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The Duffy antigen receptor is a seven-transmembrane (7TM) protein expressed primarily at the surface of red blood cells and displays strikingly promiscuous binding to multiple inflammatory and homeostatic chemokines. It serves as the basis of the Duffy blood group system in humans and also acts as the primary attachment site for malarial parasite Plasmodium vivax and pore-forming toxins secreted by Staphylococcus aureus. Here, we comprehensively profile transducer coupling of this receptor, discover potential non-canonical signaling pathways, and determine the cryoelectron microscopy (cryo-EM) structure in complex with the chemokine CCL7. The structure reveals a distinct binding mode of chemokines, as reflected by relatively superficial binding and a partially formed orthosteric binding pocket. We also observe a dramatic shortening of TM5 and 6 on the intracellular side, which precludes the formation of the docking site for canonical signal transducers, thereby providing a possible explanation for the distinct pharmacological and functional phenotype of this receptor.
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Microscopia Crioeletrônica , Sistema do Grupo Sanguíneo Duffy , Receptores de Superfície Celular , Humanos , Receptores de Superfície Celular/metabolismo , Receptores de Superfície Celular/química , Sistema do Grupo Sanguíneo Duffy/metabolismo , Sistema do Grupo Sanguíneo Duffy/química , Transdução de Sinais , Sítios de Ligação , Quimiocinas/metabolismo , Quimiocinas/química , Ligação ProteicaRESUMO
A unique class of multimeric proteins made of covalently linked subunits known as pili, or fimbriae, are assembled and displayed on the gram-positive bacterial cell surface by a conserved transpeptidase enzyme named pilus-specific sortase. Sortase-assembled pili are produced by a wide range of gram-positive commensal and pathogenic bacteria inhabiting diverse niches such as the human oral cavity, gut, urogenital tract, and skin. These surface appendages serve many functions, such as molecular adhesins, immunomodulators, and virulence determinants, that significantly contribute to both the commensal and pathogenic attributes of producer microbes. Intensive genetic, biochemical, physiological, and structural studies have been devoted to unveiling the assembly mechanism and functions, as well as the utility of these proteins in vaccine development and other biotechnological applications. We provide a comprehensive review of these topics and discuss the current status and future prospects of the field.
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Sirtuin 7 (SIRT7) is a member of the mammalian family of nicotinamide adenine dinucleotide (NAD+)-dependent histone/protein deacetylases, known as sirtuins. It acts as a potent oncogene in numerous malignancies, but the molecular mechanisms employed by SIRT7 to sustain lung cancer progression remain largely uncharacterized. We demonstrate that SIRT7 exerts oncogenic functions in lung cancer cells by destabilizing the tumor suppressor alternative reading frame (ARF). SIRT7 directly interacts with ARF and prevents binding of ARF to nucleophosmin, thereby promoting proteasomal-dependent degradation of ARF. We show that SIRT7-mediated degradation of ARF increases expression of protumorigenic genes and stimulates proliferation of non-small-cell lung cancer (NSCLC) cells both in vitro and in vivo in a mouse xenograft model. Bioinformatics analysis of transcriptome data from human lung adenocarcinomas revealed a correlation between SIRT7 expression and increased activity of genes normally repressed by ARF. We propose that disruption of SIRT7-ARF signaling stabilizes ARF and thus attenuates cancer cell proliferation, offering a strategy to mitigate NSCLC progression.
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Carcinoma Pulmonar de Células não Pequenas , Proliferação de Células , Progressão da Doença , Neoplasias Pulmonares , Sirtuínas , Humanos , Sirtuínas/metabolismo , Sirtuínas/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Animais , Camundongos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Regulação Neoplásica da Expressão Gênica , Linhagem Celular TumoralRESUMO
Six red-light-emitting Eu(III) complexes having a ß-hydroxyketone as ligand and heterocyclic ring containing compounds as ancillary ligands were synthesized to explore their use in displays and optoelectronics. The coordinating behavior of complexes was determined by various techniques such as FTIR (Fourier transform infrared), 1H-NMR (Nuclear magnetic resonance), and 13C-NMR that establishes a bonding of ligand and ancillary ligand with the Eu(III) ion. Morphology and purity were investigated through XRD (X-ray diffraction), SEM (scanning electron microscopy) and EDS (energy-dispersive X-ray spectroscopy) analyses that suggest semicrystalline and pure complex formation. Thermal analysis of complexes by TGA/DTG (thermogravimetric/derivative thermogravimetric) indicates that complexes are stable upto 200 ºC temperature making them suitable for use in display devices. Analysis of the photophysical properties was carried out in both solid and solution states using PL (photoluminescence) studies, color parameters, J-O (Judd-Ofelt) analysis and bandgap. Most emissive transition (5D0 â 7F2) is responsible for the red emission in the complexes. The CIE (Commission International de I'Eclairage) coordinates of complexes also indicate the red emission on UV excitation. The bandgap which was obtained in the range of 2.54-3.02 eV reveals the semiconducting behavior of complexes. Values of J-O parameters and Ω2 in the complexes reflect asymmetric chemical environment around Eu (III) and less covalence and the Ω4 indicates that complexes are less rigid. Bandgap calculated through DFT (density function theory) for complexes is in range of 2.37-2.77 eV, and intensity parameters (J-O), energy transfer rates, and spherical coordinates were determined by LUMPAC software. The computational data are in good harmony with the experimental data. Further biological aspects of complexes were studied using antioxidant and antimicrobial studies.
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Xanthomonas oryzae pv. oryzae (Xoo), the causative agent of bacterial blight (BB), has developed a unique strategy to infect rice by hijacking the host's methylglyoxal (MG) detoxification pathway. This results in an over-accumulation of MG, which facilitates tissue colonization and evasion of host's immune responses. While MG role in abiotic stresses is well-documented, its involvement in biotic stresses has not been extensively explored. Recently, Fu et al. (2024) provided the first evidence of MG role in promoting Xoo pathogenesis in rice. This new virulence strategy contributes to the pathogen's remarkable adaptability and survival. In this mechanism of hijacking of MG detoxification pathway, Xoo induces OsWRKY62.1 to inhibit OsGLY II expression, leading to MG overaccumulation in infected rice cells. This excess MG hinders plant cell organelle function, creating a favorable environment for Xoo by compromising the rice defense system. In this article, we have presented our perspectives on how the BB pathogen adapts its virulence mechanisms to infect and cause disease in rice.
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Oryza , Doenças das Plantas , Aldeído Pirúvico , Xanthomonas , Oryza/microbiologia , Oryza/metabolismo , Aldeído Pirúvico/metabolismo , Xanthomonas/patogenicidade , Xanthomonas/fisiologia , Doenças das Plantas/microbiologia , Virulência , Interações Hospedeiro-Patógeno , Inativação Metabólica , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Regulação da Expressão Gênica de PlantasRESUMO
Six novel red photoluminescent Eu3+ complexes with 3-formyl chromone as the primary sensitizer (L) were synthesized using the solution precipitation method. These complexes are [Eu(L3).X] where X is 2H2O (C1), phen (C2), neo (C3), bipy (C4), dmph (C5), and biquno (C6). These complexes were characterized by elemental analysis, EDAX analysis, SEM, FT-IR, thermo-gravimetric analysis (TGA/DTA) and photoluminescence spectra. The transition rates, quantum efficiency, and J-O intensity parameters were calculated using emission data and luminescence decay time (τ). Complexes exhibit a strong emission peak (5D0 â 7F2) of the Eu3+ ion in their luminescence emission spectra in solid and solution states, making them an effective emitter of the red color in OLEDs. The branching ratio of these complexes ranges from 80.67-82.92 in solid and 50.53-62.65 in solution state; CIE color coordinate of complexes falls in the red region. The color purity ranges [CP(%)] values for solid 95.26-97.27% and for solution ranges 85.11-93.43%. Correlated color temperature (CCT) of the complexes (C1-C6) ranged from 2710 to 3049 K in the solid state and 1775 to 2450 K in the solution state. These complexes are promising red emitters in OLEDs, semiconductors, and leasing devices.
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KEY MESSAGE: We highlight the emerging role of the R. solani novel lipase domain effector AGLIP1 in suppressing pattern-triggered immunity and inducing plant cell death. The dynamic interplay between plants and Rhizoctonia solani constitutes a multifaceted struggle for survival and dominance. Within this complex dynamic, R. solani has evolved virulence mechanisms by secreting effectors that disrupt plants' first line of defense. A newly discovered effector, AGLIP1 in R. solani, plays a pivotal role in inducing plant cell death and subverting immune responses. AGLIP1, a protein containing a signal peptide and a lipase domain, involves complex formation in the intercellular space, followed by translocation to the plant cytoplasm, where it induces cell death (CD) and suppresses defense gene regulation. This study provides valuable insights into the intricate molecular interactions between plants and necrotrophic fungi, underscoring the imperative for further exploration in this field.
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Lipase , Doenças das Plantas , Rhizoctonia , Rhizoctonia/patogenicidade , Rhizoctonia/fisiologia , Doenças das Plantas/microbiologia , Doenças das Plantas/imunologia , Lipase/metabolismo , Lipase/genética , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/genética , Morte Celular , Imunidade Vegetal/genética , Domínios Proteicos , Regulação da Expressão Gênica de PlantasRESUMO
Holliday junction is the key homologous recombination intermediate, resolved by structure-selective endonucleases (SSEs). SLX1 is the most promiscuous SSE of the GIY-YIG nuclease superfamily. In fungi and animals, SLX1 nuclease activity relies on a non-enzymatic partner, SLX4, but no SLX1-SLX4 like complex has ever been characterized in plants. Plants exhibit specialized DNA repair and recombination machinery. Based on sequence similarity with the GIY-YIG nuclease domain of SLX1 proteins from fungi and animals, At-HIGLE was identified to be a possible SLX1 like nuclease from plants. Here, we elucidated the crystal structure of the At-HIGLE nuclease domain from Arabidopsis thaliana, establishing it as a member of the SLX1-lineage of the GIY-YIG superfamily with structural changes in DNA interacting regions. We show that At-HIGLE can process branched-DNA molecules without an SLX4 like protein. Unlike fungal SLX1, At-HIGLE exists as a catalytically active homodimer capable of generating two coordinated nicks during HJ resolution. Truncating the extended C-terminal region of At-HIGLE increases its catalytic activity, changes the nicking pattern, and monomerizes At-HIGLE. Overall, we elucidated the first structure of a plant SLX1-lineage protein, showed its HJ resolving activity independent of any regulatory protein, and identified an in-built novel regulatory mechanism engaging its C-terminal region.
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Proteínas de Arabidopsis/metabolismo , Arabidopsis , Endodesoxirribonucleases/metabolismo , Endonucleases , Endorribonucleases/metabolismo , Animais , Arabidopsis/genética , Arabidopsis/metabolismo , DNA/química , Reparo do DNA , DNA Cruciforme/genética , Endonucleases/metabolismo , Resolvases de Junção Holliday/genética , Resolvases de Junção Holliday/metabolismoRESUMO
Adaptation to different forms of environmental stress is crucial for maintaining essential cellular functions and survival. The nucleolus plays a decisive role as a signaling hub for coordinating cellular responses to various extrinsic and intrinsic cues. p53 levels are normally kept low in unstressed cells, mainly due to E3 ubiquitin ligase MDM2-mediated degradation. Under stress, nucleophosmin (NPM) relocates from the nucleolus to the nucleoplasm and binds MDM2, thereby preventing degradation of p53 and allowing cell-cycle arrest and DNA repair. Here, we demonstrate that the mammalian sirtuin SIRT7 is an essential component for the regulation of p53 stability during stress responses induced by ultraviolet (UV) irradiation. The catalytic activity of SIRT7 is substantially increased upon UV irradiation through ataxia telangiectasia mutated and Rad3 related (ATR)-mediated phosphorylation, which promotes efficient deacetylation of the SIRT7 target NPM. Deacetylation is required for stress-dependent relocation of NPM into the nucleoplasm and MDM2 binding, thereby preventing ubiquitination and degradation of p53. In the absence of SIRT7, stress-dependent stabilization of p53 is abrogated, both in vitro and in vivo, impairing cellular stress responses. The study uncovers an essential SIRT7-dependent mechanism for stabilization of the tumor suppressor p53 in response to genotoxic stress.
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Dano ao DNA , Proteínas Nucleares/metabolismo , Sirtuínas/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Raios Ultravioleta , Acetilação/efeitos da radiação , Animais , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Catálise/efeitos da radiação , Linhagem Celular Tumoral , Nucléolo Celular/metabolismo , Nucléolo Celular/efeitos da radiação , Humanos , Lisina/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Nucleofosmina , Fosforilação/efeitos da radiação , Estabilidade Proteica/efeitos da radiação , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Transcrição Gênica/efeitos da radiação , Ubiquitinação/efeitos da radiaçãoRESUMO
BACKGROUND: Professionalism among nurses plays a critical role in ensuring patient safety and quality care and involves delivering competent, safe, and ethical care while also working with clients, families, communities, and healthcare teams. AIMS AND OBJECTIVES: To assess the level of nursing professionalism and the factors affecting professionalism among nurses working at a tertiary care center in India. METHODS: A descriptive cross-sectional study was conducted from October 2022 to March 2023 using a total enumeration sampling technique. Following institutional ethics committee approval, standardized tools were administered consisting of Nursing Professionalism Scale and socio-demographic, personal, and organizational characteristics. RESULTS: A total of 270 nurses participated, with a response rate of 93.7%. The mean age of the participants was 27.33 ± 2.75 years, with the majority being female (82.6%) and belonged to the age group of 23-27 years (59.6%). More than half of the nurses exhibited high professionalism (53%), with the highest and lowest median scores for professional responsibility (29.0) and valuing human beings (13.0) respectively. Multivariate regression analysis demonstrated that, compared with their counterparts, nurses with a graduate nursing qualification (AOR = 4.77, 95% CI = 1.16-19.68), up-to-date training (AOR = 4.13, 95% CI = 1.88-9.06), and adequate career opportunity (AOR = 33.91, 95% CI = 14.48-79.39) had significant associations with high nursing professionalism. CONCLUSION/IMPLICATIONS FOR PRACTICE: The majority of the nurses had high professionalism, particularly in the domains of professional responsibility and management. Hospitals and healthcare institutions can use these findings to develop policies and prioritize opportunities for nurses to attend conferences and workshops to enhance their professional values, ultimately leading to improved patient care outcomes. PATIENT AND PUBLIC CONTRIBUTION: No patient or public contribution.
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Background and Aims: Mild to moderate sedation during bronchoscopy is essential for patient safety, comfort during and after the procedure, and to facilitate the performance of the bronchoscopist. Dexmedetomidine is a highly selective, centrally acting α-2 agonist used to provide conscious sedation during various procedures. The aim of this study was to compare the efficacy of three different doses of dexmedetomidine nebulization as an adjuvant to lignocaine during bronchoscopy. Material and Methods: Ninety American Society of Anesthesiologists physical status I/II patients, aged from 18 to 60 years, scheduled for an elective bronchoscopy, were recruited. They were divided into three groups: 30 patients in each group. Group I: The patient was nebulized with a mixture of 4 ml of 4% lignocaine and dexmedetomidine 0.5 µg/kg. Group II: The patient was nebulized with a mixture of 4% lignocaine, 4 ml, and dexmedetomidine, 1 µg/kg. Group III: The patient was nebulized with 4% lignocaine 4 ml and dexmedetomidine 1.5 µg/kg. Results: The mean cough score was (1.17 ± 0.37), (1.40 ± 0.49), and (1.70 ± 0.75) in group III, group II, and group I, respectively. A significant difference was found between the groups. Patients were more comfortable with a statistically significant difference in the comfort score in group III as compared to group II and group I. Conclusion: Dexmedetomidine nebulization in a dose of 1.5 µg/kg (compared to 1 µg/kg or 0.5 µg/kg) as an adjuvant to lignocaine, provides better bronchoscopy conditions and patient satisfaction.
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AIMS: To compare the efficacy and safety of degludec U100 versus glargine U300 for the early postoperative management of patients with type 2 diabetes mellitus (T2D) undergoing coronary artery bypass graft (CABG) surgery. METHODS: A total of 239 patients were randomly assigned (1:1) to receive a basal-bolus regimen in the early postoperative period using degludec U100 (n = 122) or glargine U300 (n = 117) as basal and glulisine before meals. The primary outcome was mean differences between groups in their daily BG concentrations. The major safety outcome was the occurrence of hypoglycemia. RESULTS: There were no differences in mean daily BG concentrations (157 vs. 162 mg/dl), mean percentage of readings within target BG of 70-180 mg/dl (74% vs. 73%), daily basal insulin dose (19 vs. 21 units/day), length of stay (median [IQR]: 9 vs. 9 days), or hospital complications (21.3% vs. 21.4%) between treatment groups. There were no differences in the proportion of patients with BG <70 mg/dl (15.6% vs. 23.1%) or <54 mg/dl (1.6% vs. 4.3%) between degludec-100 and glargine-300 groups. CONCLUSIONS: Treatment with degludec U100 is as effective and safe as glargine U300 for the early postoperative hospital management of patients with T2D undergoing CABG.
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Diabetes Mellitus Tipo 2 , Humanos , Insulina Glargina/efeitos adversos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Ponte de Artéria Coronária , Período Pós-Operatório , GlicemiaRESUMO
Many plants possess immense pharmacological properties because of the presence of various therapeutic bioactive secondary metabolites that are of great importance in many pharmaceutical industries. Therefore, to strike a balance between meeting industry demands and conserving natural habitats, medicinal plants are being cultivated on a large scale. However, to enhance the yield and simultaneously manage the various pest infestations, agrochemicals are being routinely used that have a detrimental impact on the whole ecosystem, ranging from biodiversity loss to water pollution, soil degradation, nutrient imbalance and enormous health hazards to both consumers and agricultural workers. To address the challenges, biological eco-friendly alternatives are being looked upon with high hopes where endophytes pitch in as key players due to their tight association with the host plants. The intricate interplay between plants and endophytic microorganisms has emerged as a captivating subject of scientific investigation, with profound implications for the sustainable biosynthesis of pharmaceutically important secondary metabolites. This review delves into the hidden world of the "secret wedlock" between plants and endophytes, elucidating their multifaceted interactions that underpin the synthesis of bioactive compounds with medicinal significance in their plant hosts. Here, we briefly review endophytic diversity association with medicinal plants and highlight the potential role of core endomicrobiome. We also propose that successful implementation of in situ microbiome manipulation through high-end techniques can pave the way towards a more sustainable and pharmaceutically enriched future.
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Endófitos , Plantas Medicinais , Humanos , Endófitos/metabolismo , Ecossistema , Fungos/metabolismo , BiodiversidadeRESUMO
Six samarium (III) complexes were synthesised by employing the ß-ketocarboxylic acid as main ligand and five N-donor systems as ancillary ligands through the environmentally safe liquid-assisted grinding method. Various characterisation techniques were employed to determine the structure of the complexes i.e. NMR, IR, XRD and SEM. Photoluminescent studies were carried out in solid as well as in solution form. In solid and solution form emission spectra show maximum intensity peak at 604 and 602 nm, respectively, assigned to 4G5/2 â 6H7/2 transition which explains orange emission on UV excitation in complexes. CCT, CP, colorimetric parameters and quantum yield (relative and intrinsic) of the synthesized complexes were calculated. With the help of reflectance spectra, band gap and Urbach energy were determined. Lasing parameters were also calculated by employing FWHM values obtained from Gaussian fitting. Energy transfer study revealed the efficacious energy transfer from ligand to metal's emissive level. Further antimicrobial studies revealed higher activity in case of complexes in comparison to ligand.
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Six Eu3+ complexes were synthesised with ß-keto acid as main ligand and secondary ligands through liquid assisted grinding method. These complexes were characterised by various techniques such as spectroscopic technique, XRD, EDAX, SEM analysis, thermal technique, Urbach energy and optical band gap investigation. The luminous photophysical properties were studied by PL spectroscopy in solid as well as solution phase and some theoretical calculation was done to investigate the radiative (Arad) & non-radiative (Anrad) transition rate, quantum efficiency (ɸ), Judd Ofelt parameters for 5D0 â 7F2,4 transitions in both states. Judd Ofelt parameters were also calculated by the JOES software and the outcomes are well harmonised with theoretical values. The complexes have CIE color coordinate value in ruby red region and above 88.65% color purity in both phases, which made them attractive candidates for red light-emitting displays. 5D0 â 7F2 transition was proposed as a laser emission transition owing to their high branching ratio (67.18-74.24%) in solid and (60.09-74.40%) in solution phase. Computational methods were employed to determine the structure and energy of various molecular orbitals. Antimicrobial assay of complexes was also rationalised and found that the complexes are pertinent as good bactericidal and fungicidal agents in pharmaceutical industry.
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Európio , Luminescência , Európio/química , Ligantes , LuzRESUMO
Tb3+ complexes with ß-ketocarboxylic acid as main ligand and heterocyclic systems as auxiliary ligand were synthesized and analyzed to assess their prospective relevance as green light emitting material. The complexes were characterized via various spectroscopic techniques and were found to be stable up to ≈ 200 â. Photoluminescent (PL) investigation was performed to assess the emissive nature of complexes. Longest luminescence time of decay (1.34 ms) and highest intrinsic quantum efficiency (63.05%) were fetched for complex T5. Color purity of complexes was found to be in range 97.1 - 99.8% which demonstrated the aptness of these complexes in green color display devices. NIR Absorption spectra were employed to evaluate Judd-Ofelt parameters to appraise the luminous performance and environment encircling Tb3+ ions. The JO parameters were found to follow the order: Ω2 > Ω4 > Ω6 and suggested the higher covalence character in complexes. Theoretical branching ratio in the range 65.32 - 72.68%, large stimulated emission cross section and narrow FWHM for 5D4 â 7F5 transition unlocked the relevance of these complexes as a green color laser media. Band gap and Urbach analysis were consummated via enforcing nonlinear curve fit function on absorption data. Two band gaps with values in between 2.02 - 2.93 eV established the prospective use of complexes in photovoltaic devices. Energies of HOMO and LUMO were estimated employing geometrically optimized structures of complexes. Investigation of biological properties accomplished via antioxidant and antimicrobial assays which communicated their applicability in biomedical domain.
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A series of new red luminescent Eu(III) complexes were integrated by ß-hydroxyketone ligand 2-(4-chlorophenyl)-1-(2-hydroxy-4,6-dimethoxyphenyl)ethan-1-one (CHDME) as main ligand and 1,10-phenanthroline (phen) or 5,6-dimethyl-1,10-phenanthroline (dmphen) or bathophenanthroline (bathophen) as ancillary ligand. The complexes were synthesised by solution precipitation method. The CHDME is taken as ligand and its analogous Eu(III) complexes were characterized by elemental analysis, FT-IR and 1H-NMR. The photoluminescent properties were also examined in solid state. The Judd-Ofelt intensity parameters (Ω2 and Ω4) and luminescence quantum efficiency (η) of Eu(III) complexes were additionally figured out as per luminescence spectra and decay cure. UV analysis and optical band was also calculated. Computational analysis were carried out and optical band and Judd-Ofelt intensity parameters were determined. Furthermore, the pharmacological activities such as antimicrobial and antioxidant activity of ligand CHDME and its analogous Europium complexes were also examined. The methods used were tube dilution method for calculating antimicrobial activity and DPPH free radical method for antioxidant activity.
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Background and Aims: Surgical procedure commonly performed in the advanced pediatric age group includes urogenital surgery, adenotonsillectomy, etc., Aim: The aim of this study is to determine the effect of single-dose gabapentin 15 mg/kg on acute pain in the immediate postoperative period in patients aged 8-14 years undergoing surgeries under general anesthesia. Material and Methods: After the approval from the institutional ethical committee, 60 American Society of Anesthesiologists (ASA) I and II patients aged 8-14 years undergoing urogenital surgeries (orchidopexy/urethroplasty) under general anesthesia were included in this study. The patients were assigned into one of the two treatment groups. Patients in group I received oral gabapentin 15 mg/kg dissolved in 5 mL of honey 2 h before surgery, while patients in group II received 5 mL honey orally 2 h before surgery. Results: A total of 60 patients participated. Patients in group I had lower consumption of fentanyl perioperatively (intraoperatively: 1.36 ± 0.70 mcg/kg; postoperatively: 2.36 ± 0.795 mcg/kg) than group II (intraoperatively: 1.8 ± 0.6 mcg/kg; postoperatively: 2.9 ± 0.47 mcg/kg). The differences in the two groups were significant. The time to first rescue analgesia was greater in group I (3.03 ± 0.60 h) than in group II (2.26 ± 0.57 h). There was an increase in sedation score in the treatment group. Conclusion: Our clinical study demonstrates that a 15 mg/kg single preemptive oral dose of gabapentin might reduce the requirement of analgesics perioperatively in pediatric urogenital surgery but might also be associated with undesirable effects such as increased sedation.
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Quorum sensing modulatory effect of linalool was tested for the first time against Pseudomonas syringae pv. tomato DC 3000, a bacterial plant pathogen responsible for causing huge losses worldwide. DC 3000 extensively regulates its virulence traits through quorum sensing mechanism involving expression of psyI, an acyl-homoserine lactone (AHL) synthase gene and psyR, a luxR-type regulator. In this study, exposure of DC 3000 to 80 ppm linalool concentration resulted in reduced biofilm formation, hampered motility, decreased AHL production, and reduced secretion of plant cell wall-degrading enzymes followed by negligible effect on the bacterial count and its metabolic activity. Extracellular polymeric substances (EPS), which play a crucial role in the development of biofilm and subsequent infection was significantly reduced which was further confirmed by Fourier Transform Infrared Spectroscopy. The qRT PCR analysis of the gene expression analysis of virulence genes (syringafactin production gene syfA, type III secretion system gene hrpA, flagellar genes fleQ and fliC, and coronatine production gene cfl unveiled significant downregulation of the same under Lin 80 ppm concentration. To further confirm the aforementioned possibilities, docking simulations run between PsyR and linalool suggested a strong interaction with the developed protein model. Overall, the treatment of DC 3000 with Lin 80 ppm affected the phenotypic and genotypic expressions associated with quorum sensing, thereby significantly reducing the infection rate as observed in in-vivo plant assay.
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Pseudomonas syringae , Solanum lycopersicum , Pseudomonas syringae/genética , Percepção de Quorum/genética , Virulência/genética , Proteínas de Bactérias/metabolismo , Acil-Butirolactonas/metabolismoRESUMO
INTRODUCTION: Primary hyperparathyroidism (PHPT) in India is mostly symptomatic with renal and skeletal complications. Evidence on mortality outcomes following parathyroidectomy from India, where the disease is predominantly symptomatic is limited. MATERIAL AND METHODS: This was a prospective study to evaluate mortality outcomes in the Indian PHPT registry over the past 25 years (n = 464). Pre- and postoperative parameters and mortality data were obtained from medical records and/or by verbal autopsy, a method validated by WHO for data collection in settings where several deaths are noninstitutional. Patients were divided into survivor (SG) and nonsurvivor groups (NSG) to ascertain differences in presentation and the effect of parathyroidectomy. RESULTS: The overall mortality was 8.8% at a median follow-up of 8 years (IQR 1-13) after parathyroidectomy. Chronic kidney disease was the most common background cause of death (43.5%), followed by pancreatitis (28.2%). NSG had significantly more frequent renal dysfunction (91.9% vs 73.9%), anaemia (50 vs 16.6%) and pancreatitis (24.3 vs 6.4%). PTH (61.9 vs 38.3 pmol/l) and baseline creatinine (97.2 vs 70.7 µmol/l) were significantly higher and eGFR lower (66.7 vs 90.7 ml/min/1.73m2) in the NSG than SG. By Cox proportional modelling, renal dysfunction [HR 2.88 (1.42-5.84)], anaemia [HR 2.45 (1.11-5.42)] and pancreatitis [HR 2.65 (1.24-5.66)] on univariate and renal dysfunction [HR 3.33 (1.13-9.77)] on multivariate analysis were significant for mortality. Survival curves demonstrated a significantly higher mortality with lower eGFR values. CONCLUSIONS: Nonsurvivors in PHPT had greater prevalence and more severe baseline renal dysfunction than survivors. Survival after parathyroidectomy was significantly associated with estimated glomerular filtration rate at baseline.