Copper-catalyzed ortho-thiocyanation of aromatic amines.

A copper-catalyzed direct ortho-Csp2-H thiocyanation of free anilines has been developed. This method employs stable and non-toxic ammonium thiocyanate as a thiocyanation source, and tert-butyl hydroperoxide as the oxidant, enabling the synthesis of ortho-thiocyanated anilines with good yields and broad substrate tolerance. Hitherto, no reports have been found in the literature for the ortho-thiocyanation of aromatic amines, making this reaction an important breakthrough in synthetic organic chemistry.

Piezoresistive sensitivity enhancement below threshold voltage in sub-5 nm node using junctionless multi-nanosheet FETs.

In this paper, the piezoresistive sensitivity is enhanced by applying uniform mechanical stress (MS) on the multi-nanosheet (NS) channels of sub-5 nm junctionless field-effect transistors. The piezoresistivity of the sensing device is boosted by narrowing channel conductivity using low gate biasing and reducing physical channel width, resulting in the maximum (∼6 times higher) sensitivity observed in the subthreshold regime compared to the ON-state condition. In addition, the sensitivity is extensively increased by ∼30.3% near the threshold voltage with horizontally multi-NS stacking due to the uniform MS distribution on the multi-NS channels, which can sense slight deflection of pressure on the circular diaphragm. These results show that the tunable sensitivity of junctionless multi-channel devices is superior to the inversion mode, a consequence of the less scattering effect, better thermal stability, and low electronic noise.

Pathology, target discovery, and the evolution of XO inhibitors from the first discovery to recent advances (2020-2023).

Hyperuricemia, a disease characterized by elevation of serum uric acid level beyond 6 mg/dL. This elevation led to appearance of symptoms from joint pain to gout and from gout to difficulty in mobility of the patient. So, in this review, we have summarized the pathology of hyperuricemia, discovery of target and discovery of first XO inhibitor. At last, this review provides in-sights about the recently discovered as natural XO inhibitors, followed by design, structure activity relationship and biological activity of synthetic compounds as XO inhibitors discovered between 2020 and 2023 years. At last, the pharmacophores generated in this study will guide new researchers to design and modify the structure of novel XO inhibitors.

Transcriptional and secretome analysis of Rasamsonia emersonii lytic polysaccharide mono-oxygenases.

The current study is the first to describe the temporal and differential transcriptional expression of two lytic polysaccharide monooxygenase (LPMO) genes of Rasamsonia emersonii in response to various carbon sources. The mass spectrometry based secretome analysis of carbohydrate active enzymes (CAZymes) expression in response to different carbon sources showed varying levels of LPMOs (AA9), AA3, AA7, catalase, and superoxide dismutase enzymes pointing toward the redox-interplay between the LPMOs and auxiliary enzymes. Moreover, it was observed that cello-oligosaccharides have a negative impact on the expression of LPMOs, which has not been highlighted in previous reports. The LPMO1 (30 kDa) and LPMO2 (47 kDa), cloned and expressed in Pichia pastoris, were catalytically active with (kcat/Km) of 6.6×10-2 mg-1 ml min-1 and 1.8×10-2 mg-1 ml min-1 against Avicel, respectively. The mass spectrometry of hydrolysis products of Avicel/carboxy methyl cellulose (CMC) showed presence of C1/C4 oxidized oligosaccharides indicating them to be Type 3 LPMOs. The 3D structural analysis of LPMO1 and LPMO2 revealed distinct arrangements of conserved catalytic residues at their active site. The developed enzyme cocktails consisting of cellulase from R. emersonii mutant M36 supplemented with recombinant LPMO1/LPMO2 resulted in significantly enhanced saccharification of steam/acid pretreated unwashed rice straw slurry from PRAJ industries (Pune, India). The current work indicates that LPMO1 and LPMO2 are catalytically efficient and have a high degree of thermostability, emphasizing their usefulness in improving benchmark enzyme cocktail performance. KEY POINTS: • Mass spectrometry depicts subtle interactions between LPMOs and auxiliary enzymes. • Cello-oligosaccharides strongly downregulated the LPMO1 expression. • Developed LPMO cocktails showed superior hydrolysis in comparison to CellicCTec3.

Antidiabetic potential of thiazolidinedione derivatives with efficient design, molecular docking, structural activity relationship, and biological activity: an update review (2021-2023).

Thiazolidinedione has been used successfully by medicinal chemists all over the world in the development of potent antidiabetic derivatives. The few compounds with excellent antidiabetic potency that we have identified in this review could be used as a lead for further research into additional antidiabetic mechanisms. The information provided in this review regarding the design, biological activity, structure-activity relationships, and docking studies may be useful for scientists who wish to further explore this scaffold in order to fully utilize its biological potential and develop antidiabetic agents that would overcome the limitations of currently available medications for the treatment of diabetes. This review outlines the antidiabetic potential of Thiazolidinedione-based derivatives that have been published in the year 2021- till date.

A comprehensive review of synthetic and semisynthetic xanthine oxidase inhibitors: identification of potential leads based on in-silico computed ADME characteristics.

Xanthine oxidase (XO) inhibitors, both synthetic and semisynthetic, have been developed extensively over the past few decades. The increased level of XO is not only the major cause of gout but is also responsible for various conditions associated with hyperuricemia, such as cardiovascular disorders, chronic kidney disorders, diabetes, Alzheimer's disease and chronic wounds. Marketed available XO inhibitors (allopurinol, febuxostat, and topiroxostat) are used to treat hyperuricemia but they are associated with fatal side effects, which pose serious problems for the healthcare system, rising the need for new, more potent, safer compounds. This review summarizes recent findings on XO and describes their design, synthesis, biological significance in the development of anti-hyperuricemic drugs with ADME profile, structure activity relationship (SAR) and molecular docking studies. The results might help medicinal chemists to develop more efficacious XO inhibitors.

Triazole derivatives as potential xanthine oxidase inhibitors: Design, enzyme inhibition potential, and docking studies.

Considerable ingenuity has been shown in the recent years in the discovery of novel xanthine oxidase (XO) inhibitors that fall outside the purine scaffold. The triazole nucleus has been the cornerstone for the development of many enzyme inhibitors for the clinical management of several diseases, where hyperuricemia is one of them. Here, we give a critical overview of significant research on triazole-based XO inhibitors, with respect to their design, synthesis, inhibition potential, toxicity, and docking studies, done till now. Based on these literature findings, we can expect a burst of modifications on triazole-based scaffolds in the near future by targeting XO, which will treat hyperuricemics, that is, painful conditions like gout that at present are hard to deal with.

In-vitro antioxidant and anti-inflammatory potential along with p.o. pharmacokinetic profile of key bioactive phytocompounds of Snow Mountain Garlic: a comparative analysis vis-à-vis normal garlic.

Snow mountain garlic (SMG) is a trans-Himalayan medicinal plant used in the traditional medicine system for several ailments, including inflammatory arthritis. Research studies are insufficient to validate its folk medicinal applications. In the present study, the comparative abundance of its key bioactive phytocompounds, viz., S-allyl-L-cysteine (SAC), alliin, and S-methyl-L-cysteine (SMC) against normal garlic were assessed using the LC-MS/MS-MRM method. In addition, the study also explored the antioxidant and anti-inflammatory potency of crude extract of SMG and purified signature phytocompounds (i.e., SMC, SAC, and alliin) in comparison with normal garlic and dexamethasone in LPS-stimulated RAW264.7 macrophage cells. The LC-MS/MS-MRM study revealed significant differences among SMG and normal garlic, viz., alliin 22.8-fold higher in SMG, and SMC could be detected only in SMG. In the bioassays, SMG extract and purified signature phytocompounds significantly downregulated oxidative damage in activated macrophages, boosting endogenous antioxidants' activity. SMG extract-treated macrophages significantly suppressed NF-κB expression and related inflammatory indicators such as cytokines, COX-2, iNOS, and NO. Notably, the observed anti-inflammatory and antioxidant bioactivities of SMG extract were comparable to signature phytocompounds and dexamethasone. In addition, SAC being uniformly found in SMG and normal garlic, its comparative pharmacokinetics was studied to validate the pharmacodynamic superiority of SMG over normal garlic. Significantly higher plasma concentrations (Cmax), half-life (t1/2), and area under curve (AUC) of SAC following SMG extract administration than normal garlic validated the proposed hypothesis. Thus, the abundance of bioactive phytocompounds and their better pharmacokinetics in SMG extract might be underlying its medicinal merits over normal garlic.

Recent Advancement in NMR Based Plant Metabolomics: Techniques, Tools, and Analytical Approaches.

Plant metabolomics, a rapidly advancing field within plant biology, is dedicated to comprehensively exploring the intricate array of small molecules in plant systems. This entails precisely gathering comprehensive chemical data, detecting numerous metabolites, and ensuring accurate molecular identification. Nuclear magnetic resonance (NMR) spectroscopy, with its detailed chemical insights, is crucial in obtaining metabolite profiles. Its widespread application spans various research disciplines, aiding in comprehending chemical reactions, kinetics, and molecule characterization. Biotechnological advancements have further expanded NMR's utility in metabolomics, particularly in identifying disease biomarkers across diverse fields such as agriculture, medicine, and pharmacology. This review covers the stages of NMR-based metabolomics, including historical aspects and limitations, with sample preparation, data acquisition, spectral processing, analysis, and their application parts.

Metal Ion Responsive Luminescent Bio-Templated Co-Assemblies: Label-Free Detection of Multi-Metal Ions in Aqueous Media.

Recently, anionic bio-templates have emerged as promising platforms for designing dynamic and stimuli-responsive chromophoric assemblies capable of light harvesting in aqueous media thereby mimicking natural photosynthesis. Here, we present multi-metal ion-responsive luminescent co-assemblies between cationic pyrene-imidazolium amphiphile and anionic bio-templates (ATP, heparin, and DNA) in aqueous media. The anionic bio-templates enhance Förster resonance energy transfer (FRET) in the co-assemblies, with pyrene serving as an excellent donor for generating tunable multi-luminescent materials with embedded acceptor dyes. However, a significant loss in energy transfer towards acceptor dyes was observed in the presence of various metal ions, attributed to excimeric emission quenching facilitated by electron transfer between the pyrene chromophore and metal ions. Interestingly, detailed studies revealed that only ATP-based co-assemblies exhibited quenching phenomena in the presence of metal ions, contrasting with heparin and ctDNA co-assemblies. Additionally, label-free detection of multi-metal ions in aqueous environments, such as Fe2+, Fe3+, and Cu2+ ions, was successfully achieved with lower detection limits of 0.01 µM (3 ppb), 0.12 µM (30 ppb), and 0.58 µM (150 ppb) respectively. These co-assemblies hold significant promise for practical applications in environmental and biomedical sensing, enabling sensitive monitoring of metal ion concentrations.

Formulation of Solid Lipid Nanoparticles Loaded with Rosiglitazone and Probiotic: Optimization and In-vitro Characterization.

INTRODUCTION: In the present study, solid lipid nanoparticles loaded with Rosiglitazone and probiotics were prepared via solvent emulsification diffusion method which is patented. As a lipid and surfactant, Gleceryl monostearate and Pluronic -68 were used in the formulation process. METHODS: During characterization, it was determined that ingredient quantity variations significantly impacted Rosiglitazone loading capacity, particle size, polydispersity index, etc. In an optimized formulation of RSG-PB loaded SLNs, spherical particles with a mean particle size of 147.66 ± 1.52 nm, PDI of 0.42 ± 0.02, and loading capacity of 45.36 ± 0.20 were identified. RESULTS: Moreover, the developed SLNs had the potential to discharge the drug for up to 24 hours, as predicted by Higuchi's pharmacokinetic model. The SLNs were stable at 25°C/60%RH for up to 60 days. There was little to no change in particle size, PDI, or loading capacity. In addition, the number of probiotic bacteria was determined using the standard plate count procedure. Further, the antioxidant effect of the prepared formulation is evaluated using the DPPH assay method. CONCLUSION: This study concludes that the method used to fabricate RSG-probiotic-loaded SLNs is straightforward and yields favorable results regarding various parameters, including sustained release property, particle size, PDI, and percent drug loading stability. Furthermore, DPPH radical scavenging activity shows the high antioxidant potential of RSG-PB SLNs when compared to RSG and probiotics alone.

Gamma irradiation in modulating arsenic bioremediation potential of Pseudomonas sp. AK1 and AK9.

PURPOSE: Present study deals with the role of gamma irradiation in modulating arsenic bioremediation of Pseudomonas sp. AK1 and AK9 strains. MATERIALS AND METHODS: The bacterial strains AK1 and AK9 of Pseudomonas sp. were irradiated at different doses (5 Gy, 10 Gy, 15 Gy and 20 Gy) of gamma irradiation. The effect of γ-irradiation on the growth and arsenic modulating ability of AK1 and AK9 strains was determined in the presence and absence of arsenic along with non-irradiated strains. Further, a comparative study of non-irradiated and irradiated strains by protein profiling in absence and presence of arsenic was carried out to confirm of the increased expression ofarsenite oxidase. RESULTS: Both strains were able to transform AsIII to AsV. Both strains AK1 and AK9 decrease the arsenic concentration by 626.68 ppb (13.36%) and 686.40 ppb (14.71%) after an incubation period of 96 h in presence of arsenic. Gamma irradiated AK9 strains showed doubled growth in presence of arsenic as compared to non-irradiated strains at 10 Gy treatment whereas no changes in growth was observed in irradiated AK1 strains. Gamma irradiated AK9 strain decrease 378.65 ppb (7.27%) more arsenic concentration from natural water sample supplemented with AsIII than non-irradiated AK9 strain. Further, in the protein profile, increased expression of arsenite oxidase (∼85 kDa) was observed in irradiated AK9 strains in presence of arsenic. CONCLUSIONS: Overall, the results suggested that the gamma irradiated AK9 strain having potential for arsenic accumulation and increased arsenite tolerance may play a great role in the bioremediation of the arsenite at arsenic contaminated sites.

Correction to: Post­ductal coarctation of aorta aneurysm repair in adult via left antero­axillary thoracotomy with antegrade cerebral perfusion-a case series.

[This corrects the article DOI: 10.1007/s12055-024-01734-5.].

Post-ductal coarctation of aorta aneurysm repair in adult via left antero-axillary thoracotomy with antegrade cerebral perfusion-a case series.

Coarctation of the aorta is a common congenital abnormality that may be associated with serious and rare anomalies like aneurysms. Severe coarctation or interrupted aortic arch in adults is usually managed by percutaneous interventions or extra-anatomic bypass. However, the presence of an aneurysm beyond the coarcted segment implies the opening of a collateral-rich segment of the aorta with redressal of the arch if hypoplastic. We describe our experience in managing three such patients through antero-lateral thoracotomy with antegrade cerebral perfusion. We have found this technique helpful in treating aneurysms of the distal aortic arch or proximal descending thoracic aorta.

"Pediatric Spontaneous Intracranial Dissecting Aneurysms: Impact of Ischemic and Hemorrhagic Manifestations on Endovascular Treatment Strategies - Insights from a Developing World Setting".

BACKGROUND: Pediatric spontaneous intracranial dissecting aneurysms are rare, but systematic studies comparing hemorrhagic and ischemic presentations are lacking. This study addresses gaps in understanding their epidemiology, clinical presentation, management, and outcome. METHODS: A retrospective analysis of 23 pediatric patients with nontraumatic intracranial dissecting aneurysms treated between July 2018 and December 2023 was conducted. Patients were divided into 2 groups based on presentation: hemorrhagic (n = 16) and ischemic (n = 7). Clinical data were analyzed, including demographics, radiologic findings, treatment modalities, and outcomes. RESULTS: Clinical presentations varied, with limb weakness being more prevalent in hemorrhagic cases (P = 0.014), while headache and seizures were more common in ischemic cases. Angiographic analysis revealed distinct patterns, with hemorrhagic cases showing more distal involvement on vessel segments with stenosis and dilatation (pearl string sign). At the same time, the ischemic group exhibited the double-lumen sign. Various treatments, including microsurgery and endovascular techniques, were utilized, with perioperative complications observed, including one mortality in a hemorrhagic case. Multiple regression analysis identified significant risk factors for perioperative complications, namely, the configuration of the dissecting aneurysm (P = 0.016) and the type of presentation (P = 0.0006). Long-term Glasgow Outcome Scores were comparable, but patients with hemorrhagic manifestations experienced prolonged hospital and ICU stays (P = 0.001). CONCLUSIONS: Pediatric intracranial dissecting aneurysms, particularly hemorrhagic cases, are associated with severe neurologic deficits and higher perioperative complications. Despite similar long-term outcomes, hemorrhagic cases require prolonged hospitalization, increasing treatment costs. Optimizing management strategies for pediatric intracranial dissecting aneurysms, especially those with hemorrhagic features, is essential to improve outcomes and reduce healthcare expenditures.

KLP-7/Kinesin-13 orchestrates axon-dendrite checkpoints for polarized trafficking in neurons.

The polarized nature of neurons depends on their microtubule dynamics and orientation determined by both microtubule-stabilizing and destabilizing factors. The role of destabilizing factors in developing and maintaining neuronal polarity is unclear. We investigated the function of KLP-7, a microtubule depolymerizing motor of the Kinesin-13 family, in axon-dendrite compartmentalization using PVD neurons in Caenorhabditis elegans. Loss of KLP-7 caused a mislocalization of axonal proteins, including RAB-3, SAD-1, and their motor UNC-104, to dendrites. This is rescued by cell-autonomous expression of the KLP-7 or colchicine treatment, indicating the involvement of KLP-7-dependent microtubule depolymerization. The high mobility of KLP-7 is correlated to increased microtubule dynamics in the dendrites, which restricts the enrichment of UNC-44, an integral component of Axon Initial Segment (AIS) in these processes. Due to the loss of KLP-7, ectopic enrichment of UNC-44 in the dendrite potentially redirects axonal traffic into dendrites that include plus-end out microtubules, axonal motors, and cargoes. These observations indicate that KLP-7-mediated depolymerization defines the microtubule dynamics conducive to the specific enrichment of AIS components in dendrites. This further compartmentalizes dendritic and axonal microtubules, motors, and cargoes, thereby influencing neuronal polarity.

Optimizing outcomes in multicompartmental brain tumor surgery: A comparative study of integrated endoscopic and microsurgical techniques versus endoscope-assisted microsurgery.

BACKGROUND: Multicompartmental lesions within the central nervous system are challenging due to their complex anatomy. This study evaluates the efficacy, safety, and utility of hybrid endoscopic and microsurgery versus endoscope-assisted microsurgery(EAM) for excising these lesions. METHODS: A retrospective comparative analysis was conducted on patients who underwent multicompartmental brain tumor surgery, utilizing either hybrid endoscopic and microsurgical techniques with the Endocameleon Hopkins telescope featuring a rotating lens system and knob (Karl Storz GmbH & Co., Tuttlingen, Germany), alternately used with a microscope (ZEISS PENTERO 800 S) (Group 1, n = 69), or endoscope-assisted microsurgery employing a fully high-definition, 45° angled endoscopic tool, QEVO®, integrated into the digital surgical microscope KINEVO 900 (Carl Zeiss Meditec, Oberkochen, Germany) as a plug-in feature (Group 2, n = 63), from July 2018 to March 2024. Data on demographics, clinical presentation, lesion characteristics, surgical details, and outcomes were meticulously collected and analyzed using rigorous statistical methods, including t-tests and chi-square tests. RESULTS: Compared to Group 2, Group 1 had better ease of dissection and visualization of bleeders (p = 0.01) and fewer postoperative hematomas (p = 0.04). Surgical times were similar (p = 0.134). Postoperative follow-up revealed fewer recurrences in Group 1, though not statistically significant (p = 0.33). Group 1 patients reported higher cosmetic satisfaction and shorter hospital stays (p = 0.002). Logistic regression identified tumor vascularity(p = 0.001) and ease of dissection(p = 0.008) as significant factors for recurrence. CONCLUSIONS: Hybrid endoscopic and microsurgery demonstrated superior intraoperative visualization, ease of dissection, and postoperative outcomes compared to endoscope-assisted microsurgery with the Quevo device. These findings suggest that the integrated approach may offer better outcomes for multicompartmental lesion excision regarding safety, efficacy, and patient satisfaction.

Unlocking the Battle-Clipping vs. Endovascular Therapy for Shunt-Dependent Hydrocephalus After Aneurysm Rupture: An In-Depth Institutional Analysis.

AIM: To compare microsurgical clipping and endovascular therapy (EVT) for the management of shunt-dependent hydrocephalus (SDH) in patients with subarachnoid hemorrhage (SAH) and hydrocephalus. MATERIAL AND METHODS: This retrospective study was conducted from July 2018 to December 2022 and included 67 patients with SAH accompanied by acute hydrocephalus. Patients' demographic, clinical, and radiological data, such as age, sex, Glasgow Coma Scale scores, Hunt and Hess scale, Fischer grade, external ventricular drain (EVD) duration, complications, Ommaya reservoir placement, cerebrospinal fluid drainage, and outcomes, were obtained. Statistical analyses, including univariate analysis and stepwise logistic regression, revealed significant risk factors for shunt dependence. RESULTS: Of the 67 patients, 33 underwent microsurgical clipping and 34 received EVT. Spasmolysis reduced shunt dependency, whereas early EVD placement correlated with reduced shunt dependence (p=0.002). The Ommaya reservoir helped in the management of meningitis but was found to be associated with shunt dependency (p=0.04). Multiple logistic regression analysis revealed that perioperative infarct was a significant risk factor for shunt dependence (p=0.05). No significant difference in patient outcomes was observed between the two treatment groups. However, patients who received EVT had shorter intensive care unit and hospital stays. CONCLUSION: This study shows that managing clinical vasospasm with spasmolysis may reduce shunt dependency. Overall, both microsurgical clipping and EVT offer similar long-term outcomes and efficacy in preventing shunt dependence, but the latter has the advantage of shorter hospital stay. These findings provide crucial insights for clinical decision-making and patient care in SDH after SAH.

Spontaneous thrombosis and calcification of giant cavernous carotid artery aneurysm: A rare case and management insights.

Background: Giant cavernous carotid artery aneurysms (>25 mm) are rare (3-5%), with some prone to spontaneous thrombosis (10-20% complete). We present a unique case of one of the largest aneurysms spontaneously thrombosing and calcifying. Case Description: A 57-year-old with persistent right-sided headaches had a substantial hyperdense mass in the right middle cranial fossa, eroding petrous bone. Magnetic resonance imaging and digital subtraction angiography revealed a giant cavernous segment fusiform aneurysm of the right internal carotid artery (ICA) with spontaneous thrombosis and distal ICA occlusion. Collateral circulation maintains the cerebral blood supply. Despite anatomical challenges, conservative management was chosen due to the patient's stability. Conclusion: This case highlights the complex interplay between thrombosed giant aneurysms and affected vessels, with unique features such as cross-flow, calcification, and bone erosion. We advocate conservative management for stable cases, supported by literature, emphasizing vigilant follow-up. This expands the spectrum of aneurysm presentations and encourages further research into their dynamics.

Outcomes of emergency surgical intervention for complications in the cardiac catheterization laboratory.

Background: In today's era, cardiac catheterization procedures are becoming increasingly safe, but they are still fraught with complications. We aimed to study the outcomes of patients who underwent emergency surgical intervention for complications in the cardiac catheterization laboratory. Methods: A retrospective analysis of patients who required emergency surgical management following a complication in the cardiac catheterization laboratory in our institute from July 2017 to July 2022 was done. Result: A total of 57 patients out of a total of 52,326 patients (0.1%) were included. The average age of presentation was 10.4 years. Congenital heart disease (CHD) constituted the majority of the cases (28/57-49.1%), coronary artery disease (CAD) constituted 19.3% (11/57), and rheumatic heart disease (RHD) constituted 8.8% (5/57) of the cases. Apart from this, 22.80% patients (13/57) were grouped together in the miscellaneous group. In total, 76.9% (10/13) of these patients had pericardial effusion and they developed a right ventricular (RV) rent following an attempted pigtail drainage. Also, one patient each had a RV rent following an attempted permanent pacemaker implantation for heart block and an endocardial biopsy respectively. One patient had a left bronchial rupture following thoracic endovascular aortic repair (TEVAR) for descending thoracic aorta (DTA) aneurysm. Thirty-day mortality was 7% (4/57), and the mean time of shifting the patients from the catheterization laboratory to the operating room was 8.3 h. Conclusion: Cardiac catheterization procedures have become increasingly safe, but complications can still occur, for which the cardiac surgeon should be briefed in a Heart Team meeting before taking up such cases. Even though these complications form a small percentage, the cardiologist should exercise some caution in attempting cases which could have a relatively easier surgical correction.