Stimuli Responsive Molecular Exchange of Structure Directing Agents on Gold Nanobipyramids: Cancer Cell Detection and Synergistic Therapeutics.

Surface-engineered gold nanoparticles have been considered as versatile systems for theranostics applications. Moreover, surface covering or stabilizing agents on gold nanoparticles especially gold nanobipyramids (AuNBPs) provides an extra space for cargo molecules entrapment. However, it is not well studied yet and also the preparation of AuNBPs still remains dependent largely on cetyltrimethylammonium bromide (CTAB), a cytotoxic surfactant. Therefore, the direct use of CTAB stabilized nanoparticles is not recommended for cancer theranostics applications. Herein, we address an approach of dodecyl ethyl dimethylammonium bromide (DMAB) as biocompatible structure directing agent for AuNBPs, which also accommodate anticancer drug doxorubicin (45%), an additional chemotherapeutics agent. Upon near-infrared light (NIR, 808 nm) exposure, engineered AuNBPs exhibit (i) better phototransduction (51 °C) due to NIR absorption ability (650-900 nm), (ii) photo triggered drug release (more than 80%), and (iii) synergistic chemophototherapy for breast cancer cells. Drug release response has been evaluated in tumor microenvironment conditions (84% in acidic pH and 80% at high GSH) due to protonation and high affinity of thiol binding with AuNBPs followed by DMAB replacement. Intracellular glutathione (GSH, 5-7.5 mM) replaces DMAB from AuNBPs, which cause easy aggregation of nanoparticles as corroborated by colorimetric shifts, suggesting their utilization as a molecular sensing probe of early stage cancer biomarkers. Our optimized recipe yield is monodisperse DMAB-AuNBPs with ∼90% purity even at large scales (500 mL volume per batch). DMAB-AuNBPs show better cell viability (more than 90%) across all concentrations (5-500 ug/mL) when directly compared to CTAB-AuNBPs (less than 10%). Our findings show the potential of DMAB-AuNBPs for early stage cancer detection and theranostics applications.

Sperm-Specific CatSper is Not Conserved in All Vertebrates and May Not be the Only Progesterone-Responsive Ion Channel Present in Sperm.

Progesterone (P4) acts as a key conserved signalling molecule in vertebrate reproduction. P4 is especially important for mature sperm physiology and subsequent reproductive success. "CatSpermasome", a multi-unit molecular complex, has been suggested to be the main if not the only P4-responsive atypical Ca2+-ion channel present in mature sperm. Altogether, here we analyse the protein sequences of CatSper1-4 from more than 500 vertebrates ranging from early fishes to humans. CatSper1 becomes longer in mammals due to sequence gain mainly at the N-terminus. Overall the conservation of full-length CatSper1-4 as well as the individual TM regions remain low. The lipid-water-interface residues (i.e. a 5 amino acid stretch sequence present on both sides of each TM region) also remain highly diverged. No specific patterns of amino acid distributions were observed. The total frequency of positively charged, negatively charged or their ratios do not follow in any specific pattern. Similarly, the frequency of total hydrophobic, total hydrophilic residues or even their ratios remain random and do not follow any specific pattern. We noted that the CatSper1-4 genes are missing in amphibians and the CatSper1 gene is missing in birds. The high variability of CatSper1-4 and gene-loss in certain clades indicate that the "CatSpermasome" is not the only P4-responsive ion channel. Data indicate that the molecular evolution of CatSper is mostly guided by diverse hydrophobic ligands rather than only P4. The comparative data also suggest possibilities of other Ca2+-channel/s in vertebrate sperm that can also respond to P4.

Internet-of-things-integrated molecularly imprinted polymer-based electrochemical nano-sensors for pesticide detection in the environment and food products.

To ensure environmental and health safety, relevant pollutants such as pesticides must be screened thoroughly to set their permissible limit. Various approaches have been used to identify pesticides such as capillary electrophoresis, gas and liquid-liquid chromatography, high-performance liquid chromatography, and enzyme-linked immune-absorbent tests. However, these techniques have some drawbacks, including time-consuming difficult steps, expensive bulky equipment, expert personnel, and a lack of selectivity. Recent advances in the field of biosensing have introduced biosensors for the onsite detection of pesticides which offer several advantages including rapid, simple, selective, sensitive, low-cost operation, and on-site detection. With the advent of molecularly imprinted polymer which substituted the traditional biorecognition elements (BREs) such as enzymes and antibodies, biosensors' sensitivity, selectivity, and reproducibility enhanced many folds. Molecularly imprinted polymers (MIP) are artificial polymer molecules that resemble natural BREs. They are synthesized when functional monomers are polymerized in the presence of a target analyte. Owing to the advantages of MIP, in this paper, the development of MIP-based electrochemical biosensors for pesticide detection is reviewed critically. A brief introduction to pesticides and the use of MIPs-based electrochemical sensors for pesticide detection is presented along with pros and cons. Further, Internet of Things (IoT) integrated MIP-based nanosensors for pesticide detection and information distribution have been discussed. In the end, future perspectives and challenges while implementing MIP-based nanosensors for onsite pesticide recognition have eventually been highlighted.

Biodiesel production and exploring properties of Datura stramonium L. oil with its optimization using combined approaches-Taguchi, grey relational analysis, and response surface methodology.

Biodiesel production through the synthesis of Datura stramonium L. oil is studied to explore the most efficient approaches to suggest an alternate feedstock for biodiesel production. The main objective of this work is to optimize the process variables of biodiesel synthesis by using some statistical approach (Taguchi method, grey relational analysis (GRA), and response surface methodology (RSM) analyzing three parameters, i.e., alcohol-to-oil molar ratio, catalyst (NaOH) concentration, and process temperature for achieving maximum biodiesel derived from Datura stramonium L. oil. The transesterification process is applied by using an ultrasonic-assisted technique. Grey relational analysis (GRA) was successfully applied with the Taguchi method resulting in the optimum combination of A2B1C1. Based on the findings, the best operating conditions for transesterifying are attained with the RSM approach consisting of a 5.697:1 molar ratio (level 2), 0.3 (wt.%) NaOH concentration (level 1), and 70 °C process temperature (level 1). With a value of 87.02%, these ideal operating conditions produce the maximum yield as compared to grey relational analysis (GRA) yields 83.99%. The obtained results have been verified through the characterization of oil and biodiesel as well. Also, the fuel qualities of DSL biodiesel were identified and assessed. DSL oil was found 137.6 degrees of unsaturation during fatty acid profile analysis. DSL biodiesel was found the best kinematic viscosity (4.2 mm2/s) and acid value (0.49) when compared to Karanja and palm biodiesel. D. stramonium L. was recognized as a suitable species for biodiesel feedstock according to the findings.

Bronchoscopic Electrocautery Versus Adrenaline and Cold Saline Instillation for Prophylactic Haemostasis Prior to Biopsy of Endobronchial Lesions (BEVACS): A Randomized Controlled Trial.

BACKGROUND: Flexible bronchoscopy-guided endobronchial biopsy (EBB) is routinely performed as an outpatient daycare procedure. Bleeding after EBB is a common complication, that at times disrupts the procedure and can rarely lead to a catastrophe. We aimed to compare the efficacy of prebiopsy prophylactic bronchoscopic electrocautery with adrenaline and cold saline instillation in achieving hemostasis in patients with endobronchial lesions with a higher risk of bleeding during EBB. METHODS: In this open-label, randomized controlled trial, 60 patients with endobronchial lesions were randomized to either the prophylactic electrocautery arm or the adrenaline and cold saline arm. Postbiopsy endobronchial bleed was quantified in millimeters using the Visual Analog Scale (VAS) and graded as per the British Thoracic Society grading system. Electrocautery-induced tissue damage was graded by the pathologist as "no damage," "mild," "moderate," and "severe." RESULTS: The median VAS score of bleeding was 6.14 mm (interquartile range: 8 mm) in the electrocautery arm and 10.17 mm (interquartile range: 7 mm) in the adrenaline and cold saline arm. Though the difference in the VAS score of bleeding between the two groups was statistically significant, there was no significant difference in the proportion of grade 2 or higher bleeding. CONCLUSION: No difference in postbiopsy bleed was observed between the application of electrocautery or instillation of cold saline plus adrenaline before biopsy of those endobronchial lesions which were likely to bleed more after biopsy. Although controlled prophylactic electrocautery using 15 watts did not impair the quality of EBB specimens, a higher wattage may change this observation, as well as the bleeding quantity.

Association of Thyroid Function With Lipid Profile in Patients With Metabolic Syndrome: A Prospective Cross-Sectional Study in the Indian Population.

Introduction Metabolic syndrome is a group of aberrant metabolic indicators including hypertension, dyslipidemia, impaired fasting blood glucose, and obesity. It has been reported that thyroid hormones have a strong influence on the cardiovascular system, and hypothyroidism has been linked to metabolic syndrome components. The objective of the study was to find out the association of thyroid function with lipid profile in patients with metabolic syndrome. Methods A prospective cross-sectional study was conducted in an apparently healthy adult population visiting the outpatient Department of Indira Gandhi Institute of Medical Sciences (IGIMS), Patna, Bihar, India. Metabolic syndrome was diagnosed according to the International Diabetes Federation (IDF) criteria. Fasting blood glucose, triglyceride, and HDL levels were tested using the enzymatic photometric method. Thyroid-stimulating hormone (TSH), free T4, free T3, and insulin assays were performed using chemiluminescence immunoassay (CLIA). Results Out of 197 subjects recruited, 86 (51 males and 35 females) were diagnosed with metabolic syndrome according to the IDF criteria, and the rest 111 without metabolic syndrome were considered to be the controls. The mean age of subjects with and without metabolic syndrome was 45.8±8.5 and 46.4±9.6 years, respectively. The prevalence of thyroid dysfunction in the present study was 22%. In subjects with metabolic syndrome, most of the clinical and hormonal parameters (waist circumference, waist-height ratio, fasting blood sugar, fasting insulin, triglycerides, T3, and TSH) were significantly higher (p<0.001) as compared to those without metabolic syndrome. In case of lipid profile, the triglycerides in those with metabolic syndrome (262.8±112.3 mg/dL) were significantly higher (p<0.001) than those without metabolic syndrome (137.9±19.01 mg/dL), while the serum levels of HDL were significantly higher (p<0.001) in group without metabolic syndrome (50.5±3.9 mg/dL) as compared to those with metabolic syndrome (43.4±5.2 mg/dL). Also, the TSH levels were significantly higher (p<0.001) in subjects with metabolic syndrome (5.3±3.4 µl/mL) as compared to those without metabolic syndrome (2.6±1.4 µl/mL). Among all the components of metabolic syndrome, waist circumference and HDL showed a significant strong positive correlation (r=0.51) with TSH, and systolic blood pressure (r=0.39), diastolic blood pressure (r=0.39), and fasting blood sugar levels (r=0.44) showed significantly moderate positive correlation with TSH levels. T4 (OR=8.82; 95% CI: 1.56-49.8) and TSH (OR=1.61; 95% CI: 1.19-2.18) levels were observed to have significantly higher odds as risk factors for metabolic syndrome. Conclusion There is a significant association of thyroid function with lipid profile in metabolic syndrome. It was observed that along with metabolic alterations, cardiovascular symptoms of hypothyroidism and subclinical hypothyroidism are possible. Therefore, while evaluating people with metabolic syndrome, it may be appropriate to look into how well their thyroid glands are functioning.

Green Synthesis of CdS and CdS/rGO Nanocomposites: Evaluation of Electrochemical, Antimicrobial, and Photocatalytic Properties.

The green approach has been employed for the synthesis of various types of nanomaterials including metal nanoparticles, metal oxides, and carbon-based nanomaterials. These processes involve natural sources that contain bioactive compounds that act as reducing, stabilizing, and capping agents for the formation and stabilization of nanomaterials. This study reports the green synthesis of CdS and CdS/rGO nanocomposites using Lactobacillus bacteria. The UV-visible spectrophotometer, field emission scanning electron microscopy, transmission electron microscopy, energy-dispersive X-ray spectroscopy, Raman spectroscopy, and Fourier transform infrared spectroscopy spectra confirm the synthesis of the nanocomposite. The electrochemical characterization using cyclic voltammetry, differential pulse voltammetry, and EIS revealed that the CdS/rGO nanocomposites showed a higher electron transfer rate compared with CdS nanoparticles, indicating the potential of the nanocomposites for biosensing applications. The zone of inhibition revealed significant antimicrobial activity against Escherichia coli and Staphylococcus aureus for both CdS nanoparticles and CdS/rGO nanocomposites. Additionally, CdS/rGO nanoparticles exhibited high photocatalytic activity for the degradation of methylene blue dye. Overall, this study demonstrates that the synthesized CdS and CdS/rGO nanocomposites have good electrochemical properties, photocatalytic, and antimicrobial activity and, therefore, can be employed for various applications such as biosensing, photocatalysis, and antimicrobial activity.

Phase encoded quantum key distribution up to 380 km in standard telecom grade fiber enabled by baseline error optimization.

Phase encoding in quantum key distribution (QKD) enables long-distance information-theoretic secure communication in optical fibers. We present a novel theoretical model characterizing errors from various sources in practical phase encoding-based QKD systems, namely the laser linewidth, detector dark counts, and channel dispersion. This model provides optimized optical pulse parameters and less distortion in pulses, which eliminates system imperfections and leads to a reduced quantum bit error rate (QBER) for practical QKD scenario. This analysis is applicable to various fiber-based phase and time encoding protocols. In particular, we implement this to a differential phase shift (DPS) QKD scheme operating at a 2.5 GHz clock, which produces a secure key rate of 193 bits/s at a fiber length of 265 km and an unprecedented QBER < 1[Formula: see text] up to 225 km length with standard telecom components. We show that by adjusting the quantum efficiency and dark count rates of detectors, proposed system can establish secure keys up to 380 km distance using standard telecom grade fiber with a QBER of 1.48%. Moreover, the system is compatible with existing optical fiber networks and capable of establishing a secure key exchange between two cities 432 km apart using ultra-low-loss (ULL) specialty fiber.

Clinical Utility of Bronchoalveolar Lavage Neutrophilia and Biomarkers for Evaluating Severity of Chronic Fibrosing Interstitial Lung Diseases.

Introduction It is hypothesized that bronchoalveolar lavage (BAL) neutrophilia, Krebs von den Lungen-6 (KL-6), and C-reactive protein (CRP) predict the severity of chronic fibrosing interstitial lung diseases (CF-ILDs). Methods This cross-sectional study enrolled 30 CF-ILD patients. Using Pearson's correlation analysis, BAL neutrophils, KL-6, and CRP were correlated with forced vital capacity (FVC), diffusing lung capacity for carbon monoxide (DLCO), six-minute walk distance (6MWD), partial pressure of oxygen (PaO2), computed tomography fibrosis score (CTFS), and pulmonary artery systolic pressure (PASP). Using the receiver operator characteristic (ROC) curve, BAL KL-6 and CRP were evaluated against FVC% and DLCO% in isolation and combination with BAL neutrophilia for predicting the severity of CF-ILDs. Results BAL neutrophilia significantly correlated only with FVC% (r = -0.38, P = 0.04) and DLCO% (r = -0.43, P = 0.03). BAL KL-6 showed a good correlation with FVC% (r = -0.44, P < 0.05) and DLCO% (r = -0.50, P = 0.02), while BAL CRP poorly correlated with all parameters (r = 0.0-0.2). Subset analysis of BAL CRP in patients with CTFS ≤ 15 showed a better association with FVC% (r = -0.28, P = 0.05) and DLCO% (r = -0.36, P = 0.04). BAL KL-6 cut-off ≥ 72.32 U/ml and BAL CRP ≥ 14.55 mg/L predicted severe disease with area under the curve (AUC) values of 0.77 and 0.71, respectively. The combination of BAL neutrophilia, KL-6, and CRP predicted severity with an AUC value of 0.89. Conclusion The combination of BAL neutrophilia, KL-6, and CRP facilitates the severity stratification of CF-ILDs complementing existing severity parameters.

Evaluation of the Prevalence of White Spot Lesions During Fixed Orthodontic Treatment Among Patients Reporting for Correction of Malocclusion: A Prevalence Study.

BACKGROUND: Despite recent breakthroughs in caries preventive measures, one of the biggest issues clinicians confront is preventing demineralization while undergoing orthodontic therapy. The buildup of plaques around orthodontic brackets over time causes white spot lesions (WSLs). The goal of the present research was to assess the prevalence of WSLs in patients undergoing orthodontic treatment before starting therapy and at six and 12 months into therapy, adopting the visual examination approach. MATERIALS AND METHODS: We looked for WSLs on tooth surfaces gingival to an archwire because this is the area most likely to experience enamel demineralization during orthodontic treatment. The visual assessment was conducted using the following scale at baseline, six months, and 12 months for orthodontic patients: score 0: no demineralization or noticeable white patches on the surface; score 1: mild demineralization with a visible white spot but no surface disruption; score 2: moderate demineralization with a noticeable WSL that has a roughened surface but does not need repair; and score 3: severe demineralization with a noticeable WSL that needs repair. Fisher's exact test was used after a chi-square analysis to determine whether there were any differences between all three categories (six months, 12 months, and control). RESULTS: The frequency of WSL in patients at 12 months of orthodontic treatment was 46.57%, while it was 11.86% in patients who just started orthodontic treatment. The difference was statistically significant (p = 0.01), showing that the frequency was greater in patients at 12 months of orthodontic treatment as compared to patients who had just started undergoing orthodontic treatment. The frequency of WSL in patients at six months of orthodontic treatment was 37.34%, while it was 11.86% in patients who just started orthodontic treatment. The difference was statistically significant (p = 0.03), showing that the frequency was greater in patients at six months of orthodontic treatment as compared to patients who had just started undergoing orthodontic treatment. The frequency of WSL in patients at six months of orthodontic treatment was 37.34%, while it was 46.57% in patients at 12 months of orthodontic treatment. The frequency was greater in patients at 12 months of orthodontic treatment as compared to patients at six months of orthodontic treatment; however, the difference was non-significant statistically (p = 0.76). CONCLUSION: This clinical investigation revealed that the number of WSLs increased significantly during the first six months of treatment and then increased gradually until the final 12 months. During the first few months of treatment, doctors should assess the patients' dental hygiene habits and, if necessary, take further precautions to prevent demineralization.

Cellulose-based bioabsorbable and antibiotic coated surgical staple with bioinspired design for efficient wound closure.

The quest to design a flawless wound closure system began long ago and is still underway. Introducing surgical staples is one of the most significant breakthroughs in this effort. In this work, we developed a biodegradable surgical staple to meet the optimal wound closure system criteria and other clinical requirements, such as radiography compatibility and secondary infection prevention. To meet these requirements, a naturally derived cellulose acetate (CA) fiber-reinforced poly-(l-lactic acid) (PLLA) composite was synthesized, and its physicochemical properties were determined using several characterizations such as Fourier-transform infrared spectroscopy (FTIR), Differential scanning calorimetry (DSC) and Universal testing machine (UTM), etc. Taking cues from the Mantis's foreleg, a novel staple design was implemented and verified using Finite Element Analysis (FEA). The CA + PLLA staples were fabricated using melt-casted/3D-printing processes. The staples exhibited excellent biodegradation in both wound and physiological microenvironments with sufficient puncturing strength and later closed the wound's edges mechanically. In addition, the CA + PLLA staples also exhibit metal-like ductility properties to withstand horizontal skin tensions during the healing process. Further, the staples are coated with an antibiotic to combat infections effectively to provide better healing.

Comparison between all-on-four and all-on-six treatment concepts on stress distribution for full-mouth rehabilitation using three-dimensional finite element analysis: A biomechanical study.

Purpose: The current study intended to provide a comparison of biomechanical behaviors of two different treatment concepts for full-mouth rehabilitation with dental implants placed according to the "All-on-four" concept and "All-on-six" concept with analysis of the stress patterns of the implant support system using three-dimensional finite element analysis (FEA). Materials and Methods: The edentulous mandible was treated with two different implant designs. "All-on-Four" implant placement concept was used in Model 1 with two central axial implants and two distally tilted implants at 17° and in Model 2, "All-on-Six" concept was applied with six vertically placed implants. Individual vertical and horizontal load of 100 N and oblique load of 141 N at 45° was applied to all implants. To evaluate and compare the results in terms of maximum principal stress, we used FEA. Results: All-on-six showed smaller maximum principal stress values on the cortical bone and implants. However, maximum principal stress values obtained on trabecular bone was smaller in the All-on-four design for vertical and horizontal loading conditions. Conclusions: The All-on-six approach showed more favorable biomechanical behavior.

Progesterone interacts with the mutational hot-spot of TRPV4 and acts as a ligand relevant for fast Ca2+-signalling.

Steroids are also known to induce immediate physiological and cellular response which occurs within minutes to seconds, or even faster. Such non-genomic actions of steroids are rapid and are proposed to be mediated by different ion channels. Transient receptor potential vanilloid sub-type 4 (TRPV4), is a non-specific polymodal ion channel which is involved in several physiological and cellular processes. In this work, we explored the possibilities of Progesterone (P4) as an endogenous ligand for TRPV4. We demonstrate that P4 docks as well as physically interacts with the TM4-loop-TM5 region of TRPV4, a region which is a mutational hotspot for different diseases. Live cell imaging experiments with a genetically encoded Ca2+-sensor suggests that P4 causes quick influx of Ca2+ specifically in the TRPV4 expressing cells, which can be partially blocked by TRPV4-specific inhibitor, suggesting that P4 can act as a ligand for TRPV4. Such P4-mediated Ca2+-influx is altered in cells expressing disease causing TRPV4 mutants, namely in L596P, R616Q, and also in embryonic lethal mutant L618P. P4 dampens, both in terms of "extent" as well as the "pattern" of the Ca2+-influx by other stimulus too in cells expressing TRPV4-Wt, suggesting that P4 crosstalk with the TRPV4-mediated Ca2+-signalling, both in quick and long-term manner. We propose that P4 crosstalk with TRPV4 might be relevant for both acute and chronic pain as well as for other health-related functions.

Molecular basis of differential HLA class I-restricted T cell recognition of a highly networked HIV peptide.

Cytotoxic-T-lymphocyte (CTL) mediated control of HIV-1 is enhanced by targeting highly networked epitopes in complex with human-leukocyte-antigen-class-I (HLA-I). However, the extent to which the presenting HLA allele contributes to this process is unknown. Here we examine the CTL response to QW9, a highly networked epitope presented by the disease-protective HLA-B57 and disease-neutral HLA-B53. Despite robust targeting of QW9 in persons expressing either allele, T cell receptor (TCR) cross-recognition of the naturally occurring variant QW9_S3T is consistently reduced when presented by HLA-B53 but not by HLA-B57. Crystal structures show substantial conformational changes from QW9-HLA to QW9_S3T-HLA by both alleles. The TCR-QW9-B53 ternary complex structure manifests how the QW9-B53 can elicit effective CTLs and suggests sterically hindered cross-recognition by QW9_S3T-B53. We observe populations of cross-reactive TCRs for B57, but not B53 and also find greater peptide-HLA stability for B57 in comparison to B53. These data demonstrate differential impacts of HLAs on TCR cross-recognition and antigen presentation of a naturally arising variant, with important implications for vaccine design.

Vinyl substituted triphenylamine based turn-off fluorescent probe for selective and sensitive detection of mercury (II) in water and live cells.

Here, we report vinyl substituted triphenylamine (TPA-alk) fluorescent probe for the rapid and efficient detection of mercury ion (Hg2+) in water and biological environment. TPA-alk detects Hg2+ selectively over a wide range of competitive metal ions with a blue shift of 43 nm in the UV absorbance spectrum. The detection limit is found to be 0.146 µM (29.2 ppb) with high selectivity over a wide range of competitive metal ions. DFT study explains the blue shift in the UV-vis absorption band of the optical probe upon the addition of Hg2+. Cell viability assay illustrates that the probe is biocompatible and it has low cytotoxicity even at its higher concentration. Cell imaging studies demonstrate the efficiency of the TPA-alk probe for the micromolar detection of mercury (II) in live BMG1 cells.

MXene-based aptasensor for the detection of aflatoxin in food and agricultural products.

The detection of toxins that contaminate food needs highly sensitive and selective techniques to prevent substantial monitory loss. In this regard, various nanostructured material-enabled biosensors, have recently been developed to improve the detection of food toxins among them aflatoxin is the prevalent one. The biosensor-based detection of aflatoxin is quick, cheaper, and needs less skilled personnel, therefore overcoming the shortcomings of conventional techniques such as LC/MS-MS, HPLC, and ELISA assays. 2D MXenes manifest as an efficient material for biosensing due to their desirable biocompatibility, magnificent mechanical strength, easiness of surface functionalization, and tuneable optical and electronic features. Contrary to this, aptamers as biorecognition elements (BREs) possess high selectivity, sensitivity, and ease of synthesis when compared to conventional BREs. In this review, we explored the most cutting-edge aptamer-based MXene-enabled biosensing technologies for the detection of the most poisonous mycotoxins (i.e., Aflatoxins) in food and environmental matrices. The discussion begins with the synthesis processes and surface functionalization/modification of MXenes. Computational approaches for designing aptasensors and advanced data analysis based on artificial intelligence and machine learning with special emphasis over Internet-of-Thing integrated biosensing devices has been presented. Besides, the advantages of aptasensors over conventional methods along with their limitations have been briefed. Their benefits, drawbacks, and future potential are discussed concerning their analytical performance, utility, and on-site adaptability. Additionally, next-generation MXene-enabled biosensing technologies that provide end users with simple handling and improved sensitivity and selectivity have been emphasized. Owing to massive applicability, economic/commercial potential of MXene in current and future perspective have been highlighted. Finally, the existing difficulties are scrutinized and a roadmap for developing sophisticated biosensing technologies to detect toxins in various samples in the future is projected.

Human skeletal dysplasia causing L596P-mutant alters the conserved amino acid pattern at the lipid-water-Interface of TRPV4.

TRPV4 is a polymodal and non-selective cation channel that is activated by multiple physical and chemical stimuli. >50 naturally occurring point-mutation of TRPV4 have been identified in human, most of which induce different diseases commonly termed as channelopathies. While, these mutations are either "gain-of-function" or "loss-of-function" in nature, the exact molecular and cellular mechanisms behind such diverse channelopathies are largely unknown. In this work, we analyze the evolutionary conservation of individual amino acids present in the lipid-water-interface (LWI) regions and the relationship of TRPV4 with membrane cholesterol. Our data suggests that the positive-negative charges and hydrophobic-hydrophilic amino acids form "specific patterns" in the LWI region which remain conserved throughout the vertebrate evolution and thus suggesting for the specific microenvironment where TRPV4 remain functional. Notably, Spondylometaphyseal Dysplasia, Kozlowski (SMDK) disease causing L596P mutation disrupts this pattern significantly at the LWI region. L596P mutant also sequesters Caveolin-1 differently, especially in partial cholesterol-depleted (~40 % reduction) conditions. L596P shows altered localization in membrane and enhanced Ca2+-influx properties in cell as well as in filopodia-like structures. We propose that conserved pattern of amino acids is an important parameter for proper localization and functions of TRPV4 in physiological conditions. These findings also offer a new paradigm to analyze the channelopathies caused by mutations in LWI regions of other channels as well.

Aqua-(2-formylbenzoato)triphenyltin(IV) induces cell cycle arrest and apoptosis in hypoxic triple negative breast cancer cells.

Hypoxia plays a vital role in tumor microenvironment by allowing development and maintenance of cancer cells thereby led to major hindrance for effective anticancer therapy and main reason for failure of most anticancer drugs. We herein investigated the therapeutic efficacy and molecular mechanism of action of aqua-(2-formylbenzoato) triphenyltin (IV) compound (OTC) in MDA-MB-231 cell line. Cobalt chloride induced hypoxic MDA-MB-231 cells treated with OTC were used to access cytotoxicity, ROS, cellular apoptosis, and cell cycle progression. Further, expression of HIF-1α and VEGF, as well as apoptotic proteins like p53, Bax, Bcl-2 and caspase 3 were assessed. The findings indicated that OTC is more effective towards CoCl2 induced hypoxic cells when compared to normoxic cells and the results are far superior to doxorubicin. Additionally, our study revealed that OTC facilitates more ROS production induced cell cycle arrest and promote apoptosis. Furthermore, OTC significantly down regulates the expression of Hif-1α, VEGF and Bcl-2 in hypoxic condition and elevates the level of p53, Bax, cytochrome-C and Caspase 3. Our in vitro studies demonstrated that OTC showed better efficacy than doxorubicin, corroborating that OTC could be a promising compound for hypoxic cancer that also display multi drug resistant.

Platelet Rich Fibrin Membrane Grafting After Laser Excision for Oral Mucosal Lesions.

Platelet rich fibrin (PRF) is a novel surgical biomaterial which has shown immense healing and regenerative potential with diverse clinical applications. Surgical excision is a routinely employed treatment modality for mucosal oral lesions with or without grafting or repair of the base of the wound. We proposed a hypothesis that covering of the base of excised lesion with this platelet rich fibrin membrane can accelerate the rate of physiological healing process and regeneration. To evaluate the role, efficacy, advantages and adverse effects if any, of placement of PRF membrane grafts over surgical excision sites of oral mucosal lesions. Platelet rich fibrin membrane graft was prepared as per recommendation and established protocols. Patients were selected for surgical excision of localized, superficial oral mucosal lesions after meticulous clinical and radiological considerations and informed consent was taken. After laser excision with safe margins, the base of wound was covered with PRF membrane graft, stitched in place by 3-0 vicryl sutures. The operated site was clinically evaluated at regular intervals and a healing score was calculated and statistically tabulated on the basis of various parameters of healing. A total of 34 patients were included in the study with a male preponderance (21 males and 13 females). Satisfactory and clinically acceptable wound healing was observed in most of the patient with minimal morbidities. Surgical site demonstrated good healing score and clinically complete healing with good epithelialisation was achieved in all patients. Platelet rich fibrin membrane is an effective grafting biomaterial after excision of oral mucosal lesions as it enhances the rate of healing with minimal complications. We recommend further multicentre studies with higher sample size to explore its utility and clinical applications in different avenues of oral and head neck surgery.