High-speed forward-viewing optical coherence tomography probe based on Lissajous sampling and sparse reconstruction.

We present a novel endoscopy probe using optical coherence tomography (OCT) that combines sparse Lissajous scanning and compressed sensing (CS) for faster data collection. This compact probe is only 4 mm in diameter and achieves a large field of view (FOV) of 2.25 mm2 and a 10 mm working distance. Unlike traditional OCT systems that use bulky raster scanning, our design features a dual-axis piezoelectric mechanism for efficient Lissajous pattern scanning. It employs compressive data reconstruction algorithms that minimize data collection requirements for efficient, high-speed imaging. This approach significantly enhances imaging speed by over 40%, substantially improving miniaturization and performance for endoscopic applications.

Nanoapatite-Loaded κ-Carrageenan/Poly(vinyl alcohol)-Based Injectable Cryogel for Hemostasis and Wound Healing.

Immediate control of excessive bleeding and prevention of infections are of utmost importance in the management of wounds. Cryogels have emerged as promising materials for the rapid release of medication and achieving hemostasis. However, their quick release properties pose the challenge of exposing patients to high concentrations of drugs. In this study, hybrid nanocomposites were developed to address this issue by combining poly(vinyl alcohol) and κ-carrageenan with whitlockite nanoapatite (WNA) particles and ciprofloxacin, aiming to achieve rapid hemostasis and sustained antibacterial effects. A physically cross-linked cryogel was obtained by subjecting a blend of poly(vinyl alcohol) and κ-carrageenan to successive freezing-thawing cycles, followed by the addition of WNA. Furthermore, ciprofloxacin was introduced into the cryogel matrix for subsequent evaluation of its wound healing properties. The resulting gel system exhibited a 3D microporous structure and demonstrated excellent swelling, low cytotoxicity, and outstanding mechanical properties. These characteristics were evaluated through analytical and rheological experiments. The nanocomposite cryogel with 4% whitlockite showed extended drug release of 71.21 ± 3.5% over 21 days and antibacterial activity with a considerable growth inhibition zone (4.19 ± 3.55 cm). Experiments on a rat model demonstrated a rapid hemostasis property of cryogels within an average of 83 ± 4 s and accelerated the process of wound healing with 96.34% contraction compared to the standard, which exhibited only ∼78% after 14 days. The histopathological analysis revealed that the process of epidermal re-epithelialization took around 14 days following the skin incision. The cryogel loaded with WNAs and ciprofloxacin holds great potential for strategic utilization in wound management applications as an effective material for hemostasis and anti-infection purposes.

Quantification of Radiomics features of Peritumoral Vasogenic Edema extracted from fluid-attenuated inversion recovery images in glioblastoma and isolated brain metastasis, using T1-dynamic contrast-enhanced Perfusion analysis.

The peritumoral vasogenic edema (PVE) in brain tumors exhibits varied characteristics. Brain metastasis (BM) and meningioma barely have tumor cells in PVE, while glioblastoma (GB) show tumor cell infiltration in most subjects. The purpose of this study was to investigate the PVE of these three pathologies using radiomics features in FLAIR images, with the hypothesis that the tumor cells might influence textural variation. Ex vivo experimentation of radiomics analysis of T1-weighted images of the culture medium with and without suspended tumor cells was also attempted to infer the possible influence of increasing tumor cells on radiomics features. This retrospective study involved magnetic resonance (MR) images acquired using a 3.0-T MR machine from 83 patients with 48 GB, 21 BM, and 14 meningioma. The 93 radiomics features were extracted from each subject's PVE mask from three pathologies using T1-dynamic contrast-enhanced MR imaging. Statistically significant (< 0.05, independent samples T-test) features were considered. Features maps were also computed for qualitative investigation. The same was carried out for T1-weighted cell line images but group comparison was carried out using one-way analysis of variance. Further, a random forest (RF)-based machine learning model was designed to classify the PVE of GB and BM. Texture-based variations, especially higher nonuniformity values, were observed in the PVE of GB. No significance was observed between BM and meningioma PVE. In cell line images, the culture medium had higher nonuniformity and was considerably reduced with increasing cell densities in four features. The RF model implemented with highly significant features provided improved area under the curve results. The possible infiltrative tumor cells in the PVE of the GB are likely influencing the texture values and are higher in comparison with BM PVE and may be of value in the differentiation of solitary metastasis from GB. However, the robustness of the features needs to be investigated with a larger cohort and across different scanners in the future.

Design, development and characterisation of an optimised scaffold to enhance cell proliferation for tissue repair.

Scaffolds are implanted to spur the regeneration of damaged tissues. The inappropriate construction of scaffolds laden with cells is not efficient. The optimisation of the scaffolds' constituents is essential for tissue repair. In this study, a scaffold embedded with Raloxifene drug was optimised via Response Surface Methodology (RSM), targeting controlled cell proliferation. The independent variables for RSM (fibronectin, collagen I, glutaraldehyde, and Raloxifene) were screened in Swiss target prediction software (probability ≥99%) to optimise dependent variables (porosity, cell viability, degradation, and swelling) by ANOVA and characterised with FTIR, SEM and contact angle measurement. The scaffold was tested for antimicrobial property, and proliferation and attachment of mouse mesenchymal stem cells. The ANOVA analysis with p value ≤ 0.0001 suggested the optimal concentration of biomaterials and drugs. The optimised scaffold displayed 80% porosity with pore size 33 ± 3 µm. We also observed significant cell attachment and proliferation (p value ≤ 0.05) in optimised scaffold. The scaffold may be further evaluated for its potential for tissue repair.

Platelet-rich plasma: a comparative and economical therapy for wound healing and tissue regeneration.

Rise in the incidences of chronic degenerative diseases with aging makes wound care a socio-economic burden and unceasingly necessitates a novel, economical, and efficient wound healing treatment. Platelets have a crucial role in hemostasis and thrombosis by modulating distinct mechanistic phases of wound healing, such as promoting and stabilizing the clot. Platelet-rich plasma (PRP) contains a high concentration of platelets than naïve plasma and has an autologous origin with no immunogenic adverse reactions. As a consequence, PRP has gained significant attention as a therapeutic to augment the healing process. Since the past few decades, a robust volume of research and clinical trials have been performed to exploit extensive role of PRP in wound healing/tissue regeneration. Despite these rigorous studies and their application in diversified medical fields, efficacy of PRP-based therapies is continuously questioned owing to the paucity of large samplesizes, controlled clinical trials, and standard protocols. This review systematically delineates the process of wound healing and involvement of platelets in tissue repair mechanisms. Additionally, emphasis is laid on PRP, its preparation methods, handling, classification,application in wound healing, and PRP as regenerative therapeutics combined with biomaterials and mesenchymal stem cells (MSCs).

Fibronectin modified alginate coating enhances cell targeting and homing to bone marrow in BALB/c mice.

Stem cell homing to bone marrow (BM) suffers from premature differentiation of transfused cells within the blood stream, thereby reducing the efficiency of stem cell transplantation (SCT). This work is attempted to enhance the homing of cells in BM. Fibronectin modified alginate (A-F) was prepared and used to coat the cells. Biodistribution and survival advantage provided by A-F coating was evaluated in BALB/c mice. The A-F conjugate showed characteristic FT-IR peaks of alginate at 3308 cm-1 and 1634 cm-1, and Fibronectin peak at 675 cm-1. The A-F coating prevented antibodies from binding to their respective cell surface receptors. The A-F coat abolished haemagglutination. Significant distribution of coated cells was observed in BM after 24 h. This provided protection to 7 Gy irradiated mice. The A-F coating showed no histological toxicity in vivo. The coating formulation is likely to be useful for shielding clinically relevant cell types to improve targeting for organ regeneration.

Vaccine efficacy against persistent human papillomavirus (HPV) 16/18 infection at 10 years after one, two, and three doses of quadrivalent HPV vaccine in girls in India: a multicentre, prospective, cohort study.

BACKGROUND: A randomised trial designed to compare three and two doses of quadrivalent human papillomavirus (HPV) vaccine in adolescent girls in India was converted to a cohort study after suspension of HPV vaccination in trials by the Indian Government. In this Article, the revised aim of the cohort study was to compare vaccine efficacy of single dose to that of three and two doses in protecting against persistent HPV 16 and 18 infection at 10 years post vaccination. METHODS: In the randomised trial, unmarried girls aged 10-18 years were recruited from nine centres across India and randomly assigned to either two doses or three doses of the quadrivalent HPV vaccine (Gardasil [Merck Sharp & Dohme, Whitehouse Station, NJ, USA]; 0·5 mL administered intramuscularly). After suspension of recruitment and vaccination, the study became a longitudinal, prospective cohort study by default, and participants were allocated to four cohorts on the basis of the number vaccine doses received per protocol: the two-dose cohort (received vaccine on days 1 and 180 or later), three-dose cohort (days 1, 60, and 180 or later), two-dose default cohort (days 1 and 60 or later), and the single-dose default cohort. Participants were followed up yearly. Cervical specimens were collected from participants 18 months after marriage or 6 months after first childbirth, whichever was earlier, to assess incident and persistent HPV infections. Married participants were screened for cervical cancer as they reached 25 years of age. Unvaccinated women age-matched to the married vaccinated participants were recruited to serve as controls. Vaccine efficacy against persistent HPV 16 and 18 infections (the primary endpoint) was analysed for single-dose recipients and compared with that in two-dose and three-dose recipients after adjusting for imbalance in the distribution of potential confounders between the unvaccinated and vaccinated cohorts. This trial is registered with ISRCTN, ISRCTN98283094, and ClinicalTrials.gov, NCT00923702. FINDINGS: Vaccinated participants were recruited between Sept 1, 2009, and April 8, 2010 (date of vaccination suspension), and followed up over a median duration of 9·0 years (IQR 8·2-9·6). 4348 participants had three doses, 4980 had two doses (0 and 6 months), and 4949 had a single dose. Vaccine efficacy against persistent HPV 16 and 18 infection among participants evaluable for the endpoint was 95·4% (95% CI 85·0-99·9) in the single-dose default cohort (2135 women assessed), 93·1% (77·3-99·8) in the two-dose cohort (1452 women assessed), and 93·3% (77·5-99·7) in three-dose recipients (1460 women assessed). INTERPRETATION: A single dose of HPV vaccine provides similar protection against persistent infection from HPV 16 and 18, the genotypes responsible for nearly 70% of cervical cancers, to that provided by two or three doses. FUNDING: Bill & Melinda Gates Foundation.

In-line optical fiber metallic mirror reflector for monolithic common path optical coherence tomography probes.

BACKGROUND AND OBJECTIVES: Endoscopic optical coherence tomography probes suffer from various artifacts due to dispersion imbalance and polarization mismatch between reference and sample arm light. Such artifacts can be minimized using a common path approach. In this work, we demonstrate a miniaturized common path probe for optical coherence tomography using an inline fiber mirror. MATERIALS AND METHODS: A common path optical fiber probe suitable for performing high-resolution endoscopic optical coherence tomography imaging was developed. To achieve common path functionality, an inline fiber mirror was fabricated using a thin gold layer. A commercially available swept source engine was used to test the designed probe in a cadaver human coronary artery ex vivo. RESULTS: We achieved a sensitivity of 104 dB for this probe using a swept source optical coherence tomography system. To test the probe, images of a cadaver human coronary artery were obtained, demonstrating the quality that is comparable to those obtained by OCT systems with separate reference arms. Additionally, we demonstrate recovery of ranging depth by use of a Michelson interferometer in the detection path. CONCLUSION: We developed a miniaturized monolithic inline fiber mirror-based common path probe for optical coherence tomography. Owing to its simplicity, our design will be helpful in endoscopic applications that require high-resolution probes in a compact form factor while reducing system complexity. Lasers Surg. Med. 50:230-235, 2018. © 2017 Wiley Periodicals, Inc.

Human ex-vivo oral tissue imaging using spectral domain polarization sensitive optical coherence tomography.

We report the use of spectral domain polarization sensitive optical coherence tomography for ex-vivo imaging of human oral mandibular tissue samples. Our results show that compared to the changes observed in the epithelium thickness and the decay constant of A-scan intensity profile, a much larger degree of change was observed in the phase retardation for tissue sites progressing from normal to the malignant state. These results suggest that monitoring of tissue retardance can help in better differentiation of normal and cancerous oral tissue sites.

Immunogenicity and HPV infection after one, two, and three doses of quadrivalent HPV vaccine in girls in India: a multicentre prospective cohort study.

BACKGROUND: An increase in worldwide HPV vaccination could be facilitated if fewer than three doses of vaccine are as effective as three doses. We originally aimed to compare the immunogenicity and frequency of persistent infection and cervical precancerous lesions caused by vaccine-targeted HPV after vaccination with two doses of quadrivalent vaccine on days 1 and 180 or later, with three doses on days 1, 60, and 180 or later, in a cluster-randomised trial. Suspension of the recruitment and vaccination due to events unrelated to our study meant that some enrolled girls could not be vaccinated and some vaccinated girls received fewer than the planned number of vaccinations by default. As a result, we re-analysed our data as an observational cohort study. METHODS: Our study was designed to be done in nine locations (188 clusters) in India. Participants were unmarried girls aged 10-18 years vaccinated in four cohorts: girls who received three doses of vaccine on days 1, 60, and 180 or later, two doses on days 1 and 180 or later, two doses on days 1 and 60 by default, and one dose by default. The primary outcomes were immunogenicity in terms of L1 genotype-specific binding antibody titres, neutralising antibody titres, and antibody avidity after vaccination for the vaccine-targeted HPV types 16, 18, 6, and 11 and incident and persistent infections with these HPVs. Analysis was per actual number of vaccine doses received. This study is registered with ISRCTN, number ISRCTN98283094; and with ClinicalTrials.gov, number NCT00923702. FINDINGS: Vaccination of eligible girls was initiated on Sept 1, 2009, and continued until April 8, 2010. Of 21 258 eligible girls identified at 188 clusters, 17 729 girls were recruited from 178 clusters before suspension. 4348 (25%) girls received three doses, 4979 (28%) received two doses on days 1 and 180 or later, 3452 (19%) received two doses at days 1 and 60, and 4950 (28%) received one dose. Immune response in the two-dose HPV vaccine group was non-inferior to the three-dose group (median fluorescence intensity ratio for HPV 16 1·12 [95% CI 1·02-1·23] and for HPV 18 1·04 [0·92-1·19]) at 7 months, but was inferior in the two-dose default (0·33 [0·29-0·38] for HPV 16 and 0·51 [0·43-0·59] for HPV 18) and one-dose default (0·09 [0·08-0·11] for HPV 16 and 0·12 [0·10-0·14] for HPV 18) groups at 18 months. The geometric mean avidity indices after fewer than three doses by design or default were non-inferior to those after three doses of vaccine. Fewer than three doses by design and default induced detectable concentrations of neutralising antibodies to all four vaccine-targeted HPV types, but at much lower concentration after one dose. Cervical samples from 2649 participants were tested and the frequency of incident HPV 16, 18, 6, and 11 infections was similar irrespective of the number of vaccine doses received. The testing of at least two samples from 838 participants showed that there was no persistent HPV 16 or 18 infections in any study group at a median follow-up of 4·7 years (IQR 4·2-5·1). INTERPRETATION: Despite the limitations imposed by the suspension of the HPV vaccination, our findings lend support to the WHO recommendation of two doses, at least 6 months apart, for routine vaccination of young girls. The short-term protection afforded by one dose of HPV vaccine against persistent infection with HPV 16, 18, 6, and 11 is similar to that afforded by two or three doses of vaccine and merits further assessment. FUNDING: Bill & Melinda Gates Foundation.

Report from a symposium on catalyzing primary and secondary prevention of cancer in India.

PURPOSE: Oral, breast, and cervical cancers are amenable to early detection and account for a third of India's cancer burden. We convened a symposium of diverse stakeholders to identify gaps in evidence, policy, and advocacy for the primary and secondary prevention of these cancers and recommendations to accelerate these efforts. METHODS: Indian and global experts from government, academia, private sector (health care, media), donor organizations, and civil society (including cancer survivors and patient advocates) presented and discussed challenges and solutions related to strategic communication and implementation of prevention, early detection, and treatment linkages. RESULTS: Innovative approaches to implementing and scaling up primary and secondary prevention were discussed using examples from India and elsewhere in the world. Participants also reflected on existing global guidelines and national cancer prevention policies and experiences. CONCLUSIONS: Symposium participants proposed implementation-focused research, advocacy, and policy/program priorities to strengthen primary and secondary prevention efforts in India to address the burden of oral, breast, and cervical cancers and improve survival.

Design, Synthesis, and Evaluation of Novel 1,2,3-Triazole-Tethered Glycolipids as Vaccine Adjuvants.

A Cu-mediated azide-alkyne click chemistry protocol was employed for the synthesis of a focused library of novel 1,2,3-triazolyl conjugates bearing various carbohydrate-steroid/triterpenoid entities. The immunogenicity of these compounds was examined initially by ex vivo assays. The lead compound 15g was further subjected to in vivo evaluation in BALB/c mice immunized with ovalbumin. These in vivo biological studies revealed an increase in B cell-mediated proliferation, higher expression levels of IL-2, TNF-α, IL-12, and IFN-γ indicating Th1 activation, together with an enhanced OVA-specific antibody (IgG) response compared to alum, affirming adjuvanticity of these glycolipids. The primary indications of response skewed toward Th1 immunity induced by the new triazoyl analogs indicate the potential of these molecules for possible application as adjuvants.

Copy number polymorphism of glutathione-S-transferase genes (GSTM1 & GSTT1) in susceptibility to lung cancer in a high-risk population from north-east India.

BACKGROUND & OBJECTIVES: Genetic polymorphisms in glutathione-S-transferase genes ( GSTM1 and GSTT1 ) have been studied intensively for their potential role in lung cancer susceptibility. However, most of the studies on association between the polymorphisms and lung cancer do not distinguish between genotypes with one or two copies of the genes. The present study investigates the gene dosage effects of GSTT1 and GSTM1 copy number and their environmental interactions to examine the association of lung cancer risk with trimodular genotypes of the GSTs in a high-risk population from north-east India. METHODS: A total of 154 lung cancer cases and 154 age and sex matched controls from the high risk region of north-east India were analyzed by multiplex real-time PCR to determine the trimodal genotypes (+/+, +/- and -/-) in both the genes ( GSTM1 and GSTT1 ). RESULTS: No significant association and gene dosage effect of GSTM1 gene copy number with lung cancer risk ( P trend =0.13) were found. However, absence of GSTT1 conferred 68 per cent (OR=0.32;95%CI=0.15-0.71;P=0.005) reduced risk compared to the two copy number of the gene. t0 here was evidence of gene dosage effect of GSTT1 gene ( P trend =0.006). Tobacco smoking was a major environmental risk factor to lung cancer (OR=3.03;95%CI=1.73-5.31;P<0.001). However, its interaction with null genotype of GSTT1 conferred significant reduced risk to lung cancer (OR=0.30;95%CI=0.10-0.91;P=0.03). Further in only tobacco smokers, null genotype was associated with increased reduced risk [0.03(0.001-0.78)0.03; P trend =0.006]. No effect modification of GSTM1 was observed with lung cancer risk by environmental risk factors. INTERPRETATION & CONCLUSIONS: The results suggest that absence of GSTT1 null genotype may be associated with a reduced risk of lung cancer and the effect remains unchanged after interaction with smoking.

Carbon quantum dot-nanocomposite hydrogel as Denovo Nexus in rapid chondrogenesis.

The incapability of cartilage to naturally regenerate and repair chronic muscular injuries urges the development of competent bionic rostrums. There is a need to explore faster strategies for chondrogenic engineering using mesenchymal stem cells (MSCs). Along these lines, rapid chondrocyte differentiation would benefit the transplantation demand affecting osteoarthritis (OA) and rheumatoid arthritis (RA) patients. In this report, a de novo nanocomposite was constructed by integrating biogenic carbon quantum dot (CQD) filler into synthetic hydrogel prepared from dimethylaminoethyl methacrylate (DMAEMA) and acrylic acid (AAc). The dominant structural integrity of synthetic hydrogel along with the chondrogenic differentiation potential of garlic peel derived CQDs led to faster chondrogenesis within 14 days. By means of extensive chemical and morphological characterization techniques, we illustrate that the hydrogel nanocomposite possesses lucrative features to influence rapid chondrogenesis. These results were further corroborated by bright field imaging, Alcian blue staining and Masson trichome staining. Thus, this stratagem of chondrogenic engineering conceptualizes to be a paragon in clinical wound care for the rapid manufacturing of chondrocytes.

Enhanced heterodimerization of Bax by Bcl-2 mutants improves irradiated cell survival.

B Cell Lymphoma-2 (Bcl-2) protein suppresses ionizing radiation-induced apoptosis in hemato-lymphoid system. To enhance the survival of irradiated cells, we have compared the effects and mechanism of Bcl-2 and its functional variants, D34A (caspase-3 resistant) and S70E (mimics phosphorylation on S70). Bcl-2 and its mutants were transfected into hematopoietic cell line and assessed for cell survival, clonogenicity and cell cycle perturbations upon exposure to ionizing radiation. The electrostatic potential of BH3 cleft of Bcl-2/mutants and their heterodimerization with Bcl-2 associated X protein (Bax) were computationally evaluated. Correspondingly, these results were verified by co-immunoprecipitation and western blotting. The mutants afford higher radioprotective effect than Bcl-2 in apoptotic and clonogenic assays at D(0) (radiation dose at which 37 % cell survival was observed). The computational and functional analysis indicates that mutants have higher propensity to neutralize Bax protein by heterodimerization and have increased caspase-9 suppression capability, which is responsible for enhanced survival. This study implies potential of Bcl-2 mutants or their chemical/peptide mimics to elicit radioprotective effect in cells exposed to radiation.

Humans and robots: Friends of the future? A bird's eye view of biomanufacturing industry 5.0.

The evolution of industries have introduced versatile technologies, motivating limitless possibilities of tackling pivotal global predicaments in the arenas of medicine, environment, defence, and national security. In this direction, ardently emerges the new era of Industry 5.0 through the eyes of biomanufacturing, which integrates the most advanced systems 21st century has to offer by means of integrating artificial systems to mimic and nativize the natural milieu to substitute the deficits of nature, thence leading to a new meta world. Albeit, it questions the natural order of the living world, which necessitates certain paramount stipulations to be addressed for a successful expansion of biomanufacturing Industry 5.0. Can humans live in synergism with artificial beings? How can humans establish dominance of hierarchy with artificial counterparts? This perspective provides a bird's eye view on the plausible direction of a new meta world inquisitively. For this purpose, we propose the influence of internet of things (IoT) via new generation interfacial systems, such as, human-machine interface (HMI) and brain-computer interface (BCI) in the domain of tissue engineering and regenerative medicine, which can be extended to target modern warfare and smart healthcare.

Exploring STAT3 stimulatory potential of novel wound healing molecules by virtual screening and molecular dynamics simulations.

STAT3 signaling is a major intrinsic pathway for cell proliferation owing to its frequent activation in injured tissues. Various STAT3-regulated genes encode cytokines and growth factors, the receptors of which in turn activate the same STAT3 pathways, thereby regulating cell proliferation. In present study, we aimed to analyze several compounds for their wound healing and tissue repair potential by computer-aided virtual screening and Molecular dynamics (MD) simulation. Based on literature studies, a total of 36 drug molecules were selected having critical functions in wound healing and tissue repair. The pharmacological features (ADME and toxicity) of these molecules were predicted to find lead molecules among them. Further, a comparative study was performed to screen binding efficiency of STAT3 with many conventional wound healers by molecular docking. Among all, W6S, Strychnin, Prednisone and N-(6-(4-(3-(4-((4-Methylpiperazin-1-yl) methyl)-3- (trifluoromethyl)phenyl)ureido)phenoxy)pyrimidin-4-yl)cyclopropanecarboxamide showed best docking with STAT3 protein. The calculated binding energy of these molecules with STAT3 was found to be -8.9 Kca/mol for N-(6-(4-(3-(4-((4-Methylpiperazin-1-yl) methyl)-3-(trifluoromethyl) phenyl)ureido)phenoxy)pyrimidin-4-yl)cyclopropanecarboxamide, -8.7 Kcal/mol for W6S, -8.5 Kcal/mol for Strychnine and -8.4 Kcal/mol for Prednisone . The result was reconsidered for MD simulation. The simulation result showed stable binding of the ligand with STAT3 protein for 100 ns. These compounds showed better interaction potential with STAT3 was compared to known tissue repair molecules. Our data paves way for further exploration of these molecules as novel cell proliferators to be tested in various types of wound and tissue injuries.Communicated by Ramaswamy H. Sarma.

Identification of natural products against enoyl-acyl-carrier-protein reductase in malaria via combined pharmacophore modeling, molecular docking and simulations studies.

Plasmodium falciparum is counted as one of the deadly species causing malaria. In that respect, enoyl acyl carrier protein reductase is recognized as one of the attractive druggable targets for the identification of antimalarials. Thus, from the structural proteome of ENR, common feature pharmacophores were constructed. To identify the representative models, all the hypotheses were subjected to validation methods, like, test set, enrichment factor, and Güner-Henry method, and the selected representative hypotheses were used to screen out the drug-like natural products. Further, the screened candidates were advanced to molecular docking calculations. Based on the docking score criteria and presence of essential interaction with Tyr277, seven candidates were shortlisted to conduct the HYDE and QSAR assessment. Further, the stability of these complexes was evaluated by employing molecular dynamics simulations, molecular mechanics-generalized born surface area approach-based free binding energy calculations with the residue-wise contribution of PfENR to the total binding free energy of the complex. On comparing the root mean square deviation, and fluctuation plots of the docked candidates with the reference, all the candidates displayed stable behavior, and the same outcome was depicted from the secondary structure element. However, from the free energy calculations, and residue-wise contribution conducted after dynamics, it was observed that out of seven, only five candidates sustain the binding with Tyr277 and cofactor of PfENR. Therefore, in the current work, the hybrid study of screening and stability lead to the identification of five structurally diverse candidates that can be employed for the design of novel antimalarials.Communicated by Ramaswamy H. Sarma.

Data mining and structural analysis for multi-tissue regeneration potential of BMP-4 and activator drugs.

Despite substantial progress in surgery, managing multi-tissue injuries is strenuous to accomplish and requires a multi-staged serial treatment of individual tissues. Stimulated regeneration affects the complete structural and functional repair of both hard and soft tissues post-injury and thus serves as an attractive therapeutic option to target multi-tissue injuries. This study utilized data mining and structural analysis to identify a target that has the ability to evoke healing of the two most commonly injured tissues i.e., bone and muscle, and stimulate the inherent vascular connectivity between the tissues. To find out the multipotential molecule the gene expression profile from GSE34747 was extracted and processed to identify the differentially expressed genes (DEGs). The DEGs were then subjected to gene ontology enrichment analysis to filter out a target that is likely to regulate the multi-tissue regeneration. Further, STITCH and PubChem databases were screened to determine a stimulatory drug against the identified target molecule. Finally, the binding affinity and stability of the potential drug candidate(s) against the target were analysed by molecular docking and molecular dynamics simulation. The results revealed that bone morphogenetic protein-4 (BMP-4) was associated with the regulation of the multiple regeneration processes. The computational screening results suggested Retinoic acid and Torularhodin as potential drug candidates for the stimulation of BMP-4. Both drugs demonstrated slightly different but stable interactions with BMP-4, suggesting that the identified drug candidates are likely to serve as potential leads to further enhance tissues regeneration.Communicated by Ramaswamy H. Sarma.

Correction: Injectable organo-hydrogels influenced by click chemistry as a paramount stratagem in the conveyor belt of pharmaceutical revolution.

Correction for 'Injectable organo-hydrogels influenced by click chemistry as a paramount stratagem in the conveyor belt of pharmaceutical revolution' by Abhyavartin Selvam et al., J. Mater. Chem. B, 2023, https://doi.org/10.1039/d3tb01674a.