Insights to Phenylalanine Ammonia Lyase (PAL) and Secondary Metabolism in Orchids: An in silico Approach.

The phenylalanine ammonia lyase (PAL) catalyses the first step of phenylpropanoid metabolic pathway which leads to the biosynthesis of a diverse group of secondary metabolites. Orchids serve as a rich source of metabolites and the availability of genome or transcriptome for selected orchid species provides an opportunity to analyse the PAL genes in orchids. In the present study, 21 PAL genes were characterized using bioinformatics tools in nine orchid species (Apostasia shenzhenica, Cypripedium formosanum, Dendrobium catenatum, Phalaenopsis aphrodite, Phalaenopsis bellina, Phalaenopsis equestris, Phalaenopsis lueddemanniana, Phalaenopsis modesta and Phalaenopsis schilleriana). Multiple sequence alignment confirmed the presence of PAL-specific conserved domains (N-terminal, MIO, core, shielding and C-terminal domain). All these proteins were predicted to be hydrophobic in nature and to have cytoplasmic localisation. Structural modelling depicted the presence of alpha helices, extended strands, beta turns and random coils in their structure. Ala-Ser-Gly triad known for substrate binding and catalysis of MIO-domain was found to be completely conserved in all the proteins. Phylogenetic study showed that the PALs of pteridophytes, gymnosperms and angiosperms clustered together in separate clades. Expression profiling showed tissue-specific expression for all the 21 PAL genes in the various reproductive and vegetative tissues which suggested their diverse role in growth and development. This study provides insights to the molecular characterization of PAL genes which may help in developing biotechnological strategies to enhance the synthesis of phenylpropanoids in orchids and other heterologous systems for pharmaceutical applications.

Physiological and psychological stress response of blood donors during the blood donation process.

BACKGROUND AND OBJECTIVES: Blood donation can be a potentially stressful event, leading to the activation of an acute stress response. Knowing and identifying potential stressors could help in optimizing the donation experience. The present study aimed to measure the physiological and psychological stress changes before, during and after blood donation. MATERIALS AND METHODS: Physiological and psychological stress response was assessed in 70 blood donors. To evaluate physiological stress response, pulse rate, respiratory rate, blood pressure (BP), beat-to-beat BP and lead II electrocardiogram were recorded. Baroreflex sensitivity was calculated using the available software. Psychological stress response was assessed using the State-Trait Anxiety Inventory scale. RESULTS: A significant increase in systolic blood pressure, diastolic blood pressure and mean arterial pressure was observed in the pre-donation period (p < 0.001). Among the time-domain parameters, SDSD (standard deviation of differences between adjacent respiratory rate intervals) and RMSSD (root mean square of the successive differences) were significantly lower during the post-donation period (p < 0.005, p < 0.007, respectively). Among the frequency-domain parameters, LF nu (relative power of the low-frequency band in normalized units), HF nu (relative power of the high-frequency band in normalized units) and LF% (relative power of the low-frequency band in percentage) were significantly lower before donation compared to during donation (p < 0.001, p < 0.001 and p < 0.012, respectively). LF nu, LF% and LF/HF ratio were also significantly lower during donation compared to after donation (p < 0.05, p < 0.016 and p < 0.042, respectively). Baroreflex sensitivity was also statistically higher during the pre-donation period. State score was significantly higher among the blood donors during the pre-donation period. CONCLUSION: Physiological and psychological stress is experienced by blood donors during the pre-donation period. A pre-donation informative conversation should be carried out with each blood donor and potential stressors should be identified in each.

Major depressive disorder (mdd): emerging immune targets at preclinical level.

BACKGROUND: Major depressive disorder is a mental health disorder that is characterized by a persistently low mood and loss of interest. MDD is affecting over 3.8% of the global population as a major health problem. Its etiology is complex, and involves the interaction between a number of factors, including genetic predisposition and the presence of environmental stresses. AREAS COVERED: The role of the immune and inflammatory systems in depression has been gaining interest, with evidence suggesting the potential involvement of pro-inflammatory molecules like TNF, interleukins, prostaglandins, and other cytokines, among others, has been put forth. Along with this, the potential of agents, from NSAIDs to antibiotics, are being evaluated in therapy for depression. The current review will discuss emerging immune targets at the preclinical level. EXPERT OPINION: With increasing evidence to show that immune and inflammatory mediators are implicated in MDD, increasing research toward their potential as drug targets is encouraged. At the same time, agents acting on these mediators and possessing anti-inflammatory potential are also being evaluated as future therapeutic options for MDD, and increasing focus toward non-conventional drugs which can act through these mechanisms is important as regards the future prospects of the use of anti-inflammatory agents in depression.

Pharmaceutical Considerations of Translabial Formulations for Treatment of Parkinson's Disease: A Concept of Drug Delivery for Unconscious Patients.

PURPOSE: The goal of the present research was to isolate a biopolymer from Phaseolus vulgaris (P. vulgaris) and Zea mays (Z. mays) plants and used it to construct Resveratrol (RES)-loaded translabial films. METHODS: Biopolymers were extracted from P. vulgaris and Z. mays seeds using a simple process. Separated biopolymers, sodium carboxymethylcellulose (SCMC) and tragacanth were subjected to formulation development by incorporating RES-loaded translabial films. The Fourier-transform infrared spectroscopy (FTIR), physical appearance, weight, thickness, folding endurance, swelling index, surface pH, percent moisture absorption, percent moisture loss, vapor transfer rate, and content uniformity of the translabial films were examined. The mucoadhesive, ex-vivo permeation, in vivo and stability studies, were performed. RESULTS: The results showed that RES-loaded translabial films produced from P. vulgaris and Z. mays biopolymers exhibited exceptional mucoadhesive, stability, and permeation properties. Results revealed that the best formulations were prepared from a combination of biopolymer (P. vulgaris C or Z. mays C) with tragacanth. Formulations with tragacanth revealed good swelling and thus permeation profiles. In vivo release of TL 11 was found to be 24.05 ng/ml in 10 hours and it was stable enough at 45°C. CONCLUSION: This research suggested that RES-loaded translabial formulations can be potentially used for the treatment of Parkinson's disease with good patient compliance to geriatric and unconscious patients.

Biopolymer templated strategized greener protocols for fabrication of ZnO nanostructures and their application in photocatalytic technology for phasing out priority pollutants.

Zinc oxide (ZnO) nanostructures have been successfully synthesized via template-assisted and template-free route using three different synthetic methods, i.e., sonochemical, mechanochemical, and hydrothermal. Biopolymer xanthan gum (XG) served as sacrificial template for ZnO synthesis as provided the surface for the growth of nanostructures in a controlled manner. The employment of multifarious synthetic techniques resulted in fabrication of ZnO nanoparticles with diverse morphologies such as needle shaped, hexagonal, and spherical particles. Further, the template-assisted protocols generated thermally stable highly crystalline nanostructures along with high surface area, larger pore size, and low band gap energies in contrast to template-free protocol. The structural and other physicochemical studies were manifested by XRD, N2 adsorption desorption, FESEM, TGA, and UV-Vis spectral analysis. The template-assisted ZnO nanostructures were explored as a potential photocatalyst for the catalytic degradation of emerging pollutants, i.e., triclosan (TCS) and imidacloprid (IMD) under the exposure of UV light. The products formed during the photocatalytic reaction were monitored by UV-Vis spectroscopy and HPLC. The results obtained revealed the high catalytic efficiency of ZnO synthesized via template-assisted sonochemical method for TCS (99.60%) and IMD (96.09%) which is attributed to the high surface area and lower band gap energy of the catalyst. The high catalytic potential of the sonochemically synthesized ZnO also substantiated from the kinetic data as high-rate constant was obtained. Thus, the template-assisted protocols developed led to preparation of nanostructures having tailored properties for efficient photocatalysis and can rapidly degrade selected emerging contaminants such as personal care products and organophosphate pesticides. Hence, environment-friendly synthesized photocatalyst can be appropriately employed to wastewater treatment contaminated with emerging pollutants.

Polyketide synthases (PKSs) of secondary metabolism: in silico identification and characterization in orchids.

Type III polyketide synthases (PKSs) catalyse the formation of an array of polyketides with diverse structures that play an important role in secondary metabolism in plants. This group of enzymes is encoded by a multigene family, the Type III polyketide synthase (PKS) gene family. Vast reserves of secondary metabolites in orchids make these plants suitable candidates for research in the area. In this study, genome-wide searches lead to the identification of five PeqPKS, eight DcaPKS and six AshPKS genes in Phalaenopsis equestris, Dendrobium catenatum and Apostasia shenzhenica, respectively. All the members showed the presence of two characteristic conserved domains (Chal_sti_synt_N and Chal_sti_synt_C) and were generally localised in the cytoplasm. The phylogenetic analysis led to the classification of these proteins into two groups: CHS (chalcone synthase (CHS) and non-CHS. A single protein in P. equestris and two proteins each in D. catenatum and A. shenzhenica clustered within the CHS clade. The majority of the genes exhibited similar structural patterns with a single intron. Expression profiling revealed the tissue-specific expression of these genes with high expression in reproductive tissues for most genes. A number of stress-responsive cis-regulatory elements were predicted, noteworthy amongst these are, ABRE and CGTCA that are chiefly responsible for responding to abscisic acid and methyl jasmonate, respectively. Our study provides a reference framework for future studies involving functional elucidation of PKS genes and biotechnological production of polyketides.Communicated by Ramaswamy H. Sarma.

Identification of five PeqPKS, eight DcaPKS and six AshPKS genes in Phalaenopsis equestris, Dendrobium catenatum and Apostasia shenzhenica based on genome-wide analysisPresence of characteristic conserved domains (Chal_sti_synt_N, Chal_sti_synt_C) with cytological localisationPhylogenetic clustering into two groups, CHS chalcone synthase (CHS) and non-CHSExpression profiling revealing high expression in reproductive tissuesPrediction of stress-responsive cis-regulatory elements like ABRE and CGTCA.

Toll-like receptor (TLR) agonists as a driving force behind next-generation vaccine adjuvants and cancer therapeutics.

Until recently, the development of new human adjuvants was held back by a poor understanding of their mechanisms of action. The field was revolutionized by the discovery of the toll-like receptors (TLRs), innate immune receptors that directly or indirectly are responsible for detecting pathogen-associated molecular patterns (PAMPs) and respond to them by activating innate and adaptive immune pathways. Hundreds of ligands targeting various TLRs have since been identified and characterized as vaccine adjuvants. This work has important implications not only for the development of vaccines against infectious diseases but also for immuno-therapies against cancer, allergy, Alzheimer's disease, drug addiction and other diseases. Each TLR has its own specific tissue localization and downstream gene signalling pathways, providing researchers the opportunity to precisely tailor adjuvants with specific immune effects. TLR agonists can be combined with other TLR or alternative adjuvants to create combination adjuvants with synergistic or modulatory effects. This review provides an introduction to the various classes of TLR adjuvants and their respective signalling pathways. It provides an overview of recent advancements in the TLR field in the past 2-3 years and discusses criteria for selecting specific TLR adjuvants based on considerations, such as disease mechanisms and correlates of protection, TLR immune biasing capabilities, route of administration, antigen compatibility, new vaccine technology platforms, and age- and species-specific effects.

Stereoisomeric Pam2CS based TLR2 agonists: synthesis, structural modelling and activity as vaccine adjuvants.

Lipopeptides including diacylated Pam2CSK4 as well as triacylated Pam3CSK4 act as ligands of toll-like receptor (TLR)-2, a promising target for the development of vaccine adjuvants. The highly investigated Pam2CSK4 and Pam3CSK4, despite their aqueous solubility have not performed well as vaccine adjuvants which may be attributable to potential denaturation of protein antigens by these cationic surfactant-like lipopeptides. In the present investigation, we synthesized (R), (S) and racemic Pam2CS(OMe) analogs and their N-acetyl derivatives without the tetralysine component to systematically investigate the effect of stereochemistry at the thio-glycerol lipopeptide core of these lipopeptide based TLR2 agonists. The resulting compounds were compared using TLR2 reporter cell-based assays and the ability of the synthesized lipopeptides to stimulate cytokine production (IL-6, IL-10 and TNF-α) by freshly collected human PBMCs and CD40 and CD86 expressions by mouse spleen cells was also investigated. Notably, few synthesized lipopeptides were found to be potent TLR2/6 agonists, inducing cytokine production and upregulating CD40 and CD86 expressions. The TLR2/6 agonistic lipopeptides were further assessed for vaccine adjuvant effects in mice. The results confirmed that the R-stereochemistry at the thio-glycerol lipopeptide core was preferred for maximal TLR2/6 activity, as reflected in Th1 immune deviation, higher antibody levels and enhanced vaccine protection against a lethal influenza challenge.

Recognition of Protein Network for Bioinformatics Knowledge Analysis Using Support Vector Machine.

Protein is the material foundation of living things, and it directly takes part in and runs the process of living things itself. Predicting protein complexes helps us understand the structure and function of complexes, and it is an important foundation for studying how cells work. Genome-wide protein interaction (PPI) data is growing as high-throughput experiments become more common. The aim of this research is that it provides a dual-tree complex wavelet transform which is used to find out about the structure of proteins. It also identifies the secondary structure of protein network. Many computer-based methods for predicting protein complexes have also been developed in the field. Identifying the secondary structure of a protein is very important when you are studying protein characteristics and properties. This is how the protein sequence is added to the distance matrix. The scope of this research is that it can confidently predict certain protein complexes rapidly, which compensates for shortcomings in biological research. The three-dimensional coordinates of C atom are used to do this. According to the texture information in the distance matrix, the matrix is broken down into four levels by the double-tree complex wavelet transform because it has four levels. The subband energy and standard deviation in different directions are taken, and then, the two-dimensional feature vector is used to show the secondary structure features of the protein in a way that is easy to understand. Then, the KNN and SVM classifiers are used to classify the features that were found. Experiments show that a new feature called a dual-tree complex wavelet can improve the texture granularity and directionality of the traditional feature extraction method, which is called secondary structure.

Classification of EEG Signal-Based Encephalon Magnetic Signs for Identification of Epilepsy-Based Neurological Disorder.

Magnetoencephalography (MEG) is now widely used in clinical examinations and medical research in many fields. Resting-state magnetoencephalography-based brain network analysis can be used to study the physiological or pathological mechanisms of the brain. Furthermore, magnetoencephalography analysis has a significant reference value for the diagnosis of epilepsy. The scope of the proposed research is that this research demonstrates how to locate spikes in the phase locking functional brain connectivity network of the Desikan-Killiany brain region division using a neural network approach. It also improves detection accuracy and reduces missed and false detection rates. The automatic classification of epilepsy encephalomagnetic signals can make timely judgments on the patient's condition, which is of tremendous clinical significance. The existing literature's research on the automatic type of epilepsy EEG signals is relatively sufficient, but the research on epilepsy EEG signals is relatively weak. A full-band machine learning automatic discrimination method of epilepsy brain magnetic spikes based on the brain functional connection network is proposed. The four classifiers are comprehensively compared. The classifier with the best effect is selected, and the discrimination accuracy can reach 93.8%. Therefore, this method has a good application prospect in automatically identifying and labeling epileptic spikes in magnetoencephalography.

A Walk Through the Maze of Secondary Metabolism in Orchids: A Transcriptomic Approach.

Orchids have a huge reservoir of secondary metabolites making these plants of immense therapeutic importance. Their potential as curatives has been realized since times immemorial and are extensively studied for their medicinal properties. Secondary metabolism is under stringent genetic control in plants and several molecular factors are involved in regulating the production of the metabolites. However, due to the complex molecular networks, a complete understanding of the specific molecular cues is lacking. High-throughput omics technologies have the potential to fill up this lacuna. The present study deals with comparative analysis of high-throughput transcript data involving gene identification, functional annotation, and differential expression in more than 30 orchid transcriptome data sets, with a focus to elucidate the role of various factors in alkaloid and flavonoid biosynthesis. Comprehensive analysis of the mevalonate (MVA) pathway, methyl-d-erythritol 4-phosphate (MEP) pathway, and phenylpropanoid pathway provide specific insights to the potential gene targets for drug discovery. It is envisaged that a positive stimulation of these pathways through regulation of pivotal genes and alteration of specific gene expression, could facilitate the production of secondary metabolites and enable efficient tapping of the therapeutic potential of orchids. This further would lay the foundation for developing strategies for genetic and epigenetic improvement of these plants for development of therapeutic products.

Combined delivery of TLR2 and TLR7 agonists by Nanostructured lipid carriers induces potent vaccine adjuvant activity in mice.

Toll-like receptor (TLR) agonists are promising adjuvants and the combination of TLR agonists enhance immune responses by providing synergistic immune activity via triggering different signalling pathways. However, systematic cytotoxicity due to the immediate release of such immune potentiators from the site of injection hampers its clinical performance. Nanostructured lipid carriers (NLCs) offer a possibility to incorporate multiple TLR agonists with high encapsulation efficiency and slow drug release. Herein, we synthesized NLCs from didodecyldimethylammonium bromide (D12DAB) and oleic acid and used these to co-encapsulate a Pam2CS derivative (T-2, TLR2 agonist) with an imidazoquinoline derivative (T-7, TLR7 agonist) as a combination vaccine adjuvant. Hydrodynamic diameter and zeta potential of the prepared NLCs were found to be in the range of 200-500 nm and 23-27 mV, respectively. Spherical shape and size of prepared NLCs were also assessed through Field Emission Scanning Electron Microscopy (FE-SEM) and Transmission Electron Microscopy (TEM) analysis. In-vitro release studies of T-7 demonstrated sustained release and the addition of lipopeptide T-2 augmented encapsulation efficiency (from 84 to 92.9%) with a slight trigger in the release percentage. All NLC formulations were screened in TLR2/1, TLR2/6, TLR7 and TLR8 reporter cell lines and loaded NLC formulation showed high TLR2 and TLR7 agonistic activity. Adjuvant potency was evaluated through intramuscular immunization of female C57BL/6 mice with recombinant hepatitis B surface antigen and influenza hemagglutinin protein. T-2 and T-7 loaded NLCs induced good protective efficacy in mice challenged with a lethal dose of influenza virus.

Resveratrol: A Vital Therapeutic Agent with Multiple Health Benefits.

Resveratrol (RSV), the most effective stilbene phytoalexin synthesized naturally or induced in plants as part of their defense mechanism, is a key component of natural phenolic compounds and is being considered as a treatment option for a variety of diseases. RSV was discovered in the skin of red grapes, mulberries, peanuts, pines, and Polygonum cuspidatum weed root extracts. It was first extracted from white hellebore (Veratrum grandiflorum O. Loes) roots in 1940, then from Polygonum cuspidatum roots in 1963. However, RSV's use as a drug is limited due to its initial conformational strength and poor stability. The research focused on a set of RSV biological activity data. RSV has been the subject of growing concern, despite its wide range of biological and therapeutic applications. According to the literature, RSV has antioxidant, anti-cancer, cardioprotective, neuroprotective, anti- inflammatory, anti-microbial, immunomodulatory, and radioprotective properties. The current analysis summarized biological applications of RSV, their mechanisms of action, and recent scientific development in the area of their delivery. It is possible to infer that RSV has many effects on infected cells' cellular functions.

Implementation of stacking based ARIMA model for prediction of Covid-19 cases in India.

BACKGROUND: Time-series forecasting has a critical role during pandemics as it provides essential information that can lead to abstaining from the spread of the disease. The novel coronavirus disease, COVID-19, is spreading rapidly all over the world. The countries with dense populations, in particular, such as India, await imminent risk in tackling the epidemic. Different forecasting models are being used to predict future cases of COVID-19. The predicament for most of them is that they are not able to capture both the linear and nonlinear features of the data solely. METHODS: We propose an ensemble model integrating an autoregressive integrated moving average model (ARIMA) and a nonlinear autoregressive neural network (NAR). ARIMA models are used to extract the linear correlations and the NAR neural network for modeling the residuals of ARIMA containing nonlinear components of the data. Comparison: Single ARIMA model, ARIMA-NAR model and few other existing models which have been applied on the COVID-19 data in different countries are compared based on performance evaluation parameters. RESULT: The hybrid combination displayed significant reduction in RMSE (16.23%), MAE (37.89%) and MAPE (39.53%) values when compared with single ARIMA model for daily observed cases. Similar results with reduced error percentages were found for daily reported deaths and cases of recovery as well. RMSE value of our hybrid model was lesser in comparison to other models used for forecasting COVID-19 in different countries. CONCLUSION: Results suggested the effectiveness of the new hybrid model over a single ARIMA model in capturing the linear as well as nonlinear patterns of the COVID-19 data.

Structural evolution of toll-like receptor 7/8 agonists from imidazoquinolines to imidazoles.

Several synthetic heterocyclic small molecules like imiquimod, resiquimod, CL097, CL075, bromopirone, tilorone, loxoribine and isatoribine demonstrated TLR7/8 agonistic activity and relatively modest structural changes in such molecules result in major variation in the TLR7 and/or TLR8 activity. A strict dependency of the electronic configuration of the heterocyclic system was also observed to influence the agonistic activity. In the present review, an evolution of imidazole based TLR7/8 agonist from imidazoquinoline based scaffold is delineated along with the elaboration of detailed structure activity relationship (SAR) in each chemotype. The structural and activity details of not only the active compounds but also the related inactive compounds are included to better understand the SAR. TLR7/8 agonists are emerging as promising vaccine adjuvant candidates and the present SAR and structural information will provide a road map towards the identification of more potent and appropriate candidates for further drug discovery.

Structure activity relationship in ß-carboline derived anti-malarial agents.

Malaria, even though an avoidable and treatable disease, can be fatal if ignored. Artemisinin Combination Therapy (ACT) and RTS, S/AS01 vaccine (Mosquirix™) are the only modest means available with humans to overcome malaria, a lethal affliction wreaking havoc across the globe. Employment of ACT is associated with problems such as 'Artemisinin Resistance' and the 'Hypnozoite conundrum' that hinder the complete eradication of malaria. In this view, the natural products specifically comprising ß-carboline scaffold have shown good antiplasmodial responses against different strains of malaria. Taking these observations forward, researchers have performed structure-activity relationship (SAR) studies around three different ß-carboline skeletons (tetrahydro ß-carbolines, dihydro ß-carbolines, ß-carbolines) to design new ß-carboline derived heterocyclic structures or modified naturally occurring derivatives. In addition, different approaches such as dimerization and linkage to other moieties have also been adopted to enhance the antimalarial activity. The present review describes a comprehensive SAR study encapsulating various natural and synthetic ß-carbolines to elaborate upon the utility of these skeletons in designing drugs to subdue this deadly disease.

Implications of the use of mechanical thrombectomy on outcome in large vessel occlusion following the 2015 landmark trials.

BACKGROUND: The effectiveness of mechanical thrombectomy (MT) was demonstrated in five landmark trials published in2015.Mechanical thrombectomy is now standard of care for acute ischemic stroke and has been growing in popularity after publication of landmark trials. OBJECTIVE: To analyze outcomes and trends of the use of MT and intravenous thrombolysis (IVT) in patients with acute ischemic stroke in US hospitals before and after publication of these trials. METHODS: Patients discharged with a diagnosis of ischemic stroke between 2012 to 2017 were diagnosed using ICD codes from the National Inpatient Sample. Thereafter, patients given acute stroke treatment were identified using the corresponding procedure codes for IVT and MT. The primary clinical outcomes of in-hospital mortality and disability were then compared between two time periods: 2012-2014 (pre-landmark trials) and 2015-2017 (post-landmark trials). Binary logistic regression and Χ2 tests were used for statistical analysis. RESULTS: A total of 57 675 patients (median age 68.9 years (range 18-90), 50.1% female) were identified with acute procedures. Of these patients, 57.6% were from the post-landmark trials time period. Despite an increased number of cases, the rate of IVT decreased from 84.3% to 75.9% and the rate of IVT+MT decreased from 7.1% to 6.3%. After publication of the pivotal trials in 2015, the rates of MT increased from 8.7% to 17.8%. Significant reductions of in-hospital mortality (7.1% vs 8.7%, p<0.001) and disability (64% vs 66.2%, p<0.001) were noted. CONCLUSION: The analysis showed a significant increase in the proportion of patients receiving MT after 2015. This has translated into reduction of in-hospital mortality and improvement in disability.

TLR2 Agonistic Small Molecules: Detailed Structure-Activity Relationship, Applications, and Future Prospects.

Toll-like receptors (TLRs) are the pattern recognition receptors (PRRs) that recognize pathogen-associated molecular patterns (PAMPs) in microbial species. Among the various TLRs, TLR2 has a special place due to its ability to sense the widest repertoire of PAMPs owing to its heterodimerization with either TLR1 or TLR6, broadening its ligand diversity against pathogens. Various scaffolds are reported to activate TLR2, which include naturally occurring lipoproteins, synthetic lipopeptides, and small heterocyclic molecules. We described a detailed SAR in TLR2 agonistic scaffolds and also covered the design and chemistry for the conjugation of TLR2 agonists to antigens, carbohydrates, polymers, and fluorophores. The approaches involved in delivery of TLR2 agonists such as lipidation of antigen, conjugation to polymers, phosphonic acids, and other linkers to achieve surface adsorption, liposomal formulation, and encapsulating nanoparticles are elaborated. The crystal structure analysis and computational modeling are also included with the structural features that facilitate TLR2 activation.

Male pseudohermaphrodite with persistent Mullerian duct: A radiologist's and patient's dilemma alike.

This case study highlights that how a disorder of sexual development when goes unnoticed at birth and unreported during childhood or adolescence can present with major problems and even complications in adulthood. Since our patient was young and in a childbearing age, he presented with bilateral undescended testes and orgasmic anejaculation when he first came to the hospital. Subsequently, having a normal 46XY karyotype but remnants of persistent Mullerian duct made him little confused about his identity. After giving him the confidence, that he was still a male and could lead the life he did previously, the explanation about future risk of malignancy in the intra-abdominal testes was another difficult task. Early detection and management of male pseudohermaphroditism with persistent Mullerian duct requires a co-ordinated approach of a team of endocrinologist, physician, surgeon and radiologist. Integrated imaging in the form of ultrasound, genitography and MRI is important in demonstrating the anatomy, classification, possible effects or congenital malformations in other organs, warning patients of any risk of neoplasia and guiding the clinician to plan other investigations, hormonal replacement or reconstruction surgery if required. Such a systemic approach that allays anxiety and gives psychological relief to the patient should be taken as it can deeply change the life of a person and their family.