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In the realm of biomedical applications, the inclusion of plant-derived components stands out as a critical consideration due to their non-toxic nature and antioxidant properties. In our research, we opt for Colocasia esculenta plant extract, utilizing microwave technology to create dually doped ZnO nanopowder with copper (Cu) and cerium (Ce). Authors employ XRD analysis to explore the structural attributes and crystallite size of the nanoparticles, which are found to be within the range of 16–19 nm. The surface and internal characteristics of these nanoparticles are precisely scrutinized using SEM-EDS and TEM characterization techniques. Additionally, ultraviolet-visible spectroscopy is utilized to determine the forbidden energy gap of the samples, providing insights into their potential applications in UV-protected devices. The synthesized nanoparticles exhibit significant antibacterial and antioxidant properties, highlighting their adaptability for various biomedical uses.

This research intends to formulate Ocimum sanctum mediated pure and transition metal (Co2+/Cu2+/Zn2+) doped magnesium oxide nanoparticles (MgO NPs). The cubic structure of so synthesized MgO NPs was confirmed by XRD analysis. As per UV–visible spectral analysis, band gap (Eg) is tuned upon doping; doping with Co, Cu and Zn, their respective Eg are 1.65 eV, 1.96 eV and 3.66 eV in relation to MgO, Eg = 3.50 eV. The average particle size decreased from 17 nm for MgO NPs to 8–13 nm for doped MgO NPs, based on TEM analysis. EDX and XPS analysis verified the presence of Mg, O and dopants, Co, Cu and Zn in synthesized NPs. SEM investigations showed that NPs are agglomerated and spherical. Zn–MgO NPs outperform Co/Cu doped MgO NPs in their photocatalytic efficacy and comparative degradation of methyl orange (MO) and malachite green (MG) dyes confirmed that they are more efficient in degrading MG. Antibacterial investigation revealed that Cu and Zn doped MgO NPs are efficient antibacterial agents against B. subtilis and E. coli than MgO NPs. In this study, Co–MgO NPs were ineffective as antibacterial agents. S. aureus was found resistant to all NPs. Using the DPPH radical scavenging technique, these biosynthesized nanoparticles displayed 62–69 % antioxidant activity.

Aggregation behavior of conventional surfactants; SDS (anionic) and CTAB (cationic) in aqueous medium has been investigated in the presence of anti-HIV drugs; Emtricitabine (ECT) and Lamivudine (LMV) using conductometry, UV–Visible spectroscopy, and fluoroscence measurements over a temperature range of T = (298.15–313.15) K. The CMC values calculated from the conventional study i.e. conductance measurements corroborate very well with those obtained from spectroscopic techniques i.e. UV–Visible spectroscopy and fluorometry. The calculated CMC values have been used to determine thermodynamic parameters such as standard changes in enthalpy of micellization (ΔHmo), entropy of micellization (ΔSmo) and free energy of micellization (ΔGmo) using pseudo-phase separation model. These parameters have been analyzed in terms of the hydrophobic-hydrophilic interactions present in the surfactant-water-drug ternary system. It has been observed from the thermodynamic analysis that both the drugs favor micellization of studied ionic surfactants (SDS and CTAB) in aqueous medium, with Lamivudine exhibiting a more pronounced effect. Further, the micellar stability of studied systems has been analyzed in terms of enthalpy-entropy compensation graphs. This in-depth exploration of anti-HIV drug-surfactant interactions holds promising implications for enhancing pharmaceutical formulations in the context of HIV infection diseases.

Abstract Mutations that constitutively activate G protein-coupled receptors (GPCRs), known as constitutively activating mutations (CAMs), modify cell signaling and interfere with drugs, resulting in diseases with limited treatment options. We utilize fluorescence imaging at the single-molecule level to visualize the dynamic process of CAM-mediated activation of the human A2A adenosine receptor (A2AAR) in real time. We observe an active-state population for all CAMs without agonist stimulation. Importantly, activating mutations significantly increase the population of an intermediate state crucial for receptor activation, notably distinct from the addition of a partner G protein. Activation kinetics show that while CAMs increase the frequency of transitions to the intermediate state, mutations altering sodium sensitivity increase transitions away from it. These findings indicate changes in GPCR function caused by mutations may be predicted based on whether they favor or disfavor formation of an intermediate state, providing a framework for designing receptors with altered functions or therapies that target intermediate states.

In this current investigation, we elucidated the microwave-assisted green synthesis of 90:10, 80:20, and 70:30 CuO–Co3O4 nanocomposites (NCs) from Ipomoea carnea leaf extract, manifesting their remarkable antibacterial, photocatalytic, and antioxidant capabilities. The spectroscopic techniques of XRD, SEM, EDX, TEM, FTIR, and UV–visible spectroscopy were employed to validate the formation of the synthesized NCs. SEM and TEM images revealed distinctive snowball-rod and distorted spherical structures in the synthesized nanocomposites, with average particle sizes of 33.36, 26.17, and 29.10 nm. The estimated energy band gap values were 1.20, 1.40, and 1.50 eV for the respective nanocomposites. The well diffusion method was utilized to explore the zone of inhibition (ZOI) against bacteria, namely Bacillus subtilis, Staphylococcus aureus, and Escherichia coli. The nanocomposites, specifically the 90:10 and 80:20 CuO–Co3O4 blends, exhibited a noteworthy Zone of Inhibition (ZOI) during testing against B. subtilis, with approximate values of 34.76 ± 0.23 and 33.33 ± 0.32 mm, respectively. Furthermore, the photocatalytic potential has been investigated against the dyes Malachite green (MG) and Congo red (CR). Notably, the 90:10 NCs displayed an exceptional photodegradation rate of 97.69 % for MG and 95 % for CR within a mere 45 min. Moreover, the 70:30 NCs exhibited a commendable radical scavenging activity of approximately 97.53 % at a concentration of 800 μg/mL, while ascorbic acid, used as a standard, displayed a scavenging activity of 98.63 %. These investigations unveil the environmentally friendly, innovative, and cost-effective attributes of CuO–Co3O4 NCs derived from Ipomoea carnea leaf extract, which demonstrated excellent antibacterial, photocatalytic, and antioxidant properties.

In this study, a microwave-assisted method was used to encapsulate dual doped nickel-copper titanium dioxide (TiO2) nanoparticles (Ni-Cu TNPs) with polymer polyvinylpyrrolidone (PVP) and plant Tinospora Cordifolia (TC). The catalytic efficiency of encapsulated TNPs was performed through photocatalytic activity against Methyl Orange (MO) and Methylene Blue (MB) dyes as considered as water pollutants released by textiles industries. Also, these encapsulated TNPs were incubated in scavenging activity to eliminate the free radicals 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. The physicochemical properties of the encapsulated TNPs were analyzed using different characterization techniques. X-Ray Diffraction (XRD revealed that the encapsulated dual doped Ni-Cu TNPs had a tetragonal crystal lattice structure. The scanning electron microscopy (SEM) confirms the spherical morphology of encapsulated dual doped Ni-Cu TNPs with an average particle size ranging from 33 to 41 nm. The bandgap of the encapsulated dual doped Ni-Cu TNPs was found to be between 3.47 and 3.54 eV. Under UV radiation, the photocatalytic activity was performed with using control experiment and using encapsulated dual doped Ni-Cu TNPs against MO and MB dyes. The rate of degradation reached up to 99% for both dyes on increasing with an increase in TNPs catalyst dosage. Also, the encapsulated dual doped Ni-Cu TNPs demonstrated antioxidant activity of up to 93% against the DPPH assay.

In cell membranes, lipids are ubiquitous regulators of protein function. Here, Thakur et al. observe anionic phospholipids impact the conformational dynamics of a class A human GPCR.

Microbial infections and antibiotic resistance are some of the prime factors that are ascribed to endanger human health. Several reports have highlighted that drug-resistant pathogens assist in the etiology of various chronic diseases and lead to fatality. The present study deciphered the role of zinc oxide nanoparticles (ZnO NPs) as therapeutics against selected bacterial strains. The plant-based technique was followed to synthesize ZnO NPs. The synthesis was confirmed with different techniques viz. X-ray diffraction, transmission electron microscope (interplanar spacing at 0.126 nm), scanning electron microscope (flower-like structure), and Fourier transform infrared spectroscopy. The antibacterial analysis revealed that ZnO NPs inhibited the growth of all tested strains (Escherichia coli, Staphylococcus aureus, Salmonella typhi, Bacillus subtilis, and Klebsiella pneumoniae) to a greater extent (MIC ranged between 0.013±0.004-0.0625±0 mg/mL) as compared with ZnO compound (Bulk material). In the present study, ZnO NPs were produced in a cost-effective and environmentally sustainable way using a green process and can be used as a remedy for drug-resistant pathogens.

Membrane protein conformations and dynamics are driven by the protein-lipid interactions occurring within the local environment of the membrane. These environments remain challenging to accurately capture in structural and biophysical experiments using bilayers. Consequently, there is an increasing need for realistic cell-membrane mimetics for in vitro studies. Lipid nanodiscs provide certain advantages over vesicles for membrane protein studies. Nanodiscs are increasingly used for structural and spectroscopic characterization of membrane proteins. Despite the common use of nanodiscs, the interfacial environments of lipids confined to a ∼10-nm diameter area have remained relatively underexplored. Here, we use ultrafast two-dimensional infrared spectroscopy and temperature-dependent infrared absorption measurements of the ester carbonyls to compare the interfacial hydrogen bond structure and dynamics in lipid nanodiscs of varying lipid compositions and sizes with ∼100-nm vesicles. We examine the effects of lipid composition and nanodisc size. We found that nanodiscs and vesicles share largely similar lipid-water H-bond environments and interfacial dynamics. Differences in measured enthalpies of H-bonding suggest that H-bond dynamics in nanodiscs are modulated by the interaction between the annular lipids and the scaffold protein.

Summary: We describe production of the human A2A adenosine receptor (A2AAR), a class A G protein-coupled receptor (GPCR) for 19F-NMR and single-molecule fluorescence (SMF) spectroscopy. We explain in detail steps shared between the two sample preparation strategies, including expression and isolation of A2AAR and assembly of A2AAR in lipid nanodiscs and procedures for incorporation of either 19F-NMR or fluorescence probes. Protocols for SMF experiments include sample setup, data acquisition, data processing, and error analysis.For complete details on the use and execution of this protocol, please refer to Wei et al. (2022) and Sušac et al. (2018). : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Members of the Ebolavirus genus demonstrate a marked differences in pathogenicity in humans with Ebola (EBOV) being the most pathogenic, Bundibugyo (BDBV) less pathogenic, and Reston (RESTV) is not known to cause a disease in humans. The VP24 protein encoded by members of the Ebolavirus genus blocks type I interferon (IFN-I) signaling through interaction with host karyopherin alpha nuclear transporters, potentially contributing to virulence. Previously, we demonstrated that BDBV VP24 (bVP24) binds with lower affinities to karyopherin alpha proteins relative to EBOV VP24 (eVP24), and this correlated with a reduced inhibition in IFN-I signaling. We hypothesized that modification of eVP24-karyopherin alpha interface to make it similar to bVP24 would attenuate the ability to antagonize IFN-I response. We generated a panel of recombinant EBOVs containing single or combinations of point mutations in the eVP24-karyopherin alpha interface. Most of the viruses appeared to be attenuated in both IFN-I-competent 769-P and IFN-I-deficient Vero-E6 cells in the presence of IFNs. However, the R140A mutant grew at reduced levels even in the absence of IFNs in both cell lines, as well as in U3A STAT1 knockout cells. Both the R140A mutation and its combination with the N135A mutation greatly reduced the amounts of viral genomic RNA and mRNA suggesting that these mutations attenuate the virus in an IFN-I-independent attenuation. Additionally, we found that unlike eVP24, bVP24 does not inhibit interferon lambda 1 (IFN-λ1), interferon beta (IFN-β), and ISG15, which potentially explains the lower pathogenicity of BDBV relative to EBOV. Thus, the VP24 residues binding karyopherin alpha attenuates the virus by IFN-I-dependent and independent mechanisms.

Mycobacterium tuberculosis (Mtb) produces an unconventional flavohemoglobin (MtbFHb) that carries a FAD-binding site similar to D-lactate dehydrogenases (D-LDH) and oxidizes D-lactate into pyruvate. The molecular mechanism by which MtbFHb functions in Mtb remains unknown. We discovered that the D-LDH-type FAD-binding site in MtbFHb overlaps with another FAD-binding motif similar to thioredoxin reductases and reduces DTNB in the presence of NADPH similar to trxB of Mtb. These results suggested that MtbFHb is functioning as a disulfide oxidoreductase. Interestingly, D-lactate created a conformational change in MtbFHb and attenuated its ability to oxidize NADPH. Mass spectroscopy demonstrated that MtbFHb reduces des-myo-inositol mycothiol in the presence of D-lactate unlike NADPH, indicating that D-lactate changes the specificity of MtbFHb from di-thiol to di-mycothiol. When M. smegmatis carrying deletion in the fhbII gene (encoding a homolog of MtbFHb) was complemented with the fhb gene of Mtb, it exhibited four- to fivefold reductions in lipid peroxidation and significant enhancement in the cell survival under oxidative stress. These results were corroborated by reduced lipid peroxidation and enhanced cell survival of wild-type M. smegmatis after overexpression of the fhb gene of Mtb. Since D-lactate is a by-product of lipid peroxidation and MtbFHb is a membrane-associated protein, D-lactate-mediated reduction of mycothiol disulfide by MtbFHb may uniquely equip Mtb to relieve the toxicity of D-lactate accumulation and protect the cell from oxidative damage, simultaneously balancing the redox environment under oxidative stress that may be vital for the pathogenesis of Mtb.

SARS-CoV-2 claimed numerous lives and put nations on high alert. The lack of antiviral medications and the small number of approved vaccines, as well as the recurrence of adverse effects, necessitates the development of novel treatment ways to combat COVID-19. In this context, using databases such as PubMed, Google Scholar, and Science Direct, we gathered information about nanotechnology’s involvement in the prevention, diagnosis and virus-like particle vaccine development. This review revealed that various nanomaterials like gold, polymeric, graphene and poly amino ester with carboxyl group coated magnetic nanoparticles have been explored for the fast detection of SARS-CoV-2. Personal protective equipment fabricated with nanoparticles, such as gloves, masks, clothes, surfactants, and Ag, TiO2 based disinfectants played an essential role in halting COVID-19 transmission. Nanoparticles are used not only in vaccine delivery, such as lipid nanoparticles mediated transport of mRNA-based Pfizer and Moderna vaccines, but also in the development of vaccine as the virus-like particles elicit an immune response. There are now 18 virus-like particle vaccines in pre-clinical development, with one of them, developed by Novavax, reported being in phase 3 trials. Due to the probability of upcoming COVID-19 waves, and the rise of new diseases, the future relevance of virus-like particles is imperative. Furthermore, psychosocial variables linked to vaccine reluctance constitute a critical problem that must be addressed immediately to avert pandemic.

Management of ureteric stricture especially long length upper one-third poses a challenging job for most urologists. With the successful use of buccal mucosa graft (BMG) for stricture urethra leads the foundation for its use in ureteric stricture also. A 35-year-old male diagnosedcase of left upper ureteric stricture, postureteroscopy with left percutaneous nephrostomy (PCN) in situ. Cysto-retrograde pyelography and nephrostogram done simultaneously suggestive of left upper ureteric stricture of 3 cm at L3 level. On exploration, diseased ureteral segment exposed, BMG harvested and sutured as onlay patch graft with supportive omental wrap. The treatment choice for upper ureteric long length stricture is inferior nephropexy, autotransplantation, or bowel interposition. With PCN in situ, inferior nephropexy becomes technically difficult, other two are morbid procedures. Use of BMG in this situation is technically better choice with all the advantages of buccal mucosa. Onlay BMG for ureteral stricture is technically easy, less morbid procedure and can be important choice in future.

Out pouching of the urethral wall could be congenital or acquired. Male urethral diverticulum (UD) is a rare entity. We present 2 cases of acquired and 1 case of congenital male UD. Case 1A: 40 year male presented with SPC and dribbling urine. Clinically he had hard perineal swelling. RGU revealed large diverticulum in proximal bulbar, irregular narrow distal urethra and stricture just beyond diverticulum. Managed with perineal exploration, stone removal, diverticulum repair and urethroplasty using excess diverticular wall. Case 2A: 30 year male with obstructive lower urinary tract symptoms (LUTS). Retrograde urethrogram (RGU) revealed bulbar urethral diverticulum akin to anterior urethral valve, managed endoscopically. 1 year follow up urine stream satisfactory. Case 3A: 27 year male previously operated large proximal bulbar urethral stone with incontinence. RGU large proximal bulbar UD with wide open sphincter. Treated with excision of excess diverticular wall and penile clamp with pelvic exercises for incontinence. Congenital UD develops due to imperfect closure of urethral fold, Acquired UDs occurs secondary to stricture, infection, trauma, long standing impacted urethral stones or scrotal / skin flap urethroplasties. RGU and MCU are the best diagnostic technique to confirm and characterize the UD. Urethral diverticulectomy with urethral reconstruction is the recommended treatment for UD. UD is a rare entity. Especially in males, congenital are even more rare. Management should be individualized. Surgery can involve innovation and/or surgical modifications. We used excess diverticular flap for stricture urethroplasty in one case.

Introduction: Percutaneous nephrolithotomy (PCNL) is the treatment of choice for staghorn and large renal stones. The success of PCNL is highly related to optimal renal access. Upper calyceal puncture being more difficult and more demanding have relatively few studies presented. Aims and Objectives: This prospective study was carried out to evaluate the effectiveness and safety of upper calyceal versus lower calyceal puncture for the removal of complex renal stones through PCNL. Materials and Methods: A total of 94 patients underwent PCNL for complex renal stone in our institute. Fifty-one of them underwent lower calyceal, while 43 underwent upper calyceal puncture. The two approaches are compared as per total duration of surgery, intraoperative blood loss, infundibular/pelvic tear, rate of complete clearance and rate of postoperative complications (pulmonary, bleeding, fever and sepsis, etc.). Observation and Results: In our study, the success rate was 76.47% for those in the lower, 90.70% for those in the upper calyceal access group. Thoracic complications (hydrothorax) occurred to 1 patient in upper calyceal supracostal access group. Bleeding requiring blood transfusion happened to 5 patients in lower calyceal access and 1 in upper calyceal group. Conclusion: In our study for the management of complex renal calculi, we conclude that in a previously unoperated kidney, upper calyceal puncture through subcostal or supra 12 th rib is a feasible option minimizing lung/pleural rupture and gives a better clearance rate. We suggest that with due precautions, there should not be any hesitation for upper calyceal puncture in indicated patients.