAs in improving patient outcomes in this challenging cancer.

lncRNAs and cyclin-dependent kinases: Unveiling their critical roles in cancer progression.

Long non-coding RNAs (lncRNAs) are a diverse class of RNA molecules that do not code for proteins but play critical roles in gene regulation. One such role involves the modulation of cell cycle progression and proliferation through interactions with cyclin-dependent kinases (CDKs), key regulators of cell division. Dysregulation of CDK activity is a hallmark of cancer, contributing to uncontrolled cell growth and tumor formation. These lncRNA-CDK interactions are part of a complex network of molecular mechanisms underlying cancer pathogenesis, involving various signaling pathways and regulatory circuits. Understanding the interplay between lncRNAs, CDKs, and cancer biology holds promise for developing novel therapeutic strategies targeting these molecular targets for more effective cancer treatment. Furthermore, targeting CDKs, key cell cycle progression and proliferation regulators, offers another avenue for disrupting cancer pathways and overcoming drug resistance. This can open new possibilities for individualized treatment plans and focused therapeutic interventions.

The plant endomicrobiome: Structure and strategies to produce stress resilient future crop.

Plants have a microbiome, a diverse community of microorganisms, including bacteria, fungi, and viruses, living inside and on their tissues. Versatile endophytic microorganisms inhabited in every plant part without causing disease and develop endophytic microbiome or endo-microbiome. Plant endo-microbiome are drawn by the nutrient rich micro-environment, and in turn some microbes mutualistically endorse and protect plant from adverse environmental stresses. Plant endo-microbiome interact within well-designed host equilibrium containing xylem, phloem, nutrients, phytohormones, metabolites and shift according to environmental and nutritional change. Plant endo-microbiome regulate and respond to environmental variations, pathogens, herbivores by producing stress regulators, organic acids, secondary metabolites, stress hormones as well as unknown substances and signalling molecules. Endomicrobiome efficiently synthesizes multiple bioactive compounds, stress phytohormones with high competence. The technological innovation as next generation genomics biology and high-throughput multiomics techniques stepping stones on the illumination of critical endo-microbiome communities and functional characterization that aid in improving plant physiology, biochemistry and immunity interplay for best crop productivity. This review article contains deeper insight in endomicrobiome related research work in last years, recruitment, niche development, nutrient dynamics, stress removal mechanisms, bioactive services in plant health development, community architecture and communication, and immunity interplay in producing stress resilient future crop.

Similar and divergent responses to salinity stress of jamun (Syzygium cumini L. Skeels) genotypes.

Background: Genetic variation for salt tolerance remains elusive in jamun (Syzygium cumini). Methods: Effects of gradually increased salinity (2.0-12.0 dS/m) were examined in 20 monoembryonic and 28 polyembryonic genotypes of jamun. Six genotypes were additionally assessed for understanding salt-induced changes in gas exchange attributes and antioxidant enzymes. Results: Salt-induced reductions in leaf, stem, root and plant dry mass (PDM) were relatively greater in mono- than in poly-embryonic types. Reductions in PDM relative to control implied more adverse impacts of salinity on genotypes CSJ-28, CSJ-31, CSJ-43 and CSJ-47 (mono) and CSJ-1, CSJ-24, CSJ-26 and CSJ-27 (poly). Comparably, some mono- (CSJ-5, CSJ-18) and poly-embryonic (CSJ-7, CSJ-8, CSJ-14, CSJ-19) genotypes exhibited least reductions in PDM following salt treatment. Most polyembryonic genotypes showed lower reductions in root than in shoot mass, indicating that they may be more adept at absorbing water and nutrients when exposed to salt. The majority of genotypes did not exhibit leaf tip burn and marginal scorch despite significant increases in Na+ and Cl-, suggesting that tissue tolerance existed for storing excess Na+ and Cl- in vacuoles. Jamun genotypes were likely more efficient in Cl- exclusion because leaf, stem and root Cl- levels were consistently lower than those of Na+ under salt treatment. Leaf K+ was particularly little affected in genotypes with high leaf Na+. Lack of discernible differences in leaf, stem and root Ca2+ and Mg2+ contents between control and salt treatments was likely due to their preferential uptake. Correlation analysis suggested that Na+ probably had a greater inhibitory effect on biomass in both mono- and poly-embryonic types. Discriminant analysis revealed that while stem and root Cl- probably accounted for shared responses, root Na+, leaf K+ and leaf Cl- explained divergent responses to salt stress of mono- and poly-embryonic types. Genotypes CSJ-18 and CSJ-19 seemed efficient in fending off oxidative damage caused by salt because of their stronger antioxidant defences. Conclusions: Polyembryonic genotypes CSJ-7, CSJ-8, CSJ-14 and CSJ-19, which showed least reductions in biomass even after prolonged exposure to salinity stress, may be used as salt-tolerant rootstocks. The biochemical and molecular underpinnings of tissue tolerance to excess Na+ and Cl- as well as preferential uptake of K+, Ca2+, and Mg2+ need to be elucidated.

A molecular survey of zoonotic pathogens of public health importance in rodents/shrews and their ectoparasites trapped in Puducherry, India.

BACKGROUND: Globally, India has a high zoonotic disease burden and lacks surveillance data in humans and animals. Rodents are known reservoirs for many zoonotic diseases and their synanthropic behavior poses a great public health threat. METHODS: In this study, trapped rodents/shrews from randomly selected villages within Puducherry, India, and their ectoparasites were screened for zoonotic pathogens, namely, Orientia tsutsugamushi, other pathogenic rickettsiae, Leptospira spp., Cryptosporidium spp., Coxiella burnetii and methicillin-resistant Staphylococcus aureus (MRSA) using conventional PCR. A total of 58 rodents/shrews were trapped from 11 villages. The species trapped were Suncus murinus (49/58, 84.48%), Rattus rattus (8/58, 13.79%) and Rattus norvegicus (1/58, 1.72%). All ectoparasites collected were identified as mites and its infestation rate was 46.55% (27/58). RESULTS: Real-time PCR targeting the 47 kDa gene of O. tsutsugamushi revealed positivity in one rodent and one shrew (3.45%) and two mite pools (7.41%). Conventional PCR targeting the 56 kDa gene revealed positivity in one shrew and two mite pools and the phylogenetic analysis of all three amplicons indicated the circulation of the Gilliam-related serotype. MRSA was detected in the alimentary tract of a shrew (1/32, 3.13%). Leptospira spp., Rickettsia, Cryptosporidium spp. and Co. burnetii tested negative. CONCLUSIONS: The detection of zoonotic pathogens within reservoir hosts and vectors poses a risk of transmission to humans. This study signifies the need for zoonotic pathogen surveillance in synanthropic rodents/shrews.

Perceived needs of disease vector control programs: A review and synthesis of (sub)national assessments from South Asia and the Middle East.

Systems for disease vector control should be effective, efficient, and flexible to be able to tackle contemporary challenges and threats in the control and elimination of vector-borne diseases. As a priority activity towards the strengthening of vector control systems, it has been advocated that countries conduct a vector-control needs assessment. A review was carried out of the perceived needs for disease vector control programs among eleven countries and subnational states in South Asia and the Middle East. In each country or state, independent teams conducted vector control needs assessment with engagement of stakeholders. Important weaknesses were described for malaria, dengue and leishmaniases regarding vector surveillance, insecticide susceptibility testing, monitoring and evaluation of operations, entomological capacity and laboratory infrastructure. In addition, community mobilization and intersectoral collaboration showed important gaps. Countries and states expressed concern about insecticide resistance that could reduce the continued effectiveness of interventions, which demands improved monitoring. Moreover, attainment of disease elimination necessitates enhanced vector surveillance. Vector control needs assessment provided a useful planning tool for systematic strengthening of vector control systems. A limitation in conducting the vector control needs assessment was that it is time- and resource-intensive. To increase the feasibility and utility of national assessments, an abridged version of the guidance should focus on operationally relevant topics of the assessment. Similar reviews are needed in other regions with different contextual conditions.

Targeting notch-related lncRNAs in cancer: Insights into molecular regulation and therapeutic potential.

Cancer is a group of diseases marked by unchecked cell proliferation and the ability for the disease to metastasize to different body areas. Enhancements in treatment and early detection are crucial for improved outcomes. LncRNAs are RNA molecules that encode proteins and have a length of more than 200 nucleotides. LncRNAs are crucial for chromatin architecture, gene regulation, and other cellular activities that impact both normal growth & pathological processes, even though they are unable to code for proteins. LncRNAs have emerged as significant regulators in the study of cancer biology, with a focus on their intricate function in the Notch signaling pathway. The imbalance of this pathway is often linked to a variety of malignancies. Notch signaling is essential for cellular functions like proliferation, differentiation, and death. The cellular response is shaped by these lncRNAs through their modulation of essential Notch pathway constituents such as receptors, ligands, and downstream effectors around it. Furthermore, a variety of cancer types exhibit irregular expression of Notch-related lncRNAs, underscoring their potential use as therapeutic targets and diagnostic markers. Gaining an understanding of the molecular processes behind the interaction between the Notch pathway and lncRNAs will help you better understand the intricate regulatory networks that control the development of cancer. This can open up new possibilities for individualized treatment plans and focused therapeutic interventions. The intricate relationships between lncRNAs & the Notch pathway in cancer are examined in this review.

Host Plant Modulated Physio-Biochemical Process Enhances Adaptive Response of Sandalwood (Santalum album L.) under Salinity Stress.

Salinity is one of the most significant abiotic stress that affects the growth and development of high-value tree species, including sandalwood, which can also be managed effectively on saline soils with the help of suitable host species. Therefore, the current investigation was conducted to understand the physiological processes and antioxidant mechanisms in sandalwood along the different salinity gradients to explore the host species that could support sandalwood growth in salt-affected agro-ecosystems. Sandalwood seedlings were grown with ten diverse host species with saline water irrigation gradients (ECiw~3, 6, and 9 dS m-1) and control (ECiw~0.82 dS m-1). Experimental findings indicate a decline in the chlorophyll content (13-33%), relative water content (3-23%), photosynthetic (27-61%) and transpiration rate (23-66%), water and osmotic potential (up to 137%), and ion dynamics (up to 61%) with increasing salinity levels. Conversely, the carotenoid content (23-43%), antioxidant activity (up to 285%), and membrane injury (82-205%) were enhanced with increasing salinity stress. Specifically, among the hosts, Dalbergia sissoo and Melia dubia showed a minimum reduction in chlorophyll content, relative water content, and plant water relation and gas exchange parameters of sandalwood plants. Surprisingly, most of the host tree species maintained K+/Na+ of sandalwood up to moderate water salinity of ECiw~6 dS m-1; however, a further increase in water salinity decreased the K+/Na+ ratio of sandalwood by many-fold. Salinity stress also enhanced the antioxidative enzyme activity, although the maximum increase was noted with host plants M. dubia, followed by D. sissoo and Azadirachta indica. Overall, the investigation concluded that sandalwood with the host D. sissoo can be successfully grown in nurseries using saline irrigation water and, with the host M. dubia, it can be grown using good quality irrigation water.

Multi-level, forming and filament free, bulk switching trilayer RRAM for neuromorphic computing at the edge.

CMOS-RRAM integration holds great promise for low energy and high throughput neuromorphic computing. However, most RRAM technologies relying on filamentary switching suffer from variations and noise, leading to computational accuracy loss, increased energy consumption, and overhead by expensive program and verify schemes. We developed a filament-free, bulk switching RRAM technology to address these challenges. We systematically engineered a trilayer metal-oxide stack and investigated the switching characteristics of RRAM with varying thicknesses and oxygen vacancy distributions to achieve reliable bulk switching without any filament formation. We demonstrated bulk switching at megaohm regime with high current nonlinearity, up to 100 levels without compliance current. We developed a neuromorphic compute-in-memory platform and showcased edge computing by implementing a spiking neural network for an autonomous navigation/racing task. Our work addresses challenges posed by existing RRAM technologies and paves the way for neuromorphic computing at the edge under strict size, weight, and power constraints.

Delineating the role of host plants in regulating the water and salinity stress induced changes in sandalwood roots.

The interaction of root hemi-parasite (sandalwood) with its hosts is crucial for establishing successful plantations under abiotic stresses. In the present study, we explored the best possible host for sandalwood along with its effect on sandalwood physiology in terms of water and nutrients. Interactive effects of host species (Alternanthera sp., Azadirachta indica, Dalbergia sissoo, Melia dubia, and Aquilaria malaccensis) with sandalwood were observed under eight treatments {100% best available water (BAW); 100% BAW + nutrient medium; 50% water deficit; 50% water deficit + nutrient medium; 100% saline water (ECiw 8ds/m); 100% saline water (ECiw 8ds/m) + nutrient medium; 50% water deficit + saline water (ECiw 8ds/m); and 50% water deficit + saline water (ECiw 8ds/m) + nutrient medium}. A significant change in morpho-physiological traits of sandalwood roots was observed under different stress conditions, which were slightly improved through external supply of nutrient medium. Dalbergia sissoo (Shisham) and Melia dubia (Dek) seemed to be the best host plants providing better environment for sandalwood growth and development, i.e., higher plant height (59.7 and 53.68 cm) and collar diameter (3.24 and 3.07 mm) under stresses by maintaining water and ionic balance. Root length is an important parameter that was reduced by 27.58%, 19.22%, and 36.3% under water deficit, salinity, and combined stress of water deficit and salinity. Sandalwood grown with D. sissoo and M. dubia maintained the lowest Ψw (- 1.38 MPa) and Ψs (- 1.47 and - 1.48 MPa), respectively. In addition, sandalwood cultivated with D. sissoo and A. indica had higher accumulation of soluble proteins (0.48 and 0.42 mg/g) and soluble sugars (98.56 and 91.04 mg/g) in their roots. Results also showed that sandalwood roots had higher K+/Na+ with compatible host, i.e., with A. indica (1.85) and D. sissoo (1.83) than other studied hosts. It was also observed that sandalwood plants could not grow and survive alone under stress conditions even with application of nutrient medium. Based on the morphological traits, it was observed that sandalwood grown with hosts, Dalbergia sissoo and Melia dubia, was able to tolerate stress conditions better than other studied hosts. We can further recommend growing sandalwood with D. sissoo and M. dubia as a viable option to endure adverse environmental conditions.

Crystal structure of a newly identified M61 family aminopeptidase with broad substrate specificity that is solely responsible for recycling acidic amino acids.

Aminopeptidases with varied substrate specificities are involved in different crucial physiological processes of cellular homeostasis. They also have wide applications in food and pharma industries. Within the bacterial cell, broad specificity aminopeptidases primarily participate in the recycling of amino acids by degrading oligopeptides generated via primary proteolysis mediated by cellular ATP-dependent proteases. However, in bacteria, a truly broad specificity enzyme, which can cleave off acidic, basic, Gly and hydrophobic amino acid residues, is extremely rare. Here, we report structure-function of a putative glycyl aminopeptidase (M61xc) from Xanthomonas campestris pv campestris (Xcc) belonging to the M61 peptidase family. The enzyme exhibits broad specificity and cleaves Ala, Leu, Asp, Glu, Met, Ser, Phe, Tyr, Gly, Arg, and Lys at the N terminus, optimally of peptides with a length of 3-7 amino acids. Further, we report the high-resolution crystal structure of M61xc in the apo form (2.1 Å) and bestatin-bound form (1.95 Å), detailing its catalytic and substrate preference mechanisms. Comparative analysis of enzyme activity in crude cell extracts from both wild-type and m61xc-knockout mutant strains of Xcc has elucidated the unique intracellular role of M61xc. This study suggests that M61xc is the exclusive enzyme in these bacteria that is responsible for liberating Asp/Glu residues from the N-termini of peptides. Also, in view of its broad specificity and peptide degradation ability, it could be considered equivalent to M1 or other oligomeric peptidases from families like M17, M18, M42 or S9, who have an important auxiliary role in post-proteasomal protein degradation in prokaryotes.

In vitro antibacterial activity of antibiotics and plant essential oils against Escherichia coli MTCC443 supported through the molecular docking and pharmacokinetics study.

Most of the Escherichia coli turned into serious pathogens or developed antibiotic resistance, mainly due to their ability to show different phenotypic traits. In order to overcome the resistance to these antibiotics, the use of essential oils (EOs) is of great significance against highly pathogenic microorganisms. This study has been made to compare the in vitro antibacterial activity and further validated the same through the molecular docking study of 13 antibiotics such as ciprofloxacin, chloramphenicol, erythromycin, ampicillin, cefotaxime, rifampicin, kanamycin, vancomycin, streptomycin, penicillin, nalidixic acid, trimethoprim, and polymyxin, and 10 EOs such as garlic, tulsi, neem, clove, thyme, peppermint, coriander, tea, lavender, and eucalyptus against the target protein (DNA gyrase) of E. coli MTCC443. E. coli Microbial Type Culture Collection 443 was found to be highly sensitive to ciprofloxacin (zone of inhibition [ZOI], 2.5 cm ±0.1) and chloramphenicol (ZOI, 1.8 cm ±0.1), whereas garlic oil (ZOI, 5.5 cm ±0.1) and coriander oil (ZOI, 4.4 cm ±0.1) were found comparatively most effective. Further, the in silico investigation observed the same; ciprofloxacin (binding affinity: -7.2 kcal/mol) and chloramphenicol (binding affinity: -6.6 kcal/mol). Penicillin (binding affinity: -4.2 kcal/mol) and polymyxin (binding affinity: -0.3 kcal/mol) were found to be least effective against the tested microbe, whereas vancomycin (binding affinity: +0.8 kcal/mol) had no effect on it. Garlic (binding affinity: -7.8 kcal/mol), coriander (binding affinity: -6.8 kcal/mol), peppermint (binding affinity: -6.2 kcal/mol), and neem (binding affinity: -6.2 kcal/mol) oil exhibited the potent antibacterial activity against E. coli MTCC443, whereas thyme (binding affinity: -6.1 kcal/mol), tea tree (binding affinity: -4.9 kcal/mol), and tulsi (binding affinity: -3.8 kcal/mol) oil were observed moderately effective. Eucalyptus (binding affinity: -2.9 kcal/mol) and lavender (binding affinity: -2.8 kcal/mol) oil were found to be the least effective among all the oils tested. The pharmacokinetics and networking were performed to the pharmacology of the potential compounds.

A sustainable approach to prepare green synthesis of copper nanoparticles of Bauhinia variegata & Saussurea lappa: Unveiling in-vitro anti-obesity applications.

Nanoparticles have different shapes and sizes between the range of 1-100 nm, which show advantages for stabilizing compounds, higher carrier capacity, and lower costs. Metal nanoparticles such as copper, gold, silver, and zinc are favorable components for various applications due to their interesting properties. In the present study, nanoparticles were synthesized by reduction with flower extracts of Bauhinia variegate & Saussurea lappa that were used to stabilize the copper nanoparticles. Furthermore, the characterization of plants synthesized copper nanoparticles was carried out through UV-visible dynamic light scattering. Additionally, morphological characterization of nanoparticles was confirmed by scanning electron microscopy and energy dispersive X-ray spectroscopy confirmed the elemental composition of copper nanoparticles. Powder X-ray diffraction was conducted for the analysis of crystallinity, purity, and crystal size of plant-synthesized copper nanoparticles. The average particle size was evaluated and exhibited the particle size at the peak of 8.721 nm and 98.03 nm for flower extracts of Bauhinia variegate & Saussurea lappa copper nanoparticles. The Fourier Transform Infrared spectrum was taken to scrutinize the various functional groups that were responsible for the reduction of the copper ions. The antimicrobial results against the bacterial strains with the positive test results of the zone of inhibition were for Bauhinia variegate (17 mm, 18 mm, 19 mm, and 18 mm) and Saussurea lappa (17 mm, 19 mm, 18 mm, and 18 mm) respectively for plants synthesized copper nanoparticles against the Staphylococcus aureus, Escherichia coli, Klebsiella pneumonia and Pseudomonas aeruginosa. Lipase inhibition assay and Amylase inhibition assay with different concentrations (20 µg/mL to 100 µg/mL) for Bauhinia variegate & Saussurea lappa (12.34 %-59.67 % and 10.50 %-47.01 %) and (34.52 %-89.02 % and 22.34 %-56.45 %) confirmed the anti-obesity and anti-diabetic activities of plants extract synthesized copper nanoparticles.