Synthesis and Structural and Optical Behavior of Dehydrohelicene-Containing Polycyclic Compounds.

Dehydrohelicene-based molecules stand out as highly promising scaffolds and captivating chiroptical materials, characterized by their unique chirality. Their quasi-helical π-conjugated molecular architecture, featuring successively ortho-annulated aromatic rings, endows them with remarkable thermal stability and optical properties. Over the past decade, diverse approaches have emerged for synthesizing these scaffolds, reinvigorating this field, with anticipated increased attention in the coming years. This review provides a comprehensive overview of the historical evolution of dehydrohelicene chemistry since the pioneering work of Zander and Franke in 1969 and highlights recent advancements in the synthesis of various molecules incorporating dehydrohelicene motifs. We elucidate the intriguing structural features and optical merits of these molecules, occasionally drawing comparisons with their helicene or circulene analogs to underscore the significance of the bond between the helical termini.

Structure-guided affinity maturation of a single-chain variable fragment antibody against the Fu-bc epitope of the dengue virus envelope protein.

Dengue is one of the most dominant arthropod-borne viral diseases, infecting at least 390 million people every year throughout the world. Despite this, there is no effective treatment against dengue, and the only available vaccine has already been withdrawn owing to the significant adverse effects. Therefore, passive immunotherapy using monoclonal antibodies is now being sought as a therapeutic option. To date, many dengue monoclonal antibodies have been identified, most of which are serotype-specific, and only a few of which are cross-reactive. Furthermore, antibodies that cross-react within serotypes are weakly neutralizing and frequently induce antibody-dependent enhancement, which promotes viral entry and replication. Therefore, broadly neutralizing antibodies with no risk of antibody-dependent enhancement are required for the treatment of dengue. Here, we developed a single-chain variable fragment (scFv) antibody from an anti-fusion loop E53 antibody (PDB: 2IGF). We introduced previously predicted favorable complementarity-determining region (CDR) mutations into the gene encoding the scFv antibody for affinity maturation, and the resultant variants were tested in vitro against the highly conserved fusion and bc epitope of the dengue virus envelope protein. We show some of these scFv variants with two to three substitution mutations in three different CDRs possess affinity constants (KD) ranging from 20 to 200 nM. The scFv-mutant15, containing D31L, Y105W, and S227W substitutions, showed the lowest affinity constant, (KD = 24 ± 7 nM), approximately 100-fold lower than its parental construct. We propose that the scFv-derivative antibody may be a good candidate for the development of an effective and safe immunotherapy.

Impact assessment of e-trainings in occupational safety and health: a literature review.

BACKGROUND: Implementing workplace preventive interventions reduces occupational accidents and injuries, as well as the negative consequences of those accidents and injuries. Online occupational safety and health training is one of the most effective preventive interventions. This study aims to present current knowledge on e-training interventions, make recommendations on the flexibility, accessibility, and cost-effectiveness of online training, and identify research gaps and obstacles. METHOD: All studies that addressed occupational safety and health e-training interventions designed to address worker injuries, accidents, and diseases were chosen from PubMed and Scopus until 2021. Two independent reviewers conducted the screening process for titles, abstracts, and full texts, and disagreements on the inclusion or exclusion of an article were resolved by consensus and, if necessary, by a third reviewer. The included articles were analyzed and synthesized using the constant comparative analysis method. RESULT: The search identified 7,497 articles and 7,325 unique records. Following the title, abstract, and full-text screening, 25 studies met the review criteria. Of the 25 studies, 23 were conducted in developed and two in developing countries. The interventions were carried out on either the mobile platform, the website platform, or both. The study designs and the number of outcomes of the interventions varied significantly (multi-outcomes vs. single-outcome). Obesity, hypertension, neck/shoulder pain, office ergonomics issues, sedentary behaviors, heart disease, physical inactivity, dairy farm injuries, nutrition, respiratory problems, and diabetes were all addressed in the articles. CONCLUSION: According to the findings of this literature study, e-trainings can significantly improve occupational safety and health. E-training is adaptable, affordable, and can increase workers' knowledge and abilities, resulting in fewer workplace injuries and accidents. Furthermore, e-training platforms can assist businesses in tracking employee development and ensuring that training needs are completed. Overall, this analysis reveals that e-training has enormous promise in the field of occupational safety and health for both businesses and employees.

Two-Step Synthesis, Structure, and Optical Features of a Double Hetero[7]helicene.

A novel double aza-oxa[7]helicene was synthesized from the commercially available N1,N4-di(naphthalen-2-yl)benzene-1,4-diamine and p-benzoquinone in two steps. Combining the acid-mediated annulation with the electrochemical sequential reaction (oxidative coupling and dehydrative cyclization) afforded this double hetero[7]helicene. Moreover, the structural and optical features of this molecule have been studied using X-ray crystallographic analysis, and the absorption and emission behaviors were rationalized based on DFT calculations.

Evaluation of the Recombinant Bacterial Chitinases as Anti-proliferative and Anti-migratory Agents for the Human Breast Cancer Cell Line, MCF-7.

Chitinases, a glycosyl hydrolase family 18 members, have a wide distribution in both prokaryotes and eukaryotes, including humans. Regardless of the absence of endogenous chitin polymer, various chitinases and chitinase-like proteins (CLPs) have been reported in mammals. However, several other carbohydrate polymers, such as hyaluronic acid and heparan sulfate, show structural similarities with chitin, which could be a potential target of chitinase and CLPs. Heparan sulfate is part of the integral membrane proteins and involves in cell adherence and migration. Hence, to demonstrate the effect of chitinase on cancer cell progression, we selected two chitinases from Serratia marcescens, ChiB and ChiC, which function as exo- and endo-chitinase, respectively. The ChiB and ChiC proteins were produced recombinantly by cloning chiB and chiC genes from Serratia marcescens. The cell viability of the Michigan Cancer Foundation-7 (MCF-7) cells was studied using different concentrations of the purified recombinant proteins. Cell viability assay was performed using 3-(4, 5-dimethyl thiazolyl-2)-2, 5-diphenyltetrazolium bromide and water-soluble tetrazolium salt, and the effect of ChiB and ChiC on cell proliferation was studied by clonogenic assay. The cell migration study was analysed by wound healing, transwell migration, and invasion assays. Cell cycle analysis of propidium iodide-stained cells and cell proliferation markers such as pERK1/2, pAKT, and SMP30 were also done. It was observed that both ChiB and ChiC were able to impede cell viability, cell migration, and invasion significantly. These observations and our in silico molecular docking analysis suggest that ChiC is a potential anticancer agent and is more efficient than ChiB. Since the ChiC is able to inhibit both cancer cell proliferation and migration, it could be a potential candidate for the treatment of metastatic cancer.

Electrochemical synthesis of heterodehydro[7]helicenes.

Dehydrohelicenes are some of the most attractive chiroptical materials with unique helical chirality. However, to our knowledge, there are no prior reports on their direct construction by asymmetric methods. In this work, sequential synthesis of aza-oxa-dehydro[7]helicenes via the electrochemical oxidative hetero-coupling of 3-hydoxycarbazoles and 2-naphthols followed by dehydrative cyclization and intramolecular C-C bond formation has been realized. In addition, an efficient enantioselective synthesis through chiral vanadium-catalyzed hetero-coupling and electrochemical oxidative transformations afforded heterodehydro[7]helicene without any racemization. The obtained dehydro[7]helicenes showed intense blue-colored circularly polarized luminescence (|glum| ≈ 2.5 × 10-3 at 433 nm). Thermodynamic and kinetic studies of the racemization barrier of heterodehydro[7]helicenes indicated significant chiral stability with ΔG‡> 140 kJ mol-1.

Variability in alkaloid and phenolic content vis-a-vis antigout potential among the natural population of Gloriosa superba (L.) collected from Central India.

The variation in alkaloid metabolites (colchicine and gloriosine) was found significant in the nine germplasms of G. superba (L.), collected from Central India. The maximum content of colchicine and gloriosine was in NBG-15 (Chitrakoot, M.P) and NBG-13 (Bheraghat, M.P). The phenolic acids viz. quercetin and kaempferol was first ever quantified in G. superba tuber. Cluster analysis on chemical variability (colchicine and gloriosine content) results in the identification of three elite germplasm(s). The radical scavenging potential was also found promising in the selected elite germplasm viz. NBG-13, NBG-14 and NBG-15. Further, the protein denaturation potential of elite chemotypes was found at par with standard colchicine. The study will aid in site specific exploration of high metabolite yielding chemotype(s) with validated pharmacological action to meet out the industrial demands. This will also promotes the commercial cultivation of species for socio economical upliftment in the area having similar phyto geographical conditions.

Right middle cerebral artery infarct after minor head trauma in an infant: Case report and literature review.

Ishaemic stroke (IS) in the paediatric population is extremely rare. In this age group, the occurrence of IS often concurs with underlying congenital heart disease, haematological, metabolic or immunological conditions. In contrast, the association between IS and minor head injury in children has been sparse in current literature. The authors report a case of a healthy 9-month-old male who was found to have a right middle cerebral artery territory infarct after a minor head injury. An extensive medical workup was performed, and it was negative for any previously undiagnosed co-morbidities. Given the paucity of such cases, the condition and its management are discussed in corroboration with current literature.

Characterization of Pyramidal Tract Shift in High-Grade Glioma Resection.

OBJECTIVE: This study aimed to characterize pyramidal tract shift in different regions of the brain during glioma resection and its association with head position and tumor location. METHODS: From 2008-2013, 14 patients presenting at the National Neuroscience Institute with high-grade glioma (World Health Organization III or IV) underwent preoperative and intraoperative diffusion tensor imaging. A novel method of placing landmarks along the preoperative and intraoperative tracts, with anterior commissure as the origin, was used to determine pyramidal tract shift. Shift was evaluated in x (lateromedial), y (anteroposterior), and z (craniocaudal) directions for 3 brain regions: brainstem, around third and lateral ventricles, and above ventricles. Shift radius is calculated as the distance between preoperative and postoperative landmarks. RESULTS: Mean shift radius was 2.72 ± 0.55, 2.98 ± 0.53, and 4.04 ± 0.58 mm at the brainstem, third and lateral ventricles, and above the ventricles, respectively (P < 0.001). Only shift in the y direction (P < 0.03) and shift radius (P < 0.03) were significantly different among regions. Head position during surgery strongly influenced shift radius above the ventricles (P < 0.005), but tumor location had no significant effect. The z-direction shift did not differ significantly among regions. CONCLUSION: Direction of pyramidal tract shift in 3 dimensions is unpredictable; hence shift radius is a more clinical useful concept. Shift radius was largest above the ventricles and was strongly influenced by head position, with a trend for temporal lobe tumors to exhibit larger shifts.

High-performance Thin-layer Chromatographic-densitometric Quantification and Recovery of Bioactive Compounds for Identification of Elite Chemotypes of Gloriosa superba L. Collected from Sikkim Himalayas (India).

BACKGROUND: Gloriosa superba L. (Colchicaceae) is used as adjuvant therapy in gout for its potential antimitotic activity due to high colchicine(s) alkaloids. OBJECTIVE: This study aimed to develop an easy, cheap, precise, and accurate high-performance thin-layer chromatographic (HPTLC) validated method for simultaneous quantification of bioactive alkaloids (colchicine and gloriosine) in G. superba L. and to identify its elite chemotype(s) from Sikkim Himalayas (India). METHODS: The HPTLC chromatographic method was developed using mobile phase of chloroform: acetone: diethyl amine (5:4:1) at λmax of 350 nm. RESULTS: Five germplasms were collected from targeted region, and on morpho-anatomical inspection, no significant variation was observed among them. Quantification data reveal that content of colchicine (Rf: 0.72) and gloriosine (Rf: 0.61) varies from 0.035%-0.150% to 0.006%-0.032% (dry wt. basis). Linearity of method was obtained in the concentration range of 100-400 ng/spot of marker(s), exhibiting regression coefficient of 0.9987 (colchicine) and 0.9983 (gloriosine) with optimum recovery of 97.79 ± 3.86 and 100.023% ± 0.01%, respectively. Limit of detection and limit of quantification were analyzed, respectively, as 6.245, 18.926 and 8.024, 24.316 (ng). Two germplasms, namely NBG-27 and NBG-26, were found to be elite chemotype of both the markers. CONCLUSION: The developed method is validated in terms of accuracy, recovery, and precision studies as per the ICH guidelines (2005) and can be adopted for the simultaneous quantification of colchicine and gloriosine in phytopharmaceuticals. In addition, this study is relevant to explore the chemotypic variability in metabolite content for commercial and medicinal purposes. SUMMARY: An easy, cheap, precise, and accurate high performance thin layer chromatographic (HPTLC) validated method for simultaneous quantification of bioactive alkaloids (colchicine and gloriosine) in G. superba L.Five germplasms were collected from targeted region, and on morpho anatomical inspection, no significant variation was observed among themQuantification data reveal that content of colchicine (Rf: 0.72) and gloriosine (Rf: 0.61) varies from 0.035%-0.150% to 0.006%-0.032% (dry wt. basis)Two germplasms, namely NBG 27 and NBG 26, were found to be elite chemotype of both the markers.

Surgery for spinal tuberculosis: a multi-center experience of 582 cases.

BACKGROUND: Tuberculosis (TB) of the spine is a common site of osseous TB, accounting for 50%-60% of cases. Spinal TB still occurs in both developed and developing countries. The diagnosis of spinal TB is difficult and it commonly presents at an advanced stage. Delays in establishing diagnosis and management result in complications such as spinal cord compression and spinal deformity. METHODS: A total of 582 patients with TB of the cervical, thoracic and lumbar spine with moderate to severe cord compression were studied. Variable degrees of neurological deficit with deformity were treated from January, 2003 to July, 2014. Thoracotomy along with anterolateral decompression and autogenous strut bone grafting with simultaneous fixation by screws and rods were performed in 113 cases. Posterior decompression, posterior interbody and posterolateral fusion by bone graft with stabilization by transpedicular screws and rods were done in the remaining 469 cases. Appropriate anti-TB drugs were given to all patients for 18-24 months. The follow-up period was 3 months to 10 years. RESULTS: The average age was 32.5 years. All patients survived surgery. There were 7 cases of superficial infections (1.2%) whilst there were 4 cases (0.7%) of deep infections. Revision surgery was performed in 6 patients (1.0%). Implant failure occurred in 4 cases (0.7%) whilst malposition of screws occurred in 12 cases (2.1%). Perioperative bleeding complications were reported for 4 patients (0.7%). Neurological improvement occurred in all patients except for 2 cases (0.3%). Preoperatively, the majority of patients (n=221, 38%) were classified with Class A on the American Spinal Injury Association (ASIS) neurological impairment scale. This was significantly reduced postoperatively to 0.4%. CONCLUSIONS: For patients with spinal TB anterior debridement, auto graft bone fusion, anterior or posterior fixation appears to be effective in arresting disease, correcting kyphotic deformity and maintaining correction until solid spinal fusion.